Seismic evidence for melt-rich lithosphere-asthenosphere boundary beneath young slab at Cascadia.

The Lithosphere-Asthenosphere Boundary (LAB) beneath oceanic plates is generally imaged as a sharp seismic velocity reduction, suggesting the presence of partial melts. However, the fate of a melt-rich LAB is unclear after these plates descend into the mantle at subduction zones. Recent geophysical studies suggest its persistence with down-going old and cold slabs, but whether or not it is commonly present remains unclear, especially for young and warm slabs such as in the Cascadia subduction zone. Here we provide evidence for its presence at Cascadia in the form of a large (9.8 ± 1.5 % ) decrease in shear-wave velocity over a very small (<3 km) depth interval. Similarly large and sharp seismic velocity reduction at the bottom of both old and young slabs, as well as along the base of oceanic plates before subduction, possibly represents widespread presence of melts. The melt-rich sub-slab LAB may strongly influence subduction dynamics and viscoelastic earthquake cycles.

Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.