Production of recombinant Immunoglobulin A in plants for passive immunotherapy

Mucosal passive immunization is the transfer of active antibodies from one organism to the mucosal surfaces of another organism for preventing or treating infectious diseases. Mucosal passive immunization has a great potential for the prevention and treatment of enteric infections like Rotavirus, which causes more than 114 million episodes of diarrhoea annually with a death toll of more than 450.000 per year. However, the high cost of recombinant antibodies with the current manufacturing systems based on mammalian cells hampers the production of the high antibody quantities required for passive immunization strategies. Alternative expression platforms such as plants could provide higher scalability and reduced costs. Moreover, the use of edible plant organs, which are Generally¿Regarded¿As¿ Safe (GRAS), could reduce manufacturing costs even further by easing the requirements for antibody purification. We analyze here the feasibility of utilizing fruits as inexpensive biofactories of human antibodies that can be orally delivered as crude extracts or partially purified formulations in mucosal passive immunization strategies. In the first section of this thesis, the construction of tomato plants producing a model human Immunoglobulin A (IgA) against rotavirus in their fruits is described. As a result, an elite homozygous line was obtained whose fruits produced on average 41 ¿g of IgA per gram of fresh weigh, equivalent to 0.69 mg IgA per gram of dry tomato powder. Minimally processed products derived from IgA¿expressing tomatoes were shown to strongly inhibit virus infection in an in vitro neutralization assay. Moreover, in order to make IgA¿expressing tomatoes easily distinguishable from wild¿type tomatoes, they were sexually crossed with a transgenic tomato line expressing the genes encoding Antirrhinum majus Rosea1 and Delila transcription factors, which confer purple colour to the fruit. The resulting transgenically¿labelled purple tomatoes contained not only high levels of recombinant neutralizing human IgA but also increased amounts of anthocyanins. In the second section of the thesis the composition of IgA¿expressing tomatoes was analyzed in search of possible unintended effects that could compromise the GRAS status of the final product. To this end, transgenic IgA¿tomatoes were compared with wild type tomatoes and also commercial tomato varieties using proteomic and metabolomic approaches. 2D¿DIGE gels coupled with LC¿MSMS for protein identification showed that all the uptrend differential proteins detected corresponded only to immunoglobulin chains or antibody fragments. On the other hand, non¿targeted metabolite data obtained by UPLC¿MSJuárez Ortega, P. (2014). Production of recombinant Immunoglobulin A in plants for passive immunotherapy [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/37015TESI

Fuel Poverty: Evidence from housing perspective

The literature has traditionally approached fuel poverty as a result of poverty. Fuel poor are those households who cannot pay fuel bill and have to live in cold ambient, with grave effects on their health. As fuel poverty is actually considered in poverty’s analysis, there is little discussion about whether homeowners (who own housing wealth and, theoretically, cannot be poor) could suffer this problem. This paper assesses fuel poverty amongst Spanish households. It deeps on how poverty situations triggers fuel poverty in the context of housing and discusses whether or not housing tenure causes fuel poverty due to housing characteristics, those usually evaluated as poverty component. The paper finds empirical evidence about the relevance of tenancy when it comes to explain the likelihood of falling under the poverty line as well as about the fact that fuel poverty has become a systematic situation in all poor Spanish households regardless of their tenant status. Using micro-data obtained from the Quality of Life Survey (EU-SILC) for Spain, the data are segmented by residential tenure and household type, calculating poverty lines for homeowners, renters (both at market prices and below them), and free-rent housing ‒the four tenure formulas existing in the Spanish housing market‒ and including two variables to capture fuel poverty situations. A logistic regression model is applied and results suggest that fuel poverty clearly appears as an expression of poverty at any tenancy type

CXCL12-induced neurotoxicity critically depends on NMDA receptor-gated and L-type Ca2+ channels upstream of p38 MAPK.

BackgroundThe chemokine receptor CXCR4 (CD184) and its natural ligand CXCL12 contribute to many physiological processes, including decisions about cell death and survival in the central nervous system. In addition, CXCR4 is a co-receptor for human immunodeficiency virus (HIV)-1 and mediates the neurotoxicity of the viral envelope protein gp120. However, we previously observed that CXCL12 also causes toxicity in cerebrocortical neurons but the cellular mechanism remained incompletely defined.MethodsPrimary neuronal-glial cerebrocortical cell cultures from rat were exposed to a neurotoxicity-inducing CXCL12 concentration for different times and the activity of the stress-associated mitogen-activated protein kinase p38 (p38 MAPK) was assessed using an in vitro kinase assay. Neurotoxicity of CXCL12 and cellular localization of p38 MAPK was analyzed by immunofluorescence microscopy. Pharmacological inhibition of NMDA-type glutamate receptor-gated ion channels (NMDAR) of L-type Ca2+ channels was employed during 12- and 24-h exposure to neurotoxic amounts of CXCL12 to study the effects on active p38 MAPK and neuronal survival by Western blotting and microscopy, respectively. Neurotoxicity of CXCL12 was also assessed during pharmacological inhibition of p38 MAPK.ResultsHere, we show that a neurotoxic amount of CXCL12 triggers a significant increase of endogenous p38 MAPK activity in cerebrocortical cells. Immunofluorescence and Western blotting experiments with mixed neuronal-glial and neuron-depleted glial cerebrocortical cells revealed that the majority of active/phosphorylated p38 MAPK was located in neurons. Blockade of NMDAR-gated ion channels or L-type Ca2+ channels both abrogated an increase of active p38 MAPK and toxicity of CXCL12 in cerebrocortical neurons. Inhibition of L-type Ca2+ channels with nimodipine kept the active kinase at levels not significantly different from baseline while blocking NMDAR with MK-801 strongly reduced phosphorylated p38 MAPK below baseline. Finally, we confirmed that directly blocking p38 MAPK also abrogated neurotoxicity of CXCL12.ConclusionsOur findings link CXCL12-induced neuronal death to the regulation of NMDAR-gated ion channels and L-type Ca2+ channels upstream of p38 MAPK activation

EL PLAGIO ACADÉMICO: FORMAR EN COMPETENCIAS Y BUENAS PRÁCTICAS UNIVERSITARIAS

El plagio académico es una práctica demasiado frecuente entre los estudiantes universitarios ya que las nuevas tecnologías, y en especial, Internet permiten realizarlo con facilidad. Se analiza el concepto de plagio desde diversos puntos de vista y se profundiza en las competencias informacionales del uso ético y legal de la información que debe ser acometido desde diversos frentes para inculcar la honestidad académica en la enseñanza superior. New technology and in particular the Internet, have caused a rise in academic plagiarism; a widely spread practice amongst today’s university students. The meaning of plagiarism is analyzed from different points of view. The ethical and legal use of information is explored to show that this must be taken from different sources in order to instill a sense of academic honesty in higher education

Estudio sobre la situación de la vivienda pública en la Comunitat Valenciana

El objetivo de este estudio se sitúa, en primer lugar, en la identificación de la situación en la que se halla la vivienda pública en la Comunitat Valenciana, entendiendo por tal la vivienda que se encuentra gestionada por las administraciones públicas con competencias en la materia; y ello desde un doble punto de vista: tanto la situación de la oferta de vivienda pública, como el estado de la demanda de la misma. Se observa la vivienda pública como un instrumento más de la política social destinada a proteger a los sectores más desfavorecidos, por lo que se evalúa la demanda actual de vivienda pública, se estiman los niveles de demanda potencial de vivienda pública en caso de deterioro o colapso económico, con la finalidad de programar y ejecutar unos instrumentos de intervención y, en especial, un parque público de vivienda acorde a las necesidades de una vivienda, especialmente en los casos de extrema necesidad. El objetivo final del estudio es la comparación de las variables estudiadas (oferta y demanda) y la obtención de conclusiones útiles para el diseño, por parte de las administraciones competentes, de una política social de vivienda. El trabajo busca identificar las cuestiones transcendentales para la política social de vivienda, como es saber cuántos son los demandantes actuales y futuros de vivienda, qué tipología y necesidades en vivienda presentan, dónde se ubican y, por lo tanto, dónde se debe construir las viviendas sociales destinadas a satisfacer sus necesidades, cuál es el nivel exacto de pobreza en vivienda y pobreza asociada a la vivienda de los hogares valencianos, entre otras cuestiones relacionadas con este mercado, como son la identificación de los ciclos de edificación históricos, de las series de precios, la evaluación de la distribución de la renta a nivel provincial y en áreas locales, y la estimación de la pobreza energética asociada a los hogares en la Comunidad Valenciana

Una serie histórica de precios residenciales para España

Este artículo reconstruye la serie de precios residenciales para España desde la década de los sesenta hasta los ochenta del siglo XX utilizando el crédito hipotecario como variable que aproxima su comportamiento. El análisis se realiza en dos fases. En la primera, se muestra la validez de la variable elegida mediante la evaluación de sus similitudes estadísticas con la evolución de los precios durante el período en que se observan ambas (1987-2014). En la segunda, se define un modelo donde se estima el comportamiento de largo plazo de los precios residenciales en relación al PIB, como indicador fundamental en su evolución, y a la hipoteca unitaria, para predecir hacia atrás la serie de precios residenciales, desde 1959 a 1986. Las fases de cálculo utilizan metodologías ARIMA dentro de entornos de regresión para la obtención de señales de los precios y la estimación del modelo de comportamiento y la predicción. A continuación, se contrasta la lógica de la serie obtenida con un análisis de los principales hechos económicos en España, y se compara la serie estimada con la evolución de los precios residenciales en otros países como los del Reino Unido, Francia, Estados Unidos, Alemania, los Países Bajos, Italia y Japón. Este enfoque muestra similitudes en el comportamiento de los precios residenciales a lo largo de 50 años. La serie resultante del cálculo muestra la existencia de un fuerte aumento de los precios de las viviendas durante dos décadas (1960 y 1970), casi ininterrumpidamente, que llevaron a niveles de precios reales similares a los alcanzados en 2007, seguidos de una corrección súbita similar en dureza a la que hoy día han experimentado los precios residenciales en España

Synchronisation among short-term rental markets, co-movements and cycles in 39 European cities

This paper presents new evidence of the short-term rental market's prices and transactions from a daily time-series perspective in 39 European cities from 2015 to 2020. It uses Airbnb micro datasets to build time-series cycles by extracting the original observations containing total bookings (rent transactions), rental units supply, and asking rent, with a daily periodicity. The cycles show the periods in which short-rental activity was more relevant for each city, and the level of rents across Europe. The paper provides empirical evidence of a long-term relationship among the city variables (tested via mean and variance). Causality supporting co-movements across cities was found by estimating a short-term naïve market equilibrium model using the vector error correction model approach, supporting the hypothesis that the short-term rental market performs according to housing-market principles. Short-run elasticities among rents and contracts across the 39 cities show causal evidence of co-movements among rents and the supply and demand of properties. The market adjustment on the supply side estimates new units responding to changes in prices within 15 lags (days) and longer (350 lags) from the demand side, equivalent to eight to nine months. Evidence of the pandemic's limited effect on housing supply and prices' positive effect is also provided. A robust negative weekend impact on prices was found, suggesting stronger market relevance on weekdays

Energy Poverty in Ecuador

This paper aims to identify the presence of energy poverty in Ecuador. Three indicators proposed by the European Union Energy Poverty Observatory (EPOV) are used to construct a multidimensional energy poverty index (MEPI) based on measure conditions associated with energy poverty, in areas related to delays in the payment of electricity bills, disproportionate expenses, hidden energy poverty, and the 10% Boardman (1991) rule. The information comes from the Ecuatorian Life Conditions Survey. The results show that energy poverty is present in Ecuadorian households, at the national level, and just as these indicators have restrictions, advantages and disadvantages, which demand decisions about the choice of their use

Characterization of the heteropolysaccharides produced by Liquorilactobacillus sicerae CUPV261 and Secundilactobacillus collinoides CUPV237 isolated from cider

Some lactic acid bacteria (LAB) strains isolated from alcoholic beverages are able to produce exopolysaccharides (EPS). The present work focuses on the physico-chemical characterization of the heteropolysaccharides (HePS) produced by Liquorilactobacillus sicerae CUPV261T (formerly known as Lactobacillus sicerae) and Secundilactobacillus collinoides CUPV237 (formerly known as Lactobacillus collinoides) strains isolated from cider. Genome sequencing and assembly enabled the identification of at least four putative HePS gene clusters in each strain, which correlated with the ability of both strains to secrete EPS. The crude EPS preparation from CUPV261T contained glucose, galactose and rhamnose, and that of CUPV237 was composed of glucose, galactose and N-acetylglucosamine. Both EPS were mixtures of HePS of different composition, with two major soluble components of average molecular weights (Mw) in the range of 106 and 104 g.mol−1. These HePS were resistant to gastric stress conditions in an in vitro model, and they significantly reduced zebrafish larvae mortality in an in vivo model of inflammatory bowel disease.This research was funded by the Spanish Ministry of Science, Innovation and Universities (grant RTI2018-097114-B-I00 to P.L. and M.T.D.), by the Basque Government (grants KK-2019/00076, KK-2021/00034, KK-2022/00107, IT1662-22 and PIBA_2020_1_0032 to M.T.D and O.E.) and by the University of the Basque Country (GIU19/014)

Desarrollo de una práctica de Estadística Descriptiva con GeoGebra

El presente trabajo pretende dar una pauta para emplear el potencial de las herramientas TIC con el propósito de facilitar en el aula y fuera de ella, el aprendizaje de conceptos propios de la estadística a un nivel universitario. Existen diversos programas computacionales capaces de realizar análisis estadísticos de alto nivel: SPSS, Minitab, Matlab, por mencionar algunos; estos programas funcionan muy bien cuando se trata de encontrar respuestas a planteamientos complicados o cuando se tiene un enorme banco de datos. Para emplear de la forma correcta este tipo de software y no malinterpretar sus resultados, es necesario en primer lugar, que el usuario entienda perfectamente los conceptos básicos de la estadística descriptiva, como son el análisis para datos agrupados y no agrupados, medidas de tendencia central y de dispersión, así como los diversos gráficos y tablas de datos que describen la frecuencia con la cual sucede un evento; para lo cual es necesario el uso de un software dinámico y en este caso diseñado específicamente para el aprendizaje didáctico de las matemáticas como lo es GeoGebra