bluuebunny/crossref_metadata_2025_split huggingface dataset:
Du corps et des origines dans l’institution : l’empreinte incestuelle
Authors: Le Clef Bruno 
Published: October 2015

L’atmosphère incestuelle peut-elle infiltrer l’institution de soins ? Ce thème est interrogé à partir de l’existence d’une asymétrie anthropologique adulte-enfant issue d’une unité psychosomatique originaire et pourvoyeuse de mouvements de séduction. L’institution sera appréhendée comme une métaphore d’un organisme vivant accueillant, telle une matrice, les constructions narcissiques des intervenants professionnels et des usagers, lesquelles sont invitées à un travail de transformation. Selon un gradient variable, les défenses que recouvrent les divers mouvements de séduction peuvent mener vers un dévoiement des asymétries structurantes et entraver la capacité de penser par divers agirs. Ces propos sont éclairés par une clinique centrée sur la question des origines, celle de l’IVG.
Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis
Authors: Hainzl Eva , Stockinger Silvia , Rauch Isabella , Heider Susanne , Berry David , Lassnig Caroline , Schwab Clarissa , Rosebrock Felix , Milinovich Gabriel , Schlederer Michaela , Wagner Michael , Schleper Christa , Loy Alexander , Urich Tim , Kenner Lukas , Han Xiaonan , Decker Thomas , Strobl Birgit , Müller Mathias 
Published: October 2015

Abstract
In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease. Colitic Tyk2−/− mice have less p-STAT3 in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22–STAT3 target genes is reduced in IECs from healthy and colitic Tyk2−/− mice. Experiments with conditional Tyk2−/− mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of rIL-22–Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22–dependent colitis was confirmed in Citrobacter rodentium–induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3.
Cutting Edge: Inhibiting TBK1 by Compound II Ameliorates Autoimmune Disease in Mice
Authors: Hasan Maroof , Dobbs Nicole , Khan Shaheen , White Michael A. , Wakeland Edward K. , Li Quan-Zhen , Yan Nan 
Published: October 2015

Abstract
TANK-binding kinase 1 (TBK1) is a serine/threonine protein kinase that plays a crucial role in innate immunity. Enhanced TBK1 function is associated with autoimmune diseases and cancer, implicating the potential benefit of therapeutically targeting TBK1. In this article, we examined a recently identified TBK1 inhibitor Compound II on treating autoimmune diseases. We found that Compound II is a potent and specific inhibitor of TBK1-mediated IFN response. Compound II inhibited polyinosinic-polycytidylic acid–induced immune activation in vitro and in vivo. Compound II treatment also ameliorated autoimmune disease phenotypes of Trex1−/− mice, increased mouse survival, and dampened the IFN gene signature in TREX1 mutant patient lymphoblasts. In addition, we found that TBK1 gene expression is elevated in systemic lupus erythematosus patient cells, and systemic lupus erythematosus cells with high IFN signature responded well to Compound II treatment. Together, our findings provided critical experimental evidence for inhibiting TBK1 with Compound II as an effective treatment for TREX1-associated autoimmune diseases and potentially other interferonopathies.
Novel Role of TRPML2 in the Regulation of the Innate Immune Response
Authors: Sun Lu , Hua Yinan , Vergarajauregui Silvia , Diab Heba I. , Puertollano Rosa 
Published: October 2015

Abstract
TRPMLs (or mucolipins) constitute a family of endosomal cation channels with homology to the transient receptor potential superfamily. In mammals, the TRPML family includes three members: TRPML1–3. Although TRPML1 and TRPML3 have been well characterized, the cellular function of TRPML2 has remained elusive. To address TRPML2 function in a physiologically relevant cell type, we first analyzed TRPML2 expression in different mouse tissues and organs and found that it was predominantly expressed in lymphoid organs and kidney. Quantitative RT-PCR revealed tight regulation of TRPML2 at the transcriptional level. Although TRPML2 expression was negligible in resting macrophages, TRPML2 mRNA and protein levels dramatically increased in response to TLR activation both in vitro and in vivo. Conversely, TRPML1 and TRPML3 levels did not change upon TLR activation. Immunofluorescence analysis demonstrated that endogenous TRPML2 primarily localized to recycling endosomes both in culture and primary cells, in contrast with TRPML1 and TRPML3, which distribute to the late and early endosomal pathway, respectively. To better understand the in vivo function of TRPML2, we generated a TRPML2-knockout mouse. We found that the production of several chemokines, in particular CCL2, was severely reduced in TRPML2-knockout mice. Furthermore, TRPML2-knockout mice displayed impaired recruitment of peripheral macrophages in response to i.p. injections of LPS or live bacteria, suggesting a potential defect in the immune response. Overall, our study reveals interesting differences in the regulation and distribution of the members of the TRPML family and identifies a novel role for TRPML2 in the innate immune response.
Regulatory B Cells with a Partial Defect in CD40 Signaling and Overexpressing Granzyme B Transfer Allograft Tolerance in Rodents
Authors: Durand Justine , Huchet Virginie , Merieau Emmanuel , Usal Claire , Chesneau Melanie , Remy Severine , Heslan Michele , Anegon Ignacio , Cuturi Maria-Cristina , Brouard Sophie , Chiffoleau Elise 
Published: October 2015

Abstract
Emerging knowledge regarding B cells in organ transplantation has demonstrated that these cells can no longer be taken as mere generators of deleterious Abs but can also act as beneficial players. We previously demonstrated in a rat model of cardiac allograft tolerance induced by short-term immunosuppression an accumulation in the blood of B cells overexpressing inhibitory molecules, a phenotype also observed in the blood of patients that spontaneously develop graft tolerance. In this study, we demonstrated the presence in the spleen of regulatory B cells enriched in the CD24intCD38+CD27+IgD−IgM+/low subpopulation, which are able to transfer donor-specific tolerance via IL-10 and TGF-β1–dependent mechanisms and to suppress in vitro TNF-α secretion. Following anti-CD40 stimulation, IgD−IgM+/low B cells were blocked in their plasma cell differentiation pathway, maintained high expression of the inhibitory molecules CD23 and Bank1, and upregulated Granzyme B and Irf4, two molecules described as highly expressed by regulatory B cells. Interestingly, these B cells recognized specifically a dominant donor Ag, suggesting restricted specificity that could lead to a particular B cell response. Regulatory B cells were not required for induction of tolerance and appeared following Foxp3+CD4+CD25+ regulatory T cells, suggesting cooperation with regulatory T cells for their expansion. Nevertheless, following transfer to new recipients, these B cells migrated to the allograft, kept their regulatory profile, and promoted local accumulation of Foxp3+CD4+CD25+ regulatory T cells. Mechanisms of regulatory B cells and their cell therapy potential are important to decipher in experimental models to pave the way for future developments in the clinic.
Targeting Anti-Insulin B Cell Receptors Improves Receptor Editing in Type 1 Diabetes–Prone Mice
Authors: Bonami Rachel H. , Thomas James W. 
Published: October 2015

Abstract
Autoreactive B lymphocytes that commonly arise in the developing repertoire can be salvaged by receptor editing, a central tolerance mechanism that alters BCR specificity through continued L chain rearrangement. It is unknown whether autoantigens with weak cross-linking potential, such as insulin, elicit receptor editing, or whether this process is dysregulated in related autoimmunity. To resolve these issues, we developed an editing-competent model in which anti-insulin Vκ125 was targeted to the Igκ locus and paired with anti-insulin VH125Tg. Physiologic, circulating insulin increased RAG-2 expression and was associated with BCR replacement that eliminated autoantigen recognition in a proportion of developing anti-insulin B lymphocytes. The proportion of anti-insulin B cells that underwent receptor editing was reduced in the type 1 diabetes–prone NOD strain relative to a nonautoimmune strain. Resistance to editing was associated with increased surface IgM expression on immature (but not transitional or mature) anti-insulin B cells in the NOD strain. The actions of mAb123 on central tolerance were also investigated, because selective targeting of insulin-occupied BCR by mAb123 eliminates anti-insulin B lymphocytes and prevents type 1 diabetes. Autoantigen targeting by mAb123 increased RAG-2 expression and dramatically enhanced BCR replacement in newly developed B lymphocytes. Administering F(ab′)2123 induced IgM downregulation and reduced the frequency of anti-insulin B lymphocytes within the polyclonal repertoire of VH125Tg/NOD mice, suggesting enhanced central tolerance by direct BCR interaction. These findings indicate that weak or faulty checkpoints for central tolerance can be overcome by autoantigen-specific immunomodulatory therapy.
U.S. and Swedish Student Learning Through Online Synchronous International Interactions
Authors: Aldrich Rebecca M. , Johansson Karin E. 
Published: October 2015

Abstract
There is a continued need to communicate global perspectives in occupational therapy education, but the literature addressing how to incorporate firsthand global experiences into campus learning environments is scant. This article describes how course-based synchronous interactions between U.S. undergraduate occupational science students and Swedish undergraduate occupational therapy students occur via online technology. In a 2014 pilot study, we thematically analyzed students’ open-ended survey responses to discern what students learned through the interactive sessions. We also performed a content analysis of four audio-recorded interactive sessions to understand the content and nature of students’ learning. Our findings suggest that course-based online synchronous interactions provide a positive way for students to learn about other cultures and global differences in occupational therapy practice. The findings also highlight needs for improvement relative to the structure and aims of the interactive sessions. We relate these findings to the global availability of technology and occupational therapists’ cultural competence.
“Ahí me aguanté mi dolor”. Contexto sociocultural y económico de mujeres con síndrome con coronario residentes en Cali y otros municipios del Valle del Cauca
Authors: Valencia Micolta Susana Genith , Rodríguez Torres Estela 
Published: October 2015

La investigación forma parte del “Estudio Multicéntrico, Comparación de la caracterización de los síntomas de angina en la mujer en ocho ciudades de Colombia”. Aborda las condiciones de desigualdad en empleo, educación, género y etnia, situaciones de violencia y desplazamiento forzoso, factores fisiológicos que desencadenan una serie de síntomas y aparición del síndrome coronario, angina e infarto agudo de miocardio.<br /><br />Objetivo: Determinar aspectos socioculturales y económicos que influyen en la aparición de síntomas de angina en mujeres de Cali y municipios del Valle del Cauca<br /><br />Material y método. Estudio descriptivo con abordaje cualitativo, en 23 mujeres. Con criterios de haber experimentado molestia, dolor o sensación de disconfort torácico, hemodinámicamente estables, arteriografía coronaria con lesión de vasos mayor de 70%, y postsíndrome coronario agudo. Las entrevistas son analizadas con técnica de análisis de contenido de Klipendorf y Teoría de Síntomas Desagradables de Lenz y colaboradores <br /><br />Resultados. Los síntomas desagradables, tienen relación con antecedentes fisiológicos y factores influyentes del ambiente físico, familiar y social. Emergen categorías acerca de responsabilidades laborales y domésticas, asumir roles, apoyo a la familia y conviviendo con sus dificultades, viviendo con incertidumbre e inseguridad, relaciones con el entorno, cumpliendo con el tratamiento. <br /><br />Conclusión. El modo de vida en las mujeres que padecen de síndrome coronario agudo es un factor influyente en el agravamiento de los síntomas. Las mujeres están expuestas a experiencias y entornos desventajosos en condiciones de vulnerabilidad e inequidad. <br /><br />
Interpreting de novo Variation in Human Disease Using denovolyzeR
Authors: Ware James S. , Samocha Kaitlin E. , Homsy Jason , Daly Mark J. 
Published: October 2015

AbstractSpontaneously arising (de novo) genetic variants are important in human disease, yet every individual carries many such variants, with a median of 1 de novo variant affecting the protein‐coding portion of the genome. A recently described mutational model provides a powerful framework for the robust statistical evaluation of such coding variants, enabling the interpretation of de novo variation in human disease. Here we describe a new open‐source software package, denovolyzeR, that implements this model and provides tools for the analysis of de novo coding sequence variants. © 2015 by John Wiley & Sons, Inc.
Huntington Disease: Molecular Diagnostics Approach
Authors: Bastepe Murat , Xin Winnie 
Published: October 2015

AbstractHuntington disease (HD) is caused by expansion of a CAG trinucleotide repeat in the first exon of the Huntingtin (HTT) gene. Molecular testing of Huntington disease for diagnostic confirmation and disease prediction requires detection of the CAG repeat expansion. There are three main types of HD genetic testing: (1) diagnostic testing to confirm or rule out disease, (2) presymptomatic testing to determine whether an at‐risk individual inherited the expanded allele, and (3) prenatal testing to determine whether the fetus has inherited the expanded allele. This unit includes protocols that describe the complementary use of polymerase chain reactions (PCR) and Southern blot hybridization to accurately measure the CAG trinucleotide repeat size and interpret the test results. In addition, an indirect linkage analysis that does not reveal the unwanted parental HD status in a prenatal testing will also be discussed. © 2015 by John Wiley & Sons, Inc.
Magnetostratigraphic constraints on the age of the lower Beaufort Group, western Karoo basin, South Africa, and a critical analysis of existing U‐Pb geochronological data
Authors: Tohver E. , Lanci L. , Wilson A. , Hansma J. , Flint S. 
Published: October 2015

AbstractWe studied three partially overlapping sections with a composite thickness of ∼600 m in the upper Permian fluvial siltstones and fine‐grained sandstones of the Abrahamskraal Formation, the basal unit of the Beaufort Group, in the Karoo Basin of Western Cape Province, South Africa. Paleomagnetic analysis reveals three components of Natural Remanent Magnetization (NRM). Heating to ∼180°C removes a remanent magnetization parallel to the present‐day field, which is interpreted as a viscous overprint. An intermediate unblocking temperature component is removed by heating to 450°C; this direction is always of normal polarity and is identical to a regional overprint imparted during the Early Jurassic emplacement of the Karoo Large Igneous Province. A high‐temperature component isolated above 450°C is of dual polarity and is interpreted as primary on the basis of a positive reversals test. The virtual geomagnetic pole position for the Abrahamskraal Formation computed from the average high‐temperature characteristic remanent magnetization direction is in agreement with the late Permian directions for stable Gondwana and with previous results from the lowermost Abrahamskraal Formation and Waterford Formation at the Ouberg Pass section. The predominantly normal polarity of this magnetization is in agreement with either a middle‐late Lopingian age (ca. 254–256 Ma) or a late Guadalupian age (ca. 262 Ma) according to the global geomagnetic polarity time scale. We integrate these new results with existing magnetostratigraphic, biostratigraphic, and geochronological results from the Karoo Basin, with particular emphasis on the controversy over zircon age data reported from the underlying Ecca Group.
Receiver function imaging of the mantle transition zone beneath the South China Block
Authors: Huang Haibo , Tosi Nicola , Chang Sung‐Joon , Xia Shaohong , Qiu Xuelin 
Published: October 2015

AbstractUpper mantle discontinuities are influenced by convection‐related thermal heterogeneities arising in complex geodynamic settings. Slab rollback of the Pacific plate and mantle upwelling in the Meso‐Cenozoic caused the extension and spreading of continental segments in the South China Block leading to profound variations of the local temperature conditions. We processed 201 teleseismic events beneath 87 stations in the Hainan, Guangdong, and Fujian provinces in the South China Block, and extracted 4172 high‐quality receiver functions. We imaged the topography of the local mantle discontinuities by using phase‐weighted common conversion point stacking of the receiver functions, which effectively improves the P‐to‐S‐converted phases. We found that the average depths of the discontinuities at 410 and 660 km depth are 414 and 657 km, respectively, while no clearly defined discontinuity at 520 km depth was detected. We mapped the thickness of the mantle transition zone (MTZ), which can reflect temperature and/or compositional heterogeneities as well as the presence of water, and discussed possible geodynamic implications. In particular, we found that the MTZ beneath the Leizhou Peninsula in the Hainan province is 42 km thinner than average. This scenario suggests that the Hainan plume is responsible for positive temperature anomalies between ∼270 and 380 K and between ∼200 and 240 K at the 660 and 410 km discontinuities, respectively. We also observed a prominent uplifting of the 660 km boundary beneath the coast regions that may be indicative of lateral flow of the Hainan plume.
Nucleation and dynamic rupture on weakly stressed faults sustained by thermal pressurization
Authors: Schmitt Stuart V. , Segall Paul , Dunham Eric M. 
Published: October 2015

AbstractEarthquake nucleation requires that the shear stress τ locally reaches a fault's static strength, fσeff, the product of the friction coefficient and effective normal stress. Once rupture initiates, shear heating‐induced thermal pressurization can sustain rupture at much lower τ/σeff ratios, a stress condition believed to be the case during most earthquakes. This requires that earthquakes nucleate at heterogeneities. We model nucleation and dynamic rupture on faults in a 2‐D elastic medium with rate/state friction and thermal pressurization, subjected to globally low τ but with local stress heterogeneities that permit nucleation. We examine end‐member cases of either high‐τ or low‐σeff heterogeneities. We find that thermal pressurization can sustain slip at τ/σeff values as low as 0.13, compared to static friction of ∼0.7. Background τ (and, to lesser extent, heterogeneity width) controls whether ruptures arrest or are sustained, with extremely low values resulting in arrest. For a small range of background τ, sustained slip is pulse‐like. Cessation of slip in a pulse tail can result from either diffusive restrengthening of σeff or a wave‐mediated stopping phase that follows the rupture tip. Slightly larger background τ leads to sustained crack‐like rupture. Thermal pressurization is stronger at high‐τ heterogeneities, resulting in a lower background τ threshold for sustained rupture and potentially larger arresting ruptures. High‐stress events also initiate with higher moment rate, although this may be difficult to observe in nature. For arresting ruptures, stress drops and the dependence of fracture energy on mean slip are both consistent with values inferred for small earthquakes.
Backscattering by very small particles in coastal waters
Authors: Zhang Xiaodong , Gray Deric J. 
Published: October 2015

AbstractThe volume scattering and backscattering by very small particles (VSPs) of sizes <0.2 µm in four coastal waters in U.S. (Chesapeake Bay, Monterey Bay, Mobile Bay, and the LEO‐15 site) were estimated by inverting the measured volume scattering functions (VSFs) at 532 nm. The measured VSFs are consistent with concurrent measurements of total scattering coefficients by the ac‐meters and angular scattering at 100, 125, and 150° by the ECO‐VSF sensor and at 140° by the HydroScat‐6 sensor. The inferred backscattering coefficients by the VSPs correlate strongly with the absorption coefficients measured for the colored dissolved organic matter, indicating that the dissolved portion of particles do scatter light. In the coastal waters that we studied, the backscattering by VSPs dominate over larger particles (of sizes >0.2 µm), accounting for 40–80% of total backscattering at 532 nm, while only account for <5% of total scattering.
Downward lee wave radiation from tropical instability waves in the central equatorial Pacific Ocean: A possible energy pathway to turbulent mixing
Authors: Tanaka Yuki , Hibiya Toshiyuki , Sasaki Hideharu 
Published: October 2015

AbstractTurbulent mixing in the equatorial Pacific Ocean is an important process that controls diapycnal heat transport and hence affects the air‐sea interactions and global climate. It is recently shown that, in the eastern equatorial Pacific, strong mixing is induced in the thermocline by enhanced vertical shear associated with tropical instability waves (TIWs), which propagate westward along the equator at a speed of
with a wavelength of
. In this study, using a high‐resolution ocean general circulation model, we show that the TIWs can play an important role in inducing turbulent mixing in the thermocline also in the central equatorial Pacific, although the thermocline is too deep to be directly affected by the vertical shear of the TIWs. The front of the TIW is clearly manifested as a narrow strip of strong convergence of horizontal surface flow, from which area downward and westward propagating internal waves are intermittently emanated. These internal waves can be interpreted as lee waves generated by the surface‐flow convergence zone, which acts like an inverted obstacle moving along the stratified ocean surface by inducing downward flow. The associated downward energy flux below the surface mixed layer increases as the TIW structure becomes deeper toward the central equatorial Pacific, so that the energy pathway to turbulent mixing in the thermocline can be created. The downward energy flux integrated over the entire equatorial Pacific and averaged during January 2011 amounts to ∼8.1 GW, occupying a significant fraction of the energy input to the TIWs.