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.

Gramática de las gráficas: pistas para mejorar las representaciones de datos

Periodistas, científicos, sociólogos, ingenieros, economistas... En multitud de profesiones nos encontramos con la necesidad de interpretar o de realizar gráficas. Las gráficas son elementos habituales en multitud de textos: periódicos, revistas, informes, publicaciones científicas, etc. Y no es de extrañar dado que constituyen un excelente método de comunicación de información cuantitativa. No es improbable, sin embargo, encontrar gráficas que no resultan adecuadas, que no se entienden o que transmitan impresiones equívocas. Del mismo modo que los textos están sujetos a una gramática que aprendemos desde pequeños en la escuela, las gráficas también disponen de una estructura, sólo que mucho menos formalizada y, que desde luego, no se enseña en la escuela. El objetivo de este texto es ofrecer unas guías muy simples, basadas en la analogía con la gramática del lenguaje, que ayuden a comprender y especialmente a realizar representaciones gráficas correctas. Está dirigido a todos los públicos, buscándose la máxima sencillez en las ideas, sin ninguna apoyatura matemática o lingüística. Del mismo modo, los ejemplos están tomados casi exclusivamente de periódicos, de forma que el contenido de las gráficas tampoco despiste de su forma, que es lo que se pretende analizar aquí.

A survey of fingerprint classification Part I: taxonomies on feature extraction methods and learning models

This paper reviews the fingerprint classification literature looking at the problem from a double perspective. We first deal with feature extraction methods, including the different models considered for singular point detection and for orientation map extraction. Then, we focus on the different learning models considered to build the classifiers used to label new fingerprints. Taxonomies and classifications for the feature extraction, singular point detection, orientation extraction and learning methods are presented. A critical view of the existing literature have led us to present a discussion on the existing methods and their drawbacks such as difficulty in their reimplementation, lack of details or major differences in their evaluations procedures. On this account, an experimental analysis of the most relevant methods is carried out in the second part of this paper, and a new method based on their combination is presented.

A survey of fingerprint classification Part II: experimental analysis and ensemble proposal

In the first part of this paper we reviewed the fingerprint classification literature from two different perspectives: the feature extraction and the classifier learning. Aiming at answering the question of which among the reviewed methods would perform better in a real implementation we end up in a discussion which showed the difficulty in answering this question. No previous comparison exists in the literature and comparisons among papers are done with different experimental frameworks. Moreover, the difficulty in implementing published methods was stated due to the lack of details in their description, parameters and the fact that no source code is shared. For this reason, in this paper we will go through a deep experimental study following the proposed double perspective. In order to do so, we have carefully implemented some of the most relevant feature extraction methods according to the explanations found in the corresponding papers and we have tested their performance with different classifiers, including those specific proposals made by the authors. Our aim is to develop an objective experimental study in a common framework, which has not been done before and which can serve as a baseline for future works on the topic. This way, we will not only test their quality, but their reusability by other researchers and will be able to indicate which proposals could be considered for future developments. Furthermore, we will show that combining different feature extraction models in an ensemble can lead to a superior performance, significantly increasing the results obtained by individual models.

Vidas de los varones ilustres del Monasterio de la Trapa

Signaturas: [ ]1, [*]4, [¶]-2[¶]4, 3[¶]8, A-Z4, 2A-2L4 ; [ ]2, A-Z4, 2A-2K4 ; [ ]2, A-Z4, 2A-2Q4.

SS.PP. Toletanorum quotquot extant Opera : tomus primus [-tertius]

Nunc primum simul edita, ad codices mss. recognita, nonnullis notis illustrata atque in duos tomos distributa.

Razones trigonométricas

Este capítulo es nuestro informe final de la unidad didáctica sobre razones trigonométricas. Es el trabajo final de MAD, la concentración en Educación Matemática de la maestría en Educación de la Universidad de los Andes. Este trabajo nace de constatar que muchos profesores de matemáticas de grado décimo usan las razones trigonométricas como herramienta para solucionar ejercicios de resolución de triángulos, aplicados a problemas, sin tener en cuenta el contexto propio del estudiante. De otro lado, la implementación en el aula de recursos o materiales para la enseñanza de la trigonometría se ha restringido al uso de la calculadora de funciones para determinar ángulos y longitudes en función de una razón trigonométrica particular. Desde esta problemática diseñamos, implementamos y evaluamos la unidad didáctica de razones trigonométricas como propuesta de innovación en la Institución de Educación Distrital (IED) José Joaquín Castro Martínez. Esta unidad didáctica promueve la construcción del concepto razones trigonométricas a partir de situaciones que tienen sentido para el estudiante y que son cercanas a su propio contexto.

La acción tutorial en los trabajos de investigación en el bachillerato

En este artículo presentamos un modelo de acción tutorial de los trabajos de investigación en el bachillerato, que estamos poniendo en práctica. Clasificamos los diferentes tipos de investigaciones y analizamos los puntos más significativos de tal modelo, cuya finalidad es la de mejorar las capacidades de investigación del alumnado.

Recuperación de instrumentos y unidades de medida tradicionales en Extremadura como motivación al estudio de la medida

Este artículo es una breve descripción del proyecto innovación educativa llevada acabo en los colegios públicos de Badajoz, que obtuvo el primer premio Joaquín Sama a la innovación educativa convocado por la consejería de educación y juventud de la junta Extremadura. Culminó con una exposición en ICME de Sevilla en julio de 1996. Se investiga el uso y se recogen unidades e instrumentos de medida tradicionales en Extremadura, estudiando su evolución hasta llegar al sistema métrico decimal, equivalencias, uso actual incluso la distribución geográfica.

Problemática de la enseñanza de conceptos de cálculo

Teniendo en cuenta que las dificultades de aprendizaje de conceptos que tienen los estudiantes se localizan en las mentes, las matemáticas y el mensaje, se debe realizar una revisión del curriculum encaminada a potenciar el aprendizaje comprensivo de los contenidos del cálculo.

Los espinales de la Pruno-Rubion ulmifolii en Galicia

A partir del análisis florístico y corológico, presentamos un estudio de los espinales mesótrofos integrables en la alianza Pruno-Rubion ulmifolii. Reconocemos, en este territorio, las asociaciones Rubo ulmifolii-Tametum communis y Rubo-Rosetum corymbiferae. 

Estudio fitosociológico de los sabinares de Juniperus phoenicea L. en el sector Malacitano-Almijarense (provincia corológica Bética)

Se describe una nueva asociación (Rhamno myrtifoli-Juniperetum phoeniceae) de la alianza Rhamno-Quercion cocciferae distribuida en el sector Malacitano-Almijarense (provincia corológica Bética).

Estudio de formaciones arbóreas termófilo-continentales próximas a la ciudad de Granada

Se da cuenta de la estructura de los bosques de Quercus rotundifolia Lam. presentes en las localidades cercanas a la ciudad de Granada, así como de los matorrales de sustitución. Se propone una nueva subasociación ulicetosum parviflori dentro de la asociación clímax Paeonio-Quercetum rotundifoliae Rivas-Martínez 1964. Para el matorral de sustitución se describe unanueva asociación, Stipo tenacissimae-Anthyllidetum cytisoidis.

Places making: participatory construction of scientifi c culture cities

In the framework of the European project Platform of Local Authorities and Communicators Engaged in Science (PLACES), we analyse the articulations between scientifi c communication, public perception of science, processes of citizen participation and apropiation of space, based on a case study of the inhabitants of Teruel city, Autonomous Community of Aragon, Spain. On the interrelationships between these issues, there are a number of contradictions, such as the difference between a high interest for information about science and technology and a low level of recognition and interaction with local institutions involved in those activities, the complex conceptualization of scientifi c space in relation to the “public-private” pair, or an articulation of a claiming civic rethoric and an insuffi cient co-responsibility. We conclude that, in a local context, the dimension of territoriality and, in particular, the identifi cation with the town, is a central mediation for activating citizen participation as part of processes of appropriation of space for setting up cities of scientifi c culture.