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

Interaction between karstic aquifers and allogenic rivers: the aquifer of the national park of the ephemeral river Lobos Canyon (Spain)

A methodology is described for understanding the interaction of karstic aquifers with allogenic rivers, where little information is available. This methodology includes conventional hydrogen- ology methods tracer tests and measurements of flow into, out of and circulating within the karstic system. The method is designed to un- derstand the hydrogeological behaviour of a river in sufficient detail, given a short study pe- riod. The methodology is applied to a karstic system in Spain, obtaining useful, quantitative results for a hydrological year, such as an esti- mate of the water balance, differentiation be- tween autogenic and allogenic natural recharge, relationship and connection between the river and the aquifer, and measurements of infiltration capacity in watercourses under different hydro- logical situations. The paper deals with a useful example that could be applied to other rivers and aquifers where few data are available. It can be applied to aquifers under a natural regime and Mediterranean climate.