570 research outputs found

    Distinct gene signatures in aortic tissue from ApoE-/- mice exposed to pathogens or Western diet

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    BACKGROUND: Atherosclerosis is a progressive disease characterized by inflammation and accumulation of lipids in vascular tissue. Porphyromonas gingivalis (Pg) and Chlamydia pneumoniae (Cp) are associated with inflammatory atherosclerosis in humans. Similar to endogenous mediators arising from excessive dietary lipids, these Gram-negative pathogens are pro-atherogenic in animal models, although the specific inflammatory/atherogenic pathways induced by these stimuli are not well defined. In this study, we identified gene expression profiles that characterize P. gingivalis, C. pneumoniae, and Western diet (WD) at acute and chronic time points in aortas of Apolipoprotein E (ApoE-/-) mice. RESULTS: At the chronic time point, we observed that P. gingivalis was associated with a high number of unique differentially expressed genes compared to C. pneumoniae or WD. For the top 500 differentially expressed genes unique to each group, we observed a high percentage (76%) that exhibited decreased expression in P. gingivalis-treated mice in contrast to a high percentage (96%) that exhibited increased expression in WD mice. C. pneumoniae treatment resulted in approximately equal numbers of genes that exhibited increased and decreased expression. Gene Set Enrichment Analysis (GSEA) revealed distinct stimuli-associated phenotypes, including decreased expression of mitochondrion, glucose metabolism, and PPAR pathways in response to P. gingivalis but increased expression of mitochondrion, lipid metabolism, carbohydrate and amino acid metabolism, and PPAR pathways in response to C. pneumoniae; WD was associated with increased expression of immune and inflammatory pathways. DAVID analysis of gene clusters identified by two-way ANOVA at acute and chronic time points revealed a set of core genes that exhibited altered expression during the natural progression of atherosclerosis in ApoE-/- mice; these changes were enhanced in P. gingivalis-treated mice but attenuated in C. pneumoniae-treated mice. Notable differences in the expression of genes associated with unstable plaques were also observed among the three pro-atherogenic stimuli. CONCLUSIONS: Despite the common outcome of P. gingivalis, C. pneumoniae, and WD on the induction of vascular inflammation and atherosclerosis, distinct gene signatures and pathways unique to each pro-atherogenic stimulus were identified. Our results suggest that pathogen exposure results in dysregulated cellular responses that may impact plaque progression and regression pathways

    Energy dependence of particle ratio fluctuations in central Pb+Pb collisions from sNN=\sqrt{s_{_{NN}}} =~6.3 to 17.3 GeV

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    We present measurements of the energy dependence of event-by-event fluctuations in the K/pi and (p + \bar{p})/pi multiplicity ratios in heavy ion collisions at the CERN SPS. The particle ratio fluctuations were obtained for central Pb+Pb collisions at five collision energies, \sqrt{s_{_{NN}}}, between 6.3 and 17.3 GeV. After accounting for the effects of finite-number statistics and detector resolution, we extract the strength of non-statistical fluctuations at each energy. For the K/pi ratio, larger fluctuations than expected for independent particle production are found at all collision energies. The fluctuations in the (p + \bar{p})/pi ratio are smaller than expectations from independent particle production, indicating correlated pion and proton production from resonance decays. For both ratios, the deviation from purely statistical fluctuations shows an increase towards lower collision energies. The results are compared to transport model calculations, which fail to describe the energy dependence of the K/pi ratio fluctuations.Comment: 11 pages, 10 figures, update to published versio

    Upper Limit of D0 Production in Central Pb-Pb Collisions at 158A GeV

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    Results are presented from a search for the decays D0 -> Kmin piplus and D0bar -> Kplus pimin in a sample of 3.8x10^6 central Pb-Pb events collected with a beam energy of 158A GeV by NA49 at the CERN SPS. No signal is observed. An upper limit on D0 production is derived and compared to predictions from several models.Comment: REVTEX 5 pages, 4 figure

    Inclusive production of charged pions in p+C collisions at 158 GeV/c beam momentum

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    The production of charged pions in minimum bias p+C interactions is studied using a sample of 377000 inelastic events obtained with the NA49 detector at the CERN SPS at 158 GeV/c beam momentum. The data cover a phase space area ranging from 0 to 1.8 GeV/c in transverse momentum and from -0.1 to 0.5 in Feynman x. Inclusive invariant cross sections are given on a grid of 270 bins per charge thus offering for the first time a dense coverage of the projectile hemisphere and of the cross-over region into the target fragmentation zone.Comment: 31 pages, 30 figures, submitted to European Journal of Physic

    New Human Papilloma Virus E2 Transcription Factor Mimics: A Tripyrrole-Peptide Conjugate with Tight and Specific DNA-Recognition

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    BACKGROUND: Human papillomavirus (HPV) is the main causative agent of cervical cancer, particularly high risk strains such us HPV-16, -18 and -31. The viral encoded E2 protein acts as a transcriptional modulator and exerts a key role in viral DNA replication. Thus, E2 constitutes an attractive target for developing antiviral agents. E2 is a homodimeric protein that interacts with the DNA target through an α-helix of each monomer. However, a peptide corresponding to the DNA recognition helix of HPV-16 E2 binds DNA with lower affinity than its full-length DNA binding domain. Therefore, in an attempt to promote the DNA binding of the isolated peptide, we have designed a conjugate compound of the E2 α-helix peptide and a derivative of the antibiotic distamycin, which involves simultaneous minor- and major-groove interactions. METHODOLOGY/PRINCIPAL FINDINGS: An E2 α-helix peptide-distamycin conjugate was designed and synthesized. It was characterized by NMR and CD spectroscopy, and its DNA binding properties were investigated by CD, DNA melting and gel shift experiments. The coupling of E2 peptide with distamycin does not affect its structural properties. The conjugate improves significantly the affinity of the peptide for specific DNA. In addition, stoichiometric amounts of specific DNA increase meaningfully the helical population of the peptide. The conjugate enhances the DNA binding constant 50-fold, maintaining its specificity. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that peptide-distamycin conjugates are a promising tool to obtain compounds that bind the E2 target DNA-sequences with remarkable affinity and suggest that a bipartite major/minor groove binding scaffold can be a useful approach for therapeutic treatment of HPV infection

    Rapidity and energy dependence of the electric charge correlations in A+A collisions at the SPS energies

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    Results from electric charge correlations studied with the Balance Function method in A+A collisions from 20\emph{A} to 158\emph{A} GeV are presented in two different rapidity intervals: In the mid-rapidity region we observe a decrease of the width of the Balance Function distribution with increasing centrality of the collision, whereas this effect vanishes in the forward rapidity region. Results from the energy dependence study in central Pb+Pb collisions show that the narrowing of the Balance Function expressed by the normalised width parameter \textit{W} increases with energy towards the highest SPS and RHIC energies. Finally we compare our experimental data points with predictions of several models. The hadronic string models UrQMD and HIJING do not reproduce the observed narrowing of the Balance Function. However, AMPT which contains a quark-parton transport phase before hadronization can reproduce the narrowing of the BF's width with centrality. This confirms the proposed sensitivity of the Balance Function analysis to the time of hadronization.Comment: Submitted in Phys. Rev.

    Bose-Einstein correlations of pion pairs in central Pb+Pb collisions at CERN SPS energies

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    Measurements of Bose-Einstein correlations of pion pairs in central Pb+Pb collisions were performed with the NA49 detector at the CERN SPS for beam energies of 20A, 30A, 40A, 80A, and 158A GeV. Correlation functions were measured in the longitudinally co-moving ``out-side-long'' reference frame as a function of rapidity and transverse momentum in the forward hemisphere of the reaction. Radius and correlation strength parameters were obtained from fits of a Gaussian parametrization. The results show a decrease of the radius parameters with increasing transverse momentum characteristic of strong radial flow in the pion source. No striking dependence on pion-pair rapidity or beam energy is observed. Static and dynamic properties of the pion source are obtained from simultaneous fits with a blast-wave model to radius parameters and midrapidity transverse momentum spectra. Predictions of hydrodynamic and microscopic models of Pb+Pb collisions are discussed.Comment: 22 pages, 23 figure
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