503 research outputs found

    Time periodicity and dynamical stability in two-boson systems

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    We calculate the period of recurrence of dynamical systems comprising two interacting bosons. A number of theoretical issues related to this problem are discussed, in particular, the conditions for small periodicity. The knowledge gathered in this way is then used to propose a notion of dynamical stability based on the stability of the period. Dynamical simulations show good agreement with the proposed scheme. We also apply the results to the phenomenon known as coherent population trapping and find stability conditions in this specific case.Comment: 7+ pages, 5 figure

    NS1 Specific CD8(+) T-Cells with Effector Function and TRBV11 Dominance in a Patient with Parvovirus B19 Associated Inflammatory Cardiomyopathy

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    Background: Parvovirus B19 (B19V) is the most commonly detected virus in endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy (DCMi). Despite the importance of T-cells in antiviral defense, little is known about the role of B19V specific T-cells in this entity. Methodology and Principal Findings: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mg nucleic acids), peripheral blood mononuclear cells (PBMCs) and serum was measured in a DCMi patient at initial presentation, suggesting B19V viremia. The B19V viral load in EMBs had decreased substantially 6 and 12 months afterwards, and was not traceable in PBMCs and the serum at these times. Using pools of overlapping peptides spanning the whole B19V proteome, strong CD8(+) T-cell responses were elicited to the 10-amico-acid peptides SALKLAIYKA (19.7% of all CD8(+) cells) and QSALKLAIYK (10%) and additional weaker responses to GLCPHCINVG (0.71%) and LLHTDFEQVM (0.06%). Real-time RT-PCR of IFN gamma secretion-assay-enriched T-cells responding to the peptides, SALKLAIYKA and GLCPHCINVG, revealed a disproportionately high T-cell receptor Vbeta (TRBV) 11 expression in this population. Furthermore, dominant expression of type-1 (IFN gamma, IL2, IL27 and Tbet) and of cytotoxic T-cell markers (Perforin and Granzyme B) was found, whereas gene expression indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low. Conclusions: Our results indicate that B19V Ag-specific CD8(+) T-cells with effector function are involved in B19V associated DCMi. In particular, a dominant role of TRBV11 and type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested. The persistence of B19V in the endomyocardium is a likely antigen source for the maintenance of CD8(+) T-cell responses to the identified epitopes

    Long-term cycles in the history of life: Periodic biodiversity in the Paleobiology Database

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    Time series analysis of fossil biodiversity of marine invertebrates in the Paleobiology Database (PBDB) shows a significant periodicity at approximately 63 My, in agreement with previous analyses based on the Sepkoski database. I discuss how this result did not appear in a previous analysis of the PBDB. The existence of the 63 My periodicity, despite very different treatment of systematic error in both PBDB and Sepkoski databases strongly argues for consideration of its reality in the fossil record. Cross-spectral analysis of the two datasets finds that a 62 My periodicity coincides in phase by 1.6 My, equivalent to better than the errors in either measurement. Consequently, the two data sets not only contain the same strong periodicity, but its peaks and valleys closely correspond in time. Two other spectral peaks appear in the PBDB analysis, but appear to be artifacts associated with detrending and with the increased interval length. Sampling-standardization procedures implemented by the PBDB collaboration suggest that the signal is not an artifact of sampling bias. Further work should focus on finding the cause of the 62 My periodicity.Comment: Published in PLoS ONE. 5 pages, 3 figures. Version with live links, discussion available at http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004044#to

    Improved Culture-Based Isolation of Differentiating Endothelial Progenitor Cells from Mouse Bone Marrow Mononuclear Cells

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    Numerous endothelial progenitor cell (EPC)-related investigations have been performed in mouse experiments. However, defined characteristics of mouse cultured EPC have not been examined. We focused on fast versus slow adherent cell population in bone marrow mononuclear cells (BMMNCs) in culture and examined their characteristics. After 24 h-culture of BMMNCs, attached (AT) cells and floating (FL) cells were further cultured in endothelial differentiation medium separately. Immunological and molecular analyses exhibited more endothelial-like and less monocyte/macrophage-like characteristics in FL cells compared with AT cells. FL cells formed thick/stable tube and hypoxia or shear stress overload further enhanced these endothelial-like features with increased angiogenic cytokine/growth factor mRNA expressions. Finally, FL cells exhibited therapeutic potential in a mouse myocardial infarction model showing the specific local recruitment to ischemic border zone and tissue preservation. These findings suggest that slow adherent (FL) but not fast attached (AT) BMMNCs in culture are EPC-rich population in mouse

    Host-Pathogen O-Methyltransferase Similarity and Its Specific Presence in Highly Virulent Strains of Francisella tularensis Suggests Molecular Mimicry

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    Whole genome comparative studies of many bacterial pathogens have shown an overall high similarity of gene content (>95%) between phylogenetically distinct subspecies. In highly clonal species that share the bulk of their genomes subtle changes in gene content and small-scale polymorphisms, especially those that may alter gene expression and protein-protein interactions, are more likely to have a significant effect on the pathogen's biology. In order to better understand molecular attributes that may mediate the adaptation of virulence in infectious bacteria, a comparative study was done to further analyze the evolution of a gene encoding an o-methyltransferase that was previously identified as a candidate virulence factor due to its conservation specifically in highly pathogenic Francisella tularensis subsp. tularensis strains. The o-methyltransferase gene is located in the genomic neighborhood of a known pathogenicity island and predicted site of rearrangement. Distinct o-methyltransferase subtypes are present in different Francisella tularensis subspecies. Related protein families were identified in several host species as well as species of pathogenic bacteria that are otherwise very distant phylogenetically from Francisella, including species of Mycobacterium. A conserved sequence motif profile is present in the mammalian host and pathogen protein sequences, and sites of non-synonymous variation conserved in Francisella subspecies specific o-methyltransferases map proximally to the predicted active site of the orthologous human protein structure. Altogether, evidence suggests a role of the F. t. subsp. tularensis protein in a mechanism of molecular mimicry, similar perhaps to Legionella and Coxiella. These findings therefore provide insights into the evolution of niche-restriction and virulence in Francisella, and have broader implications regarding the molecular mechanisms that mediate host-pathogen relationships

    Association of the TLR4 Asp299Gly polymorphism with lung function in relation to body mass index

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    <p>Abstract</p> <p>Background</p> <p>Previous studies have shown conflicting results for the association between TLR4 polymorphism (Asp299Gly) and lung function. We investigated the influence of TLR4 Asp299Gly, a polymorphism, on lung function in a community population.</p> <p>Methods</p> <p>In 2003, a cross-sectional survey was conducted to assess the respiratory health of residents living in and around the town of Humboldt, Saskatchewan, Canada. There were 2090 adults age 18-79 years who completed a questionnaire that included a medical and smoking history, as well as socio-economic and lifestyle variables. Genetic information and lung function test measurements were available on 1725 subjects (754 males and 971 females) of the 2090 respondents. These subjects were selected for further analysis to investigate the association between TLR4 Asp299Gly genotype and forced expiratory volume in the first second in liters (FEV<sub>1</sub>), forced vital capacity in liters (FVC), FEV<sub>1</sub>/FVC ratio, and forced expiratory flow rate in liters/second (FEF<sub>25-75</sub>). Multivariable linear regression analysis was used to investigate associations.</p> <p>Results</p> <p><b>A</b>djusted mean values of FEV<sub>1 </sub>and FVC were significantly different between TLR4 wild type and TLR4 variant groups [Mean ± S.E.: (TLR4 wild type - FEV<sub>1</sub>: 3.18 ± 0.02, FVC: 3.95 ± 0.03; TLR4 variant - FEV<sub>1</sub>: 3.31 ± 0.06, FVC: 4.14 ± 0.07)]. Based on multivariable regression analysis, we observed that body mass index (BMI) was associated with decreased FEV<sub>1</sub>/FVC ratio and FEF<sub>25-75 </sub>in TLR4 variant group but not in wild type group.</p> <p>Conclusion</p> <p>BMI may modify the associations of TLR4 Asp299Gly polymorphism with FEV<sub>1</sub>/FVC ratio and FEF<sub>25-75</sub>.</p
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