Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program

Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle-wasting disease. A defined molecular basis underlying these performance-enhancing properties of GCs in skeletal muscle remains obscure. Here, we demonstrate that ergogenic effects of GCs are mediated by direct induction of the metabolic transcription factor KLF15, defining a downstream pathway distinct from that resulting in GC-related muscle atrophy. Furthermore, we establish that KLF15 deficiency exacerbates dystrophic severity and muscle GC-KLF15 signaling mediates salutary therapeutic effects in the mdx mouse model of DMD. Thus, although glucocorticoid receptor (GR)-mediated transactivation is often associated with muscle atrophy and other adverse effects of pharmacologic GC administration, our data define a distinct GR-induced gene regulatory pathway that contributes to therapeutic effects of GCs in DMD through proergogenic metabolic programming

Cosmic-ray muon flux at Canfranc Underground Laboratory

Abstract Residual flux and angular distribution of high-energy cosmic muons have been measured in two underground locations at the Canfranc Underground Laboratory (LSC) using a dedicated Muon Monitor. The instrument consists of three layers of fast scintillation detector modules operating as 352 independent pixels. The monitor has a flux-defining area of 1 m² and covers all azimuth angles, and zenith angles up to 80°. The measured integrated muon flux is (5.26±0.21)×10⁻³ m⁻²s⁻¹ in the Hall A of the LAB2400 and (4.29±0.17)×10⁻³3 m⁻²s⁻¹ in LAB2500. The angular dependence is consistent with the known profile and rock density of the surrounding mountains. In particular, there is a clear maximum in the flux coming from the direction of the Rioseta valley