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Chelation-induced anti-Ostwald ripening: Ultrafine bismuth nanocrystals for ultrastable aqueous sodium storage

Aqueous sodium-ion batteries (ASIBs) are gaining attention for their inherent safety and the use of abundant sodium resources. Bismuth (Bi) anode, with its high theoretical capacity and low cost, enhances the performance and competitiveness of ASIBs in energy storage applications. However, as a conversion-type material, Bi inevitably undergoes dramatic volume changes during cycling, limiting the structural stability and calendar life of the electrode. Herein, we present a Bi-carbon composite electrode with ultrafine Bi nanocrystals (< 10 nm) uniformly integrated into nitrogen-doped carbon nanofibers (UF Bi@NCF). Despite Bi’s low melting point (271 °C), Ostwald ripening of metallic Bi during carbonization (750 °C) is effectively suppressed by incorporating polyacrylic acid as a chelating polymer in the electrospun Bi(III)/polyacrylonitrile precursor solutions. The high dispersity of Bi nanocrystals at elevated temperature is attributed to the strong coordination and electrostatic interactions between carboxyl groups and Bi 3+ . This structural refinement significantly reduces localized stress concentrations during sodiation/desodiation. The UF Bi@NCF anode demonstrates a reversible capacity of 237.5 mAh g −1 at 0.5 C, and negligible capacity decay even after 5,700 cycles at an extremely high current rate of 20 C for ASIBs. These findings highlight the potential of the anti-Ostwald ripening effect in enhancing the stability and performance of metal-carbon composite electrodes, providing valuable insights into the design of advanced materials for next-generation aqueous batteries.

Characterizing population-level changes in human behavior during the COVID-19 pandemic in the United States

The transmission of communicable diseases in human populations is known to be modulated by behavioral patterns. However, detailed characterizations of how population-level behaviors change over time during multiple disease outbreaks and spatial resolutions are still not widely available. We used data from 431,211 survey responses collected in the United States, between April 2020 and June 2022, to provide a description of how human behaviors fluctuated during the first 2 y of the COVID-19 pandemic. Our analysis suggests that at the national and state levels, people’s adherence to recommendations to avoid contact with others (a preventive behavior) was highest early in the pandemic but gradually—and linearly—decreased over time. Importantly, during periods of intense COVID-19 mortality, adaption to preventive behaviors increased—despite the overall temporal decrease. These spatial-temporal characterizations help improve our understanding of the bidirectional feedback loop between outbreak severity and human behavior. Our findings should benefit both computational modeling teams developing methodologies to predict the dynamics of future epidemics and policymakers designing strategies to mitigate the effects of future disease outbreaks.

Learning stochastic processes with intrinsic noise from cross-sectional biological data

Inferring dynamical models from data continues to be a significant challenge in computational biology, especially given the stochastic nature of many biological processes. We explore a common scenario in omics, where statistically independent cross-sectional samples are available at a few time points, and the goal is to infer the underlying diffusion process that generated the data. Existing inference approaches often simplify or ignore noise intrinsic to the system, compromising accuracy for the sake of optimization ease. We circumvent this compromise by inferring the phase-space probability flow that shares the same time-dependent marginal distributions as the underlying stochastic process. Our approach, probability flow inference (PFI), disentangles force from intrinsic stochasticity while retaining the algorithmic ease of ordinary differential equation (ODE) inference. Analytically, we prove that for Ornstein–Uhlenbeck processes the regularized PFI formalism yields a unique solution in the limit of well-sampled distributions. In practical applications, we show that PFI enables accurate parameter and force estimation in high-dimensional stochastic reaction networks, and that it allows inference of cell differentiation dynamics with molecular noise, outperforming state-of-the-art approaches.

Cystic fibrosis: Correction of a fatal disease

The 2025 Lasker~DeBakey Clinical Medical Research Award has been given to Michael Welsh, Jesús (Tito) González, and Paul Negulescu for their key roles in developing a novel treatment for cystic fibrosis (CF)—a three-drug combination that saves the lives of people with this lethal genetic disease [D. Keating et al. , N. Engl. J. Med. 379, 1612–1620 (2018)]. The disease is caused by mutations that disrupt the function of a gene known as CF Transmembrane Conductance Regulator which encodes a chloride channel expressed in epithelial cells including the lung. Collectively the three recipients were responsible for the development of novel high-throughput drug screens that led to the development of the new drugs. Welsh is a pulmonologist who played a key role in understanding the physiology and pathophysiology of the disease. González is a physical organic chemist who developed a novel technology that enabled robust high-throughput screens for drugs that correct the channel defects. Negulescu led a group of extremely talented biologists, chemists, and physicians who built on these advances to develop novel three-drug combinations that have miraculous benefits for the majority of afflicted patients. This advance represents a true milestone in medicine and fulfills a dream of research scientists and families—the conversion of a fatal disease into a fully treatable one. It is also a stunning example of the power of medical research to save people’s lives.

Emergent depth-mechanosensing of epithelial collectives regulates cell clustering and dispersal on layered matrices

During wound healing, tumor growth, and organ formation, epithelial cells migrate and cluster in layered tissue environments. Although cellular mechanosensing of adhered extracellular matrices is now well recognized, it is unclear how deeply cells sense through distant matrix layers. Since single cells can mechanosense stiff basal surfaces through soft hydrogels of <10 μm thickness, here we ask whether cellular collectives can perform such “depth-mechanosensing” through thicker matrix layers. Using a collagen-polyacrylamide double-layer hydrogel, we found that epithelial cell collectives can mechanosense basal substrates at a depth of >100 μm, assessed by cell clustering and collagen deformation. On collagen layers with stiffer basal substrates, cells initially migrate slower while performing higher collagen deformation and stiffening, resulting in reduced dispersal of epithelial clusters. These processes occur in two broad phases: cellular clustering and dynamic collagen deformation, followed by cell migration and dispersal. Using a cell-populated collagen-polyacrylamide computational model, we show that stiffer basal substrates enable higher collagen deformation, which in turn extends the clustering phase of epithelial cells and reduces their dispersal. Disruption of collective collagen deformation, by either α-catenin depletion or myosin-II inhibition, disables the depth-mechanosensitive differences in epithelial responses between soft and stiff basal substrates. These findings suggest that depth-mechanosensing is an emergent property that arises from collective collagen deformation caused by epithelial cell clusters. This work broadens the conventional understanding of epithelial mechanosensing from immediate surfaces to underlying basal matrices, providing insights relevant to tissue contexts with layers of varying stiffness, such as wound healing and tumor invasion.

Structure of a polymorphic repeat at the <i>CACNA1C</i> schizophrenia locus

Genetic variation within intron 3 of the CACNA1C calcium channel gene is associated with schizophrenia and other neuropsychiatric disorders, but analysis of the causal variants and their effect is complicated by a nearby variable-number tandem repeat (VNTR). Here, we explored the structure and population variability of the CACNA1C intron 3 VNTR using 155 long-read genome assemblies from 78 diverse individuals. Based on sequence differences among repeat units, we clustered individual sequences into 7 VNTR structural alleles called Types. Three Types were related through large duplications, but the other Types diverged much earlier such that only 12 repeat units at the 5′ end of the VNTR were shared across most Types. The most diverged Types were rare and present only in individuals with African ancestry, but a multiallelic structural polymorphism was present across populations at different frequencies, consistent with expansion of the VNTR preceding the emergence of early hominins. We demonstrated that this polymorphism was in complete linkage disequilibrium with fine-mapped schizophrenia variants from genome-wide association studies (GWAS) and that this risk haplotype was associated with decreased CACNA1C gene expression in the brain. Our work suggests that sequence variation within a human-specific VNTR affects gene expression and provides a detailed characterization of new alleles at a flagship neuropsychiatric GWAS locus.

The Lasker~Koshland Special Achievement Award in Medical Science awarded to Lucy Shapiro

Scientists can contribute to society in numerous ways. Some scientists discover new biological principles and found entirely new fields. Some scientists are inspiring mentors and create the next generation of inclusive lab leaders. Some scientists are entrepreneurs who develop clinically effective therapeutics. Some scientists are trusted advisors to government and pharmaceutical companies. Some scientists are visionary institutional leaders who build new departments. From this menu of activities, most scientists select two or at most three. It is exceedingly rare for a single scientist to excel in all of these areas, consistently, over the course of a career. Lucy Shapiro is this extraordinary scientist. She founded the field of bacterial cell biology and trained the next generation of microbiologists, launched biotech companies to develop new antifungal drugs, served as an unofficial advisor to two presidential administrations and numerous companies, institutions, and foundations, and built and led successful academic departments. The 2025 Lasker~Koshland Special Achievement Award in Medical Science is awarded to Lucy Shapiro “for a 55-y career in biomedical science—honored for discovering how bacteria coordinate their genetic logic in time and space to generate distinct daughter cells; for founding Stanford’s distinguished Department of Developmental Biology; and for exemplary leadership at the national level.”

Extracellular salt bridge networks around S4 implicated in HCN channel gating and heart disease

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a voltage-gated cation channel that plays a crucial role in regulating cellular excitability, especially in cardiac pacemaker cells and neurons. Its dysregulation is linked to heart diseases such as bradycardia and neurological disorders such as epilepsy, Parkinson’s disease, and neuropathic pain. Structural and functional studies have revealed that the S4 voltage sensor of the HCN channel moves downward during hyperpolarization. Recent structural studies of HCN channels have shown that the extracellular portion of the S4 segment is approximately three helical turns longer than that of voltage-gated K + (Kv) channels. However, whether this extended extracellular part of S4 plays a functional role in gating is still unknown. In this study, utilizing the available HCN4 channel structures, we examined the formation of salt bridges in the extracellular part of S4 with the S5 segment and the S1-S2 linker. Results from charge-swapped mutants and double cysteine mutants suggested that sequential, stepwise salt bridge formation involving the extracellular positively charged amino acids of S4 plays a role in the voltage-dependent gating of HCN channels. Furthermore, we applied voltage clamp fluorometry to confirm that the extracellular salt bridge network affects the S4 movement. This extracellular S4 portion includes disease-related arginine residues, R375 and R378. Our results suggest that disruption of salt bridge formation may perturb the smooth transition of S4 movement and cause HCN channel dysfunction.

Directed evolution of a plant Rubisco chaperone with altered client recognition

Improving the Calvin–Benson–Bassham cycle enzyme Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) has the potential to increase crop productivity. However, the selectivity of the chaperones mediating Rubisco assembly in vascular plants toward their cognate Rubisco presents a substantive roadblock to both Rubisco protein engineering and transgenic expression of heterologous Rubisco orthologs, both of which necessitate changes to the Rubisco sequence. Here, we ask whether a plant Rubisco chaperone can be reprogrammed by directed evolution to accommodate a nonnative client. We developed a selection strategy to assess Rubisco assembly factor activity in high-throughput and used this selection to identify mutants of the chaperone Raf1 from Arabidopsis thaliana ( At Raf1) that assemble Nicotiana tabacum Rubisco, for which wild-type At Raf1 has minimal activity. We show that directed evolution can generate At Raf1 variants that enable significantly increased N. tabacum Rubisco assembly compared to wild-type At Raf1. Evaluation of evolved At Raf1s indicates that they retain the ability to assemble their native client and can assemble other dicot Rubisco orthologs that they were not evolved to recognize. This work may provide a strategy for addressing the constraints chaperone selectivity impose upon Rubisco-centric efforts to improve plant photosynthesis.

Adaptation of seed dormancy to maternal climate occurs via intergenerational transport of abscisic acid

How or whether organisms can inherit parental adaptations to the prevailing environment is a major topic in biology. In plants, seed traits such as size, yield, and dormancy are all affected by the environment during reproduction, but whether developing progeny sense temperature within the fruit or whether seasonal climate information is inherited intergenerationally from the parents remains unclear. In this study, we use intergenerational single-nucleus omics to understand the mechanisms underlying the effects of seasonal temperature changes in fruits containing developing seeds of the next generation. We show that the sensing of temperature takes place specifically in maternal fruit tissues and that mothers preadapt their progeny to maternal temperature through the intergenerational flux of the hormone ABA to the zygote itself where it is sensed to affect dormancy. We conclude that mothers can control filial traits via direct transfer of hormones to progeny and propose that this is an important mechanism by which populations can rapidly adapt to environmental change.

ApoD mediates age-associated increase in vulnerability to influenza virus infection

Influenza A virus (IAV) infection causes significantly greater morbidity and mortality in the elderly population, but the molecular mechanisms in the aging process responsible for severe infection remain unclear. In this study, we found that increased severity in IAV infection and reduced innate immune response correlated with extensive mitophagy in senescent human cells and in the lung of aged mice. Apolipoprotein D (ApoD) was identified as strongly elevated in the lungs and sera of aged human (&gt;65 y old) and mouse (&gt;21 mo old). ApoD was able to localize to mitochondria and interact, through its WXXI motif in the LC3B-Interacting Region domain, with LC3B to trigger mitophagy during IAV infection, in a PINK1 pathway independent manner, which attenuated type I interferon response and promoted virus replication. ApoD deficiency, on the other hand, protected older mice from severe influenza and improved survival. Likewise, depletion of senescent cells by ABT-263, a senolytic compound, in aged mice lowered ApoD level and restored innate immune antiviral response, limiting virus propagation and associated pulmonary damage. Thus, age-induced ApoD drives IAV-mediated mitophagy, and promotes virus replication and infection severity, and is therefore a promising target for inhibition to improve disease outcome in older patients.

Making sense of low-complexity domains: The 2025 Lasker Basic Science Award

Up to 10 to 20% of the proteome contains regions with much lower amino acid diversity than would be expected by chance. This year’s Lasker Basic Science Award is given to Steven McKnight and Dirk Görlich for their pioneering work on such low-complexity domains (LCDs). They showed, using a variety of elegant approaches, that such LCDs can form homotypic and heterotypic interactions that lead to reversible phase separations in cells. These phase separations, which in the laboratory manifest as hydrogels and in cells as membrane free structures (liquid condensates) such as P bodies and stress granules, form hubs for molecular processes such as transcription and messenger RNA (mRNA) splicing and also underlie the selectivity of nuclear pore complexes (NPCs), which act a barriers to large molecules unless they are escorted by specific LCD containing nuclear transporters that interact with LCD containing nucleoporins within NPC channels. Naturally occurring LCD mutations linked to neurodegeneration and other diseases cause the formation of irreversible (rather than reversible) LCD polymers, resulting in insoluble, amyloid-like, fibrils, underscoring the critical importance of these domains.

Binding of <i>Fusobacterium nucleatum</i> autotransporter adhesin CbpF to human CEACAM1 and CEACAM5: A Velcro model for bacterium adhesion

In eukaryotic systems, three major types of cell junctions have been well characterized. While bacterial adhesion mechanisms also exhibit remarkable diversity, the molecular processes that regulate the dynamic modulation of binding strength between elongated bacterial cells and host cells remain poorly understood. Fusobacterium nucleatum ( F. nucleatum ) utilizes the surface adhesin CbpF to interact with the highly expressed host receptors CEACAM1 and CEACAM5 on cancer cells to facilitate tumor colonization. By elucidating the structural details of CbpF binding to human CEACAM1/CEACAM5 receptors, and through mechanistic investigations, we identified that the prominent EFNGQYQ loop on CbpF and the key Q78 residue of CEACAM1/CEACAM5 constitute the molecular linchpin of this pathogen–host interface. Furthermore, we found a distinct type of binding particle and proposed a Velcro-like adhesion model. In this model, CbpF mediates robust attachment through the simultaneous interaction of multiple binding sites, akin to the interlocking mechanism of Velcro. This multivalent interaction allows F. nucleatum to dynamically switch between firm anchoring and easy detachment, adapting to varying physiological microenvironments. Our study elucidates the dynamic modulation of bacterial adhesion strength and lays the foundation for developing therapeutic interventions to disrupt the bacterium–host interface.

Correction for Sharma and DiVincenzo, <i>g</i> -factor symmetry and topology in semiconductor band states

The RecBC complex protects single-stranded DNA gaps during lesion bypass

Following encounter with an unrepaired DNA lesion, replication is halted and can restart downstream of the lesion leading to the formation of a single-stranded DNA (ssDNA) gap. To complete replication, this ssDNA gap is filled in by one of the two lesion tolerance pathways: the error-prone Translesion Synthesis (TLS) or the error-free Homology Directed Gap Repair (HDGR). In the present work, we evidence a role for the RecBC complex distinct from its canonical function in homologous recombination at DNA double strand breaks. We show that upon lesion encounter RecBC (independently of its catalytic activity and of the RecD subunit) is required to protect the nascent DNA in order to promote efficient lesion bypass. In the absence of RecBC, our data indicate that the nuclease ExoI can access and degrade the nascent DNA, affecting both TLS and HDGR mechanisms. We show that the recruitment of RecBC becomes particularly important at strong blocking lesions, when postreplicative ssDNA gaps persist and are covered by the ssDNA binding proteins. This protective role of RecBC is reminiscent of the role of BRCA2 in protecting the nascent DNA in human cells, highlighting once again the evolutionary conservation of DNA replication mechanisms across all living organisms.

Experimentally enhancing dispersal reveals the outsized importance of transient dynamics in a fluctuating environment

The size and composition of local species pools are, in part, determined by past dispersal events. Predicting how communities respond to future disturbances, such as fluctuating environmental conditions, requires knowledge of such histories. We assessed the influence of a historical dispersal event on community assembly by simulating various scales of dispersal for 240 serpentine annual plant communities that experienced a large shift from drought to high rainfall conditions over three years. We collected, aggregated, and redistributed the aboveground seed bank (i.e., all loose seed present on the soil surface before the growing season initiates) from 30 sites across five nested spatial scales ( ∼ 1 m, 5 m, 100 m, 5 km, and 10 km), and annually censused communities to identify change in community structure among dispersal scales and over time. Our one-time dispersal manipulation diversified aboveground seed banks, provided insurance against temporal variability at intermediate and large dispersal distances ( ≥ 100 m), and even supported community reassembly toward a new compositional state at the 10 km scale. We also found evidence that temporal lags directed community responses to environmental fluctuations, preventing rare species extirpations and providing subordinate species discrete windows of time to supplement their seed banks. Our results reveal a joint spatiotemporal equilibrium in this system where dispersal through space interacts with temporal fluctuations in climate to support species’ persistence via aboveground seed banks. This experiment underscores the importance of dispersal for diversity maintenance in this global biodiversity hotspot, where the magnitude and frequency of future climate fluctuations is uncertain.

Correction for Gibbons et al., Motivational trade-offs and modulation of nociception in bumblebees

Replication stress–induced nuclear hypertrophy alters chromatin topology and impacts cancer cell fitness

Microscopic examination of biopsy tissues remains essential for cancer diagnosis, despite advancements in sequencing technologies. Alterations in nuclear size or the nuclear-to-cytoplasmic ratio are hallmark features of cancer cells and often correlate with disease progression. However, the mechanisms underlying nuclear size abnormalities and their impact on tumor progression remain unclear. In this study, we demonstrate that nuclear hypertrophy occurs in response to enhanced DNA replication stress, a key characteristic of cancer cells. Increased actin polymerization within the nucleus appears to be the primary mechanism driving nuclear hypertrophy downstream of the ATR-CHEK1 pathway. Replication stress–induced nuclear hypertrophy alters transcriptomic profiles and chromatin topology, while reducing the migratory and metastatic capacity of cancer cells. In addition, nuclear hypertrophy in cancer cells is associated with increased infiltration of antitumor immune cells. Our findings suggest that cell-autonomous effects of nuclear hypertrophy do not promote cellular fitness or aggressive characteristics in cancer cells. This may explain why cells with nuclear hypertrophy are not positively selected and persist as a subpopulation during tumor progression and metastasis. Furthermore, the link between replication stress and nuclear hypertrophy provides insights into why enlarged nuclei are consistently observed in advanced-stage cancers.

The redox rhythm gates immune-induced cell death distinctly from the genetic clock

Organisms use circadian clocks to synchronize physiological processes to anticipate the Earth’s day-night cycles and regulate responses to environmental signals to gain competitive advantage. While divergent genetic clocks have been studied extensively in bacteria, fungi, plants, and animals, an ancient conserved circadian redox rhythm has been recently reported. However, its biological function and physiological outputs remain elusive. Here, we uncovered the coexistence of redox and genetic rhythms with distinct period lengths and transcriptional targets through concurrent metabolic and transcriptional time-course measurements in an Arabidopsis long-period clock mutant. Analysis of the target genes indicated regulation of the immune-induced programmed cell death (PCD) by the redox rhythm. Moreover, this time-of-day-sensitive PCD was eliminated by redox perturbations and by blocking the signaling pathway of the plant defense hormones jasmonic acid/ethylene, while remaining intact in genetic clock-defective backgrounds. This study shows that compared to robust genetic clocks, the more sensitive circadian redox rhythm serves as a signaling hub in regulating incidental energy-intensive processes, such as immune-induced PCD involving reprogramming of chloroplast and mitochondria activities, to provide organisms a flexible strategy to mitigate metabolic overload during stress responses.

Bridging feeling and motion: Insula–premotor dynamics in the processing of action vitality forms

Typically, people perform actions in a valenced—positive or negative—way, depending on their attitudes or desires. These forms of action are named vitality forms (VFs). While it is well established that action goals are mediated by a parieto-frontal network, less is known about the processing of VFs. Recent fMRI studies suggest that the insula (INS)—and its connections with the parieto-frontal circuit—plays a crucial role in VFs processing. However, a key question remains: How does our internal affective state shape our motor behavior? To explore this issue, we conducted an fMRI study. Participants were required to perform two sequential tasks: 1) to evoke either a positive (enthusiastic) or a negative (angry) affective state (feeling task); 2) to execute an action while maintaining these affective states (execution task). Univariate analysis revealed activation of the INS and dorsolateral prefrontal cortex (PFC) during the feeling task, which extended to the premotor (PM) and parietal areas during the execution task. To determine the directionality of information flow among these nodes, we employed dynamic causal modeling. Bayesian model comparison showed that, during the feeling task, affect generation involves INS, which, together with the PFC, modulates the activity of PM. In contrast, during execution, motor commands emerge from PM and influence activity in the INS and PFC. These findings indicate that while the internal states crucially imply the INS, their regulation is mediated by PFC. The PM cortex plays a crucial role in the selection of the corresponding action VFs.