Gene Expression Profiling in Limb-Girdle Muscular Dystrophy 2A

Limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder caused by mutations in calpain 3 (CAPN3). Calpain 3 plays different roles in muscular cells, but little is known about its functions or in vivo substrates. The aim of this study was to identify the genes showing an altered expression in LGMD2A patients and the possible pathways they are implicated in. Ten muscle samples from LGMD2A patients with in which molecular diagnosis was ascertained were investigated using array technology to analyze gene expression profiling as compared to ten normal muscle samples. Upregulated genes were mostly those related to extracellular matrix (different collagens), cell adhesion (fibronectin), muscle development (myosins and melusin) and signal transduction. It is therefore suggested that different proteins located or participating in the costameric region are implicated in processes regulated by calpain 3 during skeletal muscle development. Genes participating in the ubiquitin proteasome degradation pathway were found to be deregulated in LGMD2A patients, suggesting that regulation of this pathway may be under the control of calpain 3 activity. As frizzled-related protein (FRZB) is upregulated in LGMD2A muscle samples, it could be hypothesized that β-catenin regulation is also altered at the Wnt signaling pathway, leading to an incorrect myogenesis. Conversely, expression of most transcription factor genes was downregulated (MYC, FOS and EGR1). Finally, the upregulation of IL-32 and immunoglobulin genes may induce the eosinophil chemoattraction explaining the inflammatory findings observed in presymptomatic stages. The obtained results try to shed some light on identification of novel therapeutic targets for limb-girdle muscular dystrophies

Análisis teórico-experimental de pilares y vigas de hormigón armado reforzados con fibra de carbono

El presente trabajo se refiere al estudio teórico-experimental del comportamiento de pilares y vigas de hormigón armado reforzados con fibra de carbono o CFRP. El análisis se realiza considerando que los pilares se refuerzan mediante la técnica de adhesión de tejidos de fibra de carbono, generando un efecto de confinamiento. Las vigas se refuerzan mediante la incorporación de barras del mismo material, con refuerzos a cortante. El objetivo es poder comparar el estudio analítico de este tipo de refuerzos con resultados experimentales obtenidos con anterioridad a la realización de este documento, y así poder obtener conclusiones de las posibles diferencias. Hay que señalar que los modelos experimentales no forman parte de este estudio. Los ensayos en pilares fueron realizados en sección cuadrada y circular evaluando la rotura a compresión de las piezas, habiendo sido éstas escaladas con un factor de reducción de 2,3. Los ensayos correspondientes a vigas se realizaron en sección rectangular, centrándose en la evaluación de la rotura a flexión y habiendo sido escaladas igualmente, pero con un factor de reducción de 1:2. El documento se estructura en cuatro capítulos, cuyo contenido se expone de forma concisa a continuación. En el capítulo uno o marco teórico se exponen los principios de comportamiento y tipologías de los pilares y vigas de hormigón armado, las bases teóricas de su refuerzo y confinamiento, así como las diversas técnicas de refuerzo existentes. Se detalla la técnica con FRP, comparando y analizando sus ventajas e inconvenientes. En el capítulo dos se expone el proceso de fabricación, refuerzo y resultados de los modelos experimentales realizados para ambos elementos estructurales. La obtención de los modelos teóricos forma parte del capítulo tres, comparándose con los resultados experimentales en el cuarto capítulo. Finalmente, en el último capítulo se presentan las conclusiones obtenidas al realizar esta comparativa en el refuerzo de vigas y pilares con fibra de carbono. This work refers to the theoretical and experimental study of the behavior of CFRP reinforced concrete columns and beams. The analysis was done considering that the pillars are reinforced by CFRP wrapping technique, resulting in a confinement effect. The beams are reinforced by the addition of bars of the same material, with shear reinforcements. The objective is to compare the analytical study of this type of reinforcement with experimental results obtained prior to the performance of this document, and draw conclusions for any differences. Notice that experimental models are not part of this study. The tests were performed on circular and square section pillars, evaluating compression fracture of the pieces, having been scaled down with a factor of 2.3. The tests were performed on rectangular section beams, focusing on evaluation of the bending fracture and being scaled down equally, but with a factor of 1:2. The document is divided into four chapters, whose content is set out concisely below. The chapter one or theoretical framework sets out the principles of behavior and types of columns and beams of reinforced concrete, the theoretical basis of its reinforcement and confinement, as well as various existing reinforcement techniques. CFRP technique it’s detailed, comparing and analyzing their advantages and disadvantages. Chapter two describes the process of manufacture, reinforcement and results of experimental models made for both structural elements. Chapter three shows the obtaining of the theoretical models, comparing them with the experimental results in the fourth chapter. Finally, the last chapter presents the conclusions to make this comparison in the strengthening of beams and columns with carbon fiber.