Methionine sulfoxide reductase A (MSRA) protects proteins from oxidation, and also helps remove reactive oxygen species (ROS) by recovering antioxidant enzymes inactivated by oxidation. Although its functions have been investigated extensively, little is known about the mechanism by which MSRA is regulated. Arrest defective 1 (ARD1) is an enzyme that catalyzes not only N-terminal acetylation as a cotranslational modification but also lysine acetylation as a posttranslational modification. ARD1, which is expressed in most cell types, is believed to participate in diverse biological processes, but its roles are poorly understood. Given that MSRA was hunted in a yeast two-hybrid screen with ARD1 as the bait, we here investigated whether ARD1 is a novel regulator of MSRA. ARD1 was shown to interact with and acetylate MSRA in both cells and test tubes. It specifically acetylated the K49 residue of MSRA, and by doing so repressed the enzymatic function of MSRA. ARD1 increased cellular levels of ROS, carbonylated proteins and DNA breaks under oxidative stress. Moreover, it promoted cell death induced by pro-oxidants, which was attenuated in MSRA-deficient cells. When mice were exposed to hyperoxic conditions for 2 days, their livers and kidneys were injured and protein carbonylation was increased. The oxidative tissue injury was more severe in ARD1 transgenic mice than in their wild-type littermates. In conclusion, ARD1 has a crucial role in the cellular response to oxidative stress as a bona fide regulator of MSRA. ARD1 is a potential target for ameliorating oxidative injury or for potentiating ROS-producing anticancer agents.

Background:Although hepatocellular carcinoma (HCC) usually develops in cirrhotic livers, a minority of cases occur in noncirrhotic livers (NCLs). We investigated etiology, clinicopathological features, and occult hepatitis B virus (HBV) infection (OBI) in patients with NCL HCC in an HBV-endemic area.Methods:A total of 710 patients who underwent resection or transplantation for HCC at the National Cancer Center (NCC), Korea, were enrolled. HCC and fibrosis stage were diagnosed pathologically.Results:A total of 178 patients (25%) did not have cirrhosis (NCL group). The main cause of HCC was HBV infection (77.2%), followed by cryptogenic disease (11.0%). The prevalence of NCL was 19.2%, 32.5%, 50.0%, and 48.7% among patients with HBV, hepatitis C virus (HCV), alcoholic, and cryptogenic disease, respectively (p < 0.05); corresponding nonfibrosis rates were 8.1%, 0%, 19.0%, and 24.3%, respectively. The NCL group was significantly older, with a larger tumor size, smaller tumor number, lower tumor stage, and more frequent non-HBV etiology. Among non-HBV HCC cases, 130 (80.2%) had antibodies against HBV core (HBc) and 55 (38.5%) had OBI. OBI-positive rates of 0%, 31.8%, and 52.6% were detected among HCV, alcoholic, and cryptogenic HCC cases, respectively. OBI did not correlate with advanced fibrosis. The NCL and liver cirrhosis (LC) groups did not differ in median overall survival.Conclusion:Regardless of etiology, a significant number of HCC patients, including half of nonviral cases, did not have LC. Half of cryptogenic HCC cases had OBI. This study promotes an understanding of fibrosis and OBI among patients with HCC in an HBV-endemic area.

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The fiber optic ingress/egress is one of the important issues for the application of fiber optic sensors to real structures because the optical fiber is so fragile at the ingress/egress point. Little attention has been paid to methods of practically accessing embedded optical fibers in the literature of sensor activities. In this paper, we proposed the novel out-of-plane ingress/egress method to improve the limit of the existing inplane ingress/egress method. For the safety of the embedded optical fiber, we developed the component to protect the optical fiber at the ingress/egress point and the preservation method of an optical fiber against the composite curing environment of high temperature and pressure. And we also developed an optical connection fixture to integrate the connection part and a composite structure. Some tests were performed to confirm the safety and survivability of the embedded optical fiber using the devised ingress/egress method.

Antisera obtained from flounder Paralichthys o l~v a c e u s immunized with EdwardsieUa tarda were fractionated using Sephacryl S-300 gel filtration. The flounder was found to contain various sizes of immunoglobulins (Igs) ranging from <200 to >700 kDa. These lgs were combined into 3 pools according to molecular weight; pool 1 consisted of high molecular weight (HMW] Igs of >700 kDa, pools I1 and 111 consisted of low molecular weight (LMW) Igs of 230 to 700 kDa (pool 11) and <230 kDa (pool 111). After being further purified by hydroxyapatite column chromatography and isoelectric focusing, HMW Ig in pool I and LMW Ig in pool 111 were compared with each other by SDS-PAGE under reducing conditions. They were found to be composed of 1 size of heavy chain and 2 sizes of light chain. While HMW Ig in pool I contained 68 kDa H chains and 22 kDa and 24 kDa L chains, LMW Ig in pool 111 contained 69 kDa H chains and 22 kDa and 26 kDa L chains. A set of 5 monoclonal antibodies (MAbs) against HMW Igs was prepared. The reactivities of these MAbs with Igs in the 3 pools were determined by enzyme linked immunosorbent assay (ELISA) and dot immunoassay. All 5 MAbs reacted strongly only to the HMW Igs. Results suggest that flounder Igs comprise LMW Igs as well as HMW Igs and the physicochemical and antigenical characterlstlcs of LMW Igs are different from those of HMW Igs.