Spinal muscular atrophy (SMA) is caused by mutations of the survival of motor neuron (SMN1) gene and deficiency of full-length SMN protein (FL-SMN). All SMA patients retain one or more copies of the SMN2 gene, but the principal protein product of SMN2 lacks exon 7 (SMN⌬7) and is unable to compensate for a deficiency of FL-SMN. SMN is known to oligomerize and form a multimeric protein complex; however, the mechanisms regulating stability and degradation of FL-SMN and SMN⌬7 proteins have been largely unexplored. Using pulsechase analysis, we characterized SMN protein turnover and confirmed that SMN was ubiquitinated and degraded by the ubiquitin proteasome system (UPS). The SMN⌬7 protein had a twofold shorter half-life than FL-SMN in cells despite similar intrinsic rates of turnover by the UPS in a cell-free assay. Mutations that inhibited SMN oligomerization and complex formation reduced the FL-SMN half-life. Furthermore, recruitment of SMN into large macromolecular complexes as well as increased association with several Gemin proteins was regulated in part by protein kinase A. Together, our data indicate that SMN protein stability is modulated by complex formation. Promotion of the SMN complex formation may be an important novel therapeutic strategy for SMA.

Seismocardiography (SCG) is a measure of chest vibration associated with heartbeats. While skin soft electronic tattoos (e‐tattoos) have been widely reported for electrocardiogram (ECG) sensing, wearable SCG sensors are still based on either rigid accelerometers or non‐stretchable piezoelectric membranes. This work reports an ultrathin and stretchable SCG sensing e‐tattoo based on the filamentary serpentine mesh of 28‐µm‐thick piezoelectric polymer, polyvinylidene fluoride (PVDF). 3D digital image correlation (DIC) is used to map chest vibration to identify the best location to mount the e‐tattoo and to investigate the effects of substrate stiffness. As piezoelectric sensors easily suffer from motion artifacts, motion artifacts are effectively reduced by performing subtraction between a pair of identical SCG tattoos placed adjacent to each other. Integrating the soft SCG sensor with a pair of soft gold electrodes on a single e‐tattoo platform forms a soft electro‐mechano‐acoustic cardiovascular (EMAC) sensing tattoo, which can perform synchronous ECG and SCG measurements and extract various cardiac time intervals including systolic time interval (STI). Using the EMAC tattoo, strong correlations between STI and the systolic/diastolic blood pressures, are found, which may provide a simple way to estimate blood pressure continuously and noninvasively using one chest‐mounted e‐tattoo.

Background Patients with Duchenne muscular dystrophy exhibit progressive cardiac and skeletal muscle dysfunction. Based on prior data, cardiac dysfunction in Duchenne muscular dystrophy patients may be influenced by myocardial fibrosis and steroid therapy. We examined the longitudinal relationship of myocardial fibrosis and ventricular dysfunction using cardiac magnetic resonance in a large Duchenne muscular dystrophy cohort. Methods and Results We reviewed 465 serial cardiac magnetic resonance studies (98 Duchenne muscular dystrophy patients with ≥4 cardiac magnetic resonance studies) for left ventricular ejection fraction (LVEF) and presence of late gadolinium enhancement (LGE), a marker for myocardial fibrosis. LVEF was modeled by examining LGE status, myocardial fibrosis burden (as assessed by the number of LGE‐positive left ventricular segments), patient age, and steroid treatment duration. An age‐only model demonstrated that LVEF declined 0.58±0.10% per year. In patients with both LGE‐negative and LGE‐positive studies (n=51), LVEF did not decline significantly over time if LGE was absent but declined 2.2±0.31% per year when LGE was present. Univariate modeling showed significant associations between LVEF and steroid treatment duration, presence of LGE, and number of LGE‐positive left ventricular segments; multivariate modeling showed that LVEF declined by 0.93±0.09% for each LGE‐positive left ventricular segment, whereas age and steroid treatment duration were not significant. The number of LGE‐positive left ventricular segments increased with age, and longer steroid treatment duration was associated with lower age‐related increases. Conclusion Progressive myocardial fibrosis, as detected by LGE, was strongly correlated with the LVEF decline in Duchenne muscular dystrophy patients. Longer steroid treatment duration was associated with a lower age‐related increase in myocardial fibrosis burden.