bluuebunny/crossref_metadata_2025 huggingface dataset:
Représentation des traitements de substitution aux opiacés et de leur arrêt. Regards croisés patients/médecins
Authors: Guillou Landreat Morgane , Rozaire Charles , Vigneau Victorri Caroline , Grall-Bronnec Marie
Published: January 2014

Les traitements de substitution de la dépendance aux opiacés sont commercialisés depuis la fin des années 1960 aux États-Unis et depuis 1996 en France. Les objectifs de ces traitements se sont élargis : au-delà de l’arrêt des consommations d’héroïne, ils sont recentrés sur l’amélioration du fonctionnement psychosocial du patient et de sa qualité de vie. Ils sont désormais envisagés comme des prescriptions au long cours, ce qui modifie les « carrières » des patients et leur profil clinique sous traitement. Mais après une réadaptation psychosociale et une amélioration des conduites addictives, souvent obtenues après plusieurs années, est-il possible d’envisager l’arrêt de ce traitement ? Les durées optimales de prescription et les modalités d’arrêt des traitements de substitution dans le cadre de la dépendance aux opiacés sont très débattues et dépendent en partie des représentations des patients et des prescripteurs vis-à-vis du traitement. Face à ces questionnements, nous avons mené un travail explorant les représentations des traitements de substitution et de leur arrêt du point de vue du patient et du médecin. L’objectif est tout d’abord de croiser les représentations des patients et des médecins vis-à-vis des TSO, et secondairement d’identifier la place du désir d’arrêt du traitement de substitution chez les patients. Ce travail se constitue en trois volets : un premier volet exploratoire sur les représentations des patients vis-à-vis de leur MSO, un second concernant les représentations des médecins vis-à-vis des MSO et enfin un troisième volet abordant la question de l’arrêt des MSO chez les patients. La buprénorphine et la méthadone sont des traitements médicamenteux dont la place aux yeux des patients et des prescripteurs est effectivement bien particulière. La majorité des patients interrogés considèrent qu’il ne s’agit pas de traitements comme les autres, et l’arrêt de la buprénorphine est un motif de demande de soins en addictologie au même titre que les SPA non médicamenteuses. De plus, la majorité des médecins interrogés, expérimentés ou non dans le domaine ont des avis très disparates et n’identifient pas clairement la buprénorphine comme un médicament. Cette perception complexe et ambivalente chez les patients et les prescripteurs dépend de plusieurs facteurs : les interactions entre les caractéristiques interindividuelles des patients, l’histoire de leurs troubles, les caractéristiques des médecins et leurs modalités de pratiques professionnelles et enfin la relation thérapeutique instaurée.
Étude rétrospective à deux ans des hospitalisations pour arrêt de la méthadone au Centre Médical Marmottan
Authors: Pham-Orsetti Héloïse
Published: January 2014

Si l’efficacité des traitements de substitution n’est plus à démontrer en termes d’impact sociosanitaire, de nombreux patients sous traitement de substitution expriment le désir d’arrêter la substitution, évoquant souvent une lassitude de la dépendance, des impératifs familiaux ou professionnels. Au Centre Médical Marmottan, de nombreux patients viennent ainsi demander une hospitalisation pour sevrage de méthadone ou de buprénorphine. Nous avons réalisé une étude rétrospective portant sur les caractéristiques et le devenir des 21 patients hospitalisés pour arrêt de la méthadone au cours de l’année 2011 au Centre Médical Marmottan. En 2013, parmi ces 21 patients, 9 avaient repris un traitement par méthadone, 8 étaient perdus de vue, 4 étaient toujours suivis au centre et n’avaient pas repris de traitement par méthadone. Parmi ces 4 patients, 2 étaient dépendants à l’alcool. Si la demande initiale est souvent celle de sevrage définitif de la méthadone, les résultats de notre étude montrent que la réalité est plus complexe, et que l’hospitalisation n’est souvent qu’une étape dans le parcours du patient dépendant. Répondant aux demandes de patients souhaitant arrêter la substitution, l’hospitalisation – moment de rupture avec le produit, mais aussi avec l’environnement – participe ainsi d’une clinique de l’addiction qui, au-delà du sevrage et de l’abstinence, accompagne le patient dans son questionnement sur la dépendance et le rôle qu’elle joue dans son lien aux autres et à lui-même.
Les métaphysiques dans l' Encyclopédie
Authors: Groult Martine
Published: January 2014

Le projet de l’ Encyclopédie de Diderot et d’Alembert constitue un tournant dans l’histoire de la philosophie dans la mesure où d’Alembert a procédé à une pluralisation de la métaphysique. À la métaphysique traditionnelle et singulière se sont ajoutées des métaphysiques. Examinons plus particulièrement les trois métaphysiques que sont la métaphysique des corps, la métaphysique des propositions et la métaphysique des sciences exposées dans l’ Encyclopédie  : on s’aperçoit alors que la nouveauté est moins le progrès des sciences que le processus philosophique comme herméneutique du génie de l’invention, dans les sciences comme dans les arts. Ce processus remplace désormais la métaphysique traditionnelle et ouvre la voie aux théories de la connaissance.
Nueva especie de grillo mirmecófilo de Mallorca, islas Baleares, España (Orthoptera, Myrmecophilidae)
Authors: Stalling T.
Published: January 2014

Se describe e ilustra una nueva especie de grillo mirmecófilo, Myrmecophilus fuscus sp. n., procedente de la isla de Mallorca (islas Baleares, España). Lasius lasioides (Emery, 1869) es la especie hospedadora y su hábitat es el bosque perenne de roble. El holotipo se ha depositado en la colección del Muséum d’Histoire Naturelle de Ginebra. La nueva especie está estrechamente relacionada con Myrmecophilus acervorum (Panzer, [1799]) y pertenece al subgénero Myrmecophilus Berthold, 1827.
Identidad y estatus taxonómico de Sitaris lativentris Schaufuss, 1861 y Sitaris melanurus Küster, 1849, dos enigmáticos táxones ibéricos (Coleoptera, Meloidae)
Authors: Ruiz J. L. , Bologna M. A. , García-París M.
Published: January 2014

La amplia varibilidad morfológica en Nemognathinae a menudo ha originado una proliferación en la descripción de especies distintas. La mayoría de la especies de Nemognathinae rara vez se encuentran en la naturaleza y algunas sólo son conocidas por los ejemplares utilizados en las descripciones originales. Dos ejemplos de este problema son los casos de Sitaris lativentris Schaufuss, 1861 y Sitaris melanurus Küster, 1849, ambas descritas de España. El redescubrimiento de ejemplares morfológicamente asignables a S. lativentris en el sur de España, y una detallada lectura crítica de la descripción original de S. melanurus, nos permiten dilucidar el estatus taxonómico de estos taxones enigmáticos. Sitaris lativentris ha sido considerado hasta ahora un sinónimo de Sitaris solieri Pecchioli, 1840; sin embargo, ni el lectotipo de S. lativentris (aquí designado) ni los nuevos especímenes encontrados asignables a S. lativentris, se corresponden con S. solieri, excepto en que ambos presentan una coloración similar. Alternativamente, el estudio comparativo de S. lativentris y Sitaris muralis (Forster, 1771) no muestra diferencias entre ellas, excepto en el patrón cromático elitral y la coloración de la pilosidad, ambos caracteres ampliamente variables en otras especies de Nemognathinae. Por tanto, se sinonimiza S. lativentris con S. muralis (nuevo sinónimo). La identidad de Sitaris melanurus ha sido pasada por alto por la mayoría de los investigadores, posiblemente porque los ejemplares tipo parecen estar perdidos. No obstante, la descripción original ofrece suficiente información para descartar la adscripción de este taxón a Sitaris. Los caracteres morfológicos expuestos en la descripción corresponden a rasgos que, en el ámbito de los sitarinos europeos, se encuentran sólo en Stenoria apicalis (Latreille, 1804). La descripción de Küster (1849) corresponde a una de la variantes cromáticas más frecuentes en esa especie. Como consecuencia, incluimos el nombre S. melanurus como un nuevo sinónimo de S. apicalis.
Integrando ADN y taxonomía morfológica para describir una nueva especie de la familia Bathynellidae (Crustacea, Syncarida) de España
Authors: Camacho A. I. , Dorda B. A. , Rey I.
Published: January 2014

Se describe una nueva especie de la familia Bathynellidae Grobben, 1905 de España. Vejdovskybathynella vasconica sp. nov. presenta un carácter único dentro del género, tener la antena de 8 segmentos. Además la nueva especie exhibe una única combinación de caracteres morfológicos que incluye: seda mediana presente en el exopodio de la antena, anténula y antena de igual longitud, palpo mandibular de tres segmentos y sin dimorfismo sexual, cuatro segmentos en el endopodio de todas las patas, tres espinas en el simpodio del urópodo, dos uñas en el endopodio del urópodo, la primera espina de la furca más larga que las demás, toracópodo VIII hembra con exopodio más pequeño que el endopodio, toracópodo VIII macho con una larga prolongación frontal y una protuberancia externa de tamaño medio en la región peneana, así como una cresta frontal de tamaño medio con un pequeño espolón en el basipodio.
Se han obtenido sequencias parciales del gen mitocondrial citocromo oxidasa I (COI) y del gen ribosomal 18S ARNr de especímenes de la localidad tipo de la nueva especie. El análisis de estos datos moleculares ha demostrado la presencia de dos unidades genéticas altamente divergentes entre ejemplares de la familia Bathynellidae correspondientes a dos géneros morfológicamente bien diferenciados. La información molecular obtenida en este trabajo complementa la descripción taxonómica tradicional, morfológica, apoyando la validez de la nueva especie perteneciente al género Vejdovskybathynella.
Nueva especie of Separatoppia Mahunka, 1983 (Acari, Oribatida, Oppiidae) de la India
Authors: Ermilov S. G. , Pešić V.
Published: January 2014

Se redescribe una nueva especie de ácaro oribátido de la familia Oppiidae –Separatoppia indica n. sp.– de India. La nueva especie es muy similar morfológicamente a Separatoppia concava Ermilov & Rybalov de Etiopía, pero se diferencia de ella por la longitud de las setas interlamelares y notogastrales y el desarrollo del proceso humeral. Es la primera cira del género Separatoppia Mahunka, 1983 en India y en la región oriental.
Nuevos táxones animales descritos en la península Ibérica y Macaronesia desde 1994 (XVII)
Authors: Fernández J.
Published: January 2014

No disponible
El modelo de demandas-control-apoyo y su relación con el riesgo percibido de enfermedad-accidente. Una aplicación a la Comunidad Autónoma andaluza
Authors: Montero Simó María José , Rivera Torres Pilar , Araque Padilla Rafael Ángel
Published: January 2014

El presente trabajo analiza de qué modo los componentes del modelo de Demandas-Control-Apoyo-JDC(-S) influyen en el riesgo percibido de enfermedad o accidente en el lugar de trabajo y, en concreto, el papel del Control y del Apoyo como variables moduladoras entre las Demandas y el Riesgo percibido. Para ello se ha analizado la estructura dimensional de las componentes de dicho modelo a partir de la Primera Encuesta Andaluza de Condiciones de Trabajo. La muestra final está formada por 7.512 trabajadores y la aproximación metodológica se concreta en los Modelos de Ecuaciones Estructurales con Variables Latentes. Los resultados indican que cabe diferenciar cuatro dimensiones en dicho modelo, de las cuales únicamente tres se muestran condicionantes del Riesgo percibido (Demanda Cuantitativa, Control y Apoyo). Paralelamente, no se obtiene evidencia que sustente la modulación del Control y del Apoyo entre las Demandas y el Riesgo percibido.
Combining Expert Systems and Multiple Intelligences in an Adaptive and Intelligent Tutoring System
Authors: Mohamed Hafidi , Taher Bensebaa
Published: January 2014

This paper describes an adaptive and intelligent tutoring system (AITS) based on multiple intelligences and expert system. Most of adaptive and intelligent tutoring systems based their adaptation to user’s skill level. Other learner features taken into account are background, hyperspace experience, preferences and interests. However, less attention was paid to multiple intelligences and their effects on learning. Moreover, to design AITS which can manage both different disciplinary domains and a guide for the learner is difficult. The specialization of the analysis treatments is responsible for the loss of reusability for the other disciplinary domains. To overcome these limitations, the authors will try to combine the benefits of paradigms (adaptive hypermedia, intelligent tutoring system, multiple intelligences) in order to adapt the course to the needs and intellectual abilities of each learner.
The Path Travelled from Thinking to Perception
Authors: Jiménez-Zarco Ana Isabel , González-González Inés , Castillo-Merino David
Published: January 2014

Both academics and practitioners recognize the importance of certain variables such as organizational culture, a company’s size and age or the entrepreneur's profile in explaining the success of a new company’s service. However, it remains unclear if there is a direct and significant relationship, especially when the entrepreneur uses different indicators for measuring the performance of a new released service. (1) objective indicators, -such as financial-, or (2) subjective indicators, -based on entrepreneur's judgements, preferences and expectations-. The analysis of a sample of 354 Spanish SMEs belonging to the service sector that have developed new services in the last two years confirms that the importance and significance of these variables vary according to the type of indicator used.
The Impact of Corporate Culture on the Absorptive Capacity and Innovative Capacity of Companies
Authors: López Enric Serradell , Alguero Carlos Grau
Published: January 2014

The purpose of this study is to gain a better understanding of the influence of corporate culture in the absorptive and innovative capacities of Spanish enterprises. This is an exploratory study conducted involving top managers from a sample of 53 large Spanish companies. An empirical analysis is performed using a structural equations model and bootstrapping methodology. The paper highlights the role of corporate culture as a concept that has a significant influence on the absorptive capacity and also on the innovative capacity of enterprises. The absorptive capacity is presented as a system that makes a work of observation, identification, collection and use of information and knowledge from abroad, which is considered essential to achieving and sustaining competitive advantage. The research performed shows how the different components of absorptive capacity, found in the literature are significant configuring the capacity as a latent variable with economic sense. Furthermore, regarding the sample studied, corporate culture has a significant influence on the innovative capacity. The model explains the influence of culture in the innovative capacity, and in the two components of it, incremental and radical innovation. The investigation has found also some interactions not included in the model proposed, as for example the relationship between the recognition as the part of the absorptive capacity component more related with radical innovation. The empirical model performed need to be replicated with other samples for further findings and possible generalization. Deconstructing corporate culture in eight dimensions permits to use some of them in a prescriptive way. The adoption of certain cultural values and attitudes and the use of management strategies designed to promote these values and attitudes, encourage the company to more easily benefit from the opportunities of their environment, increasing the ability to manage information of the environment.
Feature Ranking Computation Algorithm
Authors: Igelnik Boris
Published: January 2014

This journal paper describes an algorithm of feature ranking computation, based both on a data set with a potentially excessive number of features and a neural network trained and tested on this set. Each member of the data set contains many features (inputs) and one output. The essence of the method is that: 1) a mathematical measure (rank) of a contribution to the output is defined for each feature; 2) a rank of a feature is efficiently computed; 3) a subset of the total set of the features, having a total rank less than a preliminary installed threshold, is deleted from the total set of features. An example from the area of power engineering confirms that the method may lead to a significant reduction of a search space in the tasks of modeling, optimization, and data fusion.
Information Technology Management Practice
Authors: Phillips Brandis
Published: January 2014

The purpose of this research is to put forth a model that examines the impact of information technology (IT) related management practices upon IT effectiveness. Given the nature and use of these practices as a management activity, control theory is used as a framework to determine if IT management practices serving as controls can achieve positive outcomes. A portion of the Control Objectives for IT (COBIT) framework is used as a proxy for management practices due to the ability to ground the COBIT practices in previous literature and serve as IT controls. The results of a survey of IT and audit professionals suggest that the model put forth with IT related management practices as an independent second order factor, does indeed explain variance in perceptions of IT effectiveness as mediated through perceptions of IT value and perceptions of IT risk however only IT value is a significant predictor of IT effectiveness.
CD4+ T Cell Responses to the Plasmodium falciparum Erythrocyte Membrane Protein 1 in Children with Mild Malaria
Authors: Gitau Evelyn N. , Tuju James , Karanja Henry , Stevenson Liz , Requena Pilar , Kimani Eva , Olotu Ally , Kimani Domtila , Marsh Kevin , Bull Peter , Urban Britta C.
Published: January 2014

The immune response against the variant surface Ag Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a key component of clinical immunity against malaria. We have investigated the development and maintenance of CD4+ T cell responses to a small semiconserved area of the Duffy binding–like domain (DBL)α–domain of PfEMP1, the DBLα-tag. Young children were followed up longitudinally, and parasites and PBMCs were isolated from 35 patients presenting with an acute case of uncomplicated malaria. The DBLα-tag from the PfEMP1 dominantly expressed by the homologous parasite isolate was cloned and expressed as recombinant protein. The recombinant DBLα-tag was used to activate PBMCs collected from each acute episode and from an annual cross-sectional survey performed after the acute malaria episode. In this article, we report that CD4+ T cell responses to the homologous DBLα-tag were induced in 75% of the children at the time of the acute episode and in 62% of the children at the following cross-sectional survey on average 235 d later. Furthermore, children who had induced DBLα-tag–specific CD4+IL-4+ T cells at the acute episode remained episode free for longer than children who induced other types of CD4+ T cell responses. These results suggest that a wide range of DBLα-tag–specific CD4+ T cell responses were induced in children with mild malaria and, in the case of CD4+IL-4+ T cell responses, were associated with protection from clinical episodes.
Infection and Cellular Defense Dynamics in a Novel 17β-Estradiol Murine Model of Chronic Human Group B Streptococcus Genital Tract Colonization Reveal a Role for Hemolysin in Persistence and Neutrophil Accumulation
Authors: Carey Alison J. , Tan Chee Keong , Mirza Shaper , Irving-Rodgers Helen , Webb Richard I. , Lam Alfred , Ulett Glen C.
Published: January 2014

Genital tract carriage of group B streptococcus (GBS) is prevalent among adult women; however, the dynamics of chronic GBS genital tract carriage, including how GBS persists in this immunologically active host niche long term, are not well defined. To our knowledge, in this study, we report the first animal model of chronic GBS genital tract colonization using female mice synchronized into estrus by delivery of 17β-estradiol prior to intravaginal challenge with wild-type GBS 874391. Cervicovaginal swabs, which were used to measure bacterial persistence, showed that GBS colonized the vaginal mucosa of mice at high numbers (106–107 CFU/swab) for at least 90 d. Cellular and histological analyses showed that chronic GBS colonization of the murine genital tract caused significant lymphocyte and PMN cell infiltrates, which were localized to the vaginal mucosal surface. Long-term colonization was independent of regular hormone cycling. Immunological analyses of 23 soluble proteins related to chemotaxis and inflammation showed that the host response to GBS in the genital tract comprised markers of innate immune activation including cytokines such as GM-CSF and TNF-α. A nonhemolytic isogenic mutant of GBS 874391, Δcyle9, was impaired for colonization and was associated with amplified local PMN responses. Induction of DNA neutrophil extracellular traps, which was observed in GBS-infected human PMNs in vitro in a hemolysin-dependent manner, appeared to be part of this response. Overall, this study defines key infection dynamics in a novel murine model of chronic GBS genital tract colonization and establishes previously unknown cellular and soluble defense responses to GBS in the female genital tract.
IL-37 Ameliorates the Inflammatory Process in Psoriasis by Suppressing Proinflammatory Cytokine Production
Authors: Teng Xiu , Hu Zhonglan , Wei Xiaoqiong , Wang Zhen , Guan Ting , Liu Ning , Liu Xiao , Ye Ning , Deng Guohua , Luo Can , Huang Nongyu , Sun Changyan , Xu Minyan , Zhou Xikun , Deng Hongxin , Edwards Carl Keith , Chen Xiancheng , Wang Xiaoxia , Cui Kaijun , Wei Yuquan , Li Jiong
Published: January 2014

IL-37 is a potent inhibitor of innate immunity by shifting the cytokine equilibrium away from excessive inflammation. Psoriasis is thought to be initiated by abnormal interactions between the cutaneous keratinocytes and systemic immune cells, triggering keratinocyte hyperproliferation. In the current study, we assessed IL-37 in two well-known psoriasis models: a human keratinocyte cell line (HaCaT) and the keratin 14 VEGF-A–transgenic mouse model. First, we used the HaCaT cell line, which was transiently transfected with an overexpressing IL-37 vector, and tested the effect of IL-37 on these cells using a mixture of five proinflammatory cytokines. IL-37 was effective in suppressing the production of CXCL8, IL-6, and S100A7, which were highly upregulated by the mixture of five proinflammatory cytokines. Keratin 14 VEGF-A–transgenic mice were treated with plasmid coding human IL-37 sequence–formulated cationic liposomes, and we observed potent immunosuppressive effects over the 18-d period. In this model, we observed reduced systemic IL-10 levels, local IFN-γ gene transcripts, as well as mild mast cell infiltration into the psoriatic lesions of the mice. Immunohistochemical analysis indicated that IL-37 was expressed by effector memory T cells, as well as macrophages, in human psoriatic plaques. In conclusion, our studies strongly indicate that IL-37 plays a potent immunosuppressive role in the pathogenesis of both experimental psoriasis models in vitro and in vivo by downregulating proinflammatory cytokines. Importantly, our findings highlight new therapeutic strategies that can be designed to use this immunosuppressive anti-inflammatory cytokine in psoriasis and other inflammatory cutaneous diseases.
Bruton’s Tyrosine Kinase Promotes Persistence of Mature Anti-Insulin B Cells
Authors: Bonami Rachel H. , Sullivan Allison M. , Case James B. , Steinberg Hannah E. , Hoek Kristen L. , Khan Wasif N. , Kendall Peggy L.
Published: January 2014

Autoreactive B lymphocytes are essential for the development of T cell–mediated type 1 diabetes (T1D). Cytoplasmic Bruton’s tyrosine kinase (BTK) is a key component of B cell signaling, and its deletion in T1D-prone NOD mice significantly reduces diabetes. However, the role of BTK in the survival and function of autoreactive B cells is not clear. To evaluate the contributions of BTK, we used mice in which B cells express an anti-insulin BCR (125Tg) and promote T1D, despite being anergic. Crossing Btk deficiency onto 125Tg mice reveals that, in contrast to immature B cells, mature anti-insulin B cells are exquisitely dependent upon BTK, because their numbers are reduced by 95%. BTK kinase domain inhibition reproduces this effect in mature anti-insulin B cells, with less impact at transitional stages. The increased dependence of anti-insulin B cells on BTK became particularly evident in an Igκ locus site–directed model, in which 50% of B cells edit their BCRs to noninsulin specificities; Btk deficiency preferentially depletes insulin binders from the follicular and marginal zone B cell subsets. The persistent few Btk-deficient anti-insulin B cells remain competent to internalize Ag and invade pancreatic islets. As such, loss of BTK does not significantly reduce diabetes incidence in 125Tg/NOD mice as it does in NOD mice with a normal B cell repertoire. Thus, BTK targeting may not impair autoreactive anti-insulin B cell function, yet it may provide protection in an endogenous repertoire by decreasing the relative availability of mature autoreactive B cells.
Binding of HLA-G to ITIM-Bearing Ig-like Transcript 2 Receptor Suppresses B Cell Responses
Authors: Naji Abderrahim , Menier Catherine , Morandi Fabio , Agaugué Sophie , Maki Guitta , Ferretti Elisa , Bruel Sylvie , Pistoia Vito , Carosella Edgardo D. , Rouas-Freiss Nathalie
Published: January 2014

Inhibition of B cells constitutes a rational approach for treating B cell–mediated disorders. We demonstrate in this article that the engagement of the surface Ig-like transcript 2 (ILT2) inhibitory receptor with its preferential ligand HLA-G is critical to inhibit B cell functions. Indeed, ILT2–HLA-G interaction impedes both naive and memory B cell functions in vitro and in vivo. Particularly, HLA-G inhibits B cell proliferation, differentiation, and Ig secretion in both T cell–dependent and –independent models of B cell activation. HLA-G mediates phenotypic and functional downregulation of CXCR4 and CXCR5 chemokine receptors on germinal center B cells. In-depth analysis of the molecular mechanisms mediated by ILT2–HLA-G interaction showed a G0/G1 cell cycle arrest through dephosphorylation of AKT, GSK-3β, c-Raf, and Foxo proteins. Crucially, we provide in vivo evidence that HLA-G acts as a negative B cell regulator in modulating B cell Ab secretion in a xenograft mouse model. This B cell regulatory mechanism involving ILT2–HLA-G interaction brings important insight to design future B cell–targeted therapies aimed at reducing inappropriate immune reaction in allotransplantation and autoimmune diseases.
Mast Cells Contribute to Bleomycin-Induced Lung Inflammation and Injury in Mice through a Chymase/Mast Cell Protease 4–Dependent Mechanism
Authors: Reber Laurent L. , Daubeuf François , Pejler Gunnar , Abrink Magnus , Frossard Nelly
Published: January 2014

Mast cells (MCs) are found in large numbers in lungs of patients with pulmonary fibrosis. However, the functions of MCs in lung fibrosis remain largely unknown. We assessed the role of MCs and MC protease 4 (MCPT4), the mouse counterpart of human MC chymase, in a mouse model of bleomycin (BLM)-induced lung injury. We found that levels of inflammation in the bronchoalveolar lavage and the lung, as well as levels of lung fibrosis, were reduced 7 d after intranasal delivery of BLM MC-deficient KitW-sh/W-sh mice compared with wild-type (WT) mice. Confirming the implication of MCs in these processes, we report that the levels of inflammation and fibrosis observed in KitW-sh/W-sh mice can be restored to those observed in WT mice after the adoptive transfer of bone marrow–derived cultured MCs into KitW-sh/W-sh mice. Additionally, we show that levels of inflammation and fibrosis are also reduced in MC chymase MCPT4-deficient mice as compared with WT mice at day 7, suggesting a role for MC-derived MCPT4 in these processes. Our results support the conclusion that MCs can contribute to the initial lung injury induced by BLM through release of the MCPT4 chymase.
Dectin-2 Regulates the Effector Phase of House Dust Mite–Elicited Pulmonary Inflammation Independently from Its Role in Sensitization
Authors: Parsons Matthew W. , Li Li , Wallace Aaron M. , Lee Min Jung , Katz Howard R. , Fernandez James M. , Saijo Shinobu , Iwakura Yoichiro , Austen K. Frank , Kanaoka Yoshihide , Barrett Nora A.
Published: January 2014

The myeloid C-type lectin receptor Dectin-2 directs the generation of Th2 and Th17 immune responses to the house dust mite Dermatophagoides farinae through the generation of cysteinyl leukotrienes and proinflammatory cytokines, respectively, but a role for Dectin-2 in effector phase responses has not been described. In this study, we demonstrate that administration of the Dectin-2 mAb solely at the time of D. farinae challenge abrogated eosinophilic and neutrophilic inflammation in the bronchoalveolar lavage fluid and Th1, Th2, and Th17 inflammation in the lung of previously sensitized mice. Furthermore, Dectin-2 null mice (Clec4n−/−) sensitized with the adoptive transfer of D. farinae–pulsed wild-type (WT) bone marrow–derived dendritic cells (DCs) also had less D. farinae–elicited pulmonary inflammation, supporting an effector function for Dectin-2. The protection from pulmonary inflammation seen with the Dectin-2 mAb or in Clec4n−/− mice was associated with little or no reduction in lung-draining lymph node cells or their cytokine production and with no reduction in serum IgE. WT and Clec4n−/− mice recipients, sensitized with D. farinae–pulsed WT bone marrow–derived DCs, had comparable levels of D. farinae–elicited IL-6, IL-23, TNF-α, and cysteinyl leukotrienes in the lung. By contrast, D. farinae–elicited CCL4 and CCL8 production from pulmonary CD11c+CD11b+Ly6C+ and CD11c+CD11b+Ly6C–CD64+ monocyte–derived DCs was reduced in Clec4n−/− recipients. Addition of CCL8 at the time of D. farinae challenge abrogated the protection from eosinophilic, neutrophilic, and Th2 pulmonary inflammation seen in Clec4n−/− recipients. Taken together, these results reveal that Dectin-2 regulates monocyte-derived DC function in the pulmonary microenvironment at D. farinae challenge to promote the local inflammatory response.
A Spliced Antigenic Peptide Comprising a Single Spliced Amino Acid Is Produced in the Proteasome by Reverse Splicing of a Longer Peptide Fragment followed by Trimming
Authors: Michaux Alexandre , Larrieu Pierre , Stroobant Vincent , Fonteneau Jean-François , Jotereau Francine , Van den Eynde Benoît J. , Moreau-Aubry Agnès , Vigneron Nathalie
Published: January 2014

Peptide splicing is a novel mechanism of production of peptides relying on the proteasome and involving the linkage of fragments originally distant in the parental protein. Peptides produced by splicing can be presented on class I molecules of the MHC and recognized by CTLs. In this study, we describe a new antigenic peptide, which is presented by HLA-A3 and comprises two noncontiguous fragments of the melanoma differentiation Ag gp100PMEL17 spliced together in the reverse order to that in which they appear in the parental protein. Contrary to the previously described spliced peptides, which are produced by the association of fragments of 3–6 aa, the peptide described in this work results from the ultimate association of an 8-aa fragment with a single arginine residue. As described before, peptide splicing takes place in the proteasome by transpeptidation involving an acyl-enzyme intermediate linking one of the peptide fragment to a catalytic subunit of the proteasome. Interestingly, we observe that the peptide causing the nucleophilic attack on the acyl-enzyme intermediate must be at least 3 aa long to give rise to a spliced peptide. The spliced peptide produced from this reaction therefore bears an extended C terminus that needs to be further trimmed to produce the final antigenic peptide. We show that the proteasome is able to perform the final trimming step required to produce the antigenic peptide described in this work.
FLT3-Ligand Treatment of Humanized Mice Results in the Generation of Large Numbers of CD141+ and CD1c+ Dendritic Cells In Vivo
Authors: Ding Yitian , Wilkinson Andrew , Idris Adi , Fancke Ben , O’Keeffe Meredith , Khalil Dalia , Ju Xinsheng , Lahoud Mireille H. , Caminschi Irina , Shortman Ken , Rodwell Robyn , Vuckovic Slavica , Radford Kristen J.
Published: January 2014

We established a humanized mouse model incorporating FLT3-ligand (FLT3-L) administration after hematopoietic cell reconstitution to investigate expansion, phenotype, and function of human dendritic cells (DC). FLT3-L increased numbers of human CD141+ DC, CD1c+ DC, and, to a lesser extent, plasmacytoid DC (pDC) in the blood, spleen, and bone marrow of humanized mice. CD1c+ DC and CD141+ DC subsets were expanded to a similar degree in blood and spleen, with a bias toward expansion of the CD1c+ DC subset in the bone marrow. Importantly, the human DC subsets generated after FLT3-L treatment of humanized mice are phenotypically and functionally similar to their human blood counterparts. CD141+ DC in humanized mice express C-type lectin-like receptor 9A, XCR1, CADM1, and TLR3 but lack TLR4 and TLR9. They are major producers of IFN-λ in response to polyinosinic-polycytidylic acid but are similar to CD1c+ DC in their capacity to produce IL-12p70. Although all DC subsets in humanized mice are efficient at presenting peptide to CD8+ T cells, CD141+ DC are superior in their capacity to cross-present protein Ag to CD8+ T cells following activation with polyinosinic-polycytidylic acid. CD141+ DC can be targeted in vivo following injection of Abs against human DEC-205 or C-type lectin-like receptor 9A. This model provides a feasible and practical approach to dissect the function of human CD141+ and CD1c+ DC and evaluate adjuvants and DC-targeting strategies in vivo.
PTPN22 Controls the Germinal Center by Influencing the Numbers and Activity of T Follicular Helper Cells
Authors: Maine Christian J. , Marquardt Kristi , Cheung Jocelyn , Sherman Linda A.
Published: January 2014

A single nucleotide polymorphism in PTPN22 (R620W), which encodes the Lyp tyrosine phosphatase, has been linked to a number of autoimmune diseases including type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. Studies in PTPN22 knockout (KO) mice and in mice expressing the mouse homolog of the pro-autoimmune allele, PEPR619W, have reported increased germinal center activity and enhanced Ab production. In this article, we present findings that explain the basis for increased germinal center activity in PTPN22 mutant mice. As compared with their wild type equivalents, T follicular helper cells from PTPN22 KO mice proliferate and accumulate to a greater extent, and exhibit enhanced production of IL-21. The follicular regulatory T cells in PTPN22 KO mice do not expand to effectively regulate these T follicular helper cells, resulting in an increase in B cell numbers and Ab production. This is evident in the KBxN mouse model of arthritis in which PTPN22 deficiency results in increased severity of disease. Our findings demonstrate the importance of cell type–specific PTPN22 activity on regulation of Ab production.
Computational Approach To Characterize Causative Factors and Molecular Indicators of Chronic Wound Inflammation
Authors: Nagaraja Sridevi , Wallqvist Anders , Reifman Jaques , Mitrophanov Alexander Y.
Published: January 2014

Chronic inflammation is rapidly becoming recognized as a key contributor to numerous pathologies. Despite detailed investigations, understanding of the molecular mechanisms regulating inflammation is incomplete. Knowledge of such critical regulatory processes and informative indicators of chronic inflammation is necessary for efficacious therapeutic interventions and diagnostic support to clinicians. We used a computational modeling approach to elucidate the critical factors responsible for chronic inflammation and to identify robust molecular indicators of chronic inflammatory conditions. Our kinetic model successfully captured experimentally observed cell and cytokine dynamics for both acute and chronic inflammatory responses. Using sensitivity analysis, we identified macrophage influx and efflux rate modulation as the strongest inducing factor of chronic inflammation for a wide range of scenarios. Moreover, our model predicted that, among all major inflammatory mediators, IL-6, TGF-β, and PDGF may generally be considered the most sensitive and robust indicators of chronic inflammation, which is supported by existing, but limited, experimental evidence.
Intradermal Delivery of Shigella IpaB and IpaD Type III Secretion Proteins: Kinetics of Cell Recruitment and Antigen Uptake, Mucosal and Systemic Immunity, and Protection across Serotypes
Authors: Heine Shannon J. , Diaz-McNair Jovita , Andar Abhay U. , Drachenberg Cinthia B. , van de Verg Lillian , Walker Richard , Picking Wendy L. , Pasetti Marcela F.
Published: January 2014

Shigella is one of the leading pathogens contributing to the vast pediatric diarrheal disease burden in low-income countries. No licensed vaccine is available, and the existing candidates are only partially effective and serotype specific. Shigella type III secretion system proteins IpaB and IpaD, which are conserved across Shigella spp., are candidates for a broadly protective, subunit-based vaccine. In this study, we investigated the immunogenicity and protective efficacy of IpaB and IpaD administered intradermally (i.d.) with a double-mutant of the Escherichia coli heat-labile enterotoxin (dmLT) adjuvant using microneedles. Different dosage levels of IpaB and IpaD, with or without dmLT, were tested in mice. Vaccine delivery into the dermis, recruitment of neutrophils, macrophages, dendritic cells, and Langerhans cells, and colocalization of vaccine Ag within skin-activated APC were demonstrated through histology and immunofluorescence microscopy. Ag-loaded neutrophils, macrophages, dendritic cells, and Langerhans cells remained in the tissue at least 1 wk. IpaB, IpaD, and dmLT-specific serum IgG- and IgG-secreting cells were produced following i.d. immunization. The protective efficacy was 70% against Shigella flexneri and 50% against Shigella sonnei. Similar results were obtained when the vaccine was administered intranasally, with the i.d. route requiring 25–40 times lower doses. Distinctively, IgG was detected in mucosal secretions; secretory IgA, as well as mucosal and systemic IgA Ab-secreting cells, were seemingly absent. Vaccine-induced T cells produced IFN-γ, IL-2, TNF-α, IL-17, IL-4, IL-5, and IL-10. These results demonstrate the potential of i.d. vaccination with IpaB and IpaD to prevent Shigella infection and support further studies in humans.
FADD and Caspase-8 Mediate Priming and Activation of the Canonical and Noncanonical Nlrp3 Inflammasomes
Authors: Gurung Prajwal , Anand Paras K. , Malireddi R. K. Subbarao , Vande Walle Lieselotte , Van Opdenbosch Nina , Dillon Christopher P. , Weinlich Ricardo , Green Douglas R. , Lamkanfi Mohamed , Kanneganti Thirumala-Devi
Published: January 2014

The Nlrp3 inflammasome is critical for host immunity, but the mechanisms controlling its activation are enigmatic. In this study, we show that loss of FADD or caspase-8 in a RIP3-deficient background, but not RIP3 deficiency alone, hampered transcriptional priming and posttranslational activation of the canonical and noncanonical Nlrp3 inflammasome. Deletion of caspase-8 in the presence or absence of RIP3 inhibited caspase-1 and caspase-11 activation by Nlrp3 stimuli but not the Nlrc4 inflammasome. In addition, FADD deletion prevented caspase-8 maturation, positioning FADD upstream of caspase-8. Consequently, FADD- and caspase-8–deficient mice had impaired IL-1β production when challenged with LPS or infected with the enteropathogen Citrobacter rodentium. Thus, our results reveal FADD and caspase-8 as apical mediators of canonical and noncanonical Nlrp3 inflammasome priming and activation.
JJP Valeton jr as godsdienshistorikus
Authors: Loader J. A.
Published: January 2014

JJP Valeton Jnr was one of the main founders of the theological current in nineteenth century Holland called 'the ethical theology'. Some of the most prominent members of this current were, like Valeton, Old Testament specialists. One of the main characteristics of the ethicals was their distinction between scientific knowledge and the knowledge of faith. This enabled them to adopt a critical approach to the Bible while at the same time remaining active in the service of the church. In this article it is shown how Valeton applied this principle in his work on the history of Israelite religion. An attempt is made to demonstrate how his insight was more penetrating than that of even the great Abraham Kuenen.
Die opskrifte van die profeteboeke II
Authors: Oberholzer J. P.
Published: January 2014

This is a continuation of a survey of the headings of the prophetic books. In this article special attention is given to the headings in Jeremiah, the possible motives for their formation and the consequences to be inferred in view of the evaluation of the prophet's words during and after his lifetime.
Geloofsgroei by Paulus?
Authors: Pelser G. M.M.
Published: January 2014

In this essay the question is posed as to whether Paul viewed faith as essentially an entity that can grow or increase within the believer or is given by God in different degrees to different people. The investigation is limited to Rm 12:3; 14:1; 2 Cor 10:15; Phlp 1:25 and 1 Th 3:10. The conclusion is reached that as far as these passages are concerned, the answer to the question is negative, with the possible exception of 2 Cor 10:15. It seems therefore that according to Paul, faith is faith, nothing less and nothing more. In so far, however, as there is mention in Paul of growth connected with faith, it concerns the believer's answer to the imperative in the indicative by living up daily (and increasingly) to his faith. Essentially faith cannot be weak or mediocre. If this should be the case, it is not faith any more.
Tien eeue leksikografie: Van woordelys tot woordeboek
Authors: Van Wyk Wouter C.
Published: January 2014

Ten centuries of lexicography: From vocabulary list to dictionary The aim of the article is to illuminate the development in the lexicography of Biblical Hebrew through ten centuries from the first vocabularly list to a dictionary based on linguistic, comparative Semitic and encyclopedic principles. The writer treats several stages through the Middle Ages, the Reformation period, the Enlightenment and the Twentieth century up to a contemporary project of South African scholars working on a new Semantic Hebrew 'wordbook'. The conclusion in the article is that the nature of a specific dictionary or vocabularly list, for example philological, theological or linguistic, serves particular, legitimate needs.
Bybelse teologie - dogmatiese teologie
Authors: Smith D. J.
Published: January 2014

Biblical theology - dogmatic theology The purpose of this article is to make a contribution to the discussion between systematic theology and biblical theology from the point of view of what systematic theology can expect of the latter. In this discussion the ideas of JP Gabler, as portrayed by H Boers, can play an important role. The following notions are identified: Dogmatic tendencies should not play a part in the presentation of a biblical theology. Biblical theology should accept a responsibility only to the biblical material which is employed; form a bridge between the exegesis and the exegetical results on the one hand and the systematic theology on the other hand; keep its purpose aligned to dogmatic theology and help to construct methods as how to incorporate the diversities and unity in the biblical witness.
Huldrich Zwingli se Von dem Touff, vom Widertouff und vom Kindertouff: Enkele aspekte van Zwingli se teologiese denke
Authors: Smith D. J.
Published: January 2014

Huldrich Zwingli's 'Von dem Touff, vom Widertouff und vom Kindertouff': Some aspects of Zwringli's theological thought The aim of this article is to let Zwingli speak for himself as he expresses himself in his treatise on baptism: Von dem Touff, vom Widertouff und vom Kindertouff. The use of secondary literature is avoided in an attempt to steer clear of an interpretation of Zvkfingli, predetermined by views formed by traditional conceptions handed down and tainted by dogmatic considerations. Zwingli's views on the following themes are discussed and certain conclusions are drawn: Zwingli as pioneer in the founding of infant baptism in both the New Testament as well as the covenant in the Old Testament; Zwingli's distinction of a fourfold usage and meaning of the word baptism; Zwingli and baptism as sign of obligation; Zwingli and the institution of baptism; Zwingli's usage of Scripture; Zwingli and the Holy Ghost.
Die verhouding tradisie-redaksie in gelykenisinterpretasie
Authors: Pelser G. M.M.
Published: January 2014

The interrelationship between tradition and redaction in parable interpretation This paper investigates the legitimacy and possibility of isolating the parables from their holistic literary gospel-context for the purpose of hearing and understanding them from other possible angles. The conclusion reached is that the parables as aesthetic objects (Via) have a certain independence and that they contend with the gospels for the focal attention of the reader. As metaphors they are generative of multiple meanings and their 'meaning' cannot be one-sidedly forclosed in their present literary context or in some historical moment. When the parables are read as part and parcel of Ihe gospels as Hterary macro-Gestalten this holistic context, however, should not be ignored.
Skrifgebruik: Hermeneutiese riglyne
Authors: Van Aarde A. G.
Published: January 2014

The use of Scripture: Principles in hermeneutics The use of Scripture encompasses the total hermeneutical circuit which includes the act of preaching. This context of interaction represents a melting-pot where the exegete's informed reading of the Bible melts into the church-member's naive reading. In this process the text, contextless as it is, is supplied with a context. The reconstruction of context leads to the construction of an applicable meaning of the text. However, the following hermeneutical fallacies have to be avoided: intentional, genetic, referential, affective and the fallacy of misplaced concreteness. The emphasis in the article is laid on a discussion of these fallacies.
Geskiedsfilosofie in 'n krisis: Die noodwendigheid en aktualiteit van die nasionale staatsidee
Authors: Schoeman M. J.
Published: January 2014

Philosophy of history in crisis: The actuality and necessity of the concept of the national state The aim of this essay is to explicate the thesis of an intrinsic relationship between the Enlightenment philosophy of history and the (ideological) war amongst world citizens in which we are entangled today. This is explained in terms of certain 'deficiencies' (philosophical, theological, political and historical) inherent in the Enlightenment view of history. It is argued that a truly modern approach to history (as opposed to the antimodern, eschatological and moralistic view of the Enlightenment) should take its bearing from the idea of the nation, thereby acknowledging the rise of a global network of national states as one of the most remarkable features of our age.