One century later: dissecting genetic effects for looking over old paradigms

José M. Álvarez-Castro has been supported by the Autonomous Administration Xunta de Galicia through project EM2014/024 to edit this Research Topic IssueS

Multiallelic models of genetic effects and variance decomposition in non-equilibrium populations

Quantitative genetics stems from the theoretical models of genetic effects, which are re-parameterizations of the genotypic values into parameters of biological (genetic) relevance. Different formulations of genetic effects are adequate to address different subjects. We thus need to generalize and unify them under a common framework for enabling researchers to easily transform genetic effects between different biological meanings. The Natural and Orthogonal Interactions (NOIA) model of genetic effects has been developed to achieve this aim. Here, we further implement the statistical formulation of NOIA with multiple alleles under Hardy–Weinberg departures (HWD). We show that our developments are straightforwardly connected to the decomposition of the genetic variance and we point out several emergent properties of multiallelic quantitative genetic models, as compared to the biallelic ones. Further, NOIA entails a natural extension of one-locus developments to multiple epistatic loci under linkage equilibrium. Therefore, we present an extension of the orthogonal decomposition of the genetic variance to multiple epistatic, multiallelic loci under HWD. We illustrate this theory with a graphical interpretation and an analysis of published data on the human acid phosphatase (ACP1) polymorphismJAC acknowledges funding by an “Isidro Parga Pondal” contract from the autonomous administration Xunta de Galicia. This research has been partially supported by projects BFU2009-11988 and BFU2010-20003 form the Spanish Ministry of Science (JAC) and the Natural Sciences and Engineering Research Council of Canada, Grant OGP0183983 (RCY)S

Localizations at hyperplane arrangements: combinatorics and D-modules

We describe an algorithm deciding if the annihilating ideal of the meromorphic function 1 f , where f = 0 defines an arrangement of hyperplanes, is generated by linear differential operators of order 1. The algorithm is based on the comparison of two characteristic cycles and uses a combinatorial description due to `Alvarez-Montaner, Garc´ıa–L´opez and Zarzuela of the characteristic cycle of the D-module of meromorphic functions with respect to f

Bioplástico a base de celulosa de Papa para empaques

La distribución inadecuada de residuos orgánicos en la cafetería de la I.E. Tulio Ospina genera afectación al bienestar de la comunidad y al medio ambiente escolar por la contaminación que se produce, debido a la pobre cadena de aprovechamiento. Actualmente, el interés por encontrar nuevas fuentes de bioplástico a las existentes, y que posiblemente sustituyan plásticos a base de derivados del petróleo, conforma un gran precedente, por lo tanto, se propone utilizar los residuos orgánicos con alto contenido de celulosa como la cáscara de papa de establecimientos de la institución para desarrollar un prototipo de bioplástico para diferentes utilidades. Este aprovechamiento, ayuda a la disminución de impactos generados y la higiene que podrá tener el establecimiento gastronómico. Se recolecta cáscara de papa, pasa por hidrólisis alcalina (NaOH al 3%) por 30 minutos a 40°C; seguidamente, se hace el lavado y el post-blanqueamiento con hipoclorito de sodio al 2%. Teniendo como resultado dos prototipos: uno, con óxido de magnesio y el otro, con carbonato de calcio; cada uno, con tres muestras. Se realizan pruebas de resistencia, solubilidad y biodegradabilidad, arroja que en promedio son resistentes, poco solubles y que tienen un grado menor de biodegradabilidad. Lo anterior, realizado a corto plazo.na1 págin

Violencia a través de las tecnologías de la información y la comunicación en estudiantes de secundaria

The aim of this paper was to analyze violence through Informa- tion and Communication Technologies (ICT) in Compulsory Secondary Education students. To achieve this objective, the School Violence Question- naire-Revised was applied to 638 Compulsory Secondary Education stu- dents, from six high schools in Asturias (Spain). Results show that vio- lence through ICT occurs with a remarkable frequency, although less than some kinds of traditional school violence. Statistically significative differ- ences were found among grades of Compulsory Secondary Education and between rural and urban centers. Violence through ICT is more frequent in second grade and in urban high schools. However, statistically significa- tive differences were barely found between genders. Also, a strong correla- tion between violence through ICT and some kinds of traditional school violence was found. These outcomes are compared with the results of the main previous works about this subject. Some educative implications of these results are discussed.El objetivo de este estudio fue analizar la violencia a través de las Tecnologías de la Información y la Comunicación (TIC) en estudiantes de Educación Secundaria Obligatoria. Para ello, se aplicó el Cuestionario de Violencia Escolar-Revisado (CUVE-R) a 638 estudiantes de 1º a 4º de ESO, pertenecientes a seis centros educativos de Asturias (España). Los resultados obtenidos muestran que, a pesar de ser menos habitual que otros tipos más tradicionales de violencia escolar, la violencia a través de las TIC aparece con una frecuencia que la hace digna de atención. Se han encontrado diferencias estadísticamente significativas en función del curso y del entorno -rural o urbano- del centro: la violencia a través de las TIC aparece con mayor frecuencia en 2º de ESO que en los demás niveles educativos, y en los centros urbanos que en los rurales. En cambio, apenas se han encontrado diferencias en función del género. Se ha hallado, asimismo, una fuerte correlación entre la presencia de violencia a través de las TIC y de otros tipos de violencia escolar más tradicionales. Estos resultados se contrastan con los obtenidos por los estudios previos más relevantes sobre esta temática. Se discuten algunas implicaciones educativas de estos resultados

Determination of 18 organophosphorus flame retardants/plasticizers in mussel samples by matrix solid-phase dispersion combined to liquid chromatography-tandem mass spectrometry

This study presents the development and validation of a new analytical method based on matrix solid-phase dispersion (MSPD), integrating sample extraction and clean-up in one single step, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of 18 organophosphorus flame retardants and/or plasticizers (OPEs) in marine mussel (Mytilus edulis and Mytilus galloprovincialis) samples. Among these OPEs, 5 (tetraethyl 1,2-ethanediylbis(phosphonate), 6H-dibenzo[c,e] [1,2]oxaphosphinine 6-oxide, tris(2,3-dibromopropyl) phosphate, 2,2-propanediyldi-4,1-phenylene bis(phosphate) and resorcinol bis(diphenyl phosphate)) are considered here for the first time in marine samples. Different parameters affecting the MSPD (clean-up sorbent and elution solvent) were optimized to obtain a good compromise between analyte recoveries and extract clean-up. Also, particular attention was paid to tackle blank issues. The overall method was validated in terms of trueness, precision and detection and quantification limits. Percentages of recovery varied from 69% to 122% with relative standard deviations below 24%. Detection limits ranged from 0.06 to 5 ng g−1 and quantification limits from 0.19 to 17 ng g−1 dry weight. Finally, the method was applied to the analysis of 7 mussel samples collected in the coast of Galicia (Spain). 8 OPEs were detected in these samples at concentrations ranging from the LOQ to 291 ng g−1 dry weight.This work was financially supported by the Spanish Agencia Estatal de Investigación (ref. CTM2017-84763-C3-2-R), the Galician Council of Culture, Education and Universities (ref. ED431C2017/36 and Verónica Castro predoctoral contract, ref. ED481A-2017/156), cofunded by FEDER/ERDFS

Proteomic analysis in morquio a cells treated with immobilized enzymatic replacement therapy on nanostructured lipid systems

[ENG]Morquio A syndrome, or mucopolysaccharidosis type IVA (MPS IVA), is a lysosomal storage disease due to mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. Systemic skeletal dysplasia and the related clinical features of MPS IVA are due to disruption of cartilage and its extracellular matrix, leading to an imbalance of growth. Enzyme replacement therapy (ERT) with recombinant human GALNS, alpha elosulfase, provides a systemic treatment. However, this therapy has a limited impact on skeletal dysplasia because the infused enzyme cannot penetrate cartilage and bone. Therefore, an alternative therapeutic approach to reach the cartilage is an unmet challenge. We have developed a new drug delivery system based on a nanostructure lipid carrier with the capacity to immobilize enzymes used for ERT and to target the lysosomes. This study aimed to assess the effect of the encapsulated enzyme in this new delivery system, using in vitro proteomic technology. We found a greater internalization of the enzyme carried by nanoparticles inside the cells and an improvement of cellular protein routes previously impaired by the disease, compared with conventional ERT. This is the first qualitative and quantitative proteomic assay that demonstrates the advantages of a new delivery system to improve the MPS IVA ERTS

Rolling contact fatigue study of railway rails

This work analyses the wheel-rail interaction in terms of rolling contact fatigue (RCF). For this purpose, a full scale testing machine was designed and built in order to apply the loads and boundary conditions appearing in the railway (up to 30 tons per wheel, application of lateral load in bends, inclination, angle of attack, presence of dust, water…) Eight tests were performed under different load conditions and rail grades and RCF cracks were generated after 50000 to 100000 cycles. The occurrence of cracks was determined by magnetic particle inspection at regular intervals in the course of the tests. When the non-destructive inspection showed the existence of cracks, the test was stopped and the rail longitudinally and transversally cut to perform a metallographic analysis in order to know the nature, growth direction, shape and size of the cracks. The cracks generated in the laboratory tests were identical to those seen in RCF affected railways and significant variations were found in the behavior of the different rail grades. The proposed test was able to simulate the damage produced in rails by RCF and allows the comparison of the fatigue behavior of different rail grades under highly controlled conditions

Nose-to-brain delivery of enveloped RNA - cell permeating peptide nanocomplexes for the treatment of neurodegenerative diseases

This document is the preprint manuscript version of a published work that appeared in final form in Biomaterials, © 2019 Elsevier Ltd. after peer review and technical editing by the publisher. To access the final edited and published work see: https://doi.org/10.1016/j.biomaterials.2019.119657Direct nose-to-brain (N-to-B) delivery enables the rapid transport of drugs to the brain, while minimizing systemic exposure. The objective of this work was to engineer a nanocarrier intended to enhance N-to-B delivery of RNA and to explore its potential utility for the treatment of neurological disorders. Our approach involved the formation of electrostatically driven nanocomplexes between a hydrophobic derivative of octaarginine (r8), chemically conjugated with lauric acid (C12), and the RNA of interest. Subsequently, these cationic nanocomplexes were enveloped (enveloped nanocomplexes, ENCPs) with different protective polymers, i.e. polyethyleneglycol - polyglutamic acid (PEG-PGA) or hyaluronic acid (HA), intended to enhance their stability and mucodiffusion across the olfactory nasal mucosa. These rationally designed ENCPs were produced in bulk format and also using a microfluidics-based technique. This technique enabled the production of a scalable nanoformulation, exhibiting; (i) a unimodal size distribution with a tunable mean size, (ii) the capacity to highly associate (100%) and protect RNA from degradation, (iii) the ability to preserve its physicochemical properties in biorelevant media and prevent the premature RNA release. Moreover, in vitro cell culture studies showed the capacity of ENCPs to interact and be efficiently taken-up by CHO cells. Finally, in vivo experiments in a mouse model of Alzheimer's disease provided evidence of a statistically significant increase of a potentially therapeutic miRNA mimic in the hippocampus area and its further effect on two mRNA targets, following its intranasal administration. Overall, these findings stress the value of the rational design of nanocarriers towards overcoming the biological barriers associated to N-to-B RNA delivery and reveal their potential value as therapeutic strategies in Alzheimer's diseaseThe work was supported by the European B-Smart Consortium, which received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 721058S

Emergency surgery in chronic intestinal pseudo-obstruction due to mitochondrial neurogastrointestinal encephalomyopathy: case reports

Chronic intestinal pseudo-obstruction (CIPO) is a syndrome characterized by recurrent clinical episodes of intestinal obstruction in the absence of any mechanical cause occluding the gut. There are multiple causes related to this rare syndrome. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is one of the causes related to primary CIPO. MNGIE is caused by mutations in the gene encoding thymidine phosphorylase. These mutations lead to an accumulation of thymidine and deoxyuridine in blood and tissues of these patients. Toxic levels of these nucleosides induce mitochondrial DNA abnormalities leading to an abnormal intestinal motility