Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β.

Mutations in human CLC-1 chloride channel are associated with the skeletal muscle disorder myotonia congenita. The disease-causing mutant A531V manifests enhanced proteasomal degradation of CLC-1. We recently found that CLC-1 degradation is mediated by cullin 4 ubiquitin ligase complex. It is currently unclear how quality control and protein degradation systems coordinate with each other to process the biosynthesis of CLC-1. Herein we aim to ascertain the molecular nature of the protein quality control system for CLC-1. We identified three CLC-1-interacting proteins that are well-known heat shock protein 90 (Hsp90)-associated co-chaperones: FK506-binding protein 8 (FKBP8), activator of Hsp90 ATPase homolog 1 (Aha1), and Hsp70/Hsp90 organizing protein (HOP). These co-chaperones promote both the protein level and the functional expression of CLC-1 wild-type and A531V mutant. CLC-1 biosynthesis is also facilitated by the molecular chaperones Hsc70 and Hsp90β. The protein stability of CLC-1 is notably increased by FKBP8 and the Hsp90β inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) that substantially suppresses cullin 4 expression. We further confirmed that cullin 4 may interact with Hsp90β and FKBP8. Our data are consistent with the idea that FKBP8 and Hsp90β play an essential role in the late phase of CLC-1 quality control by dynamically coordinating protein folding and degradation

The characteristics and determinants of capital structure in SME: empirical evidence from U.S. companies

Abstract This study investigates the determinants of capital structure of small and medium size enterprises (SMEs) in U.S. by using a panel data consisting of 100 firms from 2002 to 2010. In order to examine the financial crisis effects on SMEs’ gearing decision, the research period is divided into two time frames: pre-crisis (2002-2007) and post-crisis (2008-2010). Using the Fixed Effect Model through STATA software, the seven variables including profitability, firm size, firm age, tangibility, earnings volatility, non-debt tax shield and growth opportunity are tested against the short-term debt and the long-term debt. The evidence suggests that profitability and size are significant determinants for both short-term and long-term debt structure of the firm. Growth opportunity and non-debt tax shield have significant influence on long-term debt decisions. The other variables such as tangibility, age and earnings volatility do not contribute significantly to the SMEs’ capital structure. Furthermore, it is observed that financial crisis have considerable impacts on U.S. small firms as the average values of most of the proxies of the determinants are reducing after 2008. Key words: capital structure, SMEs, trade- off theory, pecking order theory, information asymmetr

The Aesthetics of Minimalist Music and a Schenkerian-Oriented Analysis of the First Movement "Opening" of Philip Glass' Glassworks

Philip Glass' Glassworks (1981) is a six-movement composition for two flutes, two soprano saxophones/clarinets, two tenor saxophones/bass clarinets, two French horns, violas, cellos, and the DX7 electric piano. Glassworks consists of six movements titled "Opening," "Floe," "Island," "Rubric," "Facades," and "Closing." This thesis covers the first movement "Opening." Repetition in musical minimalism confronts traditional prescriptive codes of tonal music and post-tonal music. While challenging the traditional codes, repetition in musical minimalism established new codes for listening to minimal music. This thesis explores the implications of these ideas