Somatic alpha-synuclein mutations in Parkinson's disease: Hypothesis and preliminary data.

Alpha-synuclein (SNCA) is crucial in the pathogenesis of Parkinson's disease (PD), yet mutations in the SNCA gene are rare. Evidence for somatic genetic variation in normal humans, also involving the brain, is increasing, but its role in disease is unknown. Somatic SNCA mutations, arising in early development and leading to mosaicism, could contribute to PD pathogenesis and yet be absent or undetectable in DNA derived from peripheral lymphocytes. Such mutations could underlie the widespread pathology in PD, with the precise clinical outcome dependent on their type and the timing and location of their occurrence. We recently reported a novel SNCA mutation (c.150T>G, p.H50Q) in PD brain-derived DNA. To determine if there was mosaicism for this, a PCR and cloning strategy was used to take advantage of a nearby heterozygous intronic polymorphism. No evidence of mosaicism was found. High-resolution melting curve analysis of SNCA coding exons, which was shown to be sensitive enough to detect low proportions of 2 known mutations, did not reveal any further mutations in DNA from 28 PD brain-derived samples. We outline the grounds that make the somatic SNCA mutation hypothesis consistent with genetic, embryological, and pathological data. Further studies of brain-derived DNA are warranted and should include DNA from multiple regions and methods for detecting other types of genomic variation. © 2013 Movement Disorder Society

トンネル掘削に伴う周辺地盤の変形と数値解析に基づく安定性評価に関する研究

鳥取大学博士(工学)doctoral thesi

Evaluating face stability in mountain tunnel excavation by inclination monitoring at the tunnel crown - Atoda tunnel case study

Abstract The authors have been developing a prediction method for changes of ground stiffness ahead of a tunnel face by monitoring inclination at the tunnel crown (along the face advance axis). During the Atoda tunnel construction project, inclination monitoring was conducted at measurement intervals of 10 m. This is the first tunneling project practically using the proposed method throughout the excavation length. There is used a newly developed tilt sensor equipped with a Low-Power and Wide-Area (LPWA) wireless communication system that collects inclination data and transmits it to a data gateway automatically. During excavation work zones of weathered and fractured tuff breccia were recognized; face instability and partial collapse were experienced at those locations, though tunnel deformation was generally no more than 10 mm. Inclination values had a tendency to decrease in tunnel advance direction before the face encountered the soft/weak weathered rock, verifying the effectiveness of the method for monitoring tunnel stability and safety.</jats:p