Xanthine oxidase pathway and muscle damage: Insights from McArdle disease

The intent of this review is to summarize current body of knowledge on the potential implication of the xanthine oxidase pathway (XO) on skeletal muscle damage. The possible involvement of the XO pathway in muscle damage is exemplified by the role of XO inhibitors (e.g., allopurinol) in attenuating muscle damage. Reliance on this pathway (as well as on the purine nucleotide cycle) could be exacerbated in conditions of low muscle glycogen availability. Thus, we also summarize current hypotheses on the etiology of both baseline and exertional muscle damage in McArdle disease, a condition caused by inherited deficiency of myophosphorylase. Because myophosphorylase catalyzes the first step of muscle glycogen breakdown, patients are unable to obtain energy from their muscle glycogen stores. Finally, we provide preliminary data from our laboratory on the potential implication of the XO pathway in the muscle damage that is commonly experienced by these patients.

Taking advantage of an old concept, "illegitimate transcription", for a proposed novel method of genetic diagnosis of McArdle disease

McArdle disease is a metabolic disorder caused by pathogenic mutations in the PYGM gene. Timely diagnosis can sometimes be difficult with direct genomic analysis, which requires additional studies of cDNA from muscle transcripts. Although the "nonsense-mediated mRNA decay" (NMD) eliminates tissue-specific aberrant transcripts, there is some residual transcription of tissue-specific genes in virtually all cells, such as peripheral blood mononuclear cells (PBMCs).We studied a subset of the main types of PYGM mutations (deletions, missense, nonsense, silent, or splicing mutations) in cDNA from easily accessible cells (PBMCs) in 12 McArdle patients.Analysis of cDNA from PBMCs allowed detection of all mutations. Importantly, the effects of mutations with unknown pathogenicity (silent and splicing mutations) were characterized in PBMCs. Because the NMD mechanism does not seem to operate in nonspecific cells, PBMCs were more suitable than muscle biopsies for detecting the pathogenicity of some PYGM mutations, notably the silent mutation c.645G>A (p.K215=), whose effect in the splicing of intron 6 was unnoticed in previous muscle transcriptomic studies.We propose considering the use of PBMCs for detecting mutations that are thought to cause McArdle disease, particularly for studying their actual pathogenicity.

Muscle signaling in exercise intolerance: Insights from the McArdle mouse model

We recently generated a knock-in mouse model (PYGM p.R50X/p.R50X) of McArdle disease (myophosphorylase deficiency). One mechanistic approach to unveil the molecular alterations caused by myophosphorylase deficiency, which is arguably the paradigm of 'exercise intolerance', is to compare the skeletal-muscle tissue of McArdle, heterozygous, and healthy (wild type (wt)) mice. We analyzed in quadriceps muscle of p.R50X/p.R50X (n=4), p.R50X/wt (n=6) and wt/wt mice (n=5) (all male, 8 wk-old) molecular markers of energy-sensing pathways, oxidative phosphorylation (OXPHOS) and autophagy/proteasome systems, oxidative damage and sarcoplamic reticulum (SR) Ca handling. We found a significant group effect for total AMPK (tAMPK) and ratio of phosphorylated (pAMPK)/tAMPK (P=0.012 and 0.033), with higher mean values in p.R50X/p.R50X mice vs. the other two groups. The absence of massive accumulation of ubiquitinated proteins, autophagosomes or lysosomes in p.R50X/p.R50X mice suggested no major alterations in autophagy/proteasome systems. Citrate synthase activity was lower in p.R50X/p.R50X mice vs. the other two groups (P=0.036) but no statistical effect existed for respiratory chain complexes. We found higher levels of 4-hydroxy-2-nonenal-modified proteins in p.R50X/p.R50X and p.R50X/wt mice compared with the wt/wt group (P=0.011). Sarco(endo)plasmic reticulum ATPase 1 (SERCA1) levels detected at 110kDa tended to be higher in p.R50X/p.R50X and p.R50X/wt mice compared with wt/wt animals (P=0.076), but their enzyme activity was normal. We also found an accumulation of phosphorylated SERCA1 in p.R50X/p.R50X animals. Myophosphorylase deficiency causes alterations in sensory energetic pathways together with some evidence of oxidative damage and alterations in Ca handling but with no major alterations in OXPHOS capacity or autophagy/ubiquitination pathways, which suggests that the muscle tissue of patients is likely to adapt overall favorably to exercise training interventions.

Ictus: incidencia, factores de riesgo y repercusión

El término ictus fue definido por la Organización Mundial de la Salud (OMS) en 1978 como un "síndrome clínico de origen vascular, caracterizado por signos de alteración focal o global de las funciones cerebrales de rápida evolución, que perduran más de 24 horas o provocan la muerte". El término Ictus, supone una de las primeras causas de mortalidad en el mundo occidental y la primera causa de incapacidad y coste económico. Con este trabajo lo que se pretende es dar a conocer la tanto la incidencia y prevalencia como los factores predictores susceptibles que provocan la enfermedad. Así como la repercusión que lleva a cabo a nivel personal

Theory of elasticity and electric polarization effects in the group-III nitrides

In this work, the properties of strained tetrahedrally bonded materials are explored theoretically, with special focus on group-III nitrides. In order to do so, a multiscale approach is taken: accurate quantitative calculations of material properties are carried out in a quantum first-principles frame, for small systems. These properties are then extrapolated and empirical methods are employed to make predictions for larger systems, such as alloys or nanostructures. We focus our attention on elasticity and electric polarization in semiconductors. These quantities serve as input for the calculation of the optoelectronic properties of these systems. Regarding the methods employed, our first-principles calculations use highly- accurate density functional theory (DFT) within both standard Kohn-Sham and generalized (hybrid functional) Kohn-Sham approaches. We have developed our own empirical methods, including valence force field (VFF) and a point-dipole model for the calculation of local polarization and local polarization potential. Our local polarization model gives insight for the first time to local fluctuations of the electric polarization at an atomistic level. At the continuum level, we have studied composition-engineering optimization of nitride nanostructures for built-in electrostatic field reduction, and have developed a highly efficient hybrid analytical-numerical staggered-grid computational implementation of continuum elasticity theory, that is used to treat larger systems, such as quantum dots.

Estrategias inductivas para el logro de la competencia matemática

En este trabajo nos centramos en la descripción de estrategias de resolución de problemas en los que el razonamiento inductivo puede ser un heurístico. La resolución de diferentes tipos de problemas puede contribuir a la adquisición de la competencia matemática. Presentamos y comparamos parte de los resultados de dos problemas propuestos en una investigación más amplia (Cañadas, 2007).

Las relaciones pedagógicas entre profesores y alumnos al incorporar el uso de las tecnologías computacionales en el ámbito escolar

El presente trabajo muestra algunas de las experiencias obtenidas en la puesta en práctica del proceso didáctico que propone el programa EMAT –Hidalgo con un grupo de docentes que imparten la asignatura de matemáticas en el nivel de educación secundaria modalidad técnica. La investigación permitió identificar el tipo de relaciones entre profesores y estudiantes al incorporar el uso de las tecnologías computacionales en el ámbito escolar. Para ello, se hicieron entrevistas, encuestas y observaciones en los tres grados de educación secundaria.

Las prácticas sociales de modelación y la emergencia de lo exponencial

El presente trabajo se inserta en la línea de investigación que intenta explicar las relaciones entre las prácticas sociales y la construcción social del conocimiento. Sostenemos que es en el ejercicio de las prácticas sociales donde los actores construyen herramientas que han de constituirse en su conocimiento y éstas a su vez modifican las prácticas. En este trabajo hemos elegido a las prácticas sociales de modelación y su relación con la construcción de lo exponencial como herramienta. Modelando el enfriamiento del silicón los actores construyen modelos y con ellos realizan predicciones, articulando los diferentes modelos con el fenómeno. Se hace énfasis en el análisis epistemológico y como es que lo exponencial se construye al ejercer la modelación.

Cine policíaco del tardofranquismo: El thriller en el “Período Oscuro” del cine español (1969-1975)

Definición de la etapa de crisis del aparato cinematográfico franquista, llamada aquí “Período Oscuro” (1969-1975), discusión de la etiqueta de subgéneros aplicada al cinema bis de la época, y caracterización histórica del thriller español y de sus corrientes estéticas y conceptuales internas en dicho período. La acotación del período 1969-1975 es clarificada previamente ante el vacío historiográfico al respecto. Se caracteriza la crisis que tiene lugar en el “Período Oscuro”, desde su comienzo oficial en 1969, que supuso el definitivo cierre de las políticas proteccionistas emprendidas por el Director General de Cinematografía García Escudero en 1962. Después se define y discute la etiqueta de subgéneros aplicada tradicionalmente al cine español de género de bajo presupuesto. Luego, se especifican, definen y analizan las diversas categorías dentro del thriller español de 1969-1975: se trata de categorías temáticas y argumentales, estéticas, o bien relacionadas con corrientes internacionales del policíaco europeo. Por último, se extraen las conclusiones pertinentes.

The Afroporteña press and Afro-Argentine’s thought in the late nineteenth century

The journalistic boom that occurred in Argentina from the second half of the nineteenth century saw the emergence of an active afroporteña press that defend the interests of the black community. This paper, in addition to reviewing the history of the Afro-Argentines newspapers, emphasizes the role played by the elite of African descent in the promotion of modernity among his brothers, while exploring the possible bases for an identity in the ideas spread.

Reality Shows in Chile, origin and road map. Historical-Communication Dialogues

Reality shows are TV programs which represent a format used in television nowadays; however, the observation practices of individual and/or group intimacy dates from thousands years ago. Sometimes this was driven by voyeurism or morbid fascination, some others, by the purpose of guarding, supervising and maintaining status quo. This work offers an alternative answer to the explanation of this type of TV program emergence and relates this appearance to a government procedure bound up with modern State terrorism which began at the end of the eighteenth century and has been recalled by different regimes until present days.

Co-evaluation as a strategy to improve working group dynamics: an experience in Sport Sciences

The aim of this study was to analyze if the perceptions of students before and after carrying out the work, that is, their perception of different aspects of the functioning of the group, the working skills acquired as well as those they think that need to be improved, varied depending on whether the contribution of the different members of the group was being co-evaluated or not. 144 students of Physical Activity and Sport Sciences participated in this study. In order to analyze the students' perception of group work the adapted questionnaire by Bourne et al. (2001) was used. Results showed that groups which implemented co-evaluation assessed more negatively the experience in general than those which did not. However, co-evaluation groups perceived their competence to work as a team had improved to a greater extent than the groups without co-evaluation, evaluating more positively both the performance and the result of work and increasing their knowledge of the other team members. Using a co-evaluation system seems to generate both a better assessment of the running of the team and the result of its work.

Dogs in the paradise: The influence of the cynical philosophy in the construction of the myth of the good savage

This paper studies the influence of cynic philosophy in the construction of the myth of the good savage. In the first part it studies the importance of cynicism in the XVI century and how the cynic influence of Erasmus, More and Montaigne was fundamental to the way that Europe approached the American indigenous. In the second part it studies the cynic motives that could have influenced in the construction of the myth of the good savage.

De artista a andragogo. Experiencias educativas de docencia no reglada en cursos dirigidos por artistas contemporáneos.

This article focuses mainly on identifying innovative andragogical experiences and educational links established between contemporary artists and university students outside the formal teaching. Its structure consists of an introduction that defines the theoretical and contextual framework, the objectives pursued, the methodology and analytical development results. The analysis of educational concepts, resulting in the kind of knowledge and artistic andragogic, conceptually form a generative teaching in the context of non-formal teaching. Delimiting the complex responsibilities of university professors, linked to Art, through analysis of experiences in higher education andragogic which, initially part of the model of “artist educator” (Barrett, 1995; Laferrière, 2000), plunging into the innovative and alternative educational settings that are currently the compliance with the declaration of 2009 as the International Year of Creativity and Innovation.

Some thoughts on Juan Antonio Ramírez´s iconologic-paranoid method for the study of Dali´s works

In 1990, Juan Antonio Ramírez made known his iconological paranoiac method to the academic world. It is a system devised to study Dalí´s work, born of happy matrimony between the catalonian artist´s critical paranoiac method and the first iconographic school of Warburg and Panofsky. What, at first sight, seemed to be an extravagant methodology with little academic credibility, turned out to be, by going forward in time, an effective research method when analyzing Dali´s initial works. It is no wonder that, at the beginning of XXI century, this hybridization between Dalí´s and Panofsky’s methods, were regarded as a strange and nonsensical idea. Nevertheless, twenty years after, blatant examples have been noted, which endorse the advantages of this new system for “iconographic” study. As usual, this new contribution by Juan Antonio Ramirez to art history methodology is called upon to have a successful future survival, in forthcoming generations. This article, attempts to analyze this method, inquiring into the validity, effectiveness and practical utility.