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There is no doubt that works that incorporate or build upon existing copyrighted works are derivative works, but what encouraging those works means legally for companies and creators can be muddy. There remains an uncertainty as to who owns user-created content in a video game "co-created" by the players such as Roblox and Minecraft. While user-created content is not new in the video game industry, the ramifications of allowing and encouraging creation have not been discussed in great enough detail and are in dire need of a modern reassessment. The Dota 2 controversy shed light on how the industry's failure to properly address user-created content has led to companies missing opportunities to take control of genre-defining content made in their own games and using their own tools. Despite this spotlight, companies still have wildly varying solutions that are each insufficient in one manner or another in resolving the uncertainty or the issues stemming from it. This note aims to examine usercreated content and its copyright implications in detail, critique the current legal framework used to determine copyrightable elements in video games, analyze the approaches developers have used to capture user-created content into their intellectual property portfolios or mitigate the risk of indirect infringement, and offer a route of future study to better evaluate how to balance minimizing the risk of indirect infringement and players' interest in creating mods. [ABSTRACT FROM AUTHOR]

Amyloid precursor protein (APP) is a key molecule in the pathogenesis of Alzheimer’s disease (AD) as the pathogenic amyloid-β peptide is derived from it. Two closely related APP family proteins (APPs) have also been identified in mammals. Current knowledge, including genetic analyses of gain- and loss-of-function mutants, highlights the importance of APPs in various physiological functions. Notably, APPs consist of multiple extracellular and intracellular protein-binding regions/domains. Protein–protein interactions are crucial for many cellular processes. In past decades, many APPs interactors have been identified which assist the revelation of the putative roles of APPs. Importantly, some of these interactors have been shown to influence several APPs-mediated neuronal processes which are found defective in AD and other neurodegenerative disorders. Studying APPs–interactor complexes would not only advance our understanding of the physiological roles of APPs but also provide further insights into the association of these processes to neurodegeneration, which may lead to the development of novel therapies. In this mini-review, we summarize the roles of APPs–interactor complexes in neurodevelopmental processes including neurogenesis, neurite outgrowth, axonal guidance and synaptogenesis. [ABSTRACT FROM AUTHOR]

This paper explores the metalinguistic tactics used by Hong Kong protesters in 2014 and 2019 and how they reflected and exploited a range of dominant ideologies about language in the city. These tactics are considered both in terms of their rhetorical utility in the "message war" between protesters and authorities, and their significance in the broader sociolinguistic context of Hong Kong. The analysis reveals how such tactics entailed both opportunities and risks, allowing protesters to create shareable discursive artifacts that spread quickly over social media and to promote in-group solidarity and distrust of their political opponents, but also limiting their ability to broaden the appeal of their messages to certain segments of the population and implicating them in upholding language ideologies that promote exclusion and marginalization. [ABSTRACT FROM AUTHOR]

Amyloid-β (Aβ) is derived from the proteolytic processing of amyloid precursor protein (APP), and the deposition of extracellular Aβ to form amyloid plaques is a pathologic hallmark of Alzheimer's disease (AD). Although reducing Aβ generation and accumulation has been proposed as a means of treating the disease, adverse side effects and unsatisfactory efficacy have been reported in several clinical trials that sought to lower Aβ levels. Engulfment adaptor phosphotyrosine-binding (PTB) domain containing 1 (GULP1) is a molecular adaptor that has been shown to interact with APP to alter Aβ production. Therefore, the modulation of the GULP1-APP interaction may be an alternative approach to reducing Aβ. However, the mechanisms that regulate GULP1-APP binding remain elusive. As GULP1 is a phosphoprotein, and because phosphorylation is a common mechanism that regulates protein interaction, we anticipated that GULP1 phosphorylation would influence GULP1-APP interaction and thereby Aβ production. We show here that the phosphorylation of GULP1 threonine 35 (T35) reduces GULP1-APP interaction and suppresses the stimulatory effect of GULP1 on APP processing. The residue is phosphorylated by an isoform of atypical PKC (PKCζ). Overexpression of PKCζ reduces both GULP1-APP interaction and GULP1-mediated Aβ generation. Moreover, the activation of PKCζ via insulin suppresses APP processing. In contrast, GULP1-mediated APP processing is enhanced in PKCζ knockout cells. Similarly, PKC ι, another member of atypical PKC, also decreases GULP1-mediated APP processing. Intriguingly, our X-ray crystal structure of GULP1 PTB-APP intracellular domain (AICD) peptide reveals that GULP1 T35 is not located at the GULP1-AICD binding interface; rather, it immediately precedes the β1-α2 loop that forms a portion of the binding groove for the APP helix αC. Phosphorylating the residue may induce an allosteric effect on the conformation of the binding groove. Our results indicate that GULP1 T35 phosphorylation is a mechanism for the regulation of GULP1-APP interaction and thereby APP processing. Moreover, the activation of atypical PKC, such as by insulin, may confer a beneficial effect on AD by lowering GULP1-mediated Aβ production. [ABSTRACT FROM AUTHOR]

Competing Interests: None