352 research outputs found

    Bioengineering commensal bacteria-derived outer membrane vesicles for delivery of biologics to the gastrointestinal and respiratory tract.

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    Gram-negative bacteria naturally produce and secrete nanosized outer membrane vesicles (OMVs). In the human gastrointestinal tract, OMVs produced by commensal Gram-negative bacteria can mediate interactions amongst host cells (including between epithelial cells and immune cells) and maintain microbial homeostasis. This OMV-mediated pathway for host-microbe interactions could be exploited to deliver biologically active proteins to the body. To test this we engineered the Gram-negative bacterium Bacteroides thetaiotaomicron (Bt), a prominent member of the intestinal microbiota of all animals, to incorporate bacteria-, virus- and human-derived proteins into its OMVs. We then used the engineered Bt OMVs to deliver these proteins to the respiratory and gastrointestinal (GI)-tract to protect against infection, tissue inflammation and injury. Our findings demonstrate the ability to express and package both Salmonella enterica ser. Typhimurium-derived vaccine antigens and influenza A virus (IAV)-derived vaccine antigens within or on the outer membrane of Bt OMVs. These antigens were in a form capable of eliciting antigen-specific immune and antibody responses in both mucosal tissues and systemically. Furthermore, immunisation with OMVs containing the core stalk region of the IAV H5 hemagglutinin from an H5N1 strain induced heterotypic protection in mice to a 10-fold lethal dose of an unrelated subtype (H1N1) of IAV. We also showed that OMVs could express the human therapeutic protein, keratinocyte growth factor-2 (KGF-2), in a stable form that, when delivered orally, reduced disease severity and promoted intestinal epithelial repair and recovery in animals administered colitis-inducing dextran sodium sulfate. Collectively, our data demonstrates the utility and effectiveness of using Bt OMVs as a mucosal biologics and drug delivery platform technology

    From managing transitions towards building movements of affect: Advancing agroecological practices and transformation in Brazil

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    Policy and scholarly efforts to foster sustainable transformations focus on the contribution of practices and institutions; thus far, however, the affects that encourage and enable people to mobilise for and establish these transformative practices and institutions have received less attention. Drawing on the example of the agroecology movement in Brazil, this article examines how affects foster the creation of new farming, community and market relations. It argues that affects play a decisive role in mobilising people and encouraging them to identify and challenge unsustainable relations and practices, develop alternatives, and translate local concerns into policy proposals. It also shows that affects support the establishment of transformative practices by enabling caring relations with nature, and by fostering knowledge and institutional arrangements that support human and non-human others. We conclude that mainstream approaches to sustainability transformations should focus more on building movements of affect, as these not only address sustainability issues but also build and draw on the potential of people to bring about transformation

    Chemical and Microbiological Contamination in Limpet (Patella spp.) of the Portuguese Coast

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    Coastal production areas can be impacted by anthropogenic contamination from urban, agro-industrial and leisure activities. Some contaminants, such as chemical substances might also have a telluric origin. Non filter feeding univalve mollusks, such as limpets, which are collected in rocky shores either for sale or for auto-consumption, are very appreciated in Portugal, but have been excluded from provisions on the classification of production areas, although can present relevant contamination. Thus, the aim of this study was to assess the microbiological and toxic metal contaminations in limpets (Patella spp) of the Portuguese coast, taking into account the production area and seasonal variation, and comparing their contamination levels with those occurring in bivalve mollusk indicator species, mussel (Mytilus edulis). The risks associated to the consumption of limpet meals were also assessed. For that, microbial total and fecal levels and cadmium, lead and mercury contents in limpets and mussels samples from three coastal areas over several months were analyzed based on standard methodologies. Contents of mercury and lead in limpets from the three areas studied, were always below the limits of 0.50 mg kg-1 and 1.5 mg kg-1 allowed by the EU, respectively. Regarding cadmium, levels in limpet were always above the limit of 1.0 mg kg-1, reaching about 3.0 mg kg-1 in some samples. These values probably indicate contamination from telluric origin (soil or rocks) in the coastal studied areas. Results indicated that microbiological contamination of fecal origin was low and in general below the detection level. Contamination levels did not show a clear seasonal pattern. The two mollusk species, limpets and mussels, differed statistically in all contaminants analyzed, being cadmium the most of concern, and always higher in limpets than in mussel samples. Thus, the potential risk associated with limpet consumption, taking into account the cadmium tolerable weekly intake (TWI), was investigated, being possible to reach a reliable recommendation of less than a monthly meal of 160 g. As recreational picking of limpets is common in Portugal, official 4recommendations of maximum periodic human consumption should be published and enforcement increased in forbidden areasinfo:eu-repo/semantics/acceptedVersio

    Dispersed free phytosterols as structuring agents in lipid systems with reduced saturated fat

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    The negative effects of trans fatty acids and saturated fatty acids in food have been widely discussed and this has led to progressive changes in the legislation of many countries. The use of structuring agents or crystallization modifiers, as specific triacylglycerol and minor lipids have been indicated as the only viable alternative for obtaining low saturated fats with properties which are compatible with food application. In this context, phytosterols, natural products with hypocholesterolemic action, and hard fat-crystallization modulators, present a new option for structuring lipid matrices. This work characterized the effects of fully hydrogenated soybean oil and free phytosterols on the physical properties and crystallization behavior of palm oil and canola oil blends for the development of zero trans-fat bases with low levels of saturated fatty acids. The systems were evaluated for chemical composition, atherogenic index, solid fat profiles, microstructure, consistency, thermal behavior and polymorphism

    Measurements of long-range near-side angular correlations in sNN=5\sqrt{s_{\text{NN}}}=5TeV proton-lead collisions in the forward region

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    Two-particle angular correlations are studied in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of sNN=5\sqrt{s_{\text{NN}}}=5TeV, collected with the LHCb detector at the LHC. The analysis is based on data recorded in two beam configurations, in which either the direction of the proton or that of the lead ion is analysed. The correlations are measured in the laboratory system as a function of relative pseudorapidity, Δη\Delta\eta, and relative azimuthal angle, Δϕ\Delta\phi, for events in different classes of event activity and for different bins of particle transverse momentum. In high-activity events a long-range correlation on the near side, Δϕ0\Delta\phi \approx 0, is observed in the pseudorapidity range 2.0<η<4.92.0<\eta<4.9. This measurement of long-range correlations on the near side in proton-lead collisions extends previous observations into the forward region up to η=4.9\eta=4.9. The correlation increases with growing event activity and is found to be more pronounced in the direction of the lead beam. However, the correlation in the direction of the lead and proton beams are found to be compatible when comparing events with similar absolute activity in the direction analysed.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-040.htm

    Study of the production of Λb0\Lambda_b^0 and B0\overline{B}^0 hadrons in pppp collisions and first measurement of the Λb0J/ψpK\Lambda_b^0\rightarrow J/\psi pK^- branching fraction

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    The product of the Λb0\Lambda_b^0 (B0\overline{B}^0) differential production cross-section and the branching fraction of the decay Λb0J/ψpK\Lambda_b^0\rightarrow J/\psi pK^- (B0J/ψK(892)0\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0) is measured as a function of the beauty hadron transverse momentum, pTp_{\rm T}, and rapidity, yy. The kinematic region of the measurements is pT<20 GeV/cp_{\rm T}<20~{\rm GeV}/c and 2.0<y<4.52.0<y<4.5. The measurements use a data sample corresponding to an integrated luminosity of 3 fb13~{\rm fb}^{-1} collected by the LHCb detector in pppp collisions at centre-of-mass energies s=7 TeV\sqrt{s}=7~{\rm TeV} in 2011 and s=8 TeV\sqrt{s}=8~{\rm TeV} in 2012. Based on previous LHCb results of the fragmentation fraction ratio, fΛB0/fdf_{\Lambda_B^0}/f_d, the branching fraction of the decay Λb0J/ψpK\Lambda_b^0\rightarrow J/\psi pK^- is measured to be \begin{equation*} \mathcal{B}(\Lambda_b^0\rightarrow J/\psi pK^-)= (3.17\pm0.04\pm0.07\pm0.34^{+0.45}_{-0.28})\times10^{-4}, \end{equation*} where the first uncertainty is statistical, the second is systematic, the third is due to the uncertainty on the branching fraction of the decay B0J/ψK(892)0\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0, and the fourth is due to the knowledge of fΛb0/fdf_{\Lambda_b^0}/f_d. The sum of the asymmetries in the production and decay between Λb0\Lambda_b^0 and Λb0\overline{\Lambda}_b^0 is also measured as a function of pTp_{\rm T} and yy. The previously published branching fraction of Λb0J/ψpπ\Lambda_b^0\rightarrow J/\psi p\pi^-, relative to that of Λb0J/ψpK\Lambda_b^0\rightarrow J/\psi pK^-, is updated. The branching fractions of Λb0Pc+(J/ψp)K\Lambda_b^0\rightarrow P_c^+(\rightarrow J/\psi p)K^- are determined.Comment: 29 pages, 19figures. All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-032.htm

    Evidence for the strangeness-changing weak decay ΞbΛb0π\Xi_b^-\to\Lambda_b^0\pi^-

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    Using a pppp collision data sample corresponding to an integrated luminosity of 3.0~fb1^{-1}, collected by the LHCb detector, we present the first search for the strangeness-changing weak decay ΞbΛb0π\Xi_b^-\to\Lambda_b^0\pi^-. No bb hadron decay of this type has been seen before. A signal for this decay, corresponding to a significance of 3.2 standard deviations, is reported. The relative rate is measured to be fΞbfΛb0B(ΞbΛb0π)=(5.7±1.80.9+0.8)×104{{f_{\Xi_b^-}}\over{f_{\Lambda_b^0}}}{\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) = (5.7\pm1.8^{+0.8}_{-0.9})\times10^{-4}, where fΞbf_{\Xi_b^-} and fΛb0f_{\Lambda_b^0} are the bΞbb\to\Xi_b^- and bΛb0b\to\Lambda_b^0 fragmentation fractions, and B(ΞbΛb0π){\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) is the branching fraction. Assuming fΞb/fΛb0f_{\Xi_b^-}/f_{\Lambda_b^0} is bounded between 0.1 and 0.3, the branching fraction B(ΞbΛb0π){\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) would lie in the range from (0.57±0.21)%(0.57\pm0.21)\% to (0.19±0.07)%(0.19\pm0.07)\%.Comment: 7 pages, 2 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-047.htm

    BB flavour tagging using charm decays at the LHCb experiment

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    An algorithm is described for tagging the flavour content at production of neutral BB mesons in the LHCb experiment. The algorithm exploits the correlation of the flavour of a BB meson with the charge of a reconstructed secondary charm hadron from the decay of the other bb hadron produced in the proton-proton collision. Charm hadron candidates are identified in a number of fully or partially reconstructed Cabibbo-favoured decay modes. The algorithm is calibrated on the self-tagged decay modes B+J/ψK+B^+ \to J/\psi \, K^+ and B0J/ψK0B^0 \to J/\psi \, K^{*0} using 3.0fb13.0\mathrm{\,fb}^{-1} of data collected by the LHCb experiment at pppp centre-of-mass energies of 7TeV7\mathrm{\,TeV} and 8TeV8\mathrm{\,TeV}. Its tagging power on these samples of BJ/ψXB \to J/\psi \, X decays is (0.30±0.01±0.01)%(0.30 \pm 0.01 \pm 0.01) \%.Comment: All figures and tables, along with any supplementary material and additional information, are available at http://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-027.htm
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