81 research outputs found
ConstrucciĂłn de Servicios Interactivos en Entornos de TelevisiĂłn Digital
Context: In order to expand the range of virtual education opportunities, itâs important to consider two technological aspects: the great potential of TV penetration and the Web 2.0 services boom in social networks and Internet communities, spaces in which users share and generate knowledge around a topic. So, itâs necessary to define how to implement and deploy these interactive services in television environments, given the particularcharacteristics of this scenario.Method: For the purpose of guiding the building process of interactive services, in this paper we propose a scheme of service consumption in scenarios of interactive digital television (iDTV), which has been adapted from the REST-JSON (Representational State Transfer â Javascript Object Notation) architectural style.Results: As a result of the use of the proposed scheme, we implemented the message board, chat and e-mail services, in the television scenarios of digital terrestrial television (DTT) and Mobile TV of the ST-CAV project (T-Learning services for the support of virtual academic communities). Likewise, another result obtained in the present paper, was the evaluation of the implemented services through network traffic and memory consumptiontests.Conclusions: According to processing and response times obtained in the evaluation of implemented interactive services, the presented scheme can be considered as a viable alternative for the design and building of services in iDTV scenarios, allowing convergence with Internet applications (Web 2.0).Contexto: Con el fin de ampliar el abanico de oportunidades de la educaciĂłn virtual, es importante considerar dos aspectos tecnolĂłgicos relevantes: el gran potencial de la penetraciĂłn de la televisiĂłn y el auge de servicios de la web 2.0 en redes sociales y comunidades en Internet, espacios en los cuales los usuarios comparten y generan conocimiento alrededor de una temĂĄtica. AsĂ, se hace necesario definir la forma adecuada de implementar y desplegar estos servicios interactivos en entornos de televisiĂłn, dadas las caracterĂsticas particulares de este escenario.MĂ©todo: Con el propĂłsito de guiar el proceso de construcciĂłn de servicios interactivos de televisiĂłn, en este artĂculo se propone un esquema para el consumo de servicios para escenarios de televisiĂłn digital interactiva (TVDi), el cual fue adaptado a partir del estilo arquitectĂłnico REST-JSON (Representational State Transfer â Javascript Object Notation).Resultados: Como resultados del uso del esquema propuesto, se construyeron los servicios de chat, tablĂłn de mensajes y acceso a correo electrĂłnico, en los escenarios de televisiĂłn digital terrestre (TDT) y TV MĂłvil del proyecto ST-CAV (Servicios de T-Learning para el soporte de Comunidades AcadĂ©micas Virtuales). AsĂ mismo, otro de los resultados del presente artĂculo fue la evaluaciĂłn de los servicios implementados, mediante pruebas de trĂĄfico de red y consumo de memoria.Conclusiones: De acuerdo a los tiempos de procesamiento y respuesta obtenidos en la evaluaciĂłn de los servicios interactivos implementados, es posible concluir que el esquema planteado en este artĂculo, puede considerarse como una alternativa adecuada para el diseño y construcciĂłn de servicios en escenarios de TVDi, permitiendo la convergencia con aplicaciones de Internet (web 2.0)
Characterization of Phosphofructokinase Activity in Mycobacterium tuberculosis Reveals That a Functional Glycolytic Carbon Flow Is Necessary to Limit the Accumulation of Toxic Metabolic Intermediates under Hypoxia
10.1371/journal.pone.0056037PLoS ONE82
Towards a Synthetic Chloroplast
The evolution of eukaryotic cells is widely agreed to have proceeded through a series of endosymbiotic events between larger cells and proteobacteria or cyanobacteria, leading to the formation of mitochondria or chloroplasts, respectively. Engineered endosymbiotic relationships between different species of cells are a valuable tool for synthetic biology, where engineered pathways based on two species could take advantage of the unique abilities of each mutualistic partner.We explored the possibility of using the photosynthetic bacterium Synechococcus elongatus PCC 7942 as a platform for studying evolutionary dynamics and for designing two-species synthetic biological systems. We observed that the cyanobacteria were relatively harmless to eukaryotic host cells compared to Escherichia coli when injected into the embryos of zebrafish, Danio rerio, or taken up by mammalian macrophages. In addition, when engineered with invasin from Yersinia pestis and listeriolysin O from Listeria monocytogenes, S. elongatus was able to invade cultured mammalian cells and divide inside macrophages.Our results show that it is possible to engineer photosynthetic bacteria to invade the cytoplasm of mammalian cells for further engineering and applications in synthetic biology. Engineered invasive but non-pathogenic or immunogenic photosynthetic bacteria have great potential as synthetic biological devices
Ionospheric response modeling under eclipse conditions: Evaluation of 14 December 2020, total solar eclipse prediction over the South American sector
In this work, we evaluate the SUPIM-INPE model prediction of the 14 December 2020, total solar eclipse over the South American continent. We compare the predictions with data from multiple instruments for monitoring the ionosphere and with different obscuration percentages (i.e., Jicamarca, 12.0°S, 76.8°W, 17%; TucumĂĄn 26.9°S, 65.4° W, 49%; ChillĂĄn 36.6°S, 72.0°W; and BahĂa Blanca, 38.7°S, 62.3°W, reach 95% obscuration) due to the eclipse. The analysis is done under total eclipse conditions and non-total eclipse conditions. Results obtained suggest that the model was able to reproduce with high accuracy both the daily variation and the eclipse impacts of E and F1 layers in the majority of the stations evaluated (except in Jicamarca station). The comparison at the F2 layer indicates small differences (<7.8%) between the predictions and observations at all stations during the eclipse periods. Additionally, statistical metrics reinforce the conclusion of a good performance of the model. Predicted and calibrated Total Electron Content (TEC, using 3 different techniques) are also compared. Results show that, although none of the selected TEC calibration methods have a good agreement with the SUPIM-INPE prediction, they exhibit similar trends in most of the cases. We also analyze data from the Jicamarca Incoherent Scatter Radar (ISR), and Swarm-A and GOLD missions. The electron temperature changes observed in ISR and Swarm-A are underestimated by the prediction. Also, important changes in the O/N2 ratio due to the eclipse, have been observed with GOLD mission data. Thus, future versions of the SUPIM-INPE model for eclipse conditions should consider effects on thermospheric winds and changes in composition, specifically in the O/N2 ratio
Modulation of GABAA receptors and of GABAergic synapses by the natural alkaloid gelsemine
The Gelsemium elegans plant preparations have shown beneficial activity against common diseases, including chronic pain and anxiety. Nevertheless, their clinical uses are limited by their toxicity. Gelsemine, one of the most abundant alkaloids in the Gelsemium plants, have replicated these therapeutic and toxic actions in experimental behavioral models. However, the molecular targets underlying these biological effects remain unclear. The behavioral activity profile of gelsemine suggests the involvement of GABAA receptors (GABAARs), which are the main biological targets of benzodiazepines (BDZs), a group of drugs with anxiolytic, hypnotic, and analgesic properties. Here, we aim to define the modulation of GABAARs by gelsemine, with a special focus on the subtypes involved in the BDZ actions. The gelsemine actions were determined by electrophysiological recordings of recombinant GABAARs expressed in HEK293 cells, and of native receptors in cortical neurons. Gelsemine inhibited the agonist-evoked currents of recombinant and native receptors. The functional inhibition was not associated with the BDZ binding site. We determined in addition that gelsemine diminished the frequency of GABAergic synaptic events, likely through a presynaptic modulation. Our findings establish gelsemine as a negative modulator of GABAARs and of GABAergic synaptic function. These pharmacological features discard direct anxiolytic or analgesic actions of gelsemine through GABAARs but support a role of GABAARs on the alkaloid induced toxicity. On the other hand, the presynaptic effects of the alkaloid provide an additional mechanism to explain their beneficial effects. Collectively, our results contribute novel information to improve understanding of gelsemine actions in the mammalian nervous system
Metabolic adaptation of two in silico mutants of Mycobacterium tuberculosis during infection
ABSTRACT: Background: Up to date, Mycobacterium tuberculosis (Mtb) remains as the worst intracellular killer pathogen. To
establish infection, inside the granuloma, Mtb reprograms its metabolism to support both growth and survival,
keeping a balance between catabolism, anabolism and energy supply. Mtb knockouts with the faculty of being
essential on a wide range of nutritional conditions are deemed as target candidates for tuberculosis (TB) treatment.
Constraint-based genome-scale modeling is considered as a promising tool for evaluating genetic and nutritional perturbations on Mtb metabolic reprogramming. Nonetheless, few in silico assessments of the effect of nutritional conditions on Mtbâs vulnerability and metabolic adaptation have been carried out.
Results: A genome-scale model (GEM) of Mtb, modified from the H37Rv iOSDD890, was used to explore the
metabolic reprogramming of two Mtb knockout mutants (pfkA- and icl-mutants), lacking key enzymes of central
carbon metabolism, while exposed to changing nutritional conditions (oxygen, and carbon and nitrogen sources).
A combination of shadow pricing, sensitivity analysis, and flux distributions patterns allowed us to identify
metabolic behaviors that are in agreement with phenotypes reported in the literature. During hypoxia, at high
glucose consumption, the Mtb pfkA-mutant showed a detrimental growth effect derived from the accumulation of toxic sugar phosphate intermediates (glucose-6-phosphate and fructose-6-phosphate) along with an increment of carbon fluxes towards the reductive direction of the tricarboxylic acid cycle (TCA). Furthermore, metabolic reprogramming of the icl-mutant (icl1&icl2) showed the importance of the methylmalonyl pathway for the detoxification of propionyl-CoA, during growth at high fatty acid consumption rates and aerobic conditions. At elevated levels of fatty acid uptake and hypoxia, we found a drop in TCA cycle intermediate accumulation that might create redox imbalance. Finally, findings regarding Mtb-mutant metabolic adaptation associated with
asparagine consumption and acetate, succinate and alanine production, were in agreement with literature reports.
Conclusions: This study demonstrates the potential application of genome-scale modeling, flux balance analysis (FBA), phenotypic phase plane (PhPP) analysis and shadow pricing to generate valuable insights about Mtb metabolic reprogramming in the context of human granulomas
Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019
Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population
Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry
Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) ”g/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) ”g/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%
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