bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of CCL15 Expression and Monocyte Adhesion to Endothelial Cells (ECs) after Hypoxia/Reoxygenation and Induction of ICAM-1 Expression by CCL15 via the JAK2/STAT3 Pathway in ECs
Authors: Park Keun Hyung , Lee Tae Hoon , Kim Chan Woo , Kim Jiyoung
Published: May 2013

CCL15, a member of the CC chemokine family, is a potent chemoattractant for leukocytes and endothelial cells (ECs). Given that chemokines play key roles in vascular inflammation, we investigated the effects of hypoxia/reoxygenation (H/R) on expression of human CCL15 and a role of CCL15 in upregulating ICAM-1 in ECs. We found that exposure of ECs to H/R increased expression of CCL15 and ICAM-1, which resulted in an increase in monocyte adhesivity to the ECs. Further studies revealed that knockdown of CCL15 or CCR1 attenuated expression of ICAM-1 in ECs after H/R, suggesting that expression of ICAM-1 is upregulated by CCL15. Stimulation of ECs with CCL15 significantly increased expression of ICAM-1 predominantly via the CCR1 receptor. We observed that phosphorylation of JAK2 and STAT3 was stimulated by CCL15 treatment of ECs. Results from reporter and chromatin immunoprecipitation assays revealed that CCL15 activates transcription from the IFN-γ activation site promoter and stimulates binding of STAT3 to the ICAM-1 promoter. Our data also showed that CCL15 increased cell adhesion of human monocytes to ECs under static and shear-stress conditions. Pretreatment of these cells with inhibitors for JAK, PI3K, and AKT prevented the CCL15-induced expression of ICAM-1 and monocyte adhesion to ECs, suggesting the involvement of those signaling molecules in ICAM-1 gene activation by CCL15. The results suggest that CCR1 and its ligands may be a potential target for treating inflammatory diseases involving upregulation of cell adhesion molecules.
IL-7 Produced by Thymic Epithelial Cells Plays a Major Role in the Development of Thymocytes and TCRγδ+ Intraepithelial Lymphocytes
Authors: Shitara Soichiro , Hara Takahiro , Liang Bingfei , Wagatsuma Keisuke , Zuklys Saulius , Holländer Georg A. , Nakase Hiroshi , Chiba Tsutomu , Tani-ichi Shizue , Ikuta Koichi
Published: May 2013

IL-7 is a cytokine essential for T cell development and survival. However, the local function of IL-7 produced by thymic epithelial cells (TECs) is poorly understood. To address this question, we generated IL-7–floxed mice and crossed them with FoxN1 promoter–driven Cre (FoxN1-Cre) mice to establish knockout mice conditionally deficient for the expression of IL-7 by TECs. We found that αβ and γδ T cells were significantly reduced in the thymus of IL-7f/f FoxN1-Cre mice. Proportion of mature single-positive thymocytes was increased. In lymph nodes and the spleen, the numbers of T cells were partially restored in IL-7f/f FoxN1-Cre mice. In addition, γδ T cells were absent from the fetal thymus and epidermis of IL-7f/f FoxN1-Cre mice. Furthermore, TCRγδ+ intraepithelial lymphocytes (IELs) were significantly decreased in the small intestines of IL-7f/f FoxN1-Cre mice. To evaluate the function of IL-7 produced in the intestine, we crossed the IL-7f/f mice with villin promoter–driven Cre (Vil-Cre) mice to obtain the mice deficient in IL-7 production from intestinal epithelial cells. We observed that αβ and γδ IELs of IL-7f/f Vil-Cre mice were comparable to control mice. Collectively, our results suggest that TEC-derived IL-7 plays a major role in proliferation, survival, and maturation of thymocytes and is indispensable for γδ T cell development. This study also demonstrates that IL-7 produced in the thymus is essential for the development of γδ IELs and indicates the thymic origin of γδ IELs.
SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress
Authors: Do Kee Hun , Choi Hye Jin , Kim Juil , Park Seong-Hwan , Kim Ki-Hyung , Moon Yuseok
Published: May 2013

Although the activation of B cells in the gastrointestinal tract is of great importance in the context of immunity to pathogens and mucosal inflammatory diseases, little is known about the mechanisms responsible for the local activation of B cells in the subepithelial area of the intestine. Epithelium-derived BAFF is the major modulator of B cell development and Ig class switching. The present study was performed to address the molecular mechanism of BAFF expression in gut epithelial cells in the presence of proinflammatory stimuli. Inflammation-induced BAFF expression in mucosal epithelial cells might be responsible for diverse mucosa-associated diseases linked to intestinal inflammation and autoimmunity. Although BAFF was marginally expressed in unstimulated epithelial cells, BAFF mRNA was significantly upregulated by proinflammatory IFN-γ. Furthermore, IFN-γ triggered JAK/STAT1 signals via the cytokine receptor, which contributed to epithelial BAFF upregulation. In terms of signaling intervention, ribosomal insult attenuated IFN-γ–activated JAK/STAT signal transduction and subsequent BAFF induction in gut epithelial cells. Ribosomal insults led to the superinduction of SOCS3 by enhancing its mRNA stability via HuR RNA-binding protein. Upregulated SOCS3 then contributed to the blocking of the JAK/STAT-linked signal, which mediated BAFF suppression by ribosomal stress. All of these findings show that ribosomal stress–induced SOCS3 plays a novel regulatory role in epithelial BAFF production, suggesting that epithelial ribosomal dysfunction in association with SOCS3 may be a promising therapeutic point in BAFF-associated human mucosal diseases.
Helicobacter pylori Infection Inhibits Phagocyte Clearance of Apoptotic Gastric Epithelial Cells
Authors: Bimczok Diane , Smythies Lesley E. , Waites Ken B. , Grams Jayleen M. , Stahl Richard D. , Mannon Peter J. , Peter Shajan , Wilcox C. Mel , Harris Paul R. , Das Soumita , Ernst Peter B. , Smith Phillip D.
Published: May 2013

Increased apoptotic death of gastric epithelial cells is a hallmark of Helicobacter pylori infection, and altered epithelial cell turnover is an important contributor to gastric carcinogenesis. To address the fate of apoptotic gastric epithelial cells and their role in H. pylori mucosal disease, we investigated phagocyte clearance of apoptotic gastric epithelial cells in H. pylori infection. Human gastric mononuclear phagocytes were analyzed for their ability to take up apoptotic epithelial cells (AECs) in vivo using immunofluorescence analysis. We then used primary human gastric epithelial cells induced to undergo apoptosis by exposure to live H. pylori to study apoptotic cell uptake by autologous monocyte-derived macrophages. We show that HLA-DR+ mononuclear phagocytes in human gastric mucosa contain cytokeratin-positive and TUNEL-positive AEC material, indicating that gastric phagocytes are involved in AEC clearance. We further show that H. pylori both increased apoptosis in primary gastric epithelial cells and decreased phagocytosis of the AECs by autologous monocyte-derived macrophages. Reduced macrophage clearance of apoptotic cells was mediated in part by H. pylori–induced macrophage TNF-α, which was expressed at higher levels in H. pylori–infected, compared with uninfected, gastric mucosa. Importantly, we show that H. pylori–infected gastric mucosa contained significantly higher numbers of AECs and higher levels of nonphagocytosed TUNEL-positive apoptotic material, consistent with a defect in apoptotic cell clearance. Thus, as shown in other autoimmune and chronic inflammatory diseases, insufficient phagocyte clearance may contribute to the chronic and self-perpetuating inflammation in human H. pylori infection.
CD40 Mediates Downregulation of CD32B on Specific Memory B Cell Populations in Rheumatoid Arthritis
Authors: Zhang Xiaoyu , Burch Erin , Cai Ling , So Edward , Hubbard Fleesie , Matteson Eric L. , Strome Scott E.
Published: May 2013

Altered B cell function is important in the pathogenesis of rheumatoid arthritis (RA). In this report, we show that patients with active RA have an increased frequency of CD32B low/neg cells in the CD27+IgD− memory B cell subset and that these changes are associated with phenotypic and functional B cell activation. Studies using PBMCs from healthy donors revealed that downregulation of CD32B on B cells is mediated by CD40–CD40L interactions and is potentiated by IL-4 and inhibited by both IL-10 and IL-21. These findings appear physiologically relevant because CD4 T cell expression of CD40L correlated with the frequency of CD32B low/neg cells in the CD27+IgD− memory B subset in patients with RA. Our data support a model in which high levels of CD40L, present on circulating T cells in patients with RA, causes B cell activation and CD32B downregulation, resulting in secondary protection of memory B cells from CD32B-mediated cell death.
Galectin-1–Mediated Suppression of Pseudomonas aeruginosa–Induced Corneal Immunopathology
Authors: Suryawanshi Amol , Cao Zhiyi , Thitiprasert Thananya , Zaidi Tanveer S. , Panjwani Noorjahan
Published: May 2013

Corneal infection with Pseudomonas aeruginosa leads to a severe immunoinflammatory lesion, often causing vision impairment and blindness. Although past studies have indicated a critical role for CD4+ T cells, particularly Th1 cells, in corneal immunopathology, the relative contribution of recently discovered Th17 and regulatory T cells is undefined. In this study, we demonstrate that after corneal P. aeruginosa infection, both Th1 and Th17 cells infiltrate the cornea with increased representation of Th17 cells. In addition to Th1 and Th17 cells, regulatory T cells also migrate into the cornea during early as well as late stages of corneal pathology. Moreover, using galectin-1 (Gal-1), an immunomodulatory carbohydrate-binding molecule, we investigated whether shifting the balance among various CD4+ T cell subsets can modulate P. aeruginosa–induced corneal immunopathology. We demonstrate in this study that local recombinant Gal-1 (rGal-1) treatment by subconjunctival injections significantly diminishes P. aeruginosa–mediated corneal inflammation through multiple mechanisms. Specifically, in our study, rGal-1 treatment significantly diminished corneal infiltration of total CD45+ T cells, neutrophils, and CD4+ T cells. Furthermore, rGal-1 treatment significantly reduced proinflammatory Th17 cell response in the cornea as well as local draining lymph nodes. Also, rGal-1 therapy promoted anti-inflammatory Th2 and IL-10 response in secondary lymphoid organs. Collectively, our results indicate that corneal P. aeruginosa infection induces a strong Th17-mediated corneal pathology, and treatment with endogenously derived protein such as Gal-1 may be of therapeutic value for the management of bacterial keratitis, a prevalent cause of vision loss and blindness in humans worldwide.
Antigen-Specific Effector CD4 T Lymphocytes School Lamina Propria Dendritic Cells To Transfer Innate Tolerance
Authors: Cascio Jason A. , Haymaker Cara L. , Divekar Rohit D. , Zaghouani Sarah , Khairallah Marie-Therese , Wan Xiaoxiao , Rowland Linda M. , Dhakal Mermagya , Chen Weirong , Zaghouani Habib
Published: May 2013

Dendritic cells (DCs) have been shown to play a major role in oral tolerance, and this function has been associated with their ability to produce anti-inflammatory cytokines and to induce suppressive regulatory T cells. In this study, we demonstrate that upon oral administration of Ag, lamina propia (LP) DCs engage specific T cells and acquire a novel mechanism by which they transfer tolerance against diverse T cell specificities. Indeed, when Ig-myelin oligodendrocyte glycoprotein (MOG) carrying the MOG35–55 epitope was orally administered into either T cell–sufficient or –deficient mice, only the T cell–sufficient hosts yielded CD8α+ and CD8α− LP DCs that were able to transfer tolerance to a variety of MHC class II–restricted effector T cells. Surprisingly, these LP DCs upregulated programmed cell death ligand 1 during the initial interaction with MOG-specific T cells and used this inhibitory molecule to suppress activation of T cells regardless of Ag specificity. Furthermore, oral Ig-MOG was able to overcome experimental autoimmune encephalomyelitis induced with CNS homogenate, indicating that the DCs are able to modulate disease involving diverse T cell specificities. This previously unrecognized attribute potentiates DCs against autoimmunity.
IL-1α Signaling Initiates the Inflammatory Response to Virulent Legionella pneumophila In Vivo
Authors: Barry Kevin C. , Fontana Mary F. , Portman Jonathan L. , Dugan Aisling S. , Vance Russell E.
Published: May 2013

Legionella pneumophila is an intracellular bacterial pathogen that is the cause of a severe pneumonia in humans called Legionnaires’ disease. A key feature of L. pneumophila pathogenesis is the rapid influx of neutrophils into the lungs, which occurs in response to signaling via the IL-1R. Two distinct cytokines, IL-1α and IL-1β, can stimulate the type I IL-1R. IL-1β is produced upon activation of cytosolic sensors called inflammasomes that detect L. pneumophila in vitro and in vivo. Surprisingly, we find no essential role for IL-1β in neutrophil recruitment to the lungs in response to L. pneumophila. Instead, we show that IL-1α is a critical initiator of neutrophil recruitment to the lungs of L. pneumophila–infected mice. We find that neutrophil recruitment in response to virulent L. pneumophila requires the production of IL-1α specifically by hematopoietic cells. In contrast to IL-1β, the innate signaling pathways that lead to the production of IL-1α in response to L. pneumophila remain poorly defined. In particular, although we confirm a role for inflammasomes for initiation of IL-1β signaling in vivo, we find no essential role for inflammasomes in production of IL-1α. Instead, we propose that a novel host pathway, perhaps involving inhibition of host protein synthesis, is responsible for IL-1α production in response to virulent L. pneumophila. Our results establish IL-1α as a critical initiator of the inflammatory response to L. pneumophila in vivo and point to an important role for IL-1α in providing an alternative to inflammasome-mediated immune responses in vivo.
Recent Thymic Emigrants and Mature Naive T Cells Exhibit Differential DNA Methylation at Key Cytokine Loci
Authors: Berkley Amy M. , Hendricks Deborah W. , Simmons Kalynn B. , Fink Pamela J.
Published: May 2013

Recent thymic emigrants (RTEs) are the youngest T cells in the lymphoid periphery and exhibit phenotypic and functional characteristics distinct from those of their more mature counterparts in the naive peripheral T cell pool. We show in this study that the Il2 and Il4 promoter regions of naive CD4+ RTEs are characterized by site-specific hypermethylation compared with those of both mature naive (MN) T cells and the thymocyte precursors of RTEs. Thus, RTEs do not merely occupy a midpoint between the thymus and the mature T cell pool, but represent a distinct transitional T cell population. Furthermore, RTEs and MN T cells exhibit distinct CpG DNA methylation patterns both before and after activation. Compared with MN T cells, RTEs express higher levels of several enzymes that modify DNA methylation, and inhibiting methylation during culture allows RTEs to reach MN T cell levels of cytokine production. Collectively, these data suggest that the functional differences that distinguish RTEs from MN T cells are influenced by epigenetic mechanisms and provide clues to a mechanistic basis for postthymic maturation.
Transglutaminase 2–Specific Autoantibodies in Celiac Disease Target Clustered, N-Terminal Epitopes Not Displayed on the Surface of Cells
Authors: Iversen Rasmus , Di Niro Roberto , Stamnaes Jorunn , Lundin Knut E. A. , Wilson Patrick C. , Sollid Ludvig M.
Published: May 2013

The gluten-sensitive enteropathy celiac disease is tightly associated with the production of autoantibodies specific for the enzyme transglutaminase 2 (TG2). The mechanisms underlying the activation of autoreactive B cells, however, are not well defined. To gain more insight into this autoimmune response we have characterized the binding of TG2 by a panel of human mAbs generated by expression cloning of Ig genes from single plasma cells of the celiac disease lesion. The Abs were highly specific to TG2 and bound preferentially to the open, Ca2+-activated enzyme conformation. Epitope mapping revealed that they recognize few distinct conformational epitopes that cluster in the N-terminal half of the enzyme. Two of the epitopes were overlapping with the fibronectin binding site in TG2, and none of the epitopes was accessible when TG2 was in a cell surface–bound form. Based on our findings, we propose that the autoantibodies are generated against the soluble, catalytically active enzyme, whereas Abs reactive with cell surface–associated TG2 are absent from the response due to negative selection of B cells recognizing membrane-bound self-Ag. The findings give insight into the mechanisms controlling the formation of anti-TG2 autoantibodies in celiac disease.
Truncated Form of TGF-βRII, But Not Its Absence, Induces Memory CD8+ T Cell Expansion and Lymphoproliferative Disorder in Mice
Authors: Ishigame Harumichi , Mosaheb Munir M. , Sanjabi Shomyseh , Flavell Richard A.
Published: May 2013

Inflammatory and anti-inflammatory cytokines play an important role in the generation of effector and memory CD8+ T cells. We used two different models, transgenic expression of truncated (dominant negative) form of TGF-βRII (dnTGFβRII) and Cre-mediated deletion of the floxed TGF-βRII to examine the role of TGF-β signaling in the formation, function, and homeostatic proliferation of memory CD8+ T cells. Blocking TGF-β signaling in effector CD8+ T cells using both of these models demonstrated a role for TGF-β in regulating the number of short-lived effector cells but did not alter memory CD8+ T cell formation and their function upon Listeria monocytogenes infection in mice. Interestingly, however, a massive lymphoproliferative disorder and cellular transformation were observed in Ag-experienced and homeostatically generated memory CD8+ T cells only in cells that express the dnTGFβRII and not in cells with a complete deletion of TGF-βRII. Furthermore, the development of transformed memory CD8+ T cells expressing dnTGFβRII was IL-7– and IL-15–independent, and MHC class I was not required for their proliferation. We show that transgenic expression of the dnTGFβRII, rather than the absence of TGF-βRII–mediated signaling, is responsible for dysregulated expansion of memory CD8+ T cells. This study uncovers a previously unrecognized dominant function of the dnTGFβRII in CD8+ T cell proliferation and cellular transformation, which is caused by a mechanism that is different from the absence of TGF-β signaling. These results should be considered during both basic and translational studies where there is a desire to block TGF-β signaling in CD8+ T cells.
A Novel Targeting Therapy of Malignant Mesothelioma Using Anti-Podoplanin Antibody
Authors: Abe Shinji , Morita Yuki , Kaneko Mika Kato , Hanibuchi Masaki , Tsujimoto Yuta , Goto Hisatsugu , Kakiuchi Soji , Aono Yoshinori , Huang Jun , Sato Seidai , Kishuku Masatoshi , Taniguchi Yuki , Azuma Mami , Kawazoe Kazuyoshi , Sekido Yoshitaka , Yano Seiji , Akiyama Shin-ichi , Sone Saburo , Minakuchi Kazuo , Kato Yukinari , Nishioka Yasuhiko
Published: May 2013

Podoplanin (Aggrus), which is a type I transmembrane sialomucin-like glycoprotein, is highly expressed in malignant pleural mesothelioma (MPM). We previously reported the generation of a rat anti-human podoplanin Ab, NZ-1, which inhibited podoplanin-induced platelet aggregation and hematogenous metastasis. In this study, we examined the antitumor effector functions of NZ-1 and NZ-8, a novel rat-human chimeric Ab generated from NZ-1 including Ab-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against MPM in vitro and in vivo. Immunostaining with NZ-1 showed the expression of podoplanin in 73% (11 out of 15) of MPM cell lines and 92% (33 out of 36) of malignant mesothelioma tissues. NZ-1 could induce potent ADCC against podoplanin-positive MPM cells mediated by rat NK (CD161a+) cells, but not murine splenocytes or human mononuclear cells. Treatment with NZ-1 significantly reduced the growth of s.c. established tumors of MPM cells (ACC-MESO-4 or podoplanin-transfected MSTO-211H) in SCID mice, only when NZ-1 was administered with rat NK cells. In in vivo imaging, NZ-1 efficiently accumulated to xenograft of MPM, and its accumulation continued for 3 wk after systemic administration. Furthermore, NZ-8 preferentially recognized podoplanin expressing in MPM, but not in normal tissues. NZ-8 could induce higher ADCC mediated by human NK cells and complement-dependent cytotoxicity as compared with NZ-1. Treatment with NZ-8 and human NK cells significantly inhibited the growth of MPM cells in vivo. These results strongly suggest that targeting therapy to podoplanin with therapeutic Abs (i.e., NZ-8) derived from NZ-1 might be useful as a novel immunotherapy against MPM.
GB Virus C Particles Inhibit T Cell Activation via Envelope E2 Protein-Mediated Inhibition of TCR Signaling
Authors: Bhattarai Nirjal , McLinden James H. , Xiang Jinhua , Landay Alan L. , Chivero Ernest T. , Stapleton Jack T.
Published: May 2013

Viruses enter into complex interactions within human hosts, leading to facilitation or suppression of each other’s replication. Upon coinfection, GB virus C (GBV-C) suppresses HIV-1 replication in vivo and in vitro, and GBV-C coinfection is associated with prolonged survival in HIV-infected people. GBV-C is a lymphotropic virus capable of persistent infection. GBV-C infection is associated with reduced T cell activation in HIV-infected humans, and immune activation is a critical component of HIV disease pathogenesis. We demonstrate that serum GBV-C particles inhibited activation of primary human T cells. T cell activation inhibition was mediated by the envelope glycoprotein E2, because expression of E2 inhibited TCR-mediated activation of Lck. The region on the E2 protein was characterized and revealed a highly conserved peptide motif sufficient to inhibit TCR-mediated signaling. The E2 region contained a predicted Lck substrate site, and substitution of an alanine or histidine for the tyrosine reversed TCR-signaling inhibition. GBV-C E2 protein and a synthetic peptide representing the inhibitory amino acid sequence were phosphorylated by Lck in vitro. The synthetic peptide also inhibited TCR-mediated activation of primary human CD4+ and CD8+ T cells. Extracellular microvesicles from GBV-C E2–expressing cells contained E2 protein and inhibited TCR signaling in bystander T cells not expressing E2. Thus, GBV-C reduced global T cell activation via competition between its envelope protein E2 and Lck following TCR engagement. This novel inhibitory mechanism of T cell activation may provide new approaches for HIV and immunoactivation therapy.
Association between a Multi-Locus Genetic Risk Score and Inflammatory Bowel Disease
Authors: Hu Pingzhao , Muise Aleixo M. , Xing Xiang , Brumell John H. , Silverberg Mark S. , Xu Wei
Published: May 2013

To date, the utility of single genetic markers to improve disease risk assessment still explains only a small proportion of genetic variance for many complex diseases. This missing heritability may be explained by additional variants with weak effects. To discover and incorporate these additional genetic factors, statistical and computational methods must be evaluated and developed. We develop a multi-locus genetic risk score (GRS) based approach to analyze genes in NADPH oxidase complex which may result in susceptibility to development of inflammatory bowel disease (IBD). We find the complex is highly associated with IBD ( P = 7.86 × 10–14) using the GRS-based association method. Similar results are also shown in permutation analysis ( P = 6.65 × 10–11). Likelihood ratio test shows that the single nucleotide polymorphisms (SNPs) in the complex without nominal signals have significant contribution to the overall genetic effect within the complex ( P = 0.015). Our results show that the multi-locus GRS association model can improve the genetic risk assessment on IBD by taking into account both confirmed and as yet unconfirmed disease susceptibility variants.
Biomarkers of Dose and Effect of Inhaled Ozone in Resting versus Exercising Human Subjects: Comparison with Resting Rats
Authors: Hatch Gary E. , McKee John , Brown James , McDonnell William , Seal Elston , Soukup Joleen , Slade Ralph , Crissman Kay , Devlin Robert
Published: May 2013

To determine the influence of exercise on pulmonary dose of inhaled pollutants, we compared biomarkers of inhaled ozone (O3) dose and toxic effect between exercise levels in humans, and between humans and rats. Resting human subjects were exposed to labeled O3 (18O3, 0.4 ppm, for 2 hours) and alveolar O3 dose measured as the concentration of excess 18O in cells and extracellular material of nasal, bronchial, and bronchoalveolar lavage fluid (BALF). We related O3 dose to effects (changes in BALF protein, LDH, IL-6, and antioxidant substances) measurable in the BALF. A parallel study of resting subjects examined lung function (FEV1) changes following O3. Subjects exposed while resting had 18O concentrations in BALF cells that were 1/5th of those of exercising subjects and directly proportional to the amount of O3 breathed during exposure. Quantitative measures of alveolar O3 dose and toxicity that were observed previously in exercising subjects were greatly reduced or non-observable in O3 exposed resting subjects. Resting rats and resting humans were found to have a similar alveolar O3 dose.
Measuring Restriction Sizes Using Diffusion Weighted Magnetic Resonance Imaging: A Review
Authors: Martin Melanie
Published: May 2013

This article reviews a new concept in magnetic resonance as applied to cellular and biological systems. Diffusion weighted magnetic resonance imaging can be used to infer information about restriction sizes of samples being measured. The measurements rely on the apparent diffusion coefficient changing with diffusion times as measurements move from restricted to free diffusion regimes. Pulsed gradient spin echo (PGSE) measurements are limited in the ability to shorten diffusion times and thus are limited in restriction sizes which can be probed. Oscillating gradient spin echo (OGSE) measurements could provide shorter diffusion times so smaller restriction sizes could be probed.
Excess Vitamin Intake before Starvation does not Affect Body Mass, Organ Mass, or Blood Variables but Affects Urinary Excretion of Riboflavin in Starving Rats
Authors: Moriya Aya , Fukuwatari Tsutomu , Shibata Katsumi
Published: May 2013

B-vitamins are important for producing energy from amino acids, fatty acids, and glucose. The aim of this study was to elucidate the effects of excess vitamin intake before starvation on body mass, organ mass, blood, and biological variables as well as on urinary excretion of riboflavin in rats. Adult rats were fed two types of diets, one with a low vitamin content (minimum vitamin diet for optimum growth) and one with a sufficient amount of vitamins (excess vitamin diet). Body mass, organ mass, and blood variables were not affected by excess vitamin intake before starvation. Interestingly, urinary riboflavin excretion showed a different pattern. Urine riboflavin in the excess vitamin intake group declined gradually during starvation, whereas it increased in the low vitamin intake group. Excess vitamin intake before starvation does not affect body mass, organ mass, or blood variables but does affect the urinary excretion of riboflavin in starving rats.
On Braided and Ribbon Unitary Fusion Categories
Authors: Galindo César
Published: May 2013

We prove that every braiding over a unitary fusion category is unitary and every unitary braided fusion category admits a unique unitary ribbon structure.
Air/sea DMS gas transfer in the North Atlantic: evidence for limited interfacial gas exchange at high wind speed
Authors: Bell T. G. , De Bruyn W. , Miller S. D. , Ward B. , Christensen K. , Saltzman E. S.
Published: May 2013

Abstract. Shipboard measurements of eddy covariance DMS air/sea fluxes and seawater concentration were carried out in the North Atlantic bloom region in June/July 2011. Gas transfer coefficients (k660) show a linear dependence on mean horizontal wind speed at wind speeds up to 11 m s−1. At higher wind speeds the relationship between k660 and wind speed weakens. At high winds, measured DMS fluxes were lower than predicted based on the linear relationship between wind speed and interfacial stress extrapolated from low to intermediate wind speeds. In contrast, the transfer coefficient for sensible heat did not exhibit this effect. The apparent suppression of air/sea gas flux at higher wind speeds appears to be related to sea state, as determined from shipboard wave measurements. These observations are consistent with the idea that long waves suppress near surface water side turbulence, and decrease interfacial gas transfer. This effect may be more easily observed for DMS than for less soluble gases, such as CO2, because the air/sea exchange of DMS is controlled by interfacial rather than bubble-mediated gas transfer under high wind speed conditions.
Biology and air–sea gas exchange controls on the distribution of carbon isotope ratios (δ13C) in the ocean
Authors: Schmittner A. , Gruber N. , Mix A. C. , Key R. M. , Tagliabue A. , Westberry T. K.
Published: May 2013

Abstract. Analysis of observations and sensitivity experiments with a new three-dimensional global model of stable carbon isotope cycling elucidate the processes that control the distribution of δ13C in the contemporary and preindustrial ocean. Biological fractionation dominates the distribution of δ13CDIC of dissolved inorganic carbon (DIC) due to the sinking of isotopically light δ13C organic matter from the surface into the interior ocean. This process leads to low δ13CDIC values at dephs and in high latitude surface waters and high values in the upper ocean at low latitudes with maxima in the subtropics. Air–sea gas exchange provides an important secondary influence due to two effects. First, it acts to reduce the spatial gradients created by biology. Second, the associated temperature dependent fractionation tends to increase (decrease) δ13CDIC values of colder (warmer) water, which generates gradients that oppose those arising from biology. Our model results suggest that both effects are similarly important in influencing surface and interior δ13CDIC distributions. However, air-sea gas exchange is slow, so biological effect dominate spatial δ13CDIC gradients both in the interior and at the surface, in constrast to conclusions from some previous studies. Analysis of a new synthesis of δ13CDIC measurements from years 1990 to 2005 is used to quantify preformed (δ13Cpre) and remineralized (δ13Crem) contributions as well as the effects of biology (Δδ13Cbio) and air–sea gas exchange (δ13C*). The model reproduces major features of the observed large-scale distribution of δ13CDIC, δ13Cpre, δ13Crem, δ13C*, and Δδ13Cbio. Residual misfits are documented and analyzed. Simulated surface and subsurface δ13CDIC are influenced by details of the ecosystem model formulation. For example, inclusion of a simple parameterization of iron limitation of phytoplankton growth rates and temperature-dependent zooplankton grazing rates improves the agreement with δ13CDIC observations and satellite estimates of phytoplankton growth rates and biomass, suggesting that δ13C can also be a useful test of ecosystem models.
German politicians and their Twitter networks in the Bundestag Election 2009
Authors: Plotkowiak Thomas , Stanoevska-Slabeva Katarina
Published: May 2013

In this paper we present an analysis of 599 Twitter accounts of politicians, who for the first time became involved with social networking, becoming their own "reputational entrepreneurs" in social media (Fine, 1996) while running for an office the German Bundestag election in 2009. They did so by creating their own Twitter accounts, tweeting their own content and deciding whom to connect with. We were able to investigate how and with whom politicians established connections and which topics they discussed by tracking almost 20,000 connections of over 599 Twitter accounts, monitoring over 240,000 tweets over a period of three weeks. Our findings contribute to the open question whether the political social media ecosphere is fragmented or not, whether the structure of the social network influences communication flow and sentiment among members of the medium. The analysis of the network shows that the majority of connections were established between members of the same party while connections between different parties were significantly less represented. An analysis of the exchanged tweets demonstrated that the majority of discussions took place between members of the same party cluster and was more positive towards members of the same political party rather than towards members of other political parties.
Estimating online audiences: Understanding the limitations of competitive intelligence services
Authors: Kamerer David
Published: May 2013

How much traffic does a Web site receive? While many may want to know the relative influence of someone else's site, generally only the site owner has access to accurate data. JavaScript-based Web analytics, such as Google Analytics or Omniture, are widely considered the gold standard for tracking audiences. These services are census- rather than sample-based. They also have the virtues of being entirely passive (requiring no input from the visitor) as well as providing true measures of behavior.If you're not the site owner, you'll have to use competitive intelligence services to estimate the traffic. These services a wide range of methodological approaches, generally recruiting panel members using an opt-in mechanism, sometimes mixing in anonymized data bought from Internet service providers. Three of the leading free services of this type are Alexa, Compete, and Quantcast.This study examines the methodology of these four methods of measuring online audiences. It compares the results from all three services using a panel of 18 Web sites that have agreed to share analytics data with the author.Results show high variability in the quality of the estimated audience data from competitive intelligence services. Using analytics as the reference, Compete underestimated traffic by more than 300 percent. Quantcast underestimated traffic by more than 200 percent. Confounding this pattern were occasional overestimates of traffic by these services. Alexa data, which is presented differently than Compete and Quantcast data, showed one significant correlation (page views) with analytics data, while three other variables showed no relationship to data from analytics.Overall, these services performed poorly. But are the data worthless? The report concludes with recommendations for understanding the limitations of competitive intelligence services and appropriately reporting audience activity based upon differing methodologies.
Envisioning the Internet: Implementing ‘disruptive innovation’ in media organizations
Authors: Ashuri Tamar
Published: May 2013

When incorporating networked technologies, many established organizations face immense challenges, as these media involve new economic and cultural components. Predictions based on models concerning the incorporation of the so-called ‘disruptive innovations’ in established firms, are being offered in this article, viewing networked technologies as ‘disruptive innovations’. The study underscores the obstacles that limit implementation of such technologies in mainstream media organizations, and considers the strategies that might be used to overcome them. Analyzing the case of Israel’s leading newspaper, Yedioth Ahronoth, between the years 1995–2000, it shows how managers of this traditional business approached the Internet. The article analyzes how they respond to the ostensibly ‘disruptive’ networked innovation, eventually turning their organization’s Web site into the country’s chief news and content provider. The study offers lessons that extend beyond this specific case onto the broader vista of the implementation of ‘disruptive’ (networked) technologies in mainstream media environments.
Measuring monographs: A quantitative method to assess scientific impact and societal relevance
Authors: Snijder Ronald
Published: May 2013

In the Humanities and Social Sciences (HSS), the monograph is an important means of communicating scientific results. As in the field of STM, the quality of research needs to be assessed. This is done by bibliometric measures and qualitative methods. Bibliometric measures based on articles do not function well in the field of HSS, where monographs are the norm. The qualitative methods which take into account several stakeholders are labour intensive and the results are dependent on self-assessment of the respondents, which may introduce bias. In the case of humanities, the picture becomes even less clear due to uncertainties about the stakeholders. This article describes a method that may complement the current research on scientific impact and societal relevance. This method measures the usage of online monographs and identifies the internet provider involved. The providers are categorized as academic; government; business; non-profit organisations and the general public. The usage is further cat-egorised in national and international. Combining this data makes it possible to assess the scientific impact and the societal relevance of the monographs. The method is quantitative, which makes the results easier to validate. It is not necessary to know the stakeholders in advance: the readers are identified through the method. The used data set consists of over 25,000 downloads by more than 1,500 providers, spread over 859 monographs. More than two thirds of the usage can be categorised, and almost 45% of all usage comes from non-academics. This might indicate that the monographs have an relevance in society. Two possible influences on monograph usage were analysed: subject and language. Most of the subjects that received a higher than average number of downloads come from the field of the social sciences; the humanities were less ‘popular’. Books in English – the ‘lingua franca’ of science – were downloaded the most. Languages such as Dutch were read much less outside of national borders that Italian or German. A Dutch or Belgian scholar would need a translation in order to have more influence abroad; this applies far less for Germans or Italians. While further research is needed, the results are promising and the proposed method could be used as an addition to the existing tools to measure the scholarly impact and societal relevance of the field of HSS.
The pedagogical foundations of massive open online courses
Authors: Glance David George , Forsey Martin , Riley Myles
Published: May 2013

In 2011, the respective roles of higher education institutions and students worldwide were brought into question by the rise of the massive open online course (MOOC). MOOCs are defined by signature characteristics that include: lectures formatted as short videos combined with formative quizzes; automated assessment and/or peer and self–assessment and an online forum for peer support and discussion. Although not specifically designed to optimise learning, claims have been made that MOOCs are based on sound pedagogical foundations that are at the very least comparable with courses offered by universities in face–to–face mode. To validate this, we examined the literature for empirical evidence substantiating such claims. Although empirical evidence directly related to MOOCs was difficult to find, the evidence suggests that there is no reason to believe that MOOCs are any less effective a learning experience than their face–to–face counterparts. Indeed, in some aspects, they may actually improve learning outcomes.
Mapping the global Twitter heartbeat: The geography of Twitter
Authors: Leetaru Kalev , Wang Shaowen , Cao Guofeng , Padmanabhan Anand , Shook Eric
Published: May 2013

In just under seven years, Twitter has grown to count nearly 3% of the entire global population among its active users who have sent more than 170 billion 140-character messages. Today the service plays such a significant role in American culture that the Library of Congress has assembled a permanent archive of the site back to its first tweet, updated daily. With its open API, Twitter has become one of the most popular data sources for social research, yet the majority of the literature has focused on it as a text or network graph source, with only limited efforts to date focusing exclusively on the geography of Twitter, assessing the various sources of geographic information on the service and their accuracy. More than 3% of all tweets are found to have native location information available, while a naive geocoder based on a simple major cities gazetteer and relying on the user-provided Location and Profile fields is able to geolocate more than a third of all tweets with high accuracy when measured against the GPS-based baseline. Geographic proximity is found to play a minimal role both in who users communicate with and what they communicate about, providing evidence that social media is shifting the communicative landscape.
Navigating an imagined Middle–earth: Finding and analyzing text–based and film–based mental images of Middle–earth through TheOneRing.net online fan community
Authors: Grek Martin Jennifer M. , Gruzd Anatoliy , Howard Vivian
Published: May 2013

The proliferation of social media brings new opportunities to discover the ways in which we receive, process, and disseminate information — even information that seems confined to our imaginations. Mental imagery — those images we create in our imaginations as we read a text or watch a film — is not well understood. Netlytic, a Web-based system for automated text analysis, permitted the capture and analysis of online discussions relating to mental images of J.R.R. Tolkien’s and Peter Jackson’s The Lord of the Rings as text and as film adaptation, giving insight to our understanding of mental imagery as a form of human cognition and information processing. Furthermore, this study serves as a starting point for further development of academic research using Web-based text analysis systems and online communities.
Variation of Proteinuria in Dogs with Leishmaniasis Treated with Meglumine Antimoniate and Allopurinol: A Retrospective Study
Authors: Pierantozzi Marco , Roura Xavier , Paltrinieri Saverio , Poggi Marco , Zatelli Andrea
Published: May 2013

A retrospective study was performed using 53 client owned dogs with leishmaniasis to determine whether the degree of proteinuria, evaluated by the urine protein/creatinine ratio (UP/C), changes following treatment with meglumine antimoniate and allopurinol. Medical records of dogs with leishmaniasis in clinical stage C (according to the Canine Leishmaniasis Working Group staging system) and either proteinuric or borderline proteinuric (according to the International Renal Interest Society [IRIS] staging system) were reviewed. All dogs were treated with meglumine antimoniate and allopurinol for 4–8 wk. After treatment, UP/C, total protein, and total globulin significantly decreased and albumin and the albumin/globulin ratio (A/G) increased. After treatment, 7 of the 53 dogs (13.4%) became nonproteinuric following either a proteinuric or borderline proteinuric stage. Moreover, 12 of the 53 proteinuric dogs (22.6%) changed their stage to borderline proteinuric. The antileishmaniasis treatment with meglumine antimoniate in combination with allopurinol in dogs significantly reduced the degree of proteinuria in a short period of time. The results of the current study may be useful to the veterinary practitioner in the clinical management of canine leishmaniasis (CanL) in dogs with proteinuric chronic kidney disease.
MRI Findings in a Rottweiler with Leukoencephalomyelopathy
Authors: Eagleson Joseph S. , Kent Marc , Platt Simon R. , Rech Raquel R. , Howerth Elizabeth W.
Published: May 2013

A 22 mo old male rottweiler presented with a 1 mo progressive history of general proprioceptive ataxia and upper motor neuron tetraparesis. Neurologic examination was consistent with a lesion affecting the first through fifth cervical spinal cord segments. MRI disclosed bilaterally symmetric hyperintensities on T2-weighted (T2W) images in the crus cerebri and pyramidal tracts of the brain and the dorsal portion of the lateral funiculi of the cervical spinal cord. Fifty days after initial presentation, the dog was euthanized due to disease progression. Pathologic examination of the central nervous system (CNS) revealed a bilaterally symmetric chronic leukoencephalomyelopathy (LEM) consistent with previous reports of LEM in rottweilers. To the authors’ knowledge, this is the first report to describe the MRI characteristics of LEM in the rottweiler. The topography of the changes observed with MRI paralleled the pathologic changes, which were widespread loss of myelin, decreased axon numbers, and astroglial proliferation. Consequently, MRI of the CNS of affected rottweilers may aid in establishing a presumptive antemortem diagnosis of LEM.
MRI Findings in a Dog with Kernicterus
Authors: Belz Katie M. , Specht Andrew J. , Johnson Victoria S. , Conway Julia A.
Published: May 2013

A severe increase in total bilirubin coincided with a decline in neurologic status to comatose in a 9 yr old spayed female mixed-breed dog being treated for immune-mediated hemolytic anemia. MRI of the brain was performed to investigate potential causes for the neurologic signs. MRI revealed bilaterally symmetrical hyperintensities within the caudate nuclei, globus pallidus, thalamus, deep cerebellar nuclei, and cortical gray matter on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, which coincided with areas of bilirubin deposition and neuronal necrosis (kernicterus) identified on necropsy examination. This is the second case report of an adult dog exhibiting kernicterus, and the first report to document MRI findings associated with that condition. Kernicterus is an uncommonly reported complication of hyperbilirubinemia in dogs, but is potentially underreported due to difficulties in recognizing subtle lesions and distinguishing kernicterus from other potential causes of neurologic abnormalities with readily available antemortem tests. MRI may be helpful in supporting the diagnosis of kernicterus.
Sound Practice Exploring Options for Pipe Location and Leak Detection
Authors: Hughes David M. , Titus Russel , Oxenford Jeff
Published: May 2013

North American water utilities increasingly are mandating water audits and other initiatives to improve water supply efficiency. But before selecting the best water loss reduction strategy, a utility must understand the nature and extent of its losses. Numerous technologies are available to assist with an active leakage management program.
Distribution System Optimization Starts with Data
Authors: Martin Barb , Ries Tom
Published: May 2013

Although producing safe drinking water at treatment plants is highly regulated, only a limited but increasing number of regulations directly apply to distribution systems. The regulations exist to ensure delivery of safe water to consumers, providing an additional layer of public health protection after water leaves the water treatment plant.