🗣 Communication Paper Picnic 🧺: Multidisciplinary

I checked 6 multidisciplinary journals on Friday, February 27, 2026 using the Crossref API. For the period February 20 to February 26, I found 12 new paper(s) in 5 journal(s).

Nature

GPT-4o mini: Non-social science research article

Author Correction: Natural behaviour is learned through dopamine-mediated reinforcement

Jonathan Kasdin, Alison Duffy, Nathan Nadler, Arnav Raha, Adrienne L. Fairhall, Kimberly L. Stachenfeld, Vikram Gadagkar

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GPT-4o mini: Non-social science research article

Editorial Expression of Concern: Opposing roles for calcineurin and ATF3 in squamous skin cancer

Xunwei Wu, Bach-Cuc Nguyen, Piotr Dziunycz, Sungeun Chang, Yang Brooks, Karine Lefort, Günther F. L. Hofbauer, G. Paolo Dotto

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GPT-4o mini: Non-social science research article

Hydrofluorocarbon electrolytes for energy-dense and low-temperature batteries

Lanqing Wu, Jinyu Zhang, Yong Li, Zhenyu Fan, Shuangxin Ren, Jie Zhang, Yawen Li, Youxuan Ni, Weiwei Xie, Yong Lu, Jun Chen, Qing Zhao

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Electrolyte solvents for electrochemical devices have been dominated by oxygen (O)-based and nitrogen (N)-based ligands over the past decades1,2,3,4,5, for which the dipole–ion (Li+, Na+ and so on) interaction usually lays the foundations of ion dissociation and transport but frustrates the charge transfer process at the electrolyte–electrode interface6,7,8,9. Here, by synthesizing alkanes with monofluorinated structures, we show that fluorine (F)-based ligands with designed steric hindrance and Lewis basicity enable salt dissolution of more than 2 mol l−1. Among them, 1,3-difluoro-propane (DFP)-based Li-ion electrolyte is endowed with all merits for energy-dense and low-temperature batteries, including low viscosity (0.95 cp), high oxidation stability (>4.9 V) and ionic conductivity of 0.29 mS cm−1 at −70 °C. By incorporating F atoms in the first solvation shell, the weak F–Li+ coordination facilitates the Li plating/stripping process with Coulombic efficiency (CE) up to 99.7% and exchange current density one magnitude larger than O–Li+ coordination at −50 °C. The electrolytes further enable the operation of lithium-metal pouch cells under an electrolyte amount of less than 0.5 g Ah−1, achieving energy densities greater than 700 Wh kg−1 at room temperature and about 400 Wh kg−1 at −50 °C. The hydrofluorocarbon (HFC) electrolytes in this work provide a feasible approach to building electrochemical systems beyond traditional coordination chemistry.

GPT-4o mini: Non-social science research article

Limitations of probing field-induced response with STM

Christopher Candelora, Ilija Zeljkovic

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GPT-4o mini: Non-social science research article

Uncovering origins of heterogeneous superconductivity in La3Ni2O7

S. V. Mandyam, E. Wang, Z. Wang, B. Chen, N. C. Jayarama, A. Gupta, E. A. Riesel, V. I. Levitas, C. R. Laumann, N. Y. Yao

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The family of nickelate superconductors have long been explored as analogues of the high-temperature cuprates 1–6 . Nonetheless, the recent discovery that certain stoichiometric nickelates superconduct up to high critical temperatures ( T c ) under pressure came as a surprise 7–13 . The mechanisms underlying the superconducting state remain experimentally unclear. Apart from the practical challenges posed by working in a high-pressure environment, typical samples exhibit anomalously weak diamagnetic responses, which have been conjectured to reflect inhomogeneous ‘filamentary’ superconducting states 7,9,14–17 . Here we perform wide-field, high-pressure, optically detected magnetic resonance spectroscopy to image the local diamagnetic responses of as-grown La 3 Ni 2 O 7 samples in situ, using nitrogen vacancy quantum sensors embedded in the diamond anvil cell 18–23 . These maps confirm marked inhomogeneity of the functional superconducting responses at the few μm scale. By spatially correlating the diamagnetic Meissner response with both the local tensorial stress environment, also imaged in situ, and stoichiometric composition, we show the dominant mechanisms suppressing and enhancing superconductivity. Our wide-field technique simultaneously provides a broad view of sample behaviour and excellent local sensitivity, enabling the rapid construction of multi-parameter phase diagrams from the local structure–function correlations observed at the sub-μm pixel scale.

GPT-4o mini: Non-social science research article

Argentine fossil rewrites evolutionary history of a baffling dinosaur clade

Peter J. Makovicky, Jonathan S. Mitchell, Jorge G. Meso, Federico A. Gianechini, Ignacio Cerda, Sebastian Apesteguía

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Alvarezsauroids are an enigmatic clade of predominantly small-bodied theropod dinosaurs that are known mainly from the Jurassic to Cretaceous periods of Asia and South America1,2,3. Late Cretaceous alvarezsauroids possess specialized forelimbs adapted for digging4,5, minute supernumerary teeth and heightened sensory capacities6, and are interpreted as myrmecophagous. They are hypothesized to exhibit evolutionary miniaturization coupled to their dietary specialization2. Fragmentary South American taxa are traditionally arrayed as a paraphyletic grade with respect to the Late Cretaceous Asian subclade Parvicursorinae2,3, invoking dispersal to explain their disjunct distributions. Here we describe a skeleton of the alvarezsauroid Alnashetri cerropoliciensis7 representing to our knowledge the most complete and smallest South American taxon to date. We also recognize two alvarezsauroids among historic taxa from the Northern Hemisphere. Phylogenetic analysis recovers Alnashetri among basal non-alvarezsaurids, rendering South American taxa polyphyletic. Combined with the new taxa recognized here, our biogeographical analyses infer a Pangaean ancestral distribution for Alvarezsauroidea, with vicariance dominating the early history of the clade. The early branching position of Alnashetri among larger-bodied relatives revises best-fit models of body size evolution in alvarezsauroids—we find no support for evolutionary miniaturization but, rather, find support for repeated evolution within a narrow body size range.

GPT-4o mini: Non-social science research article

Clonal-aggregative multicellularity tuned by salinity in a choanoflagellate

Núria Ros-Rocher, Josean Reyes-Rivera, Uzuki Horo, Chantal Combredet, Yeganeh Foroughijabbari, Ben T. Larson, Maxwell C. Coyle, Erik A. T. Houtepen, Mark J. A. Vermeij, Jacob L. Steenwyk, Thibaut Brunet

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Multicellularity evolved independently multiple times in eukaryotes 1–4 . Two distinct mechanisms underpin multicellularity 5 : clonality (serial cell division without sister-cell separation) and aggregation (whereby independent cells assemble into a multicellular entity). Clonal and aggregative multicellularity are traditionally considered to be mutually exclusive 1,6–8 , with rare exceptions 9 , and evolutionary hypotheses have addressed why multicellularity might diverge towards one or the other extreme 3,4 . Both animals and their sister group, the choanoflagellates, are currently known to acquire multicellularity only clonally 4,10,11 . Here we show that the choanoflagellate Choanoeca flexa 12 forms motile and contractile cell monolayers (sheets) through multiple mechanisms— C. flexa sheets can form purely clonally, purely aggregatively or through a combination of both processes. We characterize the life history of C. flexa in its natural environment—ephemeral splash pools on the island of Curaçao—and show that C. flexa undergoes reversible transitions between unicellularity and multicellularity during evaporation–refilling cycles. Different splash pools house genetically distinct strains of C. flexa and kin recognition constrains aggregation between them. We show that clonal-aggregative multicellularity is a versatile strategy for the robust establishment of multicellularity in this variable and fast-fluctuating environment. Our findings challenge former generalizations about choanoflagellates and expand the option space of choanozoan multicellularity.

GPT-4o mini: Non-social science research article

Dynamic antigen expression and cytotoxic T cell resistance in HIV reservoir clones

Isabella A. T. M. Ferreira, Alberto Herrera, Tan Thinh Huynh, Emily Stone, Noemi L. Linden, Cristian Ovies, Yanqin Ren, Cintia Bittar, Virender K. Pal, Ethan Naing, Parul Sinha, Ali Danesh, Eva Stevenson, Shane Vedova, Fitty Liu, Louise Leyre, Skylar Shea, Elina Wells, Itzayana G. Miller, Marie Canis, Ana Rafaela Teixeira, Susan Moir, Tae-Wook Chun, Colin Kovacs, Madeleine S. Gastonguay, Alison L. Hill, Shy Genel, Paul Zumbo, Doron Betel, Elias K. Halvas, Guinevere Q. Lee, Rachel Scheck, Marina Caskey, Paul D. Bieniasz, Nathan L. Board, Michel C. Nussenzweig, R. Brad Jones

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Clonally expanded CD4+ T-cells harboring rebound-competent HIV persist lifelong during ART1-5. Latency is considered the principal barrier to viral eradication and has resisted pharmacological reversal6,7, yet sustained immune pressure appears to erode reservoirs8-15. Recent advances have yielded glimpses into exceptionally rare reservoir-harboring cells, implicating pro-survival properties in persistence16-18. Here, we isolate and characterize authentic reservoir clones (ARCs) that robustly proliferate and accumulate while producing infectious virus, without overtly succumbing to cytopathicity. At any moment, only small fractions of ARCs expressed HIV proteins, a state associated with conserved host transcriptional programs but remarkably refractory to potent T-cell stimulation. Nevertheless, sustained co-culture with a CD8+ cytotoxic T-lymphocyte clone substantially culled proliferating ARCs, revealing time-integrated vulnerability to immune pressure. The corresponding ex vivo CD8+ T-cell response was poorly cytotoxic and in vivo erosion of ARCs occurred only slowly. A regulatory T-cell ARC displayed pronounced cell-intrinsic resistance to CTL—a longstanding hypothesis now directly demonstrated—linked to low oxidative stress and reversed with deferoxamine19, a hypoxic stress inducer and FDA-approved therapeutic. Overall, we provide novel insights into the vulnerabilities of reservoir clones to potent, sustained CTL pressure and highlight intrinsic resistance pathways as actionable therapeutic targets, opening opportunities for advancing immune-based HIV cure strategies.

GPT-4o mini: Non-social science research article

CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly

Alyssa J. Mathiowetz, Emily S. Meymand, Güneş Parlakgül, Niek van Hilten, Emily F. Torres, Leonardo L. Artico, Kirandeep K. Deol, Mike Lange, Stephany P. Pang, Cody E. Doubravsky, Melissa A. Roberts, Danielle M. Jorgens, Reena Zalpuri, Misun Kang, Casadora Boone, Brian W. Parks, Yaohuan Zhang, David W. Morgens, Emily Tso Newman, Yingjiang Zhou, Saswata Talukdar, Michael Grabe, Gregory Ku, Tim P. Levine, Ana Paula Arruda, James A. Olzmann

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Imbalances in lipid storage and secretion lead to hepatic steatosis, the accumulation of lipid droplets in hepatocytes 1,2 . Our understanding of the mechanisms that govern the channelling of neutral lipids in hepatocytes towards cytosolic lipid droplets or secreted lipoproteins remains incomplete 3,4 . Here we performed a series of CRISPR–Cas9 screens under different metabolic states that led to the identification of CLCC1 as a critical regulator of neutral lipid storage and secretion in hepatocytes. Loss of CLCC1 resulted in the buildup of large lipid droplets in hepatoma cells and Clcc1 knockout in mice caused liver steatosis. Lipid droplets were present in the lumen of the endoplasmic reticulum of the Clcc1 -knockout hepatocytes and exhibited properties of lipoproteins, indicating a profound shift in neutral lipid flux. The loss of CLCC1 also led to the accumulation of nuclear membrane herniations accompanied by a reduction in nuclear pores. Remote homology searches identified a domain in CLCC1 that is homologous to yeast Brl1 and Brr6, factors that promote nuclear envelope fusion during nuclear pore complex assembly. Molecular dynamics simulations and mutagenesis studies support a model in which CLCC1 mediates membrane bending and fusion. We propose that CLCC1 mediates membrane fusion to promote hepatic neutral lipid flux and nuclear pore complex assembly.

GPT-4o mini: Non-social science research article

Vectorized instructive signals in cortical dendrites

Valerio Francioni, Vincent D. Tang, Enrique H. S. Toloza, Zilan Ding, Norma J. Brown, Mark T. Harnett

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Vectorization of teaching signals is a key element of almost all modern machine learning algorithms, including backpropagation, target propagation and reinforcement learning. Vectorization allows a scalable and computationally efficient solution to the credit assignment problem by tailoring instructive signals to individual neurons. Recent theoretical models have suggested that neural circuits could implement single-phase vectorized learning at the cellular level by processing feedforward and feedback information streams in separate dendritic compartments1,2,3,4,5. This presents a compelling, but untested, hypothesis for how cortical circuits could solve credit assignment in the brain. Here we used a neurofeedback brain–computer interface task with an experimenter-defined reward function to test for vectorized instructive signals in dendrites. We trained mice to modulate the activity of two spatially intermingled populations (four or five neurons each) of layer 5 pyramidal neurons in the retrosplenial cortex to rotate a visual grating towards a target orientation while we recorded GCaMP activity from somas and corresponding distal apical dendrites. We observed that the relative magnitudes of somatic and dendritic signals could be predicted using the activity of the surrounding network and contained information about task-related variables that could serve as instructive signals, including reward and error. The signs of these putative teaching signals depended on the causal role of individual neurons in the task and predicted changes in overall activity over the course of learning. Furthermore, targeted optogenetic perturbation of these signals disrupted learning. These results demonstrate a vectorized instructive signal in the brain, implemented via semi-independent computation in cortical dendrites, unveiling a potential mechanism for solving credit assignment in the brain.

GPT-4o mini: Non-social science research article

A disease model resource reveals core principles of tissue-specific cancer evolution

Sebastian Mueller, Niklas de Andrade Krätzig, Markus Tschurtschenthaler, Miguel G. Silva, Chiara Thordsen, Riccardo Trozzo, Perrine Simon, Frederic Saab, Thorsten Kaltenbacher, Magdalena Zukowska, Daniele Lucarelli, Rupert Öllinger, Joscha Griger, Nina Groß, Tanja Groll, Jessica Löprich, Antonio E. Zaurito, Linus R. Schömig, Jeroen M. Bugter, Stefanie Bärthel, Chiara Falcomatà, Alexander Strong, Cordelia Brandt, Mulham Najajreh, Aristeidis Papargyriou, Roman Maresch, Katharina A. N. Collins, David Sailer, Christian Schneeweis, Sebastian Burger, Lisa M. Fröhlich, Christine Klement, Alexander Belka, Juan J. Montero, Ute Jungwirth, Maximilian Reichert, Markus Moser, Jens Neumann, George Vassiliou, Juan Cadiñanos, Ignacio Varela, Carsten Marr, Daniel F. Alonso, Pier-Luigi Lollini, Jean Zhao, Louis Chesler, Clare M. Isacke, Angela Riedel, Christian J. Braun, Martin L. Sos, Filippo Beleggia, Hans C. Reinhardt, Monica Musteanu, Mariano Barbacid, Michael Quante, Marc Schmidt-Supprian, Günter Schneider, Simon Clare, Trevor D. Lawley, Gordon Dougan, Katja Steiger, Nathalie Conte, Allan Bradley, Lena Rad, Dieter Saur, Roland Rad

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Oncogenes such as KRAS display marked tissue specificity in their oncogenic potential, genetic interactions and phenotypic effects, but the underlying determinants remain largely unresolved 1–5 . Here, to address these questions, we developed the Mouse Cancer Cell line Atlas, a broad-utility resource of 590 comprehensively characterized models across a wide range of entities ( www.mcca.tum.de ). Comparative and functional studies using this platform, human cohorts and mice identified core principles underlying tissue-specific evolution of KRAS -initiated cancers. First, we show that mutant KRAS dosage gain through allelic imbalance exerts cell-type-specific effects, defining its timing across entities, as exemplified by dosage-sensitive developmental reprogramming during pancreatic cancer initiation. Second, we highlight how tissue- and stage-specific evolutionary requirements, such as block of differentiation in the intestine, select for KRAS -collaborating alterations. Third, we identified context-dependent epistatic KRAS –tumour suppressor interactions and show that reciprocal dosage sensitivities dictate the entity-specific patterns of cancer gene alterations, explaining their frequency, zygosity and acquisition chronology. These findings highlight how intrinsic and acquired determinants instruct cancer evolution in different tissues, with predictable molecular patterns, temporal dynamics and phenotypic outcomes. Our study provides major advances towards a mechanistic understanding of cancer genomes.

GPT-4o mini: Non-social science research article

Cavity-altered superconductivity

Itai Keren, Tatiana A. Webb, Shuai Zhang, Jikai Xu, Dihao Sun, Brian S. Y. Kim, Dongbin Shin, Songtian S. Zhang, Junhe Zhang, Giancarlo Pereira, Juntao Yao, Takuya Okugawa, Marios H. Michael, Emil Viñas Boström, James H. Edgar, Stuart Wolf, Matthew Julian, Rohit P. Prasankumar, Kazuya Miyagawa, Kazushi Kanoda, Genda Gu, Matthew Cothrine, David Mandrus, Michele Buzzi, Andrea Cavalleri, Cory R. Dean, Dante M. Kennes, Andrew J. Millis, Qiang Li, Michael A. Sentef, Angel Rubio, Abhay N. Pasupathy, D. N. Basov

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Is it feasible to alter the ground-state properties of a material by engineering its electromagnetic environment? Inspired by theoretical predictions1,2,3,4,5,6,7,8,9,10,11,12, experimental realizations of such cavity-controlled properties without optical excitation are beginning to emerge13,14,15,16,17,18,19. Here we devised and implemented a new platform to realize cavity-altered materials. Single crystals of hyperbolic van der Waals (vdW) compounds provide a resonant electromagnetic environment with enhanced density of photonic states and prominent mode confinement20,21,22,23,24. We interfaced hexagonal boron nitride (hBN) with the molecular superconductor κ-(BEDT-TTF)2Cu[N(CN)2]Br (κ-ET). The frequencies of infrared hyperbolic modes (HMs) of hBN (refs. 25,26) match the infrared-active carbon–carbon (C=C) stretching molecular resonance of κ-ET implicated in superconductivity27. Nano-optical data supported by first-principles molecular Langevin dynamics simulations confirm the presence of resonant coupling between the hBN hyperbolic cavity modes and the C=C stretching mode in κ-ET. Meissner-effect measurements using magnetic force microscopy (MFM) demonstrate a strong suppression of superfluid density near the hBN/κ-ET interface. Non-resonant control heterostructures, including RuCl3/κ-ET and hBN/Bi2Sr2CaCu2O8+x (BSCCO), do not show the pronounced superfluid suppression. These observations suggest that hBN/κ-ET realizes a cavity-altered superconducting ground state. Our work highlights the potential of dark cavities devoid of external photons for engineering electronic ground-state properties of complex quantum materials.

GPT-4o mini: Non-social science research article

Compact deep neural network models of the visual cortex

Benjamin R. Cowley, Patricia L. Stan, Jonathan W. Pillow, Matthew A. Smith

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A powerful approach to understand the computations carried out by the visual cortex is to build models that predict neural responses to any arbitrary image. Deep neural networks (DNNs) have emerged as the leading predictive models1,2, yet their underlying computations remain buried beneath millions of parameters. Here we challenge the need for models at this scale by seeking predictive and parsimonious DNN models of the primate visual cortex. We first built a highly predictive DNN model of neural responses in macaque visual area V4 by alternating data collection and model training in adaptive closed-loop experiments. We then compressed this large, black-box DNN model, which comprised 60 million parameters, to identify compact models with 5,000 times fewer parameters yet comparable accuracy. This dramatic compression enabled us to investigate the inner workings of the compact models. We discovered a salient computational motif: compact models share similar filters in early processing, but individual models then specialize their feature selectivity by ‘consolidating’ this shared high-dimensional representation in distinct ways. We examined this consolidation step in a dot-detecting model neuron, revealing a computational mechanism that leads to a testable circuit hypothesis for dot-selective V4 neurons. Beyond V4, we found strong model compression for macaque visual areas V1 and IT (inferior temporal cortex), revealing a general computational principle of the visual cortex. Overall, our work challenges the notion that large DNNs are necessary to predict individual neurons and establishes a modelling framework that balances prediction and parsimony.

GPT-4o mini: Non-social science research article

Coral microbiomes as reservoirs of unknown genomic and biosynthetic diversity

Fabienne Wiederkehr, Lucas Paoli, Daniel Richter, Dora Racunica, Hans-Joachim Ruscheweyh, Martin Sperfeld, James O’Brien, Samuel Miravet-Verde, Alena B. Streiff, Jessica Ransome, Clara Chepkirui, Taylor Priest, Anna Sintsova, Guillem Salazar, Kalia S. I. Bistolas, Teresa Sawyer, Karine Labadie, Kim-Isabelle Mayer, Aude Perdereau, Maggie M. Reddy, Clémentine Moulin, Emilie Boissin, Guillaume Bourdin, Juliette Cailliau, Guillaume Iwankow, Julie Poulain, Sarah Romac, character(0), Colomban de Vargas, J. Michel Flores, Paola Furla, Eric Gilson, Stéphane Pesant, Stephanie Reynaud, Didier Zoccola, Serge Planes, Denis Allemand, Sylvain Agostini, Chris Bowler, Eric Douville, Didier Forcioli, Pierre E. Galand, Fabien Lombard, Pedro H. Oliveira, Olivier P. Thomas, Rebecca Vega Thurber, Romain Troublé, Christian R. Voolstra, Patrick Wincker, Maren Ziegler, Jörn Piel, Shinichi Sunagawa

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Coral reefs are marine biodiversity hotspots that provide a wide range of ecosystem services 1 . They are reservoirs of bioactive metabolites, many produced by microorganisms associated with reef invertebrate hosts 2 . However, for the keystone species of coral reefs—the reef-building corals—we still lack a systematic assessment of their microbially encoded biosynthetic potential and the molecular resources at stake due to the alarming decline in reef biodiversity. Here we analysed microbial genomes reconstructed from 820 reef-building coral samples of three representative coral genera collected at 99 reefs across 32 islands throughout the Pacific Ocean ( Tara Pacific expedition) 3 . By contextualizing our analyses with the microbiomes of other reef species, we found that only 10% of the 4,224 microbial species and less than 1% of the 645 species exclusively identified in Tara Pacific samples had genomic information available. Furthermore, the biosynthetic potential of reef-building coral microbiomes rivalled or surpassed that of traditional natural product sources such as sponges. Among the biosynthetically rich bacteria in the reef microbiome, we identified new groups of Acidobacteriota that encode previously unknown enzymology, in turn opening promising avenues for functional protein engineering. Together, this study underscores the importance of conserving coral reefs as vital reservoirs of molecular diversity.

GPT-4o mini: Non-social science research article

Reply to: Limitations of probing field-induced response with STM

Yuqing Xing, Seokjin Bae, Stephen D. Wilson, Ziqiang Wang, Rafael M. Fernandes, Vidya Madhavan

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GPT-4o mini: Non-social science research article

Markovnikov hydroamination of terminal alkenes via phosphine redox catalysis

Flora Fan, Kassandra F. Sedillo, Alexander J. Maertens, Abigail G. Doyle

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Main-group catalysts that mimic transition metal reactivity can expand substrate tolerance and enable transformations not currently possible with metal catalysis1. The discovery that PIII and PV phosphorus intermediates can undergo transition metal-like two-electron chemistry raises the question whether radical PIV intermediates can mimic other elementary steps in organometallic chemistry2,3. Here we describe a phosphine-photoredox catalyst system that promotes intermolecular Markovnikov hydroamination of unactivated terminal alkenes with numerous classes of N–H azoles, a reaction that is not possible with late transition metal catalysis. Experimental and computational mechanistic studies support a new elementary step for main group catalysis wherein a phosphine radical cation activates the alkene to nucleophilic amination by the azole, a step otherwise associated with transition metals. Given the broad value of nucleophilic alkene functionalization in transition metal catalysis, this PIV mechanism could offer new opportunities for main group element catalysis and chemical synthesis.

GPT-4o mini: Non-social science research article

Human hippocampal neurogenesis in adulthood, ageing and Alzheimer’s disease

Ahmed Disouky, Mark A. Sanborn, K. R. Sabitha, Mostafa M. Mostafa, Ivan Alejandro Ayala, David A. Bennett, Yisha Lu, Yi Zhou, C. Dirk Keene, Sandra Weintraub, Tamar Gefen, M.-Marsel Mesulam, Changiz Geula, Mark Maienschein-Cline, Jalees Rehman, Orly Lazarov

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The existence of human hippocampal neurogenesis has long been disputed1,2,3,4,5,6,7,8,9,10,11,12 and its relevance in cognition remains unknown. Recent studies have established the presence of proliferating progenitors and immature neurons and a reduction in the latter in Alzheimer’s disease (AD)11,13. However, their origin and the molecular networks that regulate neurogenesis and function are poorly understood. Here we studied human post-mortem hippocampi obtained from different cohorts: young adults with intact memory, aged adults with no cognitive impairments, aged adults with extraordinary memory capacity (SuperAgers)14,15, adults with preclinical intermediate pathology or adults with AD. Using multiomic single-cell sequencing (single-nucleus RNA sequencing and single-nuclei assay for transposase-accessible chromatin with sequencing), we analysed the profiles of 355,997 nuclei isolated from the hippocampus samples and identified neural stem cells, neuroblasts and immature granule neurons. Dysregulated neurogenesis was largely associated with changes in chromatin accessibility. Analyses of transcription factors and target gene signatures that distinguished each of the groups revealed early alterations in chromatin accessibility of neurogenic cells from individuals with preclinical AD, and such changes were even more evident in samples from individuals with AD. We identified a distinct profile of neurogenesis in SuperAgers that may reflect a ‘resilience signature’. Finally, alterations in the profile of astrocytes and CA1 neurons govern cognitive function in the ageing hippocampus. Together, our study points to a multiomic molecular signature of the hippocampus that distinguishes cognitive resilience and deterioration with ageing.

GPT-4o mini: Non-social science research article

Squeaking at soft–rigid frictional interfaces

Adel Djellouli, Gabriele Albertini, Jackson Wilt, Vincent Tournat, David Weitz, Shmuel Rubinstein, Katia Bertoldi

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Squeaking is a constant companion in various aspects of our daily lives, whether we slide rubber-soled shoes across hardwood floors1, scrape chalk on a blackboard2, engage the brakes on a bicycle3 or walk with a hip replacement4,5. When two rigid bodies slide over each other, squeaking is widely understood to result from self-excited stick–slip oscillations, triggered by a decrease in the friction coefficient with increasing slip velocity6,7,8,9,10. However, sliding of extended interfaces can involve crack or slip-pulse propagation11,12,13,14,15,16,17,18,19,20,21. This distinction is amplified when a soft body slides on a rigid one, in which large deformations and material mismatch can cause detachment by opening slip pulses22,23,24,25,26,27. Previous studies focused mainly on slow sliding17,26,28,29,30,31,32,33,34, in which pulses are slow and squeaking is absent. Although squeaking at soft–rigid interfaces has been linked to stick–slip oscillations35,36,37, the mechanisms remain unclear. Here we experimentally investigate soft–rigid interfaces sliding at velocities that produce squeaking. High-speed imaging and acoustic analysis show that opening pulses propagate at approximately the shear wave speed of the soft material, mediating local slip across diverse materials. In flat samples, these pulses are irregular and generate broadband acoustic emissions. Introducing thin surface ridges confines pulse propagation, yielding a consistent repetition frequency matching the first shear mode of the sliding block and squeaking at that frequency. These findings show a structure-driven mechanism that stabilizes rupture in bimaterial friction. Geometric confinement suppresses competing modes, transforming irregular two-dimensional dynamics into coherent one-dimensional pulse trains, offering new insights into frictional rupture from engineered surfaces to geological faults.

GPT-4o mini: Non-social science research article

Entanglement-assisted non-local optical interferometry in a quantum network

P.-J. Stas, Y.-C. Wei, M. Sirotin, Y. Q. Huan, U. Yazlar, F. Abdo Arias, E. Knyazev, G. Baranes, B. Machielse, S. Grandi, D. Riedel, J. Borregaard, H. Park, M. Lončar, A. Suleymanzade, M. D. Lukin

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The sensitivity of non-local optical measurements at low light intensities, such as those involved in long-baseline telescope arrays1,2, is limited by fundamental quantum noise and photon losses3. Distributed quantum entanglement has been proposed as a route towards overcoming these limitations and accessing new regimes of non-local optical sensing4,5,6. Here we demonstrate the use of entangled quantum memories in a quantum network of silicon–vacancy centres in diamond nanocavities7,8,9 to experimentally perform such non-local phase measurements. Specifically, we combine the generation of event-ready remote quantum entanglement, photon mode erasure that hides the ‘which-path’ information of temporally and spatially separated incoming optical modes and non-local, non-destructive photon heralding enabled by remote entanglement to perform a proof-of-concept entanglement-assisted differential phase measurement of weak incident light between two spatially separate stations. Demonstrating successful operation of the remote phase sensing protocol with a fibre link baseline up to 1.55 km, our results provide an opportunity for a new class of quantum-enhanced optical imaging methods with potential applications ranging from long-baseline interferometry and astronomy to microscopy10,11.

GPT-4o mini: Non-social science research article

Rewiring an E3 ligase enhances cold resilience and phosphate use in maize

Huan Liao, Xiaoyun Zhao, Keyu Ren, Li Guo, Zhuoyang Li, Zhicheng Liu, Xiaoyan Zhang, Tianhang Su, Diyi Fu, Zhaoyang Zhang, Junhong Zhuang, Xiaohong Yang, Feng Tian, Zhizhong Gong, Wen Song, Zhen Li, Yiting Shi, Shuhua Yang

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Cold stress restricts plant growth and inorganic phosphate (Pi) uptake, reducing yield and increasing fertilizer demand1,2,3. Enhancing both cold tolerance and phosphorus use efficiency (PUE) is crucial for sustainable crop productivity. Here we identify the SPX-domain-containing E3 ubiquitin ligase NITROGEN LIMITATION ADAPTATION (NLA) as a central regulator that links cold signalling to Pi homeostasis in maize (Zea mays L.). Under cold conditions, NLA promotes the degradation of the transcriptional repressor JAZ11, activating jasmonate signalling to enhance cold tolerance; however, NLA also simultaneously represses Pi uptake, through inositol polyphosphate (InsP)-dependent ubiquitination of the Pi transporter PT4. A ubiquitinome-informed genome-wide association study identified a natural PT4(K267A) (lysine-to-alanine substitution) variant that attenuates NLA-mediated degradation and increases Pi uptake in cold conditions. To overcome this nutrient–stress trade-off, we combined artificial-intelligence-guided structural modelling and ligand docking with genome editing to generate the nlaΔ12 allele, which encodes an NLA variant in which binding to InsP is impaired but JAZ11 targeting is retained. The Δ12 modification selectively redirects the activity of NLA towards jasmonate signalling, resulting in improved cold resilience, higher PUE and increased yield in multi-site field trials. These findings reveal a tunable SPX regulatory module that integrates environmental and nutrient signals, and provide a molecular framework for engineering climate-resilient, nutrient-efficient crops.

GPT-4o mini: Non-social science research article

Peripheral immune-inducer dendritic cells drive early-life allergic inflammation

Yue Xing, Ilana Reznikov, Abonti Nur Ahmed, Ikjot Sidhu, Jill Wisnewski, Asma Farhat, Aleksandr Prystupa, Piotr Konieczny, Kody Mansfield, Melissa L. Cooper, Stephen T. Yeung, Madeline Kim, Sophia Adeghe, Katherine D. Gaines, Meredith Manson, Ji Hyun Sim, Qingrong Huang, Ata S. Moshiri, Kamal M. Khanna, Theresa T. Lu, Emma Guttman-Yassky, Amanda W. Lund, Niroshana Anandasabapathy, Shruti Naik

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Atopic diseases associated with allergens, as well as allergic diseases, frequently arise early in life; however, the age-dependent mechanisms governing immune responses to allergens remain poorly understood1. Here we find that in early life, exposure to common allergens triggers a distinct bifurcated immune response, simultaneously triggering type 17 inflammation in the skin and initiating canonical T helper 2 sensitization in the lymph nodes. This early-life γδ type 17-mediated dermatitis primes the exaggerated allergic lung inflammation upon secondary allergen exposure. Mechanistically, we find dendritic cell (DC)-mediated type 17 activation directly in the skin without requiring migration to lymph nodes; we term this state ‘peripheral immune inducer’ (pii) DC. CD301b+ conventional type 2 DCs acquire allergen, adopt the pii-DC state, produce IL-23 and activate local γδ type 17 cells independently of lymph-node engagement. The pii-DC state is enabled by the immature hypothalamic–pituitary–adrenal axis and physiologically low systemic glucocorticoids characteristic of early life2,3; DC-specific deletion of the glucocorticoid receptor recapitulates the pii-DC phenotype. These findings define a developmental checkpoint, set by neuroendocrine maturation, that enables in situ DC activation and immune induction, thereby shaping age-dependent responses to allergens.

GPT-4o mini: Non-social science research article

Pivoting colloidal assemblies exhibit mechanical metamaterial behaviour

Julio Melio, Martin van Hecke, Silke E. Henkes, Daniela J. Kraft

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Biological machines use targeted deformations that can be actuated by Brownian fluctuations. However, although synthetic micromachines can similarly make use of targeted deformations, they are too stiff to be driven by thermal fluctuations and require strong forcing1,2,3. Furthermore, systems that are able to change their conformation by thermal fluctuations do so uncontrollably4,5 or require external control6. Here we use DNA-based sliding contacts7,8,9 to create colloidal pivots, rigid anisotropic objects that freely fluctuate around their pivot point and use a hierarchical strategy to assemble these into Brownian metamaterials with targeted deformation modes. We realize the archetypical rotating diamond and rotating triangle, or kagome, geometries and quantitatively show how thermal fluctuations drive their predicted auxetic deformations10,11,12,13,14,15. Finally, we implement magnetic particles into the colloidal pivots to achieve colloidal metamaterials that can be controlled externally as well as use Brownian fluctuations for precisely controlled shape changes. Together, our work introduces a strategy for creating Brownian mechanical metamaterials with easily actuatable deformation modes.

GPT-4o mini: Non-social science research article

Pancreatic-targeted lipid nanoparticles based on organ capsule filtration

Jiaqi Lei, Kai Yang, Wanyue Cao, Shaolong Qi, Xianlong Du, Hongjian Li, Yangfan Wang, Jinqun Gan, Yunxuan Feng, Yongcan Li, Wenjie Zhang, Bing Bai, Xin Lin, Xinhui Su, Qi Zhang, Tingbo Liang, Guocan Yu

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Achieving pancreatic-targeted delivery marks a breakthrough in treating pancreatic diseases, yet precise delivery remains challenging1. Here we identify an explicit and universal principle for pancreatic-selective delivery and propose a pancreatic-targeted lipid nanoparticle (AH-LNP) for mRNA delivery. AH-LNP exhibits size enlargement after assembly with proteins, facilitating capsule-filter-mediated pancreas-selective accumulation and receptor-mediated endocytosis, thereby boosting the pancreatic-targeted ability. Benefiting from this, AH-LNP enables precise and efficient genome editing in the pancreas through the delivery of Cas9 mRNA and single guide RNA (sgRNA), exhibiting promising potential in the treatment of autoimmune pancreatic diseases. Furthermore, pancreatic-targeted delivery of mRNA encoding therapeutic cytokines through AH-LNP demonstrates superior antitumour efficacy when combined with a cancer vaccine or chimeric antigen receptor T cell therapy in multiple pancreatic cancer models. The safety and pancreatic mRNA delivery of AH-LNP were verified in multiple animal models, including non-human primates, demonstrating great promise for clinical translation. Our findings highlight the transformative potential of this pancreatic-targeted mechanism and the derived LNP platform, opening avenues for developing precision therapeutics against diverse pancreatic diseases.

GPT-4o mini: Non-social science research article

OR7A10 GPCR engineering boosts CAR-NK therapy against solid tumours

Luojia Yang, Paul A. Renauer, Kaiyuan Tang, Josh Saskin, Liqun Zhou, Charles Zou, Seok-Hoon Lee, Madison Fox, Samuel Johnson-Noya, Benedict Weiss, Stephanie Deng, Paris Fang, Binfan Chen, Giacomo Sferruzza, Saba Fooladi, Kai Zhao, Daniel Park, Feifei Zhang, Jiayi Tu, Jing Chen, Jennifer Moliterno, Murat Gunel, Lei Peng, Sidi Chen

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Chimeric antigen receptor (CAR)-natural killer (NK) cell therapies hold promise for solid tumours but remain limited because of poor tumour infiltration, persistence and resistance in the tumour microenvironment1,2,3,4. Here, to identify gain-of-function targets that enhance CAR-NK cell efficacy, we performed an unbiased in vivo CRISPR activation screen followed by a barcoded targeted in vivo open reading frame screen in primary human CAR-NK cells. We identified and comprehensively validated OR7A10, a G protein-coupled receptor (GPCR), as the top candidate. Engineering CAR-NK cells with OR7A10 cDNA (a CRISPR-independent method with a simple manufacturing strategy) enhanced their proliferation, activation, degranulation, cytokine production, death ligand expression, chemokine receptor expression, cytotoxicity, persistence, metabolic fitness and tumour microenvironment resistance. Moreover, exhaustion in primary human NK cells derived from multiple peripheral blood and cord blood donors was reduced. OR7A10 gain-of-function CAR-NK cells displayed strong in vivo efficacy across multiple solid tumour models. For example, 100% complete response with long-term tumour control and survival benefit in an orthotopic breast cancer mouse model were achieved. These findings establish OR7A10-engineered CAR-NK cells as a highly potent and scalable off-the-shelf therapeutic for solid tumours.

GPT-4o mini: Non-social science research article

Convergent MurJ flippase inhibition by phage lysis proteins

Yancheng E. Li, S. Francesca Antillon, Grace F. Baron, Karthik Chamakura, Ry Young, William M. Clemons

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Antimicrobial drug resistance poses a global health challenge that necessitates the identification of new druggable targets1,2,3. The essential lipid II flippase MurJ is a promising yet underexplored antimicrobial target in bacterial cell wall biosynthesis4,5,6,7. The only known inhibitors of Gram-negative (diderm) MurJ are the single-gene lysis proteins (Sgls) from the lytic single-strand RNA phages M (SglM) and PP7 (SglPP7)8,9. SglM and SglPP7 have distinct evolutionary origins and share no sequence similarity. Here we describe a common mechanism of MurJ inhibition by these phage-encoded Sgls. We determined the structures of MurJ-bound SglM and SglPP7 and discovered a third distinct MurJ-targeting Sgl from the predicted phage Changjiang3 (SglCJ3) that we also characterized structurally. Our findings demonstrate that all three Sgls evolved convergently to trap MurJ in a periplasm-open conformation through a common MurJ interface, revealing a pathway for drug design.

GPT-4o mini: Non-social science research article

CLCC1 governs ER bilayer equilibration to maintain lipid homeostasis

Lingzhi Wu, Jianqin Wang, Yawei Wang, Junhan Yang, Yuanhang Yao, Yonglun Wang, Dong Huang, Yating Hu, Xinxuan Xu, Renqian Wang, Wenjing Du, Yiting Shi, Quan Li, Lu Liu, Yuangang Zhu, Shijie Li, Feng-Jung Chen, Xiuqin Zhang, Xiao Wang, Qiang Guo, Li Xu, Peng Li, Xiao-Wei Chen

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Orchestration of lipid production, storage and mobilization is vital for cellular and systemic homeostasis1,2. Dysfunctional plasma lipid control represents the major risk factor for cardiometabolic diseases—the leading cause of human mortality3,4. Within the cellular landscape, the endoplasmic reticulum (ER) is the central hub of lipid synthesis and secretion, particularly in metabolically active hepatocytes in the liver or enterocytes in the gut5,6. Initially assembled in the ER lumen, lipid-ferrying lipoproteins necessitate the cross-membrane transfer of both neutral and phospholipids onto the lumenal apolipoprotein B (APOB), in a poorly defined process7,8,9,10. Here we show that the ER protein CLCC1 regulates cellular lipid partition and, consequently, systemic lipid homeostasis by participating in trans-bilayer equilibration of phospholipids. CLCC1 partners with the phospholipid scramblase TMEM41B11,12 to recognize imbalanced bilayers and promote lipid scrambling, thereby supporting lipoprotein biogenesis and the subsequent bulk lipid transport. Loss of CLCC1 or TMEM41B leads to the emergence of giant lumenal lipid droplets enclosed by imbalanced ER bilayers and, consequently, accelerated pathogenesis of metabolic-dysfunction-associated liver steatohepatitis. The results reveal that phospholipid scrambling at the ER is essential for establishing a dynamic equilibrium. Considering the requirement of trans-bilayer phospholipid equilibration in numerous biological processes, ranging from catabolic autophagy to viral infection13,14,15,16, we anticipate that future work will elucidate a homeostatic control mechanism intrinsic to ER function in lipid biogenesis and distribution.

GPT-4o mini: Non-social science research article

Author Correction: Global subsidence of river deltas

L. O. Ohenhen, M. Shirzaei, J. L. Davis, A. Tiwari, R. Nicholls, O. Dasho, N. Sadhasivam, K. Seeger, S. Werth, A. J. Chadwick, F. Onyike, J. Lucy, C. Atkins, S. Daramola, A. Ankamah, P. S. J. Minderhoud, J. Oelsmann, G. C. Yemele

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GPT-4o mini: Non-social science research article

Echinoderm stereom gradient structures enable mechanoelectrical perception

Annan Chen, Ziqin Wang, Zhizi Guan, Jiajun Wu, Qi Wei Shi, Senlin Wang, Yusheng Shi, Bin Su, Chunze Yan, Zuankai Wang, Jian Lu

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Cellular solids ubiquitously exist in natural systems and are crucial for living organisms1,2. Their unique smooth branch and node morphologies are often seen as adaptations for enhanced mechanical performance3,4. Exploring alternative evolutionary functions can enrich the understanding of cellular solids, but it is frequently neglected. Here we show that the biomineralized cellular solids in echinoderm stereom (for example, sea urchin spine) have unexpected mechanoelectrical perception with response potential and response time, both of which are one to three orders of magnitude greater than those of echinoderm vision5. This exceptional perception originates from the gradient cellular solids (with varying void- or solid-phase diameters) along the [001] spine axis, generating a differential charge density across the stereom surface during liquid flow. Inspired by this natural wisdom, we create artificial spine-like structures using three-dimensional printing technology that exhibit three-fold higher voltage output and eight-fold greater amplitude differential than gradient-free samples, as well as a nature-inspired metamaterial mechanoreceptor capable of time-resolved self-monitoring information underwater. Our findings advance the understanding of load-sensitive biomimetic cellular solids (such as wood, sponge and trabecular bone), with the potential to develop functional gradient cellular materials towards underwater spatiotemporal sensing and water resource utilization.

GPT-4o mini: Non-social science research article

Functional dissection of complex trait variants at single-nucleotide resolution

Layla Siraj, Rodrigo I. Castro, Hannah B. Dewey, Susan Kales, John C. Butts, Thanh Thanh L. Nguyen, Masahiro Kanai, Daniel Berenzy, Kousuke Mouri, Qingbo S. Wang, Petko P. Fiziev, Kristin Tsuo, Zachary R. McCaw, Sager J. Gosai, François Aguet, Ran Cui, Irfahan Kassam, Jeremy McRae, Christopher M. Vockley, Caleb A. Lareau, Sergey Abramov, Alexandr Boystov, Jeff Vierstra, Yukinori Okada, Alexander Gusev, Thouis R. Jones, Eric S. Lander, Pardis C. Sabeti, Hilary K. Finucane, Steven K. Reilly, Jacob C. Ulirsch, Ryan Tewhey

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Identifying the causal variants and mechanisms that drive complex traits and diseases remains a core problem in human genetics 1–5 . Most of these variants individually have weak effects 6 and lie in non-coding gene-regulatory elements 7–10 , for which we lack a complete understanding of how single-nucleotide alterations modulate transcriptional processes to affect human phenotypes 5,11–15 . To address this problem, we measured the activity of 221,412 fine-mapped trait-associated variants using a massively parallel reporter assay 16–20 in 5 diverse cell types. We show that this assay effectively discriminates between likely causal variants and controls, and identified 13,121 regulatory variants with high precision. Although the effects of these variants largely agree with orthogonal measures of function, only 69% of them can plausibly be explained by the disruption of a known transcription factor binding motif. We investigated the mechanisms of 136 variants using saturation mutagenesis and assigned affected transcription factors for 91% of variants without a clear canonical mechanism. Finally, we detected regulatory epistasis at 11% of tested regulatory variants in close proximity and identified multiple functional variants on the same haplotype at a small, but important, subset of trait-associated loci. Overall, our study provides a systematic functional characterization of likely causal common variants that underlie complex and molecular human traits, enabling new insights into the regulatory grammar underlying disease risk.

GPT-4o mini: Non-social science research article

Author Correction: Myocardial reprogramming by HMGN1 underlies heart defects in trisomy 21

Sanjeev S. Ranade, Feiya Li, Sean Whalen, Angelo Pelonero, Lin Ye, Yu Huang, Abigail Brand, Tomohiro Nishino, Rahul Mital, Ryan M. Boileau, Frances Koback, Arun Padmanabhan, Victoria Yu, Bastien Cimarosti, Diana Presas-Ramos, Alexander F. Merriman, Langley Grace Wallace, Annie Nguyen, Nikolaos Poulis, Mauro W. Costa, Casey A. Gifford, Katherine S. Pollard, Deepak Srivastava

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GPT-4o mini: Non-social science research article

Field-free full switching of chiral antiferromagnetic order

Zhiyuan Zhou, Yanzhang Cao, Zhuorui Pan, Yingying Zhang, Shixuan Liang, Feng Pan, Cheng Song

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Chiral antiferromagnets1,2 host octupole order3,4 and combine the advantages of antiferromagnets and ferromagnets. Despite the development of numerous switching strategies5,6,7,8,9, the field-free full switching remains unknown, posing an important obstacle to their practical application in memory technology. Here we prepared a homo-junction constituted of Mn3Sn(0001) bottom layer and polycrystalline Mn3Sn top layer. The tilted Kagomé geometry in polycrystalline Mn3Sn divides the out-of-plane spin polarization from Mn3Sn(0001) layer10,11 into the out-of-Kagomé-plane and in-Kagomé-plane components, generating the symmetric (antiferromagnet-type) and asymmetric (ferromagnet-type) driving forces, respectively. The former accelerates octupole rotation, whereas the latter determines switching chirality. Field-free full switching is realized in the unconventional protocol that integrates the advantages of both antiferromagnetic and ferromagnetic switching. It goes beyond the conventional full-switching framework requiring perpendicular uniaxial anisotropy7,12. An unprecedented switching efficiency is achieved, with both current density and power consumption an order of magnitude lower than in previous configurations, by virtue of the highly efficient driving forces due to spin-torque characteristics of octupole order and the ultralow energy barrier arising from easy-plane anisotropy, overcoming their trade-off in conventional protocols. The zero-field switching also shows the advantages of octupole-programmable chirality and robustness to external magnetic field.

GPT-4o mini: Non-social science research article

A membrane-bound nuclease directly cleaves phage DNA during genome injection

Daniel S. Saxton, Peter C. DeWeirdt, Christopher R. Doering, Ian J. Roney, Michael T. Laub

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From mammals to bacteria, the direct recognition and cleavage of viral nucleic acids is a potent defence strategy against viral infection, but it requires mechanisms for distinguishing self from non-self 1,2 . In bacteria, CRISPR–Cas and restriction-modification systems achieve this discrimination by recognizing specific DNA sequences or DNA modifications, respectively. Alternative mechanisms probably remain to be discovered. Here, we characterize SNIPE, an anti-bacteriophage defence system that constitutively localizes to the bacterial cell membrane in Escherichia coli to block phage λ infection. Using radiolabelled phage DNA and time-lapse microscopy to track phage genomes, we demonstrate that SNIPE directly cleaves phage DNA during genome injection. Based on proximity labelling, we find that SNIPE associates with host proteins essential for λ genome entry and with the λ tape measure protein, which facilitates λ genome injection across the inner membrane. SNIPE also defends against diverse siphoviruses, probably through direct interactions with their tape measure proteins. Our findings establish SNIPE as a widespread bacterial defence system that exploits the spatial organization of phage genome injection to specifically target viral DNA, representing a previously unknown strategy for distinguishing self from non-self in prokaryotic immune systems.

GPT-4o mini: Non-social science research article

Publisher Correction: PtdIns(3,5)P2 is an endogenous ligand of STING in innate immune signalling

Jay Xiaojun Tan, Bo Lv, Jie Li, Tuo Li, Fenghe Du, Xiang Chen, Xuewu Zhang, Xiao-chen Bai, Zhijian J. Chen

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Nature DOI suffix ≠ "/s...": Not a research article

We need a global assessment of avoidable climate-change risks

Peter A. Stott, Y. T. Eunice Lo, John H. Marsham, David Obura, Tom H. Oliver, Matthew D. Palmer, Nicola Ranger, Simon Sharpe, Rowan Sutton

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Nature DOI suffix ≠ "/s...": Not a research article

Daily briefing: New AI drug-discovery engine is ‘on the scale of an AlphaFold4’

Flora Graham

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Nature DOI suffix ≠ "/s...": Not a research article

Why an industry career move is a taboo topic in academia

Adam Levy

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Nature DOI suffix ≠ "/s...": Not a research article

Five ways increased militarization could change scientific careers

Christine Ro

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Nature DOI suffix ≠ "/s...": Not a research article

Health effects linger 20 generations after rats are exposed to fungicide

Rachel Fieldhouse

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Nature DOI suffix ≠ "/s...": Not a research article

How big is the ‘motherhood penalty’? In Denmark, it adds up to $120,000

Sarah Wild

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Nature DOI suffix ≠ "/s...": Not a research article

Flexible paths to multicellularity

Jaruwatana Sodai Lotharukpong, Susana M. Coelho

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Nature DOI suffix ≠ "/s...": Not a research article

Daily briefing: What we know about autism and ageing — and what we don’t

Jacob Smith

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Nature DOI suffix ≠ "/s...": Not a research article

From Victorian voyages to vanishing maps: Books in brief

Andrew Robinson

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Nature DOI suffix ≠ "/s...": Not a research article

Ultra-sensitive CAR T cells eliminate hard-to-treat tumours in mice

Felicity Nelson

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Nature DOI suffix ≠ "/s...": Not a research article

China is waging war on Alzheimer’s. What can its approach teach the rest of the world?

Rachel Fieldhouse

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Nature DOI suffix ≠ "/s...": Not a research article

Defunding Chile’s climate research will undermine science and the region

Germán Poveda, Jhan-Carlo Espinoza, Paola A. Arias, Mariano H. Masiokas

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Nature DOI suffix ≠ "/s...": Not a research article

First-of-a-kind stem-cell therapies set for approval in Japan

Asher Mullard

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Nature DOI suffix ≠ "/s...": Not a research article

The age of animal experiments is waning. Where will science go next?

Diana Kwon

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Nature DOI suffix ≠ "/s...": Not a research article

This AI can improve your peer review — and make it more polite

Nicola Jones

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Nature DOI suffix ≠ "/s...": Not a research article

Are obesity drugs causing a severe complication? What the science says

Mariana Lenharo

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Nature DOI suffix ≠ "/s...": Not a research article

Protein engineering fixes a major crop trade-off

Jie Liu, Jianbing Yan

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Nature DOI suffix ≠ "/s...": Not a research article

Briefing chat: How hovering bumblebees keep their cool

Shamini Bundell, Nick Petrić Howe

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Nature DOI suffix ≠ "/s...": Not a research article

How earthquakes and lightning help explain squeaky sneakers

Nick Petrić Howe, Dan Fox

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Nature DOI suffix ≠ "/s...": Not a research article

AI tools can design genomes. Will they upend how life evolves?

Kate Adamala

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Nature DOI suffix ≠ "/s...": Not a research article

Why do curling stones slide across ice the way they do?

Jenna Ahart

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Nature DOI suffix ≠ "/s...": Not a research article

Scientists must step up to avert a nuclear breakout

Karen Hallberg

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Nature DOI suffix ≠ "/s...": Not a research article

What's the best way to change research fields? These three scientists have ideas

Laura Woodrow

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Nature DOI suffix ≠ "/s...": Not a research article

Stem cells provide a potent treatment for frailty

Edward Chen

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Nature DOI suffix ≠ "/s...": Not a research article

Account for AI in the environmental footprint of scientific publishing

Giovanni Bacaro

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Nature DOI suffix ≠ "/s...": Not a research article

Sea-urchin spines generate electrical signals in flowing water

Pupa U. P. A. Gilbert

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Nature DOI suffix ≠ "/s...": Not a research article

Environmental exposure trains the immune system to dampen allergic responses

Talal A. Chatila

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Nature DOI suffix ≠ "/s...": Not a research article

The Contributor Role Taxonomy tool must serve to record extent of authorship

Xiaohui Xia

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Nature DOI suffix ≠ "/s...": Not a research article

The future perfect continuous passive and other transitive disorders of the mind

Timothy Quinn

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Nature DOI suffix ≠ "/s...": Not a research article

UN creates new scientific AI advisory panel: what will it do?

Elizabeth Gibney

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Nature DOI suffix ≠ "/s...": Not a research article

Daily briefing: Automated robot ‘scientists’ spark debate over the future of lab work

Jacob Smith

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Nature DOI suffix ≠ "/s...": Not a research article

Why every scientist needs a librarian

Amber Dance

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Nature DOI suffix ≠ "/s...": Not a research article

Music is not a universal language — but it can bring us together when words fail

Patrick E. Savage

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Nature DOI suffix ≠ "/s...": Not a research article

Iron Age mass grave reveals unprecedented violence against women and children

Katie Kavanagh

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Nature DOI suffix ≠ "/s...": Not a research article

Scientists face fallout for past associations with Epstein

Natasha Gilbert

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Nature DOI suffix ≠ "/s...": Not a research article

Daily briefing: The new alternatives to animal testing

Flora Graham

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Nature DOI suffix ≠ "/s...": Not a research article

The secret of squeaky basketball shoes

Bart Weber

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Nature DOI suffix ≠ "/s...": Not a research article

Daily briefing: COVID’s origins — what we do and don’t know

Flora Graham

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Nature DOI suffix ≠ "/s...": Not a research article

Light-confining device can control superconductivity — even in the dark

Angela Montanaro, Daniele Fausti

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Nature DOI suffix ≠ "/s...": Not a research article

World-first stem-cell therapy shows promise for treating spina bifida in the womb

Rachel Fieldhouse

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Nature DOI suffix ≠ "/s...": Not a research article

The surprising science of squeaky sneakers

Dan Fox

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Nature DOI suffix ≠ "/s...": Not a research article

Historically Black US universities chase top research ranking

Alexandra Witze

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Nature DOI suffix ≠ "/s...": Not a research article

Daily briefing: ‘Universal’ vaccine protects mice from multiple pathogens

Jacob Smith

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Nature DOI suffix ≠ "/s...": Not a research article

Lipid nanoparticles engineered to target therapeutic RNA to the pancreas

Aviad Elisha, Dan Peer

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Nature DOI suffix ≠ "/s...": Not a research article

Brains of ‘super agers’ are strong producers of new neurons

Mariana Lenharo

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Nature DOI suffix ≠ "/s...": Not a research article

Five ways to spot when a paper is a fraud

Stephanie Melchor

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Nature DOI suffix ≠ "/s...": Not a research article

Evidence alone won’t save biodiversity: the golden apple snail reveals an implementation gap

Fengbo Li, Tianlun Zheng, Zhen Yang, Ming Li

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Nature DOI suffix ≠ "/s...": Not a research article

Whistle while you whinny: researchers identify two sounds straight from the horse’s mouth

Katherine Bourzac

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Nature DOI suffix ≠ "/s...": Not a research article

AI is threatening science jobs. Which ones are most at risk?

Edward Chen

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Nature DOI suffix ≠ "/s...": Not a research article

Pop-up journals for policy research: can temporary titles deliver answers?

Dalmeet Singh Chawla

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Nature DOI suffix ≠ "/s...": Not a research article

Neanderthal dad, human mum: study reveals ancient procreation pattern

Freda Kreier

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Nature DOI suffix ≠ "/s...": Not a research article

COVID’s origins: what we do and don’t know

Marietjie Venter, Jean-Claude Manuguerra, John M. Watson, Thea K. Fischer, Stuart D. Blacksell, Kathrina Summermatter, Inger K. Damon, Christian Drosten, Phillip Alviola, Abdullah Assiri, Elmoubasher Farag, Raman Gangakhedkar, Nada Ghosn, Maria G. Guzman, Christian Happi, Gladys Kalema-Zikusoka, Normand Labbé, Khin Myint, Hung Nguyen-Viet, Chinwe Ochu, Masayuki Saijo, Rosemary Sang, Supaporn Wacharapluesadee

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Nature DOI suffix ≠ "/s...": Not a research article

This compound enhances long-term memory of mice — but only in females

Mohana Basu

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Nature Human Behaviour

GPT-4o mini: Non-social science research article

A large mass grave from the Early Iron Age indicates selective violence towards women and children in the Carpathian Basin

Linda Fibiger, Miren Iraeta-Orbegozo, Jovan Koledin, Jason E. Laffoon, Cheryl A. Makarewicz, Dorothea Mylopotamitaki, Caroline Bruyere, Thomas Booth, Christopher Bronk Ramsey, Robert Layfield, Lucas Anchieri, Yuejiao Huang, Anna Kjær Knudsen, Jonas Niemann, Darko Radmanović, Neil J. Oldham, Barry Shaw, Saoirse Tracy, Sara Nylund, J. Stephen Daly, Christine Winter-Schuh, David van Acken, Harald Ringbauer, Alissa Mittnik, Jazmin Ramos-Madrigal, Hannes Schroeder, Barry Molloy

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Narratives about the motivations and conditions for mass violence as a persistent feature of conflict throughout human history have evolved in complexity and materiality. Victims of these events are key for understanding the evolution and transformative power of violent behaviour as it developed from simple intergroup conflict to more strategic mass violence. Here we present the results of a bioarchaeological study of 77 and biomolecular analysis of 25 individuals from a ninth-century BCE mass grave from Gomolava in the Carpathian Basin, Southeast Europe. The site is located at the interface of complex sociospatial relations, divergent cultural traditions and values, and competing ideologies of landscape use. We show that excessive lethal violence enacted mostly on women and children suggests a selective demographic bias. The people buried together shared few, even distant, genetic relationships, and so their killing presents striking evidence for an episode of cross-regional conflict and an underlying aggressive shift in power, violence and gender relations in the region. Gomolava provides evidence consistent with deliberate annihilation of select sections of a regional population as a motivation for mass violence behaviour in later prehistoric Europe. It also shines new light on the socioeconomic agency and importance of women and young individuals in later European prehistory.

How to foster a supportive research group culture

Irmgard Mausz, Paul Sauseng

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Digital mental health needs a purpose-driven approach

Mowafa Househ, Hurmat Ali Shah, Zain Ul Abideen Tariq, Diana Alsayed Hassan, Mohamed Khalifa, Jens Schneider, Mounir Hamdi, Alaa Abd-Alrazaq, Arfan Ahmad, Barry Solaiman, Andre Kushniruk, Saleem Khaldoon Al-Nuaimi

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Digital mental health (DMH) encompasses telepsychiatry, mobile apps, games and artificial intelligence (AI)-augmented interventions. In recent years, there has been a steady increase in the development and deployment of DMH solutions, particularly those incorporating AI-based mental health support. In this Perspective, we consider both the technological and clinical design spaces and advocate for purpose-driven, patient-centred solutions rather than a technology-first approach. The purpose of DMH should be to address societal gaps in mental healthcare, following established frameworks for chronic illness management to meet the specific needs of each patient. We examine the ethical dimensions of DMH, underscoring the importance of procedural justice, harm prevention and data privacy. Additionally, we highlight the unique challenges faced by marginalized and vulnerable populations, emphasizing the role of DMH in promoting equal availability of mental healthcare. Aligning DMH with user perspectives, ethical considerations and clinician involvement can result in more effective and empathetic digital interventions, thereby transforming mental healthcare delivery.

How to research ethically with online data

Nicolas Gold

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Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article

The Nemp1–Nesprin complex mediates cellular responses to matrix mechanics

Abira Ganguly, Hannah Zmuda, Javier Abello, Danielle Illy, Christopher Walter, Yonit Tsatskis, Nattapon Thanintorn, Ying Zhang, Bilal Ahmad Hakim, Didier Hodzic, Amber N. Stratman, Andrea Jurisicova, Amit Pathak, Helen McNeill

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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.

GPT-4o mini: Non-social science research article

Aerophilic debubbling

Bert J. C. Vandereydt, Saurabh Nath, Kripa K. Varanasi

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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.

GPT-4o mini: Non-social science research article

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

Thomas M. J. Green, Jack G. Rayner, Daniel A. Villar, Nathan W. Bailey

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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.

GPT-4o mini: Non-social science research article

Nonoxidative pentose phosphate pathway regulates CD8 + T cell immunity by maintaining NADPH homeostasis

Jingyu Feng, Qian Zhang, Li Luo, Zhichao Gu, Wen Liu, Jingsong Xu, Mengxin Qi, Zhongji Meng, Lin Li, Liangliang Lin, Zhuoshun Yang, Huafeng Zhang

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NADPH is essential for cellular biosynthesis and redox balance in CD8 + T cells. Here, we demonstrate that the nonoxidative pentose phosphate pathway (non-oxPPP), mediated by transketolase (TKT) and transaldolase (TALDO1), is critical for CD8 + T cell activation, proliferation, and memory formation by maintaining NADPH homeostasis. Metabolomic profiling and isotopic tracing revealed upregulated non-oxPPP flux in effector (T eff ) and memory (T m ) CD8 + T cells, enabling a pentose cycle that amplifies NADPH yield and sustains metabolic fitness for T cell immunity. Genetic knockdown or pharmacological inhibition of Tkt or Taldo1 impaired NADPH production, leading to ribose-5-phosphate (R5P) accumulation, oxidative stress, reduced lipid synthesis, mitochondrial dysfunction, and compromised T eff cell proliferation, cytokine production, and antitumor efficacy. Conversely, enhancing non-oxPPP activity promoted T m differentiation, persistence, and recall responses. Targeting the non-oxPPP represents a promising strategy to enhance cancer immunotherapy and vaccine efficacy by bolstering T cell effector and memory responses.

GPT-4o mini: Non-social science research article

Insulin and leucokinin pathways coordinate adaptive salt appetite in Drosophila

Sonali Puri, Jiun Sang, Prakash Pandey, Youngseok Lee

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Salt intake must be tightly regulated: Too little compromises physiological function, while too much is harmful. Animals therefore display an adaptive salt appetite, dynamically switching between attraction and avoidance depending on internal sodium status. Although this behavioral flexibility is well documented, the central brain mechanisms that link internal salt need to changes in sensory-driven behavior remain poorly understood. Here, we identify a brain-centered neuroendocrine circuit that enables adaptive regulation of salt appetite in Drosophila melanogaster . Using targeted genetic screens, we show that leucokinin ( Lk ), its receptor ( Lkr ), and the insulin-like peptide Ilp2 are essential for shifting salt preference according to sodium deprivation. Under salt-sated conditions, high salt remains aversive. In contrast, salt-deprivation selectively activates Lk neurons in the anterior leucokinin (ALK) region, which in turn recruit Lkr -expressing insulin-producing cells (IPCs), also referred to as medial neurosecretory cells, to promote salt-seeking behavior. Functional imaging and circuit manipulation demonstrate that silencing either neuronal population abolishes this adaptive switch, whereas pathway activation overrides innate salt aversion through PKA-dependent signaling. Notably, both ALK neurons and IPCs directly detect extracellular sodium independent of synaptic input, identifying them as central sodium sensors that couple internal state to behavioral output. Together, our findings define a neuroendocrine mechanism by which the brain adaptively recalibrates salt appetite to maintain internal homeostasis. This work provides a conceptual framework for state-dependent nutrient seeking and suggests conserved principles relevant to salt balance disorders in mammals.

GPT-4o mini: Non-social science research article

Capturing ribosomal structures in cellular extracts with cryoPRISM: A purification-free cryoEM approach reveals novel structural states

Mira B. May, Gabriella S. Lopez-Perez, Joseph H. Davis

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Structural analyses of ribosomes by single particle cryogenic electron microscopy (cryoEM) have traditionally relied on purified or reconstituted samples, with particles often trapped in desired states using genetic, pharmacological, or biochemical perturbations. While informative, such in vitro methods often fail to capture the full diversity of structural states and associated protein factors present in cells. In contrast, in situ cryoelectron tomography preserves cellular context but is limited by low throughput and modest resolution. Here, we present cryoPRISM (purification-free ribosome imaging from subcellular mixtures), a rapid ex vivo workflow encompassing cell lysis, vitrification, and image analysis methods for high-resolution analyses of ribosomal structures directly from cell lysates. Applying cryoPRISM in Escherichia coli , we resolved more than 20 distinct ribosomal states spanning assembly, translation initiation, elongation, trans-translation, and quiescence, including a novel configuration of EF-G bound to idle ribosomes with the ribosome hibernation factor ribosome-associated inhibitor A. Given its speed, accessibility, and ability to preserve native interactions and structural heterogeneity, we anticipate that cryoPRISM will be broadly applicable for uncovering ribosomal biology across diverse organisms and conditions.

GPT-4o mini: Non-social science research article

Clemastine fumarate promotes myelin repair in a nonhuman primate model of demyelination characterized by absent spontaneous remyelination

Nadège Sarrazin, Rafik Arab, Christian Cordano, Elena Brazhnikova, Jérémy Chazot, Fabrice Arcizet, Corinne Bachelin, Dominique Langui, Daniel J. Bennett, Ahmed Abdelhak, Harkeerat Halait, Pierre Moissonnier, Céline Nouvel-Jaillard, Pierre Pouget, Ari J. Green, Anne Baron-Van Evercooren

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Promotion of remyelination has become a new therapeutic avenue, to prevent neuronal degeneration and promote recovery in white matter diseases such as multiple sclerosis. Clemastine fumarate among several promyelinating agents, has been validated as a promyelinating agent in rodents and has led to a first successful double-blind, placebo-controlled clinical trial evaluating a remyelinating therapy for multiple sclerosis (MS) [A. J. Green et al. , Lancet 390 , 2481–2489 (2017)]. To date, most of promyelinating strategies have been developed in short-lived rodent models of demyelination, which spontaneously repair. Well-defined nonhuman primate models closer to man would allow to efficiently advance therapeutic approaches, and namely to assess noninvasively, their efficacy in promoting functional repair. We developed a nonhuman primate model of optic nerve demyelination which leads to failed remyelination, progressive neuronal degeneration, and visual dysfunction, thus recapitulating several features of MS lesions and providing the missing link to translate emerging preclinical therapies to the clinic for myelin disorders such as multiple sclerosis [N. Sarrazin et al. , Proc. Natl. Acad. Sci. U.S.A. 119 , e2115973119 (2022)]. We used this model to assay the therapeutic benefits of clemastine. Our histological and ultrastructural findings show that clemastine is able to overcome the failed remyelination of the nonhuman primate optic nerve. We also used visual evoked potential, optical coherence tomography, and electroretinogram as noninvasive means to follow up the optic nerve de/remyelination process and correlated these findings with postmortem analysis to establish the safety and efficacy of clemastine therapy in promoting functional and morphological recovery in nonhuman primates. We demonstrate that clemastine can overcome chronic demyelination in nonhuman primates.

GPT-4o mini: Non-social science research article

Differential disease tolerance mediates sex-biased illness severity in sepsis

Breenna Dobson, Kathryn Strayer, Ayesha Wijesinghe, Jared Schlechte, Oscar Tejada, Alexandria Bartlett, Matthew Stephens, Diana Changirwa, Nicole A. Cho, Ian-ling Yu, Nargis Khan, Braedon McDonald

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Sepsis in humans, as well as mouse models of infection, demonstrates sex-biased outcomes in which males tend to have a higher incidence, higher severity, and higher mortality compared to females. Despite this important sex-bias in sepsis outcomes, little is known about its mechanistic drivers nor therapeutic implications. Much of the foundational data on sepsis pathogenesis is derived from animal studies that included only male subjects, potentially contributing to the notable paucity of successful mouse-to-human translation of sepsis therapeutics. In this study, we demonstrate that male-biased illness severity and organ dysfunction in mouse models of bacterial sepsis are mediated by impaired disease tolerance in males, involving impaired tolerogenic shifts in mitochondrial oxidative metabolism compared to females. Microbiological and immunological analyses of sepsis between males and females revealed that sex-biased disease tolerance was independent of infection resistance mechanisms, as well as canonical immune/inflammatory dysregulation. Therapeutic potentiation of mitochondrial tolerance with doxycycline neutralized sexual dimorphism of illness severity and organ dysfunction through a male-predominant treatment effect. These data reveal that biological sex is a fundamental determinant of illness severity and treatment responsiveness in sepsis through modulation of disease tolerance, which may be harnessed therapeutically to address sex-biased outcomes in sepsis.

GPT-4o mini: Non-social science research article

Uniqueness and predictability in evolution and the history of mollusks

Geerat J. Vermeij, Tracy J. Thomson

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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.

GPT-4o mini: Non-social science research article

Stress and resilience in northern European marine ecosystems

Marcos Llope, Thorsten Blenckner, Paraskevas Vasilakopoulos, Niall McGinty, Christopher P. Lynam, Pierre Hélaouët, Christian Möllmann, Romain Frelat, Joël M. Durant, Leif C. Stige, Nils Chr. Stenseth

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Marine ecosystems are facing multiple pressures from human activities, such as fishing and nutrient inputs from farming and agriculture, compounded by the global effects of climate change. As a result, the ecosystem services that societies depend on are at risk from the cumulative impact of these pressures. To better understand how different ecosystems respond, it is essential to assess their resilience. While predicting ecosystem resilience remains challenging, significant progress has been made in developing methods to measure it. In this study, we assessed resilience in four northern European marine ecosystems: the Icelandic Waters, the Barents Sea, the Baltic Sea, and the North Sea, spanning 3 to 5 decades. “Folded stability landscapes” were constructed for the Baltic and North Sea. This region provides a unique setting, with a south-north gradient from temperate to subarctic environments and a southeast-northwest gradient from open to semienclosed topographies. The Icelandic Waters and Barents Sea evolved relatively continuously, while the Baltic Sea and North Sea underwent more drastic changes. By comparing results across these gradients, we explore the role of isolation, level of pressures, and food web complexity in shaping resilience patterns and discuss the implications for managing resilient marine ecosystems in the future.

GPT-4o mini: Non-social science research article

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

Brian Guay, Tyler Marghetis, Cara Wong, David Landy

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GPT-4o mini: Non-social science research article

Detectable global temperature responses to wildfires and volcanic eruptions

Yaowei Li, Benjamin D. Santer, Susan Solomon, David W. J. Thompson, Qiang Fu

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Large volcanic eruptions and intense wildfires perturb Earth’s atmospheric temperature. Understanding the climate response to such natural forcings is essential for obtaining reliable estimates of its response to anthropogenic greenhouse gas emissions. While the climate impacts of volcanic sulfate aerosols are well documented, other natural forcings—including wildfire smoke reaching the stratosphere and water vapor injections from a submarine eruption—pose new challenges for detecting and attributing their atmospheric temperature impacts. Here, we demonstrate robust detection of statistically significant temperature anomalies in the troposphere and stratosphere using multidecadal satellite observations and internal variability estimates from a climate model ensemble and from observations. We analyze three landmark events: the 1991 Pinatubo eruption, the 2019-2020 Australian wildfires, and the 2022 Hunga Tonga eruption. Each leaves a fingerprint with distinct altitudinal, geographical, and temporal structure. The global-mean stratospheric signal from Australian wildfires is detectable even in time averages extending beyond 10 mo, despite injecting only ~5% of Pinatubo’s aerosol mass. For Hunga Tonga, we detect significant and prolonged stratospheric cooling, but no robust tropospheric signal in the first 2 y. These findings show that both sulfate and nonsulfate stratospheric perturbations produce distinct, statistically identifiable global temperature signals. Accounting for such forcings in climate model simulations is therefore essential for improving comparisons of simulated and observed variability.

GPT-4o mini: Non-social science research article

Class-I myosin responds to changes in membrane tension during clathrin-mediated endocytosis in human induced pluripotent stem cells

Samantha L. Smith, Tong Zhan, Wan Li, Henry De Belly, Qing Zhang, Ke Xu, Orion D. Weiner, David G. Drubin

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Clathrin-mediated endocytosis (CME) is an essential cellular process that needs to operate efficiently across a wide range of conditions. Internalization of the endocytic site involves forces generated by membrane-bound proteins and Arp2/3-mediated branched actin filament assembly to bend the plasma membrane from flat to omega-shaped. In mammalian CME, the requirement for a branched actin filament network varies depending on cell type and differences in membrane tension. However, how the actin network adapts to changes in load in order to ensure robustness of this process over a range of membrane tensions is not understood. Here, we combine live-cell imaging and superresolution microscopy of genome-edited human induced pluripotent stem cells to investigate the role of the mammalian class-I myosin, Myosin1E (Myo1E), in load adaptation. Under normal conditions, sites that recruit Myo1E are rare and exhibit slow CME dynamics. However, as membrane tension increases and CME dynamics are slowed globally, Myo1E is recruited to more sites, likely to increase actin assembly and motor activity, resulting in increased force generation to rescue stalled sites and promote internalization. Loss of Myo1E results in increased Arp2/3 complex lifetime at CME sites under normal conditions, and at high membrane tension, these sites fail to recruit as many Arp2/3 molecules. We propose that Myo1E is recruited to CME sites that have stalled due to increased membrane tension, where it helps build a more effective branched actin network by generating force through motor activity and recruiting additional Arp2/3 complexes to rescue stalled sites.

GPT-4o mini: Non-social science research article

Sibling number and early interactions shape social competence for life

Bruno Camargo-dos-Santos, Barbara Taborsky

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The social environment experienced during development plays a crucial role in shaping social competence—the ability to respond appropriately to social challenges. Sibling number and the social interactions between them are key components of the early lives in many animals. While these components are well known to influence social development in humans, their role in nonhuman animals remains unclear. Here, we show that both the number of siblings and opportunities for social interaction are essential for developing social competence in the highly social cichlid Neolamprologus pulcher . Fish reared in large broods (LB) displayed more affiliative and fewer aggressive or submissive behaviors during early life compared to those reared in small broods (SB) or in large broods with restricted opportunities for interactions (4 × 8). Later in life, LB fish were more socially competent. Thus, social competence arises not from the number of individuals or interactions alone, but from the combination of both.

GPT-4o mini: Non-social science research article

A Meier–Gorlin syndrome mutation impairs the loading of the MCM2–7 complex during DNA replication initiation

Yusong Liu, Mengquan Yang, Ping Lu, Haishan Gao, Maozhou He, Yitao Wang, Ao Qi, Ting Cao, Qiuqin Zhang, Shutao Qi, Yigong Shi, Hongtao Yu

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Chromatin loading of the hexameric replicative helicase MCM2–7 complex requires coordinated interactions with the origin recognition complex (ORC), CDC6, and CDT1. MCM2–7 not bound to DNA forms a single hexamer (SH) with an open DNA entry gate between MCM2 and MCM5. Two MCM2–7 SHs can be loaded sequentially to form the double hexamer (DH) that encircles the DNA duplex. Activated MCM2–7 then unwinds DNA and initiates DNA replication. Our cryoelectron microscopy analyses show that a fraction of human MCM2–7 without DNA exists as DH. Unexpectedly, we find that the MCM3 winged helix domain (WHD) docks on MCM2 in both DNA-free DH and SH, creating a safety latch across the DNA entry gate to block DNA entry into the central channel. The safety latch can be opened by ORC-CDC6 binding. Perturbing this latch by structure-based or disease-related mutations of MCM3 causes replication defects and DNA damage checkpoint activation. Shortening the MCM3 linker between the helicase domain and WHD alleviates the cell cycle defects of the latch-strengthening mutation. Our findings uncover a regulated step in MCM2–7 loading with implications for human diseases.

GPT-4o mini: Non-social science research article

Robust input disentanglement through dendritic calcium–mediated action potentials

Sima Hashemi, Shirin Shafiee, Christian Tetzlaff

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In daily life, living beings encounter a continuous stream of mixed information, which has to be disentangled by the brain to form proper representations. Using computational modeling, we demonstrate that the interplay between dendritic calcium–mediated action potentials (dCaAPs) with synaptic plasticity and rewiring can enable single neurons to successfully perform this complex task. Compared to other types of dendritic spikes, dCaAPs exhibit a high triggering threshold, large, but graded spike amplitude, with lower amplitudes for stronger synaptic inputs. We show that these properties enable neurons to successfully learn to represent discrete items from a continuous input stream by facilitating the clustering of synapses with temporally correlated presynaptic activities onto the same dendritic branch. In comparison to N-methyl-D-aspartate spikes, dendrites generating dCaAPs can form representations of individual items more efficiently, independent of the temporal order of their presentation during learning—whether randomly, sequentially, as part of a random stream of simultaneously shown input items, or even as items with shared properties. Thus, our results provide further evidence about the critical role of dCaAPs for the computational capabilities of single neurons.

GPT-4o mini: Non-social science research article

Neuronal TDP-43 regulates myelin formation via neurexin 1 mRNA stabilization

Jiayi Li, Yohei Iguchi, Kenji Yoshida, Daisuke Kato, Kunihiko Araki, Kenta Kobayashi, Satoshi Yokoi, Rei Yoshimoto, Madoka Iida, Yoshinobu Amakusa, Yu Kawakami, Takashi Yoshimura, Ryo Chikuchi, Koyo Tsujikawa, Yuichi Riku, Yasushi Iwasaki, Yohei Okada, Nobuhiko Ohno, Hiroaki Wake, Masahisa Katsuno

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Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) develop as spatial pathologies in which neurons and glial cells are interconnected. TAR DNA-binding protein 43 (TDP-43) is a major pathological protein that is inextricably associated with ALS and FTLD. In this study, we investigated the roles of neuronal TDP-43 in neuron–oligodendrocyte interactions using neuron-specific TDP-43 knockout (TDP-43cKO) mice. TDP-43 depletion in neurons induced hypomyelination, which was confirmed by immunohistochemistry and ultrastructural analysis. In addition, conduction disturbance was revealed by electrophysiological analysis. The hypomyelination of TDP-43cKO mouse was restored by cytoplasmic TDP-43 supplementation in neurons. Neuron-specific transcriptome analysis revealed that neurexin 1 (NRXN1) is the regulatory target of TDP-43, which promotes myelin formation. The hypomyelination of TDP-43cKO mice was also restored by NRXN1b supplementation in neurons. We further confirmed that TDP-43 stabilizes Nrxn1 mRNA by binding to the Nrxn1 3’untranslated region (3’UTR). Although TDP-43cKO exhibited impaired recognition memory, the supplementation of NRXN1 in the hippocampus recovered the memory disturbances. In conclusion, this study demonstrates the neuron–oligodendrocyte interaction mediated by neuronal TDP-43 via NRXN1 mRNA stabilization. These findings shed light on neuron–oligodendrocyte interaction in the disease mechanisms of ALS/FTLD.

GPT-4o mini: Non-social science research article

An accurate and efficient framework for modeling multimetal competitive adsorption on clay minerals

Pengyuan Gao, Xiandong Liu, Xiancai Lu, Christophe Tournassat

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Multiple toxic metal elements usually coexist and thus their competitive adsorption always occurs in natural and engineered clay-rich systems. Currently, however, the competitive adsorption mechanisms of multicomponent metal systems on clay mineral surfaces are still unclear, hindering the accurate prediction of toxic metal distribution in soil-water environments. In this study, we uncovered the microscopic mechanism of competitive adsorption of multimetals on heterogeneous clay mineral surfaces using first principles calculation, which indicates that metal ion size largely dominates their complexation on clay mineral surfaces, and competitive adsorption of metals plays a key modulatory role in the adsorption process on clay minerals. By integrating theoretically and experimentally derived multiscale information, a state-of-the-art surface complexation model (SCM) framework has been developed for modeling competitive adsorption. Extensive tests showed that the SCM framework accurately and efficiently reproduces the toxic metal distribution, which enables the quantitative prediction and understanding in realistic environmental conditions. Our results have wide applications in future fundamental studies and the design of environmental materials for toxic metal removal from aquatic systems.

GPT-4o mini: Non-social science research article

HOP2–MND1 chaperones a diffusing DMC1–ssDNA complex to survey dsDNA for homology recognition during meiotic recombination

Bingkai Cheng, Yanan Li, Yi Zhao, Yuting Zhang, Xia Zhang, Lishuang Chen, Hao Yang, Xiaoxuan Song, Zhiyun Ren, Cong Liu, Jingdong Xue, Bing Li, Chao Liu, Wei Li, Bo Sun

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Meiotic recombination ensures genetic diversity and accurate chromosome segregation by mediating reciprocal DNA exchange between homologous chromosomes. In this process, the meiosis-specific recombinase DMC1 plays a pivotal role in homology search and pairing, but the molecular mechanisms underlying its function remain unclear. Using single-molecule imaging, we demonstrate that the human DMC1–ssDNA presynaptic complex employs a diffusion-based mechanism to search for homologous DNA. Although this diffusing complex generates a migrating DNA “bubble,” it cannot align with the homologous sequence in the absence of free DMC1 protein. Strikingly, the meiosis-specific cofactor complex HOP2–MND1 compensates for the lack of free DMC1 and enables homology recognition. Notably, HOP2–MND1 achieves this by codiffusing with the presynaptic complex, acting to clamp the ssDNA–dsDNA junctions and maintain an expanded DNA bubble conducive to sequence alignment. Our findings identify DMC1 together with HOP2–MND1 as a functional homology search unit and provide mechanistic insights into how auxiliary factors regulate DMC1-driven strand exchange during meiotic recombination.

GPT-4o mini: Non-social science research article

mtDNA leakage promotes neuron–glia crosstalk to induce epilepsy by cGAS–STING-driven neuroinflammation and serine metabolic reprogramming

Jie Jiang, Meiling Zuo, Kehan Zhao, Zhihao Ling, Zhida Wu, Dongfang Xue, Shouyong Mo, Yuanhui Liu, Yongjun Chen, Jie Wang, Bin Lu, Chuanzhou Li, Yaqi Duan, He He, Zhiyin Song

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Epilepsy is increasingly recognized as a disorder involving metabolic dysregulation beyond neural hyperexcitability, yet the underlying metabolic mechanisms remain poorly defined. Here, we identify a mitochondrion–immunity–metabolism axis that drives spontaneous chronic epilepsy. Brain-specific deletion of Mic19 impairs mitochondrial cristae structure and mitochondrial integrity in neurons, leading to activation of the Z-mitochondrial DNA (mtDNA)–ZBP1–RIPK3–mixed lineage kinase domain-like protein (MLKL) axis and p-MLKL-mediated pore formation on the mitochondrial membrane. This process results in cytosolic and extracellular leakage of mtDNA, which is subsequently taken up by microglia and triggers cyclic GMP-AMP synthase (cGAS)–STING-dependent inflammatory signaling. The resulting neuroinflammation promotes sustained activation of astrocytes. Critically, reactive astrocytes undergo profound metabolic reprogramming, marked by upregulated glycolysis and enhanced L-serine biosynthesis. Astrocyte-derived L-serine is subsequently transferred to neurons and converted into D-serine, a key NMDA receptor coagonist that enhances neuronal excitability. This metabolic shift in astrocytes exacerbates excitotoxicity and sustains epileptic activity. Importantly, pharmacologic inhibition of STING with H-151 treatment markedly suppresses seizures, reinforcing the therapeutic potential of targeting immunometabolic crosstalk in epilepsy. Our findings reveal that mtDNA-mediated cGAS–STING activation and D-serine act as important drivers of epilepsy initiation, offering mechanistic insights into neuron–microglia–astrocyte crosstalk and highlighting immunometabolic modulation as a promising therapeutic strategy for epilepsy.

GPT-4o mini: Non-social science research article

Operator-level quantum acceleration of non-logconcave sampling

Jiaqi Leng, Zhiyan Ding, Zherui Chen, Lin Lin

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Sampling from probability distributions of the form σ ∝ e − β V , where V is a continuous potential, is a fundamental task across physics, chemistry, biology, computer science, and statistics. However, when V is nonconvex, the resulting distribution becomes non-logconcave, and classical methods such as Langevin dynamics often exhibit poor performance. We introduce a quantum algorithm that provably accelerates a broad class of continuous-time sampling dynamics. For Langevin dynamics, our method encodes the target Gibbs measure into the amplitudes of a quantum state, identified as the kernel of a block matrix derived from a factorization of the Witten Laplacian operator. This connection enables Gibbs sampling via singular value thresholding and yields up to a quartic quantum speedup over best-known classical Langevin-based methods in the non-logconcave setting. Building on this framework, we further develop the first quantum algorithm that accelerates replica exchange Langevin diffusion, a widely used method for sampling from complex, rugged energy landscapes.

GPT-4o mini: Non-social science research article

Decadal extreme drought reduces alpine subsoil carbon stocks

Ronglei Zhou, Jinsong Wang, Quancheng Wang, Ning Liu, Chenglong Ye, Jingjing Shi, Mengjie Liu, Zhangwei Gao, Houkun Chu, Zhenrui Zhang, Bin Niu, Song Wang, Ruiyang Zhang, Dashuan Tian, Shuli Niu

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Grassland soil organic carbon (SOC) stocks are increasingly vulnerable to intensified drought. Yet, how long-term, especially extreme, drought affects these C reserves across soil profiles remains unresolved. Here, we present the response of SOC stocks at various depths (0 to 60 cm) using an experiment involving a 10-year drought gradient (P, 1/2 P, 1/4 P, and 1/12 P, where P is ambient precipitation) in an alpine grassland. We found that extreme drought (1/12 P) caused significant SOC losses in the subsoil, whereas mild to moderate droughts had no significant effects on SOC at any depth. Under extreme drought, SOC stocks declined by 27% in the 20 to 30 cm layer and by 37% in the 30 to 40 cm layer, while no significant changes were observed in the topsoil (0 to 20 cm) and the deeper layer (40 to 60 cm). Subsoil C losses were primarily driven by reductions in mineral-associated organic C (MAOC) rather than particulate organic C. Multiyear extreme drought disrupted soil–microbe–mineral interactions, as indicated by reductions in soil nitrogen availability, microbial biomass, carbon use efficiency, and mineral-binding agents. These changes collectively undermined the formation and stabilization of MAOC. Our findings suggest that prolonged extreme drought can weaken subsoil C storage and stability, highlighting the need to incorporate subsoil processes into Earth System Models to better predict soil C–climate feedback under future drought scenarios.

GPT-4o mini: Non-social science research article

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

Dasom Ham, Owen Kay, Catherine Hausman

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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.

GPT-4o mini: Non-social science research article

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

Chengpin Liang, Qingting Li, Bin Chen, Tingting Zhai, Xiaoqian Luo, Yang Yang, Jiang Qian, Dan Zhao, Shihua Luo, Fei Wang, Qian Li, Jianlei Shen, Chunhai Fan

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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.

GPT-4o mini: Non-social science research article

Programmed meiotic errors facilitate dichotomous sperm production in the silkworm, Bombyx mori

Leif Benner, Makenzie Richmond, Youbin Xiang, LingSze Lee, Clio B. Hockens, Tianwei Li, Zulin Yu, Dai Tsuchiya, Shengping Huang, Eelco C. Tromer, R. Scott Hawley, Leah F. Rosin

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The goal of meiosis is typically to produce haploid gametes (eggs or sperm). Failure to do so is catastrophic for fertility. However, Lepidopteran (moths and butterflies) males produce two sperm morphs: nucleated (eupyrene) sperm and anucleated (apyrene) sperm, both of which are essential for fertilization. The meiotic differences in the two types of spermatogenesis are unclear, and our knowledge of the molecular differences between eupyrene and apyrene spermatogenesis is extremely limited in all systems. The only factor identified as being required for apyrene spermatogenesis is Sex-lethal ( Sxl ). Here, we show through cytological analysis of meiotic events that there are several key differences in the genesis of apyrene and eupyrene sperm. Specifically, during meiosis I, apyrene spermatocytes fail to decondense and pair their chromosomes during meiotic prophase I. Telomeres fail to localize to the nuclear periphery, and full-length synaptonemal complex does not form. We also find evidence of an abnormal second cell division during apyrene meiosis. RNA sequencing of both eupyrene- and apyrene-producing testes reveals distinct changes in transcriptional programs, including down-regulation of a myriad of cell division genes during apyrene meiosis. By comparing wildtype and Sxl -knockout apyrene testes, we found that Sxl is not required for regulating the expression of the cell division genes but instead may play a role in blocking hormone signaling from altering testis cell identity. Together, our findings reveal significant insights into two converging molecular pathways that promote the formation of dimorphic sperm in Lepidoptera.

GPT-4o mini: Non-social science research article

Geometrical preference of anchoring sites in the unicellular organism Stentor coeruleus

Syun Echigoya, Takuya Ohmura, Katsuhiko Sato, Toshiyuki Nakagaki, Yukinori Nishigami

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Organisms often inhabit environments comprising complex structures across various scales. Animals rely on visual information from surrounding geometrical structures for navigation. Even at the microscale, various microsediments form complex structures in microbial habitats. The movement of microorganisms is passively affected by collisions and hydrodynamic interactions with surrounding structures. However, the influence of microenvironmental geometry on behavioral changes of unicellular organisms that lack visual perception remains unclear. Here, we developed geometrically structured chambers to investigate anchoring site preferences in the swimming ciliate Stentor coeruleus . Our experiments revealed that S. coeruleus preferentially anchored in narrow regions characterized by specific geometrical features, including corner angle, depth, and curvature at the corner end. Before anchoring, free-swimming S. coeruleus changed its behavior to move along the boundary wall of the chambers, accompanied by Ca 2+ -induced asymmetrical body deformation. To further investigate how S. coeruleus moves along the wall continuously, we conducted a hydrodynamic simulation and revealed that the asymmetric morphology causes asymmetric propulsive forces, explaining wall-following behavior through physical interactions with a wall. Thus, morphological change near a wall causes wall-following behavior, facilitating the identification of these narrow anchoring sites. Our findings indicate that environmental geometry drives behavioral transitions in S. coeruleus through simple biophysical processes, enabling spatial selection without visual cues. Overall, these results suggest that microgeometry plays a key role in shaping ecological niches for unicellular microorganisms.

GPT-4o mini: Non-social science research article

Glycosylation of glyphosate drives residue reduction and herbicide tolerance in rice

Fulai Yang, Yuehua Wang, Wentao Zhou, Chengfeng Xue, Fengshou Dong, Yongquan Zheng, Meng Zhang, Li Chen, Jun Zhang, Xinglu Pan, Ruifeng Yao

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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.

GPT-4o mini: Non-social science research article

Evolutionary remodeling of a remnant GET pathway factor into PEX38, an essential peroxin

Chethan K. Krishna, Stefan Gaussmann, Hirak Das, Martin Jung, Silke Oeljeklaus, Michael Sattler, Bettina Warscheid, Vishal C. Kalel, Ralf Erdmann

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PEX19 is a cytosolic receptor that directs membrane proteins posttranslationally to peroxisomes, as well as to mitochondria, lipid droplets, and the endoplasmic reticulum. A comprehensive Trypanosoma PEX19 interactome analysis uncovered PEX38 as an essential Euglenozoa-specific peroxin. PEX38 contains distinct domains that bind the cochaperone Hip and the PEX3-binding motif of PEX19, suggesting a role in stabilizing membrane proteins and preventing premature membrane docking. PEX38 illustrates functional repurposing in organelle biogenesis. It originated from a remnant of the GET/TRC pathway, typically responsible for the targeting of tail-anchored (TA) proteins to the endoplasmic reticulum. While most components of this machinery are absent in Euglenozoa, PEX38 has been retained and adapted to mediate peroxisomal membrane protein targeting. This evolutionary adaptation is unique to Euglenozoa. Because the PEX19–PEX38 interaction is essential for parasite viability and PEX38 has no human homologs, this complex is a promising therapeutic target against trypanosomatid parasites.

GPT-4o mini: Non-social science research article

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

Christian Bentz, Ewa Dutkiewicz

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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.

GPT-4o mini: Non-social science research article

Chiral gliding: Right-handed navigation of filamentous cyanobacteria

Andrej Vilfan, Leila Abbaspour, Stefano Villa, Vahid Nasirimarekani

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Cyanobacteria are the earliest known organisms that produced oxygen through photosynthesis, leading to the oxygen atmosphere that allowed the evolution of more complex life forms. Many species of cyanobacteria exhibit gliding motility along surfaces to navigate complex environments and adapt to fluctuating conditions. Here, we studied the gliding motility of filamentous cyanobacteria Lyngbya lagerheimii at the transition between different physical environments. We show that on a dry surface, a filament adopts a curved shape that turns right while gliding. When a filament switches the gliding direction, the curvature is initially preserved and a filament can turn left as long as it backtracks along a slime trace. We propose a model of chiral motility that explains the bending based on the right-handed rotation of gliding filaments and a velocity mismatch between the leading and the trailing end of the filament. The mechanism involves a unique way of transferring the structural chirality to the macroscale and also a unique physical navigation mechanism.

GPT-4o mini: Non-social science research article

From peptides to DNA: All required steps can be catalyzed

Lei Shi, Mériem Senissar, Kirsten Leistner, Carsten Jers, Ivan Mijakovic

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Ensuring information flow (heredity) and metabolic processes (catalysis) are two important prerequisites for early evolution. The widely accepted “RNA world” theory proposes that ancient RNAs ensured both heredity and catalysis during the transition from prebiotic to biotic evolution. However, alternative hypothetical molecules and processes have also been proposed, suggesting that catalytic peptides may have existed before polynucleotides, and that their sequences were later reverse translated into genes. Our objective was to experimentally address these alternative theories by asking whether the steps required for the hypothetical conversion of peptide sequences into DNA could be catalyzed by the existing molecular kit. The reactions we tested comprise i) step-wise degradation of peptides by a processive amino peptidase, sequentially releasing amino acids, ii) matching the identity of released amino acids to codons by aptazymes (RNA adapters that recognize amino acids and self-cleave and release specific codon triplets in response), and iii) ligating codon triplets into longer RNAs that can be reverse-transcribed into DNA. In a hypothetical processive system based on these reactions, the resulting DNA sequence would match the sequence of amino acids in the starting peptide. Our results suggest that all these steps can be catalyzed, and therefore the possibility of reverse translation occurring at some point in early evolution should not be disregarded.

GPT-4o mini: Non-social science research article

The Rab5 effector Rabankyrin-5 mediates endosomal fusion and trafficking of human papillomavirus during early entry

Madison Love, Richard C. Dang, Jian Xie, Pengwei Zhang

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The fusion of newly formed early endosomal vesicles after endocytosis is a crucial step in viral infection. It facilitates the transition of many viruses from viral internalization to downstream intracellular trafficking within the endosomal network, ultimately enabling their delivery to intracellular replication sites. Despite its significance, the molecular mechanisms regulating the fusion of these vesicles remain poorly understood. In this study, we show that Rabankyrin-5, a Rab5 effector, is essential for the fusion of human papillomavirus (HPV)-carrying early endosomes during viral entry. Additionally, Rabankyrin-5 acts as a dynein adaptor, directly binding both the HPV minor capsid protein L2 and the dynein motor complex to link virus-carrying early endosomes to the dynein transport machinery, thereby promoting virus movement along microtubules. These dual functions enable the coordinated integration of endosomal fusion with microtubule-based transport during the early stages of viral entry.

GPT-4o mini: Non-social science research article

Overlooked and overexploited: Extensive conversion of grasslands and wetlands driven by global food, feed, and bioenergy demand

Siyi Kan, Samuel A. Levy, Elise Mazur, Leah Samberg, U. Martin Persson, Lindsey Sloat, Ana L. Reboredo Segovia, Leandro Parente, Thomas Kastner

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Natural ecosystems are increasingly threatened by global agricultural supply chains, and a narrow policy focus on forests has fueled agricultural expansion into ecologically significant but severely overlooked non-forest ecosystems, including grasslands and open wetlands. While a few emerging policies attempt to protect non-forest ecosystems, a globally consistent assessment of their conversion extent and drivers, especially related to livestock production and commodity-specific supply chain demand, remains lacking. Here, we conducted a spatially explicit analysis to identify pasture and cropland expansion into non-forest ecosystems between 2005 and 2020, as well as conversion-linked primary agricultural commodities and their underlying demand drivers (end uses and final market destinations). We found that the conversion rate of natural non-forest ecosystems was nearly four times that of lands with tree cover exceeding 5 m (a common forest height threshold), with Brazil contributing 13% of the global total and Russia, India, China, and the United States each contributing about 6%. While drivers varied greatly across regions, globally 50% of the conversion was linked to pasture, and 27, 17, and 6% to cropland for food, feed, and other uses (mainly bioenergy), respectively. Among conversion-linked commodities, most livestock-associated products served domestic demand, while 32% of feed crops and 20% of all crops were exported, with export shares reaching 70 to 80% in Brazil and Argentina. These findings reveal important areas for non-forest ecosystem conservation and highlight the need for integrated policies to prevent leakage across different ecosystems and different sustainable development goals while also aligning local actions with global supply chain governance.

GPT-4o mini: Non-social science research article

Unraveling the maturation pathway of a eukaryotic virus through cryo-EM

Roger Castells-Graells, Emma L. Hesketh, Tsutomu Matsui, John E. Johnson, Neil A. Ranson, David M. Lawson, George P. Lomonossoff

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Virus maturation is a fundamental biological process involving large-scale structural reorganizations that drive functional activation and lead to infectivity. Understanding the steps from the initial procapsid assembly to mature virions is essential, both for comprehending viral life cycles and for developing antiviral therapies. However, capturing these steps has been challenging due to the transient and elusive nature of intermediate states. The nonenveloped, T = 4, ssRNA-containing, Nudaurelia capensis omega virus (NωV) is a highly accessible model system that exemplifies the maturation process of a eukaryotic virus. During maturation, the particle shrinks in outer diameter from 482 Å (pH 7.6) to 428 Å (pH 5.0). It is possible to mimic the maturation process in vitro by lowering the pH of a population of procapsids produced in heterologous systems. Indeed, by controlling the pH in vitro, it is possible to produce homogenous populations of intermediate NωV virus-like particles (VLPs) that occur too fleetingly to be observed in vivo. Here, we report structural models, based on cryoelectron microscopy (cryo-EM), of five intermediates in the NωV maturation process. The structures of the intermediate particles reveal unique, quaternary position-dependent trajectories and refolding of subunit N and C-terminal regions, including the formation of the autocatalytic cleavage site at N570. The detailed structures reported here, coupled with previously determined structures of the procapsids and mature particles, allow the maturation pathway to be described in detail for a eukaryotic virus.

GPT-4o mini: Non-social science research article

DAPL1 restrains RPE PANoptosis in experimental AMD by inhibiting GRP75-mediated mitochondria-associated endoplasmic reticulum membranes

Yan Li, Meiyu Jing, Wanxiao Wang, Wanzhen Lin, Yingxin Zhang, Tianyin Nie, Pingping Liu, Wan-ni Lu, Yu Chen, J. Fielding Hejtmancik, Qinxiang Zheng, Ling Hou, Xiaoyin Ma

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Retinal pigment epithelium (RPE) cell damage is a critical factor of age-related macular degeneration (AMD), the leading cause of blindness among the aged population. This study focuses on the AMD susceptible gene, Death associated protein like 1 (DAPL1), and provides insights with significant therapeutic implications. DAPL1-deficient mice exhibit dry AMD-like pathological features, a phenomenon whose mechanisms have remained largely unknown. Here, we reveal that DAPL1 deficiency promotes the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs) to cause mitochondrial Ca 2+ overload and dysfunction, which triggers the activation of inflammasomes, leading RPE cells to RIPK1-mediated PANoptosis, an inflammatory programmed cell death, in an experimental dry AMD (dAMD) mouse model. Knockdown of Ripk1 in the Dapl1−/− mice RPE inhibits RPE cell PANoptosis and ameliorates the severity of dAMD pathological features. Conversely, overexpression of DAPL1 inhibits MAM formation and protects RPE cells from PANoptosis in the model. Mechanistically, DAPL1 suppresses MAM formation by downregulating GRP75 expression. This disrupts the formation of the VDAC–GRP75–IP3R axis, which comprises critical tethering proteins responsible for endoplasmic reticulum to mitochondria coupling and Ca 2+ trafficking. Knockdown of Grp75 inhibits the formation of MAM and prevents mitochondrial Ca 2+ overload, improving mitochondrial quality and inhibiting PANoptosis in RPE cells, thereby interrupting the progression of experimental dAMD in Dapl1 -deficient mice. These results unveil the role of MAMs regulated by DAPL1 in RPE cell PANoptosis and AMD progression, highlighting targeting MAM formation as a potential therapeutic strategy for treating dAMD.

GPT-4o mini: Non-social science research article

When alternative becomes essential: The role of mitochondrial glycerol-3-phosphate dehydrogenase

Léa Herpe, Mélanie Aminot, Nicolas Pichaud

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Complex I is known as the primary entry point for electrons within the mitochondrial electron transport system (ETS). However, the glycerol-3-phosphate (G3P) shuttle, composed of cytosolic and mitochondrial G3P dehydrogenase (cG3PDH and mtG3PDH, respectively), transfer reducing equivalents from the cytosol to the mitochondrial matrix. The mtG3PDH feeds electrons into the ETS via FADH 2 oxidation, but with theoretically lower energy conversion efficiency than complex I. It is thus believed to be an “alternative” pathway, only supporting mitochondrial respiration when complex I fails. mtG3PDH also plays an important role in reactive oxygen species (ROS) production. To investigate the role of this understudied protein in mitochondrial bioenergetics and redox homeostasis, we generated Drosophila melanogaster mutant lines for mtG3PDH (GPO1) using a CRISPR/Cas9-based approach and determined several physiological and metabolic parameters. A drastically higher mortality rate was observed among the GPO1 flies, as well as a lethargic behavior characterized by an inability to climb. These results are in accordance with an impaired mitochondrial efficiency (ATP/O) mainly due to decreased ATP production (~60% decrease) and O 2 consumption (~33% decrease), rather than elevated ROS. In fact, GPO1 flies produced ~70% less ROS than controls, likely due to the reduced direct and reverse electron transfer-related ROS production from mtG3PDH. These results support an essential role of mtG3PDH in mitochondrial bioenergetic, challenging its alternative aspect, and confirming its importance in mitochondrial redox homeostasis.

GPT-4o mini: Non-social science research article

The Crohn’s disease–related RNF123 prevents NLRP3 inflammasome assembly by catalyzing unanchored K63-linked ubiquitination on NEK7

Feng Liu, Wanxin Zhuang, Yuan Yang, Wenting Zhao, Siyuan Li, Ziyue Zhang, Yifan Liu, Bingyu Liu, Xiaopeng Qi, Wei Zhao, Lintai Da, Chengjiang Gao

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The NLRP3 inflammasome is crucial for host defense against pathogen invasion and is implicated in various inflammatory disorders. The pathogenic association and the involved mechanism between the NLRP3 inflammasome and inflammatory diseases have garnered significant attention. Here, we demonstrate that Crohn’s disease–associated SNP RNF123-R854H aggravates colitis in vivo through the NLRP3-dependent pathway. Deficiency of RNF123 also aggravates dextran sodium sulfate-induced colitis, LPS (lipopolysaccharide)-induced endotoxemia, and Alum-induced peritonitis and enhances host defense against bacterial infection via the NLRP3-dependent pathway in vivo and promotes the NLRP3 inflammasome activation in cells. We establish RNF123 as a regulator for the NLRP3 inflammasome, highlighting its implication in the NLRP3 inflammasome-driven inflammatory diseases. Mechanistically, RNF123 catalyzes unanchored K63-linked ubiquitination of NEK7, thereby preventing NEK7-mediated dissociation of the inactive cage-like NLRP3 aggregates and the subsequent NLRP3 inflammasome assembly. Additionally, we prove that K63-linked polyubiquitin chains can be specifically captured by NEK7 in vitro and inhibit the NEK7-licensed NLRP3 inflammasome assembly. We propose that NEK7-captured unanchored K63-polyubiquitin chains serve as a key determinant for the NLRP3 inflammasome activation, acting as a molecular brake to limit the excessive NLRP3 inflammasome activation and preserve immune homeostasis. Our work yields mechanistic insights into the NLRP3 inflammasome regulation and its pathogenic link to inflammatory disease.

GPT-4o mini: Non-social science research article

Absolute hand determination of glycofibrils from natural sources in cryo-EM

Qi Zhang, Lanju Qin, Tongtong Wang, Zhangqiang Li, Yilin Zhang, Sheng Chen, Qijun Ge, Jialing Wen, Nieng Yan, Jiawei Wang, Mingxu Hu

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Glycans are not only one of the four fundamental macromolecular classes that constitute life, but also the most abundant among these four across the Earth. However, compared with proteins and nucleic acids, our understanding of the structures and functional mechanisms of glycans remains limited. Moreover, it is generally challenging to obtain high-resolution three-dimensional structures of glycans. Recent studies have demonstrated the potential of the CryoSeek strategy in enabling high-throughput structural determination of glycans, thereby presenting novel avenues for their structural investigation. Meanwhile, unlike proteins, near atomic resolution density maps of glycofibrils do not inherently facilitate the determination of absolute hand, which is a prerequisite for building atomic models of glycofibrils. Existing absolute hand determination methods have severe limitations in the case of glycofibrils from natural sources. In this study, we introduce Ahaha, a straightforward and efficient method for determining such absolute hand in cryogenic electron microscopy. With their absolute hand measured by Ahaha, we built atomic models of four glycofibrils derived from a natural water sample, facilitating the study of glycans. The online service of Ahaha is available at https://cryoseek.org/ahaha .

GPT-4o mini: Non-social science research article

Navigating the mysterious space of evolutionary histories

Alexei J. Drummond, Alex Popinga

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GPT-4o mini: Non-social science research article

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

Catherine Chen, Xue L. Gong, Christine Tseng, Daniel L. Klein, Jack L. Gallant, Fatma Deniz

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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.

GPT-4o mini: Non-social science research article

The way of life: The network challenge of blood flow in the brain

Franca Schmid

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GPT-4o mini: Non-social science research article

Studying adaptation at the invisible scale

Ashleigh S. Griffin, Stuart A. West

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In order to understand adaptation by natural selection, it is necessary to observe organisms in their natural habitat. For this reason, the field of behavioral ecology, which specializes in testing adaptive explanations for biological observations, is dominated by research on larger multicellular animals such as insects, mammals, fish, and birds. The vast majority of modern life sciences, however, is concerned with the study of cells, genes, and molecules, which are often impossible to observe directly in nature. This severely compromises our ability to complement mechanistic understand of traits of interest with adaptive understanding. This matters because only the theory of adaptation can provide an explanation for why biology operates in the way that it does, why it varies across individuals and species, a formal tool for making predictions about the future. The good news is that technological advances are creating new opportunities for understanding cellular and subcellular traits as the products of natural selection.

GPT-4o mini: Non-social science research article

Terrestrial ecosystem nitrogen cycling in response to field warming: Global patterns and future trends

Xudong Wang, Chenrui Ni, Ziyi Fan, Wenao Wu, Changlin Xu, Jiguang Feng, Rui Yin, Joshua P. Schimel, Margaret S. Torn, Biao Zhu

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Nitrogen cycling regulates terrestrial ecosystem productivity and carbon sequestration, yet its response to climate warming remains uncertain. Here, we compiled the most comprehensive dataset to date, integrating 7,941 observations from 413 field warming experiments worldwide with random forest regression and Community Land Model (CLM) simulations. Field warming significantly accelerated nitrogen cycling, increasing N 2 O emissions (+24.7%), mineralization (+25.8%), nitrification (+51.7%), and denitrification (+41.1%). Soil inorganic nitrogen also increased, while plant nitrogen remained largely unchanged. Elevated natural abundance of 15 N indicated that warming alleviates nitrogen limitation and promotes more open nitrogen cycles. Soil moisture, ecosystem type, and warming magnitude were key drivers. N 2 O emission and nitrification further intensified with increased warming magnitude in random forest analyses. In contrast, CLM5-BGC simulated weak responses in N 2 O emissions and nitrification and negative changes in nitrogen mineralization, substantially diverging from field observations. These discrepancies highlight the omission of microbial processes and the oversimplification of large-scale ecosystem feedbacks, respectively. Uniquely, this study provides a direct comparison among empirical data, random forest regression, and CLM simulations, revealing discrepancies and their potential causes. Collectively, our findings demonstrate that terrestrial nitrogen cycling is more responsive to climate warming than previously recognized and underscore the importance of integrating multiple analytical approaches to synthesize cross-scale ecological data.

GPT-4o mini: Non-social science research article

Mesophases as stepping stones to enhance crystallization kinetics in nanoparticle self-assembly

Prajwal B. Prakash, Fernando A. Escobedo

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Manipulation of kinetic pathways is essential to self-assemble nanoparticle building blocks into complex ordered structures, as the emergence of intermediate metastable states could either facilitate or hinder crystallization of the target lattice. Molecular simulations and Markovian and transition state theory are used to validate our conjecture that intermediary mesophases, with partial but long-range translational or orientational structural ordering, accelerate crystallization kinetics from the disordered structure. Using four representative models, two lyotropic single-component and two thermotropic binary mixture systems, we demonstrate that mesophases with intermediate entropies, such as nematic fluid, rotator solid, and microsegregated mesophases, speed up the overall crystallization rate. This enhancement occurs by effectively splitting a larger isotropic-to-crystal free energy barrier into two smaller barriers corresponding to isotropic-to-mesophase and mesophase-to-crystal transitions, with mesophase “bulk” macrostates being kinetically more favorable than microscopic fluctuations. The single-step isotropic-to-crystal transition occurs through a composite-cluster pathway that includes mesophase microdomains; an isotropic-crystal interfacial energy greater than or comparable to the sum of the isotropic-mesophase and mesophase-crystal interfacial energies is associated with enhanced two-step crystallization rate. Overall, our findings validate the conjecture, which offers additional guidance for selecting nanoparticle designs and conditions that promote efficient crystallization pathways.

GPT-4o mini: Non-social science research article

Phenotypic polymorphism via mate copying

Srishti Patil, Sabine Nöbel, Chaitanya S. Gokhale

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Classical mate choice theories assume independent decision-making, yet mounting evidence shows that individuals often use social information and copy conspecifics’ mate choices, a behavior termed mate copying. While this nonindependent mate choice has been documented across vertebrates and notably in Drosophila melanogaster , theoretical and experimental frameworks have been mainly restricted to binary choice scenarios, limiting our understanding of its evolutionary implications in natural populations. Here, we develop a theoretical model of mate copying applicable to populations with multiple morphs, incorporating both private (inherent) and public (cultural) information in mate choice decisions. The population dynamics of the different male morphs are driven by the differing intensities of conformist and anticonformist mate copying. We demonstrate that mate copying can lead to the fixation of low-quality morphs and identify the conditions necessary for the existence of a polymorphism consisting of all male morphs in the population. Furthermore, we identify a plausible mechanism that could maintain a stable polymorphism in the case of conformist mate copying with two morphs. Our findings provide a theoretical framework for understanding how social learning in mate choice can influence evolutionary trajectories and contribute to maintaining phenotypic diversity in populations, with potential implications for sexual selection and speciation.

GPT-4o mini: Non-social science research article

Pheromone receptors for japonilure in Anomala corpulenta and Popillia japonica

Yinliang Wang, Kun Feng, Haoqin Ke, Huanhuan Dong, Kebin Li, Bingzhong Ren, Chen Luo, Cheng Qu, Ran Wang, Jiao Yin, Walter S. Leal

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Using gas chromatography-electroantennographic detection (GC-EAD), gas chromatography-mass spectrometry (GC-MS), and chiral capillary GC with synthetic stereoisomers, followed by laboratory and field validation, we identified the sex pheromone of the copper green chafer ( Anomala corpulenta ) as ( R )-japonilure, with its antipode, ( S )-japonilure, acting as a behavioral antagonist. Single sensillum recordings (SSR) revealed two types of pheromone-responsive sensilla, one narrowly tuned to the sex pheromone, and another that responded to both ( R )- and ( S )-japonilure, albeit with lower sensitivity to the latter. Functional characterization of A. corpulenta odorant receptors (ORs) by two-electrode voltage clamp (TEVC) led to the identification of two key receptors, AcorOR18, which was selective for ( R )-japonilure, and AcorOR29, which was activated by both enantiomers, and 10 ORs sensitive to plant-derived compounds. SSR combined with fluorescence in situ hybridization (FISH) experiments suggested that AcorOR18 is expressed in pheromone-specific sensilla, whereas AcorOR29 is localized in sensilla responsive to both the pheromone and its antagonist. RNA interference (RNAi) knockdown of either receptor reduced male attraction to ( R )-japonilure, while simultaneous knockdown of both genes abolished behavioral responses, confirming that both receptors are required for full pheromone detection. Three orthologous receptors were identified in the Japanese beetle ( Popillia japonica ) genome. Two of them, PjapOR42 and PjapOR37, exhibited strict enantioselectivity for ( R )-japonilure, whereas PjapOR39 showed a relaxed enantiospecificity, responding to both enantiomers and preferentially to the behavioral antagonist. These results suggest that PjapOR39 may mediate detection of ( S )-japonilure and contribute to behavioral antagonism, revealing a shared molecular mechanism of enantiomeric discrimination in scarab beetles.

GPT-4o mini: Non-social science research article

Efficient evaluation of optical quantum modules via two-photon high-dimensional interference

Xiaoqian Zhang, Maolin Luo, Xiaoqi Zhou

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The rapid advancement of quantum information technology has increased the demand for precise testing and calibration of quantum modules, especially in optical quantum circuits where module reliability directly impacts system performance. To address this need, we propose a two-photon quantum module evaluation method based on high-dimensional Hong–Ou–Mandel interference. Our method uses multi-degree-of-freedom photon encoding to enable rapid and accurate evaluation of optical quantum modules. Compared to traditional methods such as quantum process tomography and direct fidelity estimation, our method not only simplifies implementation but also significantly minimizes the measurement resources required. Notably, the resource demands remain invariant as the system dimensionality scales, ensuring efficient evaluation even in high-dimensional quantum systems. We validated this method on a programmable silicon photonic chip, demonstrating its ability to accurately evaluate optical quantum module performance while significantly reducing resource consumption. This quantum module evaluation method holds promise for broader applications in the field of optical quantum information technologies.

GPT-4o mini: Non-social science research article

Structural and evolutionary constraints of organophosphate resistance in dipteran carboxylesterases

Rebecca L. Frkic, Alex Giang, Sacha B. Pulsford, Jian-Wei Liu, Mojtaba Esmaeily, Paul D. Carr, Nicholas J. Fraser, Davis Hopkins, John G. Oakeshott, Philip Batterham, Peter D. Mabbitt, Colin J. Jackson

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Enzymatic detoxification of organophosphate (OP) insecticides can confer resistance in some insects, yet the precise molecular basis of this trait, and how it has evolved, remains poorly understood. In certain dipteran species, a G→D mutation in the oxyanion hole of α-carboxylesterases (CBEs) enhances OP hydrolysis, yet this adaptation is not widespread despite the presence of orthologous CBEs in other insect species that are also exposed to OPs. The extent, and molecular basis, of evolutionary contingency and epistasis in this catalytic OP resistance has not been explored, and how further mutations might optimize OP detoxification in the future is not clear. Here, we systematically compare OP hydrolysis and analyze structures of CBE orthologs across several dipteran species, revealing that the success of the G137D mutation is sequence context-dependent. We employed laboratory-directed evolution to enhance OP turnover over 1,000-fold vs. the wildtype enzyme and tested these variants in transgenic Drosophila melanogaster , demonstrating that improved catalytic rates do not directly translate to increased resistance. By highlighting the trade-off between organophosphate affinity and turnover, this work further clarifies the complex evolutionary trajectories determining why a particular resistance mechanism may evolve in some species but not others.

GPT-4o mini: Non-social science research article

Understanding human metacontrol and its pathologies using deep neural networks

Kai J. Sandbrink, Laurence T. Hunt, Christopher Summerfield

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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.

GPT-4o mini: Non-social science research article

Anomalous enhancement of thermal conduction across twisted van der Waals heterointerfaces

Yufeng Zhang, Yanzheng Du, Xiao Wan, Meng An, Aoran Fan, Fengyi Li, Weigang Ma, Xing Zhang

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The advent of interlayer twist has introduced a groundbreaking paradigm, unveiling novel physical phenomena spanning from correlated insulating states to superconductivity. This unprecedented platform facilitates the manipulation of electrons and extends its capabilities to the effective control of bosons. For phonons, a consensus has been reached that interlayer twist greatly suppresses phonon transport as it breaks the symmetry of the lattice. Here, we report a counterintuitive experimental observation in which the interlayer twist can significantly promote the transportation of phonons across an intrinsically asymmetric heterointerface. Employing the time-domain thermoreflectance mapping technique, our results show a 2.5-fold increase in interfacial thermal conductance (ITC) in twisted bilayer MoS 2 /WS 2 heterostructures relative to initial commensurate configurations. Combined experimental and atomic simulation results reveal the inelastic scattering-dominated nature of thermal transport at MoS 2 /WS 2 heterointerfaces. The introduction of interlayer twist amplifies this effect, triggering a reconstruction of nonequilibrium phonon temperature distributions at the interface. This phenomenon activates efficient optical-to-acoustic phonon conversion through inelastic scattering and creates additional transport channels that overcome the intrinsic phonon mismatch in heterostructures. Our work establishes a paradigm for enhancing ITC by strategically introducing interlayer perturbations to amplify inelastic scattering effects. This breakthrough opens broad avenues for advanced thermal management in integrated circuits.

GPT-4o mini: Non-social science research article

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

Dipayan Bose, Nian Ma, Rajnish Kumar Singh, Ramakrishna Vangala, Atharva Torne, Kiran Chunduru, Erle S. Robertson

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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.

GPT-4o mini: Non-social science research article

Cell fate acquisition at a de novo developmental boundary in the maize leaf

Lukas J. Evans, Ruqiang Zhang, Maria Camila Medina, Elizabeth A. Fitzgerald, Anne W. Sylvester, George Chuck, Samuel Leiboff, Michael J. Scanlon

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The formation of boundaries separating developmental fields with distinct gene expression and cell fate trajectories is a universal feature of noncolonial multicellular organisms. Developmental boundaries arise reiteratively during ontogeny and are characterized by stiff, slowly dividing cells that demarcate adjacent and divergent morphogenetic domains; the genetic mechanisms of cell fate acquisition within these boundaries are incompletely understood. Grass leaves are initiated at a developmental boundary in the periphery of the shoot apical meristem, an organogenic pool of plant stem cells that generates all lateral organs in the plant shoot. During later primordial growth, maize leaves form a de novo developmental boundary that ultimately separates the distal, photosynthetic leaf blade from the proximal, clasping leaf sheath. Morphogenesis at this blade/sheath boundary in maize leaves generates an epidermal outgrowth called the ligule and two tissue-wedges forming the auricle, a hinge-like structure with major effects on leaf angle, light capture, and yield. Here, we use cell lineage mapping, morphometric measures of cell division and expansion, cell-specific multidimensional transcriptomic analyses, and topological landscape modeling to investigate the mechanisms of cell fate acquisition at the ligule/auricle morphogenetic boundary in the maize leaf. The data suggest a model where auricle initial cells are recruited from blade founder cells at this boundary, via repression of blade identity during early stages in auricle ontogeny. Thereafter, auricle primordial cells assume a developmental genetic trajectory that is distinct from the blade, sheath, and ligule, thereby acquiring a unique auricle cell fate in the maize leaf.

GPT-4o mini: Non-social science research article

Aging-associated differences in mammary tumor–initiating populations and immune evasion pathways in breast cancer

Pengze Yan, Triet Bui, Ernesto Rojas Jimenez, Yanan Kuang, Shidong Xu, Cloud P. Paweletz, Hodaya Haimov, Menachem Sklartz, Ofir Cohen, Sandra S. McAllister, Kornelia Polyak

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Aging is a major risk factor for breast cancer, yet how it shapes tumor development, molecular phenotype, and immune evasion remains incompletely understood. Deciphering how aging influences cancer evolution is critical for improving risk assessment, prevention, and treatment. Here, using a N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model that recapitulates key features of human breast cancer, we integrated bulk and single-cell transcriptomics, whole-exome sequencing, and histopathological analysis to dissect age-associated differences in mammary tumorigenesis. We found that the age at NMU exposure critically influences tumor incidence, mutational burden, molecular subtype, and the tumor immune microenvironment. Tumors arising in aged rats originated from aging luminal progenitor-like cells, exhibited increased genomic instability, reduced immune cell infiltration, and impaired antigen presentation linked to loss of heterozygosity at chromosome (Chr) 20p. The age-associated epithelial and immune changes we identified were conserved in human breast cancers, where the loss of the homologous Chr 6p region correlated with reduced lymphocyte infiltration and shorter relapse-free survival. These findings reveal that aging profoundly affects tumor-initiating cell populations and promotes immune evasion through chromosomal instability-driven defects in antigen presentation. Our work provides a molecular basis for understanding disease onset and progression that may impact efficacy of immunotherapy in older breast cancer patients.

GPT-4o mini: Non-social science research article

Human lncRNA RMRP interacts with DEAD-box helicases and modulates mitochondrial function

Higor Sette Pereira, Jason Luddu, Govardhan Reddy Veerareddygari, Shridhar Kiran Sanghvi, Priyanshi B. Patel, Zachary E. Robinson, M. Quadir Siddiqui, Harpreet Singh, Trushar R. Patel

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The human long noncoding RNA (lncRNA) RMRP , initially identified as part of the RNase MRP complex, is linked to various human diseases. However, its structural flexibility and broader cellular roles are not well understood. Here, we offer a comprehensive analysis of RMRP ’s structure in solution, its interactions with human proteins, and its mitochondrial functions. Using small-angle X-ray scattering (SAXS), we show that RMRP adopts different Mg 2+ -dependent shapes, shifting from an extended Y-shaped form to a more compact one as Mg 2+ levels increase. We identified and characterized interactions between RMRP and the DEAD-box RNA helicases DDX5 and DDX3X, with DDX5 binding strongly and exhibiting ATP-dependent helicase activity on RMRP , while DDX3X mainly acts as an expression regulator. Both helicases are crucial for the proper mitochondrial localization of RMRP , working within a complex regulatory network. Functionally, reducing RMRP levels disrupts mitochondrial stability, leading to membrane depolarization and an increase in reactive oxygen species, without affecting cell growth. Mechanistically, RMRP specifically controls nuclear-encoded mitochondrial proteins involved in cristae structure (DNAJC11) and respiratory chain function (NDUFS8). Our results position RMRP as a structurally adaptable lncRNA that collaborates with RNA helicases to preserve mitochondrial health through specific gene regulation. These insights provide perspectives on RMRP ’s biology and the molecular mechanisms underlying RMRP -related disorders, which could inform future therapies for conditions resulting from RMRP dysfunction.

GPT-4o mini: Non-social science research article

Tectonism rather than “snowball Earth” glaciation is responsible for the Great Unconformity

Rong-Ruo Zhan, Liang Duan, Massimiliano Zattin, Nicholas Christie-Blick, Bo Wan, Rong-Hao Wei, Zhao Yang, Jianqiang Wang, Longlong Gou, Valerio Olivetti, Kai-Yun Chen, Xingliang Zhang

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The Great Unconformity (GUn)—a widely recognized discontinuity and associated gap in the rock record between Precambrian and Cambrian rocks—represents a globally important interval of continental exposure and erosion that is notable also for the first appearance of all major animal phyla on Earth. However, its origin remains the subject of vigorous debate. Here, we present field relationships, and zircon and monazite U–Pb, biotite and muscovite Rb–Sr, and zircon (U–Th)/He thermochronology data for Precambrian crystalline basement rocks from North China to constrain the exhumation history below the unconformity. Dates from multichronometers and thermal history inversions show that the most substantial cooling of continental basement took place from ~2,100 to 1,600 Ma. Comparison with thermal history data from Laurentia, Baltica, and Amazonia suggests that protracted plate tectonics broadly modulated by supercontinent cycles, and not “snowball Earth” glaciation, is responsible for crustal exhumation below the unconformity. The most pronounced erosion evident in both the thermochronologic record and geochemical indicators of continental weathering is shown to correspond with development of Earth’s first true supercontinent (Columbia), rather than with either the Cambrian explosion or the emergence of modern plate tectonics.

GPT-4o mini: Non-social science research article

Lipoprotein diffusion in dense yolk plasma is governed by softness, hydrodynamics, and caging: Insights from MHz-XPCS

Nimmi Das Anthuparambil, Michelle Dargasz, Sonja Timmermann, Anita Girelli, Sebastian Retzbach, Johannes Möller, Wonhyuk Jo, Agha Mohammad Raza, Aliaksandr Leonau, James Wrigley, Frederik Unger, Maddalena Bin, Prince Prabhu Rajaiah, Iason Andronis, William Chèvremont, Jörg Hallmann, Angel Rodriguez-Fernandez, Jan-Etienne Pudell, Felix Brausse, Ulrike Boesenberg, Mohamed Youssef, Roman Shayduk, Rustam Rysov, Anders Madsen, Felix Lehmkühler, Michael Paulus, Fajun Zhang, Fivos Perakis, Frank Schreiber, Christian Gutt

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Low-density lipoproteins (LDLs) are central to nutrient transport in egg yolk and have emerged as natural nanocarriers for drug delivery. Their biological function critically depends on mobility within densely crowded environments, yet the mechanisms governing their motion remain elusive, largely because conventional techniques cannot access the relevant microsecond timescales. Here, we employ megahertz X-ray photon correlation spectroscopy at the European X-ray Free Electron Laser facility to resolve LDL dynamics in native yolk-plasma. This approach reveals transient caging and memory effects and shows that the combined influence of particle softness and hydrodynamic coupling slows diffusion by nearly two orders of magnitude compared to dilute solutions. However, this reduction could not be scaled with an increase in macroscopic viscosity obtained from rheometry, indicating deviations from the Stokes–Einstein relation. Despite this slowdown, yolk-plasma remains a “sluggish yet liquid state”, balancing dense packing and the fluidity required for lipid release during embryonic development. These results establish a quantitative framework connecting microstructure, hydrodynamics, and transport in crowded soft-matter systems, with implications for developmental biology and nanomedicine.

GPT-4o mini: Non-social science research article

Leveraging the kinetic isotope effect by compact H-bond motifs for electrochemical hydrogen isotope separation

Guobin Wen, Haiqi Liang, Shuxuan Liu, Ningce Zhang, Shuai Chen, Guoqiang Shen, Tehua Wang, Ru Chen, Li Tao, Bohua Ren, Shuangyin Wang

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Electrochemical hydrogen isotope separation has been constrained for decades by the similar energy barriers of the rate-determining O–H and O–D bond cleavage step in water isotopologues. Herein, we compact H-bond connectivity through screening a series of additives to stimulate electrochemical proton quantum tunneling (QT) behaviors of “through-barrier”, which are virtually impossible for heavier D-relevant motions. The average H-bond length of H 2 O⋯OH − is 3.4% shorter (2.78 Å) with isopropanol additive at the engineered interface. Fundamentally, QT effects are magnified by selectively promoting proton transfer-involved reactions through strengthening the H-bond and filling the H-bond gap, which are further proved by both experimental Arrhenius plots with near small-curvature tunneling approximation and a stronger proton excursion in path integral molecular dynamics simulations. Hence, a record-high H 2 O separation factor of 276 is realized at room temperature with a three-order-of-magnitude growth of H/D kinetic isotope effect constant up to 10,165. Significantly, a large-scale multistage reactor is engineered to obtain continuous enrichment of heavy water with a deuterium atomic fraction over 80%.

GPT-4o mini: Non-social science research article

Accelerated north–east shift of the global green wave trajectory

Miguel D. Mahecha, Guido Kraemer, Martin Reinhardt, David Montero, Fabian Gans, Ana Bastos, Hannes Feilhauer, Ida Flik, Chaonan Ji, Teja Kattenborn, Mirco Migliavacca, Milena Mönks, Johannes Quaas, Sebastian Sippel, Sophia Walther, Sebastian Wieneke, Christian Wirth, Gustau Camps-Valls

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Viewed from space, a “green wave” seasonally traverses Earth’s surface, from the north in boreal summer to the south in austral summer. This wave represents vegetation phenology, driven primarily by solar irradiation and modulated by climate variability and ecosystem dynamics. Despite its significance for multiple Earth system processes, we lack a unified metric to characterize and understand its dynamics. Here, we propose a concept to quantify global phenology by tracking the green wave’s centroid using satellite and Earth system model data. The resulting trajectory summarizes global phenological dynamics and directional trends. Earlier reports on global greening led us to hypothesize a rapidly northward shifting trajectory during boreal summer and a moderate southward shift during austral summer. Contrary to this expectation, we find that the centroid moves northward during both summer periods, with the austral summer shift consistently exceeding the boreal shift across datasets. As a consequence, the amplitude of the green wave trajectory is decreasing, a trend projected to intensify throughout this century. We also detect an accelerating eastward shift, a phenomenon not previously reported. Tracking the green wave’s centroid reveals how regionally changing land dynamics affect the global functioning of Earth’s terrestrial biosphere.

GPT-4o mini: Non-social science research article

Effects of correlated collisions and intermittency on the growth of lucky droplets

Tobias Bätge, Johannes Zierenberg, Michael Wilczek

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To trigger precipitation, water droplets in warm clouds need to attain a sufficient size. Theoretical estimates based on condensation and gravitational collisions alone fail to explain the observed timescales for the onset of precipitation for a range of droplet sizes. This suggests the involvement of collisional growth mediated by turbulence to resolve the so-called “size-gap problem.” For the onset of rain, it is sufficient that statistical outliers, coined “lucky droplets,” cross the size gap. In this study, we explore the influence of turbulence on droplet growth, focusing on correlated collisions and intermittency. Using direct numerical simulations of droplets in turbulent flow, we constrain a non-Markovian stochastic framework that allows us to assess memory effects on the droplet-size distribution arising from correlations between consecutive collisions. Using our framework, we find that correlated collisions accelerate the initial growth of lucky droplets but have subleading effect at later stages. Consequently, we neglect correlations from collisions and model an ensemble of cloud parcels representing fluctuations in the volume-averaged dissipation rate. Here, the distribution of droplet sizes in each parcel is described by a linear master equation with a time-dependent collision rate according to the volume-averaged dissipation rate. Our analyses of this toy model show that intermittency can significantly reduce the time required by lucky droplets to cross the size gap.

GPT-4o mini: Non-social science research article

Phenotypic CRISPR screens identify NLRX1 as an essential activator of the human mitochondrial permeability transition

William C. Valinsky, Robert P. Ray, Kathy S. Schaefer, Jonathan B. Grimm, Carla Nicolini, Luke D. Lavis, David E. Clapham

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The mitochondrial permeability transition (mPT) is an evolutionarily conserved destructive process that permeabilizes the inner mitochondrial membrane in response to calcium overload. The molecular mechanism underlying the mPT is not established. To unambiguously identify essential proteins, we designed two phenotypic assays for mitochondrial calcium overload and applied them to FACS-based CRISPR screening in human cells, ultimately evaluating 19,113 genes. The first screen studied mitochondrial membrane potential (MMP) collapse in response to calcium overload. Top-ranked genes were the essential proteins of the mitochondrial calcium uniporter complex, MCU and EMRE, reflecting that the calcium-induced MMP collapse results from mitochondrial calcium entry and not the mPT. The second screen measured the permeability of the inner mitochondrial membrane. Here, the fluorescent interaction of a membrane impermeant ~600 Da dye and a mitochondrial-targeted HaloTag protein was studied under mPT activating conditions; calcium overload and the thiol-reactive molecule phenylarsine oxide. With secondary validation, we identified four protein-encoding genes that delayed or prevented the mPT under knockout: NF2, REST, BPTF, and NRLX1. Knockout of the nonmitochondrial proteins BPTF, NF2, or REST increased mitochondrial calcium retention capacity (CRC). However, calcium release or sensitivity to cyclosporin A (CsA) persisted, indicative of mPT sensitizers. Only knockout of the mitochondrial matrix protein, NLRX1, increased CRC, abolished calcium release, and was CsA-insensitive. This top-ranked hit of the mitochondrial permeability screen meets the definition of an essential mPT activator. Integral membrane proteins, including all previously proposed mPT candidates, were not essential activators.

Academic journals’ AI policies fail to curb the surge in AI-assisted academic writing

Yongyuan He, Yi Bu

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The rapid integration of generative AI into academic writing has prompted widespread policy responses from journals and publishers. However, the effectiveness of these policies remains unclear. Here, we analyze 5,114 journals and over 5.2 million papers to evaluate the real-world impact of AI usage guidelines. We show that despite 70% of journals adopting AI policies (primarily requiring disclosure), researchers’ use of AI writing tools has increased dramatically across disciplines, with no significant difference between journals with or without policies. Non-English-speaking countries, physical sciences, and high-OA journals exhibit the highest growth rates. Crucially, full-text analysis on 164 k scientific publications reveals a striking transparency gap: Of the 75 k papers published since 2023, only 76 (~0.1%) explicitly disclosed AI use. Our findings suggest that current policies have largely failed to promote transparency or restrain AI adoption. We urge a reevaluation of ethical frameworks to foster responsible AI integration in science.

Why Biden-era clean energy investment policies had limited political returns

Alexander F. Gazmararian, Nathan M. Jensen, Dustin Tingley

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The Biden Administration enacted the largest federal policy framework to incentivize clean energy and decarbonization in U.S. history. We examine whether Biden-era green investments produced political returns by affecting public opinion. Using geolocated survey data linked to investment records and a database of company and politician statements, we assess project visibility and credit attribution. People closer to new renewable energy and green manufacturing facilities are more likely to notice these investments but are not more likely to credit the Biden Administration. Instead, the public sees governors as most responsible. This credit allocation pattern aligns with the political message environment: Governors more frequently claim credit than the White House and companies spread recognition broadly across political actors. This fragmented information environment illustrates the limits of using less traceable forms of green spending to generate electoral gains and public support for climate policy.

Social mobilizations for sustainability transformations

Fiona J. Gladstone, Arun Agrawal

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In the wake of USAID cuts, we can create a Demographic and Health Survey Program founded on more equitable data infrastructure and stronger research integrity

Jasmin Abdel Ghany, Aasli A. Nur, Kerry L. D. MacQuarrie, Joshua Wilde, Elizabeth A. Sully, Mahesh Karra, Ursula Gazeley, Ben M. John, Livia Montana

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The cognitive underpinnings of minority overestimation

Rasha Kardosh, Asael Y. Sklar

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Kava consumption and the rise of sociopolitical complexity in Oceania

Václav Hrnčíř, Oliver Sheehan, Scott Claessens, Russell D. Gray

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Humans have been using psychoactive substances for millennia, despite their potential negative health and social consequences. According to some scholars, our craving for mind-altering drugs is an evolutionary mistake—a hijacking of our reward system. In contrast, the “drunk hypothesis” argues that intoxication has been adaptive and essential for the rise of large-scale societies because it promotes social bonding, increases cooperation, alleviates stress, and enhances human creativity. Here, we test this hypothesis using the example of kava, a traditional Pacific beverage with a range of psychoactive effects, made from the root of Piper methysticum . Our analysis of 83 Oceanic-speaking societies shows a positive relationship between traditional kava consumption and both political complexity and social stratification. However, the results are not robust to controls for nonindependence. Moreover, we found no evidence of coevolution between kava drinking and either of the two sociopolitical traits after controlling for spatial nonindependence. Despite the cultural significance of kava in many Pacific societies, our results suggest that its consumption was unlikely to have been a major driver of sociopolitical complexity, underscoring the importance of controlling for nonindependence in cross-cultural studies.

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

Eric A. Baldwin, Takuma Iwasaki, John J. Donohue

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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.

Science

GPT-4o mini: Non-social science research article

Hafnium oxide interface stabilization for efficient, photothermally stable perovskite solar cells

Yuanhang Yang, Siyang Cheng, Xiaotian Yang, Mubai Li, Xueliang Zhu, Zhongji Yang, Yixuan Zheng, Yong Liu, Qianqian Lin, Ning Yan, Shengjun Yuan, Zhiping Wang

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Organic molecular layers at both hole- and electron-selective interfaces are essential for achieving high-efficiency perovskite solar cells, yet their limited photothermal stability hinders long-term device operation. We used atomic layer deposition to deposit hafnium oxide (HfO x ) interlayers to stabilize these molecular interfaces under operational stress. At the NiO x /self-assembled monolayer (SAM) interface, a hydroxyl-rich, Lewis-acidic n-HfO x layer (n denotes negative fixed-charge polarity) promoted tridentate phosphonic acid coordination and enhanced SAM retention and thermal durability. At the perovskite/C 60 interface, the p-HfO x layer (p denotes positive fixed-charge polarity) anchored 3-fluorophenylethylammonium iodide (3F-PEAI) through Hf⋯F interactions that also acted as a diffusion barrier against halide- and silver-ion migration. Devices achieved a power conversion efficiency of 27.1% (26.6% certified) and retained more than 90% of their initial efficiency for ~5000 hours under 1-sun equivalent illumination at 85°C in ambient air.

GPT-4o mini: Non-social science research article

Interbreeding between Neanderthals and modern humans was strongly sex biased

Alexander Platt, Daniel N. Harris, Sarah A. Tishkoff

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Sex biases in admixture and other demographic processes are recurrent features throughout human evolution. For admixture between Neanderthals and anatomically modern humans (AMHs), sex bias has been proposed as an explanation for the relative lack of Neanderthal ancestry in modern human X chromosomes compared with that in modern human autosomes. By observing a 62% relative excess of AMH ancestry in Neanderthal X chromosomes, we characterized the interbreeding between the two groups as predominantly male Neanderthals with female AMHs. Analytic and numerical modeling presents mate preference as a more parsimonious cause of the sex bias than purely demographic processes with differential patterns of male and female migration.

GPT-4o mini: Non-social science research article

Organocatalyst-controlled stereoselective head-to-tail macrocyclizations

Jonas W. Rackl, Linus B. Boll, Helma Wennemers

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Chiral macrocycles are key to the discovery of new medicines. Their synthesis is, however, challenging and typically requires the often-cumbersome installation of stereochemical features in a linear precursor. In this study, we report a catalyst-controlled stereoselective head-to-tail macrocyclization. The method utilizes a bifunctional peptide catalyst to template the terminal functional groups of the linear precursor, thereby favoring intra- over intermolecular reaction and enabling exquisite control over the stereochemistry of the emerging stereogenic centers. Diverse 12- to 18‐membered macrocyclic lactones and lactams were obtained from achiral linear precursors. The organocatalyst even dictates the stereochemical outcome upon cyclizing a chiral linear precursor. This catalyst-controlled stereoselective head-to-tail macrocyclization provides a practical route to chiral macrocycles with predictable stereochemical outcomes. The utility was highlighted by synthesizing the core of the natural product robotnikinin.

GPT-4o mini: Non-social science research article

Counting trees together in the EU

Gert-Jan Nabuurs

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The European Commission, the executive body of the European Union (EU), has long sought to improve the monitoring of one of Europe’s critical resources, its forests. Forests and the pressures they face need not acknowledge political boundaries, yet monitoring is scattered and heterogeneous, delivering an uncoordinated patchwork of outdated, incomplete information from across member states’ individual monitoring efforts. However, in late 2025, the European Parliament rejected the proposed EU forest monitoring law that aimed at enhancing, harmonizing, and coordinating European forest monitoring. Despite this setback, the need for better monitoring and analysis at EU scale grows. New opportunities arise to create a workable and bottom-up solution.

GPT-4o mini: Non-social science research article

OsWRI1a coordinates systemic growth responses to nitrogen availability in rice

Chengbo Shen, Zhe Ji, Wu Jiao, Siyu Zhang, Yunzhi Huang, Yaojun Qin, Menghan Huang, Shuming Kang, Zulong Mo, Bingyu Jiang, Ying Yu, Yajing Song, Yue Li, Jiayi Xu, Yanan Tian, Yanjie Xie, Guosheng Xiong, Shaokui Wang, Guohua Xu, Xiangdong Fu, Shan Li

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Nitrogen (N) deficiency–induced increases in the root-to-shoot biomass ratio in plants are adaptive in nature but suboptimal for agriculture. Understanding the regulatory mechanisms governing this developmental plasticity could help improve crop performance while reducing fertilizer application. We identified OsWRI1a (WRINKLED1a) as a regulatory hub coordinating rice root and shoot growth in response to external N supply, thereby stabilizing the root-to-shoot ratio. In roots, OsWRI1a enhances N-responsive development by promoting auxin accumulation. Meanwhile, shoot OsWRI1a stimulates tiller development and therefore shoot growth. We identified an elite OsWRI1a haplotype that minimizes root-to-shoot ratio fluctuation under N deficiency, improving N-use efficiency and grain yield. Our findings reveal a central mechanism coordinating N-responsive growth allocation for sustainable agriculture.

GPT-4o mini: Non-social science research article

A cellular basis for the mammalian nocturnal-diurnal switch

Andrew D. Beale, Matthew J. Christmas, Nina M. Rzechorzek, Andrei Mihut, Aiwei Zeng, Christopher Ellis, Nathan R. James, Nicola J. Smyllie, Violetta Pilorz, Rose Richardson, Mads F. Bertelsen, Shaline V. Fazal, Zanna Voysey, Kevin Moreau, Jerry Pelletier, Priya Crosby, Sew Y. Peak-Chew, Rachel S. Edgar, Madeline A. Lancaster, Roelof A. Hut, John S. O’Neill

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Early mammals were nocturnal while dinosaurs dominated the daytime. Mammalian transition to daytime activity accelerated after the Cretaceous-Paleogene extinction, but the underlying mechanisms remain unclear. We identified a conserved cell-intrinsic, thermodynamic mechanism that likely facilitated this shift. In cells from diurnal mammals, protein synthesis, phosphorylation, and circadian timing were less sensitive to temperature changes than were cells from nocturnal mammals. Comparative genomics revealed accelerated evolution within essential signaling pathways, including mechanistic target of rapamycin (mTOR), that increase the robustness of diurnal cellular clocks to thermal and osmotic perturbation. In nocturnal mice, mTOR inhibition shifted cells, tissues, and behavior toward diurnal activity. These findings uncover a genetic and biochemical basis for nocturnal-diurnal switching, emphasizing how cellular signaling networks can encode complex phenotypes such as temporal niche selection.

GPT-4o mini: Non-social science research article

Reconstitution of sex determination and the testicular niche using mouse pluripotent stem cells

Takashi Yoshino, Hiromichi Sasada, Takuya Sato, Tomonori Nakamura, Kenjiro Shirane, Hiroshi Ohta, Maki Kamoshita, Miki Inoue, Yuki Matsudaira, Chao Liu, Minatsu Matsufuji, Makoto Tachibana, Ken-Ichirou Morohashi, Masahito Ikawa, Mitinori Saitou, Takehiko Ogawa, Katsuhiko Hayashi

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Proper differentiation of gonadal somatic cells is crucial for sex determination and the production of sex hormones and gametes, and reconstituting this process in culture would both deepen our understanding of this process and enable the generation of gametes in vitro. Here, we report the reconstitution of testicular somatic cells using mouse pluripotent stem cells. The reconstitution recapitulated the sex-determination process, yielding cell types that formed seminiferous tubules and adjacent interstitial tissues. The reconstituted testicular tissue incorporated pluripotent stem cell–derived primordial germ cells and supported their differentiation into spermatogonial stem cells. These spermatogonial stem cells differentiated into functional spermatozoa upon transplantation into testis. This study contributes to a deeper understanding of the sex-determination process and to the creation of an alternative source for the male germ line in culture.

GPT-4o mini: Non-social science research article

Concurrent L1 retrotransposition events promote reciprocal translocations in human tumorigenesis

Sonia Zumalave, Martin Santamarina, Nuria P. Espasandín, Jorge Zamora, Daniel Garcia-Souto, Javier Temes, Toby M. Baker, Jorge Rodríguez-Castro, Paula Otero, Ana Pequeño-Valtierra, Iago Otero, Ana Oitabén, Eva G. Álvarez, Iria Díaz-Arias, Mónica Martínez-Fernández, Miguel G. Blanco, Peter Van Loo, Gael Cristofari, Bernardo Rodriguez-Martin, Jose M. C. Tubio

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LINE-1 (L1) retrotransposition generates somatic genomic variation in human cancer, but short-read sequencing has limited our understanding of its structural consequences and dynamics. Using long-read sequencing, we analyzed 10 tumors with exceptionally high retrotransposition activity, comprising over 6,000 somatic events. We reveal that L1-mediated reciprocal translocations occur frequently, typically driven by two concurrent L1 retrotransposition events on non-homologous chromosomes. Using an independent tumor cohort spanning low to high L1 activity, we estimate that retrotransposon-mediated rearrangements arise at a frequency of one event per 60 somatic retrotranspositions. Molecular timing analyses indicate that these events arise early in tumorigenesis, establishing L1 activity as an early driver of chromosomal instability. Our findings demonstrate that L1 contributes substantially to cancer genome evolution in certain tumors.

GPT-4o mini: Non-social science research article

Imbalance in gut microbial interactions as a marker of health and disease

Roberto Corral López, Juan A. Bonachela, Maria Gloria Dominguez-Bello, Michael Manhart, Simon A. Levin, Martin J. Blaser, Miguel A. Muñoz

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Imbalances in the human gut microbiome, or dysbioses, are associated with multiple diseases but remain poorly understood. Existing biomarkers of dysbiosis fail to capture the ecological mechanisms that differentiate healthy from diseased microbiomes. We have developed a metric, the ecological network balance index (ENBI), that quantifies the balance between positive and negative microbial interactions. This metric was inspired by the phenomenology observed in a model for gut microbiome dynamics that we introduce in this work, which revealed alternative stable states with distinct emergent microbial communities: a healthy state dominated by negative interactions and a dysbiotic state dominated by positive interactions. The ENBI robustly differentiates these states in both simulated and empirical datasets spanning multiple diseases and correlates with disease progression in conditions such as colorectal cancer, which underscores its potential as a diagnostic tool.

GPT-4o mini: Non-social science research article

Convergent and lineage-specific genomic changes shape adaptations in sugar-consuming birds

Ekaterina Osipova, Meng-Ching Ko, Konstantin M. Petricek, Simon Yung Wa Sin, Thomas Brown, Sylke Winkler, Martin Pippel, Julia Jarrells, Susanne Weiche, Mai-Britt Mosbech, Fanny Taborsak-Lines, Chuan Wang, Orlando Contreras-Lopez, Remi-Andre Olsen, Philip Ewels, Daniel Mendez-Aranda, Andrea H. Gaede, Keren Sadanandan, Gabriel Weijie Low, Amanda Monte, Ninon Ballerstädt, Nicolas M. Adreani, Lucia Mentesana, Auguste von Bayern, Alejandro Rico-Guevara, Scott V. Edwards, Carolina Frankl-Vilches, Heiner Kuhl, Antje Bakker, Manfred Gahr, Douglas L. Altshuler, William A. Buttemer, Michael Schupp, Maude W. Baldwin, Michael Hiller, Timothy B. Sackton

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High-sugar diets cause human metabolic diseases, yet several bird lineages convergently adapted to feeding on sugar-rich nectar or fruits. We investigated the underlying molecular mechanisms in hummingbirds, parrots, honeyeaters, and sunbirds by generating nine new genomes and 90 tissue-specific transcriptomes. Comparative screens revealed an excess of repeated selection in both protein-coding and regulatory sequences in sugar-feeding birds, suggesting reuse of genetic elements. Sequence or expression changes in sugar-feeders affect genes involved in blood pressure regulation and lipid, amino acid, and carbohydrate metabolism, with experiments showing functional changes in honeyeater hexokinase 3. MLXIPL , a key regulator of sugar and lipid homeostasis, showed convergent sequence and regulatory changes across all sugar-feeding clades; experiments revealed enhanced sugar-induced transcriptional activity of hummingbird MLXIPL , highlighting its adaptive role in high-sugar diets.

GPT-4o mini: Non-social science research article

Sensitive CAR T cells redefine targetable CD70 expression in solid tumors

Sophie A. Hanina, Tyler Park, Michael Lopez, Vinagolu K. Rajasekhar, Jorge Mansilla-Soto, Sascha Haubner, Huiyong Zhao, Friederike Kogel, Sarah Nataraj, Priyam Banerjee, Richard Koche, Pierre-Jacques Hamard, Zeynep C. Tarcan, Dennis S. Chi, Dmitriy Zamarin, John H. Healey, Elisa de Stanchina, Robert J. Motzer, Ritesh R. Kotecha, A. Ari Hakimi, Christina S. Leslie, Michel Sadelain

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Solid tumor antigen heterogeneity is a major challenge for cancer immunotherapies, including chimeric antigen receptor (CAR) T cells. Unlike CD19 for B cell malignancies, no target with pan-cellular expression in solid tumors and absence in normal vital cells has been identified. CD70 is a promising candidate, physiologically confined to immune cell subsets and aberrantly expressed in many cancers. We show that heterogeneous CD70 expression in tumors is epigenetically regulated, ranging from high to very low in individual cells, appearing negative by conventional detection methods. Using a highly sensitive CD70 receptor, HLA-independent T cell (HIT) receptor coexpressing CD80 and 4-1BBL for costimulation, we efficiently eliminated CD70-heterogeneous tumors that evade prototypic CAR T cells. These findings provide a potential strategy to treat a broad range of solid tumors.

GPT-4o mini: Non-social science research article

Acceleration hotspots of North American birds’ decline are associated with agriculture

François Leroy, Marta A. Jarzyna, Petr Keil

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Human activities might have accelerated declines of population abundance, but this acceleration remains underexplored. Using 1033 North American Breeding Bird Survey routes, we analyze abundance change and its acceleration for 261 bird species, 54 avian families, and 10 habitats from 1987 to 2021. We show an average continent-wide decline of abundance of all birds per local route, with hotspots of decline in southern and warm parts of North America and hotspots of accelerating decline in the Mid-Atlantic, Midwest, and California, matching patterns of agricultural intensity. Overall, 122 species (47%) exhibit significant declines, of which 63 also show acceleration of this decline, and 67 show declining per-capita growth rate, raising concerns for a large part of North American bird populations. These findings suggest that bird abundance decline is mostly accelerating, with spatial patterns of this acceleration indicating that agricultural intensity may be a driver of this trend.

GPT-4o mini: Non-social science research article

Organism-wide cellular dynamics and epigenomic remodeling in mammalian aging

Ziyu Lu, Zehao Zhang, Zihan Xu, Abdulraouf Abdulraouf, Wei Zhou, Junyue Cao

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To investigate organism-wide cellular alterations and epigenomic dynamics during aging, we constructed a single-cell chromatin accessibility atlas spanning 21 mouse tissues across three age groups and both sexes. We found that around one-quarter of 536 organ-specific cell types and 1828 finer-grained subtypes exhibited considerable age-related population shifts. Cellular states from broadly distributed lineages displayed synchronized dynamics with age, indicating systemic signals that coordinate these changes. Molecular analyses identified both intrinsic regulators (chromatin peaks, transcription factor activity) and extrinsic factors (cytokine programs) underlying these shifts. Moreover, ~40% of aging-associated population dynamics were sex-dependent, with tens of thousands of peaks altered exclusively in one sex. Together, these findings present a comprehensive framework for how aging reshapes the chromatin landscape and cellular composition across diverse tissues.

GPT-4o mini: Non-social science research article

STING–NF-κB signaling builds an influenza spillover barrier

Runxin Ye, Songdi Wang, Ying Hu, Yiran Pan, Wenwen Zheng, Fengyan Xia, Yanpu Wang, Haoran Guo, Shu Zheng, Wei Wei, Xiao-Fang Yu

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Influenza pandemics are often traced back to the spillover of avian influenza A viruses (IAVs) to humans. However, barriers against IAV transmission remain elusive. We demonstrated human stimulator of interferon genes (STING) as a transmission barrier against IAVs. STING activated nuclear factor κB (NF-κB) and downstream NF-κB–stimulated genes (NSGs) through a specific domain. Among these NSGs, growth arrest and DNA damage–inducible protein 34 ( GADD34 ) was crucial for IAV restriction. Some IAVs have evolved to evade activating human STING by mutating residue 115 in their matrix protein 1 (M1), which is essential for efficient viral replication in human respiratory cells. This barrier against the zoonotic threat of IAVs provides a tool for future investigations into the biological functions of the cyclic guanosine monophosphate–adenosine monosphosphate (cGMP-AMP) synthase (cGAS)–STING–NF-κB signaling pathway.

GPT-4o mini: Non-social science research article

Different DNA repair pathways support intact or truncated insertions by R2 retrotransposon protein

Jeremy J. R. McIntyre, Connor A. Horton, Kathleen Collins

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Non–long terminal repeat (non-LTR) retrotransposon proteins copy their RNA template into a genome through coordinated nicking and reverse transcriptase activities of target-primed reverse transcription. Mechanisms by which the first-strand complementary DNA (cDNA) becomes a stably inserted duplex, including requirements for junction formation at the cDNA 3′ end and second-strand synthesis, are unknown. We screened for cellular factors that influence site-specific transgene synthesis into the human genome by an R2 retrotransposon protein. We discovered that insertion lengths and junction signatures differ based on alternative repair processes involving ATR-dependent polymerase θ end joining, 53BP1-directed shieldin and CST–polymerase α–primase fill-in synthesis, or limited strand annealing dependent on CtIP-MRN. These insights shed light on how genome-primed cDNA synthesis by a non-LTR retrotransposon protein can support stable new gene insertion, with major implications for native retrotransposon mobility and genome engineering.

GPT-4o mini: Non-social science research article

A precessing jet from an active galactic nucleus drives gas outflow from a disk galaxy

Justin A. Kader, Vivian U, Loreto Barcos-Muñoz, Marina Bianchin, Yiqing Song, Sean T. Linden, Gabriela Canalizo, Archana Aravindan, George C. Privon, Tanio Díaz-Santos, Christopher Hayward, Matthew A. Malkan, Lee Armus, Rosalie C. McGurk, Jeffrey A. Rich, Anne M. Medling, Sabrina Stierwalt, Claire E. Max, Aaron S. Evans, Christopher J. Agostino, Vassilis Charmandaris, Tianmu Gao, Justin H. Howell, Hanae Inami, Thomas S.-Y. Lai, Kirsten L. Larson, Christopher D. Martin, Mateusz Matuszewski, Joseph M. Mazzarella, James D. Neill, Nikolaus Z. Prusinski, Raymond Remigio, David B. Sanders, Jason Surace

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To reproduce observed galaxy properties, cosmological simulations require that massive galaxies experience feedback from active galactic nuclei, which regulates star formation within those galaxies. However, the energetics and timescales of these feedback processes are poorly constrained. We combined optical, infrared, submillimeter, and radio observations of the active galaxy VV 340a, which is hosting a low-power jet launched from a supermassive black hole at its center. We found that the jet undergoes precession, with a period of (8.2 ± 5.5) × 10 5 years, and drives an outflow of gas at a rate of 19.4 ± 7.9 solar masses per year. The jet shocks the gas, producing highly ionized plasma that extends several kiloparsecs from the nucleus. The outflow ejects sufficient gas from the galaxy to influence its star-formation rate.

GPT-4o mini: Non-social science research article

Gigantic piezoelectricity in a polycrystalline ceramic actively maintained at a quadruple point

Yanshuang Hao, Dipak Kumar Khatua, Dong Wang, Jinghui Gao, Shuai Ren, Yang Yang, Minxia Fang, Dezhen Xue, Jingzhe Xu, Guanqi Wang, Xiaoqin Ke, Zhizhi Xu, Chang Liu, Qichao Fan, Yuanchao Ji, Le Zhang, Sen Yang, Genshui Wang, Xiaobing Ren

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Transformative technologies demand polycrystalline piezoelectric ceramics with piezoelectric coefficients ( d 33 ) exceeding 6000 picocoulomb per Newton (pC/N), but this goal has remained elusive because of the intrinsically weak nature of piezoelectricity and incomplete polarization alignment in polycrystals. We overcome this barrier by placing a polycrystalline lead zirconate titanate (PZT) ceramic in a temperature and electric-field control module so that it operates at a quadruple phase point (QP). This QP ceramic exhibited a d 33 of ~6850 pC/N, which surpasses that of commercial PZT ceramics by 10 to 30 times and commercial lead magnesium niobate–lead titanate single crystals by ~4 times. This exceptional property arises from the tricritical nature of the QP, a thermodynamic singularity that produces an ultrasoft lattice and enables complete polarization alignment in polycrystals. The module maintained this performance for surrounding ambient temperature ranging from 25° to 350°C.

GPT-4o mini: Non-social science research article

Cryo–electron microscopic visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2

Luke A. Greenhough, Lorenzo Galanti, Chih-Chao Liang, Simon J. Boulton, Stephen C. West

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Homologous recombination repairs DNA double-strand breaks and protects stalled replication forks, but how the five RAD51 paralogs contribute to these processes remains unclear. Mutations in the RAD51 paralogs are linked to heritable breast and ovarian cancers and the cancer-prone disease Fanconi anemia. In this work, we show that the RAD51 paralogs assemble into two distinct heterotetrameric complexes, RAD51B-RAD51C-RAD51D-XRCC2 (RAD51B complex) and XRCC3-RAD51C-RAD51D-XRCC2 (XRCC3 complex). The RAD51B complex promotes dynamic adenosine triphosphate hydrolysis–dependent assembly of RAD51 filaments, whereas the XRCC3 complex stably caps the 5′ termini of RAD51 filaments to promote homologous pairing, as visualized by cryo–electron microscopy. Highly conserved across evolution, the XRCC3 complex reveals insights into RAD51 filament formation and capping during DNA repair and replication fork stabilization.

Science abstract < 200 char.: Not a research article

Fading melodies

Warren Cornwall

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Intact tropical forests are seeing mysterious bird declines. Is another “silent spring” brewing?

Science abstract < 200 char.: Not a research article

Curing a Black family’s distrust in medicine

Jasmine Gabriel Hughes

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Science abstract < 200 char.: Not a research article

Investor nominated to head NSF in agency shake-up

Jocelyn Kaiser, Jeffrey Mervis

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Move leaves CDC leadership vacancy—to be filled by NIH director

Science abstract < 200 char.: Not a research article

An email of one’s own

Feng Li

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Science abstract < 200 char.: Not a research article

In Other Journals

Madeleine Seale, Mattia Maroso, Sacha Vignieri, Stella M. Hurtley, Jack Huang, Jesse Smith, Brad Wible

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Editors’ selections from the current scientific literature

Science abstract < 200 char.: Not a research article

In Science Journals

Corinne Simonti, Di Jiang, Priscilla N. Kelly, Phil Szuromi, Keith T. Smith, Bianca Lopez, Claire Olingy, Peter U. Clark, Caroline Ash, Yevgeniya Nusinovich, Sarah H. Ross, Jake S. Yeston, Madeleine Seale, L. Bryan Ray, Julius Baeck, Leslie K. Ferrarelli, Navdeep Chandel

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Highlights from the Science family of journals

Science abstract < 200 char.: Not a research article

Chromatin dynamics shape aging across organs

Sam N. Barnett, Michela Noseda

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Age-related chromatin remodeling includes shared and specific signatures across cell types, sex, and organs

Science abstract < 200 char.: Not a research article

Two free ends make a match

Ziyang Dong, Changgui Zhao

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A peptide catalyst turns a linear molecule into a ring through two synchronous reactions

Science abstract < 200 char.: Not a research article

Alleged Chinese nuclear blast may reignite testing

Richard Stone

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As new global arms race looms, accusation highlights limits to monitoring low-yield tests

Science abstract < 200 char.: Not a research article

Neanderthal males paired with modern human females

Bridget Alex

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X chromosomes in both kinds of human testify to ancient mating bias

Science abstract < 200 char.: Not a research article

The enigmatic Isthmian inscriptions The Isthmian Script Martha J. Macri University of Oklahoma Press, 2026. 168 pp.

Andrew Robinson

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A long-undeciphered script receives renewed attention and a contested interpretation

Science abstract < 200 char.: Not a research article

STING takes on RNA viruses

Nan Yan

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A signaling pathway that inhibits DNA virus replication is also protective against RNA viruses

Science abstract < 200 char.: Not a research article

Medical preparedness in deep-space missions

Farhan M. Asrar, Barry Wilmore

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Science abstract < 200 char.: Not a research article

How to build a testis, cell by cell

Rod T. Mitchell

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Engineered pluripotent stem cells form somatic and germ cells that mimic a functional testis

Science abstract < 200 char.: Not a research article

Genetic information in insurance: Guiding questions for state regulation

Anya E. R. Prince, Theresa Eckel

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Many legislative efforts do not adequately address public concerns of genetic discrimination in insurance

Science abstract < 200 char.: Not a research article

Data show sharp drops in NIH funding success in 2025

Jocelyn Kaiser

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Young investigators lose out as result of multiyear funding policy imposed by White House

Science abstract < 200 char.: Not a research article

Private money cannot replace public funding of science

Naomi Oreskes

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Science abstract < 200 char.: Not a research article

The challengers Traversal Maria Popova Farrar, Straus and Giroux, 2026. 608 pp.

Philip Ball

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Radical rejectors of orthodoxy take center stage in a rich history of ideas

Science abstract < 200 char.: Not a research article

In a first, ChatGPT helps break new ground in theoretical physics

Perri Thaler

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Physicists combined human acumen and AI-assisted math to show that a doubted particle interaction is possible after all

Science abstract < 200 char.: Not a research article

Integrating root and shoot nitrogen responses

Mao Suganami, Makoto Matsuoka

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A transcription factor may enable high-yield rice plants to use nitrogen more efficiently

Science abstract < 200 char.: Not a research article

AAAS announces 2026 award winners

Becky Ham

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Science abstract < 200 char.: Not a research article

Islamic influence on the scientific method

Muhammad Shehryar Khan

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Science Advances

GPT-4o mini: Non-social science research article

Molecular level combination of coordination and interfacial regulations via functional ligands for industrial AEM water electrolysis

Xinyi Li, Jiyu Liu, Zhongfeng Wang, Hong Huang, Xiaoyuan Sun, Wenting Lu, Xiao Zhao

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Coordination engineering is often used to tune the electronic structures of active sites, while their catalytic performances are determined not only by electronic structures but also by microenvironments. Herein, we introduce interfacial functional ligands that not only optimize the electronic structures of active sites but also regulate the interfacial microenvironment for oxygen evolution reaction (OER). Specifically, the pore edge–hosted FeF 3 O 2 sites enable a favorable electronic structure to generate * OOH intermediates and simultaneously promote the interfacial transport of hydroxide for enhanced OER kinetics. The F ligands in FeF 3 O 2 sites interact with interfacial water strongly via H-bonding to promote H-bond network connectivity, thus encouraging the temporally concerted proton transfer during hydroxide diffusion. Consequently, FeF 3 O 2 sites realize the 331.5-fold enhancement in turnover frequency for alkaline OER over the NiOOH and efficient water electrolyzers (1.663 voltage at 1.0 amperes per square centimeter at 60°C, durably operating at 1.0 amperes per square centimeter > 1200 hours).

GPT-4o mini: Non-social science research article

Structure and dynamics of a multidomain nitric oxide synthase regulated by a C2 domain

Dhruva Nair, Brian R. Crane

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Nitric oxide synthase (NOS) is a widely studied multidomain redox enzyme that produces the key signaling molecule and cytotoxic agent nitric oxide (NO) for functions that range from mammalian vasodilation to prokaryotic antibiotic resistance. NOS enzymes from metazoans and cyanobacteria rely on dynamic associations of their oxygenase and coupled diflavin reductase domains that have largely evaded detailed structural characterization. Cryo–electron microscopy studies of a representative dimeric six-domain Synechococcus NOS reveal the architecture of the full-length enzyme, which contains an unusual regulatory C2 domain, and additional nitric oxide dioxygenase (NOD) and pseudoglobin modules. Five distinct structural states depict how pterin binding couples to tight and loose oxygenase conformations and how the Ca 2+ -sensitive C2 domain moves over 85 angstroms to alternatively regulate either the NOS or NOD heme center. The extended carboxyl-terminal tail and its dynamic interactions highlight an added layer of regulation required by multidomain NOSs compared to other diflavin reductases.

GPT-4o mini: Non-social science research article

KRAS G12V /HLA-A*02:01–targeted chimeric antigen receptor T cells exhibit potent preclinical activity against solid tumors

Huimin Shao, Fei Xu, Jiangyue Xu, Lingjie Zhou, Yao Wu, Lianjun He, Xueyi Qian, Weijie He, Nanlin Jiao, Yabin Xia, Jun Zhao, Lili Sheng, Guoliang Mao, Tao Ma, Wei Wang, Shaoxiang Luo, Li Fu, Zhenyu Xu

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Despite advances in chimeric antigen receptor T cell (CAR T cell) therapy for leukemia and lymphoma, solid tumors remain challenging because of limited target specificity and safety concerns. Neoantigens like KRAS G12V , a highly prevalent yet undruggable mutation in solid tumors, offer tumor-exclusive specificity. This study developed CAR T cells targeting KRAS G12V /HLA-A*02:01 using phage antibody display to identify high-affinity single-chain variable fragments. Engineered B9 CAR T cells specifically lysed tumor cells and patient-derived cancer organoids expressing KRAS G12V /HLA-A*02:01, demonstrating potent antitumor activity. Animal studies showed that B9 CAR T cells effectively controlled tumor growth in subcutaneous pancreatic ductal adenocarcinoma (PDAC) xenografts, as well as in metastatic and peritoneal PDAC models. Safety assessments in NCG-HLA-A2.1 and C57BL/6 mice revealed no detectable in vivo toxicity, supporting the clinical applicability of B9 CAR T cells. Collectively, our neoantigen-targeted CAR T cell therapy against solid tumors shows great potential for future clinical trials in patients with KRAS G12V /HLA-A*02:01, paving the way for clinical translation.

GPT-4o mini: Non-social science research article

Immunometabolic resistors of aging in long-lived golden spiny mice

Hee-Hoon Kim, Tali Sagiv-Zangi, Yun-Hee Youm, Hagar Vardi-Naim, Tamara Dlugos, Francesco Strino, Mila Kazavchinsky-Bar, Lian Egulsky, Monica Bodogai, Arya Biragyn, Yuval Kluger, Noga Kronfeld-Schor, Vishwa Deep Dixit

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Long-lived wild rodents closely related to laboratory mice on the evolutionary scale may allow identification of dormant pathways that resist aging. Spiny mice ( Acomys ) are known for their exceptional regenerative capacity, but their resilience to aging is unknown. Here, we report that aged golden spiny mice ( Acomys russatus ), reared in a non–pathogen-free environment, resist functional decline, have a greater repair capacity with reduced senescence in immune-metabolic organs compared to their sister species, eastern spiny mice ( Acomys dimidiatus ). Aged A. russatus maintains transcriptional integrity akin to young mice, highlighting experimental checkpoints for inflammation and mortality. We identified that elevated levels of clusterin in A. russatus macrophages restrain inflammaging and enhance health span in aged mice. Thus, A. russatus biology reveals therapeutically actionable targets that may enhance or maintain function during aging.

GPT-4o mini: Non-social science research article

Skin CO 2 sniffing for wearable metabolic monitoring

Seung-Rok Kim, Noelle Davis, Kalynna Tang, George A. Brooks, Ali Javey

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CO 2 is a key physiological parameter used to assess hypoventilation and to estimate metabolic rates. However, current CO 2 monitoring relies on bulky breath-analysis systems that are impractical for continuous use in daily life. Here, we present a wearable on-skin gas-sniffing system that quantifies skin-emitted CO 2 and establishes its physiological relevance through direct correlation with exhaled CO 2 and metabolic rate. Participant studies demonstrate strong correlations between CO 2 flow rates from the skin and breath during both rest and exercise, with skin-emitted CO 2 approximately four orders of magnitude lower than exhaled CO 2 . Skin-emitted CO 2 also correlates with metabolic rate, suggesting its potential as a surrogate for breath-based indirect calorimetry. With its wearable form factor and physiological relevance, this skin gas sniffing system enables continuous, noninvasive metabolic monitoring and opens opportunities for studying skin gas exchange.

GPT-4o mini: Non-social science research article

Repurposing Si CMOS nonidealities for stochastic and analog image processing

Been Kwak, Ryun-Han Koo, Changhyeon Han, Yunho Shin, Joonhyeok Choi, Dongbin Kim, Jongwoo Lee, Jiseong Im, Youngchan Cho, Jong-Ho Lee, Wonjun Shin, Daewoong Kwon

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Conventional semiconductor device engineering regards intrinsic device nonidealities as reliability concerns to be minimized or eliminated. Here, we demonstrate the strategic repurposing of these nonidealities as functional resources for advanced stochastic analog computing. We leverage two underutilized phenomena—deep-level channel trap-induced generation-recombination (G-R) noise and impact ionization–induced negative differential resistance (NDR) in body current—which have received limited attention compared to the extensively studied 1/ f noise and monotonic drain current behavior in logic-centric transistors. By exploiting G-R noise with controllable temporal correlation and NDR with an unprecedented peak-to-valley ratio (2.78 × 10 4 ) within fully depleted silicon-on-insulator transistors fabricated in industry silicon complementary metal-oxide semiconductor (CMOS) process, we achieve multifunctional analog computation at the single-device level. Our transistor seamlessly performs stochastic encryption, deterministic signal readout, and analog inversion simply through reconfiguration of applied bias conditions, thereby eliminating the need for peripheral random-number generators, dedicated analog inverters, or amplifiers. This approach not only reveals the previously unrecognized computational potential embedded in mature CMOS technologies but also presents a scalable and energy-efficient alternative to architecture based on exotic materials, laying the foundation for next-generation analog computing systems.

GPT-4o mini: Non-social science research article

Coupled geomorphic and climate-driven biogeochemical processes regulate soil organic carbon stocks in agricultural terraces

Pengzhi Zhao, Daniel J. Fallu, Sebastian Doetterl, Sara Cucchiaro, Paolo Tarolli, Ben R. Pears, Andreas Lang, Moritz F. Mainka, Xiaojing Ou, Jeanette Whitaker, Zhengang Wang, Antony G. Brown, Johan Six, Kristof Van Oost

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Agricultural terraces are among the most widespread human-made landforms. They profoundly reshape soil landscapes and influence the carbon cycle, yet the extent and drivers of their impact remain highly uncertain. By integrating field observations from 14 well-drained terrace landforms across a climatic-geochemical gradient with a data synthesis, we show that changes in soil organic carbon (SOC) stocks after terracing are governed by two coupled C turnover-geomorphic processes: replacement of lost topsoil C at eroding positions and stabilization of buried SOC at depositional positions. Climate strongly modulates these processes by shaping soil geochemistry and plant productivity, which in turn control SOC replacement and stabilization within terraces. Thus, terracing effects on SOC stocks shift from consistently positive in humid regions to mixed (positive and negative) outcomes in dry regions. This study establishes a framework for elucidating SOC dynamics in well-drained terrace systems and provides a scientific basis for targeted management strategies to enhance C sequestration in agricultural terraces globally.

GPT-4o mini: Non-social science research article

Intermediate excited state relaxation dynamics of boron vacancy spin defects in hexagonal boron nitride

Paul Konrad, Mehran Kianinia, Lesley Spencer, Andreas Sperlich, Lukas Hein, Selin Steinicke, Igor Aharonovich, Vladimir Dyakonov

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Optically addressable spin defects in hexagonal boron nitride offer promising potential for 2D quantum sensing, although excited-state dynamics remain poorly understood. In particular, the nonradiative relaxation paths from the excited triplet states to the ground state, especially those involving a shelving intermediate state (IS), remain largely hypothetical, and the rate constants have yet to be directly measured. In this work, we investigate the relaxation dynamics of the IS in the optical pumping cycle in a broad temperature range. We measure a 24.0(3)-nanosecond relaxation time from IS to the ground state at room temperature, which approximately doubles at low temperatures. Simulations reveal how spin populations and ground-state polarization evolve with varying excitation rates. Accordingly, we optimize optically detected magnetic resonance pulse sequences to account for the effects of IS relaxation. This considerably enhances spin manipulation efficiency, allowing substantial optimization of the quantum sensor’s sensitivity based on boron vacancies.

GPT-4o mini: Non-social science research article

Assessing the health risks of rice cadmium content standards in China

Haiyan Chu, Huilin Zhang, Dahua Ren, Xuanying Jiang, Yang Yu, Jialei Zhu, Kexin Li, Haiping Liu, Linfan Xu, Xiaoting Li, Zhen Ding

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With increasing understanding of cadmium (Cd) exposure levels and toxicity mechanisms, the adequacy of current Cd limit standards for protecting public health requires comprehensive evaluation. Here, we found that 39.04% of rice Cd content surpassed the fifth percentile of benchmark dose lower limit (BMDL 5 ; 17.100 micrograms per day) threshold for dietary Cd associated with chronic kidney disease in Jiangsu Province. Moreover, more than 90% of rice Cd levels posed potential health hazards, with some samples presenting lifetime carcinogenic risks. Blood and urinary Cd levels demonstrated age-dependent increases, with 48.40 and 20.61% of participants exceeding BMDL 5 levels for blood Cd (0.640 micrograms per liter) and urinary Cd (0.120 micrograms per liter), respectively. The derived reference values for dietary Cd were 0.149 and 0.018 micrograms per kilogram of body weight per day for adults and children, respectively. The lowest concentrations of Cd in rice consumed by adults and children were also observed, which indicated that current Cd limit standards appear insufficient to protect public health, indicating a need for more stringent safety thresholds.

GPT-4o mini: Non-social science research article

Inflamed vessel–anchored release of H 2 across the blood-brain barrier for ischemic stroke neuroprotection

Yuanman Yu, Mingjian Fan, Gaoyi Wu, Yongcheng Li, Chao Xia, Wenjiang Ding, Guanglin Li, Qianjun He, Wei Tang, Changsheng Liu

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Ischemic stroke followed by reperfusion urgently requires safe and efficient cytoprotective strategies, a need still unmet by current pharmacotherapies. Nanotechnology holds promise for improved drug delivery to the brain, yet the efficacy of nanomaterials crossing the blood-brain barrier (BBB) is quite limited, and long-term intracranial retention of nanomaterials may provoke neurotoxicity. Leveraging the anti-inflammatory, BBB-crossing, and biosafe properties of hydrogen (H 2 ), we develop an inflamed vessel–targeted/anchored H 2 –producing system by modifying ZrSi 2 nanoparticles with a P-selectin–binding peptide (ZSNP), mimicking P-selectin/P-selectin glycoprotein ligand–mediated innate immune recruitment. Rather than relying on nanoparticle penetration into the brain parenchyma, this design enables ZSNP to anchor at the BBB vasculature, where it locally and continuously generates H 2 via hydrolysis. The released H 2 traverses the BBB, exerting cytoprotection through antioxidant and immunomodulatory mechanisms that coordinate multicellular recovery processes. Furthermore, ZSNP promotes microglia-mediated angiogenesis and neurogenesis, guides axonal projections along neovascular trajectories, and facilitates microglia-neuron interaction via the noncanonical Wnt/Ca 2+ pathway. This reconstruction of the neurovascular network supports the reintegration of functional neural circuits, leading to structural and functional recovery that surpasses the effects of edaravone. By enabling sustained H 2 release at the BBB interface without requiring nanoparticle intracranial accumulation, this strategy represents a promising and low-burden neuroprotective approach for ischemic stroke.

GPT-4o mini: Non-social science research article

Enteric botulinum neurotoxins facilitate infection by Salmonella and Shigella

Federico Fabris, Paola Brun, Aram Megighian, Giulia Bernabè, Ignazio Castagliuolo, Ilenia Drigo, Luca Bano, Florigio Lista, Maria Lina Bernardini, Eric A. Johnson, Cesare Montecucco, Ornella Rossetto

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Botulism is a life-threatening disease caused by botulinum neurotoxins (BoNTs) released by Clostridium bacteria. BoNTs induce a flaccid paralysis by blocking neurotransmitter release from peripheral cholinergic neurons via soluble N -ethylmaleimide–sensitive factor attachment protein receptor (SNARE) cleavage. The enteric nervous system (ENS) controls antimicrobial defense reactions within the intestine through neuron-released mediators. Here, we show that subclinical doses of BoNT/A and BoNT/B, which are not sufficient to cause botulism when released in the intestinal lumen, paralyze ENS neurons favoring infection by prototypic bacterial pathogens such as Salmonella enterica and Shigella flexneri . The BoNTs reduce the release of mucin, decreasing the protective barrier against bacterial infection. These findings disclose previously unrecognized functions of BoNTs and roles in intestinal infections. Moreover, they indicate that BoNTs are valuable tools for investigating the ENS neuron involvement in the intestinal defense reactions.

GPT-4o mini: Non-social science research article

3D Anderson localization of classical scalar waves

Fanambinana Delmotte, Thomas Brunet, Jacques Leng, John H. Page

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Anderson localization, first predicted in 1958, is one of the most fascinating and remarkable wave phenomena. The experimental search for this halt of diffusive transport in three-dimensional (3D) disordered systems, which is still very actively pursued for classical waves (light or sound), has never been demonstrated for the fundamental case of scalar waves. Inspired by recent advances in 3D metamaterials, we show that a locally resonant ultrasonic metafluid consisting of a suspension of soft metallic beads is the innovation needed for 3D Anderson localization of scalar acoustic waves to be definitively observed. By reporting two independent sets of time- and position-resolved ultrasonic experiments, we present clear evidence of Anderson transitions between diffusion and localization, accurately determining the mobility edges and the localization phase diagram.

GPT-4o mini: Non-social science research article

Fluidic torque–enabled object manipulation by microrobot collectives

Steven Ceron, Gaurav Gardi, Kirstin Petersen, Metin Sitti

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Microscale systems experience strong viscous interactions because of the low–Reynolds-number regime in which they exist. This means that fluidic manipulation and actuation of passive objects can be enabled and influenced by the individual spin rate of microscale robots, the number of microrobots, and their positions relative to the objects. We explore these parameter spaces and find that the fluidic torque generated by a magnetic microrobot collective can be exploited to apply bidirectional torque to concentric ring structures and demonstrate this through physical experiments and numerical simulations. Additionally, we demonstrate how the fluidic torque of the microrobots can be exploited to actuate gear trains, rotate comparatively large three-dimensional objects, dynamically self-assemble internally driven ring structures, and absorb and expel large numbers of circular objects. Last, we show emergent behaviors where the microrobot collective’s morphology and method of locomotion changes as a function of the spin rate of the microrobots and the size and shape of the surrounding objects.

GPT-4o mini: Non-social science research article

The thermodynamic opportunities hypothesis: Metabolic temperature insensitivity across flatfish species

Brad A. Seibel

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This study challenges widely held metabolic theory, which suggests that whole-animal metabolic rates increase with temperature because of its universal effects on the kinetics of the underlying biochemical reactions. Here, we show that metabolic rates across flatfish species are largely invariant from poles to the equator, which points to an explanation for interspecific thermal sensitivity based on ecology and evolution rather than thermodynamic constraints. The explanation proposed here is that warm water provides a thermodynamic opportunity, not a mandate, for metabolic rate escalation when required for predator-prey interactions. Flatfish do not require metabolic escalation because of their reliance on camouflage that mitigates the greater predation intensity in tropical waters. These findings have strong implications for models attempting to diagnose the response of organisms to climate change and for macroecological patterns more generally.

GPT-4o mini: Non-social science research article

Century-long coral records of the South China Sea throughflow slowdown

Feng Nan, Huijie Xue, Fei Yu, Mingting Li, Xiaohua Li, Dongxiao Wang

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The South China Sea throughflow (SCSTF) serves as a heat and freshwater conveyor, playing a pivotal role in regulating physical processes and biogeochemical cycles in the SCS. Because of limited observations, the long-term changes of the SCSTF under a warming climate and underlying dynamics remain unclear. In this study, we reconstructed centennial-scale variability of the SCSTF (1894–2022) using coral oxygen isotope (δ 18 O) and satellite observations. Besides prominent interannual and decadal variabilities, there exists a marked long-term decreasing trend at −0.14 ± 0.02 Sv (1 Sv = 10 6 m 3 s −1 ) per decade for the total SCSTF volume transport. Consequently, the SCSTF transport decreased by 35 ± 5% over the past 129 years in comparison with the mean value of 5.15 Sv. Using the Time-dependent Island Rule theory, we further reveal that the intensified trade wind in the tropical western Pacific drives the SCSTF slowdown. The findings substantially contribute to investigating the physical, ecological, and biogeochemical changes in the SCS and the Indo-Pacific Oceans.

GPT-4o mini: Non-social science research article

DNA framework–based molecular transformer for logic-driven precision diagnostics

Shuyang Zhang, Kai Xia, Lihua Wang, Chunhai Fan, Fangfei Yin, Xiaolei Zuo

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Precision diagnostics requires logical integration of diverse biomarker information, but molecular heterogeneity and inconsistent identification kinetics hinder robust logic analysis. To overcome this, we develop a universal molecular transformer using DNA tetrahedral frameworks (DTFs) as programmable scaffolds. This system converts diverse biomarkers including proteins and variable-length nucleic acids into uniform 22-nucleotide DNA sequences, normalizing information dimensionality and identification kinetics. These uniform sequences serve as inputs for three fundamentals Boolean logic gates (AND, OR, and INHIBIT), enabling programmable molecular decision-making. Integrated on a gold-chip platform, the DTF transformer and logic system achieved statistically significant discrimination ( P < 0.0001) among patients with prostate cancer, patients with benign prostatic hyperplasia, and healthy individuals using only two biomarkers (prostate-specific antigen and ALU115). By unifying signal transformation for Boolean logic computation, we resolve the critical challenges in molecular heterogeneity and establish a versatile platform for next-generation precision diagnostics.

GPT-4o mini: Non-social science research article

CH•••S hydrogen bonds drive molecular recognition of ergothioneine by the microbial transporter

Katherine A. Legg, Giovanni Gonzalez-Gutierrez, Katherine A. Edmonds, Philip G. Shushkov, David P. Giedroc

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Many bacteria harbor an ATP-binding cassette (ABC) transporter named EgtU specific for the human dietary antioxidant and 2-thioimidazole–containing low–molecular weight thiol ergothioneine (ET). How the solute binding domain, EgtUC, discriminates among ET and other similar molecules is unknown. Here, we use a “chimeric” mutagenesis strategy and two distantly related EgtUCs from Streptococcus pneumoniae and Helicobacter pylori to show that a suite of EgtUC alkyl CH•••S hydrogen bonds to the ET thione S atom are central determinants of molecular recognition. Small perturbations in CH•••S distance and angle give rise to sharply attenuated transport-competent ET-bound “closed” state lifetimes and increased motional disorder in the binding pocket, not around the S atom itself, but distally in weakening NH•••O hydrogen bonds. This work highlights the impact of alkyl CH•••S H bonding in a biological protein-ligand complex in water.

GPT-4o mini: Non-social science research article

Bees flexibly adjust decision strategies to information content in a foraging task

Johannes Spaethe, Selma Hutzenthaler, Alexander Dietz, Karl Gehrig, James Foster, Anna Stöckl

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When making decisions, animals often rely on multiple cues simultaneously. These provide complementary sources of information, which can increase the accuracy of decisions. In this study, we tested the decision and learning strategies of insects faced with multiple cues in a foraging task, using the bumblebee Bombus terrestris . We presented combinations of visual-only features, as found in natural flowers: colors of varying discriminability, paired with shapes or patterns. We found that the bees relied exclusively on colors when these were easy to discriminate, and did not learn pattern or shape features simultaneously. With harder to discriminate colors, the bees learned both color and shape or pattern features. Our results demonstrate that bumblebees flexibly adjust their learning strategies when presented with visual features of varying discriminability, to balance the investment in learning time and accuracy during multicue learning and decision making. A difference in learning dynamics suggests that blocking could serve as a mechanism to implement this strategy switch.

GPT-4o mini: Non-social science research article

Electroluminescent perovskite QD–based neural networks for energy-efficient and accelerate multitasking learning

Young Ran Park, Gunuk Wang

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The ability of multitasking (MT) learning in neuro-inspired artificial intelligence (AI) systems offers promise for energy-efficient deployment in robotics, health care, and autonomous vehicles. Here, an MT learning framework is established using a dual-output electroluminescent synaptic device array based on a mixed-dimensional stacked configuration with Cs 1− x FA x PbBr 3 (0.00 ≤ x ≤ 0.15) quantum dots. The device concurrently processes postsynaptic current (PSC) and postsynaptic electroluminescence (PSEL) signals, demonstrating stable and adjustable long-term plasticity with ~1000 individual states, along with spike rate-dependent plasticity and paired-pulse facilitation. By synthesizing the update behavior of both PSC and PSEL pathways, the MT framework simultaneously executes classification-regression and classification-image reconstruction tasks. This approach achieves computational speed improvements of up to 47.09 and 29.17% while reducing energy consumption by up to 8.2- and 32.4-fold compared to a combined single-tasking framework and graphics processing unit–based hardware accelerators, respectively. This innovative method emphasizes the potential of dual-output electroluminescent artificial synapse for MT learning applications.

GPT-4o mini: Non-social science research article

Electrochemical conversion of oxalic acid to glycolic acid via oxygen vacancy–mediated tandem catalysis

Min Li, Fantao Kong, Hao Zhuo, Wenshu Luo, Xiangzhi Cui, Jianlin Shi

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The electrochemical conversion of oxalic acid (OX) to glycolic acid (GC) offers a sustainable route for biomass valorization yet suffers from inefficient proton-coupled electron transfer and competitive hydrogen evolution. We report an oxygen vacancy (O V )–mediated atomic interface strategy to construct Fe δ- -O V -Ti 3+ dual-active sites in TiO 2 , enabling tandem activation of H + and C═O bond through a (2e − + 2e − ) relay mechanism. The Fe-TiO X /titanium paper electrocatalyst achieves a faradaic efficiency of 74.3% with >60% GC selectivity at industrially relevant current densities (~100 milliamperes per square centimeter), stable for ~60 hours, which is a record high in electrochemical conversion of OX to GC. In situ spectroscopy and density functional theory calculations reveal that the Fe δ- sites dynamically stabilize H* intermediates while inhibiting H 2 formation, while Ti 3+ sites form a σ─π coordination bond with the carbonyl oxygen in OX, lowering the energy barrier of the rate-determining step. This work provides a paradigm for designing a dual site in electrochemical tandem reactions, offering fundamental insights in sustainable chemical synthesis.

GPT-4o mini: Non-social science research article

Structures of the 26 S proteasome in complex with the Hsp70 co-chaperone Bag1 reveal a mechanism for direct substrate transfer

Moisés Maestro-López, Tat Cheung Cheng, Jimena Muntaner, Margarita Menéndez, Melissa Alonso, Andreas Schweitzer, Masato Ishizaka, Robert J. Tomko, Jorge Cuéllar, José María Valpuesta, Eri Sakata

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Coupling between the chaperone and degradation systems, particularly under stress, is essential for eliminating unfolded proteins. The co-chaperone Bag1 links Hsp70 to the 26 S proteasome, recruiting Hsp70-bound clients for proteasomal degradation. Here, we present cryo–electron microscopy structures of the Bag1-bound 26 S proteasome, revealing unprecedented conformational rearrangements within the 19 S regulatory particle. Bag1 binding to the Rpn1 induces a marked reconfiguration of AAA + adenosine triphosphatase (ATPase) ring, disrupting its canonical spiral staircase and remodeling the central channel architecture. This reconfiguration generates a large cavity above the substrate entry gate of the 20 S core particle. The conserved pore-2 loops of ATPases Rpt2 and Rpt5 play critical roles in opening of the 20 S gate, enabling substrate entry into proteolytic chamber independently of ubiquitination. These findings suggest a previously unknown mechanism of the proteasomal degradation, by which remodeling the central cavity and 20 S gate in the presence of Bag1, possibly bypassing the need for ubiquitination.

GPT-4o mini: Non-social science research article

The conserved noncoding sequence CNS11 is a master control region for Rorc transcription in type 17 immune cells

Hao Zhang, Dehui Chang, Shiyuan Xie, Ruifeng Li, Qian Zhang, Qi Xing, Tian Xie, Gongrui Zhang, Xinyi Lou, Shijie Li, Lin Yang, Vivian Dong, Jing Ge, Xiaohu Wang, Chen Dong

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Retinoic acid receptor–related orphan receptor γt (RORγt) is the master transcription factor for type 17 immune cells, including T helper 17 (T H 17) cells, group 3 innate lymphoid cells (ILC3s), RORγt + regulatory T (T reg ) cells, and RORγt + γδT cells. While trans-regulatory mechanisms governing Rorc expression are well characterized, cis-regulatory mechanisms, particularly in innate lymphocytes, remain partially understood. Here, we identify CNS11 as an essential cis-regulatory element of Rorc . In T H 17 cells, CNS11 was dispensable for induction but critical for maintaining RORγt expression. In contrast, CNS11 deletion blocked ILC3 progenitor induction, abolishing secondary lymphoid organ formation. CNS11 deletion also abolished the development of RORγt + T reg , RORγt + γδT, and RORγt + antigen-presenting cells. Mechanistically, CNS11 functioned through a RORγt-dependent feed-forward loop with cell type–specific cofactors: cooperating with RORγt and runt-related transcription factor 3 to direct ILC3 development and with RORγt and/or c-MAF to sustain RORγt expression in T H 17, RORγt + T reg , and RORγt + γδT cells. Our study reveals CNS11 as a key transcription factor binding hub and master control region for Rorc transcription in distinct lymphocytes.

GPT-4o mini: Non-social science research article

Diverse database and machine learning model to narrow the generalization gap in RNA structure prediction

Albéric A. de Lajarte, Yves J. Martin des Taillades, Justin Aruda, Pierre Bongrand, Federico Fuchs Wightman, Dragui Salazar, Matthew F. Allan, Colin Kalicki, Casper L’Esperance-Kerckhoff, Alex Kashi, Fabrice Jossinet, Silvi Rouskin

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Understanding macromolecular structures of proteins and nucleic acids is critical for discerning their functions and biological roles. Advanced techniques—crystallography, nuclear magnetic resonance, and cryo–electron microscopy—have facilitated the determination of more than 180,000 protein structures, all cataloged in the Protein Data Bank. This comprehensive repository has been pivotal in developing deep learning algorithms for predicting protein structures directly from sequences. In contrast, RNA structure prediction has lagged and suffers from a scarcity of structural data. Here, we present the secondary structure models of 1098 primary microRNAs and 1456 human messenger RNA regions determined through chemical probing. We develop a deep learning architecture inspired from the Evoformer model of Alphafold and traditional architectures for secondary structure prediction. This model, eFold, was trained on our newly generated database and more than 300,000 secondary structures across multiple sources. We benchmark eFold on two challenging test sets of long and diverse RNA structures and show that our dataset and architecture contribute to increasing the prediction performance, compared to similar state-of-the-art methods. Together, our results reveal that merely expanding the database size is insufficient for generalization across families, whereas incorporating a greater diversity and complexity of RNA structures allows for enhanced model performance.

GPT-4o mini: Non-social science research article

Engineering controlled-release steroid therapeutics: fabrication and molecular design of self-assembled microparticles

Oluwaseun D. Akanbi, Michael L. Felder, Daniel Kupor, Jiachen Feng, Luana Janaína de Campos, Lisa J. Bain, Crystal Sanchez, Hanieh Safari, Thi Vo, Martin Conda-Sheridan, Omolola Eniola-Adefeso

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Steroids, specifically bile salts and corticosteroids, treat bile synthesis disorders, liver dysfunction, and inflammation. However, these water-soluble steroid drugs are rapidly cleared from the desired sites of action in the body, necessitating multiple doses. Therefore, the development of particle-based steroid medications that offer elongated therapeutic activity is of paramount medical importance. Accordingly, steroid microparticles were developed via three fabrication processes in this work, where a metal or an organic acid facilitates steroid microparticle formation. Particles fabricated using these methods exhibit consistent shape, size, and crystallinity. Furthermore, results from our coarse-grained computational model show that hydrogen bonding dictates steroid monomer-monomer interactions that determine overall particle shape and size. In addition, we demonstrate the ability to induce steroid particle formation and tune the morphology of steroid drug particles by replacing the C21 side group (tail) with chemical analogs. Thus, this study opens opportunities for the clinical translation of particle-based steroid therapeutics as an alternative to the current steroid drug formulations.

GPT-4o mini: Non-social science research article

12R-HETE acts as an endogenous ligand for Nur77 in the intestines and regulates NKp46 + ILC3 development

Ningning Huang, Zhipeng Yang, Yaojie You, Ling Ye, Hao Li, Jian Peng, Hongkui Wei

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How intestinal immunity develops during early life remains a key question in understanding defense against infections. Group 3 innate lymphoid cells (ILC3s) are critical for this defense, and their developmental progression and subset balance are essential for effective immune function. Here, we show that the nuclear receptor Nur77 helps control NKp46 + ILC3 development in newborn mice. Mice lacking Nur77 have fewer ILC3s and failed to convert one ILC3 subtype (NKp46 − ) into a more protective form (NKp46 + ), reducing their ability to fight Salmonella enterica serovar Typhimurium infection. We found that 12R-hydroxyeicosatetraenoic acid (12R-HETE), a natural lipid found in the intestine, binds to Nur77 and boosts the expression of transcription factor T-box expressed in T cells (T-bet), promoting the shift to NKp46 + ILC3s and increasing the production of interferon-γ (IFN-γ), a key immune molecule. This response is dependent on Nur77. Further analyses have revealed that Nur77 directly regulates a gene called Impdh1 , which supports this immune transition. Our findings uncover a Nur77-driven pathway that helps shape gut immunity in early life.

GPT-4o mini: Non-social science research article

Intratumoral Parvimonas micra promotes esophageal squamous cell carcinoma via p -cresol–induced T reg differentiation

Guoyu Cheng, Xuan Jiang, Lingxuan Zhu, Xinjie Chen, Rucheng Liu, Liang Zhu, Xiao Hu, Shaosen Zhang, Wen Tan, Dongxin Lin, Li Zhang, Chen Wu, Mingkun Li

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Intratumoral microbiota has emerged as a notable factor influencing cancer initiation and progression. However, its composition and functional impact in esophageal squamous cell carcinoma (ESCC) remain largely unexplored. Here, we performed metagenomic sequencing on 119 paired tumor-normal tissues from patients with ESCC and single-cell RNA sequencing on 45 samples to investigate microbe-host interactions. We identified Parvimonas micra ( P. micra ), an anaerobic oral-derived bacterium, as significantly enriched in tumor tissues and associated with poor prognosis. Moreover, the abundance of P. micra correlated with increased regulatory T cell (T reg cell) infiltration in the ESCC tumor microenvironment. Through cellular and animal experiments, we demonstrate that P. micra promotes tumor growth by secreting p -cresol, a metabolite of amino acid fermentation, which elevates reactive oxygen species levels and induces FOXP3 + T reg differentiation, thereby fostering immunosuppression and tumor growth. Our study establishes a mechanistic link between intratumoral microbiota and the immune microenvironment, highlighting the microbial contribution to ESCC progression and prognosis.

GPT-4o mini: Non-social science research article

Evidence that extra copies of chromosome 1q play a role in the early phases of pancreatic neoplasia

Christopher Douville, Jeeun Parksong, Marco Dal Molin, Sarah Graham, Patricia T. Greipp, Ryan Knudson, Samuel Curtis, Yuxuan Wang, Lisa Dobbyn, Maria Popoli, Janine Ptak, Natalie Silliman, Katharine Romans, Christine A. Iacobuzio-Donahue, Alvin P. Makoohon-Moore, Anne Marie Lennon, Michael Goggins, Ralph H. Hruban, Ashley Kiemen, Chetan Bettegowda, Kenneth W. Kinzler, Nickolas Papadopoulos, Laura D. Wood, Bert Vogelstein

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We searched for oncogenes activated by copy number increases using whole-genome sequencing data of 535 pancreatic ductal adenocarcinomas (PDACs). We found that gains of 1q were the second most common gain, occurring in 213 (39.8%) of PDACs. Single-cell analysis via fluorescence in situ hybridization on 33 cancers confirmed these results. A portion of 1q, rather than the entire 1q arm, was gained in 75 (14.0%) PDACs, allowing us to pinpoint two ~3-megabase regions of 1q that were nearly always gained. These two regions contained NCSTN and PSEN2 , genes that code two subunits of the γ-secretase complex. Evaluation of 267 precancerous lesions revealed that extra copies of NCSTN and PSEN2 were common (49%) in noninvasive neoplasms (high-grade pancreatic intraepithelial neoplasms), which are at relatively high risk for progression to PDACs, but uncommon (6%) in low-grade pancreatic intraepithelial neoplasia lesions, which have low malignant potential. We hypothesize that γ-secretase genes are genetically activated oncogenes in the early phases of pancreatic neoplasia.

GPT-4o mini: Non-social science research article

Hemizygous loss of helicases promotes genomic instability and cancer development

Karolin Voßgröne, Francesco Favero, Krushanka Kashyap, Francisco G. Rodríguez-González, André V. Olsen, Xin Li, Balca R. Mardin, Joachim Weischenfeldt, Claus S. Sørensen

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Cancer mutations perturb key processes, driving uncontrolled cell proliferation. With critical roles of enzymes in cell function and growth, we hypothesized that cancer driver mutations alter specific and recurrent enzymatic functions. Leveraging large pan-cancer genomic datasets and curated mutation catalogs, we identified frequent mutations in helicases, enzymes involved in nucleic acid unwinding and processing. Helicases emerged as the most commonly mutated cancer driver enzyme family, altered in two-thirds of all cancers. Functional screens and genomic analyses revealed that helicase dysfunctions contribute to genomic instability and faulty DNA repair. We observed a marked phenotype of Aquarius helicase ( AQR ), which was recurrently hemizygously deleted as an early clonal event in cancer genomes. These deletions were associated with high genomic instability and homologous recombination deficiency signatures. Furthermore, we found hemizygous loss to be a common tumor suppression mechanism among helicases, present in 35% of all cancers. Overall, our enzyme-family approach highlights helicases, including AQR , as key potential cancer drivers.

GPT-4o mini: Non-social science research article

Out of Africa comes no support for global biodiversity catastrophes

Stuart L. Pimm, T. Jonathan Davies, John L. Gittleman

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The Living Planet Index and the ever-changing iterations of planetary boundaries for biodiversity integrity or health are inappropriate, misleading, and will harm on-the-ground conservation efforts.

GPT-4o mini: Non-social science research article

Spatiotemporal Raman probing of molecular transport in sub–2-nm plasmonic quasi-2D nanochannels

Haoran Liu, Zihe Jiang, Zhiwei Hu, Banghuan Zhang, Tao He, Xiaohui Dong, Chaowei Sun, Jun Tian, Wei Jiang, Ferruccio Pisanello, Huatian Hu, Wen Chen, Hongxing Xu

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Capturing molecular dynamics in nanoconfined channels with high spatiotemporal resolution is a key challenge in nanoscience, crucial for advancing catalysis, energy conversion, and molecular sensing. Bottom-up ultrathin plasmonic nanogaps, such as nanoparticle-on-mirror (NPoM) structures, are ideal for ultrasensitive probing due to their extreme light confinement, but their perceived sealed geometry has cast doubt on the existence of accessible transport pathways. Here, counterintuitively, we demonstrate that ubiquitous ligand-capped NPoM-type nanogaps can form a natural quasi–two-dimensional nanochannel, supporting molecular exchange and infiltration over unprecedented length scales (≳5 micrometers) with an extreme aspect ratio (>10 3 ). Using wavelength-multiplexed Raman spectroscopy, we resolve the underlying centripetal infiltration pathway with a spatial resolving power of ~20 nanometers. This redefines the NPoM architecture as a sensitive and hotspot-accessible platform, enabling in situ, real-time, reusable monitoring of analyte with ~10 −11 molar. This work establishes a versatile platform for advancing super-resolved in situ molecular sensing, nanoscale physicochemical studies, and on-chip nanophotofluidics.

GPT-4o mini: Non-social science research article

Glomerular routing of tumor-derived extracellular vesicles substantiates urinary biopsy

Shota Kawaguchi, Taiga Ajiri, Rina Mitsuya, Reiko Tsuchiya, Koki Kunitake, Yoshikazu Tanaka, Takeshi Yokoyama, Kiichi Sato, Yusuke Sato, Zetao Zhu, Kunanon Chattrairat, Yasuko Kobayashi, Kimiko Inoue, Keisuke Imaeda, Kosei Ueno, Sou Ryuzaki, Akira Kato, Yasuyuki Kimura, Atsushi Natsume, Ryosuke Kojima, Takao Yasui

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Urinary small extracellular vesicles (sEVs), which can reflect systemic conditions, hold great promise for noninvasive cancer diagnostics, yet the mechanism by which tumor-derived sEVs reach urine remains unclear. Here, we demonstrate that the glomerulus actively transcytoses circulating tumor-derived sEVs into urine. Using CRISPR guide RNA–tagged glioma sEVs and bioluminescent/fluorescent green-enhanced nano-lantern (GeNL)–tagged lung and pancreatic cancer sEVs, we tracked their journey from tumors to urine in multiple mouse models. In vivo and in vitro analyses revealed endocytic uptake and transcytotic release by glomerular cells, accompanied by changes in sEV size and surface composition. GeNL-tagged sEVs consistently showed higher signals in urine than plasma, indicating selective excretion. These findings redefine the glomerulus as a dynamic regulator of sEV processing and establish a mechanistic foundation for urinary liquid biopsy.

GPT-4o mini: Non-social science research article

Chronic intermittent hypoxia reshapes circadian metabolic architecture in a model of sleep apnea

Emilie Montellier, Guillaume Vial, Sophie Bouyon, Kousha Changizi Ashtiani, Sherif Abdelkarim, Emeline Lemarie, Antoine Boutin, Kenichiro Kinouchi, Pierre Baldi, Jean-Louis Pépin, Jonathan Gaucher

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Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (IH) during sleep, is increasingly recognized as a driver of metabolic dysfunction. However, its impact on circadian metabolic regulation remains poorly understood. Here, we investigated how chronic IH reshapes 24-hour hepatic and systemic metabolic programs in a mouse model mimicking OSA-associated chronic hypoxia. Through integrated circadian transcriptomic, metabolomic, and physiological 24-hour profiling, we show that 4 weeks of rest phase–restricted IH reprograms hepatic and systemic metabolism in a time-specific manner. This reorganization involves the coordinated circadian regulation of glucose, lipid, and redox pathways, with a shift away from oxidative metabolism toward oxygen-sparing processes such as gluconeogenesis, glycogen turnover, and lipid mobilization. These changes align with the hypoxic phase exposure and coincide with reshaped hepatic metabolite oscillations and systemic autonomic rhythms, supporting a functional adaptation to intermittent oxygen availability. Mechanistically, we identify the cAMP-CREB1 pathway as a driver of circadian transcriptional remodeling in the liver and a central integrator of IH-dependent adrenergic stress. Our findings establish chronic IH as a potent metabolic zeitgeber that rewires hepatic transcriptional and metabolic programs, revealing a circadian dimension to the metabolic consequences of sleep-disordered breathing.

GPT-4o mini: Non-social science research article

Upper mantle low-velocity layer tied to volatile-charged carbonate melts

Yongsheng Huang, Guoji Wu, Xuran Liang, Kaiwei Tao, Yu Wang, Michihiko Nakamura, Yuan Li

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Recent geophysical observations indicate the presence of small-volume, carbonate-rich melts in Earth’s deep interior. However, the mechanisms by which such minute melt fractions migrate through largely solid rocks and generate large-scale geophysical anomalies have remained unclear. Here, our high-pressure experiments demonstrate that, in the presence of H 2 O and NaCl, carbonate-rich melts act as super-spreaders, completely wetting and coating the surfaces of surrounding mantle minerals. This perfect wetting enables even trace amounts of melt (0.02 to 0.08 vol%) to form fully interconnected networks. Such connectivity facilitates efficient melt migration and chemical exchange, driving global material recycling between the surface and planetary interior.

GPT-4o mini: Non-social science research article

Boosting capacitive energy storage in relaxor ferroelectrics through polymorphic phase engineering

Yang Zhang, Huan Liang, Yajing Liu, Dong Li, Shuai Dong, Jing Wang, Weiwei Li, Ce-Wen Nan

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Relaxor ferroelectric materials are promising for next-generation capacitors due to their high energy storage capacity. Polymorphic phase engineering, where different ferroelectric phases coexist, has been widely demonstrated as an effective approach to further boost capacitive energy storage performance of relaxor ferroelectrics, but the reasons for these improvements and how they compare to single-phase systems remain unclear. Here, taking dendrite-like PbZr 1- x Ti x O 3 /MgO nanocomposites with defected as a model system, we systematically examine properties and capacitive energy storage performance for rhombohedral-dominant, rhombohedral/tetragonal-mixed, and tetragonal-dominant phases through phase-field simulations. We find that the rhombohedral/tetragonal mixtures deliver the best results in most cases, mainly due to their low switching barriers and substantial local inhomogeneity. These results offer a detailed view of improved energy storage in relaxor ferroelectrics and provide theoretical guidance for designing high-performance capacitors.

GPT-4o mini: Non-social science research article

Systematic analysis of functional genetic and epigenetic variants in colorectal cancer

Erfei Chen, Qiqi Yang, Haoyang Dai, Yixin Chen, Yihui Zhang, Qianglong Wang, Rongrong Hou, Ming Chen, Jie Wang, Qianwen Xie, Wenju Sun, Yong-Qiang Ning, Ligang Fan, Jian Yan

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Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, yet the functional impact of noncoding variants on enhancer activity remains largely unexplored. In this study, we adapted and applied two high-throughput techniques, SNP-STARR-seq and Methyl-STARR-seq, to systematically evaluate the influence of 30,790 noncoding SNPs and more than 134,000 CpG sites on enhancer activity in primary and metastatic CRC cells. We identified 922 SNPs and 487 CpG-containing elements modulating enhancer activity in primary cells and found 3136 SNPs and 3008 methylation-sensitive elements with metastasis-specific regulatory effects. Multi-omics integration linked these variants to target genes, and CRISPR editing validated their roles in driving tumorigenic and metastatic phenotypes. Furthermore, we identified two CRC-specific hypermethylated loci, cg08640619 and cg25982657, as exceptional tissue-based early detection biomarkers (AUC > 0.96). Mechanistically, hypermethylation at cg08640619 disrupts RUNX2 binding, leading to inhibition of KIRREL1 and ETV3 . Our study provides a comprehensive platform for understanding how genetic and epigenetic variants disrupt transcriptional programs in CRC, offering insights into disease susceptibility and identifying potential diagnostic and therapeutic targets.

GPT-4o mini: Non-social science research article

Precise modulation of MOF pore structures via functional group dimensions and spatial configuration for membrane separation

Weijian Sun, Kaicheng Yang, Yifan Zhao, Liping Sun, Qingchi Xu, Jian Weng, Jun Xu

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Traditional petroleum distillation faces high energy demands, necessitating innovative alternatives like membrane separation. This study presents a breakthrough in dual-range and precise pore size modulation of metal-organic frameworks (MOFs) through a ligand functionalization strategy. By tailoring steric configurations and spatial orientations of light-responsive azobenzene groups, we achieved broad-range pore tuning (0.41 to 0.68 nanometers) via functional group length variation, coupled with subnanometer precision through reversible trans-to-cis photoisomerization. Four representative branched alkanes were selected to validate the MOF’s high selectivity. Results showed its capacity to generate a constant carbon-atom-count–dependent permeation gradient, realizing a four-step sequential separation that increased C 6 H 14 purity from 25 to 92.2%. This synergistic approach uniquely combines large-scale pore adjustment with dynamic fine-tuning, decoupling separation efficiency from energy-intensive processes. The membranes’ structural stability and reversible light responsiveness further highlight their potential for sustainable hydrocarbon processing. By integrating molecular design with stimuli-responsive control, this work advances MOF-based membranes as a transformative solution for energy-efficient petroleum fractionation and precise molecular sieving.

GPT-4o mini: Non-social science research article

Causal parametric language mapping with electrical stimulation during awake neurosurgery

J. Raouf Belkhir, Frank E. Garcea, Eduardo Navarrete, Benjamin L. Chernoff, Max H. Sims, Sam Haber, Arka N. Mallela, Matthew Pease, Susan O. Smith, Eric B. Hintz, Thandar Aung, Eliza M. Reedy, Kevin Walter, Tyler Schmidt, Jorge Gonzalez-Martinez, Nduka Amankulor, Webster H. Pilcher, Bradford Z. Mahon

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Functional mapping with direct electrical stimulation (DES) is widely used during awake neurosurgery to generate causal evidence about person-specific neuroanatomical organization. According to a long-standing clinical and scientific paradigm, if the application of DES to a given brain region does not result in performance errors, that site is considered to be uninvolved in the task. Here, we show that both error rates and performance speed on correct trials are parametrically modulated by when DES starts and stops relative to the timeline of task-driven processing in stimulated brain areas and networks. We propose a framework, causal parametric mapping, which moves beyond the classic approach of binarizing the effects of DES on behavior into “positive” and “negative” mapping trials. Causal parametric mapping offers a method to functionally dissect separable processing stages in the human brain, in real time, with reversible causal evidence during invasive neurosurgical procedures.

GPT-4o mini: Non-social science research article

Complement C3 recognition by C3 convertases

Changhao Jia, Xiaoke Yang, Ming-hui Zhao, Ying Tan, Junyu Xiao

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The complement system plays a fundamental role in immunity, and its dysregulation is implicated in numerous human diseases. Activation of complement occurs through three main pathways: classical, lectin, and alternative; which converge at the central component, component of complement 3 (C3). The classical and lectin pathways use the C4b2a convertase to cleave C3 and initiate complement activation, while the alternative pathway uses the C3bBb convertase, which is further stabilized by properdin. The molecular mechanisms governing C3 recognition by these convertase complexes remain incompletely understood. Here, we present the 3.1-angstrom cryo–electron microscopy structure of the C4b2a-C3 Michaelis complex, alongside 2.9- and 3.1-angstrom structures of the C4b2 zymogen in loading and activation states, elucidating the structural basis for C3 engagement by C4b2a and conformational changes during the classical and lectin pathway convertase maturation. Furthermore, a 2.6-angstrom structure of C3bBb-properdin in complex with C3 uncovers unique substrate-binding features of C3bBb and properdin’s stabilizing role in the alternative pathway. These results offer comprehensive mechanistic insights into complement activation.

GPT-4o mini: Non-social science research article

Machine learning-based paleobathymetric reconstructions using archaeal lipid biomarkers

Jiaming Zhou, Dujuan Kang, Shijie Chen, Liang Dong

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Accurate reconstruction of paleo-ocean depths is essential for understanding the interplay between tectonic evolution and global climate change, yet existing methods face substantial limitations. Here, we assess the potential of glycerol dialkyl glycerol tetraethers (GDGTs)—archaeal lipid biomarkers—as a quantitative proxy for paleobathymetry. Analyzing a global dataset of marine surface sediments, we find that GDGT distributions exhibit systematic shifts with water depth. Using random forest machine learning models trained on combined isoGDGT and OH-GDGT profiles, we achieve high predictive performance ( R 2 = 0.85, RMSE = 646 m). Applying this approach to a 6-million-year sedimentary record from the northwest Australian Shelf reproduces key features captured by foraminifera-based reconstructions and reveals tectonically driven bathymetric evolution, including potential influences on the development of the Leeuwin Current. These results demonstrate the GDGT-based machine learning models offer a robust and effective framework for reconstructing paleo-ocean depths and probing the links between oceanography and tectonics.

GPT-4o mini: Non-social science research article

Selective attention to auditory and visual modalities converges onto noncholinergic basal forebrain neurons

Sz-Wen Liu, Shih-Chieh Lin

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Selective attention enables animals and humans to prioritize behaviorally relevant stimuli among competing sensory inputs. Although the basal forebrain (BF) is known to modulate cortical activity and support attention, it remains unclear whether BF activity directly conveys an attention signal. Here, we show that selective attention to auditory and visual stimuli converges onto a shared population of noncholinergic BF neurons. Using a cross-modal task where rats rapidly switched attention between modalities, we found that these neurons responded strongly to attended targets but weakly to the same stimuli when ignored, regardless of modality. These effects closely tracked both task-driven and spontaneous attention shifts on a single-trial basis. Moreover, BF responses reflected the linear summation of attended and ignored inputs, suggesting that sensory streams are filtered in parallel before converging in the BF. These findings suggest that the BF may serve as a subcortical hub integrating attention signals across modalities to guide adaptive behavior.

GPT-4o mini: Non-social science research article

Ampk alpha2 T172 activation dictates exercise performance and energy transduction in skeletal muscle

Ryan N. Montalvo, Xiaolu Li, Gina M. Many, Tyler J. Sagendorf, Qing Yu, Wenqing Shen, Nishikant Wase, A. Robert Burgardt, Tong Zhang, Marina A. Gritsenko, Matthew J. Gaffrey, Hemangi Bhonsle, Yuntian Guan, Xuansong Mao, Mei Zhang, Wei-Jun Qian, Zhen Yan

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Adenosine 5′-monophosphate–activated protein kinase (AMPK) is an energetic sensor for metabolic regulation and integration. Here, we used CRISPR-Cas9 to generate nonactivatable Ampkα knock-in (KI) mice with mutation of threonine-172 phosphorylation site to alanine (T172A), circumventing the limitations of previous genetic interventions that disrupt the protein stoichiometry. KI mice of Ampkα2, but not Ampkα1, demonstrated phenotypic changes with increased fat-to-lean mass, impaired endurance exercise capacity, and diminished mitochondrial maximal respiration and conductance in skeletal muscle. Integrated temporal multiomics analysis (proteomics/phosphoproteomics/metabolomics) in skeletal muscle at rest and during exercise establishes a pleiotropic yet imperative role of Ampkα2 T172 activation for glycolytic and oxidative metabolism, mitochondrial respiration, and contractile function. There is a substantial overlap of skeletal muscle proteomic changes in Ampkα2 T172A KI mice with that of patients with type 2 diabetes. Our findings suggest that Ampkα2 T172 activation is critical for exercise performance and energy transduction in skeletal muscle and may serve as a therapeutic target for type 2 diabetes.

GPT-4o mini: Non-social science research article

Preclinical development of a well-defined semisynthetic glycoconjugate vaccine against Haemophilus influenzae type b

Wei Han, Chunjun Qin, Wei Tong, Kexin Yang, Xianbin Tian, Jing-Ren Zhang, Jiankai Liu, Peter. H. Seeberger, Jing Hu, Jian Yin

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Vaccines are the most effective method for preventing bacterial infections. Identification of the best hapten is an essential step in the development of third-generation Haemophilus influenzae type b (Hib) conjugate vaccines. A comprehensive understanding of the relationship between Hib oligosaccharide chain length and immunological activities remains elusive. A series of Hib capsular polysaccharide (CPS) oligosaccharide derivatives of different lengths were synthesized to establish carbohydrate structure-function relationships. Glycan microarray screening and immunological evaluation of oligosaccharides revealed that tetramer 4 , comprising four repeated disaccharide units, is the key immunogenic epitope of CPS. The investigation into the influence of carrier proteins, adjuvants, and vaccination dose on immunogenicity demonstrated that an equivalent dose of glycoconjugate 4 -TT without adjuvant can induce a similar immune response as a licensed Hib vaccine (MINHAI Hib). Adjuvant-free 4 -TT glycoconjugates can induce both a humoral and a cellular immune response as efficiently as licensed Hib vaccine. This formulation exhibited protective efficacy in a mouse septic infection model through effective pathogen clearance from the circulation to the liver-resident macrophage Kupffer cells and sinusoidal endothelial cells in a mouse septic infection model. In conclusion, a well-defined semisynthetic glycoconjugate vaccine candidate 4 -TT was developed with a more straightforward and adaptable manufacturing process and demonstrated excellent efficacy comparable to licensed Hib vaccine, providing a rationale for further evaluation in clinical trials.

GPT-4o mini: Non-social science research article

Accretion of volatile elements on Earth without the need of a late veneer

Lucas Calvo, Julien Siebert, Dongyang Huang, Ingrid Blanchard, Edith Kubik, Valentina Bonino, Anja Schreiber, Guillaume Avice, Jabrane Labidi

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Volatile elements are essential for life development and planetary evolution. However, the timing of their delivery to terrestrial planets remains unclear. Sulfur, selenium, and tellurium are volatiles, but also siderophile elements. Their abundances in Earth’s mantle can be used to determine whether volatile elements were delivered to Earth during or after the segregation of the core. Here, we experimentally measured their partition coefficients between core-forming metal and mantle silicate under pressure, temperature, and oxygen fugacity conditions relevant to a deep magma ocean. Our results show that these elements exhibit similar partitioning behaviors, indicating that core-mantle equilibrium preserves their chondritic relative abundances. If a volatile-rich late veneer has been delivered to Earth after core segregation, it must have been limited in mass, making up a maximum of 0.1% Earth’s mass. This suggests that volatile elements, including water, were accreted continuously during Earth’s growth rather than being delivered predominantly by a late veneer of volatile-rich material such as carbonaceous chondrites.

GPT-4o mini: Non-social science research article

Single-cell epigenetic profiling reveals a tumor-intrinsic interferon response program in ccRCC tied to poor prognosis and BAP1 loss

Sabrina Y. Camp, Meng Xiao He, Michael S. Cuoco, Amanda E. Garza, Sherin Xirenayi, Ziad Bakouny, Eddy Saad, Jad El Masri, Erica Pimenta, Kevin Meli, Chris Labaki, Breanna M. Titchen, Yun Jee Kang, Jack Horst, Rachel Trowbridge, Erin Shannon, Karla Helvie, Aaron R. Thorner, Sébastien Vigneau, Angie Mayorga, Jahnavi Kodali, Hannah Lachmayr, Meredith Bemus, Pengsheng Chen, Haiteng Deng, Jihye Park, Toni K. Choueiri, Kevin Bi, Eliezer M. Van Allen

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Transcriptional programs in renal cell carcinoma (RCC) have been linked to tumor heterogeneity and clinical outcomes, but analogous efforts to define chromatin programs shaping disease biology have been limited. Here, we generated single-cell ATAC-seq profiles from patients with RCC and integrated them with three previously published datasets to identify chromatin programs in tumor cells. We identified an interferon response program enriched in BAP1 -mutant tumors, and, in bulk ATAC-seq cohorts with linked clinical data, this program was associated with poor prognosis. Mechanistic analyses in isogenic models suggested that BAP1 loss induces a tumor-intrinsic interferon response, with dysregulated endogenous retroviruses as a potential upstream trigger. We further characterized the BAP1 mutation–associated tumor microenvironment across single-cell, bulk, and multiplex immunofluorescence data, identifying features of both inflammation and immune evasion. Together, our findings nominate tumor-intrinsic interferon signaling as a candidate driver of BAP1 -associated aggressiveness in RCC and highlight immune evasion pathways as potential therapeutic targets.

GPT-4o mini: Non-social science research article

Direct cyanation of aromatic rings using dinitrogen and methane promoted by nonthermal plasma

Lei Yu, Shixiong Zhang, Liang Liu, Di Li, Yongli Cai, Chenxin Wu, Lei Hua, Haiyang Li, Dehui Deng, Ping Chen, Zhenfeng Xi, Jianping Guo, Junnian Wei

Full text

Directly converting dinitrogen (N 2 ) into valuable nitrogen-containing compounds remains an enduring challenge in chemical synthesis. Here, we report the direct cyanation of aromatic substrates using N 2 and methane (CH 4 ) at atmospheric pressure facilitated by a custom-built, air-free dielectric barrier discharge (DBD) plasma system. A broad range of aromatic compounds, including benzene, were successfully transformed into their corresponding aromatic nitriles. Both experimental and computational evidence suggested that the reaction proceeds primarily via the in situ generation of •CN radicals from N 2 and CH 4 within the plasma zone. Subsequent radical addition to aromatic rings allowed the one-pot formation of aryl nitriles. This approach represents a major advancement in dinitrogen-based organic methodologies, providing an efficient alternative to conventional cyanation methods that heavily rely on lengthy synthetic routes and hazardous cyanide reagents.

GPT-4o mini: Non-social science research article

cPLA 2 α targeting to exosomes connects nuclear deformation to LTB 4 -signaling during neutrophil chemotaxis

Subhash B. Arya, Fatima Jordan-Javed, Kristen Loesel, Yehyun Choi, Samuel P. Collie, Lauren E. Hein, Brendon M. Baker, Euisik Yoon, Carole A. Parent

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Efficient neutrophil chemotaxis requires the integration of mechanical forces and lipid-mediated signaling. While the signaling lipid leukotriene B4 (LTB 4 ) reinforces cellular polarity, how mechanical cues regulate its production remains unclear. We now show that cytosolic phospholipase A2α (cPLA 2 α), which is essential for the synthesis of LTB 4 , functions as a nuclear curvosensor. cPLA 2 α responds to nuclear squeezing by localizing to ceramide-rich inner nuclear membrane microdomains and incorporating onto the exofacial surface of nuclear envelope–derived exosomes. This unique topology enables localized LTB 4 synthesis, which synchronizes calcium spikes, promotes myosin light chain II phosphorylation, and sustains polarity and directional persistence after constriction. In neutrophils passing through tight spaces, cPLA 2 α activity drives the chemotactic response to nuclear squeezing by promoting exosomal LTB 4 production and persistence after constriction. These findings uncover a cPLA 2 α-dependent mechanochemical axis linking nuclear architecture to chemotactic efficiency and offer alternative strategies to modulate inflammatory responses.

GPT-4o mini: Non-social science research article

Ink-state preaggregation control enables scalable and automated fabrication of highly efficient and stable organic photovoltaics

Hua Tang, Dingqin Hu, Rong Wang, Yaohui Li, Peihao Huang, Jie Lv, Zesheng Zhang, Yakun He, Tobias Osterrieder, Marco Marengo, Hongxiang Li, Heng Liu, Lingyun Zhao, Qianqian Chen, Jiaming Huang, Xinhui Lu, Yang (Michael) Yang, Stefaan De Wolf, Duu-Jong Lee, Gang Li, Larry Lüer, Frédéric Laquai, Christoph J. Brabec

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Scalability and automation are critical for advancing organic solar cells (OSCs) toward high-throughput production, yet both remain notable challenges. Here, we report a simple yet effective strategy using Tz6T as a multifunctional additive to regulate ink-state preaggregation to address both concerns. Tz6T interacts with both donor and acceptor molecules in ink, enabling improved and more ordered preaggregation. This facilitates uniform film formation and significantly reduces bimolecular recombination, enables 16.4% efficiency large-area green solvent–processed OSC modules (19.3 cm 2 ), ranking it among the best reported values to date. Furthermore, the preagggregated ink mitigates the morphology drift caused by time delays in preprogrammed robotic fabrication, yielding device efficiency exceeding 16%, highlighting strong potential for high-throughput production. Beyond efficiency, Tz6T also enhances long-term stability and exhibits compatibility across diverse material systems, underscoring its broad applicability. This work offers a promising pathway for accelerating the translation toward sustainable, scalable, and automated fabricable high-performance and stable OSCs, paving the way for their industrialization.

GPT-4o mini: Non-social science research article

KIT supports small intestinal tuft cell hyperplasia

Heber I. Lara, Madeleine R. Bell, Shealyn O’Connor, Hung-An Ting, Jakob von Moltke

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The small intestine balances the competing tasks of nutrient absorption, immune tolerance, and defense through dynamic differentiation of short-lived epithelial cells. During helminth infection, interleukin-13 (IL-13) or IL-4 drive a 10-fold expansion of tuft cells to promote helminth clearance. While IL-4/13 signaling in epithelial cells is required for tuft cell hyperplasia, few signals that support this process have been identified. Here, we show that tuft cells across all tissues express the receptor tyrosine kinase KIT and that IL-4/13 is necessary and sufficient to up-regulate KIT on small intestinal (SI) tuft cells. Although epithelial KIT is dispensable for homeostatic turnover, KIT deletion from tuft cells during helminth infection reduces tuft cell hyperplasia and delays helminth clearance. Mechanistically, KIT signaling supports the generation of new tuft cells in SI crypts. These findings thus identify a unique tuft cell-specific function for KIT in type 2 immunity.

GPT-4o mini: Non-social science research article

Evolving synchronization of the Gulf Stream and Kuroshio-Oyashio Extension in a changing climate

Youngji Joh, Sang-Wook Yeh, Thomas L. Delworth, Zachary M. Labe, Andrew T. Wittenberg, William F. Cooke, Jiale Lou, Young-Gyu Park

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Decadal synchronization between the Gulf Stream and Kuroshio currents has recently been reported. Given the large-scale coupled variability of western boundary currents and extensions (WBCEs), further investigation into its seasonality, predictability, and potential future changes is needed. Observations and high-resolution climate simulations reveal distinctive covariance between North Pacific and North Atlantic WBCE sea surface temperatures during boreal summer, possibly linked to preceding Arctic sea-ice variability. Model simulations suggest that cold-season Greenland and Barents Sea ice loss enhances anomalous planetary-scale atmospheric waves and meridional jet shifts, contributing to summertime WBCE temperature anomalies. Although we show that summer WBCE covariability arises from intrinsic variability, future climate projections and targeted model experiments imply that this internal coupled variability may be modulated by radiatively forced changes. Our findings suggest that summer WBCE covariability has increased in the historical record but may weaken in response to future reductions in Arctic sea ice under higher radiative forcing.

GPT-4o mini: Non-social science research article

Specific SLC25 carriers regulate mitochondrial protein synthesis

Danielle L. Rudler, Laetitia A. Hughes, Martin S. King, Jessica Baker, Richard G. Lee, Andrianto P. Gandadireja, Anisha Sunil, Samuel V. Fagan, Blake Payne, Nicola Gray, Tim McCubbin, Edmund R. S. Kunji, Oliver Rackham, Aleksandra Filipovska

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A genome-wide knockout screen identified members of the SLC25 family of mitochondrial carrier proteins as important regulators of the rate of de novo mitochondrial protein synthesis. To elucidate this relationship, we generated human cell knockouts for SLC25A25, SLC25A44, SLC25A45, and SLC25A48, which have been shown to exchange adenosine triphosphate-magnesium (ATP-Mg) and phosphate, branched-chain amino acids, methylated basic amino acids, and choline, respectively. Multiomic and functional analyses identified that these four carriers are crucial for mitochondrial translation, biogenesis and function of the oxidative phosphorylation system, as well as mitochondrial morphology. Thermostability screens showed that SLC25A48 is specifically stabilized by choline, and changes in the mitochondrial metabolome and lipidome indicated defects in choline biosynthetic pathways and remodeling of mitochondrial membranes, both consistent with SLC25A48 being a choline transporter. These results highlight the essential roles of specific SLC25 transporters in maintaining mitochondrial structure and function and show that impaired transport of branched-chain amino acids, methylated basic amino acids, ATP-Mg, and choline affects mitochondrial translation.

GPT-4o mini: Non-social science research article

Planar cell polarity emerges through polarized accumulation of Wnt11

Yusuke Mii, Minako Suzuki, Hiroshi Koyama, Kei Nakayama, Ritsuko Takada, Tomoe Kobayashi, Motosuke Tsutsumi, Tomomi Nemoto, Makoto Matsuyama, Toshihiko Fujimori, Shinji Takada

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Planar cell polarity (PCP) is established by asymmetric localization of core PCP components in each cell. Because some Wnt proteins can induce PCP in vertebrates, it has been proposed that Wnt concentration gradients provide spatial cues for polarization. However, here, we present evidence that Wnt11 can regulate PCP in a gradient-independent manner. In the neural plate of Xenopus embryos, endogenous Wnt11 does not form an obvious gradient in the direction of PCP, but is polarized at cell boundaries together with core PCP components. Wnt11 polarization is dependent on core PCP components, while polarization of core PCP components can also be induced by Wnt11, indicating a mutual amplification loop between Wnt11 and core PCP components in PCP formation. Furthermore, Wnt11 and core PCP components compose an intercellular loop to coordinate the direction of polarity. Thus, we propose that local and reciprocal interactions between Wnt11 and core PCP components can generate PCP.

GPT-4o mini: Non-social science research article

Taurine-driven chemotaxis and metamorphosis in ascidian tadpole larvae

Li-Kun Yang, Qishu Qin, Jin Zhang, Ziyu Zhang, Haiyan Yu, Chengtian Zhao, Bo Dong

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Settlement of marine invertebrate larvae at suitable sites for metamorphosis, growth, and reproduction is crucial for propagating populations, but often causes ecological problems such as bioinvasion and biofouling. Chemosensation plays an essential role in larval settlement preferences. However, the mechanisms for sensing chemical cues underlying these preferences remain unknown. Using urochordate ascidian larvae, the prominent marine fouling organisms affecting coastal ecosystems, we explored the mechanism of larval chemosensation and its role in settlement preference. Here, we identified taurine, a specific sulfur-containing amino acid secreted from marine adult animals, as a chemical attractant for ascidian larvae to locate salubrious environments for metamorphosis. Taurine stimulates primary sensory neurons within larval papillae, and this neuronal excitation is integrated in the simple brain (also known as sensory vesicle) to elicit chemoattraction and attachment of swimming larvae. We discuss the implications of this study in the emerging field of marine Eco-Evo-Devo research by establishing a model system for understanding developmental mechanisms in the context of marine ecosystems and aquaculture. Of interest is the potential development of antifouling strategies by targeting taurine chemosensation.

GPT-4o mini: Non-social science research article

Generation of functionally competent testicular somatic cells from pluripotent stem cells

Takuya Sato, Takashi Yoshino, Mai Ohtsuka, Takahiro Suzuki, Takafumi Matsumura, Yuki Matsudaira, Yu Ishikawa-Yamauchi, Shiori Maeda, Haruka Yabukami, Yoshiakira Kanai, Miki Inoue, Yuichi Shima, Makoto Tachibana, Shogo Matoba, Kimiko Inoue, Narumi Ogonuki, Atsuo Ogura, Katsuhiko Hayashi, Takehiko Ogawa

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Cellular interactions between germ cells and gonadal somatic cells are essential for the progression of gametogenesis. Here, we report a culture method for generating fetal testicular somatic cell–like cells (fTeSLCs) from embryonic stem cells. These fTeSLCs exhibit a transcriptomic profile closely resembling that of their in vivo counterparts, including distinct cell populations corresponding to Sertoli cells and interstitial cells. For functional assessment, interstitial cell–like cells (ICLCs) and Sertoli-like cells (SerLCs) were isolated from fTeSLCs. ICLCs differentiated into Leydig cells when cocultured with testes lacking endogenous Leydig cells, thereby restoring androgenic support. SerLCs reconstituted the seminiferous epithelium following selective ablation of endogenous Sertoli cells. Both cell types supported spermatogenesis and generated spermatids reaching the elongating stage. Notably, round spermatids derived from these reconstructed systems produced viable offspring by round spermatid injection. These findings demonstrate that fTeSLCs can generate functional testicular somatic cells, providing a valuable platform for studying testis development and spermatogenesis.

GPT-4o mini: Non-social science research article

The Antarctic coastal ocean heat budget is dominated by heat loss to land ice melt

Ruth Moorman, Andrew F. Thompson, Madeleine K. Youngs, Andrew L. Stewart

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Transport of warm Circumpolar Deep Water (CDW) across the Antarctic continental shelf break is the primary source of heat to Antarctica’s marginal seas. Net heat supplied by CDW is ultimately lost to: (i) the ocean surface, either to the atmosphere or sea ice, or (ii) the ice sheet, by melting the base of ice shelves and calved icebergs. Ocean models often neglect the heat exchange needed to melt ice shelves and icebergs. Simulations presented here indicate that this omits the largest ocean heat sink on the Antarctic continental shelf, representing 60% of heat supplied across the shelf break. Suppressing this heat sink in simulations drives enhanced heat loss to the atmosphere through thinned sea ice cover as well as nonlocal reductions in heat supply to the continental shelf via sea ice–mediated stratification changes. These results highlight a source of climate model bias and clarify the dynamics of heat transport to Antarctic ice shelves.

GPT-4o mini: Non-social science research article

RAD51C-XRCC3 complex regulates FANCM-mediated R-loop resolution to safeguard genome integrity

Satyaranjan Sahoo, Tarun Nagraj, Debanjali Bhattacharya, Nupur Nagar, Kumar Somyajit, Krishna Mohan Poluri, Ganesh Nagaraju

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Fanconi anemia (FA) is characterized by bone marrow failure, congenital abnormalities, and cancer predisposition. Mutations in RAD51 paralogs have been identified in FA-like disorders and cancers. Although the role of RAD51 paralogs is well established in homologous recombination (HR)–mediated DNA repair, little is known about their role during replication stress responses. Here, we report that the RAD51C-XRCC3 (CX3) complex of RAD51 paralogs participates in the FA pathway of R-loop tolerance mechanism. CX3 complex suppresses R-loops, transcription-replication collisions (TRCs), and associated genome instability under physiological and replication stress conditions. Mechanistically, the CX3 complex physically interacts with FANCM and facilitates its recruitment to the R-loop sites to promote its resolution. Notably, cells expressing the RAD51C R258H pathological mutant exhibit defective interaction with FANCM and display inefficient R-loop processing. The CX3 complex–mediated R-loop resolution is independent of its fork maintenance function. Collectively, we demonstrate a previously unidentified role of the CX3 complex in preventing R-loop–induced genome instability by regulating FANCM-mediated R-loop resolution.

GPT-4o mini: Non-social science research article

Covalent capture and genetic code expansion enables chemoproteomic profiling and functional characterization of lysine acetoacetylation

Xiaohan Song, Yuhan Lu, Xinlong Guo, Yanan Zheng, He Huang

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Lysine acetoacetylation (Kacac) driven by metabolite acetoacetic acid represents a molecular mechanism by which ketone bodies regulate cellular functions beyond energy provision. However, comprehensive characterization of Kacac has been hindered by technical limitations in detection and functional validation. Here, we report an integrated platform for systematic Kacac investigation. Exploiting the unique reactive ketone carbonyl moiety, we developed Aca-Bio, a hydroxylamine-based probe enabling specific enrichment of Kacac peptides through ketone-targeted covalent labeling and pH-controlled reversible enrichment. Application to mouse liver identified 260 Kacac sites across 125 proteins, revealing notable enrichment in metabolic pathways. Concurrently, we established a genetic code expansion system enabling site-specific Kacac incorporation. Using this approach, we demonstrated that K310acac in HMGCS2 substantially attenuates catalytic activity through impaired substrate binding. This dual-platform approach establishes a comprehensive framework for global profiling and site-specific functional characterization of Kacac, thereby facilitating systematic exploration of its physiological roles and pathological implications.

GPT-4o mini: Non-social science research article

Degradation of fish food webs in the Anthropocene

Juan D. Carvajal-Quintero, Maria Dornelas, Lise Comte, Juliana Herrera-Pérez, Pablo A. Tedesco, Xingli Giam, Ulrich Brose, Jonathan M. Chase

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Global change reshapes biodiversity through shifts in species composition, richness, and body size. How these shifts combine to alter higher-level ecological processes within food webs can have important implications for entire ecosystems. However, the strength and direction of these shifts will depend on combinations of ways that species and trait compositions change through time. We combine long-term data from ~15,000 freshwater and marine fish communities (1949–2019) with information about their size, diets, and trophic status to evaluate how food webs change through time at local spatial scale. We found that selective species turnover driven by body size reductions is associated with widespread alteration to fish food web topology and function, including increased connectance and generalism, leading to higher predation pressure and increased prey vulnerability. Food webs were also less modular. These changes extend across food web trophic structures, causing a cascading shift in the proportion of species across trophic levels. Our study highlights complex biodiversity responses to confluent changes across multiple facets.

GPT-4o mini: Non-social science research article

Human microglia in brain assembloids display region-specific diversity and respond to hyperexcitable neurons carrying SCN2A mutation

Jiaxiang Wu, Xiaoling Chen, Jingliang Zhang, Kyle Wettschurack, Morgan Robinson, Weihao Li, Yuanrui Zhao, Ye-Eun Yoo, Brody A. Deming, Yue Shu, Akila D. Abeyaratna, Zhefu Que, Dongshu Du, Matthew Tegtmeyer, Chongli Yuan, William C. Skarnes, Zhong-Yin Zhang, Jean-Christophe Rochet, Long-Jun Wu, Yang Yang

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Microglia critically shape neuronal circuit development and function, yet their region-specific properties and roles in distinct circuits of the human brain remain poorly understood. In this study, we generated region-specific brain organoids (cortical, striatal, and midbrain), each integrated with human microglia, to fill this critical gap. Single-cell RNA sequencing uncovered six distinct microglial subtypes exhibiting unique regional signatures, including a subtype highly enriched for the GABA B receptor gene within striatal organoids. To investigate the contributions of microglia to neural circuitry, we created microglia-incorporated midbrain-striatal assembloids, modeling a core circuit node for many neuropsychiatric disorders, including autism. Using chemogenetics to activate this midbrain-striatal circuit, we observed increased calcium signaling in microglia involving GABA B receptors. Leveraging this model, we examined microglial responses within neural circuits harboring an SCN2A nonsense (C959X) mutation associated with profound autism. Microglia displayed heightened calcium responses to SCN2A mutation–mediated neuronal hyperactivity and engaged in excessive synaptic pruning. These pathological effects were reversed not only by pharmacological inhibition of microglial GABA B receptors but also by knockout of the GABBR1 gene in microglia. Collectively, our findings establish an advanced platform that can be used to dissect human neuroimmune interactions in subcortical regions and to evaluate previously undiscovered therapies, highlighting the important role of microglia in shaping critical circuitry related to neuropsychiatric disorders.

GPT-4o mini: Non-social science research article

3D reconstruction of human liver tissue at cellular resolution

Wesley B. Fabyan, Chelsea L. Fortin, Dorice L. Goune, Heidi L. Kenerson, Susana P. Simmonds Bohorquez, Jonathan T. C. Liu, Matthew M. Yeh, Rotonya M. Carr, Raymond S. W. Yeung, Kelly R. Stevens

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The liver contains an intricate microstructure that is critical for proper liver function. Architectural disruption of this spatial structure is pathologic. Unfortunately, two-dimensional (2D) histopathology—the gold standard for pathological understanding of many liver diseases—can misrepresent or leave gaps in our understanding of complex 3D structural features. Here, we used immunostaining, tissue clearing, microscopy, and computational software to create 3D multilobular reconstructions of both nonfibrotic and cirrhotic human liver tissue. We found that spatial architecture in human cirrhotic liver samples with varying etiologies had sinusoid zonal dysregulation, reduction in glutamine synthetase–expressing pericentral hepatocytes, regression of central vein networks, disruption of hepatic arterial networks, and fragmentation of biliary networks, which together suggest a pro-portalization/decentralization phenotype in cirrhotic tissue. Further implementation of 3D pathological analyses may provide a deeper understanding of cirrhotic pathobiology and inspire treatments for liver disease.

GPT-4o mini: Non-social science research article

Tuning of the RBR1-E2F/DP transcriptional module by the F-box protein FBL17

Juliette Espanet, Xiaoning He, Ting Pan, Naomie Gentric, Thomas Potuschak, Bénédicte Desvoyes, Philippe Hammann, Johana Chicher, Rim Brik, Esther Lechner, David Latrasse, Aladár Pettkó-Szandtner, Crisanto Gutierrez, Cécile Raynaud, Zoltán Magyar, Moussa Benhamed, Shunping Yan, Sandra Noir, Pascal Genschik

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F-box proteins of SCF E3 ligases have been documented to control the abundance of numerous critical regulatory proteins. In Arabidopsis , one of them, F-BOX-LIKE17 (FBL17), stands out for playing a key role in DNA replication, DNA damage, and, more recently, for the control of cell size. FBL17 null mutants exhibit severe cellular defects leading to lethality. However, the molecular mechanisms by which FBL17 operate remain poorly understood. Here, we show that FBL17 interacts with different components of the RETINOBLASTOMA-RELATED1/E2F module and is involved in the protein turnover of E2Fa and E2Fb. However, mutations in E2Fa or E2Fb do not alleviate the severe fbl17 phenotype but worsen it. By contrast, it is the accumulation of the transcriptional repressor E2Fc that causes fbl17 mutant lethality. Our results highlight a key role for FBL17 in modulating the transcriptional control of E2F target genes ensuring precise control of cell cycle progression and avoiding uncontrolled DNA damage response.

GPT-4o mini: Non-social science research article

Metal-organic framework/graphene nanoribbon/polyimide mixed-matrix membranes for high-temperature H 2 /N 2 separation

Soon Hyeong So, Sunwoo Kim, Minsu Kim, Donghyun Kim, Taehwan Kim, Kiwon Eum, Yun Ho Kim, Junghwan Kim, Dae Woo Kim

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We report the application of mixed-matrix membranes for high-temperature hydrogen separation. To enhance hydrogen selectivity, graphene nanoribbons (GNRs) were incorporated into ZIF-8 fillers, forming a physically confined structure conducive to hydrogen transport. The metal-organic framework (MOF)/GNR filler embedded into a polyimide (PI) matrix yielded a much higher H 2 permeability (298 Barrer, +40%) and H 2 /N 2 selectivity (15, +25%) than the neat PI membrane. In particular, the as-prepared asymmetric membrane achieved a H 2 permeance of 212 ± 45 Gas Permeation Unit (GPU) and H 2 /N 2 selectivity of 19 ± 2 at 35°C. Remarkably, at 300°C, the H 2 permeance rose to 775 ± 139 GPU while maintaining a H 2 /N 2 selectivity of 13 ± 1, outperforming polymer-based membranes. A techno-economic analysis of an NH 3 cracking process demonstrated that this high permeance reduces membrane area requirements by 68.2% and lowers H 2 separation costs by 35.1% compared with operation at 35°C, leading to a 9.8% reduction in the levelized cost of hydrogen.

GPT-4o mini: Non-social science research article

Multiple southward migrations of Neolithic Chinese farmers into Southeast Asia revealed from large-scale Y-chromosome sequences

Mengge Wang, Yunhui Liu, Lintao Luo, Zhiyong Wang, Yuhang Feng, Ting Yang, Jing Chen, Yufeng Liu, Yuguo Huang, Qiuxia Sun, Shuhan Duan, Xinyu Lin, Jie Zhong, Bowen Li, Kaijun Liu, Haibing Yuan, Chao Liu, Renkuan Tang, Guanglin He

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The scale and timing of genetic contributions from ancient millet- and rice-farming populations in China to Southeast Asian populations remain incompletely understood, particularly concerning Y-chromosome diversity. Here, a comprehensive dataset of Chinese Y-chromosome variations, including 1507 high-coverage sequences from ethnolinguistically diverse groups, was analyzed alongside 780 ancient genomes from eastern Eurasia and 1748 low-coverage sequences from Southeast Asia. We reconstructed a high-resolution, time-calibrated Y-chromosome phylogeny, revealing multiple male-biased expansions associated with Neolithic cultural innovations in South China. These expansions markedly shaped the paternal ancestry of both South China and mainland Southeast Asia. Founding lineages linked to Hmong-Mien and Tai-Kadai speakers were traced, revealing notable growth during the Middle Neolithic. Phylogeographic structure, network analyses, and haplogroup distributions indicate complex demographic interactions that established the genetic legacy of Neolithic farmers in Southeast Asia. These findings highlight recurrent southward migrations of Chinese farmer-related groups and their enduring influence on the paternal genetic landscape of ancient and present-day Southeast Asians.

GPT-4o mini: Non-social science research article

The oldest in situ Homo erectus crania in eastern Asia: The Yunxian site dates to ~1.77 Ma

Hua Tu, Xiaobo Feng, Lan Luo, Zhongping Lai, Darryl Granger, Christopher Bae, Guanjun Shen

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With the discovery of three almost complete Homo erectus crania, Yunxian is one of the most important early Pleistocene hominin sites in eastern Asia. Yet, the age of the Yunxian fossils has remained debated because of the lack of reliable numerical dating results. Here, we apply the well-established isochron 26 Al/ 10 Be burial dating to quartz gravels from two sediment layers of the site. The age results push the Yunxian crania back to 1.77 ± 0.08 million years ago (±1σ internal error), representing the oldest H. erectus fossils discovered in situ in eastern Asia. A much older age assignment to Yunxian supports the model of rapid dispersal and widespread distribution of early H. erectus and contributes to narrowing the chronological gap between the earliest archaeology and hominin paleontology in eastern Asia.

GPT-4o mini: Non-social science research article

Inertia-driven amphibious robot with asymmetric microundulatory fin arrays

Lingqi Tang, Yongzun Yang, Bing Li, Bingfu Zhang, Qiguang He, Hongliang Ren, Yao Li

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Centimeter-scale amphibious robots are promising for versatile tasks. Existing solutions use active and multiple mechanisms for environmental interaction; however, such designs face sealing challenges at small scales and are often complex and unreliable. Here, we present an inertia-driven actuation strategy combining a variable-output voice coil motor (VCM) with a fully sealed rigid shell. By modulating the VCM output, the robot achieves jumping, full-stroke vibration for terrestrial locomotion and small-stroke vibration for aquatic propulsion. Terrestrial tests demonstrate rapid motion on granular media, continuous jumping, and load carrying. The robot also uses passive tilted fins that convert reciprocating motion into steerable aquatic thrust, realizing an inertia-driven multidirectional propulsion mechanism. Thrust generation and frequency-dependent propulsion were analyzed through aquatic experiments, high-speed particle image velocimetry, and simulations. Last, a 24-gram legless prototype (Leglessbot) demonstrated effective locomotion across diverse terrain, offering a compact solution for underactuated amphibious mobility.

GPT-4o mini: Non-social science research article

Design and preclinical feasibility of a pediatric heart valve stent that spontaneously adapts to growth via a spring mechanism

Giselle Ventura, Masaki Kajimoto, Mossab Saeed, J. Scott Malloy, Ian McGinty, Lyubomyr Bohuta, Kevin A. Charette, Kyle Bilodeau, Gianna Dafflisio, Shannen B. Kizilski, Peter E. Hammer, John P. Carney, David W. Sutherland, Baturalp Arslan, Daniel F. King, David J. Carter, Sitaram M. Emani, Michael A. Portman, Corin Williams

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Congenital heart valve defects often require surgical intervention for survival. Now, there are no valve prosthetics on the market that are designed for babies and toddlers who grow rapidly. Recent advancements in expandable valves hold promise for these young patients but currently require invasive balloon catheter procedures for device expansion. Here, we describe the design and preclinical feasibility of a pediatric heart valve stent that spontaneously adapts to growth via a springlike mechanism imparted by the superelastic properties of nitinol. Studies in piglets demonstrated appropriate constraint of the device to small diameters (8 to 9 millimeters) upon implantation, acute valve function, and the ability of the stent to proportionately expand with growth up to 13 millimeters after 6 weeks without subsequent interventions after implantation. We expect that the growth-adaptive stent concept could be broadly leveraged to eliminate surgeries and invasive procedures as young patients grow.

GPT-4o mini: Non-social science research article

Efficient AgInGaS-based QLEDs and full-color displays via uniform silver vacancy distribution

Tianchen Li, Yuchen Yue, Hui Li, Ning Guo, Fengmian Li, Hanfei Gao, Lei Jiang, Yuchen Wu

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AgInGaS (AIGS) quantum dots (QDs) are promising for displays due to their narrow full width at half maximum (FWHM) and tunable emission. However, nonuniform silver vacancy ( V Ag ) distribution causes emission broadening and hinders device performance improvement. Here, we present a multistep temperature control strategy that precisely regulates reaction temperature to control nucleation, cation exchange, and defect reconstruction, thereby enabling uniform V Ag distribution in AIGS QDs. Simultaneously, we construct a dual-layer shell structure (AgGaS 2 /GaS x ), which efficiently passivates surface defects. The synthesized red, green, and blue AIGS QDs achieve photoluminescence quantum yields (92.6, 98.5, and 53.3%) and narrow FWHMs (32, 29, and 21 nm). On the basis of these materials, we fabricated red, green, and blue QD light-emitting diodes that demonstrate external quantum efficiencies of 13.2, 8.0, and 2.9%. Moreover, the interfacial confinement self-assembly strategy enables the fabrication of full-color QD pixel arrays with resolutions up to 2032 pixels per inch, further highlighting the potential of AIGS QDs for near-eye displays.

GPT-4o mini: Non-social science research article

Increasing synchronicity of global extreme fire weather

Cong Yin, John T. Abatzoglou, Matthew W. Jones, Alison C. Cullen, Mojtaba Sadegh, Juanle Wang, Yangxiaoyue Liu

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Concurrent extreme fire weather creates favorable conditions for widespread large fires, which can complicate the coordination of fire suppression resources and degrade regional air quality. Here, we examine the patterns and trends of intra- and interregional synchronous fire weather (SFW) and explore their links to climate variability and air quality impacts. We find climatologically elevated intraregional SFW in boreal regions, as well as interregional synchronicity among northern temperate and boreal regions. Significant increases in SFW occurred during 1979 to 2024, with more than a twofold increase observed in most regions. We estimate that over half of the observed increase is attributable to anthropogenic climate change. Internal modes of climate variability strongly influence SFW in several regions, including Equatorial Asia, which experiences 43 additional intraregional SFW days during El Niño years. Furthermore, SFW is strongly correlated with regional fire-sourced PM 2.5 in multiple regions globally. These findings highlight the growing challenges posed by SFW for firefighting coordination and human health.

GPT-4o mini: Non-social science research article

Propagation of the Madden-Julian oscillation as a deterministic chaotic phenomenon

Daisuke Takasuka, Tamaki Suematsu, Hiroaki Miura, Masuo Nakano

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The Madden-Julian oscillation (MJO) is a planetary-scale tropical weather disturbance marked by eastward-propagating cumulus cloud clusters over the Indo-Pacific region, causing severe weather and climate events worldwide. The mechanism and predictability of MJO propagation remain elusive, partly because relevant multiscale processes are poorly understood. Here, we reveal chaotic MJO propagation arising from cross-scale nonlinear interactions, based on 4000-member ensemble simulations of two MJO events with a global cloud-system–resolving model. Against conventional linear thinking, multiple regimes with distinct timings of MJO propagation emerge under a single atmosphere-ocean background. The emergence of regime bifurcation depends critically on the equatorial asymmetry of climatological sea surface temperature. Selection of the bifurcated regimes is probabilistic, influenced by whether tropical-extratropical interplay promotes moistening associated with westward-propagating tropical waves over the western Pacific. These results contribute to a more complete MJO conceptual model and help foresee when coherent MJO propagation emerges.

GPT-4o mini: Non-social science research article

Morphology-adaptive Au-Ag nanowire elastronics for integrated FlexoSERS and bioelectrical sensing

Heng Zhang, Yi Chen, Gangsheng Chen, Wuxing Zhang, Cheng Yang, Fan Zhou, Yunqi Zhao, Haoran Deng, Xuan Huang, Yuan An, Guoqun Li, Shuqi Tang, Biao Ma, Wenlong Cheng, Ning Gu

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We introduce a morphology-adaptive Au-Ag nanowire elastronic platform that conforms to diverse geometries while enabling multimodal optical-electrical sensing. Using a facile yet versatile template-guided growth strategy, vertically aligned Au-Ag nanowire arrays are directly fabricated on 1D nano/microneedles, 2D elastic films, and 3D porous architectures. On 2D substrates, the arrays act as FlexoSERS interfaces with high sensitivity, uniformity (RSD = 7.2%), and durability, maintaining stable SERS signals under 100% strain and after 2500 cycles. On 3D porous sponges, the NWs serve as dry bioelectrical electrodes, enabling stable electrocardiogram (ECG) and electromyogram (EMG) monitoring with long-term stability. Continuous ECG recording, combined with deep learning analysis, enables accurate classification between sleep and wake states. Meanwhile, the EMG signals capture subtle motor activities such as finger bending, typing, and clicking. By uniting strain-tolerant FlexoSERS with reliable bioelectrical sensing across 1D-3D substrates, this platform provides a robust material foundation and a scalable route toward next-generation wearable health monitors, intelligent sleep evaluation, and human-machine interfaces.

GPT-4o mini: Non-social science research article

The mechanical properties of Arabidopsis thaliana roots adapt dynamically during development and to stress

Luis Alonso Baez, Astrid Bjørkøy, Francesco Saffioti, Sara Morghen, Dhika Amanda, Michaela Tichá, Maarten Besten, Anastasiia Ivanova, Joris Sprakel, Bjørn Torger Stokke, Thorsten Hamann

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Mechanical properties of plant cells and tissues change dynamically, influencing plant growth, development, and interactions with the environment. Despite their central roles in plant life, current knowledge of how these properties change in vivo is very limited. Here, we have combined Brillouin microscopy and molecular rotors to investigate stiffness, viscosity, and porosity in living Arabidopsis thaliana seedling roots during differentiation and in response to stress and genetic manipulation. We found that mechanical properties change in a cell- and tissue-specific manner. The properties change dynamically during differentiation to support directional cell expansion. Cell type–specific adaptation of the properties is induced within hours in response to stress or changes in cell wall metabolism. Hyperosmotic stress–induced reduction of cell wall stiffness requires intact abscisic acid metabolism and cell wall integrity signaling. The findings form the foundation for future studies to characterize the regulatory mechanisms linking cell wall homeostasis, signaling, and mechanical properties in plants.

GPT-4o mini: Non-social science research article

Transmembrane proteins mediate basal complex assembly and individual daughter cell formation in malaria parasites

Peter S. Back, Erinn Wagner, Paula Montero Llopis, Ramon G. de Oliveira, Marco Mottinelli, Lori Ferrins, Jeffrey D. Dvorin

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Asexual reproduction of malaria parasites requires the basal complex, the equivalent of a eukaryotic contractile ring. Despite its central role, basal complex biogenesis remains largely unknown. Here, we use expansion microscopy and DNA points accumulation for imaging in nanoscale topography to investigate three transmembrane basal complex proteins in Plasmodium falciparum —basal complex transmembrane protein 1 (BTP1), BTP2, and basolateral expansion boundary (BLEB). Parasites lacking BTP2 are still enveloped by membranes but fail to separate from each other, resulting in multiorganellar mutants. We isolate the defect to a specific step during basal complex development and demonstrate that the contractile ability remains intact. By revisiting BLEB, we identify a distinct plasma membrane region that is excluded from daughter cells and associated with the basal complex. Integrating these findings, we propose a three-step model for basal complex biogenesis that highlights the specific role of BTP2 and suggests a role for the BLEB-associated membrane. This study offers a mechanistic framework for how multiple daughter cells are formed simultaneously and highlights the importance of transmembrane proteins for cell division.

GPT-4o mini: Non-social science research article

The actin cytoskeleton is required to maintain plant cell division orientation against cellular geometry

Camila Goldy, Samantha Moulin, Yutaro Shimizu, Guillaume Cerutti, Vincent Bayle, Magali Grison, Yvon Jaillais, David Bouchez, Yohann Boutté, Martine Pastuglia, Philippe Andrey, Marie-Cécile Caillaud

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In multicellular organisms, cell division shapes tissue architecture, cell identity, and function. In walled organisms like plants, division plane orientation irreversibly defines tissue topology and is tightly regulated. While divisions often follow the shortest path enclosing cell volume, certain cells deviate, dividing perpendicular to the growth axis. Tissue-scale mechanical stress has been proposed to guide such orientation, but how these cues are integrated remains unclear. Here, we reexamine the role of the actin cytoskeleton in orienting cell division in Arabidopsis root epidermis. Combining cell biology, genetics, pharmacological treatments, 3D segmentation, and modeling, we show that actin is a central molecular actor required to establish cell division orientation against the geometrical rules, highlighting its role in integrating spatial information.

GPT-4o mini: Non-social science research article

Conformation-programmed DNA computing

Qian Ling, Bozhao Li, Yuhua Feng, Jing Yang, Shi’an Wang, Suping Li, Cheng Zhang

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Natural biological systems achieve precise cellular control through multidimensional signaling architectures that integrate sequence specificity, structural dynamics, and conformational switching. While synthetic DNA networks have been engineered primarily using sequence programmability, exclusive reliance on this dimension constrains signaling range and integrated regulation. Here, we report an allosteric DNA computing framework enabling the simultaneous integration of sequence programmability with conformational dynamics for integrated multilevel signal processing. By encoding conformational signals within polythymidine loops (0 to 40 nucleotides), this system executes loop-dependent logic operations with expanded signaling ranges. Moreover, catalytic allosteric hairpin assemblies achieve ~30-fold signal amplification with enhanced signal-to-noise ratios. Concurrently, allosteric DNA neural networks discriminate conformational signals based on loop lengths (7 to 15 nucleotides) at two-nucleotide resolution. Crucially, microRNA-responsive versions of this framework regulate gene expression, thereby bridging conformational signaling with genetic control regulations in vivo. Collectively, this work establishes a conformational signal-processing paradigm for adaptive DNA computing, paving the way for advanced synthetic biology and precision therapeutics.

GPT-4o mini: Non-social science research article

The vault particle is enclosed by a C 13-symmetric cap with a positively charged exterior

Huan Li, Francesca Vallese, Oliver B. Clarke

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Vaults are some of the largest ribonucleoprotein complexes known and are highly conserved across eukaryotes, but both their function and key details of their architecture remain unclear. While high-resolution structures of the vault shell are available, the architecture and symmetry of the cap have remained unresolved. Here, we present a 2.25-angstrom cryo–electron microscopy structure of the vault cap, revealing an unexpected 13-fold symmetric arrangement that contrasts with the 39-fold symmetry of the vault body, with each repeating module of the cap formed by an asymmetric homotrimer of adjacent subunits. The center of the cap features an unusual architecture, consisting of two concentric β barrels surrounded by an interwoven two-layer stack of α helices. The vault cap features a positively charged exterior and a negatively charged interior surface, with implications for binding partner recruitment and engineering of modified vault particles.

GPT-4o mini: Non-social science research article

Redox therapy for neuropsychiatric disorders: Molecular mechanisms and biomarker development

Kyle W. Cuklanz, Abigail Stein, Virginie-Anne Chouinard, Dost Ongur, Fei Du

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Redox dysregulation, characterized by an imbalance in the NAD + [nicotinamide adenine dinucleotide (oxidized form)]/NADH (reduced form of NAD + ) ratio, is implicated in neurodegenerative and psychiatric disorders such as Alzheimer’s disease and schizophrenia. This imbalance contributes to mitochondrial dysregulation, oxidative stress, and inflammation. Despite promising preclinical studies supporting therapeutic strategies aimed at restoring redox balance and thereby rescuing brain bioenergetic deficits, clinical outcomes and efficacy remain limited. Progress has been hindered by the incomplete understanding of NAD + subcellular cycling, as well as a lack of in vivo biomarkers measuring target engagement of redox status and mitochondrial function. Thus, this review examines molecular mechanisms of NAD (nicotinamide adenine dinucleotide)–related bioenergetic deficits, current and emerging NAD-targeted therapies, and recent advances in the development of neuroimaging biomarkers, emphasizing personalized and mechanism-driven approaches.

GPT-4o mini: Non-social science research article

Optimal choice of proxy for cloud condensation nuclei reduces uncertainty in aerosol-cloud-climate forcing

Hailing Jia, Johannes Quaas, Willem Kroese, Bastiaan van Diedenhoven, Edward Gryspeerdt, Christoph Böhm, Karoline Block, Otto Hasekamp

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Aerosol-cloud interactions (ACI) remain the largest uncertainty in anthropogenic climate forcings. Observation-based estimates of instantaneous radiative forcing from ACI (RF aci ; the Twomey effect) rely on the choice of aerosol quantities as proxies for cloud condensation nuclei (CCN) concentrations, which differ in their ability to represent cloud-base CCN and data accuracy. Using diverse observations and aerosol-climate models, we evaluate the utility of different proxies with two independent approaches. Both approaches reveal that surface CCN exhibits the smallest bias in predicting RF aci (+5%), followed by aerosol index, surface sulfate and column CCN with similar biases of +25%, while aerosol optical depth and column sulfate show the largest biases (−60% and +92%). Constraining RF aci with the optimal proxy reduces uncertainty from 66 to 43%, yielding a less negative RF aci (−1.0 W m −2 ) than the unconstrained case (−1.2 W m −2 ). Our findings highlight the crucial role of proxy constraint in reconciling and improving RF aci estimates.

GPT-4o mini: Non-social science research article

“Direct” measurement of delocalized molecular excitonic wave functions through excitonic and vibronic photon imaging

Yang Luo, Gong Chen, Li Zhang, Yun-Jie Yu, Qiu-Shi Meng, Fan-Fang Kong, Xiao-Jun Tian, Yao Zhang, Yang Zhang, Zhen-Chao Dong

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Delocalized excitons govern the optoelectronic properties of molecular materials, yet the real-space reconstruction of their wave functions—the spatial distribution of amplitude and phase—has remained a long-standing scientific goal. Here, we demonstrate that scanning tunneling microscopy–induced luminescence enables real-space reconstruction of amplitude and phase of delocalized excitonic states in molecular chains. Through subnanometer-resolved photon imaging of linear molecular chains, coherent purely excitonic (0–0) emission patterns reveal the wave function’s relative phases, while incoherent vibronic (0–1) emission maps the squared wave function amplitudes. This near-field technique enables the reconstruction of wave functions for both bright superradiant states and optically dark subradiant states inaccessible by conventional far-field optics. Furthermore, the submolecular resolution of the vibronic maps allows for the contributions of different vibrational symmetries, namely, Franck-Condon and Herzberg-Teller modes, to be distinguished. Our findings establish a unique approach for the excitonic wave function reconstruction and open a route for exploring exciton dynamics and interactions in molecular systems.

GPT-4o mini: Non-social science research article

R-loop processing via REXO4-RNaseH1–mediated endo- and exo-cleavage coupling mode prevents genome instability and antitumor immunity

Han Yang, Chen Nie, Yingyu Qin, Xinxin Liang, Yifan Chen, Zenan Zhou, Tao Zhou, Tao Zhang, Yilin Cui, Ming Pang, Jiadong Wang, Weibin Wang

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R-loop metabolism is closely associated with genome stability and tumors. Here, we identify an exonuclease REXO4, which collaborates with RNaseH1 endonuclease to degrade R-loops in an “endo/exo-cleavage coupling” manner. Specifically, REXO4 directly degrades the RNA strand in R-loops from the end or internal nick through its 3′-5′ exonuclease activity and stimulates RNaseH1 endonuclease activity. The genome-wide R-loop regions regulated by REXO4 highly overlap with those regulated by RNaseH1, and REXO4 overexpression counteracts genome-wide R-loop accumulation caused by RNaseH1 deficiency. Furthermore, REXO4-deficient tumors display elevated R-loop mutation burden, and tumor patient-derived mutations in REXO4 enzymatic region all impair R-loop cleavage activity. Besides, we identify a compound 17 (named REXO4-IN-17) capable of inhibiting REXO4 nuclease activity. Interfering with REXO4 increases the sensitivity of tumor cells to alkylating and G4 stabilizing chemotherapeutic drugs and activates cGAS-mediated antitumor immunity. Therefore, our study proposes an endo/exo-cleavage coupling the R-loop processing model, which provides additional insights into the link between R-loop–associated genome instability, antitumor immunity, and tumors.

GPT-4o mini: Non-social science research article

Engineering surgery-free prosthetic heart valve growth

Jonathan T. Butcher

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Children with congenital heart valve disease require repeat surgical procedures to resize grafts. A new option is a valved stent that grows spontaneously.

GPT-4o mini: Non-social science research article

miRNA gene mutations commonly disrupt the proper functioning of miRNA genes

Magdalena Machowska, Natalia Szostak, Adrian Tire, Wladyslaw Wegorek, Malwina Suszynska, Arkadiusz Kajdasz, Paulina Galka-Marciniak, Anna Philips, Piotr Kozlowski

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A growing number of mutations are being identified in the noncoding genome, including microRNA (miRNA) genes; however, little is known about the consequences of these mutations and how harmful they are to the functioning of miRNA genes. To evaluate the effects of miRNA gene mutations, we took advantage of a large collection of somatic mutations identified in miRNA genes in >10,000 The Cancer Genome Atlas cancer samples and compared them with the corresponding miRNA sequencing data. Using different analytical approaches and rigorous statistical criteria, we revealed that a substantial fraction of mutations is deleterious for the proper functioning of miRNA genes affecting the level of mature miRNAs, isomiR profiles (precision of DROSHA/DICER1 cleavage), and/or 5p/3p miRNA strand balance. We also showed that most mutations, especially those identified as deleterious, destabilize the structure of miRNA precursors. The analysis showed that many miRNA gene mutations can damage miRNA genes and, if located in disease-related miRNA genes, may be pathogenic variants.

GPT-4o mini: Non-social science research article

Activation of the YAP1/pSTAT3/NRP1 axis in peritendinous sensory nerves promotes tendon healing

Jiayi Wang, Fan Wang, Jingwen Liu, Yao Xiao, Zhaoyang Li, Xiaonan Liu, Peilin Zhang, Fei Wang, Wenguo Cui, Shen Liu

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Chemotactic migration of peritendinous nerves is essential for tendon regeneration, yet the underlying neuroelectrical mechanisms remain unclear. Here, we identify an electrically responsive yes-associated protein 1 (YAP1)/phosphorylated signal transducer and activator of transcription 3 (pSTAT3)/neuropilin-1 (NRP1) signaling axis in sensory neurons. Electrical stimulation enhances YAP1-pSTAT3 interaction, promotes pSTAT3 nuclear translocation and transcriptional activity, and up-regulates NRP1 to support growth of calcitonin gene-related peptide (CGRP)–positive sensory fibers. Guided by these findings, we engineered a bifunctional piezoelectric patch composed of poly(vinylidene difluoride-trifluoroethylene) [P(VDF-TrFE)] and regenerated silk fibroin@poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (RSF@P:P), coupling mechanically induced electrical cues with dynamic lubrication. Under ultrasound activation, the P(VDF-TrFE) layer generates localized electrical signals that facilitate sensory-nerve and vascular ingrowth, while the RSF@P:P layer undergoes piezoelectric-triggered gel-sol transition to form a low-friction interface and reduce adhesion. In rat and Bama minipig models, the patch markedly enhanced tendon regeneration and decreased adhesion scores by ~50%. These findings establish a neuroelectrically guided strategy for enhancing tendon healing.

GPT-4o mini: Non-social science research article

Aneuploidy of chromosome 8 promotes the mesenchymal lineage during cell fate transitions

Cai Liang, Guanchen Li, Qiuqin Zhang, Xinlei Wang, Yu Liu, Wenjuan Yin, Ting Tao, Jinhu Wang, Haishan Gao, Shutao Qi, Hongtao Yu

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Aneuploidy is present in about 90% human solid tumors. Certain tumors remain addicted to aneuploidy. Paradoxically, artificially induced aneuploidy in normal cells elicits cellular stresses and decreases cell fitness. How aneuploidy initially emerges during tumorigenesis is thus unclear. Using human embryonic stem cells (ESCs) as a model, we show that aneuploid ESCs form immature teratomas with an enrichment of mesenchymal tissues. Specifically, chromosome 8 (chr8) gain, a prevalent form of aneuploidy in human cancers, promotes the expansion of mesenchymal stem cells (MSCs) in teratomas and MSC proliferation in vitro. We further show that human embryonal rhabdomyosarcomas, tumors of mesenchymal origin, lack dominant driver mutations but frequently harbor chr8 gain. Our study suggests a plausible mechanism for aneuploidy emergence during tumorigenesis, links specific aneuploidy to the mesenchymal lineage, and paves the way for identifying vulnerabilities of aneuploid MSCs, which may have important roles in tumorigenesis.

GPT-4o mini: Non-social science research article

Tephra seismites—Understanding seismic hazard of hidden faults by analyzing liquefied tephra layers in lakes

Max O. Kluger, Richard A. Melchert, José M. Moratalla, Tehnuka Ilanko, David J. Lowe, Vicki G. Moon, Pilar Villamor, Jordanka Chaneva, Nic Ross, Rolando P. Orense

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Assessing seismic hazards in regions with hidden or poorly expressed faults is one of the major challenges in paleoseismology today. Here, we used computed tomography imaging to quantify the dimensions and distribution of liquefaction structures in ≤17.5–thousand-year-old tephra layers in 18 lakes scattered across the poorly expressed Hamilton Basin fault system in northern New Zealand. These “tephra seismites,” embedded in unconsolidated, organic-bearing lake sediment, increase in occurrence and dimensions toward known faults and indicate the occurrence of a local hidden fault segment. Through incorporating peak ground acceleration modeling, we found that the spatial distribution of tephra seismites directly relates to the ground shaking induced by near-field fault ruptures. We used the variability in tephra seismites within the stratigraphic record and tephrochronology to better constrain the recurrence intervals and magnitudes of paleoearthquakes from both the Hamilton Basin and adjacent Hauraki Basin fault systems. Our methodology is globally applicable in volcanic and tectonic regions where liquefaction structures are preserved among (hidden) faults.

GPT-4o mini: Non-social science research article

Disrupted energy metabolism is associated with retinal ganglion cell degeneration in autosomal dominant optic atrophy

Eugene Yu-Chuan Kang, Yun-Ju Tseng, Wei-Hao Peng, Hui-Chuan Hung, Pei-Hsuan Lin, Katrina P. Montales, Emmet Sherman, John Peregrin, Ethan Hunghsi Wang, Chunya Kang, Yu-Chuan Teng, Chen-Yang Huang, Chia-Lung Tsai, Ian Yi-Feng Chang, Jiazhang Chen, Gülgün Tezel, Ye He, Tai-De Li, Linsey Stiles, Orian Shirihai, Stephen H. Tsang, Chi-Chun Lai, Chi-Neu Tsai, Chyuan-Sheng Lin, Nan-Kai Wang

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Autosomal dominant optic atrophy (ADOA) is a hereditary optic neuropathy caused by OPA1 variants, leading to retinal ganglion cell (RGC) degeneration and vision loss. The mechanisms behind RGC vulnerability to mitochondrial dysfunction remain unclear. We developed a patient-specific Opa1 V291D/+ knock-in mouse model to investigate mitochondrial dysfunction and retinal metabolism in ADOA. We observed that Opa1 V291D/+ mice exhibited anatomical and functional RGC abnormalities recapitulating the ADOA phenotypes. Reduced optic atrophy 1 (OPA1) protein levels were noted in Opa1 V291D/+ mice, accompanied by decreased protein stability. Moreover, mitochondrial function was compromised, as indicated by reduced Complex I activity, increased oxidative stress, and diminished adenosine triphosphate production in the retinas of Opa1 V291D/+ mice. Spatial metabolomics revealed energy deficits in the inner retina and heightened glycolysis in the outer retina. Immunostaining showed decreased expression of glycolytic proteins in the ganglion cell layer. Single-nucleus RNA sequencing disclosed significant down-regulation of energy-production genes in RGCs, while other retinal cell types remained unaffected. These findings emphasize the specific vulnerability of RGCs to bioenergetic crises, connecting disrupted energy homeostasis to their degeneration. By increasing the nicotinamide adenine dinucleotide (NAD + )/reduced form of NAD + (NADH) redox ratio through the overexpression of mitochondrial-targeted Lactobacillus brevis NADH oxidase ( MitoLbNOX ) in RGCs, we demonstrated improved RGC function and survival through enhanced energy metabolism and reduced oxidative stress. These findings confirm that disrupted energy metabolism leads to RGC degeneration and emphasize the enhancement of the NAD + /NADH redox ratio as a promising treatment strategy to protect RGCs from degeneration in ADOA.

Deciding for others alters metacognition leading to responsibility aversion

Sherry Dongqi Bao, Micah G. Edelson, Todd A. Hare

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People are often faced with choices whose outcomes will affect other individuals in addition to themselves. Being responsible for deciding on behalf of others alters choice behavior and increases delegation rates in decisions involving risk and ambiguity. However, it is unknown whether the influence of social responsibility on decision-making acts primarily or directly on risk, loss, and ambiguity attitudes versus more general aspects of cognition. We report a series of experiments on objective magnitude judgments that demonstrate that the influences of responsibility on cognition and behavior extend beyond risk or ambiguity and act at the metacognitive level. Specifically, responsibility for others changes metacognitive biases, leading to a decrease in decision confidence without affecting choice accuracy. Last, we propose and empirically test a normative computational framework based on decision confidence that can explain decisions to assume or delegate responsibility for others without needing to assume changes in risk preferences.

The marginal majority effect: When social influence produces lock-in

Alexandros Gelastopoulos, Pantelis P. Analytis, Gaël Le Mens, Arnout van de Rijt

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People are influenced by the choices of others, a phenomenon observed across contexts in the social and behavioral sciences. Social influence can lock in an initial popularity advantage of an option over a higher quality alternative. Yet, several experiments designed to enable social influence have found that social systems self-correct rather than lock in. Here, we identify a behavioral phenomenon that makes inferior lock-in possible, which we call the “marginal majority effect”: a discontinuous increase in the choice probability of an option as its popularity exceeds that of a competing option. We demonstrate the existence of a marginal majority effect in several recent experiments and show that lock-in always occurs when the effect is large enough to offset the quality effect on choice but rarely otherwise. Our results reconcile conflicting past empirical evidence and connect a behavioral phenomenon to the possibility of social lock-in.