Modulation of human macrophage responses to mycobacterium tuberculosis by silver nanoparticles of different size and surface modification

Exposure to silver nanoparticles (AgNP) used in consumer products carries potential health risks including increased susceptibility to infectious pathogens. Systematic assessments of antimicrobial macrophage immune responses in the context of AgNP exposure are important because uptake of AgNP by macrophages may lead to alterations of innate immune cell functions. In this study we examined the effects of exposure to AgNP with different particle sizes (20 and 110 nm diameters) and surface chemistry (citrate or polyvinlypyrrolidone capping) on cellular toxicity and innate immune responses against Mycobacterium tuberculosis (M.tb) by human monocyte-derived macrophages (MDM). Exposures of MDM to AgNP significantly reduced cellular viability, increased IL8 and decreased IL10 mRNA expression. Exposure of M.tb-infected MDM to AgNP suppressed M.tb-induced expression of IL1B, IL10, and TNFA mRNA. Furthermore, M.tb-induced IL-1β, a cytokine critical for host resistance to M.tb, was inhibited by AgNP but not by carbon black particles indicating that the observed immunosuppressive effects of AgNP are particle specific. Suppressive effects of AgNP on the M.tb-induced host immune responses were in part due to AgNP-mediated interferences with the TLR signaling pathways that culminate in the activation of the transcription factor NF-κB. AgNP exposure suppressed M.tb-induced expression of a subset of NF-κB mediated genes (CSF2, CSF3, IFNG, IL1A, IL1B, IL6, IL10, TNFA, NFKB1A). In addition, AgNP exposure increased the expression of HSPA1A mRNA and the corresponding stress-induced Hsp72 protein. Up-regulation of Hsp72 by AgNP can suppress M.tb-induced NF-κB activation and host immune responses. The observed ability of AgNP to modulate infectious pathogen-induced immune responses has important public health implications

Partial complementation of Sinorhizobium meliloti bacA mutant phenotypes by the Mycobacterium tuberculosis BacA protein

The Sinorhizobium meliloti BacA ABC transporter protein plays an important role in its nodulating symbiosis with the legume alfalfa (Medicago sativa). The Mycobacterium tuberculosis BacA homolog was found to be important for the maintenance of chronic murine infections, yet its in vivo function is unknown. In the legume plant as well as in the mammalian host, bacteria encounter host antimicrobial peptides (AMPs). We found that the M. tuberculosis BacA protein was able to partially complement the symbiotic defect of an S. meliloti BacA-deficient mutant on alfalfa plants and to protect this mutant in vitro from the antimicrobial activity of a synthetic legume peptide, NCR247, and a recombinant human \u3b2-defensin 2 (HBD2). This finding was also confirmed using an M. tuberculosis insertion mutant. Furthermore, M. tuberculosis BacA-mediated protection of the legume symbiont S. meliloti against legume defensins as well as HBD2 is dependent on its attached ATPase domain. In addition, we show that M. tuberculosis BacA mediates peptide uptake of the truncated bovine AMP, Bac71-16. This process required a functional ATPase domain. We therefore suggest that M. tuberculosis BacA is important for the transport of peptides across the cytoplasmic membrane and is part of a complete ABC transporter. Hence, BacA-mediated protection against host AMPs might be important for the maintenance of latent infections

Combining interdisciplinarity and creative design - A powerful strategy to increase palliative care awareness within a university community

Society’s understanding of palliative care has room for improvement. Although the World Health Organisation highlighted palliative care as a human right, many people still lack access to this crucial form of treatment. The paucity of understanding and social discussion surrounding palliative care has, moreover, negatively impacted its development and implementation. This study therefore aims to construct a strategy that will empower a specific community to solve their own palliative care-related misunderstandings. Using Participatory Action Research and Design Thinking methodologies and adopting the strategy of Public Engagement in Responsible Research and Innovation, a design group worked for three months through five virtual focus groups. Moving through the phases of empathizing, defining, ideation, prototyping, and testing, the design group generated 33 ideas to address palliative care-related problems. Ideas related to self- learning, the use of technology, and the exchange of personal experiences are highlighted as innovative ways to promote palliative care. The design group adopted a variety of strategies, used disruptive tools, and created and tested rapid prototypes to discover novel solutions. This method of working, centred on interdisciplinarity and creativity, presents an efficient way to involve the members of a community in solving their own problems

Performance evaluation of a multiscale modelling system applied to particulate matter dispersion in a real traffic hot spot in Madrid (Spain)

Urban air pollution is one of the most important environmental problems nowadays. Understanding urban pollution is rather challenging due to different factors that produce a strongly heterogeneous pollutant distribution within streets. Observed concentrations depend on processes occurring at a wide range of spatial and temporal scales, complex wind flow and turbulence patterns induced by urban obstacles and irregular traffic emissions. The main objective of this paper is to model particulate matter dispersion at microscale while considering the effects of mesoscale processes. Computational Fluid Dynamic (CFD) PM10 simulations were performed taking into account high spatial resolution traffic emissions from a microscale traffic model and inlet vertical profiles of meteorological variables from Weather Research and Forecasting (WRF) model. This modelling system is evaluated by using meteorological and PM10 concentration data from intensive experimental campaigns carried out on 25th February and 6th July, 2015 in a real urban traffic hot-spot in Madrid. The effect of uncertainties in the inlet profiles from mesoscale input data on microscale results is assessed. Additionally, the importance of the sensible surface heat fluxes (SHF) provided by WRF and the selection of an appropriate turbulent Schmidt number in the dispersion equation are investigated. The main conclusion is that the modelling system accurately reproduces PM10 dispersion imposing appropriate inputs (meteorological variables and SHF) and a suitable turbulent Schmidt number. Better agreement is found for simulation with a low turbulent Schmidt number. This approach improves the standard microscale modelling alone because more realistic boundary conditions and mesoscale processes are considered

Interplay between SUMOylation and NEDDylation regulates RPL11 localization and function

The ribosomal protein L11 (RPL11) integrates different types of stress into a p53‐mediated response. Here, we analyzed the impact of the ubiquitin‐like protein SUMO on the RPL11‐mouse double‐minute 2 homolog‐p53 signaling. We show that small ubiquitin‐related modifier (SUMO)1 and SUMO2 covalently modify RPL11. We find that SUMO negatively modulates the conjugation of the ubiquitin‐like protein neural precursor cell‐expressed developmentally downregulated 8 (NEDD8) to RPL11 and promotes the translocation of the RP outside of the nucleoli. Moreover, the SUMO‐conjugating enzyme, Ubc9, is required for RPL11‐mediated activation of p53. SUMOylation of RPL11 is triggered by ribosomal stress, as well as by alternate reading frame protein upregulation. Collectively, our data identify SUMO protein conjugation to RPL11 as a new regulator of the p53‐mediated cellular response to different types of stress and reveal a previously unknown SUMO‐NEDD8 interplay

Validation of a Questionnaire Designed to Study Knowledge, Attitudes, and HabitsRelated to Sun Exposure Among Young Adults: The CHACES Questionnaire

Las campañas escolares de prevención del cáncer cutáneo han demostrado ser eficaces y costo-efectivas. Su éxito depende de un adecuado dise˜no, basado en la encuestación previa de la población diana (alumnos, profesores y padres). Sin embargo, son escasos los cuestionarios validados en castellano que estudien hábitos y conocimientos sobre exposición solar en infancia, y nulos en la población adultojuvenil. Objetivos: Elaborar y validar un cuestionario que explore las conductas relacionadas con la exposición solar en población adultojuvenil. Metodología: Se elaboraron 2 cuestionarios, dirigidos a población adulta (mayor de 18 a˜nos) y juvenil (11-17 a˜nos), incluyendo datos demográficos, color de piel, fototipo, quemaduras solares, prácticas, actitudes y conocimientos relacionados con la exposición solar. Tras el pilotaje y análisis de validez de contenido, se dise˜nó un estudio de validación en 2 fases: I) Análisis de la validez y consistencia interna de los ítems (estudio trasversal sobre 1.482 adolescentes-adultos, con estudio de validez de constructo [mediante análisis factorial exploratorio] y de consistencia interna [alfa de Cronbach]), II) Estudio de la estabilidad (test-retest sobre 39 sujetos). Resultados: El pilotaje demostró la validez de contenido de sendos cuestionarios. El análisis de los componentes principales reveló 2 componentes en cada dimensión estudiada, explicando más del 50% de la varianza. Todos los ítems mostraron buena correlación entre ellos. Se demostró validez en la fase i (coeficiente alfa de Cronbach entre 0,45-0,8, excepto el área de conocimientos [0,335]) y estabilidad en la fase ii (acuerdo absoluto > 60%).Skin cancer prevention campaigns in schools have been shown to be both effectiveand cost-effective. The success of such programs depends on the use of an appropriate designinformed by a prior survey of the target population (pupils, teachers, and parents). There are,however, very few validated Spanish-language questionnaires designed to study the habits andknowledge of this population with respect to sun exposure in childhood and none designed foruse with a young adult population.Objectives: To construct and validate a questionnaire designed to explore sun exposure beha-viors in a young adult population.Methodology: Two questionnaires were developed, one for adults (18+) and the other for youngadults (11-17); both included demographic information, skin color, Fitzpatrick skin type, andhistory of sunburn as well as questions on knowledge, attitudes and practices related to sunexposure. The content was then piloted and its validity analyzed. The subsequent validationstudy was divided into 2 phases as follows: 1) analysis of the validity and internal consistencyof the items in a cross-sectional study of 1,482 adults and adolescents, using exploratory factoranalysis to test construct validity and Cronbach to measure internal consistency; and 2)evaluation of test-retest reliability in 39 individuals.Results: The pilot study demonstrated the content validity of both questionnaires. Principalcomponent analysis revealed that 2 components in each of the dimensions studied accountedfor over 50% of the variance. A good correlation was found between the items studied. Validitywas demonstrated in the first phase of the analysis with a Cronbach of between 0.45 and 0.8for all components except knowledge (0.335). In the second phase, test-retest reliability wasdemonstrated (absolute agreement > 60%).Conclusions: The psychometric properties of the questionnaire make it a valid and reliable toolfor the study of knowledge, attitudes, and habits with respect to sun exposure in the youngadult school population

The co-creation space: Supporting asynchronous artistic co-creation dynamics

Artistic co-creation empowers communities to shape their narratives, however HCI research does not support this multifaceted discussion and reflection process. In the context of community opera, we consider how to support co-creation through the design, implementation, and initial evaluation of the Co-Creation Space (CCS) to help community artists 1) generate raw artistic ideas, and 2) discuss and reflect on the shared meaning of those ideas. This work describes our user-centered process to gather requirements and design the tool, and validates its' usability with 6 community opera participants. Our findings support the value of our tool for group discussion and personal reflection during the creative process

Co-creation stage: A web-based tool for collaborative and participatory co-located art performances

In recent years, artists and communities have expressed the desire to work with tools that facilitate co-creation and allow distributed community performances. These performances can be spread over several physical stages, connecting them on real-time towards a single experience with the audience distributed along them. This enables a wider remote audience consuming the performance through their own devices, and even grants the participation of remote users in the show. In this paper we introduce the Co-creation Stage, a web-based tool that allows managing heterogeneous content sources, with a particular focus on live and on-demand media, across several distributed devices. The Co-creation Stage is part of the toolset developed in the Traction H2020 project which enables community performing art shows, where professional artists and non-professional participants perform together from different stages and locations. Here we present the design process, the architecture and the main functionaliti

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000