Study of autophagy regulation and innate immunity in African Swine Fever Virus infection

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 31-10-2014In this current work, we have investigated the role of the African swine fever virus (AFSV) in the context of autophagy and in the innate immune response of the host cell. These two processes have been recently linked together in the early cell defense mechanism against external pathogens, including viruses. We have characterized a complex regulation of the autophagic process mediated by the ASFV, using the autophagosome-­‐related LC3 protein. Upon viral entry, ASFV inhibits autophagy persistently throughout the infectious cycle to facilitate replication and to avoid virus clearance. Further analysis revealed that ASFV-­‐mediated autophagy inhibition depends on the specific interaction of ASFV Bcl2 homolog and apoptotic inhibitor A179L with autophagy-­‐related cell protein Beclin1. The ASFV-­‐mediated autophagy inhibition is a tightly regulated process, since altering key autophagy factors impairs infectivity, the formation of the ASFV viral factories and the replication of the virus overall. Analysis of viral factory formation and distribution revealed that even though viral factories of ASFV resemble sequestering of cytoplasmic material in structures called aggresomes, they are not consistent with aggresome formation mechanisms. In fact, inhibition of canonical BAG3 and HDAC6-­‐ mediated aggresome formation pathways, did not alter the formation of ASFV viral factories. Finally, our studies established a link between autophagy, ASFV infection and innate immunity by the expression of the interferon-­‐induced transmembrane (IFITM) protein family, which possesses antiviral properties against several viruses. ASFV infection was impaired by IFITM2 and IFITM3 but not IFITM1, due to alterations in endosomal compartments, changes in the cholesterol homeostasis, as well as induction of autophagy. Taking together these results, we propose that the mechanism underlying the antiviral effect of IFITM against ASFV could be inhibiting ASFV infection through the endosomal pathway. Interestingly, expression of IFITM2 induces accumulation of autophagosomal marker LC3, colocalizing with late endosomal compartments. Future studies will reveal more details about the crosstalk between autophagy and IFITM-­‐related innate immunity in ASFV infection, allowing better and more efficient antiviral intervention strategies against the disease.En el presente trabajo hemos investigado el papel que juega el Virus de la Peste Porcina Africana (VPPA) en el proceso de autofagia y respuesta inmune celular. Se ha descrito recientemente la estrecha relación que existe entre ambos procesos por formar parte del mecanismo de defensa de la célula ante la llegada externa de patógenos como son los virus. Haciendo uso de la proteína LC3, que se encuentra asociada a los autofagosomas, hemos logrado caracterizar la compleja regulación de la autofagia llevada a cabo por el VPPA. Tras la entrada del virus en la célula, el VPPA inhibe la autofagia y dicha inhibición persiste a lo largo de todo el ciclo infectivo para facilitar su posterior replicación y evitar así ser eliminado. Análisis posteriores han revelado que esta inhibición del proceso autofágico está mediado por la interacción específica entre el homólogo celular a Bcl2 e inhibidor de apoptosis codificado por VPPA (A179L) y la proteína Beclin1. Esta inhibición de la autofagia mediada por el virus es un proceso minuciosamente regulado ya que si se alteran alguno de sus componentes, se bloquea la formación de las factorías virales y la consecuente replicación del virus. Haciendo un análisis de las factorías virales y de su distribución hemos podido concluir que a pesar de que son orgánulos muy similares a los agresomas, realmente no se trata de la misma estructura. De hecho, la inhibición de las dos principales vías implicadas en la formación del agresoma mediadas por las proteínas BAG3 y HDAC6 no afectó a la formación de las factorías virales. Finalmente nuestros estudios nos han permitido establecer un vínculo entre la autofagia, la infección por VPPA y la inmunidad innata mediante el estudio de una familia de proteínas transmembrana que se inducen en respuesta a interferón (IFITMs), y que se ha descrito que poseen propiedades antivirales frente a algunos virus. La infección por VPPA se vio afectada en presencia de IFITM2 y 3 pero no de IFITM1, debido a alteraciones en compartimentos endosomales , cambios en la homeostasis del colesterol e inducción de autofagia. Haciendo una valoración global de los resultados obtenidos, hemos propuesto que el papel antiviral propiciado por los IFITMs es debido a alteraciones que producen en la ruta endosomal. Además, la expresión de IFITM2 induce la acumulación de LC3 que se distribuye colocalizando con compartimentos endosomales tardíos. Futuras investigaciones revelarán mas detalles a cerca de la interrelación existente entre autofagia y la regulación de la inmunidad innata en la infección por VPPA, permitiendo así desarrollar mejores y mas eficientes terapias antivirales frente a esta enfermedad

Failure management insights in 5G using ns-3 network simulator

Failure management has been one of the most researched fields in cellular networks paradigm. Networks operators has experienced many problems on their deployments with each of the past generations. 5G networks aim high to encompass a wide variety of services, which means a large amount of resources on network management and failure resolution. The objective of the present work is to use the previous generation as base and provide, together with the updates on 3GPP specification, insights about what would be the problems that networks will handle. For this, they were identified and categorized some of these failures at the same time their effect on system performance was evaluated.This work was supported by the European Union’s Horizon 2020 research and innovation program under Grant no. 871249, project LOCUS. This work has been also funded by: Junta de Andalucía and ERDF: projects IDADE-5G (UMA18-FEDERJA-201) and OptiRAN5G (UMA18-FEDERJA-174), and postdoctoral grant (Ref., DOC 01154, “selección de personal investigador doctor convocado mediante Resolución de 21 de mayo de 2020”, PAIDI 2020); University of Malaga, through the I Plan Propio de Investigación, Transferencia y Divulgación Científica de la Universidad de Málaga. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Effect of Bentonite Addition to Pedro Ximénez White Grape Musts before Their Fermentation with Selected Yeasts on the Major Volatile Compounds and Polyols of Wines and Tentative Relationships with the Sensorial Evaluation

In this work, we study the effect of bentonite addition to the grape must before alcoholic fermentation on the chemical composition and sensorial profile of the obtained wines. Fermentations were carried out with two Saccharomyces cerevisiae commercial active dry yeasts treated or not with bentonite and were compared with a control wine obtained by spontaneous fermentation (using the grape must microbiota). Several significant effects on the chemical and sensorial attributes were established by statistical treatments. The selection by multiple variable analysis of seven volatile molecules (ethyl acetate; methanol; 1-propanol; isobutanol; 2-methyl-1-butanol; 3-metyl-1-butanol and 2-phenylethanol) provided several footprints that provide an easy visualization of bentonite effects on wine volatile compounds. A Principal Component Analysis carried out with all the compounds quantified by Gas-Chromatography revealed that the first two Principal Components explain 60.15 and 25.91%, respectively, of the total variance and established five groups that match with the five wines analyzed. Lastly, predictive models at p ≤ 0.05 level for the attributes sight, smell and taste were obtained by Partial Least Squared regression analysis of selected chemical variables

UE side Application Layer metrics For QoE-based Network Management.

Cellular networks are being improved by the automation of management tasks in order to optimize the performance while improving the efficiency. This is based on the vast amount of data which is available from the network side. Nonetheless, the network side perspective is limited and the focus is being redirected to the user side. Here, Drive Tests are in charge of collecting useful information, but at high costs. Thus, the present work presents a key source of information regarding network management: user side application layer metrics. In this regard, this work exploits this user side data by using different techniques to estimate the users’ quality of experience with the aim of network management.This work was supported by the project MUSE (Massive User Experience Assessment and Prediction for Mobile Networks) - Ref. UMA-CEIATECH-15, and the Spanish Ministry of economic affairs and Digital Transformation and European Union - NextGenerationEU within the framework “Recuperación, Transformación y Resiliencia y el Mecanismo de Recuperación y Resiliencia” - project MAORI, and Univer- sidad de Málaga through the “II Plan Propio de Investigación, Transferencia y Divulgación Científica” This work was possible thanks to the partnership with Metricell Limited to provide a very large dataset of anonymized metrics from real cellular network users. This work has been also funded by: Spanish Ministry of Universities - Ref. FPU20/02863

Exosomal microRNAs isolated from plasma of mesenteric veins linked to liver metastases in resected patients with colon cancer

Before reaching a peripheral vein (PV), miRNAs released by the tumor are diluted and dispersed throughout the body or even retained in a specific organ. We hypothesized that blood drawn from the tumor-draining vein could provide more homogeneous information than blood drawn from the PV as that blood would contain all the biomarkers released by the tumor before they reach a potential metastatic site. We have profiled 754 miRNAs in 15 colon cancer plasma samples from the tumor-draining vein, the mesenteric vein (MV), identifying 13 microRNAs associated with relapse. The prognostic impact of these miRNAs were validated in 50 MV and 50 paired PV plasma samples of stage I-III colon cancer patients. Four miRNAs, let-7g, miR-15b, miR-155 and miR-328, were found overexpressed in MV compared to PV, and patients with high levels of those miRNAs in MV plasma had shorter time to relapse. Interestingly, in patients developing liver metastases, the exosomal cargo of miR-328 was much greater in MV than in PV plasma indicating a possible role of miR-328 in the development of liver metastases. Our results indicate that in colon cancer, the primary tumor releases high concentrations of miRNAs through the MV, and some of them are contained in tumor derived exosomes

Plan de intervención de fisioterapia convencional complementado con fisioterapia digital para un paciente con enfermedad de parkinson y apnea obstructiva del sueño. A propósito de un caso

Introducción: la AOS es un trastorno caracterizado por la obstrucción de las vías respiratorias superiores durante el sueño, asociada con una somnolencia diurna excesiva y manifestaciones neurocognitivas. La EP es una patología neurodegenerativa con una alteración progresiva del SNC afectando al sistema extrapiramidal. Ante los síntomas motores y no motores, resulta imprescindible la figura del fisioterapeuta. Además, la fisioterapia digital está adquiriendo un papel fundamental en el ámbito de la neurorrehabilitación por lo que se complementa el tratamiento con el uso de apps.Objetivos: analizar la relación entre la EP y AOS; además de medir la efectividad del plan de intervención de fisioterapia convencional complementado con fisioterapia digital.Metodología: Caso clínico de tipo descriptivo, prospectivo, longitudinal e intrasujeto (tipo A-B). Se realiza una valoración inicial, se plantea el diagnóstico fisioterápico y los objetivos terapéuticos; en función de estos, se desarrolla el plan de intervención fisioterápico con una duración de 10 semanas y se realiza una valoración final.Resultados: Se observa tras el tratamiento una disminución de la somnolencia, aumento de la calidad del sueño, mayor calidad de vida, menor impacto de la EP, aumento de la capacidad física y mejora en equilibrio, transferencias, marcha y destreza manual.Discusión: tras comparar los resultados con la bibliografía existente se obtiene evidencia sobre la efectividad del plan de intervención propuesto. Pese a la mejora de los resultados, no son estadísticamente significativos.Conclusiones: el estudio muestra la eficacia de la intervención fisioterápica, aunque los resultados no se pueden extrapolar a otros pacientes con las mismas patologías debido a la escasa calidad metodológica.Palabras clave: "apnea obstructiva del sueño", "enfermedad de Parkinson", "fisioterapia", "fisioterapia digital".<br /

Turismo cultural en la región de Murcia (España)

Una de las características más significativas de la actividad turística en los últimos años es la diversificación de su oferta debido a las nuevas demandas de los consumidores. Los destinos cuyo modelo turístico se ha vertebrado en la modalidad de sol y playa tratan de ofrecer nuevas actividades que ayuden a diversificar la oferta turística y satisfacer las necesidades de los turistas. En la actualidad, el principal motor económico de la Región de Murcia es el turismo, fruto de la combinación de la bonanza climática y la longitud de costa. Esto propicia la llegada de turistas no solo nacionales, sino de otros países como Alemania, Reino Unido o Francia. Sin embargo, el modelo turístico actual tiene una gran estacionalidad, concentrada en los meses estivales principalmente. Desde la Administración Pública se intenta potenciar el turismo cultural, con el fin de valorizar los recursos patrimoniales y generar un desarrollo territorial endógeno a lo largo de todo el año. Por ello, en este estudio se analizan las potencialidades del turismo cultural en la Región de Murcia, especialmente en los lugares donde se ha desarrollado con más fuerza.2018-201

Infraestructura 5G Standalone para Investigación y Desarrollo

The deployment of 5G infrastructures has been notably addressed during the last years. In contrast, most of the cellular operators are opting for deploying 5G Non- Standalone (NSA), which relies on LTE as anchor technology (signaling, guaranteed coverage...). Nevertheless, 5G NSA is not able to provide all the enhancements that 5G envisions to introduce, including a wide variety of services and use cases. At the University of Ma ́laga, a complete 5G Standanlone (SA) private network has been deployed for research and development purposes. This infrastructure is composed by both indoor and outdoor cells with different equipment, respectively. It enables the use novel technologies such as beamforming to achieve better capacity and coverage, which means higher bandwidths and lower latencies. The aim of this work is to analyze the benefits in terms of transmission bandwidth and latency with reference to a LTE private network. To accomplish this, some tests have been performed over the 5G SA network, providing also some insights about the use of MEC (Multi-access Edge Computing) in 5G.Este trabajo está parcialmente financiado por el programa de “Ayudas para la formación de profesorado universitario” (Ref. FPU20/02863) del Ministerio de Universidades, la beca postdoctoral (Ref. DOC 01154, “Selección de personal investigador doctor convocado mediante Resolución de 21 de mayo de 2020”, PAIDI 2020), y el Ministerio de Asuntos Económicos y Transformación Digital y la Unión Europea - NextGenerationEU, en el marco del Plan de Recuperación, Transformación y Resiliencia y el Mecanismo de Recuperación y Resiliencia bajo el proyecto MAORI. La infraestructura descrita fue concedida mediante la convocatoria de “Ayudas para la adquisición de equipamiento científico-técnico (Plan Estatal I+D+I 2017-2020)”, Ref. EQC2018-005173-P. El trabajo también ha sido parcialmente financiado por la Universidad de Málaga, a través del II Plan Propio de Investigación y Transferencia. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Association of beverage consumption with subclinical atherosclerosis in a Spanish working population

Beverages play a substantial role meeting water, calorie, and nutrient requirements; however, they are presented as being major contributors to the current obesity epidemic. Although, the relationship between beverage consumption and metabolic risk factors for cardiovascular disease (CVD) in adults has been frequently studied, its association with subclinical atherosclerosis is of increased interest. We studied the association of beverage consumption with the presence of peripheral subclinical atherosclerosis among Spanish workers. We performed a cross-sectional study of 2089 middle-aged males, with a mean age of 50.9 (SD 3.9), and without CVD, carried out in the Aragon Workers’ Health Study (AWHS). A food frequency questionnaire was used to measure beverage consumption of low-fat milk, coffee and tea (unsweetened), whole-fat milk, sugar-sweetened beverages, bottled fruit juice, artificially-sweetened beverages and 100% fruit juice. Atherosclerotic plaques were measured by ultrasound (in carotid arteries, and in femoral arteries). Atherosclerotic plaque was defined as a focal structure protruding ≥ 0.5 mm into the lumen, or reaching a thickness ≥ 50% of the surrounding intima-media thickness. As statistical analysis, we use logistic regression models, simultaneously adjusted for all beverage groups. As results, unsweetened coffee was the beverage most associated with peripheral subclinical atherosclerosis with an odds ratio (OR) of 1.25 (1.10–1.41), and 1.23 (1.09–1.40) 100g/day] for carotid, and femoral territories respectively. Moreover, subclinical atherosclerosis was positively associated with whole-fat milk [OR 1.10 (1.02–1.18) 100 g/day] in the femoral territory. The association was protective for low-fat milk in the carotid territory [OR 0.93 (0.88–0.99) 100g/day]. There was also a protective association with bottled fruit juices in the femoral territory [0.84 (0.74–0.94) 100g/day]. Our results suggest a detrimental association with the consumption of coffee, as well as with whole-fat milk and the presence of subclinical atherosclerosis. Therefore, an element of prudence excluding water and low-fat milk, must be applied when recommending beverage consumption

Análisis de Interferencia Cross-Link sobre un escenario 5G mmWave

The use of Time Division Duplex (TDD) has not been fully adopted by operators in LTE networks and its previous generations. In contrast, the fifth generation (5G) is introducing new technical motivations for its use. In order to achieve network flexibility as well as to provide service to every use case, it is necesary to adapt the resources allocated to DL and UL. On the other hand, beamforming techniques require sharing channel state information regularly in both directions. Hence, TDD is a promising option, although it may cause various interference types. The aim of this work is to analyze the Cross-Link Interference (CLI). To do this, a complete scenario simulation has been configured with different conditions, while the signal- to-interference-plus-noise ratio (SINR) has been monitored.Este trabajo está parcialmente financiado dentro del proyecto H2020 LOCUS (grant agreement n. 871249), la Junta de Andalucía y fondos FEDER (Programa Operativo FEDER Andalucía 2014-2020), en los proyectos IDADE-5G (UMA18- FEDERJA-201) y OptiRAN5G (UMA18-FEDERJA-174), y la beca postdoctoral (Ref. DOC_01154, “Selección de personal investigador doctor convocado mediante Resolución de 21 de mayo de 2020”, PAIDI 2020). También ha sido parcialmente financiado por la Universidad de Málaga, a través del I Plan Propio de Investigación y Transferencia. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech