bluuebunny/crossref_metadata_2025 huggingface dataset:
Scanning the HIV Genome for CD4+ T Cell Epitopes Restricted to HLA-DP4, the Most Prevalent HLA Class II Molecule
Authors: Cohen William M. , Pouvelle-Moratille Sandra , Wang Xiao-Fei , Farci Sandrine , Munier Gaetan , Charron Dominique , Ménez André , Busson Marc , Maillère Bernard
Published: April 2014

HLA-DP4 alleles are carried by 75% of individuals and are the most frequent HLA II alleles worldwide. Because we have recently characterized the peptide-binding specificity of HLA-DP4 molecules, we developed a peptide-binding prediction method to identify HLA-DP4-restricted peptides in multiple Ags. CD4+ T cell response plays a key role in the immune control of HIV infection, but few HIV-specific T cell epitopes with multi-individual specificity have been identified. They are mostly restricted to HLA-DR molecules, which are very polymorphic molecules. We therefore looked for HLA-DP4-restricted CD4+ T cell epitopes in the whole genome of HIV. Twenty-one peptides were selected from the HXB2 HIV genome based on the prediction of binding to HLA-DP4 molecules. They were submitted to HLA-DP4-binding assays. Seventeen peptides bound to the HLA-DP401 molecule, whereas 15 peptides bound to HLA-DP402. Six peptides bound very tightly to HLA-DP401 and were investigated for their capacity to induce specific CD4+ T cell lines in vitro using dendritic cells and CD4+ T cells collected from eight seronegative HLA-DP4+ donors. Four peptides from env and reverse transcriptase proteins induced in vitro-specific T cell lines restricted to HLA-DP4 molecules. Peptide-induced T cells recognized variants other than the HXB2 sequence and were stimulated by native Ags processed by immature dendritic cells. The reverse transcriptase peptide is present in 65% of the isolated HIV variants. To our knowledge, we describe the first HIV epitopes restricted to HLA-DP4 molecules.
Activation of V(D)J Recombination at the IgH Chain JH Locus Occurs within a 6-Kilobase Chromatin Domain and Is Associated with Nucleosomal Remodeling
Authors: Maës Jérôme , Chappaz Stéphane , Cavelier Patricia , O’Neill Laura , Turner Bryan , Rougeon François , Goodhardt Michele
Published: April 2014

IgH genes are assembled during early B cell development by a series of regulated DNA recombination reactions in which DH and JH segments are first joined followed by VH to DJH rearrangement. Recent studies have highlighted the role of chromatin structure in the control of V(D)J recombination. In this study, we show that, in murine pro-B cell precursors, the JH segments are located within a 6-kb DNase I-sensitive chromatin domain containing acetylated histones H3 and H4, which is delimited 5′ by the DQ52 promoter element and 3′ by the intronic enhancer. Within this domain, the JH segments are covered by phased nucleosomes. High-resolution mapping of nucleosomes reveals that, in pro-B cells, unlike recombination refractory nonlymphoid cells, the recombination signal sequences flanking the four JH segments are located in regions of enhanced micrococcal nuclease and restriction enzyme accessibility, corresponding to either nucleosome-free regions or DNA rendered accessible within a nucleosome. These results support the idea that nucleosome remodeling provides an additional level of control in the regulation of Ig locus accessibility to recombination factors in B cell precursors.
A Role for the MutL Mismatch Repair Mlh3 Protein in Immunoglobulin Class Switch DNA Recombination and Somatic Hypermutation
Authors: Wu Xiaoping , Tsai Connie Y. , Patam Marienida B. , Zan Hong , Chen Jessica P. , Lipkin Steve M. , Casali Paolo
Published: April 2014

Class switch DNA recombination (CSR) and somatic hypermutation (SHM) are central to the maturation of the Ab response. Both processes involve DNA mismatch repair (MMR). MMR proteins are recruited to dU:dG mispairs generated by activation-induced cytidine deaminase-mediated deamination of dC residues, thereby promoting S-S region synapses and introduction of mismatches (mutations). The MutL homolog Mlh3 is the last complement of the mammalian set of MMR proteins. It is highly conserved in evolution and is essential to meiosis and microsatellite stability. We used the recently generated knockout mlh3−/− mice to address the role of Mlh3 in CSR and SHM. We found that Mlh3 deficiency alters both CSR and SHM. mlh3−/− B cells switched in vitro to IgG and IgA but displayed preferential targeting of the RGYW/WRCY (R = A or G, Y = C or T, W = A or T) motif by Sγ1 and Sγ3 breakpoints and introduced more insertions and fewer donor/acceptor microhomologies in Sμ-Sγ1 and Sμ-Sγ3 DNA junctions, as compared with mlh3+/+ B cells. mlh3−/− mice showed only a slight decrease in the frequency of mutations in the intronic DNA downstream of the rearranged JH4 gene. However, the residual mutations were altered in spectrum. They comprised a decreased proportion of mutations at dA/dT and showed preferential RGYW/WRCY targeting by mutations at dC/dG. Thus, the MMR Mlh3 protein plays a role in both CSR and SHM.
Triggering of T Cell Activation via CD4 Dimers
Authors: Moldovan Maria-Cristina , Sabbagh Laurent , Breton Gaëlle , Sékaly Rafick-Pierre , Krummel Matthew F.
Published: April 2014

The onset of activation in Th cells is triggered by localized coengagement of TCRs and the coreceptor CD4. A CD4 crystal suggested that CD4 may form dimers in some circumstances. In this study, we use live-cell fluorescence resonance energy transfer imaging to demonstrate that CD4 dimers are present at a basal level on the cell surface and accumulate at the synapse. Mechanistically, we reveal two conditions under which dimers are highly relevant. First, CD4 dimers are more proficient in mediating prolonged cell contacts with APCs in the presence or absence of Ag. This is consistent with a model whereby the dimer functions to increase T-APC avidity. Second, we show that dimer mutations result in an increased level of an inactive lckTyr505 bound to the CD4 molecule relative to dimer-competent CD4. We also find a consistent defect in signaling onset in these cells. This supports a role for CD4 dimerization in maintaining active signaling machinery. We suggest that modulation of the dimer/monomer ratio may permit tuning of activation thresholds during initial engagement.
Replication Initiation from a Novel Origin Identified in the Th2 Cytokine Cluster Locus Requires a Distant Conserved Noncoding Sequence
Authors: Hayashida Toshiro , Oda Masako , Ohsawa Kanako , Yamaguchi Atsumi , Hosozawa Takumi , Locksley Richard M. , Giacca Mauro , Masai Hisao , Miyatake Shoichiro
Published: April 2014

Lineage commitment of Th cells is associated with the establishment of specific transcriptional programs of cytokines. However, how Th cell differentiation affects the program of DNA replication has not been addressed. To gain insight into interplays between differentiation-induced transcription regulation and initiation of DNA replication, we took advantage of an in vitro differentiation system of naive T cells, in which one can manipulate their differentiation into Th1 or Th2 cells. We searched for replication origins in the murine IL-4/IL-13 locus and compared their profiles in the two Th cell lineages which were derived in vitro from the same precursor T cells. We identified a replication origin (oriIL-13) downstream from exon 4 of IL-13 and showed that this origin functions in both Th2 and Th1 cells. A distant regulatory element called CNS-1 (conserved noncoding sequence 1) in the IL-4/IL-13 intergenic region coincides with a Th2-specific DNase I-hypersensitive site and is required for efficient, coordinated expression of Th2 cytokines. Replication initiation from oriIL-13 is significantly reduced in Th1 and Th2 cells derived from CNS-1-deficient mice. However, the replication timing of this locus is consistently early during S phase in both Th1 and Th2 cells under either the wild-type or CNS-1 deletion background. Thus, the conserved noncoding element in the intergenic region regulates replication initiation from a distant replication origin in a manner independent from its effect on lineage-specific transcription but not the replication timing of the segment surrounding this origin.
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

CMV 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

The 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

Previous 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

Respiratory 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

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

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

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

Molecular 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

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

We 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

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

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

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.
Bilateral pathological neck of femur fractures associated with low grade splenic marginal zone lymphoma: Case report, and review of the literature
Authors: Fallahi F , Waton A , Mansha M , Cope W , O’Brien H , Young C F
Published: April 2014

We report a case involving a 64 year old lady with bilateral pathological fractures of the neck of the femur secondary to Low Grade Splenic Marginal Zone Lymphoma, a pathology that has not previously been described in clinical literature. This particular case also highlights the value of the diagnosis and management of patients presenting with subtle and unusual symptoms, and supports the current guidance of the National Institute for Health and Care Excellence regarding the investigation of patients with suspected pathological neck of femur fracture.
Clase social de origen y rendimiento escolar como predictores de las trayectorias educativas
Authors: Cebolla- Boado Hector , Bernardi Fabrizio
Published: April 2014

En este artículo exploramos el impacto del rendimiento escolar (conocidocomo efectos primarios) y la estructura de costes y beneficios a los quese enfrentan los individuos de distinta clase social de origen (efectossecundarios) cuando afrontan la transición entre la educación obligatoriay no obligatoria en España. Ambos predictores de las trayectorias operana través de un efecto de interacción contribuyendo a la reproducción dedesigualdades educativas. Esta interacción parece sugerir que elrendimiento escolar no es interpretado de la misma forma por losindividuos de distinto origen social. En concreto, existe un efecto decompensación por el que los estudiantes de clase alta tienen unaprobabilidad mayor de alcanzar estudios secundarios superiores ouniversitarios con respecto a los estudiantes de clase baja, cuando sus«notas» son malas. Por lo tanto, la desigualdad por clase social de origenes máxima entre los peores estudiantes.
Authenticity of Mathematical Modeling
Authors: Tran Dung , Dougherty Barbara J.
Published: April 2014

The choice and context of authentic problems—such as designing a staircase or a soda can—illustrate the modeling process in several stages.
Equivalent Expressions Using CAS and Paper-and-Pencil Techniques
Authors: Fonger Nicole L.
Published: April 2014

Designing activities to reconcile multiple representations supports students' focus and fluency.
Activities for Students: Predicting Future Gas Prices Using the Standards for Mathematical Practice
Authors: Bismarck Stephen F. , Zelkowski Jeremy , Gleason Jim
Published: April 2014

“How much do you think gas will cost when I graduate from high school?” Like many commodities, the price of gasoline continues to rise, and these price changes are readily observed in gas stations' signage. Moreover, algebraic methods are well suited to model price change and answer the student's question. Over the course of one ninetyminute block or two forty-five-minute classes, students build functions and interpret them in context. This article presents the activity, describes its implementation, provides sample student work, and discusses its relationship to the Standards for Mathematical Practice from the Common Core State Standards. Data used in the activity are available athttp://data.bls.gov/cgi-bin/surveymost?ap.
Connecting Research to Teaching: Evaluating and Writing Dynamic Geometry Tasks
Authors: Trocki Aaron
Published: April 2014

The advent of dynamic geometry software has changed the way students draw, construct, and measure by using virtual tools instead of or along with physical tools. Use of technology in general and of dynamic geometry in particular has gained traction in mathematics education, as evidenced in the Common Core State Standards for Mathematics (CCSSI 2010).
The Back Page: My Favorite Lesson: Algebra about Me
Authors: Miles Victoria
Published: April 2014

Performance tasks provide effective ways to differentiate mathematics instruction while allowing students to be creative and to incorporate mathematics content that is suitable for their interest and readiness. A project that I have enjoyed assigning to my high school students, Algebra about Me, is designed to introduce, reinforce, and review equation-solving concepts and skills (for a customizable activity sheet, go to www.nctm.org/mt).
Hegemons, empires, and their elites
Authors: Lachmann Richard
Published: April 2014

I compare ancient with modern empires and show why hegemony beyond the militaryrealm is possible only in the modern capitalist world. I examine Germany, Spain and France, whichfailed to achieve hegemony, along with the three successive hegemons: the Netherlands, Britain,and the United States. I identify the elites that were created and strengthened by their homepolity’s empire or hegemony, and enumerate the factors that allowed some colonial elites to achievehigh levels of autonomy. Colonial elite autonomy or high levels of elite unity in the metropoleprevented or undermined hegemony.
Perceptions of occupational risks in the railway sector
Authors: Areosa João
Published: April 2014

The primary objective of this article is to present the results of research in an organisational context on the ways in which workers perceive risks linked to their work. The organisation observed by the author is an urban rail transport company, where staff run various types of risk. It was found that workers have heterogeneous perceptions of their occupational risks. However, this diversity ended up providing information that is quite useful for improving both knowledge about the risks in the organisation and the proposed ways of preventing accidents. The article begins by describing a theoretical framework for the topic, and the methodology used in the research (essentially, participative observation and semi-structured interviews).
Clusters of religiosity of Portuguese undergraduate youth
Authors: Coutinho José Pereira
Published: April 2014

This article presents results of the author’s PhD thesis based on religious beliefs and practices, and attitudes of towards marriage, life, and sexuality. The sample included 500 undergraduate students from public universities of Lisbon. Applying multiple correspondence analysis and cluster analysis to these beliefs, practices, and attitudes, three clusters or types of religiosity were produced: nuclear Catholics, intermediate Catholics, and non-Catholics. These clusters were characterised in terms of religious socialisation, as well as of non-Catholic beliefs and practices, and aspects of life. When crossed with these last items, the clusters were renamed respectively: socio-centred orthodox, ambitious heterodox, activist and hedonist non-believers.
Wikipedia vs Peer-Reviewed Medical Literature for Information About the 10 Most Costly Medical Conditions
Authors: Hasty Robert T. , Garbalosa Ryan C. , Barbato Vincenzo A. , Valdes Pedro J. , Powers David W. , Hernandez Emmanuel , John Jones S. , Suciu Gabriel , Qureshi Farheen , Popa-Radu Matei , Jose Sergio San , Drexler Nathaniel , Patankar Rohan , Paz Jose R. , King Christopher W. , Gerber Hilary N. , Valladares Michael G. , Somji Alyaz A.
Published: April 2014

Context: Since its launch in 2001, Wikipedia has become the most popular general reference site on the Internet and a popular source of health care information. To evaluate the accuracy of this resource, the authors compared Wikipedia articles on the most costly medical conditions with standard, evidence-based, peer-reviewed sources.

Methods: The top 10 most costly conditions in terms of public and private expenditure in the United States were identified, and a Wikipedia article corresponding to each topic was chosen. In a blinded process, 2 randomly assigned investigators independently reviewed each article and identified all assertions (ie, implication or statement of fact) made in it. The reviewer then conducted a literature search to determine whether each assertion was supported by evidence. The assertions found by each reviewer were compared and analyzed to determine whether assertions made by Wikipedia for these conditions were supported by peer-reviewed sources.

Results: For commonly identified assertions, there was statistically significant discordance between 9 of the 10 selected Wikipedia articles (coronary artery disease, lung cancer, major depressive disorder, osteoarthritis, chronic obstructive pulmonary disease, hypertension, diabetes mellitus, back pain, and hyperlipidemia) and their corresponding peer-reviewed sources (P<.05) and for all assertions made by Wikipedia for these medical conditions (P<.05 for all 9).

Conclusion: Most Wikipedia articles representing the 10 most costly medical conditions in the United States contain many errors when checked against standard peer-reviewed sources. Caution should be used when using Wikipedia to answer questions regarding patient care.
Effect of Osteopathic Manipulative Therapy in the Attentive Performance of Children With Attention-Deficit/Hyperactivity Disorder
Authors: Accorsi Alessandro , Lucci Chiara , Di Mattia Lorenzo , Granchelli Cristina , Barlafante Gina , Fini Federica , Pizzolorusso Gianfranco , Cerritelli Francesco , Pincherle Maurizio
Published: April 2014

Context: Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder most commonly affecting children and teenagers. It is characterized by the coexistence of attention problems and impulsivity and hyperactivity. Although several studies have been conducted on the efficacy of conventional and alternative therapies in children with ADHD, few studies have specifically investigated the efficacy of osteopathic manipulative therapy (OMTh).

Objective: To evaluate the efficacy of OMTh in the treatment of children with ADHD.

Methods: Children aged 5 to 15 years with a primary diagnosis of ADHD who were admitted to a single neuropsychiatry unit from November 2008 to September 2009 were randomly assigned to an intervention group (OMTh + conventional care) or a control group (conventional care only). Biancardi-Stroppa Modified Bell Cancellation Test accuracy and rapidity scores were recorded for both groups at baseline and after 10 weeks. Statistical analyses included univariate tests and multivariate linear regressions.

Results: A total of 28 participants were included in the study: 14 in the OMTh group and 14 in the control group. Univariate statistical analysis showed no statistically significant differences between the intervention and control groups in terms of characteristics measured at baseline, except for psychosocial intervention (P=.05). Multivariate linear regression showed that OMTh was positively associated with changes in the Biancardi-Stroppa Test accuracy (β=7.948 points; P=.04) and rapidity (β=9.089 points; P=.03) scores.

Conclusion: Participants who received OMTh had greater improvement in Biancardi-Stroppa Test scores than participants who received conventional care only, suggesting that OMTh can potentially increase performances of selective and sustained attention in children with ADHD. To confirm these findings, studies of larger and more diverse populations are warranted.
The ‘little m.d.’ or the ‘Big D.O.’: The Path to the California Merger
Authors: Gevitz Norman
Published: April 2014

In the years following the American Osteopathic Association's sanctioning of the broad teaching of chemical and biological agents, osteopathic physicians moved closer to allopathic physicians with respect to diagnosis and treatment. In the 1930s, osteopathic colleges began to adopt standards and improve their basic science and clinical training, which allowed them to produce graduates who did substantially better in passing external examinations to become licensed as physicians and surgeons. Nevertheless, many state legislatures refused to grant DOs unlimited licenses and osteopathic physicians were unable to obtain medical commissions during the Second World War. In California, despite significant accomplishments on the social and legislative fronts, a growing number of osteopathic physicians believed that their DO degree and independent status as a separate medical profession was an impediment to achieving equality with their allopathic counterparts, and they worked toward a merger or amalgamation with their long-time opponents.
Radiosurgery with Helical Tomotherapy
Authors: Barra Salvina , Agostinelli Stefano , Vagge Stefano , Giannelli Flavio , Siccardi Desiderio , Garelli Stefania , Aloi Deborah , Belgioia Liliana , Bosetti Davide , Zeverino Michele , Corvò Renzo
Published: April 2014

To evaluate the feasibility and report the preliminary results for stereotactic radiosurgery (SRS) treatments of single or multiple brain metastases delivered with helical tomotherapy (HT) by means of the InterFix™ Radiosurgery kit. Between September 2010 and August 2012, thirty patients underwent SRS for treatment of 46 brain metastases with a median prescription dose of 20 Gy (range 15-21 Gy). Clinical response was assessed with 2-3 month intervals by magnetic resonance imaging (MRI). Dose distribution indexes were computed and compared with published data for SRS performed with dedicated machines. After a median follow-up of 14 months (range 4-31) the estimated overall survival (OS) rate was 70% at 6 months, 60% at 12 months and 44% at 18 months. Local control (LC) was 72% at 6 months, 65% at 12 months and 50% at 18 months. Acute toxicity as headache and epileptic crisis occurred in only two patients. The mean values of conformity, homogeneity and gradient score indexes were 1.36, 1.04 and 50 respectively. HT-SRS for single or multiple brain metastases appears a reliable technique with encouraging clinical outcomes and competitive dosimetrical results.
Folate Conjugated Cellulose Nanocrystals Potentiate Irreversible Electroporation-induced Cytotoxicity for the Selective Treatment of Cancer Cells
Authors: Colacino Katelyn R. , Arena Christopher B. , Dong Shuping , Roman Maren , Davalos Rafael V. , Lee Yong W.
Published: April 2014

Cellulose nanocrystals are rod-shaped, crystalline nanoparticles that have shown prom-ise in a number of industrial applications for their unique chemical and physical properties. However, investigations of their abilities in the biomedical field are limited. The goal of this study is to show the potential use of folic acid-conjugated cellulose nanocrystals in the potentiation of irreversible electroporation-induced cell death in folate receptor (FR)-positive cancers. We optimized key pulse parameters including pulse duration, intensity, and incubation time with nanoparticles prior to electroporation. FR-positive cancer cells, KB and MDA-MB-468, were preincubated with cellulose nanocrystals (CNCs) conjugated with the targeting molecule folic acid (FA), 10 and 20 min respectively, prior to application of the optimized pulse electric field (PEF), 600 and 500 V/cm respectively. We have shown cellulose nanocrystals’ ability to potentiate a new technique for tumor ablation, irreversible electroporation. Pre-incubation with FA-conjugated CNCs (CNC-FA) has shown a significant increase in cytotoxicity induced by irreversible electroporation in FR-positive cancer cells, KB and MDA-MB-468. Non-targeted CNCs (CNC-COOH) did not potentiate IRE when preincubated at the same parameters as previously stated in these cell types. In addition, CNC-FA did not potentiate irreversible electroporation-induced cytotoxicity in a FR-negative cancer cell type, A549. Without changing irreversible electroporation parameters it is possible to increase the cytotoxic effect on FR-positive cancer cells by exploiting the specific binding of FA to the FR, while not causing further damage to FR-negative tissue.