A universal new generation vaccine against type I Porcine Respiratory and Reproductive Syndrome Virus

Porcine respiratory-reproductive syndrome (PRRS) is a devastating disease for the global porcine industry. PRRS leads to economic losses above 664 million dollars per year only in the USA and showing an increasing trend. The disease is affecting with a similar magnitude the porcine industry of the European Union. PRRS is caused by an enveloped, single stranded RNA virus (PRRSV) from the Arteviridae family. PRRSV interacts with porcine monocytes, weakening the immune system of the host and leading to pathologies affecting the respiratory and reproductive systems. Because of their immaturity, piglets are very vulnerable to PRRSV infection. Treatment and quarantine are not viable choices for the porcine industry. Therefore, prophylactic vaccines are the best alternative to prevent PRRS. However, the currently marketed vaccines are failing in protecting piglets in all regions of the world. The causes of failure are basically two. On one hand, the use of live attenuated vaccines needed for a complete antigenic presentation is preserving the immune evasion mechanisms of the wild-type virus. On the other hand, high divergence between viral serotypes leads to almost no cross-reactivity of the immune response between viral strains.This project aims to develop a new PRRS vaccine capable of creating a complete immune response in piglets that neutralizes early-stage infection by any of the viral serotypes running in the USA and the EU. These premises could be possible thanks to the flexibility typical of a recombinant subunit vaccine, which has been designed to improve the usual low antigenic presentation of this type of vaccines. We have successfully produced a recombinant baculovirus for accumulation of the vaccine’s active ingredient in insect cells, in the form of protein bodies formed by using a tag derived from vegetal zein proteins (Zera® technology). Expression tests in insect cells confirmed the viability of this production system, obtaining 13 mg/L of purified antigen. The preliminary immunogenicity tests in murine model showed that the new vaccine is immunogenic in vivo and that it could be manufactured formulating the final product in a lyophilized format. We have made experimental batches of the vaccine and designed an experimental trial with challenge in piglets, in order to test the efficacy of our vaccine in comparison with commercial gold-standards. The trial will begin in March 2020 and the results will be part of this work

Materiales Moleculares y Polímeros basados en Ftalocianinas para Aplicaciones en Células Solares Orgánicas

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura:28-04-0

A new biological entity with antitumor activity produced by using the baculovirus expression system

Cancer is one of the diseases with the greatest impact in today's society, being the second cause of death in the world. Currenttreatments have many effects for the patient since they are not specific for tumor cells, so new strategies are being sought todevelop more specific drugs.This project aims to develop a new biological entity with antitumor activity. We have engineered an antagonist of a cellulartarget involved in progression of 90% of cancers. The design is based on the fusion of selected peptidic sequences withimproved antagonistic properties to sequences that directs the drug to the cellular compartment where the target is located.The final goal is to develop a molecule more powerful than the common antagonists currently used (e.g. monoclonalantibodies).The expression of the recombinant protein has been carried out in Bionaturis’ FLYLIFE platform, which is based on the useof recombinant baculoviruses as vectors for the expression of the protein of interest in insect larvae. Different recombinantbaculoviruses were generated, including different designs for the purification of the protein of interest by affinitychromatography. The candidates were expressed, recovered, and characterized either using insect cells or larvae asbiofactories..Results showed that the proteins of interest were expressed successfully in both insect cells and larvae, although they werehighly insoluble. We have developed a specific solubilization protocol and analyzed the conditions for obtaining purifiedproteins to perform activity tests

Analysis of Sliding-mode controlled impedance matching circuits for inductive harvesting devices

A sea-wave energy harvesting, articulated device is presented in this work. This hand-made, wooden device is made combining the coil windings of an array of three single transducers. Taking advantage of the sea waves sway, a linear oscillating motion is produced in each transducer generating an electric pulse. Magnetic fundamentals are used to deduce the electrical model of a single transducer, a solenoid-magnet device, and after the model of the whole harvesting array. The energy obtained is stored in a battery and is used to supply a stand-alone system pay-load, for instance a telecom relay or weather station. To maximize the harvested energy, an impedance matching circuit between the generator array and the system battery is required. Two dc-to-dc converters, a buck-boost hybrid cell and a Sepic converter are proposed as impedance adaptors. To achieve this purpose, sliding mode control laws are introduced to impose a loss free resistor behavior to the converters. Although some converters operating at discontinuous conduction mode, like the buck-boost converter, can exhibit also this loss free resistor behavior, they usually require a small input voltage variation range. By means of sliding mode control the loss free resistor behavior can be assured for any range of input voltage variation. After the theoretical analysis, several simulation and experimental results to compare both converters performance are given

La evaluación inicial de la competencia digital del alumnado de primer curso de educación secundaria obligatoria en el proyecto 1x1

La implementación de las Tecnologías de la Información y la Comunicación (TIC) en un instituto público de Educación Secundaria Obligatoria (ESO) entraña necesariamente una reflexión sobre las competencias digitales que deberá asumir el alumnado y, con ello, el cambio metodológico necesario para su completa impregnación. Un primer paso es el cuestionario que aquí se presenta, en el contexto de la implementación del plan Escuela 2.0 en Cataluña, el innovador «Educat 1 x 1». Con él se pretende concoer el punto de partida respecto a la competencia TIC del alumnado de primero de ESO para estar en mejores condiciones al planificar la inclusión de las TIC en el proceso de enseñanza aprendizaje.The implementation of Information Technology and Communication (ICT) in a public institute of Secondary Education (ESO) must be preceded by a reflection about the digital skills students should assume, and thus the desirable methodological change for their full utilization. A first step is a questionnaire we present here within the context of the implementation of the School 2.0 plan in Catalonia, called «Educat 1 x 1». It aims to offer an initial assessment of our students’ ICT competence when they arrive to High Schools: only then we will do our best for planning the teachinglearning process of this competence

Variación de la línea de costa en la aldea de Cedeño, y cartografía de amenaza ante marejadas y ascenso del nivel del mar

The village of Cedeño is highly vulnerable to the onslaught of hydrometeorological phenomena that periodically occur on its beaches (Swells), to which must be added the effects produced by climate change. All of the above will cause irreversible damage such as retreat of the coastline, flooding due to the increase of the ocean, loss of wetlands, an intrusion of saline water, and displacement of people. The negative impacts on the territorial system and therefore on the quality of life of its inhabitants will be great. The general objective was to develop a baseline on the variability patterns of the Cedeño Aldea coast (erosion/accretion rates), as well as the cartography of threats to natural phenomena (flood tidal maps/inundation floods) of the sea), which serves as a support to propose appropriate planning and land management policies.The methodology used was based on geospatial analysis, using tools of geographic information systems, remote sensing, citizen participation and statistical tools. The results showed an erosive behavior on the beaches of the village of Cedeño, as well as a large area vulnerable to flooding before the swells and scenarios of sea level rise.La aldea de Cedeño es altamente vulnerable al embate de los fenómenos hidro meteorológicos que periódicamente ocurren en sus playas (Marejadas), a esto se le debe sumar los efectos que producirá el cambio climático. Todo lo anterior ocasionara daños irreversibles como retroceso de la línea de costa, inundaciones debido al aumento del océano, perdida de humedales, intrusión de agua salina, y desplazamiento de personas. Los impactos negativos en el sistema territorial y por ende en la calidad de vida de sus pobladores serán grandes. El objetivo general, consistió en elaborar una línea base sobre los patrones de variabilidad de la costa de la Aldea de Cedeño (tasas de erosión/acreción), además de la cartografía de amenazas ante fenómenos naturales (Mapas de inundación marejadas/ inundación ante el ascenso del mar), que sirva de apoyo para proponer políticas de planificación y gestión del territorio adecuadas. La metodología empleada se basó en análisis geoespacial, usando herramientas de sistemas de información geográfica, teledetección, participación ciudadana y herramientas estadísticas. Los resultados evidenciaron un comportamiento erosivo en las playas de la aldea de Cedeño, así como también una gran área vulnerable a inundación ante las marejadas y escenarios de ascenso del nivel del mar

Surface modulation of single-walled carbon nanotubes for selective bacterial cell agglutination

Background: Bacterial resistance to antibiotics is one of the biggest challenges facing medicine today. Anti-adhesive therapy, using inhibitors of bacterial adhesion to epithelial cells, one of the first stages of infection, is a promising approximation in this area. The size, shape, number of sugar and their placement are variables that have to be taken into account in order to develop multivalent systems able to inhibit the bacterial adhesion based on sugar-lectin interaction. Materials and methods: In the present work we report a modular approach for the synthesis of water-soluble 1D-carbon nanotube-sugar nanoconstructs, with the necessary flexibility to allow an efficient sugar-lectin interaction. The method is based on the reaction of aryl diazonium salts generated in situ from aniline-substituted mannose and lactose derivatives with single wall carbon nanotubes (SWCNTs) sidewalls. Results: Two hybrid nanosystems, I-II, exposing mannose or lactose and having a tetraethylene glycol spacer between the sugar and the nanotube sidewall were rapidly assembled and adequately characterized. The sweet nano-objects were then tested for their ability to agglutinate and selectively inhibit the growth of uropathogenic Escherichia coli. These studies have shown that nanosystem I, exposing mannose on the nanotube surface is able to agglutinate and to inhibit the bacterial growth unlike nano-objects II exposing lactose. Conclusion: The results reported constitute a proof of principle in using mannose-coated 1D-carbon nanotubes as antiadhesive drugs that compete for FimH binding and prevent the uropathogenic bacteria from adhering to the urothelial surface.Andalusian Government (FQM-313 to NK, BIO-026 to REW)Spanish Ministry of Economy and Competitiveness (CTQ2016-78580-C2-1-R to NK)University of Seville (V PLAN PROPIO to REW)European Regional Development Fund (FEDER

Validating GIC modeling in the Spanish power grid by differential magnetometry

series of experiences and recommendations are presented concerning the derivation of geomagnetically induced currents (GIC) by use of the differential magnetometry method (DMM) under power lines. This indirect technique, intended to obtain observations to validate GIC models, is an alternative to measuring the current flow in the transformer neutrals. It is a non-intrusive and autonomous technique, as the procedure does not depend on the grid operator. In contrast, the selection of suitable sites devoid of human interferences, the need for power to supply the magnetometer, the data acquisition and transmission system, along with the choice of the appropriate instrumentation are difficulties that make not just any site suitable for installation and often require costly solutions. We focus on the methodology followed to estimate the GIC flowing in several transmission lines of the Spanish power grid with the aim of validating our GIC models, and we share our experience on the installation of the measuring points. Uncertainty inherent in the DMM is assessed, showing that noise is the main handicap, although it can be minimized with appropriate filtering. According to such experience, on some occasions only total DC currents above a significant fraction of 1 A give magnetic signatures well above the noise level, so this figure can roughly be considered as the threshold limit for detection. The low solar activity, combined with the mid-latitude condition of Spain, limited the significance of available recorded data, but we can already report and analyze the results for several minor geomagnetic storms

Producción de una hormona animal recombinante estable y con actividad in vivo.

Actualmente, en ganadería vacuna intensiva, la fertilización de las vacas se produce por inseminación artificial. Para obtener un mayor rendimiento, se extraen hormonas naturales de determinados animales para inyectarlas al ganado vacuno y conseguir la hiperovulación de éstos, pudiendo inseminar todas al mismo tiempo y con mayor probabilidad de éxito. El problema es que la extracción de estas hormonas es compleja y cara. Se ha intentado solventar este problema produciendo esta hormona en cultivos celulares de mamíferos o insectos mediante ingeniería genética. Aunque las enzimas recombinantes demuestran actividad in vitro, al inyectarlas a modelos animales o ganado no inducen la hiperovulación debido a una vida media en suero mucho más corta (minutos) que la versión natural (horas), ya que son eliminadas de la sangre rápidamente por la orina. Bionaturis ha propuesto la estabilización en suero de esta hormona recombinante mediante la fusión de secuencias estabilizadoras desarrolladas por la empresa a la secuencia hormonal.Bionaturis utiliza la plataforma FLYLIFE, que consiste en el uso del sistema baculovírico para la producción de proteínas recombinantes. A partir de secuencias estabilizadoras ya sintetizadas, se creó un vector de transferencia con las secuencias de interés mediante técnicas de clonación. Luego, mediante recombinación homóloga, se insertarán estas secuencias en baculovirus modificados genéticamente (Master Viral DNA de Bionaturis) que, en vez de sintetizar polihedrina, sintetizan la secuencia de interés, y así obtener baculovirus recombinantes de trabajo (Working Viral Banks). La obtención de los Working Virus Bank (WBK) se realiza mediante la co-transfección en células de insecto con el Master Viral DNA y el vector de transferencia. Hasta ahora, se ha llevado a cabo la construcción del vector de transferencia con éxito, los siguientes pasos a dar son la co-transfección para la obtención del WVB y su posterior caracterización mediante test de expresión de proteínas en cultivo celular. Posteriormente, se pretende la infección de larvas de lepidóptero con el virus recombinante obtenido que, al multiplicarse en su interior, producirá la proteína recombinante. Finalmente, se extraerá y se purificará la proteína de interés y se evaluará su actividad in vitro e in vivo

Infrequent loss of luminal differentiation in ductal breast cancer metastasis

Lymph node involvement is a major prognostic variable in breast cancer. Whether the molecular mechanisms that drive breast cancer cells to colonize lymph nodes are shared with their capacity to form distant metastases is yet to be established. In a transcriptomic survey aimed at identifying molecular factors associated with lymph node involvement of ductal breast cancer, we found that luminal differentiation, assessed by the expression of estrogen receptor (ER) and/or progesterone receptor (PR) and GATA3, was only infrequently lost in node-positive primary tumors and in matched lymph node metastases. The transcription factor GATA3 critically determines luminal lineage specification of mammary epithelium and is widely considered a tumor and metastasis suppressor in breast cancer. Strong expression of GATA3 and ER in a majority of primary node-positive ductal breast cancer was corroborated by quantitative RT-PCR and immunohistochemistry in the initial sample set, and by immunohistochemistry in an additional set from 167 patients diagnosed of node-negative and -positive primary infiltrating ductal breast cancer, including 102 samples from loco-regional lymph node metastases matched to their primary tumors, as well as 37 distant metastases. These observations suggest that loss of luminal differentiation is not a major factor driving the ability of breast cancer cells to colonize regional lymph nodes