Population Mobility, Globalization, and Antimicrobial Drug Resistance

Human travel contributes to antimicrobial drug resistance around the world

The cis/trans interconversion of the calcium regulating hormone calcitonin is catalyzed by cyclophilin

AbstractThe cytosolic peptidyl-prolyl cis/trans isomerase cyclophilin from pig kidney can accelerate catalytically the cis/trans isomerization of prolyl peptide bonds. One- and two-dimensional 1H NMR spectroscopy was used to prove that the polypeptide hormone calcitonin is a substrate for cyclophilin. Isomerization of only one of the two prolyl peptide bonds is catalyzed significantly. The efficiency of catalysis was calculated by lineshape analysis and NOESY spectroscopy. Cyclosporin A completely blocks the effect of the enzyme on the conformational dynamics of the polypeptide

Artificial reefs: from ecological processes to fishing enhancement tools

info:eu-repo/semantics/publishedVersio

Facility and home based HIV Counseling and Testing: a comparative analysis of uptake of services by rural communities in southwestern Uganda

<p>Abstract</p> <p>Background</p> <p>In Uganda, public human immunodeficiency virus (HIV) Voluntary Counseling and Testing (VCT) services are mainly provided through the facility based model, although the home based approach is being promoted as a strategy for improving access to VCT. However the uptake of VCT varies according to service delivery model and is influenced by a number of factors. The aim of this study therefore, was to compare predictors for uptake of facility and home based VCT in a rural context.</p> <p>Methods</p> <p>A longitudinal study with cross-sectional investigative phases was conducted at two sites (Rugando and Kabingo) in southwestern Uganda between November 2007 (baseline) and March 2008 (follow up). During the baseline visit, facility based VCT was offered at the main health centre in Rugando while home based VCT was offered at the household level in Kabingo and a mixed survey questionnaire administered to the respondents. The results presented in this paper are derived from only the baseline data.</p> <p>Results</p> <p>Nine hundred ninety four (994) respondents were interviewed, of whom 500 received facility based VCT in Rugando and 494 home based VCT in Kabingo during the baseline visit. The respondents had a mean age of 32.2 years (SD 10.9) and were mainly female (68 percent). Clients who received facility based VCT were less likely to be residents of the more rural households (adjusted Odds Ratio (aOR) = 0.14, 95% CI 0.07, 0.22). The clients who received home based VCT were less likely to report having an STI symptom (aOR = 0.63, 95% CI 0.46, 0.86), and more likely to be worried about discrimination if they contracted AIDS (aOR = 1.78, 95% CI 1.22, 2.61).</p> <p>Conclusion</p> <p>The uptake of VCT provided through either the facility or home based models is influenced by client characteristics such as proximity to service delivery points, HIV related symptoms, and fear of discrimination in rural Uganda. Interventions that seek to improve uptake of VCT should provide potential clients with both facility and home based VCT options within a given setting. The clients are then able to select a model for VCT that best fits their characteristics. This is likely to have positive implications for both service coverage and uptake by different sub-groups within particular communities.</p

Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection

<p>Abstract</p> <p>Background</p> <p>Sex differences have been described in a number of pulmonary diseases. However, the impact of ozone exposure followed by pneumonia infection on sex-related survival and macrophage function have not been reported. The purpose of this study was to determine whether ozone exposure differentially affects: 1) survival of male and female mice infected with <it>Klebsiella pneumoniae</it>, and 2) the phagocytic ability of macrophages from these mice.</p> <p>Methods</p> <p>Male and female C57BL/6 mice were exposed to O₃or to filtered air (FA) (control) and then infected intratracheally with <it>K. pneumoniae </it>bacteria. Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen <it>in vivo </it>was investigated after 1 h.</p> <p>Results</p> <p>1) Both male and female mice exposed to O₃are significantly more susceptible to <it>K. pneumoniae </it>infection than mice treated with FA; 2) although females appeared to be more resistant to <it>K. pneumoniae </it>than males, O₃exposure significantly increased the susceptibility of females to <it>K. pneumoniae </it>infection to a greater degree than males; 3) alveolar macrophages from O₃-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O₃-dependent reduction in phagocytic ability is greater in female mice.</p> <p>Conclusion</p> <p>O₃exposure reduces the ability of mice to survive <it>K. pneumoniae </it>infection and the reduced phagocytic ability of alveolar macrophages may be one of the contributing factors. Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.</p

Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling

Contains fulltext : 108719.pdf (publisher's version ) (Open Access)BACKGROUND: T lymphocytes are orchestrators of adaptive immunity. Naive T cells may differentiate into Th1, Th2, Th17 or iTreg phenotypes, depending on environmental co-stimulatory signals. To identify genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli and pathway inhibitors. Results from these experiments were validated in a human experimental setting using whole blood and purified CD4+ Tcells. RESULTS: Calcium-dependent activation of T cells using CD3/CD28 and PMA/CD3 stimulation induced a Th1 expression profile reflected by increased expression of T-bet, RUNX3, IL-2, and IFNgamma, whereas calcium-independent activation via PMA/CD28 induced a Th2 expression profile which included GATA3, RXRA, CCL1 and Itk. Knock down with siRNA and gene expression profiling in the presence of selective kinase inhibitors showed that proximal kinases Lck and PKCtheta are crucial signaling hubs during T helper cell activation, revealing a clear role for Lck in Th1 development and for PKCtheta in both Th1 and Th2 development. Medial signaling via MAPkinases appeared to be less important in these pathways, since specific inhibitors of these kinases displayed a minor effect on gene expression. Translation towards a primary, whole blood setting and purified human CD4+ T cells revealed that PMA/CD3 stimulation induced a more pronounced Th1 specific, Lck and PKCtheta dependent IFNgamma production, whereas PMA/CD28 induced Th2 specific IL-5 and IL-13 production, independent of Lck activation. PMA/CD3-mediated skewing towards a Th1 phenotype was also reflected in mRNA expression of the master transcription factor Tbet, whereas PMA/CD28-mediated stimulation enhanced GATA3 mRNA expression in primary human CD4+ Tcells. CONCLUSIONS: This study identifies stimulatory pathways and gene expression profiles for in vitro skewing of T helper cell activation. PMA/CD3 stimulation enhances a Th1-like response in an Lck and PKCtheta dependent fashion, whereas PMA/CD28 stimulation results in a Th2-like phenotype independent of the proximal TCR-tyrosine kinase Lck. This approach offers a robust and fast translational in vitro system for skewed T helper cell responses in Jurkat T cells, primary human CD4+ Tcells and in a more complex matrix such as human whole blood