11,590 research outputs found

    The Three Strikes Policy in Korean Copyright Act 2009: Safe or Out?

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    Korea has grown to be one of the Internet powers in a short period. Because of insufficient copyright protection, Korea recently revised the Korean Copyright Act to reinforce protection of copyright and promote sound distribution of copyrighted works. The new law allows the Minister of Culture, Sports and Tourism to issue orders and the Korea Copyright Commission to issue recommendations. Orders and recommendations are distinguished by the subject of the issuance and the legal force. Orders and recommendations enable online service providers to delete or stop transmission of illegal reproductions, give warning notices to infringers, or suspend the account of repetitive infringers. The “three strikes” policy is controversial and has raised several constitutional concerns. First, the suspension of the repeat infringer’s account may be an unconstitutional violation of the infringer’s freedom of speech. Second, an executive agency’s decision to issue a correction order could be an unconstitutional violation of the separation of powers. The final concern is that the policy violates the principles of due process. This Article examines the “three strikes” policy, the constitutional concerns regarding the policy, and possible policy revisions for more effective copyright protection

    Phosphorylation of α-syntrophin is responsible for its subcellular localization and interaction with dystrophin in muscle cells

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    79-85Syntrophin is a well-known adaptor protein that links intracellular proteins with the dystrophin-glycoprotein complex (DGC) at the sarcolemma. However, little is known about the underlying mechanism that regulates the intracellular localization of α-syntrophin and its interaction with dystrophin. In this study, we demonstrate that α-syntrophin phosphorylation determines its intracellular localization and interaction with dystrophin in muscle cells. α-Syntrophin, a predominant isoform in skeletal muscles, directly interacts with ion channels, enzymes, receptors, and DGC proteins. Despite α-syntrophin being a potential signaling molecule, most studies focus on its function as a dystrophin-associated protein. However, we previously reported that α-syntrophin has a variety of DGC-independent functions to modulate cell migration, differentiation, survival, and protein stability. According to the results of the in vitro phosphorylation assays using subcellular fractions, the phosphorylated α-syntrophin accumulated only at the plasma membrane, and this event occurred regardless of dystrophin expression. However, the α-syntrophin interacting with dystrophin at the membrane was not in a phosphorylated state. We also identified that protein kinase C (PKC) was involved in the phosphorylation of α-syntrophin, which restricted α-syntrophin to interact with dystrophin. In conclusion, we demonstrate that the phosphorylation of α-syntrophin by PKC regulates its intracellular localization and interaction with dystrophin

    Phosphorylation of α-syntrophin is responsible for its subcellular localization and interaction with dystrophin in muscle cells

    Get PDF
    Syntrophin is a well-known adaptor protein that links intracellular proteins with the dystrophin-glycoprotein complex (DGC) at the sarcolemma. However, little is known about the underlying mechanism that regulates the intracellular localization of α-syntrophin and its interaction with dystrophin. In this study, we demonstrate that α-syntrophin phosphorylation determines its intracellular localization and interaction with dystrophin in muscle cells. α-Syntrophin, a predominant isoform in skeletal muscles, directly interacts with ion channels, enzymes, receptors, and DGC proteins. Despite α-syntrophin being a potential signaling molecule, most studies focus on its function as a dystrophin-associated protein. However, we previously reported that α-syntrophin has a variety of DGC-independent functions to modulate cell migration, differentiation, survival, and protein stability. According to the results of the in vitro phosphorylation assays using subcellular fractions, the phosphorylated α-syntrophin accumulated only at the plasma membrane, and this event occurred regardless of dystrophin expression. However, the α-syntrophin interacting with dystrophin at the membrane was not in a phosphorylated state. We also identified that protein kinase C (PKC) was involved in the phosphorylation of α-syntrophin, which restricted α-syntrophin to interact with dystrophin. In conclusion, we demonstrate that the phosphorylation of α-syntrophin by PKC regulates its intracellular localization and interaction with dystrophin

    Replica Higher-Order Topology of Hofstadter Butterflies in Twisted Bilayer Graphene

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    The Hofstadter energy spectrum of twisted bilayer graphene is found to have recursive higher-order topological properties. We demonstrate that higher-order topological insulator (HOTI) phases, characterized by localized corner states, occur as replicas of the original HOTIs to fulfill the self-similarity of the Hofstadter spectrum. We show the existence of the exact flux translational symmetry of twisted bilayer graphene at all commensurate angles. Based on this result, we carefully identify that the original HOTI phase at zero flux is re-entrant at a half-flux periodicity, where the effective twofold rotation is preserved. In addition, numerous replicas of the original HOTIs are found for fluxes without protecting symmetries. Similar to the original HOTIs, replica HOTIs feature both localized corner states and edge-localized real-space topological markers. The replica HOTIs originate from the different interaction scales, namely, intralayer and interlayer couplings, in twisted bilayer graphene. The topological aspect of Hofstadter butterflies revealed in our results highlights symmetry-protected topology in quantum fractals.Comment: 6 pages, 4 figures + Supplemental Materia

    Structure-activity relationships of fluorene compounds inhibiting HCV variants

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    Approximately 71 million people suffer from hepatitis C virus (HCV) infection worldwide. Persistent HCV infection causes liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, resulting in approximately 400,000 deaths annually. Effective direct-acting antiviral agents (DAAs) have been developed and are currently used for HCV treatment targeting the following three proteins: NS3/4A proteinase that cleaves the HCV polyprotein into various functional proteins, RNA-dependent RNA polymerase (designated as NS5B), and NS5A, which is required for the formation of double membrane vesicles serving as RNA replication organelles. At least one compound inhibiting NS5A is included in current HCV treatment regimens due to the high efficacy and low toxicity of drugs targeting NS5A. Here we report fluorene compounds showing strong inhibitory effects on GT 1b and 3a of HCV. Moreover, some compounds were effective against resistance-associated variants to DAAs. The structure-activity relationships of the compounds were analyzed. Furthermore, we investigated the molecular bases of the inhibitory activities of some compounds by the molecular docking method.11Ysciescopu

    Meteorin regulates mesendoderm development by enhancing nodal expression

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    During gastrulation, distinct lineage specification into three germ layers, the mesoderm, endoderm and ectoderm, occurs through an elaborate harmony between signaling molecules along the embryonic proximo-distal and anterior-posterior axes, and Nodal signaling plays a key role in the early embryonic development governing embryonic axis formation, mesoderm and endoderm specification, and left-right asymmetry determination. However, the mechanism by which Nodal expression is regulated is largely unknown. Here, we show that Meteorin regulates Nodal expression and is required for mesendoderm development. It is highly expressed in the inner cell mass of blastocysts and further in the epiblast and extra-embryonic ectoderm during gastrulation. Genetic ablation of the Meteorin gene resulted in early embryonic lethality, presumably due to impaired lineage allocation and subsequent cell accumulation. Embryoid body culture using Meteorin-null embryonic stem (ES) cells showed reduced Nodal expression and concomitant impairment of mesendoderm specification. Meteorin-null embryos displayed reduced levels of Nodal transcripts before the gastrulation stage, and impaired expression of Goosecoid, a definitive endoderm marker, during gastrulation, while the proximo-distal and anterior-posterior axes and primitive streak formation were preserved. Our results show that Meteorin is a novel regulator of Nodal transcription and is required to maintain sufficient Nodal levels for endoderm formation, thereby providing new insights in the regulation of mesendoderm allocation.open1113sciescopu
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