36 research outputs found

    Mesoporous Silica Nanoparticles as a Potential Platform for Vaccine Development against Tuberculosis.

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    The increasing emergence of new strains of Mycobacterium tuberculosis (Mtb) highly resistant to antibiotics constitute a public health issue, since tuberculosis still constitutes the primary cause of death in the world due to bacterial infection. Mtb has been shown to produce membrane-derived extracellular vesicles (EVs) containing proteins responsible for modulating the pathological immune response after infection. These natural vesicles were considered a promising alternative to the development of novel vaccines. However, their use was compromised by the observed lack of reproducibility between preparations. In this work, with the aim of developing nanosystems mimicking the extracellular vesicles produced by Mtb, mesoporous silica nanoparticles (MSNs) have been used as nanocarriers of immunomodulatory and vesicle-associated proteins (Ag85B, LprG and LprA). These novel nanosystems have been designed and extensively characterized, demonstrating the e ectiveness of the covalent anchorage of the immunomodulatory proteins to the surface of the MSNs. The immunostimulatory capacity of the designed nanosystems has been demonstrated by measuring the levels of pro- (TNF) and anti-inflammatory (IL-10) cytokines in exposed macrophages. These results open a new possibility for the development of more complex nanosystems, including additional vesicle components or even antitubercular drugs, thus allowing for the combination of immunomodulatory and bactericidal e ects against Mtb.post-print2418 K

    Difusión del software libre en la universidad : la experiencia piloto Moodle en la Universidad del País Vasco

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    La experiencia piloto Moodle UPV/EHU que aquí se presenta, comenzó en 2003 impulsada por un pequeño grupo de profesores apoyados por el centro informático de la universidad (CIDIR). Este grupo ha colaborado de manera desinteresada con los profesores investigadores de la Universidad que han solicitado su ayuda en el uso de Moodle, ofreciéndoles soporte técnico y formación. A partir del curso 2004-2005, este colectivo de profesores ha conformado el Grupo iKide. En este artículo se muestra cómo la filosofía del software libre puede ayudar a impulsar la innovación docente.The UPV-EHU Moodle pilot experience presented in this paper was set up in 2003, driven by a small group of lecturers with the help of the Computer Centre of the UPV/EHU (CIDIR). This group has voluntarily collaborated with those university teachers who were interested in working with Moodle and offered them technical support and training. From the course 2004-2005 onwards, the foremencioned group of lecturers became the iKide Group. This paper shows how Open Source philosophy can help to foster teaching innovation

    Antimycobacterial effect of selenium nanoparticles on Mycobacterium tuberculosis.

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    Tuberculosis remains the leading cause of death from a single infection agent worldwide. In recent years, the occurrence of tuberculosis cases caused by drug-resistant strains has spread, and is expected to continue to grow. Therefore, the development of new alternative treatments to the use of antibiotics is highly important. In that sense, nanotechnology can play a very relevant role, due to the unique characteristics of nanoparticles. In fact, different types of nanoparticles have already been evaluated both as potential bactericides and as efficient drug delivery vehicles. In this work, the use of selenium nanoparticles has been evaluated to inhibit the growth of two types of mycobacteria: Mycobacterium smegmatis and Mycobacterium tuberculosis. The results showed that selenium nanoparticles are able to inhibit the growth of both types of mycobacteria by damaging their cell envelope integrity. These results open a new opportunity for the use of this type of nanoparticles as antimycobacterial agents by themselves, or for the development of novel nanosystems that combine the action of these nanoparticles with other drugs

    Mitochondrial complex I dysfunction alters the balance of soluble and membrane-bound TNF during chronic experimental colitis.

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    Inflammatory bowel disease (IBD) is a complex, chronic, relapsing and heterogeneous disease induced by environmental, genomic, microbial and immunological factors. MCJ is a mitochondrial protein that regulates the metabolic status of macrophages and their response to translocated bacteria. Previously, an acute murine model of DSS-induced colitis showed increased disease severity due to MCJ deficiency. Unexpectedly, we now show that MCJ-deficient mice have augmented tumor necrosis factor alpha converting enzyme (TACE) activity in the context of chronic inflammation. This adaptative change likely affects the balance between soluble and transmembrane TNF and supports the association of the soluble form and a milder phenotype. Interestingly, the general shifts in microbial composition previously observed during acute inflammation were absent in the chronic model of inflammation in MCJ-deficient mice. However, the lack of the mitochondrial protein resulted in increased alpha diversity and the reduction in critical microbial members associated with inflammation, such as Ruminococcus gnavus, which could be associated with TACE activity. These results provide evidence of the dynamic metabolic adaptation of the colon tissue to chronic inflammatory changes mediated by the control of mitochondrial function

    Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart

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    Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.Supported by grants from the Spanish Ministry of Science, Innovation and Universities (MCIU) co-financed with FEDER funds (SAF2015-65327-R and RTI2018-096494-B-100 to JA; BFU2016-76872-R to EB, AGL2017-86757-R to LA, SAF2017-87301-R to MLMC, SAF2015-64111-R to AP, SAF2015-73549-JIN to HR), Instituto de Salud Carlos III (PIE13/0004 to AP), the Basque Government Department of Health (2015111117 to LA), the Basque Foundation for Innovation and Health Research (BIOEF), through the EiTB Maratoia grant BIO15/CA/016/BS to MLMC, the regional Government of Andalusia co-funded by CEC and FEDER funds (Proyectos de Excelencia P12-CTS-2232) and Fundación Domingo Martínez (to AP). LA is supported by the Ramon y Cajal program (RYC-2013-13666). DB, MMR and TMM are recipients of MCIU FPI fellowships. ACG and AP are recipients of fellowships form the Basque Government. APC is a recipient of a fellowship from the University of the Basque Country. We thank the MCIU for the Severo Ochoa Excellence accreditation (SEV-2016-0644), the Basque Department of Industry, Tourism and Trade (Etortek and Elkartek programs), the Innovation Technology Department of the Bizkaia Province and the CIBERehd network. DB and JA are supported by a grant from the Jesús de Gangoiti Barrera Foundation

    Crítica, periodismo y divulgación musical en espacios digitales

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    Mediante el presente proyecto se ha ofrecido formación en recursos y prácticas de crítica y periodismo musical, profundizando en la importancia de la divulgación en espacios digitales. Se trata de la continuación del anterior proyecto de innovación no 21 "Herramientas de comunicación y divulgación musical orientadas a la transferencia: entornos digitales 2.0". El nuevo proyecto se ha centrado en los ámbitos de la crítica y el periodismo, concretamente en la actualidad de la prensa escrita y la radio, así como ha tenido en cuenta el uso extendido de redes sociales y plataformas online en tareas de divulgación de contenidos. Dicha formación ha querido dar respuesta a la necesidad de que el profesorado y el alumnado en Musicología actualice y refuerce su conocimiento sobre los códigos, recursos, y entornos en los que se desarrollan estos campos, ya que se trata actualmente de uno de los ámbitos principales de proyección profesional de los egresados de Musicología, a través de la demanda de publicaciones digitales que requieren especialización en música, , radios - en las cuales la interacción con el usuario de internet es crucial-, e instituciones culturales y musicales que necesitan reseñas, crónicas, y breves escritos enfocados a sus espacios de difusión y promoción en internet. Se trata de un proyecto interfacultativo e interdepartamental ya que ha implicado a profesionales, docentes, investigadores y alumnado del Departamento de Musicología, el ICCMU (ambos de la Facultad de Geografía e Historia), y el Departamento de Periodismo y Nuevos medios (Facultad de Ciencias de la Información)
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