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The dual face of miR-146a in ALS
Public responses to atrocities depend on partisanship and context, not legal labels
Legal labels such as genocide and crimes against humanity carry substantial legal and diplomatic weight in elite and institutional arenas, where classification shapes treaty obligations, ICC jurisdiction, and the perceived stakes of inaction. A common assumption in advocacy and policy discourse is that these labels also shape mass public judgment. Direct evidence is limited and ambiguous. We test this assumption in a preregistered, nationally representative survey experiment ( N = 2 , 000 ) comparing four legally salient atrocity terms—genocide, war crimes, crimes against humanity, and ethnic cleansing—against a nonlegal control across five real-world conflict contexts, measuring support for punitive and humanitarian policies as well as moral attributions of responsibility. Across outcomes, estimated label effects are small and rarely distinguishable from zero. Critically, even within a given partisan and country context, swapping legal labels produces smaller shifts than the baseline gaps across partisan and geopolitical contexts—indicating that where you stand and who you are matter far more than what word is used. Any departures from zero are narrow and do not accumulate into a consistent pattern across outcomes or conflicts. These results suggest that the political significance of atrocity labeling lies primarily in elite and institutional arenas; for mass publics, legal terminology is a weak lever compared to country context and partisan commitments.
Posttranslational generation of carboxylate ligands from aliphatic side chains in the photosynthetic oxygen-evolving complex
Photosynthetic oxygen evolution is catalyzed by the Mn 4 CaO 5 cluster within the oxygen-evolving complex (OEC) of photosystem II (PSII). Although oxygenic photosynthesis likely arose before the Great Oxidation Event (~2.4 billion years ago), how the OEC emerged in ancestral PSII remains unresolved. We previously showed that cyanobacterial mutants in which Asp or Glu ligands of the Mn 4 CaO 5 cluster were replaced with His or Asn/Gln underwent posttranslational conversion back to the original carboxylate residues. Here, we examined whether aliphatic amino acids lacking reactive side chains can also undergo similar conversion, thereby testing the generality of this phenomenon. Mutations of D1-Asp170 to Val/Leu/Ile and of D1-Glu189 to Leu/Ile resulted in posttranslational generation of Asp/Glu or their derivatives, partially restoring O 2 -evolving activity. Notably, nonstandard Asp/Glu derivatives also appear capable of functioning as carboxylate ligands for the Mn 4 CaO 5 cluster. This transformation of aliphatic residues represents a distinct type of posttranslational modification. Together, these findings demonstrate that posttranslational generation of carboxylate ligands from diverse amino acid residues, including aliphatic side chains, is a general feature of the OEC. Such intrinsic chemical plasticity of the OEC supports the hypothesis that posttranslational amino acid conversion played a critical role in the origin and evolution of the OEC, enabling photosynthetic oxygen production that transformed Earth’s environment and promoted the evolution of life.
Gender pay gaps in the social sciences
We provide a longitudinal, multifield analysis of the gender pay gap in academia that directly links individual-level salaries to measures of scholarly productivity. Using administrative data from the ten campuses that comprise the University of California system, we combine detailed pay records with bibliometric data on publications and citations for faculty in five major social science fields. We find a raw gender pay gap of 23%, which decreases to 4.3% after controlling for field, campus, and cohort. Including controls for job title and scholarly productivity has little effect on the estimated gap, although they substantially increase explanatory power. A decomposition shows that 17% of the gap is unexplained, persisting across junior and senior faculty. We also find a large, persistent gender gap in publications, but no citation gap once output and career length are considered. Field-level analysis reveals that pay gaps are not universal: They persist in Business, Sociology, and Anthropology, but are absent in Economics, Political Science, and smaller social science fields. Our results suggest that pay transparency is insufficient to eliminate salary disparities and that more equal representation within the field is not a prerequisite for pay equity. Our study isolates the residual gap that remains unexplained by productivity or seniority, challenging the view that these factors fully account for gender pay differences. Taken together, our findings highlight the role of field-specific norms and institutional structures, offering directions to promote equitable compensation in academia.
Record-low 2025 and 2026 ice extents restore Arctic winter sea-ice decline
Recent analyses have suggested that the decadal rate of Arctic winter sea-ice extent decline weakened in the early 2020s, with 20-y trends becoming statistically insignificant. Here we show from more up-to-date observations that the exceptionally low 2025 and 2026 ice extent winters reversed this picture, with sea-ice extent during the growth and peak phases returning to record lows and 20-y decline trends becoming significant again. Further analysis of CMIP6 model analogues shows that the observed 2025 decline was unusual but physically plausible under comparable Arctic warming, and is more consistent with ongoing winter sea ice reduction than with a return to values seen in the early 2020s.
Severe floods increase long-term opioid overdose mortality
The relationship between climate disasters and substance use-related harms has been understudied. This study employed a mixed methods research design to assess the impact of severe floods on opioid overdose mortality and identify mechanisms driving this relationship. Drawing on opioid overdose death data from NCHS, presidential disaster declarations from FEMA, and severe storm event data from NOAA, we found severe floods in rural Appalachia led to a significant increase in county-level overdose mortality that persisted for a decade postflood. We then collected retrospective qualitative data from 17 stakeholders regarding the floods that occurred in Eastern Kentucky in July 2022. Interviews suggested this increase in overdose mortality was perpetuated by decreased access to treatment, recovery, and harm reduction services; increased trauma; increased instability; and persistent stigma around help-seeking. Due to the predicted continuation of these disasters, understanding their impact on substance use-related harms is essential to mitigating future damage.
The 2026 western US snow drought was about four times more likely due to climate change
In the spring of 2026, anomalously low snow conditions in the western United States threatened winter recreation and water supplies. Here, we investigate: to what extent was this snow drought attributable to the climate change that has occurred since the pre-industrial period? We find that a snow drought this severe across the western United States was approximately 4.4 [95% CI: 2.6, 9.4] times more likely in the current climate than in the preindustrial period. In the Upper Colorado River Basin, the snow drought was approximately 14 times more likely [0.09, 4,300]. Given a projected increase in the frequency of snow droughts at least this severe in a moderately high emissions warming scenario, the lived experience of this event may help scientists, resource managers, and the public consider what western US snow might look like if greenhouse gas emissions are not aggressively reduced.
Particles of echovirus 18 open to release their genomes in vivo
Enteroviruses cause a broad spectrum of human diseases, ranging from mild respiratory or gastrointestinal infections to severe neurological disorders such as aseptic meningitis and encephalitis. Enterovirus cell entry involves receptor-mediated endocytosis followed by destabilizing rearrangements of the virus capsid that enable genome release. However, the mechanism of enterovirus genome release has not been visualized in infected cells. Here, we used cryoelectron tomography and microscopy to image echovirus 18 (E18) entry into host cells and its interaction with the neonatal Fc receptor (FcRn). 30 min postinfection, endosomes and cytoplasm contained empty capsids missing one or several pentamers of capsid proteins, providing evidence that in vivo E18 releases its genome through capsid opening. In vitro, FcRn binding induced the expulsion of pocket factors from hydrophobic pockets in VP1, priming the virus for uncoating. The cryoelectron microscopy reconstruction of genome-containing particles of E18 inside infected cells did not reveal pocket factors, indicating that receptor binding triggers the same priming process during infection. We did not detect activated particles in infected cells, suggesting that these intermediates are short-lived and rapidly release their genomes in vivo. Our results identify capsid opening as the in vivo mechanism of echovirus 18 genome release, providing structural evidence for a process previously only inferred from in vitro experiments.
Guanidine fuels rapid resurrection of desert cyanobacteria
In desert ecosystems, microbial activity is driven by brief hydration pulses but is severely limited by persistent nutrient scarcity. Cyanobacteria serve as essential pioneer photoautotrophs, maintaining biogeochemical cycles and ecosystem stability in these arid landscapes. However, their ability to quickly reactivate after rehydration is critically restricted by nitrogen availability. Although the nitrogen demand can be met later by biological nitrogen fixation, it is ineffective and irrelevant during early rehydration due to the high energy costs and delayed activation of nitrogenase, creating a critical metabolic bottleneck. Here we demonstrate that the desert cyanobacterium Nostoc flagelliforme overcomes this limitation by activating a previously overlooked guanidine carboxylase pathway, which sustains the rapid remobilization of internal nitrogen reserves upon rehydration. Transcriptional analysis using a luciferase reporter system reveals that pathway activity is tightly coupled to both hydration and nitrogen status. Disruption of the guanidine-specific riboswitch abolishes induction of the guanidine carboxylase pathway, underscoring its essential role in recovery from desiccation. Furthermore, comparative genomics reveals that the genes encoding this pathway, along with its cognate riboswitch, are widespread among terrestrial cyanobacteria. Phylogenetic analysis indicates they were acquired via horizontal gene transfer from nonphotosynthetic bacteria. Our findings establish an ecological role for guanidine in desert ecosystems and uncover a conserved mechanism that aids cyanobacterial resilience in xeric environments.
α-fluoro-β-alanine functions as a β-arrestin1-biased ligand of S1PR2 to upregulate DPD expression in cancer cells
α-fluoro-β-alanine (FBAL), a catabolite of the chemotherapeutic agent 5-fluorouracil (5-FU), has attracted significant attention due to its cardiotoxicity and neurotoxicity. However, its association with 5-FU resistance, a major obstacle in cancer treatment, has rarely been reported. In this study, FBAL was identified as a β-arrestin1-biased ligand of sphingosine 1-phosphate receptor 2 (S1PR2), which upregulates dihydropyrimidine dehydrogenase (DPD) expression and drives 5-FU resistance in colorectal cancer. Mechanistically, following exposure to FBAL, S1PR2, a G protein–coupled receptor (GPCR), is phosphorylated by recruiting G protein–coupled receptor kinase 6 (GRK6). Phosphorylated S1PR2 coupled with β-arrestin1, but not G proteins, to activate the MEK/ERK/AP-1 pathway and promote DPYD transcription. Ser343 was identified as the key phosphorylation site of S1PR2 using IP-MS analysis. This residue within the C-terminal domain mediates receptor interaction with β-arrestin-1 to activate the β-arrestin-1-dependent ERK pathway, as was confirmed in HCT116 S1PR2KO-ΔC cells and HCT116 S1PR2KO-S343A cells. In vivo , mice bearing orthotopic xenografts of HCT116 S1PR2KO-S343A cells exhibited significantly enhanced higher sensitivity to 5-FU treatment compared to those HCT116 S1PR2KO-WT cells following FBAL. Taken together, this study showed that exposure to FBAL induces S1PR2 phosphorylation at Ser343 within the C-terminal mediated by GRK6, activating the β-arrestin1-dependent ERK pathway to upregulate DPD expression. This study not only delineates a phosphorylation-dependent signaling pathway in chemoresistance but also establishes S1PR2 as a promising therapeutic target for overcoming 5-FU resistance in cancer.
Electrochemical lateral flow assay with ELISA-level performance for detecting plant diseases in East Africa
Cassava brown streak disease (CBSD) threatens food security for millions in East Africa, yet its control remains limited by the absence of field-deployable molecular diagnostics. Here, we introduce ELLA (Electrochemical Lateral flow assay with Linked Analytics), a battery-free, smartphone-powered electrochemical lateral flow assay that delivers enzyme-linked immunosorbent assay (ELISA)-grade protein detection directly in the field. ELLA integrates near-field communication, a single-chip potentiostat, metal-pin electrodes, and ferrocene-labeled nanoparticles into a fully disposable cassette, enabling quantitative immunoassays without optical instrumentation or centralized laboratory infrastructure. Validated across laboratory studies and extensive field trials in Tanzania, ELLA achieved 95% agreement with ELISA and 89% agreement with RT-qPCR, outperforming ELISA’s limit of detection while maintaining a material cost below US$1. By coupling molecular test results with cloud-linked analytics, we further trained DeepELLA, a smartphone-based image classification model that enables scalable surveillance from field-acquired leaf images. Together, these advances unify electrochemical sensing, digital connectivity, and AI-assisted interpretation, enabling portable, ELISA-level diagnostics for plant, environmental, and health monitoring in resource-limited regions.
One step forward, two steps back: A first look at the planetary health implications of the 2025–2030 Dietary Guidelines for Americans
Active linking through narratives facilitates associative inference
In daily life, we often draw inferences about novel associations from prior experiences. This ability, associative inference, is thought to be a key process by which memory guides future behavior. Prior studies have typically instructed participants to use narratives or mental imagery to aid memory of object associations. However, these studies have not explicitly tested the role of narratives, leaving an important question: how crucial are narratives in associative inference, and what role might they play? We used a modified associative inference paradigm to answer these questions. Our design factorially combined two factors during associative encoding: use of narratives, and explicitly linking the two objects. Participants separately learned AB and BC object pairs within ABC triads using four sets of instructions: i) generate narratives to link objects together, ii) generate narratives for objects separately, iii) compare perceptual properties of two objects, and iv) describe perceptual properties of objects individually. We tested participants’ ability to infer AC associations as a function of encoding strategy. Across two experiments, using narratives to actively link objects produced a robust associative memory advantage that persisted across 1-day delay and remained substantial under more stringent retrieval conditions. This benefit was not attributable to a simple linking effect or to surface-level linguistic similarity between stories. A follow-up experiment revealed that this benefit did not generalize to perceptual memory for individual objects; instead, perceptual encoding facilitated perceptual object memory. These results reveal that deep, extended encoding emphasizing either narrativity or perceptual processing can benefit different aspects of retrieval.
Race-conscious admissions algorithms and the law
In recent years, colleges and universities have begun to use machine learning (ML) systems to inform admissions decisions. Meanwhile, in the 2023 case Students for Fair Admissions, Inc. v. President and Fellows of Harvard College , the Supreme Court held that colleges and universities may not make admissions decisions “on the basis of race.” These parallel developments—the rise of ML in admissions and the fall of race-based affirmative action—will force educational institutions, and ultimately courts, to confront the difficult question of what it means for ML systems to differentiate “on the basis of race.” We begin by mapping the Students for Fair Admissions decision onto different uses of race in predictive AI. We distinguish between “first-order” and “second-order” race consciousness at both the training and predictive phases of machine learning, and we argue that each category of race consciousness raises distinct legal and normative issues. We go on to show that the Students for Fair Admissions decision potentially permits—and even endorses—certain forms of race consciousness. Our analysis is grounded in the observation that the process of developing ML-based systems enables policymakers to calibrate decision making algorithms much more precisely and explicitly in response to specific criticisms of race-conscious affirmative action.