bluuebunny/crossref_metadata_2025 huggingface dataset:
Sport, rivalité et solidarité dans les ghettos
Authors: Duret Pascal , Cubizolles Sylvain
Published: October 2010

Résumé La communauté de Kayamandi se nourrit des rivalités entre ses trois principaux clubs de football. Toutefois, à domicile, le respect mutuel entre équipes du township est de mise ; il y prévaut une règle de retenue dans les manières d’encourager. Cette règle est dictée par le sentiment d’appartenance à une même communauté menacée. L’esprit solidaire du township prime sur l’esprit partisan du club. Par contre, à l’extérieur, en déplacement hors du township , on retrouve des formes plus marquées de partisanerie. Les supporters modulent alors leurs encouragements en fonction de la communauté rencontrée (noire, coloured ou blanche).
Retour aux fondamentaux méthodologiques
Authors: Le Guirriec Patrick
Published: October 2010

Résumé Dans cet article principalement méthodologique, nous souhaitons montrer que l’observation d’un événement mettant en scène les relations entre les groupes de Marocains dans une ville de la banlieue parisienne et entre ceux-ci et les représentants de l’État permet d’aller au-delà des discours et de comprendre des phénomènes qui ne peuvent être appréhendés par la méthode de l’entretien.
Le mouvement ouvrier contre la peinture au plomb
Authors: Rainhorn Judith
Published: October 2010

Résumé Dans les premières années du XX e siècle, la revendication de la suppression de la peinture au plomb, responsable du saturnisme des peintres en bâtiment, est apparue brutalement dans le discours et la propagande de la CGT. Après des décennies de silence sur la santé au travail, l’étude de cette irruption tardive permet de réfléchir à l’usage que les instances syndicales font de la question sanitaire qui, toute marginale qu’elle reste, qui peut s’avérer un précieux outil de mobilisation, comme lors des grèves de peintres à Lille en 1906. La question de l’interdiction de la céruse contribue également à revaloriser le rôle de personnalités exceptionnelles (Abel Craissac) et d’expériences locales de coopération sociale (médecins et ouvriers peintres à Lille) qui sont autant de transgressions, à l’échelle nationale et locale, du discours ouvriériste dominant dans le syndicat avant la Première Guerre mondiale. Participant de la « nébuleuse réformatrice », ces acteurs jouent un rôle de premier ordre dans la prohibition du produit toxique et participent, de ce fait, à la lente élaboration d’un discours social et institutionnel sur la santé au travail.
La médecine du travail sans les médecins ?
Authors: Marichalar Pascal
Published: October 2010

Résumé À partir d’une enquête historique et sociologique, l’article montre que la réforme des services français de prévention des risques professionnels engagée par l’État depuis 2002 n’est qu’un moment dans une politique plus large initiée par le patronat depuis le début des années 1970. L’association patronale qui gère ces services (CISME) a usé de leviers politiques et managériaux pour réduire l’autonomie professionnelle des médecins du travail, au nom du passage à une approche « pluridisciplinaire » dans le cadre de la « santé au travail ». Cette évolution a été conduite pour réduire les coûts de la prévention et de la réparation des risques professionnels, ainsi que les risques juridiques pour les employeurs.
Les cobayes portent plainte
Authors: Jobin Paul
Published: October 2010

Résumé Cet article présente les deux premières grandes affaires de maladies industrielles portées en justice à Taiwan. La première, qui se déroule dans le nord de l’île près de Taipei, concerne plus d’un millier de femmes, aujourd’hui atteintes de diverses formes de cancer. Elles ont été exposées à toute une gamme de solvants organiques lorsqu’elles travaillaient pour une usine de télévision du fabriquant américain RCA. Les accusés de ce procès sont l’actuel et l’ancien propriétaire de l’entreprise, General Electric et Thomson. La deuxième affaire se passe près de Tainan, dans le sud de l’île, qui enregistre l’une des plus importantes concentrations de dioxine au monde, laissée par une ancienne usine chimique. Dans les deux cas, les plaignants ont le sentiment de servir de cobayes pour la science sans pour autant bénéficier de ses résultats. Ils sont assistés par une mobilisation citoyenne originale et un réseau d’avocats. Bien que les auditions viennent seulement de commencer, la controverse médico-légale et le propos des acteurs suggèrent d’ores et déjà que l’incertitude scientifique implique toutes sortes de compromis, entre le peut-être et le probable, l’épidémiologie et la toxicologie, l’humain et l’animal, et par là même, toute une gamme des possibles pour une traduction de ce flottement en décision juridique ou politique.
Cause politique et « politique des causes »
Authors: Barthe Yannick
Published: October 2010

Résumé Dans la plupart des controverses en santé au travail et santé environnementale, défendre une cause consiste avant tout à établir des liens de causalité entre des faits et des dommages. À partir de l’étude de la mobilisation récente des vétérans des essais nucléaires français et de la controverse autour de leur impact sanitaire, cet article analyse les processus qui sont au cœur de cette « politique des causes » et les formes qu’elle peut prendre. Il montre également que cette politique des causes n’est pas sans effet en retour sur la définition même de la cause politique et de l’identité du groupe qu’il s’agit de défendre. Saisir la dynamique des mobilisations revient dès lors à étudier l’articulation souvent délicate entre cause politique et politique des causes.
Experts « bruts » et médecins critiques
Authors: Pitti Laure
Published: October 2010

Résumé L’objet de cet article est d’étudier comment la santé en situation de travail devient un enjeu de luttes et d’acceptions concurrentes à l’aune des mobilisations qui, durant les « années 1968 » en France, font émerger en terrain ouvrier la revendication d’un droit à la santé et à sa protection, amplifiée et relayée par le courant critique qui traverse alors le champ médical. En traitant du cas d’une pathologie professionnelle : le saturnisme ou maladie du plomb, et d’un exemple de mobilisation : la lutte menée à partir de l’usine Peñarroya à Lyon par deux catégories d’acteurs, ouvriers et médecins critiques, pour son dépistage plus précoce, l’article analyse les conditions d’émergence et de reconnaissance de ce droit à la santé. Il montre en particulier comment la mise en débats des protocoles d’expertise médicale a constitué la pièce maîtresse d’un contre-savoir, support d’un contre-pouvoir efficace à l’ordre productif et médical institué.
Les effets dissimulés du travail sur la santé de populations au chômage : le cas des contrats aidés dans le dispositif du RMI
Authors: Frigul Nathalie
Published: October 2010

Résumé L’article propose de s’intéresser aux catégories de travailleurs relevant de contrats aidés réalisés dans le cadre des politiques d’insertion. Ces candidats à l’emploi aidé ont connu des parcours de déclassement, des trajets professionnels discontinus, instables, ponctués de périodes de chômage de plus en plus longues avant l’entrée dans les dispositifs de l’aide sociale, dont le RMI, aujourd’hui le RSA, constitue la figure emblématique. Usuellement considérés à la marge de l’emploi ordinaire, ces contrats aidés sont décrits comme une étape nécessaire de « remobilisation » vers le travail. L’un des paradoxes réside dans le fait que ces emplois peuvent présenter des expositions professionnelles, celles-là même qui, dans l’activité antérieure, ont généré des atteintes à la santé. À partir d’études de cas permettant de reconstituer les parcours de travail et de santé de personnes percevant le RMI, nous étudierons les manières dont les acteurs, allocataires et professionnels de l’insertion, se sont saisis de ces questions de santé, les ont articulées ou non au travail et à l’emploi, contribuant souvent à masquer leurs origines professionnelles.
La « gestionnarisation » des politiques de protection de la nature aux Pays-Bas
Authors: Daniel François-Joseph
Published: October 2010

Résumé Comme dans bien d’autres domaines d’action publique, l’institutionnalisation des politiques environnementales a donné lieu à un ensemble de procédures administratives destinées à mettre enœuvre et faire respecter les normes environnementales. Par bien des aspects, ces formes procédurales se sont matérialisées dans le cadre de dispositifs gestionnaires où le recours à la contractualisation et la mise en place d’indicateurs de résultats et de procédures de contrôles sont devenus les maîtres mots. En prenant l’exemple d’une politique néerlandaise de protection de la nature – le Programme de gestion –, cet article suggère que ces dispositifs sont parcourus par des logiques rationalisatrices et disciplinaires permettant d’opérationnaliser le projet de conservation de la nature. Cette double vocation du dispositif de gestion permet tout à la fois de standardiser les objectifs de protection, d’enrôler les agriculteurs et les organisations conservationnistes et de contrôler le produit de leurs activités. Le dispositif ne pourrait tenir, toutefois, sans qu’une fonction plus pédagogique de médiation y soit associée.
Promotion et marginalisation des candidats de la « diversité » dans une commune de la banlieue parisienne
Authors: Cartier Marie , Coutant Isabelle , Masclet Olivier , Siblot Yasmine
Published: October 2010

Résumé À partir d’une enquête auprès des candidats aux élections municipales de 2008 à Villenois, en région parisienne, nous nous intéressons aux personnes entrées sur la scène politique lors de ce scrutin, où la « diversité » fut un enjeu important. Nous mettons en évidence le lien entre « diversification » des listes et transformations de la population et étudions les caractéristiques sociales de ceux qui ont été désignés ou se sont désignés pour représenter ce renouvellement. Si le maire PS met en avant l’engagement local, il a aussi privilégié des personnes aux ressources professionnelles et/ou scolaires importantes. Ce qui s’est joué autour d’une liste sans étiquette concurrente témoigne à l’inverse de la marginalisation d’autres représentants de la « diversité », dont les prétentions politiques sont apparues illégitimes. S’intéresser à l’ensemble des listes permet ainsi de rendre compte du double processus d’ouverture et de fermeture du jeu politique local.
Digital Child Pornography
Authors: Law Frank Y.W. , Chow K.P. , Lai Pierre K.Y. , Tse Hayson K.S. , Tse Kenneth W.H.
Published: November 2010

Child pornography has become a major cyber crime in recent years. One of the challenging problems in child pornography cases is to distinguish if the subject files were downloaded intentionally or by accident without the knowledge of the computer user. The suspect may admit that he is an erotomania, but argue that the child porn materials were downloaded accidentally while surfing the pornographic web sites. In many jurisdictions, possession of child pornography without user knowledge is not a crime, while the burden of proof is on the prosecution. It is therefore important to identify if the child pornography exists by accident or not. In this chapter, the authors first review the technologies which sustain the prevalence of online child pornography and the recent research on child pornography investigation. Then, the authors present a set of practical investigation techniques. Subsequently, they apply the techniques in a case study with an attempt to distinguish if a suspect is a child pornography offender or just a normal erotomania. This is an important distinction to be made, since a person guilty of child pornography offenses is likely to be punished more seriously under most legal jurisdictions.
Child Pornography and IT
Authors: Ibrahim Amin
Published: November 2010

The sexual exploitation of children remains a very serious problem and is rapidly increasing globally through the use of the Internet. This chapter focuses on the child pornography and IT, and the various methods to combat this problem. The ease of acquiring IT and digital equipments, the global reach of Internet and freely available peer-to-peer services have made child pornography a very complex issue to undertake. The borderless nature of the Internet and the lack of unified criminal code among nations further escalated the complexity of law enforcement against child pornography.
Humanitarian Demining Action Plan
Authors: Habib Maki K.
Published: November 2010

The presence of landmines and Explosive Remnants of War (ERW) in a place represents a major threat to civlian and affects the rebuilding process and the life of the people at that place. Hence, one of the fundamental goals of humanitarian demining is to detect and clear all forms of danger from infected areas efficiently, reliably and as safely and as rapidly as possible while keeping cost minimized. Although demining has been given top priority, currently mine’s clearing operation is a dangerous, complex, time consuming, slow, labor-intensive, and costly operation. The currently available technologies are not suited to achieve the objectives of humanitarian demining. In the context of humanitarian demining it is essential to have a reliable and accurate sensor and/or an integration of heterogeneous/ homogeneous sensors with efficient and reliable data fusion and processing technique that can quickly discriminates mines from innocuous buried objects. In addition, it is necessary to overcome the constrain on the resources by developing innovative, cost effective and practical technology inspired by locality and real minefield needs to help in speeding up the demining process and enhance accuracy, productivity, operation and personnel safety, achieve higher quality of the service, and contribute to local economy.This chapter presents the facts and problems associated with landmines and their impact on health, economy, land and environment along with the difficulties in detecting and removing them. It highlights the main requirements for humanitarian demining action plan and list up solutions and priorities.Then, it presents the challenges facing technological development in different directions and concludes with the suitable actions to save human and environment from such complex problem facing humanity.
Human Factors Required for Building NLP Systems
Authors: Daoud Daout , Abou El-Seoud Samir
Published: November 2010

The chapter illustrates the importance of human factors required for building natural language processing (NLP) systems. The authors will examine different NL interface style and processing and correlate them with human factors such as: domain, interface, text style and medium of communication. They verified our assumption by presenting a NLP system which was built as a proof-of- concept. However, because of semantics and the very nature of language, the authors discuss our concern with possible abuse by unscrupulous persons who would attempt to exploit NLP systems for reasons other than legitimate information exchange.
Transitioning to Software as a Service
Authors: Sly Dave
Published: November 2010

Managing a digital product company in 2010, and beyond, is a very unique and challenging experience when compared to the traditional product development and deployment models of the late 20th century taught in many MBA schools today. This chapter presents the benefits, challenges, and lessons learned of a CEO who is transforming a traditional “Software as a Product” engineering software firm that he founded in the mid 1980‘s to a Web-based, “Software as a Service” firm that is positioned for 2010 and beyond.
Characterization of Lymphocyte Subsets in Patients with Common Variable Immunodeficiency Reveals Subsets of Naive Human B Cells Marked by CD24 Expression
Authors: Vlková Marcela , Froňková Eva , Kanderová Veronika , Janda Aleš , Růžičková Šárka , Litzman Jiří , Šedivá Anna , Kalina Tomáš
Published: November 2010

Increased proportions of naive B cell subset and B cells defined as CD27negCD21negCD38neg are frequently found in patients with common variable immunodeficiency (CVID) syndrome. Current methods of polychromatic flow cytometry and PCR-based detection of κ deletion excision circles allow for fine definitions and replication history mapping of infrequent B cell subsets. We have analyzed B cells from 48 patients with CVID and 49 healthy controls to examine phenotype, frequency, and proliferation history of naive B cell subsets. Consistent with previous studies, we have described two groups of patients with normal (CVID-21norm) or increased (CVID-21lo) proportions of CD27negCD21negCD38neg B cells. Upon further analyses, we found two discrete subpopulations of this subset based on the expression of CD24. The B cell subsets showed a markedly increased proliferation in CVID-21lo patients as compared with healthy controls, suggesting developmental arrest rather than increased bone marrow output. Furthermore, when we analyzed CD21pos naive B cells, we found two different subpopulations based on IgM and CD24 expression. They correspond to follicular (FO) I and FO II cells previously described in mice. FO I subset is significantly underrepresented in CVID-21lo patients. A comparison of the replication history of naive B cell subsets in CVID patients and healthy controls implies refined naive B cell developmental scheme, in which human transitional B cells develop into FO II and FO I. We propose that the CD27negCD21negCD38neg B cells increased in some of the CVID patients originate from the two FO subsets after loss of CD21 expression.
Cutting Edge: Mechanisms of IL-2–Dependent Maintenance of Functional Regulatory T Cells
Authors: Barron Luke , Dooms Hans , Hoyer Katrina K. , Kuswanto Wilson , Hofmann Jerry , O’Gorman William E. , Abbas Abul K.
Published: October 2010

IL-2 controls the survival of regulatory T cells (Tregs), but it is unclear whether IL-2 also directly affects Treg suppressive capacity in vivo. We have found that eliminating Bim-dependent apoptosis in IL-2– and CD25-deficient mice restored Treg numbers but failed to cure their lethal autoimmune disease, demonstrating that IL-2–dependent survival and suppressive activity can be uncoupled in Tregs. Treatment with IL-2–anti–IL-2–Ab complexes enhanced the numbers and suppressive capacity of IL-2–deprived Tregs with striking increases in CD25, CTLA-4, and CD39/CD73 expression. Although cytokine treatment induced these suppressive mechanisms in both IL-2−/− and IL-2−/−Bim−/− mice, it only reversed autoimmune disease in the latter. Our results suggest that successful IL-2 therapy of established autoimmune diseases will require a threshold quantity of Tregs present at the start of treatment and show that the suppressive capacity of Tregs critically depends on IL-2 even when Treg survival is independent of this cytokine.
Differential TRAF3 Utilization by a Variant Human CD40 Receptor with Enhanced Signaling
Authors: Peters Anna L. , Bishop Gail A.
Published: November 2010

CD40 is required for T cell-dependent humoral immunity, but it can also contribute to the pathogenesis of autoimmunity and B cell malignancy. The TNFR-associated factor (TRAF)2 and TRAF6 adaptor proteins are positive regulators of CD40 signaling required to activate downstream kinase cascades and transcription factors. In contrast, TRAF3 can serve as a negative regulator of CD40 signaling, and CD40 signals are amplified in TRAF3−/− B cells. We previously reported a gain-of-function polymorphism of the human CD40 receptor, hCD40-P227A, which signals in an amplified manner to B lymphocytes. In this study, we show that hCD40-P227A binds more TRAF3 and TRAF5, as well as certain associated proteins, than wild-type–CD40. Studies in TRAF-deficient B cell lines revealed that hCD40-P227A uses TRAF3 as a positive rather than negative regulator. Although located outside of any known TRAF binding sites, the P227A polymorphism can alter TRAF binding and dramatically changes the role played by TRAF3 in CD40 signaling.
Hyaluronan Fragments Contribute to the Ozone-Primed Immune Response to Lipopolysaccharide
Authors: Li Zhuowei , Potts Erin N. , Piantadosi Claude A. , Foster W. Michael , Hollingsworth John W.
Published: October 2010

Hyaluronan is a high-molecular mass component of pulmonary extracelluar matrix, and lung injury can generate a low-molecular mass hyaluronan (HA) fragment that functions as endogenous ligand to cell surface receptors CD44 and TLR4. This leads to activation of intracellular NF-κB signaling and proinflammatory cytokine production. Based on previous information that ozone exposure causes increased HA in bronchial alveolar lavage fluid and ozone pre-exposure primes immune response to inhaled LPS, we hypothesized that HA production during ozone exposure augments the inflammatory response to LPS. We demonstrate that acute ozone exposure at 1 part per million for 3 h primes the immune response to low-dose aerosolized LPS in C57BL/6J mice, resulting in increased neutrophil recruitment into the airspaces, increased levels of protein and proinflammatory cytokines in the bronchoalveolar lavage fluid, and increased airway hyperresponsiveness. Intratracheal instillation of endotoxin-free HA (25 μg) enhances the biological response to inhaled LPS in a manner similar to ozone pre-exposure. In vitro studies using bone marrow-derived macrophages indicate that HA enhances LPS responses measured by TNF-α production, while immunofluorescence staining of murine alveolar macrophages demonstrates that HA induces TLR4 peripheralization and lipid raft colocalization. Collectively, our observations support that ozone primes macrophage responsiveness to low-dose LPS, in part, due to HA-induced TLR4 peripheralization in lung macrophages.
Phosphoryl Moieties of Lipid A from Neisseria meningitidis and N. gonorrhoeae Lipooligosaccharides Play an Important Role in Activation of Both MyD88- and TRIF-Dependent TLR4–MD-2 Signaling Pathways
Authors: Liu Mingfeng , John Constance M. , Jarvis Gary A.
Published: October 2010

We have previously shown that the lipooligosaccharide (LOS) from Neisseria meningitidis and N. gonorrhoeae engages the TLR4–MD-2 complex. In this study, we report that LOS from different meningococcal and gonococcal strains have different potencies to activate NF-κB through TLR4–MD-2 and that the relative activation can be correlated with ion abundances in MALDI-TOF mass spectrometry that are indicative of the number of phosphoryl substituents on the lipid A (LA) component of the LOS. The LOSs from three of the strains, meningococcal strain 89I and gonococcal strains 1291 and GC56, representing high, intermediate, and low potency on NF-κB activation, respectively, differently activated cytokine expression through the TLR4–MD-2 pathway in monocytes. In addition to induction of typical inflammatory cytokines such as TNF-α, IL-1β, and IL-6, MIP-1α and MIP-1β also were significantly higher in cells treated with 89I LOS, which had the most phosphoryl substitutions on the LA compared with 1291 LOS and GC56 LOS. We found that LOS activated both the MyD88- and TRIF-dependent pathways through NF-κB and IFN regulatory factor 3 transcription factors, respectively. Moreover, LOS induced the expression of costimulatory molecule CD80 on the surfaces of monocytes via upregulation of IFN regulatory factor 1. These results suggest that phosphoryl moieties of LA from N. meningitidis and N. gonorrhoeae LOSs play an important role in activation of both the MyD88- and TRIF-dependent pathways. Our findings are consistent with the concept that bacteria modulate pathogen-associated molecular patterns by expression of phosphoryl moieties on the LA to optimize interactions with the host.
IL-2 Complex Treatment Can Protect Naive Mice from Bacterial and Viral Infection
Authors: Hamilton Sara E. , Schenkel Jason M. , Akue Adovi D. , Jameson Stephen C.
Published: October 2010

IL-2 complexes have substantial effects on the cellular immune system, and this approach is being explored for therapeutic application in infection and cancer. However, the impact of such treatments on subsequent encounter with pathogens has not been investigated. In this study, we report that naive mice treated with a short course of IL-2 complexes show enhanced protection from newly encountered bacterial and viral infections. IL-2 complex treatment expands both the NK and CD8 memory cell pool, including a recently described population of preexisting memory-phenotype T cells responsive to previously unencountered foreign Ags. Surprisingly, prolonged IL-2 complex treatment decreased CD8 T cell function and protective immunity. These data reveal the impact of cytokine complex treatment on the primary response to infection.
Secreted M-Ficolin Anchors onto Monocyte Transmembrane G Protein-Coupled Receptor 43 and Cross Talks with Plasma C-Reactive Protein to Mediate Immune Signaling and Regulate Host Defense
Authors: Zhang Jing , Yang Lifeng , Ang Zhiwei , Yoong Sia Lee , Tran Thi Thu Thuy , Anand Ganesh Srinivasan , Tan Nguan Soon , Ho Bow , Ding Jeak Ling
Published: October 2010

Although transmembrane C-type lectins (CLs) are known to initiate immune signaling, the participation and mechanism of action of soluble CLs have remained enigmatic. In this study, we found that M-ficolin, a conserved soluble CL of monocyte origin, overcomes its lack of membrane-anchor domain by docking constitutively onto a monocyte transmembrane receptor, G protein-coupled receptor 43 (GPCR43), to form a pathogen sensor-cum-signal transducer. On encountering microbial invaders, the M-ficolin–GPCR43 complex activates the NF-κB cascade to upregulate IL-8 production. We showed that mild acidosis at the local site of infection induces conformational changes in the M-ficolin molecule, which provokes a strong interaction between the C-reactive protein (CRP) and the M-ficolin–GPCR43 complex. The collaboration among CRP–M-ficolin–GPCR43 under acidosis curtails IL-8 production thus preventing immune overactivation. Therefore, we propose that a soluble CL may become membrane-associated through interaction with a transmembrane protein, whereupon infection collaborates with other plasma protein to transduce the infection signal and regulate host defense. Our finding implies a possible mechanism whereby the host might expand its repertoire of immune recognition-cum-regulation tactics by promiscuous protein networking. Furthermore, our identification of the pH-sensitive interfaces of M-ficolin–CRP provides a powerful template for future design of potential immunomodulators.
NFAT5 Regulates T Lymphocyte Homeostasis and CD24-Dependent T Cell Expansion under Pathologic Hypernatremia
Authors: Berga-Bolaños Rosa , Drews-Elger Katherine , Aramburu Jose , López-Rodríguez Cristina
Published: October 2010

Immune cells rely on the transcription factor NFAT5 to adapt to hypertonic stress. The hypertonicity-dependent role of NFAT5 in T cells in vivo remains unclear because mouse models of NFAT5 deficiency have produced substantially different T cell phenotypes. In this study, we analyzed the T cell compartment in NFAT5-null and T cell-specific NFAT5 knockout mice. We found that NFAT5-null mice had constitutive, pronounced hypernatremia and suffered a severe immunodeficiency, with T cell lymphopenia, altered CD8 naive/memory homeostasis, and inability to reject allogeneic tumors. By contrast, T cell-specific NFAT5 knockout mice had normal plasma tonicity, rejected allogeneic tumors, and exhibited only a mild, low-penetrance memory bias in CD8 cells. Notably, when T cells from these mice were cultured ex vivo in hypernatremic media, they exhibited features found in NFAT5-null mice, with pronounced naive/memory imbalance and impaired homeostatic survival in response to IL-7, as well as a severe inhibition of their mitogen-induced proliferation. By analyzing surface receptors whose expression might be affected in NFAT5-deficient cells, we identified CD24 as a novel NFAT5 target induced by hypertonicity both in vitro and in vivo, and required to sustain T cell expansion under osmostress. NFAT5 bound to the Cd24 promoter in response to hypertonicity facilitated the local derepression of chromatin and enhanced the expression of CD24 mRNA and protein. Altogether, our results indicate that the systemic hypernatremia of NFAT5-null mice is a major contributor to their immunodeficiency, and highlight the role of NFAT5 and CD24 in the homeostasis of T cells under osmostress in vivo.
IL-17 Regulates Adipogenesis, Glucose Homeostasis, and Obesity
Authors: Zúñiga Luis A. , Shen Wen-Jun , Joyce-Shaikh Barbara , Pyatnova Ekaterina A. , Richards Andrew G. , Thom Colin , Andrade Sofia M. , Cua Daniel J. , Kraemer Fredric B. , Butcher Eugene C.
Published: October 2010

Inflammatory mediators have the potential to impact a surprising range of diseases, including obesity and its associated metabolic syndrome. In this paper, we show that the proinflammatory cytokine IL-17 inhibits adipogenesis, moderates adipose tissue (AT) accumulation, and regulates glucose metabolism in mice. IL-17 deficiency enhances diet-induced obesity in mice and accelerates AT accumulation even in mice fed a low-fat diet. In addition to potential systemic effects, IL-17 is expressed locally in AT by leukocytes, predominantly by γδ T cells. IL-17 suppresses adipocyte differentiation from mouse-derived 3T3-L1 preadipocytes in vitro, and inhibits expression of genes encoding proadipogenic transcription factors, adipokines, and molecules involved in lipid and glucose metabolism. IL-17 also acts on differentiated adipocytes, impairing glucose uptake, and young IL-17–deficient mice show enhanced glucose tolerance and insulin sensitivity. Our findings implicate IL-17 as a negative regulator of adipogenesis and glucose metabolism in mice, and show that it delays the development of obesity.
TIM-4, a Receptor for Phosphatidylserine, Controls Adaptive Immunity by Regulating the Removal of Antigen-Specific T Cells
Authors: Albacker Lee A. , Karisola Piia , Chang Ya-Jen , Umetsu Sarah E. , Zhou Meixia , Akbari Omid , Kobayashi Norimoto , Baumgarth Nicole , Freeman Gordon J. , Umetsu Dale T. , DeKruyff Rosemarie H.
Published: October 2010

Adaptive immunity is characterized by the expansion of an Ag-specific T cell population following Ag exposure. The precise mechanisms, however, that control the expansion and subsequent contraction in the number of Ag-specific T cells are not fully understood. We show that T cell/transmembrane, Ig, and mucin (TIM)-4, a receptor for phosphatidylserine, a marker of apoptotic cells, regulates adaptive immunity in part by mediating the removal of Ag-specific T cells during the contraction phase of the response. During Ag immunization or during infection with influenza A virus, blockade of TIM-4 on APCs increased the expansion of Ag-specific T cells, resulting in an increase in secondary immune responses. Conversely, overexpression of TIM-4 on APCs in transgenic mice reduced the number of Ag-specific T cells that remained after immunization, resulting in reduced secondary T cell responses. There was no change in the total number of cell divisions that T cells completed, no change in the per cell proliferative capacity of the remaining Ag-specific T cells, and no increase in the development of Ag-specific regulatory T cells in TIM-4 transgenic mice. Thus, TIM-4–expressing cells regulate adaptive immunity by mediating the removal of phosphatidylserine-expressing apoptotic, Ag-specific T cells, thereby controlling the number of Ag-specific T cells that remain after the clearance of Ag or infection.
LFA-1 and Mac-1 Define Characteristically Different Intralumenal Crawling and Emigration Patterns for Monocytes and Neutrophils In Situ
Authors: Sumagin Ronen , Prizant Hen , Lomakina Elena , Waugh Richard E. , Sarelius Ingrid H.
Published: October 2010

To exit blood vessels, most (∼80%) of the lumenally adhered monocytes and neutrophils crawl toward locations that support transmigration. Using intravital confocal microscopy of anesthetized mouse cremaster muscle, we separately examined the crawling and emigration patterns of monocytes and neutrophils in blood-perfused unstimulated or TNF-α–activated venules. Most of the interacting cells in microvessels are neutrophils; however, in unstimulated venules, a greater percentage of the total monocyte population is adherent compared with neutrophils (58.2 ± 6.1% versus 13.6 ± 0.9%, adhered/total interacting), and they crawl for significantly longer distances (147.3 ± 13.4 versus 61.8 ± 5.4 μm). Intriguingly, after TNF-α activation, monocytes crawled for significantly shorter distances (67.4 ± 9.6 μm), resembling neutrophil crawling. Using function-blocking Abs, we show that these different crawling patterns were due to CD11a/CD18 (LFA-1)- versus CD11b/CD18 (Mac-1)-mediated crawling. Blockade of either Mac-1 or LFA-1 revealed that both LFA-1 and Mac-1 contribute to monocyte crawling; however, the LFA-1–dependent crawling in unstimulated venules becomes Mac-1 dependent upon inflammation, likely due to increased expression of Mac-1. Mac-1 alone was responsible for neutrophil crawling in both unstimulated and TNF-α–activated venules. Consistent with the role of Mac-1 in crawling, Mac-1 block (compared with LFA-1) was also significantly more efficient in blocking TNF-α–induced extravasation of both monocytes and neutrophils in cremaster tissue and the peritoneal cavity. Thus, mechanisms underlying leukocyte crawling are important in regulating the inflammatory responses by regulating the numbers of leukocytes that transmigrate.
Differential Regulation of Caspase-1 Activation via NLRP3/NLRC4 Inflammasomes Mediated by Aerolysin and Type III Secretion System during Aeromonas veronii Infection
Authors: McCoy Andrea J. , Koizumi Yukiko , Higa Naomi , Suzuki Toshihiko
Published: October 2010

Aeromonas spp. are Gram-negative bacteria that cause serious infectious disease in humans. Such bacteria have been shown to induce apoptosis in infected macrophages, yet the host responses triggered by macrophage death are largely unknown. In this study, we demonstrate that the infection of mouse bone marrow-derived macrophages with Aeromonas veronii biotype sobria triggers activation of caspase-1 with the ensuing release of IL-1β and pyroptosis. Caspase-1 activation in response to A. veronii infection requires the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain and both the NLRP3 and NLRC4 inflammasomes. Furthermore, caspase-1 activation requires aerolysin and a functional type III secretion system in A. veronii. Aerolysin-inducing caspase-1 activation is mediated through the NLRP3 inflammasome, with aerolysin-mediated cell death being largely dependent on the NLRP3 inflammasome. In contrast, the type III secretion system activates both the NLRP3 and NLRC4 inflammasomes. Inflammasome-mediated caspase-1 activation is also involved in host defenses against systemic A veronii infection in mice. Our results indicated that multiple factors from both the bacteria and the host play a role in eliciting caspase-1 activation during A. veronii infection.
Cutting Edge: Adaptive Versus Innate Receptor Signals Selectively Control the Pool Sizes of Murine IFN-γ– or IL-17–Producing γδ T Cells upon Infection
Authors: Ribot Julie C. , Chaves-Ferreira Miguel , d’Orey Francisco , Wencker Mélanie , Gonçalves-Sousa Natacha , Decalf Jérémie , Simas João P. , Hayday Adrian C. , Silva-Santos Bruno
Published: October 2010

γδ T lymphocytes are commonly viewed as embracing properties of both adaptive and innate immunity. Contributing to this is their responsiveness to pathogen products, either with or without the involvement of the TCR and its coreceptors. This study clarifies this paradoxical behavior by showing that these two modes of responsiveness are the properties of two discrete sets of murine lymphoid γδ T cells. Thus, MyD88 deficiency severely impaired the response to malaria infection of CD27(−), IL-17A–producing γδ T cells, but not of IFN-γ–producing γδ cells. Instead, the latter compartment was severely contracted by ablating CD27, which synergizes with TCRγδ in the induction of antiapoptotic mediators and cell cycle-promoting genes in CD27(+), IFN-γ–secreting γδ T cells. Hence, innate versus adaptive receptors differentially control the peripheral pool sizes of discrete proinflammatory γδ T cell subsets during immune responses to infection.
IgG1 Is Pathogenic in Leishmania mexicana Infection
Authors: Chu Niansheng , Thomas Bolaji N. , Patel Supriya R. , Buxbaum Laurence U.
Published: October 2010

There are >2 million new cases of leishmaniasis annually, and no effective vaccine has been developed to prevent infection. In murine infection, Leishmania mexicana, which lives intracellularly in host macrophages, has developed pathways to hijack host IgG to induce a suppressive IL-10 response through FcγRs, the cell-surface receptors for IgG. To guide vaccine development away from detrimental Ab responses, which can accompany attempts to induce cell-mediated immunity, it is crucial to know which isotypes of IgG are pathogenic in this infection. We found that IgG1 and IgG2a/c induce IL-10 from macrophages in vitro equally well but through different FcγR subtypes: IgG1 through FcγRIII and IgG2a/c through FcγRI primarily, but also through FcγRIII. In sharp contrast, mice lacking IgG1 develop earlier and stronger IgG2a/c, IgG3, and IgM responses to L. mexicana infection and yet are more resistant to the infection. Thus, IgG1, but not IgG2a/c or IgG3, is pathogenic in vivo, in agreement with prior studies indicating that FcγRIII is required for chronic disease. This calls into question the assumption that macrophages, which should secrete IL-10 in response to IgG1 and IgG2a/c immune complexes, are the most important source of IL-10 generated by IgG–FcγR engagement in L. mexicana infection. Further investigations are required to better determine the cell type responsible for this immunosuppressive FcγRIII-induced IL-10 pathway and whether IgG2a/c is protective.
Chlamydia-Specific CD4 T Cell Clones Control Chlamydia muridarum Replication in Epithelial Cells by Nitric Oxide-Dependent and -Independent Mechanisms
Authors: Jayarapu Krupakar , Kerr Micah , Ofner Susan , Johnson Raymond M.
Published: October 2010

Chlamydia trachomatis serovars D–K are sexually transmitted intracellular bacterial pathogens that replicate in epithelial cells lining the human reproductive tract. It is clear from knockout mice and T cell depletion studies using Chlamydia muridarum that MHC class II and CD4 T cells are critical for clearing bacteria from the murine genital tract. It is not clear how CD4 T cells interact with infected epithelial cells to mediate bacterial clearance in vivo. Previous work using an epithelial tumor cell line showed that a Chlamydia-specific CD4 T cell clone was able to inhibit C. muridarum replication in vitro via induction of epithelial NO production. We have previously shown that Chlamydia-specific CD4 T cell clones can recognize and be activated by infected reproductive tract epithelial cells and block Chlamydia replication in them. We extend those observations by investigating the mechanism used by a panel of CD4 T cell clones to control Chlamydia replication in epithelial cells. We found that Chlamydia-specific CD4 T cell clones were cytolytic, but that cytolysis was not likely critical for controlling C. muridarum replication. For one, CD4 T cell clone-induced epithelial NO production was critical for controlling replication; however, the most potent CD4 T cell clones were dependent on T cell degranulation for replication control with only a minor additional contribution from NO production. We discuss our data as they relate to existing knockout mouse studies addressing mechanisms of T cell-mediated control of Chlamydia replication and their implications for intracellular epithelial pathogens in mouse models.
Protective Endogenous Cyclic Adenosine 5′-Monophosphate Signaling Triggered by Pemphigus Autoantibodies
Authors: Spindler Volker , Vielmuth Franziska , Schmidt Enno , Rubenstein David S. , Waschke Jens
Published: October 2010

Pemphigus vulgaris (PV) is an autoimmune skin disease mediated by autoantibodies directed against the cadherin-type cell adhesion molecules desmoglein (Dsg) 3 and Dsg1 and is characterized by loss of keratinocyte cohesion and epidermal blistering. Several intracellular signaling pathways, such as p38MAPK activation and RhoA inhibition, have been demonstrated to be altered following autoantibody binding and to be causally involved in loss of keratinocyte cohesion. In this paper, we demonstrate that cAMP-mediated signaling completely prevented blister formation in a neonatal pemphigus mouse model. Furthermore, elevation of cellular cAMP levels by forskolin/rolipram or β receptor agonist isoproterenol blocked loss of intercellular adhesion, depletion of cellular Dsg3, and morphologic changes induced by Ab fractions of PV patients (PV-IgG) in cultured keratinocytes. Incubation with PV-IgG alone increased cAMP levels, indicating that cAMP elevation may be a cellular response pathway to strengthen intercellular adhesion. Our data furthermore demonstrate that this protective pathway may involve protein kinase A signaling because protein kinase A inhibition attenuated recovery from PV-IgG–induced cell dissociation. Finally, cAMP increase interfered with PV-IgG–induced signaling by preventing p38MAPK activation both in vitro and in vivo. Taken together, our data provide insights into the cellular response mechanisms following pemphigus autoantibody binding and point to a possible novel and more specific therapeutic approach in pemphigus.
Human Papillomavirus 16-Associated Cervical Intraepithelial Neoplasia in Humans Excludes CD8 T Cells from Dysplastic Epithelium
Authors: Trimble Cornelia L. , Clark Rachael A. , Thoburn Christopher , Hanson Nicole C. , Tassello Jodie , Frosina Denise , Kos Ferdynand , Teague Jessica , Jiang Ying , Barat Nicole C. , Jungbluth Achim A.
Published: October 2010

High-grade cervical dysplasia caused by human papillomavirus (HPV) type 16 is a lesion that should be susceptible to an HPV-specific immune response; disease initiation and persistence is predicated on expression of two viral Ags, E6 and E7. In immune-competent subjects, at least 25% of HPV16+ high-grade cervical dysplasia lesions undergo complete regression. However, in the peripheral blood, naturally occurring IFN-γ T cell responses to HPV E6 and E7 are weak, requiring ex vivo sensitization to detect, and are not sufficiently sensitive to predict regression. In this study, we present immunologic data directly assessing cervical lymphocytes from this cohort. We found that nearly all cervical tissue T cells express the mucosal homing receptor, α4β7 surface integrin. T cells isolated from dysplastic mucosa were skewed toward a central memory phenotype compared with normal mucosal resident T cells, and dysplastic lesions expressed transcripts for CCL19 and CCL21, raising the possibility that the tissue itself sustains a response that is not detectable in the blood. Moreover, lesion regression in the study window could retrospectively be predicted at study entry by the ability of CD8+ T cells to gain access to lesional epithelium. Vascular endothelial expression of mucosal addressin cell adhesion molecule-1, the ligand that supports entry of α4β7+ T cells into tissues, colocalized tightly with the distribution of CD8 T cells and was not expressed in persistent dysplastic epithelium. These findings suggest that dysregulated expression of vascular adhesion molecules plays a role in immune evasion very early in the course of HPV disease.
Cross-platform Comparison of Two Pancreatic Cancer Phenotypes
Authors: Scharpf Robert B. , Iacobuzio-Donahue Christine A. , Cope Leslie , Ruczinski Ingo , Garrett-Mayer Elizabeth , Lakkur Sindhu , Campagna Domenico , Parmigiani Giovanni
Published: November 2010

Model-based approaches for combining gene expression data from multiple high throughput platforms can be sensitive to technological artifacts when the number of samples in each platform is small. This paper proposes simple tools for quantifying concordance in a small study of pancreatic cancer cells lines with an emphasis on visualizations that uncover intra- and inter-platform variation. Using this approach, we identify several transcripts from the integrative analysis whose over-or under-expression in pancreatic cancer cell lines was validated by qPCR.
Review: Behaviour and its role in the nutritional management of the growing dairy heifer
Authors: DeVries T J
Published: November 2010

There has recently been a significant increase in the amount of scientific research relating dairy cattle behaviour to nutritional management, particularly with respect to the interaction with health. Much of this research has been focused on using information on the natural behavioural patterns of dairy cattle to improve management practices. As with calves and mature dairy cattle, the behaviour of growing replacement dairy heifers interacts with various nutritional management practices. For replacement dairy heifers, much of the research in this area has been focused on how these interactions relate to different feed delivery methods, the amount of feed provided, and stocking density at the feed bunk. This review describes empirical work focused on understanding how nutritional management practices affect heifer behaviour, and how these practices may affect the health, productivity, and welfare of these animals. In particular, evidence will be provided for those practices (such as total mixed ration feeding, feeding for ad libitum intake, and reducing feed bunk competition) that promote feeding behaviour patterns related to more consistent nutrient intake and improved rumen health. Even though the behavioural effects of these nutritional practices are known, additional research is still needed to further demonstrate the possible physiological consequences (e.g., rumen pH, growth rate) of these changes in behaviour. This information is needed so that further recommendations can be made on these practices so these animals may be raised for maximum production potential, while maintaining their behavioural needs, health and overall welfare.Key words: Behaviour, nutritional management, replacement dairy heifer
A mechanistic model for simulating methane emissions from unstirred liquid manure storages
Authors: Huang Q. , Wohlgemut O. , Cicek N. , France J. , Kebreab E.
Published: November 2010

The objective of the study was to develop a mechanistic model of methane (CH4) producing processes in unstirred conditions with potential application for estimating CH4 emissions from anaerobic manure storage facilities. Although models for describing anaerobic digestion processes are available, they largely relate to anaerobic digesters, and do not directly apply to the prediction of CH4 emissions from liquid manure storage. Based on extant models, six biochemical steps were described: hydrolysis, acetogenesis, hydrogenogenesis, homoacetogenesis, hydrogenous methanogenesis and acetic methanogenesis, performed by five bacterial groups. The model contains six state variables, and mass flow is mostly generated and quantified using bacterial kinetics. The model was coded in acslX and a fourth-order Runge-Kutta method with an integration step size of 0.05 d was used for numerical integration. The time courses of CH4 production and volatile fatty acid (VFA) concentration of two laboratory-scale liquid manure storage tanks, both filled with liquid sow manures and running in unstirred and constant 25°C conditions, were well predicted, with correlation coefficients over 0.90. Discrepancies between predicted and measured CH4 production and VFA concentration were mainly due to random variation of observed data. The model was sensitive to parameters describing hydrolysis and the kinetics of acetogenic and acetate methanogenic bacteria. Simulations based on the Intergovernmental Panel on Climate Change model (Tier II) predicted 260 g CH4 kg-1 volatile solids (VS, assuming maximum CH4 producing capacity of 0.48 and methane conversion factor of 80%), whereas the measured value was 78.3 g CH4 kg-1 VS after 146 d and the mechanistic model predicted 74.8 g CH4 kg-1 VS. The model developed in this study appears to be better suited to batch manure storage than the IPCC model.