1,244 research outputs found

    Oxidative stress in asthmatic and non-asthmatic adolescent swimmers - a breathomics approach

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    We hypothesize that oxidative stress induced by trichloramine exposure during swimming could be related to etiopathogenesis of asthma among elite swimmers. Aim: To investigate the effect of a swimming training session on oxidative stress markers of asthmatic compared to non‐asthmatic elite swimmers using exhaled breath (EB) metabolomics. Methods: Elite swimmers annually screened in our department (n=27) were invited and those who agreed to participate (n=20, of which 9 with asthma) had EB collected (Tedlar¼ bags) before and after a swimming training session. SPME fiber (DVB/CAR/PDMS) was used to extract EB metabolites followed by a multidimensional gas chromatography analysis (GC×GC‐ToFMS). Dataset comprises eight metabolites end products of lipid peroxidation: five aliphatic alkanes (nonane, 2,2,4,6,6‐pentamethylheptane, decane, dodecane, and tetradecane) and three aldehydes (nonanal, decanal, and dodecanal). To assess exercise impact on lipid peroxidation markers, data were analyzed using principle component analysis (PCA), which was run on the original data set and on the data set constructed using differences in the metabolite total areas before and after exercise session. Results: Heatmap representation revealed that metabolites content decreased after exercise, both for control and asthma groups; however, the greater decrease was observed for controls. Asthmatics and controls did not form separated clusters; however, control swimmers demonstrated a more varied response to the exercise being dispersed along all score plot. Conclusion: In well‐trained athletes, swimming is associated with a decrease in oxidative stress markers independently of the presence of asthma, although a more pronounced decrease was seen in controls.European Regional Development Fund FEDER through the Competitive Factors Thematic Operational Programme (COMPETE) and FCT, Portugal, under projects PEST-C/QUI/UI0062/2013 (Research Unit 62/94 QOPNA) and PTDC/QUI-QUI/117803/2010

    The Terminal Immunoglobulin-Like Repeats of LigA and LigB of Leptospira Enhance Their Binding to Gelatin Binding Domain of Fibronectin and Host Cells

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    Leptospira spp. are pathogenic spirochetes that cause the zoonotic disease leptospirosis. Leptospiral immunoglobulin (Ig)-like protein B (LigB) contributes to the binding of Leptospira to extracellular matrix proteins such as fibronectin, fibrinogen, laminin, elastin, tropoelastin and collagen. A high-affinity Fn-binding region of LigB has been localized to LigBCen2, which contains the partial 11th and full 12th Ig-like repeats (LigBCen2R) and 47 amino acids of the non-repeat region (LigBCen2NR) of LigB. In this study, the gelatin binding domain of fibronectin was shown to interact with LigBCen2R (KD = 1.91±0.40 ”M). Not only LigBCen2R but also other Ig-like domains of Lig proteins including LigAVar7'-8, LigAVar10, LigAVar11, LigAVar12, LigAVar13, LigBCen7'-8, and LigBCen9 bind to GBD. Interestingly, a large gain in affinity was achieved through an avidity effect, with the terminal domains, 13th (LigA) or 12th (LigB) Ig-like repeat of Lig protein (LigAVar7'-13 and LigBCen7'-12) enhancing binding affinity approximately 51 and 28 fold, respectively, compared to recombinant proteins without this terminal repeat. In addition, the inhibited effect on MDCKs cells can also be promoted by Lig proteins with terminal domains, but these two domains are not required for gelatin binding domain binding and cell adhesion. Interestingly, Lig proteins with the terminal domains could form compact structures with a round shape mediated by multidomain interaction. This is the first report about the interaction of gelatin binding domain of Fn and Lig proteins and provides an example of Lig-gelatin binding domain binding mediating bacterial-host interaction

    Jogo educativo sobre drogas para cegos: construção e avaliação

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    Estudo realizado com o objetivo de construir e avaliar um jogo educativo sobre drogas psicoativas acessĂ­vel a pessoas cegas, desenvolvido em trĂȘs etapas: construção do jogo educativo, avaliação por trĂȘs especialistas em educação especial e doze cegos. Foi construĂ­do um jogo de tabuleiro denominado Drogas: jogando limpo . Na VersĂŁo Alfa os especialistas fizeram sugestĂ”es em relação Ă s e instruçÔes e ao tabuleiro: textura das casas, peças do jogo e escrita em Braille. Na VersĂŁo Beta, procedeu-se Ă  avaliação pelos cegos, os quais sugeriram alteraçÔes na textura das casas e colocação de velcro para fixação do pino no tabuleiro. Passou-se, entĂŁo, Ă  VersĂŁo Gama, jogada pelas Ășltimas trĂȘs duplas de cegos e considerada adequada. Na avaliação dos juĂ­zes, o jogo revelou-se adequado, pois permite o acesso Ă  informação sobre drogas psicoativas de maneira lĂșdica

    Cryptococcus neoformans induces IL-8 secretion and CXCL1 expression by human bronchial epithelial cells

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    <p>Abstract</p> <p>Background</p> <p><it>Cryptococcus neoformans </it>(<it>C. neoformans</it>) is a globally distributed fungal pathogen with the potential to cause serious disease, particularly among immune compromised hosts. Exposure to this organism is believed to occur by inhalation and may result in pneumonia and/or disseminated infection of the brain as well as other organs. Little is known about the role of airway epithelial cells in cryptococcal recognition or their ability to induce an inflammatory response.</p> <p>Methods</p> <p>Immortalized BEAS-2B bronchial epithelial cells and primary normal human bronchial epithelium (NHBE) were stimulated <it>in vitro </it>with encapsulated or acapsular <it>C. neoformans </it>cultivated at room temperature or 37°C. Activation of bronchial epithelial cells was characterized by analysis of inflammatory cytokine and chemokine expression, transcription factor activation, fungal-host cell association, and host cell damage.</p> <p>Results</p> <p>Viable <it>C. neoformans </it>is a strong activator of BEAS-2B cells, resulting in the production of the neutrophil chemokine Interleukin (IL)-8 in a time- and dose-dependent manner. IL-8 production was observed only in response to acapsular <it>C. neoformans </it>that was grown at 37°C. <it>C. neoformans </it>was also able to induce the expression of the chemokine CXCL1 and the transcription factor CAAT/enhancer-binding protein beta (CEBP/ÎČ) in BEAS-2B cells. NHBE was highly responsive to stimulation with <it>C. neoformans</it>; in addition to transcriptional up regulation of CXCL1, these primary cells exhibited the greatest IL-8 secretion and cell damage in response to stimulation with an acapsular strain of <it>C. neoformans</it>.</p> <p>Conclusion</p> <p>This study demonstrates that human bronchial epithelial cells mediate an acute inflammatory response to <it>C. neoformans </it>and are susceptible to damage by this fungal pathogen. The presence of capsular polysaccharide and <it>in vitro </it>fungal culture conditions modulate the host inflammatory response to <it>C. neoformans</it>. Human bronchial epithelial cells are likely to contribute to the initial stages of pulmonary host defense <it>in vivo</it>.</p

    The Choice of the Filtering Method in Microarrays Affects the Inference Regarding Dosage Compensation of the Active X-Chromosome

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    The hypothesis of dosage compensation of genes of the X chromosome, supported by previous microarray studies, was recently challenged by RNA-sequencing data. It was suggested that microarray studies were biased toward an over-estimation of X-linked expression levels as a consequence of the filtering of genes below the detection threshold of microarrays.To investigate this hypothesis, we used microarray expression data from circulating monocytes in 1,467 individuals. In total, 25,349 and 1,156 probes were unambiguously assigned to autosomes and the X chromosome, respectively. Globally, there was a clear shift of X-linked expressions toward lower levels than autosomes. We compared the ratio of expression levels of X-linked to autosomal transcripts (X∶AA) using two different filtering methods: 1. gene expressions were filtered out using a detection threshold irrespective of gene chromosomal location (the standard method in microarrays); 2. equal proportions of genes were filtered out separately on the X and on autosomes. For a wide range of filtering proportions, the X∶AA ratio estimated with the first method was not significantly different from 1, the value expected if dosage compensation was achieved, whereas it was significantly lower than 1 with the second method, leading to the rejection of the hypothesis of dosage compensation. We further showed in simulated data that the choice of the most appropriate method was dependent on biological assumptions regarding the proportion of actively expressed genes on the X chromosome comparative to the autosomes and the extent of dosage compensation.This study shows that the method used for filtering out lowly expressed genes in microarrays may have a major impact according to the hypothesis investigated. The hypothesis of dosage compensation of X-linked genes cannot be firmly accepted or rejected using microarray-based data

    Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

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    Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{6×10196\times 10^{19}eV}. The anisotropy was measured by the fraction of arrival directions that are less than 3.1∘3.1^\circ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron 12th12^{\rm th} catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is (38−6+7)(38^{+7}_{-6})%, compared with 2121% expected for isotropic cosmic rays. This is down from the early estimate of (69−13+11)(69^{+11}_{-13})%. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201
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