Although ubiquitin-enriched protein inclusions represent an almost invariant feature of neurodegenerative diseases, the mechanism underlying their biogenesis remains unclear. In particular, whether ...the topology of ubiquitin linkages influences the dynamics of inclusions is not well explored. Here, we report that lysine 48 (K48)- and lysine 63 (K63)-linked polyubiquitination, as well as monoubiquitin modification contribute to the biogenesis of inclusions. K63-linked polyubiquitin is the most consistent enhancer of inclusions formation. Under basal conditions, ectopic expression of K63 mutant ubiquitin in cultured cells promotes the accumulation of proteins and the formation of intracellular inclusions in the apparent absence of proteasome impairment. When co-expressed with disease-associated tau and SOD1 mutants, K63 ubiquitin mutant facilitates the formation of tau- and SOD-1–positive inclusions. Moreover, K63-linked ubiquitination was found to selectively facilitate the clearance of inclusions via autophagy. These data indicate that K63-linked ubiquitin chains may represent a common denominator underlying inclusions biogenesis, as well as a general cellular strategy for defining cargo destined for the autophagic system. Collectively, our results provide a novel mechanistic route that underlies the life cycle of an inclusion body. Harnessing this pathway may offer innovative approaches in the treatment of neurodegenerative disorders.
In this introduction, we highlight the developments and transformations that have been put forward and situate our examination of Queer Asias within that context. We then turn to the contributions in ...this special issue, which collectively examine the intricate and imbricated flows of capital, power, intimacy, citizenship, sexual politics, and categories of gender and sexual (self-)identification in and across Japan, Taiwan, Indonesia, Hong Kong, the Philippines, and the United States. The articles in this special issue take up the following questions through an exploration of local genealogies of sexual practices, intimacies, and meanings in people’s everyday lives: What forms of categories, politics, and activism have gender and sexually diverse peoples across East and Southeast Asia embraced, constructed, and challenged in the 2010s through the early 2020s? What new theories have scholars developed and to what end? Whose politics are now being advocated and how might their activism contest older strategies and discourses?
This article investigates “toransujendā” (transgender), “josō” (male-to-female crossdressing), and “otoko no ko” (boy/male daughter) as categories that bind through ethnographic research in Tokyo’s ...contemporary josō gyōkai (scene and business circles). Building on queer and transgender scholarship, I ask what these categories mean, what they do, and how they figure in trans people’s everyday lives and the institutionalization of seidōitsuseishōgai (Japanese translation of Gender Identity Disorder). I argue that categories are imbued with asymmetrical power relations and operate affectively, emerging from contact between bodies and practices. Ultimately, they are important sites for questioning categories of “gender” and “sexuality” in transnational sexuality and transgender studies.
In 2015 and 2016, Ariana Miyamoto and Priyanka Yoshikawa became the first and second "hāfu" (half; multiracial) contestants to be crowned Miss Universe Japan and Miss World Japan respectively. ...Following their win, they were alternately ignored in mainstream media, lambasted online for not being "jun-nihonjin" (pure Japanese), and celebrated for heralding a multiracial and multiethnic Japan. I explore these discourses by examining how the two beauty queens were represented in Japanese-language and English-language news media and Girls Channel, an online forum popular among young women. Drawing on discourse analysis, I argue beauty pageants are important sites for understanding how race, gender, and ethnicity are complexly constructed in Japan. On one level, this stems from Japan's racialized ideologies of nation and long history of subjugating racioethnic minorities, but on another level, it is intertwined with classist and gendered beauty ideals of looking Japanese in beauty pageants. Looking Japanese is also informed by what I call "racialized privilege," invisible unearned advantages conferred upon jun-nihonjin based on their racioethnicity and, for women, tied to lineage (one's ancestors) and colorism (preference for lighter skin). Ultimately, this article aims to decenter EuroAmerican-centric media research on gender, beauty, and racioethnicity.
In sport and sport media, figure skating is often perceived as ‘feminine’ and male skaters frequently occupy an ambiguous position, especially for Asian (American) athletes in a historically ...White-dominated sport. Based on discourse analysis, this article compares how English- and Japanese-language news narratives represent elite male figure skaters Nathan Chen and Yuzuru Hanyu, who are close rivals and skate for the United States and Japan respectively. We demonstrate how English-language media reinforce (U.S.) nationalism by portraying ‘Quad King’ Chen as hypermasculine for his athleticism and ‘Ice Prince’ Hanyu as feminized for his exceptional artistry. Despite being pitted against each other, we argue that in Japanese media narratives, their convivial rivalry and sportsmanship reveal what we call ‘Asian sporting masculinities’, alternative constructions of masculinities complicating monolithic stable understandings of masculinity in or congruous with the West. This study advances critical media and cultural studies by rethinking masculinities in Asian sporting bodies.
Mutations in the parkin gene are a predominant cause of familial parkinsonism. Although initially described as a recessive disorder, emerging evidence suggest that single parkin mutations alone may ...confer increased susceptibility to Parkinson's disease. To better understand the effects of parkin mutations in vivo, we generated transgenic Drosophila overexpressing two human parkin missense mutants, R275W and G328E. Transgenic flies that overexpress R275W, but not wild-type or G328E, human parkin display an age-dependent degeneration of specific dopaminergic neuronal clusters and concomitant locomotor deficits that accelerate with age or in response to rotenone treatment. Furthermore, R275W mutant flies also exhibit prominent mitochondrial abnormalities in their flight muscles. Interestingly, these defects caused by the expression of human R275W parkin are highly similar to those triggered by the loss of endogenous parkin in parkin null flies. Together, our results provide the first in vivo evidence demonstrating that parkin R275W mutant expression mediates pathogenic outcomes and suggest the interesting possibility that select parkin mutations may directly exert neurotoxicity in vivo.
Scholars have criticized how tarento (television personalities) who might be considered “transgender” have for decades provided comic relief on Japanese mainstream television, but few have considered ...the recent emergence of a different kind of trans celebrity who rejects the entertainment narrative to embrace the “wrong body” discourse (having mismatched corporeality). This article explores this phenomenon through the example of Nishihara Satsuki, a trans-identified internet celebrity-turned-tarento, drawing mainly on discourse analysis of their blog, memoir, and variety program appearances. I demonstrate how Satsuki’s celebrity departs from narratives of trans tarento as objects of entertainment to align with hegemonic discourses of the wrong body, which govern how trans individuals are understood in Japan and reflect the broader context of heightened trans visibility elsewhere. In doing so, Satsuki offers an important platform for discussing trans issues and experiences today, which I argue has encouraged the media to take trans representation more seriously.
Storage and controlled distribution of water have been key elements of a human strategy to overcome the space and time variability of water, which have been marked by catastrophic droughts and floods ...throughout the course of civilization. In the United States, the peak of dam building occurred in the mid‐20th century with knowledge limited to the scientific understanding and hydrologic records of the time. Ecological impacts were considered differently than current legislative and regulatory controls would potentially dictate. Additionally, future costs such as maintenance or removal beyond the economic design life were not fully considered. The converging risks associated with aging water storage infrastructure and uncertainty in climate in addition to the continuing need for water storage, flood protection, and hydropower result in a pressing need to address the state of dam infrastructure across the nation. Decisions regarding the future of dams in the United States may, in turn, influence regional water futures through groundwater outcomes, economic productivity, migration, and urban growth. We advocate for a comprehensive national water assessment and a formal analysis of the role dams play in our water future. We emphasize the urgent need for environmentally and economically sound strategies to integrate surface and groundwater storage infrastructure in local, regional, and national water planning considerations. A research agenda is proposed to assess dam failure impacts and the design, operation, and need for dams considering both paleo and future climate, utilization of groundwater resources, and the changing societal values toward the environment.
Plain Language Summary
Water storage and control have been key elements of a human strategy to overcome differences between water availability and water needs. The future promises changes to when and where water will be available and many regions in the USA will likely see an increase in the imbalance between existing water storage and evolving demands for water. This indicates the need for more storage or new dams to meet human and ecological needs. The current trend for removal of old, hazardous or unpopular dams now and into the future may impact regional groundwater outcomes, food and energy production, migration, and urban growth. We advocate for a formal analysis of the role dams play in the future of the USA's water landscape. We also stress the need for national water planning considerations to develop environmentally and economically sound strategies to integrate the management of surface and groundwater storage infrastructure in the USA.
Key Points:
Climate change projections suggest more hydrologic extremes. Are more dams subsequently needed?
Most US dams now exceed their economic design life and represent a need for infrastructure investment and recognition of associated risks
A national water assessment is needed to examine dam removal and modified storage provision options considering hydroclimatic risk exposure
This article explores the role of social media in athlete activism and sport commodification through the case studies of two elite multiracial athletes who represent Japan, professional tennis player ...Naomi Osaka and professional basketball player Rui Hachimura. Osaka’s mother is Japanese and her father is Haitian-American, whereas Hachimura’s mother is Japanese and his father is Beninese. Employing critical discourse analysis of Twitter and Instagram, we ask: How do they use social media to amplify their voices and advocacy for race and ethnicity? How do their athlete activism and multiracial identity appeal to fans and sponsors? We argue that social media lend them various ways for resistance through defying monoracial labeling and racialized sport stereotypes, manifesting their multiracial identity, speaking up against social justice issues, and affiliating with certain sponsors. We demonstrate how their “silent activism” is subtle, situated in everyday life, and not antithetical to the commodification of their (athlete-activist) image.
Targeted genome editing technology can correct the sickle cell disease mutation of the β-globin gene in hematopoietic stem cells. This correction supports production of red blood cells that ...synthesize normal hemoglobin proteins. Here, we demonstrate that Transcription Activator-Like Effector Nucleases (TALENs) and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease system can target DNA sequences around the sickle-cell mutation in the β-globin gene for site-specific cleavage and facilitate precise correction when a homologous donor template is codelivered. Several pairs of TALENs and multiple CRISPR guide RNAs were evaluated for both on-target and off-target cleavage rates. Delivery of the CRISPR/Cas9 components to CD34+ cells led to over 18% gene modification in vitro. Additionally, we demonstrate the correction of the sickle cell disease mutation in bone marrow derived CD34+ hematopoietic stem and progenitor cells from sickle cell disease patients, leading to the production of wild-type hemoglobin. These results demonstrate correction of the sickle mutation in patient-derived CD34+ cells using CRISPR/Cas9 technology.
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