🗣 Communication Paper Picnic 🧺: Multidisciplinary

I checked 6 multidisciplinary journals on Saturday, October 10, 2026 using the Crossref API. For the period October 03 to October 09, I found 13 new paper(s) in 5 journal(s).

Nature

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

5-oxoETE links redox control of epithelial damage detection and resilience

Yanan Ma, Miklós Lengyel, King Lam Hui, Yohannes A. Ambaw, Zaza Gelashvili, Leehyeon Kim, Ritchie Ly, Siyang Peng, Meysoon Quraishi, Tobias C. Walther, Robert V. Farese, Philipp Niethammer

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Organisms harness oxidative stress to rapidly attract white blood cells to wound sites and to kill pathogens 1–3 . To this end, host tissues increase their own oxidative stress resilience and repair capacity via adaptive redox signalling 4–6 . Here, using live zebrafish and human cells, we identify a metabolic redox signalling mechanism that integrates oxidative immune defence with tissue adaptation. We demonstrate that DHRS7, an orphan short-chain fatty acid dehydrogenase–reductase, generates or consumes the pro-inflammatory lipid 5-oxoETE as a function of cytoplasmic NADP + /NADPH ratio. At wounds, where oxidative stress and NADP + are high, 5-oxo-eicosatetraenoic acid (5-oxoETE) production by DHRS7 rapidly alerts antimicrobial white blood cells through the G-protein-coupled receptor OXER1. In undamaged tissue, where NADP + is low, DHRS7 quenches unnecessary inflammation. Notably, we find that 5-oxoETE also supports epithelial redox resilience; OXER1-deficient zebrafish exhibit intestinal apoptosis, barrier disruption and microbial inflammation. Mechanistically, 5-oxoETE induces the expression of NUDIX hydrolases, which protect the cytoplasmic nucleotide pool from oxidation and prevent apoptosis in zebrafish and human intestinal cells. Thus, our data reveal a conserved mode of redox sensing and signalling—beyond classic thiol oxidation—that leverages NADPH metabolism to orchestrate the antimicrobial and pro-resilience functions of oxidative stress.

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

Dynamics of human cardiogenesis and its disruption in trisomy 21

James Cranley, Kazumasa Kanemaru, Semih Bayraktar, Vincent Knight-Schrijver, Rebecca Hulbert, Eva Lana-Elola, Rifdat Aoidi, Jan Patrick Pett, Anna Wilbrey-Clark, Krzysztof Polanski, Monika Dabrowska, Ilaria Mulas, Harriet Johnson, Noemie Combemorel, Yizhou Yu, Jack A. Palmer, Woochan Lee, Jore Van Wauwe, John-Poul Ng-Blichfeldt, Laura Richardson, Claudia I. Semprich, Rakeshlal Kapuge, Shani Perera, Xiaoling He, Siew Yen Ho, Nadav Yayon, Liz Tuck, Kenny Roberts, Hongorzul Davaapil, Laure Gambardella, Anna Philpott, Minal Patel, Richard C. V. Tyser, Andreia Sofia Bernardo, Victor L. J. Tybulewicz, Sanjay Sinha, Sarah A. Teichmann

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Developmental dynamics involve the specification of diverse cell types and their spatial organization into multicellular niches 1 . Here we combine single-cell and spatial multiomics to define 21 distinct tissue niches in the developing heart, which we use to develop a context-aware, resolution-agnostic niche classification tool (TissueTypist). Applying high-resolution spatial profiling to the developing sinoatrial node, we resolve three pacemaker cell subtypes arrayed along a linear axis. First trimester subpopulations, such as pacemaker cells in the sinus horn and sinoatrial node head region, display neuroattractant programs and interact with parasympathetic neurons via interactions that include Eph–ephrin and semaphorin–plexin signalling. Temporal trajectories map the maturation of atrial and ventricular cardiomyocytes and uncover a lipid–metabolic switch and potential key regulators of cell-type identity. In the ventricle, we identify cellular and transcriptional gradients along both pseudotime and transmural axes, which provide molecular insights into myocardial compaction and maturation. Comparative profiling revealed that hearts with trisomy 21 are depleted in compact cardiomyocytes and exhibit increased apoptosis relative to euploid hearts. This finding was validated in isogenic-matched trisomy 21 and euploid cardiomyocytes derived from induced pluripotent stem cells. These early developmental perturbations may contribute to the increased risk of congenital heart disease associated with Down’s syndrome. In summary, we present a spatially resolved framework of human cardiac development to enable systematic explorations of developmental niches in health and disease.

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

Human lung organoid modelling of tissue-resident antiviral T cell responses

Joseph K. Rathkey, Shannon S. Choi, Vincent van Unen, Huimin Zhang, Min Liu, Jie Ding, Samira A. Alwahabi, António J. M. Santos, Vamsee Mallajosyula, Joshua E. Chan, Azam Mohsin, Maher M. Elsheikh, Arjun Rustagi, Brandon Lam, Steven M. Chirieleison, Bailey Wallen, Daniel Solis, Jordan Mah, Hudson T. Horn, Katharina Röltgen, Ramesh Nair, Winston Trope, Alexander Guh-Siesel, Zhongqi Lin, Hannah S. Powell, Ahmad Salehi, Aimee Beck, Caitlin Edwards, Brock A. Martin, James C. Y. Dunn, Joseph Shrager, Ralph S. Baric, Benjamin Pinsky, Scott D. Boyd, Catherine A. Blish, Alessandro Sette, Alba Grifoni, Mark M. Davis, Calvin J. Kuo

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Tissue-resident immunity constitutes a first line of defence against pathogens and enables rapid innate and adaptive memory responses1,2,3. However, experimental studies have been hindered by a lack of holistic human in vitro models that enable epithelial infection in the context of tissue-resident immune subsets. In lung, differing notions of transient versus sustained residency of tissue-resident memory T cells (TRM cells) have challenged the extent to which anamnestic recall immunity to respiratory pathogens occurs locally or in concert with secondary lymphoid organs4,5,6. Here we generated long-term adult human distal lung organoids from intact tissue fragments in 3D air–liquid interface culture, which co-preserved epithelial and stromal components with endogenous lung-resident immune cells (T cells, B cells, natural killer cells and myeloid cells). The organoid T cells expressed residency and memory markers and preserved T cell receptor repertoires of cognate fresh tissue. SARS-CoV-2 infected the organoid lung epithelium, stimulated inflammatory cytokine production and, crucially, induced SARS-CoV-2-specific, tissue-resident T cell responses. Furthermore, boosting T cells within intact organoids with SARS-CoV-2 peptide pools blunted subsequent SARS-CoV-2 infection, consistent with a component of virus-specific protective TRM cell function in the absence of secondary lymphoid tissues. Overall, this immunocompetent lung organoid system demonstrates functional control of viral infection by lung-intrinsic memory T cell responses, provides a rationale for local vaccination strategies and validates a general platform for investigation of human tissue-resident immunity in health and disease.

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

Hydrogen bonding in water under extreme confinement

Xintong Xu, Matthias Kuehne, Harrison A. Walker, De-Liang Bao, Xin Jin, Yu-Ming Tu, Cody L. Ritt, Joel Martis, Juan Carlos Idrobo, Sokrates T. Pantelides, Michael S. Strano, Jordan A. Hachtel, Arun Majumdar

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Fluids under extreme confinement or near interfaces exhibit molecular structures and intermolecular bonding distinct from their bulk analogues. Optical vibrational studies have shown that interfacial and confined water can exhibit altered intramolecular O–H stretching frequencies, a sensitive spectral signature of changes in intermolecular hydrogen bonding1,2,3,4. Investigating confined water experimentally at the length scale of intermolecular and surface forces has, however, remained a challenge. Here we report direct molecular-level observations of hydrogen bonding in water confined inside individual carbon nanotubes (CNTs), enabled by in situ vibrational electron energy loss spectroscopy (vEELS) with nanoscale resolution. Water in larger CNTs exhibits the bonded O–H vibrations of bulk water, but at smaller diameters, and the frequency blueshifts to near the free O–H stretch found in water vapour and water located near hydrophobic surfaces, indicating a highly dispersed, non-H-bonded environment. Theoretical analysis based on quantum vibrational oscillators links the observed spectral features to local hydrogen-bonding configurations, consistent with the experimental observation. Furthermore, cryogenic experiments provide insights into complex structural phase transitions of confined water. This research reveals the quantum and dynamic nature of hydrogen bonds under confinement and the potential impact of unveiling molecular-level structure and bonding in confined fluids.

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

Alveolar stem cells transdifferentiate to drive bronchiolar regeneration

Kuo Liu, Zixin Liu, Xinfeng Meng, Muxue Tang, Fanglin Di, Zhongxiao Wang, Chenfei Li, Shan Yang, Yanli Zhang, Xueying Yang, Zan Lv, Xufeng Li, Hengwei Jin, Wenjuan Pu, Huan Zhao, Feng Li, Pengfei Sui, Bin Zhou

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The lung consists of two anatomically distinct compartments: the airways and the alveoli. Although airway epithelial stem cells are known to mobilize for alveolar regeneration, whether alveolar cells can reciprocally traverse these anatomical boundaries and contribute to bronchial repair remains unclear1,2,3,4. Here we developed dual-recombinase-mediated lineage-tracing techniques in mice to demonstrate that alveolar type 2 (AT2) cells migrate into injured bronchioles and transdifferentiate into club cells and ciliated cells, thereby actively contributing to airway regeneration. Mechanistically, after bronchial injury, infiltrating immune cells secrete SPP1, establishing a chemotactic gradient directing cell migration. Peribronchiolar AT2 cells sense this SPP1 signal through the integrin ITGB1 and migrate towards the injured bronchioles. On arrival, these migrated AT2 cells receive Notch ligands from resident ciliated cells, leading to Notch pathway activation, which in turn drives their transdifferentiation into club cells. This transdifferentiation process is accompanied by an intermediate stage marked by Cldn4 expression. Functional blockade of either SPP1 or ITGB1 impairs AT2 cell migration, whereas inhibition of Notch signalling prevents their transdifferentiation into club cells. Collectively, our findings reveal a cross-compartmental cellular mechanism for bronchiolar epithelial repair, expanding the current understanding of lung regenerative plasticity and potentially informing therapeutic strategies for airway injury.

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

A preinvasive regulatory T cell axis for lung cancer interception

Samuel Gamble, Zoe E. Whiteman, Claudia Peinador-Marín, Marta Lebrusant-Fernandez, Abigail Y. L. Shurr, Andrei Enica, Teerapon Sahwangarrom, Seng Kuong Anakin Ung, Amber Rogers, Petros Fessas, Chuen Ryan Khaw, Lukas Kalinke, Constantin Ahlmann-Eltze, Ahmed S. N. Alhendi, Kate Otter, Xiuchuan Hu, Krupa Thakkar, Betty Gration, Izzy Newsham, Imran Uddin, Ellen Nuttall Musson, Kyren A. Lazarus, Moritz J. Przybilla, Adam Pennycuick, Helen Hall, Zoe Hagel, Charlotte Percival, Ruth Prendecki, Sophie Tisi, Georgia Constantinou, Pascal F. Durrenberger, NA, Kate H. C. Gowers, Yien Ning Sophia Wong, Mark Linch, Kevin Litchfield, Elspeth M. Payne, Se-Hoon Lee, Sergio A. Quezada, Peter J. Campbell, Jennifer E. Beane, Sarah A. Mazzilli, David A. Moore, Vitor H. Teixeira, Sandra Gómez-López, Bart Vanhaesebroeck, Sam M. Janes, James L. Reading

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Late-stage non-small cell lung cancer (NSCLC) is rarely curable 1 , underscoring a need to intervene earlier in the disease process. Growing evidence suggests that antitumour T cell responses are mounted but become progressively dysregulated during early tumorigenesis 2,3 . Tracking and targeting preinvasive T cell regulation may inform new approaches to detect and intercept lung cancer development. Here we explore how the T cell network is remodelled during NSCLC development via multi-omic, cross-tissue immune profiling in patients with preinvasive lung lesions surveilled by autofluorescence bronchoscopy and computed tomography (CT) imaging. Effector regulatory CD4 + T cells (eT reg cells) expressing basic leucine zipper ATF-like transcription factor (BATF) accumulated in high-grade premalignant airway lesions and were clonally related to circulating eT reg cells. Circulating eT reg cells were increasingly elevated during preinvasive progression, enabling lung tumorigenesis to be tracked through analysis of peripheral blood. Emergence of this clonally coordinated eT reg cell circuit defined rapid progression in patients with early-stage NSCLC detected during CT screening. In mice, carcinogen-driven lung tumorigenesis triggered an analogous preinvasive eT reg cell axis across the blood, airways and draining lymph nodes (dLNs). This culminated in an expansion of lung BATF + T reg cells and T reg cell-rich peribronchial immature tertiary lymphoid structures (iTLSs). Immune interception via phosphoinositide 3-kinase-δ (PI3Kδ) inhibition abrogated formation of T reg cell-rich iTLSs, reduced circulating and pulmonary T reg cells, increased local conventional type 1 dendritic cells (cDC1s) and reduced lung tumour incidence and size. These data reveal a conserved eT reg cell network that emerges across tissues during early pulmonary tumorigenesis and provide a theranostic framework to track and target preinvasive immune regulation for lung cancer interception.

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

Author Correction: Histone readers MLLT1 and MLLT3 concentrate AID to confer locus specificity

Noé Seija, Sophia Gannon, Kíra A. Häfner, Tim M. Gemeinhardt, Jana Ridani, Diego Alvarez, Mélanie Provencher, Poorani Ganesh Subramani, Christian Poitras, Eva-Maria Piskor, Tarik Möröy, Nicholas Vonniessen, Bruce Mazer, Marcelo A. Navarrete, Nicole J. Francis, François Robert, Javier M. Di Noia

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

A thorium-229 optical nuclear clock with feedback loop

L. Toscani De Col, T. Riebner, I. Morawetz, F. Schneider, N. Sempelmann, J. Schlachet-Lépinay, F. Schaden, M. Bartokos, G. A. Kazakov, K. Beeks, B. Gerstenecker, M. Pimon, S. Lahs, A. Hellerschmied, T. Lercher, H. Denker, J. Premper, A. Niessner, M. Matus, M. Čížek, O. Číp, V. Lal, G. Zitzer, V. Petrov, J. Tiedau, M. V. Okhapkin, E. Peik, T. Schumm

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The laser-accessible nuclear transition in the thorium-229 isotope has been identified as a candidate for realizing an optical nuclear clock 1 that might outperform current optical clocks based on electron-shell transitions in atoms or ions 2 . It is expected to be more robust against external perturbations 3,4 and to provide enhanced sensitivity in clock-based tests of the fundamental principles of physics 5,6 . Here we realize a thorium-229 nuclear clock by stabilizing a continuous-wave laser to the 148-nm nuclear transition with rapid feedback based on absorption spectroscopy 7 . The thorium-229 nuclei are embedded in a millimetre-sized, room-temperature calcium fluoride crystal. A subharmonic of the 148-nm radiation is continuously compared with a Yb + single-ion clock. The nuclear clock shows a shot-noise-limited fractional frequency instability of $$3\times 1{0}^{-12}/\sqrt{\tau /{\rm{s}}}$$ 3 × 1 0 − 12 / τ / s where τ is the averaging time, approaching 10 −15 instabilities over 1 day of operation. Improvements to the instability by several orders of magnitude are projected for future devices. We use the nuclear clock to constrain models of ultralight dark matter by searching for periodic fluctuations and slow drifts in the nuclear transition energy, on timescales between 20 s and 1 day. Benefitting from the enhanced sensitivity of the thorium-229 transition, these constraints compete with the best atomic clocks concerning dark matter coupling to photons and go beyond previous measurements regarding coupling to the strong force.

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

A gut microbial odd-chain fatty acid alleviates atherosclerosis in mice

Chao Yin, Youzhe Chen, Gan Lin, Mingwei Cai, Cuiping Pang, Xianzun Xiao, Kaining Han, Chaoxiong Mei, Miaomiao Qin, Peizhi Fan, Yibo Zhao, Lihong Du, Yanqin Xie, Jiang Wang, Yudan Mao, Xiangting Zhou, Xue Gao, Li Jin, Peijie Li, Zepeng Qu, Zhipeng Tan, Ruolan Sun, Xiahong Lin, Yang Zhang, Lei Dai, Zhaofan Luo, Xiangyu Mou, Xiaoyu Tang, Wenjing Zhao

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The gut microbiota plays a pivotal part in human health, yet the molecular mechanisms that underlie its effects are largely unexplored. Bacteroides, a dominant genus in the human gut microbiota, is depleted in patients with atherosclerosis1, but its causal relationship with disease remains unclear. Here, using a mouse model, we show that administration of Bacteroides uniformis alleviates atherosclerosis through the upregulation of hepatic low-density lipoprotein receptor expression. Bioactivity-guided screening revealed pentadecanoic acid (PA, C15:0), a saturated odd-chain fatty acid, as a principal bioactive metabolite. PA supplementation reduced atherosclerotic plaque burden by around 50% and significantly improved plasma lipid profiles, a result that underscores its therapeutic potential. Mechanistically, PA enhances cholesterol clearance by directly inhibiting HMG-CoA reductase, suppressing hepatic cholesterol biosynthesis and promoting plasma low-density lipoprotein cholesterol removal. Analyses of 100 gut bacterial strains revealed that PA production occurs across multiple Bacteroidota genera. Notably, PA is markedly depleted in patients with dyslipidaemia. In summary, a Bacteroidota-derived odd-chain fatty acid regulates gut–liver crosstalk, and modulation of the microbial–metabolic axis has atheroprotective potential.

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

Retrofitting language models to operate over bytes

Benjamin Minixhofer, Tyler Murray, Tomasz Limisiewicz, Anna Korhonen, Luke Zettlemoyer, Noah A. Smith, Edoardo M. Ponti, Luca Soldaini, Valentin Hofmann

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Recent advances in artificial intelligence (AI) have largely been driven by large language models, deep neural networks that operate over discrete units called tokens. To represent text, most large language models use words or word fragments as the tokens, known as subword tokenization 1 . Subword tokenization obscures fine-grained information, which is problematic, especially for scientific data—such as computer code or biological sequences—where meaning depends on the individual characters or bytes 2 . Models that instead operate directly on the byte encoding of text avoid these limitations, but until now they have lagged behind subword-based models in performance. Here we introduce a general method for creating byte-level large language models through byteification that approach the capabilities of subword-based systems. We use a two-stage conversion procedure to retrofit existing subword-based models into byte-level models with minimal extra training. The resulting models outperform earlier byte-level approaches and excel on character-level reasoning tasks, achieving practical inference speeds by efficiently processing byte-level information and adaptability by reusing the existing ecosystem around the source large language model. Our results remove a long-standing performance barrier to end-to-end byte-level language modelling, demonstrating that models operating on raw text encodings can scale competitively while offering advantages in domains requiring fine-grained textual understanding.

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

Structural basis for regulating lipopolysaccharide transmembrane transport

Rebecca J. Taylor, Karanbir S. Pahil, Alessio Caruso, Bailey Plaman, Stephen A. Early, Sebastian J. Rowe, Vadim Baidin, Andrew Wilson, Natividad Ruiz, Richard M. Walsh, Stephen C. Harrison, Daniel Kahne

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Gram-negative bacteria are surrounded by a multilayered cell envelope with a mostly impermeable outer membrane that provides intrinsic resistance to many antibiotics1,2,3,4,5. The outer membrane is an asymmetrical bilayer with phospholipids in the inner leaflet and lipopolysaccharide (LPS) in the outer leaflet6,7. An LPS transport (Lpt) machine called LptB2FGCADE moves LPS across a protein bridge from the inner membrane to the outer membrane8,9. LPS biosynthesis is regulated to prevent toxic accumulation of LPS molecules in the inner membrane during growth10,11,12. Whether LPS transport across the Lpt bridge is also regulated has been unclear. Here we present three structures of the trans-envelope Lpt complex in LPS-free, LPS-bound and ATP-bound states, along with a structure of a partial bridge. These structures, combined with biochemical experiments, show that Lpt bridge assembly triggers movement of the transmembrane helix of LptC (TM-LptC) in an LPS-dependent manner, resulting in increased ATP binding and hydrolysis. We also show that LPS transport in vivo requires bridge formation and movement of the TM-LptC. Our data support a model in which assembled Lpt bridges respond to the presence of LPS in the inner membrane to turn on transport by moving the TM-LptC, thus coordinating LPS transport activity with bridge assembly and the presence of LPS at the inner membrane.

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

Mechanism of spliceosome termination

Vytaute Boreikaite, Rupert Faraway, Matthias K. Vorländer, Alexander W. Phillips, Leonie Opitz, Moritz Wanke, George Yakoub, Gerald Raffl, Laura Fin, Román González-Prieto, Martijn S. Luijsterburg, Stefan L. Ameres, Clemens Plaschka

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After excising an intron from pre-mRNA, the spliceosome remains trapped in a non-productive complex bound to the intron 1–5 . Termination of this complex is critical for spliceosome recycling and intron decay 6 , but the mechanism remains unknown. Here we present cryo-electron microscopy structures of human spliceosomes at two sequential stages of termination. First, the RNA helicases DHX15 and Aquarius unwind the RNA active site of the spliceosome, releasing bound components including U2 snRNA and extracting the buried intron–lariat branch point. The branch point is then debranched by the spliceosome-tethered enzyme DBR1, generating the previously unknown debranched intron spliceosome. This state recruits the RNA helicase DHX35 with its co-factors GPATCH1–WDR83, assisted by YJU2B. DHX35 ejects the debranched intron from the U6 snRNA–5′ splice site duplex, driving spliceosome disassembly and intron turnover. In defective spliceosomes stalled on aberrant introns, YJU2B partners with LENG1 to guide DHX35–GPATCH1–WDR83 for termination through spliceosome quality control. Together, we reveal the mechanism of regular spliceosome termination and its parallels with spliceosome quality control, ensuring accurate and efficient pre-mRNA splicing.

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

A Jurassic mammaliaform swimmer and transformation of the mammalian pharynx

Y. Li, P. Li, A. I. Neander, H. Zhang, C.-F. Zhou, T. Martin, Z.-X. Luo

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The discovery of a well-preserved mammaliaform fossil from the Middle Jurassic period of China reveals evidence on the evolutionary transformation of the feeding apparatus and the ecological diversity of Mesozoic era mammals. Mammaliaforms are evolutionary predecessors to modern Mammalia1,2,3, and their morphologies provide primary insights into the evolutionary origin of mammals. The rare preservation of a therian-like pharyngeal vault (throat passage) and hyoid skeletal anatomy (throat bones) in this mammaliaform suggests that critical soft-tissue anatomy for therian-like swallowing, drinking and suckling behaviours had evolved in the common ancestors of Docodonta and Mammalia, long before the rise of modern mammals. This fossil exhibits a wealth of features specialized for swimming, filling in a major gap of anatomical knowledge of pelvis and hindlimb for early mammals. It is characterized by highly distinctive canines and pseudo-carnassial sectorial teeth for a faunivorous diet. We interpret that this mammaliaform was semiaquatic, swimming and foraging in water, with a lifestyle analogous to the extant platypus. This species is the largest of Jurassic mammaliaforms. It expands the body size range of docodontans, and adds to a growing body of evidence that multiple docodontans exploited diverse niches with semiaquatic and other ecomorphotypes. Docodontans are an early example of replicated evolution of the semiaquatic and other ecomorphotypes in the Mesozoic ecosystem dominated by dinosaurs, long before the diversification of extant mammals.

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

Author Correction: Anodic Pd membrane H2 extraction enhances thermochemical dehydrogenation

Rui Zeng, Julian Ufert, Bryan Y. Tang, Ryan P. Bisbey, Yogesh Surendranath

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

tRNA dosage regulates lineage dependency and resistance in prostate cancer

Yeon Soo Kim, Sonali Arora, Dave Young, Ava Tsou, Amy Shiuan, Cynthia L. Wladyka, Dmytro Rudoy, Jin Yeong Kim, Jennifer A. Waters, Samantha L. Schuster, Ilsa M. Coleman, Mridu Kapur, Marek Sobczyk, Christopher D. Katanski, Amin M. Bayat Tork, Wen Zhang, Peter S. Nelson, Gavin Ha, Michael C. Haffner, Eva Corey, Colm Morrissey, Yuzhuo Wang, Arvind R. Subramaniam, John K. Lee, Susan L. Ackerman, Tao Pan, Andrew C. Hsieh

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Lineage plasticity underlies therapeutic resistance in cancer1,2, yet the translational mechanisms that enable this phenotypic flexibility remain largely unknown. Here using prostate cancer as a model of lineage dependence, we performed unbiased small RNA sequencing and identified tRNA1Arg(UCU) as a regulator of lineage transitions and therapy resistance. tRNA1Arg(UCU) is capable of reprogramming lineage dependence, which can be tuned to restore sensitivity to therapies that target the androgen receptor. We identify TARDBP and ZSCAN29 as DNA-binding proteins that directly engage the genomic locus of tRNA1Arg(UCU) to regulate its expression, a result that highlights the importance of non-canonical tRNA-specific gene regulation. Mechanistically, tRNA1Arg(UCU) controls a translational program centred on SWI/SNF chromatin remodellers, which is necessary to maintain lineage fidelity. In patients, tRNA1Arg(UCU) is downregulated in neuroendocrine prostate cancer and its loss is associated with accelerated metastasis and poor survival. These findings uncover a previously unrecognized tRNA-specific regulatory axis that links codon biology to lineage dependence and therapy resistance in prostate cancer.

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

Observation of critical topological phase transition

Zheyu Cheng, Xiuhai Zhang, Xue-Jia Yu, Longwen Zhou, Jiangbin Gong, Baile Zhang

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Phase transitions are traditionally understood within two seemingly incompatible theoretical paradigms. Landau–Ginzburg phase transitions1,2 are continuous, occurring at critical points where microscopic details become irrelevant and universal behaviour emerges, driven by gapless fluctuations with scale-invariant correlations3. By contrast, topological phase transitions connect gapped phases characterized by quantized topological invariants4,5 and, in doing so, necessarily pass through gapless phase boundaries where such invariants become ill-defined6,7,8,9. Here using an acoustic metamaterial platform, we experimentally demonstrate a unifying scenario—a critical topological phase transition—in which topology becomes well-defined at criticality10,11,12,13, overcoming this conventional incompatibility, and reorganizes critical behaviour by driving a phase transition along critical phase boundaries14. This transition gives rise to a topology-enforced multicritical point at an isolated intersection of critical boundaries with distinct topology. Along these boundaries, we observe topological edge states and diagnose criticality by means of logarithmic entanglement-entropy scaling15,16,17. At the multicritical point, the entanglement entropy shows additive logarithmic scaling given by the sum of contributions from adjacent boundaries, directly evidencing topology-enforced multicriticality. These findings establish a hierarchical organization of phase transitions, in which topology shapes criticality beyond the conventional Landau–Ginzburg paradigm and standard topological phase transitions.

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

Experimental observation of critical topology

Zhi-Kang Lin, Li-Wei Wang, Ze-Lin Kong, Yao Zhou, Hai-Qing Lin, Xuejia Yu, Shuang Zhang, Jian-Hua Jiang

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Understanding phases of matter and their transitions stands as a central pursuit in physical sciences, representing a continuously evolving frontier that drives fundamental discovery. Conventional phase transitions are marked by continuous order-parameter evolution and universal critical behaviour, whereas topological phase transitions are defined by abrupt changes of quantized topological invariants—two frameworks long viewed as distinct and even incompatible1,2. Recent theories have predicted quantum criticality endowed with nontrivial topology mostly in one-dimensional (1D) systems3,4,5, pointing to a potential unification of the two patterns. Yet experimental observation of such critical topology, that is, topology at phase boundaries and its extension to higher dimensions, remain outstanding. Here we report experimental evidence indicating that critical gapless topological states can be characterized by the entanglement spectrum (ES) and entanglement wavefunctions in both one and two dimensions, complemented by direct imaging of the topological boundary modes in gapless bulk continuum using engineered phononic crystals. Although implemented in a classical platform, our experimental approach gives results equivalent to those in the quantum limit and is in fact readily extensible to quantum systems. Through entanglement-based analysis, we illustrate that transitions among phase boundaries with distinct critical topology lead to multi-critical points in the phase diagram, evidencing topology-driven multi-criticality and a hierarchical structure of topological phases. Our work demonstrates a fundamental connection between topology and criticality, paving the way for an experimental route towards exploring topological physics at phase transitions.

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

Observation of relativistic bond weakening in seaborgium hexacarbonyl

Alexander Yakushev, Jadambaa Khuyagbaatar, Christoph E. Düllmann, Valeria Pershina, Matthias Schädel, Jochen Ballof, Pavel Bartl, Michael Block, Raul-Andrei Cantemir, Dominik Dietzel, Francesca Giacoppo, Katharina Hermainski, Rolf-Dietmar Herzberg, Jan John, Jörg Krier, Nikolaus Kurz, Sven Löchner, Moumita Maiti, Pavol Mošať, Sebastian Raeder, Tetsuya K. Sato, Brigitta Schausten, Juha Uusitalo, Peter Wieczorek

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The seventh row of the periodic table of the elements has been completed with the discovery of the five heaviest elements from flerovium (Fl, Z = 114) through oganesson (Og, Z = 118) 1 . Chemical properties of the superheavy elements (SHE, Z ≥ 104) are unique owing to the strong influence of relativistic effects on their valence electron shells 2 . The stability of the metal–ligand bonding in carbonyl complexes is a property that is predicted to be affected by such effects 3,4 . Here we present an experimental gas chromatography study on the stability of the Sg(CO) 6 complex. The measured formation yields of Sg(CO) 6 and W(CO) 6 enabled determining the first bond dissociation energy (FBDE) of Sg(CO) 6 , which is 4(2) kJ mol −1 lower than that of W(CO) 6 and corresponds to a value of 188(9) kJ mol −1 . Thus, the trend of increasing FBDE values of hexacarbonyls within group 6 of the periodic table is reversed from W to Sg. Our result agrees with state-of-the-art theoretical calculations, which predict a decrease in the FBDE from W(CO) 6 to Sg(CO) 6 owing to the relativistic destabilization of the 6d atomic orbitals (AOs) in Sg (ref. 4 ). Also, the adsorption enthalpy value of Sg(CO) 6 on gold of $${45}_{-6}^{+4}\,{\rm{kJ}}\,{{\rm{mol}}}^{-1}$$ 45 − 6 + 4 kJ mol − 1 is reported.

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

Spatially deterministic nucleation of 2D semiconductors by etching flux

Jeongwon Park, Jiyun Kim, Sumin Kang, Jieun Oh, Youngmin Sunwoo, Saeyoung Oh, Seunghye Shin, Sera Yang, Seonghwan Jo, Jaehyun Lee, Donghyeop Lee, Minsu Kim, Changhun Eom, Seohyun Jeong, Chan Lim, Gunho Moon, Mingu Kang, Min-gyu Kim, Junhyeok Kim, Chaejeong Yun, Gichang Noh, Donggeon Park, Dongyoung Kim, Seongdae Kwon, Chengyun Hong, Hyeongjin Lim, Minseok Choi, Yongjoon Lee, Joonghoon Choi, Junhyuk Tak, Guanning Shao, Seung Jae Kwak, Tae Soo Kim, Jeehwan Kim, YongJoo Kim, Young Joon Hong, Sung-Yool Choi, Heejun Yang, Jonghwan Kim, Byungjo Kim, Woo-Hee Kim, Chang-Soo Lee, Kibum Kang

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Nucleation control is fundamental to semiconductor deposition, governing when, where and how crystalline materials form. Conventional strategies can regulate nucleation density and, through area-selective growth, confine deposition to designated regions 1–13 . However, they generally do not determine where an individual nucleus forms within the growth regions, leaving even single-nucleation events spatially stochastic and limiting deterministic construction of crystalline materials. Here we report etching-flux-mediated single-centred nucleation of two-dimensional (2D) semiconductors to deterministically localize a single nucleation event. The etching flux released from the barrier suppresses nuclei near the pattern boundary, leaving a single surviving nucleus at the pattern centre, and systematic experiments elucidate the mechanism and establish nucleation design rules for zero, single and multiple nucleation regimes. Etching-flux-mediated single-centred nucleation enables single-crystal molybdenum disulfide growth at the 10-μm scale, field-effect mobilities of up to 117 cm 2 V −1 s −1 and large-area uniformity with process compatibility. This in-plane chemical-flux strategy realizes spatially programmed growth, demonstrating nucleation–growth decoupling for line-shaped single crystals, multiple transistors integrated within a large common crystal, and aligned 2D lateral heterostructures for self-aligned contacts. These capabilities open a path towards advanced 2D electronic integration and expand semiconductor deposition from controlling where materials grow to controlling where and how crystals can begin to form.

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

A 7-eV bandgap semiconductor based on silicon-doped α-(AlxGa1−x)2O3

Jacob Steele, Debaditya Bhattacharya, Kazuki Nomoto, Naomi A. Pieczulewski, Preston Sorensen, Viet-Anh Ha, Nick Pant, Ihit Shukla, Shaon Das, Ufuk Kilic, Madhav Ramesh, Feliciano Giustino, Baishakhi Mazumder, M. K. Indika Senevirathna, Michael D. Williams, Mathias Schubert, David A. Muller, Huili G. Xing, Debdeep Jena, Darrell. G. Schlom

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In rectifying power electronics, wider-bandgap (Eg) semiconductors allow higher efficiency and power density with the Baliga figure of merit proportional to Eg5.5 (refs. 1,2). Unfortunately, the unique ability of semiconductors to have their conductivities controllably modulated over orders of magnitude by equilibrium doping methods becomes increasingly elusive as the bandgap increases. Increasing demand for wider-bandgap semiconductors has led to many materials previously considered insulators—including GaN, SiC, AlN, Ga2O3 and GeO2—to emerge as useful semiconductors after decreasing defect densities and finding appropriate dopants. Here we report silicon-doped α-(AlxGa1−x)2O3 films with bandgaps exceeding 7.0 eV grown by suboxide molecular-beam epitaxy, surpassing that of cubic boron nitride, the next-widest-bandgap semiconductor known3,4,5. In the colossal-bandgap regime, >6 eV, our silicon-doped α-(AlxGa1−x)2O3 films have room-temperature conductivities over 100 million times higher than all previous reports6. We fabricate a Schottky diode and a field-effect transistor (the AlphaFET) with colossal-bandgap channels. These α-(AlxGa1−x)2O3 films and devices use sapphire, an abundant, inexpensive substrate with excellent quality that is produced at massive scale, facilitating the development and adoption of colossal-bandgap electronics. Our achievement breaks the trend of increasing synthesis difficulty, cost and small size of ever-wider-bandgap semiconductors, for example, diamond and cubic boron nitride.

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

Prehistoric global migration of vanishing gut microbes with humans

Matthew M. Carter, Zhiru Liu, Matthew R. Olm, Melanie Martin, Daniel D. Sprockett, Parsa Ghadermazi, Benjamin C. Trumble, Hillard Kaplan, Jonathan Stieglitz, Daniel Eid Rodriguez, David A. Relman, Erica D. Sonnenburg, Michael Gurven, Benjamin H. Good, Justin L. Sonnenburg

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The gut microbiome is crucial for health and is affected strongly by lifestyle1. Many microorganisms commonly found in non-industrialized populations are disappearing or have become extinct in industrialized populations2,3,4,5,6. Studying which microorganisms have been long-term residents of the human gut and may have co-evolved with humans2,7,8 could provide insights into how microbial biodiversity loss affects human health. However, the genetic complexities of microbial evolution and the plasticity of gut microbiome composition have made it challenging to resolve the evolutionary history of these long-term associations. Here we performed deep metagenomic sequencing of the Tsimane horticulturalists of Bolivia and compared their gut microbiomes with those of the Hadza hunter-gatherers of Tanzania3. These two populations, whose ancestors have been separated for tens of thousands of years, share 1,231 microbial species, most of which are rare in or absent from industrialized populations. Population genetic analyses of 636 of the shared species revealed patterns of microbial divergence and gene flow consistent with prehistoric human co-migration, with estimated split times that approximately align with human migration out of Africa and into the Americas. Our findings indicate that a diverse gut microbiome co-migrated with humans worldwide and has persisted over millennia. However, many of these species are now vanishing from industrialized populations and the consequences for human health remain uncertain.

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

A chiral superlattice route to spin-split topological antiferromagnetism

Thao Dinh, Mengke Liu, Jian-Xiang Qiu, Sougata Mardanya, Suk Hyun Sung, Xuan Hoang Le, Christopher Broyles, Chengfeng Zhu, Qiaozhi Xu, Haotian Chen, Zack Rehfuss, Yu-Fei Liu, Xiaoyu Zeng, Houchen Li, Peng Guo, Jinchen Liu, Tianye Huang, Jingtian Shi, Michael Smith, Joanna M. Blawat, John Singleton, Ross McDonald, Iván E. Arvizo, Dongtao Cui, Shao-Liang Zheng, Kenji Watanabe, Takashi Taniguchi, Vineet Kumar Sharma, Sudip Ghorai, Barun Ghosh, Hsin Lin, Ting Yong Lim, Tay-Rong Chang, Arun Bansil, Ivar Martin, Ashvin Vishwanath, Weiwei Xie, Claudia Felser, Jairo Sinova, Anyuan Gao, Mikhail D. Lukin, Jennifer E. Hoffman, Sugata Chowdhury, Qiong Ma, Kai Sun, Ismail El Baggari, Sheng Ran, Talieh S. Ghiasi, Hongkun Park, Philip Kim, Su-Yang Xu

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Chirality has emerged as a new mechanism for inducing spin and Berry-curvature phenomena in quantum materials and molecular chemistry1,2,3,4,5,6,7. Collinear antiferromagnets (AFMs) are promising for spintronics and topological magnetism, yet realizing large Berry curvature and spin-split bands remains challenging8,9. Here we report a chiral-superlattice route to spin-split topological phenomena from collinear antiferromagnetism. We study the collinear AFM UOTe, in which we show a spontaneous chiral superlattice arising from frozen chiral phonons at a finite wave vector. Without the superlattice, the pristine collinear AFM in UOTe has neither Berry curvature nor spin-split bands. When electrons move through the chiral superlattice, their orbital Bloch wavefunction and quantum geometry are modulated by the strong chiral superlattice potential, generating large Berry curvature, which we detect by the nonlinear Hall effect. At 150 K, the chiral-superlattice-induced Berry curvature couples to the collinear AFM order, leading to an anomalous Hall angle of about 0.14 abruptly near the Néel temperature TN which is among the largest in bulk magnets. Moreover, our spin Hanle precession measurement shows that the chiral superlattice also generates spin-polarized current from the collinear AFM, a long-standing goal in spintronics. We shed light on the supermodulation formation mechanism based on chemical ion size and physical interlayer–intralayer energy competitions, which we use to propose a design principle to discover similar bond-mismatch superlattices, providing a chiral superlattice pathway through real-space engineering of quantum geometry10,11.

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

A split attractor design for rapidly writing a navigational goal

Aaron J. Lanz, Nicholas D. Kathman, Emily Hao, Bard Ermentrout, Katherine I. Nagel

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Recurrent attractor networks are widely thought to form the basis of working memory1,2,3, but how they can be rapidly switched on and off is unclear4,5,6,7. Here we investigate stability and switching in a recurrent circuit of the fly navigation centre8. h∆K and PFG neurons are recurrently connected in a ring structure and exhibit shared persistent bump activity that turns on with odour and terminates at the end of a goal-directed run. Using whole-cell recordings, we show that persistence in h∆K depends on recurrence, and that h∆K receives slow recurrent excitation and fast inhibition from its synaptic partners. Computational modelling reveals that these synaptic dynamics yield persistent attractor dynamics over a range of synaptic strengths. Next we examine the mechanisms of rapid switching. We find that whereas both populations show similar activity during runs, they become decoupled during turns and rest. We can reproduce these differential dynamics in our model by using inhibition to dynamically uncouple activity in h∆K from PFG. When h∆K is inhibited, PFG neurons follow their inputs from the compass system; when h∆K is disinhibited, recurrent interactions lock this input into place, forming a heading memory. Consistent with this model, we find that inhibitory inputs onto h∆K increase during turns and are suppressed during odour and goal-directed runs. Our work reveals how disinhibition can serve as a gate to rapidly write an ongoing measurement to a recurrent circuit.

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

Editorial Expression of Concern: Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring

Sangdoo Kim, Hyunju Kim, Yeong Shin Yim, Soyoung Ha, Koji Atarashi, Tze Guan Tan, Randy S. Longman, Kenya Honda, Dan R. Littman, Gloria B. Choi, Jun R. Huh

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

A nuclear clock synchronized to 229Th

Beichen Huang, Gaowei Yan, Qi Xiao, Wenhao Bu, Chengchun Zhao, Zhen Zhang, Chao Yan, Zhi-Ang Chen, Peixiong Zhang, Gleb Penyazkov, Zhenhai Zhan, Lingfeng Yan, Yuefei Wang, Lin Li, Shanming Li, Dapeng Jiang, Xiaobo Qian, Xuegang Liu, Qiange He, Taoxiang Sun, Haochen Tian, Bingkun Lu, Ningyuan Ma, Juxian Li, Yanzhang Wu, Qiaorui Gong, Yuxiang Li, Haoyu Shi, Xiangliang Li, Longsheng Ma, Shining Zhu, Yuxiang Mo, Jun Lin, Li You, Yige Lin, Xibo Zhang, Yin Hang, Liangbi Su, Shiqian Ding

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Atomic clocks have made time and frequency the most precisely measured quantities in physics, progressing from microwave standards that realize the SI second 1 to optical clocks with unprecedented precision 2 . A nuclear clock transfers the frequency reference from an electronic to a nuclear transition and the uniquely low-lying, laser-accessible, isomeric transition in 229 Th currently offers the most practical route to compact, robust timekeeping and sensitive tests of fundamental physics 3–8 . Realizing such a clock requires turning spectroscopy of the 229 Th nuclear resonance 9–17 into a stable discriminator for steering a traceable oscillator. Here we demonstrate a 229 Th nuclear clock by stabilizing a continuous-wave, narrow-linewidth 148.4 nm vacuum-ultraviolet (VUV) laser 18 to a resolved, weakly temperature-sensitive nuclear transition 17,19 in 229 Th:CaF 2 crystals 20–22 . A 10-μW VUV source generated by four-wave mixing in cadmium vapour 18,23,24 and phototube-based frequency modulation absorption readout provide a fast, high-signal-to-noise nuclear discriminator. The clock reaches a fractional frequency instability of $$5\times 1{0}^{-13}/\sqrt{\tau /{\rm{s}}}$$ 5 × 1 0 − 13 / τ / s for averaging time τ . Clock-transition frequencies measured in two independently fabricated crystals agree at the 10 −13 level and are consistent with previous VUV-comb measurements on other 229 Th:CaF 2 crystals 17 . These results establish laser-addressed nuclei as operational clock references and provide a reproducible solid-state platform for compact nuclear clocks, nuclear quantum sensors and precision tests of fundamental physics.

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

RNA catalysis emerges from dynamic structural ensembles

Maximilia F. S. Degenhardt, Hermann F. Degenhardt, Bapurao A. Bhoge, Yun-Tzai Lee, Ping Yu, Jinwei Zhang, Justin C. Deme, Jason R. Stagno, Yun-Xing Wang

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The dynamic interplay between RNA structure and its associated Mg 2+ ions is central to RNA function yet remains poorly understood at a near-atomic level 1–4 . Here, using a heterogeneity-focused protocol for cryo-electron microscopy data analysis of conformationally flexible RNA particles, we determined the structures of RNase P RNA ensembles composed of 76 coexisting active and inactive conformers that differ in a transient tertiary interaction that is critical for activity. The binding of the accessory protein does not change the local structure but induces thermodynamic allostery that enhances catalysis by altering the dynamics of the tertiary interaction. Four distinct classes of Mg 2+ ions have critical roles in the structure, dynamics and catalysis of the conformational ensembles. Together, these findings establish a new paradigm in which catalysis is regulated through multimodal communications coupled with the dynamics of RNA–Mg 2+ conformational ensembles, rather than a single static catalytic structure in a single action mode.

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

Overcoming key challenges in the evolutionary transition to multicellularity

G. Ozan Bozdag, Kai Tong, Peter J. Yunker, Matthew D. Herron, William C. Ratcliff

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Dozens of independent origins of multicellularity have profoundly shaped Earth’s evolutionary and ecological history. These transitions have given rise to massive radiations encompassing thousands to millions of species and the evolution of increasingly complex bodies. Multicellular taxa now constitute the majority of Earth’s biomass and have fundamentally transformed global ecosystems, underpinning diverse biomes from forests and grasslands to coral reefs. While these macroevolutionary patterns have long been recognized, the microevolutionary processes driving the transition to multicellularity have remained unclear. Questions remain on how solitary cells form cohesive groups, how these groups become evolutionary units capable of adaptation at the multicellular level, and how novel cell types and developmental patterns emerge. Recent discoveries of previously unknown multicellular species and the development of experimental models have provided important insights into these questions. This work reveals that seemingly insurmountable evolutionary hurdles are often readily overcome either through the repurposing of ancestral unicellular traits or through emergent properties of multicellular collectives that arise spontaneously. Here we review key breakthroughs in our understanding of the microevolutionary processes that underpin the evolution of increasingly complex multicellularity, focusing on mechanisms through which single cells can evolve into functionally integrated multicellular organisms.

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

Cryo-EM structure of a methanogen nitrogenase–PII protein supercomplex

Rajnandani Kashyap, Thomas M. Deere, Ahmed Dhamad, Melissa Chanderban, Monika Tokmina-Lukaszewska, Brian Bothner, Daniel J. Lessner, Edwin Antony

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Nitrogenases are metalloenzymes that catalyse the reduction of atmospheric dinitrogen to ammonia, sustaining the global nitrogen cycle1,2. Although bacterial nitrogenase has been extensively characterized, the architecture and regulation of archaeal nitrogenases have remained unknown despite longstanding evidence of nitrogen fixation in methanogens. Here we report a cryo-electron microscopy structure of a native nitrogenase–PII protein supercomplex from Methanosarcina acetivorans. The structure reveals an assembly of three NifDK heterotetramers bridged by six NifI1,2 heterotrimeric PII complexes, which sterically block NifH association and lock the enzyme in an inactive state. The PII complexes show asymmetric binding of ADP and 2-oxoglutarate, coupling nitrogenase inhibition directly to cellular energy and nitrogen status. Addition of 2-oxoglutarate and ATP releases the NifI complexes, stimulating a threefold increase in NifDK activity in vitro. This higher-order architecture identifies a regulatory strategy in methanogens in which PII proteins drive nitrogenase oligomerization to control activity. The finding that nitrogenase activity may be modulated through direct assembly into higher-order structures indicates future directions for the exploration of nitrogenase evolution, regulation and biotechnological applications.

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

Publisher Correction: Sleep chart of biological ageing clocks in middle and late life

NA, Cliodhna Kate O’Toole, Zhiyuan Song, Filippos Anagnostakis, Zhijian Yang, Ye Ella Tian, Michael R. Duggan, Chunrui Zou, Yue Leng, Yi Cai, Wenjia Bai, Cynthia H. Y. Fu, Michael S. Rafii, Paul Aisen, Gao Wang, Philip L. De Jager, Jian Zeng, Hamilton Se-Hwee Oh, Xia Zhou, Keenan A. Walker, Daniel W. Belsky, Andrew Zalesky, Eleanor M. Simonsick, Susan M. Resnick, Luigi Ferrucci, Christos Davatzikos, Junhao Wen

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

How to respond to hate speech without fuelling it further

Dhruv Shenai

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

Daily briefing: Can you name every female Nobel laureate?

Flora Graham

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

‘Learning about physics changed my life’: author Hernan Diaz on his new novel Ply

Benjamin Thompson

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

Medicine Nobel awarded for brain ‘switch’ that controls neurons with light

Miryam Naddaf, Ewen Callaway

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

Can pancreatic cancer be stopped in its tracks? Radical tactic raises hopes

Heidi Ledford

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

Stunning fossil shows dinosaurs’ distinctive path to flight

Sarah Wild

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

NASA releases trove of Moon data from historic Artemis II flight

Alexandra Witze

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

Nobel physics prize awarded for detection of cosmic neutrinos

Elizabeth Gibney, Davide Castelvecchi

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

Prozac use for childhood depression skewed by single flawed medical trial

Richard Van Noorden

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

Semiconductors pushed into insulator territory

Hironori Okumura

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

Nobel prizes 2026: ‘ghost’ particles, mirror molecules and light switches in the brain

Benjamin Thompson, Nick Petrić Howe

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

Rising numbers of Asian and African PhD students choose to study in China

Xiaoying You

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

Will AI scoop your science? Some researchers see a gloomy future

Kaia Glickman

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

Watch this invisible tattoo appear under UV light

Rachel Fieldhouse

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

The life of Darwin and the science of clouds: Books in brief

Andrew Robinson

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

Nature has rights — it is time the world recognized them

Juan Carlos Navarro, Callie Veelenturf

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

Why we must advocate for proper care on the frontlines of the Ebola outbreak

Melissa Hobson

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

The science of superintelligence and why AI is still a useful word

Jenna Ahart

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

Blend

E. J. Kavounas

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

Daily briefing: Chemistry Nobel goes to mirror-molecule researchers

Flora Graham

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

The Great Barrier Reef requires special attention in the developing super El Niño

Awais Shakoor

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

‘Vibe coding’ makes the dictionary: AI terms recognized by Merriam-Webster

Kaia Glickman

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

Why smart glasses are about to create a major privacy crisis

Joy Buolamwini

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

Why sound, strong science alone isn’t enough in pandemic preparedness

Melissa Hobson

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

Daily briefing: The sky as you’ve never seen it — the month’s best science images

Jacob Smith

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

Daily briefing: Physics Nobel for founder of neutrino-hunting observatory

Flora Graham

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

The top cancer success stories of the past 50 years, by the numbers

Heidi Ledford

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

Five movements from the edge of the singularity

D. Thomas Minton

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

Flu season could kick off ‘incredibly’ early — what scientists are watching

Mariana Lenharo

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

‘When prevention disappears, infections rise’: can the world still end AIDS?

Bianca Nogrady

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

Brain organoids grafted into cortex-free mice will advance human brain research

Marty G. Yang, Aparna Bhaduri

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

Maintaining global science collaboration during conflict requires fairer rules

Emmanuel Chidiebere Edeh, Ehizuelen Michael Mitchell Omoruyi

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

How we ditched presentations and embraced silence in our lab meetings

Manuel Spitschan

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

Big dogs age faster than little ones — rogue ‘jumping genes’ might be to blame

Heidi Ledford

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

Plague scare: what scientists know — and what Russia won’t say

Max Kozlov

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

Daily briefing: Medicine Nobel prize goes to optogenetics

Flora Graham

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

Gut microbes that trace ancient human journeys

Carina M. Schlebusch, Maja Vukovikj

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

Can you name the women who have won a science Nobel prize?

Richard Van Noorden

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

Circular DNA exposes a weakness in cancer cells

Nikolaus A. Watson, Jan O. Korbel

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

Strong evidence that ‘baryon junctions’ give proton its identity

José Guilherme Milhano, Néstor Armesto

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

Cells, who needs them? Biochemists turn to proteins in a tube

Amber Dance

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

How big tech is building a military–industrial complex in the age of AI

Chris Stokel-Walker

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

Woody ‘blankets’ are being deployed on Arctic permafrost to reduce carbon emissions

James Dinneen

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

Can we have class outside? Seven tips to breeze through outdoor lectures

Hannah Docter-Loeb

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Australia’s bush fires got worse after British colonization — this is why

James Dinneen

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Preprints must not leak sensitive research information

Jingyi Chen

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

Chemistry Nobel awarded for solving mystery of how ‘handed’ organic molecules can emerge

Elizabeth Gibney, Miryam Naddaf, Anne Pichon, Davide Castelvecchi, Ewen Callaway

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

How to build a mouse: embryo development captured in stunning detail

Ewen Callaway

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

‘What took them so long?’ This year’s medicine Nobel winner is overdue

Ewen Callaway

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

Can your brain grow new neurons? How researchers are solving a century-old puzzle

Mariana Lenharo

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

Nuclear clocks tick for the first time

Akio Kawasaki

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

An experiment to glimpse the future Amazon — in pictures

Meghie Rodrigues

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

Retrofitted LLM can count the letter ‘i’s in ‘artificial intelligence’

Zhao Zhang, Yingfei Xiong

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

UAE completes Arab world's first solo space probe – and sets course for an asteroid

Elizabeth Gibney

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

AI could undermine scientific independence in subtle ways

Fabio Y. S. Motoki

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Women are talking about menopause — health systems must listen

Hala Zahreddine Fahs

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US proposes $100,000 charge for international students to do post-graduate work

Dan Garisto

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OpenAI posts 700 maths preprints online: mathematicians are up in arms

Davide Castelvecchi

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

Briefing Chat: Top researchers are being misled by sham academic societies

Benjamin Thompson, Max Kozlov

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

Astronomy’s ‘adrenaline junkies’: Nobel prize captures the thrill of neutrino physics

Davide Castelvecchi

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

Revealed: how this common gut microbe protects against heart disease

Max Kozlov

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

How digital breakdowns affect supply chains — and endanger the global economy

Dabo Guan

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Australia’s current wildfire crisis linked to colonial land-use change

Michael-Shawn Fletcher, Anthony Romano, Caitlin O’Shea, S. Yoshi Maezumi, Harriet Magee, Simon Connor, Russell Mullett, Patricia Menéndez, Patricia S. Gadd, Michela Mariani, Manuel Chevalier, NA, Russell Mullett

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The global wildfire crisis1 is often attributed to climate change, a framing that overlooks crucial historical drivers. Biomes at the forefront of this crisis, such as the temperate eucalypt forests of Australia, have seen alarming increases in large, intense wildfires in recent decades. Yet evidence of how colonial land-use change and the disruption of Indigenous fire use altered vegetation structure and fuel dynamics remains scarce. Here we reconstruct 1,000 years of vegetation and fire change in a temperate eucalypt forest in southeastern Australia. Before the British invasion (from 1788 ce), fire use by the Indigenous Gunaikurnai people maintained stable, open woodlands through frequent, fine-grained, low-temperature cultural burning. Colonial disruption drove cascading changes: increased fire temperature, a fourfold rise in eucalypt cover, a shift from open woodland to forest and increased soil erosion. These transformations preceded anthropogenic warming, indicating that the vulnerability of these forests to wildfire is shaped by colonial land-use legacies. By creating more flammable landscapes, colonial land use amplified the influence of climate change, suggesting a reinforcing feedback (the ‘catastrophic wildfire loop’) in which high-intensity wildfires raise fuel loads and further increase the likelihood of climate-driven fire. Integrating Indigenous knowledge into fire management is therefore essential to restoring resilience and mitigating future wildfire risk.

Nature Human Behaviour

Algorithm-assisted personalized risk communication to encourage flu vaccination in the USA: three randomized field trials

Gail M. Rosenbaum, Amir Goren, Maheen Shermohammed, Donna M. Wolk, Ann Marie Tice, Joseph J. Doyle, Michelle N. Meyer, Christopher F. Chabris

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Artificial intelligence (AI) is increasingly used in healthcare to identify high-risk patients. Laboratory studies are mixed regarding patient attitudes towards AI use. Here we field-tested whether informing patients of their risk for influenza and its complications can serve as an effective behaviour-change intervention to increase vaccination, and whether disclosing AI use in the risk determination or providing personalized reasons for the algorithm’s prediction (a form of explainable AI) influence message effectiveness. We ran three preregistered randomized controlled trials with over 90,000 unique healthcare system patients in the USA (ClinicalTrials.gov identifiers: NCT04323137, NCT05009251 and NCT05509283). Patients identified by a previously validated machine learning algorithm as being at high risk for influenza and related complications were randomized to be sent no message or one of several different messages encouraging influenza vaccination (the primary outcome). High-risk nudges increased vaccination: among patients informed of their high risk, vaccination was 1.1–1.4 percentage points (3.3–5.4%) higher than those simply reminded to get a vaccine, and 1.7–3.5 percentage points (3.3–14.7%) higher than non-messaged patients. Vaccination was similar across message arms that did versus did not disclose ‘algorithm’ involvement or its risk explanations, indicating that patients are neither averse to nor appreciative of algorithm use or explainability in this realistic health application. This work was partially funded by the National Institute on Aging of the National Institutes of Health under award number P30AG034532.

Microdelays disrupt online learning

Asaf Mazar, Geoff Tomaino, Abubakir Siedahmed, Ahmad Abdolsaheb, Neil T. Heffernan, Ziv Carmon, Angela L. Duckworth

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An ever-growing share of education happens on screens. We examine an overlooked feature of modern education: ‘microdelays’—brief loading lags that could hinder learners with slower internet connections. In two longitudinal quasi-experimental field studies, microdelays as short as 1–2 s predicted impaired learner engagement and achievement. When faced with microdelays, US primary and secondary school students (N = 26,707) completed fewer online math assignments, took longer to complete assignments, were more likely to get distracted mid-task and earned lower scores. Likewise, when aspiring coders, primarily in Latin America (N = 55,184), experienced microdelays, they spent less time actively engaged, multitasked more often, completed fewer lessons and were less likely to attain a key course milestone. Our results held across a range of model specifications, and leverage within-person variation in load times to support a causal interpretation. These findings identify microdelays as a hitherto-overlooked barrier in online learning.

Contract incentives and behaviours of medical consultants in Ireland

Xidong Guo, Eóin T. Flaherty, Huihui Li, Jiming Zhu

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In publicly funded healthcare systems that also allow private hospital treatment, there is often a concern that consultants might prioritize private patients. Here we examine how a 2014 reform in Ireland, which allowed public hospitals to accommodate private patients in public wards, affected consultant behaviours and patient outcomes. Using nationwide inpatient discharge data from 2009 to 2015 (2.3 million observations) and applying Little’s Law with a difference-in-differences method, we find no evidence that the share of private patients increased. We attribute this pattern to contracts requiring consultants to treat an additional three or four public patients for each treated private patient. The reform incentivized consultants to treat more public patients by shortening the lengths of stay for both public and private patients. However, such efficiency gains may come at the expense of care quality for public patients.

Recreational screen use and internalizing problems from preadolescence to young adulthood in a longitudinal twin cohort with co-twin comparison

Tong Gong, Emma Frans, Anna Ohlis, Shuyang Yao, Ruyue Zhang, Anders Nilsson, Yasmina Molero, Miriam A. Mosing, Isabell Brikell, Henrik Larsson, Paul Lichtenstein, Lisa B. Thorell, Patrik KE Magnusson, Ralf Kuja-Halkola, Yi Lu

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The mental health impact of increasing recreational screen use among youth has raised substantial concerns, yet questions about causality remain unresolved. Here, leveraging a co-twin control design, we examined associations between screen use and internalizing problems from childhood to early adulthood among 21,797 Swedish twins, accounting for shared familial factors. Recreational screen use was associated with increased internalizing symptoms and clinical diagnosed depression and anxiety. However, these associations were substantially attenuated within discordant twin pairs and did not remain statistically significant after correction for multiple testing. These findings suggest that shared genetic and environmental factors partly explain the association between youth screen use and mental health. Although co-twin estimates provided limited evidence for clear causal effects, the association between heavy interactive screen use and clinical risk highlights the need to understand potential mechanisms linking digital behaviours and youth mental health.

Proceedings of the National Academy of Sciences

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

Causality-integrated graph learning for multi-endpoint toxicity prediction

Haoyue Tan, Tong Bao, Yin Fang, Rong Zhang, Jinsha Jin, Dan Xu, Lan Xie, Huan Zhong, Xuezhi Xiao, Huixiao Hong, Emilio Benfenati, Tadahaya Mizuno, Qing Zhou, Jingfan Qiu, Changsheng Qu, Yan Mao, Xiangyi Yu, Jing Guo, Hongxia Yu, Xiaowei Zhang, Wei Shi

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Toxicity prediction remains a longstanding challenge in the safety assessment of numerous artificial chemicals. While conventional single-endpoint models are effective for predicting many molecular properties, they fail to capture the complex mechanisms underlying toxicity, which involve multiple molecular targets, interconnected pathways, and diverse outcomes. We present a causality-integrated graph learning framework that embeds toxicological mechanisms extracted from large-scale literature mining as directed graphs within deep learning (DL) models. By using chemical structure as input, the framework generates compound-specific perturbation profiles within a fixed causal space, enabling system-level classification, quantitative prioritization, and mechanistic interpretation across multiple outcomes. Focusing on endocrine-disrupting chemicals, we constructed a large-scale, causally organized knowledge graph (EDKG) and implemented the framework as EDKG-DL, a predictive model that incorporates mechanism-aware graph reasoning. Through extensive external validations, EDKG-DL outperforms structure-driven state-of-the-art approaches in both stability and cross-scenario generalization. This work establishes a mechanism-constrained, causality-informed learning paradigm that is highly relevant for multi-endpoint toxicity assessment and regulatory decision-making.

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

Vaccine data suggest immunity could mitigate dementia. What’s the biology behind these apparent effects?

Jyoti Madhusoodanan

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

Opposing activity of SOX9 and Wnt in the developing otocyst ensures SOX10 control of endolymphatic development

Ka Chi Chu, Jianning Lu, Keith K. H. Leung, Nelson W. F. Dung, Kathryn S. E. Cheah

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Proper development of the inner ear, including specification and differentiation of progenitors for the endolymphatic sac, is crucial for hearing and balance. In a mouse model of the SOX9 Y440X/+ mutation that causes campomelic dysplasia and deafness, impaired development of the endolymphatic system at mid-gestation was associated with SOX10 downregulation. The underlying molecular causes and significance are unclear. Here, we found in Sox9 Y440X/+ mice, Sox10 expression was downregulated, prior to overt differentiation, in the dorsomedial aspect of the E10.5 otic vesicle that normally becomes the endolymphatic duct and sac. Single-cell transcriptomic profiling of E10.5 otic vesicles showed increased expression of Wnt pathway genes that was associated with the domain-specific decrease in Sox10 expression. Forced elevation of Wnt signaling by expression of stabilized β-catenin in the early otocyst and more developed inner ears, suppressed Sox10 expression. Wnt exerted an inhibitory effect on SOX10 expression in otocyst-like organoids derived from human pluripotent stem cells. In vitro transactivation assays reveal antagonistic action of SOX9 and Wnt signaling on Sox10 transactivation mediated by conserved enhancers with neighboring/overlapping SOX9- and TCF/LEF-binding (Wnt effectors) motifs. We propose a conserved SOX9-Wnt antagonism acting via conserved enhancers, regulates SOX10 to modulate endolymphatic cell fate. The SOX9 Y440X/+ mutation disrupts this regulatory circuit through both dominant-negative and haploinsufficient effects culminating in impaired establishment of progenitors in the otocyst that are essential for the development of the endolymphatic system for hearing and balance.

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

Global divergence in urban–rural vegetation resilience driven by broken ecological trade-offs

Zhengfei Guo, Giovanni Forzieri, Manuel Esperon-Rodriguez, Jianguo Wu, Yuhao Feng, Yingyi Zhao, Guangqin Song, Xiang Zeng, Kun Zhang, Hongsheng Zhang, Peng Gong, Nate McDowell, Yuyu Zhou, Jin Wu

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While urban environments are known to extend growing seasons and enhance vegetation growth, whether these benefits also improve resilience to climate stress or instead create productive but vulnerable ecosystems remains uncertain. Using satellite observations from 2001 to 2022 across 751 large cities in 109 countries, we find that urban vegetation is more resilient than surrounding rural vegetation in 78% of cities. This urban–rural resilience gap has widened over time, driven by declining rural resilience alongside slightly improving urban recovery dynamics, particularly in arid regions where rural vegetation shows progressively slower recovery. Among the factors examined, the urban irrigation proxy, quantified as the urban–rural difference in evapotranspiration, was the strongest correlate of the urban resilience advantage, followed by canopy structure. In 32% of cities, predominantly located in arid regions, urban vegetation exhibited a dual advantage, combining smaller disturbance-related greenness losses with faster recovery than rural vegetation, consistent with management-mediated relaxation of the resistance–resilience trade-off. These findings challenge the view of cities as uniformly detrimental to ecosystem stability and suggest that, when supported by sustainable and equitable management, urban green spaces may serve as managed refugia for vegetation resilience under climate change.

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

Interventions to mitigate post-infection morbidity: Management insights from simple models

Prakhar Jaiswal, Daniel Coombs, Caroline E. Wagner, Troy Day, Chadi M. Saad-Roy

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A variety of pathogens that cause acute disease can also affect their host long after recovery. These post-infection effects lead to elevated costs for individuals and societies, which can be mitigated by large-scale interventions. Here, we examine the management of post-infection morbidity with mathematical models. First, we show that long-term usage of nonpharmaceutical interventions can reduce post-acute burden. Second, to investigate how post-infection effects affect optimal vaccination coverage, we generalize and expand on classic epidemiological-economic models. We include post-infection costs, and consider the cost of vaccination as a general increasing function of coverage. If there is some sub-elimination coverage that locally minimizes costs (beyond elimination), we show that the decision of whether to vaccinate or not is independent of the transmission rate (however elimination does depend on this). Echoing existing theoretical results with exponentially increasing costs, we find that if vaccination costs either only accelerate or only decelerate with increased coverage, there is a unique, transmission-independent interior level of vaccination coverage (nonzero and sub-elimination) that locally minimizes or maximizes societal costs, respectively. In all settings, we show that post-infection effects can substantially shift societal incentives toward elimination. Furthermore, when costs of vaccination change concavity, the optimal coverage level is very sensitive to post-infection costs: a small increase can shift optimal coverage from none (or low coverage) to elimination. Our findings demonstrate that post-infection morbidity has important implications for policy and management, and that there is an urgent need to quantify costs of post-infection effects and of large-scale vaccine deployment.

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

Late-onset preeclampsia is characterized by accelerated placental aging

Anya L. Arthurs, Rudrarup Bhattacharjee, Melanie D. Smith, Dulce L. Medina Garcia, Ellen Menkhorst, German Mora, Jessica M. Williamson, Lynda K. Harris, Jose M. Polo, David A. MacIntyre, Claire T. Roberts

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Late-onset preeclampsia (LOPE) is a major pregnancy complication characterized by hypertension and placental dysfunction, resolving only upon delivery. Here, we show that LOPE placentae undergo accelerated molecular aging, marked by telomere attrition, DNA damage, and trophoblast senescence. Using primary placental tissue and trophoblast organoids, we demonstrate oxidative stress as a driver of telomere shortening and angiogenic imbalance. Inflammation did not alter placental aging trajectories. Antioxidant treatment (superoxide dismutase) preserved telomere length, reduced DNA damage, and restored angiogenic balance, highlighting oxidative stress as a modifiable determinant of placental aging. We identify reduced expression of telomeric repeat-containing RNAs (TERRAs) as a molecular hallmark of LOPE, and show that antisense oligonucleotide-mediated TERRA depletion exacerbates telomere erosion and senescence. Together, these findings delineate oxidative stress and TERRA loss as mechanisms driving placental decline, establish trophoblast organoids as a tractable model of placental aging, and reveal potential therapeutic avenues for mitigating preeclampsia-associated placental dysfunction.

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

Untangling microbial diversification in Antarctic soils—One strain at a time

Jill A. Mikucki

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

Enhancement of hippocampal synaptic AMPA receptor function by the antidepressant tianeptine and by opioid peptides

Anna Mariano, Andrei Rozov, Grant D. Phillips, Sam Singleton, Daniel Baptista-Hon, Fliza Valiullina-Rakhmatullina, Rolf Sprengel, Rosamund Langston, Stephen J. Martin, Tim G. Hales, Jeremy J. Lambert

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Management of major depressive disorder (MDD) with conventional therapeutics that enhance monoaminergic neurotransmission requires prolonged treatment prior to clinical benefit and a substantial proportion of patients show little or no improvement. Identifying alternative molecular targets is required to develop efficacious, rapid acting antidepressants. In this regard, tianeptine, an established but atypical clinical antidepressant, is of interest. Tianeptine does not directly influence monoamine levels; in rodents it has a relatively rapid onset of antidepressant-like efficacy and, unusually for an antidepressant, exhibits procognitive properties. Here, voltage-clamp recordings from mouse hippocampal CA1 pyramidal neurons demonstrated tianeptine enhanced the amplitude of neurally evoked excitatory postsynaptic currents mediated by glutamate activation of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). The effect required intracellular polyamines and expression of the GluA1 subunit. These observations suggest that tianeptine relieves the channel block by endogenous polyamines of synaptic GluA1 containing AMPARs (GluA1-AMPARs). The tianeptine effect was abolished by postsynaptic inhibition of G-protein signaling, was reduced in mice lacking either the µ- or the δ-opioid receptor, and inhibited by selective antagonists of these receptors, collectively demonstrating that the facilitation of excitatory transmission was indirectly mediated by activation of opioid receptors. Importantly, enhancement of GluA1-AMPAR function was mimicked by opioid peptide and nonpeptide agonists selective for µ- or δ-receptors. These observations improve understanding of how the antidepressant tianeptine enhances glutamatergic transmission but more generally suggest that endogenous and exogenous opioids act in a similar manner, which may contribute to their behavioral effects.

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

SETDB1 preferentially silences evolutionarily young retroelements

Bercin K. Cenik, Simai Wang, Marta Iwanaszko, Benjamin C. Howard, Irem Aydin, Sarah Gold, Vijay Ramani, Ali Shilatifard

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Transposable elements (TEs) are epigenetically silenced through multiple mechanisms, including heterochromatin formation and DNA methylation. Prior studies have implicated SETDB1 and the Human Silencing Hub (HUSH) complex in heterochromatin formation-based TE repression, but precise characterization of repeat subclass and locus-specific effects for SETDB1 and related mechanisms has been limited by short-read transcriptome mapping. Here, we use long-read RNA sequencing mapped to a telomere-to-telomere mouse genome assembly to resolve the specific contributions of SETDB1 to TE silencing at single-locus resolution. Knockdown of SETDB1 or core HUSH factors reveals robust and reproducible derepression of a restricted subset of long terminal repeat (LTR) retroelements distinct from those of global DNA demethylation. This derepression is heterogeneous within TE subclasses and is confined to discrete genomic loci, highlighting regulatory diversity that is obscured by aggregate, family-level analyses. Time-resolved SETDB1 depletion followed by histone 3 lysine 9 (H3K9)me3, H3K9me2, and Pol II ChIP-seq reveals a stratified derepression response: ERVK and ERV1 elements show concordant H3K9 methylation loss, Pol II gain, and RNA expression induction, consistent with direct H3K9me3-mediated silencing, whereas LINE/L1 elements show transcriptional activation without corresponding H3K9me3 loss, implicating parallel repressive mechanisms. These data support a model in which SETDB1-dependent H3K9 methylation maintains silencing of evolutionarily young LTRs, while long interspersed nuclear element (LINE) repression engages broader heterochromatic pathways not fully captured by any single chromatin readout. Collectively, our findings refine current models of heterochromatin-mediated TE control and provide a framework for dissecting how chromatin-based mechanisms cooperate to maintain subclass-selective TE repression.

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

Density-dependent aggregation underlies spatial self-organization in coastal dunes

Paul M. J. Berghuis, Koen Siteur, Valérie C. Reijers, Angeles G. Mayor, Tjisse van der Heide, Johan van de Koppel, Max Rietkerk

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Across coastal ecosystems, habitat-forming organisms interact with wind and water to generate biogeomorphic feedbacks that produce spatially patterned landscapes. Such spatial patterns can emerge through different self-organizing mechanisms, with contrasting implications for ecosystem resilience. Here, we test whether spatial dynamics in developing coastal dunes are better explained by scale-dependent feedback or by density-dependent aggregation (DDA), the latter being a more recently proposed mechanism of spatial self-organization. Using high-resolution aerial imagery and coupled time series of elevation, we tracked the spatial dynamics of dune-grass patches and sand accumulation during early dune development. Rather than converging toward a dominant size or spacing, both dune-grass patches and the dune bodies they collectively form coarsened through time, with self-similar size distributions shifting toward larger scales. Sand accumulation was disproportionately concentrated in already-dense vegetation, with a density–growth relationship that changes sign at a critical threshold. Together, these findings are consistent with DDA rather than scale-dependent feedback as the dominant mechanism of spatial self-organization in developing coastal dunes. The resulting density–growth relationship implies threshold-dependent resilience to local disturbances. Once local vegetation density falls below a critical point, decline is self-reinforcing rather than self-dampening, with direct consequences for how dune disturbance and recovery are understood and managed.

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

Neutralization titers reveal the structure of polyclonal antibody responses

Henry Alston, Thierry Mora, Aleksandra M. Walczak

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The composition of a polyclonal antibody response is hard to measure experimentally but contains vital information about the robustness of immunity. Here, we argue that the statistics of neutralization titers alone can be used to make quantitative predictions about the composition of the response, circumventing challenges arising through sequencing and monoclonal antibody expression. We show that the response against influenza within a cohort can be either driven by a collective phenomenon where many antibodies contribute to neutralization, or dominated by just a few strong binders, leading to a broad distribution of titers across individuals described by a Gumbel distribution from extreme value theory. Comparing titers across cohorts, we find that Gumbel statistics accurately describe individuals prior to an immune challenge. We propose an equilibrium binding model that quantitatively captures titer data and illustrates the structure of the polyclonal response. Our approach extends generically to immune responses to other pathogens.

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

Titin extension explains residual force enhancement in skeletal muscle

Christopher Tiessen, Armaan Sekhon, Dhairya Desai, Tim Leonard, Fatima Abu Shagra, Samhar Samer Alouch, Walter Herzog

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Residual force enhancement (RFE) is an inherent property of mammalian skeletal muscle. After eccentric stretch, muscle produces increased steady-state force compared to purely isometric contraction at the same sarcomere length and activation level. This property has been known for over 70 y and yet remains largely unexplained. Titin, a giant spring-like protein responsible for passive force generation and stabilization of the sarcomere, has been suggested as a potential candidate for causing RFE. To test whether titin may be responsible for RFE, we used multiple titin immunolabels on single isolated myofibrils to approximately track the migration of individual titin segments in real-time. In comparison to many previous attempts to label titin in sarcomeres, our labeling using N2A and distal PEVK labels did not impact mechanical properties of the myofibril and thus permitted accurate tracking of titin segments within single sarcomeres. We found the approximate length of titin’s PEVK segment was significantly longer in RFE compared to isometric control activations at similar final sarcomere lengths, indicating increased force on titin filaments in RFE. Using a modified worm-like chain model, we predict titin-associated force contributes up to 62% of increased force during RFE. Additionally, using a continuous eccentric stretch protocol, we provide indirect evidence suggesting titin–actin interactions may be responsible for increased force on titin during RFE. To date, this represents one of the most convincing pieces of evidence suggesting that titin is responsible for RFE. Thus, our data indirectly support the proposed “three-filament model” where muscle activation induces cross-bridge interactions and titin–actin interactions.

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

Dystrophic changes of nigrostriatal axons harboring a SYNJ1 Parkinson’s mutation suggest catastrophic failure of endocytic mechanisms

Yumei Wu, Peng Xu, James Moran, C. Shan Xu, Kenneth J. Hayworth, Mian Cao, Lin Shao, D. James Surmeier, Harald F. Hess, Pietro De Camilli

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Synaptojanin 1 is a brain enriched phosphoinositide phosphatase implicated in endocytosis at the synapse. A mutation (R258Q) that selectively impairs its Sac1 phosphatase domain causes early onset familial Parkinsonism. Neurons of mice with this mutation display synaptic vesicle traffic defects across the brain, but selective dystrophic changes in a subset of dopaminergic axons in the dorsolateral striatum. Using correlative light microscopy-FIB-SEM of mutant mouse striata to visualize in 3D these abnormal structures we show that they represent clusters of focal axonal dilations harboring massive, onion-like DAT enriched plasma membrane infoldings, generally localized next to cell bodies of neighboring cells, often engulfing evaginations of such cells. This dysmorphia was associated with a deficit in dopamine release in the same striatal region. Given the involvement of Synj1 in endocytic mechanisms, these structures may reflect an imbalance between exocytosis and endocytosis. Their occurrence only in a subset of axons suggests a vulnerability threshold of these axons beyond which the expansion of the plasma membrane is not counteracted by compensatory mechanisms.

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

Structural basis for membrane-dependent positive feedback regulation of DOCK11 by activated Cdc42

Tamao Hisano, Takehiro Shinoda, Mutsuko Kukimoto-Niino, Kazushige Katsura, Ryohei Kondo, Yoshiko Ishizuka-Katsura, Yukako Miyata-Yabuki, Kazuharu Hanada, Reiko Nakagawa, Akihiko Nishikimi, Mikako Shirouzu

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The guanine nucleotide exchange factor DOCK11 is widely expressed across tissues and activates Cdc42, a Rho family GTPase that regulates cytoskeletal remodeling and cell polarity. Loss-of-function mutations in DOCK11 have recently been linked to inborn errors of immunity. DOCK11 has also been implicated in facilitating hepatitis B virus infection in hepatocytes and has emerged as a potential target for therapeutic interventions. A positive feedback mechanism has been proposed for DOCK11-mediated Cdc42 activation; however, the structural basis for this regulation has remained unclear. Here we report the cryoelectron microscopy structures of full-length DOCK11 as an apo dimer, a binary complex with nucleotide-free Cdc42, and a ternary complex containing both nucleotide-free and activated Cdc42. DOCK11 predominantly adopts a U-shaped dimer that binds to nucleotide-free Cdc42 via the catalytic domain, whereas activated Cdc42 engages a distal site within the armadillo-repeat domain. Biochemical and cellular analyses demonstrate that binding of activated Cdc42 is critical for enhancing the membrane-dependent nucleotide exchange activity of DOCK11, promoting its localization to the plasma membrane, and facilitating intracellular activation of Cdc42. We also determined the structure of the membrane-bound ternary complex using membrane-coated grids. Strikingly, the ternary complex adopts an extended conformation that aligns multiple membrane-contact elements, revealing how activated Cdc42 stabilizes DOCK11 membrane binding for efficient exchange activity. Collectively, these findings provide a structural framework for the coordinated mechanism underlying membrane-dependent positive feedback in Rho GTPase signaling.

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

53BP1 condensates regulate DNA replication progression and completion

Fangfang Wang, Xinran Geng, Junqiu Zhang, Yen-Jui Su, Franklin Mayca Pozo, Akram Osman, Christophe E. Redon, Anjali Dhall, Michael Leffak, Zihua Gong, Mirit I. Aladjem, Masaru Miyagi, Youwei Zhang

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DNA replication in mammalian cells proceeds in chromosomal domains during defined windows of S phase; however, the mechanisms coordinating replication with restoration of chromatin states remain incompletely understood. Here, we identify p53-binding protein 1 (53BP1) condensates as regulators of heterochromatin replication and epigenetic restoration. Loss of 53BP1 delays mid-to-late S-phase progression, compromises recruitment of epigenetic restoration factors, and impairs timely completion of heterochromatin replication and restoration of heterochromatin-associated epigenetic marks. These defects were rescued by wild-type or condensate-competent 53BP1, but not by condensate-deficient mutants. Further, 53BP1 condensate formation and its role in heterochromatin replication depend on interaction with proliferating cell nuclear antigen, which also mediates 53BP1 relocalization from condensates to DNA damage foci upon genotoxic stress. Together, our findings reveal a previously unrecognized role for 53BP1 condensates in coordinating heterochromatin replication and epigenetic restoration, while serving as a reservoir for DNA damage response.

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

NA-CDQuant: Quantitative spectral analysis of nucleic acid structure by circular dichroism spectroscopy

Kevin Mosca, Søren Vrønning Hoffmann, Nykola C. Jones, Richard R. Sinden, Frank Wien, Sergio Marco, Véronique Arluison

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Understanding the structural conformation and dynamics of nucleic acids in solution is critical for the development of nucleic acid therapeutics involving antisense or mRNA therapies, where controlling stability, efficacy, and manufacturability are important. Circular dichroism (CD) spectroscopy allows rapid and nondestructive solution analysis of the spatial arrangements of nucleic acids. While widely used to analyze protein structure, the potential of CD for DNA- and RNA-based pharmaceutical applications has remained largely unrealized because nucleic acid spectra are complex and difficult to interpret quantitatively. We introduce herein a framework (NA-CDQuant) that transforms CD from a qualitative fingerprinting method into a quantitative tool for nucleic acid structure prediction by combining spectral deconvolution with a rigorously curated synchrotron radiation circular dichroism reference library comprising 18 structurally defined conformational families. This systematic classification overcomes long-standing challenges posed by spectral overlap and structural polymorphism, enabling estimation of the fractional composition of coexisting conformations during real-time monitoring of structural transitions in solution. NA-CDQuant provides mechanistic insight into subtle conformational redistributions that may affect molecular recognition and functional performance assisting pharmaceutical development and medical application by facilitating formulation optimization, stability assessment, quality control, and regulatory support of nucleic acid–based therapeutics.

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

Bone morphogenetic protein signaling as a key regulator of retinal fibrosis

Sonali Sharma, Gieth Alahdab, Muhammad Nazmul Haque, Ikbal Karkoukli, Alee Assaf, Yuichiro Ishida, Ahmed Abu Elasrar, Mohamed Moustafa, Mohamed Tarek, Xiao Zhang, Kenneth P. Mitton, Natasha Josifovska, Goran Petrovski, Hiroki Ueharu, Yuji Mishina, Mohamed Al-Shabrawey

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Retinal fibrosis is a blinding complication of proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD) and idiopathic epiretinal membrane (iERM), yet effective therapies remain lacking. The purpose of this study was to investigate the role of BMP2 and BMP4 (BMP2/4)–activin receptor-like kinase (ALK) signaling in retinal fibrosis. BMP2 was detected in the vitreous of PDR, PVR, and rhegmatogenous retinal detachment (RRD) samples at concentration of 70, 180, and 85 pg/mL respectively, whereas it was present only at trace levels or was undetectable in the vitreous of macular hole and idiopathic ERM samples (~0.1 pg/mL). PDR, PVR, and idiopathic ERMs exhibited strong immunoreactivity for BMP2, BMP4, ALK3 (Bmpr1a), pSMAD1/5/9, and pSMAD4. Formation of preretinal fibronectin-containing membranes resulted from intravitreal injection of wild-type mice with BMP2 and similar membranes formed in mice expressing constitutively active ALK3 (caBmpr1a). The presence of preretinal membrane in caBmpr1a was confirmed by optical coherence tomography. The limited hyperoxia-induced proliferative retinopathy (LIHPR) model demonstrated a progressive increase in the retinal expression of BMP2 and BMP4and development of preretinal membrane. Administration of BMP/ALK inhibitor LDN193189 induced regression of the preretinal membrane in LHIPR. BMP2 and BMP4 induced a significant increase in the expression of Glial Fibrillary Acidic Protein (GFAP), fibronectin, and collagen-VI in cultured rat Muller glial cells, and increased fibronectin was reversed by BMP/ALK inhibition. BMP2 also significantly upregulated fibronectin and activated matrix metalloproteinase-2 in human retinal endothelial cells. These findings support BMP2/4–ALK signaling as a potential mediator and therapeutic target in retinal fibrosis.

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

Transcriptional regulation and function of GPR18 in macrophage subtype specification

Hebe Agustina Mena, Andreas Patsalos, Jake Altomare, Filippa Davidsson, Gergely Nagy, Wilhelm K. Berger, Blenda Wong, Allison Rahtes, Gabrielle Fredman, Laszlo Nagy, Matthew Spite

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Resolution of inflammation is mediated in part by agonists that engage immune cells to dampen inflammatory signaling, promote phagocytic functions, and facilitate tissue repair. G protein–coupled receptor 18 (GPR18) has emerged as an important proresolving receptor that is activated by endogenous mediators including Resolvin D2. However, very little is known about how GPR18 expression is controlled in immune cells, and its cell-autonomous roles during resolution of inflammation remain of interest. Here, we elucidated transcriptional and epigenetic regulation of Gpr18 in macrophages (MFs). We identified binding of monocyte/macrophage lineage-determining transcription factors (LDTFs) including PU.1, IRF8, and RUNX1 at the Gpr18 locus in the basal state in murine bone marrow–derived macrophages (BMDM). We found that Gpr18 is highly induced in BMDM by inflammatory stimuli including interferon gamma (IFNγ) and ligands for multiple toll-like receptors. Motif analysis predicted enrichment for LDTFs and signal-dependent TFs including nuclear factor κB (NFκB) and interferon regulatory factors (IRF) at the Gpr18 locus. Stimulation of BMDM with lipopolysaccharide (LPS) or IFNγ increased the binding of NFκB p65 and IRF1 at the Gpr18 locus, which played a causal role in the induction of Gpr18 by LPS or IFNγ, respectively. Mice with myeloid deficiency of Gpr18 had increased tissue swelling and accumulation of “inflammatory” Ly6C hi monocytes/MFs during contact hypersensitivity, which was recapitulated during acute peritonitis and led to altered transcriptomes of resolution-phase MFs. These results demonstrate that inflammatory signaling primes MFs for resolution in part by inducing Gpr18 , which plays a cell-autonomous role to regulate MF phenotypic transitions.

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

Multiple-oxygen isotope constraints on aerobic respiration and gross primary productivity

Eleanor R. Hughes, Kevin M. Sutherland, David T. Johnston

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Primary production on land and in the surface ocean is a critical component of Earth’s carbon and oxygen cycles, controlling the uptake of CO 2 and the release of O 2 to the atmosphere. Quantitative estimates of these O 2 and CO 2 fluxes remain challenging. Of the methods used, the triple-oxygen-isotope analysis of O 2 is considered to provide the most robust in situ estimate of gross productivity. However, this method relies on one key assumption—that the oxygen isotope fractionation of aerobic respiration is constant—and recent experimental studies have shown that it can vary significantly. When applied to the same calculation of gross productivity, the experimentally determined variation in fractionation could produce > 100% error. In this work, the mechanistic origin of the variation in respiratory fractionation is explored using experiments on the model organism Escherichia coli . These experiments suggest that the fractionation is strongly correlated with the cell-specific O 2 consumption rate, weakly correlated with the dissolved-O 2 concentration, and may also depend on the identity of the terminal oxidase enzyme used to reduce O 2 . Modeling suggests that these influences on fractionation are likely to be important in the marine water column, and could produce up to ± 120% error in estimates of gross productivity made using triple-oxygen-isotope analyses. This error may be significantly reduced through concurrent analyses of the “clumped” (multiply substituted) isotopologue abundances in O 2 .

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

Pelvis shows Neanderthals differed from humans in locomotion but not in birth

Robert G. Tague

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

MATRIN3 deficiency in human cells triggers an autoinflammatory response via cGAS–STING activation

Zohirul Islam, Ahsan H. Polash, Colin L. Sweeney, Masataka Suzawa, Bryan Chim, Sabrina Sultana, Skyler Kuhn, Nicholas Cutrona, Xiuhuai Liu, Patrick T. Smith, Tibor Z. Veres, Juraj Kabat, Sundar Ganesan, Amir K. Foroushani, Markus Hafner, Stefan A. Muljo

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MATRIN3 (MATR3) is a broadly expressed nuclear RNA-binding protein. However, the mechanisms by which MATR3 maintains human cellular health remain poorly understood. In this study, we employed gene editing to model MATR3 deficiency in human induced pluripotent stem cells (iPSCs) and the HAP1 haploid cell line. To investigate the consequences of MATR3 loss-of-function, we profiled gene expression changes by RNA sequencing, which revealed significant upregulation of interferon-stimulated genes (ISGs) in MATR3-deficient cells, indicating activation of innate immune signaling. To elucidate the mechanism underlying ISG upregulation, we identified direct targets of MATR3 using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP). In one of these targets, TDRD3 , a gene required for R-loop metabolism in conjunction with Topoisomerase III Beta ( TOP3B ), MATR3 loss induced the incorporation of a 53-nucleotide-long poison exon that triggered nonsense-mediated decay and subsequent reduction in its expression. Consistent with dysfunction of the TDRD3–TOP3B complex, MATR3 loss led to the aberrant accumulation of cytoplasmic RNA–DNA hybrids, which activated the inflammatory cGAS–STING pathway. These findings uncover a previously unrecognized role of MATR3 in maintaining RNA processing fidelity and cellular homeostasis, and establish a mechanistic link between MATR3 dysfunction and innate immune activation. This molecular cascade has significant implications, hinting at a plausible disease mechanism underlying MATR3-associated neurodegenerative diseases, and other conditions of MATR3 deficiency yet to be discovered. Furthermore, these molecular insights provide potential avenues for diagnosing and treating MATR3 loss-of-function in humans.

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

Tailored speckle illumination microscopy with enhanced sectioning and image quality

SeungYun Han, KyeoReh Lee, Young Seo Kim, Chuan Li, Nicholas Bender, Kabish Wisal, Taeyun Ku, Jerome Mertz, Hui Cao

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Optical speckle patterns have been widely used for illumination in computational imaging, optical sectioning microscopy, and superresolution imaging. However, commonly used speckles satisfy Rayleigh statistics, which are not ideal for diverse imaging applications. Here we tailor three-dimensional speckle intensity statistics for dynamic speckle illumination microscopy based on linear fluorescence. Optical sectioning is enhanced by axially varying speckle contrast, and image reconstruction noise is minimized with in-focus speckles of binary intensities. The customized speckle statistics are shown to tolerate sample-induced aberration and scattering. We apply tailored speckle illumination to mouse brain vascular imaging and demonstrate much improved image quality than optical-sectioning structured illumination. These results establish customization of speckle intensity statistics as a promising strategy for robust, high-throughput fluorescence imaging in thick, scattering biological specimens.

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

Chronic intermittent heat exposure induces anxiety in female mice via TLR4 upregulation in paraventricular nucleus CRH neurons

Shuqing Zhu, Meng Sun, Ziyuan Ye, Ying Zhou, Yiheng Wu, Wenxi Chen, Jieshan Li, Xiaohua Feng, Shangwu Ye, Xiaomin Chen, Yuhe Wang, Gang Shu, Songbo Wang, Qingyan Jiang, Lina Wang

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Environmental stress has long been recognized as a pivotal contributor to the onset of anxiety. In this study, we reported that two weeks of chronic intermittent heat exposure (CIHE) induces anxiety only in female mice and is accompanied by a significant reduction in the responsiveness of corticotropin-releasing hormone (CRH) neurons located in the paraventricular nucleus (PVN). Moreover, toll-like receptor 4 (TLR4), which is expressed on CRH neurons, has been identified as a critical mediator of this process. Further research has demonstrated that the overexpression of TLR4 in CRH neurons in the PVN contributes to the development of anxiety in mice by disrupting synaptic signaling in supramammillary nucleus (SuMM) projections from CRH neurons. Oral ester β-hydroxybutyl (HBET) can effectively prevent anxiety induced by CIHE in mice. In summary, our research provides compelling evidence that TLR4 expressed on PVN CRH neurons plays a pivotal role in mediating anxiety-like behaviors in mice induced by CIHE and offers potential therapeutic strategies for addressing stress-related metabolic and psychiatric complications.

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

Reply to Roff: Ecological readiness must evolve with AI

Gayatri Mishra

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

Reaction-based cryo-EM resolves the continuous conformational spectrum of CTP synthase catalysis

Chen-Jun Guo, Yu-Fen Wu, Shu-Ying Guo, You Fu, Wei Wang, Ji-Long Liu

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Capturing enzymes under native turnover conditions remains a grand challenge in structural biology. Here, we develop a reaction-based cryo–electron microscopy (cryo-EM) strategy that directly samples Drosophila melanogaster cytidine triphosphate synthase (CTPS) from actively catalyzing mixtures containing only natural substrates and allosteric effectors. By integrating reaction-based sampling with three-dimensional variability analysis, we resolve a continuous conformational spectrum of CTPS during catalysis. This approach visualizes the chemical progression of 4-phosphoryl-uridine triphosphate (4Pi-UTP) formation and reveals a previously unobserved co-occupancy pattern of adenosine triphosphate (ATP) and CTP at the reaction end point. Cross-validation with nonhydrolyzable ATP analogs demonstrates that UTP phosphorylation by ATP, rather than mere ATP binding, shifts the conformational ensemble toward more closed states. Our findings establish reaction-based cryo-EM as a framework for resolving chemically annotated conformational ensembles without predefining a single trapped intermediate.

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

Reply to Fattorini and Borges: Conditional CIs and sensitivity analysis characterize uncertainty in global insect richness estimates

Robert K. Colwell, Laura Melissa Guzman, Dirk Steinke, Anne Chao, Daniel H. Janzen, Winnie Hallwachs, Austin Baker, José L. Fernández-Triana, Paul D. N. Hebert, Frank Joyce, Robert Puschendorf, Donald L. J. Quicke, Rodolphe Rougerie, M. Alex Smith, Nelson Zamora, Michael J. Sharkey

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

Myeloid cell reprogramming drives enhanced defense against Streptococcus pneumoniae lung infection following exposure to commensal Prevotella

Sara N. Stoner, Eric D. Larson, Sam Fulte, Steven C. Shaw, Erin R. Fish, Edward N. Janoff, Matthias Mack, Sarah E. Clark

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Clinical data link the prevalent respiratory tract anaerobe Prevotella with reduced pneumonia mortality, but the mechanisms directing Prevotella regulation of lung immune homeostasis are unclear. Here, single-cell RNA sequencing was employed to define the transcriptional immune signatures underlying improved clearance of Streptococcus pneumoniae following lung exposure to Prevotella melaninogenica . Overall, we observed a substantial shift in myeloid cell transcriptional programming from interferon-dominant to a more antibacterial profile in S. pneumoniae –infected mice after pre-exposure to P. melaninogenica , correlating with increased macrophage and neutrophil phagocytosis of S. pneumoniae and improved pathogen clearance. In neutrophils, tumor necrosis factor (TNF) signaling through TNFR2 was essential for increased antimicrobial function. Moreover, improved defense required CCR2-dependent monocyte-derived macrophages, with selective enrichment of more a mature Cxcl3+ population which was distinct from the hallmark S. pneumoniae –associated C1qa+ population enriched in the absence of effective clearance. Together, these findings inform the myeloid cell transcriptional changes associated with natural infection resistance mediated by pulmonary microbial exposures.

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

Efficient and robust control with spikes that constrain free energy

André Urbano, Pablo Lanillos, Sander Keemink

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Animal brains exhibit remarkable efficiency in perception and action, while being robust to both external and internal perturbations. The means by which brains accomplish this remains, for now, poorly understood, hindering our understanding of animal and human cognition, as well as our own implementation of efficient algorithms for control of dynamical systems. A potential candidate for a robust mechanism of state estimation and action computation is the free energy principle, but existing implementations of this principle have largely relied on conventional, biologically implausible approaches without spikes. We propose an efficient and robust spiking control framework with realistic biological characteristics. The resulting networks function as free energy constrainers, in which neurons only fire if they reduce the free energy of their internal representation. The networks offer efficient operation through highly sparse activity while matching performance with other similar spiking frameworks, and have high resilience against both external (e.g., sensory noise or collisions) and internal perturbations (e.g., synaptic noise and delays or neuron silencing) that such a network would be faced with when deployed by either an organism or an engineer. Overall, our work provides a mathematical account for spiking control through constraining free energy, providing both better insight into how brain networks might leverage their spiking substrate and a route for implementing efficient control algorithms in neuromorphic hardware.

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

Cell jamming transition is regulated by mitochondrial pyruvate transport and endocytosis

Alexandra Bermudez, Zoe Latham, Johnny Diaz, Weihong Yan, Jerry Chen, Dapeng Bi, Andrew S. Goldstein, Jimmy K. Hu, Neil Y. C. Lin

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Epithelial tissues undergo dynamic transitions between fluid-like collective motion and mechanically jammed states during development, injury repair, and disease progression. However, the cellular programs that drive these transitions and regulate collective behavior remain unclear. Using a controlled crowding model integrated with live-cell imaging and time-resolved multiomics, we demonstrate that epithelial crowding triggers early metabolic changes characterized by increased mitochondrial pyruvate anaplerosis that precedes the jamming transition. Restricting mitochondrial pyruvate import increased collective cell motility and delayed jamming in crowded monolayers. This unjammed state is driven by enhanced cytoskeletal remodeling and requires RhoA-myosin II activity. Mechanistically, we show that elevated cytoskeletal signaling promotes macropinocytic uptake, which serves as a required feedback loop to maintain motility. These findings identify mitochondrial pyruvate utilization as an important regulatory input linking metabolic remodeling to the endocytic control of epithelial fluidity.

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

Quantum Fisher information and photon statistics from shift current shot noise

Evgenii Barts, Takahiro Morimoto, Naoto Nagaosa

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Quantum Fisher information (QFI) sets the ultimate precision of optical phase measurements and can reveal multiphoton entanglement. Yet the photon-number fluctuations that encode this sensitivity are difficult to convert into an electrical signal. We theoretically predict that a photodetector utilizing the shot noise of the quantum-geometric shift current of exciton polaritons can measure photon-number statistics and, for pure states, infer the QFI. By solving the Lindblad equation, we obtain the time-dependent nonlinear photocurrent for an arbitrary initial photon state. It turns out that, regardless of the quantum state of the incident light, the integrated current depends only on the mean photon number. In contrast, the shot noise retains information about photon-number fluctuations: Its Fano factor is proportional to the photon-number variance. Numerical calculations confirm these relations for optical Schrödinger cat and squeezed-vacuum states. A photodetector based on shift current noise can therefore provide a solid-state platform for high-precision measurements of quantum-optical statistics without relying on mobile photocarriers.

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

KAT5/TIP60 orchestrates H4K16 and H2A.Z acetylation to drive the gonocyte-to-spermatogonia transition

Yijing Wang, Zihuan Du, Shanze Li, Jingwei Fan, Dan Xu, Huiqi Li, Qiang Zhang, Xi Lin, Fengchao Wang, Shuai Gao

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Spermatogenesis begins with the gonocyte-to-spermatogonia transition (GST) during the perinatal window, yet how chromatin regulation orchestrates this developmental transition remains elusive. Transcriptomic analysis identified histone acetylation as a significantly enriched pathway during the GST, and immunofluorescence revealed a progressive increase in H4K16 acetylation alongside high levels of H2A.Z acetylation. Conditional deletion of the acetyltransferase Kat5/Tip60 drastically reduced both marks, leading to GST failure characterized by impaired prospermatogonial mitotic resumption, migration, and survival. While the loss of either H4K16ac or H2A.Zac alone causes only moderate defects, their combined depletion largely phenocopies Kat5 deficiency, revealing a functional synergy between the two modifications. CUT&Tag and RNA-seq analyses showed that gene-body-enriched H4K16ac and TSS-enriched H2A.Zac cooperate to promote chromatin accessibility and RNA polymerase II recruitment, thereby activating cell-cycle and spermatogonial developmental programs. Notably, we observed a dynamic, KAT5-dependent spatial shift of H4K16ac from the TSS toward the gene body regions during this transition, indicating a distinct role for this spatial redistribution during early germline development. Together, these findings establish KAT5 as an essential epigenetic factor that integrates dual acetylation pathways to coordinate the GST and safeguard male germline development.

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

Bypass of the canonical biotin synthesis pathway in yeast

Rayeed M. Ihsan, John E. Cronan

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Biotin serves as an essential cofactor for several carboxylation enzymes that catalyze reactions vital for cell survival and proliferation. While bacterial biotin synthesis pathways are well characterized, the mechanisms in eukaryotic organisms remain poorly understood. In Saccharomyces cerevisiae , Bio1 catalyzes the initial and rate-limiting step in the yeast biosynthetic pathway. Previous workers demonstrated that the Bio1 ortholog from the related yeast, Cyberlindnera fabianii, functionally substituted for S. cerevisiae Bio1 and greatly increased growth in the absence of biotin. However, we show this enzyme has far more remarkable capabilities. Through combined in vivo and in vitro experiments, we report that C. fabianii Bio1 (CfBio1) is a 2-oxoglutarate-dependent nonheme iron (II) dioxygenase. The enzyme utilizes the free fatty acid, oleic acid (C18:1 Δ9 ), as substrate, a departure from all previously characterized biotin pathways. Our study shows that CfBio1 catalyzes multiple rounds of oxidation and produces a nine-carbon intermediate, 7-oxononanoate, as opposed to the conventional seven-carbon initial intermediate, pimelate. Moreover, CfBio1 effectively replaces the well-studied Escherichia coli BioC–BioH enzymes that initiate biotin synthesis and remarkably, also bypasses BioF, the second enzymatic step in the pathway. The enzyme bypasses the first two steps of the canonical biotin synthesis pathway both in vivo and in vitro.

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

Reply to Cantwell Chater and Shahsavar: Clarifying PDB deposition records and local model interpretation in GlyT2 structures

Yuhang Wang, Qinru Bai, Yan Zhao

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

Brain weight across the adult lifespan in great apes

Branka Hrvoj-Mihic, Cheryl D. Stimpson, Mary Ann Cree, Madison E. Hillegas, Bridget Wicinski, Todd M. Preuss, Patrick R. Hof, Mary Ann Raghanti, Melissa K. Edler, Elaine E. Guevara, William D. Hopkins, Chet C. Sherwood

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Reduction in brain weight is a hallmark feature of human aging, which is exacerbated in pathologies, such as Alzheimer’s disease and other dementias. However, it remains unclear whether a decrease in brain weight with age reflects a vulnerability unique to the human lineage or represents a consequence of an extension of aging processes shared with other primates. To address this question, we examined age-related changes in brain weight across our closest living relatives, the great apes (chimpanzees, bonobos, gorillas, and orangutans). The sample spanned the full adult age range in each species and included individuals reaching ages comparable to those at which age-related brain changes become apparent in humans. Across species, brain weight did not show significant change throughout adulthood and into advanced age. The observed pattern held even when body weight was included in the analysis in a subsample of chimpanzees. Overall, these results indicate that marked brain weight loss is not a general feature of great ape aging and instead appears largely specific to humans, with implications for understanding susceptibility to late-life brain pathology.

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

Mechanisms of intracellular pH gating and local anesthetic inhibition of the two-pore domain K + channel TASK-2

Trevor Docter, Ben Sorum, Baobin Li, Robert A. Rietmeijer, Annan S. I. Cook, Abhay Kotecha, Stephen G. Brohawn

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TWIK-related acid-sensitive K+ channel 2 (TASK-2) is a pH sensing two-pore K + (K2P) channel that regulates respiration in brainstem neurons and systemic pH homeostasis in kidney. Despite its physiological importance and implication in disease, the molecular basis for intracellular gating and pharmacological inhibition of TASK-2 is incompletely understood. Here, we combine cryo-EM and single-channel electrophysiology to resolve the mechanisms of TASK-2 gating by intracellular protons and inhibition by the anesthetic bupivacaine. We show protonation of intracellular lysines triggers a unique stacked gating mechanism distinct from other K + channels. Inner helices unwind and domain swap to form a β-zipper, which we call a Z-gate, that seals the cytoplasmic channel entrance. These conformational changes open lateral fenestrations to the membrane that permit lipids to invade the channel cavity and block the pore. Furthermore, we find bupivacaine inhibits the channel by competing with lipids in the cavity site in a state-dependent manner. These results define a paradigm for intracellular gating of K2Ps and provide a structural foundation for designing more potent and selective channel modulators.

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

A second-generation “hypoxia in a pill” rescues neurodegenerative phenotypes across distinct mouse models

Hong Wang, Eizo Marutani, Luca Zazzeron, Marissa Menard, Laura Volpicelli-Daley, Fumito Ichinose, Vamsi K. Mootha

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A growing body of preclinical research is demonstrating the therapeutic potential of chronic, continuous hypoxia (11% FIO 2 ) for rare and common diseases. However, the chronic delivery of hypoxic gas poses both practical challenges and long-term safety concerns. We previously introduced a small-molecule, “hypoxia-in-a-pill” combining a hemoglobin affinity enhancer (GBT440) to limit oxygen delivery with a HIF-2α inhibitor (PT2399) to prevent detrimental compensatory erythropoiesis. Although this small-molecule regimen extended the lifespan of the Ndufs4 knockout (KO) mouse model of mitochondrial complex I deficiency and Leigh syndrome, its efficacy did not match chronic 11% FIO 2 . Here we optimize this regimen using GBT601, a second-generation hemoglobin affinity enhancer with longer half-life and greater hemoglobin occupancy, and show it rescues key neurodegenerative phenotypes in multiple models. When we initiate therapy in 50 d old Ndufs4 KO mice with advanced disease, GBT601 monotherapy alleviated neurological disease phenotypes and extended median lifespan from 62 to 105 d, while dual therapy with the GBT601/PT2399 combination extended median lifespan to 158 d. When initiated after onset of advanced disease in a mouse model of Friedreich’s ataxia, the combination halted further progression of motor phenotypes. In a mouse model of Parkinson’s disease due to α-synuclein toxicity, initiating the GBT601/PT2399 combination after onset of motor dysfunction attenuates brain hyperoxia and lipid peroxidation and reverses motor phenotypes. Importantly, the combination maintained body weight without inducing any signs of pulmonary hypertension. Our findings motivate further preclinical and clinical evaluation of our “hypoxia in a pill” approach for diseases with high unmet need.

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

Barry Bloom and the convergence of immunology, infectious disease, and public health

Sarah M. Fortune, William R. Jacobs, Arturo Casadevall

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In early 2026, the world lost Barry Bloom, a great advocate for public health, an extraordinarily accomplished immunologist, and a science advisor who helped refocus policy on controlling infectious diseases, including neglected diseases such as leprosy. Barry’s career took him from a life of laboratory discovery where he was enormously influential in catalyzing the late 20th century shift from studying the immune response of simple molecules to pathogenic microbes. As Dean of Harvard T.H. Chan School of Public Health he had a profound influence on the growth of the institution and the careers of many who have continued his work.

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

Tyrosine phosphorylation unfolds nucleophosmin and disrupts its integration into the nucleolus

Rafael L. Giner-Arroyo, Adrián Velázquez-Campoy, Miguel A. De la Rosa, Irene Díaz-Moreno

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Nucleophosmin (NPM1) is a multifunctional nucleolar protein essential for ribosome biogenesis, genome stability, and stress responses. Its integration into the nucleolus depends on its oligomerization and multivalent interactions that enable liquid–liquid phase separation (LLPS). Here, we investigate how tyrosine phosphorylation at Tyr17, Tyr29, and Tyr67 located within the interface between monomers at the N-terminal oligomerization domain regulates NPM1 structure and function. Replacing tyrosines with p- carboxymethyl-L-phenylalanine as phosphomimetic substitutions, we show that phosphorylation at Tyr17 and Tyr67 disrupts key intermonomer interactions and destabilizes the NPM1 pentameric assembly, which drives an order-to-disorder transition and impairs binding to nuclear partners. Consequently, dual phosphorylation at Tyr17 and Tyr67 disturbs both homotypic and heterotypic LLPS, thereby impairing incorporation of NPM1 into the nucleolus. This altered localization of NPM1 serves as a hallmark of p53 activation, driven both by nucleoplasmic NPM1 and by the release of ARF from NPM1-dependent sequestration in the nucleolus. Altogether, our results provide a molecular mechanistic explanation on how phosphorylation-induced structural and dynamic changes drive the release of NPM1 from the nucleolus under genotoxic stress.

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

Conformational switch of NPC1 epitomizes a lumen-to-membrane alternating access model for nonpolar substrates

Xuelan Wu, Sepehr Dehghani-Ghahnaviyeh, Ali Rasouli, John A. Malona, Mitchell Antalek, Lyn H. Jones, Xiao Fan, Adele Peng, Emad Tajkhorshid, Hongwu Qian, Nieng Yan

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Niemann-Pick disease type C (NPC) arises from failure of the NPC1 and/or NPC2 proteins to mobilize lysosomal cholesterol, yet the mechanism by which the complex drives sterol translocation lacks a thorough understanding. Here, we capture an NPC1–NPC2 complex conformation at lysosomal pH using a bis-sterol ligand (JM046), fortifying NPC2 engagement with NPC1 and enabling structural characterization of an alternative transport state. In this complex, the sterol moiety is absent from the NPC1 central tunnel, and the neck site adopts an expanded architecture that resembles a previously observed NPC1 conformation at neutral pH, indicating that the tunnel geometry may not be influenced by the pH alone. Instead, we provide evidence that cholesterol occupancy in the neck site is a key determinant of tunnel contraction. Supporting this notion, NPC1 purified from cholesterol-auxotrophic insect cells exhibits a similarly expanded neck conformation. Integrating these structures and molecular dynamics (MD) simulations exploring the directional cholesterol handoff from NPC2 to the NPC1 tunnel, we propose a substrate-induced gating cycle where luminal and membrane-facing openings of NPC1 switch states in a coordinated manner to transfer cholesterol across the hydrophilic glycocalyx, reminiscent of the alternating access mechanism of membrane transporters. This framework synthesizes NPC1 conformational states into a mechanistic basis that may be used to map pathogenic NPC variants to their relevant transport steps.

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

Profile of Michael N. Shadlen

Jennifer Viegas

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Neuroscientist and neurologist Michael N. Shadlen is a world leader in the neurobiology of decision-making, a field of study he helped establish. His research explores higher brain functions—memory retrieval, reasoning, and multitasking, among others—that he theorizes share underlying mechanisms. His work suggests that a holy grail of neuroscience—the “hard problem” of consciousness, or the mechanism(s) by which physical brain operations are translated into lived experiences—could be resolved. Shadlen’s Inaugural Article explains what distinguishes conscious from nonconscious thought.

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

Breaking trait scaling via the evolution and regulation of dimorphic decoupling in ants

Erica Vong, Shannon Parisien, Hélène Orfali, Rajendhran Rajakumar

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The evolution of allometry, changing how morphological traits scale to body size, has fueled adaptive radiations. In ants, allometry has facilitated the repeated evolution of a worker–soldier caste system. Here, we reveal an unexpected morphological pattern and its superorganismal regulation within the hyperdiverse genus Pheidole . We uncovered that antennal sizing between the small worker and the big soldier is identical, lacking intercaste scaling (antennae-body scaling is decoupled) yet retaining intracaste scaling. Furthermore, we have pinpointed the evolutionary origin of this decoupling. Finally, manipulations of social environment, developmental hormones, and interorgan signaling influence the modularity-integration of trait-body covariation, uncovering head-to-body decoupling and the production of novel nanoworkers and nanosoldiers. Collectively, this challenges our previous understandings of trait covariation, modularity, and their regulation, from individual to society and across species.

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

Chronic cigarette smoke exposure induces distinct stem cell states driving genetic driver–specific non–small cell lung cancer subtypes

Na Wang, Raksha Padaki, Sara-Jayne Thursby, Ray-Whay Chiu Yen, Leslie M. Cope, Malcolm V. Brock, Edward Gabrielson, Hariharan Easwaran, Stephen B. Baylin, Michelle Vaz

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Cigarette smoke-induced chronic inflammation (CI) potentiates development of non–small cell lung cancer (NSCLC) by mediating genetic and epigenetic events. Using normal lung organoids (LOs), we define how chronic cigarette smoke condensate (CSC) exposure drives two separate stem cell populations to evolve premalignant states harboring progressive epigenetic and linked transcriptomic abnormalities in the absence of major driver mutations. These dynamics facilitate evolution of an immune evasive state with downregulation of inflammatory pathways and accompanying death signals mediated by epigenetic silencing of PANoptosis regulator, Zbp1. The stem cell populations evolve through distinct trajectories to respond differently to subsequent introduction of oncogenic mutations, Kras G12V and loss of Tp53, to induce one step transformation of CSC exposed organoids resulting in two major NSCLC subtypes. Kras mutations drive tumorigenesis primarily in a bronchioalveolar stem cell–derived state producing adenocarcinomas while TP53 loss drives tumorigenesis in a basal stem cell–derived state resulting in squamous cell carcinomas. CSC-induced downregulation of Zbp1 and interferon signaling is further potentiated in tumors with mutation-specific changes marked by decreased expression in Kras-mutant contexts. Our findings define unique transcriptomic profiles in CI-induced stem cell states and reveal a key role for cell death pathway-associated genes in potentiating oncogenic drivers to promote NSCLC. Together, our data suggest strategies to predict cancer risk and enable early interception.

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

A-to-I RNA editing–mediated stop codon read-through in Fusarium graminearum is not generally adaptive

Jiachen Li, Jianzhi Zhang

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

Spatiotemporal noise stabilizes unbounded diversity in strongly competitive communities

Amer Al-Hiyasat, Daniel W. Swartz, Jeff Gore, Mehran Kardar

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Classical ecological models predict that diverse communities should be unstable, presenting a central challenge to explaining the stable biodiversity seen in nature. We revisit this long-standing problem by extending the generalized Lotka–Volterra model to include both spatial structure and environmental fluctuations across space and time. We find that neither space nor environmental noise alone can resolve the tension between diversity and stability, but that together they permit arbitrarily many species to stably coexist in a sufficiently large system, despite strongly disordered competitive interactions. We analytically characterize the noise-induced transition to coexistence, showing that spatiotemporal noise drives power-law abundance fluctuations, leading to an anomalous scaling of moments known empirically as Taylor’s law. At the metacommunity level, this manifests as an emergent sublinear self-inhibition that stabilizes diversity and renders the interaction disorder irrelevant in the high-diversity limit. Spatiotemporal noise thus provides a resolution to the diversity-stability paradox and a generic mechanism by which complex communities can persist.

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

Maternal ranging strategies facilitate offspring social play at energetic cost in the most solitary ape

Odd T. Jacobson, Alison M. Ashbury, Brendan J. Barrett, Margaret C. Crofoot, Paulina Kukofka, Julia A. Kunz, Sri Suci Utami Atmoko, Caroline Schuppli, Erin R. Vogel, Carel P. van Schaik, Maria A. van Noordwijk

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In most vertebrates, social play among peers is considered essential for behavioral development. Yet in solitary species bearing single offspring, opportunities for social play are inherently scarce. Whether mothers of such species actively facilitate play opportunities for their offspring, and at what cost, remains unknown. We used 15 y of behavioral and movement data (∼32,600 observation hours) from 31 wild Bornean orangutan ( Pongo pygmaeus wurmbii ) mother-offspring pairs to test whether mothers adjust ranging behavior to increase their offspring’s access to play with neighboring peers. Neighboring mothers with similarly aged offspring showed disproportionately high annual overlap in space use, independent of their relatedness or fruit availability. Correspondingly, peer play between neighboring offspring was more frequent when they were closer in age. Mothers also incurred energetic costs; on days their offspring played with peers, mothers traveled farther and spent less time feeding. Travel distances were also elevated on the days before and after play, with mothers orienting movement toward play partners’ core areas before play and back toward their own core areas after play. This suggests these encounters are planned and actively pursued over multiple days rather than arising by chance. These findings reveal that orangutan mothers incorporate their infants’ social needs into daily ranging decisions, at a cost to their own energy budgets. This points toward an underappreciated form of maternal investment and illustrates how the social requirements of development can be met even near the solitary extreme of animal social organization.

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

Nocturnal neurons shape daytime visual receptive fields in the retina

Jeffrey S. Diamond

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

Ecology must shape AI before AI reshapes ecology

George Roff

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

A 2,623-year temperature reconstruction from the Colorado Rocky Mountains reveals warm and cool droughts

Alexandre F. Nolin, Connie A. Woodhouse, Cody C. Routson

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Recent hydrological drought in the US Southwest has occurred under exceptional warming, intensifying water deficits in the Colorado River and Rio Grande basins. Yet the long-term role of temperature in modulating severe and persistent droughts remains poorly understood because regional temperature reconstructions are scarce. We present a 2,623-y June–September minimum temperature reconstruction from the southern Colorado Rocky Mountains based on Pinus aristata tree rings, spanning 600 BCE to 2022 CE. The reconstruction reveals decadal-to-multidecadal variability but limited expression of sustained hemispheric climate phases. In contrast, late 20th and early 21st century warming is unprecedented in magnitude, persistence, and spatial coherence across western North America. By pairing this reconstruction with a continuous 2,000-y reconstruction of upper Colorado River streamflow, we evaluate temperature conditions during major droughts. The most severe and persistent drought of the Common Era, during the 2nd century CE, developed under a persistent cool anomaly, indicating that extreme hydrologic deficit can arise from precipitation forcing alone. Over the last two millennia, warm droughts were more frequent than cool droughts (56% vs. 44%), but both produced comparable cumulative flow deficits. In contrast to the conventional characterization of droughts as hot and dry, these findings demonstrate that extreme droughts developed under both cool and warm regimes and suggest that natural climate variability in this region can produce extremely persistent drought without the added influence of anthropogenic warming.

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

Regulation of morphogen signaling pathways by recurrent hypermotif circuits

Miri Adler, Ruslan Medzhitov

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Morphogen signaling pathways orchestrate cell fate and tissue patterning during embryo development through intricate intercellular communication. While much is known about the molecular components of these pathways, the underlying regulatory logic shaping their integration remains unclear. Here, we develop a computational framework to uncover higher-order network structures, hypermotifs , that link gene regulatory circuits within and between cells via morphogen signaling. Applying this framework to single-cell RNA sequencing data from human intestinal development, we identify recurrent hypermotif topologies that mediate communication between epithelial and fibroblast populations. These cell-cell hypermotif circuits involve feedback and feedforward loops embedded within signaling pathways. Dynamical modeling reveals that such circuits can generate emergent behaviors, including oscillatory and antagonistic responses. Our results highlight hypermotifs as key design principles in developmental regulatory networks, providing a systems-level understanding of morphogen signal integration across cell types.

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

Hyperfunction of PSD-95 leads to hyperexcitability and cognitive abnormalities in MEF2C haploinsufficiency

Meijin Pan, Anirudh Acharya, Kwan Young Lee, Justin S. Rhodes, Nien-Pei Tsai

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Myocyte enhancer factor 2C (MEF2C) is a transcription factor critical for brain circuit development and cognitive behavior. The loss of one copy of MEF2C leads to MEF2C haploinsufficiency syndrome (MCHS), a neurodevelopmental disorder characterized by intellectual disability, epilepsy, and behavioral phenotypes associated with autism spectrum disorders. Given that numerous genes are regulated by MEF2C, the neuronal and behavioral deficits in MCHS are complex, and there is currently no effective disease-modifying strategy for this disorder. Here, we show that MEF2C haploinsufficiency in forebrain excitability neurons led to an elevation of postsynaptic density protein 95 (PSD-95) in mice. This elevation of PSD-95 coincided with an increased number of structural synapses, facilitated surface expression of N-methyl-D-aspartate (NMDA) receptors, augmented neuronal excitability, and increased susceptibility to seizures. Knocking down PSD-95 or inhibiting the interaction between PSD-95 and NMDA receptors efficiently reduced hyperexcitability phenotypes in MEF2C haploinsufficiency. Most importantly, knocking down PSD-95 significantly improved cognitive behaviors in mice with MEF2C haploinsufficiency. In summary, our study revealed a mechanism underlying hyperexcitability and cognitive defects associated with MCHS and suggests PSD-95 as a therapeutic target for MCHS.

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

Spatial and single-nucleus transcriptomics reveals the molecular pathology of type 2 diabetes–associated cognitive dysfunction

Wei Wu, Yumeng Yang, Xixi Zhang, Baojian Liao, Siyu Kong, Bingbing Xie, Yanping Lu, Mingyue Jiang, Xiu Liang, Lei Zhang, Meiyi Zhou, Xiaojing Zhang, Ningyi Shao, Gholson J. Lyon, Yaqing Shu, Shengbao Suo, Ning Ma

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The mechanisms underlying type 2 diabetes–associated cognitive dysfunction (DACD) remain poorly understood, hindering therapeutic progress. Here, we integrated spatial transcriptomics and single-nucleus RNA sequencing to delineate the spatiotemporal molecular and cellular landscape of DACD in brain tissues from 3- and 6-mo-old mouse models. Our findings revealed region- and cell-type-specific transcriptomic alterations, with excitatory neurons in the hippocampus and isocortex emerging as the most severely affected populations with pronounced synaptic dysfunction. Further analysis of these two regions identified disease-associated transcription factors, such as Rfx3 and Mef2c . In parallel, we uncovered multiple ligand–receptor pairs, including Hsp90b1 – Lrp6 and S100a1 – Ryr2 , whose downstream signaling networks converged on lactate dehydrogenase B ( Ldhb ) as a shared effector, thereby prompting functional validation. Notably, brain-wide and excitatory neuron-specific Ldhb overexpression alleviated DACD-induced mitochondrial dysfunction, oxidative stress, neuronal apoptosis, and cognitive impairment. Collectively, our study delineates the spatiotemporal transcriptomic landscape of DACD, offers a valuable resource for mechanistic exploration, and highlights Ldhb as a potential therapeutic target in DACD.

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

Mechanotherapy enhances nanodrug uptake by overcoming the actin cytoskeleton damping effect

Hao Wu, Xue Shen, Tian Zhao, Hanxi Zhang, Yungchang Chen, Jiaxuan Yu, Ye Huang, Xiangyan Chen, Weijie Wu, Ran Yan, Xiang Qin, Shun Li, Chuan Zheng, Fengming You, Yiyao Liu, Tingting Li

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Efficient nanodrug therapy in solid tumors is limited not only by extracellular barriers but also by the mechanical state of the plasma membrane (PM). Although mechanotherapy remodels the extracellular matrix (ECM) and improves tissue-level delivery, its effect on transmembrane transport remains unclear. Here, we show that matrix stiffness is transmitted to the PM through the actomyosin cytoskeleton and thereby regulates nanoparticle (NP) uptake. Within a hepatocellular carcinoma-relevant stiffness range, matrix stiffening promoted excessive F-actin polymerization and stress-fiber formation, producing a mechanically damped PM–actin interface that resisted membrane deformation and suppressed NP uptake. Pharmacological and genetic perturbations indicated that this mechanical barrier was reversible. In vivo, β-aminopropionitrile-mediated tumor softening loosened ECM architecture, increased NP penetration, and promoted cellular uptake by reducing F-actin-associated mechanical resistance. Intratumoral spatial analyses and paired bilateral tumor experiments further supported local regulation of NP uptake by the actomyosin state under matched matrix conditions. Combined tumor softening and donafenib-loaded PLGA NPs reduced endpoint tumor weight by 87.8% relative to free donafenib but increased pulmonary metastasis, revealing a potential efficacy-safety trade-off. These findings identify a multiscale mechanical mechanism linking tumor-matrix mechanics to nanomedicine delivery and the PM–actin interface as a potential therapeutic target.

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

GTP orchestrates CTP synthase via an allosteric effector–cycling mechanism

Chen-Jun Guo, Yu-Fen Wu, Shu-Ying Guo, Jia-Li Lu, Liang Xu, You Fu, Xian Zhou, Jiale Zhong, Zherong Zhang, Ji-Long Liu

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Cytidine triphosphate (CTP), a fundamental building block of RNA, plays vital roles in diverse biological processes. CTP synthase (CTPS) is the only known enzyme for de novo synthesis of CTP. Efficient CTPS catalysis requires guanosine triphosphate (GTP) in a dose-dependent, nonconsumptive manner; however, the precise mechanism by which GTP drives CTP formation remains unclear. Here, we integrate a series of cryo-EM structures of Drosophila melanogaster CTPS captured from actively catalyzing samples with biochemical and mutagenesis analyses, yielding 34 distinct CTPS states at resolutions up to 2.0 Å. We find that GTP binds to and dissociates from CTPS once per catalytic cycle, thereby enabling the production of a single CTP molecule. Initial GTP engagement requires formation of 4-phosphoryl-UTP in the AL domain, whereas full stabilization of GTP binding is promoted by occupancy of the GAT active site. Together, these two checkpoints couple GTP recruitment and stabilization to catalytic progress in the two domains, enabling the coordinated synthesis of one CTP molecule per GTP binding–dissociation cycle. Moreover, the GTP-recognition site is highly conserved across the three domains of life. These findings establish a comprehensive mechanistic framework for efficient CTPS catalysis and define “effector-cycling”—in which GTP undergoes obligatory binding and dissociation during each catalytic cycle to regulate an intermediate step in a multistep catalytic process—as a distinct mode of allosteric regulation.

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

Apomixis imposes evolutionary costs by reducing recombination efficiency and disrupting segregation

Nan Wang, Weiping Zhang, Yuting Yang, Siqi Zhang, Lijun Chai, Wenwu Guo, Qiang Xu, Yongfeng Zhou, Martin Lascoux, Xiuxin Deng

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Sexual reproduction facilitates the purging of deleterious mutations via recombination. Apomixis, defined by asexual seed formation, involves suppressed meiosis, thereby reducing the efficacy of purifying selection. However, the evolutionary consequences of apomixis remain poorly understood. In this study, we used wild citrus ( Citrus hindsii ), which has both sexual and apomictic (adventitious embryony) lineages, as a diploid genetic system (2n = 2x = 18). We performed a cross between a sexual and an apomictic individual (pollen donor), generated haplotype-resolved genome assemblies for the two parents, and deep-sequenced 226 progeny. These data were integrated into a graph pangenome to characterize the meiotic recombination landscape. The apomictic lineage harbors 1.28-fold more heterozygous structural variations, which may locally suppress crossovers. Furthermore, apomictic recombination efficiency is reduced by 24.2% relative to the sexual lineage. Crucially, the contribution of male function through outcrossing exposes a substantial recessive genetic load, including a putative gamete-lethal mutation, triggering significant segregation distortion across 31.7% of the genome. We established that these distortion profiles are driven by the cumulative effects of multiple loci, with the magnitude of distortion depending on haplotype interactions. Collectively, our study quantifies the recombination landscape of apomixis and provides a framework for unmasking and mitigating genetic load in asexual crops.

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

DNAAF19–RUVBL1/2 complex recruits multiple adaptors to promote dynein arm assembly

Mafalda de Almeida Gomes, Emma Wood, Thomas Burgoyne, Franziska Klose, Denisa Batrinu, Karsten Boldt, Glenn Carrington, Yehuda Halfon, Rachel George, G. Nasir Khan, Tina Beyer, Hannah M. Mitchison, Takashi Ochi

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Cilia are microtubule-based organelles essential for sensing, motility, and fluid transport. Motile cilia rely on inner and outer dynein arms, large multiprotein motor complexes, for force generation and the characteristic bending motion required for ciliary beating. Before being incorporated into cilia, these dynein arms are preassembled in the cytoplasm by dynein axonemal assembly factors (DNAAFs). Defects in this assembly pathway often cause the inherited genetic condition primary ciliary dyskinesia (PCD), in which the loss of dynein arms impairs ciliary motility. The molecular mechanisms governing the precise and timely assembly of dynein arms by DNAAFs remain elusive. Here, we investigated the role of dynein axonemal assembly factor 19 (DNAAF19), a DNAAF frequently mutated in PCD patients with combined inner and outer dynein arm defects. Using biochemical, structural, and proteomic approaches, we find that DNAAF19 is a monomeric protein that interacts directly with the heterohexamer of RUVBL1 and RUVBL2, a multifunctional cochaperone complex involved in ciliary dynein arm assembly. The recurrent PCD-causing variant p.His154Pro partially destabilizes the interaction of DNAAF19 with RUVBL1-RUVBL2. Moreover, we identify Deleted in Primary Ciliary Dyskinesia forming a cocomplex with RUVBL1/2-DNAAF19 in vivo and in vitro. This indicates similarity to R2TP, the HSP90 cochaperone composed of RUVBL1/2-RPAP3-PIH1D1 that assembles different molecular machineries in cells, and to the RUVBL1/2–SPAG1–PIH1D2 complex associated with ciliary dynein arm assembly and PCD. Our results suggest that DNAAF19 acts as a DNAAF in concert with RUVBL1/2 and its interacting proteins, providing insights into the molecular coordination of dynein arm assembly and cell biology of PCD.

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

Recurrent hypermotif regulatory circuits in developmental programs

Miri Adler, Ruslan Medzhitov

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During development, cells self-organize into complex spatial and temporal patterns driven by regulatory circuits of transcription factors and morphogen signaling. However, the principles that govern these regulatory interactions remain poorly understood. Here, we introduce a framework to dissect the building-block circuits of developmental gene regulatory networks and explore their integration into higher-order hypermotif circuits. Using single-cell RNA-sequencing data spanning human intestinal development, we identify five recurrent network motifs, including feedforward and feedback loops, and investigate their roles in the regulation of gene expression. Our analysis reveals distinct categories of developmental genes based on their roles within network motifs, highlighting major transitions in regulatory architecture across developmental stages. Furthermore, we model the emergent dynamical properties of hypermotif circuits, including their potential roles in regulating morphogen signaling. This study uncovers a common theme in regulatory circuits of developmental programs, emphasizing how the combinatorial wiring of regulatory motifs enables robust and diverse tissue formation.

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

Pyrrolysine supply and demand shapes the translational landscape in Methanosarcina acetivorans

Grace D. Britt, Daniel R. Utter, Yeonsoo Park, Victoria J. Orphan, Rodney Tollerson

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The amber stop codon (UAG) can encode for pyrrolysine (Pyl) or be read as a stop codon by methylamine-metabolizing organisms including methanogenic archaea. The fate of UAG is decided during the decoding step of translation by competition between the pyrrolysine-aminoacylated transfer RNA (Pyl-tRNA Pyl ) and release factor. To further understand the consequences of pyrrolysine based genetic code expansion, we integrated RNA sequencing, tRNA charging analysis, and codon-resolved mono- and disome ribosome profiling in Methanosarcina acetivorans . During conditions of high pyrrolysine demand, we observed increased expression of the pyrrolysine biosynthetic operon with a concurrent increase in acylation of tRNA Pyl and ribosome occupancy at UAG codons. During low pyrrolysine demand, the population of Pyl-tRNA Pyl decreases and we observe a strong ribosome pausing signal during UAG decoding. We find that the dwell time on UAG codons is shorter during high demand, but ribosome collisions increase due to greater ribosome density on UAG-containing transcripts. Together, these results show how pyrrolysine demand modulates tRNA charging and controls elongation dynamics, clarifying the cellular consequences of decoding an ambiguous stop codon.

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

Latent causal diffusions for single-cell perturbation modeling

Lars Lorch, Jiaqi Zhang, Charlotte Bunne, Andreas Krause, Bernhard Schölkopf, Caroline Uhler

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Perturbation screens hold the potential to systematically map regulatory processes at single-cell resolution, yet modeling and predicting transcriptome-wide responses to perturbations remains a major computational challenge. Existing methods often underperform simple baselines, fail to disentangle measurement noise from biological signal, and provide limited insight into the causal structure governing cellular responses. Here, we present the latent causal diffusion (LCD), a generative model that frames single-cell gene expression as a stationary diffusion process observed under measurement noise. LCD outperforms established approaches in predicting the distributional shifts of unseen perturbation combinations in single-cell RNA-sequencing screens while simultaneously learning a mechanistic dynamical system of gene regulation. To interpret these learned dynamics, we develop an approach we call causal linearization via perturbation responses (CLIPR), which yields an approximation of the direct causal effects between all genes modeled by the diffusion. CLIPR provably identifies causal effects under a linear drift assumption and recovers causal structure in both simulated systems and a genome-wide perturbation screen, where it clusters genes into coherent functional modules and resolves causal relationships that standard differential expression analysis cannot. The LCD-CLIPR framework bridges generative modeling with causal inference to predict unseen perturbation effects and map the underlying regulatory mechanisms of the transcriptome.

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

Trans - and cis -interaction dynamics of cadherin complexes on membranes visualized by high-speed atomic force microscopy

Shigetaka Nishiguchi, Tadaomi Furuta, Takayuki Uchihashi

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Classical cadherin-mediated cell–cell adhesion is important for maintaining the animal body and defects in adhesion cause severe diseases. The combination of trans - (between cells) and cis - (on the same membrane) interactions of the extracellular domains of cadherins is necessary for cadherin clustering in cell–cell junctions, which is essential for robust tissue formation. However, the solution structure and interaction dynamics of trans / cis -binding cadherin complexes have not been observed because of technical limitations; therefore, the cadherin clustering mechanism is not well understood. In this study, we reconstituted trans / cis -binding cadherin complexes on membranes and visualized their structure and dynamics using high-speed atomic force microscopy. Our method revealed trans -strand-swap interactions through flipping and hopping motions and cis -interactions, which contributed to multiple interaction patterns on the membrane. In addition, we observed cadherin complex structures that were distinct from those in crystal structures. These results suggest that cadherins adopt dynamic and diverse conformations through multiple assembly pathways on the membrane.

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

Chemoreceptor complexes signal through a protein-ordering and stabilization mechanism

Jessica J. Allen, Edward A. Esposito, Isabella J. Jankowski, Katherine W. Lu-Diaz, Lynmarie K. Thompson

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Membrane protein complexes are critical to many cellular processes and have proven to be good targets for a variety of therapeutics. One such complex is the bacterial chemoreceptor signaling complex, which has potential as a target for novel antibiotics. This complex is responsible for sensing chemical signals in the environment to bias swimming of the bacterial cell toward more favorable conditions. While these complexes are well studied, the mechanisms of signal transduction and kinase control are still not fully understood. We have applied multiple thermal stability measurements and limited proteolysis to gain insight into how complex formation and signaling state change the thermal stability and structural properties of the proteins and complexes. We show that the activated signaling complexes are more strongly associated, ordered, and thermally stable than the inactive complexes. This direct evidence that both the chemoreceptor and the kinase are significantly stabilized by assembly into kinase-active complexes is consistent with our previous hydrogen deuterium exchange mass spectrometry results and our proposed order-induced activation model. We propose that signaling inputs modulate the structural order and stability of the partially disordered cytoplasmic domain, which in turn modulates the stability of the catalytic domain of the kinase, such that ordering of the cytoplasmic domain stabilizes and activates the kinase.

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

Dopamine suppresses pathological retinal oscillations and enhances the signal-to-noise ratio

B. Semihcan Sermet, Wouter Kamermans, Beerend H. J. Winkelman, Chris I. De Zeeuw, Maarten Kamermans

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Infantile nystagmus is a debilitating involuntary eye movement disorder often associated with retinal diseases such as congenital stationary night blindness (CSNB). The oscillating eye movements of infantile nystagmus come with reduced visual acuity and strongly impair quality of life. No cure exists for this condition. Previously, we demonstrated that nystagmus in the CSNB mouse model Nyx nob has a retinal cause. Specifically, we found that synchronized oscillations of retinal ganglion cells (RGCs) are transmitted to the accessory optic system, triggering compensatory eye movements. The RGC oscillations appear to originate from a specific retinal cell type, the A II amacrine cell (A II AC), making these cells the preferred target for treatment. The reason for the oscillations in the A II ACs is not fully understood. Here, we found that pharmacologically activating the D1 dopaminergic receptors on the A II ACs in Nyx nob mice down-regulated their voltage-gated sodium and potassium channels, leading to a complete suppression of the pathological oscillations of both A II ACs and RGCs. Furthermore, the signal fidelity of RGCs significantly improved due to the absence of the pathological oscillations. Our retinal network simulations confirm that the experimentally observed changes in properties of the A II AC voltage-gated currents are necessary and sufficient to account for the dopamine-dependent abolishment of these oscillations. Our findings provide a mechanistic understanding of dopaminergic regulation of A II ACs underlying infantile nystagmus.

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

The Benjamini–Hochberg procedure can fail to control the FDR for correlated two-sided Gaussian tests

Edgar Dobriban

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The Benjamini–Hochberg (BH) procedure is the standard method for controlling the false discovery rate (FDR) in large-scale studies involving testing multiple hypotheses. Whether the BH procedure controls the FDR for every correlation structure among two-sided Gaussian tests has been a long-standing question, and a positive answer has been believed. Here, we settle the question negatively, by providing examples of Gaussian factor models for which the BH method fails to control the FDR at the nominal level. We prove mathematically that the violation holds, and also provide simulation results which are consistent with the theory. The level of violation can be characterized as mild but nonnegligible. In one of our examples, empirical FDR levels of ≈0.0106 and ≈0.053 are achieved for nominal FDR levels 0.01 and 0.05, respectively. Larger violations are also possible. The violation appears most prominently for large numbers (thousands) of tests; though we also present an example with a moderate number of 85 tests. We also briefly discuss the implications of our findings.

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

An unidentified reservoir of comet 81P/Wild 2 chondrules

Mingming Zhang, Donald E. Brownlee, Dave J. Joswiak, Noriko T. Kita

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Comets, which have been stored in the cryogenic regions for billions of years, preserve key records of the solar system’s formation and the dynamic evolution of planets and other small bodies. Twenty years ago, NASA Stardust mission returned samples from a Jupiter-family comet, 81P/Wild 2, for laboratory analysis, and uncovered an unexpected truth that this comet is not entirely made of interstellar grains but contains significant amounts of high-temperature silicate fragments. However, the sources of these fragments remain ambiguous. Here, we report the petrography and oxygen three-isotopes of ~100 silicate fragments from track 227, one of the largest impact tracks in the Stardust aerogel collector. The fragments are mostly pieces of small chondrules (typically <60 µm) with many exhibiting igneous textures such as microporphyritic olivine and, occasionally, nonporphyritic barred olivine and cryptocrystalline. Approximately 90% of the fragments define a modest negative correlation between the mass-independent fractionation of oxygen isotopes (Δ 17 O = δ 17 O –0.52 × δ 18 O, –4 to 0‰) and the redox state [Mg# = mol% Mg/(Mg + Fe), 100 to 62]. The remaining 10% are markedly FeO-rich (Mg# <60) and 16 O-depleted (Δ 17 O up to 7‰). These characteristics distinguish them from chondrules in any known chondrite groups, nor can they be reproduced by mixing chondrule populations in any proportion. Instead, these fragments are from an unidentified chondrule reservoir in a more distant outer disk region. These chondrules were possibly formed in a highly oxidized, ice-rich environment ≥3 Ma after solar system formation.

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

Cooperation in binary mixtures of active colloids

Laura Alvarez, Elena Sesé-Sansa, Demian Levis, Ignacio Pagonabarraga, Lucio Isa

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The complex interactions underlying collective motion in biological systems give rise to emergent behaviors such as flocking, sorting, and cooperative transport. These dynamics often involve species with different motilities coordinating movement to optimize navigation and survival. Synthetic analogues based on active colloids offer a controlled platform to explore such behaviors, yet most experimental realizations remain limited to monodisperse systems or mixtures of passive and active particles. Here, we investigate dense binary mixtures of active Janus colloids with two different metal caps leading to distinct motilities and independently tunable mutual alignment, actuated by AC electric fields. We demonstrate experimentally and numerically that binary mixtures form highly dynamic polar clusters. Moreover, particles segregate according to their motility, leading to cooperative “catch-and-run”-like dynamics in which slow particles are locally advected and pushed by fast polar clusters, producing a transient enhancement of slow-particle motility. Our results reveal how motility contrast and alignment combine to drive self-organization in active mixtures, offering strategies for designing reconfigurable materials with collective functionalities.

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

Diversity and spatial segregation of TRP channels in the closest relatives of animals

Simen Mannsåker, Pawel Burkhardt, Jeffrey Colgren

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Sensory systems, built around specialized cell types, are central to how animals perceive and respond to their environments. However, the evolutionary origin of these systems remains unclear. Here, we show that choanoflagellates, the sister group of animals, possess remarkably diverse repertoires of transient receptor potential (TRP) channels, an ancient superfamily of sensory ion channels. Comparative analyses indicate that most major animal TRP channel families predate the origin of animals and reveal extensive radiations of the TRPM and TRPW families within choanoflagellates, with the latter family likely being lost in the animal lineage. Furthermore, in the choanoflagellate model Salpingoeca rosetta , TRPA, TRPC and TRPV occupy discrete microdomains within the collar complex, a key interface for environmental sensing and feeding. We propose that the evolution of animal sensory systems involved both expansion and reorganization of this ancestral repertoire, with subcellular patterning in unicellular organisms representing a precursor to cell-type specialization in multicellular animals.

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

Geometric criterion for capillary thread breakup in rectangular microchannels

Luyao He, Xiaodong Chen

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Capillary breakup of fluid threads underlies lab-on-a-chip diagnostics, drug encapsulation, and oil trapping in underground rock. Rectangular channels are the practical norm, yet no unified geometric criterion explains how their shape controls the onset and geometry of breakup. Combining direct numerical simulations, stop-flow analysis, and static equilibrium analysis, we show that breakup is triggered when the family of equilibrium neck shapes terminates. The associated critical continuous-phase volume depends only on the channel aspect ratio W / H , and the critical neck geometry transitions between two distinct collapse modes at a threshold W / H ≈ 2.0 . Below this threshold, the neck detaches from the top and bottom walls before pinch-off, with a slow three-dimensional necking stage intervening between the two events. Above it, detachment and pinch-off coincide. This geometry-derived critical volume serves as the mechanism-based input to a semiempirical thread-length model, validated for both primary thread breakup and secondary thread breakup across W / H from 1.0 to 3.0. Turning this principle into a design rule, we design a curved junction that matches the critical neck profile and directly reduces the critical volume, enabling on-chip production of densely packed emulsions beyond the close-packing limit of monodisperse spheres. By linking confined thread breakup in rectangular microchannels to a single dimensionless ratio, these results provide geometry-based design rules for droplet microfluidics, enhanced oil recovery, and precision emulsion manufacturing.

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

Infection of macrophages by mpox virus activates inflammasome and cell death, informing multitarget therapeutic strategies

Yining Wang, Xin Wang, Theano Tsikari, Fang Qin, Fangfang Chang, Fuxiang Wang, Ana Maria Gonçalves da Silva, Rick Schraauwen, Dewy Mae Offermans, Yijin Wang, Harry L. A. Janssen, Pengfei Li, Wenshi Wang, Valeria V. Orlova, Amaro Nunes Duarte-Neto, Yang Yang, Qiuwei Pan

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Severe mpox virus (MPXV) infection causes immunopathological manifestations in patients. Here, we provide clinical evidence of MPXV-induced inflammation in a large patient cohort and demonstrate direct macrophage infection in skin tissues from an autopsied mpox patient. In human macrophages, MPXV efficiently enters, replicates, and produces infectious particles. Infection activates both AIM2 and NLRP3 inflammasomes, triggering inflammatory responses and three forms of programmed cell death: pyroptosis, apoptosis, and necroptosis. Inflammasome inhibition reduces MPXV-induced inflammation and cell death without affecting viral replication. Screening clinically used anti-inflammatory drugs identified flufenamic acid, which suppresses MPXV-induced inflammation and cell death and, unexpectedly, also inhibits viral infection. Combined treatment with flufenamic acid and the antiviral brincidofovir further enhances suppression of viral infection, inflammatory response, and cell death, while largely preventing MPXV-induced transcriptomic reprogramming in macrophages. These effects were consistent across clade IIb, Ia, and Ib strains associated with the 2022–2023 global and recent African outbreaks. Together, our findings provide insight into MPXV immunopathology and support multitarget therapeutic strategies for severe mpox.

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

Cycles upon cycles—Temperature scaling of medaka development

Sapna Chhabra, Victoria Mochulska, Carina B. Vibe, Anubhuti Anushree, Kristina S. Stapornwongkul, Thomas Thumberger, Joachim Wittbrodt, Paul François, Alexander Aulehla

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How organisms develop in dynamic environmental conditions is a fundamental question. We asked how day-night temperature cycles impact embryonic axis elongation and segmentation, itself a cyclic process linked to the segmentation clock, using the Japanese rice fish medaka. We developed an unbiased dimensional reduction approach, based on Singular Value Decomposition, to reliably identify the dynamic modes of segmentation clock oscillations across all temperature conditions. We reveal that the two major dynamic modes show opposite temperature sensitivities: While the temporal oscillation (mode 1) varies strongly with temperature, the spatial phase gradient (mode 2) appears largely temperature invariant. In addition, we found developmental parameters with intermediate, subscaled temperature responses, such as axis elongation. We used theoretical modeling to understand how dynamic modes emerge from the underlying local oscillation dynamics and axis elongation. We then exposed embryos to circadian and ultradian temperature cycles to reveal dynamic response patterns of oscillations and axis elongation, and found how these responses are integrated into morphological features. Combined, our theoretical–experimental results support a model in which the dynamic integration of temporal (i.e. segmentation clock related) and spatial (i.e. axis elongation) processes, in particular their subscaled temperature response patterns, quantitatively compensate each other to yield a robust, temperature-invariant axis patterning outcome.

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

Selective sparsity–enhanced synchronization in disordered semiconductor laser networks

Li-Li Ye, Nathan Vigne, Fan-Yi Lin, Hui Cao, Ying-Cheng Lai

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Biological networks tend to leverage selective sparsity as an economic strategy to optimize function while minimizing wiring costs. In contrast, achieving synchronization in engineered systems such as semiconductor laser arrays is traditionally expected to require resource-intensive coupling to overcome intrinsic frequency disorders. We demonstrate that selectively coupled sparse networks can outperform fully connected architectures, achieving near-complete synchronization with a significantly reduced coupling budget. Using an evolutionary algorithm, we identify a “pairing opposites” principle: optimal structures specifically prioritize connections between oscillators with the largest opposite frequency detuning. This topology neutralizes dynamical interference induced by redundant links, leading to stable synchronization. We formalize this mechanism through a thermodynamic potential framework, mapping time-delayed phase dynamics to an energy landscape where optimal sparsity prunes additional states to stabilize global phase-locking. Furthermore, we show that the optimal connectivity scales inversely with system size. This principle provides a resource-efficient blueprint for synchronizing and stabilizing diverse complex networks, from photonic arrays to neuromorphic hardware.

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

Bioinspired negative-curvature monomer architecture accelerates on-surface topochemical polymerization

Md. Iqbal Hossain, Joseph A. Garfield, MaryAnne W. Gachema, Soumya Paul, Shelley A. Claridge

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On-surface chemical reactions are often limited by competing requirements for long range molecular order and the local atomic scale dynamics needed for bond formation. In many topochemical reactions, including diacetylene photopolymerization, alkyl-chain ordering provides the required geometric registry but can also restrict the conformational motion necessary for efficient reaction. Here, we show that bioinspired phospholipid architectures accelerate topochemical polymerization at interfaces by introducing multiple, distinct forms of packing frustration that operate on both molecular and nanoscopic scales. Diacetylene phosphocholines (dPCs) and phosphoethanolamines (dPEs), when confined to striped lamellar morphologies on graphitic substrates, undergo substantially faster on-surface photopolymerization than structurally analogous 10,12-tricosadiynoic acid (TCDA) monolayers (t 1/2 ~ 36 min for TCDA, 26 min for dPC, and 3 min for dPE). Molecular dynamics simulations show that topological constraints imposed by the glycerol linkage reduce alkyl-chain segmental order in both phospholipids, increasing the frequency of short separation distances between bond-forming carbons required for reaction. For dPE, typically considered a negative-curvature phospholipid, confinement to a lamellar geometry also frustrates directional headgroup hydrogen bond networks, further increasing reactivity. Together, these results identify complementary mechanisms by which topologically constrained monomers can accelerate on-surface reactions through hierarchical packing frustration. Building on this framework, we design a monomer that exhibits rapid on-surface reaction kinetics.

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

Physics-informed single-frame end-to-end learning for denoising and background removal in fluorescence imaging

Xinxiang You, Shuyue Xie, Chengen Li, Ke Hu, Xueyang Fu, Cuifang Kuang, Longhua Tang, Ziyi Lu, Chuanhai Fu, Zheng-Jun Zha, Xu Liu, Douguo Zhang

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Fluorescence microscopy is often limited by low signal-to-noise ratios arising from the finite number of detected photons and by an out-of-focus background that obscures structural details. Here, we introduce a physics-informed end-to-end learning framework that enables denoising and background suppression from a single fluorescence image. By integrating a microscope-parameterized forward model, the proposed framework generates realistic training datasets entirely through simulation, eliminating the need for experimentally acquired ground-truth images. Once trained for a given imaging condition, the deep neural network can be deployed directly to previously unseen biological specimens without specimen-specific retraining, as demonstrated across the structurally distinct biological samples examined in this study. We experimentally validate the robust single-frame denoising performance in both wide-field and confocal fluorescence microscopy. The enhanced photon efficiency further enables superresolution optical fluctuation imaging using only tens of frames, substantially improving temporal resolution while preserving spatial fidelity. In addition, the proposed single-frame end-to-end learning framework can be extended to remove out-of-focus background in thick samples. These results establish physics-guided, simulation-based end-to-end learning as a general and practical strategy for rapid, data-efficient fluorescence image restoration under photon-limited conditions.

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

IGF2BP1 in 17q-gain cooperates with MYCN to regulate purine biosynthesis and immunotherapy efficacy in neuroblastoma

Jiaxu Liu, Yingzhe Fang, Rongrong Fan, Honghong Wang, Hao Huang, Fan Yang, Lihui Yu, Zhinang Yin, Mingyue Zhao, Pingping Zeng, Ganggang Song, Yu Liu, Jinfang Zhang, Qianqian Yuan, Kaiwei Liang, Baishan Jiang, Hudan Liu, Guoliang Qing

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Concurrent chromosomal 17q-gain and MYCN amplification define a subset of neuroblastoma associated with particularly adverse clinical outcomes. However, how these genetic alterations synergize to promote tumor progression and whether their cooperation confers therapeutic vulnerabilities remain elusive. We herein performed a CRISPR-based functional screen targeting 17q-gain genes and identified the RNA m 6 A reader IGF2BP1 as a critical MYCN collaborator to promote aggressive neuroblastomas via activation of phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), a key enzyme involved in de novo purine biosynthesis. Rewiring of PAICS-mediated nucleotide metabolism enabled tumor cells to sustain necessary purine pools for productive transcription of replicative stress-responsive genes, including CHK1 , to cope with the exacerbated replication stress. Pharmacological inhibition of CHK1 elicited a robust immune reprogramming, leading to activation of cGAS–STING signaling, upregulation of Major Histocompatibility Complex class I expression, and synergistic tumor suppression with immune checkpoint blockade. Altogether, we identify an IGF2BP1/MYCN–PAICS–CHK1 axis that drives aggressive neuroblastoma phenotypes and constitutes an actionable vulnerability for therapeutic intervention.

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

Structural considerations on xeGlyT2 substrate and inhibitor recognition

Ryan P. Cantwell Chater, Azadeh Shahsavar

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

Global grassland productivity and carbon storage benefit from functional diversity under climate change

Stephen Björn Wirth, Christoph Müller, Friedhelm Taube, Jens Heinke, Britta Tietjen, Susanne Rolinski

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Functional diversity plays an important role for ecosystem services of managed grasslands such as their gross primary productivity (GPP) and soil organic carbon (SOC) stocks. Yet vegetation models assessing functional diversity have been limited to small spatial scales. We used the Lund-Potsdam-Jena managed land (LPJmL) competitor stress-tolerant ruderal (CSR) model to assess the role of functional diversity for managed grassland GPP and SOC under climate change at the global scale. LPJmL-CSR simulates functional diversity using plant functional types representing different ecological strategies based on functional traits connected to CSR strategies. Our simulation experiments assumed low and high functional diversity levels and moderate and strong climate change scenarios. Results show that functional diversity plays an important role for GPP and SOC stocks already under moderate climate change. Strong loss of functional diversity prohibits communities’ adaptation to climate change, resulting in loss of GPP and SOC. Spatial patterns of GPP and SOC stocks show substantial differences between the low and high functional diversity scenarios dependent on regional conditions. These results are consistent with empirical findings and support the importance of functional diversity as insurance against climate change. The results of our global-scale model assessment show that enhancing functional diversity could be crucial for maintaining grassland productivity and thus human well-being under global change. In combination with empirical findings, they underpin the need for management practices that support functional diversity of managed grasslands.

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

The more you automate, the less you see: Hidden pitfalls of autonomous AI scientists

Ziming Luo, Atoosa Kasirzadeh, Nihar B. Shah

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The rapid rise of autonomous AI scientists marks a paradigm shift in scientific discovery by automating the research lifecycle. Yet their rushed development has outpaced critical oversight, leaving key workflow decisions dangerously unscrutinized. We present a much-needed systematic analysis of open-source AI scientist systems, investigating four primary pitfalls: inappropriate benchmark selection, data leakage, metric misuse, and post hoc selection bias. Through controlled experiments that isolate each pitfall, we find systematic vulnerabilities across two representative open-source systems. Crucially, we find that these flaws are largely invisible at the level of the final manuscript, suggesting that current manuscript-centric peer review paradigms are fundamentally insufficient for ensuring the integrity of automated research. We further propose mitigation strategies and demonstrate that access to full workflow artifacts (log traces and code) enables more effective auditing. Our findings suggest that journals, conferences, and researchers should move beyond manuscript-only evaluation toward process auditing the end-to-end workflow artifacts of AI scientist systems.

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

The lack of characterization of inferential operators leaves the robustness of global insect richness estimates undetermined

Simone Fattorini, Paulo A. V. Borges

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

How biological synapses self-assemble gradient learning

Qianli Liao, Liu Ziyin, Yulu Gan, Brian Cheung, Mark T. Harnett, Tomaso Poggio

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Existing models of learning in the brain explain how given circuits learn, but not how biology could assemble those circuits in the first place. To address this gap, we formulate Self-Assembling Learning—the study of how learning systems can emerge from lower-level interactions—and introduce one example mechanism, the Self-Assembling Motif (SAM). SAM is self-assembling at two scales: The motif emerges from initially random connectivity under heterosynaptic plasticity rules, and networks of SAMs, composed hierarchically, self-organize into dynamics that provably approximate a generalized form of stochastic gradient descent—matching backpropagation-level performance. This suggests that biological learning need not be prescribed but can emerge from local rules—and to a far greater extent than previously thought.

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

Reply to Li & Zhang: Adaptive evolution of stop-loss RNA editing in Fusarium graminearum

Yanfei Du, Qinhu Wang, Huiquan Liu

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

An opto-microperfusion neural probe for multiplexed detection of optogenetically evoked neurochemical release dynamics

Yuxuan Zhang, Ian Bain, Yi Huang, Alev Ecevitoglu, Fuying Dong, Jingyi Chen, Gayle Edelstein, Xincheng Zhang, Huijie Li, Zhengyan Weng, Xiaoting Xue, Simiao Niu, Michael R. Bruchas, John D. Salamone, Alexander C. Jackson, Robert T. Kennedy, Yi Zhang

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Probing the spatiotemporal release dynamics of multiple neurochemicals simultaneously in vivo is essential for understanding the molecular basis of brain function and behavior. Microdialysis enables multiplexed neurochemical analysis when combined with advanced molecular tools such as mass spectrometry, but existing microdialysis probes typically exhibit low recovery rates and provide temporal resolution of several minutes, which is insufficient to capture rapid neurochemical release events. Moreover, it remains challenging to investigate the release of multiple neurochemicals upon cell type–specific neuromodulation with a single probe. Here, we present an opto-microperfusion platform that integrates time-sequential microfluidics with cell type–specific optogenetic neuromodulation and push–pull microsampling capabilities. We demonstrated subminute temporal resolution in vitro and near-minute temporal resolution in vivo, with in vivo sampling intervals limited by downstream analytical requirements. The platform achieved high recovery rates for both small molecules and neuropeptides, including 76% for serotonin, 69% for dopamine, and approximately 14% for neuropeptide Y, representing a significant improvement over conventional microdialysis probes. In vivo studies in rats demonstrated reliable microsampling of multiple neurochemicals with minimal sample-to-sample variation. Studies in mice demonstrated the simultaneous detection of the release dynamics of up to 23 different neurochemicals following optogenetic stimulation when coupled with mass spectrometry. Together, this multimodal neural probe paves the way for investigating the molecular mechanisms underlying behavior and neurological disorders.

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

Two D-loop resolution systems enable natural genetic transformation in bacteria

Léo Hardy, Violette Morales, Clothilde J. Rousseau, Mathieu Bergé, Fanny Mazzamurro, Julie Plantade, Triana N. Dalia, Ankur B. Dalia, Eduardo P. C. Rocha, Xavier Charpentier, Patrice Polard

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Natural transformation is a widespread mechanism driving genetic exchanges in bacteria. It proceeds from the capture of extracellular DNA released by other cells. Internalized in linear single strands, this exogenous DNA is ultimately integrated into the genome by homologous recombination. It is unknown how the RecA-directed D-loop intermediate of this dedicated recombination pathway is processed. We report that resolution of the transformation D-loop depends on two endonucleases of opposing phylogenetic distribution in bacteria. One is YraN, which has coevolved and interacts with the ComM helicase, known to extend DNA recombination at the transformation D-loop. The other is CoiA, which is restricted to the Bacillota. CoiA is shown to be a resolvase of the transformation D-loop, extended by the RadA helicase in these species. We demonstrate that both YraN and CoiA act synergistically with their cognate helicases. These findings reveal that bacteria have evolved two helicase/nuclease pairs for the maturation and recombination extension of the transformation D-loop. The wide distribution of this dual system indicates that recombination of exogenous DNA by natural transformation is an ancestral and pervasive feature of bacteria.

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

Ancient DNA challenges to admixture narratives: Insights from Notre-Dame Cemetery (1683–1796) in Colonial Montreal, Canada

Diane Martin-Moya, Jean-Christophe Grenier, Liam Thomas Lanigan, Justin Pelletier, Evan K. Irving Pease, Fernando Racimo, Claude Bhérer, Hannes Schroeder, Julie Hussin, Emmanuel Milot, Isabelle Ribot

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Historical narratives of early colonization in Quebec frequently portray French–Indigenous relations as cooperative and characterized by admixture; which are often mobilized in modern debates on false-indigeneity. These narratives have been studied through genealogical, genetic, and bioarchaeological analyses, yet individuals of African descent remain mostly absent from them, while Indigenous peoples are framed largely in relation to colonists. Notre-Dame Cemetery (1683–1796) in Tiohtià:ke-Montréal offers a unique window onto one of the earliest urban colonial populations in Nouvelle France, but previous bioarchaeological studies have produced conflicting interpretations regarding the presence of non-European or admixed individuals. Here, we generated ancient DNA from 45 individuals and applied genotype imputation, runs-of-homozygosity, and identity-by-descent analyses to reevaluate genetic relatedness and cemetery organization. Our results show exclusively French European ancestry. We observe low levels of close-kin unions and identify several genetic lineages distributed across the cemetery’s successive burial phases rather than family clustering or religious ordering. The spatial organization of the graves is consistent with rapid demographic growth, with successive burials overlapping one another, before being disrupted by urban development. Rooted in Indigenous decolonial frameworks, these findings challenge the ‘admixed founding population’ narrative, aligning with historical evidence of Indigenous and African-descended marginalization while highlighting the social inequalities shaping this colonial urban cemetery. Québec’s bioarchaeological practices must move beyond blood ties as the sole measure of kinship and commit to legal frameworks that better reflect reciprocal obligations of care, in order to overcome the colonial structures that still define heritage.

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

Extended fractional Hofstadter states at high field in twisted bilayer graphene above the magic angle

Joe Finney, Aaron Sharpe, Linsey K. Rodenbach, Jian Kang, Xiaoyu Wang, Kenji Watanabe, Takashi Taniguchi, Marc A. Kastner, Oskar Vafek, David Goldhaber-Gordon

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When a Chern band is partially filled, a fractional Chern insulator (FCI)—the lattice analog of a fractional quantum Hall state—can arise. Though the full range of possible scenarios for producing such a state is not established, the most tractable models combine strong electronic interactions with the quantum geometry of the parent Chern band meeting specific criteria. In twisted bilayer graphene, the importance of interactions can be tuned by varying the interlayer twist. Here, we study a sample with twist near 1.4 ° , large enough to suppress the zero-field correlated states. We find that applying a strong magnetic field restores the importance of electron–electron interactions: at nearly half a magnetic flux quantum per moiré unit cell, deep in the Hofstadter regime, odd-denominator fractional states appear in multiple Hofstadter subbands. These fractional states persist over larger ranges of density, and are more robustly quantized, than nearby integer states, opposite to what is seen in other fractional quantum Hall and FCI systems.

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

Organic imprint: Natural matter dictates crystallization of manganese oxides on hematite

Chenfei Zhang, Wenxiong Shi, Runliang Zhu, Lan Ling

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Mineral–organic interfaces regulate crystallization processes central to mineral evolution and biogeochemical cycling, yet how organic matter (OM) actively directs nucleation and growth pathways remains unresolved. Here, we reveal a pivotal role of humic acid (HA), a representative OM, in orchestrating the crystallization of Mn oxides on hematite by influencing both the spatial distribution of Mn ions and the subsequent pathways of Mn oxides nucleation and growth. Our findings reveal that mineral-associated organic matter (MAOM) facilitates the formation of fine-grained Mn oxides through a distinct three-step mechanism: i) formation of Mn-rich and Mn-poor OM domains on hematite surface, ii) catalytic oxidation of Mn(II) and nucleation of Mn ions to form primary particles within the Mn-rich domain, and iii) subsequent assembly of Mn oxide particles via particle attachment, leading to a structurally integrated Mn oxide phase (hausmannite and manganite). Spectroscopic analysis and molecular dynamics simulations further reveal that HA adopts facet-specific conformations, which modulate Mn accumulation and particle assembly. Our findings demonstrate that OM not only associates with minerals but can modify mineral–OM interfacial reactivity and crystallization pathways, offering insights into mineral crystallization mechanisms, soil evolution, and mineral–OM interactions.

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

Phenotypic screening identifies kenpaullone as a prolymphangiogenic compound to improve heart repair following myocardial infarction

Christophe Ravaud, Caroline A. Cuoco, Sarah Sigal, Hannah M. Unsworth, Susanna T. E. Cooper, Adam B. Lokman, Carole J. R. Bataille, Angela J. Russell, Paul R. Riley

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Myocardial infarction (MI) induces cardiac muscle death and its subsequent replacement by a noncontractile fibrotic scar, which underlies progression to heart failure. Current treatments restore blood flow and assist with cardiac workload but do not promote regeneration. We have previously shown endogenous growth of the cardiac lymphatic system following MI and further stimulation with the lymphatic endothelial specific mutated Vascular Endothelial Growth Factor-C (VEGF-C) isoform, VEGFC-C156S, resolves the immune response and improves cardiac function. However, the short half-life of VEGFC-C156S makes it suboptimal for clinical use, highlighting the need for alternative prolymphangiogenic strategies. We established a spheroid-based sprouting assay using human lymphatic endothelial cells to mimic lymphangiogenesis and performed a phenotypic screen of focused libraries of epigenetic regulators, kinase inhibitors, and stem cell modulators. Automated imaging and quantitative analysis identified several kinase inhibitors, previously characterized as GSK3ß inhibitors, as prolymphangiogenic regulators. Among them, the most potent was kenpaullone, which activated the same canonical prolymphangiogenic ERK pathway as VEGF-C, but induced a distinct transcriptional response in treated spheroids. Using kenpaullone-derived chemical probes and target-validation approaches, we identified MAP4K4 as a molecular target mediating the prolymphangiogenic effect observed. Finally, in a mouse MI model, kenpaullone enhanced cardiac lymphangiogenesis and improved cardiac function.

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

Large language models unlock the ecology of species interactions

Heng-Xing Zou, Xiaohao Yang, Thabassum H. Hajamaideen, Olivia J. Stein, Roxanne S. Beltran, Benjamin G. Freeman, Mark Lindquist, Eliot T. Miller, Summer Mengarelli, Charlotte M. Probst, Fernanda S. Valdovinos, Derek B. Van Berkel, Phoebe L. Zarnetske, Brian C. Weeks, Kai Zhu

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Species interactions shape population dynamics, geographic distributions, evolutionary trajectories, and responses to environmental change. Yet data on these interactions remain scarce across broad spatial, temporal, and taxonomic scales because they are difficult to collect in the field. One promising source of interaction data is citizen science platforms, which contain billions of biodiversity observations, often accompanied by unstructured text comments that may document interactions among organisms. Advances in large language models (LLMs) make it increasingly feasible to identify, extract, and categorize biotic interactions from these unstructured data at scale. Here, we present an LLM workflow that collects species interaction observations from multilingual citizen science comments. Using two case studies—bird–bird and plant–pollinator interactions—we show that LLMs can rapidly extract interaction types and participating species with high accuracy. These data can greatly expand the spatial, temporal, and taxonomic coverage and resolution of species interactions data, enable new tests of long-standing ecological questions, and improve our ability to track ecological changes. With appropriate validation, expert review, and attention to data privacy for both users and sensitive species, this approach opens new opportunities to characterize, forecast, and conserve biodiversity under global change.

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

Formation of a swelling gel underlies a morphological transition in Bacillus subtilis biofilms

Ayantika Saha, Joshua M. Jones, Abigail Plummer, Joseph W. Larkin

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Microbes across diverse species and environments form biofilms, living materials composed of cells and extracellular polymers. Biofilm-dwelling cells benefit from emergent soft matter physics, which sculpts three-dimensional morphologies and facilitates osmotic nutrient uptake. Although biofilms are modeled as viscoelastic gels, the physical origins of the phase transition underlying their conversion from groups of cells to living gels have not been systematically investigated. Here, we show that Bacillus subtilis biofilms use polymer composition to tune their physical properties and drive gel formation. Using imaging, water immersion experiments, and rheological measurements with matrix knockout strains, we demonstrate the complementary roles of two polymers in this developmental transition: hydrophilic poly- γ -glutamic acid swells colonies by absorbing water while exopolysaccharides serve as effective cross-linkers, causing a sol–gel-like phase transition that imparts structural integrity. With matrix knockout coculture biofilms, we independently modulate the production of each polymer and reveal a phase space of biofilm morphologies. Colonies that produce both polymers develop macroscopic wrinkles. A thin-film model predicts biofilm wrinkling from swelling-induced internal strain coupled with elasticity. The model reproduces the shape of our observed morphological phase diagram. Our results demonstrate that bacteria leverage gelation to vary their material properties and morphologies, with implications for microbial ecology and engineering living matter.

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

A receptor-like kinase pair integrates extracellular ATP and salicylic acid signaling to activate plant immunity

Mengran Yang, Daewon Kim, Jae hyo Song, Abigail M. Jensen, Kiwamu Tanaka, Gary Stacey

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Extracellular Adenosine 5′-triphosphate (eATP) is a damage-associated molecular pattern in both plants and animals, playing an important role as a danger signal in response to various environmental stresses. eATP works both independently and in coordination with other signaling pathways. Here, we identify a previously uncharacterized p roline-rich e xtensin-like r eceptor k inase 15 (PERK15), which interacts with the plant eATP receptor P2K1 and integrates eATP and salicylic acid (SA)-mediated pathogen defense responses. perk15 mutant plants display reduced eATP responses and compromised pathogen resistance, whereas ectopic overexpression of PERK15 triggers autoimmunity. eATP treatment enhances PERK15–P2K1 interaction. P2K1-mediated phosphorylation of a Ser/Thr cluster in the PERK15 kinase domain is essential for its activation. PERK15 transcript levels are upregulated by SA, and PERK15 overexpression promotes the protein accumulation of the SA receptor NPR1. Data show that eATP and SA act synergistically to regulate plant defense responses in a PERK15-dependent manner. Together, the findings identify PERK15 as a key node linking eATP and SA signaling, providing insights into how plants integrate extracellular danger signals and defense hormone signals to mount effective immune responses.

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

Exact solutions produce a full picture of crack behavior in dynamic fracture

Jacqueline Jensen, Michael Marder

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The theory of fracture normally describes cracks as propagating discontinuities in a continuous medium where stresses vanish on free crack faces. We describe cracks instead at the particle level and obtain more general analytical results than were available previously. Using dynamical crack solutions for widely varying dissipation and general isotropic elastic moduli, we construct a catalog of 100,000 crack solutions and from it a general picture of when cracks are stable. For our exactly solvable model of dynamic fracture, the surface wave speed sometimes sets an upper limit on crack velocity, as expected. However tensile cracks traveling faster than the shear wave speed are possible and their stability is enhanced when they travel along weak interfaces, when dissipation increases, and when system sizes are small. Our results reinforce a standard view that supersonic cracks require supersonic energy transport near the tip, but we show it can come from dissipation as well as hyperelasticity.

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

The NAC transcription factor SOMBRERO controls auxin gradients for columella root cap maturation and turnover

Pengfei Wang, Zhongyuan Liu, Yuling Zhou, Linjun Sun, Junxian He, Linlin Qi, Byung-Ho Kang

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The plant root cap consists of continuously renewed cells that collectively protect meristematic stem cells, sense environmental stimuli, and guide root growth direction. Auxin gradients within the root cap are essential for cell turnover, root responses to external cues, and root cap development. However, our understanding of how the auxin gradient is established and maintained remains limited. Here, we show that the root cap-specific NAC transcription factor SOMBRERO (SMB), previously implicated in root cap maturation, turnover, and programmed cell death, coordinates auxin homeostasis, and signaling in the columella root cap. Inactivation of SMB ( smb-3 ) disrupted the subcellular maturation program of root cap cells and diminished the auxin response gradient in the columella root cap. Root tip-specific transcriptomic profiling of wild-type (Col-0) and smb-3 revealed that transcript levels of auxin biosynthesis, transport, and signaling were significantly altered in smb-3 . EMSA and promoter reporter assays further showed that SMB binds promoter fragments of multiple auxin-related genes and modulates their transcriptional activity, supporting a transcriptional role for SMB in auxin regulation. Perturbation of auxin transport impaired Golgi remodeling, xylogalacturonan accumulation, and border-like cell turnover. Exogenous auxin partially restored Golgi morphology but failed to rescue root cap organization and border-like cell turnover, indicating that proper auxin dynamics, rather than auxin levels alone, are required for root cap development. Taken together, these results extend previous understanding of SMB function and identify SMB as a versatile transcription factor that coordinates auxin dynamics with Golgi remodeling and root cap turnover.

Understanding consciousness (biological and artificial) as a society of self-schemas

Michael S. A. Graziano

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This article argues that human cognition is more than the performance of functions such as memory, decision-making, and attention. The brain also builds schematic models of those cognitive functions and uses those models to monitor, predict, and partially control them. When you introspect, your understanding of who you are and what is happening inside of you is derived from those schematic, sometimes inaccurate, but generally useful models, rather than from the actual cognitive functions that are represented by those models. The proposal expands the previously proposed attention schema theory to a more general schema theory, in which the mind as we know it introspectively is a society of interacting self-schemas. The article focuses on five self-schemas including the attention schema (which is proposed to give us our intuitions about a conscious mind that takes possession of items in a vivid manner), a decision schema (which generates simplified, sometimes confabulated accounts of the decision-making process and gives us our intuitive understanding of agency and will), emotion schemas (which create complex interpretations of the physiological state of the body and provide us with our understanding of emotional experience), the body schema (which provides our understanding of who we are as physical beings), and personas (which give us our understanding of our emotional, social, and moral character, and act as a framework to guide our behavior). The article includes a discussion of how consciousness in a machine requires a similar suite of self-schemas used for similar functional purposes and may already be partially present.

Team science: Progress, barriers, and pathways forward

Mo Wang, Diana L. Burley

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Reproducibility of social science research using aggregate statistics with noise infused for differential privacy

Ryan Steed, Eduardo Abraham Schnadower Mustri, Alessandro Acquisti

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Privacy-preserving analytics such as differential privacy are designed to allow the analysis of sensitive datasets while protecting individuals’ privacy. Their deployment, however, has been controversial. Critics maintain that statistical noise injected to preserve privacy can degrade the quality and feasibility of social science research. We select a benchmark of empirical findings from 93 published social science studies involving regression analyses over aggregate statistics. We evaluate whether their findings replicate on privacy noise-infused data. Under privacy budgets typical in industry, around 91% of simulated findings still support the original claims at significance level α = 0.1 . Claims based on weaker original effect sizes are more likely to be nullified or sometimes reversed. We compare distortions caused by privacy noise to those due to measurement errors and other kinds of nonsampling errors common in social statistics, and we find that the marginal impacts of privacy protection are smaller. Moreover, discrepancies due to privacy noise are often much smaller than discrepancies observed in traditional replication and robustness studies.

An evil much exaggerated? The consequences of cousin marriage

David W. Lawson

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Everyday adaptation in a gilded trap: Risk-taking and resilience in Maine’s lobster fishery

Joelle Kilchenmann, Theresa L. U. Burnham, Heather M. Leslie, Kathleen M. Reardon, Jameal F. Samhouri, Joshua S. Stoll

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Flexibility is widely regarded as an enabling factor of adaptive capacity among natural resource users. Yet, as ecological systems around the world become increasingly simplified and social environments reduce diversification options, flexibility is becoming limited. Despite this trend, efforts to study how people adapt within the confines of constrained social–ecological systems have been sparse. Here, we broaden the analysis of resilience through a study of the American lobster fishery in Maine, United States, one of the most valuable fisheries in the world. Drawing on 307,000 observations from 3,515 harvesters over a 13-y period (2010–2022), we used a generalized linear mixed-effects model to analyze how sociodemographic characteristics, economic conditions, and time shape the probability of fishing during poor weather conditions, which we define as high-risk. We find demographic and socioeconomic heterogeneity in risk-taking: Men, mid-career harvesters, and captains of larger businesses were more likely to fish in risky conditions, and both low landings and high catch prices increased risk-taking. Contrary to our prediction, however, we observed an overall decline in risk-taking through time. We argue that harvesters instead relied on everyday adaptation—individual-scale, short- and medium-term adjustments in business strategy that occur within the constraints of the existing social–ecological system—to maintain resilience without increasing risk. Observable shifts in fleet composition, including use of larger vessels and higher-capacity licenses, lend support to this understanding. These results suggest that even in highly constrained social–ecological systems, protected response spaces and comanagement structures can enable often overlooked forms of flexibility.

Science

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

High-fidelity entangling gates and nonlocal circuits with neutral atoms

Simon J. Evered, Muqing Xu, Sophie H. Li, Alexandra A. Geim, J. Pablo Bonilla Ataides, Marcin Kalinowski, Dolev Bluvstein, Nishad Maskara, Christian Kokail, Markus Greiner, Vladan Vuletić, Mikhail D. Lukin

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The generation and manipulation of entanglement with low error are essential in quantum information systems. In practice, two-qubit entangling gates constitute a dominant error source, limiting circuit depths and performance in fault-tolerant architectures. Using a neutral-atom quantum processor, we realized entangling controlled- Z gates with a high-Rabi-frequency smooth-amplitude pulse, employing state-selective readout and qubit reuse for fast calibration, and achieved a fidelity of 99.854(4)%, which improved to 99.941(3)% upon loss postselection, with stable performance for 10 hours. We then used these low-error gates in quantum circuits with coherent atom rearrangement. Performance was benchmarked by creating and disentangling cluster states, and subsequently, we studied nonlocally entangled states with scrambling circuits featuring longer-range connectivity. Our approach provides a route toward deep-circuit, efficient fault-tolerant quantum computation.

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

Insights from more than a year of ongoing episodic lava fountaining at Kīlauea

A. F. Flinders, N. I. Deligne, K. Hon, D. T. Downs, K. J. Lynn, P. A. Nadeau, K. Mulliken, J. C. Chang, P. J. Dotray, M. Bagnardi, I. A. Johanson, M. H. Zoeller, K. R. Anderson, M. R. Patrick, C. Kern, C. R. Sealing, M. P. Poland, D. Phillips, M. Cappos, L. DeSmither, A. P. Ellis, S. Fuke, P. Fukunaga, M. Hawk, T.-J. Hoomanawanui, J. Jamora, A. Kamakeʻeaina, K. Kamibayashi, S. Lowman, W. Tollett, K. Rubio, S. Swaney, S. M. Warren, H. Winslow, N. L. Bennington, A. Jolly, R. G. Adams, M. Decker, L. Forster, E. Gallant, C. Gansecki, R. Hazlett, B. F. Houghton, N. Kohagura, S. Lundblad, N. G. Pasqualon, K. Poepoe, H. Neuman, C. Cauley, K. Wilde

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Episodic lava fountaining is rare globally, with only three occurrences from Kīlauea (Hawaii) since 1823. Beginning in December 2024, an eruption within the summit crater, Halemaʻumaʻu, has produced 54 fountaining episodes to date, each lasting typically for hours and separated by days to weeks. Although multiple mechanisms have been proposed, fundamental questions remain about how magma reservoir pressure, conduit permeability, and volatile exsolution control fountaining onset. We present a multiparameter record of episodic fountaining at Kīlauea using modern geochemical, geophysical, and geologic monitoring. These observations revealed systematic correlations between fountaining and summit inflation, enabling unprecedented quantitative forecasts. This eruption will provide new constraints on the timing, evolution, and processes driving episodic fountaining globally, and highlights Kīlauea’s role as a natural laboratory for studying volcanic processes.

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

The genetic basis for the production of toxic quinolizidine alkaloids in lupins

Davide Mancinotti, Hajar Golshadi Ghalehshahi, Isabella Kruse-Andersen, Louise Kjaerulff, Ting Yang, Dan Stærk, Fernando Geu-Flores

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Lupins ( Lupinus spp.) are promising protein crops that accumulate bitter and toxic quinolizidine alkaloids (QAs). The effective removal of QAs through new breeding technologies is hampered by a poor understanding of their biosynthesis. In this study, we used pathway reconstruction and mutant analysis to elucidate the full QA pathway in L. angustifolius [narrow-leafed lupin (NLL)] comprising 15 enzymatic steps. Major latex protein–like proteins play a prominent role in the pathway by accelerating spontaneous chemical equilibria, and an oxidoreductase-like protein ensures stereoselectivity. We also engineered a new low-alkaloid NLL line and identified the causal mutation in an existing low-alkaloid line of L. albus. Our work reveals the genetic and biochemical basis of toxic QA production and streamlines the de novo domestication of wild lupins and other QA-containing legumes.

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

Nutritional interventions’ impacts on human milk: Three trials in low-resource settings

Trenton Dailey-Chwalibóg, Andrew Mertens, Kelsey Fehr, Chi-Hung Shu, April Jauhal, Melissa B. Manus, Lishi Deng, Laeticia Celine Toe, Ameer Muhammed, Aneela Pasha, Yasir Shafiq, Naveed Iqbal, Waqasuddin Khan, Muhammad Imran Nisar, Jo-Anna B. Baxter, Megan R. Beggs, Niveda Sundararaman, Jennifer E. Van Eyk, Lars Bode, Alan Hubbard, Kim A. Lagerborg, Mohit Jain, Daniela Hampel, Setareh Shahab-Ferdows, Lindsay H. Allen, Carl Lachat, Mark D. DeBoer, Fyezah Jehan, Nima Aghaeepour, Liat Shenhav, Joann M. McDermid, Meghan B. Azad

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Human milk (HM) composition is variable to support changing infant needs and is influenced by maternal diet and health. We harmonized HM data from three randomized trials in Burkina Faso (MISAME-III), Pakistan (Mumta-LW), and Tanzania (ELICIT) within the International Milk Composition (IMiC) Consortium to test how maternal nutrition affects HM composition. Balanced energy-protein (BEP) supplements or nicotinamide given to lactating mothers increased milk B-vitamins, while macronutrients, oligosaccharides, bioactive proteins, and microbiome composition were physiologically buffered. Metabolomic and proteomic analyses revealed shifts in vitamin-related metabolites, triglyceride profiles, and intracellular protein representation. In a MISAME-III subset, maternal and infant blood showed concordant changes. Postnatal BEP improved infant growth only in the more undernourished cohort. Improved milk micronutrient quality across settings supports extending maternal supplementation into lactation.

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

A fast radio burst at redshift 2, three billion years after the Big Bang

Manisha Caleb, Themiya Nanayakkara, Benjamin W. Stappers, Inés Pastor-Marazuela, Ilya S. Khrykin, Karl Glazebrook, Nicolas Tejos, J. Xavier Prochaska, Kaustubh Rajwade, Lluis Mas-Ribas, Laura N. Driessen, Wen-fai Fong, Alexa C. Gordon, Jordan L. Hoffmann, Clancy W. James, Fabian Jankowski, Lordrick Kahinga, Michael Kramer, Sunil Simha, Ewan D. Barr, Mechiel Christiaan Bezuidenhout, Xihan Deng, Zeren Lin, Lachlan Marnoch, Christopher D. Martin, Anya Nugent, Kavya Shaji, Jun Tian

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Fast radio bursts (FRBs) are millisecond-duration radio transients from extragalactic sources. Their frequency and polarization properties are affected by plasma and magnetic fields along the line of sight to Earth. We report radio observations of FRB 20240304B and near-infrared follow-up to identify its host galaxy. The host is a low-mass, clumpy, star-forming galaxy at redshift 2.148 ± 0.0013, corresponding to 3 billion years after the Big Bang. This FRB occurred during the peak of cosmic star formation and probes ionized gas over approximately 80% of cosmic history. The highly scattered burst emission implies that there is a population of FRBs that are undetected by current surveys.

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

Marine snow viscosity regulates microbial degradation and the ocean carbon sink

Bryce G. Inman, Stuart Humphries, Farooq Azam

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Bacterial degradation of marine snow aggregates is a major component of global carbon cycling. Whether aggregate carbon is released in the upper ocean or is sequestered at depth depends on its sinking speed and degradation rate. However, little is known about the physical constraints of bacterial colonization and degradation of individual aggregates. Using molecular rotors to measure the nanoscale viscosity field of natural aggregates, we show that aggregates are highly structured microhabitats with less-viscous regions that are accessible for colonization and more-viscous regions that correlate to a barrier to bacterial infiltration. By quantifying the viscosity degradation rate, we demonstrate that more viscous aggregates take longer to degrade, sink farther, and contribute more to carbon sequestration, revealing a microscale physical constraint of the global ocean carbon pump.

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

Volatile eutectics to tailor crystallization for perovskite optoelectronics

Jason J. Yoo, Connor J. Dolan, Seongsik Nam, Jinho Lee, Kyu Min Kang, Bong Joo Kang, Rushik Desai, Niranjana Mohan Kumar, Arkita Chakrabarti, Daesoo Kim, Jang Hee Cho, Donghyuk Chung, Jack R. Palmer, Kelly X. Vences, Zhewen J. D. Deng, Yanqi Luo, Barry Lai, Tao Zhou, Zhonghou Cai, Martin V. Holt, Andrew M. Kiss, In Sun Cho, Dong Hyun Kim, Jun Hong Noh, Mariana I. Bertoni, Arun Mannodi-Kanakkithodi, Dane W. deQuilettes, David P. Fenning, Seong Sik Shin

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Improvements to the radiative efficiency of halide perovskite thin films are necessary to approach fundamental solar cell performance limits. We tailored perovskite crystallization by leveraging the eutectic interaction between zinc bromide and methylammonium chloride additives. The resulting films had high photoluminescence quantum yield and charge carrier decay times and low surface recombination velocity. Nanoprobe x-ray microscopy revealed local melting of the eutectic at grain boundaries during annealing that reduced intragranular structural defect density. Annealing also homogenized the halide distribution and caused zinc segregation to grain boundaries. Solar cells fabricated with the volatile eutectic reached 26.5% power conversion efficiency (PCE, certified 25.9%), and perovskite minimodules (areas more than 15 square centimeters) had 23.9% PCE. Small-area cells with a poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] hole transporter retained 85.8% of their initial 24.1% PCE after 1400 hours of continuous operation at 85°C. Furthermore, this approach enables 26.1% external quantum efficiency as light-emitting diodes.

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

The human gut microbiome primes fever after vaccination

Kelsey E. Huus, NA, Hirohito Abo, Yi Han Tan, Ezgi Atay, Héloïse Rytter, Ronald Keller, Silke Dauser, Dai Long Vu, Meghan B. Azad, Rob Knight, Alfred Ke, Larisa Lotoski, Marc-André Langlois, Rong Liu, Alexander V. Tyakht, Nicholas Youngblut, Sang-Moo Kang, Julie Parsonnet, Lisa Maier, Benoit Chassaing, Peter G. Kremsner, Andrew T. Gewirtz, Meral Esen, Ruth E. Ley, Julian J. Gabor, Johanna M. Gaile, Wim A. Fleischmann, Alex S. Siebner, Geerten Smeenk, Judith Flügge, Roberta Allgayer De Moraes, Dennis Jakob, Alina Prokipchuk, Carolin Wilhelm

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Fever is a common adverse reaction to vaccination, contributing to vaccine hesitancy and reduced uptake. To understand variation in fever risk, we longitudinally profiled fecal microbiota, oral temperature, and serological markers in 171 healthy adults receiving Severe acute respiratory syndrome coronavirus 2 mRNA vaccines. Fever risk correlated with low-grade intestinal inflammation, increased abundance of flagellated Lachnospiraceae bacteria, and increased flagellin expression prevaccine. Microbiomes from fever-high donors triggered stronger inflammation in human intestinal organoids and drove flagellin-dependent vaccine reactions in gnotobiotic mice. Moreover, microbiome flagellin phenotypes and murine vaccine reactions were modifiable by diet. Consistent with this, human fever risk was associated with self-reported diet and metabolic markers. These findings identify the gut microbiome as a driver of vaccine-induced fever, suggesting that microbiome-targeting strategies could modulate immune tone and improve vaccine side effects.

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

Asymmetric enzymatic hydrophosphorylation through O 2 activation

Yi Zhou, Yifei Ge, Wesley Harrison, Huimin Zhao

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Enzymatic carbon-phosphorus bond formation is extremely rare in nature, limiting biocatalytic access to phosphorus-containing compounds that are widely used in pharmaceuticals and agrochemicals. Here, we report an asymmetric enzymatic hydrophosphorylation through oxygen activation using a repurposed flavin-dependent enzyme. Mechanistic studies revealed that reactive oxygen species are converted into productive phosphorus-centered radicals, followed by radical addition and enzymatic hydrogen atom transfer, achieving high enantioselectivity. The enzyme accommodates diverse phosphorus-hydrogen donors that pose challenges to chemical catalysis, enabling the biosynthesis of valuable phosphorus-containing scaffolds. This work expands the scope of biocatalysis to programmable carbon-phosphorus bond formation and establishes a paradigm for channeling oxygen reactivity in enzymes.

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

Shared patterns of human milk composition link mammary gland function to infant growth

April Jauhal, Bianca Cordazzo-Vargas, Daniel Sunko, Pratima Niroula, Lishi Deng, Laeticia Celine Toe, Ameer Muhammad, Aneela Pasha, Yasir Shafiq, Naveed Iqbal, Waqasuddin Khan, Andrew Mertens, Kelsey Fehr, Joann M. McDermid, Melissa B. Manus, Chi-Hung Shu, Daniela Hampel, Setareh Shahab-Ferdows, Megan R. Beggs, Kim A. Lagerborg, Mohit Jain, Carl Lachat, Mark D. DeBoer, Jennifer Van Eyk, Natalie Rodriguez, Theo J. Moraes, Padmaja Subbarao, Alan Hubbard, Muhammad Imran Nisar, Lars Bode, Lindsay Allen, Donna Geddes, Michelle Kay McGuire, Nima Aghaeepour, Trenton Dailey-Chwalibóg, Fyezah Jehan, Meghan B. Azad, Liat Shenhav

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The mammary gland produces nutrient-rich human milk (HM), yet how mammary functional state shapes HM composition and infant outcomes remains poorly understood. We used HM multi-omics - metabolomics, proteomics, micronutrients, macronutrients, and HM oligosaccharides - across 1,543 samples from three cohorts, including two randomized trials, as a noninvasive readout of mammary functional state. Trajectory modeling and multi-omic integration showed that maternal supplementation improved recovery from early growth faltering and revealed a shared HM compositional axis linking maternal nutrition to infant growth. Machine learning, with Human Protein Atlas–informed proteomics, identified seven HM biomarkers reflecting variation across key mammary domains, indexing milk synthesis, barrier integrity, and immune/repair activity. Elevated valerylcarnitine and low pantothenic acid emerged as metabolic signals linking mammary functional state to infant growth.

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

Safeguarding global terrestrial vertebrate species from future sea-level rise

Zhong-Wen Jiang, Heng-Bin Xiao, Jeffrey O. Hanson, Yiwen Zeng, David S. Wilcove, Mark Schuerch, Matthew L. Kirwan, Qin-Fang Yan, Yaping Chen, Liang Ma

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Sea-level rise (SLR) threatens terrestrial biodiversity, yet its spatiotemporal and species-specific impacts remain unclear. Integrating relative SLR projections across five Shared Socioeconomic Pathways (SSPs) with Area of Habitat (AOH) maps for 34,120 terrestrial vertebrate species, we project species exposed to SLR will increase from up to 13,680 in 2050 to 15,324 by 2100, including 57–63% of birds, 47–52% of mammals, 28–36% of reptiles, and 20–24% of amphibians. In Southeast Asia, inland inundation areas support high richness. Under SSP5-8.5, species facing >10% habitat inundation surges from 18 in 2050 to 109 by 2100, with reptiles and already threatened species overrepresented. Safeguarding SLR refugia, the non-inundated habitats for exposed species, is critical, yet over 96% lie outside protected areas, demanding early international action.

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

Golgi-derived vesicles containing PI(3,4)P 2 drive mitochondrial fusion

Sho Aki, Mayuko Segawa, Vincent Anton, Suvagata R. Chowdhury, Shun Nagashima, Isshin Shiiba, Dane M. Wolf, Ikuko Koyama-Honda, Ayumu Sugiura, Joe Ganellin, Mark Johnson, Sakie Katsumura, Maki Sugaya, Yasunori Fujita, Koki Nakamura, Kazuaki Yoshioka, Hisamichi Naito, Yoh Takuwa, Ikuroh Ohsawa, Yusuke Hirabayashi, Shigeru Yanagi, Masahiro Morita, Tsuyoshi Osawa, Julien Prudent

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Mitochondria are dynamic organelles that remodel their shape to regulate cell fate. Mitochondrial division involves interactions with the endoplasmic reticulum (ER), lysosomes, and trans-Golgi network–derived vesicles to facilitate membrane scission. How interorganelle contacts regulate mitochondrial membrane fusion remains largely unknown. Here, we identified a role for Golgi-derived vesicles enriched in phosphatidylinositol 3,4-bisphosphate [PI(3,4)P 2 ] in regulating mitochondrial fusion. We found that these vesicles were recruited to ER- and mitofusin-marked fusion sites. Accordingly, loss of class II PI3-kinase isoforms α and β (PI3K-C2α and PI3K-C2β), which generate PI(3,4)P 2 , led to mitochondrial fragmentation resulting from impaired fusion. Furthermore, cardiomyocyte-specific PI3K-C2α and PI3K-C2β double-deletion mice exhibited mitochondrial fragmentation and heart failure. Thus, subpopulations of Golgi-derived vesicles carrying different phosphoinositides control mitochondrial membrane remodeling and homeostasis.

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

Message in a bottleneck: Nested founder effects from French Polynesia to Rapa Nui and Hawaiʻi

Cole Shanks, Edward C. Huang, Christophe Thomassin, Anne-Katrin Emde, Vahinetua Rodière, Mauricio Moraga, Karla Sandoval, Tony Merriman, Tristan Pascart, Andrés Moreno-Estrada, Stephane E. Castel, Keolu Fox, Alexander G. Ioannidis

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Founder effects can lead to strong, population-specific allele frequency differentiation, including autosomal recessive conditions. Their characterization in European-descent groups, such as the Finnish and Amish, has resulted in actionable genetic tests for each. We show that Polynesians experienced order-of-magnitude stronger cumulative founder effects during their settlement of Eastern Polynesia. Using whole-genome sequences spanning Polynesia, we show that two of the most bottlenecked populations are Hawaiʻi and Easter Island (Rapa Nui) and that these two most closely genetically related yet geographically distant islands were likely settled by the same ultravoyagers with earlier ancestral roots in Mangareva. We identify clinical genetic variation generated by this sequence of successive oceanic founder events, including a loss-of-function FAN1 mutation common in Eastern Polynesia (>1%) but entirely absent from gnomAD.

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

Natural 15 N 15 N abundances constrain fixed nitrogen loss

Jiarui Liu, David L. Valentine, Annie Bourbonnais, Dale T. Andersen, Daniele Bianchi, Grace Brown, M. Bayani Cardenas, Daniel Fillion, Claudia Frey, Kelsey M. Gosselin, Aoshuang Ji, Franklin S. Kinnaman, Denis Lacelle, Moritz F. Lehmann, Katelyn McPaul, James Mullahoo, Victoria J. Orphan, André Pellerin, Elen Reji, Elizabeth D. Swanner, Tina Treude, Alan M. Seltzer, Edward D. Young

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Nitrogen regulates primary productivity across much of the biosphere, yet fixed nitrogen loss remains poorly constrained because existing methods rely on indirect proxies or ex situ experiments. In this study, we show that natural abundances of the rare 15 N 15 N isotopologue of dinitrogen (N 2 ) provide a direct tracer of biological N 2 production across diverse aquatic environments. N 2 produced by denitrification and anammox has a near-stochastic 15 N 15 N distribution [0 per mil (‰)], whereas atmospheric N 2 carries a distinct 15 N 15 N excess (19‰), allowing the two sources to be quantitatively distinguished. Across aquifers, stratified lakes, coastal basins, oxygen minimum zones, and marine sediments, 15 N 15 N measurements reveal widespread nitrogen loss previously obscured by physical gas accumulation and nitrogen fixation. Natural 15 N 15 N abundances therefore provide a general framework for directly constraining fixed nitrogen loss across the aquatic nitrogen cycle.

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

A DNA Typewriter records the cell lineage history of a mouse, from zygote to late organogenesis

Qi Yu, Haedong Kim, Sophie Seidel, James F. Acosta-Clark, Beth K. Martin, Kyle O’Connor, Riza M. Daza, Molly Gasperini, Jenny F. Nathans, Maggie Lam, Elena Gamo, Shruthi Vijay Kumar, Lauren Kuo, Jean-Benoît Lalanne, Kamen P. Simeonov, Marion Pepper, Cole Trapnell, Jesse M. Gray, Junhong Choi, Chengxiang Qiu, Jay Shendure

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Mammalian biology unfolds over time, within tissues and organs opaque to our eyes and instruments. We applied DNA Typewriter, a sequential molecular recorder, to record the cell lineage of a mouse over nearly two weeks of development. From one embryo, we reconstruct a time-calibrated, parsimony-supported, zygote-rooted phylogeny of 1.28 million transcriptionally profiled cells. A burst of editing unequivocally marks the daughters of the first cleavage, which serve as inline replicates. We quantify clonal dominance arising during gastrulation. Tree siblings share cell type far above chance; heterotypic siblings mark terminal differentiations. Temporal sweeps of clade co-occurrence recover a dated hierarchy of cell-type couplings; imputed labels for internal nodes recapitulate known state paths. A lineage-anchored ontogeny of mammalian development, long out of reach, is coming into view.

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

Advancing mathematics research with AI-driven formal proof search

George Tsoukalas, Anton Kovsharov, Sergey Shirobokov, Anja Surina, Moritz Firsching, Gergely Bérczi, Francisco J. R. Ruiz, Arun Suggala, Adam Zsolt Wagner, Eric Wieser, Lei Yu, Aja Huang, Miklós Z. Horváth, Andrew Ferraiuolo, Henryk Michalewski, Codrut Grosu, Edward Lockhart, Thomas Hubert, Matej Balog, Pushmeet Kohli, Swarat Chaudhuri

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Large language models (LLMs) increasingly excel at mathematics tasks, but their unreliability limits their utility in mathematics research. A mitigation is to use LLMs to generate formal proofs in languages such as Lean, in which the compiler verifies every proof step. We present the first demonstration of this method’s value in solving open problems at scale. We built an artificial intelligence agent for formal proof search that autonomously resolved nine of 353 open Erdős problems, proved 44/492 On-Line Encyclopedia of Integer Sequences conjectures, and is being deployed in combinatorics, optimization, graph theory, algebraic geometry, and quantum optics research. Even a basic agent alternating LLM-based generation with Lean-based verification replicated the Erdős successes. These findings demonstrate the power of formal proof search as an enabler of autonomous mathematical discovery.

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

Epigenetic aging and transposon dysregulation reflect size-related lifespan compression in dogs

Blaise L. Mariner, Brianah M. McCoy, Ashlee Greenier, Layla Brassington, Elizabeth Slikas, Christine Adjangba, Claire Cheng, Abbey Marye, Benjamin R. Harrison, Tal Bamberger, Yadid Algavi, Efrat Muller, Adam Harris, Emily Rout, Cindy Reichel, Vista Sohrab, NA, Elinor Karlsson, Joshua M. Akey, Anne C. Avery, Elhanan Borenstein, Daniel E. L. Promislow, Noah Snyder-Mackler, Joshua M. Akey, Rozalyn M. Anderson, Elhanan Borenstein, Marta G. Castelhano, Amanda E. Coleman, Kate E. Creevy, Matthew D. Dunbar, Virginia R. Fajt, Jessica M. Hoffman, Erica C. Jonlin, Matt Kaeberlein, Elinor K. Karlsson, Kathleen F. Kerr, Jing Ma, Evan L. MacLean, Stephanie McGrath, Natasha J. Olby, Daniel E.L. Promislow, May J. Reed, Audrey Ruple, Stephen M. Schwartz, Sandi Shrager, Noah Snyder-Mackler, M. Katherine Tolbert

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The extraordinary lifespan variation in domestic dogs provides a natural experiment for testing how intrinsic rates of biological aging shape lifespan. Using 1640 methylomes from 894 dogs, we developed an epigenetic clock that predicted mortality and demonstrated that epigenetic aging is fastest early in life. At orthologs of human age-associated genes, dogs exhibited concordant age effects on promoter methylation, highlighting conserved remodeling of immune pathways. We found that larger and male dogs, which are shorter lived, exhibit accelerated molecular aging. Distinct epigenetic architectures mediated these effects: Sex-dependent methylation changes were concentrated on the X chromosome, whereas size-associated methylation was especially pronounced at transposable elements (TEs). These findings show that epigenetics reflects lifespan differences in dogs and identifies TEs as potential mediators of size-associated lifespan.

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

Wafer-scale low-symmetry graphene moiré superlattice for integrated quantum rectifiers

Wenhao Tan, Jiuming Liu, Zhenhao Gong, Yunyu Hong, Hao Sheng, Haiyang Zhang, Zirui Wang, Shipeng Lu, Hao Wu, Shujie Tang, Pai Li, Haitao Jiang, Zhongying Xue, Miao Zhang, Paul K. Chu, Lin He, Pan He, Yongfeng Mei, Haizhou Lu, Xufeng Kou, Ziao Tian, Zengfeng Di

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Low-symmetry materials unlock rich Berry curvature physics and anomalous transport phenomena that are forbidden in high-symmetry quantum systems through rigorous crystalline symmetry constraints. Current approaches rely on external fields or complex heterogeneous stacking to break crystalline symmetries, which hinders scalable device integration. In this work, we demonstrate surface premelting engineering to create wafer-scale low-symmetry graphene on germanium-110 [Ge(110)]. Controlled premelting forms striped germanium surface patterns that reduce graphene symmetry from D 6h to C 1v , producing a room-temperature nonlinear Hall conductivity of ~11 micrometers per volt per ohm. First-principles calculations attribute this to originating from overtilted massive Dirac cones of hybridized germanium bands and the graphene Dirac cone. Integrated nonlinear Hall rectifiers generate >20 millivolts of output from radio frequency input and drive commercial voltage boosters and light-emitting diodes, establishing a complementary metal-oxide semiconductor–compatible route toward wafer-scale nonlinear quantum devices.

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

Recent strengthening of eastern Pacific ENSO in the last millennium paleorecord

J. E. Cole, D. M. Thompson, K. A. Dyez, C. J. Tripp, A. W. Tudhope, M. Lofverstrom, S. Stevenson, J. M. Okun, A. E. Lawman, J. L. Conroy, J. T. Overpeck, G. Jimenez, R. L. Edwards

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The Pacific El Niño–Southern Oscillation (ENSO) generates climate extremes that endanger ecosystems, infrastructure, and human well-being worldwide. The response of this system to climate warming is poorly constrained, owing to both data scarcity and uncertainties in climate models. The geochemistry of Galápagos coral skeletons across the past millennium reveals a large recent increase in interannual variability of sea surface temperature in the eastern equatorial Pacific compared with that in existing paleorecords that exceeds simulated natural variability. This increase parallels rising global temperature and results from stronger El Niño events. Central Pacific coral data also show increased variability, although less distinctly than in the Galápagos. Our results provide long-term context for understanding ENSO variability trends, with troubling implications for climate extremes.

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

High-capacity associative memory in a quantum-optical spin glass

Brendan P. Marsh, David Atri Schuller, Yunpeng Ji, Henry S. Hunt, Surya Ganguli, Sarang Gopalakrishnan, Jonathan Keeling, Benjamin L. Lev

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The Hopfield neural network stores memories using all-to-all-coupled spins and recalls those memories through equilibrium dynamics. Storing too many hampers recall because frustration causes an exponential number of spurious patterns to arise as the network becomes a spin glass. Despite this, we show that memory recall can be restored, and even enhanced, under quantum-optical nonequilibrium dynamics that convert spurious patterns into reliable memories. We experimentally observe associative memory with high storage capacity in a driven-dissipative spin glass made of atoms and photons. The capacity surpasses that of the Hopfield model under Hebbian learning by up to sevenfold in a 16-spin network. Atomic motion boosts capacity by dynamically modifying connectivity akin to short-term synaptic plasticity in neural networks, realizing a precursor to learning in a quantum-optical system.

Science abstract < 200 char.: Not a research article

Nazi Germany had no hope of making an atomic bomb, uranium cubes reveal

Richard Stone

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Experimental reactor needed much more uranium and heavy water than the country could muster

Science abstract < 200 char.: Not a research article

An AI agent emailed hundreds of researchers for help. It told us why

Celina Zhao

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To get to the bottom of this perplexing behavior, Science interviewed the agent

Science abstract < 200 char.: Not a research article

Wooden tool trove reveals Neanderthal domestic life

Andrew Curry

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Spanish rock shelter finds suggest our ancient cousins were highly skilled woodworkers

Science abstract < 200 char.: Not a research article

Phones impede learning: Evidence from a massive phone-free classroom experiment

Alp Sungu, Pradeep Kumar Choudhury, Andreas Bjerre-Nielsen

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Lower-performing students benefited the most, but even higher-performing students expressed support for the policy

Science abstract < 200 char.: Not a research article

Returning home

Hamid Khazaei

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Science abstract < 200 char.: Not a research article

‘Complete devastation’: How NSF gutted its social sciences directorate

Daniel Garisto

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The directorate made 90% fewer new grants this year than average and hemorrhaged two-thirds of its staff

Science abstract < 200 char.: Not a research article

Demographic “doomsday” misses the mark

Javier A. Birchenall

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A dire prediction published in Science in 1960 anticipated a population singularity in 2026—we are not even close

Science abstract < 200 char.: Not a research article

In Other Journals

Priscilla N. Kelly, Cheri Sirois, Joana Osório, Marc S. Lavine, Bianca Lopez, Ian S. Osborne, Jack Huang

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Editors’ selections from the current scientific literature

Science abstract < 200 char.: Not a research article

Respiratory infections could increase as extreme heat forces more people indoors

Jingxuan Zhou, Ziyi Zheng

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Science abstract < 200 char.: Not a research article

The Phobos heist

Robin George Andrews

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Japan’s MMX mission aims to retrieve samples from Mars’s mysterious moon. They could reveal how it formed—and hold pieces of Mars itself

Science abstract < 200 char.: Not a research article

Shifting the equilibrium on lupin alkaloids

Zhouqian Jiang, Benjamin R. Lichman

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A biosynthesis breakthrough promises applications in food and chemistry

Science abstract < 200 char.: Not a research article

In Science Journals

Jesse Smith, Phil Szuromi, Corinne Simonti, Edward Holmes, Jelena Stajic, Seth Thomas Scanlon, Ian S. Osborne, Stella M. Hurtley, Angela Hessler, Michael A. Funk, Unnati Sonawala, Cheri Sirois, Yury Suleymanov, John Foley

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Highlights from the Science family of journals

Science abstract < 200 char.: Not a research article

Climate change reshapes the global mercury cycle

Aryeh Feinberg, Alfonso Saiz-Lopez

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How will climate change shape future human risks to mercury exposure?

Science abstract < 200 char.: Not a research article

AI has solved many math problems, but it has not solved math

Emily Riehl

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Science abstract < 200 char.: Not a research article

Before the immunological Big Bang

Bali Pulendran

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The nature of the gut microbiome before vaccination influences later inflammatory reactions and fever

Science abstract < 200 char.: Not a research article

AI for research mathematics has arrived

Jeremy Avigad, Matthew Ballard

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Artificial intelligence can now solve research problems in mathematics and verify the answers

Science abstract < 200 char.: Not a research article

Careful governance is needed to balance the benefits and risks of landfill mining in China

Jiangwei Zhu, Min Wang, Li Fu, Meixia Guo, Kun Xie

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Science abstract < 200 char.: Not a research article

New studies probe how menopause puts brain at risk

Jennie Erin Smith

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Shifts in blood proteins could point to ways to fight menopause “brain fog” and prevent later dementia

Science abstract < 200 char.: Not a research article

Climate policies neglect risks posed by legacy landfills

Zhiping Zhang, William T. Sloan, Siming You

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Science abstract < 200 char.: Not a research article

How did Rosalind Franklin miss the helix in her iconic DNA image? She didn’t

Tim Appenzeller

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Analysis refutes James Watson’s claim he was first to recognize significance of famed photograph 51

Data everywhere, but are they fit for purpose?

Julia Lane, Natasha Noy

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Vast amounts of new data are fundamentally shaping how people manage their lives and do their work. The volume is overwhelming—Google Dataset Search discovers 2 million new datasets every month—and so are the uses by scientists, governments, and the public. Governments across the world are treating data as a strategic asset. But data alone are not enough. Infrastructure must be developed that can provide signals about which data are “fit for purpose” for the increasingly vast number of potential uses. Informed and appropriate use is, after all, the ultimate objective of making data available for the public good.

Science Advances

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

Extracellular matrix–targeted TNC-scFv armoring enhances CAR T cell persistence and antitumor activity in solid tumors

Kaizhao Chen, Qi Fu, Wei Zhang, Ziyang Lin, Longjun Chen, Youxi Zhou, Yongkun Huo, Ziqing Gao, Haoyang Wan, Caifang Wang, Xingxu Huang, Shuaishuai Zhang, Ming Liu, Xiaodong Ma

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Chimeric antigen receptor T cell (CAR T cell) therapy has shown limited efficacy in solid tumors, largely due to physical and immunosuppressive barriers imposed by the tumor microenvironment (TME). Tenascin-C (TNC), an extracellular matrix protein highly expressed in multiple solid malignancies, contributes to immune exclusion and T cell dysfunction. Here, we engineer an armored CAR T cell platform that locally targets the extracellular matrix by secreting a TNC-specific single-chain variable fragment (TNC-scFv) linked to conventional CAR architecture. TNC-scFv–armored CAR T cells exhibit enhanced cytotoxic activity, improved persistence, and reduced exhaustion in vitro and in xenograft tumor models. Single-cell transcriptomic analysis reveals that TNC targeting reprograms the TME toward a CD8 + T cell–enriched and functionally active immune landscape. In humanized tumor models, TNC-scFv–armored CAR T cells mediate robust antitumor responses with minimal systemic toxicity. This extracellular matrix–targeted armoring framework is compatible with additional immunomodulatory payloads, as illustrated by combinatorial armoring with interleukin-2, which further enhances efficacy while mitigating cytokine-associated toxicity. Together, these results establish extracellular matrix–directed armoring as a generalizable strategy to improve CAR T cell therapy for solid tumors.

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

Neanderthal woodworking at Abric Romaní: Insights into the role of wood in a Middle Palaeolithic domestic context

Palmira Saladié, M. Gema Chacón, Alex Solé, Ethel Allué, Juan Marín-Hernando, Bruno Gómez de Soler, Francesca Romagnoli, Amelia Bargalló, Manuel Vaquero, Paula Mateo-Lomba, Marcos García-Millán, M. Joana Gabucio, Antonio Pineda, Mónica Fernández-Garcia, Gerard Campeny, Amanda Merino-Pelaz, Lila Warnitz, Tomás Fernández-Iriarte, Raül Bartrolí, Eudald Carbonell, Josep Vallverdú

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Wood technology likely played a key role in human evolution, yet it remains poorly documented because organic materials rarely preserve in archaeological contexts. The Middle Palaeolithic site of Abric Romaní (Capellades, Barcelona) provides exceptional evidence of Neanderthal woodworking preserved through travertine incrustation. We document 597 wooden imprints and charred wood remains recovered from 16 archaeological levels dated between ∼62,000 and 40,000 years ago. The assemblage includes wood imprints, charred wood imprints, and charred macroremains, among which several anthropogenic objects can be identified. These include tools and weapons, domestic artifacts, and structural elements, revealing a wide range of woodworking activities. Key discoveries include wooden spears, pointed sticks, and domestic objects such as trays and tripods. A club-like artifact recovered from level P represents a unique object with no clear parallel in the prehistoric record. The Abric Romaní assemblage highlights the importance of wood within Neanderthal technological systems and provides previously unknown insights into the role of organic materials in Middle Palaeolithic societies.

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

Human trilayer engineered blood vessel reveals influence of fibroblasts on disease progression in model of Hutchinson-Gilford progeria

Kevin L. Shores, Xin D. Gao, David R. Liu, George A. Truskey

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In vitro models of vascular disease have focused primarily on the pathophysiology of smooth muscle cell (SMC) or endothelial cell (EC). Adventitial fibroblasts can contribute to disease progression, but their specific influence is not well understood in different disease contexts. To elucidate fibroblast’s impact on vascular pathology, we developed trilayer tissue-engineered blood vessels (TEBVs) with SMCs, ECs, and fibroblasts. We modeled atherosclerosis in the accelerated aging disease, Hutchinson-Gilford progeria syndrome (HGPS). HGPS fibroblasts substantially elevated several features of the vascular pathology. Correcting the HGPS-associated mutation using base editing returned many disease characteristics to healthy levels. By generating TEBVs with different combinations of vascular cells with or without the HGPS mutation, we found that fibroblasts contributed to extracellular matrix dysregulation and fibrotic signaling, SMCs to collagen accumulation, and ECs to inflammation. These results clarify the poorly understood influence of fibroblasts in progression of HGPS vascular pathology. The trilayer TEBV model could enable further mechanistic insights or therapeutic discovery for other vascular diseases.

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

Herpes simplex virus pUL56 abolishes neuronal activity by removing voltage-gated ion channels from the plasma membrane

Daniel A. Nash, Henry G. Barrow, P. Robin Antrobus, Alex S. Nicholson, John Suberu, Harvey E. Johnston, Martin Potts, Marta A. Almeida, Valeria Lulla, Colin M. Crump, Anton J. Enright, Michael P. Weekes, Janet E. Deane, Stephen C. Graham

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Herpes simplex virus 1 (HSV-1) infections of the central nervous system cause encephalitis and are associated with increased risk of neurodegeneration, yet the molecular consequences of lytic infection in human neurons remain incompletely defined. We map the transcriptomic, proteomic, and surface-proteome changes induced by HSV-1 across the lytic infection cycle in human induced pluripotent stem cell–derived cortical glutamatergic neurons. HSV-1 drives extensive plasma-membrane remodeling, including the removal of voltage-gated sodium, potassium, and calcium channels, resulting in a profound loss of synchronous calcium signaling. We identify the viral ubiquitin-ligase adaptor pUL56 as the principal effector of this process: pUL56-dependent degradation of ion channels abolishes coordinated calcium signaling, whereas mutation of its E3-ligase–binding motifs preserves synchrony. Furthermore, expression of pUL56 alone is sufficient to abolish neuronal electrical activity. These findings establish pUL56 as a potent viral suppressor of neuronal excitability.

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

Influenza A virus infection induces immune dysregulation in the placenta and fetus without vertical transmission in nonhuman primates

Orlando Cervantes, Sidney Sun, Hazel Huang, Briana Del Rosario, Hong Zhao, Amanda Li, Andrew Vo, Gygeria Manuel, Roslyn Van Abel, Jeff Munson, John Cornelius, Raj P. Kapur, Miranda Li, Edmunda Li, Hanning Li, Alexandra Christodoulou, Melissa Berg, Britni Curtis, Elizabeth Miller, Shannon Ruff, Brenna Menz, Solomon Wangari, Audrey Germond, Audrey Baldessari, Chris English, W. McIntyre Durning, Thomas B. Lewis, Megan N. Fredericks, Mara Maughan, Austyn Orvis, Michelle Coleman, Lakshmi Rajagopal, Deborah H. Fuller, Kristina M. Adams Waldorf

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Influenza A virus (IAV) infection during pregnancy is associated with stillbirth and preterm birth. We hypothesized that maternal IAV infection disrupts placental and fetal immune networks in ways that correlate with disease severity. Pregnant pigtail macaques were inoculated with IAV [A/California/07/2009 (H1N1)] and underwent delivery and fetal necropsy 5 days postinfection ( N = 11), with comparison to uninfected controls ( N = 16). Stillbirth occurred in 18% of infected pregnancies and in no controls. Although vertical transmission was not observed, low levels of viral RNA were detected in two placentas. Maternal infection was associated with induction of a type I interferon response in the placenta and altered innate and adaptive immune cell populations in the fetus. Maternal disease metrics (e.g., lung viral load and interferon-α) were rarely associated with placental immune perturbations but frequently linked to fetal immune cell populations (CD4 + and CD8 + T cells and monocyte subsets). Collectively, these data indicate that maternal IAV disease severity is associated with dysregulated fetal immunity.

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

Epigenetic insights into extreme longevity in the world’s oldest terrestrial animal, Jonathan

Benjamin Vaisvil, Daniel P. Schmitt, Angela Jones, Vinayak Kapatral, James M. Ford, Madison L. Taylor, Mathia Colwell, Jonathan Hollins, Sam Pascucci, Konstantin Weissenow, Burkhard Rost, Pascal Notin, Justin Gerlach, Thomas C. Terwilliger, Li-Wei Hung, Lars Juhl Jensen, Kathlyn Reed, Todd R. Robeck, Steve Horvath, Christopher Faulk, Yanjun Ma, Stephen W. Clark

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Aldabra giant tortoises ( Aldabrachelys gigantea ) are exceptionally long-lived. We sequenced the genome and methylome of Jonathan, a 194-year-old Aldabra, to explore the molecular basis of his longevity. Relative to other giant tortoises ( A. gigantea and Chelonoidis abingdonii ), Jonathan has unique gene variants in most aging pathways. Moreover, Jonathan has substantial DNA methylation and methylation entropy changes compared to four other Aldabras ranging in age from a 5-year-old juvenile to older adults. Notably, we found that lower-entropy regions in Jonathan’s methylome were enriched for the promoters of genes involved in the mitochondrial electron transport chain, and RNA metabolism. This suggests that high-fidelity transcription of the genes in these pathways may be crucial for long-lived species. Our findings support a model for aging wherein the maintenance of low methylation entropy in gene promoters is coupled to efficient mitochondrial energy production, efficient RNA processing, and efficient genomic repair.

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

Minimal-actuation feather star–inspired soft swimmers for multimodal 3D maneuverability

Haitao Qing, Yuanhang Zhu, Jiacheng Guo, Caizhi Zhou, Haoze Sun, Haibo Dong, Daniel Quinn, Jie Yin

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Complex, three-dimensional (3D) motions typically require actuator arrays and complex control architectures. Here, we present a feather star–inspired soft robotic swimmer that uses only two pneumatic inputs to produce three distinct and switchable swimming modes: jellyfish-like pulsation, fishlike propulsion, and rotor-like reorientation. The robot owes this ability to mechanical intelligence: It leverages a monostable instability in its flexible arms to convert two control actuation inputs into 3D swimming modes, including ascension and descension, forward and backward swimming, hovering, and rotation. The robot achieves a maximum swimming speed of 1.64 body lengths per second, minimum cost of transport of 17.6, and peak rotation speed of 90° per second. Particle image velocimetry analyses and computational fluid dynamics simulations reveal distinct vortex structures governing thrust generation and/or rotational torque in each swimming mode. The robot’s minimal input yet multimodal output demonstrates how mechanical intelligence can enable adaptive and multifunctional, yet simple and energy-efficient, robotic and biological swimming mechanisms.

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

Record-setting heavy precipitation occurrence in 2024

Chad W. Thackeray, Jesse Norris, Alex Hall, Mark D. Zelinka, Stephen Po-Chedley

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Precipitation extremes have increased globally in recent decades, consistent with a warming climate. We find that 2024 experienced a record-high frequency of heavy (≥99th percentile; F P≥99 ) precipitation events globally based on MSWEP (Multi-Source Weighted-Ensemble Precipitation) observations from 1979 to 2025. This extends a long-term trend of ∼0.03%/decade in F P≥99 , with similar but more uncertain increases for the 99.9th percentile. Unlike prior high F P≥99 years, 2024’s record was more globally distributed and emerged from a distinct seasonal evolution. El Niño and rare concurrent multi-basin tropical ocean warmth drove elevated extremes early in the year, before lagged global tropospheric responses and long-term warming sustained and amplified extremes through boreal summer. Climate models indicate that years with 2024-level F P≥99 typically require either stronger El Niño forcing or concurrent multi-basin sea surface temperature (SST) anomalies. Diagnostic projections within constrained ensemble members suggest that ∼40% of the 2024 anomaly aligns with global mean temperatures and ∼20% with El Niño variability, with some of the remainder linked to basin-scale SST structure.

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

Hydration channel engineering in Tröger’s base-POP membranes for mono/multivalent cation and anion discrimination

Haopan Sun, Ning Gan, Baolong Wu, Chenglin Liu, Yan Jin, Yuzhu Sun, Jianguo Yu, Zhaoliang Cui, Yuqing Lin, Hideto Matsuyama, Young Moo Lee

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Sustainable recovery of critical resources from complex aqueous streams is constrained by membranes that fail to combine rapid ion transport with precise mono/multivalent discrimination. Here, we report Tröger’s base-derived porous organic polymer (POP) membranes with rigid, covalently crosslinked microporous frameworks that stabilize angstrom-scale transport channels while suppressing hydration-induced swelling. These membranes render rapid monovalent-ion transport with near-complete exclusion of multivalent cations and anions, including Mg 2+ , Al 3+ , SO 4 2− , and PO 4 3− . Experiments and simulations show that steric confinement, dehydration penalties, and electrostatic interactions cooperatively raise migration barriers for multivalent ions in confined channels. The membranes achieve comprehensive mono/multivalent discrimination across both cationic and anionic systems. In multistage electrodialysis, they enable stage-amplified lithium enrichment from high-Mg brines with stable long-term operation and downstream recovery of crystalline Li 2 CO 3 . They also facilitate high-purity NaCl enrichment from simulated seawater. Overall, this platform offers a durable and energy-efficient route to selective resource recovery from complex aqueous streams.

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

Surface temperatures drive strong seasonality in urban reactive carbon emissions

Michael P. Vermeuel, Dylan B. Millet, Róisín Commane, Timothy J. Griffis, Trey A. Maddaleno, Emily B. Franklin, Katelyn L. Richard, Rose K. Rossell, Jeff Peischl, Delphine K. Farmer

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Urban air quality is affected by diverse volatile organic compounds (VOCs), and prior studies reveal a need to understand their seasonal sources. We combine high-resolution mass spectrometry with eddy covariance to quantify VOC fluxes from an urban/suburban New York site during summer and winter. Emissions are strongly seasonal: During summer, twice as many VOCs undergo surface-atmosphere exchange, and molar and reactivity-based fluxes are 2 to 4× higher than in winter. Temperature-dependent emissions from volatile chemical products (VCPs), vegetation, and residences dominate during summer. Ethanol alone accounts for ∼25% of the total flux. During winter, temperature-dependent emissions are reduced and traffic sources dominate. An updated inventory agrees with summer observations within 40% but overestimates winter fluxes by >2.5×. The winter discrepancy reflects overestimated VCP/cooking emissions and missing temperature-dependent volatilization. Results highlight the need to account for seasonal and temperature-dependent urban emissions to support pollution and mitigation assessment in the context of global change.

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

Chromatin interaction landscape of epimorphic regeneration in teleost fish

Xiaohui Jia, Xianglei Zhang, Weifeng Lin, Tengfei Ren, Shiqi Liu, Yufei Lou, Wei Wang

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Reorganization of chromatin architecture—including chromatin loops, topologically associating domains (TADs), and A/B compartments—has been increasingly linked to development and cell differentiation. However, how chromatin architecture reorganizes during the shift from homeostasis to regeneration remains poorly characterized. Here, we used zebrafish fin regeneration as a model to systematically investigate, via micro-C, the chromatin architecture associated with blastema formation. Our analyses unveiled that the alteration of chromatin looping upon amputation was dominant compared with that of TADs and compartments. Genes directly linked to injury-altered loop interactions, including essential regeneration regulators, were mainly related to morphogenesis and cell division. A side-by-side comparison between zebrafish and African killifish uncovered conserved and species-specific chromatin reorganization following injury. Notably, perturbing injury-altered loop interactions at the il11a locus suppressed its expression and impaired fin regeneration efficiency. Further, CTCF/CTCFL and Atf7 binding motifs were the top shared motifs enriched in regeneration-altered loop anchors. Our study uncovers the landscape of chromatin interactions during fin regeneration.

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

Solution-processed organic infrared photodetectors operating beyond 1.4 μm for sensitive environmental monitoring

Yifei Geng, Tengfei Li, Zhenzhen Zhang, Huiqing Hou, Yuze Lin

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Photon energies in the short-wave infrared (SWIR) beyond 1.4 μm enable access to vibrational-overtone signatures of O–H, C–H, and N–H bonds in pollutants and waste materials, offering an imaging-based nondestructive approach for environmental monitoring. However, current SWIR imaging technologies rely on costly epitaxial semiconductors incompatible with monolithic integration, limiting consumer-grade deployment. Here we report a cost-effective organic SWIR imager with response beyond 1.4 μm, integrating high-detectivity organic photodetectors (OPDs) with amorphous silicon thin-film transistors via solution processing. The developed highly-ordered SWIR organic semiconductors with (halogenated) thiophene-fused quinoid terminals exhibit ultra-narrow optical bandgaps of 0.68–0.94 eV and Urbach energies down to 23 meV. The SWIR OPDs achieve spectral response from 0.3 μm to 1.5–1.7 μm with responsivities up to ∼0.1 A W −1 and specific detectivities of 2.03–4.60 × 10 10 Jones at 1.4 μm. The active-matrix SWIR imagers achieve accurate oil-leak monitoring in simulated seawater (R 2 = 0.993–0.997) and reliable waste-textile classification (silhouette score = 0.824), demonstrating their capabilities in environmental monitoring.

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

A biohybrid mesh harvester for distributed energy harvesting in living tissues

Siqi Wang, Xiaoyu Wang, Shuai Fu, Claire Senger, Jacob Pfund, Menka Jain, Reika Katsumata, Jun Yao

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Harnessing bio-origin resources for energy conversion offers a promising pathway toward energy sustainability matched to biosystems, addressing a fundamental limitation in powering bio-integrated electronics. However, existing approaches by integrating harvesters onto continuous substrates follow a “centralized” paradigm that differs markedly from the inherently distributed energy conversion found in living tissues, limiting both biocompatibility and scalability. We demonstrate a distributed harvesting strategy by integrating individual harvesting units within a mesh network that closely mimics the structural and mechanical properties of biological tissues. This architecture enables seamless embedding within in vitro cardiac tissue to form a bio-hybridization with cellular-scale intimacy across both device and substrate, transcending conventional approaches limited to a surface contact. This strategy achieves effective energy density more than an order of magnitude higher than that of existing approaches based on the centralized paradigm. While the concept is currently demonstrated in an in vitro cardiac system for converting biomechanical energy, the approach can provide a generalizable framework for integrating diverse energy-harvesting modalities and offers a pathway toward in vivo biohybrid systems.

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

Atomic structure and dynamics of the mechanosensitive channel MscL from Escherichia coli by cryo-EM and solid-state NMR

Taoran Xiao, Alexandra Kovinko, Chaowei Shi, Henry Sawczyc, Denis Qoraj, Carl Öster, Thiemo Sprink, Anton F. Ketzel, Sascha Lange, Spyridon Kosteletos, Han Sun, Daniel Roderer, Shanshuang Chen, Adam Lange

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Mechanosensitive channels are central to cellular responses to membrane tension, yet the structural basis of their gating remains incompletely understood. Here, we determine the structures of wild-type and Gly22→Ser (G22S) mutants of MscL from Escherichia coli ( Ec MscL) by cryogenic electron microscopy (cryo-EM) in peptide-based lipid nanodiscs and complement them with solid-state nuclear magnetic resonance (NMR) measurements in liposomes to capture their dynamics in a native-like membrane environment. The cryo-EM structures reveal a closed conformation, whereas analysis of the low-threshold G22S mutant by NMR uncovers widespread conformational changes in both cytoplasmic and periplasmic regions. These data indicate enhanced dynamics and conformational heterogeneity in the mutant, revealing the early transitions from the closed toward the open state. Together, our results establish a synergistic framework integrating cryo-EM and NMR to resolve both structure and dynamics of mechanosensitive channels, and identify lipid-protein interactions as key determinants of MscL gating and mechanosensitivity. Our study further provides a quantitative benchmark for computational investigations of mechanogating and lays the foundation for the rational design of channels with tunable gating kinetics.

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

Dishevelled-mediated clustering stabilizes Frizzled6 and Vangl2 to establish planar cell polarity in the mammalian skin

Parijat Sil, Brandon Trejo, Katherine A. Little, Danelle Devenport

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Planar cell polarity (PCP) in epithelia is characterized by the polarized distribution of two opposing, membrane-associated PCP complexes across cell junctions. Transmembrane components of the PCP complex bridge cell junctions and organize into punctate, intercellular assemblies that exhibit a high degree of stability. Here, we define the contributions of the cytoplasmic PCP protein, Dishevelled (Dvl), in the submicrometer scale organization and stability of PCP complexes. Using endogenously tagged fluorescent PCP reporters in the embryonic mouse epidermis, we quantify PCP protein mobility and clustering during polarization. We find that as transmembrane proteins immobilize into puncta, Dvl2/3 coaccumulates with its transmembrane partner Frizzled 6 in a polarized manner and stabilizes clusters of PCP complexes. We identify a previously unknown function for the oligomerizing Dishevelled/Axin (DIX) domain of Dvl3, typically associated with Wnt signaling, in Dvl3 asymmetric localization. These observations underscore a role for Dvl oligomerization in assembly and stabilization of asymmetric PCP puncta.

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

Real-time single-molecule imaging in zebrafish embryos uncovers noncanonical translation

Maëlle Bellec, Jie Liang, Kenny Mattonet, Tatsuya Morisaki, Margaux Lay, Hans-Martin Maischein, Damien Avinens, Vincent Martinet, Delphine Muriaux, Timothy J. Stasevich, Jérémy Dufourt, Didier Y. R. Stainier

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Precise spatiotemporal control of protein synthesis is essential during embryogenesis, yet directly measuring translation kinetics in vivo remains challenging in vertebrates. In particular, it remains unclear how translation efficiency is determined for key developmental regulators and which kinetic steps limit their production. Here, we used ALFA array–based nascent chain labeling combined with lattice light-sheet microscopy to visualize bmp2b translation in real time and at single-molecule resolution in early zebrafish embryos. When combined with MS2/MCP labeling to visualize all bmp2b messenger RNA (mRNAs), we found that only some of them are being actively translated, suggesting that limited mRNA translation competence contributes to overall translation efficiency. We found that bmp2b translation operates below a maximal initiation regime, as replacement of its untranslated regions (UTRs) with viral UTRs increases ribosome loading. Furthermore, the bmp2b , but not actb2 , 5′UTR supports cap-independent translation with ribosome loading comparable to cap-dependent initiation. Together, this approach provides a quantitative in vivo framework to dissect translation kinetics during early vertebrate development.

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

Contagion-preserving compression for multiscale epidemic modeling

Leyang Xue, Zengru Di, An Zeng

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Understanding how contagion unfolds on large, heterogeneous networks is essential for predicting and controlling spreading processes, yet structural complexity often obscures the mechanisms governing transmission across scales. Here, we show that contagion is naturally organized around dense local structures that become dynamical spreading units once infection saturates within them. Building on this principle, we introduce iterative structural coarse-graining (ISCG), a framework that compresses large networks into interpretable multiscale representations while retaining the contagion dynamics of the original system. In this saturation regime, these representations reproduce macroscopic outbreak sizes, node-level infection risks, and spatiotemporal infection trajectories across scales. Beyond this regime, ISCG enables controlled trade-offs between dynamical fidelity and structural compression. The resulting multiscale representations support mechanism-driven intervention strategies, including influence maximization, immunization, and surveillance, that consistently outperform adaptive centrality–based methods. These results establish a general multiscale framework for representing, understanding, and controlling contagion in networked systems.

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

Effects of probiotics on joint homeostasis and osteoarthritis: Development of microbe-gut-cartilage axis-on-a-chip

Jun Liu, Ning Zhang, Yiting Lei, Xiaoshuai Wang, Xiang Zhang, Wei Huang, Changhai Ding, Denghui Xie, Jun Yu, Rocky S. Tuan, Zhong Alan Li

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Although emerging evidence implicates gut microbiome-cartilage cross-talk in the pathogenesis of osteoarthritis (OA), the most common joint disease, studying this microbe-gut-joint axis remains challenging due to limitations of animal models and conventional in vitro systems. Here, we report a microbe-gut-cartilage axis-on-a-chip (MGCAoC) that recreates tissue-specific microenvironments with oxygen gradients and physiological fluid shear. The computer simulation–optimized chip design generates an anoxic-oxic interface for the gut module and enables perfusion of probiotic metabolites to human cartilage organoids without cross-contamination. Multiomics profiling suggested that probiotic metabolites may promote cartilage anabolism, potentially involving PI3K and MAPK pathway, and this effect was associated with up-regulated collagen type II and aggrecan expression while suppressing metalloproteinases. In inflamed cartilage organoids, these metabolites were associated with reduced proinflammatory signaling while preserving matrix integrity. The chondroprotective effects were confirmed using cartilage organoids derived from patients with OA treated with identified metabolites. This MGCAoC enables mechanistic investigation of gut-joint axis physiology and provides a versatile preclinical tool for screening probiotic-based OA therapeutics.

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

Buffaloed in Brandenburg: Germany’s first brush with foot-and-mouth disease after four decades of freedom

Michael Eschbaumer, Christoph Staubach, Florian Pfaff, Jörn Gethmann, Katja Schulz, Lisa Rogoll, Sabine Bock, Wulf-Iwo Bock, Christoph Schulze, Ronny Marquart, Nicole Reinhardt, Stephan Nickisch, Nadine Kakerow, Sabrina Freter, Annett Rudovsky, Kerstin Albrecht, Sandra Leo, Christina Haarmann, Sarah Lenz, Barbara Hoffmann, Sten Calvelage, Dirk Höper, Patrick Zitzow, Angele Breithaupt, Can Çokçalişkan, Ünal Parlak, Sharon Karniely, Laith Mohammed Salih Abdulrasool, Nick Knowles, Guillaume Girault, Aurore Romey, Labib Bakkali Kassimi, Donald P. King, Christa Kühn, Carola Sauter-Louis, Martin Beer

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Foot-and-mouth disease (FMD) virus is one of the most feared and most consequential pathogens of livestock worldwide. It can be spread rapidly by the transboundary movement of animals, animal products, and by-products. In January 2025, Germany detected its first FMD outbreak since 1988 in extensively reared water buffalo on a small farm in the state of Brandenburg, directly outside Berlin, the federal capital. Immediate control measures including a standstill for movements of susceptible animals and pre-emptive culling were implemented by the veterinary authorities. Whole-genome sequencing identified the virus as serotype O, topotype ME-SA, lineage SA-2018 and revealed extensive recombination, but cross-neutralization assays suggested good heterologous protection by an O/PanAsia-2 vaccine strain. Epidemiological back-calculation placed the time of virus introduction in late December 2024. Although the entry route remains unresolved, human-associated introduction is most likely. Network analysis revealed minimal farm connectivity, and simulations predicted low potential for onward transmission, which is consistent with the outbreak being ultimately restricted to a single herd. This event underscores the constant and unpredictable risk of introduction of the virus. Early detection through increased awareness and comprehensive differential diagnostics as well as the international collaboration of veterinary services, laboratories, and experts are essential in the face of the global presence of FMD.

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

Cis-regulatory inactivation of vitamin D signaling confers extreme calcium tolerance in Jialing fish

Nan Zhang, Yongsen Zhou, Jianbin Feng, Tianhao Yang, Huilin Liu, Yongsheng Zhang, Lingyun Chen, Weiyang Xiao, Tai Wang, Aaron J. W Hsueh, Jianzhen Li

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The turquoise karst lakes of China’s Jiuzhaigou Nature Reserve harbor among the highest natural calcium concentrations known in freshwater, around threefold higher than adjacent rivers. Yet the Jialing fish ( Schizopygopsis kialingensis ) thrives there with serum calcium levels indistinguishable from river-dwelling conspecifics. We show that this calcium tolerance arose through evolutionary loss of vitamin D signaling. Lake and river populations diverged ∼410,000 years ago. Gill transcriptomics revealed >90% suppression of vitamin D receptor b ( vdrb ) and 99% reduction of its downstream calcium transporter calb2a in lake fish. Zebrafish knockout of either gene enhanced survival under hypercalcemia. We traced this suppression to specific mutations in a vdrb enhancer that reduce its activity. These findings reveal that regulatory dismantling of a canonical endocrine pathway can drive vertebrate adaptation to extreme environments, providing a clear example of how cis-regulatory evolution can drive ecological adaptation.

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

Mitigating lateral sensing blind spots: A dual-segment bronchoscopic robot with a bioinspired skin

Qiqi Pan, Wenke Duan, Jingjing Luo, Lei Wang, Shijie Guo, Yongfei Feng, Hongbo Wang

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Lateral force blind spots frequently trigger airway injuries during robotic bronchoscopy. Traditional sensing approaches lack fine spatial resolution, and single-segment robots suffer poor posture adjustment flexibility, worsening unmonitored tissue contact. We integrate a snake-scale-inspired 64-channel gradient piezoelectric film with a dual-segment manipulator to resolve lateral blind spots for secure bronchial navigation. The conformally wrapped sensor delivers fast (<10 ms), precise force detection ( R 2 > 0.98, RMSE < 0.145 N, CV < 2%) and filters bending pseudo-forces. The dual-segment design enables coordinated proximal-distal motion to avoid overcontact in tortuous lumens. Phantom and ex vivo porcine lung tests confirm real-time force localization, 5.0 N safety alarms, and autonomous tuning to keep contact forces below 3.0 N. This synergistic robot-sensor design supplies a translatable safety control strategy for flexible surgical manipulators.

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

Ocean circulation changes rather than global warming drove temperature trends across the Miocene Climatic Optimum

Evi Wubben, Xiaoqing Liu, Tjerk J. T. Veenstra, R. Paul Acosta, Joyce den Hollander, Chris Overduin, Matthew Huber, Francesca Sangiorgi, Francien Peterse, Appy Sluijs

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Early-to-Middle Miocene [23 to 13.8 million years ago (Ma)] climates were ∼6° to 9°C warmer than today. Around 16.9 Ma, benthic foraminiferal oxygen isotope (δ 18 O) records suggest pronounced warming, known as the Miocene Climatic Optimum (MCO) onset. However, explaining this putative global warming with carbon dioxide (CO 2 ) forcing faces challenges in terms of timing and forcing magnitude. Our new biomarker-based ocean temperature records, combined with published data, reveal no substantial mean global upper ocean warming across the MCO. Instead, temperature changes differ considerably between sites, with some regions showing cooling. Climate model sensitivity tests indicate that these patterns are best explained by ocean circulation changes, likely due to gateway changes and Antarctic ice sheet variations. This suggests that the MCO signature is better attributed to ocean circulation changes rather than a CO 2 -driven global warming event. The δ 18 O signal therefore represents warmer deepwater sourcing and/or reduced Antarctic glacial volume, resolving the longstanding challenge of explaining MCO warming without a pronounced CO 2 rise.

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

A solid magnesium zincate for hydrogen-methane evolution

Sheetal Kathayat Bisht, Poorna Gomathisankaran, Alex P. Andrews, Ajay Venugopal

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Hydrogen-methane blends are gaining attention as transitional fuels, but their safe storage and controlled release remain a challenge. Advancing this approach necessitates the development of compounds and materials capable of solid-state storage of mixed fuel gases. Molecular precursors capable of delivering both gases from a single source are not known. In this context, we report a low–molecular weight magnesium hydridomethylzincate, Mg[(CH 3 )ZnH 3 ], a crystalline, hydride-rich organometallic compound that does not rely on bulky supporting ligands. Under solvent-free, anaerobic conditions, it releases hydrogen and methane at temperatures as low as 80°C via reductive elimination, leaving behind elemental magnesium and zinc. The ability to liberate mixed fuel gases at relatively low temperatures underscores the potential of well-defined organometallic compounds as single-source precursors for these gases.

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

Rapid protamine evolution suppresses meiotic drive in Drosophila

Ching-Ho Chang, Aida Flor A. de la Cruz, Hung-Yu Lai, Isabel Mejia Natividad, Alex Noyola, Elian Angelo Magsino Abellanosa, Nicolas D. Lee, Harmit S. Malik

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Many animal species replace histones with protamines during spermatogenesis. Although essential for sperm function, protamines evolve rapidly for reasons that remain unknown. Using in vivo gene replacement, we examined the causes and consequences of the rapid evolution of Mst77F , a protamine essential for male fertility in Drosophila melanogaster ( D. melanogaster ). Replacing Mst77F with divergent orthologs caused DNA compaction defects in X-bearing sperm, resulting in fewer mature X-bearing sperm and male-biased progeny. Reducing D. melanogaster Mst77F dosage caused the same bias, whereas increasing the dosage of Mst77F orthologs rescued it. Engineered sex chromosome fusions revealed that Mst77F protects the D. melanogaster X chromosome from a killer-target meiotic drive system in a dosage- and sequence-dependent manner. Unlike in D. melanogaster , Mst77F was dispensable for fertility in Drosophila yakuba ( D. yakuba ) but remained important for suppressing sex ratio distortion. Our findings show that relentless pressure to suppress sex chromosome meiotic drive underlies the rapid evolution of protamines.

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

Citron kinase activity controls alternative splicing events that drive prostate cancer growth

Chitra Rawat, Nidhi Singh, Ujjwal R. Dahiya, Qiang Hu, Sarah Ng, Dingxiao Zhang, Shaun R. Stauffer, Amina Zoubeidi, Eva Corey, Jesse McKenney, Christopher J. Weight, Samuel C. Haywood, Song Liu, Tao Liu, Hannelore V. Heemers

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Prostate cancer (CaP) remains a major cause of cancer death in men, underscoring the need for mechanistically novel therapies. We previously identified the action of the mitotic kinase citron (CIT) kinase as a key driver of CaP progression and promising therapeutic target, but selective CIT inhibitors are not available. We therefore asked whether a better understanding of the action of CIT substrates, which execute CIT kinase action in CaP cells, can lead to novel approaches and/or alternative targets to indirectly interfere with CIT’s activity during CaP progression. In view of the enrichment in functions in alternative splicing among CIT substrates, we focus on the RNA splicing regulator THRAP3 as a representative substrate. Direct THRAP3 phosphorylation by CIT determined THRAP3’s RNA binding to CIT-controlled pre–messenger RNA targets. Cross-linking and immunoprecipitation sequencing identified a subset of CIT-dependent THRAP3-bound genes that were preferentially involved in cell proliferation. THRAP3 RNA binding was enriched in genes that undergo alternative splicing during CaP progression. CIT-dependent THRAP3-bound transcripts stimulated the growth of CaP cell lines, xenografts, patient-derived organoids, and patient-derived xenograft (PDX)–derived organoids, whereas CIT-independent THRAP3-bound transcripts from the same gene did not. An antisense oligo that blocks THRAP3’s recruitment to a CIT-dependent RNA binding site prevented the production of CIT- and THRAP3-dependent transcripts and inhibited the growth of cell lines and PDX-derived organoids representing different CaP stages and lineages but not of benign cells. Thus, CIT-mediated alternative splicing drives CaP progression, and its inhibition is a new therapeutic strategy in treatment-resistant CaP.

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

Dopamine release-associated striatal blood oxygenation and whole-brain dynamics during associative learning

Amir Lawen, Isabella K. Succi, Daniela Lichtman, Darcy S. Peterka, Ishmail J. Abdus-Saboor, Itamar Kahn

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Dopaminergic signaling in the nucleus accumbens (NAc) is central to reward-based learning, but its relationship to brain-wide hemodynamics remains unclear. Using concurrent fMRI and dopamine photometry in awake, behaving mice, we reveal that associative learning induces a gradual temporal shift in NAc blood oxygenation responses that mirrors dopamine release dynamics. This shift emerges with cue-reward learning and extends across a distributed network encompassing the lateral septal complex, as well as prefrontal, insular, and hypothalamic regions. Further, dopamine transients tightly correspond with local blood oxygenation level dependent (BOLD) signals, and variations in reward value modulate delayed BOLD responses in both the NAc and additional subcortical structures. Regressing out the measured dopaminergic signal abolishes this reward-related modulation, suggesting that BOLD signals track dopaminergic reward prediction. These findings reveal a close relationship between dopamine signaling and widespread changes in brain activity during learning.

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

Specific expertise from diffuse feedback: A feedforward-gated mechanism

Ruining Guo, An Yan, Minggui Chen, Wu Li, Yin Yan

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Perceptual learning improves sensory sensitivity through practice but is typically specific to trained stimuli. Two contrasting accounts have been proposed: fine-tuning of feature-selective neurons in early sensory cortex, which raises a stability-plasticity dilemma, and reweighting of stable sensory inputs by higher-level readout. To reconcile these views, we recorded neuronal populations in macaque visual area V4 during training on a camouflaged collinear contour detection task. Behavioral improvements were strictly orientation specific, yet learning-related neural enhancements were unexpectedly widespread, regardless of neuronal tuning. Critically, these enhancements were confined to late, feedback-influenced response components, whereas early feedforward activity remained stable. These results support a feedforward-gated feedback mechanism: Learning potentiates higher-order representations that deliver diffuse feedback, broadly recruiting early cortical neurons, while behavioral specificity arises because this modulation is gated by feature-selective feedforward inputs associated with the trained stimulus. Rather than being sequestered in a single locus or process, perceptual expertise emerges from hierarchical, bidirectional interactions that enable learning while preserving core sensory stability.

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

Spin force from a nitrogen-vacancy ensemble drives a 100-mg levitated resonator

Anshuman Nayak, Daehee Kim, Shilu Tian, Jason Twamley

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The force experienced by a spin in a magnetic field gradient underlies many proposals for hybrid quantum systems. These include schemes for mechanically mediated quantum gates, spin squeezing, searches for exotic forces, and motional superpositions for probing the interface between quantum and gravity. Yet, experimentally observing this spin force for anything larger than atomic scales has proved challenging. In our work, we demonstrate controllable center-of-mass motion of a 128-milligram diamagnetically levitated oscillator due to force from an ensemble of nitrogen-vacancy (NV) defects in diamond. We induce coherent motion in the oscillator by periodic optical initialization of the NV spin states, achieving motional amplitudes exceeding 100 nanometers. Our results mark a key milestone toward spin-based engineering of motional states deep in the high-mass regime.

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

Optical resolution of H/D isotopic chirality via asymmetric C–H amination

Tatsuya Uchida, Yuta Nakagawa, Naoki Watari, Yuuya Kawasaki

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Isotopic chirality arising from hydrogen/deuterium substitution has long resisted optical resolution because isotopic substitution introduces only minimal stereochemical differences, rendering such molecules structurally pseudo-achiral. Recognizing that the small yet distinct difference in C–H/C–D bond dissociation energies (BDEs) creates an energetic asymmetry, we envisioned that an enantioselective C–H functionalization exploiting this disparity could achieve the kinetic resolution of isotopically chiral molecules. Here, we report a catalytic method for the optical resolution of benzylic and allylic H/D isotopic chirality. This method achieved a remarkably high separation factor ( S = 83.1), enabling the isolation of highly enantioenriched isotopically chiral substrates from racemic mixtures and revealing retention of stereochemical memory during radical recombination in asymmetric C–H functionalization.

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

Correlated one-dimensional electron conduction in ferroelastic domain walls through nematic-like charge stripes

Minho Kang, Gyubin Lee, Wooin Yang, Shinhee Yun, Kyung Song, Jeongdae Seo, Si-Young Choi, Tae-Hwan Kim, Yeongkwan Kim, Chan-Ho Yang

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One-dimensional electronic transport reveals many-body quantum phenomena and serves as a foundation for quantum devices, sensors, and reconfigurable electronics. Here, we demonstrate that surface-exposed ferroelastic twin walls in epitaxial WO 3 films function as intrinsic one-dimensional channels, confining electrons to screen surface-bound charges induced by flexoelectric polarization. Scanning tunneling microscopy uncovers a self-organized nematic-like phase forming periodic stripes perpendicular to the walls. Conductive atomic force microscopy and angle-resolved photoemission spectroscopy resolve quantized one-dimensional states and reveal conductance enhancements exceeding two orders of magnitude along the twin walls relative to the surrounding semi-insulating surface regions at room temperature. Temperature-dependent transport follows an Efros–Shklovskii variable-range hopping law, with a crossover near 140 K and a localization length of 39 Å—identical to the stripe period—signifying Coulomb-coupled electrons confined within stripe-induced potential wells along the walls. These findings establish WO 3 ferroelastic walls as a tunable platform for engineering one-dimensional correlated electron states.

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

Long-term immunoprophylaxis by TLR9 ligand mediates macrophage-ILC cross-talk against respiratory viral infection

Asuka Joy Tobuse, Kouji Kobiyama, Jun Tsuchida, Masamitsu N. Asaka, Daichi Utsumi, Mariana Silva Almeida, Yaeko Nakajima-Takagi, Motohiko Oshima, Tomoya Hayashi, Burcu Temizoz, Etsushi Kuroda, Cevayir Coban, Yasuhiro Yasutomi, Atsushi Iwama, Ken J. Ishii

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Rapid development of host immunity is critical during the emergence of viral outbreaks when vaccines are not yet available. Here, we demonstrate that CpG oligodeoxynucleotide-schizophyllan complex (K3-SPG) induces antigen-independent, long-term protection against lethal respiratory virus infection. A single intranasal administration successfully enhanced host resistance to infection for as long as 100 days posttreatment. Mechanistically, we observed a lung-restricted biphasic innate activation of macrophages and innate lymphoid cells. Early protection was mediated by CD11b + CD11c + macrophages (DP MΦ) and monocyte-derived interstitial macrophages (IMΦ). Late protection was mediated by innate lymphoid cells that were epigenetically reprogrammed, suggesting that two distinct innate immune subsets contribute to the maintenance of disease tolerance in the lung microenvironment. Deficiency of TLR9 or TNF-α abrogated innate activation and protective immunity. Collectively, these findings demonstrate that adjuvant-induced prophylaxis is a promising approach to enhancing host resistance against respiratory virus infection, involving the biphasic cooperation between innate immune cells in the local tissue.

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

Machine learning–assisted directed evolution of plant Rubisco

Julie L. McDonald, Jiacheng Lin, Yunlong Zhao, Brian L. Hie, Rosemary Birch, Mary Gehring, Bryan D. Bryson, Spencer M. Whitney, Matthew D. Shoulders, Robert H. Wilson

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Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is foundational to life on Earth, catalyzing carbon dioxide (CO 2 ) fixation to generate biomass. However, Rubisco is a slow and inefficient enzyme that has proven challenging to engineer. We applied the structure-informed machine learning (ML) model ESM-IF1 to identify plausible amino acid sites in the large subunit of Nicotiana tabacum Rubisco to target for directed evolution. ML-assisted library design followed by selection in Rubisco-dependent Escherichia coli identified multiple enriched variants displaying improved catalytic efficiency. Several improved variants carried amino acid changes not found in the evolutionary lineage of plants, despite being assembly competent in plant chloroplasts, demonstrating that ML-assisted protein design can explore functional sequence space beyond what is observed from natural sequence diversity. Most prominently, the T391I substitution improved carboxylation rate by 29% and aerobic carboxylation efficiency by 43%. Our findings illustrate the utility of ML-assisted evolution for engineering Rubisco with improved carboxylation efficiency and potential for enhancing crop productivity.

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

AIMNet2-rxn: A machine-learned potential for generalized reaction modeling on a millions-of-pathways scale

Dylan M. Anstine, Qiyuan Zhao, Roman Zubatyuk, Shuhao Zhang, Veerupaksh Singla, Filipp Nikitin, Brett M. Savoie, Olexandr Isayev

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Mechanistic modeling of chemical transformations offers a compelling basis for understanding reactivity and allows for prediction of reaction outcomes before attempting experiments. Despite progress in machine-learned interatomic potentials (MLIPs), we demonstrate that available models lack the accuracy for diverse reaction modeling. With this motivation, we developed a general MLIP for mechanistic modeling of closed-shell carbon, hydrogen, nitrogen, and oxygen reactions, AIMNet2-rxn, using a dataset of ∼4.7 × 10 6 range-separated density functional theory calculations. AIMNet2-rxn enables reaction modeling ∼10 6 faster than the reference quantum mechanical (QM) methods while substantially outperforming graph-based ML, reaffirming the value using three-dimensional chemical information for training. On a test suite of well-known reaction mechanisms—such as amide formation, proton transfers, and pericyclics—AIMNet2-rxn yields 1 to 2 kilocalories per mole accuracy across reaction coordinates without retraining or system-specific fine-tuning. To exploit graphics processing unit parallelism and AIMNet2-rxn efficiency, we introduce a batched nudged elastic band procedure that readily achieves minimum energy pathway search on a millions-of-reactions scale. To demonstrate complex reaction characterization, the thermodynamics of an 11-step pathway producing hydroxymethylfurfural, the experimentally observed major product of glucose pyrolysis, is evaluated. Overall, the accuracy and efficiency afforded by AIMNet2-rxn create opportunities in high-throughput reaction discovery and deep reaction network analysis that would be infeasible with QM methods.

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

Self-buoyant cell-spheroid culture programming multi-spheroid assembly

Yuanhang Xiang, Binqi Wei, Yueyang Sun, Weifeng Liu, Hui Zhao, Xiaojie Qin, Changfeng Zhu, Xinchun Li, Fan Yang

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Tempo-spatially controlled culture and assembly of cellular spheroids are fundamental in engineering tissue-like assembloids for scalable application, yet remain a technical challenge. Here, we show self-buoyant culture of cell spheroids and programmable assembly of multi-spheroid by microbubbles in a high-throughput, external field-free and miniaturized format. This approach allows one-step engineering of biocompatible cell-adhesive buoyancy interface that lifts the self-adaptive levitation growth of reliable one-drop-one-spheroid in an array without requiring any external fields. Using this self-floating spheroidal microarray, we find that a facile droplet ‘kiss’ facilitates the buoyancy-driven ultrafast transfer (∼1 s) of spheroids between top-down adjacent droplets, thus achieving rapid spheroid relocation, media exchange, and drug administration in parallel. Such a self-buoyant approach allows programmable horizontal/vertical bioassembly and enhanced fusion of homo/heterogeneous multi-spheroids into different “buoyantoid” patterns via sequential flash transfer along droplet array. This self-powered design provides a promising tool to enable mass production and smart manipulation of encoded assembloids for precision medicine, tissue engineering and high-throughput drug screening.

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

Observation of electrically generated polaron-polaritons in a monolayer MoSe 2 microcavity

Yuanjun Guan, Mengyao Xu, Zhen Cui, Xingzhou Chen, Chengye Ding, Xiaoqing Zhou, Kenji Watanabe, Takashi Taniguchi, Jesper Levinsen, Meera M. Parish, Pavlos G. Savvidis, Zhe-Yu Shi, Zheng Sun, Jian Wu

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Quasiparticles arising from the interaction between mobile impurities and a quantum many-body environment—known as polarons—play a pivotal role in shaping the optical and electronic properties of low-dimensional systems. Here, we report the direct observation of electrically generated polaron-polaritons within a monolayer molybdenum diselenide microcavity. By embedding the monolayer in a planar optical cavity, we achieve strong coupling between exciton-polarons and cavity photons, creating an electrically driven light-emitting diode based on polaron-polaritons. The device exhibits an external quantum efficiency of ∼0.15%, representing a 10-fold enhancement over prior exciton-polariton devices based on monolayer tungsten disulfide. This demonstration establishes a versatile platform for inversionless laser technology and for polariton-based quantum optoelectronics while offering insights into radiative many-body physics in two-dimensional semiconductors.

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

Intensification of East Asian summer extreme precipitation under a net-zero anthropogenic CO 2 emission scenario

Seungmok Paik, Daehyun Kim, Soon-Il An, So-Eun Park, Andrew D. King, Seung-Ki Min, Chao Liu, Jongsoo Shin

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Global warming has intensified extreme precipitation, a trend projected to continue as warming persists. However, how extreme precipitation characteristics respond to global warming mitigation strategies remains poorly understood. This study examines East Asian summer extreme precipitation responses under a net-zero anthropogenic carbon dioxide (CO 2 ) emission scenario. Despite substantial cooling over East Asia following atmospheric CO 2 concentration decline, the intensity of extreme precipitation events continues to increase for about 30 years and does not subsequently weaken. This counterintuitive result arises mainly from intensified upward motion during extreme precipitation events, driven by enhanced baroclinicity and strengthening of the upper-tropospheric jet, which together overcompensate the cooling effect. These are essentially due to the hysteresis in the Atlantic (i.e., Atlantic Meridional Overturning Circulation slowdown), Southern (i.e., sustained warming), and Pacific (i.e., El Niño–like warming) Oceans. Our findings highlight that achieving net-zero anthropogenic CO 2 emissions is insufficient to mitigate intensifying extreme rainfall events in the densely populated East Asian countries.

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

ALIX-dependent small extracellular vesicles from tissue-resident mesenchymal cells regulate pancreatic β cell proliferation in obesity

Yuhei Uehara, Hirofumi Nagao, Aoki Tobimatsu, Keitaro Kawada, Shunsuke Shiode, Emi Horitani, Yoshinari Obata, Shiro Fukuda, Yuya Fujishima, Shunbun Kita, Hitoshi Nishizawa, Iichiro Shimomura

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Cells throughout the body release small extracellular vesicles (sEVs), including exosomes, that function as modulators of both local and systemic metabolism. Using mice in which ALIX, a key regulator of sEV biogenesis, was selectively deleted in PDGFRα + mesenchymal progenitors (Pα-ALIXKO mice), we demonstrate a critical role for mesenchymal sEV production in metabolic regulation. In high-fat diet–induced obesity, Pα-ALIXKO mice exhibited reduced weight gain and smaller subcutaneous adipocytes compared with control mice. Despite similar insulin sensitivity, these mice showed impaired glucose tolerance, which was associated with reduced pancreatic β cell area and smaller islets. sEVs isolated from conditioned media of knockout (KO)–derived mesenchymal stem cells (MSCs) exhibited a reduced capacity to promote β cell proliferation. Furthermore, MSCs isolated from subcutaneous adipose tissue of KO mice showed elevated mRNA expression of inflammatory genes. Together, these findings indicate that ALIX in tissue-resident mesenchymal progenitors is required for pancreatic β cell proliferation and glucose homeostasis in obesity.

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

Embryos resolve the enigmatic origin of the theropod wishbone

Sebastian Jiménez-Villalón, Felipe Guajardo-Pezo, Mackarenna Narváez, Daniel Smith-Paredes, Tiana Kohlsdorf, Joao F. Botelho, Alexander O. Vargas

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The origin of the avian wishbone (furcula)—present since theropod dinosaurs—remains unsolved. Its homology is still debated, with competing hypotheses proposing derivation from the clavicles, the interclavicle, or both. To obtain comparative developmental evidence, we studied ossification and pre-ossification mesenchymal condensations in a broad sample of birds and non-avian reptiles. Relative positions of paired condensations and their ossification centers support homology between the lateral arms of the furcula and reptilian clavicles. However, in the palaeognathous bird Nothoprocta perdicaria , we observed a separate interclavicle-like medial condensation. It quickly fuses with the clavicular condensations but then develops its own ossification center. The phylogenetic distribution of this developmental pattern across reptiles and birds supports a composite origin of the furcula from clavicles and the interclavicle. Early fusion of condensations leads to seamless integration, which may explain why fossil evidence of this composite origin has remained elusive.

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

Reduced organic nitrogen compounds dominate the toxicity of PM 2.5 organics following internal exposure

Yaling Zeng, Xin Yang, Xin Yuan, Rongrong Xu, Ke Yang, Baixin Zhang, Jinghao Zhai, Baohua Cai, Shao Shi, Yin Zhang, Yujie Zhang, Ziting Hou, Antai Zhang, Zhenxing Shen, Tzung-May Fu, Lei Zhu, Huizhong Shen, Jianhuai Ye, Chen Wang, Shu Tao

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Atmospheric fine particulate matter (PM 2.5 ) remains a major global health risk, with its associated health burden continuing to rise despite decades of pollution control efforts. Air pollution studies often focus on particle levels and known toxins, missing hidden organics that may drive serious health risks. Here, we conducted a comprehensive molecular and toxicological investigation of urban atmospheric particles, integrating nontargeted analysis of high-resolution mass spectrometry, protein adductomics–based internal exposure assessment, and multi-endpoint toxicity prediction. We find reduced organic nitrogen (RON) compounds as the predominant drivers of the toxicity of the internal exposed particle-bound organic fraction. RON account for 39% of total multi-organ toxicity, exceeding the 23% contribution from traditionally emphasized oxygenated organics. RON compounds exhibit strong binding affinity to human serum albumin, facilitating systemic distribution and toxic effects across respiratory, neurological, hepatic, renal, and hematological endpoints. Our findings identify RON as a key driver of organic PM 2.5 toxicity via internal exposure pathways and highlight the urgent need to regulate reactive nitrogen species.

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

From plankton to fish: 21st-century redistribution of marine biodiversity and the changing role of rare species

Elena Couce, Lily Greig, Georg H. Engelhard, John K. Pinnegar, Keith M. Cooper, Pierre Hélaouët, Laurene Pecuchet, Myron A. Peck, Martin Lindegren, Murray S. A. Thompson

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Predictions of climate-driven marine biodiversity change typically overlook noncommercial and rare taxa, leading to an incomplete and potentially biased understanding of change. We address this gap by quantifying α-, β-, and γ-diversity using Hill numbers consistently across co-occurring phytoplankton, zooplankton, benthos, and fish taxonomic groups. Using Bayesian additive regression trees and extensive survey data, we project climate-driven biodiversity change in the northeast Atlantic until 2100. We show that climate change could redistribute biodiversity both within taxonomic groups, altering the contribution of rare species, and across the food web. Widespread increases in fish and benthos species richness, reflecting poleward migration, often coincided with declines in zooplankton and phytoplankton richness, potentially disrupting energy transfer from lower to higher trophic levels. By identifying areas with high biodiversity across taxonomic groups and predicting how these could change in the future, we provide a framework to support proactive conservation actions to help achieve global biodiversity targets in a changing climate.

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

Sensory receptor expansion and neural accommodation in butterfly color vision

Ke Gao, Julia Ainsworth, Antoine Donati, Yunchong Zhao, Michelle Franc Ragsac, Cara Genduso, Zoie Andre, Andrew Tomlinson, Michael W. Perry

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The evolution of complex brains required the incorporation of newly evolved neurons into existing circuits, yet the genetic and developmental mechanisms enabling their integration remain poorly understood. Butterflies expanded their color vision by adding a second R7 photoreceptor per ommatidium, a rare departure from the conserved insect eye ground plan. Because each R7 makes an independent stochastic fate choice, this duplication increased the number of ommatidial types from two to three. We identified the genetic basis of this expansion and demonstrated how the brain accommodates the new input. R7 duplication was achieved by converting R3/4 cells to an R1/6 fate, triggering the R7 recruitment program on both sides of the ommatidium. By manipulating transcription factor expression in Drosophila , we engineered a “butterfly-fly” that recapitulates this ancient R7 duplication and three-type stochastic mosaic. In the fly brain, two R7 subtypes connect to specific types of Dm8 neurons, which are born in excess and undergo apoptosis if they fail to find synaptic partners. In our butterfly-fly model, these surplus Dm8s are immediately rescued and form subtype-appropriate connections. These findings suggest that population-level variation maintains a reservoir of potentially interacting neurons, providing a developmental substrate that allows the brain to immediately accommodate newly evolved neurons.

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

DNA nanodevice-engineered macrophages as living sensors for dual-mode in vivo monitoring of tumor-associated macrophage polarization

Qiaomei Wei, Xixi Chen, Ping Xie, Li Wang, Li-Juan Tang, Tingting Chen, Lan Liu, Jian-Hui Jiang, Xia Chu

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Exploiting macrophages as cell-autonomous reporters of their polarization states represents a promising strategy for interrogating tumor-associated macrophage (TAM) phenotypes in cancer. Here, we develop a macrophage-based sensing platform, termed eMφ. This platform is created by engineering macrophages with a modular and multiplexable DNA origami nanodevice to report TAM polarization states within the tumor microenvironment. Upon tumor infiltration, microenvironmental cues drive macrophage polarization, triggering the engineered system to convert endogenous signals (e.g., Arg1 or iNOS mRNA) into distinct, state-specific reporter outputs. The integration of local and circulating reporters enables compartment-resolved, multiscale readouts of macrophage state. Following intravenous administration, eMφ facilitates tumor detection across multiple murine models, including B16F10 melanoma and lung metastasis, and enables precise evaluation of macrophage-reprogramming immunotherapy. Overall, this work establishes DNA nanodevice-programmed macrophages as a novel class of synthetic-living hybrid systems, paving the way for programmable and precise immune-state diagnostics and therapy.

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

Phage-ICE tandems facilitate bacterial adaptation and antimicrobial resistance spread

Jinhu Huang, Jiaqi Zhao, Pengchao Zhan, Xingyang Dai, Xinming Pan, Zhenmiao Li, Wenbin Zhao, Xiaoli Shi, Xiaoming Wang, Shengyong Mao, Jiale Ma, Liping Wang, Jinxin Liu

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Phages and integrative and conjugative elements (ICEs) drive bacterial evolution, but how their interplay shapes bacterial adaptation and antimicrobial resistance (AMR) dissemination remains unclear. Here, we characterize phage-ICE tandems formed by site-specific accretion of phages and ICEs into cotransferable units. In Streptococcus , phage-encoded integrases (IntIE Phage ) drive stress-inducible excision and circularization, after which ICE machinery mediates conduction of the tandem. When excision is impaired, phage and phage-ICE fragments disseminate by transformation and integrate via RecA-dependent homologous recombination (HR), providing a fail-safe route. This pathway enables cotransfer of flanking chromosomal DNA, generating length-variable integrations that remodel transcriptional programs and increase oxidative stress tolerance. A global screen identified 612 phage-ICE tandems across seven phyla and 135 species, including multidrug-resistant pathogens, with lineage-specific repertoires of AMR, virulence, and metabolic genes. Rather than a hybrid element, these structures represent functional interplay where prophages exploit ICE conjugation while facilitating mobilization of the composite region. By coupling excision, transfer, and recombination, phage-ICEs shape adaptation and accelerate AMR spread.

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

A neuronal GPCR modifies neuropeptide signaling to suppress proteostasis in distal tissues

Joud Hirbawi, Adam Zaretsky, Huadong Zhu, Uri Goshtchevsky, Gourab Dey, Emmanuelle Merquiol, Atif Ahmed Siddiqui, Irit Cohen, Galia Blum, Ehud Cohen

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The proteostasis network (PN) safeguards the integrity of proteins by promoting various cellular activities. However, with aging, the PN’s competence declines and aggregated proteins accrue within cells. This process underlies the development of neurodegenerative disorders such as Alzheimer’s and Huntington’s diseases. While the PN functions within cells, proteostasis is regulated across the organism by intertissue communication, which is partially governed by neurons. We previously found that reducing the expression of gtr-1 , which encodes a neuronal heterotrimeric guanine nucleotide–binding protein–coupled receptor, mitigates the toxicity of the Alzheimer’s disease cause, Aβ peptide. Here, we investigated the mechanism that is acted upon the knockdown of gtr-1 and found that it differentially modulates gene expression profiles, including of neuropeptide-coding genes, and dissimilarly modifies protein aggregation in worms that express distinct proteotoxic proteins. The knockdown of gtr-1 also enhances protein degradation. These findings highlight the roles of neuropeptides as organismal coordinators of proteostasis in the face of distinct proteotoxic challenges.

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

Multidegree fluorescence–optical rotatory dispersion (F-ORD) from submonolayer interfacial chiral films

Kevin Murati, Matthew R. Wilson, Isabela Capelozi de Freitas, TJ Pinedo, Benjamin W. Cerjan, Patrizia Polichetti, Alexander J. Higgins, Ethan T. Cox, Osama Abuhammad, Lyudmila V. Slipchenko, Garth J. Simpson

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Homochiral monomolecular thin films adsorbed to fused silica produced fluorescence–optical rotatory dispersion (F-ORD; i.e., optical rotation of the fluorescence emission relative to the excitation beam) more than seven orders of magnitude greater than anticipated by conventional origins of optical rotatory dispersion (i.e., optical rotation of the excitation beam after passing through a chiral film relative to its initial plane of polarization). Optical rotation of −4.5 ± 0.5° was observed in the principal axis of fluorescence emission relative to that of excitation for submonolayer dip-coated thin films of (S)-naproxen, with the sign of the rotation inverting for comparable films of (R)-naproxen. The chiral-specific F-ORD response was nonreciprocal, inverting in sign upon flipping of the sample orientation (i.e., source-facing versus detector-facing), suggesting selectivity to chiral molecules oriented at the interface. The interface selectivity, chiral selectivity, and large magnitude of the response were in excellent agreement with a fully electric-dipole–allowed orientational mechanism for chiral-specific fluorescence in uniaxial systems. These observations elevate fluorescence as a novel chiral-specific probe with exquisite sensitivity to chirality and interface specificity akin to that normally reserved for even-ordered nonlinear optical interactions, such as second harmonic and sum-frequency spectroscopy.

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

Senescent tumor cell membrane–based “time engine” nanosystem amplifies endoplasmic reticulum targeting for metastasis blockade

Jing Tao, Yuzhen Guo, Fengzhi Zhang, Jiahui Wu, Liyun Xing, Jinxia Kong, Lian Li, Zhou Zhou, Yuan Huang

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As an important component of biomimetic drug delivery systems, cell membrane–coated nanoparticles are widely used for subcellular delivery. However, the influence of cell membranes at different life cycles on subcellular delivery remains unexplored. Our previous study demonstrated that senescent tumor cell membrane–coated nanoparticles (SNP) displayed superior endoplasmic reticulum (ER) targeting efficiency in tumor cells. After inducing tumor cells into senescence, SNP showed greater accumulation in ER. Herein, we design a “time engine” nanosystem for amplified ER targeting: Firstly, ribociclib is encapsulated into SNP (R@SNP) to induce tumor cell senescence; then, SNP loaded with brefeldin A (B@SNP) is used to trigger ER stress. By sequential therapy, R@SNP disrupts the cytoskeleton of 4T1 tumor cells to eliminate ER-targeting barriers and remodels the tumor immune microenvironment; B@SNP boosts ER-targeting efficiency and triggers intense ER stress. Collectively, such time engine nanosystem achieves excellent ER accumulation and antimetastatic efficacy in 4T1 tumor–bearing mice, providing an innovative perspective for subcellular delivery and tumor treatment.

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

Enhancer binding kinetics explain transcription factor hub formation

Samantha Fallacaro, Manya Kapoor, Lillian Encarnation, Apratim Mukherjee, Meghan A. Turner, Hernan G. Garcia, Mustafa Mir

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Transcription factors (TFs) form dynamic, high-concentration clusters, condensates, or hubs, proposed to increase TF binding frequency at target enhancers. However, how enhancer sequence shapes hub properties remains unclear. We developed a live imaging–based framework to quantify the spatiotemporal relationship between TF hubs and actively transcribed genes in live Drosophila embryos. Examining hubs formed by the TF Dorsal across enhancers with defined binding site composition, we find that hub enrichment and persistence scale with the number of Dorsal binding motifs. However, these hub properties do not predict transcriptional bursts for a given enhancer. Combining quantitative imaging with computational modeling, we show that Dorsal hub formation can be explained by TF-DNA binding kinetics alone. These findings support a model in which TF hubs emerge from enhancer-encoded TF-DNA interactions rather than higher-order regulatory assemblies.

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

A bifunctional actuator to correct loss-of-function deficits in cardiac voltage-gated sodium channels

Lucile Fossier, Marc Yehya, Richard Z. Zhuang, Sri Karthika Shanmugam, Ryan Mahling, Timothy Cho, Audrey Kochiss, Allen L. Hsu, Sandra B. Gabelli, Gordana Vunjak-Novakovic, Henry M. Colecraft, Manu Ben-Johny

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Despite their emerging prominence, ion channelopathies have remained challenging to correct, as ion channel dysfunction linked to disease is multifaceted, involving changes in activity and/or localization. Yet, current corrective strategies typically focus on restoring only one aspect leading to incomplete efficacy. Here, focusing on the voltage-gated sodium channel, Na V 1.5, whose dysfunction is linked to life-threatening cardiac arrhythmias, we develop a genetically encoded bifunctional actuator as a proof-of-concept molecular strategy to reverse pathophysiological changes in channel function. Specifically, we engineer a high affinity nanobody targeting Na V 1.5 with two moieties: (i) a peptide that restores proper inactivation and (ii) a linkage-specific deubiquitinase that promotes surface-membrane localization. Functional validation in heterologous systems and in human and mouse cardiomyocytes demonstrated restoration of Na V 1.5 trafficking and/or gating. In all, this approach shows promise for reversing molecular deficits observed with Na V channelopathies and provides a framework to engineer multifunctional modulators targeting ion channelopathies.

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

SLC39-driven zinc influx orchestrates pleiotropic tumor–immune system cross-talk to establish immune suppression in colorectal cancer

Seok June Hong, Seheum Park, Sunghoon Kim, Young Il Park, Jun Seok Lee, Mikyung Kang, Jaewoong Lee, Martin Hemberg, Sung Eun Kim, Kwoneel Kim

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Tumor metabolic programs shape immune evasion; however, the mechanism by which nutrient-transport systems rewire tumor-immune cell interactions remains unknown. We integrated bulk multi-omics, single-cell transcriptomics, spatial profiling, and functional assays for colorectal cancer–associated zinc-driven immunosuppressive circuit identification. Multi-omics analysis of 258 patients revealed three solute carrier transporter-centered archetypes, with an SLC39-enriched subtype aligned with consensus molecular subtype 2–like immune-desert tumors. SLC39-mediated zinc influx activated CDX2, which engaged a distal enhancer to induce tumor cell-specific CD24 expression. CD24 + tumor cells formed spatial niches with SIGLEC10-expressing monocyte-derived macrophages, dendritic cells, and resident macrophages, activating pleiotropic programs that suppress phagocytosis and remodel adhesion. SLC39 overexpression increased intracellular zinc and CD24 levels and reduced macrophage-mediated engulfment, whereas CD24 blockade restored phagocytosis. The zinc-CDX2-CD24-SIGLEC10 axis defined a terminal cancer cell state associated with poor survival and immune checkpoint blockade resistance. A seven-gene signature predicted immunotherapy responses across five colorectal cancer cohorts, identifying SLC39-driven zinc influx as a metabolic checkpoint governing immune exclusion.

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

A 256-year daily rainfall record reveals multiscale rainy-season variability and emerging hydroclimatic hazard over northern East Asia

Yuqi Wang, Yong Wei, Zhonghua Yao, Shiling Yang, Feng Shi, Wei Lin

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Monsoon rainy seasons shape water supply and flood hazard across northern East Asia, but their long-term variability remains poorly understood because few daily rainfall records extend beyond the instrumental era. Here, we reconstruct rainy-season onset, retreat, and duration from a 256-year daily precipitation record for Seoul (1770–2025), providing an unusually long view of seasonal monsoon behavior. The reconstruction reveals structured quasi-decadal to multidecadal variability in rainy-season duration, indicating that recent rainy-season lengthening over northern East Asia is consistent with the latest positive excursion of a recurrent multidecadal modulation rather than a purely isolated modern anomaly. Coupled with warming-associated intensification of extreme rainfall, this prolonged-duration phase has elevated the compound-hazard probability, with recent probability peaks exceeding the long-term mean of ∼25% in Seoul. Exploratory near-term outlooks suggest that rainy-season duration in northern East Asia is likely to remain prolonged toward mid-century, sustaining heightened compound hydroclimatic hazard when seasonally extended overlaps with intensified event-scale rainfall.

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

Carbonic anhydrase VIII regulates IP3R1-dependent Ca 2+ signaling to coordinate insulin secretion and hepatic glucose production

Muhammad Fauzi, Takaaki Murakami, Ryota Usui, Ainur Botagarova, Daisuke Otani, Kentarou Sakaki, Shinsuke Tokumoto, Toshinori Imaizumi, Hisato Tatsuoka, Masahito Ogura, Jonathan Campbell, Nobuya Inagaki, Daisuke Yabe

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Intracellular Ca 2+ signaling is essential for glucose-induced insulin secretion (GIIS) and hepatic glucose production (HGP), yet how Ca 2+ dynamics are coordinated across organs remains unclear. Carbonic anhydrase VIII (CA8), an endogenous inhibitor of inositol 1,4,5-trisphosphate receptor 1 (IP3R1), was identified as a shared regulator of pancreatic and hepatic glucose metabolism. Using Car8 wdl mice, we showed that CA8 deficiency enhanced GIIS and HGP in vivo and ex vivo. In islets and hepatocytes, CA8 loss augments Ca 2+ oscillations, an effect abolished by IP3R inhibition or Car8 reexpression. Enhanced HGP persists independently of glucagon receptor, PLC, or PKA signaling and occurs without increased IP 1 , indicating heightened IP3R1 sensitivity rather than increased IP 3 production. In hepatocytes, chronic glucagon exposure attenuated acute glucagon responsiveness in a CA8-dependent manner. In obese diabetic mice, CA8 increased in islets but decreased in hepatocytes; hepatic CA8 restoration reduced excessive HGP. Collectively, these findings identify CA8 as a cross-organ regulator of IP3R1-dependent Ca 2+ signaling with translational relevance to diabetes.

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

On-fault and remote observations of exceptionally long, supershear rupture in the 2025 M 7.7 Mandalay earthquake

Kejie Chen, Haoran Meng, Zhenguo Zhang, Zijia Wang, Zaiwang Liu, Chris Milliner, Guoguang Wei, Fuhua Zheng, Jianhao Gao, Min Zhou, Solene L. Antoine, Chaofeng Wang, Zhongqiu He, Kai Huang, Jindong Song, Qiang Ma, Haipeng Luo, Xiaofei Chen, Jean-Philippe Avouac

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Straight faults are considered prone to large supershear ruptures and seismic gaps to likely host future earthquakes. Both predictions may have been fulfilled in the magnitude ( M ) 7.7 Mandalay earthquake of 28 March 2025 on the Sagaing Fault. Exceptional video footage of the fault rupture, high-rate Global Navigation Satellite System, and seismological and remote sensing data reveal a supershear slip pulse that formed early and ruptured a well-identified seismic gap but propagated well beyond it, resulting in an exceptional rupture length of 510 kilometers. By contrast, the slip pulse observed in the video footage has subshear characteristics. These observations can be reconciled by a preferred conceptual interpretation invoking depth-dependent weakening properties, stress heterogeneity, and possible dynamic triggering. These properties allow for energetic ruptures that stay confined to the depth range locked in the interseismic period but are not confined to seismic gaps along strike.

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

Wafer-scale synthesis of WSe 2 for high-performance p-type top-gated transistors and logic circuits

Jonggyu Choi, Hayoung Kim, Seungsoo Kim, Mingyu Kim, Seungmin Yang, Juyeong Hong, Seokmin Yun, Ajit K. Katiyar, Jong-Hyun Ahn

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Two-dimensional (2D) transition metal dichalcogenides (TMDs) offer a promising pathway for next-generation electronics due to their exceptional electrical characteristics at atomically thin thickness. Nevertheless, the realization of high-quality p-type 2D-FETs remains a significant challenge for CMOS device integration due to surface damage and unintended n-doping induced during dielectric deposition. In this work, we report the wafer-scale synthesis of p-type WSe 2 films using metal-organic chemical vapor deposition and the fabrication of top-gate p-FETs through a buffer layer strategy, which provides superior electrostatic control and channel stability. The transistors exhibit excellent p-type performance, achieving a hole mobility of 10.49 ± 2.35 cm 2 V −1 s −1 with on/off current ratio exceeding 10 9 . By leveraging the process’s scalability, which ensures uniform and damage-free fabrication, we successfully produced reliable wafer-scale PMOS logic circuits. This study provides a scalable, damage-free integration solution for 2D electronics, paving the way for the practical realization of all 2D-based high-density electronics and circuits.

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

Scalable design of fluidic DEMUX/MUX

Hwayeong Jeong, Jamie Paik, Jung Kim

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Fluidic logic circuits offer a foundation for decentralized onboard control in soft pneumatic robots, enabling their integration into actuator networks to generate complex movements. However, existing fluidic controllers in soft robots face scalability limitations, restricting their ability to handle growing degrees of freedom across sizes while preserving compliance. Here, we present a scalable fluidic control architecture that integrates high-radix demultiplexing with time multiplexing to achieve a high input-to-output ratio and reprogrammable actuation. We incorporate a design method based on dimensionless parameters to preserve comparable valve opening and closing pressure thresholds across different physical scales, thereby maintaining consistent addressing behavior of the demultiplexer after geometric scaling. In addition, structural stretchability enables seamless integration into soft bodies, maintaining reliable control under dynamic deformation without compromising compliance. This hybrid demultiplexer/multiplexer fluidic circuit overcomes key limitations, offering functional scalability, geometric scalability, and physical integrability in a single architecture. Our approach enables autonomous, adaptable soft robots capable of complex, multifunctional motions, functioning as self-contained systems.

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

SMCHD1 is a target for gene activation therapy to treat Prader-Willi syndrome

Megan Iminitoff, Anna Le Fevre, Tamara Cameron, Hannah K. Vanyai, Caleb Chew, Sarah A. Kinkel, Kelsey Breslin, Susanne Theiß, Quentin Gouil, Merlin Thomas, James M. Murphy, Christian P. Schaaf, Andrew Keniry, Marnie E. Blewitt

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Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by loss of expression from the active paternal allele at an imprinted cluster on chromosome 15. Current treatments address individual symptoms rather than the underlying cause of disease. Because all patients preserve a normal but epigenetically silenced maternal copy of these genes, activation of this copy offers a potential disease-modifying therapy. Here, we investigated the epigenetic regulator SMCHD1. First, we demonstrated that SMCHD1 represses the PWS locus in both mice and humans, supporting its relevance as a therapeutic target. Second, we found that SMCHD1 represses the entire PWS locus in neural lineages, extending its previously known role beyond only part of the cluster. Deleting Smchd1 after early development in vivo activated PWS genes in disease-relevant mouse tissues including hypothalamus and improved phenotypes in a PWS mouse model. Despite broader genome-wide binding, postearly development targeting of SMCHD1 appeared remarkably safe, supporting its potential for gene activation therapy for PWS.

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

Clonal lineage tracing and parallel multiomics profiling reveal transcriptional heterogeneity induced by ARID1A deficiency

Kenichi Miyata, Liying Yang, Yuxiao Yang, Kohei Kumegawa, Reo Maruyama

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Transcriptional heterogeneity drives malignant progression, yet how it emerges within tumors remains unclear. By combining genetic perturbation and lineage tracing with parallel single-cell multiomics, we tracked the consequences of ARID1A loss within individual clonal lineages. ARID1A deficiency increased transcriptional variability both within and across clones, recurrently giving rise to diverse transcriptional profiles that did not converge on a common, coordinated pattern. This variability was accompanied by broadened chromatin accessibility at normally silenced loci and depended on residual SMARCA4 activity. Clones in which this variability was prominent showed no growth advantage under standard conditions but were preferentially recovered under specific environmental stresses and during lung colonization, a context dependence consistent with bet-hedging. Our findings suggest that loss of an epigenetic regulator can promote tumor evolution by relaxing transcriptional constraints and widening the range of phenotypes accessible to a clonal lineage, rather than by imposing a single fixed phenotype.

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

Targeted integration of extrachromosomal arrays in C. elegans using PhiC31 integrase

Matthew S. Rich, Ryan Pellow, Yichen Zhang, Adam Hefel, Ofer Rog, Erik M. Jorgensen

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Extrachromosomal arrays are unique chromosome-like structures created from DNA injected into the Caenorhabditis elegans germline. However, they are unstable unless integrated into a chromosome. Current methods for integration using x-rays or CRISPR can damage DNA and exhibit low efficiency. We demonstrate that the viral integrase PhiC31, which mediates nonmutagenic recombination between short attB and attP sequences, can be used for extremely efficient and targeted integration of arrays. Arrays were integrated by PhIAT (PhiC31-mediated integration of arrays of transgenes) at attB sites on three chromosomes, including at a fluorescent landing pad. Moreover, integrations can be inserted at any arbitrary site in the genome by simultaneously co-injecting Cas9 ribonucleoprotein, an attB repair template, and the DNA components for the array—thereby providing sites on all six chromosomes. Single injections can integrate arrays ranging in size from 1 to 18 megabases. PhIAT makes it practical to study genomes of other organisms in the nematode; one of our strains incorporates 65% of the yeast genome at a single site in the worm genome. PhIAT will accelerate a shift from unstable extrachromosomal arrays to direct integration of arrays in C. elegans .

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

Dynamic self-polarization of the nuclear spins in a GaAs quantum well

Mladen Kotur, Dennis Kudlacik, Nataliia E. Kopteva, Erik Kirstein, Dmitri R. Yakovlev, Kirill V. Kavokin, Manfred Bayer

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We demonstrate the self-polarization regime of nuclear spins, originally predicted in 1972 by Dyakonov and Perel and achieved here by lattice temperature reduction into the millikelvin range. We first identify a gallium arsenide-based quantum well structure as highly suited by demonstrating a high nuclear spin polarization, corresponding to an Overhauser field of 3.1 tesla, using optical spin pumping at 1.6-kelvin lattice temperature. Here, adiabatic demagnetization leads to a nuclear spin temperature of 6.4 microkelvins, detected by time-resolved Kerr rotation. By measuring polarized photoluminescence and entering the lattice temperature regime below 500 millikelvins, a sharp zero-field feature in the Hanle electron spin depolarization curve evidences the dynamic nuclear self-polarization under unpolarized optical excitation. The self-polarization results in ultralow nuclear spin temperatures, which we estimate to become as low as 200 nanokelvins.

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

Kupffer cells are key mediators of antigen-specific immune tolerance by peptide-coupled red blood cells

Vasileia Kalaitzaki, Pietro Oldrati, Filipa M. Ferreira, Antonios Katsoulas, Ahmed Ali, Livio Baselgia, Yun Liu, Jincheng Fang, Roman Sankowski, Mai Matsushita, Florence Vallelian, Alexandre P. A. Theocharides, Cyrill Géraud, Roland Martin, Andreas Lutterotti, Thorsten Buch

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Induction of antigen-specific immune tolerance is the most precise method for reverting an autoreactive immune response in diseases such as multiple sclerosis (MS). Coupling red blood cells (RBCs) with a cocktail of MS immunodominant peptides is a promising approach to induce antigen-specific immune tolerance in patients. Here, we show that RBCs coupled with disease-inducing antigen efficiently prevent the development of experimental autoimmune encephalomyelitis, when administered prophylactically, and ameliorate disease symptoms when given therapeutically. The tolerogenic activity of peptide-coupled RBCs (pcRBC) was antigen specific and dependent on both cell and peptide dose. Kupffer cells (KC) were the primary phagocytes of pcRBC, and their uptake of pcRBC did not require complement component 3, SIRPα, and Stabilin 1 and 2. KC were indispensable for the induction of tolerance, which was accompanied by programmed death-ligand 1 up-regulation and a tolerogenic transcriptional shift. Our findings establish KC as central mediators of pcRBC-induced immune tolerance and provide mechanistic insight for the use of this therapeutic strategy in autoimmune disease.

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

A helix-loop-helix gene orchestrates male fate in common carp

Kuangxin Chen, Ji Chen, Miao Ding, Yi Rong, Yuanqi Guo, Yongming Li, Binbin Tao, Yanlong Song, Xingxing Wu, Lei Chen, Rui Li, Mouyan Jiang, Zhaoxian Li, Shaoting Jia, Yunya Wu, Yulai Wei, Yinjun Jiang, Hairong Liu, Shuhui Ji, Wenge Ma, Xishuang Shan, Wenrong Zhong, Wen Xu, Xianyao Liao, Lu Chen, Xiya Zhang, Junzhi Luo, Xuefan Cui, Hongrui Luo, Fei Liu, Houpeng Wang, Zhixian Qiao, Xiaocui Chai, Fang Zhou, Daji Luo, Shunping He, Zuoyan Zhu, Vance L. Trudeau, Chutian Ge, Wei Hu

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Fish show exceptional diversity in sex-determination mechanisms, making them a powerful system for studying how these pathways evolve. However, no definitive master sex-determining gene has yet been identified in Cyprinidae, a widely distributed and species-rich fish family. Here, we identified a male-specific gene in common carp encoding Pangu, a helix-loop-helix (HLH) domain peptide localized to Sertoli cells. Loss- and gain-of-function analyses demonstrate that pangu is both necessary and sufficient for male sex determination. Expression and reporter assays indicate that pangu represses cyp19a1a , a key regulator of ovarian differentiation, and disruption of cyp19a1a restores testicular development in the feminized phenotype of XY pangu mutants. These findings establish pangu as the master sex-determining gene in common carp and link an HLH domain peptide to sex differentiation.

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

Insights into temporal and spatial dynamics of short association fiber formation in the human fetal brain

Bo Li, Željka Krsnik, Lana Pierotich, Ivica Kostović, Simon K. Warfield, P. Ellen Grant, Davood Karimi

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Short association fibers (SAFs) form the local scaffold of cortical connectivity and support early functional specialization. However, their development before birth remains largely unknown. Using fetal diffusion magnetic resonance imaging from the Developing Human Connectome Project and histology from the Zagreb Collection of human brains, we present an in utero reconstruction of SAF pathways in the human brain. We tracked their volumetric and microstructural developmental trajectories in 243 fetuses spanning a critical period of connectome formation. We found that SAFs emerge before sulcal folding, initially as flat, loosely arranged pathways along the subplate–white matter interface, and later reorganize into coherent U-shaped bundles. Their maturation followed a sensorimotor-to-association gradient, paralleling cortical development. Nonlinear, bundle-specific trajectories captured multiphasic maturation, with subplate dynamics preceding increases in axonal coherence and early myelination. These findings reveal how the brain’s local wiring is established during prenatal development and provide insight into the origins of individual variability.

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

SUMO2 deletion changes chromatin accessibility and enhances cytotoxic T cell activation and tumor infiltration

Mohottige D. Neranjan Tharuka, Dai-Hua Chen, Maria Luisa Jurgensen Amaral, Tianchen Ren, Yixuan Kuang, Shih-Ting Huang, Nikhil Chilakapati, Bing Ren, Stephen P. Schoenberger, Ye Zheng, Yuan Chen

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Cytotoxic T cells [cytotoxic lymphocytes (CTLs)] are crucial for adaptive immunity leading to prolonged survival and potential cures for cancer. Recent clinical data have shown that pharmacological inhibition modifies the tumor microenvironment (TME) and activates CTLs, although the mechanism is not well described. In this study, we found that T cell–specific knockout (KO) of the most prevalent SUMO paralog, Sumo2 / SUMO2 , in both mouse and human CD8 + T cells significantly enhanced CD8 + T cell activation without enhanced IFN-I (type I interferon)–responsive genes in vitro but increased chromatin accessibility at enhancer regions for AP-1 (activating protein 1) family members, including BATF and JunB, which are known to promote T cell activation and proliferation. Using antigen-specific OT1 and CAR (chimeric antigen receptor) T cell models, we found that Sumo2 KO CD8 + T cells had significantly higher tumor infiltration, as revealed by flow cytometry, immunofluorescence staining, and single-nucleus RNA sequencing (snRNA-seq), and conferred greater tumor growth inhibition than wild-type control T cells. snRNA-seq also revealed that Sumo2 KO in CD8 + T cells increased the expression of TRAIL (tumor necrosis factor–related apoptosis-inducing ligand) in vivo and activated the antitumor immune microenvironment, likely through cell-cell interaction involving more activated CTLs. These findings elucidate a novel mechanism by which SUMOylation controls CTL activation and tumor infiltration that activate antitumor immunity in the TME. SUMO2 KO can also be a potential strategy to enhance adoptive T cell therapies for solid tumors by enhancing their activation, tumor infiltration and ability to modulate the TME.

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

HPSC-derived mesenchymal stromal cells ameliorate murine autistic-like phenotypes through activating oxytocinergic neurons

Yinong Huang, Yixuan Liu, Yilin Liu, Hongjie Liang, Yunli Tong, Ruijie Li, Xiaoran Zhang, Yiling Wang, Yiwen Deng, Jihao Wu, Yue Shu, Qiying Lu, Yuan Qiu, Jinsi Chen, Yucheng Ba, Jiayun Fang, Jiang Hao, Weiqiang Li, Haipeng Xiao, Weijun Huang, Andy Peng Xiang

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Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder marked by social deficits, repetitive behaviors, and psychiatric comorbidities. Despite its rising global prevalence, effective treatments remain elusive. Mesenchymal stromal cells (MSCs) offer therapeutic promise for ASD, although their mechanisms are unclear. Here, we show that induced pluripotent stem cell (iPSC)–derived MSCs alleviate anxiety, grooming, and social impairments in Shank3B knockout mice, a monogenic ASD model. Intravenously infused MSCs localize to the neurohypophysis, interface with oxytocin (OT)–producing neuron axons, and activate OT + neurons in the paraventricular nucleus (PVN). MSC treatment also reduces autistic-like phenotypes in BTBR T + Itpr3tf /J mice, a model of idiopathic ASD, in an OT + neuron–dependent manner. Mechanistically, prostaglandin E2 (PGE2) secreted by MSCs instigates the activation of OT + neuron, while suppression of PGE2 production via short hairpin RNA (shRNA)–mediated knockdown of PTGS1 and PTGES diminishes their therapeutic efficacy. These findings reveal a mechanism whereby MSCs modulate OT + neuroendocrine circuits to improve ASD-related behaviors.

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

Cell heterogeneity contributes to the variable response of HIV-1 to latency-reversing agents

Rachel Topno, Hussein Karaki, Flavia Mazzarda, Oriane Pourcelot, Manon Philippe, Kazem Zibara, Ovidiu Radulescu, Edouard Bertrand

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Transcriptional noise contributes to gene expression variability, but its origin and impact in HIV-1 latency remain incompletely characterized. Here, we combine a dual-copy MS2-tagging system with dedicated mathematical analysis to investigate the variability of HIV-1 transcription in live cells. In the basal state, the transcriptional activity of proviruses located in the same cell was uncorrelated, indicating that expression variability primarily comes from the intrinsic stochasticity of promoter dynamics. Upon stimulation with diverse latency-reversing agents, transcription of viral copies became more correlated within cells than across them, revealing a shift from promoter-driven to cell state–driven variability. Analysis of the molecular drug targets confirmed variable effects across cells. Our findings indicate that cellular heterogeneity can shape the response to latency-reversing agents and demonstrate how quantitative tools can dissect noise sources. This work offers mechanistic insights into HIV-1 latency and informs strategies to target the latent viral reservoir.

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

MIMAS: An open-source microlens-array miniature microscope for accessible large-field cortical imaging in freely behaving mice

Mian Xie, Jingyi Ma, Baoyi Zhang, Jian Lu, Hongda Yin, Yuanpeng Jiang, Yuxi Zhao, Yongjun Qian, Zengcai V. Guo, Wenhao Liu, Qiang Fu, Changliang Guo, Liangyi Chen

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Large-scale cortical dynamics during natural behavior are difficult to measure because head-mounted imaging systems must balance field of view, spatial resolution, weight, and optical complexity. Existing wide-field miniature microscopes often rely on compound or custom-corrected optical assemblies, which increase device complexity and limit accessibility for laboratories without specialized optics expertise. Here, we present the Miniature Integrated Microlens Array System (MIMAS), an open-source head-mounted fluorescence microscope that replaces conventional multi-element optics with a 4 × 5 microlens array as its sole imaging element. By combining modular subfield acquisition with computational registration and stitching, MIMAS achieves cellular-resolution imaging across an approximately 4 × 4.5 mm 2 field of view while weighing only 2.31 g. In freely behaving mice with sparse labeling of layer 2/3 cortical neurons, MIMAS enabled simultaneous calcium imaging across multiple dorsal cortical regions, with signals extracted from thousands of neurons. This broad sampling captured distributed cortical activity related to locomotor state and sparse position-modulated responses during open-field exploration without detectable disruption of locomotion or loss of signal quality over 30 min of recording. Beyond neuronal imaging, MIMAS also supported wide-field vascular imaging and resolved vessel caliber-dependent hemodynamic responses to isoflurane. These results establish MIMAS as a lightweight, accessible, and versatile platform for large-scale fluorescence imaging in freely behaving mice and demonstrate an alternative strategy for wide-field cortical imaging that lowers the optical complexity barrier for individual laboratories.

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

Endogenous retrovirus control of calbindin is essential for human early embryogenesis

Judith Pape, Afshan McCarthy, Eduardo Serna-Morales, Borzo Gharibi, Tobias Plowman, Elias Copin, Rachael Thompson, Laura Doglio, Ruta Meleckyte-Martinez, Lyn Healy, Sara Tamagno, Alberto Elosegui-Artola, Silvia D. M. Santos, Kathy K. Niakan, George Kassiotis

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The cis-regulatory potential of human endogenous retroviruses (HERVs) that have accumulated in our genome affects diverse host processes, including embryonic development and malignancy, where HERV epigenetic control is reduced. Non–small cell lung cancer optimal growth requires cancer cell–intrinsic expression of the calcium-binding protein calbindin under the control of a HERVH integrant on chromosome 8q21.3. Chimeric transcription of HERVH and CALB1 , encoding calbindin, is also observed in human embryonic stem cells (ESCs), but its significance remained uncertain. Here, we show that HERVH integration on 8q21.3 during Homininae evolution coincides with acquisition of expression of CALB1 in preimplantation embryos. We further show that CALB1 expression is critical for human ESC growth and the prevention of cellular senescence and for the formation of ESC-derived preimplantation blastoids and postgastrulation amnioids. Thus, the co-option of HERVH 8q21.3 cis-regulatory activity in lung cancer may echo its essential requirement for human embryo development.

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

Packing-accelerated consecutive NIR excitation (PACE) enables high energy photocatalysis and antitumor immunity in vivo

Yishen Liu, Shuo Wang, Wenbo Hu, Haotian Guo, Zafar Mahmood, Yuqin Liao, Yanna Pan, Xiaofen Wang, Wumei Wang, Zhiyun Zhang, Mingxuan Jia, Haolin Zhang, Xiaodong Zeng, Huaiyi Huang, Xinyuan Fan, Xuechuan Hong, Zhijun Sun, Yuling Xiao

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Near-infrared (NIR) photocatalysis promises deep-tissue compatibilities but remains fundamentally constrained by two bottlenecks: insufficient photon energy and rapid charge recombination. Here, we report packing-accelerated consecutive excitation (PACE), a mechanism enabling low energy near-infrared (NIR) photons to drive high energy single electron transfer (SET) reactions. We design a self-assembling ruthenium complex, Ru-3 , that forms densely packed nanoaggregates exhibiting aggregation-stabilized excited states, a pronounced excited state absorption band at ∼1315 nm, and nanosecond scale triplet lifetimes. Under dual NIR-I/IIa irradiation (808 nm/1310 nm), Ru-3 nanoparticles exhibit photophysical behavior consistent with consecutive photon harvesting and access to a higher-energy reactive state that supports efficient SET catalysis under aqueous conditions. This PACE-driven reactivity enables robust oxidation of mitochondrial NADH to NAD + , disrupting electron-transport homeostasis, inducing cGAS-STING dependent pyroptosis, and reprogramming tumor-associated macrophages toward an M1 phenotype. In multiple murine tumor models, PACE-mediated photocatalysis elicits strong antitumor immunity and leads to tumor regression with minimal systemic toxicity. This work establishes PACE as a new photochemical paradigm that overcomes the intrinsic energy and charge-separation limits of NIR photoredox chemistry, opening a route toward high-energy photocatalysis in complex biological environments.

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

Hydrogen isotopes reveal water leakage from the core

Yu Zhang, Wenzhong Wang, Zhongqing Wu, Bowen Chen

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Chemical heterogeneities in Earth’s deep mantle may record either preserved primordial reservoirs or later core-mantle exchange, but distinguishing between these origins remains challenging. Hydrogen isotopes offer a sensitive tracer, yet whether magma ocean crystallization could generate a deuterium-depleted deep reservoir has not been quantitatively evaluated. Here, we use machine learning–accelerated path-integral simulations to determine equilibrium hydrogen isotope fractionation between silicate melt and bridgmanite, ringwoodite, and wadsleyite under magma ocean conditions. Incorporating these fractionation factors into a magma ocean crystallization model shows that mineral-melt fractionation is intrinsically weak, producing an essentially homogeneous D/H distribution in the primitive mantle. Magma ocean crystallization therefore cannot generate the extremely low δD values observed in some ocean island basalts. Combined with exceptionally high 3 He/ 4 He ratios, these signatures more plausibly reflect selective transfer of primordial volatiles from Earth’s core, implying sustained volatile exchange across the core-mantle boundary.

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

Targeting SUV39H2 exon skipping reverses resistance to CDK4/6 inhibitors via transcriptional activation of p21

Shiyi Yu, Xue Gong, Yawen Yang, Ying Duan, Siyu Zhang, Ying Wang, Zheng Wang, Caili Bi, Haibo Sun

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Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are standard therapies for estrogen receptor–positive breast cancer, but their efficacy is limited by drug resistance. While dysregulation of alternative splicing has been implicated in cancer progression, the underlying mechanisms remain unclear. Here, we uncover a splicing-mediated mechanism whereby exon 2 inclusion in SUV39H2 drives its overexpression in CDK4/6i-resistant breast cancer cells. Clinically, elevated exon 2 inclusion in SUV39H2 correlates with poor prognosis in patients with breast cancer. Targeting SUV39H2 with gapmer antisense oligonucleotides or a methyltransferase inhibitor overcomes CDK4/6i resistance and reinstates therapy-induced senescence in breast cancer cells by reducing SUV39H2 expression or activity. Mechanistically, targeting SUV39H2 promotes transcriptional activation of senescence-associated secretory phenotype genes, including p21 , through H3K9me3 removal at enhancer regions and subsequent chromatin opening at promoters. Our work unveils a splicing-mediated resistance mechanism and presents a potential synergistic drug target for CDK4/6i therapy.

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

Rise and spread of lead-silver metallurgy deciphered from peatland archives

Hugo Delile, André-Marie Dendievel, Laura Chollet, Iscia Codjo, Adrien Barra, Janne Blichert-Toft

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How mining has shaped long-term economic and political landscapes across Europe and the Mediterranean remains poorly understood, largely because archaeological evidence is spatially fragmented and ore sources are difficult to trace from atmospheric lead (Pb) records. Here, we compile Pb isotope data from environmental archives and introduce the Environmental Match Intensity Index (EMII), a metric applied to peat records to track Pb–silver (Ag) ore-supply patterns and relative changes in the integrated mining-related atmospheric Pb signal over six millennia. EMII reveals an early mining signal centered on Laurion (Greece) during the Late Neolithic/Chalcolithic, followed by Bronze Age expansion structured by maritime routes linking the Cyclades, the Troad, and Anatolian coasts. From the Iron Age onward, our results challenge the conventional Iberian-centered mining model and instead reveal a polycentric and multimodal organization rooted in west-central European districts interconnected through major fluvial corridors and complementary terrestrial and maritime routes. EMII reaches its first major peak during the Early Roman period, declines during Late Antiquity and the Early Middle Ages, and rises again from the High Middle Ages onward. Despite these temporal fluctuations, the overall continental distribution of the contributing mining regions remains broadly stable. By connecting environmental archives with mining, transport, and urban demand, this framework provides a scalable approach for reconstructing the long-term organization of metal production and circulation and their contribution to anthropization processes across different chrono-cultural periods and geographical settings.

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

Predicting regional gray swans via translocation: AI weather models and Dubai’s unprecedented 2024 rainfall

Y. Sun, Pedram Hassanzadeh, Tiffany Shaw, Hamid A. Pahlavan, Adam Marchakitus

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Artificial intelligence (AI) models have transformed weather forecasting, but their skill for unprecedented weather extremes is unclear. Here, we analyze GraphCast, AIFS, and FuXi forecasts of the unprecedented 2024 Dubai storm, which had twice the training set’s highest rainfall in that region. GraphCast and AIFS accurately forecast this event up to 8 days ahead. FuXi forecasts the event but underestimates the rainfall. Fine-tuning and receptive field analyses suggest that these models’ success stems from “translocation”: learning from comparable/stronger dynamically similar events in other regions during training. Evidence of “extrapolation” (learning from weaker events) is not found. Even events within the global distribution’s tail are poorly forecasted, which is not only due to data imbalance (generalization error) but also spectral bias (optimization error). These findings demonstrate the potential of AI models to forecast “regional” gray swans and the opportunity to improve them through understanding the mechanisms behind their successes/limitations.

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

3D DNA origami-enabled molecularly addressable optical nanocircuit

Jaewon Lee, Hayun Ahn, Kyung Hun Rho, Shelley F. J. Wickham, William M. Shih, Seungwoo Lee

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Clusters of nanoparticles enable electric and magnetic resonances and strong light–molecule interactions, including plasmonic resonance energy transfer (PRET). The optical nanocircuit concept provides a predictive RLC framework for these responses, but experimental realization has been limited by insufficient control over nanogaps and molecular placement. Here, we introduce a molecularly addressable optical nanocircuit based on a robust three-dimensional (3D) DNA origami. We demonstrate that gold nanoparticles and dye-loaded origami function as distinct circuit elements, with the latter acting as a resistor-coupled capacitor that directly participates in resonance. This capability enables deterministic assembly of nanocircuits with controlled symmetry and tunable nanogaps. The multilayer barrel scaffold yields a non–close-packed, symmetry-broken trimer with a magnetic resonance exhibiting a Q -factor of ∼19.2, exceeding values reported for comparable plasmonic clusters. Selective dye loading onto origami enables predictive light–molecule coupling, producing a 100-fold PRET enhancement in dimers over monomers. This approach provides a versatile route to designer optical resonances for nanophotonic applications.

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

Escalating soil CO 2 degassing correlates with ground uplift and seismicity during the ongoing unrest of Campi Flegrei (2005–2025)

Giulio Bini, Giovanni Chiodini, Rosario Avino, Alessandro Santi, Francesco Rufino, Carlo Cardellini, Giancarlo Tamburello, Tullio Ricci, Prospero De Martino, Antonio Carandente, Emilio Cuoco, Raffaella S. Iovine, Carmine Minopoli, Dmitri Rouwet, Alessandra Sciarra, Renato Palmieri, Mauro Tieri, Stefano Caliro

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The mechanism driving accelerating unrest at the densely populated Campi Flegrei caldera since 2005 remains debated. Analyzing an unprecedented two-decade geochemical dataset, we show that escalating soil CO 2 fluxes closely tracks caldera uplift, revealing magmatic fluid pressurization at 3- to 4-kilometer depth and heating as the fundamental driver of the unrest. A critical magmatic gas pulse occurred between 2018 and 2022 specifically focused this outgassing beneath the Solfatara crater. Thermodynamic modeling demonstrates that an increasing mass of ascending fluid pressurizes the hydrothermal system, forcing vapor condensation within the upper kilometer. This condensation transfers latent heat to the crust. We calculate that this released thermal energy is an order of magnitude greater than that required for the 1.6-meter uplift since 2005. Ultimately, this fluid pressurization and heating drive accelerating deformation and seismicity; alongside the 2021 emergence of seismic sequences with short inter-event times, it directly signals an escalating phreatic or magmatic eruption risk.

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

Surficial carbonates in mantle plume sources revealed by magnesium isotopes

Ze-Zhou Wang, Fang-Zhen Teng, Matthew G. Jackson, Catherine Chauvel, Cédric Hamelin

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Deep recycling of surficial carbonates into the mantle may play a critical role in shaping Earth’s long-term habitability, yet its contribution to the deep mantle carbon budget remains uncertain. Magnesium isotopes provide a promising tracer for addressing this issue, because of the uniquely light isotopic signatures of sedimentary carbonates. Here, we present high-precision magnesium isotopic compositions (δ 26 Mg) for 152 globally distributed plume-related lavas sampling diverse mantle end-members. We find that δ 26 Mg values below the bulk silicate Earth range are commonly associated with increasingly pronounced radiogenic isotopic signatures indicative of recycled crustal components. These features are best explained by the incorporation of isotopically light magnesium derived from subducted carbonate-bearing crustal materials into their mantle sources. On the basis of these observations, the lower mantle is estimated to contain up to ∼130 or ∼230–parts per million recycled carbon, potentially constituting a substantial portion of its total carbon budget.

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

Rod photoreceptors have a dual dependency on both aerobic glycolysis and OXPHOS and diverge metabolically from other retinal neurons

Gabriele M. Wögenstein, Luca Ravotto, Vyara Todorova, Rachel M. Meister, Marijana Samardzija, L. Felipe Barros, Bruno Weber, Christian Grimm

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The retina metabolizes glucose into lactate, a hallmark of aerobic glycolysis known as the Warburg effect. Although evidence points to rod photoreceptors as the primary source of aerobic glycolysis, a comparison of the energy metabolism in different retinal neurons has yet to be performed. We combined two-photon fluorescence lifetime imaging of biosensors with pharmacological protocols to analyze metabolic dynamics in healthy and diseased rod photoreceptors and RBPMS-positive ganglion and calretinin-positive amacrine cells. Our data reveal distinct metabolic profiles among retinal neurons, identify rods as the drivers of aerobic glycolysis, demonstrate that inner retinal neurons rely on oxidative phosphorylation, show that rods need both glycolysis and oxidative phosphorylation to maintain ATP levels, and suggest that rods can metabolize lactate. A mutation causing retinitis pigmentosa increases lactate production in rods but changes the energy metabolism only subtly otherwise. Our results improve the understanding of retinal physiology and are relevant for pathologies involving imbalanced energy metabolism.

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

Exposure route, not dose, is the primary driver of infection patterns for a respiratory virus

Celine E. Snedden, Dylan H. Morris, Thomas C. Friedrich, James O. Lloyd-Smith

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Infectious disease severity, shedding, and within-host kinetics can vary substantially with exposure dose, inoculation route, and host factors. However, the relative contributions of these variables to infection heterogeneity remain poorly quantified because small sample sizes in controlled in vivo experiments limit their statistical power and scientific scope. Here, by compiling and jointly analyzing the largest published database of nonhuman primate challenge experiments (107 studies; 721 animals), we show that exposure route drives SARS-CoV-2 infection kinetics more strongly than dose, age, sex, or species. Aerosol inoculation yields kinetics distinct from all other respiratory exposure routes. Route and dose jointly determine which tissues become infected, and 50% infectious doses vary greatly depending on the route of exposure and on the tissue sampled. Our findings underscore the central role of exposure route in pathogenesis and transmission, and highlight the untapped potential for quantitative, cross-study syntheses to extract additional insights from costly animal experiments.

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

Magnetic omniconversion: Source-independent molding of magnetostatic fields

Jaume Cunill-Subiranas, Natanael Bort-Soldevila, Fabian Resare, Nuria Del-Valle, Witlef Wieczorek, Carles Navau

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Magnetic fields are constrained by the geometry and location of their sources, limiting the ability to freely tailor their spatial distribution. We introduce a general framework to passively convert the magnetic field generated by arbitrary sources into any prescribed desired field within a finite source-free region. Our method relies on field shaping using linear magnetic materials, enabling source-independent magnetic field molding. We provide the general recipe, analytical and numerical demonstrations for some paradigmatic examples, and a proof-of-concept experiment that validates the idea and materials implementation. This approach enables original possibilities in magnetic shielding, targeted field delivery, advanced imaging technologies, and a broad range of field-control applications.

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

Plenty of fish in the sea, but only one multimodal feather star robot

Parker McDonnell, Nicole W. Xu

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A feather star–inspired soft swimming robot achieves multimodal 3D maneuverability with minimal actuation using a mechanically intelligent body design.

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

Multiscale insights into screw dislocation-driven growth mechanisms

Peiyu Qiao, Zhongshi Zhang, Bohui Xu, Pifu Gong, Xuanze Li, Yifan Wang, Lifeng Tian, Pei Liu, Jianyu Cao, Yuye Li, Qi Zhang, Chun Zhao, Xiangmin Meng

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Spiral growth in two-dimensional (2D) materials has conventionally been explained by single screw dislocation mechanisms, yet a complete multiscale understanding remains elusive due to the intricate nature of screw dislocation structures. Here, we present a stabilization approach through metallic transition metal dichalcogenides (m-TMDs) overlayers on spiral semiconducting TMDs (s-TMDs), which enables unprecedentedly robust atomic-resolution imaging of screw dislocations in cross-sectional van der Waals heterostructures. Our multiscale investigations identify nanoscale substrate undulations as critical nucleation sites for screw dislocations and uncover a multi-screw dislocation-driven (MSDD) growth paradigm, characterized by periodic stress stripes with linear densities approaching ∼10 6 cm −1 . Furthermore, we establish that dislocation interactions govern stacking sequence reconstruction, while the kinetic competition among multiple screw dislocations determines the ultimate spiral architectures. These insights fundamentally transform our understanding of defect-mediated growth in 2D materials.

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

Wildfires diminish vegetation control on surface runoff

Yuanyuan Peng, Kun Shi, Shun Bi, Qi Guan

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Wildfires are increasingly reshaping global terrestrial ecosystems, yet their impacts on the fundamental coupling between vegetation and the hydrological cycle remain poorly understood. Here, we present a global-scale assessment of how wildfire disturbances alter the sensitivity of surface runoff to vegetation dynamics using multidecadal satellite observations and reanalysis datasets. We developed a spatially explicit framework to quantify pre- and postfire runoff-vegetation sensitivity across climatic gradients and fire regimes. We show a widespread and systematic weakening of vegetation control on runoff after wildfires, indicating a fundamental decoupling of hydrology-vegetation interactions. This attenuation is notably modulated by aridity and fire intensity, with the most pronounced sensitivity losses occurring in fragile drylands. These findings expose a critical blind spot in traditional hydrological models that overlook disturbance-driven vegetation shifts. Our study provides a mechanistic understanding of how compound climate-fire perturbations accelerate terrestrial water flux instability, suggesting that increasing fire frequency will exacerbate ecosystem vulnerability and threaten water security in a warming world.

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

Translocation-induced enhancer rewiring reveals cryptic oncogenic circuits in multiple myeloma

Enrun Zheng, Qinghua Li, Xuelin Dou, Yiping Cao, Chao Ren, Feiya Suo, Lin Lin, Yan Zhao, Zhiwei Liao, Yang Liu, Zesen Shang, Sudun Guan, Chengying Zhang, Mengyu Yang, Pengyu Xiang, Yakun Chen, Xinhua Liu, Yueyun Lai, Zhiqiang Liu, Adkhamjon Odilovich Abdullayev, Lin He, Xiaochen Bo, Yongfeng Shang, Jichuan Wang, Jin Lu, Hebing Chen, Luyang Sun

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Immunoglobulin heavy chain ( IGH ) enhancer translocations drive multiple myeloma (MM), but routine diagnostics resolve only 32 to 38% of cases. Here, we introduce TransFinder, a multiomic pipeline integrating SMRT long-read sequencing (LRS), Hi-C, H3K27ac ChIP-seq/CUT&Tag, and RNA-seq to systematically resolve cryptic translocations and their hijacked oncogenes by deconvoluting enhancer-promoter neo-loops at rearrangement breakpoints. Applied to MM, TransFinder identified that t(16;22)(q23;q11), a canonical translocation known to activate MAF , also hijacks enhancers to activate RAB36 . It further uncovered previously unrecognized t(5;8)(q35;q24) and t(1;22)(q25;q13), which activate MYC and CBX7 , respectively, through chromatin topology rewiring. CRISPR-Cas9–engineered t(1;22)(q25;q13) recapitulated CBX7 induction, and pharmacological inhibition of CBX7 suppressed myeloma cell proliferation. Beyond MM, TransFinder identified enhancer hijacking in chronic myeloid leukemia, where t(9;22)(q34;q11) repositioned an enhancer to activate BCR-ABL1 , and pancreatic ductal adenocarcinoma, where t(2;12)(p24;q24) hijacked an enhancer to activate SDC1 . Linking 3D genome architecture to oncogene activation, TransFinder decodes oncogenic structural variants and their trans-activities, establishing clinically actionable dependencies of noncoding drivers in malignancies.

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

Standardizing Cell Ontology terms for cross-study integration in the female reproductive tract

Huan Ting Ong, Diane C. Saunders, Caroline Eastwood, Aleix Puig-Barbe, Alison Kochersberger, Anna Galligos, Bailey Marshall, Benjamin K. Johnson, Caroline E. Kratka, Chen Jin, Daniela Betancur, Gabriela Rapozo Guimarães, Jordan H. Machlin, Jose V. V. Isola, Katelyn M. Adam, Osmaray Morales-Casanova, Svetlana Djirackor, Taylor Schissel, Valentina Lorenzi, Xifan Wang, Xingyu Shen, Bikem Soygur, Brian Aevermann, Eliza A. Gaylord, Mariko H. Foecke, Norbert K. Tavares, Ryan M. Samuel, Sophia Szady, Srinivasan Mahalingam, Subhasri Biswas, Will Liao, Bérénice A. Benayoun, Hattie Chung, Wipawee Winuthayanon, Jun Z. Li, Matteo A. Molè, Michael Angelo, Patricia Jeudin, Ronny Drapkin, Ariella Shikanov, Diana J. Laird, Francesca Duncan, Hui Shen, Jennifer L. Garrison, Mariana Boroni, Michael B. Stout, Roser Vento-Tormo, Sophia H. L. George, Yousin Suh, Jennifer L. Young, Monica M. Laronda

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The female reproductive tract is essential for fertility, pregnancy, and overall health, yet many of its cellular components remain poorly defined. Recent advances in single-cell and spatial transcriptomics have begun to reveal this complexity, but inconsistent naming of cell types and states has limited the ability to compare findings across studies. To address this challenge, an international group of reproductive biologists and ontology experts collaborated to harmonize annotations within Cell Ontology, focusing on the ovary, fallopian tube, and uterus. Standardized terms are proposed for major epithelial, stromal, and germ cell populations, supported by marker gene sets and anatomical linkages. This framework provides a shared reference that can be used to harmonize existing datasets and guide annotation of future studies, enabling consistent classification of oocytes, granulosa, theca, luteal, epithelial, stromal, and immune cells across tissues. By establishing a unified taxonomy, this work lays the foundation for integrating datasets, supporting cross-tissue comparisons, and advancing the understanding of reproductive biology, health, and disease.

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

Canonical Wnt induction by OTULIN prevents keratinocyte death and skin inflammation

Kim Lecomte, Pieter Hertens, Virginie Wylleman, Annagiada Toniolo, Febe Roelandt, Fleur Boone, Maarten Ciers, Lien Verboom, Katrien Staes, Geert van Loo, Esther Hoste

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Loss-of-function mutations in the human OTULIN gene, encoding a deubiquitinase with exclusive specificity for linear ubiquitin chains, cause a severe multiorgan autoinflammatory condition involving the skin. Mice lacking OTULIN selectively in keratinocytes develop inflamed skin lesions that progress into squamous tumors, a phenotype driven by excessive tumor necrosis factor (TNF)–induced cell death. Previous studies suggest a role for OTULIN in mediating Wnt signaling during development, but the physiological relevance of this association is unknown. Here, we show that OTULIN promotes Wnt signaling in keratinocytes by regulating the linear ubiquitination status of β-catenin. Stabilization of β-catenin in OTULIN-deficient keratinocytes prevents progressive skin inflammation in prophylactic and therapeutic settings by blocking keratinocyte death. We demonstrate that OTULIN prevents proteasomal degradation of β-catenin in cultured keratinocytes. Reduced Wnt signaling in OTULIN-deficient keratinocytes leads to degradation of TCF3/4, an essential survival factor for keratinocytes. Collectively, our data identify OTULIN’s linear deubiquitination activity as a key regulator of epithelial cell viability, not only by preventing cell death downstream of TNF, but also by promoting canonical Wnt signaling.

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

Insect-specific aldehyde synthase governs cuticle strength: a selective insecticide target

Yi Ding, Xue Hu, Zihan Pang, Huan Liu, Loushi Shen, Yingqian Liu, Tian Liu

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Cuticular sclerotization is crucial for insect adaptation and flight, historically thought to be dominantly driven by dopamine and its downstream products. In this study, we demonstrate that 3,4-dihydroxyphenylacetaldehyde (DHPAA)—produced by DHPAA synthase (DHPAAS) and known in humans as a toxic dopamine metabolite—plays a central role. Cross-species RNAi, mechanical testing, and precursor quantification, consistently support this conclusion. In the migratory locust, we further reveal that DHPAA is essential for cuticular mechanical properties, whereas dopamine primarily regulates pigmentation. These findings establish a new paradigm for the chemistry of insect cuticle sclerotization. Then, we elucidate the catalytic mechanism of DHPAAS, laying the groundwork for its application in biosynthesis. Furthermore, we identify 2,5,2′,4′-tetrahydroxychalcone as a selective inhibitor of DHPAAS. Given that DHPAAS is insect-specific and absent in non-insect arthropods and vertebrates, our work points to a promising strategy for developing selective insecticides.

Mesoscale structures in signed networks

Wei Zhang, Olga Boichak, Tristram J. Alexander, Tiago P. Peixoto, Eduardo G. Altmann

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Mesoscale structures in signed networks have been studied under the limiting assumption of the validity of social balance theory, which predicts positive connections within groups and negative connections between groups. Here, we propose and apply a methodology that overcomes this limitation and is able to find and characterize also the different possible unbalanced structures in signed networks. Applying our methodology to 24 empirical networks, from social-political, financial, and biological domains, we find that unbalanced mesoscale structures are prevalent in real-world networks, including cases with substantial balance at the microscale of triangles. In particular, we find that assortativity often prevails regardless of the interaction sign and that core-periphery structures are typical in online social networks. Our findings highlight the complexity of mesoscale relational structures, the importance of using computational methods that are a priori agnostic to specific patterns, and the importance of independently evaluating micro- and mesoscale predictions of social balance theory.

Costly missed connections: Visitation and misconduct in California prisons

Yilin Zhuo, Kristin Turney, Naomi F. Sugie, M. Keith Chen, Emily Owens

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Social isolation is a major public health crisis with particularly deleterious consequences for vulnerable populations including incarcerated people. Theoretically, visitation from family should reduce social isolation and improve outcomes among incarcerated people, but existing quasi-experimental research provides limited support for the relationship between visitation and in-custody outcomes. We revisit the effect of visitation on in-custody misconduct—an important but administratively defined measure of institutional safety—by exploiting the fact that fluctuations in gasoline prices create unanticipated shifts in visitation uncorrelated with other factors associated with misconduct. We combine this quasi-experimental variation with smartphone mobility data identifying prison visits from cell phone pings and administrative data on misconduct in California prisons. We find that increases in visits induced by changes in transportation costs are negatively related to misconduct (particularly use-of-force events and personal battery), with effects concentrated immediately after visitation. Although the policy implications are subtle, these findings suggest that some strategies that reduce visitation barriers could be cost-effective ways to reduce prison violence. More broadly, they suggest that social connections have causal repercussions for violence and safety in extreme institutional environments.