University of Puget Sound

ABSTRACT Early AI policymaking in the United States appeared bipartisan, but subsequent developments raise the question of whether AI policy will become more polarized over time. To examine how partisanship takes root around novel policy issues, we perform a mixed‐methods study, analyzing survey data from 129 state legislators in 44 states and performing four case studies featuring legislative debates over enacted AI regulation in Idaho, Colorado, and Illinois. We articulate four potential partisan triggers that shape the emergence of issue polarization: (1) competing problem definitions, (2) preferred policy tools, (3) stakeholder participation, and (4) issue placement in policy subsystems, and we introduce the concept of subsystem shopping. Flexibility and compromise in subnational AI policymaking were initially common due to uncertain issue ownership over diverse problem definitions, the presence of disrupted industries, and deference to nonpartisan expert voices, which enabled subsystem shopping towards less controversial policymaking. However, bipartisan windows narrowed as AI became anchored in party‐owned domains, lobbying became more coordinated, and “soft” areas of initial legislative consensus hardened into disputes over more robust policy tools. These developments offer insights into how nascent policy domains can initially sustain bipartisan cooperation, and why it may erode unless actors work to preserve it.

Abstract The surface ocean is an important source of methane to the atmosphere, contributing 4% of natural global production. The degradation of methylphosphonate (MPn) is a key methane production pathway in the aerobic euphotic zone. Methylphosphonate is an important component of dissolved organic phosphorus (DOP), and it serves as a source of phosphorus (P) for microorganisms in oligotrophic regions of the ocean. Methylphosphonate is metabolized by bacteria into labile phosphorus and methane by the C‐P lyase enzymatic pathway. This pathway is regulated by the concentration of ambient inorganic phosphate (Pi) and is utilized to access alternative forms of P when bacteria experience P limitation. However, the concentration threshold of Pi, as it relates to the onset of C‐P lyase activity, is unknown. In this study, an isolate of the methane‐producing marine bacterium Stutzerimonas frequens (Pseudomonadaceae) was cultured under a range of Pi concentrations in the presence of MPn. In treatments where the estimated Pi concentration dropped below 92 nM, methane production was observed. Isotopic mass balance confirmed the methane was derived from MPn. The drawdown of MPn and the production of methane occurred concomitantly with the uptake of other organic P compounds, demonstrating that C‐P lyase is utilized in conjunction with other P acquisition pathways to combat Pi limitation. As the global climate shifts and increased warming strengthens stratification, increased P limitation may lead to higher rates of MPn utilization and methane production in the euphotic open ocean.

ABSTRACT Animals employ many strategies to survive in extreme cold. Glacier ice worms (Mesenchytraeus solifugus) are the largest animals that spend their entire life cycle in ice. Indeed, they spend most of their lives near 0°C and accumulate adenosine trisphosphate (ATP) to mitigate the impacts of cold on their performance. However, the degree to which ice worms can survive temperatures above and below freezing has not been thoroughly investigated. Furthermore, the role of cold temperatures in shaping whole-body metabolism in ice worms is largely unknown. Here, we assessed thermal limits of ice worms as well as their whole-body metabolic rates. Notably, we found that though ice worms can survive short-term exposures to surprisingly warm temperatures (~26°C), they cannot tolerate freezing, including internal ice formation. Ice worm metabolic rates also significantly increased with temperature up to 16°C where a significant break point occurred. Taken together, our results further illuminate how ice worms survive their unique life in ice and highlight how close they live to their lower thermal limits. Looking ahead, we note the clear risks that anthropogenic climate change, glacier recession, and loss of mountain snowpack pose to the future of ice worms.

Polysubstance use is prevalent in the population but remains understudied in preclinical models. Alcohol and opioid polysubstance use is associated with negative outcomes, worse treatment prognosis, and higher overdose risk; but underlying mechanisms are still being uncovered. Examining factors that motivate use of one substance over another in different contexts in preclinical models will better our understanding of polysubstance use and improve translational value. Here we assessed baseline anxiety-like and locomotive behavior and then measured voluntary consumption of multiple doses of alcohol and fentanyl in group housed male and female mice using our novel Socially Integrated Polysubstance (SIP) system. Fifty-six male (n=32) and female (n=24) adult mice were housed in groups of 4 for one week with continuous access to food, water, two doses of ethanol (5% and 10%) and two doses of fentanyl (5 ug/ml and 20 ug/ml). Our analyses revealed sex differences across multiple domains – female mice consumed more liquid in the dark cycle, had higher activity, a higher preference for both ethanol and fentanyl over water, and their fentanyl preference increased over the seven days. Furthermore, both male and female mice displayed polysubstance consumption patterns, with female mice displaying more prolonged polysubstance use across days in the SIP chambers. We then used machine-learning techniques to reveal underlying relationships between baseline behavioral phenotypes and subsequent polysubstance consumption patterns, where anxiety- and risk-taking-like behavioral phenotypes mapped onto discrete patterns of polysubstance use, preference, and escalation. By simulating more translationally relevant substance use and improving our understanding of the motivations for different patterns of consumption, this study contributes to the developing preclinical literature on polysubstance use with the goal of facilitating better treatment outcomes and novel therapeutic strategies.

Emerging evidence suggests that RB1 inactivation may be a strong predictor of poor survival for men with prostate cancer (PC); however, large-scale validation is lacking. We analyzed whether RB1 alterations are associated with inferior survival in advanced PC and evaluated the impact of co-occurring genomic alterations on outcomes using retrospective data from the Veteran's Health Administration and Veterans Affairs Multi-Omics Analysis Platform for Prostate Cancer from 2016 to 2023. The primary outcome was overall survival (OS) from onset of metastatic castration-resistant prostate cancer (mCRPC), as well as OS from initiation of life-prolonging therapy other than androgen deprivation therapy, and time to development of mCRPC. Eighty-seven (3.5%) of the 2,512 included patients had an RB1 alteration detected. The median age at diagnosis in the RB1-altered group was 71 (IQR, 65-76) years, and 68 (IQR, 62-73) years in the RB1 wild-type group. The median overall survival from diagnosis of mCRPC was 1.31 years (95% CI, 0.89 to 1.84) in those with an RB1 alteration compared with 2.99 years (95% CI, 2.79 to 3.23). RB1 alteration alone conferred similar poor prognosis when compared with patients who had combined PTEN and TP53 alterations. A dose effect was seen with increasing numbers of tumor suppressor genes (TSGs-RB1, TP53, and PTEN) conferring poorer outcomes. The median survival of patients from diagnosis of mCRPC with zero, one, two, and three TSGs was 3.74, 2.61, 1.61, and 0.87 years, respectively. BRCA2 alterations were not associated with significantly worse outcomes unless accompanied by RB1 alteration. In this large, real-world cohort of men with mCRPC, RB1 alterations emerged as a strong indicator of poor prognosis and can be used to stratify studies alone or in conjunction with other TSG alterations.

Pelagic Sargassum, denoting the two species S. natans and S. fluitans, has become a focal point of both scientific and public interest due to recent superbloom events. As a result, investigation into the dynamics of Sargassum-associated microbiota, which was previously quite limited, has regained momentum in the past five years. This review collates the current state of knowledge relating to the Sargassum microbiome as well as synthesizes relevant biogeochemical findings which may aid future efforts in this field. We explore microbiome composition and functional roles within this holobiont, specifically in terms of taxonomic diversity, macronutrient cycling, and the fate of Sargassum-derived organic matter. Despite progress, significant gaps remain in our understanding of the dynamic interactions within these microbial communities and their broader ecological significance. Future research directions are identified alongside recommendations for standardized protocols, emphasizing the need for more in-depth studies utilizing advanced molecular and biogeochemical techniques to unravel the full complexity of the Sargassum microbiome.

The HIV-1 epidemic broadly impacts healthcare. There remains a continued need for improved anti-viral therapies resilient to the development of drug resistance. HIV-1 nucleocapsid protein 7 (NCp7) seems a prime drug target due to its unique nucleic acid chaperone activity required for multiple viral processes. NCp7 RNA binding activity has been shown to increase viral production and infectivity within the host. Here we introduce a high-throughput AlphaScreen assay to evaluate NCp7 RNA binding activity and validate its specificity and sensitivity using a known inhibitor. We also demonstrate the utility of this assay by performing a drug-repurposing screen, which identified seven confirmed inhibitors of NCp7 RNA binding and two confirmed enhancers of NCp7 RNA binding. This tool will aid in future NCp7-targeted drug discovery initiatives for the treatment of HIV-1 infection.

Oxytocin's (OT's) influence on social behavior is highly complex and dependent upon context. Here, we addressed a gap in the literature on how OT impacts the learning process in a purely behavioral study. We conducted a 2 (OT, placebo) × 2 (demonstration, no demonstration) study in which dogs received 35 IU intranasal OT spray and demonstrations of how to solve a food puzzle. We tested subjects' levels of engagement with the puzzle as well as with three social partners-the experimenter, the helper, and the owner-both while the dogs were being introduced to the puzzle and while the dogs were allowed to engage with the puzzle. During the puzzle introduction, dogs that received a demonstration increased their gaze toward puzzle and experimenter, and decreased gaze toward their owner as compared to dogs that did not receive a demonstration. When allowed to engage with the puzzle, dogs that received a demonstration gazed more at the experimenter and opened more drawers compared to those receiving no demonstration, although the difference in their general puzzle interaction only trended toward significant. Moreover, more female than male dogs gazed at the experimenter during puzzle engagement, and there was a strong trend for more male than female dogs to solve the puzzle. Finally, results showed only a modest effect of OT on social partner-directed behaviors, including a possible sex-specific effect, and no impact of OT on social learning. The difficulty of the puzzle, identity of the social partner, and dogs' perceptions of the puzzle opening demonstration are discussed as possible contributing factors. (PsycInfo Database Record (c) 2025 APA, all rights reserved).