bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cmv4, a New Locus Linked to the NK Cell Gene Complex, Controls Innate Resistance to Cytomegalovirus in Wild-Derived Mice
Authors: Adam Sonia Girard , Caraux Anouk , Fodil-Cornu Nassima , Loredo-Osti J. Concepcion , Lesjean-Pottier Sarah , Jaubert Jean , Bubic Ivan , Jonjic Stipan , Guénet Jean-Louis , Vidal Silvia M. , Colucci Francesco 
Published: April 2014

AbstractCMV can cause life-threatening disease in immunodeficient hosts. Experimental infection in mice has revealed that the genetically determined natural resistance to murine CMV (MCMV) may be mediated either by direct recognition between the NK receptor Ly49H and the pathogen-encoded glycoprotein m157 or by epistatic interaction between Ly49P and the host MHC H-2Dk. Using stocks of wild-derived inbred mice as a source of genetic diversity, we found that PWK/Pas (PWK) mice were naturally resistant to MCMV. Depletion of NK cells subverted the resistance. Analysis of backcrosses to susceptible BALB/c mice revealed that the phenotype was controlled by a major dominant locus effect linked to the NK gene complex. Haplotype analysis of 41 polymorphic markers in the Ly49h region suggested that PWK mice may share a common ancestral origin with C57BL/6 mice; in the latter, MCMV resistance is dependent on Ly49H-m157 interactions. Nevertheless, PWK mice retained viral resistance against m157-defective mutant MCMV. These results demonstrate the presence of yet another NK cell-dependent viral resistance mechanism, named Cmv4, which most likely encodes for a new NK activating receptor. Identification of Cmv4 will expand our understanding of the specificity of the innate recognition of infection by NK cells.
Loss of Dendritic Cell Migration and Impaired Resistance toLeishmania donovaniInfection in Mice Deficient in CCL19 and CCL21
Authors: Ato Manabu , Maroof Asher , Zubairi Soombul , Nakano Hideki , Kakiuchi Terutaka , Kaye Paul M. 
Published: April 2014

AbstractThe encounter between APC and T cells is crucial for initiating immune responses to infectious microorganisms. In the spleen, interaction between dendritic cells (DC) and T cells occurs in the periarteriolar lymphoid sheath (PALS) into which DC and T cells migrate from the marginal zone (MZ) along chemokine gradients. However, the importance of DC migration from the MZ into the PALS for immune responses and host resistance to microbial infection has not yet been elucidated. In this study, we report that following Leishmania donovani infection of mice, the migration of splenic DC is regulated by the CCR7 ligands CCL19/CCL21. DC in plt/plt mutant mice that lack these chemokines are less activated and produce less IL-12, compared with those in wild-type mice. Similar findings are seen when mice are treated with pertussis toxin, which blocks chemokine signaling in vivo. plt/plt mice had increased susceptibility to L. donovani infection compared with wild-type mice, as determined by spleen and liver parasite burden. Analysis of splenic cytokine profiles at day 14 postinfection demonstrated that IFN-γ and IL-4 mRNA accumulation was comparable in wild-type and plt/plt mice. In contrast, accumulation of mRNA for IL-10 was elevated in plt/plt mice. In addition, plt/plt mice mounted a delayed hepatic granulomatous response and fewer effector T cells migrated into the liver. Taken together, we conclude that DC migration from the MZ to the PALS is necessary for full activation of DC and the optimal induction of protective immunity against L. donovani.
Macrophage’s Proinflammatory Response to a Mycobacterial Infection Is Dependent on Sphingosine Kinase-Mediated Activation of Phosphatidylinositol Phospholipase C, Protein Kinase C, ERK1/2, and Phosphatidylinositol 3-Kinase
Authors: Yadav Mahesh , Clark Lindsay , Schorey Jeffrey S. 
Published: April 2014

AbstractPrevious studies have shown that the ability of Mycobacterium tuberculosis to block a Ca2+ flux is an important step in its capacity to halt phagosome maturation. This affect on Ca2+ release results from M. tuberculosis inhibition of sphingosine kinase (SPK) activity. However, these studies did not address the potential role of SPK and Ca2+ in other aspects of macrophage activation including production of proinflammatory mediators. We previously showed that nonpathogenic Mycobacterium smegmatis and to a lesser extent pathogenic Mycobacterium avium, activate Ca2+-dependent calmodulin/calmodulin kinase and MAPK pathways in murine macrophages leading to TNF-α production. However, whether SPK functions in promoting MAPK activation upon mycobacterial infection was not defined in these studies. In the present work we found that SPK is required for ERK1/2 activation in murine macrophages infected with either M. avium or M. smegmatis. Phosphoinositide-specific phospholipase C (PI-PLC) and conventional protein kinase C (cPKC) were also important for ERK1/2 activation. Moreover, there was increased activation of cPKC and PI3K in macrophages infected with M. smegmatis compared with M. avium. This cPKC and PI3K activation was dependent on SPK and PI-PLC. Finally, in macrophages infected with M. smegmatis compared with M. avium, we observed enhanced secretion of TNF-α, IL-6, RANTES, and G-CSF and found production of these inflammatory mediators to be dependent on SPK, PI-PLC, cPKC, and PI3K. These studies are the first to show that the macrophage proinflammatory response following a mycobacterial infection is regulated by SPK/PI-PLC/PKC activation of ERK1/2 and PI3K pathways.
Respiratory Syncytial Virus Inhibits Granulocyte Apoptosis through a Phosphatidylinositol 3-Kinase and NF-κB-Dependent Mechanism
Authors: Lindemans Caroline A. , Coffer Paul J. , Schellens Ingrid M. M. , de Graaff Patricia M. A. , Kimpen Jan L. L. , Koenderman Leo 
Published: April 2014

AbstractRespiratory syncytial virus (RSV) is a common cause of lower respiratory tract disease in children. It is associated with increased neutrophil numbers in the airway. In this study, we assessed whether this ssRNA virus can directly influence granulocyte longevity. By culturing RSV with granulocytes, it was observed that virus delays both constitutive neutrophil and eosinophil apoptosis. Using pharmacological inhibitors, the RSV-induced delay in neutrophil apoptosis was found to be dependent on both PI3K and NF-κB, but not p38 MAPK or MEK1/MEK2 activation. Using blocking Abs and a reporter cell line, we were able to exclude TLR4 as the receptor responsible for mediating RSV-induced delay in neutrophil apoptosis. The antiapoptotic effect was abrogated by preincubation with the lysosomotropic agent chloroquine, indicating the requirement for endolysosomal internalization. Furthermore, addition of ssRNA, a ligand for the intracellular TLR7/TLR8, also inhibited neutrophil apoptosis, suggesting that intracellular TLRs could be involved in induction of the antiapoptotic effect. Using the BioPlex cytokine detection assay (Bio-Rad), we found that IL-6 was present in supernatants from RSV-exposed neutrophils. IL-6 was found to inhibit neutrophil apoptosis, suggesting that there is an autocrine or paracrine antiapoptotic role for IL-6. Finally, RSV treatment of neutrophils resulted in increased expression of the antiapoptotic Bcl-2 protein Mcl-1. Taken together, our findings suggest involvement of multiple intracellular mechanisms responsible for RSV-induced survival of granulocytes and point toward a role for intracellular TLRs in mediating these effects.
Angiotensin II-Induced Mononuclear Leukocyte Interactions with Arteriolar and Venular Endothelium Are Mediated by the Release of Different CC Chemokines
Authors: Mateo Teresa , Naim Abu Nabah Yafa , Abu Taha May , Mata Manuel , Cerdá-Nicolás Miguel , Proudfoot Amanda E. I. , Stahl Rolf A. K. , Issekutz Andrew C. , Cortijo Julio , Morcillo Esteban J. , Jose Peter J. , Sanz Maria-Jesus 
Published: April 2014

Abstract
Angiotensin II (Ang-II) is associated with atherogenesis and arterial subendothelial mononuclear leukocyte infiltration. We have demonstrated that Ang-II causes the initial attachment of mononuclear cells to the arteriolar endothelium. We now report on the contribution of CC chemokines to this response. Intraperitoneal administration of 1 nM Ang-II induced MCP-1, RANTES, and MIP-1α generation, maximal at 4 h, followed by mononuclear leukocyte recruitment at 8 and 24 h. Using intravital microscopy within the rat mesenteric microcirculation 4 h after exposure to 1 nM Ang-II, arteriolar mononuclear cell adhesion was 80–90% inhibited by pretreatment with Met-RANTES, a CCR1 and CCR5 antagonist, or an anti-MCP-1 antiserum, without affecting the increased endothelial expression of P-selectin and VCAM-1. Conversely, leukocyte interactions with the venular endothelium, although inhibited by Met-RANTES, were little affected by the anti-MCP-1. Using rat whole blood in vitro, Ang-II (100 nM) induced the expression of monocyte CD11b that was inhibited by Met-RANTES but not by anti-MCP-1. Stimulation of human endothelial cells (human umbilical arterial endothelial cells and HUVECs) with 1–1000 nM Ang-II, predominantly acting at its AT1 receptor, induced the release of MCP-1 within 1 h, RANTES within 4 h, and MCP-3 within 24 h. Eotaxin-3, a natural CCR2 antagonist, was released within 1 h and may delay mononuclear cell responses to MCP-1. Therefore, Ang-II-induced mononuclear leukocyte recruitment at arterioles and venules is mediated by the production of different CC chemokines. Thus, Ang-II may be a key molecule in the initial attachment of mononuclear cells to the arterial endothelium in cardiovascular disease states where this event is a characteristic feature.
Absence of IL-1 Receptor Antagonist Impaired Wound Healing along with Aberrant NF-κB Activation and a Reciprocal Suppression of TGF-β Signal Pathway
Authors: Ishida Yuko , Kondo Toshikazu , Kimura Akihiko , Matsushima Kouji , Mukaida Naofumi 
Published: April 2014

Abstract
Although enhanced expression of IL-1 family proteins, including IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1ra) during wound healing has been observed, the pathophysiological roles of these factors, particularly IL-1ra, still remain elusive. We explored skin wound-healing processes in IL-1ra-deficient mice. Compared to wild-type (WT) mice, IL-1ra-deficient mice exhibited impaired wound healing, as evidenced by attenuated collagen deposition and delayed neovascularization. In contrast, neutrophil recruitment was significantly exaggerated, with the augmented expression of IL-1s, TNF-α, and CXC chemokines, MIP-2 and KC, in IL-1ra-deficient mice compared with WT mice. Because the transcription of these proinflammatory cytokines and CXC chemokines requires the activation of NF-κB, a major target of IL-1- and TNF-α-mediated signal pathway, we examined the activation states of NF-κB. Nuclear translocation of NF-κB p65 was significantly enhanced and prolonged in IL-1ra-deficient mice, compared to that in WT mice. The cross-talk between NF-κB and TGF-β-mediated signals has been proposed based on in vitro observations. Indeed, compared to WT mice, the amounts of total and phosphorylated Smad2 and Smad3 were decreased with a reciprocal increase in the amount of Smad7 in skin wound sites of IL-1ra-deficient mice. Moreover, the gene expression of vascular endothelial growth factor, a target gene of TGF-β1, was decreased in IL-1ra-deficient mice. Thus, the absence of IL-1ra may suppress TGF-β-mediated signaling pathway, which is crucial for collagen deposition and vascular endothelial growth factor-mediated neovascularization in wound healing.
Adenosine A2A Receptor Inactivation Increases Survival in Polymicrobial Sepsis
Authors: Németh Zoltán H. , Csóka Balázs , Wilmanski Jeanette , Xu DaZhong , Lu Qi , Ledent Catherine , Deitch Edwin A. , Pacher Pál , Spolarics Zoltán , Haskó György 
Published: April 2014

Abstract
The mechanisms governing the impairment of bacterial clearance and immune function in sepsis are not known. Adenosine levels are elevated during tissue hypoxia and damage associated with sepsis. Adenosine has strong immunosuppressive effects, many of which are mediated by A2A receptors (A2AR) expressed on immune cells. We examined whether A2AR are involved in the regulation of immune function in cecal ligation and puncture-induced murine polymicrobial sepsis by genetically or pharmacologically inactivating A2AR. A2AR knockout (KO) mice were protected from the lethal effect of sepsis and had improved bacterial clearance compared with wild-type animals. cDNA microarray analysis and flow cytometry revealed increased MHC II expression in A2A-inactivated mice, suggesting improved Ag presentation as a mechanism of protection. Apoptosis was attenuated in the spleen of A2A KO mice indicating preserved lymphocyte function. Levels of the immunosuppressive cytokines IL-10 and IL-6 were markedly lower following A2AR blockade. Similar to observations with A2AR KO mice, an A2AR antagonist increased survival even when administered in a delayed fashion. These studies demonstrate that A2AR blockade may be useful in the treatment of infection and sepsis.
Mimicry in Recognition of Cardiac Myosin Peptides by Heart-Intralesional T Cell Clones from Rheumatic Heart Disease
Authors: Faé Kellen C. , da Silva Danielle Diefenbach , Oshiro Sandra E. , Tanaka Ana C. , Pomerantzeff Pablo M. A. , Douay Corinne , Charron Dominique , Toubert Antoine , Cunningham Madeleine W. , Kalil Jorge , Guilherme Luiza 
Published: April 2014

AbstractMolecular mimicry between Streptococcus pyogenes Ags and human proteins has been considered as a mechanism leading to autoimmune reactions in rheumatic fever and rheumatic heart disease (RHD). Cardiac myosin has been shown as a putative autoantigen recognized by autoantibodies of rheumatic fever patients. We assessed the human heart-intralesional T cell response against human light meromyosin (LMM) and streptococcal M5 peptides and mitral-valve-derived proteins by proliferation assay. Cytokines induced by LMM peptides were also evaluated. The frequency of intralesional T cell clones that recognized LMM peptides was 63.2%. Thirty-four percent of T cell clones presented cross-reactivity with different patterns: 1) myosin and valve-derived proteins; 2) myosin and streptococcal M5 peptides; and 3) myosin, valve-derived proteins and M5 peptides. In addition, several LMM peptides were recognized simultaneously showing a multiple reactivity pattern of heart-infiltrating T cells. Inflammatory cytokines (IFN-γ and TNF-α) were predominantly produced by heart-infiltrating T cells upon stimulation with LMM peptides. The alignment of LMM and streptococcal M5 peptides showed frequent homology among conserved amino acid substitutions. This is the first study showing the cellular response by human heart-infiltrating T cells against cardiac myosin epitopes in RHD patients. The high percentage of reactivity against cardiac myosin strengthens its role as one of the major autoantigens involved in rheumatic heart lesions. T cell reactivity toward myosin epitopes in RHD patients may also trigger the broad recognition of valvular proteins with structural or functional similarities.
Neonatal Immunization with a Sindbis Virus-DNA Measles Vaccine Induces Adult-Like Neutralizing Antibodies and Cell-Mediated Immunity in the Presence of Maternal Antibodies
Authors: Capozzo Alejandra V. E. , Ramírez Karina , Polo John M. , Ulmer Jeffrey , Barry Eileen M. , Levine Myron M. , Pasetti Marcela F. 
Published: April 2014

Abstract
Infants younger than age 9 mo do not respond reliably to the live attenuated measles vaccine due the immaturity of their immune system and the presence of maternal Abs that interfere with successful immunization. We evaluated the immune responses elicited by Sindbis virus replicon-based DNA vaccines encoding measles virus (MV) hemagglutinin (H, pMSIN-H) or both hemagglutinin and fusion (F, pMSINH-FdU) glycoproteins in neonatal mice born to naive and measles-immune mothers. Despite the presence of high levels of maternal Abs, neonatal immunization with pMSIN-H induced long-lasting, high-avidity MV plaque reduction neutralization (PRN) Abs, mainly IgG2a, that also inhibited syncytium formation in CD150+ B95-8 cells. IgG secreting plasma cells were detected in spleen and bone marrow. Newborns vaccinated with pMSINH-FdU elicited PRN titers that surpassed the protective level (200 mIU/ml) but were short-lived, had low syncytium inhibition capacity, and lacked avidity maturation. This vaccine failed to induce significant PRN titers in the presence of placentally transferred Abs. Both pMSIN-H and pMSINH-FdU elicited strong Th1 type cell-mediated immunity, measured by T cell proliferation and IFN-γ production, that was unaffected by maternal Abs. Newborns responded to measles DNA vaccines with similar or even higher PRN titers and cell-mediated immunity than adult mice. This study is the first demonstration that a Sindbis virus-based measles DNA vaccine can elicit robust MV immunity in neonates bypassing maternal Abs. Such a vaccine could be followed by the current live attenuated MV vaccine in a heterologous prime-boost to protect against measles early in life.
Obstructions to Approximating Tropical Curves in Surfaces Via Intersection Theory
Authors: Brugallé Erwan , Shaw Kristin 
Published: April 2014

AbstractWe provide some new local obstructions to approximating tropical curves in smooth tropical surfaces. These obstructions are based on a relation between tropical and complex intersection theories, which is also established here. We give two applications of the methods developed in this paper. First we classify all locally irreducible approximable 3–valent fan tropical curves in a fan tropical plane. Secondly, we prove that a generic non–singular tropical surface in tropical projective 3–space contains finitely many approximable tropical lines if it is of degree 3, and contains no approximable tropical lines if it is of degree 4 or more.
Cardiovascular Change During Encoding Predicts the Nonconscious Mere Exposure Effect
Authors: Ladd Sandra L. , Toscano William B. , Cowings Patricia S. , Gabrieli John D. E. 
Published: April 2014

Abstract
These studies examined memory encoding to determine whether the mere exposure effect could be categorized as a form of conceptual or perceptual implicit priming and, if it was not conceptual or perceptual, whether cardiovascular psychophysiology could reveal its nature. Experiment 1 examined the effects of study phase level of processing on recognition, the mere exposure effect, and word identification implicit priming. Deep relative to shallow processing improved recognition but did not influence the mere exposure effect for nonwords or word identification implicit priming for words. Experiments 2 and 3 examined the effect of study-test changes in font and orientation, respectively, on the mere exposure effect and word identification implicit priming. Different study-test font and orientation reduced word identification implicit priming but had no influence on the mere exposure effect. Experiments 4 and 5 developed and used, respectively, a cardiovascular psychophysiological implicit priming paradigm to examine whether stimulus-specific cardiovascular reactivity at study predicted the mere exposure effect at test. Blood volume pulse change at study was significantly greater for nonwords that were later preferred than for nonwords that were not preferred at test. There was no difference in blood volume pulse change for words at study that were later either identified or not identified at test. Fluency effects, at encoding or retrieval, are an unlikely explanation for these behavioral and cardiovascular findings. The relation of blood volume pulse to affect suggests that an affective process that is not conceptual or perceptual contributes to the mere exposure effect.
Impulsivity and Physical Aggression: Examining the Moderating Role of Anxiety
Authors: Hatfield Joshua , Dula Chris S. 
Published: April 2014

Abstract
Individuals vary in their propensity to engage in aggressive behaviors, and recent research has sought to identify individual differences that contribute to a person’s propensity for physical aggression. Previous research has shown that impulsivity and aggression have a consistent relational pattern among many different samples. However, not all impulsive people will engage in aggressive behavior, perhaps because of other factors such as level of physiological arousal from anxiety. Specifically, one factor, namely physiological symptoms of anxiety such as those often associated with panic, may help as a predictor variable to be used in risk assessments or subclassification systems of aggression. Participants included 689 college students who completed self-report questionnaires assessing impulsivity, physical aggression, and anxiety. Multivariate hierarchical regression analyses were conducted. Greater scores on the measure of impulsivity were associated with higher levels of reported physical aggression. The interaction (impulsivity X anxiety) was not statistically significant, suggesting that impulsivity has the same effect on physical aggression regardless of the level of anxiety. There was a main effect for anxiety, which was associated with higher levels of reported physical aggression. Our findings may help inform typologies for identifying predictor variables used in risk assessment and treatment planning.
Experimental Evaluation of Tachistoscopic Measurement: A Step Beyond Wundt’s Criticism
Authors: VobořIl Dalibor , Jelínek Martin , Květon Petr 
Published: April 2014

Abstract
This study was designed to assess the possible systematic bias in measurements obtained using tachistoscopic devices from different historical periods of psychological research. Four different tachistoscopic devices were used for brief presentations of stimuli in a letter recognition task. The research sample consisted of 24 participants (12 female, 12 male) in a within-subject experimental design with complete counterbalancing of 4 conditions defined by 4 instrument types: fall tachistoscope, tachistoscope with camera-like shutter, and computer-based tachistoscopes with cathode ray tube and liquid crystal diode display screens. The effects of experimental conditions were examined using a linear mixed model analysis. Our experiment demonstrated that even in standardized settings the type of tachistoscope used for stimulus presentation systematically influenced the participants’ performance. We found that the lowest number of correctly recalled stimuli, as well as the highest number of erroneously recalled stimuli, was produced in the camera-like tachistoscope condition. Together, these findings suggest that when results from studies involving tachistoscopic experiments are reviewed, the unique characteristics of each particular instrument used must be considered carefully.