Cell fate conversion by mRNA

Recent development of a synthetic mRNA-based technology for efficient reprogramming to pluripotency and cell fate conversion without any modification to the genome has generated great interest among researchers and clinicians alike. It is hoped that this technology could contribute to unmet needs on several fronts of regenerative medicine, including mechanistic study of reprogramming, generation of safe induced pluripotent stem cells suitable for clinical applications, and derivation of desired cell types for cell-replacement therapy. We will discuss the technological advancements made by this synthetic mRNA methodology, its implications, as well as the challenges that lie ahead in the field of regenerative medicine

Microbial community changes induced by Managed Aquifer Recharge activities: linking hydrogeological and biological processes

Managed Aquifer Recharge (MAR) is a technique used worldwide to increase the availability of water resources. We study how MAR modifies microbial ecosystems and its implications for enhancing biodegradation processes to eventually improve groundwater quality. We compare soil and groundwater samples taken from a MAR facility located in NE Spain during recharge (with the facility operating continuously for several months) and after 4 months of no recharge. The study demonstrates a strong correlation between soil and water microbial prints with respect to sampling location along the mapped infiltration path. In particular, managed recharge practices disrupt groundwater ecosystems by modifying diversity indices and the composition of microbial communities, indicating that infiltration favors the growth of certain populations. Analysis of the genetic profiles showed the presence of nine different bacterial phyla in the facility, revealing high biological diversity at the highest taxonomic range. In fact, the microbial population patterns under recharge conditions agree with the intermediate disturbance hypothesis (IDH). Moreover, DNA sequence analysis of excised denaturing gradient gel electrophoresis (DGGE) band patterns revealed the existence of indicator species linked to MAR, most notably Dehalogenimonas sp., Nitrospira sp. and Vogesella sp.. Our real facility multidisciplinary study (hydrological, geochemical and microbial), involving soil and groundwater samples, indicates that MAR is a naturally based, passive and efficient technique with broad implications for the biodegradation of pollutants dissolved in water.Peer ReviewedPostprint (published version

Situación actual del personal técnico-deportivo en las empresas del sector en la Comunidad Valenciana

Actualmente, el tema de los recursos humanos está produciendo un fuerte impacto en España y sólo hay que acercarse a la bibliografía empresarial para comprobar que el estudio del sector de la actividad física y el deporte representa un campo de interés científico y social que requiere ser investigado. Mediante una metodología cuantitativa de corte descriptivo y mediante el empleo de la entrevista estandarizada como instrumento de recogida de información se reproducen aquellas características más relevantes observadas en la Comunidad Valenciana. Los resultados explican que las personas que trabajan en funciones físico-deportivas en empresas del sector son mayoritariamente hombres jóvenes que desarrollan una amplia variedad de las mismas, con situaciones laborales en las que no existe contratación y manifestando una elevada temporalidad. Asimismo, el estudio revela que más de la mitad de las personas desempeñan su trabajo con una duración laboral que no supera los cuatro años, existiendo personas sin titulación oficial de actividad física y deporte, y siendo el aspecto más importante para encontrar trabajo los contactos personales

Estudio descriptivo: Centro de Vacunación Internacional de Zaragoza

El presente trabajo tiene como objetivo principal analizar la actividad del Centro de Vacunación Internacional (CVI) de Zaragoza a lo largo de los años que lleva en funcionamiento. Para ello, fraccionaremos este objetivo general en varios objetivos específicos. El trabajo consiste en un estudio descriptivo retrospectivo del total de registros informatizados de viajeros internacionales que han acudido al CVI de Zaragoza entre los años 1999 y 2012, ambos incluidos

Improving deep learning performance with missing values via deletion and compensation

Proceedings of: International Work conference on the Interplay between Natural and Artificial Computation (IWINAC 2015)Missing values in a dataset is one of the most common difficulties in real applications. Many different techniques based on machine learning have been proposed in the literature to face this problem. In this work, the great representation capability of the stacked denoising auto-encoders is used to obtain a new method of imputating missing values based on two ideas: deletion and compensation. This method improves imputation performance by artificially deleting values in the input features and using them as targets in the training process. Nevertheless, although the deletion of samples is demonstrated to be really efficient, it may cause an imbalance between the distributions of the training and the test sets. In order to solve this issue, a compensation mechanism is proposed based on a slight modification of the error function to be optimized. Experiments over several datasets show that the deletion and compensation not only involve improvements in imputation but also in classification in comparison with other classical techniques.The work of A. R. Figueiras-Vidal has been partly supported by Grant Macro-ADOBE (TEC 2015-67719-P, MINECO/FEDER&FSE). The work of J.L. Sancho-Gómez has been partly supported by Grant AES 2017 (PI17/00771, MINECO/FEDER)

Multiple implications of an active site phenylalanine in the catalysis of aryl-alcohol oxidase

Aryl-alcohol oxidase (AAO) has demonstrated to be an enzyme with a bright future ahead due to its biotechnological potential in deracemisation of chiral compounds, production of bioplastic precursors and other reactions of interest. Expanding our understanding on the AAO reaction mechanisms, through the investigation of its structure-function relationships, is crucial for its exploitation as an industrial biocatalyst. In this regard, previous computational studies suggested an active role for AAO Phe397 at the active-site entrance. This residue is located in a loop that partially covers the access to the cofactor forming a bottleneck together with two other aromatic residues. Kinetic and affinity spectroscopic studies, complemented with computational simulations using the recently developed adaptive-PELE technology, reveal that the Phe397 residue is important for product release and to help the substrates attain a catalytically relevant position within the active-site cavity. Moreover, removal of aromaticity at the 397 position impairs the oxygen-reduction activity of the enzyme. Experimental and computational findings agree very well in the timing of product release from AAO, and the simulations help to understand the experimental results. This highlights the potential of adaptive-PELE to provide answers to the questions raised by the empirical results in the study of enzyme mechanisms.This work was supported by the EnzOx2 project (H2020-BBI-PPP-2015-720297) of the European Joint Undertaking of Bio-based Industries (http://bbi-europe.eu), the INDOX project (KBBE-2013-7-613549) of the European Seventh Framework Programme, and the NOESIS (BIO2014-56388-R), vMutate (CTQ2016-79138-R) and FLADIMOTEC (BIO2016-75183-P) projects of the Spanish Ministry of Economy and Competitiveness. J.C. acknowledges a FPU fellowship (FPU2012-2041) from the Spanish Ministry of Education, Culture and Sports.Peer ReviewedPostprint (published version

Fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 reduces bacterial translocation in rats treated with carbon tetrachloride

Citocines; Malalties del fetgeCitocinas, Enfermedades del hígadoCytokines; Liver diseasesProbiotics can prevent pathological bacterial translocation by modulating intestinal microbiota and improving the gut barrier. The aim was to evaluate the effect of a fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 on bacterial translocation in rats with carbon tetrachloride (CCl4)-induced cirrhosis. Sprague-Dawley rats treated with CCl4 were randomized into a probiotic group that received fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 in drinking water or a water group that received water only. Laparotomy was performed one week after ascites development. We evaluated bacterial translocation, intestinal microbiota, the intestinal barrier and cytokines in mesenteric lymph nodes and serum. Bacterial translocation decreased and gut dysbiosis improved in the probiotic group compared to the water group. The ileal β-defensin-1 concentration was higher and ileal malondialdehyde levels were lower in the probiotic group than in water group. There were no differences between groups in serum cytokines but TNF-α levels in mesenteric lymph nodes were lower in the probiotic group than in the water group. Fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 decreases bacterial translocation, gut dysbiosis and ileal oxidative damage and increases ileal β-defensin-1 expression in rats treated with CCl4, suggesting an improvement in the intestinal barrier integrity.This study was partially funded by Danone Research (Palaiseau, Cedex, France), and grants PI08/0262 and PI14/00680 from the Instituto de Salud Carlos III, Madrid, Spain, and cofinanced by Fondos FEDER (Fondo Europeo de Desarrollo Regional), “Una manera de hacer Europa”, European Union, and CERCA Programme, Generalitat de Catalunya. The investigational product was provided by Danone Research. Silvia Vidal was supported by Fondo de Investigaciones Sanitarias (FIS) and is a participant in the Program for Stabilization of Investigators of the Direcció d’Estrategia i Coordinació del Departament de Salut, Generalitat de Catalunya. Pau Sancho-Bru is funded by Instituto de Salud Carlos III, Miguel Servet (CP11/00071)

Novel sampling strategy for alive animal volatolome extraction combined with GC-MS based untargeted metabolomics: Identifying mouse pup pheromones

In this study, we identify 11 mouse pup volatiles putatively involved in maternal care induction in adult females. For this purpose, we have adapted the dynamic headspace methodology to extract the volatolome of whole alive animals. Untargeted metabolomic methodology was used to compare the volatolome of neonatal (4–6 days) with elder pups until the age of weaning (21–23 days old). Pup volatolome was analyzed by gas chromatography (GC) coupled to single quadrupole mass spectrometry (MS) using automated thermal desorption for sample introduction. After data processing and multivariate statistical analysis, comparison with NIST spectral library allowed identifying compounds secreted preferentially by neonatal pups: di(propylen glycol) methyl ether, 4-nonenal, di(ethylene glycol) monobutyl ether, 2-phenoxyethanol, isomethyl ionone, tridecanal, 1,3-diethylbenzene, 1,2,4,5-tetramethylbenzene, 2-ethyl-p-xylene and tri(propylene glycol) methyl ether. Palmitic acid was enriched in the volatolome of fourth week youngsters compared to neonatal pups. The results demonstrated the great potential of the new sampling procedure combined with GC-MS based untargeted volatolomics to identify volatile pheromones in mammals.Funding for open access charge: CRUE-Universitat Jaume

Pumping Metallic Nanoparticles with Spatial Precision within Magnetic Mesoporous Platforms: 3D Characterization and Catalytic Application

The present work shows an efficient strategy to assemble two types of functional nanoparticles onto mesoporous MCM-41 silica nanospheres with a high degree of spatial precision. In a first stage, magnetite nanoparticles are synthesized with a size larger than the support pores and grafted covalently through a peptide-like bonding onto their external surface. This endowed the silica nanoparticles with a strong superparamagnetic response, while preserving the highly ordered interior space for the encapsulation of other functional guest species. Second, we report the finely controlled pumping of preformed Pt nanoparticles (1.5 nm) within the channels of the magnetic MCM-41 nanospheres to confer an additional catalytic functionality to the multiassembled nanoplatform. The penetration depth of the metallic nanoparticles can be explained as a result of the interplay between the particle-wall electrostatic attraction and the repulsive forces between neighboring Pt nanoparticles. A detailed transmission electron microscopy and a 3D high-resolution high-angle annular dark-field detector electron tomography study were carried out to characterize the material and to explain the assembly mechanism. Finally, the performance of these multifunctional nanohybrids as magnetically recoverable catalysts has been evaluated in the selective hydrogenation of p-nitrophenol, a well-known pollutant and intermediate in multiple industrial processes