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Those with diabetes mellitus are at high-risk of developing psychiatric disorders, especially mood disorders, yet the link between hyperglycemia and altered motivation has not been thoroughly explored. Here, we characterized value-based decision-making behavior of a streptozocin-induced diabetic mouse model on Restaurant Row, a naturalistic neuroeconomic foraging paradigm capable of behaviorally capturing multiple decision systems known to depend on dissociable neural circuits. Mice made self-paced choices on a daily limited time-budget, accepting or rejecting reward offers based on cost (delays cued by tone pitch) and subjective value (flavors), in a closed-economy system tested across months. We found streptozocin-treated mice disproportionately undervalued less-preferred flavors and inverted their meal-consumption patterns shifted toward a more costly strategy overprioritizing high-value rewards. These foraging behaviors were driven by impairments in multiple decision-making processes, including the ability to deliberate when engaged in conflict and cache the value of the passage of time as sunk costs. Surprisingly, diabetes-induced changes in motivation depended not only on the type of choice being made, but also on the salience of reward-scarcity in the environment. These findings suggest that complex relationships between metabolic dysfunction and dissociable valuation algorithms underlying unique cognitive heuristics and sensitivity to opportunity costs can disrupt distinct computational processes leading to comorbid psychiatric vulnerabilities. A neuroeconomic approach to characterize decision-making behavior reveals alterations in distinct valuation algorithms in a mouse model of diabetes, shedding light on the interaction between metabolic disorders, energy balance, and cognitive heuristics.

Those with diabetes mellitus are at high-risk of developing psychiatric disorders, yet the link between hyperglycemia and alterations in motivated behavior has not been explored in detail. We characterized value-based decision-making behavior of a streptozocin-induced diabetic mouse model on a naturalistic neuroeconomic foraging paradigm called Restaurant Row. Mice made self-paced choices while on a limited time-budget accepting or rejecting reward offers as a function of cost (delays cued by tone-pitch) and subjective value (flavors), tested daily in a closed-economy system across months. We found streptozocin-treated mice disproportionately undervalued less-preferred flavors and inverted their meal-consumption patterns shifted toward a more costly strategy that overprioritized high-value rewards. We discovered these foraging behaviors were driven by impairments in multiple decision-making systems, including the ability to deliberate when engaged in conflict and cache the value of the passage of time in the form of sunk costs. Surprisingly, diabetes-induced changes in behavior depended not only on the type of choice being made but also the salience of reward-scarcity in the environment. These findings suggest complex relationships between glycemic regulation and dissociable valuation algorithms underlying unique cognitive heuristics and sensitivity to opportunity costs can disrupt fundamentally distinct computational processes and could give rise to psychiatric vulnerabilities.

Treatment-related neuroendocrine prostate cancer (NEPC) is an increasingly frequent mechanism of resistance to androgen receptor pathway inhibitor (ARPI) therapy in prostate adenocarcinoma (PRAD). This lineage transition is dependent on upregulation of the NE-specifying transcription factor ASCL1, typically in a genetic background of and loss. Here we identify extracellular matrix-integrin-YAP1/TEAD signaling as a critical brake on NEPC lineage transition. Deletion of , the shared B1 subunit required for collagen and laminin-mediated integrin activation, is sufficient to induce ASCL1 and NE lineage gene expression, by activating LATS1/2 kinases with subsequent inactivation of YAP1/TEAD signaling. Conversely, restoration of YAP1/TEAD signaling by pharmacological LATS1/2 inhibition, or by expression of constitutively active YAP1/TAZ mutants, prevents or reverts NEPC lineage transition. NOTCH and AR cooperate with YAP/TEAD to repress ASCL1, such that combined inhibition leads to complete reprograming of PRAD into NEPC , providing a dynamic platform to dissect the molecular events responsible for lineage transition over time. We find that lineage transition is accompanied by a redistribution of FOXA1 and TEAD cistromes from PRAD to NEPC-specific enhancers and requires the pioneering activity of FOXA1. Thus, extracellular matrix/integrin signaling in the PRAD tumor microenvironment restrains NE lineage plasticity, highlighting a potential path for pharmacological inhibitors in modulating treatment-induced lineage change.

Understanding the factors that promote civic engagement among emerging adult college students is crucial, especially considering its association with positive youth development. The current study examined ethnic-racial identity (ERI) exploration, resolution, and affirmation as mediators of the relation between cultural socialization and civic engagement. Additionally, the extent to which students were raised in predominantly minoritized neighborhoods (i.e., predominantly minoritized neighborhood racial composition; PMNRC) was included as a moderator of the associations between cultural socialization and ERI components. Last, we tested whether findings varied based on students’ ethnic-racial backgrounds (i.e., differences in the model for Asian, African American, Latinx, and Multiracial students of color; N = 1036). Results indicated that there was a significant mediation path, such that cultural socialization predicted greater ERI exploration and, in turn, greater civic engagement. Cultural socialization was also positively associated with greater ERI resolution and affirmation. The racial composition of the neighborhoods that individuals were raised in was not significantly associated with any ERI component; however, PMNRC moderated the relation between cultural socialization and ERI affirmation. Specifically, cultural socialization predicted more ERI affirmation at higher levels of PMNRC, but this relation was not significant at low levels of PMNRC. There were no significant ethnic-racial differences in relations we tested in the model. These findings highlight the importance of cultural processes in civic engagement among diverse emerging adults.

Deep learning is transforming microscopy, yet models often fail when applied to images from new instruments or acquisition settings. Conventional adversarial domain adaptation (ADDA) retrains entire networks, often disrupting learned semantic representations. Here, we overturn this paradigm by showing that adapting only the earliest convolutional layers, while freezing deeper layers, yields reliable transfer. Building on this principle, we introduce Subnetwork Image Translation ADDA with automatic depth selection (SIT-ADDA-Auto), a self-configuring framework that integrates shallow-layer adversarial alignment with predictive uncertainty to automatically select adaptation depth without target labels. We demonstrate robustness via multi-metric evaluation, blinded expert assessment, and uncertainty-depth ablations. Across exposure and illumination shifts, cross-instrument transfer, and multiple stains, SIT-ADDA improves reconstruction and downstream segmentation over full-encoder adaptation and non-adversarial baselines, with reduced drift of semantic features. Our results provide a design rule for label-free adaptation in microscopy and a recipe for field settings; the code is publicly available.