3 research outputs found

    Pneumococcal interactions with the host : threats and therapeutic approaches

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    Streptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium responsible for substantial morbidity and mortality worldwide. Apart from causing severe pneumonia, septicemia or meningitis, pneumococci are also major contributors to less severe diseases like otitis media and sinusitis. Pneumococcal autolysis was thought to be the main route that S. pneumoniae utilizes in order to deliver its virulence factors. Recently a new mechanism has been proposed, the release of extracellular vesicles (EVs).Presence of adhesins and other virulence factors on EVs leads to cell responses after contact with vesicles. We observed that pneumococcal EVs are indeed a mechanism for the delivery of virulence factors to host cells, and that interactions of vesicles with dendritic cells lead to activation of cells and release of pro-inflammatory cytokines. Since EVs mimic the outside of a bacterium, they can play a role as decoys for the immune system. Tightly linked to this decoy function is the ability of EVs to promote immune evasion through binding of serum components. Indeed, we discovered that pneumococcal EVs are able to bind several components of the human complement system, leading to formation of the membrane attack complex on vesicles.Outer membrane vesicles (OMVs) released from Gram-negative bacteria have been directly used as vaccines in numerous preclinical mouse models. We isolated pneumococcal vesicles and found that they are able to confer serotype-independent protection in mice. Moreover, these vesicles stimulate the production of antibodies directed against pneumococcal antigens. These antibodies are able to increase opsonophagocytosis of pneumococci by mouse macrophages, and are required for protection, as demonstrated by the absence of protection in mice that are not able to produce B lymphocytes. Moreover, in our model the vesicles are able to protect mice against an infection with a pneumococcal strain of serotype 3, to a higher degree than what we observed for the currently available pneumococcal vaccine PCV13. The protective effect in humans of PCV13 against IPD caused by serotype 3 is debated.The structure of the pneumococcal capsule differs vastly between serotypes. We found that these differences have profound consequences in determining the disease progression in terms of pneumonia or septicemia, in mice. In particular, we observed that serotype 2 was quickly cleared from the lungs but migrated efficiently to the blood, while serotype 3 remained in the lungs, since the thick capsule made bacteria able to adhere less to cells and better avoid opsonization by the complement system. Fate of pneumococcal disease is tightly linked to the immune response against pneumococci. We found that a compound used in traditional Chinese medicine is able to potentiate the response of dendritic cells against pathogens, as well as increase the antimicrobial activities of host cells.Overall, the work in this thesis provides information on pneumococcal interactions with the host immune system and highlights the potential use of vesicles in future vaccination strategies.List of scientific papersI. CODEMO M., MUSCHIOL S., IOVINO F., NANNAPANENI P., PLANT L., WAI S. N., HENRIQUES-NORMARK B. Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses. mBio. 2018 Apr 10, 9(2): e00559-18. https://doi.org/10.1128/mBio.00559-18 II. CODEMO M., IOVINO F., MUSCHIOL S., NANNAPANENI P., HENRIQUES-NORMARK B. Streptococcus pneumoniae microparticles evoke a heterologous serotypeindependent protection towards invasive pneumococcal disease. [Manuscript]III. NORMAN M., PATHAK A., CODEMO M., SENDER V., GALLOTTA M., NANNAPANENI P., BOOTSMA H. J., BROWALL S., JONCZYK M., HASTE L., HERMANS P., ANDREW P., HENRIQUES-NORMARK B. Growth and defence strategies affect pneumococcal disease pattern: septicaemia versus pneumonia. [Manuscript]IV. XIE S., SPELMINK L., CODEMO M., SUBRAMANIAN K., PÜTSEP K., HENRIQUES-NORMARK B., OLLIVER M. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity. PLoS ONE. 2016 Aug 16; 11(8): e0160734. https://doi.org/10.1371/journal.pone.0160734 </p

    Electron gun and CVD diamond window for a 346 GHz sheet beam BWO

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    A collaboration between UC Davis, Lancaster University, Beijing Vacuum Electronics Research Institute (BVERI), and the University of Electronic Science and Technology of China (UESTC) is developing a 346 GHz backward wave oscillator (BWO) for use as a high frequency RF source in plasma fusion diagnostics, medical, biological, and security imaging systems. Development of new electron gun optics that achieve almost 100% beam transmission based on particle-in-cell simulations is presented along with comparisons of the cold and hot beam. Also, a CVD diamond pillbox window design is presented. Additionally, the mechanical layout of the devices is being completed and prepared for fabrication

    Modelo de gestão da qualidade para a cadeia de produção de alimentos orgânicos: alinhamento do processo ao consumidor

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    Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós-Graduação em Engenharia de Produção, Florianópolis, 2011Este trabalho trata da gestão da qualidade na produção de alimentos orgânicos processados. Para tanto, foi desenvolvido um modelo estruturado em três elementos de gestão, baseado nas cinco abordagens de Garvin para qualidade e em três elos da cadeia de produção de alimentos orgânicos processados. Este modelo tem como objetivo a melhoria da qualidade da produção dos alimentos orgânicos processados alinhando o foco no processo produtivo ao foco no consumidor. Para fundamentar o desenvolvimento do modelo proposto realizou-se um levantamento bibliográfico por meio de uma análise bibliométrica. Os conceitos básicos utilizados na construção do modelo foram retirados de uma seleção de 465 artigos. O esboço metodológico utilizado envolve pesquisa teórica e empírica, com abordagem qualitativa e quantitativa. O suporte prático compreende a realização de estudos de casos de empresas que produzem e comercializam estes alimentos bem como um levantamento tipo survey com consumidores destes produtos. Conclui-se que as abordagens de Garvin baseada no usuário e no processo produtivo são adequadas à produção de alimentos orgânicos processados, enquanto que somente a primeira é adequada ao consumidor.This work deals with the management of quality in the production of processed organic foods. To that end, it was developed a model structured in three elements of management and in three players of processed organic food´s chain, based on five approaches to Garvin quality. This model aims to improve the quality of the production of processed organic foods aligning the focus in the production process to focus on the consumer. To support the development of the proposed model performed a literature review through a bibliometric analysis. The basic concepts used in constructing of the model were taken from a selection of 465 papers. The design approach used involves theoretical and empirical research, besides qualitative and quantitative approach. The support practical involves case studies of companies that produce and market these foods as well as an assessment type survey of consumers of these products. It was conclude that Garvin´s approach based on consumer and in the production process are suitable for the production of organic processed foods, while the first is only appropriate to the consumer
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