No abstract

KAGRA is a newly built gravitational-wave telescope, a laser interferometer comprising arms with a length of 3 km, located in Kamioka, Gifu, Japan. KAGRA was constructed under the ground and it is operated using cryogenic mirrors that help in reducing the seismic and thermal noise. Both technologies are expected to provide directions for the future of gravitational-wave telescopes. In 2019, KAGRA finished all installations with the designed configuration, which we call the baseline KAGRA. In this occasion, we present an overview of the baseline KAGRA from various viewpoints in a series of articles. In this article, we introduce the design configurations of KAGRA with its historical background.

Anaplastic lymphoma kinase (ALK) was originally identified from a rare subtype of non-Hodgkin's lymphomas carrying t(2;5)(p23;q35) translocation, where ALK was constitutively activated as a result of a fusion with nucleophosmin (NPM). Aberrant ALK fusion proteins were also generated in inflammatory fibrosarcoma and a subset of non-small-cell lung cancers, and these proteins are implicated in their pathogenesis. Recently, ALK has been demonstrated to be constitutively activated by gene mutations and/or amplifications in sporadic as well as familial cases of neuroblastoma. Here we describe another mechanism of aberrant ALK activation observed in a neuroblastoma-derived cell line (NB-1), in which a short-form ALK protein (ALK del2-3 ) having a truncated extracellular domain is overexpressed because of amplification of an abnormal ALK gene that lacks exons 2 and 3. ALK del2-3 was autophosphorylated in NB-1 cells as well as in ALK del2-3 -transduced cells and exhibited enhanced in vitro kinase activity compared with the wild-type kinase. ALK del2-3 -transduced NIH3T3 cells exhibited increased colony-forming capacity in soft agar and tumorigenicity in nude mice. RNAi-mediated ALK knockdown resulted in the growth suppression of ALK del2-3 -expressing cells, arguing for the oncogenic role of this mutant. Our findings provide a novel insight into the mechanism of deregulation of the ALK kinase and its roles in neuroblastoma pathogenesis.

No abstract