bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of Rheumatoid Arthritis Genetic Susceptibility Markers in the Early Rheumatoid Arthritis Study Further Replicates the TRAF1 Association with Radiological Damage
Authors: VIATTE SEBASTIEN , PLANT DARREN , LUNT MARK , FU BO , FLYNN EDWARD , PARKER BEN J. , GALLOWAY JAMES , SOLYMOSSY CSILLA , WORTHINGTON JANE , SYMMONS DEBORAH P.M. , DIXEY JOSH J. , YOUNG ADAM , BARTON ANNE 
Published: December 2012

Objective.The TRAF1 genetic region conferring susceptibility to rheumatoid arthritis (RA) has been reported to associate with radiological damage. We aimed to test RA genetic susceptibility markers for association with a continuous measure of radiological damage over time using longitudinal modeling techniques.Methods.Sixty-seven RA susceptibility variants were genotyped in 474 patients in the Early Rheumatoid Arthritis Study (ERAS) using Sequenom MassArray technology. Correlation between genetic markers and Larsen score was assessed longitudinally using zero-inflated negative binomial regression to include repeat measurements in the same individual at different timepoints. Genetic markers associated with radiological damage in ERAS were tested using the same modeling techniques on previously published data from the Norfolk Arthritis Register (NOAR).Results.The single marker associated longitudinally with Larsen score in ERAS (p = 0.02) and in NOAR (p = 0.04) was rs2900180 at the TRAF1 locus. Analysis of individual timepoints in ERAS showed that rs2900180 displays its effect primarily on the extent of Larsen score early in the disease course. Combined longitudinal analysis of the 2 cohorts suggests further association of several loci with Larsen score (KIF5A, PTPN22, AFF3, TAGAP) and therefore a significant accumulation of RA severity markers among RA susceptibility markers (p = 0.016).Conclusion.The marker rs2900180 is associated with the extent of radiological damage in the ERAS cohort. This represents the second independent study correlating rs2900180 at the TRAF1 locus with radiological severity in RA. Replication in a large dataset is required to establish the role of other RA susceptibility loci in disease severity.
Homocysteine Levels in Takayasu Arteritis — A Risk Factor for Arterial Ischemic Events
Authors: DE SOUZA ALEXANDRE WAGNER SILVA , DE LIMA CARLA SERRANO , OLIVEIRA ANA CECILIA DINIZ , MACHADO LUIZ SAMUEL GOMES , PINHEIRO FREDERICO AUGUSTO GURGEL , HIX SONIA , D’ALMEIDA VANIA 
Published: December 2012

Objective.To evaluate homocysteine levels in patients with Takayasu arteritis (TA) and in controls, and to analyze associations between homocysteine levels and paraoxonase 1 (PON1) activity, cysteine levels, methotrexate use, disease activity, extent of arterial involvement, and ischemic events in patients with TA.Methods.A cross-sectional study was performed with 29 patients with TA and 30 controls who underwent clinical evaluation and blood sample collection in the fasting state.Results.Among patients with TA, active disease was observed in 9 (31.0%) and previous arterial ischemic events in 10 (34.5%). Therapy with methotrexate was prescribed to 9 (31.0%) patients and it was associated with folic acid in 8 cases. Median homocysteine level was higher in patients with TA [10.9 μmol/l, interquartile range (IQR) 9.6–14.8] than in controls (6.9 μmol/l, IQR 5.1–11.9; p < 0.001). No difference was found regarding mean homocysteine levels between those using methotrexate and those under other therapies (12.8 ± 5.3 μmol/l vs 12.1 ± 3.2 μmol/l, respectively; p = 0.662). TA patients with active disease presented lower homocysteine levels (10.4 ± 2.1 μmol/l) compared to TA patients in remission (13.1 ± 4.2 μmol/l) (p = 0.034). A significant correlation was found between cysteine and homocysteine levels in patients with TA (ρ = 0.676, p < 0.0001), while there was no correlation between homocysteine and PON1 activity (ρ = 0.214, p = 0.265). Median homocysteine levels were higher in patients with ischemic events (13.2 μmol/l, IQR 10.9–17.5) compared to patients with no ischemic events (9.8 μmol/l, IQR 8.7–14.7; p = 0.027) and were associated with arterial ischemia in patients with TA (OR 1.31, 95% CI 1.01–1.71, p = 0.041).Conclusion.Patients with TA presented higher homocysteine levels than controls and homocysteine was associated with an increased risk of arterial ischemic events in TA.
Économie verte et développement durable : enjeux de politique économique
Authors: Barbier Edward B. 
Published: December 2012

Résumé La croissance verte et le développement durable apparaissent souvent comme des objectifs complémentaires aux yeux des décideurs internationaux. Cet article suggère que la croissance verte ne garantira pourtant pas le développement durable aussi longtemps que l’activité humaine continuera de s’accompagner d’une aggravation des problèmes de rareté écologique. Il faut surmonter ici de nouveaux défis liés à la soutenabilité et son financement. Le défi de soutenabilité est lié à de nombreuses défaillances tant des marchés que des institutions et politiques publiques, défaillances qui empêchent la reconnaissance de l’importance économique de cette rareté. Le défi du financement découle de l’écart entre les bénéfices globaux que l’humanité reçoit des écosystèmes et ce que nous sommes prêts à payer pour les maintenir et les conserver. Améliorer l’analyse économique et scientifique de la rareté écologique, évaluer la perte des bénéfices liés à celle-ci, et traduire cela dans les décisions publiques sont les étapes clés pour relever le défi de la durabilité. Quant aux réponses au défi du financement, elles comprennent l’exploration et la mise en œuvre de toute une gamme de mécanismes de financement novateurs, allant des systèmes de paiements internationaux pour les services écosystémiques aux taxes sur les transactions financières et de change, en passant par des interventions d’organismes de financement internationaux. JEL : H23, H87, Q01, Q57, Q58
« Savoir plus, pour pouvoir plus, pour être plus »
Authors: Naszályi Philippe 
Published: December 2012

« Savoir plus, pour pouvoir plus, pour être plus » selon la formule du Père Teilhard de Chardin (sj) est déclinée par Philippe Naszályi, pour annoncer le thème des deux dossiers de ce numéro. Innovation, innovateur, recherche et développement, commence par la réflexion de son auteur, Patrice Noailles. Il propose de comprendre qu’il n’y pas un effet mécanique à la transformation d’une invention en innovation. Il y faut un homme particulier fonctionnant dans un environnement favorable. L’imitation est également indissociable de l’innovation comme l’industrie agro-alimentaire française ou la gestion des marques en Chine, le démontrent. Les articles qui composent ce dossier analysent la difficulté de sortir de méthodes archaïques ou de tirer profit d’une analyse post mortem après un échec. L’innovation dans une économie fondée sur la connaissance, s’étudie dans des institutions financières, comme en Algérie. Elle découle aussi de la R&D dans les industries en France comme au Japon. Le deuxième dossier de ce numéro prolonge la réflexion entamée par le premier, en plaçant la Responsabilité sociale et le développement durable. Ces deux domaines ont une existence propre. Le premier article, confié à des spécialistes de l’innovation, Dimitri Uzunidis et Blandine Laperche, pose bien les enjeux de la RSE. Puis, le développement durable, « fruit » de la réglementation pour les grandes entreprises, « fruit » de l’engagement dans les PME, « fruit » du financement bancaire et le « développement équitable » au Cameroun forment ce dossier. Etre une «préface de l’espérance », mais instructive, raisonnée, argumentée pour « penser la croissance » !
Un autre regard sur les rapports de développement durable
Authors: Aubourg Nathalie , Canel-Depitre Béatrice , Renault-Tesson Corinne 
Published: December 2012

Après des débuts difficiles, la loi NRE semble maintenant bien acceptée par les grandes entreprises. Les informations concernant les activités environnementales et sociales sont facilement accessibles mais il est difficile d’y voir clair. À partir des rapports de développement durable de trois groupes français, nous tenterons de « tirer leur portrait ». Cette recherche s’intéresse à la question de leur volonté de faire converger leurs responsabilités économiques, légales et éthiques. Pour ce faire, le modèle de Carroll, référent de l’analyse de la RSE, nous aidera à la compréhension des niveaux d’action de trois entreprises en matière de RSE. Dans tous les cas, la formalisation de la convergence des responsabilités sous forme de portraits donne des rendus délicats et différents. Mots-clés : Responsabilité Sociale d’Entreprise, Rapport de Développement Durable, portrait, niveaux de responsabilité.
Stato, imperio, dominio. Sur l’unité des notions d’État et d’empire au XVIe siècle
Authors: Descendre Romain 
Published: December 2012

Il n’est pas sûr que l’opposition
dialectique État/empire soit un outil qui permette de comprendre
finement le processus historique qu’elle entend éclairer. Plutôt que
d’opposer ce que l’on doit aux empires à ce que l’on a cru être le
produit exclusif des États, il convient de reconnaître l’articulation
étroite et complexe entre les uns et les autres. Au même titre que
l’idée moderne d’État façonnée sur la réalité des États-nations, cette
opposition n’est-elle pas une invention récente ? Dans le
« laboratoire » italien de la politique moderne, on était conscient de
la grande variété des assises territoriales et des formes de
domination, qui ne correspondaient pas à une division si tranchée.
L’étude des concepts de la pensée politique et de l’historiographie
italienne au XVIe siècle permet ainsi d’interroger
cette dichotomie et la pertinence d’une interprétation de la modernité
sur la base de l’opposition tranchée entre deux grands modèles
territoriaux et administratifs.
Paying for Performance
Authors: Ryan Padhraig 
Published: December 2012

Deficiencies in quality arise in health systems around the world. A common yet largely unproven response is “pay for performance” (P4P), which links performance targets to financial rewards. Of particular note among P4P’s myriad problems, specifying challenging targets may demotivate low-performers and reward existing high-performers without significant improvement, and low targets are likely cost-ineffective. Trade-offs arise also in defining reward magnitude, as larger rewards may be powerful but more susceptible to adversely impacting unrewarded measures. Quality improvement should prioritize patient outcomes, but difficulties in attribution impede linking rewards to clinical outcomes. Superior performance requires a multifaceted approach that nurtures clinical and managerial skills, while fostering professionalism and pride in high quality care. Some providers have improved outcomes substantially without P4P incentives for clinicians, by emphasizing a collaborative leadership culture and evidence-based practice. Unless intimately entwined with such factors, P4P may flounder.
Ecto-Nucleoside Triphosphate Diphosphohydrolase 7 Controls Th17 Cell Responses through Regulation of Luminal ATP in the Small Intestine
Authors: Kusu Takashi , Kayama Hisako , Kinoshita Makoto , Jeon Seong Gyu , Ueda Yoshiyasu , Goto Yoshiyuki , Okumura Ryu , Saiga Hiroyuki , Kurakawa Takashi , Ikeda Kayo , Maeda Yuichi , Nishimura Jun-ichi , Arima Yasunobu , Atarashi Koji , Honda Kenya , Murakami Masaaki , Kunisawa Jun , Kiyono Hiroshi , Okumura Meinoshin , Yamamoto Masahiro , Takeda Kiyoshi 
Published: December 2012

AbstractExtracellular ATP is released from live cells in controlled conditions, as well as dying cells in inflammatory conditions, and, thereby, regulates T cell responses, including Th17 cell induction. The level of extracellular ATP is closely regulated by ATP hydrolyzing enzymes, such as ecto-nucleoside triphosphate diphosphohydrolases (ENTPDases). ENTPDase1/CD39, which is expressed in immune cells, was shown to regulate immune responses by downregulating the ATP level. In this study, we analyzed the immunomodulatory function of ENTPDase7, which is preferentially expressed in epithelial cells in the small intestine. The targeted deletion of Entpd7 encoding ENTPDase7 in mice resulted in increased ATP levels in the small intestinal lumen. The number of Th17 cells was selectively increased in the small intestinal lamina propria in Entpd7−/− mice. Th17 cells were decreased by oral administration of antibiotics or the ATP antagonist in Entpd7−/− mice, indicating that commensal microbiota-dependent ATP release mediates the enhanced Th17 cell development in the small intestinal lamina propria of Entpd7−/− mice. In accordance with the increased number of small intestinal Th17 cells, Entpd7−/− mice were resistant to oral infection with Citrobacter rodentium. Entpd7−/− mice suffered from severe experimental autoimmune encephalomyelitis, which was associated with increased numbers of CD4+ T cells producing both IL-17 and IFN-γ. Taken together, these findings demonstrate that ENTPDase7 controls the luminal ATP level and, thereby, regulates Th17 cell development in the small intestine.
Galectin-3 Facilitates Neutrophil Recruitment as an Innate Immune Response to a Parasitic Protozoa Cutaneous Infection
Authors: Bhaumik Pampa , St-Pierre Guillaume , Milot Valérie , St-Pierre Christian , Sato Sachiko 
Published: December 2012

Abstract
When infection occurs, neutrophils rapidly migrate to the affected site. Although the neutrophils neutralize microorganisms, they can also cause tissue damage or render invasion pathways to pathogens. Thus, the migration could be either beneficial or unfavorable in the initial control of infection. Studies on neutrophil recruitment revealed its complexity, especially in terms of the regulation of its initiation. Galectin-3 is a member of the galectin family that has an affinity for β-galactoside containing glycoconjugates. In this study, we investigated the role of galectin-3 in neutrophil migration and the biological significance of the rapid migration of neutrophils in an experimental parasitic cutaneous infection with Leishmania major. When the substrain of L. major, LV39, was infected, lack of galectin-3 impaired neutrophil recruitment in the footpads and the draining lymph nodes 1 d following infection. Reduced number of recruited neutrophils correlated with local high parasite burdens. In contrast, neutrophil migration, induced by the other L. major substrain, Friedlin, was unaffected, and the initial parasite burden remained similar in galectin-3 null mice as compared with wild-type mice. Infection with L. major LV39 but not Friedlin induced higher levels of extracellular release of galectin-3. Further, galectin-3 alone was able to initiate neutrophil migration even though galectin-3 is not a chemoattractant for neutrophils. Thus, our data suggest that once extracellularly released, galectin-3 can act as a damage-associated molecular pattern to facilitate early neutrophil migration, which is beneficial in the initial control of the Leishmania infection.
Resolvin E1 and Chemokine-like Receptor 1 Mediate Bone Preservation
Authors: Gao Li , Faibish Dan , Fredman Gabrielle , Herrera Bruno S. , Chiang Nan , Serhan Charles N. , Van Dyke Thomas E. , Gyurko Robert 
Published: December 2012

Abstract
The polyunsaturated ω-3 fatty acid eicosapentaenoic acid–derived resolvin E1 (RvE1) enhances resolution of inflammation, prevents bone loss, and induces bone regeneration. Although the inflammation-resolving actions of RvE1 are characterized, the molecular mechanism of its bone-protective actions are of interest. To test the hypothesis that receptor-mediated events impact bone changes, we prepared transgenic mice overexpressing the RvE1 receptor chemokine-like receptor 1 (chemR23) on leukocytes. In zymosan-initiated peritonitis, neutrophil polymorphonuclear leukocyte infiltration in response to RvE1 was limited requiring log order lower doses in chemR23tg mice. Ligature-induced alveolar bone loss was diminished in chemR23tg mice. Local RvE1 treatment of uniform craniotomy in the parietal bone significantly accelerated regeneration of the bone defect. In in vitro bone cultures, RvE1 significantly enhanced expression of osteoprotegerin (OPG) without inducing change in receptor activator of NF-κB ligand levels, whereas the osteogenic markers alkaline phosphatase, bone sialoprotein, and Runt-related transcription factor 2 remained unchanged. These results indicate that RvE1 modulates osteoclast differentiation and bone remodeling by direct actions on bone, rescuing OPG production and restoring a favorable receptor activator of NF-κB ligand/OPG ratio, in addition to known anti-inflammatory and proresolving actions.
Fam65b Is a New Transcriptional Target of FOXO1 That Regulates RhoA Signaling for T Lymphocyte Migration
Authors: Rougerie Pablo , Largeteau Quitterie , Megrelis Laura , Carrette Florent , Lejeune Thomas , Toffali Lara , Rossi Barbara , Zeghouf Mahel , Cherfils Jacqueline , Constantin Gabriela , Laudanna Carlo , Bismuth Georges , Mangeney Marianne , Delon Jérôme 
Published: December 2012

Abstract
Forkhead box O (FOXO) transcription factors favor both T cell quiescence and trafficking through their control of the expression of genes involved in cell cycle progression, adhesion, and homing. In this article, we report that the product of the fam65b gene is a new transcriptional target of FOXO1 that regulates RhoA activity. We show that family with sequence similarity 65 member b (Fam65b) binds the small GTPase RhoA via a noncanonical domain and represses its activity by decreasing its GTP loading. As a consequence, Fam65b negatively regulates chemokine-induced responses, such as adhesion, morphological polarization, and migration. These results show the existence of a new functional link between FOXO1 and RhoA pathways, through which the FOXO1 target Fam65b tonically dampens chemokine-induced migration by repressing RhoA activity.
Systemic Circulation and Bone Recruitment of Osteoclast Precursors Tracked by Using Fluorescent Imaging Techniques
Authors: Kotani Manato , Kikuta Junichi , Klauschen Frederick , Chino Takenao , Kobayashi Yasuhiro , Yasuda Hisataka , Tamai Katsuto , Miyawaki Atsushi , Kanagawa Osami , Tomura Michio , Ishii Masaru 
Published: December 2012

AbstractOsteoclasts are bone-resorbing polykaryons differentiated from monocyte/macrophage-lineage hematopoietic precursors. It remains unclear whether osteoclasts originate from circulating blood monocytes or from bone tissue–resident precursors. To address this question, we combined two different experimental procedures: 1) shared blood circulation “parabiosis” with fluorescently labeled osteoclast precursors, and 2) photoconversion-based cell tracking with a Kikume Green-Red protein (KikGR). In parabiosis, CX3CR1-EGFP knock-in mice in which osteoclast precursors were labeled with EGFP were surgically connected with wild-type mice to establish a shared circulation. Mature EGFP+ osteoclasts were found in the bones of the wild-type mice, indicating the mobilization of EGFP+ osteoclast precursors into bones from systemic circulation. Receptor activator for NF-κB ligand stimulation increased the number of EGFP+ osteoclasts in wild-type mice, suggesting that this mobilization depends on the bone resorption state. Additionally, KikGR+ monocytes (including osteoclast precursors) in the spleen were exposed to violet light, and 2 d later we detected photoconverted “red” KikGR+ osteoclasts along the bone surfaces. These results indicate that circulating monocytes from the spleen entered the bone spaces and differentiated into mature osteoclasts during a certain period. The current study used fluorescence-based methods clearly to demonstrate that osteoclasts can be generated from circulating monocytes once they home to bone tissues.
Receptor Activator for NF-κB Ligand in Acute Myeloid Leukemia: Expression, Function, and Modulation of NK Cell Immunosurveillance
Authors: Schmiedel Benjamin Joachim , Nuebling Tina , Steinbacher Julia , Malinovska Alexandra , Wende Constantin Maximilian , Azuma Miyuki , Schneider Pascal , Grosse-Hovest Ludger , Salih Helmut Rainer 
Published: December 2012

Abstract
The TNF family member receptor activator for NF-κB ligand (RANKL) and its receptors RANK and osteoprotegerin are key regulators of bone remodeling but also influence cellular functions of tumor and immune effector cells. In this work, we studied the involvement of RANK–RANKL interaction in NK cell–mediated immunosurveillance of acute myeloid leukemia (AML). Substantial levels of RANKL were found to be expressed on leukemia cells in 53 of 78 (68%) investigated patients. Signaling via RANKL into the leukemia cells stimulated their metabolic activity and induced the release of cytokines involved in AML pathophysiology. In addition, the immunomodulatory factors released by AML cells upon RANKL signaling impaired the anti-leukemia reactivity of NK cells and induced RANK expression, and NK cells of AML patients displayed significantly upregulated RANK expression compared with healthy controls. Treatment of AML cells with the clinically available RANKL Ab Denosumab resulted in enhanced NK cell anti-leukemia reactivity. This was due to both blockade of the release of NK-inhibitory factors by AML cells and prevention of RANK signaling into NK cells. The latter was found to directly impair NK anti-leukemia reactivity with a more pronounced effect on IFN-γ production compared with cytotoxicity. Together, our data unravel a previously unknown function of the RANK–RANKL molecule system in AML pathophysiology as well as NK cell function and suggest that neutralization of RANKL with therapeutic Abs may serve to reinforce NK cell reactivity in leukemia patients.
The Histone Methyltransferase MMSET Regulates Class Switch Recombination
Authors: Pei Huadong , Wu Xiaosheng , Liu Tongzheng , Yu Kefei , Jelinek Diane F. , Lou Zhenkun 
Published: December 2012

Abstract
Wolf–Hirschhorn syndrome (WHS) is a genetic disease with characteristic facial features and developmental disorders. Of interest, loss of the MMSET gene (also known as WHSC1) is considered to be responsible for the core phenotypes of this disease. Patients with WHS also display Ab deficiency, although the underlying cause of this deficiency is unclear. Recent studies suggest that the histone methyltransferase activity of MMSET plays an important role in the DNA damage response by facilitating the recruitment of 53BP1 to sites of DNA damage. We hypothesize that MMSET also regulates class switch recombination (CSR) through its effect on 53BP1. In this study, we show that MMSET indeed plays an important role in CSR through its histone methyltransferase activity. Knocking down MMSET expression impaired 53BP1 recruitment as well as the germline transcription of the Igh switch regions, resulting in defective CSR but no effect on cell growth and viability. These results suggest that defective CSR caused by MMSET deficiency could be a cause of Ab deficiency in WHS patients.