bluuebunny/crossref_metadata_2025_split huggingface dataset:
« French belongs to no one, French belongs to everyone ». Sur l’attractivité de la littérature médiévale aux États-Unis
Authors: Uhlig Marion 
Published: January 2016

À l’heure où les offres de poste comme les Masters spécialisés en langue et littérature françaises du Moyen Âge se font de plus en plus rares dans les universités américaines, il paraît urgent de réfléchir aux moyens de stimuler l’intérêt des étudiants pour cette discipline afin d’en assurer la relève outremer. Mais comment accroître l’attractivité de la littérature médiévale en français, là où rien ne prédispose les étudiants à s’y intéresser tant elle paraît éloignée de leur héritage culturel ? Le présent témoignage revient sur les solutions, toutes potentielles, que mes collègues et moi avons envisagées durant mon séjour comme professeur adjoint de littérature française médiévale à l’université du Wisconsin-Madison entre 2013 et 2015. Elles invitent d’une part à questionner le choix des langues dans lesquelles les textes sont lus et enseignés, à savoir le français moderne dans les deux cas ou, respectivement, l’ancien français et l’anglais, et d’autre part à tirer parti du formidable engouement des chercheurs et des étudiants pour les Global Studies et pour la littérature de la francophonie avec lesquelles la littérature médiévale en français entre aisément en dialogue.
C1q Modulates the Response to TLR7 Stimulation by Pristane-Primed Macrophages: Implications for Pristane-Induced Lupus
Authors: Carlucci Francesco , Ishaque Attia , Ling Guang Sheng , Szajna Marta , Sandison Ann , Donatien Philippe , Cook H. Terence , Botto Marina 
Published: January 2016

Abstract
The complement component C1q is known to play a controversial role in the pathogenesis of systemic lupus erythematosus, but the underlying mechanisms remain poorly understood. Intraperitoneal injection of pristane induces a lupus-like syndrome whose pathogenesis implicates the secretion of type I IFN by CD11b+ Ly6Chigh inflammatory monocytes in a TLR7-dependent fashion. C1q was also shown to influence the secretion of IFN-α. In this study, we explored whether C1q deficiency could affect pristane-induced lupus. Surprisingly, C1qa−/− mice developed lower titers of circulating Abs and milder arthritis compared with the controls. In keeping with the clinical scores, 2 wk after pristane injection the peritoneal recruitment of CD11b+ Ly6Chigh inflammatory monocytes in C1qa−/− mice was impaired. Furthermore, C1q-deficient pristane-primed resident peritoneal macrophages secreted significantly less CCL3, CCL2, CXCL1, and IL-6 when stimulated in vitro with TLR7 ligand. Replenishing C1q in vivo during the pristane-priming phase rectified this defect. Conversely, pristane-primed macrophages from C3-deficient mice did not show impaired cytokine production. These findings demonstrate that C1q deficiency impairs the TLR7-dependent chemokine production by pristane-primed peritoneal macrophages and suggest that C1q, and not C3, is involved in the handling of pristane by phagocytic cells, which is required to trigger disease in this model.
Ecdysone Titer Determined by 3DE-3β-Reductase Enhances the Immune Response in the Silkworm
Authors: Sun Wei , Shen Yi-Hong , Zhou Liang-Xiao , Zhang Ze 
Published: January 2016

AbstractAlthough recent studies have demonstrated that 20-hydroxyecdysone (20E), one of the two most important hormones for development, could promote the insect innate immune response, how insects regulate 20E titer to affect the immunity after suffering pathogen attack remains unknown. In this study, to our knowledge, we first found that 20E titer was significantly elevated after bacterial infection in the domesticated silkworm, Bombyx mori. Furthermore, the elevated 20E enhanced the silkworm innate immune system against invading bacteria via ecdysone receptor. During immune response, the expression of the silkworm 3-dehydroecdysone-3β-reductase (3DE-3β-reductase) that converts 3DE released from prothoracic glands into ecdysone was induced. RNA interference experiments suggested that 3DE-3β-reductase is essential to upregulate the 20E titer after bacterial infection. The rescue experiments showed that injection with the recombinant 3DE-3β-reductase protein can significantly elevate the 20E concentration and modulate the expressions of the silkworm immune-related genes. Taken together, 20E titer determined by 3DE-3β-reductase enhances the silkworm defense against the bacterial infection. Thus, our findings reveal an important role of the 20E synthesis pathway from 3DE in enhancing the silkworm immune response and have profound implications for the understanding of interaction mechanisms between insect hormone and immunity.
Fatty Acid Amide Hydrolase Regulates Peripheral B Cell Receptor Revision, Polyreactivity, and B1 Cells in Lupus
Authors: Pathak Simanta , Kumar Kirthi Raman , Kanta Hasna , Carr-Johnson Ferdicia , Han Jie , Bashmakov Anna , Faure Lionel , Ding Huihua , Vanarsa Kamala , Khan Shaheen , Li Quan-Zhen , Chapman Kent , Wakeland Edward K. , Mohan Chandra 
Published: January 2016

Abstract
C57BL/6 mice bearing the Sle2z lupus-susceptibility congenic interval on chromosome 4 display high titers of polyclonal autoantibodies with generalized B cell hyperactivity, hallmarks of systemic lupus erythematosus. In B6.Sle2zHELIg.sHEL BCR-transgenic mice, Sle2z did not breach central tolerance, but it led to heightened expression of endogenous Ig H and L chains in splenic B cells, upregulation of RAG, and serological polyreactivity, suggestive of excessive receptor revision. Fatty acid amide hydrolase (FAAH), a gene in the minimal subcongenic interval generated through recombinant mapping, was found to be upregulated in Sle2z B cells by microarray analysis, Western blot, and functional assays. Pharmacological inhibition of FAAH reversed the increase in receptor revision, RAG expression, and polyreactive autoantibodies in lupus-prone mice. These studies indicate that increased peripheral BCR revision, or selective peripheral expansion of BCR-revised B cells, may lead to systemic autoimmunity and that FAAH is a lupus-susceptibility gene that might regulate this process.
A Novel Factor H–Fc Chimeric Immunotherapeutic Molecule against Neisseria gonorrhoeae
Authors: Shaughnessy Jutamas , Gulati Sunita , Agarwal Sarika , Unemo Magnus , Ohnishi Makoto , Su Xia-Hong , Monks Brian G. , Visintin Alberto , Madico Guillermo , Lewis Lisa A. , Golenbock Douglas T. , Reed George W. , Rice Peter A. , Ram Sanjay 
Published: January 2016

Abstract
Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhea, has developed resistance to almost every conventional antibiotic. There is an urgent need to develop novel therapies against gonorrhea. Many pathogens, including N. gonorrhoeae, bind the complement inhibitor factor H (FH) to evade complement-dependent killing. Sialylation of gonococcal lipooligosaccharide, as occurs in vivo, augments binding of human FH through its domains 18–20 (FH18–20). We explored the use of fusing FH18–20 with IgG Fc (FH18–20/Fc) to create a novel anti-infective immunotherapeutic. FH18–20 also binds to select host glycosaminoglycans to limit unwanted complement activation on host cells. To identify mutation(s) in FH18–20 that eliminated complement activation on host cells, yet maintained binding to N. gonorrhoeae, we created four mutations in domains 19 or 20 described in atypical hemolytic uremic syndrome that prevented binding of mutated fH to human erythrocytes. One of the mutant proteins (D to G at position 1119 in domain 19; FHD1119G/Fc) facilitated complement-dependent killing of gonococci similar to unmodified FH18–20/Fc but, unlike FH18–20/Fc, did not lyse human erythrocytes. FHD1119G/Fc bound to all (100%) of 15 sialylated clinical N. gonorrhoeae isolates tested (including three contemporary ceftriaxone-resistant strains), mediated complement-dependent killing of 10 of 15 (67%) strains, and enhanced C3 deposition (≥10-fold above baseline levels) on each of the five isolates not directly killed by complement. FHD1119G/Fc facilitated opsonophagocytic killing of a serum-resistant strain by human polymorphonuclear neutrophils. FHD1119G/Fc administered intravaginally significantly reduced the duration and burden of gonococcal infection in the mouse vaginal colonization model. FHD1119G/Fc represents a novel immunotherapeutic against multidrug-resistant N. gonorrhoeae.
Potential Role of the Formation of Tunneling Nanotubes in HIV-1 Spread in Macrophages
Authors: Hashimoto Michihiro , Bhuyan Farzana , Hiyoshi Masateru , Noyori Osamu , Nasser Hesham , Miyazaki Mitsue , Saito Tamio , Kondoh Yasumitsu , Osada Hiroyuki , Kimura Shunsuke , Hase Koji , Ohno Hiroshi , Suzu Shinya 
Published: January 2016

Abstract
Tunneling nanotubes (TNTs), the long membrane extensions connecting distant cells, have emerged as a novel form of cell-to-cell communication. However, it is not fully understood how and to what extent TNTs contribute to intercellular spread of pathogens including HIV-1. In this study, we show that HIV-1 promotes TNT formation per se via its protein Nef and a cellular protein M-Sec, which appears to mediate approximately half of viral spread among monocyte-derived macrophages (MDMs). A small compound that inhibits M-Sec–induced TNT formation reduced HIV-1 production by almost half in MDMs. Such inhibition was not observed with Nef-deficient mutant HIV-1 that fails to promote TNT formation and replicates less efficiently than the wild-type HIV-1 in MDMs. The TNT inhibitor–sensitive/Nef-promoting viral production was also observed in a T cell line ectopically expressing M-Sec, but not in another M-Sec− T cell line. Our results suggest the importance of TNTs in HIV-1 spread among MDMs and might answer the long-standing question how Nef promotes HIV-1 production in a cell type–specific manner.
Pro- and Anti-Inflammatory Role of ChemR23 Signaling in Pollutant-Induced Inflammatory Lung Responses
Authors: Provoost Sharen , De Grove Katrien C. , Fraser Graeme L. , Lannoy Vincent J. , Tournoy Kurt G. , Brusselle Guy G. , Maes Tania , Joos Guy F. 
Published: January 2016

Abstract
Inhalation of traffic-related particulate matter (e.g., diesel exhaust particles [DEPs]) is associated with acute inflammatory responses in the lung, and it promotes the development and aggravation of allergic airway diseases. We previously demonstrated that exposure to DEP was associated with increased recruitment and maturation of monocytes and conventional dendritic cells (DCs), resulting in TH2 polarization. Monocytes and immature DCs express the G-protein coupled receptor chemR23, which binds the chemoattractant chemerin. Using chemR23 knockout (KO) and corresponding wild-type (WT) mice, we determined the role of chemR23 signaling in response to acute exposure to DEPs and in response to DEP-enhanced house dust mite (HDM)-induced allergic airway inflammation. Exposure to DEP alone, as well as combined exposure to DEP plus HDM, elevated the levels of chemerin in the bronchoalveolar lavage fluid of WT mice. In response to acute exposure to DEPs, monocytes and monocyte-derived DCs accumulated in the lungs of WT mice, but this response was significantly attenuated in chemR23 KO mice. Concomitant exposure to DEP plus HDM resulted in allergic airway inflammation with increased eosinophilia, goblet cell metaplasia, and TH2 cytokine production in WT mice, which was further enhanced in chemR23 KO mice. In conclusion, we demonstrated an opposing role for chemR23 signaling depending on the context of DEP-induced inflammation. The chemR23 axis showed proinflammatory properties in a model of DEP-induced acute lung inflammation, in contrast to anti-inflammatory effects in a model of DEP-enhanced allergic airway inflammation.
Depletion of CD8+ T Cells Exacerbates CD4+ T Cell–Induced Monocyte-to-Fibroblast Transition in Renal Fibrosis
Authors: Dong Yanjun , Yang Min , Zhang Jing , Peng Xiaogang , Cheng Jizhong , Cui Taigeng , Du Jie 
Published: January 2016

Abstract
Bone marrow–derived monocyte-to-fibroblast transition is a key step in renal fibrosis pathogenesis, which is regulated by the inflammatory microenvironment. However, the mechanism by which the inflammatory microenvironment regulates this transition is not fully understood. In this study, we examined how the CD8+ T cell/IFN-γ microenvironment regulates the monocyte-to-fibroblast transition in renal fibrosis. Genetic ablation of CD8 promoted a monocyte-to-fibroblast transition and increased renal interstitial fibrosis, whereas reconstitution of CD8 knockout (KO) mice with CD8+ T cells decreased fibrosis. However, depletion of CD4+ T cells in CD8 KO mice also reduced fibrosis. To elucidate the role of CD4+ T cells in mediating CD8-regulated monocyte-to-fibroblast transition, CD4+ T cells were isolated from obstructed kidneys of CD8 KO or wild-type mice. CD4+ T cells isolated from CD8 KO obstructed kidney expressed more IL-4 and GATA3 and less IFN-γ and T-bet and showed increased monocyte-to-fibroblast transition in vitro compared with those isolated from wild-type obstructed kidney. To examine the role of IFN-γ–expressing CD8+ T cells, we reconstituted CD8 KO mice with CD8+ T cells isolated from IFN-γ KO mice. The IFN-γ KO CD8+ cells had no effect on IL-4, GATA3, IFN-γ, and T-bet mRNA expression in obstructed kidneys or renal fibrosis. Taken together, our findings identify the axis of CD8+ T cells and IFN-γ–CD4+ T cells as an important microenvironment for the monocyte-to-fibroblast transition, which negatively regulates renal fibrosis.
Swift and Strong NK Cell Responses Protect 129 Mice against High-Dose Influenza Virus Infection
Authors: Zhou Kai , Wang Jing , Li An , Zhao Wenming , Wang Dongfang , Zhang Wei , Yan Jinghua , Gao George Fu , Liu Wenjun , Fang Min 
Published: January 2016

Abstract
It is generally unclear what roles NK cells play during influenza virus infection with regard to different host genetic backgrounds. In this study, we show that in six inbred mouse strains, NK cells play an important protective role only in 129 mice during high-dose influenza A H1N1 virus infection. Swift and strong NK cell responses efficiently control early pulmonary viral replication in 129 mice, providing survival privilege. In addition, we identified that early activation of TLRs and RIG-I signaling in 129 mice resulted in quick production of type 1 IFNs and inflammatory cytokines, which are important reasons for the swift kinetics of NK cell responses post influenza virus infection. Thus, under different microenvironments, NK cells play differential roles against viral infections. The kinetics and magnitude of NK cell responses correlate with the distinct roles that NK cells play against influenza virus infections. Thus, our works further our understandings about the complex role of NK cells during influenza virus infection.
p52 Overexpression Increases Epithelial Apoptosis, Enhances Lung Injury, and Reduces Survival after Lipopolysaccharide Treatment
Authors: Saxon Jamie A. , Cheng Dong-Sheng , Han Wei , Polosukhin Vasiliy V. , McLoed Allyson G. , Richmond Bradley W. , Gleaves Linda A. , Tanjore Harikrishna , Sherrill Taylor P. , Barham Whitney , Yull Fiona E. , Blackwell Timothy S. 
Published: January 2016

Abstract
Although numerous studies have demonstrated a critical role for canonical NF-κB signaling in inflammation and disease, the function of the noncanonical NF-κB pathway remains ill-defined. In lung tissue from patients with acute respiratory distress syndrome, we identified increased expression of the noncanonical pathway component p100/p52. To investigate the effects of p52 expression in vivo, we generated a novel transgenic mouse model with inducible expression of p52 in Clara cell secretory protein–expressing airway epithelial cells. Although p52 overexpression alone did not cause significant inflammation, p52 overexpression caused increased lung inflammation, injury, and mortality following intratracheal delivery of Escherichia coli LPS. No differences in cytokine/chemokine expression were measured between p52-overexpressing mice and controls, but increased apoptosis of Clara cell secretory protein–positive airway epithelial cells was observed in transgenic mice after LPS stimulation. In vitro studies in lung epithelial cells showed that p52 overexpression reduced cell survival and increased the expression of several proapoptotic genes during cellular stress. Collectively, these studies demonstrate a novel role for p52 in cell survival/apoptosis of airway epithelial cells and implicate noncanonical NF-κB signaling in the pathogenesis of acute respiratory distress syndrome.
NK Cell–Specific Gata3 Ablation Identifies the Maturation Program Required for Bone Marrow Exit and Control of Proliferation
Authors: Ali Alaa Kassim , Oh Jun Seok , Vivier Eric , Busslinger Meinrad , Lee Seung-Hwan 
Published: January 2016

Abstract
NK cells are innate lymphocytes capable of eliciting an innate immune response to pathogens. NK cells develop and become mature in the bone marrow (BM) before they migrate out to peripheral organs. Although the developmental program leading to mature NK cells has been studied in the context of several transcription factors, the stage-specific role of GATA3 in NK cell development has been incompletely understood. Using NKp46-Cre-Gata3fl/fl mice in which Gata3 deficiency was induced as early as the immature stage of NK cell differentiation, we demonstrated that GATA3 is required for the NK cell maturation beyond the CD27 single-positive stage and is indispensable for the maintenance of liver-resident NK cells. The frequencies of NK cells from NKp46-Cre-Gata3fl/fl mice were found higher in the BM but lower in peripheral organs compared with control littermates, indicating that GATA3 controls the maturation program required for BM egress. Despite the defect in maturation, upon murine CMV infection, NK cells from NKp46-Cre-Gata3fl/fl mice expanded vigorously, achieving NK cell frequencies surpassing those in controls and therefore provided comparable protection. The heightened proliferation of NK cells from NKp46-Cre-Gata3fl/fl mice was cell intrinsic and associated with enhanced upregulation of CD25 expression. Taken together, our results demonstrate that GATA3 is a critical regulator for NK cell terminal maturation and egress out of the BM and that immature NK cells present in the periphery of NKp46-Cre-Gata3fl/fl mice can rapidly expand and provide a reservoir of NK cells capable of mounting an efficient cytotoxic response upon virus infection.
Cutting Edge: CD99 Is a Novel Therapeutic Target for Control of T Cell–Mediated Central Nervous System Autoimmune Disease
Authors: Winger Ryan C. , Harp Christopher T. , Chiang Ming-Yi , Sullivan David P. , Watson Richard L. , Weber Evan W. , Podojil Joseph R. , Miller Stephen D. , Muller William A. 
Published: January 2016

Abstract
Leukocyte trafficking into the CNS is a prominent feature driving the immunopathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Blocking the recruitment of inflammatory leukocytes into the CNS represents an exploitable therapeutic target; however, the adhesion molecules that specifically regulate the step of leukocyte diapedesis into the CNS remain poorly understood. We report that CD99 is critical for lymphocyte transmigration without affecting adhesion in a human blood–brain barrier model. CD99 blockade in vivo ameliorated experimental autoimmune encephalomyelitis and decreased the accumulation of CNS inflammatory infiltrates, including dendritic cells, B cells, and CD4+ and CD8+ T cells. Anti-CD99 therapy was effective when administered after the onset of disease symptoms and blocked relapse when administered therapeutically after disease symptoms had recurred. These findings underscore an important role for CD99 in the pathogenesis of CNS autoimmunity and suggest that it may serve as a novel therapeutic target for controlling neuroinflammation.
CD28 Deficiency Enhances Type I IFN Production by Murine Plasmacytoid Dendritic Cells
Authors: Macal Monica , Tam Miguel A. , Hesser Charles , Di Domizio Jeremy , Leger Psylvia , Gilliet Michel , Zuniga Elina I. 
Published: January 2016

AbstractType I IFNs (IFN-I) are key innate mediators that create a profound antiviral state and orchestrate the activation of almost all immune cells. Plasmacytoid dendritic cells (pDCs) are the most powerful IFN-I–producing cells and play important roles during viral infections, cancer, and autoimmune diseases. By comparing gene expression profiles of murine pDCs and conventional DCs, we found that CD28, a prototypic T cell stimulatory receptor, was highly expressed in pDCs. Strikingly, CD28 acted as a negative regulator of pDC IFN-I production upon TLR stimulation but did not affect pDC survival or maturation. Importantly, cell-intrinsic CD28 expression restrained pDC (and systemic) IFN-I production during in vivo RNA and DNA viral infections, limiting antiviral responses and enhancing viral growth early after exposure. Finally, CD28 also downregulated IFN-I response upon skin injury. Our study identified a new pDC regulatory mechanism by which the same CD28 molecule that promotes stimulation in most cells that express it is co-opted to negatively regulate pDC IFN-I production and limit innate responses.
Fluvastatin Suppresses Mast Cell and Basophil IgE Responses: Genotype-Dependent Effects
Authors: Kolawole Elizabeth Motunrayo , McLeod Jamie Josephine Avila , Ndaw Victor , Abebayehu Daniel , Barnstein Brian O. , Faber Travis , Spence Andrew J. , Taruselli Marcela , Paranjape Anuya , Haque Tamara T. , Qayum Amina A. , Kazmi Qasim A. , Wijesinghe Dayanjan S. , Sturgill Jamie L. , Chalfant Charles E. , Straus David B. , Oskeritzian Carole A. , Ryan John J. 
Published: January 2016

Abstract
Mast cell (MC)– and basophil-associated inflammatory diseases are a considerable burden to society. A significant portion of patients have symptoms despite standard-of-care therapy. Statins, used to lower serum cholesterol, have immune-modulating activities. We tested the in vitro and in vivo effects of statins on IgE-mediated MC and basophil activation. Fluvastatin showed the most significant inhibitory effects of the six statins tested, suppressing IgE-induced cytokine secretion among mouse MCs and basophils. The effects of fluvastatin were reversed by mevalonic acid or geranylgeranyl pyrophosphatase, and mimicked by geranylgeranyl transferase inhibition. Fluvastatin selectively suppressed key FcεRI signaling pathways, including Akt and ERK. Although MCs and basophils from the C57BL/6J mouse strain were responsive to fluvastatin, those from 129/SvImJ mice were completely resistant. Resistance correlated with fluvastatin-induced upregulation of the statin target HMG-CoA reductase. Human MC cultures from eight donors showed a wide range of fluvastatin responsiveness. These data demonstrate that fluvastatin is a potent suppressor of IgE-mediated MC activation, acting at least partly via blockade of geranyl lipid production downstream of HMG-CoA reductase. Importantly, consideration of statin use for treating MC–associated disease needs to incorporate genetic background effects, which can yield drug resistance.