bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deficiency of Antigen-Specific B Cells Results in Decreased Trypanosoma cruzi Systemic but Not Mucosal Immunity Due to CD8 T Cell Exhaustion
Authors: Sullivan Nicole L. , Eickhoff Christopher S. , Sagartz John , Hoft Daniel F. 
Published: January 2015

Abstract
Vaccines against mucosally invasive, intracellular pathogens must induce a myriad of immune responses to provide optimal mucosal and systemic protection, including CD4+ T cells, CD8+ T cells, and Ab-producing B cells. In general, CD4+ T cells are known to provide important helper functions for both CD8+ T cell and B cell responses. However, the relative importance of CD4+ T cells, CD8+ T cells, and B cells for mucosal protection is less clearly defined. We have studied these questions in detail using the murine model of Trypanosoma cruzi infection. Despite our initial hypothesis that mucosal Abs would be important, we show that B cells are critical for systemic, but not mucosal, T. cruzi protective immunity. B cell–deficient mice developed normal levels of CD8+ effector T cell responses early after mucosal T. cruzi infection and T. cruzi trans-sialidase vaccination. However, after highly virulent systemic challenge, T. cruzi immune mice lacking T. cruzi–specific B cells failed to control parasitemia or prevent death. Mechanistically, T. cruzi–specific CD8+ T cells generated in the absence of B cells expressed increased PD-1 and Lag-3 and became functionally exhausted after high-level T. cruzi systemic challenge. T. cruzi immune serum prevented CD8+ T cell functional exhaustion and reduced mortality in mice lacking B cells. Overall, these results demonstrate that T. cruzi–specific B cells are necessary during systemic, but not mucosal, parasite challenge.
Transplanted Bone Marrow–Derived Circulating PDGFRα+ Cells Restore Type VII Collagen in Recessive Dystrophic Epidermolysis Bullosa Mouse Skin Graft
Authors: Iinuma Shin , Aikawa Eriko , Tamai Katsuto , Fujita Ryo , Kikuchi Yasushi , Chino Takenao , Kikuta Junichi , McGrath John A. , Uitto Jouni , Ishii Masaru , Iizuka Hajime , Kaneda Yasufumi 
Published: January 2015

Abstract
Recessive dystrophic epidermolysis bullosa (RDEB) is an intractable genetic blistering skin disease in which the epithelial structure easily separates from the underlying dermis because of genetic loss of functional type VII collagen (Col7) in the cutaneous basement membrane zone. Recent studies have demonstrated that allogeneic bone marrow transplantation (BMT) ameliorates the skin blistering phenotype of RDEB patients by restoring Col7. However, the exact therapeutic mechanism of BMT in RDEB remains unclear. In this study, we investigated the roles of transplanted bone marrow–derived circulating mesenchymal cells in RDEB (Col7-null) mice. In wild-type mice with prior GFP-BMT after lethal irradiation, lineage-negative/GFP-positive (Lin−/GFP+) cells, including platelet-derived growth factor receptor α-positive (PDGFRα+) mesenchymal cells, specifically migrated to skin grafts from RDEB mice and expressed Col7. Vascular endothelial cells and follicular keratinocytes in the deep dermis of the skin grafts expressed SDF-1α, and the bone marrow–derived PDGFRα+ cells expressed CXCR4 on their surface. Systemic administration of the CXCR4 antagonist AMD3100 markedly decreased the migration of bone marrow–derived PDGFRα+ cells into the skin graft, resulting in persistent epidermal detachment with massive necrosis and inflammation in the skin graft of RDEB mice; without AMD3100 administration, Col7 was significantly supplemented to ameliorate the pathogenic blistering phenotype. Collectively, these data suggest that the SDF1α/CXCR4 signaling axis induces transplanted bone marrow–derived circulating PDGFRα+ mesenchymal cells to migrate and supply functional Col7 to regenerate RDEB skin.
PTEN Is a Negative Regulator of NK Cell Cytolytic Function
Authors: Briercheck Edward L. , Trotta Rossana , Chen Li , Hartlage Alex S. , Cole Jordan P. , Cole Tyler D. , Mao Charlene , Banerjee Pinaki P. , Hsu Hsiang-Ting , Mace Emily M. , Ciarlariello David , Mundy-Bosse Bethany L. , Garcia-Cao Isabel , Scoville Steven D. , Yu Lianbo , Pilarski Robert , Carson William E. , Leone Gustavo , Pandolfi Pier Paolo , Yu Jianhua , Orange Jordan S. , Caligiuri Michael A. 
Published: January 2015

Abstract
Human NK cells are characterized by their ability to initiate an immediate and direct cytolytic response to virally infected or malignantly transformed cells. Within human peripheral blood, the more mature CD56dim NK cell efficiently kills malignant targets at rest, whereas the less mature CD56bright NK cells cannot. In this study, we show that resting CD56bright NK cells express significantly more phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein when compared with CD56dim NK cells. Consistent with this, forced overexpression of PTEN in NK cells resulted in decreased cytolytic activity, and loss of PTEN in CD56bright NK cells resulted in elevated cytolytic activity. Comparable studies in mice showed PTEN overexpression did not alter NK cell development or NK cell–activating and inhibitory receptor expression yet, as in humans, did decrease expression of downstream NK activation targets MAPK and AKT during early cytolysis of tumor target cells. Confocal microscopy revealed that PTEN overexpression disrupts the NK cell’s ability to organize immunological synapse components including decreases in actin accumulation, polarization of the microtubule organizing center, and the convergence of cytolytic granules. In summary, our data suggest that PTEN normally works to limit the NK cell’s PI3K/AKT and MAPK pathway activation and the consequent mobilization of cytolytic mediators toward the target cell and suggest that PTEN is among the active regulatory components prior to human NK cells transitioning from the noncytolytic CD56bright NK cell to the cytolytic CD56dim NK cells.
Loss of Mouse P2Y4 Nucleotide Receptor Protects against Myocardial Infarction through Endothelin-1 Downregulation
Authors: Horckmans Michael , Esfahani Hrag , Beauloye Christophe , Clouet Sophie , di Pietrantonio Larissa , Robaye Bernard , Balligand Jean-Luc , Boeynaems Jean-Marie , Dessy Chantal , Communi Didier 
Published: January 2015

Abstract
Nucleotides are released in the heart under pathological conditions, but little is known about their contribution to cardiac inflammation. The present study defines the P2Y4 nucleotide receptor, expressed on cardiac microvascular endothelial cells and involved in postnatal heart development, as an important regulator of the inflammatory response to cardiac ischemia. P2Y4-null mice displayed smaller infarcts in the left descending artery ligation model, as well as reduced neutrophil infiltration and fibrosis. Gene profiling identified inter alia endothelin-1 (ET-1) as one of the target genes of P2Y4 in ischemic heart. The reduced level of ET-1 was correlated with reduction of microvascular hyperpermeability, neutrophil infiltration, and endothelial adhesion molecule expression, and it could be explained by the decreased number of endothelial cells in P2Y4-null mice. Expression analysis of metalloproteinases and their tissue inhibitors in ischemic heart revealed reduced expression of matrix metalloproteinase (MMP)-9, reported to be potentially regulated by ET-1, and MMP-8, considered as neutrophil collagenase, as well as reduction of tissue inhibitor of MMP-1 and tissue inhibitor of MMP-4 in P2Y4-null mice. Reduction of cardiac permeability and neutrophil infiltration was also observed in P2Y4-null mice in LPS-induced inflammation model. Protection against infarction resulting from loss of P2Y4 brings new therapeutic perspectives for cardiac ischemia and remodeling.
Natural IgM Prevents Autoimmunity by Enforcing B Cell Central Tolerance Induction
Authors: Nguyen Trang T. T. , Elsner Rebecca A. , Baumgarth Nicole 
Published: January 2015

Abstract
It is unclear why selective deficiency in secreted (s)IgM causes Ab-mediated autoimmunity. We demonstrate that sIgM is required for normal B cell development and selection. The CD5+ B cells that were previously shown to accumulate in body cavities of sIgM−/− mice are not B-1a cells, but CD19int, CD43−, short-lived, BCR signaling–unresponsive anergic B-2 cells. Body cavity B-1 cells were &gt;10-fold reduced, including VH11+ and phosphotidylcholine-specific B-1a cells, whereas splenic B-1 cells were unaffected and marginal zone B cells increased. Follicular B cells had higher turnover rates, survived poorly after adoptive transfer, and were unresponsiveness to BCR stimulation in vitro. sIgM bound to B cell precursors and provided a positive signal to overcome a block at the pro/pre–B stage and during IgVH repertoire selection. Polyclonal IgM rescued B cell development and returned autoantibody levels to near normal. Thus, natural IgM deficiency causes primary autoimmune disease by altering B cell development, selection, and central tolerance induction.
Cutting Edge: Identification of Neutrophil PGLYRP1 as a Ligand for TREM-1
Authors: Read Christine B. , Kuijper Joseph L. , Hjorth Siv A. , Heipel Mark D. , Tang Xiaoting , Fleetwood Andrew J. , Dantzler Jeffrey L. , Grell Susanne N. , Kastrup Jesper , Wang Camilla , Brandt Cameron S. , Hansen Anker J. , Wagtmann Nicolai R. , Xu Wenfeng , Stennicke Vibeke W. 
Published: January 2015

Abstract
Triggering receptor expressed on myeloid cells (TREM)-1 is an orphan receptor implicated in innate immune activation. Inhibition of TREM-1 reduces sepsis in mouse models, suggesting a role for it in immune responses triggered by bacteria. However, the absence of an identified ligand has hampered a full understanding of TREM-1 function. We identified complexes between peptidoglycan recognition protein 1 (PGLYRP1) and bacterially derived peptidoglycan that constitute a potent ligand capable of binding TREM-1 and inducing known TREM-1 functions. Interestingly, multimerization of PGLYRP1 bypassed the need for peptidoglycan in TREM-1 activation, demonstrating that the PGLYRP1/TREM-1 axis can be activated in the absence of bacterial products. The role for PGLYRP1 as a TREM-1 activator provides a new mechanism by which bacteria can trigger myeloid cells, linking two known, but previously unrelated, pathways in innate immunity.
Evasion of Innate Cytosolic DNA Sensing by a Gammaherpesvirus Facilitates Establishment of Latent Infection
Authors: Sun Chenglong , Schattgen Stefan A. , Pisitkun Prapaporn , Jorgensen Joan P. , Hilterbrand Adam T. , Wang Lucas J. , West John A. , Hansen Kathrine , Horan Kristy A. , Jakobsen Martin R. , O’Hare Peter , Adler Heiko , Sun Ren , Ploegh Hidde L. , Damania Blossom , Upton Jason W. , Fitzgerald Katherine A. , Paludan Søren R. 
Published: January 2015

Abstract
Herpesviruses are DNA viruses harboring the capacity to establish lifelong latent-recurrent infections. There is limited knowledge about viruses targeting the innate DNA-sensing pathway, as well as how the innate system impacts on the latent reservoir of herpesvirus infections. In this article, we report that murine gammaherpesvirus 68 (MHV68), in contrast to α- and β-herpesviruses, induces very limited innate immune responses through DNA-stimulated pathways, which correspondingly played only a minor role in the control of MHV68 infections in vivo. Similarly, Kaposi’s sarcoma–associated herpesvirus also did not stimulate immune signaling through the DNA-sensing pathways. Interestingly, an MHV68 mutant lacking deubiquitinase (DUB) activity, embedded within the large tegument protein open reading frame (ORF)64, gained the capacity to stimulate the DNA-activated stimulator of IFN genes (STING) pathway. We found that ORF64 targeted a step in the DNA-activated pathways upstream of the bifurcation into the STING and absent in melanoma 2 pathways, and lack of the ORF64 DUB was associated with impaired delivery of viral DNA to the nucleus, which, instead, localized to the cytoplasm. Correspondingly, the ORF64 DUB active site mutant virus exhibited impaired ability to establish latent infection in wild-type, but not STING-deficient, mice. Thus, gammaherpesviruses evade immune activation by the cytosolic DNA-sensing pathway, which, in the MHV68 model, facilitates establishment of infections.
Cutting Edge: The BTLA–HVEM Regulatory Pathway Interferes with Protective Immunity to Intestinal Helminth Infection
Authors: Breloer Minka , Hartmann Wiebke , Blankenhaus Birte , Eschbach Marie-Luise , Pfeffer Klaus , Jacobs Thomas 
Published: January 2015

Abstract
Helminths exploit intrinsic regulatory pathways of the mammalian immune system to dampen the immune response directed against them. In this article, we show that infection with the parasitic nematode Strongyloides ratti induced upregulation of the coinhibitory receptor B and T lymphocyte attenuator (BTLA) predominantly on CD4+ T cells but also on a small fraction of innate leukocytes. Deficiency of either BTLA or its ligand herpes virus entry mediator (HVEM) resulted in reduced numbers of parasitic adults in the small intestine and reduced larval output throughout infection. Reduced parasite burden in BTLA- and HVEM-deficient mice was accompanied by accelerated degranulation of mucosal mast cells and increased Ag-specific production of the mast cell–activating cytokine IL-9. Our combined results support a model whereby BTLA on CD4+ T cells and additional innate leukocytes is triggered by HVEM and delivers negative signals into BTLA+ cells, thereby interfering with the protective immune response to this intestinal parasite.
Cutting Edge: DNase II Deficiency Prevents Activation of Autoreactive B Cells by Double-Stranded DNA Endogenous Ligands
Authors: Pawaria Sudesh , Moody Krishna , Busto Patricia , Nündel Kerstin , Choi Chee-Ho , Ghayur Tariq , Marshak-Rothstein Ann 
Published: January 2015

Abstract
In mice that fail to express the phagolysosomal endonuclease DNase II and the type I IFN receptor, excessive accrual of undegraded DNA results in a STING-dependent, TLR-independent inflammatory arthritis. These double-knockout (DKO) mice develop additional indications of systemic autoimmunity, including anti-nuclear autoantibodies and splenomegaly, that are not found in Unc93b13d/3d DKO mice and, therefore, are TLR dependent. The DKO autoantibodies predominantly detect RNA-associated autoantigens, which are commonly targeted in TLR7-dominated systemic erythematosus lupus–prone mice. To determine whether an inability of TLR9 to detect endogenous DNA could explain the absence of dsDNA-reactive autoantibodies in DKO mice, we used a novel class of bifunctional autoantibodies, IgM/DNA dual variable domain Ig molecules, to activate B cells through a BCR/TLR9-dependent mechanism. DKO B cells could not respond to the IgM/DNA dual variable domain Ig molecule, despite a normal response to both anti-IgM and CpG ODN 1826. Thus, DKO B cells only respond to RNA-associated ligands because DNase II–mediated degradation of self-DNA is required for TLR9 activation.
Clinical and radiological findings of a bilateral coronoid hyperplasia case
Authors: Torenek Kubra , Duman Suayip Burak , Bayrakdar Ibrahim Sevki , Miloglu Ozkan 
Published: January 2015

ABSTRACTCoronoid hyperplasia (CH) is an infrequent condition that can be defined as an abnormal bony elongation of histologically normal bone. Progressive and painless difficulty in opening the mouth is the main clinical finding of CH. In this case report, the clinical and radiological findings for a 23-year-old male patient with bilateral CH are presented. When plain radiographies are not sufficient for diagnosis and evaluation of the CH, cone-beam computed tomography can be used.
Les deux éditions du Rituel du diocèse de Québec de Mgr de Saint-Vallier, datées de 1703 : de l’édition janséniste à l’édition revue et corrigée par la Compagnie de Jésus
Authors: La Charité Claude 
Published: January 2015

Mgr de Saint-Vallier, deuxième évêque de Québec, publia, à l’usage des prêtres, des curés et des missionnaires de son diocèse, un Rituel qui connut deux éditions successives à quelques années d’intervalle, bien qu’elles soient toutes deux datées de 1703. Ce Rituel bilingue donne d’une part des instructions en français à l’usage des ecclésiastiques sur la manière d’administrer les sacrements et de célébrer la messe, tout en précisant d’autre part les formules, les prières et les bénédictions que les prêtres devaient prononcer en latin. Les deux éditions imprimées à Paris par Simon Langlois présentent des variantes substantielles. Alors qu’elles sont de format identique (in-8o), elles comptent respectivement 604 et 671 pages. La première édition fut vraisemblablement détruite à la demande de l’évêque de Québec, parce qu’elle témoignait trop clairement de l’influence marquée, non pas simplement du rigorisme, mais bien du jansénisme sur Mgr de Saint-Vallier, comme en témoigne la reprise du rituel d’Alet condamné par le pape Clément IX. La seconde édition, publiée sans doute vers 1713, bien qu’elle soit datée de 1703, était destinée à remplacer la première comme si celle-ci n’avait jamais existé, au moment où le pouvoir pontifical condamna le jansénisme.
Bioética y derechos humanos
Authors: Díaz Javier De la Torre , García Maria Del Carmen Massé 
Published: January 2015

El progreso biotecnológico de los últimos decenios ha tocado las profundidades de la naturaleza humana, sus derechos, sus confines, su dignidad. La necesidad de poner límites a dicha actividad humana ha llevado a que el Convenio de Oviedo, de 1997 y la Declaración Universal de Bioética y Derechos Humanos, hayan marcado las principales áreas que deben ser reguladas así como los principios por los que deben regirselos avances científico-técnicos en el ámbito de la vida humana. Sin embargo, la complejidad de este fenómeno obliga reformular nuevas cuestiones más allá del principio de autonomía y más en consonancia con el principio de justicia: el alcance universal del derecho al desarrollo ha llevado, por ejemplo, a que el derecho a la salud de millones de personas sea una prioridad frente al derecho a la propiedad, así como al establecimiento de fronteras claras y nítidas para el sujeto del derecho a la vida, en su comienzo o en su final, por su profunda vulnerabilidad social. Son los nuevos retos para unos Derechos Humanos nacidos para defender a los seres humanos, a todos los seres humanos.
Dilatant hardening of fluid‐saturated sandstone
Authors: Makhnenko Roman Y. , Labuz Joseph F. 
Published: January 2015

AbstractThe presence of pore fluid in rock affects both the elastic and inelastic deformation processes, yet laboratory testing is typically performed on dry material even though in situ the rock is often saturated. Techniques were developed for testing fluid‐saturated porous rock under the limiting conditions of drained, undrained, and unjacketed response. Confined compression experiments, both conventional triaxial and plane strain, were performed on water‐saturated Berea sandstone to investigate poroelastic and inelastic behavior. Measured drained response was used to calibrate an elasto‐plastic constitutive model that predicts undrained inelastic deformation. The experimental data show good agreement with the model: dilatant hardening in undrained triaxial and plane strain compression tests under constant mean stress was predicted and observed.
The spatial‐temporal variability of air‐sea momentum fluxes observed at a tidal inlet
Authors: Ortiz‐Suslow D. G. , Haus B. K. , Williams N. J. , Laxague N. J. M. , Reniers A. J. H. M. , Graber H. C. 
Published: January 2015

AbstractCoastal waters are an aerodynamically unique environment that has been little explored from an air‐sea interaction point of view. Consequently, most studies must assume that open ocean‐derived parameterizations of the air‐sea momentum flux are representative of the nearshore wind forcing. Observations made at the New River Inlet in North Carolina, during the Riverine and Estuarine Transport experiment (RIVET), were used to evaluate the suitability of wind speed‐dependent, wind stress parameterizations in coastal waters. As part of the field campaign, a small, agile research vessel was deployed to make high‐resolution wind velocity measurements in and around the tidal inlet. The eddy covariance method was employed to recover direct estimates of the 10 m neutral atmospheric drag coefficient from the three‐dimensional winds. Observations of wind stress angle, near‐surface currents, and heat flux were used to analyze the cross‐shore variability of wind stress steering off the mean wind azimuth. In general, for onshore winds above 5 m/s, the drag coefficient was observed to be two and a half times the predicted open ocean value. Significant wind stress steering is observed within 2 km of the inlet mouth, which is observed to be correlated with the horizontal current shear. Other mechanisms such as the reduction in wave celerity or depth‐limited breaking could also play a role. It was determined that outside the influence of these typical coastal processes, the open ocean parameterizations generally represent the wind stress field. The nearshore stress variability has significant implications for observations and simulations of coastal transport, circulation, mixing, and general surf‐zone dynamics.
The parametric sensitivity of CAM5's MJO
Authors: Boyle J. S. , Klein S. A. , Lucas D. D. , Ma H.‐Y. , Tannahill J. , Xie S. 
Published: January 2015

AbstractWe systematically explore the ability of the Community Atmospheric Model version 5 (CAM5) to simulate the Madden‐Julian Oscillation (MJO), through an analysis of MJO metrics calculated from a 1100‐member perturbed parameter ensemble of 5 year simulations with observed sea surface temperatures. Parameters from the deep convection scheme make the greatest contribution to the variance in MJO simulation quality with a much smaller contribution from parameters in the large‐scale cloud, shallow convection, and boundary layer turbulence schemes. Improved MJO variability results from a larger lateral entrainment rate and a reduction in the precipitation efficiency of deep convection that was achieved by a smaller autoconversion of cloud to rainwater and a larger evaporation of convective precipitation. Unfortunately, simulations with an improved MJO also have a significant negative impact on the climatological values of low‐level cloud and absorbed shortwave radiation, suggesting that structural in addition to parametric modifications to CAM5's parameterization suite are needed in order to simultaneously well simulate the MJO and mean‐state climate.
Grain‐scale thermoelastic stresses and spatiotemporal temperature gradients on airless bodies, implications for rock breakdown
Authors: Molaro Jamie L. , Byrne Shane , Langer Stephen A. 
Published: January 2015

AbstractThermomechanical processes such as fatigue and shock have been suggested to cause and contribute to rock breakdown on Earth, and on other planetary bodies, particularly airless bodies in the inner solar system. In this study, we modeled grain‐scale stresses induced by diurnal temperature variations on simple microstructures made of pyroxene and plagioclase on various solar system bodies. We found that a heterogeneous microstructure on the Moon experiences peak tensile stresses on the order of 100 MPa. The stresses induced are controlled by the coefficient of thermal expansion and Young's modulus of the mineral constituents, and the average stress within the microstructure is determined by relative volume of each mineral. Amplification of stresses occurs at surface‐parallel boundaries between adjacent mineral grains and at the tips of pore spaces. We also found that microscopic spatial and temporal surface temperature gradients do not correlate with high stresses, making them inappropriate proxies for investigating microcrack propagation. Although these results provide very strong evidence for the significance of thermomechanical processes on airless bodies, more work is needed to quantify crack propagation and rock breakdown rates.