🗣 Communication Paper Picnic 🧺: Multidisciplinary

I checked 6 multidisciplinary journals on Friday, February 06, 2026 using the Crossref API. For the period January 30 to February 05, I found 16 new paper(s) in 4 journal(s).

Nature

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

Bacterial immune activation via supramolecular assembly with phage triggers

Tong Zhang, Yifei Lyu, Christina R. Beck, Naseer Iqbal, Renee Barbosa, Alireza Ghanbarpour, Michael T. Laub

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Bacteria use diverse mechanisms to protect themselves against phages 1–6 . Many antiphage systems form large oligomeric complexes, but how oligomerization is regulated during phage infection remains mostly unknown 7–12 . Here we demonstrate that the bacterial immunity protein ring-activated zinc-finger RNase (RAZR) assembles into an active, 24-meric ring around the circumference of large ring structures formed by two unrelated phage proteins: a putative recombinase and a portal protein. Each multi-layered, megadalton-scale complex enables RAZR to cleave RNA nonspecifically to inhibit translation and restrict phage propagation. The recognition of unrelated phage proteins that form rings with similar diameters indicates that these proteins not only bind to RAZR but also enforce a geometry crucial to activation. The lack of large ring structures in the host probably prevents auto-immunity and RAZR activation before infection. The infection-triggered oligomerization of RAZR mirrors pathogen-induced oligomerization in eukaryotic innate immune complexes 13 , underscoring a common principle of immunity across biology.

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

Synthesizing scientific literature with retrieval-augmented language models

Akari Asai, Jacqueline He, Rulin Shao, Weijia Shi, Amanpreet Singh, Joseph Chee Chang, Kyle Lo, Luca Soldaini, Sergey Feldman, Mike D’Arcy, David Wadden, Matt Latzke, Jenna Sparks, Jena D. Hwang, Varsha Kishore, Minyang Tian, Pan Ji, Shengyan Liu, Hao Tong, Bohao Wu, Yanyu Xiong, Luke Zettlemoyer, Graham Neubig, Daniel S. Weld, Doug Downey, Wen-tau Yih, Pang Wei Koh, Hannaneh Hajishirzi

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Scientific progress depends on the ability of researchers to synthesize the growing body of literature. Can large language models (LLMs) assist scientists in this task? Here we introduce OpenScholar, a specialized retrieval-augmented language model (LM)1 that answers scientific queries by identifying relevant passages from 45 million open-access papers and synthesizing citation-backed responses. To evaluate OpenScholar, we develop ScholarQABench, the first large-scale multi-domain benchmark for literature search, comprising 2,967 expert-written queries and 208 long-form answers across computer science, physics, neuroscience and biomedicine. Despite being a smaller open model, OpenScholar-8B outperforms GPT-4o by 6.1% and PaperQA2 by 5.5% in correctness on a challenging multi-paper synthesis task from the new ScholarQABench. Although GPT-4o hallucinates citations 78–90% of the time, OpenScholar achieves citation accuracy on par with human experts. OpenScholar’s data store, retriever and self-feedback inference loop improve off-the-shelf LMs: for instance, OpenScholar-GPT-4o improves the correctness of GPT-4o by 12%. In human evaluations, experts preferred OpenScholar-8B and OpenScholar-GPT-4o responses over expert-written ones 51% and 70% of the time, respectively, compared with 32% for GPT-4o. We open-source all artefacts, including our code, models, data store, datasets and a public demo.

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

Integrated structural dynamics uncover a new B12 photoreceptor activation mode

Ronald Rios-Santacruz, Harshwardhan Poddar, Kevin Pounot, Derren J. Heyes, Nicolas Coquelle, Megan J. Mackintosh, Linus O. Johannissen, Sara Schianchi, Laura N. Jeffreys, Elke De Zitter, Rory Munro, Martin Appleby, Danny Axford, Emma V. Beale, Matthew J. Cliff, María C. Dávila-Miliani, Sylvain Engilberge, Guillaume Gotthard, Kyprianos Hadjidemetriou, Samantha J. O. Hardman, Sam Horrell, Jochen S. Hub, Kotone Ishihara, Sofia Jaho, Gabriel Karras, Machika Kataoka, Ryohei Kawakami, Thomas Mason, Hideo Okumura, Shigeki Owada, Robin L. Owen, Antoine Royant, Annica Saaret, Michiyo Sakuma, Muralidharan Shanmugam, Hiroshi Sugimoto, Kensuke Tono, Ninon Zala, John H. Beale, Takehiko Tosha, Jacques-Philippe Colletier, Matteo Levantino, Sam Hay, Pawel M. Kozlowski, David Leys, Nigel S. Scrutton, Martin Weik, Giorgio Schirò

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Photoreceptor proteins regulate fundamental biological processes such as vision, photosynthesis and circadian rhythms1. A large photoreceptor subfamily uses vitamin B12 derivatives for light sensing2, contrasting with the well-established mode of action of these organometallic derivatives in thermally activated enzymatic reactions3. The exact molecular mechanism of B12 photoreception and how this differs from the thermal pathways remains unknown. Here we provide a detailed description of photoactivation in the prototypical B12 photoreceptor CarH4,5 from nanoseconds to seconds, combining time-resolved and temperature-resolved structural and spectroscopic methods with quantum chemical calculations. Building on the crystal structures of the initial tetrameric dark and final monomeric light-activated states5, our structural snapshots of key intermediates in the truncated B12-binding domain illustrate how photocleavage of a cobalt–carbon (Co–C) bond within the B12 chromophore adenosylcobalamin triggers a series of structural changes that propagate throughout CarH. Breakage of the photolabile Co–C5′ bond leads to the formation of a previously unknown adduct that links the C4′ position of the adenosyl moiety to the Co ion and can subsequently be cleaved thermally over longer timescales to allow release of the adenosyl group, ultimately causing tetramer dissociation4,5. This adduct, which differentiates CarH from thermally activated B12 enzymes, steers the photoactivation pathway and acts as the molecular bridge between photochemical and photobiological timescales. The biological relevance of our study is corroborated by kinetic data on full-length CarH in the presence of DNA. Our results offer a spatiotemporal understanding of CarH photoactivation and pave the way for designing B12-dependent photoreceptors for optogenetic applications.

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

Signatures of fractional charges via anyon–trions in twisted MoTe2

Weijie Li, Christiano Wang Beach, Chaowei Hu, Takashi Taniguchi, Kenji Watanabe, Jiun-Haw Chu, Ataç Imamoğlu, Ting Cao, Di Xiao, Xiaodong Xu

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Fractionalization of the electron charge e is one of the most striking phenomena arising from strong electron–electron interactions. A celebrated example is the emergence of anyons with fractional charges in fractional quantum Hall effect (FQHE) states1,2,3,4,5,6,7,8,9,10,11,12,13. Recently, zero-field fractional Chern insulators (FCIs)14,15,16,17,18,19, lattice analogues of the FQHE states that form without Landau levels, have been realized20,21. FCIs provide a unique platform to investigate anyons, yet their detection remains a challenge. Here we report the observation of anyon–trions, a new type of excitonic complex formed by binding a trion with a fractional charge in twisted MoTe2 bilayers. Photoluminescence spectroscopy of quantum-confined excitons reveals emergent peaks that appear only within slightly doped FCI states. The new spectral features are red-shifted relative to the trions in undoped FCIs, but share the same electric field, temperature and magnetic field dependence. These observations suggest their origin as trions binding with elementary quasi-particles, that is, anyon–trions. Crucially, the ratio of binding energies between the anyon–trions in the −2/3 and −3/5 FCI states matches the expected fractional charge ratio of e/3 to e/5. This provides strong evidence for fractional charges in FCI—an essential property of anyons. Our results address a fundamental question in FCI physics and establish trion spectroscopy as a powerful probe of fractionally charged excitations, complementary to transport- and tunnelling-based approaches.

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

Tumour–brain crosstalk restrains cancer immunity via a sensory–sympathetic axis

Haohan K. Wei, Chuyue D. Yu, Bo Hu, Xing Zeng, Hiroshi Ichise, Liang Li, Yu Wang, Ruiqi L. Wang, Ronald N. Germain, Rui B. Chang, Chengcheng Jin

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Body–brain communication has emerged as a key regulator of tissue homeostasis 1–5 . Solid tumours are innervated by different branches of the peripheral nervous system and increased tumour innervation is associated with poor cancer outcomes 6–8 . However, it remains unclear how the brain senses and responds to tumours in peripheral organs, and how tumour–brain communication influences cancer immunity. Here we identify a tumour–brain axis that promotes oncogenesis by establishing an immune-suppressive tumour microenvironment. Combining genetically engineered mouse models with neural tracing, tissue imaging and single-cell transcriptomics, we demonstrate that lung adenocarcinoma induces innervation and functional engagement of vagal sensory neurons, a major interoceptive system connecting visceral organs to the brain. Mechanistically, Npy2r -expressing vagal sensory nerves transmit signals from lung tumours to brainstem nuclei, driving elevated sympathetic efferent activity in the tumour microenvironment. This, in turn, suppresses anti-tumour immunity via β 2 adrenergic signalling in alveolar macrophages. Disruption of this sensory-to-sympathetic pathway through genetic, pharmacological or chemogenetic approaches significantly inhibited lung tumour growth by enhancing immune responses against cancer. Collectively, these results reveal a bidirectional tumour–brain communication involving vagal sensory input and sympathetic output that cooperatively regulate anti-cancer immunity; targeting this tumour–brain circuit may provide new treatments for visceral organ cancers.

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

Efficient near-telomere-to-telomere assembly of nanopore simplex reads

Haoyu Cheng, Han Qu, Sean McKenzie, Katherine R. Lawrence, Rhydian Windsor, Mike Vella, Peter J. Park, Heng Li

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Telomere-to-telomere (T2T) assembly is the ultimate goal for de novo genome assembly. Existing algorithms1,2 capable of near-T2T assembly all require Oxford Nanopore Technologies (ONT) ultra-long reads, which are costly and experimentally challenging to obtain and are thus often unavailable for samples without established cell lines3. Here we introduce hifiasm (ONT), an algorithm that can produce near-T2T assemblies from standard ONT simplex reads, eliminating the need for ultra-long sequencing. Compared with existing methods, hifiasm (ONT) reduces computational demands by an order of magnitude and reconstructs more chromosomes from telomere to telomere on the same datasets. This advance substantially broadens the feasibility of T2T assembly for applications previously limited by the high cost and experimental requirement of ultra-long reads.

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

Cleavage of mRNAs by a minority of pachytene piRNAs improves sperm fitness

Katharine Cecchini, Mina Zamani, Nandagopal Ajaykumar, Joel Vega-Badillo, Ayca Bagci, Shannon Bailey, Phillip D. Zamore, Ildar Gainetdinov

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Animals use 18–33-nucleotide PIWI-interacting RNAs (piRNAs) to silence transposons in germ cells 1–3 . In addition to transposon-silencing piRNAs, placental mammals make pachytene piRNAs 4,5 , an abundant class of testis-specific small RNAs derived from long noncoding RNA precursors. Although the sites of pachytene piRNA precursor transcription are often conserved among placental mammals, the sequences of the piRNAs themselves are rapidly diverging, even in the human population 6 . Consequently, the biological function and mechanism of action of pachytene piRNAs remain debated. Here we report that most mouse pachytene piRNAs have no biological function but instead ‘selfishly’ promote their own production. Our data suggest that pachytene piRNAs direct endonucleolytic cleavage of partially complementary targets and neither activate nor repress mRNA translation. Although many pachytene piRNAs guide cleavage of specific mRNAs, few alter the steady-state abundance of their targets. The minority of pachytene piRNAs that reduce target mRNA abundance enhance sperm fitness, thereby ensuring production of the entire pachytene piRNA repertoire. Together, our findings explain the lack of conservation of most pachytene piRNA sequences and suggest that these ‘selfish’ small RNAs persist in mammalian evolution because target cleavage by a tiny minority of piRNAs supports male fertility.

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

Regulation of STING activation by phosphoinositide and cholesterol

Jie Li, Jay Xiaojun Tan, Zhijian J. Chen, Xuewu Zhang, Xiao-chen Bai

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Stimulator of interferon genes (STING) is an essential adaptor in the cytosolic DNA-sensing innate immune pathway1. STING is activated by cyclic GMP–AMP (cGAMP) produced by the DNA sensor cGAMP synthase (cGAS)2,3,4,5. cGAMP-induced high-order oligomerization and translocation of STING from the endoplasmic reticulum to the Golgi and post-Golgi vesicles are critical for STING activation6,7,8,9,10,11. Other studies have shown that phosphatidylinositol phosphates (PtdInsPs) and cholesterol also have important roles in STING activation, but the underlying mechanisms remain unclear12,13,14,15,16,17. Here we demonstrate that cGAMP-induced high-order oligomerization of STING is enhanced strongly by phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2 and PtdIns(4,5)P2, and by PtdIns4P to a lesser extent. Our cryo-electron microscopy structures reveal that PtdInsPs together with cholesterol bind at the interface between STING dimers, directly promoting the high-order oligomerization. The structures also provide an explanation for the preference of the STING oligomer to different PtdInsPs. Mutational and biochemical analyses confirm the binding modes of PtdInsPs and cholesterol and their roles in STING activation. Our findings shed light on the regulatory mechanisms of STING mediated by specific lipids, which may underlie the role of intracellular trafficking in dictating STING signalling.

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

Author Correction: Cotranslational assembly of protein complexes in eukaryotes revealed by ribosome profiling

Ayala Shiber, Kristina Döring, Ulrike Friedrich, Kevin Klann, Dorina Merker, Mostafa Zedan, Frank Tippmann, Günter Kramer, Bernd Bukau

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

Regulatory grammar in human promoters uncovered by MPRA-based deep learning

Lucía Barbadilla-Martínez, Noud Klaassen, Vinícius H. Franceschini-Santos, Jérémie Breda, Hatice Yücel, Miguel Hernández-Quiles, Tijs van Lieshout, Carlos G. Urzua Traslaviña, Minh Chau Luong Boi, Maryam Akbarzadeh, Celia Hermana-Garcia-Agullo, Sebastian Gregoricchio, Marcel de Haas, Roy Straver, Sarah Derks, Wilbert Zwart, Emile Voest, Lude Franke, Michiel Vermeulen, Jeroen de Ridder, Bas van Steensel

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Promoters are the core regulatory elements of all genes. Their activity ensures the correct transcription level of each individual gene, which is essential for cellular homeostasis and responses to a wide range of signals. One of the major challenges in genomics is to build computational models that accurately predict genome-wide gene expression from the sequences of regulatory elements1. Here we present promoter activity regulatory model (PARM), a cell-type-specific deep-learning model trained on specially designed massively parallel reporter assays (MPRAs) that query human promoter sequences. PARM is experimentally and computationally lightweight so that cell-type-specific and condition-specific models can be generated that reliably predict autonomous promoter activity across the genome from the DNA sequence alone. PARM can also design purely synthetic strong promoters. We leveraged PARM to systematically identify binding sites of transcription factors that probably contribute to the activity of each natural human promoter and to detect the rewiring of these regulatory interactions after various stimuli to the cells. We also uncovered and experimentally confirmed substantial positional preferences of transcription factors that differ between activating and repressive regulatory functions and a complex grammar of motif–motif interactions. Our approach provides a highly economic strategy towards a deeper understanding of the dynamic regulation of human promoters by transcription factors.

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

Mosquito–capsid interactions contribute to flavivirus vector specificity

Jichen Niu, Jun Ma, Yibin Zhu, Gang Wang, Xiang Xu, Mao Wang, Zhaoyang Wang, Xinhui Bao, Jianying Liu, Enhao Ma, Xianwen Zhang, Long Liu, Ying Zhang, Qiyong Liu, Chunxiao Li, Hang Yin, Ye Xiang, Penghua Wang, Gong Cheng

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Multiple mosquito species serve as competent vectors to carry and transmit numerous flaviviruses1,2. Several long-standing scientific questions remain to be answered, including identification of the fundamental factors that facilitate flavivirus infectivity in mosquitoes and the genetic basis that contributes to the naturally occurring interspecies specificity of mosquitoes to flaviviruses3,4,5,6,7,8, such as Aedes aegypti mosquitoes to dengue virus (DENV). Here we report that circulating mature virions are inactivated by the acidity of mosquito haemolymph; thus, extracellular vesicles carrying replication-competent viral nucleocapsids serve as the predominant means of intercellular viral dissemination. Mechanistically, mosquito valosin-containing protein (VCP) binds to the viral capsid, thereby allowing the incorporation of nucleocapsids into extracellular vesicles. The capsid of a flavivirus (such as DENV) selectively binds to the VCP of its natural vector (Ae. aegypti), but not to that of an incompetent vector (for example, Culex quinquefasciatus). Replacing the DENV capsid with that of Japanese encephalitis virus (JEV) renders DENV infectious in the haemolymph of the natural JEV vector, Cx. quinquefasciatus. Furthermore, two amino residues in Aedes (D723/N728) and Culex (E723/E728) VCP determine its binding specificity for viral capsid, thus contributing to interspecies specificity of mosquitoes to flaviviruses. In vivo ectopic expression of the Cx. quinquefasciatus VCP mutant E723D/E728N renders Cx. quinquefasciatus susceptible to DENV2 via intrathoracic microinjection. Our study provides a major molecular mechanism contributing to the selectivity and compatibility between mosquito vectors and flavivirus species, enabling systemic virus dissemination after the virus reaches the haemocoel. Upstream mechanisms that determine specificity at the midgut level remain to be determined.

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

Spin-wave band-pass filters for 6G communication

Connor Devitt, Sudhanshu Tiwari, Bill Zivasatienraj, Sunil A. Bhave

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Spin-wave (SW) filters using single-crystal yttrium iron garnet (YIG) is an attractive technology for integration in frequency-adjustable or frequency-tunable communication systems1. However, existing SW devices do not have sufficient bandwidth for future 5G and 6G communication systems2,3, are too large or have strong spurious passbands, creating unintentional cross-channel interference. Here we report a SW ladder filter architecture requiring only a single external magnetic bias, which is enabled by modern micromachining fabrication methods capable of wafer-scale production. The filters developed in this work demonstrate loss as low as 2.54 dB, bandwidths up to 663 MHz, centre-frequency tuning over several octaves from 7.08 to 21.6 GHz and high linearity with an input-referred third-order intercept point of more than 11 dBm in the passband. The operation of the filter is also experimentally demonstrated in a frequency-tunable radio system.

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

Contemporaneous mobile- and stagnant-lid tectonics on the Hadean Earth

John W. Valley, Tyler B. Blum, Kouki Kitajima, Kei Shimizu, Michael J. Spicuzza, Joseph P. Gonzalez, Noriko T. Kita, Ann M. Bauer, Stephan V. Sobolev, Charitra Jain, Aaron J. Cavosie, Alexander V. Sobolev

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The first billion years of Earth history witnessed the emergence of continental magmatism, oceans and life. Yet, the details of how continents formed remain unknown because of the absence of preserved rocks 1–8 . Two conflicting Hadean models predominate: early onset of subduction and plate tectonics 2–4 , compared with early stagnant-lid and plume processes with delayed (post-Hadean) plate tectonics 5–7 . Here we report trace-element ratios (including Nb–Sc–U–Yb) correlated with age and hafnium and oxygen isotope ratios for Hadean detrital zircons from the Jack Hills (JH), Western Australia, which record unprecedented insights into the timing and setting of early magmatism. More than 70% of Hadean JH detrital zircons have Sc/Yb > 0.1, and 47% have U/Nb > 20, fingerprints for continental-arc and subduction settings. The remainder are ocean-island-like with little evidence for ocean-ridge settings. Hadean JH zircons probably originated from distinct terranes with separate tectonic histories. Subduction-related magmatism in the Hadean, as documented by JH zircons, alternated with periods of magmatic quiescence. This contrasts with dominantly stagnant-lid-like signatures for most Barberton Hadean zircons. The diverse settings for Jack Hills and Barberton detrital zircons imply contemporaneous operation of different tectonic styles during the Hadean, as well as a broader diversity of early crustal origins than previously known.

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

Atmospheric H2 variability over the past 1,100 years

John D. Patterson, Murat Aydin, Miranda H. Miranda, Eric S. Saltzman

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Anthropogenic emissions of hydrogen (H2) are expected to rise if H2 energy technology is widely implemented as part of the green energy transition1,2. Although atmospheric H2 is not radiatively active, it warms the Earth’s climate through chemical effects on methane, ozone and water vapour1,2,3,4,5,6. Predicting the atmospheric response to anthropogenic perturbations is challenging, in part because of the limited duration of the modern instrumental record7. Ice core measurements of H2 can extend the observational record, providing information about anthropogenic and natural perturbations and the biogeochemical controls on H2 levels over long timescales. However, ice core measurements of H2 are challenging because of the high permeability of H2 in ice8,9. Here we present an ice core record of atmospheric H2 recovered from a Greenland ice core, spanning the past millennium. The record shows a 70–111% (2σ) rise in atmospheric H2 from the pre-industrial to the modern era, consistent with increasing direct emissions from fossil fuel burning and increased atmospheric concentrations of H2 precursors. The pre-industrial record also shows a 4–25% (2σ) decrease in H2 levels during the Little Ice Age (LIA), indicating that H2 biogeochemistry may be sensitive to climate change. The findings suggest that the sensitivity of H2 sources and sinks to climate warming should be considered in estimates of the radiative consequences of rising anthropogenic H2 emissions.

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

Parkinson’s disease as a somato-cognitive action network disorder

Jianxun Ren, Wei Zhang, Louisa Dahmani, Evan M. Gordon, Shenshen Li, Ying Zhou, Yang Long, Jianting Huang, Yafei Zhu, Ning Guo, Changqing Jiang, Feng Zhang, Yan Bai, Wei Wei, Yaping Wu, Alan Bush, Matteo Vissani, Luhua Wei, Carina R. Oehrn, Melanie A. Morrison, Ying Zhu, Chencheng Zhang, Qingyu Hu, Yilin Yin, Weigang Cui, Xiaoxuan Fu, Ping Zhang, Weiwei Wang, Gong-Jun Ji, Ji He, Kai Wang, Dongsheng Fan, Zhaoxia Wang, Teresa Kimberley, Simon Little, Philip A. Starr, Robert Mark Richardson, Luming Li, Meiyun Wang, Danhong Wang, Nico U. F. Dosenbach, Hesheng Liu

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Parkinson’s disease (PD) is an incurable neurological disorder that often begins insidiously with sleep disturbances and somatic symptoms, progressing to whole-body motor and cognitive symptoms1,2,3,4,5. Dysfunction of the somato-cognitive action network (SCAN)—which is thought to control action execution6,7 by coordinating arousal, organ physiology and whole-body motor plans with behavioural motivation—is a potential contributor to the diverse clinical manifestations of PD. To investigate the role of the SCAN in PD pathophysiology and treatments (medications, deep-brain stimulation (DBS), transcranial magnetic stimulation (TMS) and MRI-guided focused ultrasound stimulation (MRgFUS)), we built a large (n = 863), multimodal, multi-intervention clinical imaging dataset. Resting-state functional connectivity revealed that the substantia nigra and all PD DBS targets (subthalamic nucleus, globus pallidus and ventral intermediate thalamus) are selectively connected to the SCAN rather than to effector-specific motor regions. Importantly, PD was characterized by specific hyperconnectivity between the SCAN and the subcortex. We therefore followed six PD cohorts undergoing DBS, TMS, MRgFUS and levodopa therapy using precision resting-state functional connectivity and electrocorticography recording. Efficacious treatments reduced SCAN-to-subcortex hyperconnectivity. Targeting the SCAN instead of effector regions doubled the efficacy of TMS treatments. Focused ultrasound treatment benefits increased when the target was closer to the thalamic SCAN sweet spot. Thus, SCAN hyperconnectivity is central to PD pathophysiology and its alleviation is a hallmark of successful neuromodulation. Targeting functionally defined subcortical SCAN nodes may improve existing therapies (DBS, MRgFUS), whereas cortical SCAN targets offer effective non-invasive or minimally invasive neuromodulation for PD.

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

ZFTA–RELA ependymomas make itaconate to epigenetically drive fusion expression

Siva Kumar Natarajan, Joanna Lum, James Haggerty Skeans, Minal Nenwani, Sanjana Eyunni, Mateus Mota, Jill M. Bayliss, Akash Deogharkar, Erin Taya Hamanishi, Matthew Pun, Stefan R. Sweha, Simon Hoffman, Eleanor Young, Qiuyang Zhang, Rijul Mehta, Olamide Animasahun, Pranav Narayanan, Sushanth Sunil, Abhijit Parolia, Peter Sajjakulnukit, Pooja Panwalkar, Robert Doherty, Madison Clausen, Derek Dang, Debra Hawes, Fusheng Yang, Mariarita Santi, Alexander R. Judkins, Yelena Wilson, Thomas Vigil, Andrea Franson, Richard M. Mortensen, Tatsuya Ozawa, Andrea Griesinger, Eric C. Holland, Nicholas K. Foreman, Kulandaimanuvel Antony Michealraj, Sameer Agnihotri, Michael Taylor, Richard J. Gilbertson, Carl Koschmann, Arul M. Chinnaiyan, Costas A. Lyssiotis, Deepak Nagrath, Sriram Venneti

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ZFTA–RELA+ ependymomas are malignant brain tumours defined by fusions formed between the putative chromatin remodeller ZFTA and the NF-κB mediator RELA1. Here we show that ZFTA–RELA+ cells produce itaconate, a key macrophage-associated immunomodulatory metabolite2. Itaconate is generated by cis-aconitate decarboxylase 1 (ACOD1; also known as IRG1). However, the production of itaconate by tumour cells and its tumour-intrinsic role are not well established. ACOD1 is upregulated in a ZFTA–RELA-dependent manner. Functionally, itaconate enables a feed-forward system that is crucial for the maintenance of pathogenic ZFTA–RELA levels. Itaconate epigenetically activates ZFTA–RELA transcription by enriching for activating H3K4me3 via inhibition of the H3K4 demethylase KDM5. ZFTA–RELA+ tumours enhance glutamine metabolism to supply carbons for itaconate synthesis. Antagonism of ACOD1 or glutamine metabolism reduces pathogenic ZFTA–RELA levels and is potently therapeutic in multiple in vivo models. Mechanistically, ZFTA–RELA epigenetically suppresses PTEN expression to upregulate PI3K–mTOR signalling, a known driver of glutaminolysis. Finally, suppression of ACOD1 or a combination of glutamine antagonism with PI3K–mTOR inhibition abrogates spinal metastasis. Our data demonstrate that ZFTA–RELA+ ependymomas subvert a macrophage-like itaconate metabolic pathway to maintain expression of the ZFTA–RELA driver, which implicates itaconate as a candidate oncometabolite. Taken together, our results position itaconate upregulation as a previously unappreciated driver of ZFTA–RELA+ ependymomas. Our work has implications for future drug development to reduce pathogenic ZFTA–RELA expression for this brain tumour, and will advance our understanding of oncometabolites as a new class of therapeutic dependencies in cancers.

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

Author Correction: Albumin orchestrates a natural host defence mechanism against mucormycosis

Antonis Pikoulas, Ioannis Morianos, Vassilis Nidris, Rania Hamdy, Evangelia Intze, Ángeles López-López, Maria Moran-Garrido, Valliappan Muthu, Maria Halabalaki, Varvara Papaioanou, Maria Papadovasilaki, Irene Kyrmizi, Yiyou Gu, Sandra M. Camunas-Alberca, Robina Aerts, Toine Mercier, Yuri Vanbiervliet, Sung-Yeon Cho, Amy Spallone, Ying Jiang, Dimitrios Samonakis, Efstathios Kastritis, Carlos Lax, Maria Tzardi, Aristides Eliopoulos, Konstantina Georgila, Agostinho Carvalho, Oliver Kurzai, Shivaprakash Mandya Rudramurthy, Caroline Elie, Fanny Lanternier, Kyriakos Petratos, Victoriano Garre, Elias Drakos, Johan Maertens, Vincent M. Bruno, Dimitrios P. Kontoyiannis, Coral Barbas, Sameh S. M. Soliman, Ashraf S. Ibrahim, Georgios Chamilos

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

Publisher Correction: A domed pachycephalosaur from the early Cretaceous of Mongolia

Tsogtbaatar Chinzorig, Ryuji Takasaki, Junki Yoshida, Ryan T. Tucker, Batsaikhan Buyantegsh, Buuvei Mainbayar, Khishigjav Tsogtbaatar, Lindsay E. Zanno

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

Author Correction: Increasingly negative tropical water–interannual CO2 growth rate coupling

Laibao Liu, Philippe Ciais, Mengxi Wu, Ryan S. Padrón, Pierre Friedlingstein, Jonas Schwaab, Lukas Gudmundsson, Sonia I. Seneviratne

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

A universal concept for melting in mantle upwellings

Max W. Schmidt, Nadia Paneva, Andrea Giuliani

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Deep mantle melting marks the onset of Earth differentiation1, yet a unifying framework for how buoyancy-driven mantle upwellings initiate melting and how such incipient melts evolve within the asthenosphere has remained elusive. Here we show that the first melts generated in any solid-state mantle upwelling are kimberlitic CO2-rich silicate melts that form at about 250 km depth through oxidation of elemental carbon to CO2 (refs. 2,3). Our experiments force a range of surface melts, derived from mantle plumes4 or broad upwellings5 (kimberlites, ocean island basalts and mid-ocean ridge basalts), into equilibrium with fertile mantle at adiabatic and super-adiabatic conditions at 7 GPa. The results define a framework in which redox melting at depth universally yields kimberlitic melts, which, while ascending through the asthenosphere by reactive porous flow6,7, evolve to higher degrees of melting, lesser volatiles and incompatible elements, but higher SiO2. Channelized flow7 in the lithosphere may then enable direct extraction of these melts, leading to kimberlites, where the lithosphere commences just above the C → CO2 redox front, to alkaline Si-undersaturated intraplate magmas where lithospheric thicknesses are 150–100 km, and to tholeiitic basalts below mid-ocean ridges where voluminous ‘dry’ melting becomes overwhelming. This framework is consistent with the widespread seismic low-velocity zone at about 250 km beneath mid-ocean ridges8,9 and aligns with ocean island and mid-ocean ridge basalts sampling the various geochemical mantle components at different degrees of melting in different proportions10,11.

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

Activated ATF6α is a hepatic tumour driver restricting immunosurveillance

Xin Li, Cynthia Lebeaupin, Aikaterini Kadianaki, Clementine Druelle-Cedano, Niklas Vesper, Charlotte Rennert, Júlia Huguet-Pradell, Borja Gomez Ramos, Chaofan Fan, Robert Stefan Piecyk, Laimdota Zizmare, Pierluigi Ramadori, Luqing Li, Lukas Frick, Menjie Qiu, Cangang Zhang, Luiza Martins Nascentes Melo, Vikas Prakash Ranvir, Peng Shen, Johannes Hanselmann, Jan Kosla, Mirian Fernández-Vaquero, Mihael Vucur, Praveen Baskaran, Xuanwen Bao, Olivia I. Coleman, Yingyue Tang, Miray Cetin, Zhouji Chen, Insook Jang, Stefania Del Prete, Mohammad Rahbari, Peng Zhang, Timothy V. Pham, Yushan Hou, Aihua Sun, Li Gu, Laura C. Kim, Ulrike Rothermel, Danijela Heide, Adnan Ali, Suchira Gallage, Nana Talvard-Balland, Marta Piqué-Gili, Albert Gris-Oliver, Alessio Bevilacqua, Lisa Schlicker, Alec Duffey, Kristian Unger, Marta Szydlowska, Jenny Hetzer, Duncan T. Odom, Tim Machauer, Daniele Bucci, Pooja Sant, Jun-Hoe Lee, Jonas Rösler, Sven W. Meckelmann, Johannes Schreck, Sue Murray, M. Celeste Simon, Sven Nahnsen, Almut Schulze, Ping-Chih Ho, Manfred Jugold, Kai Breuhahn, Jan-Philipp Mallm, Peter Schirmacher, Susanne Roth, Nuh Rahbari, Darjus F. Tschaharganeh, Stephanie Roessler, Benjamin Goeppert, Bertram Bengsch, Geoffroy Andrieux, Melanie Boerries, Nisar P. Malek, Marco Prinz, Achim Weber, Robert Zeiser, Pablo Tamayo, Peter Bronsert, Konrad Kurowski, Robert Thimme, Detian Yuan, Rafael Carretero, Tom Luedde, Roser Pinyol, Felix J. Hartmann, Michael Karin, Alpaslan Tasdogan, Christoph Trautwein, Moritz Mall, Maike Hofmann, Josep M. Llovet, Dirk Haller, Randal J. Kaufman, Mathias Heikenwälder

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Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related mortality and there are limited therapies 1 . Although endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are implicated in HCC, the involvement of the UPR transducer ATF6α remains unclear 2 . Here we demonstrate the function of ATF6α as an ER-stress-inducing tumour driver and metabolic master regulator restricting cancer immunosurveillance for HCC, in contrast to its well-characterized role as an adaptive response to ER stress 3 . ATF6α activation in human HCC is significantly correlated with an aggressive tumour phenotype, characterized by reduced patient survival, enhanced tumour progression and local immunosuppression. Hepatocyte-specific ATF6α activation in mice induced progressive hepatitis with ER stress, immunosuppression and hepatocyte proliferation. Concomitantly, activated ATF6α increased glycolysis and directly repressed the gluconeogenic enzyme FBP1 by binding to gene regulatory elements. Restoring FBP1 expression limited ATF6α-activation-related pathologies. Prolonged ATF6α activation in hepatocytes triggered hepatocarcinogenesis, intratumoural T cell infiltration and nutrient-deprived immune exhaustion. Immune checkpoint blockade (ICB) 4 restored immunosurveillance and reduced HCC. Consistently, patients with HCC who achieved a complete response to immunotherapy displayed significantly increased ATF6α activation compared with those with a weaker response. Targeting Atf6 through germline ablation, hepatocyte-specific ablation or therapeutic hepatocyte delivery of antisense oligonucleotides dampened HCC in preclinical liver cancer models. Thus, prolonged ATF6α activation drives ER stress, leading to glycolysis-dependent immunosuppression in liver cancer and sensitizing to ICB. Our findings suggest that persistently activated ATF6α is a tumour driver, a potential stratification marker for ICB response and a therapeutic target for HCC.

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

Large-scale analogue quantum simulation using atom dot arrays

M. B. Donnelly, Y. Chung, R. Garreis, S. Plugge, D. Pye, M. Kiczynski, J. Támara-Isaza, M. M. Munia, S. Sutherland, B. Voisin, L. Kranz, Y. L. Hsueh, A. M. Saffat-Ee Huq, C. R. Myers, R. Rahman, J. G. Keizer, S. K. Gorman, M. Y. Simmons

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In pursuit of a practical quantum advantage 1 , analogue quantum systems provide an invaluable way to simulate the physics of quantum materials 2–4 , quantum systems out of equilibrium 5,6 or interaction-induced localization 7 . Notable recent progress to realize such systems has been achieved in ultracold atoms 8–12 , superconducting circuits 13–15 and twisted van der Waals materials 16–19 . However, so far, these platforms have struggled to simulate large-scale strongly interacting fermionic systems at low temperatures, at which electronic correlations dominate materials properties and numerical simulations remain restricted in accuracy and scope 20,21 . Here we demonstrate the realization of a new platform consisting of large-scale 2D arrays of sub-nanometre precision-engineered atom-based quantum dots (15,000 sites) to simulate strongly interacting, low-temperature physics. By observing a metal–insulator (MI) transition on a 2D square lattice of atom-based quantum dots, we demonstrate independent and precise control of the on-site interaction U and tunnelling t . Magneto-transport measurements further indicate the formation of an insulating state driven by Mott–Hubbard/Anderson physics and promising signatures of correlated electron physics. These precision-engineered analogue quantum simulators provide a unique platform to simulate quantum materials on arbitrary 2D lattices and to explore many unanswered questions in the formation of quantum magnetism, interacting topological quantum matter and unconventional superconductivity.

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

Atlas-guided discovery of transcription factors for T cell programming

H. Kay Chung, Cong Liu, Anamika Battu, Alexander N. Jambor, Brandon M. Pratt, Fucong Xie, Brian P. Riesenberg, Eduardo Casillas, Ming Sun, Elisa Landoni, Yanpei Li, Qidang Ye, Daniel Joo, Jarred Green, Zaid Syed, Nolan J. Brown, Matthew Smith, Shixin Ma, Shirong Tan, Brent Chick, Victoria Tripple, Z. Audrey Wang, Jun Wang, Bryan Mcdonald, Peixiang He, Qiyuan Yang, Timothy Chen, Siva Karthik Varanasi, Michael LaPorte, Thomas H. Mann, Dan Chen, Filipe Hoffmann, Josephine Ho, Jennifer Modliszewski, April Williams, Yusha Liu, Zhen Wang, Jieyuan Liu, Yiming Gao, Zhiting Hu, Ukrae H. Cho, Longwei Liu, Yingxiao Wang, Diana C. Hargreaves, Gianpietro Dotti, Barbara Savoldo, Jessica E. Thaxton, J. Justin Milner, Susan M. Kaech, Wei Wang

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CD8 + T cells differentiate into diverse states that shape immune outcomes in cancer and chronic infection 1–4 . To define systematically the transcription factors (TFs) driving these states, we built a comprehensive atlas integrating transcriptional and epigenetic data across nine CD8 + T cell states and inferred TF activity profiles. Our analysis catalogued TF activity fingerprints, uncovering regulatory mechanisms governing selective cell state differentiation. Leveraging this platform, we focused on two transcriptionally similar but functionally opposing states that are critical in tumour and viral contexts: terminally exhausted T (TEX term ) cells, which are dysfunctional 5–8 , and tissue-resident memory T (T RM ) cells, which are protective 9–13 . Global TF community analysis revealed distinct biological pathways and TF-driven networks underlying protective versus dysfunctional states. Through in vivo CRISPR screening integrated with single-cell RNA sequencing (in vivo Perturb-seq) we delineated several TFs that selectively govern TEX term cell differentiation. We also identified HIC1 and GFI1 as shared regulators of TEX term and T RM cell differentiation and KLF6 as a unique regulator of T RM cells. We discovered new TEX term -selective TFs, including ZSCAN20 and JDP2, with no previous known function in T cells. Targeted deletion of these TFs enhanced tumour control and synergized with immune checkpoint blockade but did not interfere with T RM cell formation. Consistently, their depletion in human T cells reduces the expression of inhibitory receptors and improves effector function. By decoupling exhaustion T EX -selective from protective T RM cell programmes, our platform enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

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

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

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

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Exposure to cytosolic DNA triggers innate immune responses through cyclic GMP–AMP (cGAMP) synthase (cGAS)1,2,3. After binding to DNA, cGAS produces cGAMP as a second messenger that binds to stimulator of interferon genes (STING), a signalling adaptor protein anchored to the endoplasmic reticulum (ER)3,4,5. STING then traffics from the ER through the Golgi to perinuclear vesicle clusters, which leads to activation of the kinases TBK1 and IKK and subsequent induction of interferons and other cytokines6,7,8,9. Here we show that phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2; also known as PI(3,5)P2) is an endogenous ligand of STING that functions together with cGAMP to induce STING activation. Proteomic analyses identified a constitutive interaction between STING and PIKFYVE, an enzyme that produces PtdIns(3,5)P2 in mammalian cells. Deletion of PIKFYVE blocked STING trafficking from the ER and TBK1 activation. In vitro reconstitution uncovered a strong and selective effect of PtdIns(3,5)P2 on STING activation by cGAMP. PtdIns(3,5)P2 bound directly to STING in fluorescence resonance energy transfer assays. Consistently, cryo-electron microscopy revealed that PtdIns(3,5)P2 promotes cGAMP-induced STING oligomerization10, functioning as a molecular glue. Similar to PIKFYVE depletion, mutation of the PtdIns(3,5)P2-binding residues in STING largely blocked its trafficking and downstream signalling. These findings reveal that PtdIns(3,5)P2 is a lipid ligand of STING with essential roles in innate immunity.

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

Rete ridges form via evolutionarily distinct mechanisms in mammalian skin

Sean M. Thompson, Violet S. Yaple, Gabriella H. Searle, Quan M. Phan, Jasson Makkar, Xiangzheng Cheng, Ruiqi Liu, Anna Pulawska-Czub, Corin Yanke, Natalie M. Williams, Isabelle V. Busch, Tommy T. Duong, Matteo V. Corneto, Zachary S. Jordan, Debarun Roy, Adam B. Salmon, Ov D. Slayden, Brian P. Hermann, David A. Stoltz, Michael J. Welsh, character(0), Ian A. Glass, Krzysztof Kobielak, Qing Nie, Suoqin Jin, Heiko T. Jansen, Michela Ciccarelli, Maksim V. Plikus, Iwona M. Driskell, Ryan R. Driskell

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The loss of fur during human evolution has long mystified scientists and the public 1–5 . Reduced hair density coincides with acquisition of epidermal rete ridges, the developmental timing and molecular mechanisms of which are poorly understood despite their prominence in humans 1,6–9 . Examination of human and pig skin development has shown that rete ridges form through a mechanism independent from those of hair follicles 10,11 and sweat glands 3,4,12–15 by establishing interconnected epidermal invaginations. Here we document the occurrence of rete ridges across Mammalia, including in grizzly bears and dolphins, and show that neonatal pig wounds can regenerate them de novo. Multispecies spatiotemporal transcriptomics identifies significant signalling interactions between epidermal and dermal cells during rete ridge morphogenesis, particularly through bone morphogenetic proteins (BMP). We also demonstrate that mouse fingerpad skin forms rete ridges and functionally requires epidermal BMP signalling. We propose that evolution of rete ridges in mammalian skin involved replacement of the molecular program for formation of discrete microscopic appendages, including hair follicles and sweat glands, with a distinct program for the interconnected appendage network. Broad epidermal activation of BMP is required for the development of rete ridge networks organized around underlying dermal pockets. Understanding rete ridge mechanisms may enable development of therapeutic approaches to regenerate epidermal appendages lost during wounding or disease in humans.

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

Discovery Learning predicts battery cycle life from minimal experiments

Jiawei Zhang, Yifei Zhang, Baozhao Yi, Yao Ren, Qi Jiao, Hanyu Bai, Weiran Jiang, Ziyou Song

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Fast and reliable validation of new designs in complex physical systems such as batteries is critical to accelerating technological innovation. However, battery development remains bottlenecked by the high time and energy costs required to evaluate the lifetime of new designs1,2. Notably, existing lifetime forecasting approaches require datasets containing battery lifetime labels for target designs to improve accuracy and cannot make reliable predictions before prototyping, thus limiting rapid feedback3,4. Here we introduce Discovery Learning, a scientific machine learning approach that integrates active learning5, physics-guided learning6 and zero-shot learning7 into a human-like reasoning loop, drawing inspiration from educational psychology. Discovery Learning can learn from historical battery designs and reduce the need for prototyping, thereby predicting the lifetime of new designs from minimal experiments. To test Discovery Learning, we present industrial-grade battery data comprising 123 large-format lithium-ion pouch cells, including diverse material–design combinations and cycling protocols. Trained on public datasets of cell designs different from ours, Discovery Learning achieves 7.2% test error in predicting cycle life using physical features from the first 50 cycles of 51% of cell prototypes. Under conservative assumptions, this results in savings of 98% in time and 95% in energy compared with conventional practices. Discovery Learning represents a key advance in accurate and efficient battery lifetime prediction and, more broadly, helps realize the promise of machine learning to accelerate scientific discovery8.

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

Resolving intervalley gaps and many-body resonances in moiré superconductors

Hyunjin Kim, Gautam Rai, Lorenzo Crippa, Dumitru Călugăru, Haoyu Hu, Youngjoon Choi, Lingyuan Kong, Eli Baum, Yiran Zhang, Ludwig Holleis, Kenji Watanabe, Takashi Taniguchi, Andrea F. Young, B. Andrei Bernevig, Roser Valentí, Giorgio Sangiovanni, Tim Wehling, Stevan Nadj-Perge

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Magic-angle twisted multilayer graphene stands out as a highly tunable class of moiré materials that exhibit strong electronic correlations and robust superconductivity1,2,3,4. However, understanding the relationships between the low-temperature superconducting phase and the preceding correlated parent states remains a challenge. Here we use scanning tunnelling microscopy (STM) and spectroscopy to track the formation sequence of correlated phases established by the interplay of dynamic correlations, intervalley coherence and superconductivity in magic-angle twisted trilayer graphene (MATTG). We discover the existence of two well-resolved gaps pinned at the Fermi level within the superconducting doping range. Although the outer gap, previously associated with the pseudogap phase5,6, persists at high temperatures and magnetic fields, the newly revealed inner gap is more fragile, in line with previous transport experiments1,2,4. Andreev reflection spectroscopy taken at the same location confirms a clear trend that closely follows the doping behaviour of the inner gap and not the outer one. Moreover, spectroscopy taken at nanoscale domain boundaries further corroborates the contrasting behaviour of the two gaps, with the inner gap remaining resilient to structural variations. By comparing our results with recent topological heavy fermion (THF) models that include dynamical correlations7,8, we find that the outer gap probably arises from a splitting of the Abrikosov–Suhl–Kondo resonance9,10 owing to the breaking of the valley symmetry. Our results indicate an intricate yet tractable hierarchy of correlated phases in twisted multilayer graphene.

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

Phenome-wide analysis of copy number variants in 470,727 UK Biobank genomes

Xueqing Zoe Zou, Fengyuan Hu, Haiyi Lou, Oliver S. Burren, Xiaoyin Li, Karyn Megy, Eleanor Wheeler, Qiang Wu, Santosh S. Atanur, Marcin Karpinski, Douglas Loesch, Zammy Fairhurst-Hunter, Sri V. V. Deevi, Erin Oerton, Sean Wen, Xiao Jiang, Cecilia Salvoro, Jonathan Mitchell, Abhishek Nag, Ben Hollis, Amanda O’Neill, character(0), Lauren Anderson-Dring, Mohammad Bohlooly-Y, Lisa Buvall, Sophia Cameron-Christie, Bram Prins, Suzanne Cohen, Regina F. Danielson, Andrew Davis, Wei Ding, Brian Dougherty, Manik Garg, Benjamin Georgi, Andrew Harper, Carolina Haefliger, Mårten Hammar, Richard N. Hanna, Ian Henry, Kousik Kundu, Zhongwu Lai, Mark Lal, Glenda Lassi, Yupu Liang, Margarida Lopes, Kieren Lythgow, Meeta Maisuria-Armer, Ruth March, Dorota Matelska, Rob Menzies, Erik Michaëlsson, Bill Mowrey, Daniel Muthas, Yoichiro Ohne, Benjamin Pullman, Sonja Hess, Arwa Raies, Anna Reznichenko, Xavier Romero Ros, Helen Stevens, Ioanna Tachmazidou, Coralie Viollet, Anna Walentinsson, Lily Wang, Qing-Dong Wang, Anna Cuomo, Daniel Elias Martin Herranz, Jared O’Connell, Jorge L. Del-Aguila, Anish Konkar, Benjamin Challis, Adam Platt, Tatiana Ort, James Garnett, Xiao-Rong Peng, Gabrielle Baumberg, Natalia Frydrych, Luca Stefanucci, Anna Szymaniak, Anna Maria Tsakiroglou, Rahul Sharma, Jen Harrow, Stewart MacArthur, Sebastian Wasilewski, Sean O’Dell, Lifeng Tian, Katherine R. Smith, Guillermo del Angel, Margarete Fabre, Ryan S. Dhindsa, Quanli Wang, Slavé Petrovski, Keren Carss

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Copy number variants (CNVs) are key drivers of human diversity and disease risk1. Here we evaluate the role of CNVs across a broad range of human phenotypes and diseases by analysing CNVs from 470,727 UK Biobank whole-genome sequences and conducting a variant- and gene-level phenome-wide association study (PheWAS) with 2,941 plasma protein abundance measurements, 13,336 binary clinical phenotypes and 1,911 quantitative traits. Proteomic analyses validated functional associations of CNVs with nearby genes (cis-protein quantitative trait loci; cis-pQTLs)—with deletions and duplications typically associated with reduced and increased protein levels, respectively—and uncovered previously unknown protein–protein interactions (trans-pQTLs). Our PheWAS recapitulated known associations and uncovered associations in both coding and non-coding regions. Notably, we identified a rare deletion in ZNF451 associated with increased leukocyte telomere length and a non-coding deletion of a SLC2A9 enhancer associated with reduced gout risk. In addition, by combining CNVs with protein-coding single nucleotide variants and indels, we enhanced the power of our study to detect gene–disease associations. Finally, we leveraged this multiomics dataset to identify several pQTLs that constitute candidate biomarkers, including TMPRSS5 for Charcot–Marie–Tooth disease type 1A. This multiancestry whole-genome-sequence CNV PheWAS offers insights into the roles of CNVs in human health outcomes and could serve as a valuable resource for therapeutic development.

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

Chemical capture of diazo metabolites reveals biosynthetic hydrazone oxidation

Katarina Pfeifer, Devon Van Cura, Kelvin J. Y. Wu, Emily P. Balskus

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Chemically reactive microbial natural products have enabled therapeutic development 1 via their well-established anticancer, antibiotic and antioxidant activities. However, discovery of reactive metabolites is particularly challenging because they may not tolerate traditional bioactivity-guided isolation workflows 2 . Diazo-containing natural products are a subset of highly reactive microbial metabolites that display potent bioactivity 3 and enable powerful biosynthetic transformations 4,5 ; however, instability of the diazo group to light 6 , heat 7 , mild acid 8 and mechanical shock 9 has precluded their efficient discovery and application. Here we develop a reactivity-based screening approach to capture diazo-containing metabolites and facilitate their discovery by mass spectrometry. This workflow revealed two novel diazo-containing natural products, 4-diazo-3-oxobutanoic acid ( 1 ) and diazoacetone ( 2 ), from the human lung pathogen Nocardia ninae . Biosynthetic investigations revealed a distinct enzymatic logic for diazo formation involving hydrazone oxidation catalysed by the metalloenzyme Dob3, and its biochemical characterization suggests promising future applications in biocatalysis. Overall, our work highlights the power of reactivity-guided strategies for identifying reactive metabolites and facilitating the discovery of unique enzymatic transformations.

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

Ontogeny and transcriptional regulation of Thetis cells

Yoselin A. Paucar Iza, Tyler Park, Eliyambuya Baker, Gayathri Shibu, Tilman Hoelting, Greyson Feather, Anushka Yadav, Yollanda Franco Parisotto, Zihan Zhao, Blossom Akagbosu, Marc Elosua Bayes, Logan Fisher, Lucas M. James, Jianping Ma, Benjamin D. Philpot, Behdad Afzali, Christina Leslie, Chrysothemis C. Brown

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Thetis cells (TCs) are a recently identified lineage of RORγt+ antigen-presenting cells comprising four subsets including a tolerogenic subset, TC IV, that instructs tolerance to gut microbiota and food antigens1–6. A developmental wave of TCs during early life creates a critical window of opportunity for establishing intestinal tolerance1,5. Yet the ontogeny of TCs and the cues shaping their abundance and heterogeneity remain unknown, limiting efforts to harness their therapeutic potential. Here we identify a population of RORγt+ progenitors, termed Thetis-Lymphoid Tissue inducer progenitors (TLP), that give rise to the immediate TC progenitor (TCP) and the Lymphoid Tissue inducer progenitor (LTiP), and identify PU.1 as the transcription factor governing TC fate. Despite transcriptional similarity to myeloid-derived conventional dendritic cells (cDCs), we show that TCs descend from the common lymphoid progenitor (CLP). Deletion of the plasmacytoid DC (pDC) lineage-determining transcription factor TCF4 expands TLPs and TCs, suggesting a shared developmental branch with pDCs. TLPs are enriched in fetal liver; however, unlike LTi cells, TCs emerge postnatally, pointing to developmentally-timed environmental cues that promote TCP differentiation. We identify one such cue–RANKL provision by lymphoid tissue organizer cells–which is essential for TC I differentiation. Together, these findings define the ontogeny of TCs and the transcription factors that promote TC differentiation and heterogeneity, facilitating future investigations of these enigmatic cells and their therapeutic potential for tolerance induction in food allergy and autoimmunity.

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

Imaging a terahertz superfluid plasmon in a two-dimensional superconductor

A. von Hoegen, T. Tai, C. J. Allington, M. Yeung, J. Pettine, M. H. Michael, E. Viñas Boström, X. Cui, K. Torres, A. E. Kossak, B. Lee, G. S. D. Beach, G. D. Gu, A. Rubio, P. Kim, N. Gedik

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The superconducting gap defines the fundamental energy scale for the emergence of dissipationless transport and collective phenomena in a superconductor1,2,3. In layered high-temperature cuprate superconductors, in which the Cooper pairs are confined to weakly coupled two-dimensional (2D) copper–oxygen (CuO2) planes4,5, terahertz (THz) spectroscopy at subgap millielectronvolt (meV) energies has provided crucial insights into the collective superfluid response perpendicular to the superconducting layers6,7,8,9. However, within the CuO2 planes, the collective superfluid response manifests as plasmonic charge oscillations at energies far exceeding the superconducting gap, obscured by strong dissipation2,6,9,10. Here we present spectroscopic evidence of a below-gap, 2D superfluid plasmon in few-layer Bi2Sr2CaCu2O8+x and spatially resolve its deeply subdiffractive THz electrodynamics. By placing the superconductor in the near field of a spintronic THz emitter, we reveal this distinct resonance—absent in bulk samples and observed only in the superconducting phase—and determine its plasmonic nature by mapping the geometric anisotropy and dispersion. Crucially, these measurements offer a direct view of the momentum-dependent and frequency-dependent superconducting transition in two dimensions.

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

Imaging the sub-moiré potential using an atomic single electron transistor

Dahlia R. Klein, Uri Zondiner, Amit Keren, John Birkbeck, Alon Inbar, Jiewen Xiao, Yuval Zamir, Mariia Sidorova, Mohammed M. Al Ezzi, Liangtao Peng, Kenji Watanabe, Takashi Taniguchi, Shaffique Adam, Shahal Ilani

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Electrons in solids owe their properties to the periodic potential landscapes they experience. The advent of moiré lattices has revolutionized our ability to engineer such landscapes on nanometre scales, leading to numerous ground-breaking discoveries. Despite this progress, direct imaging of these electrostatic potential landscapes remains elusive. Here we introduce the atomic single electron transistor (SET), a new scanning probe that uses a single atomic defect in a van der Waals material as an ultrasensitive, high-resolution potential sensor. Built on the quantum twisting microscope (QTM) platform1, this probe leverages the capability of the QTM to form a pristine, scannable two-dimensional interface between vdW heterostructures. Using the atomic SET, we present the first direct images of the electrostatic potential in a canonical moiré interface: graphene aligned to hexagonal boron nitride2,3,4,5,6,7,8,9,10. The measured potential exhibits an approximate C6 symmetry, minimal dependence on carrier density and a substantial amplitude of approximately 60 mV, even in the absence of carriers. Theory indicates that this symmetry arises from a delicate interplay of physical mechanisms with competing symmetries. The measured amplitude significantly exceeds theoretical predictions, suggesting that current understanding may be incomplete. With 1 nm spatial resolution and sensitivity to detect the potential of even a few millionths of an electron charge, the atomic SET enables ultrasensitive imaging of charge order and thermodynamic properties across a wide range of quantum phenomena, including symmetry-broken phases, quantum crystals, vortex charges and fractionalized quasiparticles.

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

A pore-forming antiphage defence is activated by oligomeric phage proteins

Pramalkumar H. Patel, Matthew R. McCarthy, Véronique L. Taylor, Gregory B. Cole, Chi Zhang, Matthew M. Edghill, Landon J. Getz, Beatrice C. M. Fung, Trevor F. Moraes, Alan R. Davidson, Michael J. Norris, Karen L. Maxwell

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Bacteria have evolved a wide array of defence systems to combat phage infection, many of which rely on complex signalling systems and large protein complexes to function1. Here we describe a 164-residue prophage-encoded protein that defends bacteria by sensing conserved oligomeric components of phage assembly. This protein, called ring interacting pore 1 (Rip1), is activated by the portal or small terminase proteins of infecting phages—oligomeric ring-shaped complexes that are essential for virion maturation. Rip1 uses these phage protein ring complexes as a template to assemble into membrane-disrupting pores that inhibit phage virion assembly and cause premature death of the host cell. Rip1 homologues are widely distributed across bacteria and provide robust defence against diverse phages. This study reveals a strategy by which a small defence protein integrates both sensing and effector activity by exploiting a conserved feature of viral assembly. The mechanism mirrors eukaryotic pore-forming immunity but is executed by a single protein, offering an evolutionarily streamlined solution to viral detection and defence.

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

Author Correction: PHGDH heterogeneity potentiates cancer cell dissemination and metastasis

Matteo Rossi, Patricia Altea-Manzano, Margherita Demicco, Ginevra Doglioni, Laura Bornes, Marina Fukano, Anke Vandekeere, Alejandro M. Cuadros, Juan Fernández-García, Carla Riera-Domingo, Cristina Jauset, Mélanie Planque, H. Furkan Alkan, David Nittner, Dongmei Zuo, Lindsay A. Broadfield, Sweta Parik, Antonino Alejandro Pane, Francesca Rizzollo, Gianmarco Rinaldi, Tao Zhang, Shao Thing Teoh, Arin B. Aurora, Panagiotis Karras, Ines Vermeire, Dorien Broekaert, Joke Van Elsen, Maximilian M. L. Knott, Martin F. Orth, Sofie Demeyer, Guy Eelen, Lacey E. Dobrolecki, Ayse Bassez, Thomas Van Brussel, Karl Sotlar, Michael T. Lewis, Harald Bartsch, Manfred Wuhrer, Peter van Veelen, Peter Carmeliet, Jan Cools, Sean J. Morrison, Jean-Christophe Marine, Diether Lambrechts, Massimiliano Mazzone, Gregory J. Hannon, Sophia Y. Lunt, Thomas G. P. Grünewald, Morag Park, Jacco van Rheenen, Sarah-Maria Fendt

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

A broadly protective antibody targeting gammaherpesvirus gB

Cong Sun, Chu Xie, Bing-Zhen Cheng, Zi-Ying Jiang, Pei-Huang Wu, Xin-Yan Fang, Peng-Lin Li, Xian-Shu Tian, Hang Zhou, Yan-Lin Yang, Jing Wang, Sen-Fang Sui, Zheng Liu, Mu-Sheng Zeng

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Gammaherpesvirus is a subfamily of herpesvirus, distinct phylogenetically from alpha- and betaherpesvirus and featured by its oncogenic subtypes, including Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus1. It broadly infects humans and other vertebrate animals and causes various diseases and malignancies2,3. However, no specific antiviral agents are available for each type or the whole family. gB is the common fusion protein vital for herpesvirus infection and an ideal target for broad vaccine development, while the lack of basis for gB as a universal antigen hinders such effort4. Here, we report the molecular basis for broad gB binding and cross-genus virus neutralization by an antibody Fab5 for the first time. This antibody confers effective protection against authentic virus challenges in immune-competent mice, non-human primates, and humanized mice with murine, rhesus, and human gammaherpesvirus. Cryo-EM structures revealed that Fab5 targeted a conservative and vulnerable epitope of gammaherpesvirus gB and antigenically exposed across pre- or post-fusion status. This finding not only demonstrates Fab5 as cross-genus antibody broadly reactive against gammaherpesvirus infection and pathogenesis progression, but offers insights into potential common mechanisms for herpesvirus infection and facilitates the development of broad-spectrum vaccines against the gammaherpesvirus.

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

Long-lived remote ion-ion entanglement for scalable quantum repeaters

Wen-Zhao Liu, Ya-Bin Zhou, Jiu-Peng Chen, Bin Wang, Ao Teng, Xiao-Wen Han, Guang-Cheng Liu, Zhi-Jiong Zhang, Yi Yang, Feng-Guang Liu, Chao-Hui Xue, Bo-Wen Yang, Jin Yang, Chao Zeng, Du-Ruo Pan, Ming-Yang Zheng, Xingjian Zhang, Shen Cao, Yi-Zheng Zhen, You Xiao, Hao Li, Lixing You, Xiongfeng Ma, Qi Zhao, Feihu Xu, Ye Wang, Yong Wan, Qiang Zhang, Jian-Wei Pan

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Quantum networks, integrating quantum communication, quantum metrology, and distributed quantum computing, could provide secure and efficient information transfer, high-resolution sensing, and an exponential speed-up in information processing1. Deterministic entanglement distribution over long distances is a prerequisite for scalable quantum networks2–5. However, the exponential photon loss in optical fibres prohibits efficient and deterministic entanglement distribution. Quantum repeaters6, incorporating entanglement swapping4,7,8 and entanglement purification9–11 with quantum memories, offer the most promising means to overcome this limitation in fibre-based quantum networks. Despite numerous pioneering efforts12–25, a critical bottleneck remains, as remote memory-memory entanglement suffers from decoherence more rapidly than it can be established and purified over long distances. Here, we demonstrate memory-memory entanglement between two nodes connected by 10 km of spooled fibre surviving beyond the average entanglement establishment time. This is enabled by the development of long-lived trapped-ion memories, an efficient telecom interface, and a high-visibility single-photon entanglement protocol26,27. As an application, we report a proof-of-principle device-independent quantum key distributio (DI-QKD) demonstration with finite-size analysis over 10 km and a positive key rate over 101 km in the asymptotic limit, with both distances exceeding previous work by more than two orders of magnitude28–30. Our work provides a critical building block for quantum repeaters and marks an important step toward scalable quantum networks.

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

Measuring spin correlation between quarks during QCD confinement

character(0), B. E. Aboona, J. Adam, L. Adamczyk, I. Aggarwal, M. M. Aggarwal, Z. Ahammed, A. K. Alshammri, E. C. Aschenauer, S. Aslam, J. Atchison, V. Bairathi, X. Bao, P. Barik, K. Barish, S. Behera, R. Bellwied, P. Bhagat, A. Bhasin, S. Bhatta, S. R. Bhosale, J. Bielcik, J. Bielcikova, J. D. Brandenburg, C. Broodo, X. Z. Cai, H. Caines, M. Calderó, D. Cebra, J. Ceska, I. Chakaberia, P. Chaloupka, Y. S. Chang, Z. Chang, A. Chatterjee, D. Chen, J. H. Chen, Q. Chen, W. Chen, Z. Chen, J. Cheng, Y. Cheng, W. Christie, X. Chu, S. Corey, H. J. Crawford, M. Csanád, G. Dale-Gau, A. Das, D. De Souza Lemos, I. M. Deppner, A. Deshpande, A. Dhamija, A. Dimri, P. Dixit, X. Dong, J. L. Drachenberg, E. Duckworth, J. C. Dunlop, Y. S. El-Feky, J. Engelage, G. Eppley, S. Esumi, O. Evdokimov, O. Eyser, B. Fan, R. Fatemi, S. Fazio, H. Feng, Y. Feng, E. Finch, Y. Fisyak, F. A. Flor, C. Fu, T. Fu, C. A. Gagliardi, T. Galatyuk, T. Gao, Y. Gao, G. Garcia, F. Geurts, A. Gibson, A. Giri, K. Gopal, X. Gou, D. Grosnick, A. Gu, J. Gu, A. Gupta, W. Guryn, A. Hamed, R. J. Hamilton, J. Han, X. Han, S. Harabasz, M. D. Harasty, J. W. Harris, H. Harrison-Smith, L. B. Havener, X. H. He, Y. He, N. Herrmann, L. Holub, C. Hu, Q. Hu, Y. Hu, H. Huang, H. Z. Huang, S. L. Huang, T. Huang, Y. Huang, Y. Huang, Y. Huang, M. Isshiki, W. W. Jacobs, A. Jalotra, C. Jena, A. Jentsch, Y. Ji, J. Jia, X. Jiang, C. Jin, Y. Jin, N. Jindal, X. Ju, E. G. Judd, S. Kabana, D. Kalinkin, J. Kang, K. Kang, A. R. Kanuganti, D. Kapukchyan, K. Kauder, D. Keane, M. Kesler, A. Khanal, Y. V. Khyzhniak, D. P. Kikoła, J. Kim, D. Kincses, I. Kisel, A. Kiselev, A. G. Knospe, J. Kołaś, B. Korodi, L. K. Kosarzewski, L. Kumar, M. C. Labonte, R. Lacey, J. M. Landgraf, C. Larson, J. Lauret, A. Lebedev, J. H. Lee, Y. H. Leung, C. Li, D. Li, H-S. Li, H. Li, H. Li, H. Li, W. Li, X. Li, Y. Li, Z. Li, Z. Li, X. Liang, R. Licenik, T. Lin, Y. Lin, M. A. Lisa, C. Liu, G. Liu, H. Liu, L. Liu, L. Liu, Z. Liu, Z. Liu, T. Ljubicic, O. Lomicky, E. M. Loyd, T. Lu, J. Luo, X. F. Luo, L. Ma, R. Ma, Y. G. Ma, N. Magdy, D. Mallick, R. Manikandhan, C. Markert, O. Matonoha, K. Mi, S. Mioduszewski, B. Mohanty, B. Mondal, M. M. Mondal, I. Mooney, J. Mrazkova, M. I. Nagy, C. J. Naim, A. S. Nain, J. D. Nam, M. Nasim, H. Nasrulloh, J. M. Nelson, M. Nie, G. Nigmatkulov, T. Niida, T. Nonaka, G. Odyniec, A. Ogawa, S. Oh, K. Okubo, B. S. Page, S. Pal, A. Pandav, A. Panday, A. K. Pandey, T. Pani, A. Paul, S. Paul, D. Pawlowska, C. Perkins, S. Ping, J. Pluta, B. R. Pokhrel, I. D. Ponce Pinto, M. Posik, E. Pottebaum, S. Prodhan, T. L. Protzman, A. Prozorov, V. Prozorova, N. K. Pruthi, M. Przybycien, J. Putschke, Y. Qi, Z. Qin, H. Qiu, C. Racz, S. K. Radhakrishnan, A. Rana, R. L. Ray, R. Reed, C. W. Robertson, M. Robotkova, M. A. Rosales Aguilar, D. Roy, P. Roy Chowdhury, L. Ruan, A. K. Sahoo, N. R. Sahoo, H. Sako, S. Salur, S. S. Sambyal, J. K. Sandhu, S. Sato, B. C. Schaefer, N. Schmitz, F-J. Seck, J. Seger, R. Seto, P. Seyboth, N. Shah, P. V. Shanmuganathan, T. Shao, M. Sharma, N. Sharma, R. Sharma, S. R. Sharma, A. I. Sheikh, D. Shen, D. Y. Shen, K. Shen, S. Shi, Y. Shi, E. Shulga, F. Si, J. Singh, S. Singha, P. Sinha, M. J. Skoby, N. Smirnov, Y. Söhngen, Y. Song, T. D. S. Stanislaus, M. Stefaniak, Y. Su, M. Sumbera, X. Sun, Y. Sun, B. Surrow, M. Svoboda, Z. W. Sweger, A. C. Tamis, A. H. Tang, Z. Tang, T. Tarnowsky, J. H. Thomas, A. R. Timmins, D. Tlusty, D. Torres Valladares, S. Trentalange, P. Tribedy, S. K. Tripathy, T. Truhlar, B. A. Trzeciak, O. D. Tsai, C. Y. Tsang, Z. Tu, J. E. Tyler, T. Ullrich, D. G. Underwood, G. Van Buren, J. Vanek, I. Vassiliev, F. Videbæk, S. A. Voloshin, F. Wang, G. Wang, G. Wang, J. S. Wang, J. Wang, K. Wang, X. Wang, Y. Wang, Y. Wang, Y. Wang, Z. Wang, Z. Wang, Z. Y. Wang, A. J. Watroba, J. C. Webb, P. C. Weidenkaff, G. D. Westfall, D. Wielanek, H. Wieman, G. Wilks, S. W. Wissink, R. Witt, C. P. Wong, J. Wu, X. Wu, X. Wu, X. Wu, B. Xi, Y. Xiao, Z. G. Xiao, G. Xie, W. Xie, H. Xu, N. Xu, Q. H. Xu, Y. Xu, Y. Xu, Y. Xu, Y. Xu, Z. Xu, Z. Xu, G. Yan, Z. Yan, C. Yang, Q. Yang, S. Yang, Y. Yang, Z. Ye, Z. Ye, L. Yi, Y. Yu, H. Zbroszczyk, W. Zha, C. Zhang, D. Zhang, J. Zhang, L. Zhang, S. Zhang, W. Zhang, X. Zhang, Y. Zhang, Y. Zhang, Y. Zhang, Y. Zhang, Z. Zhang, Z. Zhang, F. Zhao, J. Zhao, S. Zhou, Y. Zhou, X. Zhu, M. Zurek, M. Zyzak

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The vacuum is now understood to have a rich and complex structure, characterized by fluctuating energy fields1 and a condensate of virtual quark–antiquark pairs. The spontaneous breaking of the approximate chiral symmetry2, signalled by the nonvanishing quark condensate \(\langle q\bar{q}\rangle \), is dynamically generated through topologically nontrivial gauge configurations such as instantons3. The precise mechanism linking the chiral symmetry breaking to the mass generation associated with quark confinement4 remains a profound open question in quantum chromodynamics (QCD)—the fundamental theory of strong interaction. High-energy proton–proton collisions could liberate virtual quark–antiquark pairs from the vacuum that subsequently undergo confinement to form hadrons, whose properties could serve as probes into QCD confinement and the quark condensate. Here we report evidence of spin correlations in \(\Lambda \bar{\Lambda }\) hyperon pairs inherited from spin-correlated strange quark–antiquark virtual pairs. Measurements by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory reveal a relative polarization signal of (18 ± 4)% that links the virtual spin-correlated quark pairs from the QCD vacuum to their final-state hadron counterparts. Crucially, this correlation vanishes when the hyperon pairs are widely separated in angle, consistent with the decoherence of the quantum system. Our findings provide a new experimental model for exploring the dynamics and interplay of quark confinement and entanglement.

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

Biofluid biomarkers in Alzheimer’s disease and other neurodegenerative dementias

Henrik Zetterberg, Barbara B. Bendlin

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Biofluid-based biomarkers have transformed neurodegenerative disease research and care, providing insights into the molecular underpinnings of Alzheimer’s disease (AD) and other neurodegenerative dementias. This Review provides an update on recent developments in biofluid-based biomarkers for amyloid-β (Aβ) pathology, tau pathology, neurodegeneration, glial reactivity, α-synuclein pathology, TAR DNA-binding protein 43 (TDP-43) pathology, synaptic pathophysiology and cerebrovascular disease—pathologies and processes that are all relevant to neurodegenerative dementias. Complementing longstanding cerebrospinal assays, improved technologies now facilitate the detection of molecules linked to neurodegenerative brain changes at very low concentrations in the blood. This promises to complement the clinical evaluation of suspected neurodegenerative disease in healthcare with molecular phenotyping biomarkers that will help to link the clinical symptoms to ongoing pathophysiological processes in the brain and improve how patients are referred to specialty clinics for initiation and monitoring of molecularly targeted treatments. Clinically relevant breakthroughs such as the use of anti-Aβ monoclonal antibodies to address Aβ pathology in AD serve as important proof-of-concept examples of how the field is advancing toward molecularly informed prevention and treatment. This Review provides an overview of the most established biofluid-based biomarkers currently in use and offers practical guidance on their interpretation and implementation in clinical settings.

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

Single-molecule dynamics of the TRiC chaperonin system in vivo

Rongqin Li, Niko Dalheimer, Martin B. D. Müller, F. Ulrich Hartl

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The essential chaperonin T-complex protein ring complex (TRiC) (also known as chaperonin containing TCP-1 (CCT)) mediates protein folding in cooperation with the co-chaperone prefoldin (PFD) 1–5 . In vitro experiments have shown that the cylindrical TRiC complex facilitates folding through ATP-regulated client protein encapsulation 6–9 . However, the functional dynamics of the chaperonin system in vivo remain unexplored. Here we developed single-particle tracking in human cells to monitor the interactions of TRiC–PFD with newly synthesized proteins. Both chaperones engaged nascent polypeptides repeatedly in brief probing events typically lasting around one second, with PFD recruiting TRiC. As shown with the chaperonin client actin 8 , the co-translational interactions of PFD and TRiC increased in frequency and lifetime during chain elongation. Close to translation termination, PFD bound for several seconds, facilitating TRiC recruitment for post-translational folding involving multiple reaction cycles of around 2.5 s. Notably, the lifetimes of TRiC interactions with a folding-defective actin mutant were markedly prolonged, indicating that client conformational properties modulate TRiC function. Mutant actin continued cycling on TRiC until it was targeted for degradation. TRiC often remained confined near its client protein between successive binding cycles, suggesting that the chaperonin machinery operates within a localized ‘protective zone’ in which free diffusion is restricted. Together, these findings offer detailed insight into the single-molecule dynamics and supramolecular organization of the chaperonin system in the cellular environment.

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

Publisher Correction: Nanotyrannus and Tyrannosaurus coexisted at the close of the Cretaceous

Lindsay E. Zanno, James G. Napoli

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

Daily briefing: Scientists delve into the smells of history

Flora Graham

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

Who does academic consulting serve?

Nicolás C. Zanetta-Colombo

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

Machine learning slashes the testing needed to work out battery lifetimes

Chao Hu

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

Briefing Chat: What Brazilian centenarians could reveal about the science of ageing

Benjamin Thompson, Nick Petrić Howe

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

These mysterious ridges could help skin regenerate

Benjamin Thompson, Nick Petrić Howe

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

A tumour-to-brain pathway hinders anticancer defences

Aeson Chang, Simon McMullan

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

Daily briefing: What people with no ‘mind’s eye’ can tell us about consciousness

Jacob Smith

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

Eviction notice

Celso Antonio de Almeida

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

Many people have no mental imagery. What’s going on in their brains?

Elizabeth Quill

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

Quantum computers will finally be useful: what’s behind the revolution

Davide Castelvecchi

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

Immune cells from the gut drive development of Parkinson’s disease in the brain

Veerle Baekelandt

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

NASA’s latest telescope is a feat of early-career leadership

Jenna Ahart

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

First ‘practical PhDs’ awarded in China — for products rather than papers

Xiaoying You

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

The ‘bible for psychiatry’ is getting a rewrite: your guide to the next DSM

David Adam

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

What my cave stay taught me about sensors

Kiana Aran

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

Embrace diverse PhD supervision styles — but enforce essential standards

Piera Cicchetti, Rosella Visintin

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

Evolutionary insights into a skin fold

Cheng Ming Chuong, Mingxing Lei

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

How tumours trick the brain into shutting down cancer-fighting cells

Edward Chen

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

How learning handwriting trains the brain: the science behind the cursive wars

Mariana Lenharo

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

This robot hand detaches and walks by itself

Dan Fox

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

The global plastics treaty can be saved — here’s how to break the deadlock

Paul Einhäupl, Linda Del Savio, Melanie Bergmann, Annika Jahnke

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

Daily briefing: More than one-third of cancer cases are preventable

Flora Graham

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

The smart sensors improving the world’s biggest cities

Bianca Nogrady

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

Open-source AI tool beats giant LLMs in literature reviews — and gets citations right

Elizabeth Gibney

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

China is betting on ‘optical’ computer chips — will they power AI?

Mohana Basu

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

Author knows best? Top AI conference asks for self-ranked papers amid paper deluge

Dalmeet Singh Chawla

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

Innovative CAR-T therapy destroys cancer cells without dangerous side effects

Rachel Fieldhouse

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

Particle collisions cast light on how matter forms from seemingly empty space

Yasmine Amhis

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

Daily briefing: Brain–immune crosstalk worsens the damage of heart attacks

Jacob Smith

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

Is this journal legitimate? This tool can help you decide

Matthew Hutson

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See the Sun expand and contract like a pufferfish — January’s best science images

Fred Schwaller

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

Daily briefing: Why we enjoy things more when they’re hard to get

Flora Graham

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

Daily briefing: The secrets of the centenarians

Flora Graham

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AI could transform research assessment — and some academics are worried

Rodolfo Benites, Lawrie Phipps, Richard Watermeyer, Tom Crick

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

Does AI already have human-level intelligence? The evidence is clear

Eddy Keming Chen, Mikhail Belkin, Leon Bergen, David Danks

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

OpenAI-backed firm to use ultrasound to read minds. Does the science stand up?

Elizabeth Gibney

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

Calling all scientists: Support your Iranian colleagues

Mohammad Hosseini

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

‘It means I can sleep at night’: how sensors are helping to solve scientists’ problems

Nic Fleming

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Are health influencers making us sick?

Helen Pearson

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Can academia handle my religious faith?

Adam Levy

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NIH rolls back red tape on some experiments — spurring excitement and concern

Heidi Ledford

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How DeepMind’s genome AI could help solve rare-disease mysteries

Ewen Callaway

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Don’t talk science, play science: translate your data into music to improve its reach

Jane Palmer

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I know science can’t fix the world — here’s why I do it anyway

Jean Colcombet

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How a protein repurposes vitamin B12 as a light sensor

Dante M. Avalos, Catherine L. Drennan

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China’s relationship with foreign scientific powers is changing rapidly

Laurie Udesky

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More than one-third of cancer cases are preventable, massive study finds

Gemma Conroy

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Nature Human Behaviour

Author Correction: Advancing the psychology of social class with large-scale replications in four countries

Anatolia Batruch, Nicolas Sommet, Frédérique Autin

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Assessing personality using zero-shot generative AI scoring of brief open-ended text

Aidan G. C. Wright, Whitney R. Ringwald, Colin E. Vize, Johannes C. Eichstaedt, Mike Angstadt, Aman Taxali, Chandra Sripada

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Contemporary personality assessment relies heavily on psychometric scales, which offer efficiency but risk oversimplifying the rich and contextual nature of personality. Recognizing these limitations, this study explores the use of commercially available generative large language models (LLMs), such as ChatGPT, Claude and so on, to assess personality traits from open-ended qualitative narratives. Across two distinct samples and methodologies (spontaneous streams of thought and daily video diaries), we used seven commercial, generative LLMs to score Big-Five personality traits, achieving convergence with self-report measures comparable to or exceeding established benchmarks (for example, self–other agreement, ecological momentary assessment, and bespoke machine learning models). Although results differed across different LLMs, we found that using the average LLM score across models provided the strongest agreement with self-report. Further, LLM-generated trait scores also demonstrated predictive validity regarding daily behaviours and mental health outcomes. This LLM-based approach achieved quantitative rigour based on qualitative data and is easily accessible without specialized training. Importantly, our findings also reaffirm that personality is expressed ubiquitously, in that it is carried in the stream of our thoughts and is woven into the fabric of our daily lives. These results encourage broader adoption of generative LLMs for psychological assessment and—given the new generation of tools—stress the value of idiographic narratives as reliable sources of psychological insight.

Political action is now crucial for US scientists

Tatiane Russo-Tait, Summer Blanco, Eduardo Bonilla-Silva

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Hybrid neural–cognitive models reveal how memory shapes human reward learning

Maria K. Eckstein, Christopher Summerfield, Nathaniel D. Daw, Kevin J. Miller

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A long-standing challenge for psychology and neuroscience is to understand the transformations by which past experiences shape future behaviour. Reward-guided learning is typically modelled using simple reinforcement learning (RL) algorithms. In RL, a handful of incrementally updated internal variables both summarize past rewards and drive future choice. Here we describe work that questions the assumptions of many RL models. We adopt a hybrid modelling approach that integrates artificial neural networks into interpretable cognitive architectures, estimating a maximally general form for each algorithmic component and systematically evaluating its necessity and sufficiency. Applying this method to a large dataset of human reward-learning behaviour, we show that successful models require independent and flexible memory variables that can track rich representations of the past. Using a modelling approach that combines predictive accuracy and interpretability, these results call into question an entire class of popular RL models based on incremental updating of scalar reward predictions.

How personalized disaster warnings can save lives

Ilias G. Pechlivanidis, Spyros Afentoulidis, Giuliano Di Baldassarre, Florian Pappenberger, Peter Salamon, Stefan Uhlenbrook

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Social safety nets, women’s economic achievements and agency in 45 countries: a systematic review and meta-analysis

Amber Peterman, Jingying Wang, Kevin Kamto Sonke, Janina Isabel Steinert

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There are increasing calls for economic assistance in the form of social safety nets (SSNs) to be designed and implemented to promote women’s economic inclusion and agency, contributing to closing gender disparities globally. Here we investigate the extent to which SSNs affect women’s economic achievements and agency through a systematic review and meta-analysis of randomized controlled trials implemented in low- and middle-income countries. We searched six databases utilizing search strings in English, French and Spanish through December 2024. Studies were assessed for risk of bias using an adapted version of the Joanna Briggs Institute critical appraisal tool. Our sample includes 1,307 effect sizes from 93 studies, representing 218,828 women across 45 low- and middle-income countries. Using robust variance estimation meta-analysis, we show significant overall pooled effects (Hedges’ g = 0.107, P < 0.001, 95% confidence interval (CI) 0.085–0.129), driven by increases in economic achievements (productive work, savings, assets and expenditures) and agency (voice, autonomy and decision-making). We find significant treatment effects for unconditional cash transfers (Hedges’ g = 0.128, P < 0.001, 95% CI 0.097 to 0.159), social care services (Hedges’ g = 0.122, P < 0.001, 95% CI 0.071 to 0.174), asset transfers (Hedges’ g = 0.115, P < 0.001, 95% CI 0.071 to 0.160) and public work programmes (Hedges’ g = 0.127, P = 0.031, 95% CI 0.015 to 0.239). We find comparatively smaller effects for conditional cash transfers (Hedges’ g = 0.059, P = 0.019, 95% CI 0.011 to 0.108) and found no evidence of effects for in-kind transfers. SSNs can empower women economically and socially; however, limitations and evidence gaps remain, including the need for further rigorous testing of design and operational components, the role of contextual factors and cost–benefit analysis with a gender lens.

The tension between big team science and colonial power dynamics

Fanli Jia

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Why single-item measures of wellbeing are best

John F. Helliwell, Richard Layard, Jeffrey D. Sachs, Jan-Emmanuel De Neve, Lara B. Aknin, Shun Wang

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Proceedings of the National Academy of Sciences

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

Grazer exclusion is associated with higher fast-cycling carbon pools but lower slow-cycling mineral-associated carbon across grasslands

Luhong Zhou, Shangshi Liu, Maarten Schrama, Deborah Ashworth, Richard D. Bardgett

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The removal of livestock grazers from historically grazed grasslands is widely proposed as a key strategy for the enhancement of soil organic carbon (SOC) for climate mitigation. Yet, accurate assessments of how grazer exclusion impacts SOC pools of differing stability are lacking, with most studies focusing on total SOC rather than the distribution of SOC within fast and more stable, slow-cycling pools. Here, we used 12 historically grazed grassland sites along an 800 km south–north gradient across the United Kingdom to test how particulate (POC) and mineral-associated organic carbon (MAOC) pools were linked to long-term (>10 y) exclusion of large domesticated grazers. We found that grazer exclusion was associated with relatively higher fast-cycling C pools, including plant and litter C, and to a lesser extent POC, but lower more stable, slow-cycling MAOC pools compared to grazed controls. Grazer exclusion was also associated with a marked shift in vegetation composition, with greater cover of ericoid mycorrhizal (ErM) shrubs over arbuscular mycorrhizal (AM) graminoids. This vegetation shift likely played a dual role in regulating SOC, contributing to higher POC via both the input of recalcitrant litter and by the enhancement of soil moisture and lower MAOC due to priming and decreased mineral protection of SOC. Our findings provide evidence that while the exclusion of grazers tends to favor fast-cycling C pools, it coincides with lower SOC persistence, potentially increasing the vulnerability of grassland SOC stocks to future climate change.

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

Nuclear speckles are regulatory hubs for viral and host mRNA expression during HSV-1 infection

Shani Nadav-Eliyahu, Chaya Bohrer, Alon Boocholez, Noa Kinor, Vesa Aho, Jennifer I. C. Benichou, Salla Mattola, Sami Salminen, Henri Niskanen, Minna U. Kaikkonen, Maija Vihinen-Ranta, Yaron Shav-Tal

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Herpes simplex virus type 1 (HSV-1) infection remodels the host nucleus, marginalizing chromatin and forming viral replication compartments (VRCs). Nuclear speckles, nuclear bodies enriched in RNA-processing factors, reposition around VRCs and undergo structural changes. While viral mRNAs are transcribed in VRCs and host transcription is largely suppressed, the nuclear routes used by viral and upregulated host transcripts and their relationship with nuclear bodies remain unclear. We show that immediate-early (IE) viral transcripts uniquely accumulate in nuclear speckles prior to export, unlike early or late transcripts, revealing a selective nuclear speckle-dependent pathway. Similarly, host mRNAs upregulated during infection traffic into nuclear speckles after transcription. Moreover, nuclear speckles are structurally remodeled, marked by the long non-coding RNA (lncRNA) MALAT1 removal and increased dynamics of the nuclear speckle core protein SRRM2. Finally, we found that blocking mRNA export causes IE transcripts to accumulate in nuclear speckles and that nuclear speckle disassembly severely impairs IE mRNA export, preventing downstream viral gene expression. These findings establish nuclear speckles as dynamic regulatory hubs that selectively facilitate the processing and export of IE viral mRNAs during HSV-1 infection.

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

PTP1B inhibition promotes microglial phagocytosis in Alzheimer’s disease models by enhancing SYK signaling

Yuxin Cen, Steven R. Alves, Dongyan Song, Christy Felice, Jonathan B. Preall, Linda Van Aelst, Nicholas K. Tonks

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Amyloid β (Aβ) accumulation is a hallmark of Alzheimer’s disease (AD). Emerging evidence suggests that impaired microglial Aβ phagocytosis is a key feature in AD, highlighting the therapeutic potential of enhancing this innate immune function. Here, we demonstrate that genetic deletion or pharmacological inhibition of protein tyrosine phosphatase 1B (PTP1B) ameliorated memory deficits and reduced Aβ burden in APP/PS1 mice. Moreover, we show that PTP1B was highly expressed in microglia, and its deficiency promoted a transcriptional shift toward immune activation and phagocytosis. Consistently, PTP1B deletion in microglia enhanced phagocytosis and energy metabolism, supported by increased AKT-mTOR signaling, a pathway essential for meeting the energy demands of activation. Mechanistically, we identified spleen tyrosine kinase (SYK), a key regulator of microglial phagocytosis, as a direct substrate of PTP1B. Inhibition of SYK showed that PTP1B modulates microglial activation in a SYK-dependent manner. These findings established PTP1B as a critical modulator of microglial activation and a potential therapeutic target for AD.

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

Mutations and structural variants arising during double-strand break repair

Simona Dalin, Sophie Webster, Neal Sugawara, Qiuqin Wu, Shu Zhang, Carmen Macias, Elena Sapède, Tracy Cui, Victoria Liang, Laura Tran, Rameen Beroukhim, James E. Haber

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Double-strand break (DSB) repair is highly mutagenic compared to normal replication. In budding yeast, repair of an HO (homothallism) endonuclease-induced DSB at the mating-type α locus ( MAT α) can be repaired by using an ectopic heterochromatic HMR::Kl-URA3 donor, producing MAT::Kl-URA3 . Among MAT::Kl -Ura3− mutations arising during repair, 50% are base-pair substitutions. 30% are 1-bp indels in short homonucleotide runs, with −1 strongly favored over +1, whereas during replication, spontaneous −1 and +1 events are equal. Microhomology-bounded, repair-associated intragenic deletions (IDs) are recovered 12 times more frequently than tandem duplications (TDs). These data suggest a picture of the structure of the repair replication fork: IDs and TDs occur within the open structure of a migrating D-loop, where the 3’ end of a partly copied new DNA strand can dissociate and anneal with a single-stranded region of microhomology either within ~80 bp ahead or ~40 bp behind the 3’ end. Approximately ~10% of repair-associated mutations are interchromosomal template switches (ICTS), even though the Kluyveromyces lactis URA3 sequence in HMR is only 72% identical (homeologous) with Saccharomyces cerevisiae ura3-52 . ICTS events begin and end at regions of short (~7.5 bp) microhomology; however, ICTS events are constrained to the middle of the copied sequence. Whereas microhomology usage in intragenic deletions is not influenced by adjacent homeology, we show that extensive pairing of adjacent homeology plays a critical role in ICTS. Thus, although by convention, structural variants are characterized by the precise base pairs at their junction, microhomology-mediated template switching actually requires alignment of extensive adjacent homeology.

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

SARS-CoV-2 S assembly into virions facilitated by host ERM proteins

Jiaming Wang, Wanbo Tai, Zhaoyang Wang, Wenxin Dai, Mingrui Yang, Jiajian Guo, Pengfei He, Yanan Nan, Tianyu Li, Shuqi Zhou, Dongxiao Cui, Yiqun Li, Cuiyan Ma, Yue Zhang, Dongdong Li, Zhengdan Zhu, Kexin Chu, Dongdong Wang, Songhui Yang, Xinyu Zhuang, Mingyao Tian, Mingkang Huang, Xianwen Zhang, Gong Cheng, Wenfu Ma

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The host cell cytoskeleton plays a critical role in the SARS-CoV-2 life cycle, though the underlying mechanisms remain poorly understood. This study investigates the interaction between the SARS-CoV-2 spike (S) protein and the cytoskeleton-associated ezrin-radixin-moesin (ERM) proteins through biochemical and structural characterization. A previously unidentified ERM-binding motif on the SARS-CoV-2 S protein is identified, revealing that S-ERM interactions are specifically conserved among highly pathogenic coronaviruses, including SARS-CoV, MERS-CoV, and SARS-CoV-2. Functionally, these interactions facilitate S packaging into virions by directing it to assembly sites, utilizing ERM’s affinity for negatively curved membranes, akin to its role in cell surface protrusions. Silencing ERM expression significantly reduces SARS-CoV-2 titer, highlighting its essential role in viral propagation. Additionally, leveraging the established role of COPI-mediated trafficking in S localization, a compound is developed to disrupt S-COPI binding, promoting S secretion to the cell surface and effectively reducing viral titers. Our findings revealed a critical host–pathogen interaction that drives S incorporation into virions and identified ERM proteins as key facilitators of coronavirus assembly. Furthermore, our study suggests an antiviral strategy by targeting the S-COPI trafficking pathway. These insights advanced our understanding of coronavirus–host interactions and provided a potential therapeutic approach against SARS-CoV-2 and other highly pathogenic coronaviruses.

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

The role of fluctuations in the nucleation process

Yuanpeng Deng, Peilin Kang, Xiang Xu, Hui Li, Michele Parrinello

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The emergence upon cooling of an ordered solid phase from a disordered liquid is a remarkable example of self-assembly, which has also major practical relevance. Here, we use a recently developed committor-based enhanced sampling method to explore the crystallization transition in a Lennard-Jones fluid, using variational principle based on the backward Kolmogorov equation. We exploit the unique properties of our method to study in detail the nucleation mechanism, allowing us to detect and analyze the fluctuations that eventually lead to crystallization. We find that the transition state ensemble has a complex nature in which the nonspherical solid core is surrounded by an interface that is more disordered than bulk liquid. We also compute from the variational principle a nucleation rate that is consistent with the experimental results at variance with previous estimates.

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

GABA corelease guides the functional maturation of glycinergic synapses in an auditory sound localization circuit

Jongwon Lee, Brian Brockway, Karl Kandler

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In the mammalian brainstem and spinal cord, glycine is the primary inhibitory neurotransmitter. However, during development, many glycinergic neurons also corelease the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Although the acute effects of GABA corelease on immature synaptic transmission have been increasingly characterized, its role in synapse maturation and circuit formation remains poorly understood. Here, we investigated the developmental roles of GABA corelease at glycinergic synapses from the medial nucleus of the trapezoid body (MNTB) to the lateral superior olive (LSO), an auditory pathway essential for binaural integration and sound localization. During the first two postnatal weeks, MNTB-LSO synapses corelease GABA and undergo pronounced synaptic and circuit refinement. Using conditional knockout mice with severely diminished GABA corelease from MNTB neurons, we found that key aspects of circuit refinement, including synaptic silencing and strengthening, occurred normally. However, a disruption of GABA corelease resulted in significantly larger quantal amplitudes and a reduced readily releasable vesicle pool, impairing the high fidelity and temporal precision of synaptic transmission, which are essential for accurate binaural processing. These results reveal a critical developmental role for GABA corelease in shaping the functional synaptic architecture of glycinergic synapses involved in sound localization.

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

PLETHORA–autophagy axis activates organ regeneration through ROS modulation

Akansha Ganguly, Aabha Humnabadkar, Komal Gautam, Viola Willemsen, Lin Xu, Yasin Dagdas, Kalika Prasad

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Injury-induced disruption of cellular homeostasis leads to accumulation of stress at sites adjacent to a wound. How do these cells mitigate wound-induced stress and restore cellular homeostasis to promote regeneration? To address this question, we examined the role of autophagy—a conserved quality control pathway that recycles defective cellular components to sustain cellular homeostasis—in facilitating wound repair in plants. We demonstrate that transcriptional activation of autophagy-related gene 8 ( ATG8 ) genes is essential for de novo root regeneration, but dispensable for wound induced callus formation from an excised leaf. Plant-specific transcription factors PLETHORA (PLT) activate the transcription of a subset of ATG8 genes and function nonredundantly in this process. Disrupting the PLT– ATG8 regulatory axis severely impairs organelle turnover, resulting in increased intracellular stress and ectopic accumulation of reactive oxygen species (ROS). PLT– ATG8 mediated positioning of optimal ROS levels promotes the expression of stem-cell regulators for successful de novo root regeneration. Altogether, our findings illustrate how plants utilize kingdom-specific developmental regulators, such as PLTs, to activate evolutionarily conserved pathways, effectively managing wound-induced cellular stress and facilitating organ regeneration.

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

Amplified warming in tropical and subtropical cities under 2 °C climate change

S. Berk, M. M. Joshi, C. M. Goodess, P. Nowack

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Cities are often warmer than rural surroundings due to a phenomenon known as the urban heat island, which can be influenced by various factors, such as regional climate and land surface types. Under climate change, cities face not only the challenge of increasing temperatures in their surrounding hinterland but also the challenge of potential changes in their heat islands. However, even high-resolution global Earth system models (ESMs) with “urban tiles” can only properly resolve the largest urban areas or megacities. Here, we address these limitations by applying a process-based statistical learning model to ESM outputs to provide projections of changes in land surface temperature (LST) for 104 medium-sized cities of population 300 K to 1 M in the subtropics and tropics. Under a 2 °C global warming scenario, annual mean LST in 81% of these cities is projected to increase faster than the surrounding area. In 16% of these cities, mostly in India and China, mean LST is projected to increase by an additional 50-112% above ESM projections of the surrounding area. Our findings underscore the importance of investigating the specific effects of climate change on urban heat exposure.

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

Linear ubiquitination of the NMDA receptor GluN2A subunit facilitates the GluN2B-to-GluN2A switch and synaptic maturation

Yuanyuan Chu, Yiwen Xu, Maoqing Huang, Xueying Fang, Xinying Huang, Zhengwei Yao, Jian Wu, Ning Zhou, Kaiwen He, Yanfen Liu, Tong Wang

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N-methyl-D-aspartate-type glutamate receptors (NMDARs) initiate the synaptic plasticity underlying learning and memory. In forebrain excitatory neurons, NMDARs are heteromeric tetramers composed of two GluN1 subunits and two glutamate ionotropic receptor NMDA type subunit 2A (GluN2A) or GluN2B subunits. At birth, NMDARs contain primarily GluN2B, but within weeks, GluN2A-containing receptors predominate the forebrain, comprising over 65% of total NMDARs in adulthood. This rapid subunit switch is essential for neonatal cognitive development, yet mechanisms driving it remain unclear. Particularly, while GluN2B levels remain relatively constant, GluN2A increases several 100-fold, despite its mRNA rising by only ~10-fold, strongly suggesting involvement of unknown posttranslational regulation. Here, we show that in the neonatal mouse forebrain, the linear ubiquitination axis, composed of the E3 ligase complex LUBAC and the deubiquitinase OTULIN, shifts transiently toward higher activity, with HOIP upregulated and OTULIN downregulated. In neonatal mice, experimentally reducing the axis activity by OTULIN overexpression causes persistent synaptic immaturity and adult cognitive deficits. Using proteomic and biochemical assays, we identified GluN2A as a key substrate: Linear ubiquitination at six lysines in the GluN2A C-terminus stabilizes the subunit and promotes its synaptic expression, whereas disrupting this modification destabilizes GluN2A by promoting lysosomal degradation. Consistently, overexpression of wild-type GluN2A rescues OTULIN-induced synaptic immaturity, whereas the ubiquitination-deficient GluN2A-6KR mutant fails to rescue and further exacerbates this defect. OTULIN overexpression selectively promotes GluN2A degradation, thereby delaying the GluN2B-to-GluN2A switch and synaptic maturation. These findings reveal a role for the linear ubiquitination axis in selectively stabilizing GluN2A, supporting rapid synaptic and cognitive development.

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

Pleistocene demographic histories dominate contemporary genomic diversity in a continental radiation of Himalayan–Hengduan songbirds

Yadan Liu, Chih-Ming Hung, Yunrui He, Fei Wu, Dao Yan, Gang Song, Feng Dong

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Genetic diversity, the fundamental substrate for evolutionary potential, is declining globally at unprecedented rates. Yet the mechanisms governing its distribution across species remain poorly understood, with competing hypotheses emphasizing either historical demography or contemporary ecological constraints. This debate limits our capacity to predict species' responses to environmental change. Here, based on systematic sampling and a unified analytical pipeline, we de novo assembled genomes for 120 songbird species breeding in the Himalayas–Hengduan Mountains (HHMs) and conducted population genomic analysis to examine the drivers of their genomic diversity. We observed a 6.5-fold variation in genome-wide heterogeneity and a 16.4-fold variation nucleotide diversity across species. Notably, these measures of genomic diversity showed no correlation with recent population dynamics, current population size, or other contemporary factors—such as elevational distribution, or life-history traits. Instead, historical demography strongly predicted genetic diversity, with ancestral population size during the late Pleistocene emerging as the sole correlate: Larger ancestral sizes consistently coincided with higher diversity. These findings underscore the critical influence of historical demography on contemporary genetic diversity in natural populations—an insight essential for designing effective conservation strategies.

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

Harnessing hemostasis to transform surgical scars into CAR-T immunological niches

Xiao Cheng, Ke Cheng

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

A nuclear CobW/WW-domain factor represses the CO 2 -concentrating mechanism in the green alga Chlamydomonas reinhardtii

Daisuke Shimamura, Junko Yasuda, Yosuke Yamahara, Hirobumi Nakano, Shin-Ichiro Ozawa, Ryutaro Tokutsu, Ayumi Yamagami, Tomonao Matsushita, Yuichiro Takahashi, Takeshi Nakano, Hideya Fukuzawa, Takashi Yamano

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Microalgae induce a CO 2 -concentrating mechanism (CCM) to maintain photosynthesis when CO 2 is limited. Because this system consumes a substantial portion of photosynthetically generated ATP, its suppression when CO 2 levels rise is critical for energy balance, yet the underlying mechanism remains unclear. Here, we identify a nuclear repressor of the CCM in the green alga Chlamydomonas reinhardtii . A pull-down screen for interacting partners of the master activator CCM1/CIA5 revealed an uncharacterized protein that tightly associates with CCM1. This protein, CCM1-binding protein 1 (CBP1), combines a CobW/CobW_C GTP-binding metallochaperone module with a WW-domain characteristic of protein–protein interactions. CBP1 colocalizes and interacts with CCM1 in the nucleus regardless of CO 2 conditions. Disruption of CBP1 does not affect growth or CCM induction under CO 2 limitation but derepresses 27 of 41 CCM1-dependent low-CO 2 inducible genes under high-CO 2 conditions. These include the periplasmic and intracellular carbonic anhydrases (CAH1 and LCIB) and inorganic carbon transporters/channels (LCIA, LCI1, BST1, and BST3). Consistently, cbp1 mutants accumulate CAH1 and LCIB proteins and exhibit 40% higher inorganic carbon affinity under high-CO 2 conditions; this phenotype is rescued by CBP1 complementation or by acetazolamide treatment. Crucially, cbp1 mutants exhibit significant growth delays under high-CO 2 conditions, especially when light is limiting, providing direct evidence that CBP1-mediated repression is essential for energy conservation. Thus, CBP1 prevents unnecessary CCM activity when CO 2 is abundant, acting upstream of both transporter/channel and carbonic anhydrase modules. Our findings suggest a regulatory mechanism potentially linking zinc-dependent protein chemistry to CCM gene repression, providing insights into energy-efficient CO 2 sensing in aquatic photosynthetic organisms.

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

INDETERMINATE DOMAIN–DELLA protein interactions orchestrate gibberellin-mediated cell elongation in wheat and barley

Patrycja Sokolowska, Matthias Jöst, Wolfram Buss, Brett Ford, Peter Michael Chandler, Wolfgang Spielmeyer, Andrew L. Phillips, Alison K. Huttly, Danuše Tarkowská, Rocío Alarcón-Reverte, Suzanne J. Clark, Stephen Pearce, Peter Hedden, Stephen G. Thomas

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DELLA proteins, members of the GRAS-domain family of transcriptional regulators, play a crucial role in plant growth and development. They modulate transcription indirectly via interactions with hundreds of transcription factors. The phytohormone gibberellin (GA) triggers DELLA degradation, providing a mechanism by which plants can integrate developmental and environmental signals to regulate gene expression and optimize growth responses. In agriculture, DELLA mutations have been instrumental in improving crop performance. Most modern wheat ( Triticum aestivum L.) varieties carry Rht-B1b or Rht-D1b alleles that encode DELLA proteins resistant to GA-mediated degradation, resulting in constitutive partial suppression of stem growth, a semi-dwarf stature, and lodging resistance. However, these alleles also reduce early vigor and nitrogen use efficiency, limiting their utility in some environments. Understanding how DELLA proteins regulate growth and development is, therefore, critical for refining breeding strategies. In this study, we identified the orthologous C2H2 zinc-finger transcription factors INDETERMINATE DOMAIN 5 ( IDD5 ) in wheat and SEMI-DWARF 3 ( SDW3 ) in barley ( Hordeum vulgare ) as positive regulators of stem and leaf expansion. Both IDD5 and SDW3 physically interact with, and act downstream of, DELLA proteins as key components of GA-mediated growth responses. Altered expression levels of GA biosynthesis genes suggest that IDD5 contributes to GA homeostasis in addition to growth regulation. Loss-of-function mutations in IDD5 and SDW3 confer a GA-insensitive semi-dwarf phenotype comparable in height to the Rht-D1b Green Revolution allele. In field trials, idd5 lines exhibited improved grain weight per spike but were lower-yielding due to reduced spike number.

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

Stephen P. Long: Visionary, teacher, and doer

Elizabeth A. Ainsworth, Donald R. Ort

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Stephen Long pioneered a multidisciplinary approach to advance our knowledge of photosynthesis, by integrating research at the molecular, cellular, organismal, and ecological levels along with a pragmatic understanding of the implications for agriculture. This involved development of new mathematical models, patented equipment for analyzing photosynthetic efficiency, and the world’s largest open-air laboratory for understanding crop responses to atmospheric change. Long fundamentally changed our understanding of how crops respond to rising CO 2 and ozone. He inspired and led efforts to engineer photosynthesis to increase yield and respond maximally to rising CO 2 . He discovered that C 4 plants, that have highly efficient photosynthesis due to a CO 2 concentrating mechanism, could thrive in cold climates, which was a true paradigm shift as previously C 4 photosynthesis had been considered limited to tropical and subtropical climates. He provided a theoretical explanation, and his research led to the discovery that Miscanthus x giganteus could achieve the high yields in cool northern climate achieved by other C 4 plants in the tropics. This seminal finding led Long to experiment on the closely related and much more widely used maize plant, and he showed how it could be adapted to cooler conditions and achieve a significant yield jump in the Corn Belt. At a time when society critically needed new ways to achieve increases in productivity in ecologically sustainable ways, Long’s research and leadership changed the way we think about choices of plants and cropping systems.

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

A J-domain protein enhances memory by promoting physiological amyloid formation in Drosophila

Kyle Patton, Yangyang Yi, Raj Burt, Kevin Kan-Shing Ng, Mayur Mukhi, Peerzada Shariq Shaheen Khaki, Ruben Hervas, Kausik Si

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Memory requires experience-dependent alterations in the synaptic proteome. Chaperones interface between the environment and the proteome. Manipulating J-domain protein (JDP) chaperones, the most diverse family of chaperones, in a Drosophila neuronal circuit that encodes associative long-term memories, we identified yet uncharacterized JDPs that transduce sensory cues. One of these JDPs, CG10375, which we named Funes, enhances memory when overexpressed and impairs memory when functionally impaired. Funes overexpression enhances memory formation even when sensory stimuli are suboptimal. At the circuit level, Funes acts on neurons where conditioned and unconditioned stimuli converge to form associative memories. From a proteomic-based screen, we found that overexpression of Funes changes the solubility of a small subset of proteins, one of which is the mRNA-binding protein Orb2. Combining in vitro and in vivo biophysical, biochemical, and cryo-EM structural analyses, we found that Funes associates with oligomeric Orb2 and promotes the formation of translationally active amyloids. Perturbation of the conserved J domain eliminates the ability of Funes to facilitate amyloid assembly and promote memory. We posit that the brain harbors chaperones that influence memory by regulating physiological amyloid formation.

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

Water-mediated hydrogen bonds and local side-chain interactions in the cooperative collapse and expansion of PNIPAM oligomers

Wanlin Chen, Martin Gruebele, Martina Havenith, Kurt J. Hebel, Carla Scaletti

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Poly(N-isopropylacrylamide) (PNIPAM), a thermoresponsive homopolymer, is a well-established model for investigating coil-to-globule transitions. Here, we combine long molecular dynamics (MD) simulations, data sonification, and graph-theory analysis to elucidate the roles of intramolecular and PNIPAM–solvent hydrogen-bond (H-bond) patterns in the PNIPAM globule–coil equilibrium. Our analysis separates the driving forces for compaction into two contributions: the entropic gain from the loss of hydration water around hydrophobic patches and the enthalpic stabilization from water H-bonded to PNIPAM. We find that the role of the solvent in polymer compaction is more active and complex than has been previously assumed. Our observations indicate that direct, intrachain hydrogen bonds between amide groups (N–H···O=C) are not the primary stabilizing force. Instead, the collapsed globule contains an N–H···N network of local side-chain interactions and is stabilized by a dynamic network of persistent, long-distance water bridges, where individual water molecules form hydrogen bonds with multiple parts of the polymer chain.

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

Sourcing the origins of carnelian in early Chinese civilizations

Meiting Yan, Jiancheng Liu, Chunlei Qin, Xuemei He, Xiaoguang Li, Jian Yu, Ruilin Mao, Hongye Han, Zhanwei Sun, Chong Wang, Zhenbin Xie, Honglin Ran, Fei Tang, Jonathan Mark Kenoyer, Zihua Tang

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Carnelian beads in high-status burials of the Western Zhou period (ca. 1000–800 BCE) have long been seen as key evidence for long-distance exchange between East Asia and regions to the west, while their geological origins and circulation pathways have remained poorly constrained. Using a newly established geochemical database of 300 geological samples from 27 potential sources across Asia, we conducted trace-element analyses of 11 carnelian beads from the Sanxingdui pits (ca. 1200–1000 BCE), Sichuan Basin, southwest China. Canonical discriminant analysis indicates that the raw materials of these carnelian beads do not primarily derive from south China, but the Yanshan Orogeny, Central Asian Orogenic Belt and some unknown sources that might be close to Hexi Corridor, pointing to raw-material sources located over 1,000 km to the north of the Sichuan Basin. Comparative analyses of contemporaneous beads from Gansu, Shaanxi, and Beijing show similar northern provenance signatures, suggesting a broad and persistent exchange sphere spanning the southern Mongolian Plateau, Loess Plateau, eastern Tibetan Plateau, Central Plains, and Sichuan Basin between 1500–1000 BCE. Our results provide the earliest direct geochemical evidence for long-distance carnelian exchange in Bronze Age China and demonstrate the value of integrating geochemical sourcing with archaeological context to reconstruct ancient interaction networks.

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

Plant–fungi interactions in Marchantia polymorpha are associated with horizontal gene transfer and terpene metabolism

Karima El Mahboubi, Chloé Beaulieu, Baptiste Castel, Cyril Libourel, Nathanaël Jariais, Emilie Amblard, Fabian van Beveren, Jean Keller, Yves Martinez, Jessica M. Nelson, Maxime Bonhomme, Christophe Jacquet, Pierre-Marc Delaux

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The liverwort Marchantia polymorpha has emerged as a model for studying plant immunity in bryophytes, providing unique insights into conserved defense mechanisms across land plants. By contrast, Marchantia-specific immune mechanisms remained largely underexplored. In this study, we investigated the genetic basis of quantitative resistance in M. polymorpha against the fungal pathogen Colletotrichum nymphaeae , a naturally occurring compatible parasite. Through a combination of phenotypic, cytological, and transcriptomic approaches, combined with genome-wide association studies (GWAS), we identified key defense-related genes and pathways. Leveraging the biological and genetic variability present in a collection of natural M. polymorpha accessions, we highlight the role of horizontally transferred microbial-like terpene synthase genes, which may contribute to the exceptional terpene diversity of liverworts and potentially play a role in pathogen resistance. GWAS uncovered candidate loci associated with resistance traits, implicating both core immune components and specialized metabolic pathways. Transcriptomic analyses performed on two accessions with contrasting phenotypes after inoculation with C. nymphaeae revealed the upregulation of accession-specific and horizontally acquired genes. These results provide insights into the specific molecular underpinnings of bryophyte immunity and underscore the evolutionary significance of horizontal gene transfer and specialized metabolites in shaping plant–pathogen interactions.

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

Proximity-driven acceleration of challenging solid-phase peptide couplings

Joshua Parker, Brooke A. Farrell, Karlee A. Kohuth, Landon Parker, Skander A. Abboud, Thomas Kodadek

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Many important solid-phase synthesis reactions proceed slowly and inefficiently, for example, the coupling of an activated ester to a sterically hindered, bead-displayed amine, a critical step in the synthesis of many peptides. Forcing conditions are often required to achieve acceptable yields. We show here that such reactions can be accelerated by tethering to the bead a nucleophilic pyridine catalyst, which reacts with the activated ester, creating a high local concentration of a reactive acylpyridinium intermediate that couples efficiently to the bead-displayed amine. In many cases, the “cleanliness” of reactions carried out on resins equipped with an immobilized catalyst is substantially better than the analogous reactions in which the catalyst is added to the solution.

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

Apical and basolateral plasma membranes in epithelial cells have distinct lipidomes and biophysical properties

Carolyn R. Shurer, Kandice R. Levental, Ilya Levental

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Epithelial cell polarization is essential for many physiological processes, including tissue morphogenesis, nutrient absorption, barrier integrity, and directional secretion. A defining feature of such polarization is the separation of plasma membrane (PM) lipids and proteins into distinct apical and basolateral compartments. It has long been suggested that the apical compartment is rich in glycolipids and cholesterol and that this composition arises through trafficking of self-assembled membrane domains (termed lipid rafts). However, neither the detailed composition nor the mechanisms of molecular sorting between epithelial cell PM compartments have been fully resolved. Particularly, the lipid profile of the basolateral membrane and consequently the lipid disparity between the apical and basolateral membrane remain undefined. We developed a method to separately isolate the apical and basolateral PM and used lipidomics and biophysical profiling to characterize the changes in membrane composition and properties between these compartments in polarized Madin–Darby canine kidney cells. We find that the apical membrane is enriched in cholesterol, saturated lipids, and glycolipids relative to the basolateral membrane and that its biophysical properties reflect a more ordered environment. Further, we evaluate the longstanding hypothesis that lipid rafts contribute to apical protein trafficking by assessing the relationship between transmembrane domain raft affinity and apical localization and find that lipid raft affinity only modestly influences apical versus basolateral sorting. These findings define the distinct compositional and biophysical features of apical and basolateral compartments of epithelial cells and suggest mechanistic evidence for their biogenesis.

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

Theory for sequence selection via phase separation and oligomerization

Ivar S. Haugerud, Giacomo Bartolucci, Dieter Braun, Christoph A. Weber

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Nonequilibrium selection pressures were proposed for forming oligonucleotides with rich functionalities encoded in their sequences, such as catalysis. Since phase separation was shown to direct various chemical processes, we ask whether condensed phases can provide mechanisms for sequence selection. To answer this question, we use nonequilibrium thermodynamics and describe the reversible oligomerization of different monomers to sequences at nondilute conditions prone to phase separation. We find that as sequences form, their interactions can trigger phase separation, which in turn enriches some sequences while depleting others. Our main result is that phase separation creates a selection pressure leading to specific sequence patterns when fragmentation maintains the system away from equilibrium. When fragmentation is slow, alternating sequences that interact more cooperatively with their surroundings are preferred. When fragmentation is fast, sequences with longer repeating motifs capable of more specific interactions are selected instead. Our finding that out-of-equilibrium condensed phases can provide a selection mechanism highlights their potential as versatile hubs for the evolution of functional sequences, a question relevant to the molecular origin of life and de novo life.

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

RPA-independent activation of the ATR/CHK1 pathway

Min Huang, Dandan Zhu, Junjie Chen

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The ATR/CHK1 pathway governs a crucial intra-S-phase checkpoint that safeguards genome stability under replication stress by stabilizing stalled replication forks and ensuring high-fidelity DNA replication. Traditionally, activation of this pathway is thought to rely on replication protein A (RPA)-coated single-stranded DNA, which recruits the ATR–ATRIP complex to sites of stalling fork, positioning RPA as essential for ATR signaling. In this study, we report a surprising and previously unrecognized phenomenon: acute depletion of RPA2 triggers robust ATR/CHK1 activation through an RPA-independent mechanism. Using 293A and RPE-1 cells engineered with an inducible RPA2-dTAG degron system, we observed increased phosphorylation of CHK1 at Ser296 and Ser345 in the absence of RPA. Notably, this elevated CHK1 phosphorylation was abolished by ATR inhibition, confirming its dependence on ATR kinase activity. Mechanistic analyses further revealed that this RPA-independent activation requires the checkpoint mediators RAD9 and TOPBP1. These findings uncover dual mechanisms, both RPA-dependent and -independent, of ATR/CHK1 pathway activation, highlighting a robust and flexible replication stress response network that preserves genome integrity even when canonical signaling is disrupted.

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

Reply to Compton et al.: Another paradoxical misunderstanding

George Butler, Joanna Baker, Sarah R. Amend, Kenneth J. Pienta, Chris Venditti

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

Deglacial stratification of the polar Southern Ocean

François Fripiat, Daniel M. Sigman, Xuyuan E. Ai, Cédric Dumoulin, Simone Moretti, Anja S. Studer, Bernhard Diekmann, Oliver Esper, Thomas Frederichs, Frank Lamy, Ling Liu, Frank Pattyn, Mareike Schmitt, Ralf Tiedemann, Gerald H. Haug, Alfredo Martínez-García

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It is widely accepted that meltwater from northern ice sheets drove changes in the Atlantic Meridional Overturning Circulation, impacting global climate. In contrast, data are lacking on the Antarctic Ice Sheet’s (AIS) effect on Southern Ocean overturning, despite the Southern Ocean’s central role in ventilating the ocean interior. Here, we present diatom-bound nitrogen isotope evidence indicating that during deglaciations, as wind-driven upwelling in the open Antarctic Ocean increased, AIS melting strengthened density stratification in the polar Antarctic Ocean. This change coincides with reconstructions of meltwater discharge and resembles model simulations of global warming including AIS meltwater forcing. The transient input of freshwater and, thus, buoyancy weakened Southern Ocean’s “lower cell” that outcrops in the polar Antarctic Ocean even as open Antarctic Ocean’s “upper cell” strengthened. Given evidence that deep-ocean ventilation and CO 2 release were ongoing early in deglaciation, our data suggest that the open Antarctic Ocean, and not solely the most polar Antarctic Ocean, can directly ventilate the deep ocean. During the last deglaciation, the strongest density stratification in the polar Antarctic Ocean occurred just before the Antarctic Cold Reversal, when southern hemisphere warming paused and the northern hemisphere warmed sharply (i.e., during the Bølling–Allerød period). We propose that when combined with stronger wind-driven upwelling, the freshwater-driven redirection of upwelled water away from deep water formation and toward the upper cell deepened the global pycnocline, working to restart North Atlantic deep water formation in the Bølling–Allerød period. If so, polar ocean freshening in both hemispheres drove the “bipolar seesaw” events of deglaciation.

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

A factor integrating transcription and repression of surface antigen genes in African trypanosomes

María Agustina Berazategui, Ione Goodwin, Lianne I. M. Lansink, Keith Gull, Gloria Rudenko, Jack D. Sunter, Joana R. C. Faria, Richard J. Wheeler, Calvin Tiengwe

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Antigenic variation in Trypanosoma brucei ( T. brucei ) requires monoallelic expression of one variant surface glycoprotein (VSG) from one of the subtelomeric bloodstream form (BSF) expression sites (BESs). This transcription is unusually mediated by RNA polymerase I (RNA Pol I) and occurs in a specialized nuclear body, the expression site body (ESB). While factors promoting active BES transcription and silencing inactive BESs are known, how these opposing activities are integrated remains unknown. Here, we identify ESBX (Tb927.3.1660) as a BSF-specific ESB protein necessary for this coordination. We show that ESBX RNAi knockdown prevents RNA Pol I localizing to the ESB and reduces active BES transcription, while also derepressing inactive BESs with low processivity transcription. Conversely, ESBX overexpression weakly activates inactive BESs in a distinct manner from ESBX knockdown, leading to processive transcription, without disrupting the active BES or forming supernumerary ESBs. ESBX knockdown causes a similar transcriptomic defect to ESB1 and VEX2 knockdown combined, establishing ESBX as a key factor linking transcriptional activation of the active BES with inactive BES silencing through the VSG exclusion (VEX) phenomenon. This allows us to suggest models for understanding the establishment and maintenance of monoallelic expression critical for parasite immune evasion.

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

All-visible-light-responsive porous aromatic frameworks manipulate CO 2 uptake by reversible bulk isomerization of azobenzene pendants

Jinyu Sheng, Jacopo Perego, Silvia Bracco, Piotr Cieciórski, Wojciech Danowski, Angiolina Comotti, Ben L. Feringa

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Embedding light-responsive small molecules in a porous solid is a promising strategy to achieve dynamic control over material properties. Powering these systems with low-energy photons is essential for their future applications, since visible light, compared to UV light, is less damaging and offers more selective isomerization with higher penetration depth. However, the construction of visible light-responsive porous materials remains a significant challenge. Here, we report the construction of a series of visible-light-responsive porous aromatic switchable framework materials grafted with o -fluoroazobenzene pendants ( Azo-PSFs ). The materials exhibit high microporosity and reversible photoswitching upon irradiation with visible light. The highly robust materials can be cycled between two distinct states multiple times without showing any photo fatigue or decomposition. Remarkably, solid-state NMR revealed that the azobenzene moiety undergoes reversible bulk isomerization in the framework. The isomerization of azobenzene within the framework is associated with substantial changes in adsorption capacity and CO 2 uptake-release by the material. This work presents the example of visible-light-triggered bulk isomerization in an azobenzene-based porous material, providing a benchmark characterization of photoresponsive systems and paving the way for the future advancements in light-driven materials.

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

Reply to Cecchi and Palminteri: On the need to model temporal variation in learning rates

Prakhar Godara

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

Molecular tuning of DNA framework–programmed silicification by cationic silica cluster attachment

Xinxin Jing, Haozhi Wang, Jianxiang Huang, Yingying Liu, Zimu Li, Jielin Chen, Yiqun Xu, Lingyun Li, Yunxiao Lin, Damiano Buratto, Qinglin Xia, Muchen Pan, Yue Wang, Mingqiang Li, Ruhong Zhou, Stephen Mann, Chunhai Fan, Xiaoguo Liu

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The organizational complexity of biominerals has long fascinated scientists seeking to understand biological programming and implement new developments in biomimetic materials chemistry. Nonclassical crystallization pathways have been observed and analyzed in typical crystalline biominerals, such as calcium phosphate, calcium carbonate, and ferric oxide, involving the controlled attachment and reconfiguration of nanoparticles and clusters on organic templates. However, the understanding of templated amorphous silica mineralization remains limited, hindering the rational design of complex silica-based materials. Here, we report the finding of ultrastable and monodispersed cationic silica cluster (CSC) and their assembly using DNA nanostructures as programmable attachment templates. Cryo-EM imaging reveal that a typical CSC with a diameter of gyration of ~3.9 nm and an average molecular weight of ~8, 262 Da is characteristic of a branched hierarchical structure. We demonstrate high-fidelity silicification by tuning the composition and structure of CSC, providing a unified model of silicification by cluster attachment. Our findings pave the way toward the molecular tuning of pre- and postnucleation stages of sol–gel reactions and provide insights for the design of silica-based materials with controlled organization and functionality.

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

REV-ERB-alpha and -beta coordinately regulate astrocyte reactivity and proteostatic function

Collin J. Nadarajah, Michelle Y. Li, Elsa I. Quillin, Kevin Boyer, Julie M. Dimitry, Yining Chen, Melvin W. King, Ibrahim O. Saliu, Jiyeon Lee, Patrick W. Sheehan, Albert A. Davis, Mitchell A. Lazar, Guoyan Zhao, Erik S. Musiek

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The molecular circadian clock is a ubiquitous transcriptional–translational feedback loop that regulates CNS function, glial responses, and neurodegenerative pathology. The nuclear receptors REV-ERB-α ( Nr1d1 ) and REV-ERB-β ( Nr1d2 ) are components of the core circadian clock which regulate metabolism, neuroinflammatory responses, synaptic pruning, and protein aggregation, though the cell type–specific effects and relative compensatory effects of REV-ERB-α AND -β in the brain are unknown. To study the CNS functions of REV-ERBs, we developed mouse lines with global or astrocyte-specific, conditional knockout of both REV-ERB-α and -β. We demonstrate that inducible postnatal global deletion of both REV-ERB-α and -β unmasks extensive transcriptional changes in the brain in disease-relevant pathways such as protein catabolism, complement, and oxidative stress which are not observed with REV-ERB-α deletion alone, and drives spontaneous astrocyte reactivity. Astrocyte-specific deletion of REV-ERB-α/-β recapitulates this spontaneous astrocyte reactivity phenotype, indicating that REV-ERBs regulate astrocyte activation in a cell-autonomous manner downstream of the core circadian clock. Upstream transcription factor analysis revealed that REV-ERB-α/-β repress transcription of Stat3 , and astrocytic deletion of REV-ERBs induced astrocytic STAT3 expression and downstream STAT3-mediated gene expression, providing a mechanistic link to the astrocyte reactivity shift. Dual REV-ERB deletion enhanced astrocyte alpha-synuclein uptake and protein degradation in vitro and mitigated alpha-synuclein spreading pathology in an in vivo model of Parkinson’s Disease. This study reveals REV-ERBs as regulators of astrocyte function and implicates astrocyte REV-ERBs as potential therapeutic targets to prevent synucleinopathies and other neurodegenerative pathologies.

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

Stepwise differentiation from precursor intermediates and distinct Th1 checkpoints promote CD4 Th1 cell differentiation during chronic viral infection

Hongshen Niu, Siying Lin, Ryan Brown, Jian Shen, Arjun Kharel, Yuqi Zhang, Kexin Gai, Ashley Bauer, Ashley Brown, Ziyang Xu, David G. Brooks, Weiguo Cui

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CD4 + helper T cells are essential for controlling viral infections. During chronic LCMV infection, CD4 + T cells differentiate into heterogeneous populations, including a TCF-1 hi progenitor subset that serves as a reservoir to continuously replenish type 1 helper (Th1) and follicular helper (Tfh) T cells. The gradual loss of CD4 + Th1 cell responses impairs the immune system’s ability to control viral replication and contributes to the development of CD8 + T cell exhaustion. However, the mechanisms directing Th1 differentiation and the factors underlying their progressive decline during chronic infection remain poorly understood. In this study, we delineate the stepwise differentiation trajectory of Th1 cells, tracing their progression from TCF-1 hi progenitors through an intermediate state to fully differentiated Th1 cells. We identify an intermediate CD4 + T cell subset that serves as a precursor to Th1 cells, demonstrate that PD-1/PD-L1 signaling suppresses the transition from the progenitor to intermediate state, whereas the chromatin-remodeling complex PBAF restricts the terminal differentiation of CD4 + T cells into the Th1 subset. Notably, the combined blockade of PD-1/PD-L1 and genetic ablation of PBAF component (ARID2) additively enhanced Th1 differentiation and maintenance, leading to effective viral control. Thus, targeting these mechanisms driving CD4 Th1 cell differentiation and maintenance could enhance therapeutic strategies to restore Th1 function and control chronic infection.

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

Evolutionary pathways in epistatic mechanical networks

Samar Alqatari, Sidney R. Nagel

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An elastic spring network is an example of evolvable matter. It can be pruned to couple separated pairs of nodes so that when a strain is applied to one of them, the other responds either in-phase or out-of-phase. This produces two pruned networks, with incompatible functions, that are nearly identical but differ from each other by a set of “mutations” each of which removes or adds a single bond in the network. We generate ensembles of network pairs that differ by a fixed number, M , of discrete mutations and evaluate all M ! mutational paths between the in- and out-of-phase behaviors up to M = 14. With a threshold response for the network to be considered sufficiently fit for either function, so that nonfunctional networks are disallowed, only some mutational pathways are viable. We find that there is a surprisingly high critical response threshold above which no evolutionarily viable path exists between the two networks. The few remaining pathways at this critical value dictate much of the behavior along the evolutionary trajectory. The effect of multiple mutations is epistatic, that is, the impact of a mutation is not invariant but depends on what other mutations have already occurred. In most cases, the mutations break up into two distinct classes based on epistasis. The analysis clarifies how the number of mutations and the position of a mutation along the pathway affect the evolutionary outcome.

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

An interpretable molecular framework for predicting cancer driver missense mutations

Yan Yang, Weikang Sun, Yang Liu, Jian Zhang, Minghui Li

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Missense mutations play a critical role in human disease, contributing to both inherited disorders and cancer. However, accurately predicting their functional impact—particularly for cancer driver mutations—remains a major challenge due to limited validated labels and the complex molecular basis of oncogenesis. Here, we systematically characterized over 120,000 missense variants across pathogenic, benign, driver, passenger, recurrent somatic, and common population classes, using a comprehensive set of mechanistically grounded molecular features. By assessing the statistical burden of variations, we demonstrated that these features effectively discriminate among diverse variant classes and reveal a consistent enrichment of functional sites, structural integrity, and biophysical changes in pathogenic and driver mutations. Building on these insights, we developed MutaPheno, an interpretable framework for predicting the functional consequences of missense mutations. The model integrates 34 molecular-level features, encompassing structural, functional, physicochemical, and contextual descriptors, using a random forest algorithm. Trained exclusively on pathogenic and benign variants, MutaPheno achieved strong accuracy in predicting cancer driver mutations, outperforming both cancer-specific and general pathogenicity tools, while also demonstrating superior robustness when tested on unseen proteins. Our findings highlight the shared mechanisms between pathogenic and driver mutations and emphasize the role of molecular features in improving variant interpretation. MutaPheno provides a transparent and generalizable tool that can facilitate driver discovery and the development of targeted therapies.

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

Controlling for life-history traits in vertebrates reveals that effective population size does not affect mutation rate or genome size

Brooke Weinstein, Scott William Roy

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Why mutation rates ( μ ) and genome sizes (GS) vary among species remains a central question in evolutionary genetics. Two influential models, the drift-barrier hypothesis (DBH) and the mutational-hazard hypothesis, propose that effective population size ( N e ) shapes these traits via the efficiency of selection, predicting higher μ and larger genomes in small populations. A recent comparative analysis of vertebrates reported a significant negative correlation between N e and μ , interpreted as support for the DBH. Using phylogenetic path analysis, we reanalyze the same dataset of 55 vertebrate species spanning mammals, birds, reptiles, and fishes, in which μ was estimated from high-coverage parent–offspring trios, while explicitly controlling for six life-history traits within a causal framework that tests model-implied conditional independencies. We show that the reported N e - μ association is entirely mediated by generation time (GT), which independently influences both variables; once this “back-door” path is blocked, N e has no detectable effect on μ . Once GT is accounted for, mating system shows the largest association with μ . Parallel analyses of GS within the same validated life-history framework reveal that GS is unrelated to N e , μ , or their interaction and is decoupled from the life-history covariation that strongly structures μ . These results are robust to alternative N e estimators and causal model formulations. Together, our findings indicate that N e provides little explanatory power for variation in μ or GS across vertebrates, challenging the presumed universality of drift-limited genome evolution.

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

A framework for assessing the trustworthiness of scientific research findings

Brian A. Nosek, David B. Allison, Kathleen Hall Jamieson, Marcia McNutt, A. Beau Nielsen, Susan M. Wolf

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Vigorous debate has erupted over the trustworthiness of scientific research findings in a number of domains. The question “what makes research findings trustworthy?” elicits different answers depending on whether the emphasis is on research integrity and ethics, research methods, transparency, inclusion, assessment and peer review, or scholarly communication. Each provides partial insight. We offer a systems approach that focuses on whether the research is accountable, evaluable, well-formulated, has been evaluated, controls for bias, reduces error, and whether the claims are warranted by the evidence. We tie each of these components to measurable indicators of trustworthiness for evaluating the research itself, the researchers conducting the research, and the organizations supporting the research. Our goals are to offer a framework that can be applied across methods, approaches, and disciplines and to foster innovation in development of trustworthiness indicators. Developing valid indicators will improve the conduct and assessment of research and, ultimately, public understanding and trust.

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

Evolution of Pliocene-Pleistocene tropical terrestrial Andean temperature amplification

Lina C. Pérez-Angel, Julio Sepúlveda, Peter Molnar, Héctor Mora-Paez, Angélica Parrado, Katelyn Eaman, James Russell, Balaji Rajagopalan, Catalina González-Arango, Kathryn Snell, Camilo Montes, James L. Crowley, Mark Schmitz, Robin B. Trayler

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The Pliocene is the most recent epoch in which the Earth warmed under atmospheric CO 2 levels similar to today (>400 ppm). The Pliocene then transitioned to the colder Pleistocene epoch, with the initiation of large-scale Northern Hemisphere glaciations. Although ocean temperature changes across these epochs are relatively well-known, quantitative estimates of the magnitude of land temperature change in the tropics are scarce. We provide a Plio-Quaternary quantitative air temperature record based on the distribution of bacterial branched glycerol dialkyl glycerol tetraethers (brGDGTs) preserved in sediments of the Funza-II core in the Sabana de Bogotá, Colombia (~4°N). Using a refined age model based on new U-Pb zircon dates from ash layers, and a novel mixed-source model that disentangles contributions from lake- and soil-derived brGDGTs, we show that warm Pliocene (3.8 to 2.58 Ma) temperatures were 4 . 8 - 1.4 + 1.8 °C warmer than the last ~800,000 y of the colder Pleistocene. The evolution of Pliocene-Pleistocene temperature in our record largely mirrors long-term tropical sea surface temperature (SST) cooling, highlighting the linkages between sea and land temperatures in the low latitudes via greenhouse-gas forcing. The median amplitude of Pliocene-Pleistocene cooling in the northern tropical Andes exceeds that predicted by theory, highlighting the importance of regional feedbacks including lapse rate adjustments and/or changes in Pacific SST gradients to the long-term evolution of Andean temperature. This first quantitative terrestrial temperature reconstruction within 5° of the equator over the past 3.8 My highlights that both regional and global processes must be considered when constraining uncertainties for future warming scenarios.

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

Neuron-specific modulation of SLC30A10 identifies dopaminergic and glutamatergic neurons as targets of manganese-induced motor disease

Stephanie M. Grant, Ashvini Melkote, Mollie X. Bernstein, Thomas Jursa, Cherish A. Taylor, Steven Hutchens, William Shawlot, Larry S. Zweifel, Rueben A. Gonzales, Donald R. Smith, Somshuvra Mukhopadhyay

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Essential metals accumulate in the basal ganglia at elevated levels and induce incurable motor disease. But, unlike other motor diseases, the neuronal targets of essential metals are unknown, and this fundamental knowledge gap has limited therapeutic progress. Because metal efflux transporters have high specificity, we hypothesized that neuron-specific knockout or knockin (i.e., overexpression) of efflux transporters may alter metal levels in targeted neurons and define the neuronal targets of metal-induced disease. To test this, we focused on manganese (Mn)-induced motor disease, which is a public health problem. We generated six neuron-specific Slc30a10 mouse strains with knockout or knockin of the Mn efflux transporter Slc30a10 in dopaminergic, GABAergic, or glutamatergic neurons. In the knockout strains, SLC30A10 was depleted and Mn levels were elevated in targeted brain regions. However, only dopaminergic- or glutamatergic-, but not GABAergic-, specific knockouts developed motor deficits without Mn exposure. Conversely, in the knockins, SLC30A10 was elevated and the increase in Mn levels after Mn exposure was attenuated in targeted regions. However, only dopaminergic- or glutamatergic-, but not GABAergic-, specific knockins were protected against Mn-induced motor deficits. Dopaminergic-specific Slc30a10 knockouts also exhibited deficits in dopaminergic neurotransmission that were consistent with their motor phenotype. Overall, 1) elevated Mn targets dopaminergic and glutamatergic neurons to induce motor disease, and 2) neuron-specific knockout/knockin of efflux transporters is an effective strategy to isolate the neuronal targets and underlying mechanisms of metal-induced neurological disease.

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

Divergent understandings in comparative oncology

Zachary T. Compton, Amy M. Boddy, Lisa M. Abegglen, Daniel Chávez, Joshua D. Schiffman, Marc Tollis, Carlo C. Maley

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

Spatial transcriptomics reveals tumor microenvironment–driven subtypes of invasive lobular carcinoma

Matteo Serra, Mattia Rediti, Laetitia Collet, Frédéric Lifrange, David Venet, Nicola Occelli, Andreas Papagiannis, Delphine Vincent, Ghizlane Rouas, Denis Larsimont, Miikka Vikkula, Francois P. Duhoux, Françoise Rothé, Christos Sotiriou

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Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer and displays distinct clinical and biological behavior compared to breast cancer of no special type. However, current molecular classifications largely overlook its complex spatial organization and tumor microenvironment (TME). Here, we performed spatial transcriptomics on 43 hormone receptor-positive, HER2-negative (HR+/HER2−) ILC tumors with detailed morphological annotation and long-term clinical follow-up. By integrating spatial gene expression with histology and single-cell deconvolution, we characterized the composition and architecture of the TME and revealed high inter- and intratumor heterogeneity. Spatial clustering uncovered cell populations and pathways linked to clinical outcome. We then developed a multimodal classification of ILC by integrating gene expression, morphology, and spatial metrics, identifying four distinct subtypes: normal/stroma-enriched (NSE), proliferative (P), androgen receptor-enriched (ARE), and metabolic/immune-enriched (MIE). These subtypes, collectively termed ILC4TME, reflect the interplay between tumor and microenvironmental features. Gene signatures derived from the spatial data enabled subtype assignment in external bulk RNA-seq and microarray datasets (SCAN-B, METABRIC), revealing reproducible biology and significant associations with survival. In multivariable models, ILC4TME retained prognostic value beyond established gene signatures and clinicopathological variables. Notably, the P subtype was linked to poor prognosis, even in patients treated with endocrine therapy alone, while the NSE subtype was associated with favorable outcomes. Our findings uncover spatial and cellular heterogeneity in ILC that is not captured by existing classification approaches, offering a refined framework for risk stratification and therapeutic targeting based on tumor microenvironment architecture.

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

Selective peroxynitrite-mediated protein nitration catalyzed by glyoxalase domain containing protein 4

Sarah Wright, Vu C. Dang, Sami Hussain, Prasanna Kandel, Robert P. Brendza, Sahar Mazhar, Marie Whitmore, Selim Boudoukha, Jaskamaljot Kaur Banwait, Robert Van Der Linden, Edward Vertudes, Kate Markham, Marta Trzeciak, Grace Pohan, Andy Jennings, Sheerin Shahidi-Latham, Frank Kayser, Mike Beckstead, Aaron L. Lucius, Arun Kashyap, Harry Ischiropoulos, Irene Griswold-Prenner

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Tyrosine nitration alters the structure, function, and cellular localization of proteins and is implicated in the pathology of multiple diseases [G. Ferrer-Sueta et al. , Chem. Rev. 118 , 1338–1408 (2018), H. Ischiropoulos, Arch. Biochem. Biophys. 356 , 1–11 (1998), I. Griswold-Prenner et al. , J. Biol. Chem. 299 , 105038–10554 (2023)]. Although protein nitration is assumed to proceed via nonspecific chemical mechanisms, it is highly selective, suggesting the possibility of enzymatic catalysis. Here, we showed that glyoxalase domain-containing protein 4 (GLOD4), a previously uncharacterized protein, is an enzyme that catalyzes selective protein nitration. A primary in vivo target for GLOD4-mediated nitration is alpha-synuclein (α-syn), which is central to the pathogenesis of Parkinson’s disease (PD) and related disorders. We document tyrosine nitration of α-syn by GLOD4 in vitro, in cells, and in a murine model of synuclein pathology. The data identified a function of GLOD4 and other structurally related proteins that catalyze the peroxynitrite-mediated selective protein tyrosine nitration. This enzymatic catalysis of nitration may unearth pathophysiological mechanisms and potential interventions in diseases such as PD, cancer, and autoimmunity.

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

Coupled anatexis and extreme differentiation are the keys for producing giant lithium-rich pegmatites

Hai-Zhen Wei, Martin R. Palmer, Zhiqin Xu, Wenbin Zhu, Xi-Sheng Xu, Anthony Williams-Jones, Bi-Hai Zheng, Jian-Guo Gao, Qin Wang, Jing Ma, Ke Yang, Hefeng Lin, Da-Sheng Zuo

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Despite the economic importance of lithium, there is considerable disagreement over the processes that concentrate it and other rare metals in pegmatite-type lithium deposits. Two main processes have been invoked, namely extreme differentiation of a peraluminous granitic magma and direct anatexis of a sedimentary protolith. We use geochemical modeling to quantify lithium enrichment via these two processes from a study of the Jiajika lithium pegmatite field, one of the largest of its type in the world. Based on a lithium–silicon–boron–barium (Li-Si-B-Ba) isotope study involving systematic sampling along 4,211-m of core from two deep boreholes and from the regional zonation of pegmatites at outcrops, we propose a three-stage model for the formation of the pegmatite field: i) generation of a rare metal-rich melt by deep anatexis, involving ~5% partial melting of metapelitic rocks in the presence of 10 to 30% metamorphic fluid; ii) gradual enrichment of rare metals along a path of continuous magma differentiation until 75% of the initial melt had crystallized; and iii) a final stage of lithium mineralization during the escape of the water-rich magma due to the overpressures created in response to massive fluid exsolution and the extensional stress in the granite dome structure. The study provides important insights into how lithium-rich pegmatites can be targeted during exploration for pegmatite-hosted resources of lithium.

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

Rapid evolution reveals long-range spread of SARS-CoV-2

Daniel B. Weissman

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

Structural basis for pseudokinase-mediated regulation of GCN2 in the integrated stress response

Yixin Liu, Jagannath Misra, Debarshi Ryan Bhowmik, Brady O’Boyle, Kirk A. Staschke, Natarajan Kannan, Ronald C. Wek, Natalia Jura

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The general control nonderepressible 2 (GCN2) is a conserved stress-responsive protein that plays a critical role in restoring cellular homeostasis in the integrated stress response (ISR). In response to amino acid starvation or ribosome stalling and collisions, GCN2 phosphorylates the translation initiation factor eIF2α, conferring translational control to alleviate stress. GCN2 is a multidomain protein, containing a tandem kinase domain (KD) and a catalytically inactive pseudokinase domain (ψKD). Stress-induced activation of the kinase domain requires allosteric regulation and dimerization mediated by its regulatory domains. While the pseudokinase domain is essential for GCN2 function in yeast, its mechanistic role remains unclear and underexplored in other organisms. Here, we present the first crystal structure of the human GCN2 ψKD, revealing its distinct structural features. The structure visualizes an insertion N-terminal to helix αC unique to the GCN2 ψKD that interacts with the pseudoactivation loop, stabilizing an inactive conformation. Further structural analysis shows that the ψKD forms a dimer in the crystal lattice via a network of hydrophobic and electrostatic interactions spanning both the N- and C-lobes. Mutations that disrupt the dimer interface reduced downstream ATF4 expression that is important for stress adaptation, underscoring the functional significance of the GCN2 ψKD dimer in regulating GCN2 activity. Complementary AI-guided structure predictions indicate that the dimeric GCN2 ψKD architecture is conserved across evolution. These results support the role of ψKD dimerization as a regulatory feature in GCN2-mediated ISR signaling.

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

Fe metal–organic framework–derived heterojunction for metabolic diagnosis of thymic epithelial tumor

Yongpeng Liang, Haochen Han, Yuewei Zhao, Wenjun Yu, Huiying Chen, Jiachuan Liu, Haojie Jin, Yangfan Xu, Wei Chen, Kun Qian, Xiangdong Yao, Lin Huang, Xiao-Ming Chen

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Thymic epithelial tumors (TETs), rare yet clinically significant malignancies, face diagnostic challenges due to their occult presentation and lack of noninvasive risk-stratification tools, leading to systemic overtreatment and poor prognoses for high-risk subtypes. To address this unmet need, we developed a Fe 3 O 4 @Fe metal–organic framework heterojunction-enhanced laser desorption ionization mass spectrometry (LDI MS) platform for the efficient analysis of serum metabolic fingerprints (SMFs). Engineered through gradient pyrolysis, this nanomaterial synergizes ultraviolet absorption and photothermal conversion from its two constituent components with enhanced charge separation, achieving 1,000-fold improvement in sensitivity and thus enabling direct SMF acquisition from 1 μL of serum. Coupled with machine learning, the platform demonstrates robust diagnostic performance, yielding area under the curve (AUC) of 0.960 for distinguishing TETs from benign control and AUC of 0.856 for hierarchical risk stratification, outperforming clinical workflows. Beyond advancing material design for LDI MS, this work establishes a clinically translatable framework for rapid, large-scale screening, addressing critical gaps in TET management through metabolic-driven stratification.

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

Lead in archived hair documents a decline in lead exposure to humans since the establishment of the US Environmental Protection Agency

Thure E. Cerling, Diego P. Fernandez, Ken R. Smith

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Lead (Pb) is well known to be toxic to humans. We use archived hair from individuals living along the Wasatch Front in Utah to evaluate changes in exposure to lead over the last 100 y. Current concentrations of lead in hair from this population average almost 100 times lower than before the establishment of the Environmental Protection Agency. This low level of lead exposure is likely due to the environmental regulations established by Environmental Protection Agency.

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

Flagellar rotation comes full circle

Michael D. Manson

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

High-sensitivity, protein-independent detection of dsDNA sequences

Jiaqi Yan, Rajendra Bhadane, Wentao Xu, Meixin Ran, Xiaochao Ma, Yuanqiang Li, Kevin Jahnke, Xiaodong Ma, Outi M. H. Salo-Ahen, Mauri A. Kostiainen, David A. Weitz, Hongbo Zhang

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Current methodologies for detecting the sequence of double-stranded DNA (dsDNA) require amplifying and denaturing the target into single-stranded DNA (ssDNA) to enable sequence detection through Watson–Crick base pairing. However, these approaches are limited by the risks of nonspecific amplification, reliance on complex, temperature-sensitive protein enzymes, and harsh reaction conditions, such as in strong base or acidic environments. Here, we introduce a dsDNA detection platform that integrates a peptide nucleic acid (PNA) as the dsDNA denaturation agent, with multicomponent deoxyribozyme as the ssDNA detection tool, in a droplet-based system. This protein- and amplification-free method offers single-nucleotide resolution, detects down to a single dsDNA molecule, and delivers results within 1 h at room temperature. This work introduces a conceptually unique approach, that may be useful for both diagnostics and therapeutics.

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

Oxidizing pollutants can disrupt nestmate recognition in ants

Nan-Ji Jiang, Bhoomika Ashok Bhat, Eduardo Briceño-Aguilar, Angela Lehmann, Yuko Ulrich, Bill S. Hansson, Markus Knaden

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Eusocial hymenoptera recognize nestmates based on colony-specific profiles of cuticular hydrocarbons (CHCs). While these profiles contain a variety of alkanes, the less abundant alkenes are crucial for nestmate recognition [F. R. Dani et al. , Chem. Senses 30 , 477–489 (2005)]. However, due to their carbon–carbon double bonds, alkenes can easily become degraded by oxidants. One of those oxidants, ozone, that usually reaches concentrations of 10 ppb in nonurban areas and ca 30 ppb in cities nowadays has been reported to often exceed 100 ppb in highly polluted regions, with levels above 200 ppb occasionally reported. Here, we show that short exposure to such elevated levels degrades alkenes in CHC profiles of all six investigated ant species and compromises nestmate recognition in five of them. Furthermore, a separate experiment with long-term exposure to such ozone levels corrupted brood care behavior within ant colonies, resulting in the death of larvae. The oxidizing pollutants like ozone have already been shown to corrupt interactions of flowers and their pollinators [B. Cook et al. , J. Chem. Biol. 46 , 987–996 (2020)] as well as sex pheromone communication in multiple species of flies [N. J. Jiang et al. , Nat. Commun. 14 (2023)]. Our data suggest that the detrimental effects of oxidant pollutants may be even more far-reaching by jeopardizing the functionality of eusocial colonies.

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

Genuine learning biases persist after accounting for temporally decreasing learning rates: Insight from fitting six datasets

Romane Cecchi, Stefano Palminteri

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

Noncircular rolling contact joints enable programmed behavior in robotic linkages

Colter J. Decker, Tony G. Chen, Michelle C. Yuen, Robert J. Wood

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Rolling contact joints (RCJs) guide motion in robotic linkages, including manipulators, surgical devices, prosthetics, and more. In this work, we present a generalized optimization method to tailor the kinematic properties of RCJs by simultaneously optimizing both noncircular surface geometries and internal actuation pulley shapes. Our approach accommodates multiple joint types, including passively coupled systems with programmable spring stiffness as well as actuated single or multilink mechanisms. We explicitly incorporate common and practical manufacturing constraints into our optimization framework, such as size and convexity constraints. To demonstrate this approach, we optimize an RCJ designed to replicate the trajectory of a human knee, achieving a 99.6% reduction in alignment error compared to revolute joints and a 99.3% error reduction compared to circular RCJs. Additionally, we show that optimized RCJs increase the load-carrying capacity of a two-finger gripper by more than 3.5 times compared to a comparable circular-jointed design, showcasing how joint optimization can enhance robotic performance.

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

Acquired motility of Babesia microti –infected red blood cells

Chao Li, Amy L. Apgar, Danielle M. Tufts, Tagbo H. R. Niepa

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Babesia microti is an intraerythrocytic protozoan parasite and the main causative agent of human babesiosis in the United States. While extensive research has focused on the prevalence of this vector-borne pathogen in natural populations, increases of human cases and clinical manifestation, and pathogen structure, little is known about the movements of B. microti within vertebrate red blood cells (RBCs). RBCs are nonmotile due to their lack of cellular structures for active movement. Here, we report a phenomenon in which B. microti –infected RBCs exhibit an acquired motility compared to uninfected RBCs. Using live-cell tracking, we observed a subset (around 1% in whole blood and 10% in 1:100 diluted blood) of infected RBCs displayed active movement. This acquired motility suggests that B. microti may induce host cell modifications that facilitate its survival, dissemination, or immune evasion potential, allowing it to successfully move through the blood and infect new RBCs. Our findings highlight unconventional RBC dynamics and a potential broad aspect of B. microti pathogenesis. Further investigation into the molecular mechanisms underlying this phenomenon could provide insights into parasite–host interactions and reveal targets for therapeutic intervention in treatment and/or prevention of babesiosis.

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

Mapping of the viral shunt across widespread coccolithophore blooms using metabolic biomarkers

Constanze Kuhlisch, Guy Schleyer, J. Michel Flores, Flora Vincent, Karine Labadie, Marine Vallet, Daniella Schatz, Assaf Vardi

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The viral shunt is a fundamental ecosystem process which diverts the flux of organic carbon fixed through photosynthesis during algal bloom events from heterotrophic grazers to bacteria. Through the extracellular release of metabolites, lytic viral infections supply 2 to 10% of photosynthetically fixed carbon in the ocean for bacterial respiration. Despite its significance for the carbon cycle, we lack tools to detect the viral shunt in the natural environment and assess its ecological impact. Here, we investigated the use of exometabolites as biomarkers for the viral shunt by applying molecular, metabolomics, and oceanographic tools to study bloom dynamics of the cosmopolitan microalga Gephyrocapsa huxleyi (formerly Emiliania huxleyi ) across the Atlantic Ocean, spanning four biogeochemical provinces between Iceland and Patagonia. We mapped the distinct metabolic footprint of its viral infections using exo- and endometabolomics and detected nineteen organohalogen metabolites across the blooms, showing their global distribution. A time-resolved comparison of particulate and dissolved metabolite pools during an induced mesocosm bloom revealed that virocells—actively infected host cells—were the source of the halogenated metabolites. Three trichloro-iodo metabolites were present during the demise of all virus-infected oceanic blooms, highlighting them as suitable metabolic biomarkers for the viral shunt. The environmental stability of these halometabolites in the dissolved organic matter pool over a few days can recapitulate viral infections at earlier stages of phytoplankton bloom succession. The chloro-iodo metabolites thereby expand the existing repertoire of metabolic biomarkers for viral infections at sea and may advance efforts to trace the biogeochemical impact of alga–virus interactions in the ocean.

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

Projecting nitrous oxide over the 21st century, uncertainty related to stratospheric loss

Michael J. Prather, Calum P. Wilson

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Extending the N 2 O lifetime derived from Microwave Limb Sounder satellite observations, we find a mean value of 117 y and a likely decrease of –1.4 ± 0.9% per decade over the period 2004 to 2024. This trend is consistent with the previously published 2004 to 2021 value of –2.1 ± 1.2% per decade. A more careful analysis of uncertainty now provides a more robust likely (one-sigma) range. From analyses of a range of factors controlling the N 2 O lifetime, we find that the decrease in lifetime can be explained by recent changes in stratospheric circulation and temperature. Projection of the lifetime change to 2100 shows that this effect is comparable to differences across the shared socioeconomic pathways used for climate projections and cannot be ignored. An updated evaluation of the N 2 O chemical feedbacks shows that this effect produces a relatively small shift in atmospheric abundance over the 21st century, but still an important shift, –11%, in the global warming potential of N 2 O.

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

Identification of a stylet-secreted effector protein family as a core component of root-knot nematode feeding tubes

Richard S. Hussey, Melissa G. Mitchum, Rebekah L. Paul, Raquel O. Rocha, John P. Shields, Lesa J. Beamer

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Proteins secreted from a mouth stylet of sedentary plant-parasitic root-knot nematodes self-polymerize to form a unique feeding tube structure within host cells modified into giant feeding cells by the nematode. Feeding tubes have essential functions as they complex with the host endomembrane system for nutrient uptake to sustain parasitism. Despite their significance, they remain one of the least understood aspects of nematode parasitism of plants. Their small size and location within giant-cells deeply embedded within galls encasing adult females has prohibited studies to isolate and discern their molecular composition. Here, we developed a protocol for the isolation and semipurification of root-knot nematode feeding tubes from giant-cell cytoplasm of several host plant species to provide a unique view of these structures at the light and scanning electron microscopy level revealing previously undescribed features of their structure. Our methods allowed for the isolation and solubilization of sufficient quantities of enriched feeding tubes enabling a comparative proteome analysis across host species that identified proteins with an increased likelihood to function in feeding tube formation. A comparison across root-knot nematode species further narrowed candidates to a conserved class of secretory proteins that specifically localized within secretory granules of the dorsal gland of adult females and in feeding tubes formed within host cell cytoplasm to unequivocally demonstrate these proteins as core components of feeding tubes. Our finding gives scientists a look into the protein composition of feeding tubes opening the door to a better understanding of their structure and function in nematode parasitism.

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

Quantum benchmarking of high-fidelity noise-biased operations on a detuned Kerr-cat qubit

Bingcheng Qing, Ahmed Hajr, Ke Wang, Gerwin Koolstra, Long B. Nguyen, Jordan Hines, Irwin Huang, Bibek Bhandari, Larry Chen, Ziqi Kang, Christian Jünger, Noah Goss, Nikitha Jain, Hyunseong Kim, Kan-Heng Lee, Akel Hashim, Nicholas E. Frattini, Zahra Pedramrazi, Justin Dressel, Andrew N. Jordan, David I. Santiago, Irfan Siddiqi

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Ubiquitous noise sources in quantum systems remain a key obstacle to building quantum computers, necessitating the use of quantum error correction codes. Recently, error-correcting codes tailored for noise-biased systems have been shown to offer high fault-tolerance thresholds and reduced hardware overhead, positioning noise-biased qubits as promising candidates for building universal quantum computers. However, quantum operations on these platforms remain challenging, and their noise structures have not yet been rigorously benchmarked to the same extent as those of conventional quantum hardware. In this work, we develop a comprehensive quantum control toolbox for a scalable noise-biased qubit, detuned Kerr-cat qubit, including initialization, universal single-qubit gates, and quantum nondemolition readout. We systematically characterize the noise structure of these operations using gate set tomography and dihedral randomized benchmarking, achieving high local gate fidelities, with F [ Z ( π / 2 ) ] = ( 99.18 ± 0.066 ) % and F [ X ( π / 2 ) ] = ( 92.5 ± 0.23 ) % . Notably, the noise bias of the detuned Kerr-cat qubit approaches 250 with a phase-flip time of 4 μ s , which outperforms its resonant-Kerr-cat qubit counterparts as reported previously, representing a state-of-the-art performance benchmark for Kerr-cat qubits. Moreover, our results reveal a critical overestimation of operational noise bias inferred from bit-flip and phase-flip times alone, highlighting the necessity of a precise and direct benchmarking for noise-biased qubit operations. Our work thus establishes a framework for systematically characterizing and validating the performance of quantum operations in structured-noise architectures, which lays the groundwork for implementing efficient quantum error correction in next-generation architectures.

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

Conformationally gated multisite proton-coupled electron transfer in the ribonucleotide reductase β subunit

Jiahua Deng, Sharon Hammes-Schiffer

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Ribonucleotide reductase (RNR) is an essential enzyme that converts ribonucleotides into deoxyribonucleotides, enabling DNA synthesis and repair in all living organisms. Central to class Ia RNR activity is a long-range radical transport pathway spanning ∼ 32 Å across the α and β subunits by a series of proton-coupled electron transfer (PCET) reactions. Although the collinear PCET reactions in the α subunit have been extensively studied, the multisite, orthogonal PCET reactions in the β subunit are less well understood. This work focuses on orthogonal PCET between the redox-active tryptophan, W48, and interfacial tyrosine, Y356, in the β subunit. Multiscale modeling strategies are employed to explore this PCET reaction. The simulations show that radical transfer from W48 to Y356 is thermodynamically favorable and is likely to occur by electron transfer from Y356 to the W48 cationic radical in conjunction with proton transfer from Y356 to a glutamate, E52, which forms a hydrogen-bonding interaction with Y356 following oxidation of W48. The conformational gating motion of Y356 is shown to be critical for allowing this residue to participate in PCET with W48 in the β subunit and with a tyrosine in the α subunit. Application of vibronically nonadiabatic PCET theory highlights the significance of hydrogen tunneling and conformational motions that shorten the distance between Y356 and E52. This work demonstrates how conformational gating, hydrogen-bonding networks, and hydration at the α / β interface modulate PCET in RNR. These fundamental insights are also applicable to other biomolecular systems and may guide therapeutic and protein engineering applications.

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

Intronic polyadenylation–derived long noncoding RNA modulates nucleolar integrity and function

Sumana Mallick, Pranita Borkar, Jaspreet Thind, Daniel Chung, Taylor Hubbs, Irtisha Singh

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RNAs transcribed from protein-coding gene loci are widely assumed to be translated into proteins. However, intronic polyadenylation (IPA) occurring near the transcription start site or within early introns can generate noncoding RNAs derived from protein-coding loci. Despite their abundance, the functional roles of such RNAs remain largely unexplored. In this study, we investigated one such noncoding RNA, CUL1-IPA , transcribed from the CUL1 gene locus. Our study revealed that CUL1-IPA is an RNA polymerase II–dependent IPA isoform that is polyadenylated, stable, and translocates to the nucleolus. Functional characterization demonstrated CUL1-IPA to play a critical role in maintaining nucleolar integrity. RNA-protein interaction assay identified GPATCH4 and NOP58, nucleolar proteins involved in ribosomal RNA (rRNA) processing, as binding partners of CUL1-IPA . Consistent with its localization and interactions, loss of CUL1-IPA led to the reduction in rRNA levels and consequent decrease in overall protein synthesis. This effect on rRNA levels could be reversed by reintroducing CUL1-IPA , confirming its functional importance. Furthermore, as nucleolar stress is known to affect cell cycle progression, we found that CUL1-IPA loss resulted in G2/M cell cycle phase arrest. Moreover, reduced CUL1-IPA expression was associated with improved survival outcomes in cancer patients. Together, our findings demonstrate that CUL1-IPA , an IPA-derived long noncoding RNA (lncRNA), forms an RNA-protein complex in the nucleolus to support nucleolar structure and function. This study provides an insight into the biological function of a lncRNA originating from a protein-coding gene and highlights the broader significance of IPA-derived noncoding RNAs as regulatory molecules.

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

Metabolite control of enzyme activity links stress to biosynthetic regulation

Wilhelmina van de Ven, Manhoi Hur, María Fernanda Gómez-Méndez, Jingzhe Guo, Haiyan Ke, Raisul Awal Mahmood, Sunghwan Kim, Thomas D. Sharkey, Katayoon Dehesh

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Cells must continuously adjust metabolic output to maintain homeostasis under changing environmental conditions, yet the mechanisms that enable rapid and reversible control of pathway activity remain largely unknown. The methylerythritol phosphate (MEP) pathway, of bacterial origin and conserved in plastid-bearing eukaryotes, including plants and apicomplexan parasites, produces isoprenoid precursors essential for growth and stress adaptation. Here, we identify methylerythritol cyclodiphosphate (MEcPP) as a dual-function metabolite that serves both as a biosynthetic intermediate and a direct modulator of enzyme activity. Genetic perturbations and high light stress revealed step-specific MEcPP accumulation independent of transcriptional regulation. Biochemical and protease-protection assays showed that MEcPP destabilizes and inhibits methylerythritol cytidylyltransferase (MCT) while modestly stabilizing hydroxymethylbutenyl diphosphate synthase (HDS). Molecular docking analyses indicate that MEcPP interacts directly with the MCT catalytic site, displacing the natural substrate and thereby attenuating enzyme activity, suggesting a competitive, feedback-like mechanism of metabolic control. These results define MEcPP as a metabolic feedback signal that translates stress-induced changes into targeted enzymatic control. This mechanism illustrates how pathway intermediates dynamically coordinate biosynthetic activity with environmental cues, representing a broadly conserved strategy for metabolite-driven control of cellular metabolism.

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

Next-generation anti-DLL3 radiopharmaceuticals targeting high-grade neuroendocrine lung and prostate cancers

Salomon Tendler, Roberto De Gregorio, Paul Balderes, Alexa L. Michel, Tran T. Hoang, David Bauer, Kathryn M. Tully, Joshua A. Korsen, Ivo C. Lorenz, Abdul G. Khan, Lukas Carter, Olivia Vergnolle, Irina V. Lebedeva, Elisabeth K. Nyakatura, Lisa Bodei, Michael J. Morris, John T. Poirier, Charles M. Rudin, Jason S. Lewis

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Delta-like ligand 3 (DLL3) is a tumor-selective cell surface protein upregulated in high-grade neuroendocrine tumors, including small-cell lung cancer (SCLC) and neuroendocrine prostate cancer (NEPC). Here, we report on the development of anti-DLL3 radioimmunoconjugates for use as either a diagnostic imaging tracer based on the positron-emitter zirconium-89 ( 89 Zr) or a therapeutic agent utilizing the beta-emitter lutetium-177 ( 177 Lu). To begin, we generated a panel of human monoclonal antibodies targeting human DLL3 by immunizing transgenic mice engineered with a human immunoglobulin repertoire. The panel was extensively screened to identify high-affinity internalizing monoclonal antibodies (mAbs) recognizing a diversity of DLL3 epitopes. Select mAbs were reformatted as fully human Fab-arm exchange-deficient IgG4 to reduce effector function and then produced by recombinant methods. A pilot immunoPET study was performed in athymic female nude mice bearing human NCI-H82 SCLC tumors to nominate a lead candidate. ImmunoPET identified [ 89 Zr]Zr-DFO-TDI-Y-010 as the top-performing diagnostic tracer, with excellent in vivo biodistribution and tumor-to-background-organ ratios consistently >4. Therapeutic studies with [ 177 Lu]Lu-CHX-A"-DTPA-TDI-Y-010 demonstrated strong antitumor effects, significantly improving ( P <0.05) overall survival compared with the benchmark clone [ 177 Lu]Lu-CHX-A"-DTPA-SC16.56 in two SCLC tumor models (NCI-H82 and Lu149) and achieving comparable overall survival in a NEPC tumor model.

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

A framework integrating multiscale in silico modeling and experimental data predicts CAR-NK cell cytotoxicity across target cell types

Saeed Ahmad, Kun Xing, Marcelo S. F. Pereira, Stephanie Castle, Harshana Rajakaruna, Indrani Nayak, William C. Stewart, Kyle A. Beckwith, Mitchell S. Cairo, Meisam Naeimi Kararoudi, Dean A. Lee, Jayajit Das

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Natural killer (NK) cells may be engineered with chimeric antigen receptors (CARs) to recognize tumor-associated antigens which bolsters their antitumor activity. More so than CAR-T cells, CAR-NK cell responses result from an integration of signals from a wider range of innate activating cytotoxic receptors, inhibitory receptors, and adhesion receptors in addition to the engineered CAR, making computational modeling of CAR-NK cell cytotoxicity more difficult than CAR-T cells. Uncovering mechanisms and predicting tumor cell responses to CAR-NK cytotoxicity is essential for improving therapeutic efficacy. The complexity of these effector–target interactions and the donor-to-donor variations in NK cell receptor (NKR) repertoire preclude the use of predictive models based on a single receptor, requiring function to be determined experimentally for each donor, CAR, and target combination. Computational modeling generates frameworks that allow the relationships of these factors to biologic outcomes to be explored without resource-consuming experiments. Here, we developed a computational mechanistic multiscale model which considers heterogenous expression of CARs, NKRs, adhesion receptors, and their cognate ligands, signal transduction, and NK cell-target cell population kinetics. The model is trained with quantitative flow cytometry and in-vitro cytotoxicity data and accurately predicts the short-term, long-term, and in-vivo cytotoxicity of CAR-NK cells. Furthermore, using Pareto optimization we explored the effect of CAR proportion and NK cell signaling on the differential cytotoxicity of CD33CAR-NK cells to cancer and healthy cells. This model can be extended to predict CAR-NK cytotoxicity across many antigens and tumor targets and serves as a tool to mechanistically explore CAR-NK signaling and biology.

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

A silent Kv channel subunit shapes PV neuron action potential waveform and short-term synaptic plasticity during high-frequency firing

Sanika Ganesh, Theresa M. Canty, Bernardo L. Sabatini

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Fast-spiking parvalbumin-positive (PV) neurons provide precisely timed, context-dependent inhibition within cortical circuits. PV neuron firing properties are specialized among cortical neurons, suggesting that they express a unique complement of ion channels. Here, we show that the PV-specific silent voltage-gated potassium (Kv) channel subunit Kv6.4 (encoded by Kcng4 ) modulates both intrinsic and synaptic properties of cortical PV neurons. Kv6.4 does not form functional channels on its own but, as shown in prior work, assembles with Kv2 subunits to create heterotetrameric channel complexes, effectively reducing Kv2-mediated delayed rectifier current. We find that Kcng4 expression is enriched within a distinct Pvalb -expressing subclass in primary somatosensory (S1) and motor (M1) cortex and emerges during postnatal development. In PV neurons, Kv6.4 loss reduces action potential (AP) height and width, hyperpolarizes the threshold and interspike potential, and accelerates AP upstroke particularly during repetitive firing. Kv6.4 loss, potentially due to the changes in AP waveform, also alters GABA release and paired-pulse depression at synapses made by PV onto pyramidal (PYR) neurons. The effects of Kv6.4 loss are amplified during high-frequency firing, within the physiological range of fast-spiking PV neurons, likely due to altered repolarization dynamics that accumulate across successive APs. These findings are thus consistent with the function of Kv6.4 in modifying Kv2-mediated delayed rectifier currents. Hence, Kv6.4 tunes the temporal precision of PV inhibitory output, a feature that may be critical for stable excitation–inhibition ratios and adaptive circuit function underlying learning and behavior.

Health-focused frames mobilize Americans to action to address LGBTQ inequality

Pia Dietze, Riana M. Brown, Maureen A. Craig

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“More than 1 in 8 LGBTQ people live in states where doctors can refuse to treat them.” This headline describes a flurry of laws passed in 2025 allowing doctors to refuse treatment of LGBTQ patients based on personal beliefs. This and other laws like it limit healthcare access and exacerbate health inequality for LGBTQ individuals. But health is not the only domain in which LGBTQ individuals face disparities. Long-standing inequalities also exist in other domains of life, for example, gay men earn up to 32% less wages than their heterosexual peers. In the current research, we ask if exposure to LGBTQ inequality in one domain (e.g., health) motivates more support for action than exposure to inequality in other domains (e.g., economics). In six experiments (five preregistered), we test our hypothesis that emphasizing health-based LGBTQ inequality (vs. economics and belonging) spurs engagement with and support for mitigating action (S1-2). We also investigate why people support action (S1a-1b) and what boosts support (S3a-3c). As predicted and preregistered, we find greater support for action to mitigate health-based LGBTQ inequality, compared to economics and belonging. This occurs, in part, because people blame LGBTQ individuals less for health (vs. economic) disparities and perceive health inequalities to violate morally sacred values, which is associated with greater perceived injustice. Finally, we find that connecting economic inequality to health inequality in individuals’ minds can increase support for mitigating economic inequality.

The racial and ethnic gap in behavioral measures rivals the gender gap in the United States

Aurélie Dariel, John C. Ham, Nikos Nikiforakis, Jan Stoop

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Behavioral research has been criticized for relying on demographically narrow WEIRD samples-Western, Educated, Industrialized, Rich, and Democratic. While recent work has expanded to explore cross-country behavioral differences, the study of within-country variation has largely focused on gender, ignoring race and ethnicity—so much so that the “W” in WEIRD might as well stand for “White.” Using incentivized tasks and a large, stratified sample of U.S. adults, we document substantial racial and ethnic gaps in competitiveness and risk tolerance both of which are widely studied behavioral measures: (non-Hispanic) Whites are less competitive and more risk tolerant than Blacks and Hispanics. These gaps are comparable in magnitude to the corresponding gender gaps in our sample. Notably, gender differences do not generalize across racial and ethnic groups: Whereas Whites and Hispanics exhibit gender gaps in competitiveness and risk tolerance, Black women neither shy away from competition nor are they less risk tolerant than Black men. These findings challenge prevailing generalizations in the literature and underscore the importance of examining race and ethnicity in behavioral research.

Transboundary water conflicts, cooperation, and pathways forward

Amir AghaKouchak, Annika Hjelmstad, Kasra Khodkar, Debora de Oliveira, Esra Aleisa, Augustina C. Alexander, David Lewis Feldman, Temur Khujanazarov, Kaveh Madani, Ali Mirchi, Daniel Placht, Dalal Najib

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For reducing premature adult mortality in India, education matters more than income

Moradhvaj Dhakad, Erich Striessnig, Nandita Saikia, Samir K.C., Wolfgang Lutz

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Preventing premature death is a global policy objective reflected in the SDGs. While numerous studies have found socioeconomic factors to be significantly associated with premature death everywhere in the world, the debate on the relative effect of such factors on mid-age (15 to 59 ages) has not received enough attention, particularly in low-income countries, where this question is pertinent due to scant resources in the healthcare sector. Using nationally representative, longitudinal data from the India Human Development Survey, we assess the relative importance of individual- and community-level education vs. income and wealth in India, where approximately 3 million premature deaths occur annually in mid-ages. We find a clear downward gradient in mid-age mortality with increasing education within each wealth category, whereas no consistent mortality advantage with increasing wealth status is visible within education subgroups. Multilevel logistic regression models show that the decline in the risk of death across the education spectrum by far exceeds (14% for male and 13% for female) the decline moving along the wealth distribution, even after controlling for other relevant demographic, socioeconomic, regional variables. Along with the direct effect of individual-level educational attainment, we also find a protective effect of education at the community level, particularly for women. Based on these findings, we infer that educational attainment is essential for reducing mid-age mortality in India. Population and health policies in developing countries, therefore, should focus on education to prevent adult mortality.

Early psychosocial deprivation alters the refinement of neural dynamics across adolescence

Marta Andujar, Lucrezia Liuzzi, Daniel S. Pine, Charles A. Nelson, Charles H. Zeanah, Nathan A. Fox, Bruno B. Averbeck

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Adolescence is a crucial period for the refinement of neural circuits and cognitive skills. During this time, executive functions mature alongside pronounced structural changes in the brain, including reductions in synapse density. Computational models suggest that synaptic pruning enhances performance by stabilizing neural dynamics—deepening attractor basins and accelerating return to baseline after perturbation. Here, we tested these predictions using EEG data from the Bucharest Early Intervention Project, a randomized controlled trial of foster care as an alternative to institutionalized care. Trial-by-trial EEG residuals during a Flanker task were modeled as a linear dynamical system, and changes in eigenvalue magnitude were tracked across adolescence. Across all groups, eigenvalues decreased with age, consistent with maturation of recurrent computations. However, children with histories of institutional care exhibited consistently higher eigenvalues, suggesting delayed or disrupted refinement of the neural dynamics. Importantly, higher eigenvalues were associated with poorer behavioral performance on the task, linking altered neural dynamics to altered executive functions. These findings demonstrate that early deprivation leaves a lasting imprint on the developmental trajectory of neural dynamics, affecting the maturation of brain systems underlying cognitive control.

Toddlers expect ingroup loyalty to override personal preferences when outgroups are present

Lin Bian, Renée Baillargeon

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When outgroups are present, adults may endorse ingroup choices that are at odds with their personal preferences, in an outward show of ingroup loyalty. Here, we examined whether 2-y-old toddlers ( N = 108) might already understand such shows of loyalty. In three violation-of-expectation experiments, toddlers watched interactions among a target individual, an ingroup member, and an outgroup member; group memberships were marked with novel labels. In the critical trials, the target individual chose between an ingroup- and an outgroup-associated toy. When the outgroup member was present during this selection process, toddlers expected the target individual to conform to her group’s norm and select the ingroup-associated toy, even when they knew she preferred the outgroup-associated toy. This was true whether or not the ingroup member remained in the scene; as long as the outgroup member was present, toddlers expected the target individual to select the ingroup-associated toy and no other toy. When the outgroup member was absent, however, toddlers expected the target individual to act on her personal preference, if any. They also held this expectation if no information was provided about group memberships. Together, these results indicate that by 2 y of age, toddlers a) construe individuals as possessed of both a personal and a social identity, b) understand that individuals may produce different actions in different contexts depending on which identity has precedence, and c) expect individuals’ social identity to take precedence in intergroup contexts even when it conflicts with their personal identity, in a show of ingroup loyalty.

The socioeconomic returns to citizenship: A randomized controlled trial

Jens Hainmueller, Elisa Cascardi, Michael Hotard, Rey Koslowski, Duncan Lawrence, Vasil Yasenov, David D. Laitin

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Based on observational studies, conventional wisdom suggests that citizenship carries economic benefits. We leverage a randomized experiment from New York where low-income registrants with permanent residency who wanted to become citizens entered a lottery to receive fee vouchers to naturalize. Voucher recipients were about 36 p.p. more likely to naturalize. Yet, we find no discernible effects of access to citizenship on multiple economic outcomes, including income, credit scores, access to credit, financial distress, and employment. Leveraging a multidimensional immigrant integration index, we similarly find no measurable effects on noneconomic integration. However, we do find that citizenship reduces fears of deportation. Explaining divergence from past studies, our results also reveal evidence of positive selection into citizenship, suggesting that observational studies are susceptible to selection bias.

Science Advances

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

The root nodule symbiosis regulator NIN exhibits broad DNA binding specificity conferred by an NLP-inherited motif

Shohei Nosaki, Momona Noda, Hiroki Onoda, Momoyo Ito, Takuya Suzaki

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Nitrogen-fixing root nodule symbiosis (RNS) occurs in some eudicots, including legumes, and is regulated by the transcription factor NODULE INCEPTION (NIN), derived from the NIN-LIKE PROTEIN (NLP) family. However, how the NIN protein acquired RNS-specific functions remains unclear. We identify a previously undescribed motif in Lotus japonicus NIN, located downstream of the RWP-RK domain, which we term the FR. This motif broadens NIN’s DNA binding specificity by stabilizing the RWP-RK dimer interface. nin mutants lacking the FR motif show defective nodulation and impaired nitrogen fixation. Arabidopsis NLP2 carries a NIN-type FR and shares key features with NIN. Furthermore, the NIN-type FR had already emerged before the divergence of gymnosperm and angiosperm lineages, suggesting that a specific molecular feature of NIN involved in RNS regulation was inherited from ancestral NLPs prior to the emergence of RNS.

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

Neuroimmune activation in temporal lobe epilepsy patients with worsening seizure following the COVID-19 pandemic: A [ 18 F]DPA-714 PET/MR study

Ling Xiao, Li Qin, Tao Jiang, Ming Qu, Manliu Hou, Yongxiang Tang, Shuo Hu, Li Feng

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Patients with temporal lobe epilepsy (TLE) frequently experience worsening epilepsy following COVID-19, referred to as post–COVID-19 active TLE. While neuroinflammatory changes are suspected in these patients, measurements of both central and systemic inflammation in the brain remain unexplored. We investigate whether the translocator protein standardized uptake value ratio (TSPO SUVr), a quantifiable marker of neuroinflammation using positron emission tomography (PET), is elevated in the brains of patients with post–COVID-19 active TLE. In addition, we examine correlations between TSPO SUVr and inflammatory factors to identify potential peripheral blood inflammatory predictors of post–COVID-19 active epilepsy. Our study highlights the presence of widespread neuroinflammation in the brain and increased levels of inflammatory cytokines in the plasma of individuals with post–COVID-19 active TLE. Furthermore, strong correlations between plasma levels of interleukin-1β (IL-1β), IL-10, and interferon-γ (IFN-γ) and neuroimmune activation suggest the potential for integrating plasma inflammatory factors with TSPO PET as a dependable approach for clinical diagnosis, dynamic monitoring, and assessment of immune-based therapeutic efficacy in TLE-associated neuroinflammation.

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

Complex perishable technologies from the North American Great Basin reveal specialized Late Pleistocene adaptations

Richard L. Rosencrance, Geoffrey M. Smith, Katelyn N. McDonough, Christopher S. Jazwa, Mariya Antonosyan, Elizabeth A. Kallenbach, Thomas J. Connolly, Brendan J. Culleton, Kathryn Puseman, Megan McGuinness, Dennis L. Jenkins, Daniel O. Stueber, Pam E. Endzweig, Patrick Roberts

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Structurally and functionally complex technologies were a defining element of Late Pleistocene societies, but physical examples of them remain extremely rare in the archaeological record because most were made from perishable raw materials. The sparse material record of those myriad technologies limits our ability to formulate nuanced models about this critical period in human history. We present radiocarbon, Zooarchaeology by Mass Spectrometry, and other taxonomic identification data from two of the largest Late Pleistocene perishable assemblages in the world, Cougar Mountain Cave and Paisley Caves, Oregon, US. These data include 66 radiocarbon dates on 55 items made from 15 different plant and animal taxa, including the oldest known physical remains of sewn hide. We provide data on eyed bone needles from four regional sites, showing that they are among the finest bone needles made in the Pleistocene. Our study illuminates the complex interplay of culture, climate, and technology in the Pleistocene.

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

Fungal infection drives metabolic reprogramming in epithelial cells via aerobic glycolysis and an alternative TCA cycle shunt

Aize Pellon, Shervin Dokht Sadeghi Nasab, Gholamreza Bidkhori, James S. Griffiths, Stefania Vaga, Neelu Begum, Mariana Blagojevic, Nitesh Kumar Sigh, Natalia K. Kotowicz, Ifeanyi Uzochukwu, Adrien Le Guennec, Rhonda Henley-Smith, Harry Gregson-Williams, Frederick Clasen, Miranda Pryce, Nadia Karimpour, Richard Cook, Juan Anguita, Jonathan P. Richardson, Selvam Thavaraj, Julian R. Naglik, Saeed Shoaie, David L. Moyes

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Candida albicans –induced immunometabolic changes drive complex responses in immune cells. However, whether and how C. albicans causes remodeling of oral epithelial cell (OEC) metabolism is unclear. Here, we use in vitro experiments and patient biopsies to demonstrate that OECs undergo metabolic reprogramming when infected by C. albicans independently of candidalysin secretion, increasing glycolysis and decreasing tricarboxylic acid (TCA) cycle activity. Glycolysis and glucose transport inhibition show that these pathways support OEC cytokine release, highlighting the partial control of antifungal epithelial immunity by cellular metabolism. However, glucose supplementation disrupts OEC responses both in vitro and in vivo, suggesting that the fungus benefits from these metabolic shifts and that increased aerobic glycolysis in OECs is detrimental. Genome-scale metabolic modeling predicted a shutdown of the TCA cycle and a previously unidentified role for glutamic-oxaloacetic transaminase 1 (GOT1) in response to C. albicans , which was subsequently shown to be important for OEC survival during infection. This study reveals a fundamental role for hexose metabolism and identifies a GOT1-mediated TCA cycle shunt in regulating OEC survival and immune responses during mucosal fungal infections.

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

Interface-engineered plasmonic covalent organic framework nanofilms on TiO 2 nanotubes for universal mass spectrometry imaging

Yizhu Xu, Xinzhou Wu, Weifeng Li, Jiadu Hu, Xiran Chen, Yingying Chen, Zhibin Yin, Wei Hang

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Covalent organic frameworks (COFs) hold promise for surface-assisted laser desorption/ionization mass spectrometry imaging (MSI), yet their integration with plasmonic nanostructured platforms remains unexplored. Here, we report a liquid-liquid interfacial self-assembly strategy to construct plasmonic gold nanoparticle–decorated COF nanofilms on titanium dioxide nanotubes. This hierarchical design synergizes plasmonic enhancement, efficient charge transfer, and enhanced ionization efficiency, achieving sensitivity improvement over conventional matrices. The plasmonic platform affords universal compatibility with currently available biosample preparation protocols including imprinting, stamping, and cryo-sectioning for multitissue MSI. The first whole-plant imprinting MSI of Vigna unguiculata reveals tissue-specific distributions of three pollutants with distinct translocation rate and endogenous metabolites. In addition, 10-micrometer resolution lipid mapping was achieved in stamped fingerprints and cryo-sectioned murine brains. Moreover, we successfully visualized ischemic stroke biomarkers in rat brains for interrogating the pathogenesis of focal ischemia. Our findings highlight the advantages of plasmonic COF nanofilms on titanium dioxide nanoarrays for universal matrix-free MSI in complex biological systems, bridging advanced materials and life science applications.

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

Quantum state revival via coherent energy redistribution

Benjamin Crockett, Nicola Montaut, James van Howe, Piotr Roztocki, Yang Liu, Robin Helsten, Wei Zhao, Roberto Morandotti, José Azaña

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Processing and detecting quantum states with high fidelity are essential for enabling quantum advantages across many applications. However, these states are known to be fragile because of their sensitivity to losses, their inability to be amplified, and their susceptibility to decoherence. This makes them far more vulnerable to noise than classical signals, limiting their out-of-lab deployment. We demonstrate quantum coherent energy redistribution, which not only recovers entangled states buried in noise but also improves their properties, moving toward noise-robust architectures with better deployability. Using standard telecommunications infrastructure, we show an order of magnitude increase in the coincidence-to-accidental ratio for time-bin entangled photon pairs. Furthermore, we demonstrate the revival of lost entanglement by recovering quantum interference visibility and fidelity from quantum state tomography measurements of qubits corrupted by noise.

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

A synthetic Antrodia cinnamomea galactomannan library by frameshift unveils a potent immunoregulatory octasaccharide domain

Qishuai Li, Xiao-Lin Zhang, Ran Liu, Peng Wang, Hongzhi Cao, Allan Wee Ren Ng, Yuan Qiao, Han Ding, Xue-Wei Liu, Ming Li

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We report the design, synthesis, and immunological evaluation of an Antrodia cinnamomea galactomannan library consisting of 11 oligosaccharides, with chain lengths ranging from 4 to 24 sugars. These oligosaccharides maintain a consistent composition of 75% mannose and 25% galactose, mirroring the key structural features of natural galactomannan. Notably, the library includes five tetrasaccharides and four octasaccharides, exhibiting all possible frameshift patterns of A. cinnamomea galactomannan, offering valuable materials for structure-activity relationship studies to explore the role of linking modes and domain effect. The synthesis of this library was achieved through a highly effective stereoselective α-galactosylation approach. Immunological evaluations revealed that octasaccharide 4 and its two subunit tetrasaccharides 7 and 10 exhibited potent immunoregulatory activities, demonstrating a notable domain effect. Preliminary mechanistic studies unveiled that these oligosaccharides exert their effects by suppressing mitogen-activated protein kinase signaling pathway. In addition, octasaccharide 4 uniquely attenuated nuclear factor κB pathway, highlighting its compound-specific mechanism and demonstrating a 1 + 1 > 2 effect.

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

Cryo-EM structure of human AQP11 reveals a trimeric architecture with a large pore

Shota Suzuki, Akiko Kamegawa, Daisuke Kozai, Kouki Nishikawa, Katsumasa Irie, Yoshinori Fujiyoshi

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Aquaporin-11 (AQP-11) is an endoplasmic reticulum-localized water channel essential for renal development. Its structure and the molecular basis of its transport properties remained unknown. We analyzed the human AQP11 structure under cryo–electron microscopy at 2.3 Å resolution, revealing a trimeric architecture compared with other known tetrameric AQPs and a topology comprising seven transmembrane helices (Hs), including an additional N-terminal helix (H0). The channel pore is broader and more hydrophobic than that of canonical AQPs, and features a unique structure surrounding an Asn-Pro-Cys (NPC) sequence instead of the typical Asn-Pro-Ala (NPA) motif. These features provide a structural framework through which water and other small solutes can permeate AQP11. Our findings provide a blueprint for designing specific inhibitors to investigate the physiologic functions of AQP11.

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

Electrolyte design for aqueous batteries

Hu Hong, Qingshun Nian, Xun Guo, Qing Li, Chunyi Zhi

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Aqueous batteries, with their inherent safety, operational simplicity, and cost-effectiveness, have emerged as promising candidates for grid-scale energy storage applications. However, the relatively low output voltage of aqueous systems continues to limit their achievable energy density. The aqueous electrolyte occupies a central role in addressing this limitation because it mediates ion transport and interfacial reactions at both the cathode and anode; accordingly, advances in electrolyte design are indispensable to meet future performance demands. In this review, we elucidate the core bottlenecks in aqueous electrolyte design, distill molecular-level design principles, and outline feasible pathways for future practical implementation. We aim to guide the development of next-generation aqueous electrolytes that harmonize outstanding electrochemical performance, thereby accelerating the transition from laboratory concepts to transformative energy solutions.

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

Pyruvate kinase muscle 2 (PKM2) promotes CD4 T cell survival by regulating pyruvate oxidation during homeostasis and expansion

Jeff J. Subleski, Erika M. Palmieri, Jessica F. Walls, Steven Hsu, Ian A. Bettencourt, Timothy R. Gower, Scott K. Durum, Daniel W. McVicar

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Glycolysis is an essential metabolic pathway for rapidly expanding T cells, but the role of pyruvate kinase muscle 1 (PKM1) and PKM2 in regulating this process is underappreciated. Here, using a pharmacological activator and targeted deletion of PKM2 in T cells, we delineated distinct functions of PKM1 and PKM2 in regulating CD4 T cell survival during homeostasis and expansion. Expanding PKM2-deficient CD4 T cells increased PKM1 expression with associated mitochondrial reactive oxygen species–mediated cell death. Examination of T cell compartments revealed that PKM2-deficient CD4 T cells were unaltered in the thymus but were significantly reduced in peripheral tissues as mice aged. The inability of PKM1 to protect CD4 T cells in the absence of PKM2 led to less severe T cell–mediated colitis as PKM2-deficient pathogenic cells were significantly reduced compared with control cells. This study shows that PKM2 is critical for CD4 T cell survival during expansion and homeostasis.

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

Hybrid female sterility due to cohesin protection errors in mouse oocytes

Warif El Yakoubi, Bo Pan, Takashi Akera

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Hybrid incompatibility can lead to lethality and sterility of F1 hybrids, promoting speciation. The cell biological basis underlying hybrid incompatibility remains largely unknown, especially in mammals. Here, we found that female hybrids between Mus musculus domesticus and Mus spicilegus mice are sterile due to the failure of homologous-chromosome separation in oocyte meiosis, producing aneuploid eggs. This nondisjunction phenotype was driven by the mislocalization of the cohesin protector, SGO2, along the chromosome arms instead of its typical centromeric enrichment, resulting in cohesin overprotection. The upstream kinase, BUB1, showed a higher activity in hybrid oocytes, explaining SGO2 mistargeting. Higher BUB1 activity was not observed in mitosis, consistent with viable hybrid mice. Cohesion defects were also evident in hybrid mice from another genus, Peromyscus , wherein cohesin protection is weakened. Defective cohesion in oocytes is a leading cause of reduced fertility. Our work provides evidence that a major cause of human infertility may play a positive role in mammalian speciation.

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

Optoacoustically augmented magnetic guidewire for radiation-free minimally invasive therapies

Fan Wang, Xianqiang Bao, Erdost Yildiz, Yan Yu, Xosé Luís Deán-Ben, Wenbin Kang, Shuaizhong Zhang, Devin Sheehan, Ren Hao Soon, Jelena Zinnanti, Daniel Razansky, Metin Sitti

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Endovascular interventions are essential for treating cerebrovascular diseases, yet their monitoring methods commonly rely on ionizing radiation and contrast agents, posing unnecessary risks to patients and clinicians. We present a multifunctional optoacoustically augmented magnetic guidewire (OptoMaG) that integrates optoacoustic imaging with magnetic navigation to enable radiation-free, image-guided interventions. The ~250-micrometer flexible guidewire incorporates a 460-nanometer luminescent core with an enhanced optoacoustic signature and a FePt magnetic tip for precise, steerable control. Proof-of-concept studies show that OptoMaG can be actively navigated with external magnetic fields to traverse a 3D human-scale cerebrovascular phantom and accurately reach target brain sites. Beyond navigation, the FePt tip enables localized thermal ablation under remote radiofrequency stimulation, highlighting its theranostic potential for tumor treatment. In addition, OptoMaG functions as a light source for photodynamic therapy, selectively activating photosensitizers to destroy tumor cells while preserving healthy tissue. Collectively, OptoMaG provides a safe, radiation-free platform merging real-time navigation with targeted therapeutic capabilities.

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

Hydrostatic pressure induces strong leakage of dissolved organic matter from “marine snow” particles

Peter Stief, Jutta Niggemann, Margot Bligh, Hagen Buck-Wiese, Urban Wünsch, Michael Steinke, Jan-Hendrik Hehemann, Ronnie N. Glud

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Marine snow forms at the ocean surface, sinks to depth, and ultimately enables carbon sequestration in the seabed. Fast-sinking marine snow particles, such as diatom aggregates, encounter a rapid increase in hydrostatic pressure during their descent. Using incubations in rotating pressure tanks, we found that pressure levels corresponding to 2- to 6-kilometer water depth induce leakage of dissolved organic matter (DOM) from diatom aggregates equivalent to ~50% of their initial carbon contents. The leaked DOM proved to be diatom-derived and changed the amount and composition of DOM in the surrounding seawater substantially. Ultrahigh-resolution mass spectrometry, high protein-like fluorescence, and low carbon:nitrogen ratios classified the leaked DOM as labile. The bioavailability of leaked DOM was demonstrated by its rapid utilization by a pelagic microbial community, leaving mainly recalcitrant DOM behind. Pressure-induced DOM leakage likely weakens the gravitational “biological carbon pump” and supplies labile DOM to the pelagic microbiome of the deep ocean.

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

The ocean’s biological carbon pump under pressure

Jack J. Middelburg

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Increasing hydrostatic pressure induces the release of dissolved organic matter from rapidly settling marine particles and contributes to the depth attenuation of carbon fluxes.

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

The gut-brain vagal axis governs mesolimbic dopamine dynamics and reward events

Oriane Onimus, Faustine Arrivet, Tinaïg Le Borgne, Sylvie Perez, Julien Castel, Anthony Ansoult, Benoit Bertrand, Nejmeh Mashhour, Camille de Almeida, Linh-Chi Bui, Marie Vandecasteele, Serge Luquet, Laurent Venance, Nicolas Heck, Fabio Marti, Giuseppe Gangarossa

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Reward processes have traditionally been ascribed to dopamine (DA)–associated circuits. While external stimuli, such as food and drugs of abuse, are activators of DA-neuron activity, growing evidence indicates that interoceptive signals also play a critical role. Among these, the gut-brain vagal axis has emerged as a key regulator, although its precise contribution to mesolimbic DA signaling and behavior remains unclear. Here, we combine complementary ex vivo and in vivo approaches across multiple scales to show that gut-brain vagal tone is essential for gating mesolimbic DA system activity and functions, modulating DA-dependent molecular and cellular processes, and scaling both food- and drug-induced reinforcement. These findings challenge the traditional brain-centric view of reward processing, supporting a more integrated model in which vagus-mediated interoceptive signals intrinsically shape motivation and reinforcement. By uncovering the influence of gut-brain vagal communication on DA functions, this work provides insights into the neurobiology of adaptive and maladaptive reward, with broad relevance for eating disorders and addiction.

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

OsRNS4-mediated cross-kingdom RNA interference is inhibited by Ustilaginoidea virens effector SCRE2 to promote infection in rice

Han Gao, Anfei Fang, Wu Yang, Shanshan Qiu, Xinhang Zheng, Shanzhi Wang, Jing Fan, Hailong Guo, Fuhao Cui, Yong-Hwan Lee, Jiyang Wang, Wenxian Sun

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The Ustilaginoidea virens effector SCRE2 has been previously identified to be an essential virulence factor. To elucidate molecular mechanisms underlying SCRE2 virulence function, we identify that SCRE2 interacts with Oryza sativa S-like ribonuclease family member OsRNS4. As a catalytically inactive RNase, OsRNS4 positively regulates rice immunity, depending on its RNA binding ability. OsRNS4 is unconventionally secreted through tetraspanin-positive extracellular vesicles (EVs). OsRNS4 binds to certain groups of rice miRNAs, whereas SCRE2 prevents the binding of OsRNS4 to miRNAs. Especially, OsRNS4-bound miR528-5p in rice is detected in false smut balls and silences the gene UvSfk1 essential for U. virens virulence. Thus, OsRNS4 might act as a carrier to transport miRNAs from rice into fungi, which target the virulence genes in U. virens and thereby contributes to rice resistance against fungal pathogens. As an unidentified counter-defense mechanism, SCRE2 suppresses cross-kingdom RNA interference to promote infection through inhibiting OsRNS4 binding to miRNAs.

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

Computational rational design of unspecific peroxygenase for C-H oxidation

Ruichen Gao, Xiaodi Fu, Zonglin Li, Zhiyao Wang, Guanjian Li, Jun Ge, Frank Hollmann, Zhanfeng Wang, Wen-Yong Lou, Xiaoling Wu

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Computational rational design has emerged as a transformative approach to engineer enzymes with tailored selectivity and efficiency. In the context of carbon-hydrogen oxidation, a key challenge in synthetic chemistry, unspecific peroxygenases (UPOs) directly oxidize unactivated carbon-hydrogen bonds using hydrogen peroxide, yet their utility is limited by low activity and imperfect selectivity. By computational rational design, this study systematically navigated vast sequence spaces to identify mutations that enhance catalytic performance of UPOs, lastly yielded UPO variants with 13-fold enhanced activity and >99% enantioselectivity, and revealed the dominant role of residue Lys 165 in activity and enantioselectivity. This study shows how computational strategies overcome evolutionary constraints to deliver efficient biocatalysts for synthetic chemistry.

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

Introgressed mitochondrial fragments from archaic hominins alter nuclear genome function in modern humans

Qiong Zhu, Jinning Zhang, Weichen Zhou, Shen-Ao Liang, Shengmiao Wang, Xinyu Cai, Fuyuan Li, Jin Li, Guojie Zhang, Huijuan Feng, Qiaomei Fu, Joshua M. Akey, Feng Zhang, Li Jin, Shuhua Xu, Hong-Xiang Zheng, Lu Chen

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Archaic introgression introduced functionally relevant variants into modern humans, yet small-scale insertions remain understudied. Here, we leverage 2519 modern human genomes and four high-coverage archaic hominin genomes to systematically characterize nuclear mitochondrial DNA segments (NUMTs). We uncover 483 polymorphic NUMTs across globally diverse human populations and 10 in archaic genomes. By combining overlap with Neanderthal-derived and Denisovan-derived haplotypes, phylogenetic analyses, insertion time estimates, and haplotype colocalization, we identify five NUMTs introduced into modern humans via archaic hominin introgression. Functional analyses reveal that introgressed NUMTs can modulate gene expression, including allele-specific up-regulation of the immune-related gene RASGRP3 , and reshape three-dimensional chromatin structure at loci such as SCD5 and HNRNPD . These findings highlight an underappreciated mechanism by which archaic mitochondrial fragments shape nuclear genome function and evolution. Our study reframes NUMTs not as passive genomic fossils but as dynamic elements influencing modern human diversity and adaptation.

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

Overcoming host restrictions to enable continuous passaging of GII.3 human norovirus in human intestinal enteroids

Gurpreet Kaur, Sue E. Crawford, Sara Javornik Cregeen, Anil Surathu, B. Vijayalakshmi Ayyar, Carmen V. Apostol, Hoa Nguyen Phuc, Khalil Ettayebi, Aaya Boussattach, Xi-Lei Zeng, Sarah E. Blutt, Harsha Doddapaneni, Donna M. Muzny, Cristian Coarfa, Ramakrishnan Anish, B. V. Venkataram Prasad, Robert L. Atmar, Sasirekha Ramani, Mary K. Estes

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The establishment of human intestinal enteroids (HIEs) as a model for human norovirus (HuNoV) replication has been transformative for studying this leading cause of gastroenteritis. However, indefinite passaging of HuNoVs in HIEs remained a challenge, necessitating the use of patient stool samples as viral inocula. Using RNA-seq, we identified CXCL10, CXCL11, and CCL5 as up-regulated chemokines, suggesting their potential as host restriction factors. TAK-779, a CXCR3/CCR5/CCR2 antagonist, enhanced GII.3 HuNoV replication and viral spread in a dose- and time-dependent manner, enabling successful passaging of GII.3 HuNoV in two different HIE lines and generation of viral stocks. Sequencing passaged virus revealed one consensus change in the major capsid protein and several dynamic adaptations, suggesting emergence of variants. TAK-779 also enhanced replication of GI.1 and GII.17 strains, but not GII.4, suggesting strain-specific host interactions. This breakthrough in passaging provides insight into HuNoV-host interactions, establishes a scalable in vitro system for virus propagation, and opens avenues for structural, biochemical, and therapeutic studies.

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

Oriented cell divisions induce basal progenitors and regulate neural expansion across tissues and species

Benoit Boulan, Marine Lacomme, Amin Benadjal, Miranda Krueger, Ko Currie, Anna La Torre, Alain Chédotal, Michel Cayouette

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Nervous system expansion relies on progenitor proliferation, yet its regional and evolutionary regulation is incompletely understood. While basally dividing progenitors are implicated in neocortical growth, their developmental origins and relevance beyond the cortex remain unclear. We show here that double inactivation of spindle orientation regulators GPSM2 and SAPCD2 in mice completely reorients progenitor divisions in both the neocortex and retina. This shift increases basal progenitors over sixfold in the neocortex and induces their ectopic emergence in the retina, resulting in extra cell layers and ~30% tissue enlargement. Single-cell RNA sequencing reveals that the induced basal progenitors in the cortex resemble human outer radial glia, and both cortical and retinal progenitors show altered Hippo signaling. Last, macaque and human retinas display twice as many reoriented divisions as the mouse and naturally contain basal progenitors. These findings show that division orientation is critical for regulating neural progenitor output and scaling tissue growth.

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

Noninvasive photoacoustic computed mesoscopy for longitudinal brain imaging

Shijie Ruan, Wei Qin, Linyang Li, Tingting Li, Baochen Li, Xiao Liang, Lei Xi

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Photoacoustic imaging has become a powerful tool for visualizing the brain morphology, function, and metabolism. However, severe optical scattering and high-frequency acoustic attenuation within the brain degrade the performance of photoacoustic brain imaging. To address such limitation, we propose a line scanning–based photoacoustic computed mesoscopic (PACMes) approach for noninvasive, high-resolution, and longitudinal visualization of cerebral vasculature inside the intact mouse brain. This technique uses converging near-infrared (NIR) lines scanned at multiple angles for tight optical excitation; a low-frequency, full-ring ultrasound transducer array for high-sensitivity detection; and a compound reconstruction algorithm integrating filtered back-projection and optical localization of photoacoustic signals to recover the image. We perform long-term (>5 months), noninvasive imaging of the entire cortex of mice through the intact scalp and skull with a field of view of 13 millimeters and a spatial resolution of 33 micrometers. The results demonstrate the potential of PACMes for investigating brain function and disease.

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

Kilometer-scale convection-allowing model emulation using generative diffusion modeling

Jaideep Pathak, Yair Cohen, Piyush Garg, Peter Harrington, Noah Brenowitz, Dale Durran, Morteza Mardani, Arash Vahdat, Shaoming Xu, Karthik Kashinath, Michael Pritchard

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Storm-scale convection-allowing models (CAMs) explicitly resolve convective dynamics within the atmosphere to predict the evolution of thunderstorms and mesoscale convective systems that result in damaging extreme weather. Deep learning models have, thus far, not proven skillful in this regime of kilometer-scale atmospheric simulation, despite being competitive at coarser resolutions with state-of-the-art global, medium-range weather forecasting. We present a generative diffusion model called StormCast, which emulates the High-Resolution Rapid Refresh (HRRR)—National Oceanic and Atmospheric Administration’s state-of-the-art 3-kilometer operational CAM. StormCast autoregressively predicts 99 state variables at the kilometer scale using a 1-hour time step, with dense vertical resolution in the atmospheric boundary layer, conditioned on 26 synoptic variables. We show successfully learned kilometer-scale dynamics including competitive 1- to 6-hour forecast skill for composite radar reflectivity alongside physically realistic convective cluster evolution, moist updrafts, and cold pool morphology. These results present opportunities for improving kilometer-scale regional ML weather prediction and future climate hazard dynamical downscaling.

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

Self-modifying percolation governs detachment in soft suction wet adhesion

Abdallah Aly, M. Taher A. Saif

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Aquatic animals such as octopuses use soft suction cups to solve the persistent challenge of wet attachment on rough surfaces. Detachment has long been described as smooth drainage governed by a Reynolds-type pressure gradient. Combining spatiotemporal pressure mapping with confocal imaging of the fluid layer between a suction cup-substrate interface, we reveal a two-stage, nonequilibrium pathway for pressure equalization that challenges this conventional view. Suction-induced elastic deformation dynamically remodels the interfacial fluid, producing a self-coupled pressure channel system. Stage I is governed by an outward-moving invasion-percolation suction front with diffusion-like scaling. When internal suction falls below a critical value, the network opens globally, and stage II follows classical Poiseuille drainage. This mechanism defines a self-modifying percolation in which the flow remodels its own pathways, which advances our understanding of biological suction and viscous adhesion and suggests design principles for long-lived wet adhesives and hydrogel microfluidics.

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

Observation of super-ballistic Brownian motion in liquid

Jason Boynewicz, Michael C. Thumann, Mark G. Raizen

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Brownian motion is a foundational physical process characterized by a mean squared displacement that scales linearly in time in thermal equilibrium, known as diffusion. At short times, the mean squared displacement becomes ballistic, scaling as t 2 . This effect was predicted by Einstein in 1907 and recently observed experimentally. We report that this picture is only true on average; by conditioning specific initial velocities, we predict theoretically and confirm by experiment that the mean squared displacement becomes super-ballistic, with a power scaling law of t 5 / 2 . This result is due to the colored noise of incompressible fluids, resulting in a nonzero first moment for the thermal force when conditioned on nonzero initial velocities. These results are a step toward the unraveling of nonequilibrium dynamics of fluids.

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

Induction of collective behavior by β-1,3-glucans in microalgae

Lou Lambert, Richard G. Dorrell, Antoine Danon

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β-1,3-glucans are multifaceted molecules, playing a key role in aquatic ecosystems where they store atmospheric CO 2 , as well as in human health, where they help fight pathogens and have anticancer properties. Until now, no role other than sugar storage had been attributed to β-1,3-glucans in algae. We show here that in Chlamydomonas reinhardtii , β-1,3-glucans control aggregation, a collective behavior in response to stress. We have identified the enzymes specifically involved in β-1,3-glucan synthesis and degradation during aggregation. The transcriptome of β-1,3-glucan–induced aggregation revealed an early effect of this elicitor. A comparative genomic analysis allowed us to envisage a potential role for β-1,3-glucans in the transition to multicellularity in Volvocales. The finding of the function of β-1,3-glucans in the stress response of the unicellular model organism Chlamydomonas sheds light into their mode of action. This is particularly relevant given their potential roles combatting pathogenic fungi in plants and animals.

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

Single-molecule localization microscopy reveals the molecular organization of endogenous membrane receptors

Patrick Eiring, Maximilian J. Steinhardt, Nele Bauer, Cornelia Vogt, Umair Munawar, Seungbin Han, Thomas Nerreter, Hermann Einsele, K. Martin Kortüm, Sören Doose, Markus Sauer

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Super-resolution microscopy in combination with genetic labeling methods allows imaging of single proteins in cells. However, visualizing endogenous proteins on primary cells remains challenging due to the use of sterically demanding antibodies for labeling. Here, we demonstrate how immunolabeling conditions and antibody cross-linking influence the quantification and identification of membrane receptor stoichiometry on cells using single-molecule localization microscopy. We developed an optimized immunolabeling and analysis protocol and demonstrate the performance of the approach by resolving the molecular organization of endogenous CD45, CD69, and CD38 on Jurkat T cells. To demonstrate the usefulness of the method for immunotherapy applications, we investigated the interaction of primary multiple myeloma cells with the therapeutic monoclonal antibodies daratumumab and isatuximab and a polyclonal anti-CD38 antibody. Our approach might lay the foundation for improved personalized diagnostics and treatment with therapeutic antibodies.

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

Volcanism-induced collapse and recovery of the Atlantic meridional overturning circulation under glacial conditions

Guido Vettoretti, Ruei-Jia Hu, Ingo Bethke, Kirstin Krüger, Michael Sigl, Stephen Outten, Jaimei Lin, Roman Nuterman, Anders Svensson, Peter Ditlevsen, Markus Jochum

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Volcanic eruptions have considerable impacts on climate across various timescales; however, it remains uncertain if, and how, volcanic activity could drive climate change over multiple millennia. Here we incorporate realistic volcanic forcing into a large ensemble of glacial era–coupled atmosphere-ocean model simulations. These simulations are constrained by sulfate records from ice cores, which help estimate the timing of past major eruptions. We investigate how volcanic eruptions may have occasionally triggered abrupt climate change during the last glacial period. Our results show that very large equatorial eruptions can induce large changes in the Atlantic Meridional Overturning Circulation via atmospheric and ocean circulation changes and air-sea buoyancy fluxes, potentially pushing the climate system between persistent warm and cold states lasting millennia. A simplified perspective of the dynamics shows how unforced natural climate variability may exert a stabilizing influence decades after an eruption, especially as the system nears a tipping point.

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

Nanocollision promotes locomotion of dendritic cells for tumor therapy

Qiangyuan Zhu, Shenglan Liu, Lei Chen, Xin Wang, Jiayi Liu, Cen Gao, Rongbing Tang

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Mechanical stimuli originating from extracellular matrix have been proved to affect antitumor immunity by regulating dendritic cell (DC) locomotion. However, the immunological consequences of ultrasmall bioparticle–induced nanocollision remain largely an unexplored realm despite its ubiquitous and incessant occurrence within the in vivo milieu. Herein, we disclose that nanocollisions caused by endogenous bioparticles, such as extracellular vesicles, can induce localized membrane deformations. This spatially confined mechanical input activates Piezo1 at collision sites and promotes myosin IIA phosphorylation–mediated F-actin stabilization, enhancing DC intrinsic motility. Subsequent diffusion of Ca 2+ up-regulates chemotaxis machinery, improving their capacity of tumor microenvironment patrolling and lymph node homing for antitumor immunity. This finding reveals a previously unidentified mechanoimmunological mechanism of immune surveillance. To accelerate the translation of this mechanism into clinical therapeutics, we developed an ultrasound-responsive nanocollision generator using gas-liquid-solid triphase conversion. This system achieves precise nanocollision to augment DC locomotion, promoting antitumor immunity in vivo.

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

A genetic screen for modifiers of cohesin clustering identifies regulators of genome folding

Wonho Kim, Daniel S. Park, Son C. Nguyen, Rachel Yang, Eric F. Joyce, Rajan Jain

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The cohesin complex orchestrates 3D genome architecture through multiple steps including loading onto chromatin, DNA loop extrusion, stalling of extrusion, and unloading off chromatin. However, the upstream regulatory factors modulating these steps remain largely unexplored. Previous studies suggest that cohesin clustering correlates with its chromatin residence time and loop extrusion activity. Here, we developed, optimized, and performed an imaging-based genetic screen leveraging modulation of cohesin clustering to identify cohesin regulators. Using a sensitized background in which the cohesin unloader WAPL is partially degraded, we screened the druggable genome for effects on cohesin clustering. Through multiple rounds of screening and experimentation, we identified 7 enhancers and 10 suppressors of cohesin clustering. Several factors control genome folding at multiple loci and cohesin loading. Notably, our screen identified factors in mitochondrial function and epigenetic silencing, implicating these processes in the regulation of cohesin activity. This study offers a valuable resource identifying cohesin regulators and provides insights into upstream mechanisms governing genome folding.

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

Multimodal social context modulates larval behavior in Drosophila

Akhila Mudunuri, Élyse Zadigue-Dubé, Katrin Vogt

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All animals need to navigate and make decisions in social environments. They influence each other’s behavior, but how important this is and how they process and represent social information in their brain are less well understood. This includes fruit flies and larvae, usually not known as “social insects.” Using a Drosophila larva assay with reduced stimulation, we found that groups show enhanced dispersal and distance from each other in the absence of food. This social context–dependent modulation overrides responses to many external sensory cues and is shaped by developmental social experience. Leveraging the genetic toolbox available in Drosophila , we find that different sensory modalities are required for social context modulation. Our results show that even less social animals such as fly larvae are affected by conspecifics and recognize each other through multimodal sensory cues. This study provides a tractable system for future dissection of the neural circuit mechanisms underlying social interactions.

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

Monitoring glioblastoma extracellular vesicle evolution using a nanodiagnostic platform to detect glioma stem cells driving recurrent disease

Zhen Zhang, Richard J. Lobb, Paul Tooney, Jing Wang, Rebecca Lane, Quan Zhou, Xueming Niu, Sam Faulkner, Oun Al-Iedani, Bryan W. Day, Simon Puttick, Stephen Rose, Mike Fay, Matt Trau

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Assessing therapeutic response in glioblastoma (GBM) is a major factor limiting the clinical development of effective therapies. The intracranial location limits serial biopsies and only provides an intermittent view of the tumor molecular profile from the initial resection. Liquid biopsy techniques, specifically small extracellular vesicle (sEV) analysis, have the potential to overcome these limitations by providing a window into the brain using peripheral blood. To address the need for monitoring tumor evolution and therapeutic resistance, we developed a GBM biomarker panel (ATPase subunit beta-2, excitatory amino acid transporter 2, CD24, CD44, CD133, and epidermal growth factor receptor) for multiplexed profiling of sEVs using an advanced GBM Extracellular Vesicle Monitoring Phenotypic Analyzer Chip. We successfully tracked patient response to treatment by monitoring changes in glioma stem cell markers on circulating sEVs. We propose that these results provide a strong rationale for using GBM sEVs as a serial monitoring tool in the future clinical management of patients with GBM.

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

Discovery and preclinical evaluation of monoclonal antibodies and bispecific engagers targeting the NKG2A inhibitory receptor

Seungmin Shin, Yae-Jin Kim, Bernard J. C. Macatangay, Joshua C. Cyktor, Margaret G. Hines, Ze-Yu Sun, Kong Chen, John W. Mellors, Dimiter S. Dimitrov, Wei Li, Du-San Baek

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NK and T cells are key effectors that eliminate cancer cells, but upregulation of the inhibitory receptor NKG2A on these cells attenuates antitumor immune responses. To counteract NKG2A inhibitory signaling, we identified two specific fully human monoclonal anti-NKG2A antibodies that block HLA-E ligand binding. These antibodies activated NK cells and enhanced antibody-dependent cellular cytotoxicity of tumor-targeting IgG1s both in vitro and in vivo. Bispecific engagers (BiNKs), generated by fusing NKG2A antibodies with tumor targeting binders, promoted immune synapse formation and directed cytotoxicity of NK and CD8 + T cells toward cancer cells. In a human PBMC-engrafted NSG mouse xenograft lung cancer model, an anti-HER2 × anti-NKG2A BiNK markedly inhibited tumor growth as a monotherapy or in combination with pertuzumab. Cell depletion studies revealed that the BiNK enhanced antitumor activity of both NK and T cells. NKG2A blockade with potent and specific, fully human antibodies and BiNKs show promise for further development as cancer immunotherapeutics.

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

An electrophilicity-engineered magnetic sensor for MRI detection of dormant tumor cell clusters

Zeyu Liang, Bo Zhang, Xun Liu, Lin Xiao, Shangzhi Xie, Hui Du, Qiyue Wang, Fangyuan Li, Daishun Ling

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In magnetic resonance imaging (MRI), direct dipole-dipole interactions between paramagnetic metal centers and water molecules govern the T 1 relaxation of contrast agents. Metal chelates featuring multiple unpaired electrons have long dominated MRI contrast agents. Despite theoretically offering more paramagnetic centers per probe, nanoparticle-based contrast agents have struggled because of the insufficient direct dipolar interactions with water, impeding their clinical adoption. Here, we present an electrophilicity-engineered magnetic sensor (EEMS), which leverages high-electronegativity metal atoms to enhance the electrophilicity of paramagnetic centers in nanosensors, enabling direct electrophilic catalytic dipolar interactions (ECD) with water for enhanced MRI. EEMS demonstrates robust T 1 contrast with a longitudinal relaxivity of 23.2 per millimolar per second at 9 tesla, visualizing tumor cell clusters as small as 68.5 micrometer in vivo. ECD-MRI allows detecting and precise resection of axillary lymph nodes containing dormant tumor cell clusters, achieving 100% survival in mice 100 days postsurgery. EEMS-enhanced ECD-MRI presents a transformative imaging principle for noninvasive visualization of previously undetectable biological entities.

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

Inhibition of focal adhesion kinase impairs tumor formation and preserves hearing in a murine model of NF2-related schwannomatosis

Dana K. Mitchell, Kylee Brewster, Li Jiang, Henry Mang, Waylan K. Bessler, Xiaohong Li, Qingbo Lu, Shaomin Qian, Eric York, Sarah K. Morrow, Shelley A. H. Dixon, Christopher Davis, Ka-Kui Chan, Abbi Smith, Alyssa C. Flint, Victor V. Le, Anna Geisinger, Francis Enane, Behnam Nabet, Steven D. Rhodes, Steven P. Angus, D. Wade Clapp

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NF2 (neurofibromatosis type 2)–related schwannomatosis (NF2-SWN) is a cancer predisposition syndrome characterized by the development of bilateral vestibular (VS) and spinal schwannomas. While benign, these tumors can cause substantial morbidity, and effective pharmacological treatments remain limited. Here, we demonstrate that genetic ablation of focal adhesion kinase ( Fak/Ptk2 ) impairs tumor formation and preserves hearing in a murine model of NF2. Mechanistically, we show that Fak deletion decreases macrophage infiltration, attenuates nucleotide-binding oligomerization domain–containing protein 2–, leucine rich repeats (LRR)- and pyrin domain–containing protein 3 inflammasome activation, and suppresses the hepatocyte growth factor–MET axis. Pharmacological inhibition of FAK with single agent VS-4718 did not significantly reduce macroscopic tumor volume; however, its use in combination with the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib resulted in both a significant reduction in tumor volume and the preservation of dorsal root ganglion architecture. Our findings establish a critical role for FAK in schwannoma development and provide rationale for evaluation of combination FAK plus MEK inhibition in future clinical trials for NF2-associated SWN.

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

Structural insight into the glucose-6-phosphate transport by G6PT1 and inhibition mechanism of CGA

Qihao Chen, Pu Yuan, Renjie Li, Xiaoyue Du, Rilei Yu, Yan Zhao

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Human glucose-6-phosphate transporter 1 (G6PT1) is responsible for transporting glucose-6-phosphate (G6P) into the endoplasmic reticulum (ER), a crucial rate-limiting step in both glycogenolysis and gluconeogenesis. Complete and chronic dysfunction of G6PT1 can lead to the severe metabolic disorder GSD1b, whereas moderate and reversible inhibition contributes to diabetes treatment. We determined the structures of human G6PT1 in its apo state and in complex with the substrate G6P, cosubstrate phosphate, and the inhibitor chlorogenic acid (CGA). Captured in both lumen- and cytosol-facing conformations, these structures reveal the specific mechanism of phosphate-coupled G6P transport. In addition, the CGA-bound G6PT1 complex shows that CGA stabilizes the transporter in the cytosol-facing conformation, inhibiting it by competing with substrate binding and preventing conformational transitions, providing previously unreported insights into G6PT1 inhibition. Our findings provide a structural foundation for understanding the mechanisms of substrate recognition, transport, drug inhibition, and the pharmacology of G6PT1, paving the way to the rational design of potential therapeutic agents.

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

Wildfire smoke PM 2.5 and mortality rate in the contiguous United States: A causal modeling study

Min Zhang, Edgar Castro, Alexandra Shtein, Adjani A. Peralta, Mahdieh Danesh Yazdi, Xiao Wu, Joel D. Schwartz, Robert O. Wright, Yaguang Wei

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The relationships between chronic exposure to wildfire smoke PM 2.5 (particulate matter with aerodynamic diameter of ≤2.5 μm) and mortality remain poorly understood, with causal evidence being particularly scarce. In this ecological study, we used a doubly robust method, incorporating flexible generalized propensity score estimation that captured potential nonlinearity and interactions among confounders and relaxed the distribution form assumption for exposure, to estimate the effects of annual exposure to wildfire smoke PM 2.5 on all-cause and cause-specific mortality in the contiguous United States from 2006 to 2020. We found that wildfire smoke PM 2.5 was associated with increased mortality rate for all studied outcomes, except for deaths from transport accidents or falls, which served as negative outcome controls. Wildfire smoke PM 2.5 was responsible for ~24,100 all-cause deaths per year in the contiguous United States. The exposure-response curve for all-cause mortality increased monotonically, with no evidence of a “safe” threshold. Among the six cause-specific outcomes, mortality from neurological disease showed the greatest increase per 0.1 μg/m 3 increase in smoke PM 2.5 exposure. Our study provided robust evidence for the chronic effect of wildfire smoke PM 2.5 on mortality, underscoring the urgent need for targeted measures to mitigate the substantial and escalating burden of wildfires.

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

Eccentricity rhythms in the Oligocene-Miocene carbon cycle regulated by weathering and carbonate burial

Fenghao Liu, Enqing Huang, Jinlong Du, Wentao Ma, Zhonghui Liu, Lucas J. Lourens, Jun Tian

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During the Cenozoic unipolar ice ages, benthic foraminiferal oxygen and carbon isotopes (proxies for bottom-water temperature and ice volume and for the carbon cycle, respectively) exhibited in-phase changes on eccentricity timescales. However, the mechanisms underlying this synchronized relationship remain unclear. Here, we present a high-resolution reconstruction of Miocene benthic foraminiferal boron-to-calcium ratios, revealing that eccentricity-paced fluctuations in deep-sea carbonate ion saturation covaried with oxygen and carbon isotopes, as well as with pelagic carbonate deposition. Integrating model results, we propose that orbital configurations and elevated temperatures during eccentricity maxima intensified monsoon rainfall and chemical weathering, enhancing the transport of dissolved inorganic carbon and alkalinity from land to sea. These processes further redistributed massive carbonate burial from deep-ocean basins to continental shelves, lowering carbonate ion concentration and the carbon isotopic composition of seawater. Our findings underscore the crucial role of the low-latitude hydrological cycle in regulating carbon-cycle dynamics under warm climatic conditions.

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

Injury-induced electrochemical coupling triggers organ growth

Jinghui Liu, Elisa Nerli, Charlie Duclut, Amit S. Vishen, Naomi Berbee, Sylvia Kaufmann, Cesar Ponce, Aristides B. Arrenberg, Frank Jülicher, Rita Mateus

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Organ injury triggers nonneuronal electric currents essential for regeneration. However, the mechanisms by which electrical signals are generated, sensed, and transmitted upon damage to promote organ growth remain unclear. Here, we uncover that organ repair relies on dynamic electrochemical coupling between membrane potential depolarization and intracellular signaling, essential to activate cell proliferation. By subsecond live imaging of locally injured zebrafish larval fins, we identify events across time and space: a millisecond, long-range, membrane depolarization gradient, followed by second-persistent intracellular calcium responses. In the subsequent hour, voltage sensing phosphatase senses the injury-driven membrane potential change and autonomously translates the electric signal intracellularly, promoting tissue-wide cell proliferation. Connecting these dynamics with an electrodiffusive model showed that ionic fluxes and electric potential become coupled in the fin’s interstitial space, enabling organ-wide signal spreading. Our work reveals the coupling between fast electrical signals and slower intracellular signaling, ensuring complete organ recovery.

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

Day-to-day fluctuations in cognitive precision predict the domain-general intention-behavior gap

Daniel J. Wilson, Cendri A. Hutcherson

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The idea that better cognitive functioning helps to close the gap between goals and behavior seems self-evident, yet empirical work has found unusually weak interindividual associations between cognitive task performance and real-world, goal-relevant outcomes. Here, we resolve this paradox by shifting from trait-level to state-level analysis. Leveraging a microtask design to measure daily fluctuations in cognitive function, goal setting and goal progress, mood, sleep, and motivation over a 12-week intensive longitudinal study of university students ( N = 184, time points = 9248), we show that within-person upswings in domain-general cognitive processing precision precede and predict same-day self-reported goal setting and achievement across both academic and nonacademic domains, even controlling for other factors. A one-standard-deviation change in cognitive precision had an effect statistically equivalent to ~40 min of work, with similar or larger predictive effects compared to fluctuations in mood/motivation and no moderation by trait-level self-control or conscientiousness. Our work addresses long-standing controversies and highlights the power of intraindividual analysis to reveal relationships missed by cross-sectional approaches.

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

High-efficiency methane consumption by atmospheric methanotrophs in subsurface karst caves: The irrefutable methane sink

Xiaoyan Liu, Xiaoyu Cheng, Yiming Zhang, Rui Zhao, Weiqi Wang, Yang Li, Zhong-Qiang Chen, Xincheng Qiu, Olli H. Tuovinen, Ian D. Bull, Richard P. Evershed, Hongmei Wang

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Subsurface karst systems represent substantial but underexplored methane sinks, yet the identities and activities of cave-dwelling methanotrophs remain poorly characterized. We detected increased methane oxidation rates from 2.9 ± 0.1 to 90.7 ± 4.5 ng·g −1 ·hour −1 while supplied with 2 to 500 parts per million (ppm) CH 4 to cave sediments. Atmospheric methanotroph Upland Soil Clusters γ (USCγ), responsible for this oxidation, was further assigned to three genera within the family Candidatus ( Ca .) Methyloligotrophaceae, including two previously unrecognized genera. Nano-scale secondary ion mass spectrometry (NanoSIMS) imaging and the produced 13 C-PLFAs (phospholipid fatty acids) and 13 CO 2 in 13 CH 4 -fed microcosm confirmed methane as both carbon and energy sources. These methanotrophs exhibited low half-saturation constant ( K m ; 138.8 ± 15.8 ppm), high carbon assimilation efficiency (>50%), and metabolic versatility, as revealed by metagenomics and metatranscriptomics analyses. By extrapolating global distribution of Ca. Methyloligotrophaceae and comparing methane oxidation rates between caves and soil ecosystems, we conservatively estimate that subsurface karst in southwest China sequester ~0.56 Tg CH 4 annually. These findings highlight the ecological importance of karst ecosystems as a previously overlooked methane sink.

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

In vivo functional profiling and structural characterization of the human GLP1R A316T variant

Liliane El Eid, Yusman Manchanda, Gregory Austin, Kieran Deane-Alder, Roxana-Maria Rujan, Zamara Mariam, Affiong I. Oqua, Matthew J. Belousoff, Jorge Bernardino de la Serna, Kyle W. Sloop, Guy A. Rutter, Alex Montoya, Dominic J. Withers, Steven J. Millership, Karim Bouzakri, Ben Jones, Christopher A. Reynolds, Patrick M. Sexton, Denise Wootten, Giuseppe Deganutti, Alejandra Tomas

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Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective therapies for type 2 diabetes (T2D) and obesity, yet patient responses are variable, with GLP1R gene variation potentially linked to therapeutic outcomes. A GLP1R natural missense variant, A316T, protects against T2D and cardiovascular disease. Here, we generated and characterized a human GLP1R A316T mouse model. Human GLP1R A316T/A316T mice displayed lower fasting blood glucose versus wild-type littermates even under metabolic stress, as well as slower weight gain and alterations in islet cytoarchitecture, glucagon secretion, and liver metabolism under a high-fat, high-sucrose diet. This was however associated with blunted responses to pharmacological GLP-1RAs in vivo. Further investigations in β cell models demonstrated that human GLP1R A316T exhibits characteristics of constitutive activation but dampened GLP-1RA responses. Results are further supported by cryo-EM analyses and molecular dynamics simulations of GLP-1R A316T structure, collectively demonstrating that the A316T variant governs basal GLP-1R activity and pharmacological responses to GLP-1R–targeting therapies.

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

Stress ensemble in the BNST mediates comorbid anxiety and sleep disruption

Haiyan Sun, Zhentong Qiu, Xin Liu, Yan Li, Xu Zhao, Yanqin Zhou, Qingchen Guo, Kunwei Wu, Jun Ma, Junping Chen, Jun-Li Cao, Shuming An

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Anxiety and insomnia are highly comorbid; however, the underlying brain-circuit mechanisms remain inadequately explored. Here, we identify a dual-functional ensemble within the bed nucleus of the stria terminalis (BNST) that modulates both anxiety-like behaviors and insomnia through distinct neural circuits. Specifically, a subset of BNST neurons exhibits enhanced activity in response to anxiety-related cues and during wakefulness. Activation of these ensemble neurons exacerbates anxiety-like behaviors and reduces non–rapid eye movement (NREM) sleep in chronic restraint stress (CRS) mice. Conversely, inactivation of these neurons alleviates anxiety-like behaviors and promotes NREM sleep. In addition, anxiolytic-hypnotic medication attenuates BNST stress ensemble hyperactivity, mitigating both phenotypes. Furthermore, BNST stress ensembles project divergently to the dorsal raphe nucleus (DRN) and the preoptic area (POA): DRN-projecting neurons selectively modulated anxiety, whereas POA-projecting neurons specifically regulated sleep-wake states. These findings suggest that hyperactive BNST stress ensembles are responsible for inducing anxiety-like behaviors and disrupting sleep in CRS mice and achieve the modality specificity through their divergent downstream targets.

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

Photoinduced femtosecond spin-flip assisted by a single-mode linear phonon

Na Wu, En Wang, Daqiang Chen, Chao Lian, Yaxian Wang, Sheng Meng

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Optical manipulation of spin-flip on a picosecond to femtosecond timescale has long been pursued to innovate next-generation electronic devices. However, understanding the ultrafast spin-electron-lattice coupled dynamics remains challenging, especially when the system is driven far from equilibrium. Here, we demonstrate an ultrafast light-induced spin-flip within 300 fs in Fe 3 GeTe 2 , a prototypical two-dimensional itinerant ferromagnet. Notably, by varying the laser fluence, we identify three distinct regimes that emerge assisted by a photoinduced single linear phonon mode, namely demagnetization, spin-flip, and spin-melting. We resolve the dominant role of displacively excited A 1g phonons, while nonequilibrium electron occupation is essential to break the degeneracy of the spin up and down states and lower the spin-flip energy barrier. Accompanying the spin-flip, we also observe a sign change of the Berry curvature, implying involvement of nontrivial band topology. Our results provide a general guidance for optical manipulation of spin orders, holding promises for advancing future spintronics and information technology.

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

Lunar chronology model with the Chang’e-6 farside samples and implications for the early impact history

Zongyu Yue, Sheng Gou, Yexin Wang, Huacheng Li, Gregory Michael, Jianzhong Liu, Shujuan Sun, Yangting Lin, Kaichang Di, Qiuli Li, Yi Chen, Wei Yang, Bin Xie, Sen Hu, Shouding Li, Bo Zheng, Tianqiao Mao, Xianhua Li, Fuyuan Wu

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The radiometric ages of the returned samples are the cornerstone of lunar cratering chronology models. However, all the previous samples were from the lunar nearside and the radiometric ages of those samples that can be associated with particular surfaces are <4.0 billion years. On 25 June 2024, Chang’e-6 successfully returned 1.935-kilogram samples from the lunar farside. The samples included local basalts with an age of 2807 ± 3 million years and the norites with an age of 4247 ± 5 million years likely corresponding to the age of the South Pole–Aitken basin. With these radiometric ages, we refined the lunar chronology function (CF) and verified that it is still consistent with a combination of an exponential decrease and a linear rate. We further derived the impacting rate and found it supports a smooth decay instead of abrupt changes of the impactor flux at early times. The refined lunar CF can be used to obtain more reliable ages for unsampled lunar areas and provide critical constraint for the lunar early impact history.

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

Advancing quantum imaging: Electrical tunability enabled by versatile liquid crystals

Dong Zhu, Shi-Hui Ding, Rui Sun, Zhi-Xiang Li, Wen Chen, Yi-Heng Zhang, Si-Jia Liu, Yi-Ming Wang, Fang-Tianyu Chen, Peng Chen, Yan-Qing Lu

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Optical image processing techniques like edge detection demonstrate unique superiority in various applications. Synergistically combined with heralded quantum imaging, they have notable potential for identifying light-sensitive samples under minimal illumination. However, present schemes usually lack the capability to control the quantum imaging function dynamically. Here, we introduce versatile liquid crystals to realize heralded single-photon imaging and electrically tunable multimode switching. On the basis of the bichiral cholesteric liquid crystal modulator, different morphology information of the target can be extracted with a high signal-to-noise ratio, including the entire shape and its fine outline. The nematic liquid crystal, leveraging its electrically tunable properties, is explored to select specific polarizations of heralded single photons, enabling dynamic remote switching in trimode quantum imaging. To further improve the time efficiency, an ultrafast remote switching is presented on the basis of the appealing ferroelectric liquid crystals. This work supplies a unique imaging platform for photon-limited scenarios and reveals the unprecedented possibilities of soft matters in quantum information processing.

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

In situ anchoring 2D hexagonal Zn-MOF on MXene toward robust anode-less 5 V–class Li metal batteries

Yuan Tian, Zhihao Pei, Deyan Luan, Xiong Wen (David) Lou

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Anode-less 5 V–class lithium metal batteries (LMBs) promise high energy density and safety yet, in practice, face critical challenges including dendrite growth, interfacial instability, pulverization associated with “dead” lithium accumulation, and energy density compromise from the use of heavy copper collector. Here, we demonstrate an elaborate design of two-dimensional hexagonal zinc-containing metal-organic framework anchored on conductive titanium carbide (Ti 3 C 2 T x ) MXene sheets (MX/2D-Zn-MOF) as a three-dimensional lightweight host for anode-less 5 V–class LMBs. The abundant nitrogen/fluorine/zinc-rich lithiophilic sites effectively decrease lithium nucleation energy barriers, ensure uniform lithium deposition, and stabilize solid electrolyte interphase. The interconnected three-dimensional framework further guides uniform lithium deposition by spatially homogenizing lithium ion flux and reducing local current density as well as offers sufficient space to alleviate structural change, thus affording structural integrity against pulverization. As a result, the MX/2D-Zn-MOF host demonstrates uniform lithium deposition, reversible lithium plating and stripping behavior, and stable cycling performance (~1800 hours at 1.0 milliamperes per square centimeter and 5.0 milliampere hours per square centimeter). Impressively, the assembled anode-less 5 V–class lithium metal pouch cell delivers stable cycling performance and high energy density.

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

Longitudinal monitoring of type 1 diabetes progression to disease onset

Jessica L. King, Jyotirmoy Roy, Russell R. Urie, Elizabeth Bealer, Kelly Crumley, Laila Rad, Scott A. Soleimanpour, Lonnie D. Shea

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Preventing autoimmune type 1 diabetes (T1D) necessitates improved monitoring for disease progression before symptom onset. Current diagnostic methods assess circulating autoantibodies, C-peptide levels, or dysglycemia, yet these approaches fail to identify β cell destruction preceding glucose dysregulation. Here, a subcutaneous microporous scaffold is used as an immunological niche (IN), which provides a nonvital accessible tissue reflecting many immune changes occurring in the pancreas. Sequencing analysis of the IN successfully delineates at-risk from nonrisk groups, as well as disease progressors from nonprogressors at 6 weeks of age in the nonobese diabetic mouse model. Within progressors, we identify disease 5 to 7 weeks before disease onset. Collectively, disease occurring in a poorly accessible site can be identified early by sampling a distant nonvital tissue, indicating the systemic nature of the disease and informing the timing of disease modifying therapies to halt or delay the progression of T1D.

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

Guiding waves through chaos: Universal bounds for targeted mode transport

Cheng-Zhen Wang, John Guillamon, Ulrich Kuhl, Matthieu Davy, Mattis Reisner, Arthur Goetschy, Tsampikos Kottos

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Controlling wave propagation in complex environments is a central challenge across wireless communications, imaging, and acoustics, where multiple scattering and interference obscure direct transmission paths. Coherent wavefront shaping enables precise energy delivery but typically requires full knowledge of the medium. Here, we introduce a universal statistical framework for targeted mode transport (TMT) that circumvents this limitation and validate it on various platforms including microwave networks, two-dimensional chaotic cavities, and three-dimensional reverberation chambers. TMT quantifies the efficiency of transferring energy between specified input and output channels in multimode wave-chaotic systems. We develop a diagrammatic theory that predicts the eigenvalue distribution of the TMT operator and identifies the macroscopic parameters—coupling strength, absorption, and channel control—that govern performance. The theory provides explicit bounds for optimal TMT wavefronts and captures phenomena like statistical transmission gaps and reflectionless states. These findings establish design principles for energy delivery and information transfer in complex environments, with broad implications for adaptive signal processing and wave-based technologies.

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

Synergizing network topology and solvent compatibility for gels with hyperelasticity and omniadhesion

Qiqi Xue, Xinyu He, Jincheng Lei, Wei Hong, Canhui Yang

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In polymeric gels, hyperelasticity and strong adhesion are often required but difficult to achieve simultaneously. Here we propose a principle of hyperelastic and omniadhesive gels composed of polymer networks with long dangling chains and sufficient good solvents. The molecules of good solvents screen off interchain interactions for hyperelasticity. The long dangling chains disentangle and adsorb to substrate for strong adhesion. We synthesized such gels by controlling the polymerization kinetics. When a monomer solution is partially cured, some monomers form a network and others form the solvent. The resulting gel, termed homogel, consists of a polymer network with enormous dangling chains and solvent of identical chemistries. An interval exists where the dangling chains are long and disentangled substantially, and the homogel exhibits both hyperelasticity and omniadhesion. We demonstrated such a gel with a hysteresis of 4.1% (stretch = 10) and adhesion energy of ~510 joules per square meter. The principle is generic and applicable to gels of different types.

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

ML-automated microfluidic circuit design

Mehmet Tugrul Birtek, Vural Aktas, Bora Aktas, Ahmed Choukri Abdullah, Aydogan Ozcan, Savas Tasoglu

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Microfluidics enable high-precision and cost-effective processing of biological and chemical substances. However, designing and fabricating microfluidic chips typically requires substantial expertise and numerous design iterations, posing considerable barriers to entry for nonexperts. We introduce μFluidicGenius (μFG), an open-access, machine learning (ML)–augmented design tool that enables nonexpert users to rapidly create functional microfluidic circuits. Users simply define the spatial placement of reservoirs, specify the channel connections between them, and assign desired flow rates through this layout. Leveraging a hybrid algorithmic framework that integrates ML models with mathematical modeling, μFG automatically generates spatially coded maze structures that implement the precise fluidic resistances needed to meet the target flow distribution. These resistive elements are optimized to fit within the available geometry and can reproduce complex flow profiles, such as physiologically relevant flow rates in multi-organ-on-chip platforms. The resulting microfluidic designs are directly exportable for three-dimensional printing. Experimental validation demonstrates that μFG-generated circuits reproduce target flow distributions with 90% accuracy. By streamlining and automating microfluidic circuit creation, μFG not only lowers the barrier to entry for nonexperts but also showcases a principled and efficient application of ML to fluidic system design, enabling rapid and customizable development of complex microfluidic architectures.

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

Single-particle surface-enhanced coherent anti–Stokes Raman scattering: Nanoparticle design and mechanism

Sanjun Fan, Ran Cheng, Haonan Lin, Zhewen Luo, Abigail E. Smith, Chih-Feng Wang, Jinna He, Brian T. Scarpitti, Deben N. Shoup, Hannah C. Schorr, Erjun Liang, Jian Ye, Ji-Xin Cheng, Zachary D. Schultz

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Surface-enhanced coherent anti–Stokes Raman scattering (SECARS) is believed to increase the signal intensity and sensitivity by combining the localized surface plasmon resonance and coherent Raman enhancement. However, the realization of SECARS is more complex than for surface-enhanced Raman scattering (SERS) and remains challenging. Unlike SERS, the nonlinear CARS process requires the coherent interaction of three distinct fields. The interactions between the electric fields and nanoparticle (NP) morphology for single-particle SECARS remain unexplored, and the underlying mechanisms generating the SECARS signal are not fully understood. Here, 27 distinct NPs were synthesized and screened using a CARS microscope. Among them, only star-core core-satellite NPs show single-particle SECARS signals, which were affected by laser polarization, two-photon luminescence background, photoinduced heating effects, particle size, and particle morphology. The influence of NP properties on SECARS enhancement offers guidance for the design and synthesis of NPs for single-particle SECARS and opportunities in biological imaging and chemical sensing.

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

One-stop strabismus digital diagnosis via AI-integrated skin-like and wearable “Eyelectronics”

Yong Yang, Xin Liu, Jiankai Tang, Hengyi Guo, Jinsong Zhang, Yuntao Wang, Yonghong Jiao, Yihao Chen, Xue Feng

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Strabismus, affecting ~4% of children, impairs vision and psychosocial health. However, clinical diagnosis requires multiple instruments and stepwise examinations of ocular alignment, extraocular muscle function, and deviation angle. It is limited by low diagnostic objectivity, poor pediatric compliance, and high cost. Here, we propose a strategy for one-stop strabismus digital diagnosis via artificial intelligence (AI)–integrated, skin-like, and wearable “Eyelectronics.” The ultralightweight, imperceptible eye-wearable system features an ultrathin (~60 micrometers in thickness), breathable, and multidirectional (0°/45°/90°) strain-sensing array conformally adapted to the sensitive eyelid. It enables wireless, mild-restricted measurement of eyelid deformation during eye movements. Through biomechanical modeling validated by ocular magnetic resonance imaging simulations, we establish a prior correlation between eyelid deformation and eye movements. The Eyelectronics, powered by our physiology knowledge-driven end-to-end AI algorithm, achieves simultaneous measurement of strabismus angle and identification of paretic muscle. It delivers a 96.6% four-direction classification accuracy and a 1.2° measurement accuracy in ocular motility examinations. Clinical benchmarking against the clinical standard (Hess screen test) confirmed diagnostic agreement (intraclass correlation = 0.978). This system bridges quantitative biomechanical sensing with digital diagnosis, promoting a paradigm for future strabismus treatment.

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

CATSPERε extracellular domains are essential for sperm calcium channel assembly and activity modulation

Jae Yeon Hwang, Huafeng Wang, Jong-Nam Oh, Jingon Kim, Sarah F. Finnegan, Niels E. Skakkebaek, Jean-Ju Chung

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The sperm flagellar-specific CatSper Ca 2+ channel is a multiprotein complex critical for successful fertilization. The four ancillary subunits, CATSPERβ, γ, δ, and ε, form a unique canopy structure over the pore-forming channel. However, how the canopy is formed and what it does in the assembled channel complex remain unknown. Here, we report that extracellular domains (ECDs) of CATSPERε are essential for canopy and holo-complex assembly and modulate channel activity during sperm capacitation. CATSPERε-deficient males are sterile due to the absence of the entire channel and defective sperm hyperactivation. Expressing ECD-truncated CATSPERε during spermatogenesis does not rescue the knockout because it fails to incorporate into the native complex. In contrast, addition of a CATSPERε ECD fragment during sperm capacitation significantly reduces sperm hyperactivation. These findings provide insight into the underlying molecular and developmental mechanisms of CatSper assembly and how the channel can be modulated in physiological settings and by therapeutic intervention.

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

LIMCH1-enriched extracellular vesicles promote vascular permeability in early-onset preeclampsia

Seiko Matsuo, Akira Yokoi, Takafumi Ushida, Kosuke Yoshida, Hironori Suzuki, Masami Kitagawa, Eri Asano-Inami, Hiroaki Yamada, Rika Miki, Sho Tano, Kenji Imai, Ichiro Nagata, Shota Kawaguchi, Takao Yasui, Yusuke Yamamoto, Hiroaki Kajiyama, Tomomi Kotani

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Preeclampsia (PE) is a major pregnancy complication characterized by hypertension and multiple end-organ dysfunctions; however, its detailed pathogenesis remains unclear. Extracellular vesicles (EVs) play diverse and critical roles in intercellular communication, and we have demonstrated interaction between EVs and vascular endothelial cells. Through serum proteomic analysis, we identified LIM and calponin homology domain–containing protein 1 (LIMCH1) as a PE-associated EV protein that is highly expressed in PE placentas, particularly in syncytiotrophoblasts, which release EVs into the maternal circulation. LIMCH1-enriched EVs (LIMCH1-EVs) increased endothelial permeability in vitro. Transcriptome analysis revealed that LIMCH1-EVs disrupted endothelial cell-cell junction assembly by suppressing the expression of the tight junction protein ZO-1. Furthermore, administration of LIMCH1-EVs promoted pulmonary vascular permeability in vivo. These findings suggest a role of LIMCH1-EVs in EV-associated vascular endothelial dysfunction, a central pathology of PE. In addition, this study provides insights into mechanisms that may contribute to PE-associated pulmonary edema, which have not yet been clarified.

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

Complementary cortical and thalamic contributions to cell type–specific striatal activity dynamics during movement

Enida Gjoni, Ram Dyuthi Sristi, Haixin Liu, Shahar Dror, Xinlei Lin, Keelin O’Neil, Oscar M. Arroyo, Sun Woo Hong, Hannah Kim, Jeffrey Liu, Sonja Blumenstock, Byungkook Lim, Gal Mishne, Takaki Komiyama

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Coordinated motor behavior emerges from information flow across brain regions. How long-range inputs drive cell type–specific activity within motor circuits remains unclear. The dorsolateral striatum (DLS) contains direct- and indirect-pathway medium spiny neurons (dMSNs and iMSNs) with distinct roles in movement control. In mice performing skilled locomotion, we recorded from dMSNs, iMSNs, and their cortical and thalamic inputs identified by monosynaptic rabies tracing. A recurrent neural network (RNN) classifier and clustering analysis revealed functionally heterogeneous subpopulations in each population, with dMSNs preferentially activated at movement onset and offset, and iMSNs during execution. Cortical and thalamic inputs were preferentially activated during onset/offset and execution, respectively, though dMSN- and iMSN-projecting neurons in each region showed similar patterns. Locomotion phase-specific rhythmic activity was found in a subset of thalamic dMSN-projecting neurons and dMSNs. Cortex or thalamus inactivation reduced MSN activity. These findings suggest that corticostriatal and thalamostriatal inputs convey complementary motor signals via shared and cell type–specific pathways.

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

Efflux pumps control intracellular drug-target kinetics by limiting rebinding in bacteria

Subrata Dev, Keiran Stevenson, Dai Le, Minsu Kim

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Bacterial efflux pumps are major contributors to multidrug resistance, classically described as “gatekeepers” that reduce drug entry. Here, we uncover a post–entry mechanism of efflux pumps, revealing their function deep into intracellular drug-target interactions. Using quantitative live-cell imaging, we monitored the activity of major efflux systems in Escherichia coli and Pseudomonas aeruginosa with Hoechst 33342 (HCT), a DNA binding inhibitor. We found that inactivation of efflux (Δ tolC in E. coli and Δ6 in P. aeruginosa ) increased the apparent HCT-DNA affinity, mediated by a decreased apparent unbinding rate, whereas the intrinsic rate remained unchanged. Statistical physics modeling and experimental testing show that, unlike under dilute in vitro conditions, drug molecules that unbind from their targets in intracellular environments undergo successive rebinding, prolonging the total lifetime of the drug bound to the target. However, efflux pumps counteract this effect by suppressing rebinding, thereby kinetically destabilizing drug-target interactions. This biophysical mechanism acts multiplicatively with the canonical gatekeeping effect to broaden and amplify drug resistance.

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

RIN3 mutations impairing binding of the Alzheimer’s disease–associated protein BIN1 lead to RAB5 hyperactivation and endosomal pathology

Anna K. Maaser-Hecker, Jacob C. Zellmer, Michelle Kim, Grisilda Bakiasi, Amit K. Maiti, Matea P. C. Curtat, Se Hoon Choi, Dmitry Prokopenko, Rudolph E. Tanzi, Raja Bhattacharyya

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Alzheimer’s disease (AD) risk is strongly influenced by genetic variants that converge on pathways regulating endosomal homeostasis. Among these, BIN1 and RIN3 have emerged as susceptibility genes, yet their functional relationship in AD remains largely unknown. Here, we investigated how BIN1 and RIN3 interaction regulates RAB5 activity and endosomal pathology. RIN3 has been shown to bind BIN1, and we previously reported that this interaction modulates amyloid-β (Aβ) precursor protein (APP) trafficking and Aβ generation in vitro. To extend these findings, we used Rin3 constitutive knockout ( Rin3-CKO ) mice and CRISPR-Cas9–edited human induced pluripotent stem cell–derived neurons carrying either BIN1 knockout or rare familial AD RIN3 missense mutations within the BIN1-binding domain. We found that disruption of BIN1-RIN3 binding, through either genetic deletion or pathogenic RIN3 variants, resulted in RIN3-mediated RAB5 hyperactivation and enlargement of neuronal endosomes, a hallmark of early AD pathology. Transcriptomic profiling further revealed dysregulated expression of AD-related genes. Together, these findings establish BIN1 as a critical regulator of RIN3-driven RAB5 activation and neuronal endosomal homeostasis.

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

From light to sound: Seeing and hearing the placenta in health and disease

Donghyun Lee, Jiwoong Kim, Jinseok Heo, Hyunseo Jeon, Shiyang Chang, Wonseok Choi, Chulhong Kim, Zhifen Yang

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The placenta is a pregnancy-specific organ, functioning as the maternal-fetal interface and mediating essential processes including exchange, protection, and endocrine regulation. Placental abnormalities contribute to the pathophysiology, onset, progression, and prognosis of major perinatal disorders, making imaging modalities that enable their detection and monitoring crucial. Ultrasound (US) imaging is the principal modality for placental imaging, providing structural assessment with B-mode and blood flow evaluation with Doppler mode. Furthermore, advanced techniques such as 3D power Doppler, quantitative US, and shear-wave elastography expand the capabilities of placental US imaging. Photoacoustic (PA) imaging enables observation of the optical properties of endogenous chromophores (e.g., hemoglobin) with high spatial resolution and measures blood oxygenation, a key factor in placental dysfunction, offering substantial value for placental imaging. In this review, we cover US/PA imaging techniques for placental imaging, including preclinical and clinical studies. In addition, by considering current limitations and potential solutions, we suggest future trajectories for the advancement of US/PA imaging in this field.

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

Structural basis of transcription-coupled H3K36 trimethylation by Set2 in coordination with FACT

Tomoya Kujirai, Haruhiko Ehara, Tomoko Ito, Masami Henmi, Eriko Oya, Takehiko Kobayashi, Shun-ichi Sekine, Hitoshi Kurumizaka

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Trimethylation of the histone H3K36 residue (H3K36me3) plays an indispensable role in ensuring transcription fidelity by suppressing undesired cryptic transcription in chromatin. H3K36me3 modification is accomplished by Set2/SETD2 during transcription elongation by the RNA polymerase II elongation complex (EC). Here, we found that Set2-mediated H3K36me3 deposition occurs on the nucleosome reassembling behind the EC. The histone chaperone FACT suppresses H3K36me3 deposition on the downstream nucleosome, thereby ensuring that Set2 targets specifically on the reassembling upstream nucleosome. Cryo–electron microscopy structures of the nucleosome-transcribing EC complexed with Set2 revealed that Set2 is anchored by the Spt6 subunit of the EC to capture both of the H3 N-terminal tails in a stepwise manner during the nucleosome reassembly process. Abrogation of the Set2-EC interaction leads to defective transcription-coupled H3K36me3 deposition. These insights elucidate the structure-based mechanism of transcription-coupled H3K36me3 deposition in chromatin.

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

α-Synuclein expression is required for somatodendritic dopamine release and immediate early gene induction

Se Joon Choi, Anika Frank, Manu Ben-Johny, Guomei Tang, Jonas Bendig, Stavros Fanourakis, Benjamin D. Hobson, Nagendran Ramalingam, Ulf Dettmer, Ellen Kanter, David Sulzer, Eugene V. Mosharov

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α-Synuclein (αSyn) is a presynaptic protein of unestablished physiological function that plays a central role in Parkinson’s disease neuropathology. To date, the reported effects of αSyn expression on the kinetics of axonal synaptic vesicle exocytosis and membrane cycling have been relatively small. In contrast, we report that αSyn is the major modulator of substantia nigra somatodendritic dopamine release, a little-understood form of neurotransmission that is central to sensorimotor and basal ganglia circuitry. This regulation is due to a previously unknown role for αSyn in controlling the activity of the L-type calcium ion channels (LTCC), which are also implicated in Parkinson’s pathogenesis. αSyn-deficient neurons further display decreased spike frequency adaptation, hippocampal LTCC-dependent long-term potentiation, and immediate early gene induction, functions that are essential for synaptic adaptation and neuronal plasticity.

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

Seismic and mineralogical evidence for an iron-rich mega–ultralow-velocity zone beneath Hawai’i

Doyeon Kim, Jung-Hun Song, Vasilije V. Dobrosavljevic, Vedran Lekić

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Mantle plumes beneath major oceanic hot spots appear to be rooted in unusually large structures near the core-mantle boundary, which have markedly reduced seismic wave speeds. The origin of these large ultralow-velocity zones (ULVZs), referred to as mega-ULVZs, remains uncertain partly because of lack of constraints on the relative reduction in shear versus compressional wave speeds ( R S/P ). This ratio can give clues into the compositional makeup of the mega-ULVZs. Through joint seismic analysis of core-diffracted P and S waves beneath Hawai’i, we constrain the R S/P of its mega-ULVZ to 1 to 1.3. Mineralogical modeling reveals that iron enrichment via solid iron-rich magnesiowüstite [(Mg,Fe)O] matches this seismic constraint, independent of modeled ULVZ thickness. Enrichment of metallic iron-rich magnesiowüstite likely enhances the thermal conductivity of mega-ULVZs and provides a mechanism to drive localized plume upwelling. Higher reported R S/P values for smaller ULVZs near subduction zones may therefore indicate different processes at play controlling ULVZ formation across the diverse core-mantle boundary landscape.

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

Absence of dehydration due to superionic transition at Earth’s core-mantle boundary

Yu He, Wei Zhang, Qingyang Hu, Shichuan Sun, Jiaqi Hu, Daohong Liu, Li Zhou, Lidong Dai, Duck Young Kim, Simon A. T. Redfern, Yun Liu, Heping Li, Ho-kwang Mao

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The properties and stability of hydrous phases are crucial to unraveling the mysteries of the deep water cycle. Under deep lower mantle conditions, water and hydrous phases transition into a superionic state. However, superionic effect on their stability and dehydration behavior remains unclear. Using ab initio and deep learning potential molecular dynamics simulations, we discovered a doubly superionic transition in δ-AlOOH, characterized by the highly diffusive behavior of both hydrogen and aluminum ions within the oxygen sublattice. These highly diffusive elements contribute external entropy to the system, stabilizing the structure at 140 GPa and 3800 K. Our free-energy calculations reveal that water tends to freeze under deep lower mantle conditions, so dehydration becomes energetically and kinetically unfavorable even under core-mantle boundary (CMB) conditions. This implies that superionic water may accumulate in the deep lower mantle over geologic time, forming a long-term reservoir at the base of the mantle.

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

From Plato to Pareto: Defining the shape of infection’s disease space

Yael Lebel, Avni S. Gupta, Victoria Chevée, Uri Alon, David S. Schneider

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If the immune system is an interconnected network, then the evolution of an archetype that is ideal for fighting one pathogen should result in trade-offs decreasing its ability to fight others. How many archetypes are there in an immune system? We infected diverse mice with Plasmodium chabaudi and identified five distinct archetypes of responses on the basis of the host’s position in microbial load, immune activity, and host damage space. To better understand the nature of these archetypes, we developed a mathematical model of a generalized host-pathogen system. This model explains the number and distribution of archetypes across a population of diverse hosts. Mice resilient to P. chabaudi exhibited poor outcomes when challenged with influenza, SARS-CoV-1, or Mycobacterium tuberculosis , and vice versa, supporting our trade-off hypothesis.

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

Segregation passivation makes cost-effective stainless steel resistant to corrosion and hydrogen embrittlement

Hongxu Cheng, Hong Luo, Yue Li, Ziyuan Rao, Qiancheng Zhao, Zhimin Pan, Qingmao Kong, Xiaogang Li, Dierk Raabe

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Stainless steels are essential materials in sustainable energy conversion systems, particularly in hydrogen-related applications. However, their susceptibility to hydrogen embrittlement and corrosion limits their long-term use, creating a need for advanced alloys capable of resisting environmentally assisted damage and mechanical failure. Here, we design a cost-effective austenitic stainless steel. The key innovation involves the atomic-scale passivation of grain boundaries through nitrogen decoration. This enhances resistance to failure, achieving about 3.8-fold increase in corrosion resistance and a 1.35-fold increase in hydrogen embrittlement resistance compared to commercial 316L. The steel exhibits very low hydrogen diffusivity (~7.8 × 10 −17 square meters per second), mitigating hydrogen embrittlement at ambient temperature, an advantage over conventional steels. In addition, formation of a dense passive film improves corrosion resistance in environments such as dilute hydrochloric acid, sulfuric acid, and caustic soda. The outstanding resistance of the stainless steel against such harsh coupled environmental conditions qualifies it as a promising candidate for sustainable and secure infrastructure in the emerging hydrogen economy.

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

Spatial and racial/ethnic disparities in cardiovascular mortality attributable to PM 2.5 components in the contiguous United States

Ying Hu, Lingzhi Chu, Stefano Renzetti, Emma Zang, Ijeoma Opara, Yuan Lu, Erica S. Spatz, Harlan M. Krumholz, Kai Chen

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Long-term exposure to fine particulate matter (PM 2.5 ) is a well-established risk factor for cardiovascular disease (CVD) mortality, yet the contributions of its components remain unclear, particularly across geographic regions and racial/ethnic groups. We extended the generalized weighted quantile sum regression model by incorporating two-way fixed effects (gWQS-feglm) to quantify PM 2.5 component–attributable CVD deaths across the contiguous United States. PM 2.5 component–attributable CVD deaths declined from 42,200 (28,200,57,600) in 2001 to 23,500 (15,700,32,100) in 2020, driven by ammonium (NH 4 + ) and sulfate (SO 4 2− ) reductions. In 2020, high-attributable-mortality regions remained and regional disparities in PM 2.5 composition pronounced, with NH 4 + dominant in California and the East North Central, SO 4 2− in the South, and black carbon and SO 4 2− in the Middle Atlantic. Racial/ethnic disparities persisted, with non-Hispanic Blacks and Hispanics experiencing slower attributable-mortality declines compared with non-Hispanic whites. Our findings highlight the importance of targeted interventions based on components to address disparities in PM 2.5 -attributable burden.

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

Melting dynamics of freely floating ice in calm waters

Daisuke Noto, Hugo N. Ulloa

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Predicting floating ice dynamics remains a challenging problem with implications for Earth’s climate. While gigantic icebergs have garnered worldwide attention, small ice bodies have been overlooked, and we still lack their mechanistic models. Aided by a real-time tracking, we unravel the transient processes of freely floating ice in calm waters—including the kinematics, phase transition, and surrounding fluid dynamics—that govern melting. Combining the heat transfer model and our experimental results, we develop and validate a theoretical model for the melt rate, identifying ice geometry and convective regime as key controls. Furthermore, the ice-driven convective volume flux is found to exceed the meltwater flux by orders of magnitude, underscoring the ecological relevance of floating ice; it not only supplies freshwater but also acts as a destabilizing buoyancy source that redistributes mass macroscopically. Our study provides a foundation for developing mechanistic parameterizations of icebergs and ice floes melting in climate models.

School discipline disparities increase when neighborhood Black population changes

Jennifer Candipan, Chantal A. Hailey

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The racial landscape of US neighborhoods shifted tremendously over the past decade, raising questions about how these changes are reflected in local schools. This study combines school zone shapefiles with census and Civil Rights Database data to explore whether neighborhood racial change in Black populations predicts changes in Black-white school suspension disparities from 2010 to 2018. We find that racial disparities in suspensions increased, particularly in neighborhoods experiencing substantial shifts in Black populations. These increases were especially pronounced in suburban and rural areas with shifting Black populations and all predominantly White neighborhoods. Although school discipline reforms aimed to reduce racial disparities, they only declined in certain types of neighborhoods, most notably in urban areas. Our findings advance insights into processes of school and neighborhood change, school discipline, and racial stratification, with broad policy implications.