La influencia de la publicidad en el consumo de juegos de azar

El aumento en la participación en juegos de azar ha generado muchas cuestiones en torno a por qué ha surgido esta nueva coyuntura. En España, desde la aprobación de la Ley 13/2011 que reguló el juego en Internet, el gasto en juego se disparó, superándose año a año las cifras invertidas por la población. El incremento de la inversión en publicidad de la industria del juego también se ha considerado un factor influyente en el aumento del gasto de los jugadores. A través de este estudio se han obtenido algunas conclusiones en torno a esta correlación, que depende de muchas variables. Los jóvenes parecen ser los que más dinero gastan en juego y los más vulnerables al efecto publicitario. También se ha investigado sobre la percepción social de la publicidad del juego. Mayoritariamente se considera que aparece demasiada publicidad en los medios de comunicación y que se deberían adoptar medidas para regular esta situación

Bioengineered in vitro 3D model of myotonic dystrophy type 1 human skeletal muscle

Myotonic dystrophy type 1 (DM1) is the most common hereditary myopathy in the adult population. The disease is characterized by progressive skeletal muscle degeneration that produces severe disability. At present, there is still no effective treatment for DM1 patients, but the breakthroughs in understanding the molecular pathogenic mechanisms in DM1 have allowed the testing of new therapeutic strategies. Animal models and in vitro two-dimensional cell cultures have been essential for these advances. However, serious concerns exist regarding how faithfully these models reproduce the biological complexity of the disease. Biofabrication tools can be applied to engineer human three-dimensional (3D) culture systems that complement current preclinical research models. Here, we describe the development of the first in vitro 3D model of DM1 human skeletal muscle. Transdifferentiated myoblasts from patient-derived fibroblasts were encapsulated in micromolded gelatin methacryloyl-carboxymethyl cellulose methacrylate hydrogels through photomold patterning on functionalized glass coverslips. These hydrogels present a microstructured topography that promotes myoblasts alignment and differentiation resulting in highly aligned myotubes from both healthy and DM1 cells in a long-lasting cell culture. The DM1 3D microtissues recapitulate the molecular alterations detected in patient biopsies. Importantly, fusion index analyses demonstrate that 3D micropatterning significantly improved DM1 cell differentiation into multinucleated myotubes compared to standard cell cultures. Moreover, the characterization of the 3D cultures of DM1 myotubes detects phenotypes as the reduced thickness of myotubes that can be used for drug testing. Finally, we evaluated the therapeutic effect of antagomiR-23b administration on bioengineered DM1 skeletal muscle microtissues. AntagomiR-23b treatment rescues both molecular DM1 hallmarks and structural phenotype, restoring myotube diameter to healthy control sizes. Overall, these new microtissues represent an improvement over conventional cell culture models and can be used as biomimetic platforms to establish preclinical studies for myotonic dystrophy

Preclinical characterization of antagomiR-218 as a potential treatment for myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by expansion of unstable CTG repeats in a non-coding region of the DMPK gene. CUG expansions in mutant DMPK transcripts sequester MBNL1 proteins in ribonuclear foci. Depletion of this protein is a primary contributor to disease symptoms such as muscle weakness and atrophy and myotonia, yet upregulation of endogenous MBNL1 levels may compensate for this sequestration. Having previously demonstrated that antisense oligonucleotides against miR-218 boost MBNL1 expression and rescue phenotypes in disease models, here we provide preclinical characterization of an antagomiR-218 molecule using the HSALR mouse model and patient-derived myotubes. In HSALR, antagomiR-218 reached 40-60 pM 2weeks after injection, rescued molecular and functional phenotypes in a dose- and time-dependent manner, and showed a good toxicity profile after a single subcutaneous administration. In muscle tissue, antagomiR rescued the normal subcellular distribution of Mbnl1 and did not alter the proportion of myonuclei containing CUG foci. In patient-derived cells, antagomiR-218 improved defective fusion and differentiation and rescued up to 34% of the gene expression alterations found in the transcriptome of patient cells. Importantly, miR-218 was found to be upregulated in DM1 muscle biopsies, pinpointing this microRNA (miRNA) as a relevant therapeutic target.This work was funded by research grants from Instituto de Salud Carlos III, including funds from FEDER, to M.P.-A. and B.L. (PI17/00352) and HR17-00268 (TATAMI project) from the “la Caixa” Banking Foundation to R.A. I.G.-M. was funded by the Precipita Project titled “Desarrollo de una terapia innovadora contra la distrofia miotónica,” E.C.-H. and J.M.F.-C. were supported by the post-doctoral fellowships APOSTD/2019/142 and APOSTD/2017/088 from the Fondo Social Europeo for science and investigation, while J.E.-E. was the recipient of a Santiago Grisolia fellowship (Grisolip2018/098) from the Generalidad Valenciana. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014-2020). Antibody MB1a (4A8) was provided by MDA Monoclonal Antibody Resource

A FRET-based assay for characterization of alternative splicing events using peptide nucleic acid fluorescence in situ hybridization

We describe a quantitative method for detecting RNA alternative splicing variants that combines in situ hybridization of fluorescently labeled peptide nucleic acid (PNA) probes with confocal microscopy Förster resonance energy transfer (FRET). The use of PNA probes complementary to sequences flanking a given splice junction allows to specifically quantify, within the cell, the RNA isoform generating such splice junction by FRET measure. As a proof of concept we analyzed two alternative splicing events originating from lymphocyte antigen 6 (LY6) complex, locus G5B (LY6G5B) pre-mRNA. These are characterized by the removal of the first intron (Fully Spliced Isoform, FSI) or by retention of such intron (Intron-Retained Isoform, IRI). The use of PNA probe pairs labeled with donor (Cy3) and acceptor (Cy5) fluorophores, suitable to FRET, flanking FSI and IRI specific splice junctions specifically detected both mRNA isoforms in HeLa cells. We have observed that the method works efficiently with probes 5–11 nt apart. The data supports that this FRET-based PNA fluorescence in situ hybridization (FP–FISH) method offers a conceptually new approach for characterizing at the subcellular level not only splice variant isoform structure, location and dynamics but also potentially a wide variety of close range RNA–RNA interactions

The effect of physical activity on academic motivation: A systematic review

Treball Final de Grau en Psicologia. Codi: PS1048. Curs: 2020/2021The impact of physical activity on humans is a field of study that is constantly expanding, and nowadays, much research is being done in the academic field, especially in adolescents. That is why many studies investigate how physical activity affects academic performance, observing a positive relationship between both. Furthermore, academic performance has been related to different psychological variables, including motivation, and actually there is a positive relationship between academic motivation and academic performance. In view of these relationships, there are studies that have related physical activity with academic motivation and since it has been seen that there is a positive relationship between them, the aim of this research is to carry out a systematic review to find studies with certain methodological rigor that investigate the effect of physical activity on academic motivation. To this end, the databases Scopus, Pubmed, E-Journals and Psychinfo were used, using the words ("physical activity") OR ("physical exercise") OR (exercise) OR (sport) AND ("academic motivation"), filtering by title and abstract and following the inclusion criteria of (1) articles that study the effect of physical activity on motivation; (2) open access articles; and (3) articles written in English or Spanish. Subsequently, and following the exclusion criteria (1) not having a control group, (2) the sample not being between 12 and 18 years old and (3) academic motivation not being measured with an instrument that specifically measures it, the final sample of the study was reduced to 1 article. Although many investigations study the relationship between physical activity and academic motivation, concluding that physical activity has a positive effect on academic motivation, few do so with methods and/or instruments that provide them scientific rigor.El impacto de la actividad física en el ser humano es un ámbito de estudio que se está ampliando constantemente, hoy en día se indaga mucho en el ámbito académico, sobre todo en adolescentes. Es por ello que muchos estudios investigan cómo afecta la actividad física al rendimiento académico observando una relación positiva entre ambas. Por otro lado el rendimiento académico se ha tratado de relacionar con diferentes variables psicológicas, entre ellas la motivación, y realmente existe una relación positiva entre motivación académica y rendimiento académico. Viendo estas relaciones, hay estudios que han relacionado la actividad física con la motivación académica y dado que se ha visto que existe una relación positiva entre ambas el objetivo de esta investigación es realizar una revisión sistemática para encontrar estudios con cierto rigor metodológico que investiguen el efecto de la actividad física en la motivación académica. Para ello, se emplean las bases de datos Scopus, Pubmed, EJournals y Psychinfo, utilizando las palabras ("physical activity") OR ("physical exercise") OR (exercise) OR (sport) AND ("academic motivation"), filtrando por título y resumen y siguiendo los criterios de inclusión formados por (1) artículos que estudien el efecto la actividad física en la motivación académica; (2) artículos de acceso libre y (3) artículos redactados en inglés o castellano. Posteriormente y siguiendo los criterios de exclusión (1) no tener grupo control, (2) la muestra no se comprende entre 12 y 18 años y (3) la motivación académica no es medida con un instrumento que la mida específicamente, la muestra final del estudio se reduce a 1 artículo. Pese a que muchas investigaciones estudian la relación entre actividad física y motivación académica, concluyendo que la actividad física tiene un efecto positivo en la motivación académica, pocas son las que lo hacen con métodos y/o herramientas que les aporten rigor científico

Deciphering the Complex Molecular Pathogenesis of Myotonic Dystrophy Type 1 through Omics Studies

Omics studies are crucial to improve our understanding of myotonic dystrophy type 1 (DM1), the most common muscular dystrophy in adults. Employing tissue samples and cell lines derived from patients and animal models, omics approaches have revealed the myriad alterations in gene and microRNA expression, alternative splicing, 3′ polyadenylation, CpG methylation, and proteins levels, among others, that contribute to this complex multisystem disease. In addition, omics characterization of drug candidate treatment experiments provides crucial insight into the degree of therapeutic rescue and off-target effects that can be achieved. Finally, several innovative technologies such as single-cell sequencing and artificial intelligence will have a significant impact on future DM1 research

Compuestos para ser usados en el tratamiento de enfermedades basadas en la expresión de transcritos tóxicos con repeticiones CUG o CCUG

La presente invención hace referencia a moléculas peptídicas, concretamente hexapéptidos, para la prevención y/o tratamiento de enfermedades cuya etiología se basa en la presencia de transcritos tóxicos que comprenden repeticiones CUG o CCUG, preferentemente: DM1, DM2 Y SCA8.Peer reviewedUniversitat de Valencia, Fundación de la Comunidad Valenciana Centro de Investigación Principe Felipe, Consejo Superior de Investigaciones Científicas (España)A1 Solicitud de patente con informe sobre el estado de la técnic