bluuebunny/crossref_metadata_2025_split huggingface dataset:
Le rôle des traumatismes familiaux dans l’émergence des troubles délirants chez deux jeunes adultes camerounaises de culture grassfield
Authors: Mboua Pierre Célestin 
Published: August 2016

Entité tutélaire permettant l’édification des mythes et des rituels d’élaboration du psychisme, la famille, par son organisation et son fonctionnement, est susceptible de favoriser des modalités transactionnelles traumatiques l’affectant comme système. L’observation a porté sur deux cas cliniques. Cet article prend appui sur des entretiens cliniques. Il nous permet d’insister sur le fait qu’au regard de la nature des « percepts » et des contenus du « dasein » attachés au vécu familial, les membres du système familial peuvent être diversement affectés par le traumatisme, souvent associé à des troubles connexes. Dans le contexte des transactions péniblement vécues et particulièrement libidinalisées, l’analyse a mis en évidence une vulnérabilité accrue aux troubles délirants dans un contexte patriarcal très rigide, où les mythes et rituels qui organisent les transactions familiales deviennent pathogènes.
Empathie et psychothérapie systémique. Implications théoriques et cliniques
Authors: Onnis Luigi 
Published: August 2016

Après avoir proposé une définition et présenté un bref historique du concept de l’empathie, l’auteur évoque les apports scientifiques qui actuellement enrichissent le domaine l’empathie : les travaux issus de la psychologie du développement, qui accordent en particulier de l’importance à l’intersubjectivité, et les apports des neurosciences à propos de la fonction des neurones miroirs. Il ressort que l’empathie est une construction relationnelle qui implique une dimension intersubjective avec des bases émotionnelles et affectives (bien avant une base cognitive) s’exprimant au travers de langages implicites et en particulier corporels. Ces caractéristiques relationnelles de l’empathie s’intègrent parfaitement à la psychothérapie systémique relationnelle laquelle reconnaît la pertinence de la relation intersubjective ; de plus, elle accorde une grande importance à l’utilisation thérapeutique des langages analogiques afin de favoriser les échanges émotionnels entre thérapeutes et familles. Nous décrirons un cas clinique où l’activation de l’empathie au sein d’une famille et entre elle et le thérapeute est favorisée par l’usage de la méthode analogique des Sculptures du Temps Familial. En fin de l’article, nous discuterons également des risques de la surévaluation de l’empathie, en particulier lorsqu’elle est considérée comme un facteur qui, en soi, peut produire un changement.
Aging-Associated TNF Production Primes Inflammasome Activation and NLRP3-Related Metabolic Disturbances
Authors: Bauernfeind Franz , Niepmann Sven , Knolle Percy A. , Hornung Veit 
Published: August 2016

Abstract
Accumulating evidence suggests that the activation of the innate branch of the immune system plays a pivotal role in the induction and perpetuation of metabolic and aging-related diseases. In this context, the NLRP3 inflammasome pathway has been identified as an important driver of sterile inflammatory processes. De novo protein synthesis of NLRP3 induced by signals such as TLR ligands or TNF is a prerequisite for sustained NLRP3 mediated caspase-1 cleavage and inflammasome activation. Here, we demonstrate in aged mice that spontaneously elevated TNF represents a critical priming signal that functions to control NLRP3 inflammasome activation. Elevated systemic TNF levels were responsible for increased NLRP3 expression and caspase-1 activity in adipose tissues and liver. TNF dependent, spontaneous inflammasome activity in aged mice resulted in impaired glucose tolerance that could be attributed to peripheral insulin resistance. Altogether, these results implicate that TNF-driven NLRP3 expression constitutes an important checkpoint that regulates inflammasome activation, presumably by additional signals such as aging-associated DAMPs.
Rac GTPase Activating Protein ARHGAP25 Regulates Leukocyte Transendothelial Migration in Mice
Authors: Csépányi-Kömi Roland , Wisniewski Éva , Bartos Balázs , Lévai Petra , Németh Tamás , Balázs Bernadett , Kurz Angela R. M. , Bierschenk Susanne , Sperandio Markus , Ligeti Erzsébet 
Published: August 2016

Abstract
ARHGAP25 is a Rac-specific GTPase-activating protein that is expressed primarily in hematopoietic cells. The involvement of ARHGAP25 in regulating the recruitment of leukocytes to inflammatory sites was investigated in genetically modified mice. Using intravital microscopy, we show that Arhgap25 deficiency affects all steps of leukocyte recruitment with a predominant enhancement of transendothelial migration of neutrophilic granulocytes. Increased transmigration of Arhgap25-deficient leukocytes is demonstrated in inflamed cremaster muscle venules, in a peritonitis model, and in an in vitro chemotaxis assay. Using bone marrow chimeric mice lacking ARHGAP25 in the hematopoietic compartment, we show that enhanced migration in the absence of ARHGAP25 is due to defective leukocyte function. In search for potential mechanisms of ARHGAP25-regulated migration of neutrophils, we detected an increase in the amount of active, GTP-bound Rac and Rac-dependent cytoskeletal changes in the absence of ARHGAP25, suggesting a critical role of ARHGAP25 in counterbalancing the Rac-activating effect of nucleotide exchange factors. Taken together, using Arhgap25-deficient mice, we identified ARHGAP25 as a relevant negative regulator of leukocyte transendothelial migration.
CLEC12A-Mediated Antigen Uptake and Cross-Presentation by Human Dendritic Cell Subsets Efficiently Boost Tumor-Reactive T Cell Responses
Authors: Hutten Tim J. A. , Thordardottir Soley , Fredrix Hanny , Janssen Lisanne , Woestenenk Rob , Tel Jurjen , Joosten Ben , Cambi Alessandra , Heemskerk Mirjam H. M. , Franssen Gerben M. , Boerman Otto C. , Bakker Lex B. H. , Jansen Joop H. , Schaap Nicolaas , Dolstra Harry , Hobo Willemijn 
Published: August 2016

Abstract
Potent immunotherapies are urgently needed to boost antitumor immunity and control disease in cancer patients. As dendritic cells (DCs) are the most powerful APCs, they are an attractive means to reinvigorate T cell responses. An appealing strategy to use the effective Ag processing and presentation machinery, T cell stimulation and cross-talk capacity of natural DC subsets is in vivo tumor Ag delivery. In this context, endocytic C-type lectin receptors are attractive targeting molecules. In this study, we investigated whether CLEC12A efficiently delivers tumor Ags into human DC subsets, facilitating effective induction of CD4+ and CD8+ T cell responses. We confirmed that CLEC12A is selectively expressed by myeloid cells, including the myeloid DC subset (mDCs) and the plasmacytoid DC subset (pDCs). Moreover, we demonstrated that these DC subsets efficiently internalize CLEC12A, whereupon it quickly translocates to the early endosomes and subsequently routes to the lysosomes. Notably, CLEC12A Ab targeting did not negatively affect DC maturation or function. Furthermore, CLEC12A-mediated delivery of keyhole limpet hemocyanin resulted in enhanced proliferation and cytokine secretion by keyhole limpet hemocyanin–experienced CD4+ T cells. Most importantly, CLEC12A-targeted delivery of HA-1 long peptide resulted in efficient Ag cross-presentation by mDCs and pDCs, leading to strong ex vivo activation of HA-1–specific CD8+ T cells of patients after allogeneic stem cell transplantation. Collectively, these data indicate that CLEC12A is an effective new candidate with great potential for in vivo Ag delivery into mDCs and pDCs, thereby using the specialized functions and cross-talk capacity of these DC subsets to boost tumor-reactive T cell immunity in cancer patients.
Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice
Authors: Gomez John C. , Dang Hong , Martin Jessica R. , Doerschuk Claire M. 
Published: August 2016

Abstract
Nrf2 regulates the transcriptional response to oxidative stress. These studies tested the role of Nrf2 during Streptococcus pneumoniae pneumonia and identified Nrf2-dependent genes and pathways in lung tissue and in recruited neutrophils. Nrf2 null and wild type (WT) mice were studied at 6 and 24 h after instillation of S. pneumoniae or PBS. At 6 h, fewer neutrophils were recruited and the number of bacteria remaining in the lungs tended to be less (p = 0.06) in the Nrf2 null compared with WT mice. In uninfected lungs, 53 genes were already differentially expressed in Nrf2 null compared with WT mouse lungs, and gene sets involved in phagocytosis, Fc receptor function, complement, and Ig regulation are enhanced in PBS-treated Nrf2 null gene profiles compared with those of WT mice. These results suggest that initial host defense is enhanced in Nrf2 null mice, resulting in less recruitment of neutrophils. At 24 h, neutrophil recruitment was greater. The percentages of early apoptotic and late apoptotic/necrotic neutrophils were similar. At increasing inoculum numbers, mortality rates strikingly increased from 15 to 31 and 100% in Nrf2 null mice, whereas all WT mice survived, and Nrf2 null mice had a defect in clearance, particularly at the intermediate dose. The mortality was due to enhanced lung injury and greater systemic response. Gene profiling identified differentially regulated genes and pathways in neutrophils and lung tissue, including those involved in redox stress response, metabolism, inflammation, immunoregulatory pathways, and tissue repair, providing insight into the mechanisms for the greater tissue damage and increased neutrophil accumulation.
PFKFB3-Driven Macrophage Glycolytic Metabolism Is a Crucial Component of Innate Antiviral Defense
Authors: Jiang Hui , Shi Hengfei , Sun Man , Wang Yafeng , Meng Qingzhou , Guo Panpan , Cao Yanlan , Chen Jiong , Gao Xiang , Li Erguang , Liu Jianghuai 
Published: August 2016

Abstract
Signaling by viral nucleic acids and subsequently by type I IFN is central to antiviral innate immunity. These signaling events are also likely to engage metabolic changes in immune and nonimmune cells to support antiviral defense. In this study, we show that cytosolic viral recognition, by way of secondary IFN signaling, leads to upregulation of glycolysis preferentially in macrophages. This metabolic switch involves induction of glycolytic activator 6-phosphofructose-2-kinase and fructose-2,6-bisphosphatase (PFKFB3). Using a genetic inactivation approach together with pharmacological perturbations in mouse cells, we show that PFKFB3-driven glycolysis selectively promotes the extrinsic antiviral capacity of macrophages, via metabolically supporting the engulfment and removal of virus-infected cells. Furthermore, the antiviral function of PFKFB3, as well as some contribution of its action from the hematopoietic compartment, was confirmed in a mouse model of respiratory syncytial virus infection. Therefore, different from the long-standing perception of glycolysis as a proviral pathway, our findings establish an antiviral, immunometabolic aspect of glycolysis that may have therapeutic implications.
Killer Cell Lectin-like Receptor G1 Inhibits NK Cell Function through Activation of Adenosine 5′-Monophosphate–Activated Protein Kinase
Authors: Müller-Durovic Bojana , Lanna Alessio , Polaco Covre Luciana , Mills Rachel S. , Henson Sian M. , Akbar Arne N. 
Published: August 2016

Abstract
NK cells are the first line of defense against infected and transformed cells. Defective NK cell activity was shown to increase susceptibility for viral infections and reduce tumor immune-surveillance. With age, the incidence of infectious diseases and malignancy rises dramatically, suggesting that impaired NK cell function might contribute to disease in these individuals. We found an increased frequency of NK cells with high expression of the inhibitory killer cell lectin-like receptor G1 (KLRG1) in individuals &gt;70 y. The role of KLRG1 in ageing is not known, and the mechanism of KLRG1-induced inhibition of NK cell function is not fully understood. We report that NK cells with high KLRG1 expression spontaneously activate the metabolic sensor AMP-activated protein kinase (AMPK) and that activation of AMPK negatively regulates NK cell function. Pre-existing AMPK activity is further amplified by ligation of KLRG1 in these cells, which leads to internalization of the receptor and allows interaction with AMPK. We show that KLRG1 activates AMPK by preventing its inhibitory dephosphorylation by protein phosphatase-2C rather than inducing de novo kinase activation. Finally, inhibition of KLRG1 or AMPK prevented KLRG1-induced activation of AMPK and reductions in NK cell cytotoxicity, cytokine secretion, proliferation, and telomerase expression. This novel signaling pathway links metabolic sensing, effector function, and cell differentiation with inhibitory receptor signaling that may be exploited to enhance NK cell activity during ageing.
Preservation of Lymphopoietic Potential and Virus Suppressive Capacity by CD8+ T Cells in HIV-2–Infected Controllers
Authors: Angin Mathieu , Wong Glenn , Papagno Laura , Versmisse Pierre , David Annie , Bayard Charles , Charmeteau-De Muylder Bénédicte , Besseghir Amel , Thiébaut Rodolphe , Boufassa Faroudy , Pancino Gianfranco , Sauce Delphine , Lambotte Olivier , Brun-Vézinet Françoise , Matheron Sophie , Rowland-Jones Sarah L. , Cheynier Rémi , Sáez-Cirión Asier , Appay Victor ,   for the ANRS CO5 IMMUNOVIR-2 Study Group
Published: August 2016

Abstract
Compared with HIV-1, HIV-2 infection is characterized by a larger proportion of slow or nonprogressors. A better understanding of HIV-2 pathogenesis should open new therapeutic avenues to establish control of HIV-1 replication in infected patients. In this study, we studied the production of CD8+ T cells and their capacity for viral control in HIV-2 controllers from the French ANRS CO5 HIV-2 cohort. HIV-2 controllers display a robust capacity to support long-term renewal of the CD8+ T cell compartment by preserving immune resources, including hematopoietic progenitors and thymic activity, which could contribute to the long-term maintenance of the CD8+ T cell response and the avoidance of premature immune aging. Our data support the presence of HIV-2 Gag–specific CD8+ T cells that display an early memory differentiation phenotype and robust effector potential in HIV-2 controllers. Accordingly, to our knowledge, we show for the first time that HIV-2 controllers possess CD8+ T cells that show an unusually strong capacity to suppress HIV-2 infection in autologous CD4+ T cells ex vivo, an ability that likely depends on the preservation of host immune resources. This effective and durable antiviral response probably participates in a virtuous circle, during which controlled viral replication permits the preservation of potent immune functions, thus preventing HIV-2 disease progression.
Cutting Edge: Direct Sensing of TLR7 Ligands and Type I IFN by the Common Myeloid Progenitor Promotes mTOR/PI3K-Dependent Emergency Myelopoiesis
Authors: Buechler Matthew B. , Akilesh Holly M. , Hamerman Jessica A. 
Published: August 2016

Abstract
During infection, recognition of pathogens and inflammatory cytokines skews hematopoiesis toward myeloid development, although the precise mechanisms responsible for this are unclear. In this study, we show that accelerated myeloid differentiation, known as emergency myelopoiesis, involves recognition of pathogen-associated molecular patterns by the common myeloid progenitor (CMP) and is dependent on type I IFN for monocyte/macrophage differentiation. Direct sensing of TLR agonists by CMP induced rapid proliferation and induction of myeloid-differentiation genes. Lack of type I IFN signaling in CMP abrogated macrophage differentiation in response to TLR stimuli, whereas exogenous type I IFN amplified this process. Mechanistically, TLR7 induced PI3K/mammalian target of rapamycin signaling in CMP, which was enhanced by type I IFN, and this pathway was essential for emergency myelopoiesis. This work identifies a novel mechanism by which TLR and type I IFN synergize to promote monocyte/macrophage development from hematopoietic progenitors, a process critical in triggering rapid immune responses during infection.
The RNA-Binding Proteins Zfp36l1 and Zfp36l2 Enforce the Thymic β-Selection Checkpoint by Limiting DNA Damage Response Signaling and Cell Cycle Progression
Authors: Vogel Katharina U. , Bell Lewis S. , Galloway Alison , Ahlfors Helena , Turner Martin 
Published: August 2016

Abstract
The RNA-binding proteins Zfp36l1 and Zfp36l2 act redundantly to enforce the β-selection checkpoint during thymopoiesis, yet their molecular targets remain largely unknown. In this study, we identify these targets on a genome-wide scale in primary mouse thymocytes and show that Zfp36l1/l2 regulate DNA damage response and cell cycle transcripts to ensure proper β-selection. Double-negative 3 thymocytes lacking Zfp36l1/l2 share a gene expression profile with postselected double-negative 3b cells despite the absence of intracellular TCRβ and reduced IL-7 signaling. Our findings show that in addition to controlling the timing of proliferation at β-selection, posttranscriptional control by Zfp36l1/l2 limits DNA damage responses, which are known to promote thymocyte differentiation. Zfp36l1/l2 therefore act as posttranscriptional safeguards against chromosomal instability and replication stress by integrating pre-TCR and IL-7 signaling with DNA damage and cell cycle control.
A 33D1+ Dendritic Cell/Autoreactive CD4+ T Cell Circuit Maintains IL-2–Dependent Regulatory T Cells in the Spleen
Authors: Stolley J. Michael , Campbell Daniel J. 
Published: August 2016

Abstract
Phenotypically and functionally diverse regulatory T (Tr) cell subsets populate lymphoid and nonlymphoid tissues, where their maintenance and function are governed by unique homeostatic signals. Whereas Tr cells resident in nonlymphoid tissues depend on continual TCR signaling for their survival and function, phenotypically naive Tr cells occupying secondary lymphoid organs are largely supported by paracrine IL-2 signaling. Crucially, the absence of either of these distinct Tr cell subsets results in pathogenic autoimmunity, underscoring their nonredundant roles in the preservation of self-tolerance. However, the cellular and molecular factors precipitating IL-2 release and subsequent maintenance of secondary lymphoid organ–resident Tr cells are still poorly understood. In this study, we report that IL-2–dependent Tr cells in the spleen compete for a limiting supply of paracrine IL-2 generated by autoreactive CD4+ T cells in response to MHC class II–restricted autoantigen activation by 33D1+CD11bint dendritic cells. Manipulating this cellular circuit culminating in IL-2 production could have clinical benefits in settings in which diminished Tr cell abundance is desired.
Cutting Edge: IgE Plays an Active Role in Tumor Immunosurveillance in Mice
Authors: Nigro Elisa A. , Brini Anna T. , Yenagi Vijay A. , Ferreira Lorena M. , Achatz-Straussberger Gertrude , Ambrosi Alessandro , Sanvito Francesca , Soprana Elisa , van Anken Eelco , Achatz Gernot , Siccardi Antonio G. , Vangelista Luca 
Published: August 2016

AbstractExogenous IgE acts as an adjuvant in tumor vaccination in mice, and therefore a direct role of endogenous IgE in tumor immunosurveillance was investigated. By using genetically engineered mice, we found that IgE ablation rendered mice more susceptible to the growth of transplantable tumors. Conversely, a strengthened IgE response provided mice with partial or complete resistance to tumor growth, depending on the tumor type. By genetic crosses, we showed that IgE-mediated tumor protection was mostly lost in mice lacking FcεRI. Tumor protection was also lost after depletion of CD8+ T cells, highlighting a cross-talk between IgE and T cell–mediated tumor immunosurveillance. Our findings provide the rationale for clinical observations that relate atopy with a lower risk for developing cancer and open new avenues for the design of immunotherapeutics relevant for clinical oncology.
O turismo potiguar que chegou a perder 100 mil desembarques!
Authors: Araujo Maria Valéria , Barbosa de Freitas Holliver Breno , Gomes Julia Silva , Medeiros Brito Maria Isabel 
Published: August 2016

O Caso para Ensino “O turismo potiguar que chegou a perder 100 mil desembarques’” descreve um cenário de peculiaridades e desafios no qual o destino turístico Natal está inserido. Para tanto, apresenta o histórico de investimentos ocorridos na cidade para desenvolvimento da atividade, como também discute as decisões que deverão ser tomadas pelo atual Secretário de Turismo de Natal diante das dificuldades enfrentadas com a redução da demanda deste destino entre os turistas internacionais. Esta redução deu-se, principalmente, após a crise econômica mundial, com a redução de voos charters para Natal. Questões de infraestrutura e de segurança pública também contribuíram para uma redução no número de visitantes à cidade. É neste contexto que se propõe uma reflexão sobre o cenário no qual Natal está inserida, com o objetivo de mostrar a importância da implantação de políticas públicas, das ações de marketing turístico, das análises de ambientes interno e externo do destino e do estabelecimento de vantagens competitivas. Para a elaboração do caso, foram coletados dados verídicos do turismo divulgados em jornais, revistas e artigos científicos. O caso para ensino pode ser aplicado nos cursos de Graduação ou Pós- Graduação em Administração, Marketing e Turismo.
Structural properties of mobile armors formed at different flow strengths in gravel‐bed rivers
Authors: Powell D. Mark , Ockelford Annie , Rice Stephen P. , Hillier John K. , Nguyen Thao , Reid Ian , Tate Nicholas J. , Ackerley David 
Published: August 2016

AbstractDifferences in the structure of mobile armors formed at three different flow strengths have been investigated in a laboratory flume. The temporal evolution of the bed surfaces and the properties of the final beds were compared using metrics of surface grain size, microtopography, and bed organization at both grain and mesoscales. Measurements of the bed condition were obtained on nine occasions during each experiment to describe the temporal evolution of the beds. Structured mobile armors formed quickly in each experiment. At the grain scale (1–45 mm; 9 ≤ Ds50 ≤ 17 mm where Ds50 is the median surface particle size), surface complexity decreased and bed roughness increased in response to surface coarsening and the development of the mobile armor. Particles comprising the armor also became flow aligned and developed imbrication. At a larger scale (100–200 mm), the surface developed a mesoscale topography through the development of bed patches with lower and higher elevations. Metrics of mobile armor structure showed remarkable consistency over prolonged periods of near‐constant transport, demonstrating for the first time that actively transporting surfaces maintain an equilibrium bed structure. Bed structuring was least developed in the experiments conducted at the lowest flow strength. However, little difference was observed in the structural metrics of the mobile armors generated at higher flows. Although the range of transport rates studied was limited, the results suggest that the structure of mobile armors is insensitive to the formative transport rate except when rates are low (τ* ≈ 0.03 where τ* is the dimensionless shear stress).