Notch pathway is activated in cell culture and mouse models of mutant SOD1-related familial amyotrophic lateral sclerosis, with suppression of its activation as an additional mechanism of neuroprotection for lithium and valproate.

Amyotrophic lateral sclerosis (ALS) is an idiopathic and lethal neurodegenerative disease that currently has no effective treatment. A recent study found that the Notch signaling pathway was up-regulated in a TAR DNA-binding protein-43 (TDP-43) Drosophila model of ALS. Notch signaling acts as a master regulator in the central nervous system. However, the mechanisms by which Notch participates in the pathogenesis of ALS have not been completely elucidated. Recent studies have shown that the mood stabilizers lithium and valproic acid (VPA) are able to regulate Notch signaling. Our study sought to confirm the relationship between the Notch pathway and ALS and whether the Notch pathway contributes to the neuroprotective effects of lithium and VPA in ALS. We found that the Notch pathway was activated in in vitro and in vivo models of ALS, and suppression of Notch activation with a Notch signaling inhibitor, N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT) and Notch1 siRNA significantly reduced neuronal apoptotic signaling, as evidenced by the up-regulation of Bcl-2 as well as the down-regulation of Bax and cytochrome c. We also found that lithium and VPA suppressed the Notch activation associated with the superoxide dismutase-1 (SOD1) mutation, and the combination of lithium and VPA produced a more robust effect than either agent alone. Our findings indicate that the Notch pathway plays a critical role in ALS, and the neuroprotective effects of lithium and VPA against mutant SOD1-mediated neuronal damage are at least partially dependent on their suppression of Notch activation.

Intertester reliability for measuring pelvic tilt in standing.

The purpose of this study was to examine intertester reliability using a method of measuring the relaxed standing pelvic-tilt angle, active anterior and posterior pelvic-tilt angles and ranges of motion, and the total pelvic-tilt ROM in the sagittal plane. After an instructional session, 6 testers measured the pelvic-tilt angles of the right side of 12 subjects. Pelvic-tilt angles were calculated using trigonometric functions. Degrees of ROM were determined from the pelvic-tilt angles obtained. The intraclass correlation coefficient was .95 for standing pelvic-tilt angle, .93 for the anterior pelvic-tilt angle, .93 for the posterior pelvic-tilt angle, .88 for the anterior pelvic-tilt ROM, .93 for the posterior pelvic-tilt ROM, and .90 for the total pelvic-tilt ROM. We concluded that intertester reliability, using this method, was very high for measuring pelvic tilt in the sagittal plane.