Identification of the 4-hydroxyphenylacetate transport gene of Escherichia coli W : construction of a highly sensitive cellular biosensor

AbstractThe mechanism of uptake of 4-hydroxyphenylacetate (4-HPA) by Escherichia coli W. was investigated. The 4-HPA uptake was induced by 4-HPA, 3-hydroxyphenylacetate (3-HPA) or phenylacetate (PA) and showed saturation kinetics with apparent Kt and Vmax values of 25 μM and 3 nmol/min per 109 cells, respectively. Transport of 4-HPA was resistant to N,N″-dimethylcarbodiimide (DCCD), but was completely inhibited by cyanide and 4-nitrophenol, and, to a lower extent, by arsenate and azide, suggesting that energy is required for the uptake process. Competition studies showed that 4-HPA uptake was inhibited by 3-HPA or 3,4-dihydroxyphenylacetate (3,4-DHPA) but not by 2-hydroxyphenylacetate (2-HPA), l-tyrosine or other structural analogues, indicating a narrow specificity of the transport system. We have demonstrated, using two experimental approaches, that the hpaX gene of the 4-HPA catabolic cluster, which encodes a protein of the superfamily of transmembrane facilitators, is responsible for 4-HPA transport. Aside from the aromatic amino acid transport systems, hpaX is the first transport gene for an aromatic compound of enteric bacteria that has been characterized. A highly sensitive cellular biosensor has been constructed by coupling the 4-HPA transport system to a regulatory circuit that controls the production of β-galactosidase. This biosensor has allowed us to demonstrate that the transport system performs efficiently at very low external concentrations of 4-HPA, similar to levels that would be expected to occur in natural environments

Influence of relative age effect in basic physical abilities

Este trabajo se centra en el Efecto de la Edad Relativa (RAE) sobre las capacidades físicas básicas del alumnado de ESO, tras un estudio descriptivo correlacional transversal contextualizado mediante muestreo incidental en un Instituto de Educación Secundaria Obligatoria. Los instrumentos utilizados fueron pruebas físicas y un cuestionario. Los resultados muestran que no existen diferencias significativas (p>0,05) entre las medias de las pruebas físicas del alumnado nacido en el primer y segundo semestre. Las mejores marcas corresponden al alumnado nacido en los primeros meses del año. Esta tendencia se ve alterada en función del sexo, curso escolar y actividad física extraescolar. El alumnado nacido a principios de año obtuvo una mejor calificación numérica en Educación Física. Como conclusión podemos afirmar que el RAE es un factor más del proceso educativo, que está presente en las Capacidades Físicas Básicas y debe tenerse en cuenta para evitar situaciones desfavorables para el alumnadoThis paper focuses on the Relative Age Effect (RAE) over the basic physical abilities of Compulsory Secondary School (ESO) students after a descriptive, cross-sectional, correlation study in context by incidental sampling in a Compulsory Secondary Education school. The tools applied were physical tests and a questionnaire. The results reveal that there are no significant differences (p>0,05) between the mean results in the physical tests taken by students born in the first and the second semesters. The highest marks belong to the students born in the early months of the year. This tendency is altered by sex, school year and after school physical activity. Students born towards the beginning of the year attained better school marks in PE. As a conclusion we can argue that the RAE is one more factor within the education process, it is present in basic physical abilities and must be taken into account in order to prevent unfavourable situations for student

The access to broadband services as a strategy to retain population in the depopulated countryside in Spain

The aim of this paper is to analyze at what extent the connectivity of small localities is a determinant of their demography. Specifically, we pay attention to three factors: the evolution of the population; the distance, measured both in kilometres and travel time, to the province capital, the usual city where the largest set of services is available; and finally, the coverage of different kinds of broadband services (from ADSL or 3.5 G to the fastest ones FTTH) in rural areas. An econometric model was estimated where the dependent variable captures the increase of inhabitants along 2017–2020 of the 5955 Spanish municipalities with a population between 101 and 10,000 inhabitants (73.3 % of all municipalities). The results point out to the following facts: digital connectivity of small localities is a determinant of their demography, whatever the technology used, but physical distance remains being a significant factor on the population growth (both if it is measured of physical distance or travelling time) to explain the population growth of each locality

Estilos de trabajo e inteligencias múltiples

El objetivo del trabajo es determinarla validez yflabilidad del modelo dejos estilos de trabajo, fundamentado en la teoría de las Inteligencias Múltiples (IM). Primero, se analizan los componentes de dicha teoría y su incidencia en el curriculum escolar. En segundo lugar, se estudia el procedimiento de evaluación. Además, se presentan los resultados del estudio empírico realizado con una muestra de 237 alumnos pertenecientes a Educación Infantil y Primaria, escolarizados en centros públicos y privados de la Región de Murcia. Del estudio realizado se desprende que los estilos están asociados a las diferentes inteligencias; además, el inventario de estilos de trabajo arroja una validez y fiabilidad altamente consistente.________________________________ The objective of this work is to determinate the validity and reliability of the model of work styles, as set out In the theory of Multiple Intelligences (MI). First, we analyze the components of this theory and their Incidence in the school curriculum. Second, we study the evaluation procedure. Additionally, we present the results of an empirical study carried out with a sample of 237 students in public and private nursery and primary schools in the province of Murcia, Spain. The study carried out reveals that the styles are associated with the different Intelligences. Furthermore, the inventory of styles shows a highly consistent validity and reliability

Influence of the dance in the autoconcepto of the alumnado of primary education: comparative analysis with other physical activities

[Resumen] Este trabajo de investigación pretende analizar la relación que existe entre el autoconcepto y la danza en el alumnado de Educación Primaria. Se han querido relacionar estas dos cuestiones debido a la importancia que tienen, por una parte, el autoconcepto en la identidad del sujeto y por otra parte, la realización de actividad física, concretamente la danza. Para llevarlo a cabo, se ha evaluado una muestra de 74 niños/as, de edades comprendidas entre los 7 y los 12 años, pertenecientes a un colegio (n=45) y dos escuelas de danza de Vigo (n=29). El instrumento de medida que se ha utilizado es la Escala de Autoconcepto (Piers Harris), que valora tanto el autoconcepto global, como sus diferentes dimensiones. La finalidad de esta investigación es observar si existe relación entre el autoconcepto y la danza y cuáles son las dimensiones en las que ésta obtiene mayores puntuaciones, comparar con la realización de otras actividades físicas. Tras analizar los resultados obtenidos, hemos comprobado que la danza no mejora el autoconcepto global por encima de otras actividades físicas, sin embargo, cabe destacar que se observa una dimensión del autoconcepto que sí se ve favorecida por la práctica de la danza, concretamente, la felicidad-satisfacción, en la cual se valora la autoestima del sujeto.[Abstract] This research work pretends to analyse the relationship between the self-concept and the dance in the students of Primary Education. We wanted to relate these both questions because of its importance, on the one hand, the self-concept in the identity of the individual and, on the other hand, doing physical activity, specifically, dance, in the young people. To carry out this research, we have evaluated a sample of 74 children between 7 and 12 years from one school (n=45) and two dance schools in Vigo (n=29). We use the Self-Concept Questionnaire (Piers Harris), which values the global self-concept and the dimensions of the self-concept. The purpose of this research is to check if there is some kind of relationship between the self-concept and dance, and to know what dimensions of the self-concept get more score in dance than in other physical activities. We have analysed the results and verified that dance does not improve the global self-concept more than other physical activities; nevertheless, it is remarkable that there is a dimension of self-concept that gets high score in connection with practicing dance, specifically, the happiness-satisfaction, which values the self-esteem of the individual

A Note on Combining Machine Learning with Statistical Modeling for Financial Data Analysis

This note revisits the ideas of the so-called semiparametric methods that we consider to be very useful when applying machine learning in insurance. To this aim, we first recall the main essence of semiparametrics like the mixing of global and local estimation and the combining of explicit modeling with purely data adaptive inference. Then, we discuss stepwise approaches with different ways of integrating machine learning. Furthermore, for the modeling of prior knowledge, we introduce classes of distribution families for financial data. The proposed procedures are illustrated with data on stock returns for five companies of the Spanish value-weighted index IBEX35.The authors thank the Institute and Faculty of Actuaries in the U.K. for funding their research through the grant “Minimizing Longevity and Investment Risk while Optimizing Future Pension Plans” and the Spanish Ministerio de Economía y Competitividad, Project ECO2016-76203-C2-1-P, for partial support of this work

A Modal-Based Partition of Unity Finite Element Method for Elastic Wave Propagation Problems in Layered Media

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] The time-harmonic propagation of elastic waves in layered media is simulated numerically by means of a modal-based Partition of Unity Finite Element Method (PUFEM). Instead of using the standard plane waves or the Bessel solutions of the Helmholtz equation to design the discretization basis, the proposed modal-based PUFEM explicitly uses the tensor-product expressions of the eigenmodes (the so-called Love and interior modes) of a spectral elastic transverse problem, which fulfil the coupling conditions among layers. This modal-based PUFEM approach does not introduce quadrature errors since the coefficients of the discrete matrices are computed in closed-form. A preliminary analysis of the high condition number suffered by the proposed method is also analyzed in terms of the mesh size and the number of eigenmodes involved in the discretization. The numerical methodology is validated through a number of test scenarios, where the reliability of the proposed PUFEM method is discussed by considering different modal basis and source terms. Finally, some indicators are introduced to select a convenient discrete PUFEM basis taking into account the observability of cracks located on a coupling boundary between two adjacent layers.This work has been supported by Xunta de Galicia project “Numerical simulation of high-frequency hydro-acoustic problems in coastal environments - SIMNUMAR” (EM2013/052), co-funded with European Regional Development Funds (ERDF). Moreover, the second and fifth authors have been supported by MICINN projects MTM2014-52876-R, MTM2017-82724-R, PID2019-108584RB-I00, and also by ED431C 2018/33 - M2NICA (Xunta de Galicia & ERDF) and ED431G 2019/01 - CITIC (Xunta de Galicia & ERDF). Additionally, the third author has been supported by Junta de Castilla y León under projects VA024P17 and VA105G18, co-financed by ERDF funds. This work has been funded for open access charge by Universidade da Coruña/CISUGXunta de Galicia; EM2013/052Xunta de Galicia; ED431C 2018/33Xunta de Galicia; ED431G 2019/01Junta de Castilla y León; VA024P17Junta de Castilla y León; VA105G1

In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma.

Edelfosine is the prototype molecule of a family of anticancer drugs collectively known as synthetic alkyl-lysophospholipids. This drug holds promise as a selective antitumor agent, and a number of preclinical assays are in progress. In this study, we observe the accumulation of edelfosine in brain tissue after its oral administration in Compritol® and Precirol® lipid nanoparticles (LN). The high accumulation of edelfosine in brain was due to the inhibition of P-glycoprotein by Tween® 80, as verified using a P-glycoprotein drug interaction assay. Moreover, these LN were tested in vitro against the C6 glioma cell line, which was later employed to establish an in vivo xenograft mouse model of glioma. In vitro studies revealed that edelfosine-loaded LN induced an antiproliferative effect in C6 glioma cell line. In addition, in vivo oral administration of drug-loaded LN in NMRI nude mice bearing a C6 glioma xenograft tumor induced a highly significant reduction in tumor growth (p<0.01) fourteen days after the beginning of the treatment. Our results showed that Tween® 80 coated Compritol® and Precirol® LN can effectively inhibit the growth of C6 glioma cells in vitro and suggest that edelfosine-loaded LN represent an attractive option for the enhancement of antitumor activity on brain tumors in vivo

Efficacy of edelfosine lipid nanoparticles in breast cancer cells

Breast cancer is a heterogeneous group of neoplasms predominantly originating in the terminal duct lobular units. It represents the leading cause of cancer death in women and the survival frequencies for patients at advanced stages of the disease remain low. New treatment options need to be researched to improve these rates. The anti-tumor ether lipid edelfosine (ET) is the prototype of a novel generation of promising anticancer drugs. However, it presents several drawbacks for its use in cancer therapy, including gastrointestinal and hemolytic toxicity and low oral bioavailability. To overcome these obstacles, ET was encapsulated in Precirol ATO 5 lipid nanoparticles (ET-LN), and its anti-tumor potential was in vitro tested in breast cancer. The formulated ET-LN were more effective in inhibiting cell proliferation and notably decreased cell viability, showing that the cytotoxic effect of ET was considerably enhanced when ET was encapsulated. In addition, ET and ET-LN were able to promote cell cycle arrest at G1 phase. Moreover, although both treatments provoked an apoptotic effect in a time-dependent manner, such anti-tumor effects were noticeably improved with ET-LN treatment. Therefore, our results indicate that encapsulating ET in LN played an essential role in improving the efficacy of the drug

CD44-high neural crest stem-like cells are associated with tumour aggressiveness and poor survival in neuroblastoma tumours

BACKGROUND: Neuroblastoma is a paediatric tumour originated from sympathoadrenal precursors and characterized by its heterogeneity and poor outcome in advanced stages. Intra-tumoral cellular heterogeneity has emerged as an important feature in neuroblastoma, with a potential major impact on tumour aggressiveness and response to therapy. CD44 is an adhesion protein involved in tumour progression, metastasis and stemness in different cancers; however, there has been controversies about the significance of CD44 expression in neuroblastoma and its relationship with tumour progression. METHODS: We have performed transcriptomic analysis on patient tumour samples studying the outcome of patients with high CD44 expression. Adhesion, invasion and proliferation assays were performed in sorted CD44high neuroblastoma cells. Tumoursphere cultures have been used to enrich in undifferentiated stem-like cells and to asses self-renewal and differentiation potential. We have finally performed in vivo tumorigenic assays on cell line-derived or Patient-derived xenografts. FINDINGS: We show that high CD44 expression is associated with low survival in high-grade human neuroblastoma, independently of MYCN amplification. CD44 is expressed in a cell population with neural crest stem-like features, and with the capacity to generate multipotent, undifferentiated tumourspheres in culture. These cells are more invasive and proliferative in vitro. CD44 positive cells obtained from tumours are more tumorigenic and metastatic, giving rise to aggressive neuroblastic tumours at high frequency upon transplantation. INTERPRETATION: We describe an unexpected intra-tumoural heterogeneity within cellular entities expressing CD44 in neuroblastoma, and propose that CD44 has a role in neural crest stem-like undifferentiated cells, which can contribute to tumorigenesis and malignancy in this type of cancer. FUNDING: Research supported by grants from the "Asociación Española contra el Cáncer" (AECC), the Spanish Ministry of Science and Innovation SAF program (SAF2016-80412-P), and the European Research Council (ERC Starting Grant to RP).Spanish Ministry of Science and Innovation SAF program (SAF2016-80412-P