bluuebunny/crossref_metadata_2025 huggingface dataset:
PHENOMENOLOGY OF HAPPINESS AND ETHICS: FROM ARISTOTLE TO DUNS SCOTUS AND E. LÉVINAS / LAIMĖS IR ETIKOS FENOMENOLOGIJA: NUO ARISTOTELIO IKI DUNSO ŠKOTO IR E. LÉVINO
Authors: Čepulis Nerijus
Published: December 2012

In this paper I focus on the most problematic aspects of Aristotelian notion of happiness and ethics. Aristotelian ethics and the Greek wisdom on the whole strove for being, completeness and totality. Such thinking and its total attempt to achieve being, especialy rational being, that often became ideological violence, nowadays is receiving more and more incredulity and criticism. The schoolman of the 13th century Duns Scotus already stated such notions of happiness and ethics that required otherness with its radical transcendence. Also the phenomenologist of the 20th century Emmanuel Lévinas criticizes the Western view of humanity. The total(itarian) consciousness and any systematization in Lévinas’ alternative thinking are ruptured by the ideas of infinity and the other that enable to think otherwise, and outside of being.

Santrauka

Šiame straipsnyje, atsispiriant nuo Aristotelio laimės sąvokos, siekiama kritiškai apmąstyti klasikinę graikiškąją etikos sampratą. Aristotelio etika, o ir graikiškojoje ontologijoje įsišaknijusi (iš)mintis visada siekė apimti, išbaigti ir imanentiškai suvokti būties visumą. Toks vyraujančia tradicija tapęs mąstymas, pagrįstas conatus essendi ir dažnai neišvengiantis tapti ideologine prievarta, šiandien sulaukia vis daugiau nepasitikėjimo ir kritikos. Ir ne tik šiandien. Jau XIII a. scholastas Dunsas Škotas mąstė apie minėtos laimės ir etikos sampratos alternatyvą, kuri reikalauja kitybės idėjos, nurodančios į tai, kas absoliučiai transcenduoja mąstantįjį subjektą. Taip pat ir XX a. fenomenologas Emmanuelis Lévinas savo kritiką nukreipia į vakarietiškąją ontocentrinę pasaulėvoką ir iš jos išplaukiančią žmogiškumo sampratą. Totalią, sisteminančią ir neišvengiamai totalitarinę sąmonę Lévino alternatyviojoje fenomenologijoje „praplėšia“ begalybės ir kitybės idėjos, padedančios mąstyti kitaip ir anapus buvimo.
Psychiatric Illness of Systemic Lupus Erythematosus in Childhood: Spectrum of Clinically Important Manifestations
Authors: Lim Lily Siok Hoon , Lefebvre Arlette , Benseler Susanne , Peralta Michelle , Silverman Earl D.
Published: December 2012

Objective.

To determine the spectrum of manifestations in clinically important (i.e., requiring alterations of immunosuppressive therapy) psychiatric illness of pediatric systemic lupus erythematosus (pSLE) and to describe the laboratory and imaging features associated with psychiatric illness of pSLE (psySLE).

Methods.

This was a single-center cohort study of patients with pSLE followed at a pediatric SLE clinic from August 1985 to July 2009. Patients with organic psychiatric disease due to SLE were included. Data regarding psychiatric features at initial presentation and during followup were obtained from psychiatry and rheumatology visits. Data regarding concomitant SLE disease activity and laboratory results were obtained from the institutional SLE database. Information from imaging studies was abstracted from patients' charts.

Results.

Our cohort consisted of 53 pediatric patients (87% female) diagnosed with psySLE, representing 12% of the total pSLE cohort of 447 in the same time period. The median age at diagnosis of pSLE was 15.0 years and 16.1 years for psySLE. All patients reported symptoms of cognitive dysfunction and 75% of patients had additional psychotic features. Insight was preserved in 64% of patients with psychosis at diagnosis of psySLE. Visual distortion was observed among 32% of children with psySLE. Eighty-two percent of patients demonstrated clinical response to the institutional protocol of immunosuppression.

Conclusion.

Cognitive dysfunction was present in all and additional psychosis present in 75% of pediatric patients with psySLE. Visual distortion and early preservation of insight were unique features of psychosis observed in this cohort of children/adolescents with psySLE.
Screening Citrullinated Proteins in Synovial Tissues of Rheumatoid Arthritis Using 2-dimensional Western Blotting
Authors: CHANG XIAOTIAN , ZHAO YAN , WANG YUEJIAN , CHEN YU , YAN XINFENG
Published: December 2012

Objective.

Citrullination, a reaction converting arginine residue into citrulline residue, is essential for autoimmunity of rheumatoid arthritis (RA). We conducted 2-dimensional Western blot analyses (2-D WB) to screen for novel citrullinated proteins in synovial tissues from patients with RA.

Methods.

Total proteins were extracted from the synovial membranes of patients with RA (n = 10) and pooled. Four identical 2-D electrophoresis (2-DE) gels were prepared, and 2 gels were transblotted to polyvinylidene fluoride membranes that were separately probed with sera from patients with RA (n = 10) or an anticitrulline antibody. The protein profiles of the 2-DE gels were compared with the hybridization results on a global level. The immunoreactive protein spots were collected from the 2-DE gels and identified using mass spectrometry. Proteins that were detected by both RA sera and anticitrulline antibody were considered citrullinated proteins. The result was confirmed through routine WB, immunoprecipitation, and ELISA. Autoantibodies against these potential antigens were also examined in the blood of patients with RA by ELISA.

Results.

RA sera and the anticitrulline antibody on 2-D WB detected α-1-antitrypsin (A1AT), dynein heavy-chain 3, fibrinogen β chain, keratin type II cuticular Hb4 (KRT84), lumican, tubulin β-chain (TUBB), and vimentin. A1AT, KRT84, and TUBB had high expression in the synovial membranes (n = 5) of patients with RA and A1AT and KRT84 had high expression in RA synovial fluids (n = 40). A1AT, KRT84, and TUBB immunoprecipitated from synovial tissues showed citrullination. A high level of autoantibodies against KRT84 was detected in the blood of patients with RA (n = 92) compared to that of healthy controls (n = 92).

Conclusion.

Our study identified some new citrullinated proteins in RA synovial tissues using 2-D WB.
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.
Exploring Theory for Citizens’ Preferences in Health Policy
Authors: Kylänen Marika , Vuori Jari , Allen Pauline
Published: December 2012

Preferences have been analyzed extensively in health care, but few studies have examined how culture driven preference formation may impact on resource allocation decisions in public and private health service delivery. This paper explores and develops a theoretical framework that distinguishes different approaches to institutionally and culturally informed preferences. The analysis shows that the appropriate approach depends on normative considerations and the particular health policy context which it is applied. In particular health policy cultures, mediating culture driven preferences (such as fatalism, hierarchism, individualism, egalitarianism and autonomy) which have not been used as part of health policy analysis before, challenge the roles of public and private health service providers. In view of the scarcity of studies in this field, the authors suggest a rationale for studies that enhance the understanding of how health policy cultures are embedded in normative health policy and propose a research agenda on cultural biases.
Cross-Disciplinary Approach for the Risk Assessment Ontology Design
Authors: Draghici Anca , Draghici George
Published: December 2012

The article describes a cross-disciplinary approach to support the risk assessment process through an integrative tool based on a global ontology. The designed global ontology allows the risk identification and characterization, the related potential work accidents and/or diseases, and decides better for appropriate preventive/corrective measures (the risk assessment logical chain). The global ontology structure follow a matrix model with two dimensions: one related to the work system structure/components and the other related to the risk assessment logical chain. For the integrative tools, solutions there have been developed a risk assessment process modeling with the purpose of better explain and understand the relations in the risk assessment logical chain. In addition, a concept model was developed and implemented for the global ontology complete definition. Finally, an expert system and a web platform are presented as integrative tools for the risk assessment.
Optimization of Anti-Spam Systems with Multiobjective Evolutionary Algorithms
Authors: Basto-Fernandes Vitor , Yevseyeva Iryna , Méndez José R.
Published: December 2012

In this paper anti-spam filtering is presented as a cumbersome service, as opposed to a software product perspective. The huge human effort for setting up, adaptation, maintenance, and tuning of filters for spam detection in anti-spam systems is explained. Choosing the best importance scores for the spam filters is essential for the accuracy of any rules based anti-spam system, and is also one of the biggest challenges in this research area. Optimal filters score settings for Apache SpamAssassin project (the most widely adopted anti-spam open-source software) is addressed. In addition to a survey done on single/multi-objective optimization research in this area, we also present a study for filters score setting using multiobjective optimization based on two most representative evolutionary algorithms, NSGA II and SPEA2. Problem description, simulation and results analysis is done for SpamAssassin public mail corpus which is widely used for benchmarking purposes.
Structuring Information Systems-in-Use
Authors: Lin Angela , Chen Shin-Horng
Published: December 2012

It has become commonplace for companies operating in a global marketplace to relocate, extend, or establish new production facilities overseas. In this global context it is also normal for organizations to replicate the implementation and use of an established information system in a new location. Such replication is not trivial however and if not properly managed can lead to IS obsolescence. Drawing on a practice lens approach the paper presents a case study of the attempted replication of an e-procurement system within a global notebook manufacturer. The study argues that effective replication needs to take into account not only the technical aspects of the system but also the interpretive schemes of its users and their awareness of organizational routines that take together amount to a technology-in-use. The paper concludes with a discussion of the issues arising from the study and their implications for global information systems management.
Handset-Based Data Collection Process and Participant Attitudes
Authors: Karikoski Juuso
Published: December 2012

Handset-based measurements are an emerging method for collecting behavioral data about smartphone users. Setting up these kinds of measurements is challenging because of the personal nature of the data collection device and a lack of standards related to behavioral data and the method as a whole. Privacy issues related to the participants of the data collection are of major importance when dealing with behavioral data. Introduced is the process of collecting handset-based data in the OtaSizzle project in the Aalto University community in Finland together with a literature review of other similar data collection efforts in academia and industry. A survey is also deployed to study the incentives for participation, privacy concern levels and innovativeness of the user group participating in the measurements. This article contributes to the body of knowledge regarding measurements conducted with smartphones and sheds light on participant attitudes about them.
A Social-Feedback Enriched Interface for Software Download
Authors: Dini Gianluca , Foglia Pierfrancesco , Prete C. Antonio , Zanda Michele
Published: December 2012

Software downloading over the Internet is a major solution for publishers to deliver their software products. In this context, user interfaces for software downloading must be designed carefully. They should provide usable interactions and support users when deciding whether to accept the software product or not. This work proposes to enrich a common browser interface for software downloading with a reputation system - a mechanism for collecting and presenting user feedback. The reputation system is assessed with a usability study. The authors’ results show that positive user rankings are effective in increasing user download acceptances for well-known publishers and common name publishers, as well as in increasing acceptance motivations related to trust aspects. In addition, the presence of the reputation system reduces incoherent user behaviors.
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

Extracellular 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

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

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

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

Osteoclasts 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

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

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.
NK Cell Maturation and Function in C57BL/6 Mice Are Altered by Caloric Restriction
Authors: Clinthorne Jonathan F. , Beli Eleni , Duriancik David M. , Gardner Elizabeth M.
Published: December 2012

NK cells are a heterogenous population of innate lymphocytes with diverse functional attributes critical for early protection from viral infections. We have previously reported a decrease in influenza-induced NK cell cytotoxicity in 6-mo-old C57BL/6 calorically restricted (CR) mice. In the current study, we extend our findings on the influence of CR on NK cell phenotype and function in the absence of infection. We demonstrate that reduced mature NK cell subsets result in increased frequencies of CD127+ NK cells in CR mice, skewing the function of the total NK cell pool. NK cells from CR mice produced TNF-α and GM-CSF at a higher level, whereas IFN-γ production was impaired following IL-2 plus IL-12 or anti-NK1.1 stimulation. NK cells from CR mice were highly responsive to stimulation with YAC-1 cells such that CD27−CD11b+ NK cells from CR mice produced granzyme B and degranulated at a higher frequency than CD27−CD11b+ NK cells from ad libitum fed mice. CR has been shown to be a potent dietary intervention, yet the mechanisms by which the CR increases life span have yet to be fully understood. To our knowledge, these findings are the first in-depth analysis of the effects of caloric intake on NK cell phenotype and function and provide important implications regarding potential ways in which CR alters NK cell function prior to infection or cancer.
Microparticles from Mycobacteria-Infected Macrophages Promote Inflammation and Cellular Migration
Authors: Walters Shaun B. , Kieckbusch Jens , Nagalingam Gayathri , Swain Ashleigh , Latham Sharissa L. , Grau Georges E. R. , Britton Warwick J. , Combes Valéry , Saunders Bernadette M.
Published: December 2012

Mycobacterium tuberculosis infection is characterized by a strong inflammatory response whereby a few infected macrophages within the granuloma induce sustained cellular accumulation. The mechanisms coordinating this response are poorly characterized. We hypothesized that microparticles (MPs), which are submicron, plasma membrane-derived vesicles released by cells under both physiological and pathological conditions, are involved in this process. Aerosol infection of mice with M. tuberculosis increased CD45+ MPs in the blood after 4 wk of infection, and in vitro infection of human and murine macrophages with mycobacteria enhanced MP release. MPs derived from mycobacteria-infected macrophages were proinflammatory, and when injected into uninfected mice they induced significant neutrophil, macrophage, and dendritic cell recruitment to the injection site. When incubated with naive macrophages, these MPs enhanced proinflammatory cytokine and chemokine release, and they aided in the disruption of the integrity of a respiratory epithelial cell monolayer, providing a mechanism for the egress of cells to the site of M. tuberculosis infection in the lung. In addition, MPs colocalized with the endocytic recycling marker Rab11a within macrophages, and this association increased when the MPs were isolated from mycobacteria-infected cells. M. tuberculosis–derived MPs also carried mycobacterial Ag and were able to activate M. tuberculosis–specific CD4+ T cells in vivo and in vitro in a dendritic cell–dependent manner. Collectively, these data identify an unrecognized role for MPs in host response against M. tuberculosis by promoting inflammation, intercellular communication, and cell migration.
Sequential Engagement of FcεRI on Mast Cells and Basophil Histamine H4 Receptor and FcεRI in Allergic Rhinitis
Authors: Shiraishi Yoshiki , Jia Yi , Domenico Joanne , Joetham Anthony , Karasuyama Hajime , Takeda Katsuyuki , Gelfand Erwin W.
Published: December 2012

Histamine H4 receptor (H4R)–deficient mice (H4R−/−), H4R antagonist–treated wild-type (WT) mice, and WT mice depleted of basophils failed to develop early (EPR) or late phase (LPR) nasal responses following allergen sensitization and challenge. Basophil transfer from WT but not H4R−/− mice restored the EPR and LPR in H4R−/− mice. Following passive sensitization with OVA-specific IgE, FcεRI−/− recipients of WT basophils plus OVA and histamine developed an EPR and LPR. OVA-IgE passively sensitized FcεRI−/− recipients of H4R−/− basophils and OVA and histamine challenge failed to develop an EPR or LPR, and basophils were not detected in nasal tissue. In contrast, recipients of basophils from IL-13−/− and IL-4−/−/IL-13−/− mice developed an EPR but not an LPR. These results demonstrate the development of allergic rhinitis proceeded in two distinct stages: histamine release from FcεRI-activated mast cells, followed by histamine-mediated recruitment of H4R-expressing basophils to the nasal cavity and activation through FcεRI.
PGE2 Induces Macrophage IL-10 Production and a Regulatory-like Phenotype via a Protein Kinase A–SIK–CRTC3 Pathway
Authors: MacKenzie Kirsty F. , Clark Kristopher , Naqvi Shaista , McGuire Victoria A. , Nöehren Gesa , Kristariyanto Yosua , van den Bosch Mirjam , Mudaliar Manikhandan , McCarthy Pierre C. , Pattison Michael J. , Pedrioli Patrick G. A. , Barton Geoff J. , Toth Rachel , Prescott Alan , Arthur J. Simon C.
Published: December 2012

The polarization of macrophages into a regulatory-like phenotype and the production of IL-10 plays an important role in the resolution of inflammation. We show in this study that PGE2, in combination with LPS, is able to promote an anti-inflammatory phenotype in macrophages characterized by high expression of IL-10 and the regulatory markers SPHK1 and LIGHT via a protein kinase A–dependent pathway. Both TLR agonists and PGE2 promote the phosphorylation of the transcription factor CREB on Ser133. However, although CREB regulates IL-10 transcription, the mutation of Ser133 to Ala in the endogenous CREB gene did not prevent the ability of PGE2 to promote IL-10 transcription. Instead, we demonstrate that protein kinase A regulates the phosphorylation of salt-inducible kinase 2 on Ser343, inhibiting its ability to phosphorylate CREB-regulated transcription coactivator 3 in cells. This in turn allows CREB-regulated transcription coactivator 3 to translocate to the nucleus where it serves as a coactivator with the transcription factor CREB to induce IL-10 transcription. In line with this, we find that either genetic or pharmacological inhibition of salt-inducible kinases mimics the effect of PGE2 on IL-10 production.
Identifying a gas hydrate production zone using a cased-hole borehole acoustic-reflection survey, Aurora/JOGMEC/NRCan Mallik 2L-38 gas hydrate production research well
Authors: Voskamp A , Lingxia Z , Murray D R , Torii K , Yamamoto H , Noguchi S , Yamamoto K , Dallimore S R
Published: December 2012

In 2007, data were acquired from a borehole acoustic-reflection survey (BARS), using the latest Sonic Scanner tool, in a gas-hydrate-bearing formation in the Mallik field, Mackenzie Delta, Northwest Territories. The BARS data were logged in a cased-hole
environment in which no azimuthal information could be recovered, thus limiting the final migration image-processing and interpretation. Performing BARS in a cased hole is less favourable than in an open-hole environment because the high-amplitude casing arrivals make the identification of reflected
energy very challenging. In addition, no tool orientation data are usable in a cased hole due to the lack of reliable measurement of the Earth's magnetic field. In this paper, we present results acquired in a cased-hole environment and indicate correlations of BARS data with auxiliary logs.
The perforation zone is identified in the raw and filtered wave-form BARS data. Energy in the 1098 to 1105 m depth interval is significantly stronger, and this zone of higher amplitudes appears to extend into the formation. This zone is assumed to be directly related to changes in the formation
caused by the perforations and/or production in the lower half of the production-test interval. Several additional reflections can be observed in the raw and filtered wave forms. The gamma-ray and density logs indicate formation changes at the same depths at which these reflections occur. These
formation boundaries and the reflections also correlate well with the fullbore microresistivity image logs. The results indicate that BARS data can be used to achieve a more complete, detailed, and thus enhanced log interpretation.
Model comparison and estimation of genetic parameters for body weight in commercial broilers
Authors: Maniatis G. , Demiris N. , Kranis A. , Banos G. , Kominakis A.
Published: December 2012

Maniatis, G., Demiris, N., Kranis, A., Banos, G. and Kominakis, A. 2013. Model comparison and estimation of genetic parameters for body weight in commercial broilers. Can. J. Anim. Sci. 93: 67–77. The availability of powerful computing and advances in algorithmic efficiency allow for the consideration of increasingly complex models. Consequently, the development and application of appropriate statistical procedures for model evaluation is becoming increasingly important. This paper is concerned with the application of an alternative model determination criterion (conditional Akaike Information Criterion, cAIC) in a large dataset comprising 203 323 body weights of broilers, pertaining to 7 (BW7) and 35 (BW35) days of age. Seven univariate and seven bivariate models were applied. Direct genetic, maternal genetic and maternal environmental (c2) effects were estimated via REML. The model evaluation criteria included conditional Akaike Information Criterion (cAIC), Bayesian Information Criterion (BIC) and the standard Akaike Information Criterion (henceforth marginal; mAIC). According to cAIC the best-fitting model included direct genetic, maternal genetic and c2effects. Maternal heritabilities were low (0.10 and 0.03) compared to the direct heritabilities (0.17 and 0.21), while c2was 0.05 and 0.04 for BW7and BW35, respectively. BIC and mAIC favoured a model that additionally included a direct-maternal genetic covariance, resulting in highly negative direct-maternal genetic correlations (−0.47 and −0.64 for BW7and BW35, respectively) and higher direct heritabilities (0.25 and 0.28 for BW7and BW35, respectively). Results suggest that cAIC can select different animal models than mAIC and BIC with different biological properties.
Representaciones sociales y prácticas ciudadanas en la comunidad rural: Un aporte desde la comunicación estratégica
Authors: Trimano Luciana , Emanuelli Paulina Beatriz
Published: December 2012

La comunidad de Las Calles, ubicada en el Valle de Traslasierra, al oeste de la provincia de Córdoba (Argentina), se caracteriza por la combinación de lo rural y lo turístico; es escenario de un amplio movimiento de emigración de la ciudad al campo. En este sentido, conviven en dicha sociedad grupos culturales diversos y disímiles identidades. Entendiendo que esos grupos culturales forman parte de la “cultura” como espacio estratégico de comprensión de las tensiones que desgarran y recomponen el “estar juntos”.

La presentación plantea el análisis de las representaciones sociales e interacciones de actores de culturas emergentes (hippies) y preexistentes (paisas) en esta territorialidad rural y la aparición de nuevos repertorios y prácticas ciudadanas. Las interacciones y prácticas ciudadanas demandan la revisión y rediseño de “actuales” políticas de gestión e integración sociocultural. Desde ese lugar, la comunicación estratégica puede y debe realizar un aporte, tendiente a promover el desarrollo territorial y local.