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Correction to: Abstract Sun602: Lower Survival After Out-of- Hospital Cardiac Arrest in Older Females: The Joint Effect of Age and Sex

Transmission lowers US generation costs, but generator incentives are not aligned

The US electricity grid is rapidly evolving with the entry of low-cost renewable electricity. As a result, new supply is not spatially matched to demand, and the transmission network has become more strained. Better market integration could thus lower US generation costs. We document that eliminating interregional constraints would have reduced electricity generation costs across the lower US 48 states by $5.8 to 7.1 billion in 2022 and $3.4 to 5.0 billion in 2023. But market integration creates winners and losers among generation companies, and we show that producers in some regions have incentives to delay or block grid integration despite the overall system benefits.

Myocardial Recovery With Mechanical Circulatory Support Is Linked to Alternative Splicing and Subcellular Localization of CAMK2D

BACKGROUND: Cardiac reverse remodeling occurs in a small subset of patients with heart failure treated with guideline-directed therapies. This phenomenon, which is defined by reduced ventricular dilatation and improved systolic function, is most common in patients receiving left ventricular assist device (LVAD) therapy. Identifying therapeutic targets for initiating reverse remodeling is an area of great clinical interest, because these patients experience improved outcomes and quality of life. Targets may be discovered among the unique molecular changes associated with LVAD-induced partial myocardial functional recovery; however, the mechanisms underlying this favorable response are incompletely understood. METHODS: To identify molecular signatures of recovery, we studied paired pre-LVAD and post-LVAD myocardial samples from patients with heart failure who received LVAD as a bridge to transplant (10 responders and 9 nonresponders) and controls without heart failure. We performed bulk RNA sequencing, tandem mass tag quantitative proteomics, and tandem mass tag quantitative phosphoproteomics with follow-up mechanistic and functional investigations in primary rat cardiomyocytes and human engineered heart tissues. RESULTS: Alternative RNA splicing was the leading pathway associated with a favorable response to LVAD. Responders had increased RNA splicing factor expression and unique gene splice variant expression compared with nonresponders. Alternative splicing of CAMK2D (calcium/calmodulin-dependent protein kinase 2δ) was a particularly strong predictor of recovery; increased inclusion of exon 14, which encodes the nuclear splice variant CAMK2D-B, was inversely correlated with functional recovery. Nonresponders also displayed hyperphosphorylation near the nuclear localization signal in CAMK2D-B. Investigations in primary cardiomyocytes and subcellular organelle fractions from the human hearts revealed that nuclear localization signal phosphorylation prevented adrenergic stress-dependent nuclear targeting of CAMK2D-B. Expression of a cytoplasm-restricted CAMK2D-B uniquely remodeled the phosphoproteome of primary rat cardiomyocytes compared with a nuclear-competent version and blunted calcium transients in engineered heart tissues. CONCLUSIONS: This is the first study to integrate transcriptome, alternative transcriptome, proteome, and phosphoproteome analyses of heart samples from LVAD-supported patients to investigate myocardial recovery. We identified that increased expression and phosphorylation of the nuclear CAMK2D splice variant predicted poor outcomes. This phosphorylation restricted CAMK2D-B to the cytosol, leading to impaired cardiomyocyte calcium handling. These findings suggest that LVAD nonresponder patients may benefit from therapies that modulate subcellular localization of CAMK2D or inhibit its activity.

Bilingual language processing relies on shared semantic representations that are modulated by each language

Billions of people throughout the world are bilingual, and they can extract meaning from multiple languages. While some evidence suggests that there is a shared system in the human brain for processing semantic information from native and non-native languages, other evidence suggests that semantic processing is language specific. We conducted a study to determine how semantic information for different languages is represented in the brains of bilinguals. Functional magnetic resonance imaging (fMRI) was used to record brain responses while participants read several hours of natural narratives in their native (Chinese) and non-native (English) languages. These data were then used to compare semantic representations between the two languages. We find that semantic representations are largely shared between languages, while there are fine-grained differences in the representation of some semantic categories across languages. These results reconcile current competing theories of bilingual language processing.

2026 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association

BACKGROUND: The American Heart Association annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and cardiovascular-kidney-metabolic syndrome) that contribute to cardiovascular health. The 2026 Heart Disease and Stroke Statistics Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistics Update with review of published literature through the year before writing. The 2026 Statistics Update is the product of a full year’s worth of effort in 2025 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year’s edition includes a new chapter on cardiovascular-kidney-metabolic syndrome, as well as an expanded chapter on tobacco and nicotine use and exposure. RESULTS: Each of the chapters in the Statistics Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistics Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Understanding human metacontrol and its pathologies using deep neural networks

Error monitoring is crucial for inferring how controllable an environment is, and thus for estimating the value of control processes (metacontrol). In this study, we use computational simulations with deep neural networks to investigate its behavioral and neural correlates. We trained both humans and deep reinforcement learning (RL) agents to perform a reward-guided learning task that required adaptation to changes in action controllability. Deep RL agents could only solve the task when designed to explicitly predict action prediction errors that fire in the medial prefrontal cortex. When trained this way, they displayed signatures of metacontrol that closely resembled those observed in humans. Moreover, when deep RL agents were trained to over- or underestimate controllability, they developed behavioral pathologies partially matching those of humans who reported depressive, anxious, or compulsive traits on transdiagnostic questionnaires. These findings open up avenues for studying metacontrol using deep neural networks.

Response by de Veld et al to Letter Regarding Article, “Device-Related Complications in Transvenous Versus Subcutaneous Defibrillator Therapy During Long-Term Follow-Up: The PRAETORIAN-XL Trial”

Human oncogenic herpesvirus latency proteins activate NEK2 to promote chromosomal instability and tumorigenesis

Never in mitosis A (NIMA)-related kinase 2 (NEK2) is a serine/threonine kinase that plays a crucial role in cell cycle regulation and is frequently induced across multiple cancer types, where its elevated levels are associated with poor prognosis. Epstein–Barr virus (EBV) and Kaposi’s sarcoma–associated herpesvirus (KSHV), both known to drive various malignancies, were observed to induce NEK2 expression during both primary infection and latent phases of infection. Increased NEK2 expression contributes to chromosomal instability by promoting nondisjunction, leading to a rise in aneuploid cell populations and fostering uncontrolled cell proliferation. Mechanistically, EBV latent protein EBNA2 and KSHV latent antigen LANA were identified as principal regulators of NEK2 upregulation, acting through modulation of RBP-Jκ activities at the NEK2 promoter region. Additionally, we demonstrated that targeting NEK2 impaired EBV- and KSHV-mediated tumor progression, highlighting its potential as a critical driver of virus-induced oncogenesis and a promising therapeutic target.

Response by Shi and Chen to Letter Regarding Article, “Partnership Model of Regionalized Care for Congenital Heart Disease in Resource-Limited Settings: Results From the ASSIST Project”

School shootings and the strategic contributions of gun policy PACs in US House elections

The American public consistently supports stricter gun laws. We show that the gun lobby is most concerned that this support will translate into federal legislative action when fatal school shootings occur. Leveraging a dataset of political action committee (PAC) contributions and school shootings, we implement a staggered difference-in-differences design to estimate the causal effect of fatal school shootings on contributions to House candidates. We find progun Political Action Committees increase contributions by 31% to candidates in districts with fatal school shootings, and 20% for gun safety PACs. Neither show any significant response to nonfatal school shootings or mass shootings. The temporal pattern also reveals strategic behavior: For both progun and gun safety PACs, contribution spikes emerge in the wake of fatal school shootings, with effects dramatically amplified as Election Day approaches; when a shooting occurs within two months of Election Day, contributions from progun PACs increase by 2,820% while gun safety PAC contributions increase by 917%. These effects are concentrated in competitive districts ( ≤ 5% margins) where the two-sided surge in contributions offsets any measurable electoral impact. These results provide robust evidence that PACs strategically deploy contributions after school shootings, with the magnitude and timing suggesting a deliberate mobilization to advance its agenda. Our findings underscore a gap in democratic accountability: While public opinion should drive policy change, campaign contributions are wielded to blunt electoral responsiveness, providing insight into the inability of Congress to adopt broadly supported gun safety measures.

Aerophilic debubbling

Gas bubbles frequently accumulate at liquid interfaces, compromising throughput, selectivity, and stability across scales from microfluidics to natural ecosystems. Here, we experimentally show that highly permeable aerophilic membranes placed on a liquid–air interface annihilate bubbles within milliseconds. This ultrafast regime appears only above a critical permeability threshold, where the flow departs from classical Darcy-driven dynamics in micropores. We quantitatively characterize this aerophilicity-mediated debubbling process by examining local interactions at the scale of single bubbles approaching the membrane and identify three asymptotic evacuation regimes, the physics of which we capture through simple scaling laws.

The Nemp1–Nesprin complex mediates cellular responses to matrix mechanics

Nuclear Envelope Membrane Protein 1 (NEMP1) is crucial for metazoan fertility; loss of Nemp1 causes death of primordial oocytes that reside in the mechanically challenging ovarian cortex. Here, we show that softening the ovary rescues oocyte loss and restores fertility in N emp1 knockout (KO) mice. In cell culture, NEMP1 depletion on stiff substrates leads to death, while cells remain viable on soft substrates. We further show that NEMP1 regulates YAP nuclear translocation, essential for mechanotransduction. Mechanistically, Nemp1-depleted cells on stiff substrates or subjected to stretching exhibit reduced nuclear YAP localization, and expressing nuclear YAP5SA restores cell viability. Loss of NEMP1 disrupts actin organization. Inducing actin polymerization partially rescues nuclear YAP, indicating a role for F-actin in NEMP1 mediated mechanotransduction. NEMP1 forms a complex with NESPRIN’s Klarsicht, Anchorage (ANC)-1, Syne Homology (KASH) domain, strengthening the actin cytoskeleton to withstand mechanical forces, independent of SUN proteins. Thus, the Nemp1–Nesprin complex supports a mechanosensitive pathway parallel to the LINC complex, enabling cellular response to mechanical stress in vitro and in vivo.

Multispecies analysis of social effects on same-sex sexual behavior challenges mistaken identity hypotheses in insects

Same-sex sexual behavior (SSB) in insects has historically been considered a byproduct of sex recognition failure, or “mistaken identity,” and consideration of other hypotheses lags behind that of vertebrates where it is often thought to adaptively mitigate aggressive interactions. Comparative analyses to help disentangle the functions of insect SSB are lacking. To address this, we quantified male–male interactions in controlled trials across eight North American field cricket species ( Gryllus spp.). While limited taxonomic sampling precluded a formal phylogenetic comparative analysis, we were able to assess variation across species with structural equation models. Using this technique, we distinguished focal from partner influences and evaluated support for mistaken identity vs. other models of SSB. SSB expression varied extensively across species. It was always associated with reduced aggression, but the strength of this association and the balance of focal vs. partner effects varied. Temporal analysis of behavioral interactions showed that males exhibited SSB while able to discern the sex of their partner. These findings, along with observations of a previously undescribed sexual behavior not seen in different-sex interactions, imply a history of adaptive evolution inconsistent with mistaken identity SSB.

Uniqueness and predictability in evolution and the history of mollusks

Evolution is a historical process whose trajectories are determined in part by the introduction of new phenotypes. Although most phenotypes have evolved repeatedly within and among clades of organisms, others are unique and apparently originated only once, and even the earliest occurrences of repeated traits were unique for their time. To investigate the timing and circumstances of these unique events, we compiled adult skeletal phenotypes with single origins and first occurrences of repeated traits as recorded in the fossil record in the phylum Mollusca. Of the 24 unique and 72 repeated traits we considered, 46 (48%) originated during the first 96 m.y. of molluscan history (frequency 1 per 2.1 m.y.) and only 50 in the 444 m.y. since then (frequency 1 per 8.9 m.y.), with secondary peaks of frequency in the Triassic and Cenozoic. We interpret this finding to mean that molluscan evolutionary history has become substantially more predictable over time despite increasing diversity. Expansions of the phylum from its ancestral marine epifaunal benthic environment to other habitats including fresh water and dry land were generally not associated with unique or earliest occurrences of repeated phenotypes. Most of the innovations enhanced individual defense or activity and were therefore honed by interactions within and among species, although it remains possible that they originated in temporarily permissive conditions in which genetic and other constraints were relaxed.

Correction for Liao et al., Noncanonical genetic markers resolve the pre-GOE emergence of aerobic bacteria in Earth’s history

Reply to Kardosh and Sklar: Prioritizing domain-general explanations of misperception

Reactive oxygen species–resistant ultrastable super-resolution DNA framework dots

Nanoconfinement as observed in natural (e.g. green fluorescent protein, GFP) or artificial (metal-organic or covalent organic frameworks) systems effectively modulates chemical and physical properties of encapsulated molecules for various photonic, electronic, or catalytic applications. Inspired by GFP’s barrel-like peptide scaffold, which stabilizes the chromophore within a confined space, here we develop photobleaching-resistant super-resolution DNA framework (SDF) dots that enables programmable confinement of various types of fluorophores within the inner cavity resembling GFP. We find that SDF dots are resistant to reactive oxygen species-induced photobleaching due to the shielding effects of DNA frameworks. SDF dots with four fluorophores labeling inside of the cavity leads to ~1.8-fold enhancement in photostability compared to the corner labeling, whereas ~50-fold enhancement compared to single fluorophore labeled on double-stranded DNA. These ultrastable SDF dots are readily adaptable for super-resolution imaging including stimulated emission depletion (STED) and structured illumination microscopy (SIM) imaging. We realize STED imaging of live cell membranes over 30 min. We further construct ultrastable super-resolution SIM barcodes that can distinguish eighteen colored barcodes with a spatial resolution of ~70 nm. This strategy provides a versatile platform for engineering ultrastable fluorescent probes for advancing super-resolution imaging and single-particle tracking in biophysics and biomedical research.

Correction for Camacho et al., Coral species from another ocean may be the only way to save Caribbean reefs

Glycosylation of glyphosate drives residue reduction and herbicide tolerance in rice

Glyphosate is the most widely used herbicide globally, especially due to the extensive cultivation of genetically modified glyphosate-resistant crops. However, its intensive application has raised public concerns about the risks to food safety and human health. Identifying enzymes capable of metabolizing glyphosate in plants represents an ideal strategy for addressing this issue, but few are known. Here, we identified the rice variety Kitaake with natural tolerance to glyphosate and demonstrated that this tolerance is driven by glyphosate glycosylation metabolism. Seven up-regulated UDP-dependent glycosyltransferase ( UGT ) genes associated with glyphosate tolerance were identified in Kitaake. Molecular-docking analysis indicated that these UGT proteins have moderate binding affinity for glyphosate. Among these, a deletion of an adenine at position –803 in the promoter region of GLYPHOSATE RESPONSIVE GLYCOSYLTRANSFERASE 1 ( GRGT1 ) enhances its expression in Kitaake. GRGT1 localizes to the endoplasmic reticulum and catalyzes glyphosate glycosylation both in vivo and in vitro. Rice lines complemented with GRGT1–GFP rescue the inability of grgt1 knockout mutants to produce glycosylated glyphosate derivatives. Overexpression of GRGT1 in the susceptible Nipponbare cultivar confers glyphosate tolerance by up-regulating glyphosate metabolism to produce glycosylated glyphosate derivatives M329, M331, and M345. This provides a strategy for developing herbicide-tolerant crops, but also offers a potential approach to consequently reduce glyphosate residues in crops.

Humans 40,000 y ago developed a system of conventional signs

As humans, we store and share information. This allows us to distribute knowledge necessary for survival and to coordinate large groups. Our hominin ancestors harnessed the surfaces of mobile artifacts and cave walls as information carriers since the Paleolithic time period. Theories abound as to the meaning and function of these Paleolithic signs. However, very little is known about their basic, measurable properties. We here analyze a corpus of more than 200 mobile objects of a 43,000 to 34,000 y old Aurignacian culture—associated with the first modern humans to settle in Central Europe. These objects are adorned with several thousand geometric signs. We apply classification algorithms and statistical models to capture their quantitative properties. First, our analyses illustrate that these sign sequences are clearly distinguishable from modern day writing. Second, however, their statistical properties are comparable to sign sequences on the earliest protocuneiform tablets. Third, Paleolithic signs were systematically applied to yield higher information density on certain types of objects, e.g. ivory figurines compared to tools. These results cannot be taken to strictly prove that Aurignacian sign sequences encoded numero-ideographic information as in the case of protocuneiform. However, they prove that the first hunter-gatherers arriving in Europe already applied sign sequences of comparable complexity in a deliberate, systematic, and conventional manner—several ten thousand years before the advent of genuine writing.