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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]

Neurite outgrowth is a fundamental process in neurons that produces extensions and, consequently, neural connectivity. Neurite damage and atrophy are observed in various brain injuries and disorders. Understanding the intrinsic pathways of neurite outgrowth is essential for developing strategies to stimulate neurite regeneration. Insulin is a pivotal hormone in the regulation of glucose homeostasis. There is increasing evidence for the neurotrophic functions of insulin, including the induction of neurite outgrowth. However, the associated mechanism remains elusive. Here, we demonstrate that insulin potentiates neurite outgrowth mediated by the small GTPases ADP‐ribosylation factor 6 (ARF6) and Ras‐related C3 botulinum toxin substrate 1 (Rac1) through the neuronal adaptor FE65. Moreover, insulin enhances atypical protein kinase Cι/λ (PKCι/λ) activation and FE65 phosphorylation at serine 459 (S459) in neurons and mouse brains. In vitro and cellular assays show that PKCι/λ phosphorylated FE65 at S459. Consistently, insulin potentiates FE65 S459 phosphorylation only in the presence of PKCι/λ. Phosphomimetic studies show that an FE65 S459E mutant potently activates ARF6, Rac1, and neurite outgrowth. Notably, this phosphomimetic mutation enhances the FE65‐ARF6 interaction, a process that promotes ARF6‐Rac1‐mediated neurite outgrowth. Likewise, insulin treatment and PKCι/λ overexpression potentiate the FE65–ARF6 interaction. Conversely, PKCι/λ knockdown suppresses the stimulatory effect of FE65 on ARF6‐Rac1‐mediated neurite outgrowth. The effect of insulin on neurite outgrowth is also markedly attenuated in PKCι/λ knockdown neurons, in the presence and absence of FE65. Our findings reveal a novel mechanism linking insulin with ARF6‐Rac1‐dependent neurite extension through the PKCι/λ‐mediated phosphorylation of FE65. [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]

This study contributes to existing research on polymedia by probing into what we call academic polymedia, investigating the constant availability of interpersonal, professional, and social media for constructing scholarly personas. Drawing on the technobiographical narratives of a group of Hong Kong bilingual academics, we analyze academics' perceptions of their media choices as situated in their professional polymedia environments. In particular, we examine how choices between public and private media shape academic persona development, and the way polymedia engagement impacts the participants' language choice for academic purposes. This study sheds light on existing research on workplace discourse and identity in sociolinguistics by offering a polymedia dimension that draws on people's media ideology in developing their professional identities. [ABSTRACT FROM AUTHOR]

Despite a rich body of research on face-work, how it is performed in online edu-social groups remains under-explored. Drawing on posts and comments of Facebook groups created for courses at a university in Hong Kong, together with interviews with students, tutors, and the lecturer, this article examines how code-switching is deployed as a powerful discursive resource in the performance of face-work. Notwithstanding English being the medium of instruction of the courses, code-switching is noticeable. Focusing on these participants' practices, our analysis discovers that code-switching serves primarily to signal the breakdown of the expectedly formal academic participation frame and the switch to an informal frame. Multiple layers of action frames are collaboratively and constantly designed and redesigned in these 'social network-educational spaces' (Chau and Lee, 2017), where the formal-informal, public-private, and academic-social boundaries become indistinct. Closer analysis within and across the spaces further reveals that norms of appropriateness of code-switching to achieve informality and solidarity may vary depending on a combination of individual, contextual, and temporal factors. In addition to contributing to existing literature on code-switching and face-work on Facebook, the article offers practical implications for understanding the increasingly informalized discourses in institutional contexts. • Code-switching is a face-work strategy to achieve informality and express solidarity in social network-educational spaces. • Norms of appropriateness of code-switching vary depending on individual, contextual, and temporal factors. • This paper contributes to the strand of literature on face-work with a focus on online discourse in a multilingual setting. [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]

Oligomannose-type glycans are among the major targets on the gp120 component of the HIV envelope protein (Env) for broadly neutralizing antibodies (bnAbs). However, attempts to elicit oligomannose-specific nAbs by immunizing with natural or synthetic oligomannose have so far not been successful, possibly due to B cell tolerance checkpoints. Here we design and synthesize oligomannose mimetics, based on the unique chemical structure of a recently identified bacterial lipooligosaccharide, to appear foreign to the immune system. One of these mimetics is bound avidly by members of a family of oligomannose-specific bnAbs and their putative common germline precursor when presented as a glycoconjugate. The crystal structure of one of the mimetics bound to a member of this bnAb family confirms the antigenic resemblance. Lastly, immunization of human-antibody transgenic animals with a lead mimetic evokes nAbs with specificities approaching those of existing bnAbs. These results provide evidence for utilizing antigenic mimicry to elicit oligomannose-specific bnAbs to HIV-1. [ABSTRACT FROM AUTHOR]

Autophagy is a vital cellular pathway in eukaryotic cells, including neurons, where it plays significant roles in neurodevelopment and maintenance. A crucial step in autophagy is the formation of the class III phosphatidylinositol 3-kinase complex 1 (PI3KC3-C1), which is essential for initiating autophagosome biogenesis. Beclin 1 is the key component of PI3KC3-C1, and its interactors have been reported to affect autophagy. The brain-enriched adaptor protein FE65 has been shown to interact with Alzheimer's disease amyloid precursor protein (APP) to alter the processing of APP. Additionally, FE65 has been implicated in various cellular pathways, including autophagy. We demonstrate here that FE65 positively regulates autophagy. FE65, through its C-terminus, has been shown to interact with Beclin 1. Notably, the overexpression of FE65 enhances Beclin 1-mediated autophagy, whereas this process is attenuated in FE65 knockout cells. Moreover, the stimulatory effect of FE65 on Beclin 1-mediated autophagy is diminished by an FE65 C-terminus deletion mutant that disrupts the FE65-Beclin 1 interaction. Lastly, we have found that the FE65-Beclin 1 interaction modulates the kinase activity of the PI3KC3-C1 complex. Together, we have identified FE65 as a novel Beclin 1 interactor, and this interaction potentiates autophagy.

Competing Interests: None