🗣 Communication Paper Picnic 🧺: Multidisciplinary

I checked 6 multidisciplinary journals on Thursday, May 28, 2026 using the Crossref API. For the period May 21 to May 27, I found 21 new paper(s) in 5 journal(s).

Nature

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

αKG-mediated carnitine synthesis drives DNA repair via histone acetylation

Apoorva Uboveja, Baixue Yang, Raquel Buj, Amandine Amalric, Hui Wang, Naveen Kumar Tangudu, Aidan R. Cole, Julie A. Disharoon, Richard S. Fang, Evan Levasseur, Miho Naruse, Zhentai Huang, Emily Megill, Daniel S. Kantner, Adam Chatoff, Hafsah Ahmad, Mariola M. Marcinkiewicz, Sarah Graff, Ellen De Pieri, Andrea Andress Huacachino, Frank P. Vendetti, Jeff Danielson, Erika S. Dahl, Jennifer L. Pennise, Esther Elishaev, Alison Jaccard, Lauren Borho, Miriam D. Post, Kristine Cooper, Francesmary Modugno, Nadine Hempel, Wayne Stallaert, Christopher J. Bakkenist, Simone Sidoli, Kathryn E. Wellen, Benjamin G. Bitler, David T. Long, Nathaniel W. Snyder, Katherine M. Aird

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Homologous recombination (HR) deficiency increases sensitivity to DNA-damaging agents that are commonly used to treat cancer1. In HR-proficient cancers, the metabolic mechanisms that drive response or resistance to DNA-damaging agents remain unclear. Here we have identified that depletion of α-ketoglutarate (αKG) sensitizes HR-proficient cells to DNA-damaging agents by metabolic regulation of histone acetylation. αKG is required for the activity of αKG-dependent dioxygenases2 (αKGDDs), and previous work has focused almost exclusively on the demethylase functions of αKGDD. Using a targeted CRISPR knockout library consisting of 64 αKGDDs, we discovered that trimethyllysine hydroxylase epsilon (TMLHE), the first and rate-limiting enzyme in de novo carnitine synthesis, is necessary for the survival of HR-proficient cells in the presence of DNA-damaging agents. Unexpectedly, αKG-mediated TMLHE-dependent carnitine synthesis was required for histone acetylation and was non-redundant with other nucleo-cytosolic acetyl-CoA-generating pathways. The increase in histone acetylation by means of the αKG–carnitine axis promoted HR-mediated DNA repair through site-specific histone acetylation. Finally, we observed a positive correlation between TMLHE and histone acetylation in patient samples and found that high TMLHE or acetylcarnitine correlates with worse progression-free survival in patients treated with DNA-damaging agents. This study demonstrates for the first time, to our knowledge, that αKG affects site-specific histone acetylation and provides a mechanism of HR proficiency through carnitine synthesis. Moreover, these data provide a metabolic avenue for inducing HR deficiency and promoting sensitivity to DNA-damaging agents.

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

Dynamical freezing for magnetometry in an interacting spin ensemble

Ya-Nan Lu, Dong Yuan, Yixuan Ma, Yan-Qing Liu, Si Jiang, Xiang-Qian Meng, Yi-Jie Xu, Xiu-Ying Chang, Chong Zu, Hong-Zheng Zhao, Dong-Ling Deng, Lu-Ming Duan, Pan-Yu Hou

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Understanding and controlling non-equilibrium dynamics in quantum many-body systems is a fundamental challenge in modern physics1,2,3,4,5, with profound implications for advancing quantum technologies. Typically, periodically driven systems in the absence of conservation laws thermalize to a featureless ‘infinite-temperature’ state, erasing all memory of their initial conditions6,7,8. However, this pattern can break down through mechanisms such as integrability9, many-body localization2,3,10,11, quantum many-body scars4 and Hilbert space fragmentation12,13. Here we report the experimental observation of dynamical freezing, a distinct mechanism of thermalization breakdown in driven systems14,15,16,17,18,19, and demonstrate its application in quantum sensing using an ensemble of approximately 104 interacting nitrogen-vacancy (NV) spins in diamond. By precisely controlling the driving frequency and detuning, we observe emergent long-lived spin magnetization and coherent oscillatory micromotions, persisting over timescales exceeding the interaction-limited coherence time (T2) by more than an order of magnitude. By using these unconventional dynamics, we develop a dynamical-freezing-enhanced a.c. magnetometry that extends optimal sensing times far beyond T2, outperforming conventional dynamical decoupling magnetometry with a 2.7-fold sensitivity enhancement. Our results not only provide clear experimental observation of dynamical freezing—a peculiar mechanism defying thermalization through emergent conservation laws—but also establish a robust control method generally applicable to diverse physical platforms, with broad implications in quantum metrology and beyond.

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

Rising global hail damage potential in a warming world

Shiyi Zhang, Qinghong Zhang, John T. Allen, Xiangyu Lin

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Anthropogenic climate change (ACC) is expected to modify severe convective storms and their associated hazards, including hailstorms, a primary driver of weather-related economic losses1,2,3,4. Despite some research on the response of hailstorms to ACC, most studies have focused on regional-scale changes2,3,4,5,6,7,8,9, whereas global-scale assessments of hailstone size remain scarce. Here we show a 36.5–42.1% increase in global hailstorm-induced damage potential by the late twenty-first century, with the magnitude determined by the emission scenario. Our results arise from hailstone trajectory simulations conducted under historical and future scenarios, driven by EC-Earth3 ensemble outputs10 that are cross-validated through multimodel comparisons. Globally, increased low-level temperature and specific humidity drive a shift towards larger hailstones, with the frequency of ≥30-mm-diameter hailstones rising by 37.9–51.8% and <30-mm-diameter hailstones declining by 4.2–12.3%. Regionally, the mid-high latitudes predominantly exhibit increased hail damage potential owing to strong warming and weak moistening, amplifying instability sufficiently to counteract enhanced drag and melting effects. Conversely, tropical and monsoonal regions experience reduced hail damage potential owing to weak warming, strong moistening and limited hail growth depth. Our findings highlight the non-uniform impacts of ACC on global hailstorm damage, providing critical insights for future disaster prevention and mitigation strategies.

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

Genetic architecture of sugarcane traits in a polyploid genomics framework

Jungang Wang, Xiaofeng Li, Yibin Wang, Jishan Lin, Shuai Chen, Hongbo Liu, Xiao Chen, Kun Chai, Aoqian Dong, Tingting Zhao, Cuilian Feng, Ruijie Wu, Ping Zhao, Yaodong Zheng, Zhongqiang Xia, Shengcheng Zhang, Yi Liu, Shenyang Qu, Ziqi Ye, Yuhan Song, Qingyuan Deng, Xiaofei Zeng, Guangrun Yu, Ran Kong, Baoqing Zhang, Wei Zhang, Peifang Zhao, Jun Mao, Xin Lu, Haifeng Jia, Xueting Zhao, Qianqian Zhang, Shuzhen Zhang, Wenwei Cai, Dongao Huo, Ling Li, Yuqing Gong, Shiqiang Huang, Yongji Huang, Zehuai Yu, Zuhu Deng, Baoshan Chen, Yuebin Zhang, Muqing Zhang, Ray Ming, Xingtan Zhang

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Sugarcane (Saccharum spp.) is a vital sugar and bioenergy crop with an exceptionally complex polyploid genome (10–12 sets of chromosomes). This complexity resulted from nobilization—a historical breeding process involving interspecific hybridization and repeated backcrossing1. However, the extreme ploidy has long impeded efforts to elucidate the genetic basis of its considerable sucrose-storing capacity. Here we present a fully phased genome assembly of the foundational cultivar POJ2878, achieved using a Pore-C-based assembly algorithm. This assembly resolved 118 chromosomes, revealing extensive subgenome recombination and non-homologous chromosomal rearrangements. Using identity-by-descent and allele-specific expression profiling, we identified breeder-favoured haplotypes, including a SUS2 haplotype with enhanced sucrose content. Resequencing of 981 Saccharum accessions traced POJ2878’s pervasive contribution to modern cultivars and identified key domestication and improvement sweeps. Genes under selection include CBL1 for cold tolerance, TIP1 for cell size regulation and TB1 for tillering control. A genome-wide association study tailored for polyploid genomes resolved loci associated with parenchyma cell size and sucrose storage capacity, including the functionally validated sucrose transporter Saccharum hybrid SUT2. These findings clarify the genetic architecture underlying sugarcane’s biomass productivity and sugar yield, offering a genomic foundation for accelerating improvement in sugarcane and other polyploid crops critical for global food and bioenergy security.

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

Experimental randomness amplification

Anatoly Kulikov, Simon Storz, Josua D. Schär, Martin Sandfuchs, Ramona Wolf, Florence Berterottière, Christoph Hellings, Andreas Wallraff, Renato Renner

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Realistic quantum information processing devices are inherently imperfect, leading to computational errors that require quantum error correction. Likewise, random bits generated by such devices are flawed and must be enhanced to be usable for applications such as generating cryptographic keys. This enhancement of randomness quality is achieved through a protocol known as randomness amplification1. Here we report on an experiment that implements such a protocol. Randomness amplification is device-independent, making no assumptions about the internal workings of the quantum devices. It requires executing a loophole-free Bell test2,3,4 within a specific parameter regime that involves both a high Bell violation and a high repetition rate. The experimental demonstration is made possible by a combination of theoretical advances, which allow for protocols with an experimentally realistic parameter regime, and experimental progress that achieves this regime with superconducting circuits. Crucially, randomness amplification has been proven to be impossible by purely classical means5. This experiment therefore demonstrates a definitive quantum advantage—leveraging quantum technology to accomplish a task unattainable by classical information processing.

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

Four ppm measurement of the antihydrogen ground-state hyperfine splitting

R. Akbari, L. O. de Araujo Azevedo, C. J. Baker, W. Bertsche, N. M. Bhatt, G. Bonomi, A. Capra, I. Carli, C. L. Cesar, M. Charlton, A. Cridland Mathad, A. Del Vincio, D. Duque Quiceno, S. Eriksson, A. Evans, J. Fajans, T. Friesen, M. C. Fujiwara, L. M. Golino, M. B. Gomes Gonçalves, J. S. Hangst, M. E. Hayden, P. Heidari, D. Hodgkinson, C. A. Isaac, S. A. Jones, S. Jonsell, N. Madsen, V. R. Marshall, J. T. K. McKenna, T. Momose, J. Nauta, A. N. Oliveira, A. Powell, C. Ø. Rasmussen, T. Robertson-Brown, F. Robicheaux, R. L. Sacramento, E. Sarid, J. Schoonwater, D. M. Silveira, J. Singh, G. Smith, C. So, S. Stracka, J. Suh, A. G. Swadling, T. D. Tharp, K. A. Thompson, R. I. Thompson, E. Thorpe-Woods, A. J. Uribe Jimenez, M. Urioni, D. P. van de Werf, S. G. Wilson, P. Woosaree, J. S. Wurtele, character(0), C. L. Cesar, A. Del Vincio, D. P. van de Werf

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The hydrogen atom is a touchstone for the foundations, evolution and frontiers of quantum theory 1–9 . Key spectral lines of this atom have been determined to remarkable precision 10,11 . Our research focuses on the study of antihydrogen, the antimatter counterpart of hydrogen. We test fundamental symmetries of nature (such as simultaneous charge conjugation, parity inversion, and time reversal or CPT symmetry) through precision comparisons of these atomic systems 12 . Recent 1S–2S spectroscopic measurements on trapped antihydrogen have achieved relative precisions of parts per trillion (refs. 13,14 ). However, the ground-state hyperfine splitting, which is sensitive to the internal structure of the antiproton, has only been measured to 400 parts per million (ppm). Here we report a 4 ppm measurement of the antihydrogen ground-state hyperfine splitting energy a 1S , advancing the state-of-the-art precision 15 by two orders of magnitude. From microwave spectroscopy experiments with roughly 24,000 anti-atoms, we determine $${a}_{1{\rm{S}}}/h=\mathrm{1,420,404.8}\pm 1.1(\mathrm{stat.})\pm 5.6\,(\mathrm{sys.})\,\text{kHz}$$ a 1 S / h = 1,420,404.8 ± 1.1 ( stat. ) ± 5.6 ( sys. ) kHz in a 1-T magnetic field, consistent with expectations for hydrogen 11 . At this level, our measurement is sensitive to the internal structure of the antiproton, which contributes at about 40 ppm and is approaching the limit of existing theoretical analyses 16 . The gains we report are the product of marked advances in magnetic trap field control, stabilization and characterization; anti-atom spin-state manipulation; and improved antihydrogen accumulation rate 17 .

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

Cavity-driven attractive interactions in quantum materials

F. Helmrich, H. S. Adlong, M. Kroner, I. Khanonkin, G. Scalari, J. Faist, A. İmamoğlu, T. F. Nova

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Many-body phenomena in quantum materials emerge from the interplay among a broad continuum of electronic states and controlling these interactions is critical for engineering new phases. One promising approach exploits light confined within optical cavities to tailor electronic properties1. Here we demonstrate that terahertz cavity photons can mediate attractive interactions in a tunable van der Waals (vdW) material and reorganize a continuum of electron–hole transitions into an exciton-like state. We introduce a broadband, sub-wavelength time-domain microscope that integrates exfoliated, dual-gated 2D quantum materials into a terahertz cavity. This approach enables the spectroscopic measurement of the field-tunable bandgap of bilayer graphene2 (BLG) in the terahertz range and, at resonance, reveals ultrastrong coupling3 (USC) with an effective interaction strength exceeding g/ωc ≈ 40% of the bare photon energy. Crucially, we identify a cavity-induced resonance emerging from the interband continuum that resembles Coulomb-bound excitons and remains stable across a broad temperature range. Our findings propose an experimental platform for designing and investigating hybrid light–matter phases in 2D quantum matter.

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

Author Correction: Satellite megaconstellations will threaten space-based astronomy

Alejandro S. Borlaff, Pamela M. Marcum, Steve B. Howell

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

Metamaterial-enhanced near-field radiative heat transfer

Zexiao Wang, Renwen Yu, Hakan Salihoglu, Xiao Luo, Zhuo Li, Hyeonggyun Kim, Xiu Liu, Tianyi Huang, Yibai Zhong, Shanhui Fan, Sheng Shen

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When radiative thermal energy is exchanged at near field, evanescent surface waves such as surface phonon polaritons can tunnel through the gap, boosting heat transfer above the far-field blackbody limit by several orders of magnitude1,2. Such extreme radiative energy fluxes have been experimentally demonstrated in dielectric materials supporting surface phonon polaritons3,4,5. Although theories and simulations have suggested metamaterials as a promising route to further manipulate and enhance near-field radiative heat exchange beyond the limits of unstructured Drude- or Lorentz-type materials6,7,8,9,10, experimental validation remains elusive. Here we experimentally demonstrate metamaterial-mediated enhancement on near-field radiative heat transfer between gold split-ring resonators patterned on silicon nitride (SiN) membranes. Compared with unstructured gold plates on the SiN membrane or bare SiN membranes, the radiative heat transfer between the metamaterials is enhanced several-fold. This observed enhancement results from the split-ring-resonator resonant modes and their strong coupling with surface phonon polaritons in the SiN membrane, as supported by direct electromagnetic simulations and coupled-mode-theory modelling. Our work provides experimental verification of the strong capability of metamaterials in manipulating radiative energy exchange at near field, opening opportunities for thermal energy harvesting and infrared sensing applications.

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

Mechanism of age-related accumulation of mtDNA mutations in human blood

Rahul Gupta, Timothy J. Durham, Grant Chau, Masahiro Kanai, Md Mesbah Uddin, Wenhan Lu, M. Austin Argentieri, Konrad J. Karczewski, Daniel Howrigan, Pradeep Natarajan, Wei Zhou, Benjamin M. Neale, Vamsi K. Mootha

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Accumulation of mutant mitochondrial DNA (mtDNA) heteroplasmy is among the strongest signatures of ageing 1 . Here we investigated the underlying mechanism by calling mtDNA sequence, mtDNA abundance and mtDNA heteroplasmic variants in human blood using whole-genome sequences from approximately 750,000 individuals. We observed that mtDNA single-nucleotide variants (mtSNVs) accumulate sharply at age 60 years, occur at low levels of heteroplasmy, exhibit little evidence of positive selection and are likely to be predominantly neutral. The mutational spectrum of mtSNVs does not reflect oxidative lesions, as is commonly invoked, but is more consistent with mtDNA replication errors. To understand why mtSNVs become detectable with age, we performed a genome-wide association study for heteroplasmic mtSNV burden, identifying germline variants near TERT , TCL1A and SMC4 , all of which have been linked to clonal haematopoiesis (CH) 2 . Rare-variant analysis also showed that high mtSNV burden is associated with mutations in numerous CH driver genes. These genetic associations persisted even after exclusion of individuals with known CH driver mutations. Our results support a model in which ‘cryptic’ mtDNA mutations initially arise randomly as replication errors but are undetectable in bulk. They then become apparent only through age-related expansion of cellular clones in blood. We propose that the high copy number and mutation rate of mtDNA make it a sensitive blood-based marker of somatic mosaicism due to CH. Our work mechanistically unifies three prominent signatures of ageing: common germline variants in TERT , CH and observed accrual of mtDNA mutations.

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

Human haematopoietic stem cells remember inflammatory stress

Andy G. X. Zeng, Murtaza S. Nagree, Niels Asger Jakobsen, Sayyam Shah, Angelica Varesi, Jasmine Ryu Won Kang, Alex Murison, Jin-Gyu Cheong, Sven Turkalj, Xuan Zhang, Felix A. Radtke, Tsega-Ab Abera, Isabel N. X. Lim, Liqing Jin, Joana Araújo, Alicia G. Aguilar-Navarro, Darrien Parris, Jessica McLeod, Hyerin Kim, Ho Seok Lee, Lin Zhang, Mason Boulanger, Elyssa Bader, Elias Gbeha, Christopher N. Parkhurst, Elvin Wagenblast, Eugenia Flores-Figueroa, Bo Wang, Gregory W. Schwartz, Leonard D. Shultz, Anna S. Nam, H. Leighton Grimes, Steven Z. Josefowicz, Philip Awadalla, Paresh Vyas, John E. Dick, Stephanie Z. Xie

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Inflammation activates blood cells, contributing to ageing and malignancy 1–3 . Haematopoietic stem cells (HSCs) survive a lifetime of infection to sustain life-long haematopoiesis 1–9 , but how human HSCs respond and adapt to inflammatory stress is largely unknown. Here, to empirically understand this adaptation, we developed xenograft inflammation–recovery models and performed single-cell multiomics on xenografted human HSCs. Two transcriptionally and epigenetically distinct HSC subsets were identified with one, termed HSC inflammatory memory (HSC-iM), retaining a molecular memory of previous inflammatory treatments. The HSC-iM subset exhibited quiescence and restrained haematopoietic output. Molecularly, the HSC-iM program was enriched in HSCs from adult and paediatric samples across conditions ranging from COVID-19 recovery, sickle cell disease, ageing and clonal haematopoiesis, establishing both the validity of our xenograft models and the physiological relevance of HSC-iM. Clonal haematopoiesis mutations in HSC-iM attenuated the effects of inflammatory stress by promoting HSC activation and differentiation. Moreover, transmission of the pro-inflammatory HSC-iM transcriptional program to differentiated immune progeny was demonstrated in xenograft and physiological settings. Finally, HSC-iM program enrichment in circulating blood cells was associated with a heightened risk score for all-cause mortality in population cohort analyses, underscoring the clinical relevance of this newly identified HSC subset in characterizing heterogeneous health outcomes across a lifetime.

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

Author Correction: In vitro characterization of the human segmentation clock

Margarete Diaz-Cuadros, Daniel E. Wagner, Christoph Budjan, Alexis Hubaud, Oscar A. Tarazona, Sophia Donelly, Arthur Michaut, Ziad Al Tanoury, Kumiko Yoshioka-Kobayashi, Yusuke Niino, Ryoichiro Kageyama, Atsushi Miyawaki, Jonathan Touboul, Olivier Pourquié

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

Spatiotemporal transcriptome atlas of human embryos after gastrulation

Jiexue Pan, Yuejiao Li, Zhongliang Lin, Qing Lan, Ying Zhang, Huixi Chen, Shengwei Sui, Man Zhai, Gaochen Zhang, Yi Cheng, Yunhui Tang, Qingchen Wang, Yue Xu, Guoling Li, Chunyan Xu, Haoqi Yan, Yiting Mao, Xingxia Wang, Hao Li, Yiping Zhu, Qinfang Chen, Yichun Guan, Nan Meng, Chang Wang, Haiqian Lu, Xiangjuan Li, Tingting Zheng, Xiaoying Yao, Tingyu Yang, Xuan Chen, Qiuyu Qin, Bin Jiang, Yuxing Ren, Xinmei Liu, Yuxin Zhang, Minghui Yu, Lifang Wang, Yanrong Wei, Meiqi Luo, Ji Nancuo, Fuhe Ma, Ziwei Wang, Zhihua Ou, Ying Lei, Xin Jin, Jianzhong Sheng, Congjian Xu, Yanting Wu, Chenming Xu, Lijian Zhao, Hongbo Yang, Ya Gao, Guolian Ding, Xun Xu, Hefeng Huang

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The comprehensive spatiotemporal atlas of gene expression during early human embryonic development is critical for insights into embryogenesis1, organogenesis2 and disease origins3,4. Here, leveraging Stereo-seq technology, we generated spatial transcriptomic profiles across 77 sagittal sections of 13 whole-human embryos ranging from Carnegie stage 12 to 23, integrated with single-nucleus RNA sequencing to elucidate gene expression patterns within defined cellular contexts, revealing the cellular heterogeneity that drives organ-specific differentiation. Our study has established a regulatory profile for the development of 50 organs and 198 substructures, and identified potential tissue-identity regulators. Of note, it uncovered previously uncharacterized gene functions in cardiac and brain development. The atlas not only substantiates and refines the current understanding of human organ development but also highlights key organs susceptible to genetic disorders. Furthermore, we characterized the allelic gene expression within specific organs at different developmental stages. This work presents a comprehensive compilation of genome-wide gene expression profiles for each spatially defined cell population, which can be visualized as a spatial display of the embryonic transcriptional landscape. These results offer the most thorough delineation to data of the spatiotemporal transcriptomic dynamics of human organogenesis.

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

Bottom-Up Synthesis of Molecular Nanodiamond from Nanographene

Jiaxu Liang, Christopher P. Ender, Nancy C. Forero-Martinez, Ilyes Batatia, Jingyi Liu, Xin Yang, Raul Gonzalez Brouwer, Lev Kazak, Rémi Blinder, Leonardo Cancellara, Nadezda V. Tarakina, Yizhi Liu, Tobias Eklund, Mangalika Sinha, Sarah Köster, Shrikant Bhat, Fabian Rohmann, Andreas Tangemann, Kilian Lee Gallo, Rüdiger Berger, Robert Farla, Alexander Kubanek, Katrin Amann-Winkel, Manfred Wagner, Fedor Jelezko, Klaus Müllen, Gábor Csányi, Robinson Cortes-Huerto, Yingke Wu, Tanja Weil

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Nanodiamonds hosting colour centres are promising building blocks for quantum technologies, enabling advances in quantum computation1,2, nanoscale NMR spectroscopy3–6, single-spin magnetometry7,8, wide-field quantum imaging9 and single-photon sources10,11. However, the controlled bottom-up synthesis of ultrasmall and structurally uniform nanodiamonds has remained a major challenge, with existing methods producing heterogeneous materials that vary in size, morphology, impurity content and defect quality. Here we show that well-defined, hydrogen-terminated molecular nanographenes serve as chemically confined precursors for high-pressure, high-temperature synthesis of ultrasmall (3–4 nm), monodisperse and highly crystalline molecular nanodiamonds (m-NDs) with only a single sp² surface reconstruction and produced on a milligram scale. The same bottom-up platform also enables a two-component strategy for incorporating silicon- and germanium-based colour centres during synthesis, yielding SiV⁻ and GeV⁻ emitters without ion implantation, irradiation or post-treatment. Because the nanographene precursor defines both the confined carbon framework and the hydrogen content, this approach provides intrinsic, precursor-level control over nanodiamond size and composition, particularly in the low-nanometre regime relevant for biological and quantum sensing. Molecular nanographenes, ultralarge polycyclic aromatic hydrocarbons, therefore establish a scalable and modular route to high-quality molecular and fluorescent nanodiamonds and offer a general design principle for tailored quantum materials and nanoscale devices.

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

Temporary carbon dioxide removal to offset short-lived climate forcers

Yue He, Keywan Riahi, Matthew J. Gidden, Shilong Piao, Tao Wang, Thomas Gasser

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Carbon dioxide removal (CDR) is considered for achieving the long-term temperature objectives of the Paris Agreement and national net-zero emission targets1,2,3,4,5. The durability of these CDR methods varies widely, ranging from decades to theoretically permanent6. Temporary CDR dominates present deployment, whereas permanent solutions face further feasibility and cost challenges at scale1. However, efforts to integrate temporary CDR into climate policies have relied on equivalency assumptions between temporary and permanent CDR that contradict physical climate science: temporary CDR cannot fully offset CO2 emissions as permanent CDR can6,7. Here we show that temporary CDR can serve as compensation for non-CO2 climate forcers, particularly for short-lived species whose compensation ratios are fairly insensitive to the choice of time horizon. For instance, offsetting 1 kg CH4 requires 498 kg CO2 with 20-year temporary storage (such as bioplastics) or 101 kg CO2 with 100-year storage (such as durable wood products). We suggest a critical lifetime threshold separating short-lived and long-lived species for temporary CDR applications, with implementation requiring differentiated reporting of these categories. This framework can provide a physical basis for crediting temporary CDR activities in sectors such as agriculture, in which non-CO2 emissions dominate and direct emission reductions remain challenging.

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

β-Arrestin condensates regulate G-protein-coupled receptor function

Preston J. Anderson, Peng Xiao, Ya-Ni Zhong, Adam N. Kaakati, Juliana Alfonso-DeSouza, Alejandra Patino, Andrew Ahn, Chanpreet Jassal, Tianyao Zhang, Chao Zhang, Kexin Yu, Lei Qi, Wei Ding, Samuel Liu, Biswaranjan Pani, Athmika Krishnan, Oscar Chen, Joseph Strawn, Joshua C. Snyder, Jin-Peng Sun, Sudarshan Rajagopal

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β-Arrestins 1 and 2 are multifunctional adaptor proteins1 that regulate the signalling of G-protein-coupled receptors (GPCRs), the largest class of receptors, which impact nearly all aspects of physiology and are one of the most common drug targets2. Although β-arrestins interact with a wide array of signalling effectors at many GPCRs, it is unclear how β-arrestins promote such varied functions. Here we show that β-arrestins undergo liquid–liquid phase separation, forming condensates that regulate GPCR function. We show that condensation is specific to visual arrestins and β-arrestins, and demonstrate that β-arrestin oligomerization occurs in proximity to the GPCR to regulate GPCR functions such as internalization and signalling. Our work provides a paradigm for β-arrestin condensates as regulators of GPCR function, with liquid–liquid phase separation serving as an important promoter of signalling compartmentalization at GPCRs.

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

Darkness and body size shaped end-Cretaceous marine extinction patterns

Rui Ying, Fanny M. Monteiro, James D. Witts, Daniela N. Schmidt

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The Chicxulub asteroid impact at the Cretaceous–Paleogene (K–Pg) boundary (66 Ma) is thought to have caused the extinction of around 75% of species in the fossil record by triggering catastrophic environmental changes 1 . However, despite decades of research, the mechanisms linking the environmental changes to the selective extinction patterns observed in the marine fossil record remain unresolved. Here we use a global trait-based ecosystem model 2,3 to establish this causality for the marine plankton community beyond the fossilized groups. Our model simulates diversity dynamics during the initial 100 years after the K–Pg boundary and represents explicitly extinction based on biomass thresholds that scales with body size. Under K–Pg climatic forcings, the model reproduces successfully key observed extinction patterns, including the high vulnerability of planktic foraminifera and other zooplankton, the survival of small mixotrophs 4 and phytoplankton 5,6 , and potential for reduced diversity loss in high-latitude settings 7 . Our analysis suggests that impact-driven darkness and body-size-dependent extinction thresholds drove most of the observed extinction patterns. These results suggest that plankton ecologies enhance survival through differences in energy demand and acquisition. Our study bridges the gap between fossil evidence of extinction patterns and the K–Pg impact winter hypothesis, highlighting the value of trait-based models for understanding past biodiversity crises.

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

De novo design of miniproteins targeting GPCRs

Edin Muratspahić, David Feldman, David E. Kim, Xiangli Qu, Ana-Maria Bratovianu, Paula Rivera-Sánchez, Jan Hendrik Voss, Emil P. T. Hertz, Mads Jeppesen, Federica Dimitri, Kensuke Sakamoto, Amrita Nallathambi, Pia Peceli, Jianjun Cao, Brian P. Cary, Matthew J. Belousoff, Peter Keov, Phuc N. H. Trinh, Qingchao Chen, Yue Ren, Justyn Fine, Sudha Mishra, Annu Dalal, Shachie Sinha, Ramanuj Banerjee, Manisankar Ganguly, Karthik Varappalayam Karuppusamy, Isaac Sappington, Thomas Schlichthaerle, Jason Z. Zhang, Arvind Pillai, Brian Coventry, Ljubica Mihaljević, Magnus Bauer, Susana Vázquez Torres, Amir Motmaen, Gyu Rie Lee, Long Tran, Xinru Wang, Inna Goreshnik, Dionne K. Vafeados, Justin E. Svendsen, Parisa Hosseinzadeh, Nicolai Lindegaard, Matthäus Brandt, Yann Waltenspühl, Kristine Deibler, Lukas Deweid, Anja Bennett, Jendrik Schöppe, Tiantang Dong, Xiaoli Yan, Luke Oostdyk, William Cao, Lakshmi Anantharaman, Johan J. Weisser, Jesper Frank Bastlund, Christoffer Bundgaard, Ayodeji A. Asuni, Justin G. English, Lance Stewart, Lauren Halloran, Jamie B. Spangler, André Lieber, Arun K. Shukla, Patrick M. Sexton, Bryan L. Roth, Brian E. Krumm, Denise Wootten, Christopher G. Tate, Christoffer Norn, David Baker

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G protein-coupled receptors (GPCRs) play key roles in physiology and are central targets for drug discovery and development1,2, but the design of protein agonists and antagonists has been challenging as GPCRs are integral membrane proteins and conformationally dynamic3–6. Here we describe computational de novo design methods and a high-throughput “receptor diversion” microscopy-based screen for generating GPCR binding miniproteins with high affinity, potency and selectivity. We design miniprotein agonists that activate receptors involved in itch and pain, as well as antagonists that inhibit receptors implicated in cancer, metabolic disorders such as diabetes and obesity, and migraine. Cryo-electron microscopy (cryo-EM) structures of five receptor-bound designs are close to the computational design models. A designed chemokine receptor antagonist mobilizes hematopoietic stem and progenitor cells in vivo at a level comparable to a clinically used drug, with fewer adverse effects.

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

Transcription factor codes patterning neuronal groundplans of the cerebrum

Najia A. Elkahlah, Yunzhi Lin, Yijie Pan, Joseph A. Carter, Troy R. Shirangi, E. Josephine Clowney

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Brain regions that regulate motivated behaviours, including the vertebrate hypothalamus and arthropod cerebrum, house bespoke neural circuits dedicated to perceptual and internal regulation of many behavioural states1,2. These circuits are built to purpose from complex sets of cell types whose patterning has been challenging to elucidate. Here we developed methods in Drosophila melanogaster to embed well-studied neurons that regulate mating in the transcriptional contexts of the neuronal lineages that generate them3,4,5. By comparing transcription within and between lineages, we identified a large set of transcription factors expressed in complex combinations that delineate cerebral hemilineages—classes of postmitotic neurons born from the same stem cell and sharing Notch status6,7. Hemilineages comprise the major anatomic classes in the cerebrum8,9,10 and these transcription factors are required to generate their gross features. We show that subtypes of the same hemilineage can provide a common computational module to circuits regulating different drives, and identify an orthogonal set of transcription factors that stratify hemilineage subtypes of differing birth order. Our findings suggest that distinct sets of transcription factors operate in a hierarchical system to build, diversify and sexually differentiate lineally related neurons that compose motivated behaviour circuits. By linking developmental patterning to separable transcriptional axes that produce gross versus fine aspects of information flow, we provide a logical framework for cerebral control of diverse drives.

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

Author Correction: Modelling late gastrulation in stem cell-derived monkey embryo models

Jie Li, Jie Li, Jing Cao, ShenShen Shang, Liansheng Zhang, Fei Gao, Jiqiang Fu, Hongyu Chen, Guizhong Cui, Haoyuan Wu, Xiaolong Wang, Alfonso Martinez-Arias, Qiang Sun, Zhen Liu

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

Universal transcriptomic hallmarks of mammalian ageing and mortality

Alexander Tyshkovskiy, Daria Kholdina, Maria Davitadze, Adrian Molière, Alibek Moldakozhayev, Yoshiyasu Tongu, Tomoko Kasahara, Dmitrii Glubokov, Alec Eames, Leonid M. Kats, Anastasiya Vladimirova, Kejun Ying, Hanna Liu, Bohan Zhang, Uma Khasanova, Mahdi Moqri, Jeremy M. Van Raamsdonk, David E. Harrison, Randy Strong, Takaaki Abe, Sergey E. Dmitriev, Vadim N. Gladyshev

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Ageing and interventions modulate health and mortality1, yet the underlying molecular mechanisms of this modulation remain unclear. Here we integrate more than 11,000 transcriptomes from more than 25 tissues across 4 mammals (mouse, rat, macaque and human) to develop accurate, interpretable rodent and multi-species biomarkers of chronological age and expected mortality, predicting lifespan-modulating interventions, time to death, chronic diseases and rejuvenation. Ageing-related changes were conserved across species and cell types, revealing universal transcriptomic signatures of mammalian ageing and mortality, including CDKN1A and LGALS3, whose protein levels were also associated with mortality and multimorbidity in UK Biobank. Mortality-associated features were recapitulated across in vivo and in vitro damage-accumulation models, including inflammation, replicative senescence, metabolic inhibition and γ-irradiation, and were attenuated or reversed by cell immortalization, reprogramming, heterochronic parabiosis and early embryogenesis. Network analysis uncovered a modular architecture of ageing- and mortality-associated hallmarks, encompassing inflammation, interferon signalling, mitochondrial function, chromatin modification and extracellular matrix organization. To quantify ageing of individual cellular components, we developed module-specific clocks, which revealed pathway-specific effects of interventions: chronic diseases primarily accelerated inflammatory-module ageing, whereas caloric restriction and Klotho (also known as Kl) deficiency targeted mitochondrial and metabolic modules. Transcriptomic and DNA methylation clocks showed correlated age acceleration in human blood, which was strongest for the chromatin-associated module clock, highlighting mechanistic links between molecular ageing modalities. This study reveals conserved signatures and a modular architecture of mortality regulation, providing a framework for quantifying and targeting ageing of cellular subsystems across species and tissues.

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

Direct observation of the superallowed α-decay of 104Te

Ian Cox, Robert Grzywacz, T. T. King, K. P. Rykaczewski, S. Nishimura, R. Yokoyama, N. Fukuda, N. Kitamura, S. Go, C. Mazzocchi, J. M. Allmond, A. Augustyn, N. Braukman, P. Brionnet, A. Esmaylzadeh, J. Fischer, G. Garcia de Lorenzo, S. Hanai, D. Hoskins, N. Imai, K. Kolos, A. Korgul, B. Kreider, S. Michimasa, K. Nishio, V. Phong, T. J. Ruland, H. Sakurai, Y. Shimizu, A. Skruch, H. Suzuki, H. Takeda, Y. Togano, Z. Y. Xu, M. Yoshimoto

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The radioactivity of the α particle is among the most compelling evidence for the existence of cluster structures in atomic nuclei. During the decay process, a pre-existing α particle tunnels through the potential barrier formed by the residual nucleus1,2. The degree of preformation of the α particle, a strongly bound system of two protons and two neutrons, is extracted from the data by dividing the α-decay probability by the barrier penetrability for a given particle energy. The preformation probability changes rapidly near nuclear shell closures, which is direct evidence that clustering is connected to nuclear structure3. Enhanced preformation was observed in the lightest α-particle emitters, spherical tellurium and xenon isotopes decaying to magic isotopes of tin. Here we show the most extreme case of α-particle preformation from the measurement of the decay of tellurium-104 (104Te). With a half-life of $7.{2}_{-1.5}^{+2.3}\,{\rm{ns}}$, 104Te is the fastest ground-state α-emitting nucleus known so far. The deduced preformation demonstrates that the enhancement is greater for 104Te than for any other nucleus. One nuclear model that can explain our observation postulates that the α particle can exist only in the low-nuclear-matter-density regions on the surface of the nucleus. The uniquely high preformation for 104Te is attributed to its relation to doubly magic tin-100 (100Sn), creating conditions conducive to form an α particle.

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

Substrate selectivity of the human RNA m5C methyltransferase NSUN2

Jacob Canepa, Victor M. Ruiz-Arroyo, Netanya S. Schlamowitz, Yunsun Nam

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Specific deposition of RNA modifications is important for regulating gene expression1,2. 5-Methylcytosine (m5C) is a common epitranscriptomic modification, and NSUN2 is a key enzyme responsible for m5C methylation of various types of RNA. Dysregulation of NSUN2 is associated with numerous diseases, including cancers and neurological disorders3. The versatility of NSUN2 complicates our understanding of its substrate specificity and molecular roles in biology and disease. Here we show how NSUN2 interacts with RNA substrates at distinct stages of its catalytic cycle to modify cytidines. Furthermore, we show the role of RNA structure in facilitating NSUN2 activity at multiple tRNA positions. We identify RNA duplexes surrounding the m5C modification site as crucial recognition elements for methylation, which enabled us to derive a minimized substrate that captures the preferred features of an NSUN2 substrate—a dual-stem structure containing the CNNRR motif at the 5′ end of the first stem. Insights into the mechanisms underlying substrate-specific NSUN2 enzymatic activity provide opportunities for understanding and therapeutically targeting NSUN2-dependent methylation. Overall, our work highlights the roles of RNA structure and sequence in defining substrate specificity and regulating RNA-modifying enzymes.

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

Monolithic three-dimensional integration of silicon transistors

Bao Lam, Yung Man Yu, Hyunjun Nam, Hsu-Chih Ni, Shomik Chatterjee, Shaloo Rakheja, Jian-Min Zuo, Qing Cao

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Monolithic, three-dimensional (3D) integrated circuits promise advantages in packing density, energy consumption and interconnectivity bandwidth but require forming high-performance semiconductors and transistors on top tiers under the constraint of a limited thermal budget compatible with back-end-of-line integration1,2. Back-end-of-line-compatible transistors have been built on laser-annealed polycrystalline silicon, metal-oxide semiconductors, carbon nanotubes and two-dimensional chalcogenides3,4,5. However, their performance and reliability are much inferior to bottom-tier silicon metal–oxide–semiconductor field-effect transistors, which mask most of the improvements offered by monolithic 3D integration. Here we show that uniformly doped, ultrathin (≤10 nm) single-crystalline silicon nanomembranes can be vertically stacked using a roll-transfer-printing process that is scalable to wafer-scale and tolerant to substrate topology and surface roughness, enabling multi-tiers of complementary junctionless transistors to be sequentially fabricated on the same starting substrate under a processing temperature ≤400 °C. These devices achieve performance approaching that of front-end-of-line silicon metal–oxide–semiconductor field-effect transistors with current density above 650 µA µm−1 and sub-10-nm inter-tier registration for high-density vertical integration. We vertically constructed logic gates, including inverters, NAND, NOR gates and static random-access memory cells, based on up to three-tier integration at transistor-level granularity. Our demonstrations provide a promising route towards silicon-based monolithic 3D circuits, especially for research and low-volume prototyping.

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

Bohmian mechanics remains unchallenged by tunnelling experiment

Aurélien Drezet, Dustin Lazarovici, Bernard Michael Nabet

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

Distinct genetic architecture in the tails of complex traits

T. Souaiaia, H. M. Wu, A. P. S. Ori, S. W. Choi, C. J. Hoggart, P. F. O’Reilly

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Complex traits are highly polygenic, with heritability explained by many hundreds of common variants of small effect together with rare variants of large effect 1 . Yet how this genetic architecture varies along the trait continuum has been underexplored, as has the role of natural selection in shaping this variation. Here we developed an approach based on polygenic risk scores that reveals widespread departures from common-variant architecture in one or both of the tails of 74 quantitative traits. These observations were replicated across ancestries, cohorts and repeated measures and using an alternative family-based approach 2 . Incorporating rare variants identified from sequence data resulted in marked reductions in these deviations, suggesting that rare alleles of large effect are key drivers of trait-tail architecture. Forward simulations showed that stabilizing selection could generate the observed patterns, whereas modelling reproductive success provided empirical support for the role of selection. These findings show that although complex traits are polygenic in the population at large, they have a distinct and less polygenic architecture in their tails due to selection. This has implications for rare-variant discovery and complex trait and disease prediction.

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

Sparse-to-dense coding transformation between hippocampal areas CA3 and CA1

Shir R. Maimon, Tamir Eliav, Johnatan Aljadeff, Aviya Shalev, Yishai Gronich, Nikita M. Finger, Keegan E. Eveland, Cynthia F. Moss, Liora Las, Nachum Ulanovsky

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The hippocampus is crucial for spatial memory and navigation. It contains place cells1,2,3,4,5,6,7: spatially selective neurons found in areas CA1 and CA3—two distinct hippocampal subregions with substantially different anatomical connectivity8. Previous studies have found highly similar spatial coding between CA1 and CA3 place cells3,9,10,11. This raises the question of why two subregions that form consecutive processing stages would exhibit identical neural coding. Here we hypothesized that the lack of differences between CA1 and CA3 spatial coding is due to the experimental paradigm: using small arenas. We tested this hypothesis by simultaneously recording from CA1 and CA3 neurons in bats flying in flight tunnels up to 200 m in length. We identified highly distinct neural coding in CA1 and CA3: whereas CA1 neurons exhibited dense spatial coding, consisting of multiple place fields12, CA3 neurons exhibited ultrasparse spatial coding, consisting predominantly of single place fields. Despite this marked difference, the sizes of place fields were very similar between the two subregions, across 5 different environment sizes ranging from 6 m to 200 m. Using a neural-network model, we show that such a sparse-to-dense transformation can facilitate fast learning of new spatial maps. We also found that in a large multicompartment environment, place cells were strongly modulated by trajectory history—a contextual effect (retrospective coding) that could last for over 100 m. Together, by using large naturalistic environments, we identified a CA3-to-CA1 coding transformation that serves to reformat spatial information into a more efficient, compressed neural code.

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

A direct black-hole mass measurement in a little red dot at high redshift

Ignas Juodžbalis, Cosimo Marconcini, Francesco D’Eugenio, Roberto Maiolino, Alessandro Marconi, Hannah Übler, Jan Scholtz, Xihan Ji, Gareth C. Jones, Michele Perna, Santiago Arribas, Jake S. Bennett, Volker Bromm, Andrew J. Bunker, Stefano Carniani, Stéphane Charlot, Giovanni Cresci, Pratika Dayal, Eiichi Egami, Andrew Fabian, Kohei Inayoshi, Yuki Isobe, Lucy R. Ivey, Sophie Koudmani, Nicolas Laporte, Boyuan Liu, Jianwei Lyu, Giovanni Mazzolari, Stephanie Monty, Eleonora Parlanti, Pablo G. Pérez-González, Brant Robertson, Raffaella Schneider, Debora Sijacki, Sandro Tacchella, Alessandro Trinca, Rosa Valiante, Marta Volonteri, Joris Witstok, Saiyang Zhang

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Recent discoveries of faint active galactic nuclei (AGN) at the redshift frontier have revealed a plethora of broad Hα emitters with optically red continua, named little red dots (LRDs) 1 , which comprise 15–30% of the high-redshift broad-line AGN population 2 . Owing to their peculiar properties 3–6 , modelling LRDs with standard AGN scenarios has proven challenging. In particular, the validity of single-epoch virial mass estimates in determining the black-hole masses of LRDs has been called into question, with some models claiming that masses might be overestimated by up to two orders of magnitude 7–10 . Here we report a direct, dynamical black-hole mass measurement in a strongly lensed LRD at a redshift of 7.04. The combination of lensing with deep spectroscopic data reveals a rotation curve that is inconsistent with a nuclear star cluster, yet can be well explained by Keplerian rotation around a point mass of 50 million solar masses, consistent with virial black-hole mass estimates. The Keplerian rotation leaves little room for any stellar component in a host galaxy, as we conservatively infer M BH / M ⁎ > 2 (where M BH is the black-hole mass and M ⁎ is the stellar mass). Such a ‘naked’ black hole, together with its near-pristine environment 11 , indicates that this LRD is a massive black-hole seed caught in its earliest accretion phase.

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

Cellular water-potential sensing through biomolecular condensation

Yunhe Wang, Longchen Zhu, Yun Yang, Xiaoshuang Li, Xin Zhang, Xiaofeng Fang

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Water molecules, as solvents for biomolecules, are essential to cells. The water potential of the cell decreases under water-deficient conditions1,2, yet how cells sense changes in water potential remains unknown. Here we identify a sterile alpha motif (SAM)-containing protein, SAM8, that undergoes water-potential-dependent condensation both in vivo and in vitro and is crucial for hyperosmotic stress tolerance and seed germination. We use biophysical techniques, in vitro reconstitution and bioimaging to demonstrate that SAM8 is strongly hydrated under normal water conditions, preventing its macroscopic condensation. A negatively charged patch determines SAM8 hydration by creating an electric field and micropolar environment. Water-deficient conditions weaken this hydration, thereby activating SAM8 condensation by reprogramming hydrogen bond, electrostatic and hydrophobic interactions. Furthermore, we demonstrate that SAM8 condensates selectively sequester RNA export factors, leading to nuclear retention of mRNAs and translational reprogramming under hyperosmotic stress. Our findings show a mechanism by which plant cells directly sense and respond to water status, shedding light on how they adapt to water deficit conditions.

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

Global lung cancer burden shifting to middle-income countries

Ben Deighton

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

Memory on trial: the new science of when to trust eyewitness testimony

R. J. Mackenzie

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

Iran’s Internet blackout: a scholar’s month in the dark

Mohammad Sal Moslehian

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

A cautious voice on the closure of China’s journal ranking list

Xiaochuang Li, Wenhao Qian

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

Daily briefing: Bogus citations will get you banned from arXiv

Flora Graham

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

Stress impairs your brain’s ability to link memories — dampening insight

Simon Spichak

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

Vanishing tongues and life on Mars: Books in brief

Andrew Robinson

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

AI cracks 80-year-old mathematics challenge — researchers are astonished

Davide Castelvecchi

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

GDP and beyond: why treating nature as capital cannot save the planet

Walter J. Radermacher

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

Never smoked? Good, but you could still get lung cancer

Rachel Nuwer

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

Nests in an egg cell: structures of protein-storage units in oocytes

Matthias Geyer, Gregor Hagelueken

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

Too dangerous to release: is Mythos the start of the restricted-AI era?

Chris Stokel-Walker

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

How I eavesdrop on frog conversations

Elizabeth Preston

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

AI and simple blood tests could catch lung cancer earlier

Amanda Keener

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

Drugs that boost immunity are making lung cancer less deadly

Tammy Worth

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

Major Ebola outbreak is escalating: what happens next

Benjamin Thompson, Rachel Fieldhouse

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

Transistors on a roll: 3D circuits built from stacks of flexible membranes

Veeresh Deshpande

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

Meet the biologists deciphering marine-mammal histories from baleen, whiskers and tusks

Virginia Gewin

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

See the clouds streaming and vanishing around this planet — 690 light years away

Davide Castelvecchi

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

Poland’s economy is thriving, but its science is dying

Maria W. Górna, Michał Tomza, Agata Starosta, Łukasz Okruszek

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

Lung cancer in women emerges as a distinct disease

Claire Ainsworth

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

Gene clock predicts time to death in humans – and assesses ‘biological’ age

Heidi Ledford

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

Daily briefing: Why it’s hard to show insight under pressure

Jacob Smith

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

Daily briefing: Wearable robot could help kids with neuromuscular disease stand

Jacob Smith

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

Why AI can’t be trusted to write scientific reviews

Rupa Sarkar

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

How we’re using AI tools to improve psychedelic-drug research

Robin Berghaus

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

We vibe-coded a custom AI poetry lab. Here’s how you can, too.

Simon Wang, Yu Ruobin, Stuart Christie

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

Ebola outbreak spirals out of control: how might it have started?

Mohana Basu

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

When the grid can’t keep up: how South African laboratories handle power outages

Max Bennett

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

Science takes on the world’s most lethal malignancy

Herb Brody

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

Peter H. Raven obituary: visionary botanist who transformed our understanding of plant diversity

Lúcia G. Lohmann

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

Should I get a dog? What to know about pet ownership as a scientist

Hannah Docter-Loeb

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

Hard-to-detect mutations explain how common autoimmune diseases arise

Sergei B. Koralov, Timothy C. Borbet

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

Move over, AlphaFold: open source model predicts shape of 1 billion proteins

Ewen Callaway, Miryam Naddaf

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

Ebola outbreak: the data that show why researchers are so alarmed

Ewen Callaway, Mariana Lenharo, Lauren Wolf

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

AI FOMO: everyone is mastering AI except me — or are they?

Zhang-Ren Chen

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

Hit a lab project glitch? Thinking about your thesis title like a storyteller can help you focus

Dom Byrne

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

Organ formation in early human embryos captured in spatial cell atlas

Varun K. A. Sreenivasan, Malte Spielmann

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

Scraping

Laura O’Meara

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

Why Africa’s low rate of lung cancer is an illusion

Elvis Obomanu

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

Robots run this laboratory in Japan — and are changing how scientists work

Rachel Fieldhouse

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

Neuroflix

John McLaughlin

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

How to breathe life back into brain theory

Àlex Gómez-Marín

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

Child sexual abuse enabled by digital technologies is widespread and under-reported

Xiangming Fang, Greta M. Massetti

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

Five highlights from lung-cancer research

Rachel Nuwer

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

Innovation starts in schools — lessons from China

Dan Tao, Rui Wei, Yonghe Zheng

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

How the connection between lung cancer and the brain could lead to better treatments

Liam Drew

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

Conservation gains should not be at the mercy of political changes

Juan F. Ovalle, Dylan Craven

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

Gene-expression patterns can be used to estimate mortality risk and chronological age

João Pedro de Magalhães

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Technology mediation in child sexual exploitation and abuse in Africa and Asia

Sakshi Ghai, Matti Vuorre, Daniel Kardefelt-Winther, Amanda M. Ferguson, Sebastian Kurten, Sonia Livingstone, Andrew K. Przybylski, Amy Orben

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As digital access expands rapidly among children worldwide, technology-facilitated child sexual exploitation and abuse (CSEA), including online grooming, sexual solicitation, non-consensual image sharing and sexual extortion, has emerged as urgent yet underexamined category of digital harms 1 . Despite growing policy attention to online safety, evidence remains limited, particularly in low- and middle-income countries, where most of the world’s children live 2 . We analysed nationally representative survey data from 11,912 children aged 12–17 years across 12 countries in eastern and southern Africa and Southeast Asia, collected through the Disrupting Harm project in 2020–2021. We found that one in six internet-using children experienced at least one form of technology-facilitated CSEA, equivalent to over 10 million children. Despite this scale, many experiences went undisclosed, pointing to disclosure as a critical pathway for protection in the digital age. When children did disclose, they relied primarily on informal channels, especially friends, rather than formal reporting mechanisms such as police or helplines. Using Bayesian hierarchical models accounting for cross-country heterogeneity, we find that older children were less likely to disclose, whereas enabling parental mediation of online activities and children’s knowledge of where to seek help after sexual harassment or assault were associated with higher rates of disclosure. These findings provide population-level evidence to inform prevention and response across low- and middle-income countries, where coordinated action by policymakers, law enforcement and technology companies is urgently needed to protect all children.

Redesigning algorithms to intervene on social norm misperceptions during a national election

William J. Brady, Meriel Doyle, Abdo Elnakouri, Eli J. Finkel, Joshua Conrad Jackson, Nour Kteily, Victoria Parker, Curtis Puryear, Trevor Spelman, Jacob Teeny, Mark Torres

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For the first time in history, civic discourse commonly occurs in digital environments in which algorithms influence exposure to social information1,2. It is increasingly important to understand whether and how these algorithms affect political discourse3,4,5. Here we built custom feed-ranking algorithms with full control over their features, and randomly assigned 2,000 participants to use them for 8 weeks (before and after the 2024 US presidential election). We tested whether an engagement-based algorithm (used on major social media platforms6,7) amplifies intergroup, moralized and emotional (IME) information in ways that skew perceptions of social norms around political dialogue5,8, and whether it increased engagement with IME content and perceptions of partisan animosity (compared with a reverse-chronological feed9,10). We also developed and tested a ‘diversified extremity’ algorithm to reduce the influence of extreme users11,12,13 to improve the accuracy of social norm perception14,15,16 and reduce perceptions of partisan animosity. We found that engagement-based feeds amplified IME and toxic content relative to reverse-chronological feeds, with the largest increases in moral outrage and political content. Engagement-based feeds also reduced prescriptive norm perception accuracy (albeit in an unexpected direction) and increased perceived partisan animosity. However, they did not significantly alter users’ own engagement behaviours. The diversified extremity algorithm reduced IME and toxic content exposure, improved prescriptive norm accuracy, yet maintained comparable platform enjoyment—suggesting that reducing the influence of extreme users can curb algorithmic distortions without diminishing user experience. protocol registration The Stage 1 protocol for this Registered Report was accepted in principle on 17 September 2024. The protocol, as accepted by the journal, can be found at https://osf.io/c9a3m.

Nature Human Behaviour

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

Thalamic oscillations distinguish natural states of consciousness in humans

Aditya Chowdhury, Xiongbo Wu, Tara Beilner, Thomas Schreiner, Thomas Koeglsperger, Jan-Hinnerk Mehrkens, Jan Remi, Christian Vollmar, Elisabeth Kaufmann, Tobias Staudigl

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Natural states of consciousness are thought to be regulated by deep brain structures such as the thalamus. However, very little is known about the underlying electrophysiology in humans. Here, using a rare opportunity to directly record from the human thalamus, we identify a hitherto-unreported brain-state-specific oscillation of approximately 19–45 Hz. This oscillation is present only during rapid eye movement (REM) sleep and wakefulness, while being absent during non-REM sleep. The 19–45 Hz oscillation further distinguishes REM sleep microstates, co-occurring with bursts of eye movements, and is specific to the central thalamus, a structure implicated in causing global brain state transitions. The discovery of a distinct oscillatory signature in the central thalamus that distinguishes conscious states opens up avenues to further investigate thalamic contributions to states of consciousness in humans and potentially to refine interventions to treat disorders of consciousness.

Why social media research has failed policy-makers

Tobias Dahl, Njål Foldnes, Steffen Grønneberg, Craig Aaen-Stockdale

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Proceedings of the National Academy of Sciences

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

Metallodielectric photonic glass paints enable hyperchromatic, angle-independent structural color across the full visible spectrum

Yuwon Jeon, Jaewon Lee, YongDeok Cho, Minyoung Park, Kyeongsoo Kim, Soyul Kwak, Seungwoo Lee

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Colloidal photonic glasses are attractive as dye-free, solution-processable pigments that show weak angle dependence, but their red hues are notoriously washed out, because single-particle Rayleigh/Mie scattering produces a strong blue background (form factor). Here, we report metallodielectric photonic glass paints that deliver hyperchromatic structural colors, including vivid angle-independent red. We disperse monodisperse Au@SiO 2 core–shell colloids at 34 vol% in a photocurable, refractive-index-matched ethoxylated trimethylolpropane triacrylate resin. The Au core introduces selective absorption below ~500 nm wavelength, suppressing form factor scattering that would otherwise leak blue light, while index matching sharpens the structure factor-driven reflection by reducing diffuse multiple scattering. A modified Monte Carlo multiple-scattering model predicts spectral narrowing only when both effects are combined. Derjaguin, Landau, Verwey, and Overbeek calculations and Langevin molecular-dynamics simulations reveal that Au-enhanced van der Waals attraction favors reaction-limited crystallization; adding NaCl reduces the Debye length and switches assembly to diffusion-limited aggregation, yielding amorphous short-range order. After ultraviolet (UV) curing into ~100 µm-thick films, the resulting photonic glasses exhibit bright, angle-independent structural colors across the visible range through particle-size tuning. In particular, 230 nm Au@SiO 2 colloidal glasses show a reflectance band confined to 600 to 800 nm wavelengths, producing a saturated red with minimal blue leakage. Because the precursor is a stable liquid resin, the photonic glasses can be freehand-painted to create large-area coatings and fine graphics with high brightness even under sunlight. This work establishes design rules for completing the structural color palette in photonic glasses and provides a practical route to structural color paints.

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

Capturing nuclear quantum effects in high-pressure superconducting hydrides and ice with nuclear–electronic orbital theory

Logan E. Smith, Paolo Settembri, Alessio Cucciari, Lilia Boeri, Gianni Profeta, Sharon Hammes-Schiffer

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Nuclear quantum effects are essential for correctly describing hydrogen-rich materials at high pressures. Superconducting hydrides and ice are prime examples of such systems, requiring the inclusion of lattice anharmonicity and nuclear quantum effects to correctly predict and describe the structures and phase transition pressures observed experimentally. Herein, we show that the nuclear–electronic orbital density functional theory (NEO-DFT) method, which treats specified nuclei quantum mechanically on the same level as the electrons, is capable of accurately describing nuclear quantum effects in superconducting hydrides and ice. NEO-DFT predicts the hydrogen-bond symmetrization pressure in H 3 S and D 3 S, benchmarking against the more expensive stochastic self-consistent harmonic approximation method, and predicts the correct symmetric Fm 3 ¯ m structure for LaH 10 at a wide range of pressures. NEO-DFT also predicts the ice VIII to ice X phase transition pressures for H 2 O and D 2 O in agreement with experimental measurements. The accuracy, computational efficiency, and broad applicability of the NEO method opens the door for expanded large-scale studies into these types of systems.

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

Explaining the universality of biological thermal responses

Jose Ignacio Arroyo, Christopher Kempes, Geoffrey West, Pablo A. Marquet

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

A negative-hydrated constriction zone is revealed in the active state of the H v 1 channel

Juan J. Alvear-Arias, Dario Basaez, Emerson M. Carmona, Luciano Galizia, Miguel Fernandez, Antonio Peña-Pichicoi, Marcelo Ozu, Orlando Jorquera, Ramón Latorre, Alan Neely, Jose Antonio Garate, Carlos Gonzalez

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The voltage-gated proton (H v 1) channel is crucial in regulating cellular pH, yet the mechanism underlying proton permeation remains controversial. A deeper understanding of the differences between the channel’s active and resting states is essential for clarifying its conductive properties. In this study, we employ a combination of molecular dynamics simulations, site-directed mutagenesis, and electrophysiological recordings to investigate what changes occur in an active H v 1 channel and how these changes influence conduction properties in the wild-type (WT) channel, a low-conducting N264R mutant, and a superconductive N264E mutant. Our findings reveal that in the active state, interactions are weakened between the selectivity filter, aspartate D160, and the third arginine in the S4 transmembrane segment. This results in a more negatively charged and hydrated environment, which enables proton transport in the WT and N264E channels. Notably, these conformational changes are absent in the N264R mutant. Additionally, our simulations predict—and osmotic shock experiments in oocytes confirm—that an active H v 1 channel can facilitate water permeation. These observations suggest that water conduction occurs as a byproduct of a more dilated and hydrated pathway. We introduce a methodological approach to studying H v 1 by utilizing water permeation as a functional readout. Collectively, our results provide insights into the structural rearrangements of the H v 1 constriction zone, shedding light on how its resting and active configurations govern proton conduction.

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

Light-controlled disruption of cancer cell dormancy via photoswitchable stress hormone receptor degraders

Karina M. Freitag, Robin Scheuplein, Chiara Orlacchio, Viola Ansuinelli, Tommaso Fava, Vincent Fischer, Bohan Zhang, Miriam Kretschmer, Mahshid Gazorpak, Erick M. Carreira, Katharina Gapp

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Cancer cell dormancy is a key contributor to therapy resistance and disease relapse. The glucocorticoid receptor (GR), a major mediator of stress hormone signaling, has emerged as a central regulator of dormancy in non-lymphoid solid tumors, particularly lung cancer. However, systemic GR inhibition or degradation using conventional Proteolysis Targeting Chimeras (PROTACs) risks widespread on-target toxicity due to their constitutive activity. We hypothesized that integrating photoswitchable elements into PROTACs, termed photoPROTACs, would enable wavelength-specific, spatiotemporally precise modulation of GR degradation and dormancy-associated signaling pathways. Here, we synthesized a diverse series of photoPROTACs incorporating photoswitchable arylazotriazole or arylazopyrazole scaffolds, including previously unreported (OEt) 2 - and (NMe 2 ) 2 -substituted photoswitches. Arylazopyrazole-based GR photoPROTACs bearing Me 2 - and (OEt) 2 substituents exhibited near-quantitative photoisomerization (95% Z- isomer; 89 to 92% E- isomer), no photobleaching, and thermal half-lives in the range of 3 to 12.2 d in dimethyl sulfoxide (DMSO). Among them, KH-5-306 and KH-5-309 induced potent, specific, and reversible GR degradation in their thermodynamically stable E- isomeric form at low nanomolar concentrations, with markedly reduced activity in the Z- isomeric state. Transcriptomic profiling showed that E- KH-5-309 disrupts GR-driven dormancy-associated gene expression programs in a non–small cell lung cancer (NSCLC) model, while the Z- isomer remains functionally inert. Our findings establish a framework for the rational design of photoswitchable PROTACs beyond GR and demonstrate their potential to achieve spatiotemporal control of stress hormone receptor signaling, enabling mechanistic insights into GR function and the targeted disruption of cancer cell dormancy.

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

The simplicity of the Hodge bundle

Anand Patel

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This paper establishes the simplicity of the Hodge bundle, a theorem in the branch of modern mathematics known as algebraic geometry. Notably, the essential mathematical content was autonomously generated by Aletheia, a custom AI agent powered by Gemini Deep Think.

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

Polyploidy and stress

Douglas E. Soltis, Donald T. Fox, Pamela S. Soltis

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

Unsupervised and probabilistic learning with Contrastive Local Learning Networks: The Restricted Kirchhoff Machine

Marcelo Guzman, Simone Ciarella, Andrea J. Liu

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Autonomous physical learning systems modify their internal parameters and solve computational tasks without relying on external computation. Compared to traditional computers, they enjoy distributed and energy-efficient learning due to their physical dynamics. In this paper, we introduce a self-learning resistor network, the Restricted Kirchhoff Machine, capable of solving unsupervised learning tasks akin to the Restricted Boltzmann Machine algorithm. The circuit relies on existing technology based on Contrastive Local Learning Networks, in which two identical networks compare different physical states to implement a contrastive local learning rule. We simulate the training of the machine on a dataset of handwritten digits, providing a proof of concept of its learning capabilities. Finally, we compare the scaling behavior of time, power, and energy per operation as the number of nodes increases to that of a Restricted Boltzmann Machine implemented on central processing unit (CPU) and graphics processing unit (GPU) platforms.

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

The effector NlOBP1b from the brown planthopper suppresses rice immunity by manipulating the OsCK2 complex

Chao Wang, Can Wei, Chang-Lai Qiu, Supaporn Falert, Yong-Qian Zhang, Shi-Yu Yu, Man-Qun Wang

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Odorant-binding proteins (OBPs) are crucial mediators in the peripheral olfactory perception of insects, functioning as a link between the external environment and odor receptors. Recent research has revealed their noncanonical role as salivary proteins that mediate plant–herbivore interactions, though the underlying mechanisms remain poorly understood. This study investigates the molecular basis of NlOBP1b, a salivary effector protein in the brown planthopper ( Nilaparvata lugens , BPH), which suppresses plant immune responses and enhances insect fitness. NlOBP1b -RNAi BPH results in reduced adaptability to host plants. Furthermore, NlOBP1b specifically interacts with the regulatory subunits of casein kinase II, OsCK2β3 and OsCK2β4. On one hand, NlOBP1b disrupts the assembly of the OsCK2β3–OsCK2α2 holoenzyme complex; on the other hand, it competes with the bZIP superfamily transcription factor OsTGA5 for binding to the OsCK2β4–OsCK2α2 complex, results suppressing holoenzyme-mediated phosphorylation and transcriptional activity of OsTGA5, ultimately reducing lignin accumulation. This disruption undermines the defense mechanisms of rice and significantly enhances the adaptability of BPH to its host.

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

Age-based approach to characterize the dynamics of cellular processes

Elad Noor, Kirill Jefimov, Ersilia Bifulco, Evgeny Onischenko

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Cells continuously produce and degrade molecules, essential for maintaining homeostasis. The study of these dynamics has gained momentum since the development of pulse–chase methods, utilizing fluorescent or isotopic labeling to assess properties such as turnover rates or half-lives. However, standard analyses of these experiments often depend on assumptions such as the homogeneity of analyzed molecules or their immediate labeling, which do not always hold. Here, we show that the readouts of steady-state dynamic labeling experiments can be interpreted as the distribution of metabolic ages, defined as the time since each molecule entered the metabolic system, and that metabolic ages can be quantified with minimal assumptions. Using this age-based interpretation, we demonstrate how the experimentally observed labeling dynamics is connected to a variety of dynamic parameters including half-lives, decay rates, and residence times and how these interpretations are affected by the conditions of delayed input, cell growth, or complex degradation patterns. To aid in the experimental quantification of dynamic parameters, we introduce a compartmental model framework as well as an open-source software package. We illustrate the framework’s practical utility by quantifying dynamic parameters and determining the kinetic pool structure of budding yeast proteins at optimal and suboptimal growth temperatures.

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

A large-scale framework for estimating soil carbon, nitrogen, pH, and salinity dynamics for 1985–2023

Matteo Dalle Vaglie, Saverio Francini, Gherardo Chirici, Federico Martellozzo

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Soil is fundamental to sustaining life on Earth, providing ecosystem services, regulating climate, and playing a central role in global food systems. In the last decades, due to human activities and climate change, soils worldwide have experienced substantial changes in their key properties, resulting in alterations to their functions. In this context, global soil mapping is crucial for identifying degradation trends and informing effective adaptation strategies. To address these challenges, this work leverages advances in machine learning and cloud computing to develop HUMERIS, a global dataset spanning 1985 to 2023 and covering four key soil properties: salinity (EC e ), pH, nitrogen (N), and organic carbon (OC) across natural ice-free land surfaces globally. The goal of HUMERIS is to create a framework able to predict long-term soil dynamics across spatial scales, time, and depth. For topsoil over the reference period, the analysis suggests an increase in N (+0.4% per year) and OC (+0.5% per year), associated with a decrease of EC e (−0.2% per year) and stable values of pH. Looking at biomes and land cover classes two contrasting dynamics emerge. Colder regions show an increase in predicted OC and N compared to warmer ones, while land-use analysis reveals that areas converted from natural to cropland exhibit a relative decrease of −0.2%. These results suggest shifts in global soil properties with implications for agroecological modeling, socioeconomic analysis, and sustainable land management.

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

The revised three-step detour pathway in dolichol biosynthesis is evolutionarily conserved in budding yeast

Kazuki Hanaoka, Kuya Matsunaga, Souichirou Shimizu, Soshi Sakai, Harald Pichler, Kouichi Funato

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The identification of SRD5A3 , a causative gene for congenital disorders of glycosylation (CDGs), together with its yeast ortholog DFG10 , established the prevailing model that dolichol is synthesized from polyprenol in a single step. Subsequently, a recent discovery of DHRSX in CDG patients revised this view and led to the proposal of a three-step detour pathway for dolichol biosynthesis. However, it remains unclear whether this pathway represents a conserved mechanism or reflects evolutionary diversity in eukaryotes. Here, we identified TDA5 as a yeast ortholog of DHRSX . Deletion of TDA5 caused glycosylation defects, reduced dolichol levels, and accumulated polyprenol. All these phenotypes were rescued by expression of DHRSX , but not by DFG10 or SRD5A3 . These findings show that Tda5 serves the same function as DHRSX in yeast, thereby demonstrating conservation of the three-step detour pathway in yeast and supporting a broader eukaryotic framework for dolichol biosynthesis.

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

Collective motion in bacterial suspensions is scale-free

Benjamín Pérez-Estay, Vincent Martinez, Carine Douarche, Jana Schwarz-Linek, Jochen Arlt, Pierre-Henri Delville, Gail McConnell, Wilson C. K. Poon, Anke Lindner, Eric Clement

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In suspensions of swimming bacteria, individual cells interact via long-range hydrodynamic forces and self-organize into collective states that drive large-scale chaotic flows, commonly referred to as “bacterial turbulence.” Despite extensive experimental and theoretical work, it remains unclear whether an intrinsic length scale underlies the observed patterns. To directly address this question and shed light on the mechanisms driving active turbulence, we investigate the emergence of large-scale flows in E. coli suspensions confined within flat cylindrical chambers, systematically varying the confinement height over more than two orders of magnitude. We first demonstrate that the critical density for the onset of collective motion scales inversely with the confinement height without saturation. Near the onset, both the observed length and time scales increase sharply, with the length scale limited only by the vertical confinement. Importantly, both scales exhibit clear power-law dependence on the confinement height, demonstrating the absence of an intrinsic length scale in bacterial collective motion. Close to the instability onset, we observed transient coherent vortices, reaching up to 4,000 times the size of a single bacterium and spanning the full chamber width, further reinforcing the conclusion that bacterial turbulence is scale-free. Our experimental results, which characterize the onset of collective motion and demonstrate that bacterial turbulence is scale-free, discriminate between competing theoretical models and provide essential input for theories seeking to capture the dynamics and constitutive relations of wet active matter.

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

3D insights into the multiorigins of nanophase Fe 0 in the Moon surface

Yiheng Dai, Zezhou Li, Tianyi Jia, Zhiheng Xie, Ruimin Wang, Zongjun Yin, Bing Shen, Jihan Zhou

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Nanophase metallic iron (npFe 0 ) in lunar soils is a key indicator for understanding the space weathering mechanisms of airless bodies. However, the detailed three-dimensional (3D) spatial topology and distribution of layered npFe 0 have rarely been documented in lunar soil samples. Here, we reveal the unique 3D spatial multilayered distributions and morphologies of npFe 0 in the Chang’e-5 impact glass using a combination of electron tomography and spectroscopic techniques, demonstrating that npFe 0 originates from multiple effects including iron sulfide decomposition, Fe(II) disproportionation, and solar wind irradiation. We provide direct evidence for the decomposition of iron sulfide to produce irregularly shaped npFe 0 . This study quantifies the 3D abundance of npFe 0 in a piece of lunar impact glass, revealing localized Fe 0 accumulation up to 7.1 wt%. Our results provide 3D nanoscale analysis for multiple coexisting formation mechanisms of npFe 0 , elucidating the complex space weathering processes in the lunar surface.

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

Projection-defined hypothalamic outputs differentially regulate thermogenesis and lipolysis

Hyeonyoung Min, Qi Zheng, Yunlei Yang

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The ventromedial hypothalamus (VMH) is a key regulator of energy homeostasis, linking central neural activity to peripheral metabolic function. Within the VMH, neurons expressing steroidogenic factor-1 (SF-1; VMH SF1 ) are essential for regulating energy expenditure, yet the projection-defined pathways through which they differentially control distinct adipose depots remains unclear. Here, we use projection-specific optogenetic and chemogenetic manipulations in SF1-Cre mice to identify two anatomically and functionally distinct VMH SF1 output pathways with complementary metabolic roles. Activation of the VMH SF1 →rostral periaqueductal gray (rPAG) projection selectively stimulates thermogenesis in brown adipose tissue, elevating its temperature and thermogenic gene expression, whereas activation of the VMH SF1 →paraventricular thalamus (PVT) pathway promotes lipolysis in white adipose tissue without engaging thermogenic programs. Both effects require intact innervation and target-region activity. These findings reveal that VMH SF1 neurons direct distinct hypothalamic output pathways to differentially regulate thermogenesis and lipid mobilization, delineating a modular neural framework for flexible, state-dependent coordination of energy expenditure and substrate utilization.

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

Evolution of genome-wide barriers to gene flow during complex speciation in rattlesnakes

Keaka Farleigh, Dylan K. Highland, Megan G. Alderman, Yannick Francioli, Samuel R. Hirst, Ellie M. Faber, Blair W. Perry, Matthew L. Holding, Gamaliel Castañeda-Gaytán, Miguel Borja, Hector Franz-Chávez, Christopher L. Parkinson, Jason L. Strickland, Mark J. Margres, Stephen P. Mackessy, Jesse M. Meik, Todd A. Castoe, Drew R. Schield

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Speciation with gene flow poses a central paradox: how do genome-wide barriers to gene exchange accumulate as recombination continually breaks down associations among selected loci? Although theory predicts that together recombination, selection, and genome structure shape reproductive isolation, empirical studies often report conflicting patterns, suggesting that these determinants change across the speciation continuum. Here we compare genomic landscapes of introgression across rattlesnake lineages spanning a range of divergence. We generated a chromosome-level reference genome for the Southwestern Speckled Rattlesnake ( Crotalus pyrrhus ) and analyzed whole genome data from 181 individuals across two species complexes with a history of gene flow upon secondary contact. We show that reproductive isolation is highly polygenic and dynamically structured. At early divergence, introgression is most reduced in high recombination regions, consistent with increased efficacy of selection against gene flow at few large-effect loci. As divergence progresses, linked selection against gene flow dominates, generating a positive relationship between recombination and introgression expected to occur through the genome-wide coupling of polygenic barrier effects. Introgression landscapes also become increasingly correlated across species pairs as divergence increases due to repeated evolution of barriers in the same genomic regions. Here, we infer that the Z chromosome plays a prominent role in reproductive isolation, harboring a disproportionate number of barrier loci and showing reduced introgression even at early divergence. Together, these results reveal how recombination, selection, and genome organization interact to shape speciation with gene flow upon secondary contact, reconciling empirical patterns with predictions of speciation theory.

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

Transition of the presynaptic vesicle cluster from a compact to dispersed organization during long-term potentiation

Guadalupe C. Garcia, Thomas M. Bartol, Lyndsey M. Kirk, Priyal Badala, Kristen M. Harris, Terrence J. Sejnowski

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Long-term potentiation (LTP) is a lasting form of synaptic plasticity that can persist for hours or even days. It is associated with structural changes in both the presynaptic terminal and the postsynaptic spine. Presynaptically, the number and distribution of synaptic vesicles (SVs) affect synaptic efficacy. How the functional changes in synaptic efficacy after the induction of LTP are mirrored by identifiable structural alterations in the SV cluster is not fully understood. Here, we interrogated presynaptic terminals in 3DEM reconstructions from CA3-to-CA1 synapses in stratum radiatum of adult rats that had undergone control stimulation, or theta-burst stimulation to produce LTP. An increase was observed in the dispersion of SVs at 2 h after LTP induction. This dispersion resulted in greater distances between neighboring SVs, longer distances to the center of the SV cluster, and an increased variance in SV position relative to the cluster’s center. Analysis of the SV clusters distinguished terminals that were potentiated based on their degree of dispersion, distances to neighboring SVs, and SV cluster densities. Our analysis demonstrates that the density of SVs is a property independent of the bouton or SV cluster volumes and is subject to strong regulation. Comparing the spatial distribution of SVs to randomized distributions revealed increased SV mobility following LTP induction. Moreover, theoretical calculations informed by the measured SV cluster densities suggest an increase in the mobility of SVs within the cluster during LTP. These findings provide evidence that the SV cluster undergoes a transition from tight to dispersed, making SVs more mobile during LTP.

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

Illuminating proinflammatory myeloid cells with PET tracers targeting GPR84

Mausam Kalita, Renesmee C. Kuo, Valentina Straniero, Samantha T. Reyes, Mallesh Pandrala, Alessia Lanzini, Sara Marsango, Desiree D’Moore, Piper Mahn, Andrew Setiadi, Mira Sundar, Spencer Mak, Sydney Nagy, Israt S. Alam, Poorva Jain, Grace Inay, Rim Malek, Allen F. Brooks, Corinne Beinat, Ermanno Valoti, Peter J. H. Scott, Graeme Milligan, Michelle L. James

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Innate immunity mediated by myeloid cells defends against infection and injury, but when chronically activated, it drives tissue damage and neurodegeneration. Molecular imaging with positron emission tomography (PET) enables noninvasive, real-time monitoring of such processes in vivo. However, most current neuroinflammation PET tracers lack specificity for activated myeloid cells. G protein–coupled receptor 84 (GPR84) is a promising biomarker that is selectively upregulated on activated microglia and macrophages. Here, we report the development and validation of two fluorine-18-labeled GPR84 tracers, [ 18 F]MGX-110S and [ 18 F]MGX-111S. Both exhibit specific binding to human GPR84-expressing cells, with [ 18 F]MGX-110S demonstrating superior affinity, selectivity, and signal-to-background ratio. [ 18 F]MGX-110S enables sensitive detection of systemic- and neuro-inflammation in LPS-treated mice and outperforms PET images obtained using a radiotracer specific for translocator protein 18 kDa in 5xFAD mice—revealing pathology-correlated activation across cortical, hippocampal, and thalamic regions. Taken together, our data indicate that [ 18 F]MGX-110S is a highly sensitive and specific tool for visualizing maladaptive myeloid cell activation; its clinical translation could enable more precise detection and staging of inflammation in addition to improved therapeutic monitoring in neurodegenerative disorders and more broadly in inflammatory diseases.

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

CTCF directly binds G-quadruplex structures to regulate genome topology and gene expression

Daniela Samaniego-Castruita, Isabella Han, Roxroy C. Morgan, Samantha Carpenter, Bryce Williams, Abhijit Chakraborty, Ishwar Radhakrishnan, Ferhat Ay, Samuel A. Myers, Anjana Rao, Vipul Shukla

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DNA G-quadruplexes (G4s) are non-B-form secondary DNA structures that are prevalent at key regulatory regions in mammalian genome and are highly conserved across evolution. However, the mechanisms by which G4s contribute to distinct facets of genome function are not well understood. Here, we conduct a proteomics screen with G4s of diverse topologies to uncover G4 binding activities in genomic regulators of nucleosome remodeling, paraspeckle assembly, RNA splicing, and three-dimensional genome organization. Among the prominent hits, we identify the genomic architectural protein, CCCTC-binding factor (CTCF), as one of the strongest G4 binders. Building on this finding, we perform extensive biochemical validation of CTCF–G4 interaction and identify a CTCF mutant, with pronounced affinity for G4s over its consensus double-stranded DNA motif. By implementing well-established approaches and developing additional G4 mapping tools, we define a comprehensive catalog of genomic G4s and demonstrate their close association with CTCF binding. Using genetic reconstitution of mouse embryonic stem cells with a G4-specific CTCF mutant, we define the role of G4s in regulating CTCF occupancy, chromatin looping, and gene expression. Our studies reveal that G4-linked chromatin loops are stronger, persistent, and less sensitive to CTCF depletion. Collectively, our work establishes the G4 binding activity of CTCF and provides key insights into the functional significance of G4 structures.

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

Residual photoreceptors affect the response of a degenerate retina to electrical stimulation

Keith Ly, Mohajeet B. Bhuckory, Davis Pham-Howard, Anna Kochnev Goldstein, Nathan Jensen, Daniel Palanker

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Photovoltaic subretinal prosthesis can restore central vision in patients blinded by age-related macular degeneration with letter acuity matching its 100 µm pixel size. Improving resolution requires smaller pixels, but to still reach the target neurons, electric field should be less confined. However, wide-spreading field may engage adjacent photoreceptors and alter the visual perception. We studied the effects of residual photoreceptors on retinal responses to electrical stimulation using monopolar and bipolar photovoltaic arrays implanted subretinally in Long Evans rats with local photoreceptor loss, and compared that to RCS rats lacking all photoreceptors. Patterned retinal activation (880 nm, 0.5 to 10 ms) was assessed using visually evoked potentials under scotopic and photopic conditions, with and without the intravitreal injection of neurotransmitter blockers. Results were analyzed using a computational model of photoreceptor activation by various electric field configurations. We observed two mechanisms of photoreceptors engagement in electrical activation of the degenerate retina: 1) Dark-adapted photoreceptors near the implant can be simulated directly by a negative electric potential of the common return electrode along the edge of the array. 2) Light-adapted photoreceptors can reduce the stimulation threshold of bipolar cells within about 100 mm from the implant’s edge. Both effects may lead to reduced perceptual uniformity. Bipolar pixels with local return electrodes generate better confined electric fields than monopolar arrays and thus are less affected by the nearby photoreceptors. However, even such implants should be placed a few hundred micrometers from the edge of scotoma to minimize the unintended percepts.

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

Ecological opportunity and the onset of polyploid niche expansion waves

Felipe Kauai, Yves Van de Peer, Dries Bonte

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Polyploidy, the presence of more than two sets of chromosomes, has evolved many times across the tree of life, yet we still do not know why some polyploid lineages persist while most go extinct. The establishment of polyploid populations is often reported to be associated with harsh environmental conditions, and stress tolerance in particular, which has led to the widespread view that polyploidy-specific niche requirements are key to their persistence at ecological and evolutionary timescales. Here, we reevaluate this perspective using a classical mathematical model of polyploid establishment, presenting analytical and numerical results, along with an empirical case study. We show that simple eco-evolutionary processes at the margins of diploid range-expansion waves, more specifically ecological drift and dispersal limitation, can be sufficient to allow polyploid populations to carve out their own space, without any a priori adaptive advantage over their diploid ancestors. Our modeling effort reveals three key insights. First, polyploids most readily gain a foothold at the low-density front of a diploid range expansion wave, where ecological drift is strongest. Second, limited dispersal accelerates spatial clustering of polyploid organisms through assortative mating. Third, once spatially segregated along gradients, diploid and polyploid populations are expected to experience distinct environments, allowing natural selection to drive niche divergence. We illustrate these interconnected principles by simulating the phylogeographic history of a well-documented autopolyploid complex of Neobatrachus, Australian burrowing frogs. Altogether, our results provide a neutral baseline against which the ecological consequences of polyploidization can be more easily inferred within natural populations.

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

Multiple defects in macrophage antibacterial responses support intracellular survival of Mycobacterium abscessus in cystic fibrosis

Abdullah A. Tarique, Stefan Emming, Dean Kelk, Jayden Logan, Divya Ramanth, Emma K. Dalton, Kaustav Das Gupta, Tamara Blake, James E. B. Curson, Syeda Farhana Afroz, Matthew J. Sweet, Claire E. Wainwright, Ronan Kapetanovic, Laurent Kremer, Scott C. Bell, Emmanuelle Fantino, Peter D. Sly

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The prevalence of Mycobacterium abscessus (MABS) infections in people with cystic fibrosis (pwCF) is increasing. Macrophages are key phagocytic cells that recognize bacteria via cell surface receptors, engulf them into phagosomes, and then utilize diverse killing strategies. Here, we used human primary monocyte-derived macrophages (MDMs) from healthy controls (HCs) and pwCF to investigate how they processed and killed MABS. Expression of phagocytosis-related pattern recognition receptors (TLR2, Dectin-1, Dectin-2, and MARCO), engulfment of MABS, and lysosomal acidity were all reduced in CF-MDMs. MABS-infected CF-MDMs also had reduced mitochondrial mass, mitochondrial reactive oxygen species (mitoROS) production, relative intracellular zinc levels and inducible mRNA expression of the antibacterial zinc transporters, SLC30A1 and SLC39A8. Stimulation of mitoROS production in HC-MDMs with antimycin A reduced intracellular loads of MABS, confirming that MABS are sensitive to this mechanism of killing and suggesting that the mitoROS defect in MABS-infected CF-MDMs compromises bacterial killing. Accordingly, CF-MDMs failed to control MABS infection, with these cells allowing significantly increased intracellular MABS survival and expansion over 6 d. While treatment with the CFTR modulator, elexacaftor–tezacaftor–ivacaftor (ETI) did increase CFTR channel function and corrected CF macrophage functions to some degree, this was not sufficient to increase MABS killing. Taken together, our findings suggest important roles for functional CFTR in internalization and killing of MABS within macrophages, with CFTR dysfunction supporting MABS survival and replication in macrophages. Under our experimental conditions, ETI treatment failed to fully restore macrophage functions against MABS, highlighting the need for alternative, host-targeted approaches for improving macrophage functions in CF.

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

Impact of sex chromosomes and gonad type in stress susceptibility in corticostriatal brain regions

Kelly N. Barko, Micah A. Shelton, Dawson R. Kropp, Thien Quy Pham, Jennifer R. Rainville, Xiangning Xue, George C. Tseng, Georgia E. Hodes, Marianne L. Seney

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Major depressive disorder (MDD) is characterized by symptom heterogeneity and sex differences in prevalence. To gain insight into these sex differences, we utilized the subchronic variable stress paradigm (SCVS) in which female mice are susceptible, while males are behaviorally resilient. We used the Four Core Genotypes mice to differentiate between sex chromosome complement (XX vs. XY) and gonad type (ovaries vs. testes) in stress susceptibility, uncoupling these factors by removing the testes-determining SRY gene from the Y chromosome. Mice were subjected to SCVS followed by assays to assess anxiety-/depressive-like behaviors. Regardless of gonads, XX mice were stress susceptible, while XY mice were stress resilient, underscoring the importance of sex chromosome effects to sex differences in susceptibility to SCVS, independent of gonad type. We then performed RNA-sequencing of the prefrontal cortex (PFC) and nucleus accumbens (NAc). Consistent with human MDD and previous rodent SCVS findings, there was little overlap in genes altered by SCVS across sex. In stress susceptible XX mice, stress exposure altered pathways related to immune function, while in resilient XY mice, stress exposure altered pathways involved in neuronal function. There was brain region specificity to how sex chromosome complement and gonad type contributed to sex-specific stress effects. In the NAc, sex chromosome complement was the primary contributor to stress-induced gene expression, while in the PFC, both sex chromosome complement and gonad type contributed. These findings underscore a complex relationship between sex chromosome complement and gonadal factors in shaping stress vulnerability, partly through immune-related pathways.

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

Introduced species will not save Caribbean coral reefs

R. Ritson-Williams, P. J. Mumby, R. S. Steneck

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

Acoel whole-body regeneration begins with spreading, multi-tissue ERK signaling downstream of neuregulin-1

Catriona Breen, Mansi Srivastava

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Rapid activation of ERK (extracellular signal-regulated kinase) signaling drives transcriptional responses to injury across metazoans. Yet, it is unclear whether key aspects of ERK as a wound signal—its upstream inputs, activating cell type(s), and spatiotemporal pattern—are conserved. To facilitate thorough comparisons, we examined wound-induced ERK during whole-body regeneration in the acoel Hofstenia miamia . Wounding triggers rapid ERK activation, which begins in the most wound-proximal cells but expands distally over time among stem cells and muscle cells. ERK drives transcriptional responses to wounding in both cell types, and inhibiting ERK activation perturbs the progress of regeneration. Finally, neuregulin-1 , a ligand produced exclusively by muscle cells, and its putative receptor egfr-1 (epidermal growth factor receptor-1) act upstream of ERK activation upon wounding. Our data identify a key signaling role of muscle cells in driving ERK activation following injury and reveal a spatial spreading phenomenon with both parallels to and distinctions from dynamic ERK patterns in other systems.

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

Interfacial electric fields create hyperalkaline shells on fatty acid–coated microdroplet aerosols

Yangyang Liu, Sonali Srivastava, Delicia Gonsalves, Peter J. Vikesland

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Aerosol acidity (pH) is a fundamental property governing atmospheric multiphase chemistry, as it influences pollutant partitioning, secondary organic aerosol formation, and trace metal solubility. Thermodynamic models typically assume the internal homogeneity of submicron particles; however, fresh aerosols produced via biomass burning often possess complex core–shell morphologies wherein an aqueous core is coated by organic surfactants. Here, we report that a size-dependent “alkaline shell” exists for aqueous ammonium sulfate microdroplets coated with stearic acid, a ubiquitous constituent of biomass burning. Using single-droplet surface-enhanced Raman spectroscopy and confocal fluorescence imaging, we identify a critical size regime (50 to 150 µm) where alignment of the surfactant monolayer generates strong interfacial electric fields (~10 8 V/m). This field drives local partitioning of protons and hydroxide ions, sustaining a hyperalkaline surface shell (pH ~9 to 11). We attribute this phenomenon to a feedback loop, distinct from bulk equilibria, involving surfactant dipole alignment, hydrophobic confinement of hydroxide, and interfacial charge transfer. These findings add critical nuance to bulk thermodynamic predictions, demonstrating that while the aerosol core remains acidic, the interface of organic-coated aerosols can act as a unique, high-pH microreactor in the atmosphere, potentially accelerating base-catalyzed reactions and altering the environmental fate of biomass emissions.

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

Lactylation of PD-L1 by a lactyltransferase HAT1 dictates its protein stability and tumor immune evasion

Man Shang, Xujie Zhao, Yibi Zhang, Chang Zhang, Xiaohui Yang, Ya Wen, Xiaofeng Zhu, Yiwen Chen, Yinmin Gu, Yongbo Pan, Siyuan Jiang, Shuguang Tan, Xuemei Jia, Chenbo Ji, Shan Gao

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Lysine lactylation regulates protein fate and function across diverse biological processes. While PD-L1 has been widely studied posttranslationally, the role of its lactylation and the responsible enzyme have remained poorly studied. Here, we identify histone acetyltransferase 1 (HAT1) as a lactyltransferase that catalyzes programmed cell death ligand 1 (PD-L1) lactylation at residues K75 and K178 within its extracellular domain, thereby enhancing PD-L1 stability. Mechanistically, this glycosylation-dependent modification protects PD-L1 from endoplasmic reticulum (ER)-associated degradation and promotes ER-to-Golgi trafficking. Targeting PD-L1 lactylation by HAT1 knockdown, mutation of the lactylation sites or HAT1-PD-L1-interferring peptides suppresses tumor progression and enhances anti-PD-1 therapy efficacy. Clinically, lactylated PD-L1 strongly correlates with tumor progression. Together, these findings establish HAT1-mediated PD-L1 lactylation as a key mechanism of immune evasion and suggest that targeting this pathway could improve cancer immunotherapy outcomes.

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

Long-term antibody dynamics challenge the paradigm of lifelong homotypic immunity to dengue virus

Jair Andrade, Adrien Mitard de Girardier, Angkana T. Huang, Darunee Buddhari, Marco Hamins-Puertolas, Maria-Theresa Alera, Mary Noreen Chua, Taweewun Hunsawong, Derek A. T. Cummings, Stephen Thomas, Heather Friberg, Jeffrey R. Currier, Adam Waickman, Aaron Farmer, In-Kyu Yoon, Kathryn Anderson, Alan L. Rothman, Henrik Salje

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Immunity following infection with the four dengue virus serotypes (DENV1-4) remains difficult to define. Reports of individuals being reinfected with the same serotype challenge the paradigm that infection induces lifelong homotypic immunity. However, the frequency of these events and their importance for shaping immune profiles remain unknown. Here, we used data from three cohorts (N = 4,268 total participants) in two highly endemic settings (Cebu, Philippines, and Kamphaeng Phet, Thailand), which included long-term follow-up of individuals (mean follow-up of 8.8, 1.9, and 5.0 y). These data allowed us to elucidate age-specific patterns of infection and immunity, and to quantify individual long-term antibody titer dynamics following infection. We formulated mathematical models to explain these patterns, allowing for the possibility of progressive loss of immunity to homotypic reinfection. At the individual level, we found that, in the absence of subsequent infection, antibody titers exhibit a steady long-term decay following incident infections (half-life of 7 to 8 y), with the rate of decay slowing with increasing age. At the population level, incorporating homotypic reinfection was required to explain the age-specific dynamics of infection and immunity observed in our cohorts. We estimated that in highly endemic settings such as the Philippines, 60% of individuals have been homotypically reinfected by the age of 40 y. Our findings highlight homotypic reinfections as a key feature of endemic DENV settings and suggest that vaccines mimicking natural infection might not be expected to provide lifelong protection against infection.

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

Subduction modulated the long-term oxygenation of Earth’s surface

Wei Shi, Chao Li, Benjamin J. W. Mills, Michael Brown, Tim E. Johnson, Thomas J. Algeo, Mingcai Hou, Chunlian Wang, Mingyu Zhao, Simon W. Poulton

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On Earth, atmospheric oxygen is inferred to have risen over three major intervals before reaching modern levels, with each interval having a profound impact on the evolution of the biosphere. However, the principal driver behind these stepwise increases remains elusive. Here, we compile metamorphic thermobaric ratios ( T / P ) through time and use them as a first-order, probabilistic proxy for the likelihood of “cold” subduction (i.e., with T / P < 375 °C GPa –1 ) during secular cooling of Earth’s mantle. Then, we couple this tectonic forcing to biogeochemical modeling to test whether more efficient cold subduction may have enhanced the net transfer of reduced organic carbon and pyrite to Earth’s deep interior, thereby diminishing oxygen sinks and allowing surface oxygen levels to increase at geological timescales. Modeling results indicate that the progressive emergence of cold subduction could plausibly have contributed to the long-term oxygenation trajectory and associated secular trends in atmospheric carbon dioxide, seawater sulfate, sedimentary phosphorus, and marine redox conditions. Although the absolute magnitudes remain uncertain, the predicted trajectory of surface oxygenation is qualitatively consistent with the broad three-step pattern inferred from geochemical proxies. We propose that the progressive evolution of subduction may have been a key driver of long-term surface oxygenation, linking mantle cooling to the rise of conditions favorable for aerobic lifeforms.

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

Reply to Arroyo et al.: Universality and diversity in thermal performance curves

Jean-Francois Arnoldi, Andrew L. Jackson, Ignacio Peralta-Maraver, Nicolas Payne

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

Not all gut cellular circadian oscillators are food entrainable

Isabel Magaña, S. K. Tahajjul Taufique, Yongli Shan, Melody Shen, David E. Ehichioya, Joseph S. Takahashi, Shin Yamazaki, Yuuki Obata

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Circadian rhythms are ubiquitous, and most of the organs in the body contain circadian oscillators. The intestine comprises diverse cell types with distinct developmental origins and physiological functions. However, which intestinal cells contain cell-autonomous circadian oscillators and how circadian oscillators in distinct intestinal cell types synchronize with one another and with environmental daily cycles remain poorly understood. To address these questions, we generated a Cre-dependent PER2::LUCIFERASE reporter knock-in mouse that enables ex vivo measurement of circadian oscillations in defined cell populations. Ex vivo gut explants from mice expressing the reporter in one of five major cell types of the muscularis externa—enteric neurons (ENs), enteric glial cells (EGCs), interstitial cells of Cajal (ICCs), smooth muscle cells (SMCs), and muscularis macrophages (MMs)—exhibited robust, self-sustained circadian bioluminescence rhythms, demonstrating that each of these cell types harbors a cell-autonomous circadian oscillator. Importantly, circadian oscillators in ENs, EGCs, SMCs, and MMs entrained to feeding-fasting cycles, whereas circadian oscillators in ICCs remained resistant to food entrainment. These findings reveal that distinct intestinal cell types possess unique entrainment properties, and feeding during inactive time induces heterogeneous phase shifts across gut circadian oscillators, leading to temporal circadian misalignment within the intestine. As circadian disruptions, such as those associated with shift work, contribute to intestinal disorders, including inflammatory bowel disease and disorders of the gut–brain interaction, studying how intercellular circadian desynchrony influences intestinal homeostasis should provide chronobiology-based therapeutic strategies to combat these diseases.

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

Epithelial cell fusion is required for tissue repair following UV-A irradiation

Minqi Shen, Lillie G. Mitchell, Lydia W. Boer, Lydia M. Bischoff, Vicki P. Losick

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Cell cycle–dependent and independent mechanisms lead to the generation of mononucleated and multinucleated polyploid cells. The more than doubling of a cell’s nuclear genome by endoreplication has been found to be an adaptation to genotoxic stress, enabling cell survival despite DNA damage. However, it remains unknown whether cells that increase ploidy via multinucleation also arise in response to genotoxic stress. Here, we use ultraviolet light A (UV-A) to induce permanent DNA damage in cells within the adult fruit fly epithelium. UV-A irradiation causes an injury-like response where giant multinucleated, polyploid cells arise following cell death. The epithelial cells undergo endoreplication, which is required to compensate for cell loss, but is surprisingly dispensable for tissue repair. UV-A irradiation also induces cell fusion, which generates multinucleated cells that encompass almost the entire epithelial area post injury. Cell fusion can be inhibited by expression of a dominant negative Rac or Cdc42 GTPase, which then blocks epithelial tissue repair postirradiation. Apoptotic nuclei were detected at the site of cell junction breakdown, suggesting that apoptosis itself or an apoptotic signal is required for polyploidization in this model. Expression of the effector caspase inhibitor, p35, led to inhibition of apoptosis, the endocycle, and cell fusion post UV-A. Therefore, we have found that caspase activation is necessary for polyploidization post injury and enhancing cell ploidy via multinucleation is another strategy to enable cell survival and tissue repair following genotoxic stress.

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

Perturbation of RNA homeostasis impairs mitochondrial respiration during poxvirus infection through excess RNA accumulation

Djamal Brahim Belhaouari, Anil Pant, Santiago Navarro-Forero, Fernando Cantu, Zhilong Yang

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Induction of RNA degradation in infected cells is a strategy used by many viruses to promote efficient replication. Vaccinia virus, the prototype poxvirus and the vaccine platform for smallpox and mpox, encodes two decapping enzymes to accelerate mRNA and double-stranded RNA (dsRNA) degradation during infection, through functional coordination with host cell RNA exonuclease. Previous studies have largely focused on RNA degradation as a mechanism for regulating viral gene expression and evading innate immune sensing. Here, we show that impaired RNA degradation in vaccinia virus–infected cells, due to either depletion of viral decapping enzymes or cellular exonuclease, severely compromises mitochondrial respiration and integrity. We further demonstrated that accumulation of excess dsRNA and mRNA, including pseudouridine-modified RNAs, is sufficient to induce profound defects in mitochondrial respiration and integrity. Notably, this impairment occurs independently of interferon induction and dsRNA innate immune sensor Protein Kinase R. Moreover, excess RNA suppresses respiration in purified cell-free mitochondria and physically associates with mitochondria in cell-free and cellular contexts, supporting an immune-independent mechanism. Excess mRNA and dsRNA reduce mitochondrial membrane potential in both cells and purified mitochondria, indicating disruption of the proton gradient as the mechanism underlying impaired mitochondrial respiration and integrity. Together, these findings identify excess mRNA and dsRNA as perturbants of mitochondrial homeostasis in cells with dysfunctional RNA degradation during vaccinia virus infection, revealing a paradigm-shift concept linking RNA metabolism to mitochondrial function. The finding carries broad implications for understanding RNA and mitochondrial biology and RNA-based therapeutics and vaccines.

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

Epstein–Barr virus (EBV) infection causes human germinal center B cell–derived lymphomas in the absence of EBNA2 expression

Chunyan Wang, Jillian A. Bristol, Scott E. Nelson, Tony Chen, Charlotte Hendrickson, Dana C. Baiu, Mariah Riel, Mitch Hayes, Erik A. Ranheim, Jenny E. Gumperz, Eric C. Johannsen, Shannon C. Kenney

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EBV is associated with human B cell lymphomas, including Burkitt lymphomas (BLs), diffuse large B cell lymphomas (DLBCLs), Hodgkin lymphomas (HLs), and Plasmablastic lymphomas (PLs). EBV+ lymphomas in immunocompetent humans are usually derived from germinal center (GC)-experienced B cells and have stringent latency forms that do not express the viral transforming protein, EBNA2. Human EBV+ lymphomas that lack EBNA2 expression are largely driven by the viral LMP1 and LMP2A proteins, which activate NF-κB and B cell receptor-like signaling, respectively, or by Myc translocations. However, EBNA2 is required for EBV-mediated transformation of B cells in vitro and there is currently no model system for studying how EBV transforms human GC-derived B cells into lymphomas in vivo in the absence of EBNA2 expression or Myc translocation. Here, we show that human tonsil GC B cells (GCBs) infected with an EBNA2-deleted EBV mutant proliferate on a CD40L/IL21-expressing feeder layer and form lymphomas in NSG mice that resemble human DLBCLs (both ABC and GCB subtypes) and PLs. These EBV-induced lymphomas occur in the absence of Myc overexpression, often have normal karyotypes, and do not contain mutations in cellular genes (including p53) commonly mutated in uninfected human DLBCLs. Using this model system, we show that LMP2A induces plasmablast differentiation, increases expression of genes involved in lymphocyte mobility and trafficking and enhances tumor invasiveness in vivo. This new model system can thus be used to define roles of viral and cellular proteins in EBV-induced human GCB-derived lymphomas that lack EBNA2 expression.

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

Transition-state analysis of the arginine-specific human ADP-ribosyltransferase 1

Daniel P. Groom, Jennifer T. Aguilan, Amanda Lopacinski, Scott J. Garforth, Vern L. Schramm

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The ADP-ribosylation of proteins is a versatile, reversible, posttranslational modification involved in the dynamic regulation of numerous cellular processes. Human ADP-ribosyltransferase 1 ( hs ART1, EC: 2.4.2.31) is a membrane-associated, GPI-anchored, mono-ADP-ribosyltransferase selective for mono-ADP ribosylation (MARylation) of L-arginine residues. Dysregulation of hs ART1 activity has been shown to permit immune cell evasion in non–small cell lung cancer (NSCLC) through elevated MARylation at Arg125 of the purinergic type 2 receptor (P2X7) in P2X7-positive T cells, resulting in NAD + -induced cell death (NICD) of tumor-penetrating immune cells. With hs ART1 emerging as an immunotherapy target in select cancers, there is a need to develop small-molecule inhibitors. The transition state (TS) for the MARylation of P2X7 peptide was determined from kinetic isotope effect (KIE) measurements of 3 H-, 14 C-, 18 O-, and 15 N-labeled NAD + substrates. Quantum mechanical (QM) calculations of the reaction coordinate, mapped with experimental KIEs, identify a TS geometry consistent with a highly dissociative, asymmetric, concerted mechanism with minimal contributions from the leaving group nicotinamide (NAM) and minor contributions from the incoming L-arginine guanidinium. The absence of a normal deuterium solvent isotope effect identifies a positively charged guanidinium nucleophile, leading to a dication N-ribosyltransferase mechanism. Together with the unusual, normal 18 O–O4 ′ KIE, we identified unique charge accumulation across the oxocarbenium at the TS caused by an increased bond order between the C1 ′ –C2 ′ , and decreased bond order between the C4 ′ –O4 ′ of the nicotinamide mononucleotide ribose. This is the first L-arginine-specific ADP-ribosylation TS to be characterized, a step toward the design of TS analogs.

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

Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells

Andrew L. Sabol, Amanuella A. Mengiste, Prashant Singh, Vedagopuram Sreekanth, Samuel J. Hendel, Minh Thuan Nguyen Tran, Anton M. Barybin, Santosh Chaudhary, Ra’Mal M. Harris, Kristi E. Liivak, Zachary C. Severance, Cale M. Locicero, Karishma Kailass, Chaiheon Lee, Lucy Qinghua Xu, Vincent L. Butty, Amit Choudhary, Matthew D. Shoulders

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Engineering CRISPR-Cas systems for improved or altered function is critical to both research and therapeutic applications. Unfortunately, most optimization, especially directed evolution in bacterial hosts, fails to capture the functional requirements of the complex mammalian cellular milieu, where activity is usually required. Robust strategies to enable continuous directed evolution of genome-targeting agents directly in human cells remain lacking. Here, we introduce CRISPR-MACE (Mammalian cell-enabled Adenovirus-assisted Continuous Evolution) as a foundational technology to address this need. CRISPR-MACE integrates virus-based continuous evolution with anti-CRISPR-based tunable selection to generate Streptococcus pyogenes Cas9 variants with both increased and decreased DNA binding capacity and nearly 1,000-fold-enhanced resistance to AcrIIA4, the strongest known inhibitor of SpCas9. Notably, across independent evolution campaigns, the same Cas9 gatekeeper mutation reproducibly emerged first, enabling subsequent adaptive steps along two interdependent axes of Cas9 function. In addition to advancing CRISPR technologies, this work establishes key principles and synthetic circuits for continuously evolving CRISPR-Cas systems directly in human cells.

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

Phase-sensitive evidence for pair density waves in a kagome superconductor

Xiao-Yu Yan, Guowei Liu, Hanbin Deng, Xitong Xu, Haiyang Ma, Hailang Qin, Junyi Zhang, Yuanyuan Zhao, Xiuhao Fan, Wei Song, Muwei Gao, Haitian Zhao, Zhe Qu, Yigui Zhong, Kozo Okazaki, Xiquan Zheng, Yingying Peng, Zurab Guguchia, Xianxin Wu, Da Wang, Qiang-Hua Wang, Hendrik Hohmann, Matteo Dürrnagel, Ronny Thomale, Jia-Xin Yin

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Pair density wave (PDW) exhibits periodic amplitude and sign modulations of the superconducting order parameter. Such a pairing state has long been proposed to be highly sensitive to nonmagnetic scattering, but its experimental realization remains elusive. Here, we find a nonmagnetic PDW-breaking effect in a kagome superconductor, using designer atomic nonmagnetic impurities and high-precision scanning tunneling microscopy (STM) at a base temperature of 30 mK. We detect 2 × 2 pair density modulations by Josephson STM with a superconducting tip and 2 × 2 pairing gap modulations by normal STM. We find that the pairing modulations in both cases are substantially suppressed upon doping the kagome lattice with dilute isovalent nonmagnetic impurities, whereas the charge order and uniform superconductivity remain robust. We further identify the correlation between atomic dopants and the local suppression of PDW. We attribute these findings to a nonmagnetic pair-breaking effect, arising from the phase modulation of PDW in the kagome d -orbital. Taken together with its signatures in other state-of-the-art spectroscopy and transport measurements linked by theory, our findings support the ground state of the kagome superconductor as a correlated topological phase with superconducting loop currents.

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

Strain-induced deterministic moiré superlattices in 2D materials

Yu-Mi Wu, Sihun Lee, Yufeng Xi, Stephen D. Funni, Saif Siddique, Natalie L. Williams, Giovanni Sartorello, Hesam Askari, Judy J. Cha

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Moiré superlattices in two-dimensional (2D) materials have been realized through lattice mismatch or rotational misalignment between atomic layers. Here, we extend moiré formation to heterostrain in transition metal dichalcogenides using a scalable process that deterministically induces strain to 2D materials. By applying patterned thin-film stressors and probing the resulting atomic structure with scanning transmission electron microscopy, we directly resolve the induced heterostrain, lattice deformations, and stacking variations that produce the moiré superlattice. We find that uniaxial and biaxial heterostrain give rise to distinct moiré patterns, including stripes and distorted hexagonal geometries. Such reconstruction creates in-plane polar distortions at the domain boundaries of the moiré superlattice in MoS 2 , producing polarization textures different from those induced by twisting. The deterministic construction of moiré patterns using a well-established scalable process opens opportunities to design new moiré geometries in 2D materials.

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

Rates of speciation and past extinctions affect food webs on continental scales

P. David Polly

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

Plant Kelch phosphatases are Ser/Thr phosphatases involved in cell cycle regulation

Felix Rico-Resendiz, Oded Pri-Tal, Pierre Raia, Andrea Moretti, Houming Chen, Jun Yu, Larissa Broger, Christelle Fuchs, Ludwig A. Hothorn, Sylvain Loubéry, Michael Hothorn

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Brassinosteroids (BRs) are plant steroid hormones sensed by the membrane receptor kinase BRI1. Activation of BRI1 leads to the dephosphorylation of BZR1/BES1 transcription factors. Overexpression of the Kelch phosphatase BRI1 SUPPRESSOR 1 (BSU1) rescued the growth defects of bri1 mutants. Subsequent studies identified BSU1 as a protein tyrosine phosphatase, which promotes BR signaling by dephosphorylating a phosphotyrosine in the glycogen synthase kinase 3 BIN2. Crystal structures of the BSU1 phosphatase domain now reveal a high degree of structural similarity to protein phosphatase 1 (PP1), a eukaryotic serine/threonine phosphatase. Consistently, BSU1 efficiently dephosphorylated phosphothreonine- and phosphoserine-containing substrate peptides, but showed no detectable activity toward BIN2 and other phosphotyrosine substrates. A catalytically inactive BSU1 phosphatase domain suppresses the growth phenotypes of the Arabidopsis bri1-5 mutant and binds the BSU1 homologs BSL1-3. bsu1 and bsu1 bsl1 bsl2/3 loss-of-function mutants display wild-type-like BR responses, but exhibit stomatal patterning and fertility defects. Importantly, the PP1-like C-terminal tail of BSU1 is phosphorylated at Thr785 by a cyclin-dependent kinase complex. The phosphorylated tail binds to the BSU1 substrate-binding grooves, blocking access to the active site. Mutation of Thr785 to alanine activates BSU1, suggesting that Kelch phosphatases and PP1 share a common regulatory mechanism. Deletion of the Marchantia polymorpha Kelch phosphatase MpBSLM results in an undifferentiated cell mass phenotype, associated with the overactivation of a cell cycle reporter. Taken together, our experiments suggest that plant Kelch phosphatases act as PP1-like cell cycle regulators, rather than as tyrosine phosphatases in BR signaling.

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

Phosphoethanolamine cytidylyltransferase 2 integrates DAG metabolism and TBK1 activation to regulate antiviral innate immunity

Wencong Lai, Zengjie Liu, Han Hu, Wanxuan Zhang, Baolin Li, Rui Wang, Zengqi Zhao, Xueshan Li, Yihang Hu, Jinwei Duan, Dan Xu, Yongtao Liu, Xianyong Bu, Jianlong Du, Bingyuan Yang, Xiao Tang, Yueru Li, Min Wan, Yanjiao Zhang, Huihui Zhou, Kangsen Mai, Qinghui Ai

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Phosphatidylethanolamine (PE) biosynthesis is critical for membrane biology and cellular homeostasis. However, its specific role in antiviral innate immunity remains poorly understood. Here, we demonstrate that inhibition of phosphoethanolamine cytidylyltransferase 2 (PCYT2), a key enzyme in PE biosynthesis, promotes TBK1 activation to enhance the antiviral innate immune response. Mechanistically, PCYT2 deficiency leads to the accumulation of diacylglycerol, which activates protein kinase C-δ (PKCδ). We identify PKCδ as a direct kinase for TBK1 and demonstrate that it binds to and phosphorylates TBK1 at Ser716. This Ser716 phosphorylation facilitates the subsequent canonical phosphorylation of TBK1 at Ser172, resulting in hyperactivation of the TBK1–IRF3 axis. Our findings uncover a link between PE metabolism and antiviral innate immunity, suggesting that targeting the PE biosynthesis pathway could be a potential therapeutic strategy against viral infections.

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

Remote sensing enables expansion of our understanding of controls on river width and active floodplain

Giovanni Seminara

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

Reading ability in both deaf and hearing adults is linked to neural representations of abstract phonology derived from visual speech

Samuel Evans, Cathy J. Price, Jörn Diedrichsen, Tae Twomey, Indie Beedie, Maggie Fraser, Mairéad MacSweeney

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Reading is central to academic and vocational success. Some deaf children face reading challenges due to limited access to spoken or signed language. Robust phonological representations are key to reading development in hearing children. Spoken language phonology may be one of many contributors to reading development in deaf children. Indeed, speechreading ability correlates with reading skill in both deaf and hearing individuals, suggesting it is linked to reading development regardless of hearing status. Further support for this hypothesis would be provided by evidence that similar neural representations of speech phonology are evoked by visual speech and other language forms (auditory speech and text) and that these neural representations are related to reading proficiency. We used fMRI and representational similarity analysis (RSA) to identify shared neural representations of spoken language phonological structure. A group of deaf adult participants (N = 22), with a mixture of sign language and spoken language backgrounds and reading abilities, were presented with single lexical items as visual speech and dynamic text (cursive text, revealed letter-by-letter to promote a phonological reading strategy). Adult hearing participants (N = 25) were presented with the same words, but as visual speech and auditory speech. Shared neural representations of phonological structure of English words were found in each group in the superior and middle temporal cortex (STC/MTC) and these abstract representations were more similar across different language forms in better readers. Our data provide neurobiological evidence of the contribution of visual speech to abstract phonological representations of spoken language, that relate to reading proficiency, in both deaf and hearing adults.

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

Forbidden Sidon subsets of perfect difference sets, featuring a human-assisted proof

Boris Alexeev, Dustin G. Mixon

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We resolve a $1,000 Erdős prize problem, complete with formal verification generated by a large language model. In over a dozen papers, beginning in 1976 and spanning two decades, Paul Erdős repeatedly posed one of his “favorite” conjectures: every finite Sidon set can be extended to a finite perfect difference set. We establish that {1, 2, 4, 8, 13} is a counterexample to this conjecture. During the preparation of this paper, we found that although this problem was presumed to be open for half a century, Marshall Hall, Jr. published a different counterexample three decades before Erdős first posed the problem. With a healthy skepticism of this apparent oversight, and out of an abundance of caution, we used ChatGPT to vibe prove both Hall’s and our counterexamples in Lean.

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

Ecology is not yet ready for AI—and why that matters

Gayatri Mishra

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

Meiosis-specific genes play roles in ploidy reduction in Cryptococcus neoformans titan cells

Zhuyun Bian, Kayla Wilhoit, Julian Liber, Anushka Peer, Ziyan Xu, Paul M. Magwene, Sheng Sun, Joseph Heitman

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Cryptococcus neoformans is a fungal pathogen of humans that causes life-threatening meningoencephalitis. During infection, enlarged, polyploid titan cells are produced that promote persistence in the host, in part by resisting phagocytosis; under stress conditions, such as exposure to the antifungal drug fluconazole, titan cells can produce aneuploid or diploid, drug-resistant daughter cells. However, the mechanism underlying this ploidy reduction remains poorly understood. Interestingly, meiosis-related genes have been shown to be activated during Cryptococcus infection, leading us to hypothesize that the depolyploidization of C. neoformans titan cells may occur through a process resembling the ploidy reduction during meiosis. In this study, we show that titan cells developed from diploid strains predominantly produce diploid daughter cells with haploid daughters observed infrequently. We further demonstrate that meiosis-specific genes, including DMC1 and SPO11 , are critical for stable inheritance of a diploid genome in the daughter cells. Specifically, deletion of these genes in a heterozygous diploid background resulted in 1) titan cells with a significantly reduced capacity to produce daughter cells; 2) increased phenotypic variation among daughter cells produced by the titan cells, including traits that could be relevant to cell growth and viability; and 3) daughter cells produced by the titan cells exhibiting high levels of loss of heterozygosity (LOH) and aneuploidy, suggesting elevated genome instability. Taken together, these findings demonstrate the importance of meiosis-specific genes in the ploidy reduction process of titan cells derived from a heterozygous diploid background in an important human fungal pathogen.

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

Polyploidy: A macromutational force pushing bioeconomic developments

Marlies K. R. Peeters, Yves Van de Peer

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Polyploidization, the consequence of genome doubling, is a macromutation that reshapes genomes, phenotypes, and ecological interactions. Polyploidization often results in novel phenotypes, including alterations in size, physiology, biochemistry, and enhanced stress tolerance. Here, we discuss how strategically leveraging polyploidy can provide significant advancements within the modern bioeconomy committed to reducing our ecological footprint through the sustainable production and use of biological resources. The bioeconomy spans diverse sectors, including agriculture, health sciences, and biotechnology. By elucidating and leveraging the immediate, or short-term, effects of polyploidization, such as harnessing genetic diversity, extensive biomass production, diversification of metabolites, and improved stress resilience, we highlight how this process unlocks vast, underexplored bioeconomic opportunities. This includes accelerating the exploration of new breeding techniques, speeding up the domestication of new local varieties or medicinal plants, and offering possibilities for improved biofuel production, bioremediation strategies, therapies, and production and discovery of bioactive compounds. The multilayered effects of polyploidization shared across sectors can foster interdisciplinary exchange and are essential for advancing toward a more sustainable bioeconomy.

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

Volatile signaling in plant– Metarhizium –insect interactions: Implications for nitrogen cycling

Xingyuan Tang, Ting Feng, Chaonan Yu, Meihong Ni, Yubo Zhang, Xin Ma, Xinmiao Wang, Jiani Chen, Wenqi Shi, Raymond J. St.Leger, Jianhua Huang, Weiguo Fang

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Nitrogen exchange between plants and insects is a major component of ecosystem nitrogen cycling. Endophytic insect pathogenic fungi transfer insect-derived nitrogen to plants through symbiotic associations mediated by fungal mycelia, enabling plants to thrive even after losing nitrogen to insects. However, the mechanisms underlying this process remain unexplored. Here, we show that the widespread endophytic entomopathogen Metarhizium robertsii degrades the common root-derived antifungal compound caulilexin C to produce the volatile 1-methoxyindole. This compound is recognized by the Or74a olfactory receptor in Drosophila melanogaster larvae and attracts multiple Dipteran species to the plant– Metarhizium consortium. The recruited insects are subsequently infected and consumed, resulting in enhanced insect-derived nitrogen transfer to the plants. This self-reinforcing mechanism strengthens the plant–fungus symbiosis and reveals a pathway contributing to ecosystem nitrogen flux.

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

Indoor thermoregulatory homeostasis using hydrodynamic instability

Raphael Kay, Ross J. Cocks, Charles Katrycz, J. Alstan Jakubiec, Atalaya Milan Wilborn, Rafiq Omair, Joanna Aizenberg, Benjamin D. Hatton

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Branching patterns can emerge when one fluid is injected into a more viscous one within a quasi-two-dimensional cavity. While these patterns have dazzled physicists for decades, modern engineering efforts have focused on suppressing, rather than leveraging, these flow instabilities. Here, by designing fluidic devices with calibrated geometries, liquid absorptivities, and rheology, we exploit the thermal sensitivity of the Saffman–Taylor instability to achieve thermoregulatory shading systems with self-adjustment capabilities. Our devices produce negative feedback branching patterns that reduce indoor solar heating when warm but increase it when cool. Moreover, compared to existing temperature-responsive shading approaches with fixed thermal behaviors, our system can switch its thermal sensitivity and indoor temperature setpoints on-demand by adjusting the rate that patterns are grown. Experiments and models reveal the energy savings and indoor climate control capabilities enabled by this thermoregulatory framework. Overall, our work provides a blueprint for designing materials with self-regulatory behaviors based on flow instabilities.

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

On the large-scale radiative cooling induced by tropical cyclone activity

Gabriel A. Rios, Gabriel A. Vecchi, Wenchang Yang

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Tropical cyclones (TCs) are among the most energetic phenomena in the climate system. Given their energetic nature, TCs induce upscale effects on the climate system, although these effects have not been extensively assessed. Understanding the influence of TCs on climate is important given the expected changes in TC activity with a warming climate. In this study, we provide evidence that TCs induce large-scale radiative cooling. We compare the climates of a coupled global climate model in two configurations: a control configuration with Earth-like TC activity and a perturbed configuration where TC activity is reduced by suppressing wind-induced surface heat exchange in areas with TC-like conditions. By comparing climate states, we find a reduction of incoming top-of-atmosphere radiation with more TC activity, largely in the subtropics. Globally, TC activity drives increases to longwave emission that outweigh increases to absorbed solar radiation. We show that decreases in sea surface temperature occur as an adjustment to TC-induced perturbations, coincident with increases in longwave emission caused by a drying of the free troposphere and a reduction in high cloud fraction. The results demonstrate the role of TCs in organizing convection, suggesting that TCs play a role in modulating climate sensitivity and large-scale energy transport.

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

Plants tolerate substantial rates of plastid mistranslation via regulated proteostasis

Benjamin Brandt, Sebastian Schwartz, Serena Schwenkert, Moritz Krämer, Kuenzang Om, Carina Engstler, Andreas Klingl, Peter Jahns, Etienne H. Meyer, Rachael A. DeTar, Jürgen Eirich, Iris Finkemeier, Asaph B. Cousins, Hans-Henning Kunz

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In bacteria, protein mistranslation can improve stress tolerance. Mitochondria and plastids evolved from bacteria and use a prokaryotic-type expression machinery to synthesize proteins. Interestingly, fungi and animal mitochondria are highly sensitive to mistranslation, which for instance manifests in lethal mitochondrial cardiomyopathy disorder. The response in plant cells is unknown. Glutaminyl-transfer RNAs (Gln-tRNA Gln ) of bacteria and endosymbiotic organelles are synthesized indirectly. Initially, tRNA Gln is aminoacylated with glutamate. Subsequently, Gln is produced through trans-amidation by the aminoacyl-tRNA amido-transferase complex GatCAB. Consequentially, compromised GatCAB activity yields misloaded Glu-tRNA Gln . Arabidopsis mutants with decreased GatCAB levels provide global insights into organellar mistranslation in plants: Our proteomics analyses revealed mutant-specific high plastid and low mitochondrial Gln-to-Glu misincorporation rates in organellar-expressed protein complexes with only modest protein abundance changes in plastids and none in mitochondria. We identify efficient compensatory mechanisms that mitigate the physiological consequences of elevated mistranslation in mutants. Interestingly, wild-type plants under temperature stress also have altered Gln-to-Glu misincorporation while temperature acclimation differs in Gln-to-Glu hypermistranslating mutants. Our study indicates that the response toward organellar mistranslation varies among eukaryotes and enables future detailed investigation of mistranslation compensation mechanisms in plant cells.

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

Dynamic compression of whole-brain neural trajectories during human motor learning

Hoora Mohseni, Ali Rezaei, Maryam Ansari Esfeh, Corson N. Areshenkoff, Daniel J. Gale, Joseph Y. Nashed, Emily R. Oby, Juan Chen, Jeffrey D. Wammes, Douglas J. Cook, Jason P. Gallivan

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Motor learning involves the dynamic reconfiguration of brain activity across widely distributed networks. Yet, the moment-to-moment evolution of the whole-brain functional states underpinning this process remains unknown. Here, applying manifold-based trajectory analyses to human fMRI data, we uncover a fundamental signature of motor learning: Neural state transitions are sharply constrained during initial learning—manifesting as a sharp compression of trajectory geometry—and relax these constraints as performance stabilizes. This effect, which closely tracked behavioral error, was recapitulated during relearning a day later and was further validated in an independent motor learning dataset. Regional analyses indicated that these global changes were driven by a shift in the dominant source of regional activity modulation from sensorimotor to cognitive control networks. Together, our results suggest a fundamental principle of learning, where whole-brain functional dynamics are compressed in response to errors, providing a framework for understanding how large-scale neural activity guides behavioral adaptation.

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

NF1 and SPRED1/2 cooperate through RAS-MAPK-independent functions

Jillian M. Silva, Lizzeth Canche, Alice Cheng, Lucy C. Young, Frank McCormick

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Neurofibromin, the protein product of the neurofibromatosis type 1 ( NF1 ) gene, requires the direct binding interaction with SPRED to negatively regulate the RAS-MAPK pathway. Although the region of neurofibromin that stimulates the intrinsic GTPase activity of RAS represents only a small percentage of the entire protein, a large degree of the NF1 structural domains and their correlating mechanistic functions remain elusive. Here, we demonstrate RAS-independent biochemical and signaling functions regulated by the coordinate control of NF1 and SPRED1/2. Utilizing CRISPR-Cas9 methods to ablate NF1 or SPRED1/2 in isogenic “RASless” mouse embryonic fibroblast (MEF) cell lines expressing either the KRAS4b wild-type variant or an oncogenic KRAS -mutation, we show loss of SPRED1/2 phenocopies NF1 loss and their cooperation is required to modulate MAPK-AKT signaling. Moreover, NF1 or SPRED1/2 loss also resulted in a potent suppression of the RAS family GTPases, RRAS and RRAS2, occurring independently of RAS or AKT pathway activation. A transcriptome microarray analysis of the NF1 or SPRED1/2 knockout MEF cells revealed a specific subset of RAS-independent, NF1–SPRED1/2-dependent gene signatures, in which these same genes were also directly regulated by the RAS-GTPase function of neurofibromin. The modulation of these NF1–SPRED1/2-dependent downstream signaling effectors were further corroborated in Schwann cell models derived from Neurofibromatosis type I patients that consisted of either plexiform neurofibroma cells or unaffected nerve cells abrogated of NF1 or neurofibromin RAS-GAP activity. Taken together, this study provides RAS-independent functions that are dependent on the cooperation of NF1 and SPRED1/2 in a manner that is uncoupled from canonical MAPK signaling.

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

Rice paper adsorbent for gold recovery

Seung Su Shin, Seungho Lee, Sung-Joon Park, Sungkwon Jeon, Jiyun Chung, Wonhee Jo, Chan Hee Jung, Wangyun Won, Jung-Hyun Lee

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Growing global interest in gold (Au) has spurred the development of adsorption processes as sustainable technologies for effective Au recovery from industrial waste. However, the adsorbents used in such processes often require complex fabrication procedures and/or petroleum-based chemicals, aggravating economic and environmental burdens. To overcome these limitations, this study proposes the transformation of rice paper (RP), a biomass (starch)-based food material, into a high-performance Au adsorbent via facile aqueous-phase chemical modification (hydrazination). The resultant hydrazine-functionalized RP (Hz-RP) adsorbent features a stratified mesoporous structure and demonstrates high mechanical integrity in water. Hz-RP rapidly, effectively, and selectively recovers Au even in complex feed solutions (e.g., electronic waste leachate) via collaborative chemisorption and reduction, outperforming many Au adsorbents reported in the literature. Following Au adsorption, Hz-RP can be readily collected and calcined to obtain high-purity Au. System-level analyses indicate that a Hz-RP-based process to recover Au from discarded electronics is economically and environmentally beneficial. Thus, this study establishes a viable pathway toward a circular resource economy by demonstrating the sustainable recovery of Au from industrial waste and the valorization of biomass/food waste.

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

Tubulin flux at spastin-induced nanodamage sites regulates microtubule rescue frequency and EB1 lifetimes

Ewa Szczesna, Jeffrey O. Spector, Stephanie L. Sarbanes, Jiayi Chen, Agnieszka Szyk, Antonina Roll-Mecak

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Severing enzymes nanodamage microtubules by extracting tubulin subunits. This extraction is accompanied by spontaneous repair with soluble tubulin. Here, we show that GTP-, and not GDP–tubulin, incorporates preferentially at nanodamage sites where it recruits end binding protein-1 (EB1). Using GTP hydrolysis-defective recombinant tubulin mutants we show that the tubulin GTPase is a timer for EB1 association at repair sites. Tubulin on-rate controls both the size and lifetime of the spastin-catalyzed GTP-islands which promote rescues. Consistent with this, first, rescue rates in the presence of repair vary steeply with tubulin concentration, unlike in the absence of repair, and second, spastin-catalyzed lattice remodeling, and not passive binding of the enzyme alone, increases rescue rates. Furthermore, we show that, when overexpressed at low levels in cells, spastin catalyzes microtubule repair and affects microtubule growth. Thus, microtubule severing proceeds through GTP–tubulin repair intermediates both in vitro and in cells. Our work demonstrates that severing enzymes exert their effects on microtubule function through tubulin extraction and repair and strongly supports microtubule dynamics regulation through tubulin dimer exchange along the lattice.

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

amyloid-predict and LLPS-predict: Predicting phase separation propensities in the intrinsically disordered proteome

Samuel Lobo, Leif Griem, M. Scott Shell, Joan-Emma Shea

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Amyloid formation and liquid–liquid phase separation (LLPS) are two important phenomena in cellular biology, linked to both normal physiological functions and various pathologies. Here, we present a computational framework that scores amyloid propensities (amyloid-predict) or LLPS propensities (LLPS-predict) from protein language model embeddings, enabling rapid proteome-wide annotation of peptides and residues. amyloid-predict achieves classification performance that exceeds existing AI and physics-based tools on a hexapeptide benchmark while enabling substantially faster high-throughput screening; notably, amyloid-predict is sensitive to subtle mutational effects and is influenced by sequence patterning and context rather than amino acid composition alone. We apply these protein language model classifiers to all the IDRs in the human proteome and uncover several protein categories with significant enhancement in amyloid and/or LLPS propensity, suggesting insights into the biological roles of these protein categories. For example, signaling receptors, carbohydrate-binding proteins, and Ca 2+ binding proteins are enriched in aggregation propensity, while mRNA-binding proteins, ribonucleoprotein complex, and nuclear matrix proteins are enriched in LLPS propensity. Interestingly, we observe patterns of both high amyloid and LLPS propensity in several amyloid-forming and prionic proteins. Together, these results provide side-by-side landscapes of LLPS and amyloid potential across the disordered human proteome while offering a rapid screening tool for basic biology, disease-mechanism studies, and rational design of peptide therapeutics.

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

Reply to Ritson-Williams et al. and Loya and van Woesik: Coral replacement research is vital due to uncertainty and unprecedented stress

Alejandro E. Camacho, David A. Dana, Mikhail Matz

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

Force loading on molecular clutches governs the stability of cell lamellipodia

Ruihao Xue, Lezi Kang, Yonggang Chen, Haoxiang Yang, Hongyuan Jiang, Ze Gong

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Cells use lamellipodia, thin actin-rich membrane protrusions, to probe the mechanical properties of their microenvironment. During mechanosensing, lamellipodia often exhibit dynamic instability in the form of protrusion-retraction cycles. However, how this mechanical instability arises during mechanotransduction remains poorly understood. Here, we develop a minimal mechanochemical model for lamellipodial dynamics that integrates membrane deformation, myosin contractility, and binding kinetics of adhesion molecules (molecular clutches). Through stochastic simulations and analytical mean-field analysis, we demonstrate that both loading rate and force magnitude applied by myosin-driven retrograde flow control the clutch binding kinetics, governing lamellipodial stability and cellular mechanosensing. Specifically, a slow loading rate promotes sustained clutch engagement and traction buildup, while a high force magnitude ruptures bound clutches. Their temporal interplay gives rise to protrusion-retraction cycles in lamellipodia. Furthermore, the model predicts a biphasic response to myosin perturbation, consistent with quantitative experimental observations. Overall, the theoretical model highlights force loading as the key mechanical input driving lamellipodial instability and cellular mechanosensing, advancing our understanding of mechanotransduction during cell spreading.

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

Atomic layer-deposited nucleation layers to control zinc morphology and suppress hydrogen evolution

Ajay Ravi, Sanzeeda Baig Shuchi, Guangxia Feng, Yuqi Li, Pu Zhang, Junyan Li, Tzu-Ling Liu, Giulio D’Acunto, Angela Cai, Tony Li, Kenzie M. Sanroman Gutierrez, Zaichun Liu, Jing Wang, Ge Zhang, Jun Ho Lee, Junyoung Lee, Xueer Xu, Xun Guan, Xueli Zheng, Stacey F. Bent, Yi Cui

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Aqueous zinc (Zn) batteries are among the most promising candidates for safe, low-cost, and sustainable grid-scale energy storage. However, their practical application is significantly constrained by inhomogeneous Zn electrodeposition and the competitive hydrogen evolution reaction (HER). Here, we introduce an electrodeposition architecture to mitigate these challenges. Using atomic layer deposition, we coat the copper current collector with ZnO and Al 2 O 3 nanofilms—positioned below the plated Zn. Our strategy marks a significant departure from previous works in which thin films are situated above Zn foil to function as artificial solid electrolyte interphases. Notably, we achieve substantial performance improvements with our 2-nm-thick ZnO coatings, including long cycle life (>1,400 cycles) and high Coulombic efficiencies (>99.8%). Our mechanistic investigation suggests that these improvements arise from HER suppression and controlled Zn morphology. This work offers an interface engineering approach to fundamentally understand Zn nucleation and growth processes. We anticipate that our electrodeposition architecture could be applied to enhance the cyclability of other aqueous battery systems.

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

Growth under pressure: The pros and cons of polyploidy induced by stress

Lilijana Sarabia Oliver, Paulo B. Belato, Joshua Silva, Anna Selmecki, Donald T. Fox, Adrienne H. K. Roeder

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In native environments, organisms are faced with an array of acute or chronic stresses. These stresses include toxins, pathogens, and physical injury. An increasingly recognized response to diverse stresses is whole genome doubling or polyploidy. This transformative cellular property alters genome integrity, cellular structure, and tissue architecture. Whether polyploidy is a positive, negative, or neutral outcome of a stress is a current topic of investigation in numerous contexts including during fungal infection of plants and animals, during regeneration of wounded tissues, and in human diseases such as cancer. In this review, we highlight the wide range of stresses that promote polyploidy in fungal, plant, and animal contexts. Specifically, we highlight major mechanisms that lead to stress-induced polyploidy within somatic or germline tissues through alteration of the cell cycle. We discuss the impact of such stress-induced polyploidy on genomes, cells, and tissues and emphasize commonalities across organisms and biological scales. A common theme that has emerged is that polyploidy facilitates numerous subsequent genomic and cellular changes following abrupt stresses, and these changes can impact tissue architecture and function.

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

Oxidative stress and serum deprivation influence the evolution of newly formed tetraploid cells during tumorigenesis

Megan L. Sweet, Mathew Bloomfield, Nicholas Keen, Nazia Bano, Xiang Pan, Nicolaas C. Baudoin, Barath Udayasuryan, Raffae N. Ahmad, Eva Riddervold, Erica Klaiber, Scott S. Verbridge, Eva M. Schmelz, Jing Chen, Daniela Cimini

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We recently found that newly formed tetraploid (4N) cells in culture quickly lose extra centrosomes after whole genome doubling (WGD). This is inconsistent with the high incidence of centrosome number abnormalities in human cancers and with the observation that 4N cells from mouse tumors carry extra centrosomes, suggesting that centrosome numbers could be affected by certain conditions in the tumor microenvironment (TME). To determine the effect of the TME on the evolution of newly formed 4N cells, we induced WGD in DLD1 colorectal cancer cells and analyzed centrosome and chromosome numbers in mouse tumor samples. We found that the 4N cells displayed a proliferation defect in vivo, that they could enhance the recruitment of stromal cells to the tumor site, and that they were more likely to harbor extra centrosomes compared to 4N cell populations evolved in vitro. Combining a mathematical model that tracks the coevolution of ploidy and centrosome numbers in different cell populations with Bayesian inference, we identified centrosome overduplication as the mechanism underlying the supernumerary centrosome phenotype. Finally, through in vitro evolution experiments, we found that deprivation of growth factors and oxidative stress could explain, respectively, the proliferation defect and the supernumerary centrosomes identified in our in vivo experiments. Overall, our work shows that oxidative stress plays a major role in centrosome overduplication, particularly in 4N cells, suggesting that supernumerary centrosomes and WGD may coexist in certain tumors. Moreover, our findings suggest that the oncogenic effects of WGD could be due, in part, to stromal cell recruitment.

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

Genome evolution through polyploidy: Enhancing plant stress resilience in agriculture

Patrick P. Edger, Melanie J. A. Body, Sonia De Donno, Adrian E. Platts, Jianrong Wang, Jiming Jiang

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Polyploidy, also known as whole genome duplication, is a major evolutionary force in plants, driving diversification and the generation of novel phenotypic variation, including superior abiotic and biotic stress tolerance. The enhanced stress resilience observed in certain polyploids is hypothesized to arise from dynamic epigenetic and genetic changes, including variations in gene content and cis-regulatory elements (CREs), that emerge following polyploidization. These changes directly impact various regulatory, signaling, and metabolic pathways associated with stress response and adaptation. Within polyploid populations, processes like gene duplications, fractionation, and homoeologous exchanges actively shape novel gene content variation, while, simultaneously, alterations in CREs (DNA sequences controlling gene expression) lead to diverse regulatory patterns. This dynamic interplay between changes in gene content and regulation further contributes to expanded phenotypic variation, including enhanced stress resilience. We discuss how advanced genomic and epigenomic techniques, such as pangenomics and single-cell assay for transposase-accessible chromatin with sequencing, are used to uncover these variations and outline new bioinformatic approaches to reveal the underlying genetics of stress resilience and adaptation. Finally, we summarize what remains poorly understood to guide future research, with the goal of unlocking the full potential for enhancing resilience in polyploid crops.

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

An engineered closed-shell, two-component, 480-subunit nucleocapsid

Mikail D. Levasseur, Naohiro Terasaka, Angela Steinauer, Stephan Tetter, Sara Pfister, Beat H. Meier, Donald Hilvert

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Self-assembling protein cages are valuable nanoscale containers for biotechnology and medical applications. Two-component systems are especially attractive due to their potential for functional complexity. In this study, we demonstrate that the subunits of the 240-subunit nucleocapsid NC-4, which was previously evolved to package and protect its encoding mRNA, can be split into two fragments without disrupting cage assembly or structure, generating a two-component, 480-subunit capsid. This modification introduces additional termini on the cage’s exterior surface, creating opportunities for functionalization. We exploited these new sites by genetically appending peptide and protein tags to the exterior surface of split NC-4 (spNC-4), enabling site-specific glycosylation via posttranslational modification and cell-specific delivery by targeted antibody recruitment. Our findings broaden the utility of the NC-4 nucleocapsid. By extension, splitting related protein compartments that bind diverse cargoes could offer a robust platform for biotechnological applications requiring simultaneous encapsulation and customizable surface modification.

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

HHIP’s dynamic role in epithelial wound healing reveals a potential mechanism of COPD susceptibility

Dávid Deritei, Wardatul Jannat Anamika, Anny Xiaobo Zhou, Jeong H. Yun, Maor Sauler, Michael H. Cho, Edwin K. Silverman, Erzsébet Ravasz Regan, Kimberly Glass

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Genetic variants near Hedgehog interacting protein ( HHIP ) have been consistently associated with increased risk for chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide. However, HHIP ’s role in COPD pathogenesis remains elusive. Canonically, HHIP is a negative regulator of the Hedgehog pathway and downstream GLI1 and GLI2 activation. The Hedgehog pathway plays an important role in wound healing, specifically in activating transcription factors that drive the epithelial–mesenchymal transition (EMT), which in its intermediate state (partial EMT) is necessary for the collective movement of cells closing a wound. Herein, we use a systems biology approach to propose a mechanism to explain HHIP’s role in faulty epithelial wound healing, which could contribute to the development of emphysema, a key feature of COPD. Using two different Boolean models, we show dysfunctional HHIP results in a lack of negative feedback on GLI, triggering a full EMT, where cells become mesenchymal and do not properly close the wound. We validate these Boolean models with experimental evidence gathered from published scientific literature. Finally, we show evidence supporting our hypothesis in single-cell and single-nucleus RNA-Seq data from different COPD cohorts and Hhip heterozygous knockout mice. Overall, our analyses suggest that aberrant wound healing due to dysfunctional HHIP, combined with chronic epithelial damage through cigarette smoke exposure, may be a primary cause of COPD-associated emphysema.

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

Electrical stimulation promotes longevity and regeneration in a colonial chordate

Jos Domen, Yotam Voskoboynik, Tom Levy, Erica M. Domen, Katherine J. Ishizuka, Karla J. Palmeri, Chiara Anselmi, Thomas Rolander, Norma F. Neff, Angela M. Detweiler, Irving L. Weissman, Kimberly L. Gandy, Debashis Sahoo, Ayelet Voskoboynik

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Endogenous bioelectric currents regulate development and regeneration, but their influence on organismal longevity and stem cell–mediated repair is not well understood. We demonstrate that a brief, clinically safe pulse of electrical current (PEC) produces lasting rejuvenation in the colonial chordate Botryllus schlosseri . In this species where all differentiated tissues are replaced weekly and progenitor populations mediate the weekly de novo generation of new organs, organismal aging is directly driven by alterations of the precursor pool. Electrically stimulated colonies exhibited increased growth, enhanced reproductive activity, and significantly improved survival, along with improved stem cell associated function. Whole-transcriptome analysis revealed a biphasic “reboot and rebound” program across all functional paths. An acute 2-h “reboot” was defined by the synchronized downregulation of the genomic engine, mitochondrial respiratory chain, contractile apparatus, and extracellular matrix (ECM) integrity. This systemic pause transitioned into a massive 24-h “rebound”, characterized by the global reactivation of these paths, including a metabolic surge, cytoskeletal rebuilding, and ECM scaffold synthesis. Notably, PEC induced a conserved immunometabolic shift from a proinflammatory to a reparative signature, mimicking exercise-induced shifts observed in mammals. Our findings identify that PEC acts directly on progenitor-cell-driven pathways to restore homeostatic vitality, offering insights into the reversal of age-related decline.

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

Flipping plankton

Bridget S. Wade, Paul N. Pearson, David J. King, Valeria Luciani

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Sudden, global reversals in shell coiling direction are a striking and recurrent feature in the fossil record of planktonic foraminifera (marine zooplankton), yet their evolutionary significance has been a mystery. Because coiling direction is a simple, binary character, such shifts have often been interpreted as environmentally induced phenotypic responses rather than indicators of evolutionary change, although it is increasingly evident that genetic variants can have different coiling preferences. Here, we synthesize recent evidence from multiple case studies spanning the Eocene to the Recent (the last 56 Mya). Coiling flips occur on timescales of thousands of years or less, across diverse taxa and ocean basins, far too abruptly to be explained by gradual trait evolution. Instead, these rapid, synchronous coiling reversals may signal cryptic speciation and episodic population sweeps, associated with distinct habitat preferences and water mass distributions. In most cases such replacements would leave little trace in the fossil record, but when competing groups differ in coiling preference, a dramatic and geologically abrupt coiling reversal becomes visible. These findings challenge the assumption that reproductive isolation alone delimits species in planktonic foraminifera and instead supports a model of ecological speciation mediated by habitat partitioning in the open ocean. Shell coiling direction thus serves not as an adaptive trait, but as a fortuitous marker of hidden evolutionary dynamics shaping marine microplankton diversity.

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

A loaf of bread and a jug wine: The origins of the ultimate culinary pairing

Melinda Zeder

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

Navigating high-order protein fitness landscapes via deep learning on directed evolution trajectories

Chengzhi Song, Liang Ma, Lingfeng Xue, Yingfan Xu, Qihan Zhang, Yuxi Liu, Chen Song, Yihan Lin

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Accurately predicting the fitness effects of high-order mutations is a grand challenge in understanding and engineering proteins. Existing models, including pretrained protein language models, struggle to capture the multiresidue interactions that govern these effects. Here, we introduce DENet, a deep learning framework that harnesses the rich comutation information within directed evolution (DE) trajectories to reconstruct high-resolution fitness landscapes for deciphering and engineering of complex protein variants. Applied to the cancer target KRAS, DENet-guided screening systematically identified high-order mutants with potent activities and uncovered hidden allosteric mechanisms. For MEK1, DENet nominated complex variants with >1,000-fold increased drug resistance, revealed synergistic tail mutations, and retrospectively identified over 75% of known clinical mutations, largely outperforming existing models. To broaden the framework’s applicability, we developed an in silico strategy that simulates directed evolution to infer comutation information from widely available single-mutant datasets. DENet provides a quantitative framework for navigating complex fitness landscapes, uniting the rational engineering of multimutation proteins with the elucidation of their mechanisms and clinical implications.

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

Ultraslow conformational dynamics and catch bond formation of a bacterial adhesin revealed by a single-domain variant of FimH

Pearl Magala, Lisa M. Tuttle, Gianluca Interlandi, Laura A. Carlucci, Molly Y. Mollica, Maria K. Janowska, Wendy E. Thomas, Evgeni V. Sokurenko, Rachel E. Klevit

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Bacterial fimbrial adhesins such as FimH are critical for host colonization and persistence under the mechanical forces encountered at sites of infection such as the urinary tract. The molecular mechanisms by which FimH, a key virulence factor of uropathogenic Escherichia coli , regulates its binding to host cell surface mannose moieties through conformational switching remain incompletely understood. FimH operates across a range of conformations that includes low- (LAS), intermediate-, and high-affinity (HAS) states and forms catch bonds that paradoxically strengthen under force. The allosteric pathways governing these transitions remain poorly defined due to experimental limitations that restrict understanding of key dynamic phenomena that underlie ligand-triggered conformational shifts and force-induced long-lived interactions. Such understanding is central to drug discovery efforts to target bacterial adhesion. Here, we present a model system that fully recapitulates the conformational repertoire of FimH in the absence of its pilin domain. Our findings demonstrate that a single mutation in the lectin domain stabilizes the LAS while allowing for ligand-binding-induced transition to a HAS-like conformation and catch bond formation, mirroring the behavior of the native FimH adhesin. We propose a dynamic allosteric mechanism that involves ultraslow, low-frequency dynamics for the ability of FimH to sustain long-lived interactions with mannose, under both static and force conditions.

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

Evolution induced state shifts in a long-term microbial community experiment

Mikko Kivikoski, Johannes Cairns, Shane L. Hogle, Sanna Pausio, Lutz Becks, Ville Mustonen, Teppo Hiltunen

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Biological communities are complex, dynamic systems that underpin ecosystem functionality, yet their long-term dynamics and predictability remain poorly understood. Understanding how Darwinian evolution shapes these systems through eco-evolutionary feedback is a central challenge in ecology and evolution. Experimental studies using simplified microbial assemblages have yielded important insights into the ecological principles governing community states. However, an important knowledge gap is how selection within member species drives changes of community state in multispecies systems. Here, we present a four-year evolution experiment involving a 23-species synthetic bacterial community propagated in two environments: a control medium and the same medium supplemented with the antibiotic streptomycin. Through combined analyses of community composition and genome evolution, we quantified the temporal changes in species abundances and the evolutionary trajectories of individual community members. The extended duration of the experiment enabled the detection of adaptive mutations and community state shifts that occur only over long evolutionary timescales. We show that community dynamics are environment dependent and reproducible across replicates and that evolution of streptomycin resistance in a previously streptomycin-sensitive species on its own can induce abrupt community state shifts. Our results provide a direct demonstration of eco-evolutionary feedbacks within a multispecies community, revealing how a single adaptive mutation can reorganize complex ecological networks.

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

Ecological replacement versus process-based recovery of Caribbean reefs

Y. Loya, R. van Woesik

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

Elevated threat status of large-fruited plants is associated with the extinction of large frugivores in the Caribbean islands

Fabio L. Tarazona-Tubens, Seokmin Kim, Alcides L. Morales-Pérez, Eleanor M. Hay, Maximilian G. R. Vollstädt, Thomas F. Johnson, Fernando Gonçalves, Benno I. Simmons, Christopher N. Kaiser-Bunbury, Bo Dalsgaard, Mauro Galetti, Christopher A. Searcy

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Anthropogenic activities severely impair biodiversity and ecosystem functionality. A prime example is the loss of frugivores and their corresponding seed dispersal services due to defaunation (the decline of animal populations), ultimately affecting the continued persistence of plant species that lack their ecological partners. Loss of frugivores and their biotic interactions can be particularly severe on islands due to their isolation and relatively small area, which is often associated with low functional redundancy. From field observations on the Caribbean Virgin Islands, we found that only 1% of documented seed dispersal events occurred in large-fruited plants, with dispersal probability closely tied to overlap between fruit width and gape size of the largest nonthreatened frugivore. Using fruit–frugivore trait matching to extrapolate this pattern to the rest of the Caribbean, we found that large-fruited plant species are effectively “orphaned” due to the absence of animal dispersers, resulting in elevated rates of endangerment across islands. Threat status of plant species was better explained by trait matching than other pressures such as human use, suggesting that extinction or reduced abundance of large-bodied frugivores is compromising their plant mutualists’ ability to persist. These results argue strongly for the need to restore populations of large-bodied frugivores across the Caribbean, either through population enhancement of currently endangered species or rewilding with close relatives of extinct species.

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

Uncovering ParB-dependent and -independent subclasses of T-dioxygenases from bacteriophage

Katherine H. O’Toole, Lydia J. Perkins, Auriane Bouchet, Mia L. DeSanctis, Sean R. Lund, Andrew J. Mulholland, Yahya El Hariri, Sabaa Belkadi, Harold W. Bell, David M. Hough, Lana Saleh

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5-Methylpyrimidine dioxygenases (5mYOXs) are iron (II)/2-oxoglutarate-dependent enzymes that catalyze the postreplicative oxidation of DNA 5-methylpyrimidines. Here, we define two subclasses of phage thymine (T) 5mYOXs: a stand-alone enzyme and a second requiring an activator. Using bioinformatic tools, we show that the activator is homologous to the bacterial chromosomal segregation (CS) protein ParB, retaining the N - terminal nucleotide-binding domain (NBD), responsible for CTP binding and hydrolysis in CS, and the C-terminal dimerization domain (CTD), but lacking an obvious DNA-binding domain. In vivo, we demonstrate that ParB activates its cognate 5mYOX with relative specificity and that both NBD and CTD are required for function. Unlike CS-ParBs, mutation of conserved NTP-binding/hydrolysis residues does not affect the role of 5mYOX-associated ParB, suggesting a lack of CTP requirement or a regulatory mechanism not captured under our conditions. For 5mYOXs, we define subclass-specific domains essential for T oxidation and provide evidence for abolishing ParB dependency upon swapping a variable insert from a ParB-independent 5mYOX into a dependent one. In vitro, reconstitution of subclass representatives, 5mYOX97 and 176, confirms their activity as postreplicative T-dioxygenases. Both enzymes function on a wide range of DNA substrates [single and double-stranded (ds), linear, and circular]. The enzymes differ in their sequence preference and support iterative oxidation of T and 5-methylcytosine. Notably, 5mYOX176 requires activation by ParB176 only when acting on dsDNA. These findings establish an activator-dependent subclass within the iron (II)/2-oxoglutarate-dependent dioxygenase superfamily and expand the functional landscape of both 5mYOX and ParBs, suggesting regulatory mechanisms for T oxidation in bacteriophage.

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

Tuning mitotic recombination with patterned DNA nicks for precision mosaic analysis

Yifan Shen, Ann T. Yeung, Bei Wang, Chun-Ting Yeh, Payton Ditchfield, Elizabeth Korn, Chun Han

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CRISPR/Cas9-based mosaic analysis is a powerful tool for in vivo genetics but is limited by cytotoxicity and mutagenesis associated with DNA double-strand breaks. Here, we establish Cas9-derived nickases as safer and more reliable alternatives for inducing mitotic recombination in Drosophila . We demonstrate that single-strand nicks are sufficient to generate mosaic clones and systematically dissect the parameters governing this process. We find that clone frequency can be controlled by the gRNA nicking pattern, with two distant nicks on the same DNA strand synergistically enhancing recombination by over ninefold compared to a single nick. Based on these findings, we propose a mechanistic model for nick-induced crossover and provide a versatile toolkit for generating tissue-specific nickases. This work establishes nickase-based mosaic analysis by gRNA-induced crossing-over as a superior method for high-fidelity clonal analysis, enabling more precise investigation of gene function in development and disease.

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

Harnessing polyploidy for climate-resilient crops: Lessons from the evolutionary model, allotetraploid cotton

Maojun Wang, Ruipeng Wang, Guanjing Hu, Xianlong Zhang, Jonathan F. Wendel

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Escalating pressures of global climate change necessitate developing agricultural systems and crop varieties with enhanced resilience. Polyploidy, the state of possessing multiple complete sets of chromosomes arising from whole genome duplication (WGD), is a major evolutionary force in plants, often conferring novel genetic and regulatory capacities that facilitate adaptation. Allotetraploid cotton ( Gossypium spp.), which formed through the merger of distinct A and D subgenomes approximately 1 to 1.6 Mya, is an exemplary model for elucidating polyploid genome evolution and molecular mechanisms underlying stress adaptation. Whereas combining divergent genomes introduces genetic novelty and hybrid vigor, long-term adaptive success and enhanced resilience rely on complex regulatory reprogramming subsequent to the merger event. In cotton, and by extension other polyploids, this reprogramming involves dynamic structural genomic rearrangements, functional diversification of duplicated genes, and pervasive alterations in epigenetic landscapes. These processes reshape transcriptional networks, leading to homoeologous expression bias and novel regulatory interactions. These polyploidy-specific phenomena underpin differential subgenome contributions to key developmental processes and adaptive responses to major abiotic stresses including drought, salinity, and extreme temperature. A comprehensive understanding of these interconnected genetic and epigenetic control mechanisms, the resulting landscape of subgenome coordination or independence, and associated physiological consequences, are essential for designing effective strategies to breed climate-resilient crops. Here, we synthesize current insights from cotton, emphasizing their broader significance for harnessing polyploidy as a tool for future crop improvement amid global environmental change.

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

Plug-and-play assembly of biodegradable ionizable lipids for potent mRNA delivery and gene editing in vivo

Xuexiang Han, Ying Xu, Adele S. Ricciardi, Junchao Xu, Yan Xiang, Rohan Palanki, Vivek Chowdhary, Lulu Xue, Ningqiang Gong, Mohamad-Gabriel Alameh, William H. Peranteau, James M. Wilson, Daniel Reker, Drew Weissman, Michael J. Mitchell

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mRNA-based gene editing therapeutics offer the potential to permanently cure diseases but are hindered by suboptimal delivery platforms. Here, we devise a robust combinatorial chemistry for the plug-and-play assembly of structurally diverse biodegradable ionizable lipids from amines/thiols and dialkyl maleates. After screening 500 ionizable lipids, we obtained structure−activity relationships essential for effective in vitro mRNA delivery with the help of machine learning. Furthermore, we identified a lead ionizable lipid candidate that produced potent lipid nanoparticles for the delivery of various gene editing tools in wild-type and genetically modified mice compared to literature and industry benchmark lipid nanoparticles. Mechanistically, our lipid nanoparticles show favorable physicochemical properties, which could synergistically contribute to the superior delivery performance. This study highlights the utility of this synthetic method as well as the generality of this platform for potent in vivo gene editing.

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

Trait-mediated interactions drive local diversity

Lisa Buche, Oscar Godoy, Lauren G. Shoemaker, Peter Vesk, Lauren M. Hallett, Courtney G. Taylor, Wing Man Siu, Manuel Sevenello, Margaret M. Mayfield

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Identifying overarching processes that maintain biodiversity in natural communities remains a challenge in ecology. Although functional traits help explain regional species distributions, they often fall short at the local community level. We investigate whether traits can offer mechanism-based insights into local diversity maintenance due to associations with the sign and strength of plant interactions. We examine the effect of 12 plant functional traits on the sign and strength of pairwise species interactions across two Mediterranean annual plant communities. Results show that traits mediate a spectrum from facilitative to competitive interactions and are influenced by neighbor density and identity. At low densities, species with conservative resource-use traits are consistently stronger facilitators than acquisitive species. The traits of the focal species, however, explain facilitation at low densities better than the traits of neighbors or the pairwise differences in traits. When neighbor density increases, facilitation switches to competition, a pattern we hypothesize reflects a density-mediated reduction in how much neighbors’ traits drive interactions. Moreover, species frequently receiving heterospecific facilitation also display traits associated with self-competition and low intrinsic population growth rate. This study of community-level trait sorting provides insights into the persistence of co-occurring populations, showing trait-based generalizable insights into the local context dependency of species interactions.

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

Amplification-free dual-blocking autocatalytic CRISPR-Cascade for attomolar DNA detection with low nonspecific signal

Jongwon Lim, An Bao Van, Matthew Wester, Katherine Koprowski, Enrique Valera, Rashid Bashir

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Autocatalytic CRISPR architecture offers amplification-free nucleic acid detection by directly linking target recognition to self-reinforcing ribonucleoprotein (RNP) generation. However, spontaneous background activation remains a key barrier, because strand invasion or unwinding events can initiate unintended amplification and diminish assay specificity. Here, we introduce a dual-blocking CRISPR-Cascade design that independently cages both the guide RNA and trigger DNA, establishing an intrinsic AND gate to raise the effective kinetic barrier for unintended RNP formation. This strategy suppresses leakage by approximately 3- to 18-fold relative to single blocking configurations in full Cascade reactions, while preserving rapid detection (10 min), achieving single-copy sensitivity, and enabling quantitative detection. When paired with a competitive guide RNA decoy, the system further reduces background signals without affecting true target detection. Finally, we demonstrate robust Methicillin-resistant Staphylococcus aureus detection from whole blood in under 40 min including the sample purification and extraction. These results establish dual-blocking as a generalizable molecular gating framework for constructing leakage-resistant, amplification-free CRISPR systems suitable for rapid and decentralized diagnostics.

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

Observation of chiral bound states in the continuum in self-biased magneto-optical photonic crystals

Maohua Gong, Qiutong Zhen, Yujie Tang, Peng Hu, Qing-An Tu, Yan Meng, Peiheng Zhou, Zhen Gao

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Chiral bound states in the continuum (BICs) are confined photonic modes with infinite quality factors and chiral response, offering significant potential for chiral optics. Although a novel type of spin-orbital-locking chiral BIC was recently predicted in magneto-optical (MO) photonic crystals (PhCs) that break time-reversal symmetry (TRS), its experimental realization has remained elusive. Here, we report an experimental observation of such chiral BICs in self-biased MO PhCs, which operate without external magnetic fields. Moreover, we experimentally demonstrate that the chirality and the surrounding near-circular polarization of these chiral BICs can be switched simply by reversing the remanent magnetization, without any structural changes. Unlike conventional chiral BICs that preserve TRS, these magnetically induced chiral BICs exhibit exceptional robustness against structural imperfections and perturbations. This work represents a significant advancement in topological photonics for chiral BICs, opening pathways toward robust chiral optical devices.

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

Profile of John Clarke, Michel H. Devoret, and John M. Martinis: 2025 Nobel laureates in Physics

Andrew N. Cleland, Steven M. Girvin

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The Royal Swedish Academy of Sciences awarded the 2025 Nobel Prize in Physics jointly to John Clarke, Michel H. Devoret, and John M. Martinis for their foundational discovery of macroscopic quantum mechanical tunneling and energy quantization in electrical circuits. The work that was honored was conducted primarily in the mid-1980s in John Clarke’s laboratory at the University of California—Berkeley, as described in two articles in Physical Review Letters [M. H. Devoret, J. M. Martinis, J. Clarke, Phys. Rev. Lett. 55 , 1908–1911 (1985); J. M. Martinis, M. H. Devoret, J. Clarke, Phys. Rev. Lett. 55 , 1543–1546 (1985)]. This work effectively bridged the gap between the microscopic world of atoms and the macroscopic world of human-scale engineering.

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

Hybridogenesis as an intermediate step between sexual reproduction and parthenogenesis in stick insects

Alexander Brandt, Guillaume Lavanchy, Vincent Mérel, Luca Soldini, Morgane Massy, Zoé Dumas, Emelyne Gaudichau, Marjorie Labédan, Falon Pasquier Genoud, Marc Bastardot, Tanja Schwander

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Many organisms reproduce through noncanonical modes such as parthenogenesis or hybridogenesis (clonal transmission of one parent’s chromosomes), but whether these arise abruptly or stepwise from each other remains unclear. We address this in the stick-insect genus Bacillus , which harbors several hybrid lineages with diverse reproductive modes. From haplotype-resolved phylogenies of >500 wild-caught individuals, we infer a single, recent (~8,000 y) origin of all hybrids. The ancestral hybrid reproduced via hybridogenesis, which subsequently diversified into parthenogenesis and, twice independently, into triploid lineages. Laboratory crosses recapitulate this trajectory, where each step facilitated the next. These findings reveal how a single genomic perturbation can act as a catalyst for evolutionary innovation, turning the loss of sex into a driver of diversification rather than a dead end.

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

In situ evidence of self-accelerating turbidity currents

Hongbo Ma, Gefei Deng, Xingyu Chen, Yuanjian Wang, Brandon McElroy, Jeffrey Nittrouer, Yu Zhang, Toshiki Iwasaki, Matthieu Cartigny, Xudong Fu

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Self-accelerating turbidity currents (SATCs) are hypothesized to be the primary mechanism for transporting vast amounts of sediment to the deep ocean. However, theoretical predictions of SATCs have preceded field observations by decades, leaving a critical gap in our understanding of this long-distance delivery process. Here, we present results from a four-year field survey of turbidity currents and bathymetric evolution in the Xiaolangdi Reservoir on the Yellow River (China), the world’s most sediment-laden river. We provide definitive in situ evidence of SATCs, characterized by synchronous down-channel increases in sediment mass and current momentum, alongside massive channel incision at the event scale. Notably, these SATCs occur in a low-gradient lacustrine setting, challenging the prevailing hypothesis that such phenomena are restricted to steep submarine channels or high velocity conditions. We identify a dimensionless threshold, incorporating current velocity, channel slope, and sediment settling velocity, that governs SATC formation across sublacustrine and marine environments. This threshold provides a robust framework for predicting SATC occurrence and informs engineering strategies to sustain reservoir capacity and restore sediment connectivity in dammed river systems.

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

Synaptic and neural pathway redundancy enables the robustness of a sensory-motor reflex and promotes predation escape in Caenorhabditis elegans

Haoming He, Eugenia King Hin Fong, Sandeep Kumar, Ho Ming Terence Lee, Andrew M. Leifer, Martin Chalfie, Chaogu Zheng

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As a basic unit of the nervous system, the sensory-motor reflex circuit is fast and robust. However, it is not entirely clear how this robustness is achieved, given that various genetic perturbations can alter the function of the sensory neurons. By mapping the molecular basis of neuronal connections in the touch response circuit of Caenorhabditis elegans , we found prevalent genetic redundancy at neural pathway, synaptic, and molecular levels, which ensures that sensory signals can be relayed to command interneurons that control motor output. We also found developmental remodeling of the anterior circuit, which leads to the pruning of larval synapses, establishment of a second pathway that activates additional interneurons, and lateralization of the circuit. Finally, we found that the synapses that appeared to be functionally redundant in a simple touch assay contribute to the extent of reversal response in an additive manner, which may help the organism escape from predators.

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

Interaction dynamics between epithelial cysts captured by tissue rheology

Marie André, Linjie Lu, Michèle Lieb, David Gonzalez-Rodriguez, Daniel Riveline

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Epithelial cysts are minimal structures involved in morphogenesis. They are fluid-filled cavities surrounded by an epithelial monolayer. During development, cyst grow and their interactions shape organs. While their growth dynamics as single structures are well characterized, physical mechanisms underlying their interaction remain poorly understood. Here, we design a minimal assay of interacting cyst doublets based on microfabrication, quantitative biology, and theory to show that Madin–Darby canine kidney (MDCK) cysts interaction is essentially determined by rheological properties of their epithelial monolayers. We report two phases of interaction: coalescence of cellular monolayers and lumen fusion, with similar speeds of 0.3 μm/h. We modulate the distribution of interaction phenotypes by reducing cell–cell adhesion using E-cadherin knock-out MDCK cells, and we report that E-cadherin depletion promotes lumen fusion. Remarkably, dynamics of coalescence and fusion are conserved between both cell lines. To understand the conserved speeds and the effect of cell–cell adhesion, we model the mechanical behavior of cyst doublets as a complex fluid to predict a speed determined by viscosity, stretch-dependent monolayer tension, and adhesion energy between cells. We measure these parameters through rheological experiments using micropipette aspiration and lumen drainage, spanningthe full range of stretch. A key insight from this analysis is that accounting for tension’s dependence on stretch is essential to capture dynamics observed during cyst interaction. Using these rheological measurements, we successfully recapitulate the conserved speed. We show that Caco-2 cyst interactions follow similar rules. Altogether, our results open perspectives to understand tissue dynamics during organogenesis through simple physical arguments.

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

Multiplex gene editing enables the multibiofortification of essential vitamins and other health-promoting phytonutrients in tomato

Yechun Hong, Zongjun Yu, Wenbo Zhu, Jialei Sun, Zeyao Zhu, Zhen Wang, Minjie Cao, Zhaobo Lang, Yu-Xuan Lyu, Pengpeng Liu, Jian-Kang Zhu

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Dietary deficiencies in essential micronutrients and other phytonutrients represent a global health and economic burden, contributing to “hidden hunger” and chronic diseases. While genome editing has been employed to improve individual nutritional traits in crops, multibiofortification through simultaneous modification of multiple distinct metabolic pathways is more challenging. Here, we designed a multiplex CRISPR-Cas strategy to edit five key genes in tomato: Sl7-DR2 , SlGAD3 , SlSGR1 , SlGGP1 , and SlGGP2 . This approach successfully generated quintuple mutant ( 5m ) tomato lines simultaneously biofortified with seven health-promoting compounds: vitamin D 3 (from 0 to 0.70 μg/g dry weight), vitamin C (up to 2.53-fold), provitamin A/β-carotene (up to 3.86-fold), α-carotene (up to 2.47-fold), lutein (up to 3.26-fold), lycopene (up to 7.07-fold), and γ-aminobutyric acid (GABA, up to 5.26-fold). Notably, these multibiofortified tomatoes exhibited no significant trade-offs in plant growth or fruit quality. Extracts from 5m tomatoes showed enhanced suppression of colorectal cancer cell proliferation in vitro. This antiproliferative effect was validated in vivo, where dietary supplementation with 5m tomato powder significantly inhibited tumor growth in a mouse xenograft model. Our work demonstrates an effective strategy for developing a next generation of “functional foods” through multibiofortification, creating a single, nutrient-dense crop that combats both micronutrient malnutrition and chronic diseases.

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

Conscious and nonconscious thought: Insights from the neuroscience of decision-making

Michael N. Shadlen

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Conscious thought is often treated as a special class of neural processing, distinct from the nonconscious computations that guide most behavior. Here I offer a different perspective, grounded in the neuroscience of decision-making. I argue that conscious thought arises not from a unique mechanism but from a distinctive use of neural representations already engaged in nonconscious thought. Nonconscious thoughts are structured as interrogations that yield provisional intentions—decision-like commitments that guide action or inquiry without entering awareness. Using examples from perceptual decision-making and neurophysiology, I suggest that such thoughts depend on persistent neural representations that encode not only potential actions but the questions that give them meaning. These knowledge states may also preserve source-sensitive structure that supports a minimal experiential organization even when they remain nonconscious. Conscious thought, on this account, emerges when such a state is reformatted for potential report to another mind, or to oneself, recruiting theory of mind and narrative structure and placing its content in a space presumed to be shared. This proposal identifies a tractable bridge from nonconscious decision mechanisms to phenomenal consciousness, thereby placing part of the hard problem within empirical reach.

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

Genome-wide association mapping and targeted loss of function studies identify Shroom3 as a driver of hyperpolyploidy and ventricular dilation

Alexandra L. Purdy, Amirala Bakhshian Nik, Anooj A. Arkatkar, Prottoy Hasan, Michael A. Flinn, Priyanka Choudhury, Cheyret Wood, Akiko Takizawa, Lynn Malloy, Monika Tutaj, Thomas A. Drysdale, Darren Bridgewater, Brian A. Link, Timothy F. Plageman, Anne E. Kwitek, Melinda R. Dwinell, Laura M. Saba, Caitlin C. O’Meara, Michaela Patterson

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Various states of cardiomyocyte (CM) polyploidy have been associated with cardiac injury responses, including regeneration and heart failure. However, our understanding of the comprehensive mechanisms governing CM ploidy and its relationship with heart physiology is limited. To address this issue and uncover genetic regulators, we surveyed CM ploidy across a new genetic resource known as the Hybrid Rat Diversity Panel (HRDP) and found significant variation in ploidy phenotypes across the panel. Using select rat strains with divergent displays of CM ploidy, we found that CM hyperpolyploidization (≥8 N) positively correlates with various physiological parameters, namely left ventricular dilation and reduced ejection fraction. Genome-wide association mapping identified several loci significantly associated with frequency of hyperpolyploid CMs. Investigation of genes harboring damaging protein coding variants within these loci identified enrichment of cytoarchitectural genes, of which the ACTIN-binding protein, Shroom3 , was found to be strongly and specifically expressed in CMs and harbors 7 damaging protein coding variants. CM-specific deletion of Shroom3 resulted in increased hyperpolyploidization and left ventricular dilation with reduced ejection fraction. Furthermore, functional characterization of single-nucleotide variants resulting in amino acid changes within SHROOM3 confirmed two protein coding variants that disrupted SHROOM3–ACTIN interaction and led to altered expression of genes involved in DNA replication. This study elucidates the genetic determinants of CM ploidy phenotypes and solidifies a correlative relationship between CM ploidy and left ventricular function. Importantly, CM intrinsic expression of at least one gene mapped in this study, Shroom3 , is confirmed to regulate CM hyperpolyploidization and cardiac function.

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

Aging increases the cortical resources allocated to static balance maintenance

Thomas Legrand, Scott J. Mongold, Laure Müller, Maxime Niesen, Zoritsa Demerdziev, Pierre Coemelck, Esranur Yildiran Carlak, Antonella Iannotta, Gilles Naeije, Mathieu Bourguignon, Marc Vander Ghinst

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Maintaining balance requires a complex interplay between sensory and motor processes, and this ability deteriorates with age, impairing daily life activities and contributes to increased fall risks. Importantly, while cognitive-motor interference paradigms suggest an aging-related increase in the cortical involvement in balance regulation, direct evidence remains lacking. To clarify this issue, we assessed the effect of aging on sway-based corticokinematic coherence (CKC), which is a measure of the coupling between cortical electrophysiological signals and postural sway. To that end, we recorded the center-of-pressure fluctuations and electroencephalographic cortical activity of 64 young and 67 older healthy participants performing balance tasks during which sensory information was either removed or altered. We found that older adults showed increased cortical activity that appears to relate to different aspects of closed loop postural control during challenging balance conditions, and correlates with upright stance stability. They also showed increased delays between cortical activity and postural sway, indicative of slower central processing speed. Finally, despite the older cohort displaying significantly altered vestibulo-ocular reflexes, no relationship was found with CKC strength. Overall, our results provide direct evidence that cortical involvement in balance regulation increases with aging. They suggest the feasibility of assessing afferent and efferent processing during balance maintenance, paving the way for studies identifying neurophysiological determinants of fall risks.

Reply to Romano and De Dreu: Why violent extremism cannot be reduced to laboratory games

Jonas R. Kunst, Tomasz Besta, Milan Obaidi

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Emerging design principles for environmental, economic, and equity successes in land conservation

Katharine R. E. Sims, Jennifer M. Alix-Garcia

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Land conservation initiatives worldwide are poised to continue rapid growth. Ranging in scale, scope, and mechanisms, these efforts include area-based conservation, incentive-based protection, and community collective management. Evidence from across fields now indicates that it is possible for land conservation to jointly improve environmental conditions, generate positive net local economic benefits, and support social equity. Yet the key policy elements that can lead to this type of multidimensional success are not well understood. Here, we review the considerable body of existing research on land conservation and propose eight emerging design principles that conservation actors can employ to support “win-win-win” outcomes: 1) identify and support credible pathways of change, 2) set goals for all outcomes, recognizing their interdependencies, 3) accommodate multiple needs and uses through spatial or place-specific differentiation, 4) facilitate temporal resilience through diversification and limits, 5) foster nested governance, 6) integrate information structures for environmental and social outcomes, 7) assess policies using counterfactual-based analysis and adaptive management, 8) establish lasting institutions and funding mechanisms. Although these design principles will likely change and evolve, they provide an evidence-grounded framework to support current and future efforts to steward global lands.

Blindness to minority absence

Rasha Kardosh, Asael Y. Sklar, Kalman Victor, Bella Qing Dong, Ashi D. Schwartz, Gal Chen, Ran R. Hassin, Yaacov Trope

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Our cognitive processes are largely shaped by what is present in our environment, while absences are often overlooked. This fundamental tendency of the human mind can lead to a significant social bias: individuals frequently fail to notice the absence of minority groups, even in situations where that absence is meaningful and consequential (e.g., educational settings, workplaces). In three preregistered field studies conducted across two cultures, we found robust evidence for blindness to minority absence. Our findings reveal that this blindness can persist for years, even among individuals who, once the absence is pointed out, acknowledge its significance and the need to address it. Eight preregistered laboratory experiments confirm that people are unlikely to detect the absence of a minority group. As our results indicate, people are more likely to notice the presence of a single minority member than the group’s complete absence. In contrast, the absence of majority group members is far more noticeable. These patterns emerge even when monetary incentives for accuracy are introduced, regardless of participants’ ideologies or social attitudes, and are evident even among individuals from minority groups. The final experiment suggests that highlighting an overlooked minority absence leads to higher stated support for diversity-promoting policies. Taken together, our findings suggest that basic cognitive constraints bias what people spontaneously notice in social environments: minority absences often go unnoticed, while majority absences and minority presences are more readily perceived. We propose that this bias may present a significant barrier to fostering inclusive social environments.

Intentions poorly explain how and why people engage in offensive and defensive forms of violence

Angelo Romano, Carsten K. W. De Dreu

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Neural representations of popularity and leadership status relate to conformity in daily life

Ovidia A. Stanoi, Danielle Cosme, Mia Jovanova, Yoona Kang, Faustine Corbani, Amanda L. McGowan, José Carreras-Tartak, Anthony Resnick, Peter S. Bearman, Zachary M. Boyd, Dani S. Bassett, David M. Lydon-Staley, Peter J. Mucha, Emily B. Falk, Kevin N. Ochsner

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Individuals are motivated to increase their social status. To succeed in this pursuit, people must track information about others in their social sphere, monitor group norms, and adjust their behavior strategically. This study employed functional MRI and ecological momentary assessment methods in a sample of 92 college students belonging to 9 social groups to elucidate the neural mechanisms underlying these processes and their relationship to conformity in the context of alcohol use. When young adults passively looked at faces of their real-life social group peers, brain systems implicated in valuation and social cognition spontaneously tracked information about the popularity and leadership status of the social targets in an interdependent manner. Individual differences in these neural valuations were systematically associated with varying levels of conformity. Students who had stronger responses to faces of peers with relatively higher popularity and leadership status than themselves in one key valuation brain region, the ventromedial prefrontal cortex (vmPFC), were more likely to align their drinking behavior with their groups’ norms in everyday life. These results provide evidence for how brain systems involved in valuation and social cognition flexibly track information about peers’ popularity and leadership status in real-life social groups and contribute to a growing literature on the neural mechanisms through which social comparison processes shape conformity. Our study highlights the vmPFC as a central hub that spontaneously tracks status differences between the self and peers and uses this information to guide behavior to match group norms.

Cultural evolution of beauty standards

Louis Boucherie, Sagar Kumar, Katharina Ledebur, August Lohse, Karolina Śliwa

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Beauty standards shape self-perception and health through social comparison and objectification, while exposure to idealized imagery exacerbates body-image concerns. Media and fashion are central arbiters of these ideals, yet long-term, quantitative, intersectional studies on how representation has changed remain scarce. We assembled a dataset of 793,199 records spanning 25 y of advertising, magazine covers, runway shows, and editorials to quantify changes in anthropometric and demographic representation. We find a paradox in the evolution of beauty ideals: While representational diversity has increased, the median model physique remains stable. This is driven by selective plus-size inclusion at the upper tail, while the typical physique continues to diverge from the US population. Intersectionally, non-White models are 4.5 times more likely to be plus-size, suggesting that the industry consolidates multiple markers of diversity onto already underrepresented individuals rather than broadening inclusion structurally. Stratifying the industry via a data-driven prestige hierarchy, we find that thinness is overrepresented at the top tier. Finally, descriptive comparisons of two regulatory interventions suggest that numeric thresholds may be more effective than flexible guidelines at reducing underweight appearances. Our results quantify the cultural evolution in media and fashion, revealing that inclusion has increased; however, gains are uneven and intersectionally concentrated on size and ethnicity, whereas the prevailing thin ideal remains largely unchanged.

Rational sycophants and catastrophic risks

Robert Axelrod, Scott E. Page

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Sycophants praise and support leaders’ proposals to gain personal and professional advantage. A rational sycophant is an advisor who supports actions they expect to be harmful even when rewards and punishments for good and bad advice are equal in magnitude. Rational sycophancy arises when the outcome distribution of a proposed action has a negative expected value but a positive median (outcome asymmetry). The risk is greatest when a small yet meaningful fraction of outcomes are catastrophic, which occurs in long-tailed distributions. Given that single realizations from long-tailed distributions reveal little about the underlying distribution, even after outcomes are observed, a leader may be unable to distinguish rational sycophancy from wise counsel. As a result, rational sycophants may gain influence and increase the likelihood of catastrophic policy outcomes.

China’s one-child policy amplifies intergenerational inequality via enlarged differential fertility

Yewen Yu, Yi Fan, Junjian Yi

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Using the staggered rollout of China’s one-child policy (OCP) across provinces and birth cohorts as a quasi-natural experiment, we demonstrate that differential fertility between richer and poorer households exacerbates intergenerational income inequality. Rural/poorer families, who are less constrained by the OCP than their urban/richer counterparts, tend to have more children but invest less in each child’s human capital. This reduction in mobility is primarily driven by the rising economic status of children born to urban/wealthier families. Our estimates suggest that the OCP accounts for approximately 25% of the observed decline in intergenerational income mobility in China and thus highlight a demographic channel through which economic inequality persists across generations.

Semantic knowledge guides innovation and drives cultural evolution

Anil Yaman, Shen Tian, Björn Lindström

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Cultural evolution allows ideas and technologies to accumulate across generations, reaching their most complex and open-ended form in humans. While social learning enables the transmission of such innovations, the cognitive processes that generate them remain poorly understood. Classical theories typically treat innovation as random variation, a simplification insufficient for explaining the complexity of human cultural evolution. We propose that semantic knowledge—the associations linking concepts to their properties and functions—guides human innovation and drives cumulative culture. To test this, we combined an agent-based model, which examines how semantic knowledge shapes cultural evolutionary dynamics, with a large-scale behavioral experiment (N = 1,243) testing its role in human innovation. Across both approaches, we found that semantic knowledge directed exploration toward meaningful solutions, enhanced innovation success, and enabled generalization from prior discoveries. Moreover, semantic knowledge interacted synergistically with social learning to amplify innovation and accelerate cumulative cultural change. In contrast, experimental participants lacking access to semantic knowledge performed no better than chance, even when social learning was possible, and relied on shallow exploration strategies for innovation. Together, these findings suggest that semantic knowledge is a key cognitive process underpinning human cumulative culture.

Accessibility–equality dynamics in urban blue and green spaces reshape human well-being

Bin Xue, Jianing Zhang, Bingsheng Liu, Marina Alberti, Yufeng Fan, Dong Zhao, Nancy B. Grimm

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As urbanization accelerates, urban blue and green spaces are increasingly recognized as critical nature-based solutions for enhancing human well-being, delivering climate, environmental, and psychological benefits. Yet, the mechanisms by which access to these natural spaces and the equality of access by urbanites in diverse residential locations shape well-being remain poorly understood in the context of sustainable urban governance. Here, we systematically evaluated the spatiotemporal dynamics of urban blue and green space accessibility and equality across 279 Chinese cities from 2000–2100 and assessed their combined effects on well-being. We found that accessibility has a significant positive influence on well-being but follows an inverted-U-shaped pattern with distinct optimal thresholds. By contrast, equality shows a consistent, positive linear relationship with well-being. Although future accessibility is projected to improve, persistently high disparities among different segments of urban populations highlight the urgent need for equity-centered governance of blue and green spaces in cities. This perspective extends current approaches to environmental justice while revealing a structural mismatch between resource abundance and equitable distribution. To address this mismatch, we propose a prioritization framework that emphasizes context-specific, spatially targeted interventions, guided by four key drivers: the natural space to built-up area ratio, urban population size, the proportion of natural spaces with high accessibility, and urban landscape connectivity. By operationalizing these insights in an online toolkit for local governments, this work advances the fields of sustainable urban governance and equitable environmental planning.

Social interactions in isolated, confined, and extreme environments: A study of Antarctic winter teams using wearable sensors

Andrea Cantisani, Jan B. Schmutz, Pedro Marques-Quinteiro, Lorenzo Dall’Amico, Ciro Cattuto, Mirko Antino, Walter J. Eppich, Katharina Stegmayer, Sebastian Walther

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Long-duration space missions expose crews to extreme psychological and social stressors due to prolonged isolation and confinement. To examine how such conditions impact individual and team functioning, we studied a 10-mo Antarctic overwintering mission at Concordia Station, an analog for spaceflight, using self-report measures and wearable proximity sensors. Twelve crew members were assessed at four time-points. Results revealed a progressive increase in feelings of loneliness and conflict, while cohesion and individual performance declined. Close-range interactions were positively associated with conflicts and paranoid thoughts and negatively related with individual performance, suggesting that more frequent contact did not equate to social support. Social interactions became increasingly clustered within national groups, highlighting the risk of social fragmentation and crew polarization. The use of wearable sensors proved feasible for long-term use in extreme environments. These findings underscore the importance of monitoring psychosocial functioning during extended missions and suggest that close confinement, rather than isolation alone, may trigger interpersonal strain.

From free speech advocates to critics: The Trump administration’s new rhetoric promotes support for censorship among Trump voters

Matthew E. K. Hall, B. Tyler Leigh, Brittany C. Solomon

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Most Americans claim to support freedom of speech, including President Donald Trump who has portrayed himself as an ardent defender of this constitutional right. However, in the wake of Charlie Kirk’s assassination, Trump and members of his administration began to explicitly call for speech restrictions. This largely unprecedented rhetoric from a sitting president and his allies provides an opportunity to examine competing theories of public opinion: the influence of partisan elites versus the public’s purported commitment to free speech. In a preregistered survey experiment, we found that exposure to such unusually explicit antispeech rhetoric increased Trump voters’ support for government censorship of outparty media and individuals but prompted backlash among non-Trump voters, increasing their support for protecting outparty speech. While prior research has established that partisans favor censorship of outparty members, we demonstrate that partisans differentially shifted their censorship attitudes in response to the Trump administration’s new rhetoric, whether or not the source was attributed to Trump and his allies. These findings highlight the influence of elite rhetoric on public support for even the most foundational—and popular—democratic norm, raising concerns about the resilience of American democracy in the face of explicitly illiberal elites.

Peer influence on West Point cadets’ Civil War allegiances

Yuchen Guo, Matthew O. Jackson, Ruixue Jia

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Do social networks and peer influence shape major life decisions in polarized settings? We explore this question by examining how peers influenced the allegiances of West Point cadets during the American Civil War. Leveraging quasi-random variations in the proportion of cadets from Free States, we analyze how cadets’ decisions about which army to join depended on the composition of their peers. We have three main findings. First, there was a strong and significant peer effect: a higher proportion of classmates from Free States significantly increased the likelihood that cadets from Slave States joined the Union Army. Second, the peer effect varies with geography, most notably with the slave population share in cadets’ home states or counties, and with cadets’ own slave ownership in 1860. Third, peer effects were amplified by shared experiences such as having served together in the Mexican-American War, continuous military service, and belonging to the same cohort, suggesting that sustained interaction is important.

Early neural attunement to peer status predicts future social network position and popularity in adolescents

Won-Gyo Shin, Kiho Sung, Junho Bang, Sunhae Sul, Yoosik Youm, Carolyn Parkinson

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Popularity is a key marker of social status, yet the phenomena that support its emergence within newly forming social groups remain unclear. We combined functional neuroimaging and longitudinal school-wide social network analysis to track adolescents throughout their first year of high school, examining whether early neural responses to peers of varying social status predict later popularity. Here, we show that greater neural differentiation when viewing the faces of unpopular versus popular peers, particularly in the hippocampus, forecasts greater perceived popularity at the end of the school year. This relationship is mediated by midyear social network centrality, especially in-closeness centrality, which reflects being more easily reachable by peers. These findings suggest that early neural attunement to the status of their peers shapes how adolescents become embedded in their social networks, which in turn contributes to later gains in their own perceived popularity. More generally, these findings reveal how neural and social network-level processes jointly drive adolescents’ navigation of evolving social landscapes and attainment of social status.

AI assists adversarial collaboration in debate on minority salience

Barbara Mellers, Leo Yuan, Yubo Zhou, Isabelle Mauboussin, Eyana C. Lao, Bea Corio, Ville Satopaa, Lyle Ungar, Sudeep Bhatia, Cory J. Clark, Rasha Kardosh, Ran Hassin, Asael Sklar, Surya Gayet, Chris Paffen, Stefan Van der Stigchel, Andre Sahakian, Philip Tetlock

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The advancement of science depends on rigorous tests of competing hypotheses, yet many disputes are left unresolved. Adversarial collaboration—where opposing scientists jointly design decisive tests—is one proposed solution. We examine whether large language models (LLMs) can play a role by organizing information, structuring the debate and generating candidate experimental designs. This article reports an AI-assisted adversarial collaboration designed to resolve a debate in PNAS on minority salience—an overestimation of the percentage of minority faces in a visual display. The debate focused on whether there would be further overestimation when minorities in the displays were the same minorities in participants’ communities (or social environments). Using LLMs to extract and organize competing propositions, we identified central disagreements and generated initial experimental designs to test claims. Human collaborators refined the designs and created two preregistered experiments that factorially manipulated the ethnicity of minority faces and the ethnicity of participants’ communities. Data showed that people exaggerated the percentage of minorities in facial displays. Furthermore, overestimation was even greater when minorities in facial displays were also minorities in participants’ communities. When the two camps of researchers saw the results, their confidence in key hypotheses converged. We do not experimentally test AI-assisted adversarial collaboration relative to traditional adversarial collaboration or other forms of dispute resolution. Rather, our study illustrates how an AI tool can be used with adversarial collaboration to formalize claims, structure disagreements, lower barriers to collaboration, and serve as an impartial observer to strengthen perceptions of fairness.

Science

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

FERONIA orchestrates plasma membrane nanoclusters for plant thermotolerance

Kun Wang, Hanqi Yan, Xin Guo, Qihong Lin, Jing Li, Aoyang Peng, Ying Fu, Zhizhong Gong, Shuhua Yang, Yanglin Ding

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Climate warming poses increasing thermal challenges to plants, yet how plasma membrane biophysics contributes to heat adaptation remains poorly understood. In this work, we showed that the malectin-like receptor kinase FERONIA (FER) acts as a membrane-anchored thermal switch in Arabidopsis . FER organizes sterol-dependent nanoclusters that control heat acclimation. Moderate heat activated FER through the RAPID ALKALINIZATION FACTOR 34 (RALF34) peptide and promoted its recruitment to sterol-rich nanodomains. There, FER nucleated dynamic nanoclusters enriched in stress-signaling components. These nanoclusters stabilized liquid-ordered membrane phases and activated heat shock transcription factor–heat shock protein signaling, enhancing thermotolerance. However, under extreme heat the nanoclusters rapidly disassembled, preventing maladaptive responses. Our findings thus establish nanoscale membrane compartmentalization as a key mechanism linking lipid dynamics to plant thermal resilience.

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

Observation of quantum vortex core fractionalization and skyrmion formation in a superconductor

Yu Zheng, Quanxin Hu, Xin Yu, Haijiao Ji, Igor Timoshuk, Julien Garaud, Hanxiang Xu, Yongwei Li, Ye Gao, Xingye Lu, Vadim Grinenko, Egor Babaev, Noah F. Q. Yuan, Rui Wu, Baiqing Lv, Chi-Ming Yim, Hong Ding

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Magnetic fields can penetrate a superconductor in the form of quantum vortices, which consist of a core singularity with circulating currents. London’s quantization implies that there is one core singularity per quantum of magnetic flux in single-component superconductors. Here, we report signatures of quantum vortex core fractionalization on the potassium-terminated surface of a multiband superconductor KFe 2 As 2 . The observed splitting of single integer-flux vortices into several fractional vortices results in a disparity between the numbers of flux quanta and vortex cores. These fractional vortices often arrange in chains, which calculations show are characterized by a ℂP 2 skyrmionic topological invariant; this constitutes a different type of topological defect: the chiral skyrmion. The disparate natures of integer and fractional vortices comprising skyrmions lead to distinct spectroscopic signatures.

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

Abrupt stream acidification and metal mobilization from permafrost degradation

Elliott K. Skierszkan, Andras J. Szeitz, Matthew B.J. Lindsay, Sean K. Carey

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Stream chemistry and ecosystem function are being transformed by abrupt acceleration of sulfide-mineral oxidation in permafrost-underlain headwater catchments of the Yukon and Mackenzie river basins—the two largest (sub)Arctic rivers in North America. Over the past decade, dozens of acidic (pH ~3) seepages have emerged in these headwaters, causing vegetation dieback and mobilizing metals at acutely toxic concentrations in receiving streams. Acid generated during sulfide-mineral oxidation also accelerates carbon dioxide emissions by driving carbonate-mineral dissolution. Downstream (sub)Arctic rivers show statistically significant multidecadal increases in sulfate concentrations, yet their metal concentrations remain stable because of attenuation and dilution processes. Headwater stream acidification signals a major perturbation in metal, carbon, and sulfur cycling linked to permafrost thaw with far-reaching consequences for water resources, northern communities, ecosystem health, and Earth’s biogeochemical future.

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

Cloudy mornings and clear evenings on a gas giant exoplanet

Sagnick Mukherjee, David K. Sing, Guangwei Fu, Kevin B. Stevenson, Stephen P. Schmidt, Harry Baskett, Mei Ting Mak, Patrick McCreery, Natalie H. Allen, Katherine A. Bennett, Duncan A. Christie, Carlos Gascón, Jayesh Goyal, Éric Hébrard, Joshua D. Lothringer, Mercedes López-Morales, Jacob Lustig-Yaeger, Erin M. May, L. C. Mayorga, Nathan Mayne, Lakeisha M. Ramos Rosado, Henrique Reggiani, Zafar Rustamkulov, Kevin C. Schlaufman, Kristin S. Sotzen, Daniel Thorngren, Le-Chris Wang, Maria Zamyatina

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The spectra of exoplanet atmospheres are affected by aerosols (clouds and hazes) of uncertain origin. Proposed aerosol formation mechanisms include gas condensation or photochemical reactions. We measured the transmission spectrum of the tidally locked gas giant exoplanet WASP-94A b and identified asymmetry in its atmosphere. The morning limb is cooler and cloudy, whereas the evening limb is hotter and exhibits gaseous water absorption features. We interpret this difference as being due to the formation of cloud droplets near the morning limb, which evaporate during circulation to the evening limb. The dominant aerosols are clouds cycling between the day and night sides of the atmosphere, not photochemical hazes. The resulting asymmetry can severely bias chemical abundance measurements, unless limb-resolved spectroscopy is available.

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

DNA polymerization activates RNA cleavage of a reverse transcriptase–like antiviral enzyme

Xuejun Rong, Jun Xiao, Xinyuan Zhao, Yan Yan, Jing Li, Yifan Chen, Yihua Fan, Zhichao Liu, Yue Cao, Fan Chen, Rui Cheng, Xionglue Wang, Longfei Wang, Bin Zhu

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Defense-associated reverse transcriptases (DRTs) transcribe noncoding RNAs (ncRNAs) for antiviral defense, but the mechanisms of ncRNA-independent DRTs remain unclear. In this work, we show that a single DRT4 mediates RNA-targeting antiphage defense by integrating DNA polymerase, exonuclease, and RNA endonuclease activities. First, through an equilibrium between its DNA polymerase and exonuclease activities, DRT4 senses phage infection, as elevated dNTP levels shift the equilibrium toward polymerase activity, thereby promoting protein-primed single-stranded DNA (ssDNA) synthesis. Second, ssDNA of sufficient length, phage DNA-binding proteins, and deoxyguanosine triphosphate collectively activate an unusual RNA endonuclease activity of DRT4, excising 3′–guanosine monophosphate from both phage and host RNA to terminate infection. These findings reveal a distinctive immune strategy combining nucleic acid synthesis and degradation, expanding the functional landscape of DRTs for new DNA- and RNA-processing technologies.

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

Dynamics of disordered quantum systems with two- and three-dimensional tensor networks

Joseph Tindall, Antonio Francesco Mello, Matthew Fishman, E. Miles Stoudenmire, Dries Sels

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Large-scale quantum annealing dynamics of Ising spin glasses were recently implemented on D-Wave’s Advantage2 system on a range of lattices. After extensive comparison with existing numerical methods, these experiments were claimed to be beyond the reach of classical computation. Here, we simulated these spin-glass models with lattice-specific tensor networks, using belief propagation (BP) to keep up with the entanglement generated during the time evolution and then extracting expectation values with more sophisticated variants of BP. We found that state-of-the-art accuracies could be achieved with modest computational resources. Moreover, our results are scalable in both two and three dimensions, which we leveraged to verify universal Kibble-Zurek physics on systems involving hundreds of qubits.

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

A relay energy transfer paradigm for asymmetric photocatalyzed [4+2] cycloadditions

Yong-Bin Wang, Yi-An Xu, Cheng Li, Gang-Ya Cheng, Shao-Hua Xiang, Bin Tan

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In asymmetric energy transfer photocatalysis, direct incorporation of conventional chiral catalysts has achieved satisfactory enantiocontrol in several transformations. However, the efficiency and even feasibility of this mode are still limited by the energy transfer barrier that arises from the inevitable catalyst-mediated spatial segregation. To overcome this underappreciated constraint, we designed a relay energy transfer catalytic mode in which the catalyst acts as a bridge for energy transfer between the photosensitizer and the substrate. Guided by this concept, we engineered a class of chiral energy transfer acid catalysts capable of delivering high triplet energy. These catalysts effectively circumvent the inherent stoichiometric dependence on acid activators in dearomative [4+2] cyclization between quinolines and alkenes. The tunability of side arms and the proximity of the catalytic site to the chiral source optimize regio-, diastereo-, and enantioselectivities.

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

Reward magnitude determines reinforcement learning efficiency

Sheng Gong, Alyssa Martell, Joshua T. Dudman, Luke T. Coddington

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Standard animal learning studies minimize individual reward magnitudes to maximize the repetitions of reinforced behaviors. We investigated how reward magnitude influences initial learning across five behavioral paradigms in naïve mice. Especially large rewards could substantially improve learning efficiency through dissociable effects on within- and across-session learning and task engagement. The duration and magnitude of ventral striatal dopamine release scaled with reward sizes, and prolonged optogenetic enhancement of dopamine reward responses also reproduced much, but not all, of the benefits to learning produced by outsized rewards. These findings indicate that the reinforcement learning efficiency of animals has traditionally been underestimated and that dopamine signaling of rewards mediates task engagement in proportion to absolute reward magnitude.

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

Interacting effects of human presence and landscape modification on birds and mammals

Ruth Y. Oliver, Scott W. Yanco, Diego Ellis-Soto, Brett R. Jesmer, Juliet Cohen, Song Gao, Robert Patchett, Tal Avgar, Keith Bildstein, Nicholas W. Bakner, David Barber, Kristin Barker, Joseph G. Barnes, Guillaume Bastille-Rousseau, Jerrold L. Belant, John F. Benson, Joël Bêty, Dean E. Beyer, David Bird, Nathaniel Bowersock, Andy J. Boyce, Ben S. Carlson, Michael L. Casazza, Michael J. Chamberlain, Michael J. Cherry, Bret A. Collier, Alyson Courtemanch, Sarah C. Davidson, Darren DeBloois, Vickie DeNicola, Christopher R. DeSorbo, Robert C. Dowler, Daniel Dupont, L. Mark Elbroch, John Elliott, Betsy A. Evans, W. Mark Ford, David Hancock, Molly Hardesty-Moore, Jason E. Hawley, Mackenzie R. Jeffress, Scott Jennings, Matthew J. Kauffman, Roland Kays, Marcella J. Kelly, Bryan M. Kluever, Myles Lamont, Scott LaPoint, Tayler N. LaSharr, Josee Lefebvre, Pierre Legagneux, Matthias-Claudio Loretto, David Lumpkin, Lindsay A. Martinez, John M. Marzluff, Douglas McCauley, Fiona McDuie, Tony W. Mong, Kevin L. Monteith, Thomas Mueller, Levi Newediuk, Anna C. Ortega, Federico Ossi, Cory Overton, J. Clint Perkins, Tyler R. Petroelje, Laura Prugh, Kimberly A. Sager-Fradkin, Michael Seer, Avery L. Shawler, Shannon Skalos, Rachel A. Smiley, Julia Sommerfeld, Daniel R. Stahler, John A. Stephenson, Richard D. Stevens, Nathan J. Svoboda, Jean-Francois Therrien, Phillipe J. Thomas, Meredith VanAcker, Eric Vander Wal, Dan E. Varland, Tana L. Verzuh, Brittany L. Wagler, Nils Warnock, Stephen L. Webb, Christopher K. Williams, Christopher C. Wilmers, David W. Wolfson, Julie K. Young, Christian Rutz, Walter Jetz

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Sustainable human–wildlife coexistence requires a mechanistic understanding of the many ways that humans affect animals. However, progress is hampered by the lack of accessible data measuring the dynamic presence of people. Here, we leverage mobile-device data to disentangle how human presence and landscape modification differentially influence the use of geographic and environmental space for 37 mammal and bird species across the United States. Human presence affected more than 65% of species, with substantial variation across species. For ~60% of species that responded to human activities, the effects were interdependent—animals tended to react more strongly to human presence in less modified habitats. Our results demonstrate that human presence and landscape modification have complex combined effects on wildlife, which need to be considered for effective management.

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

Magnon hydrodynamics in an atomically thin ferromagnet

Ruolan Xue, Nikola Maksimovic, Pavel E. Dolgirev, Li-Qiao Xia, Aaron Müller, Ryota Kitagawa, Francisco Machado, Dahlia R. Klein, David MacNeill, Kenji Watanabe, Takashi Taniguchi, Pablo Jarillo-Herrero, Mikhail D. Lukin, Eugene Demler, Amir Yacoby

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Strong interactions between particles can lead to emergent collective excitations. Spin waves, known as magnons, have been predicted to reach a strongly interacting hydrodynamic regime, where they form a slow collective density mode. In this work, we isolate exfoliated sheets of chromium trichloride (CrCl 3 ), where magnon interactions are strong, and develop a technique to measure the collective magnon dynamics though nearby nitrogen-vacancy centers in diamond. Thermal magnetic fluctuations generated by monolayer CrCl 3 increase upon decreasing temperature; this anomalous trend may be a consequence of the damping rate of a low-energy magnon sound mode that sharpens as magnon interactions increase with increasing temperature. By measuring the magnetic fluctuations emitted by thin multilayer CrCl 3 in the presence of a variable-frequency drive field, we obtain spectroscopic evidence for this two-dimensional magnon sound mode.

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

Progression without progress

Julio M. Ottino, Brian Uzzi

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Progress in the use of artificial intelligence (AI) to advance scientific discovery has made it increasingly realistic to envision automated “end-to-end science” (ETES) systems: integrated pipelines that could generate hypotheses, run experiments (in silico or robotic), analyze results, and produce publishable outputs with minimal human intervention. The critical question is not whether AI can “do” science but whether science—as a social, evolutionary system that generates trustworthy knowledge—survives the way AI does it.

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

The oscillatory biology of sleep: Linkage to dementia

Maiken Nedergaard

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During wakefulness, neuromodulators operate largely independently to support behavior and cognition. By contrast, sleep reorganizes their activity into a coordinated brain rhythm. During sleep, the major neuromodulators—norepinephrine, acetylcholine, serotonin, and dopamine—exhibit synchronized fluctuations with a periodicity of ~50 seconds. These oscillations appear as recurrent bursts of fast (10 to 30 hertz) electroencephalography activity and are phase-coupled to cerebrospinal fluid flow. Neuromodulators are vasoactive agents and drive slow vasomotion, which provide the mechanical force that supports glymphatic clearance of metabolic waste. Disruption of neuromodulator signaling, as seen in psychiatric disorders, cardiovascular disease, aging, or with commonly prescribed drugs, impairs clearance of neurotoxic proteins, including amyloid-β and tau. Failure of this evolutionarily conserved brain rhythm may therefore represent a previously unrecognized mechanistic pathway linking diverse disorders with sleep disturbances to increased dementia risk.

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

Role of tectonic rock damage in erosional processes: A global analysis

B. Kuhasubpasin, S. Moon, C. Lithgow-Bertelloni

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The role of active faults in driving rock uplift is well known, but their influence on rock damage and erosional efficiency remains unclear globally. Using 1744 beryllium-10 ( 10 Be)–derived erosion rates, we show that erosional efficiency is elevated on average within ~15 kilometers of a fault trace and decreases with distance, up to ~100 kilometers. Reverse faults and those longer than 140 kilometers show the strongest effects. This length scale of decay suggests that tectonic damage extends beyond fault-core pulverization on primary faults, possibly including fracturing or grain-to-grain contact weakening due to seismic shaking and distributed deformation on complex fault networks. Machine learning identified fault proximity as a dominant control on erosional efficiency, exceeding precipitation and lithology, particularly when a measure of seismic shaking is included. These findings indicate that active tectonics are associated with erosion not only through uplift but also by enhancing erosional efficiency through long-range rock damage.

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

Nodeless superconducting gap and electron-boson coupling in (La,Pr,Sm) 3 Ni 2 O 7 films

Jianchang Shen, Guangdi Zhou, Yu Miao, Peng Li, Zhipeng Ou, Yaqi Chen, Zechao Wang, Runqing Luan, Hongxu Sun, Zikun Feng, Xinru Yong, Yueying Li, Lizhi Xu, Wei Lv, Zihao Nie, Heng Wang, Haoliang Huang, Yu-Jie Sun, Qi-Kun Xue, Junfeng He, Zhuoyu Chen

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The discovery of superconductivity in Ruddlesden-Popper (RP) bilayer nickelate films under ambient pressure provides an opportunity to directly investigate electronic energy scales of the superconducting state and the pairing mechanism. We report angle-resolved photoemission spectroscopy measurements of superconducting (La,Pr,Sm) 3 Ni 2 O 7 thin films by developing an ultra-high vacuum cryogenic sample quenching and transfer technique. A superconducting gap of ~18 meV with coherence peaks is observed along the Brillouin zone diagonal. The finite gap persists across the entire Brillouin zone, revealing the absence of gap nodes. A kink is observed in the energy-momentum dispersion at ~70 meV below Fermi level, indicating an electron-boson coupling. The simultaneous observation of a nodeless superconducting gap and electron-boson coupling provides insight into the pairing symmetry and gluing mechanism in RP bilayer nickelates.

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

Long-distance genetic relatedness in megalithic central Europe

Nicolas Antonio da Silva, Almut Nebel, Daniel Kolbe, Daniel Anton Myburgh, Florian Klimscha, Irina Görner, Katharina Fuchs, Christian Meyer, Kerstin Schierhold, Michael Rind, Robert Hoffmann, Andre Franke, John Meadows, Christoph Rinne, Johannes Müller, Ben Krause-Kyora

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Megalithic monuments in Late Neolithic Europe are often viewed as symbols of shared ancestry. In this study, we analyzed genome-wide data of 203 individuals buried in six megalithic grave complexes associated with the Western Funnel Beaker and Wartberg groups. Despite being considered archaeologically distinct, our results show that the studied individuals from both groups form a genetically homogeneous population. Moreover, we identified first- and second-degree relationships spanning up to 225 km, revealing unexpectedly long-distance ties and sustained intersite and intergroup mobility. The six grave complexes functioned as communal burial grounds and were not exclusively used for close genetic relatives, indicating that social kinship played an important role. Limited evidence for genetic connections to distant European megalithic populations indicates that monumentality spread culturally rather than through biological networks.

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

Complex interplay of neuronal and hormonal gut-brain responses to essential amino acid deficit

Boram Kim, Seongju Lee, Hyeyeon Bae, Shinhye Kim, Jong-Hoon Won, Dongwoo Kim, Byungkwon Jung, Makoto I. Kanai, Sung-Eun Yoon, Yangkyun Oh, Won-Jae Lee, Greg S. B. Suh

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A deficit in dietary protein elicits a nutrient-specific appetite, yet the underlying mechanisms remain poorly understood. In this work, we identify coordinated neuronal and systemic mechanisms in Drosophila that drive an essential amino acid (EAA)–specific appetite. EAA deprivation increases neuropeptide CNMamide (CNMa) expression in gut enterocytes, activating enteric neurons and ellipsoid body neurons in the brain to promote EAA intake through two complementary pathways: a rapid neuronal gut-brain axis and a slower hormonal route. CNMa suppresses the activity of sugar-sensing diuretic hormone 44 (DH44) neurons, thereby reducing carbohydrate intake and biasing feeding toward EAAs. Similarly, protein deprivation in mice promotes an EAA-specific appetite independently of fibroblast growth factor 21 ( FGF21 ). Together, these findings reveal multilayered gut-brain mechanisms that regulate nutrient-specific feeding and maintain EAA homeostasis across species.

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

Biogeographic processes underlying global patterns of plant diversity

Barnabas H. Daru, Cornelius O. Nichodemus, L. Francisco Henao-Diaz

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The uneven global distribution of plant diversity remains a fundamental question in biogeography. Using dated phylogenies of >300,000 plant species and ancestral biogeographical stochastic mapping, we show that in situ speciation is the predominant process underlying extant plant diversity and accounts for 78% of biogeographic events across realms. The Neotropic contributed 37% of in situ speciation, likely owing to its role as a center of species diversification. Dispersal between realms was less frequent (16% of events) but facilitated floristic exchanges, especially in the Eastern Hemisphere. Extinction was least frequent but more pronounced in East Asia. These findings support the tropical conservatism hypothesis in which many clades originated in the tropics and only recently expanded into temperate zones, where limited time and biome conservatism have restricted speciation and diversity.

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

Device-scaling constraints imposed by the van der Waals gap formed in two-dimensional materials

Mahdi Pourfath, Tibor Grasser

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Transistor miniaturization requires controlling gate leakage through ultrathin dielectrics and minimizing source-drain contact resistance. Although two-dimensional semiconductors offer excellent electrostatic control, their interfaces with gate dielectrics and contact metals often form a van der Waals (vdW) gap that affects device performance and acts as a tunneling barrier with a low dielectric constant. While this reduces dielectric leakage, it increases metal-channel contact resistance and introduces a parasitic series capacitance to the gate. We quantified the trade-off between leakage suppression and electrostatic and contact-resistance scaling limits. As a result of this trade-off, many insulators fail to meet scaling targets, and metal-channel contacts fall short of required resistances. Zipper-like interfaces, where quasi-covalent bonding removes the vdW gap without creating dangling bonds, offer a path toward ultrascaled transistor designs.

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

Mucosal vaccination in mice provides protection from diverse respiratory threats

Haibo Zhang, Katharine Floyd, Zhuoqing Fang, Filipe Araujo Hoffmann, Audrey Lee, Heather Marie Froggatt, Gurpreet Bharj, Xia Xie, Haleigh B. Eppler, Jordan Mariah Santagata, Yanli Wang, Mengyun Hu, Christopher B. Fox, Prabhu S. Arunachalam, Ralph Baric, Mehul S. Suthar, Bali Pulendran

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Traditional vaccines target specific pathogens, limiting their scope against diverse respiratory threats. We describe an intranasal liposomal formulation combining toll-like receptor 4 and 7/8 ligands with a model antigen, ovalbumin, which provided broad, durable protection in mice for at least 3 months against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Staphylococcus aureus . In addition, the vaccine protected mice from other viruses (SARS-CoV-2, SARS, SHC014 coronavirus), bacteria ( Acinetobacter baumannii ), and allergens. Protection was mediated by persistent ovalbumin-specific CD4 + and CD8 + memory T cells that imprinted alveolar macrophages (AMs), enhancing antigen presentation and antiviral immunity. Following infection, vaccinated mice mounted rapid pathogen-specific T cell and antibody responses and formed ectopic lymphoid structures in the lung. These results reveal a class of “universal vaccines” against diverse respiratory threats.

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

Microglia Rank signaling regulates GnRH neuronal function and the hypothalamic-pituitary-gonadal axis

Alejandro Collado-Sole, Nozha Borjini, Jing Zhai, Francisco Ruiz-Pino, Gonzalo Soria-Alcaide, Cintia Folgueira, Celia García-Vilela, Beatriz Romero-de la Rosa, Victor Lopez, Yassine Zouaghi, An Jacobs, Bella Mora-Romero, Alexandra Barranco, Guillermo Yoldi, Karine Rizzoti, Guadalupe Sabio, Gema Perez-Chacon, Patricia G. Santamaria, Jose Antonio Esteban, Nathalie Journiac, Vincent Prevot, Alberto Pascual, Rafael Fernández-Chacón, Manuel Tena-Sempere, Nelly Pitteloud, Eva Gonzalez-Suarez

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The hypothalamic-pituitary-gonadal axis (HPG) controls pubertal development, sexual maturation, and fertility. We identified a role of hypothalamic microglia in controlling the HPG axis through receptor activator of nuclear factor κB (Rank) signaling. Whole-body and microglia Rank (mouse) depletion led to hypogonadotropic hypogonadism (HH) resulting from an alteration in gonadotropin-releasing hormone (GnRH) neuron function. In addition, we identified rare gene variants of RANK (human) in patients with HH. Transcriptional profiling upon Rank loss revealed defective microglia activation and morphological alterations in the median eminence, decreasing the contacts and engulfment of GnRH terminal projections and impairing GnRH neuronal responses to kisspeptin. Overall, our data uncover the microglia as regulator of GnRH neuronal function through Rank signaling, with potential implications for reproductive maturation and fertility.

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

A deep-time landscape of plant cis-regulatory sequence evolution

Kirk R. Amundson, Anat Hendelman, Danielle Ciren, Hailong Yang, Amber E. de Neve, Shai Tal, Adar Sulema, David Jackson, Madelaine E. Bartlett, Zachary B. Lippman, Idan Efroni

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Developmental gene function is often conserved over deep time, but cis-regulatory sequence conservation is difficult to identify. Rapid sequence turnover, paleopolyploidy, structural variation, and limited phylogenomic sampling have impeded conserved noncoding sequence (CNS) discovery. Using Conservatory, an algorithm that leverages microsynteny and iterative alignments to map CNS-gene associations over evolution, we uncovered ~2.3 million CNSs, including more than 3000 predating angiosperms, from 284 plant species spanning 300 million years of diversification. Ancient CNSs were enriched near developmental regulators, and mutating CNSs near HOMEOBOX genes produced strong phenotypes. Tracing CNS evolution uncovered key principles: CNS spacing varies, but order is conserved; genomic rearrangements form new CNS-gene associations; and ancient CNSs are preferentially retained among paralogs but are often lost as cohorts or evolve into lineage-specific CNSs.

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

Divergent and programmable skeletal remodeling of complex macrocycles with a small method set

Ali Nikbakht, Xinghan Li, Jing Wan, Can Qin, Amir H. Hoveyda

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The bioactivity of complex organic macrocycles can vary unpredictably with their three-dimensional structural contours. Here, we present a streamlined, programmable, and systematic strategy for skeletal remodeling of large organic rings. The central diversification platform (hub) is a readily available macrocyclic olefin or a diene. Six transformations, all but one catalytic, are needed: macrocyclic ring-opening/cross-metathesis for cleaving a ring to generate a diene, cross-metathesis and allylic substitution for one-unit chain homologation, alkene isomerization and ethenolysis for one-unit chain clipping, and macrocyclic ring-closing metathesis for reforming a ring. The methods are practical, mild, efficient, and amenable to iteration. Fourteen analogs of anticancer agent epothilone C (the primary model macrocycle) were accessed through a divergent network of reactions that correspond to an average of three steps per analog from the diene hub.

Science abstract < 200 char.: Not a research article

Virologist accused of starting COVID-19 fights funding ban

Jon Cohen

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United States seeks to debar Ralph Baric for misleading NIAID on old coronavirus studies, which he disputes

Science abstract < 200 char.: Not a research article

Scientists play catch-up to startling Ebola outbreak

Kai Kupferschmidt

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Testing, sequencing, and clinical trial efforts spring to life as Bundibugyo virus spreads

Science abstract < 200 char.: Not a research article

Tracking human mobility for wildlife conservation

Lydia Beaudrot

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Human mobility data expand ecological analyses of people’s impact on wild animals

Science abstract < 200 char.: Not a research article

Artificial intimacies Artificially Yours Valerie Tiberius Princeton University Press, 2026. 224 pp.

Jessica M. Szczuka

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A philosopher probes the promise of AI friendships

Science abstract < 200 char.: Not a research article

A student takes on Stanford (and the world) How to Rule the World Theo Baker Penguin, 2026. 336 pp.

Valerie Thompson

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Theo Baker spills Silicon Valley secrets and revisits his efforts to expose a shocking breach of research integrity

Science abstract < 200 char.: Not a research article

Chile’s environmental policy at risk

América Paz Durán, Ariel Espinoza-Galdames, Víctor Caro, Daniela Manuschevich

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Science abstract < 200 char.: Not a research article

In Science Journals

Jesse Smith, Corinne Simonti, Keith T. Smith, Jake S. Yeston, Bianca Lopez, Jelena Stajic, Leoma Bere, Michelle L. Oyen, Stella M. Hurtley, Mattia Maroso, Peter Stern, Angela Hessler, Phil Szuromi, Sarah H. Ross, Unnati Sonawala, Madeleine Seale, John Foley, Shang-Ping Xie, Dorothy Hallberg

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Highlights from the Science family of journals

Science abstract < 200 char.: Not a research article

Can enhanced alkalinity store carbon durably?

Terry Isson, A. Joshua West

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Key questions remain about carbon removal strategies in open environmental systems

Science abstract < 200 char.: Not a research article

Generative AI use and misuse call for assessment reform in higher education

Igor Chirikov, Ivan Smirnov, René F. Kizilcec

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Growing misuse of, and unequal access to, AI tools requires universities to rethink how they evaluate learning

Science abstract < 200 char.: Not a research article

Brothers in arms

Richard Stone

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Key human defenses against pathogens were forged billions of years ago in microbial battles with viruses

Science abstract < 200 char.: Not a research article

Making eyes ‘photosynthetic’ could treat major vision problem

Mitch Leslie

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Relocating plants’ light-capturing structures to the eye may fight damage from dry eye

Science abstract < 200 char.: Not a research article

How making art freed my science

Shelley H. Liu

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Science abstract < 200 char.: Not a research article

Chile’s regulatory rollback harms biosphere

Juan G. Navedo, Hugo A. Benítez, Cristina Dorador, Luis Vargas-Chacoff

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Science abstract < 200 char.: Not a research article

In Other Journals

Sacha Vignieri, Yevgeniya Nusinovich, Jesse Smith, L. Bryan Ray, Keith T. Smith, Bianca Lopez, Yury Suleymanov

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Editors’ selections from the current scientific literature

Science abstract < 200 char.: Not a research article

“Sacrifice subjects” and a proposal for people-first technology regulation

Shobita Parthasarathy

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Science abstract < 200 char.: Not a research article

CDC plan to retire lab monkeys draws ire

David Grimm

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Critics say proposal was rushed and could endanger animals slated to be moved to a Texas sanctuary

Science abstract < 200 char.: Not a research article

Taking plant membrane temperatures

Seth J. Davis, James Ronald

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Plasma membrane nanoclusters help plants distinguish growth-promoting warmth from damaging heat

Science abstract < 200 char.: Not a research article

Fisheries sector as a mitigation wedge

William W. L. Cheung, U. Rashid Sumaila, Daniel Pauly

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Science abstract < 200 char.: Not a research article

An appetite for protein

Stephen J. Simpson, David Raubenheimer

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The fly gut integrates nutrient-specific appetite control

Science abstract < 200 char.: Not a research article

Designer molecules could power quantum computers

Zack Savitsky

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Organic qubits controlled with light could rival atoms, ions, and crystal defects

Science Advances

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

Multiregional profiling reveals THBS1 - SPP1 monocyte-macrophage axis drives immunosuppression and outcome in colorectal liver metastases

Gaia Bellomo, Jayden Gittens, Christopher Brunning, Maidinaimu Abudula, Robert P. Jones, Michael C. Schmid, Ainhoa Mielgo

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Colorectal cancer (CRC) commonly metastasizes to the liver (CRLM), where it is the leading cause of CRC-related deaths. While immune checkpoint therapies show promise, their effectiveness is limited in CRLM due to the immunosuppressive liver tumor microenvironment (TME). Using multiregional tissue sampling from CRLM patient samples, we identified distinct immune zones within CRLM. Active Granzyme + CD8 + T cells were found in normal liver tissue, while CD8 + T cells in the tumor core were dysfunctional. At the tumor margin, we observed a pre-exhausted immune zone enriched in THBS1 + monocytes and CD47 + CD8 + T cells. Trajectory analysis showed that THBS1 + monocytes differentiate into SPP1 + macrophages, which accumulate in the tumor core and promote immune suppression via TIM-3 and CTLA-4 on exhausted CD8 + T cells. The presence of SPP1 + macrophages correlates with increased T cell exhaustion and poor survival, suggesting them as potential targets to restore antitumor immunity in CRLM.

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

A plant immune receptor mediates tritrophic interactions by linking caterpillar detection to predator recruitment

Natalia Guayazán Palacios, Patrick Grof-Tisza, Brian Behnken, Carla Marques Arce, Di Wu, Antonio F. Chaparro, Benjamin D. Sheppard, Eric A. Schmelz, Ted C. J. Turlings, Betty Benrey, Adam D. Steinbrenner

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Plants deploy direct and indirect defenses in response to insect herbivory. The specific antiherbivore responses involve cell surface immune receptors that recognize herbivore-associated molecular patterns (HAMPs), yet the ecological relevance of this molecular interplay in natural settings remains unexplored. Here, we demonstrate with laboratory and field experimentation in Mexico that the inceptin receptor (INR) in the leaves of common bean orchestrates a tritrophic interaction upon recognition of inceptin, a HAMP in caterpillar oral secretions. Near-isogenic lines with a naturally occurring null mutation in INR revealed that inceptin recognition does not only amplify the wound response but activates an herbivore-specific immune pathway to trigger the emission of a distinctive volatile blend that recruits predatory wasps to effectively remove caterpillars from the plants. These findings provide a definitive molecular-to-ecological link, revealing how a single immune receptor mediates ecologically relevant plant-insect-predator interactions in nature.

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

Distinct properties of plastic-derived submicrometer particles from smoldering burning

Lin Kong, Hongru Shen, Xing Wang, Michael A. R. Tawadrous, Emily R. Halpern, Qiaorong Xie, Alexander Laskin, Kin Fai Ho, Bonnie M. Hamilton, Alex K. Y. Lee, Man Nin Chan, Arthur W. H. Chan

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Widespread plastic use and mismanaged disposal release substantial amounts of particles into the atmosphere during waste burning. We define these thermally generated particles as plastic-derived submicrometer particles (PDSPs), a poorly characterized class of contaminants. We provide direct evidence that PDSPs are distinct from conventional micro- and nanoplastic particles that are formed mainly by mechanical processes. We show that PDSPs contain mixtures of altered polymeric substances and oxygenated compounds produced by extensive thermal decomposition and chemical transformations during smoldering. Volatility distributions suggest that PDSPs exist in semisolid phase states with lower viscosities than their original polymers. Upon exposure to hydroxyl radicals, the principal oxidant in the atmosphere, PDSPs exhibit higher reactivity than the original polymer particles, forming highly oxidized aerosol species at reaction rates comparable to typical atmospheric organic aerosols. These findings demonstrate that plastic smoldering introduces a previously unrecognized class of atmospherically active particles, with implications for their contribution to global plastic budgets, persistence in the atmosphere, and potential effects on human health and climate-relevant processes.

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

53BP1 orchestrates sequence feature of RAG targets to balance DNA repair outcomes during V(D)J recombination

Sha Luo, Hailiang Zha, Zifan Yang, Shuchan Li, Leyi Yu, Ruolin Qiao, Ruoxi Kong, Yifan Wang, Junhong Guan, Xuefei Zhang

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RAG endonuclease initiates V(D)J recombination by cleaving recombination signal sequences (RSSs), subsequently repaired by classical nonhomologous end-joining (c-NHEJ). However, 53BP1, as a key DNA damage response (DDR) factor promoting c-NHEJ, is dispensable for V(D)J recombination. Here, we report that 53BP1 orchestrates sequence strength of RAG targets to shape end-joining features during V(D)J recombination. Loss of 53BP1, rather than other DDR factors, specifically increases junctional microhomology (MH) of cryptic RSS (cRSS) recombination instead of RSS recombination. This phenotype is partially recapitulated by RIF1 or Shieldin depletion, implicating the 53BP1-mediated end-joining axis. Notably, loss of RNF168, rather than other classical resection and alternative end-joining factors, fully reverts 53BP1 deficiency–mediated increase of junctional MH during cRSS recombination. RAG mutant and RSS score analyses indicate that the sequence strength of RAG targets dictates the unique roles of 53BP1 in balancing end-joining outcomes. Our findings provide deeper mechanistic insights into DNA damage repair at RAG-cleaved on- and off-targets during V(D)J recombination.

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

Spin glass in quantum paraelectric KTaO 3 : Supercritical CO 2 -induced monoclinic phase

Yuning Liang, Qun Xu

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Inducing magnetism in d 0 nonmagnetic oxides is a central challenge in condensed matter physics and a bottleneck for developing advanced spintronic devices. KTaO 3 epitomizes this challenge: Despite having strong spin-orbit coupling, its functionality is hindered by a stable nonmagnetic cubic phase. Here, we report the unlocking of magnetism in KTaO 3 via supercritical carbon dioxide (SC CO 2 ), which induces a stable monoclinic phase that has, until now, remained undiscovered. Experimentally, we demonstrate that this monoclinic phase has spontaneous magnetic moments, driving the system into a spin-glass state. Monte Carlo simulations pinpoint the origin of this glassy behavior to interfacial phase frustration, arising from the coupling between ferromagnetic facets and an antiferromagnetic bulk. To our knowledge, this work not only presents the first observation of a magnetic phase in KTaO 3 but also reveals a peculiar phenomenon of SC CO 2 –induced interfacial phase frustration, establishing a versatile strategy for engineering complex magnetic states in quantum paraelectric.

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

Unlocking translational control of specialized metabolism in plants through 5′UTR structure

Makou Lin, Doosan Shin, Jie Hao, Masood Jan, Minkyu Park, Veronica Perez, Benjamin Breuer, Ying Wang, Jeongim Kim

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Plant-specialized metabolites are essential for plant fitness and human health, with their biosynthesis pathways tightly regulated at multiple levels. However, the translational regulation of their biosynthesis remains poorly understood. Here, we reveal a 5′ untranslated region (5′UTR)–mediated translational mechanism that controls glucosinolate production in Arabidopsis . A forward genetic screen exploring the metabolic interaction between auxin and glucosinolates identified two dominant Arabidopsis alleles, each carrying a single-nucleotide substitution located 13–base pair apart within the 5′UTR of MYB28 , a master regulator of aliphatic glucosinolate biosynthesis. These mutations markedly increase MYB28 protein abundance without affecting transcript levels, leading to enhanced glucosinolate production. Mutational profiling of the 5′UTR revealed that alterations in RNA tertiary structure influence translation efficiency, establishing a link between RNA conformation and metabolic output. Our findings uncover a previously uncharacterized layer of posttranscriptional regulation in plant-specialized metabolism and highlight the 5′UTR as a potential target for precision breeding to enhance crop performance and nutritional quality.

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

A strengthened and southward-shifted westerly jet mitigates warming-induced drying across Asian drylands

Jie Jiang, Tianjun Zhou

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The Eurasian Subtropical Westerly Jet (ESWJ), a key component of the Eurasia circulation system, has weakened in summer since 1979 due to uneven aerosol emissions. Its future evolution under human activities, including clean air policies, remains uncertain yet critical for climate adaptation in mid-latitude Asian drylands. Using multiscenario projections, we show that the ESWJ is projected to reverse its historical weakening trend and turn to strengthen during 2025–2100. This intensification arises from both increasing greenhouse gas (GHG) concentrations and declining anthropogenic aerosols. Aerosol reduction primarily triggers the transition from weakening to strengthening, already emerging around 2010, while GHG forcing additionally induces a southward displacement. These circulation changes enhance dynamic moisture advection into Central Asia, partially offsetting the “dry-get-drier” paradigm and resulting in limited changes in regional water availability. While recent studies have emphasized the warming effects of aerosol reduction, our findings highlight the critical role of circulation dynamics in shaping regional hydroclimatic security.

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

High-fidelity molecular decoding through tile-guided in situ self-assembly

Xiaolin Hu, Xinlin Guo, Jie Xie, Liangting Wang, Zhengheng Yu, Heng Li, Xiaopei Qiu, Sergio Bernardini, Wei Gu, Yang Luo, Hong Zhang

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High-fidelity profiling of intracellular biomarkers is crucial for deciphering tumorigenesis and progression, as well as classifying cell types. Conventional techniques suffer from high background interference and poor stability due to the scattered, point-like signals. Herein, we present a DNA tile–driven in vivo logical encoding self-assembly (TILES) strategy for robust and signal-amplified imaging of multiple biomarkers in cancer cells and tumor-bearing mice. Capitalizing on AND-gated logic operations, the TILES assay enables confined recognition of dual biomarkers to initiate the intracellular self-assembly of DNA scaffolds, yielding nanotube-like signals. Owing to the compact nucleic acid framework, DNA scaffolds exhibit an over sevenfold nuclease resistance enhancement than double-stranded DNA probes. Moreover, the structural output, characterized by high-density fluorophore architecture and defined morphology, substantially boosts the visualization and precise classification of diverse cancer types. The proposed strategy provides a robust platform to enable the high-fidelity, multiplexed profiling of intracellular biomarkers and dynamic gene regulatory networks analysis in living organisms.

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

Critical point–based wireless sensors enabling tiny perturbation detection

Chao Ma, Ke Yin, Zhuoyu Zhang, Ruyi Huang, Yuangen Huang, Lanyue Gan, Yuxuan Liu, Fan Xia, Tian Xia, Yufan Chen, Wangchang Li, Lian-Mao Peng, Tianyu Dong, Youfan Hu

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High quality factor and sensitivity are critical to wireless sensors targeting small perturbation detection. Although introducing parity-time symmetric dynamics promises enhanced performance, the symmetric scheme often yields limited sensing behaviors. In particular, its implementation is hindered by the inherent difficulties in decoupling capacitance- and coupling strength–induced responses, the requirements of delicately matching and/or tuning both gain and loss, and the need of strong coupling strength. Here, we report a concept of critical point (CP)–based wireless sensors that do not rely on balanced gain-loss configurations, delivering ultrahigh quality factor with an extended interrogation distance. Owing to a sharp and deep reflection dip, the CP-based scheme can resolve the change in coupling coefficient down to 1.92 × 10 −4 and features frequency-independent responses. Furthermore, the CP-based scheme allows for identification of tiny asymmetric capacitive perturbations as small as 2.5 × 10 −5 without requiring active tuning of the other parameters under weak coupling.

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

Lotus japonicus VIH2 is an inositol pyrophosphate synthase that regulates arbuscular mycorrhiza

Kiran Raj, Verena Gaugler, Mengsi Lu, Maren Schädel, Philipp Gaugler, Charlotte M. M. Grothaus, Ulrike A. Jochimsen, Athanasios Makris, Simon M. Bartsch, Anna M. Frentzen, Guizhen Liu, Michael Harings, Dorothea Fiedler, Henning J. Jessen, Gabriel Schaaf, Martina K. Ried-Lasi

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Plant yield is often maximized by the extensive use of mineral fertilizers, which, however, has severe environmental consequences. Phosphate is particularly problematic as it represents a globally limited resource, and its runoff and soil erosion threaten open water bodies. Many crops engage in arbuscular mycorrhizal (AM) symbiosis with nutrient-acquiring fungi, aiding in the uptake of phosphate and other mineral nutrients. However, AM colonization is strongly reduced under high soil phosphate levels. A mechanistic understanding of phosphate sensing, phosphate starvation responses, and their connection to AM remains incomplete. Here, we show that, in Lotus japonicus , low-abundant, energy-rich inositol pyrophosphates act as important regulatory signals of AM, orchestrating the cross-talk between phosphate starvation responses, nutrient acquisition, and plant root endosymbiosis. These findings hold promise for breeding nutrient-efficient crops.

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

On-demand linkage cleavage in two-dimensional conjugated metal-organic frameworks for closed-loop recyclable electronics

Quanquan Guo, Shaohong Shi, Ningfeng You, Chenchen Wang, Leilei Zheng, Wei Wang, Changjiang Yi, Liping Shu, Hao Xu, Jianjun Zhang, Leif Riemenschneider, Shirong Huang, Mingchao Wang, Fangchao Cheng, Xiaodong Li, Gianaurelio Cuniberti, Yiqiang Wu, Claudia Felser, Minghao Yu, Xinliang Feng

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The rapid growth of modern electronics has intensified concerns about electronic waste management at the end of a product’s life. Integrating closed-loop recyclability, where electronic materials can be efficiently recovered, reprocessed, and reused in regenerated products, is essential for achieving sustainable development, minimizing environmental impact, and realizing long-term economic benefits. However, achieving closed-loop recycling remains particularly challenging for complex electronic materials. Here, we demonstrate the closed-loop recycling of emerging multifunctional two-dimensional conjugated metal-organic frameworks (2D c -MOFs) through a mechanochemistry-induced on-demand degradation strategy. Exemplified with 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP)–based 2D c -MOFs, we show that ultrasonic cavitation facilitates selective cleavage of metal-ligand linkages in alkaline solutions enabling rapid material degradation (up to 92.4% within 30 min). The HHTP monomers are subsequently recovered with high purity and yield (96.3%), and reused to regenerate 2D c -MOFs, establishing a complete circular material life cycle. Our cradle-to-cradle life-cycle assessment reveals that, compared with direct synthesis, this closed-loop recycling approach substantially reduces both total energy consumption (52 versus 358 MJ kg −1 ) and greenhouse gas (CO 2 ) emission (4.8 versus 27.4 kg CO 2 -equiv), thereby substantially lowering the overall environmental impact relative to conventional electronic materials. Moreover, we demonstrate the practical utility of these recyclable 2D c -MOFs in several applications, including hydrogen gas sensors, supercapacitor electrodes, and degradable printed electronic devices. These results highlight the potential of 2D c -MOFs to advance circular electronics, laying the groundwork for a sustainable transformation within the electronics industry.

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

Bandgap-enabled ultrasound tissue marking by a biodegradable metastructured hydrogel implant

Zhangqi Pan, Lejie Qin, Bo Gao, Na Li, Yizhou Huang, Yuchen Zhou, Mengyuan Zhou, Yibo Huang, Jie Chen, Wei Wang, Yue Lian, Zeqing Cai, Hanchuan Tang, Jianfeng Zang

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Implantation of tissue markers within lesions is standard practice in breast cancer diagnosis and treatment, which provides critical guidance for regular follow-up and precise surgical localization. However, the identification of existing markers is limited by nonspecificity and low resolution of conventional ultrasound imaging. The use of rigid materials to compensate for this constraint has resulted in inadequate biodegradability and biocompatibility. Here, we propose a biodegradable metastructured hydrogel tissue marker with acoustic bandgaps enabling specific ultrasonic reflection spectra. Through frequency-to-color mapping on B-mode images, visualization is achieved, with scalable designs allowing multiple marker distinction. Deliverable via an 18-gauge puncture needle and featuring tissue-mimicking softness, the metagel marker mitigates displacement risks, tissue damage, and inflammation. Live pig experiments demonstrate clear identification and dynamic stability. Six-week rat studies confirm long-term marking ability and biocompatibility. These results support the metagel marker’s clinical potential for breast cancer management and precise therapy.

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

Multicellular senescence impairs skeletal muscle recovery following disuse in aging

Paul-Emile Bourrant, Elena M. Yee, Zachary J. Fennel, Robert J. Castro, Chad M. Skiles, Jonathan J. Petrocelli, Naomi M. M. P. de Hart, Lisa A. Lesniewski, Anna E. Beaudin, Katsuhiko Funai, Christopher S. Fry, Micah J. Drummond

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Aged skeletal muscle has a diminished capacity to recover after disuse. Although muscle regrowth requires coordinated interactions between immune and progenitor cells, the mechanisms of impaired remodeling in aged skeletal muscle remain poorly understood yet possibly involve the accumulation of senescent cells. We used a flow cytometry approach coupled with scRNAseq to determine the muscle senescent cell identity and transcriptional landscape during skeletal muscle recovery following disuse atrophy. Young and aged mice underwent 14 days of hindlimb unloading followed by reloading (7 or 14 days). At recovery, old mice showed smaller myofibers and abnormal muscle macrophage dynamics corresponding to greater collagen content. These outcomes coincided with elevated markers of muscle senescence (p21 and γH2AX) and increased SPiDER-β-Gal + cells, which inversely correlated with muscle mass. Single-cell resolution of SPiDER + cells unmasked several senescent interstitial muscle vascular and stromal populations. Senescent interstitial cell populations were enriched in aged muscle and displayed a senescence-associated secretory phenotype (SASP) across multiple stromal, vascular, and immune cell types. Senolytic treatment reduced overall senescent cell burden, attenuated macrophage accumulation, and restored muscle mass and function in aged mice following disuse. These findings identify a multicellular senescence environment within the muscle interstitial niche as a hallmark of impaired muscle recovery following disuse.

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

Active protein-capturing hydrogel for broad-spectrum pathogen defense

Jiaming Liu, Shiqi Hu, Mengrui Liu, Savannah Weihang Zhang, Na Yan, Xuan Mei, Dashuai Zhu, Ming Shen, Ke Cheng

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Proteinaceous agents, including viral particles and allergenic proteins, play central roles in infection, inflammation, and immune dysregulation, yet few materials can broadly neutralize them through direct protein capture. Here, we present an inhalable protein trap (IPT), an active hydrogel that rapidly immobilizes diverse amine-containing biomolecules via NHS-amine chemistry. Structural optimization enables IPT to stably incorporate a high density of reactive NHS esters that remain functional under physiological conditions, allowing efficient protein capture at mucosal surfaces. Upon hydration, powdery IPT rapidly forms an active barrier that covalently traps proteins and proteinaceous particles within minutes. This nonselective capture mechanism allows IPT to bind viral particles, allergens released from pollen or fungi, and soluble immune mediators such as histamine. Across multiple animal models, including allergic rhinitis, pollen-induced allergy, and viral infection, IPT consistently outperformed commercial barrier sprays in blocking pathogenic proteins and mitigating disease progression. These results establish IPT as a versatile platform for broad-spectrum protection at biological interfaces.

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

Armadillo-inspired active morphing skeletons for soft machines

Jianyu Zhou, Weixin Zhou, Seol-Yee (Jennifer) Lee, Shuang Wu, Ali Akbari, Yong Zhu

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Armadillos can rapidly reconfigure their body into a rigid, enclosed sphere in active response to external threats, combining adaptive shape change with robust mechanical protection, which is rarely achieved in engineered systems. This rapid reconfiguration is achieved through real-time sensing and muscle activation, while the synergistic coordination of the exoskeleton and endoskeleton provides structural stiffness and impact resistance. Inspired by this natural strategy, we present an active morphing skeleton called morpho-interlocking protective module (MIPM). The architecture integrates curvature-conforming segmented exoskeleton with a spine-inspired interlocking endoskeleton framework, forming a coordinated load-bearing skeleton. A muscle-like liquid crystal elastomer composite layer drives structural transformation, while an embedded sensing layer detects external threats and autonomously triggers localized Joule heating for actuation of the liquid crystal elastomer layer. This enables multimodal morphing behaviors such as curling, rolling, and grasping, without compromising the structural integrity. The MIPM withstands impact, puncture, and concentrated loading while carrying and protecting fragile payloads in harsh conditions. An integrated Bluetooth module facilitates wireless, untethered operation, broadening its applicability to hazardous or inaccessible environments. By combining adaptive morphology, real-time sensory feedback, and on-demand mechanical stiffening within a unified internal-external skeletal framework, this work presents a previously unidentified paradigm for concurrent morphing and protection, with broad applicability across adaptive systems ranging from soft robotics to next-generation flexible electronics.

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

Tumor-targeted bispecific antibodies effectively inhibit oncogenic pathways while minimizing toxicity

Yvonne T. Kschonsak, Wei-Ching Liang, Joyce Chan, David Kan, Thao Nguyen, Karen Ruiz, Yee-Seir Kee, Wen-Ting K. Tsai, Hongkang Xi, Marina Moskalenko, Travis Morgenstern, Aurelie Herault, Lauriane Cabon, Ryo Okuda, Scott S. Stawicki, Jocelyn Chan, Matthew Grimmer, Diego Ellerman, James Mondo, Catherine F. Ruff, Gabriele Schaefer, Udi Segal, Robert Piskol, Nicholas J. Agard, Laetitia Comps-Agrar, Felipe de Sousa e Melo, James T. Koerber

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Enhancing the specificity of oncogenic pathway inhibition in cancer cells improves both efficacy and tolerability of anticancer therapies. Hyperactivated Wnt signaling is a key driver in cancers such as colorectal cancer and pancreatic ductal adenocarcinoma, but its direct inhibition is limited by severe toxicities due to the importance of Wnt signaling in normal tissues, particularly the gut and bone. To address this challenge, we designed bispecific antibodies that selectively target surface proteins of oncogenic signaling pathways in tumor cells while sparing normal cells. Using single-cell technologies, we identified tumor-specific receptors, including tumor-associated calcium signal transducer 2 (TROP2), which are absent in cells reliant on Wnt signaling. Our TROP2-targeted anti-Frizzled bispecific antibody effectively inhibited Wnt signaling in preclinical models with minimal effect on normal intestinal tissue. Expanding this approach, we developed tumor-targeted, toxicity-sparing bispecific antibodies against fibroblast growth factor receptor 1 (FGFR1) and epidermal growth factor receptor (EGFR). This work establishes a framework for designing targeted therapeutics that minimize cell type–specific toxicities in cancer and other diseases.

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

Molecular interfaces drive vertical crystallization in Dion-Jacobson perovskite solar cells

Rui Wang, Xiyue Dong, Yuting Ma, Liu Yang, Jiangnan Li, Yuping Gao, Yu Chen, Yu Zou, Wenjuan Feng, Ziyang Hu, Yongsheng Chen, Yongsheng Liu

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Two-dimensional perovskites are promising candidates for photovoltaics due to their intrinsic structural stability, but their efficiency is often limited by poor charge transport, in part due to unfavorable crystal orientation. Here, we report a molecular interface engineering strategy using dual-anchoring organic acids, croconic acid (CA) and squaric acid (SA), to direct vertical crystallization in Dion-Jacobson (DJ) perovskite films. These molecules form robust interlayers between the NiO x hole transport layer and TTDMA (thieno[3,2- b ]thiophene-2,5-diyldimethanaminium)–based DJ perovskites (nominal n = 4), with SA exhibiting ordered vertical orientation via bidentate coordination. This templated interface promotes vertical orientation, reduces interfacial defects and lattice strain, and suppresses Ni 3+ -induced oxidation of I − . As a result, devices incorporating SA achieve a champion power conversion efficiency of 22.03% (certified 21.42%) along with outstanding operational stability. This study demonstrates a general molecular interface strategy to direct vertical crystallization and improve the performance of layered perovskite solar cells.

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

Endothelial soluble APP/APLP2 promote heart repair through KIT-mediated angiogenesis

Haruya Kawase, Shangmin Liu, Sabrina Kurz, Verena Bengelsdorff, Remy Bonnavion, Young-June Jin, Kenneth Anthony Roquid, Haaglim Cho, Guozheng Liang, Marija Banićević, Niharika Shiva, Paula Sofía Yunes-Leites, Stefan Günther, Lukas Tombor, Stefanie Dimmeler, Mario Looso, Kenny Mattonet, Nina Wettschureck, Ulrike C. Müller, Stefan Offermanns

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Amyloid precursor protein (APP) gives rise to amyloid-β, a pathological factor in Alzheimer’s disease. However, the physiological role of APP and its homolog amyloid precursor–like protein 2 (APLP2), which are also widely expressed outside the nervous system, is largely unknown. Here, we show that endothelial APP and APLP2 are required for postischemia angiogenesis after myocardial infarction (MI). We found that hypoxia induced the endothelial expression of α-secretases, resulting in nonamyloidogenic processing of APP and APLP2 into the soluble forms APPsα and APLP2sα. Loss of endothelial APP and APLP2 led to decreased neovascularization as well as increased heart failure and mortality after MI, a phenotype that could be rescued by endothelial expression of APPsα. APPsα and APLP2sα exerted their proangiogenic effect by positive allosteric modulation of the endothelial receptor tyrosine kinase KIT, which promotes postischemia neovascularization. Our data identify a function of APP and APLP2 in endothelial cells, which is required for postischemia tissue repair, and suggest approaches to improve regeneration after MI and other ischemic diseases.

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

Magnetogravitationally regulated streamer accretion onto a class 0 protostellar system

Bo Huang, Josep M. Girart, Ian W. Stephens, Tom Megeath, Valentin J. M. Le Gouellec, Nadia M. Murillo, Paulo Cortés, Manuel Fernández-López, Zhi-Yun Li, Leslie W. Looney, J. A. López-Vázquez, Jaime E. Pineda, Álvaro Sánchez-Monge, Patricio Sanhueza, Sarah Sadavoy, Qizhou Zhang, Charles L. H. Hull, Nicole Karnath, Enwei Liang, Philip C. Myers

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How do magnetic fields shape the way young stars gather gas from their birth clouds? Using high-resolution Atacama Large Millimeter/submillimeter Array observations of a young triple protostellar system HOPS-182, we identify an elongated stream of gas, or accretion streamer, that extends over several thousand astronomical units (1 astronomical unit is the Earth-Sun distance) and carries a substantial flow of material toward the system. The gas speeds along this filament increase toward the star in a way consistent with gravitational free fall, while the streamer’s shape closely follows the magnetic field threading the region. By comparing the strengths of gravity and magnetic tension and measuring how the gas rotates compared with the local magnetic field, we show that the field is strong enough to help confine and guide the infalling gas and efficiently remove the angular momentum. These results suggest that a substantial fraction of the material falling onto young protostellar systems can be funneled through elongated, magnetically structured accretion streamers.

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

Noncanonical PI(4,5)P 2 coordinates lysosome positioning through cholesterol trafficking

Ryan M. Loughran, Gurpreet K. Arora, Jiachen Sun, Alicia Llorente, Sophia Crabtree, Cynthia Y. Zhang, Kyanh Ly, Ren-Li Huynh, Wonhwa Cho, Brooke M. Emerling

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In p53-deficient cancers, targeting cholesterol metabolism has emerged as a promising therapeutic approach, given that p53 loss dysregulates sterol regulatory element-binding protein 2 pathways, thereby enhancing cholesterol biosynthesis. While cholesterol synthesis inhibitors such as statins have shown initial success, their efficacy is often compromised by the development of acquired resistance. Consequently, strategies are being explored to disrupt cholesterol homeostasis more comprehensively by inhibiting its synthesis and intracellular transport. In this study, we investigate a previously underexplored function of PI5P4Ks, which catalyzes the conversion of PI(5)P to PI(4,5)P 2 at intracellular membranes. Our findings reveal that PI5P4Ks play a key role in facilitating lysosomal cholesterol transport, regulating lysosome positioning, and sustaining growth signaling via the mechanistic target of rapamycin (mTOR) pathway. While PI5P4Ks have previously been implicated in mTOR signaling and tumor proliferation in p53-deficient contexts, this work elucidates an upstream mechanism that unifies these earlier observations.

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

A rubbery semiconducting heterojunction film for fully rubbery multiplexed near-infrared phototransistor arrays

Yu-Dong Zhao, Na Li, Junmei Hu, Wei-Chen Gao, Ben Fan, Xiang Sun, Defeng Cui, Jing Qiao, Ying-Shi Guan

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High-sensitivity photodetecting semiconductors with intrinsic stretchability and excellent charge carrier collection efficiency are imperative for the advancement of rubbery phototransistors. However, the scalable manufacturing of such materials into high-performance, multiplexed rubbery near-infrared phototransistor arrays remains challenging. Herein, we report a highly doped, rubbery semiconducting nanofilm with a unique nanoweb structure, fabricated by precisely controlling the composition of a ternary blend, comprising a semiconducting polymer (DPP-TT), a molecular dopant (F4TCNQ), and an elastic matrix (polyurethane). This unique architecture provides both high charge carrier mobility and exceptional mechanical stretchability. The developed rubbery phototransistors and their multiplexed arrays maintain electrical functionality even under 50% strain. Notably, the multiplexed phototransistor array maintains high imaging fidelity, capable of reproducing well-defined patterns even in deformed states. Furthermore, we demonstrate the application of this imaging system as a two-dimensional stretchable barcode, leveraging its multichannel, illumination-dependent responses. This work provides a viable pathway for the scalable production of high-performance rubbery optoelectronics.

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

A miniaturized implantable electrochemical platform for continuous monitoring of metabolites in deep tissue

Kenneth E. Madsen, Dane Hintermueller, Elliot A. Opel, Joseph G. Ribaudo, Sara Saffari, Soongwon Cho, Joanna L. Ciatti, Yu-Ting Huang, Amanda M. Westman, Ralph G. Nuzzo, Mitchell A. Pet, John A. Rogers

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The loss or suppression of local metabolic function in living tissues brought about by a lack of oxygen availability (ischemia) serves as the origin for myriad life-threatening conditions including stroke, heart failure, and peripheral ischemic injury. Despite the pressing clinical need to evaluate local tissue health, platforms that support such analysis remain elusive. To address this need, we present a wireless, minimally invasive, multianalyte, electrochemical probe supporting the continuous profiling of local metabolites including K + and pH, and the semicontinuous profiling of lactic acid. We validate the analytical capabilities of our sensing system by ion profiling in arterial whole blood. Furthermore, we use acute compartment syndrome as a model for tissue ischemia and use our percutaneously implanted probes to track metabolic changes in living muscle in real time.

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

MR-AIV reveals in vivo brain-wide fluid flow with physics-informed AI

Juan Diego Toscano, Yisen Guo, Zhibo Wang, Mohammad Vaezi, Yuki Mori, George Em Karniadakis, Kimberly A. S. Boster, Douglas H. Kelley

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The circulation of cerebrospinal and interstitial fluid plays a vital role in clearing metabolic waste from the brain, and its disruption has been linked to neurological disorders. However, directly measuring brain-wide fluid transport, especially in the deep brain, has remained elusive. Here, we introduce magnetic resonance artificial intelligence velocimetry (MR-AIV), a framework featuring a specialized physics-informed architecture and optimization method that reconstructs three-dimensional fluid velocity fields from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MR-AIV unveils brain-wide velocity maps while providing estimates of tissue permeability and pressure fields, quantities inaccessible to other methods. Applied to the brain, MR-AIV reveals a functional landscape of interstitial and perivascular flow, quantitatively distinguishing slow diffusion-driven transport [∼0.1 micrometers per second (μm/s)] from rapid advective flow (∼3 μm/s). This approach enables new investigations into brain clearance mechanisms and fluid dynamics in health and disease, with broad potential applications to other porous medium systems, from geophysics to tissue mechanics.

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

Scalable and cost-efficient custom gene library assembly from oligopools

Chase R. Freschlin, Kevin K. Yang, Philip A. Romero

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Advances in metagenomics, deep learning, and generative protein design have enabled broad in silico exploration of sequence space, but experimental characterization is still constrained by the cost and scalability of DNA synthesis. Here, we present OMEGA (Oligo-based Multiplexed Efficient Gene Assembly), a low-cost, accessible method for assembling hundreds to thousands of full-length genes in parallel using standard laboratory techniques. OMEGA computationally fragments target genes into short, high-fidelity Golden Gate–compatible oligonucleotides that can be ordered as a pooled library and assembled across multiplexed subpools. We systematically optimized the number of fragments per gene and orthogonal ligation sites per reaction and determine that OMEGA can assemble up to 2.6-kilobase constructs using as many as 70 Golden Gate sites. To validate the approach, we assembled and functionally screened a library of 810 natural and synthetic green fluorescent protein variants, recovering 94 to 97% of target sequences with high uniformity. OMEGA enables precision library construction at scale, with per-gene costs as low as $1.50, and offers a broadly applicable solution for bridging computational protein design with high-throughput experimental validation. We have developed OMEGA as an open-source software package and an easy-to-use Colab notebook to facilitate community adaptation.

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

Mechanisms of ligand recognition and channel opening for P2X2 receptors in lipid nanodiscs

Surbhi Dhingra, Maia Moog, Kenton J. Swartz

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Extracellular adenosine 5′-triphosphate (ATP) activates P2X receptor channels (P2XRs) that serve important roles in the immune and nervous systems. Available structures of P2XRs in detergents reveal that ATP binding to the extracellular domain leads to severing of subunit interfaces within transmembrane regions as the pore opens. Here we report cryo–electron microscopy structures of the human P2X2R in lipid nanodiscs in an apo closed state, with ATP 4− , Mg-ATP 2− , and suramin bound. We find that a unique Arg residue interacts with the γ-PO 4 of ATP 4− in P2X2R and underlies the requirement of this subtype for ATP 4− . Channel opening and desensitization occur when ATP 4− binds, whereas the channel remains closed when Mg-ATP 2− binds. A continuous belt of partially resolved lipids in the outer leaflet stabilizes the closed state, and the presence of lipids prevents the severing of subunit interfaces as the channel opens. These findings establish key mechanistic principles of gating for P2X2R in a membrane-like environment, providing a framework for future mechanistic studies and therapeutic development.

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

3D imaging of an entire pancreas shows inverse proportions of extra-islet versus islet-associated β cells in late-onset type 1 diabetes

Joakim Lehrstrand, Max Hahn, Björn Morén, Wayne I. L. Davies, Olle Korsgren, Tomas Alanentalo, Ulf Ahlgren

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Residual β cell function can positively affect diabetes regulation in type 1 diabetes (T1D), but details on residual β cell mass distribution in T1D is largely lacking in a whole organ context. Implementing an optical 3D imaging pipeline, we generated a complete account of the remaining β cells throughout an entire human late onset T1D pancreas at a microscopic resolution. Our data show that most of the residual β cells were present as scattered individual cells or as punctated clusters of individual β cells, spatially separated from each other and all other endocrine cell types. Compared to islet-associated β cells, extra-islet β cells appeared in a substantially higher relative abundance in the head region of the T1D pancreas. This 3D depiction of an entire T1D pancreas shows that individual β cells may be preserved and/or formed in a highly regionalized manner, potentially reflecting key aspects of disease dynamics, advocating for increased focus on extra-islet islet β cells in attempts to develop strategies for pancreatic β cell preservation in T1D.

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

Stepwise construction of the path to doubled haploid breeding in sorghum

Yi Sui, Yao Sun, Zixiang Cheng, Yali Li, Ke Li, Xiaohui Zhang, Tao Yin, Suhua Yang, Guiying Li, Minxuan Liu, Sanyuan Tang, Chuanyin Wu

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Doubled haploid (DH) breeding greatly accelerates crop improvement, but efficient in vivo haploid induction has remained limited primarily to maize because readily available haploid inducers are lacking in other species. Here, we establish a complete DH breeding pipeline for sorghum by overcoming this key limitation. Using genome editing, we developed maternal haploid inducers that achieved haploid induction rates up to 16.04% in the P898012 background, with an average of 12.18% across 92 diverse crosses (15,156 seeds; various genetic backgrounds and environments). A dual-marker system combining fluorescence and pigmentation enabled reliable haploid identification. By optimizing a scalable emasculation protocol and using sorghum’s naturally high rate of chromosome doubling, we established an efficient in planta DH production process. This framework provides a practical, transferable approach to implementing DH technology in sorghum and other crops.

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

State-specific inhibition of NMDA receptors by memantine provides insight into NMDAR channel blocker tolerability

Matthew B. Phillips, Nadya V. Povysheva, Elizabeth G. Neureiter, Aparna Nigam, Karen A. Harnett-Scott, Johannes W. Hell, Elias Aizenman, Jon W. Johnson

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N -methyl- d -aspartate (NMDA) receptors (NMDARs) are key mediators of calcium ion (Ca 2+ ) influx required for proper neuronal function. Excessive NMDAR-mediated Ca 2+ influx is neurotoxic and associated with neurological disease. Memantine and ketamine, two NMDAR antagonists with overlapping binding sites in the NMDAR channel, are of high clinical interest. Whereas memantine is a well-tolerated Alzheimer’s disease medication, ketamine is a fast-acting antidepressant with abuse potential and psychotomimetic effects. The mechanisms underlying the disparate tolerability of memantine and ketamine remain elusive. We show here that inhibition of recombinant and native NMDARs by memantine, but not ketamine, increases with increasing intracellular Ca 2+ concentration ([Ca 2+ ] i ). [Ca 2+ ] i -dependent inhibition results from stabilization of a desensitized receptor state and depends on NMDAR subtype. Neuroprotection assays and postsynaptic current recordings show that memantine, but not ketamine, preferentially inhibits NMDARs under neurotoxic conditions. Our results reveal a form of state-specific antagonism that allows for the selective targeting of NMDAR subpopulations involved in disease.

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

The posteroventral part of the medial amygdala nucleus glutamatergic neurons encodes conspecifics’ individual identity in rodents

Lu Zheng, Libiao Pan, Xiaoyu Fu, Siyu Wang (王思羽), Yue Wu, Hanyang Xiao, Jiachao Yang, Siyu Wang (王思雨), Li Yang, Xiaotong Wu, Fada Pan, Hongbin Yang, Gao Chen, Hao Wang

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The medial amygdala (MeA) processes social olfactory cues, but its precise neural mechanisms remain unclear. We identified the posteroventral MeA (MeApv) as critical for individual conspecific odor discrimination in mice. Exposure to conspecifics or their odors markedly elevates calcium signals and c-Fos expression in MeApv VGluT2-positive neurons. Optogenetic silencing of these neurons or activating Gad2-positive neurons disrupts odor-driven social behaviors, including identity recognition, odor discrimination, and sex discrimination. Social information is directly relayed from the accessory olfactory bulb (AOB) to the MeApv, and acute AOB-MeApv pathway disruption impairs social discrimination. A distinct MeApv VGluT2-positive neuron population encodes individual-specific cues, as revealed by microendoscopic calcium imaging at a single-cell resolution. Selective silencing of these neurons induces deficits in odor-guided social interactions with related conspecifics, confirming the MeApv as a central hub for social information encoding. These findings establish the MeApv’s dual necessity and sufficiency in translating olfactory signals into social behavioral responses.

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

Hurricane air-sea drag saturation and sea-state dependence revealed by surface drones

Gregory R. Foltz, Dongxiao Zhang, Lev B. Looney, Andrew M. Chiodi, Jun A. Zhang, Chidong Zhang, Edoardo Mazza, Nan-Hsun Chi, Edward D. Cokelet

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The ocean supplies energy for tropical cyclones (TCs) and slows their winds through surface friction, which exerts a force on the ocean termed wind stress. The drag coefficient ( C d ) is the key parameter that converts wind speed to wind stress and is currently estimated in forecast models from incomplete data collected in low-to-moderate ocean winds. Here, we use measurements from 11 Atlantic hurricanes to quantify C d in winds up to 44 meters per second and surface waves up to 14 meters. It is found that C d levels off, as wind speed surpasses 30 meters per second but does not decrease appreciably as suggested by previous indirect methods. Interaction of the wind and wave fields causes C d to be 20 ± 2% higher on the motion-left side of a storm, where wind and waves are misaligned, than on the right. These results quantify directly a fundamental TC air-sea interaction parameter and demonstrate the importance of distinct TC quadrant-specific wind-wave interactions.

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

Single-nucleotide variant profiling in liquid biopsy with RECO-Cas

Chong Guo, Shuo Zhang, Ramachandra Yerramsetti, Jiongyu Zhang, Xin Guan, Rui Yang, Chengyu Hou, Minjie Pei, Kurt T. Schalper, Xingye Liu, Ziyue Li, Lorrie Perpetua, Wenqi Gan, Omar Ibrahim, Rachael A. Clark, Changchun Liu

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Mutation detection of cell-free DNA (cfDNA) through liquid biopsy is essential for precision oncology, resistance profiling, and informed clinical decision-making. However, its clinical application has remained limited by the lack of simple, rapid, accurate, and cost-effective detection approaches. Here, we report a recombined DNA construct–activated Cas12a (RECO-Cas) assay for profiling cfDNA mutations. The RECO-Cas assay uses a recombined DNA construct generated from Argonaute-nicked mutant DNA and an artificial DNA activator to selectively trigger CRISPR-Cas12a, enabling 0.01% variant allele frequency sensitivity and single-nucleotide resolution. Using the assay, we detect KRAS , EGFR , and PIK3CA point mutations in cfDNA from clinical plasma samples, demonstrating high sensitivity (90.48%) and excellent specificity (100%). We also apply it to successfully classify and identify KRAS missense variants. RECO-Cas provides a simple, rapid, and affordable solution that is compatible with a compact, wirelessly powered point-of-care diagnostic platform incorporating smartphone-based fluorescence detection. This assay enables highly sensitive and specific detection of low-frequency mutations, facilitating early cancer diagnosis and supporting the development of personalized treatment strategies.

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

Room-temperature spinor condensate in halide perovskite microcavity

Takaya Inukai, Ryohei Shibano, Taiki Ogura, Tohki Inoue, Daichi Okada, Shun Takahashi, Kenichi Yamashita

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A deeper understanding of room temperature polariton condensed phases is essential for advancing quantum applications. Spin degrees of freedom inherent in polariton particles manifest themselves in the form of spinor condensation, which has been demonstrated only at cryogenic temperatures in the past. Herein, we demonstrate room-temperature spinor polariton condensation in a lead-halide perovskite microcavity under nonresonant optical excitation. The crystalline anisotropy of the perovskite induces a linear polarization splitting of the lower polariton modes, and, above the condensation threshold, nonlinear polariton-polariton interactions drive the formation of elliptically polarized condensates. The condensation dynamics are analyzed using a spin-dependent Gross-Pitaevskii model, which provides a qualitative framework for understanding the experimentally observed polarization evolution and two-stage threshold behavior. Our findings pave the way for all-optical control of polariton spin states at room temperature, opening a path toward scalable polaritonic quantum devices.

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

Developmental candidate GHP-88310/EIDD-3608 with high tolerability and oral efficacy in measles and respiratory paramyxovirus models

Carolin M. Lieber, Josef D. Wolf, Mugunthan Govindarajan, Jeong-Joong Yoon, Zachary M. Sticher, Claire E. Ruckel, Alexander I. Leach, Lauren A. Harrison, Dariia Vyshenska, Amalia A. Cruz, Meghan K. Andrews, Rebecca E. Krueger, Robert M. Cox, George R. Painter, Alexander L. Greninger, Michael G. Natchus, Richard K. Plemper

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Orthoparamyxoviruses, such as human parainfluenza virus type 3 (HPIV3) and measles virus (MeV), are a major health threat. We discovered an orally efficacious broad-spectrum inhibitor of orthoparamyxovirus polymerases. However, here, we found that tolerability in higher mammals was limited. We report the development of the clinical candidate analog GHP-88310 (EIDD-3608), which combines improved oral efficacy with favorable tolerability in nonrodents (ferrets and dogs). GHP-88310 was active against HPIV3, Sendai virus (SeV), MeV, and related canine distemper virus (CDV). In 7-day tolerability studies, daily doses of 2000 mg/kg were well tolerated. Pharmacokinetic analysis revealed altered plasma exposure of GHP-88310 compared to the original hit. In HPIV3-infected cotton rats, GHP-88310 lowered the respiratory tract viral load. Dosing of ferrets infected with CDV, causing lethal measles-like disease, resulted in complete survival, reduction of viremia and shed viral load, and alleviated lymphocytopenia. Once-daily GHP-88310 was efficacious in the CDV-ferret and HPIV3-cotton rat models. The compound was sterilizing against HPIV3 at physiological concentrations in human airway epithelium organoids.

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

Deciphering competing elementary steps to correlate electrocatalyst chemical state with activity

Yuanfu Ren, Xingzhu Chen, Shouwei Zuo, Qingxiao Wang, Cafer T. Yavuz, Di-Jia Liu, Deyan Luan, Kuo-Wei Huang, William A. Goddard, Huabin Zhang

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The overpotential in multielectron transfer heterogeneous electrocatalysis fundamentally arises from thermodynamic and kinetic disparities among elementary steps; however, deciphering coupled and competing steps has long remained a challenge. Here, we establish an electrochemical deconvolution paradigm based on key processes in electrocatalytic reactions, such as charge accumulation, electron/proton transfer, and intermediate evolution, to resolve competing elementary steps. Taking the oxygen evolution reaction as a prototypical reaction, we design a model catalyst featuring a precise isolated cation-anion vacancy pair and track the previously elusive electrochemical behavior of lattice oxygen by disentangling interference from adsorbed oxygen intermediates. Mechanistically, the lattice oxygen oxidation pathway originates from the spontaneous, nonelectrochemical deprotonation of replenished water molecules coordinated to unsaturated cation sites. Alternating current techniques further reveal that although lattice oxygen oxidation requires a higher potential than metal oxidation, it exhibits faster kinetics, providing insight into its superior catalytic activity. These findings establish a direct experimental correlation between the initial chemical state and the catalytic activity and prove surface-confined lattice oxygen cycling. Furthermore, expanding conventional potential-current analysis into a multidimensional framework enables disentanglement of thermodynamic and kinetic contributions of key elementary steps, thereby guiding the rational optimization of various complex multielectron transfer reactions.

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

TPM1 drives cytoskeleton-immunometabolism coupling and LGALS9/CD45-mediated neuroinflammatory propagation in retinitis pigmentosa

Rong Li, Jun-Qi Fan, Bin Lin

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Retinitis pigmentosa (RP), the most prevalent inherited retinal degeneration, features progressive photoreceptor loss with no approved disease-modifying therapies. While microglia-driven neuroinflammation accelerates RP progression, its sustaining mechanisms remain elusive. Through integrated multiomics profiling of retinal degeneration 10 (rd10) mice, we identify tropomyosin 1 (TPM1) as a previously unrecognized cytoskeletal-immune regulator orchestrating spatial neuroinflammation in RP. Genetic ablation of Tpm1 attenuated microglial reactivity and preserved vision, whereas overexpression triggered self-reinforcing inflammation via four interlocked axes: (i) TPM1-mediated activator protein-1 (AP-1) hyperactivation initiates senescence-associated secretory phenotype (SASP) through mitogen-activated protein kinase (MAPK) kinase/extracellular signal–regulated kinase 3–dependent MAPK signaling; (ii) SASP subsequently mediates reduced phagocytosis; (iii) Tpm1-Apoe/Fabp5 axis disruption precipitates lipid droplet accumulation with cholesterol crystallization; (iv) galectin-9 (LGALS9)/CD45-mediated intermicroglial signaling propagates inflammatory signals across the retina. Our work redefines TPM1 as a linchpin in self-sustaining neurodegeneration cycles, where cytoskeletal dysfunction fuels immunometabolic collapse. These findings unveil precision therapeutic strategies targeting TPM1 hubs—notably the LGALS9/CD45 axis—to disrupt inflammatory cycles while preserving retinal homeostasis.

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

Structurally engineered ultrasoft PEDOT:PSS fiber microelectrodes with enhanced electrochemical performance for neural interfaces

Chihyeong Won, Young Uk Cho, Siyeon Kweon, Sungjoon Cho, Chaebeen Kwon, Hyun Woo Kim, Ju Young Lee, Sang Hoon Park, Sorim Han, Yang Tae Kim, Jumyoung Jang, Janghwan Jekal, Jae Geun Kim, Kyung-In Jang, Sheng Xu, Wei Gao, Il-Joo Cho, Ki Jun Yu, Taeyoon Lee

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Stable and reliable neural interfacing is essential for the diagnosis and treatment of chronic neurological disorders. Flexible neural probes are particularly important for this purpose, as they minimize tissue damage and inflammatory responses while maintaining stable electrode-tissue coupling; however, achieving both high electrical performance and tissue-like mechanics remains challenging. Here, we present a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) fiber microelectrode (PFME), an all-organic neural probe capable of recording single-neuron activities with potential for long-term interfacing. The PFME is entirely composed of organic components and fabricated without thermal processing. In addition, the posttreatment process enables to selectively remove PSS binder networks while promoting PEDOT chain alignment to optimize mechanical compliance and electrochemical performance. In vivo, the PFME enables stable single-unit recordings from the mouse hippocampus. Histological analysis after 1 week of implantation reveals minimal glial activation comparable to that elicited by a conventional probe. This structurally engineered PFME establishes a pathway to achieve minimally invasive neural interfacing platforms for chronic applications.

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

Evolution of a central dopamine circuit underlies adaptation of a light-evoked sensorimotor response in the blind cavefish

Robert A. Kozol, Ally Canavan, Bernadeth Tolentino, Alex C. Keene, Johanna E. Kowalko, Erik R. Duboué

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Adaptive behaviors emerge in novel environments through functional changes in neural circuits. While relationships between circuit function and behavior are well studied, how evolution shapes circuits to drive behavioral adaptation is poorly understood. The Mexican cavefish, Astyanax mexicanus , provides a unique genetically tractable model, with above ground eyed surface fish and multiple blind cavefish populations that have evolved in darkness. These differences in environment and vision offer a way to examine how neural circuits evolve. We examine differences in detection and behavioral responses to the nonvisual effects of light in cave and surface A. mexicanus . Both populations exhibit photokinesis: Surface fish become hyperactive after darkness, and cavefish after illumination. Using whole-brain functional imaging aligned to an established Astyanax brain atlas, we identify the caudal posterior tuberculum as key to light- and dark-induced photokinesis. Pan-neuronal GCaMP imaging shows that dark-sensitive neurons in surface fish are light-sensitive in cavefish. Light sensing depends on dopamine signaling, suggesting that a conserved dopamine circuit mediates photokinesis and highlighting Astyanax as a model for sensory adaptation.

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

Coral growth, retraction, defense, and regenerative strategies revealed by live microCT

Karina Araslanova, Marketa Kaiser, Anton Fetisov, Diana Gavrik, Tomas Zikmund, Daniel Abed-Navandi, Karel Katovský, Jozef Kaiser, Igor Adameyko

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Understanding how corals build and remodel their skeletons is key to explaining reef resilience, yet most insights come from static imaging. Using longitudinal live microCT, we tracked the same coral colonies over weeks to months at micrometer resolution. Coral skeleton formation is not a uniform accretion process but a dynamic integration of multiple programs, including vertical and horizontal patterned growth, previously undescribed defensive wall-building against competitors, exploratory edge behavior with reversible expansions and retractions, and skeletal regeneration favoring rapid, imprecise yet effective matrix expansion. Time-resolved imaging links colony-scale growth to microscale events, showing that all modes depend on balances between fusion of skeletal microparticles and layered matrix deposition, guided by tissue prepatterning. Beyond corals, this framework generalizes to studying skeletal dynamics across diverse biomineralizing organisms.

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

Membrane-separated electrodes enable high-rate low-energy electrochemical carbon capture

Kaige Sun, Mike Tebyetekerwa, Hongxia Zhang, Timothy T. Duignan, Rizal Evans, Lei Ge, Yi Sun, Yuhui Ge, Zhuyuan Wang, Chao Xing, Jindi Yang, Xiangkang Zeng, Darren Martin, Xiwang Zhang

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Electrochemical carbon dioxide (CO 2 ) capture using supercapacitive systems is a promising green technology but remains limited by low uptake rates and high energy requirement. Here, we present a membrane-integrated supercapacitor system that addresses these challenges by decoupling electrode environments with a cation exchange membrane. This configuration sustains high hydroxide concentration at the gas-facing negative electrode, generated through dynamic water dissociation within the electric double layer. The resulting localized alkaline interface enhances CO 2 capture by driving its conversion into (bi)carbonate species via a pH-swing mechanism. The system achieves a CO 2 uptake of up to 893 mmol/kg with a fast rate of 1281 mmol/kg/hour at −1.4 V under 20% CO 2 . Energy consumption as low as 32 kJ/mol is obtained at −0.8 V under 20% CO 2 together with a long lifetime over 200 hours at −1.0 V, 10% CO 2 . These findings establish a robust platform for electrochemical CO 2 capture and underscore the importance of localized chemical environments in supercapacitive swing adsorption.

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

Structural properties, polymorphism, and multiscale disorder unravel energy transport limitations in perylene diimide semiconductors

Christopher J. H. Smalley, Colan E. Hughes, Tom Willhammar, Raj Pandya, Semion K. Saikin, Duncan N. Johnstone, Jeffrey Gorman, Jooyoung Sung, Gianni Jacucci, Paul A. Midgley, Demie M. Kepaptsoglou, Quentin M. Ramasse, Akshay Rao, Kenneth D. M. Harris, Sean M. Collins

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Organic semiconductors continue to make substantial performance gains from photovoltaics to electronics. However, understanding how differences in solid-state structure give rise to large differences in energy transport properties remains unresolved. We report that microcrystals of two perylene diimide (PDI) derivatives differing only in their terminal groups [cyclohexyl (CH) and 4-heptyl (ST)] have exciton diffusion coefficients differing by more than two orders of magnitude. Applying state-of-the-art techniques for microcrystal structure determination, we report the crystal structures of CH-PDI and two polymorphs of ST-PDI. Scanning electron diffraction reveals a range of crystallographic defects in ST-PDI microcrystals, attributed to polymorph intergrowths, while electron energy loss spectroscopy links these defects to nanoscale electronic structure changes. Computational modeling demonstrates that rotational disorder explains the difference in exciton diffusion coefficients. Our observations establish the importance of defect-induced orientational disorder as a source of extrinsic energetic disorder, highlighting the need for defect management in organic semiconductor technologies.

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

An integrated wireless deep-UV sensing system for intelligent early fire detection

Taehyun Park, Junhwa Oh, Junhyung Cho, Seungme Kang, Nicola Gasparini, Wooseok Song, Jaehyun Hur, Garam Bae, Seyong Oh, Hocheon Yoo

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Uncontrolled fires, from wildlands to industrial facilities, have become a pressing global threat, causing widespread ecological damage, loss of life, and economic disruption. The fundamental challenge is the lack of rapid and reliable detection at the ignition stage. Once flames spread, suppression becomes increasingly difficult and damage escalates. Conventional methods such as smoke detectors and thermal imaging fall short for wildfire and large-scale fire scenarios. Effective systems require accurate detection without false activation, stable performance under varied and harsh environments, and low power or zero-bias photodetection for continuous use in remote locations. Here, we report a wireless and flexible deep-ultraviolet (DUV) sensing platform that addresses these requirements in a single integrated unit. The platform combines a zinc tin oxide nanocomposite photodetector, flexible circuit integration, portable power, and Bluetooth communication. The sensor shows a selective solar-blind DUV response, stable operation under mechanical stress and extended cycling (92.5% retention after 100 bending cycles and 96.7% after 180 days), and energy-efficient performance compatible with autonomous deployment. Data-driven analysis of response curves allows for machine learning models that classify flame types and estimate distance, extending the system beyond binary fire detection by providing additional information on flame type and relative distance. This integrated approach provides a practical route to reliable fire monitoring, relevant to early-stage fire monitoring concepts for wildfire and industrial safety applications.

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

Shifting IRES versus Cap-initiated translation during homeostatic stem cell differentiation and stress

Michael C. Mazzola, Ting Zhao, Anna Kiem, Trine A. Kristiansen, Karin Gustafsson, Lai Ping Wong, Emily Scott-Solomon, Marissa D. Fahlberg, Christina Mayerhofer, Ernst Mayerhofer, Sarah Forward, Emane Rose Assita, Giulia Schiroli, Maris Handley, Youmna Kfoury, Tsuyoshi Fukushima, Dan Li, Samuel Keyes, Azeem Sharda, Jelena Milosevic, Hiroki Kato, Pavel Ivanov, David B. Sykes, Sheldon J. J. Kwok, Ruslan I. Sadreyev, Vijay G. Sankaran, Ya-Chieh Hsu, David T. Scadden

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Cell stress can increase the use of methylated guanosine (m 7 G) cap–independent, internal ribosome entry site (IRES)–mediated translation initiation relative to cap-dependent translation (IRES/Cap). Reporters that quantify IRES/Cap have demonstrated differential activity across cultured cell types and stress conditions. By generating an IRES/Cap reporter mouse, we were able to systematically evaluate IRES/Cap across distinct tissues and cell types during physiological stresses and lineage commitment. Caloric stress invoked the expected boost in IRES/Cap translation regardless of differentiation state, but unexpectedly, IRES/Cap progressively increased during hematopoietic and epithelial (hair follicle) differentiation under normal, homeostatic conditions. This was independent of total protein output or cell cycle. Even within cells of a given differentiation state, cells with lower relative IRES utilization had markedly higher multipotent capability in vivo. The RNA processing protein PTBP1 is a mediator of this translation initiation preference. Therefore, low IRES/Cap is a signature of high stemness and suggests that modulation of translation initiation participates in cell differentiation state.

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

Warming and vegetation greening drive recent surge in flash droughts

Jun Li, Yao Zhang, Emanuele Bevacqua, Shijie Jiang, Xing Yuan, Sha Zhou, Jinghao Qiu, ZhaoLi Wang, Jakob Zscheischler, Kaicun Wang, Shilong Piao

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Flash droughts have become more frequent, yet their underlying mechanisms of such changes remain unclear. Using an explainable artificial intelligence–based clustering framework with reanalysis products and Earth system models, we show that the major driving mechanisms of global flash droughts have shifted from precipitation dominance to a compound effect of temperature, transpiration, and precipitation. This transition drives a surge in flash droughts over the past decade, with more rapidly developing, severe, and enduring soil droughts. Anthropogenic warming and vegetation greening are the main drivers of the observed surge. The transition, which has emerged beyond natural climate variability since 2017 and is mainly detected in Eurasia, Amazon, and Africa, exposes ~650 million people under threat and reduces gross primary productivity by 0.15 ± 0.1 petagrams of carbon per year. Our results demonstrate that biosphere and atmosphere responses to anthropogenic forcing have altered flash drought drivers, emphasizing the urgent need for targeted mitigation strategies.

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

Complex versus simple N -nitrosamines: Comprehensive genotoxicity and in silico carcinogenicity assessment toward future testing paradigms

Xiaowen Sun, Maik Schuler, Shaofei Zhang, Jakub Kostal, Jennifer R. Cheung, Michelle Kenyon, Eric Watt, Krista Dobo

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The detection of N -nitrosamines in pharmaceuticals has been a focus for industry and regulatory authorities since 2018. This has prompted extensive research into their mutagenic potential and mitigation strategies. We present a comprehensive evaluation of 25 structurally diverse N -nitrosamines using in vitro (Ames test), in vivo (liver comet, Big Blue transgenic mutation, and duplex sequencing), and in silico methods [quantum mechanical modeling and cytochrome P450 (CYP)–binding analysis]. Results show strong concordance across assays and reveal that complex active pharmaceutical ingredient (API)–derived or process-related impurity (PRI)–derived N -nitrosamines are often not mutagenic or have low mutagenic potency. Quantitative in vivo data enabled the derivation of compound-specific acceptable intakes (AIs), frequently exceeding regulatory limits based on an assessment of structural features. Duplex sequencing demonstrated superior sensitivity over traditional assays, and quantum mechanical models proved effective for potency prediction. A weight-of-evidence decision tree to derive AIs that integrates experimental and computational data is proposed, which reduces animal testing and supports drug product remediation efforts that are commensurate with risk.

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

Evolution of Southern Hemisphere Westerly asymmetry since the Early Miocene

Congcong Gai, Torben Struve, Andrew P. Roberts, Yiwen Li, Chenguang Zhu, Yanhong Chen, Jilin Wei, Wei Liu, Weijie Zhang, Hailong Liu, Huaichun Wu, Qingsong Liu

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The Southern Hemisphere Westerlies (SHW) are a crucial component of Earth’s climate system because they regulate moisture, temperature, and ocean circulation throughout the Southern Hemisphere. They also affect the Northern Hemisphere through atmospheric and oceanic teleconnections. Yet, their variations are poorly constrained for past warm climate intervals that could serve as analogs for possible future climate evolution. Here we present geochemical and magnetic data from South Pacific Ocean sediments to reconstruct dust provenance since the Early Miocene. We find that the eolian dust source shifted from Central South America to Australia at ~8.4 million years ago. Our climate simulations also suggest that a strong middle Miocene subtropical jet facilitated dust transport from Central South America to the South Pacific Ocean. If the middle Miocene is used as a possible analog for future warming, we suggest that the SHW tends to be more zonally asymmetric in warm climate states and that SHW asymmetry may be important for future climate projections.

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

Multiple photon field–induced topological states in bulk HgTe

Dongbin Shin, I-Te Lu, Benshu Fan, Emil Viñas Boström, Hang Liu, Mark Kamper Svendsen, Simone Latini, Peizhe Tang, Angel Rubio

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Strong light-matter interactions can be exploited to modify properties of quantum materials both in and out of thermal equilibrium. Recent studies suggest that electromagnetic fields in photonic structures can hybridize with condensed matter systems, resulting in photon field–dressed collective quantum. Here, we show that photon fields in photonic structures, including optical cavities and waveguides, induce emergent topological phases in solids through polarization-mediated symmetry-breaking mechanisms. Using state-of-the-art quantum electrodynamic density functional theory calculations, we demonstrate that strong light-matter coupling can reconfigure both the electronic and ionic structures of HgTe, driving the system into Weyl, nodal-line, or topological insulator phases. These phases depend on the relative orientation of the sample in the coupling strength. In contrast with laser-driven phenomena, the photon field–induced symmetry breaking arises from steady-state photon-matter hybridization, enabling multiple robust topological states to emerge. Our study demonstrates that vacuum fluctuations in photonic structures can be used to engineer material properties and realize rich topological phenomena in quantum materials on demand.

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

Poling-free integrated second-order nonlinear optics with evaporated organic thin films

Pierre-Luc Thériault, Arnaud Petit, Abhay Anand V.S., Stéphane Kéna-Cohen

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Integrated second-order [χ (2) ] photonics underpins next-generation classical and quantum technologies, enabling applications ranging from frequency conversion and high-speed modulation to entangled photon generation. However, the field is now limited by a lack of materials that combine high nonlinear performance with scalable, CMOS-compatible fabrication. Vapor-deposited organic thin films having large χ (2) nonlinearities without electric field poling offer a versatile solution, theoretically enabling both standalone organic circuits and heterogeneous integration on passive platforms. Yet, the translation of these films into functional photonic devices has remained speculative. Here, we demonstrate phase-matched second-harmonic generation in strip-loaded waveguides by harnessing the film’s giant birefringence (Δ n ≈ −0.2) to match fundamental modes (TE 00 → TM 00 ), thereby maintaining high modal overlap. The resulting efficiency of η L = 29 % W − 1 cm − 2 rivals that of strip-loaded waveguides on thin-film lithium niobate. These results establish spontaneously oriented organics as a promising material class for the integration of second-order nonlinear functionalities on arbitrary substrates.

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

Revitalizing dendritic lithium with atomic modulator-decorated suspension electrolyte for durable lithium metal batteries

Jian Wang, Bingbing Tang, Jian Wu, Jing Zhang, Zhenjiang Cao, Hao Li, Yidong Miao, Huihua Li, Fanglin Wu, Fangqi Liu, Dong Wang, Yongzheng Zhang, Qingbo Xiao, Hongzhen Lin, Maximilian Fichtner

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Lithium metal anodes suffer from dendrite growth, unstable solid electrolyte interphase, and “dead Li” owing to high barriers and inhomogeneous Li + desolvation/diffusion kinetics. Here, we present the suspension electrolyte endowed with atom-level catalytic inorganic particles of single atomic cobalt on defect-rich ZnO 1− x nanoparticles (SACo@ZO) in a carbonate-based electrolyte, enhancing desolvation/diffusion kinetics and revitalizing dendritic Li. As systematically investigated by in situ electrochemical sum frequency generation (SFG) spectroscopy together with theoretical simulations, the SACo@ZO-assisted suspension electrolyte decreases the potential threshold down to 20 millivolts for driving interfacial desolvation rapidly, providing uniform solvation-free Li + /Li 0 flux and capability in revitalizing dendritic Li. Consequently, we achieve a smooth but dense Li plating behavior under room or low-temperature surroundings, lasting for a long life span of 1600 hours. Meanwhile, the practical Li-LiFePO 4 cell with SACo@ZO reserves the capacity retention of ~100% at 0.5 C and survives for 1000 cycles under 0°C, demonstrating the feasibility of atomically catalytic suspension electrolyte for high-performance dendrite-free Li metal batteries.

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

Limited transmission of cervid prions to nonhuman primates provides insights into the zoonotic potential of chronic wasting disease

Samia Hannaoui, Sandra Pritzkow, Wiebke M. Jürgens-Wemheuer, Dirk Motzkus, Joo-Hee Wälzlein, Karla A. Schwenke, Yo-Ching Cheng, Hanaa Ahmed Hassan, Irina Zemlyankina, Kylee Drever, Michael Beekes, Walter J. Schulz-Schaeffer, Christiane Stahl-Hennig, Sabine Gilch, Claudio Soto, Stefanie Czub, Hermann M. Schätzl

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Chronic wasting disease (CWD) is an expanding prion disease of cervids. CWD prions persist in the environment, are shed in excreta, and accumulate in tissues of infected cervids, raising concerns about its zoonotic potential. Using cynomolgus macaques, we explored the zoonotic potential of CWD. Although most inoculated macaques remained asymptomatic, sensitive in vitro prion amplification assays revealed low levels of prions in macaque tissues. Inoculation of transgenic mice and bank voles with macaque tissues induced prion disease, achieving 100% transmission rates upon serial passage. One interpretation of these findings is that CWD prions retain infectivity across species and that primate infection may manifest atypically while still enabling transmission. Our results challenge earlier conclusions that minimize the zoonotic risk of CWD and underscore the need for continued surveillance.

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

The MsZFP1-MsWRKY40-MsWRKY41 module efficiently regulates LHCII biogenesis via ABA-dependent manner in alfalfa

Wuwu Wen, Li Gao, Liantai Su, Aimin Lv, Nana Fan, Xiangkai You, Yuehua Zhang, Peng Zhou, Zhaoming Wang, Fengling Shi, Yuan An

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The light-harvesting complex (LHC) is the antenna system of photosystem that affects the photosynthetic efficiency of plants. In this study, MsWRKY41 was demonstrated to directly activate the expression of MsAlb3 and MsDVR1 , which involved in LHC protein insertion into thylakoid membrane and chlorophyll biosynthesis, respectively. Knockdown of MsWRKY41 in alfalfa led to yellow-green leaves and abnormal thylakoid structure. MsWRKY41 was the downstream target gene of MsWRKY40, which also directly and positively regulated the expression of four LHC protein genes MsLHCB1/4.3/5/7 . Overexpression of MsWRKY40 increased the accumulation of PSII-LHCII supercomplexes. MsWRKY40 physically interacted with zinc finger protein MsZFP1, which partly inhibited the expression of MsWRKY40-targeted genes. This interaction was weakened by physiologically high levels of ABA, leading to up-regulated expression of MsWRKY40-targeted genes. These results revealed a regulatory module centered on MsWRKY40-MsWRKY41, which integrates the biosynthetic processes of LHCB subunits and chlorophyll into a gene regulatory network, efficiently regulating LHCII biogenesis.

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

Natural tissue immortality: Indefinite survival of sea cucumber explants

Sara Jobson, Emaline M. Montgomery, Jean-François Hamel, Rachel E. Sipler, Annie Mercier

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Senescence and immortality are central biological paradigms. While regenerative capabilities in Deuterostomia are known, the fate of lost and discarded tissues has been presumed terminal. Here, we demonstrate that explanted epidermal, connective, neural, and muscle tissue from the sea cucumber Psolus fabricii (Holothuroidea: Echinodermata) healed and continued to grow in natural, nonaxenic seawater without supplementation for more than 3 years. In experimental trials, these explants, termed Li Pf e (living immortal P. fabricii explants) displayed immune activity, cell cycling, tissue reorganization, and absorption of dissolved amino acids, underscoring their active living state. Comparative experiments conducted on explanted tissues from related species demonstrated no equivalent tissue survival, highlighting the unique properties of P. fabricii , which do not have parallels in the current literature. Our findings challenge conventional perceptions of tissue immortality and present a new class of experimental model, free from ethical concerns, with substantial implications for regenerative biology, biomedical research, and tissue engineering.

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

Extreme-range precipitation probability across global weather systems

Suqin Q. Duan, Wei-Ming Tsai, Fiaz Ahmed, J. David Neelin

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Precipitating weather systems are major contributors to hazardous extreme rain, yet weather and climate models struggle to capture their dynamics and relative impacts. Using high-resolution observations, we examine precipitation probability distributions at hourly timescale linked to major system types across the globe. We show that the high-intensity tails of these distributions share a typical shape, which can be characterized by an intensity scale. Dynamic processes largely govern this universal shape, while thermodynamic factors modulate its magnitude. We find that intensity scales of major contributing systems largely match those of total precipitation due to shared thermodynamic environments, dominance of intense systems, and modest variations in dynamic scales. This universality of various system types’ precipitation probability tail supports risk assessment without overly depending on weather-type identification for most regions. We identify exceptions where intense tropical low-pressure systems or mesoscale convective system co-occurrences disproportionately affect extremes, yielding gray-swan-prone distributions.

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

Sub–10-nm imprint lithography on elastomers by chain translocated crystallization in nanochannels

Yingchao Yang, Yunfei Ru, Shuanhu Qi, Yingzhi Sun, Jin Huang, Zhewei Yan, Tianyi Zhao, Biao Zuo, Lei Jiang, Mingjie Liu

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Elastomers with nanostructured surfaces exhibit substantial importance in enhancing interfacial properties including mechanics and optical diffraction. However, the structure on elastomer surfaces by imprinting is limited to microscale features due to kinetically arrested reptation diffusion and inevitable entropic recovery. Herein, we design a dynamic elastomeric network to achieve nanoimprinting with ultrahigh resolution and aspect ratios by chain translocated crystallization in nanochannels. Specifically, dynamic covalent bonds trigger network reconstruction after thermal activation and enhance chain disentanglement, which promotes chain translocation in nanochannels. Meanwhile, the crystalline phase within nanochannels creates energetic barriers that effectively restrict entropy-driven recovery. This strategy enables imprinting of elastomer surfaces with sub–10-nm structures, across a 10 7 range in length scale and aspect ratios exceeding 100:1, far outperforming conventional elastomers. Moreover, the imprinted nanostructures provide elastomer surfaces with a marked modulus enhancement by ~5 times to reach 4.2 gigapascals while simultaneously improving optical transparency, which endows elastomers with highly integrated multifunctional protective capabilities.

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

Multiplexed single-cell transcriptomics reveals diverse phenotypic outcomes for pathogenic SHP2 variants

Anne E. van Vlimmeren, Ross M. Giglio, Ziyuan Jiang, Minhee Lee, José L. McFaline-Figueroa, Neel H. Shah

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The protein tyrosine phosphatase SHP2, encoded by PTPN11 , is an important regulator of Ras/mitogen-activated protein kinase signaling that acts downstream of receptor tyrosine kinases and other transmembrane receptors. Germline PTPN11 mutations cause developmental disorders such as Noonan syndrome, whereas somatic mutations drive various cancers. While many pathogenic mutations enhance SHP2 catalytic activity, others are inactivating or affect protein interactions, confounding our understanding of SHP2-driven disease. Here, we combine single-cell transcriptional profiling of cells expressing clinically diverse SHP2 variants with protein biochemistry, structural analysis, and cell biology to explain how pathogenic mutations dysregulate signaling. Our analyses reveal that loss of catalytic activity does not phenocopy SHP2 knockout at the gene expression level, that some mechanistically distinct mutations have convergent phenotypic effects, and that different mutations at the same hotspot residue can yield divergent cell states. These findings provide a framework for understanding the connection between SHP2 structural perturbations, cellular outcomes, and human diseases.

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

Channeling teamwork: ATP and lipids cooperate to gate P2X receptors

Frank Bosmans, Toshimitsu Kawate

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P2X receptor structures resolved in a lipid environment reveal how subtype-specific ligand recognition, drug sensitivity, and channel gating are coupled.

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

Combinatorial optimization with Kerr solitons

Yan Jin, Nitesh Chauhan, Jizhao Zang, Brian Edwards, Pratik Chaudhari, Firooz Aflatouni, Scott B. Papp

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The challenge of scaling digital computing motivates innovation, especially through the evolution of physical systems that mimic neural networks and combinatorial optimization problems. Light is a hyperefficient information carrier, and if efficient interactions with it could be uncovered, then direct information processing would become far more feasible. We harness an ensemble of hundreds of Kerr microresonator solitons and implement an analog feedback network to create an Ising machine with fully programmable all-to-all interactions. By increasing the feedback for self, on-diagonal interactions, each soliton exhibits a universal spin-like bifurcation, and using this palette of interactions, we solve the canonical Boolean satisfiability problem (SAT). The combination of uniform soliton interactions and the compatibility of our Ising machine with high-speed data interconnects enables rapid and precise solutions of complex SAT problems. The well-established theoretical properties of Kerr solitons bound the trade-off of optical power and time use by the machine at ~0.15 milliwatts per soliton and 1 microsecond for a single feedback step. We performed >10,000 trials on more than 100 randomly generated SAT instances to evaluate the Ising machine, demonstrating the potential to exceed the performance of benchmark digital SAT solvers. Our work highlights the convergence of optical nonlinearity, ultralow loss photonics, and optoelectronic circuits for computation-acceleration tasks.

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

Phosphorylation remodels the mitotic centrosome matrix to generate bipartite γ-tubulin complex docking sites

Midori Ohta, Orie Arakawa, Yajie Gu, Wanying Tian, Kevin D. Corbett, Arshad Desai, Karen Oegema

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Mitotic centrosomes consist of centrioles surrounded by a proteinaceous matrix that docks and activates γ-tubulin complexes (γTuCs) to nucleate microtubules for spindle assembly. During mitotic entry, phosphorylation at centrosomes remodels CDK5 regulatory subunit associated protein 2 (CDK5RAP2) family matrix proteins to generate γTuC docking sites. We address the mechanism of this conversion using Caenorhabditis elegans SPindle Defective (SPD-5) as a model. We show that SPD-5 contains two regions, phospho-regulated γTuC binding region 1 (PRGB1) and PRGB2, that are each sufficient for polo-like kinase 1 (PLK1) phosphorylation–regulated γTuC binding. We define key phosphosites in each region and uncover autoinhibition mediated by interactions within and between them. PRGB2 is dimeric and requires γTuCs containing the Mozart family microprotein MZT-1 for binding, whereas PRGB1 is monomeric and binds independently of MZT-1. Our results support a model in which PLK1 phosphorylation induces a conformational change that enables MZT-1–dependent PRGB2 engagement, which in turn relieves PRGB1 inhibition. Such a multistep mechanism would ensure robust spindle assembly by restricting microtubule nucleation in space and time.

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

P2X7R of synovial fibroblasts is a potential therapeutic target associated with refractory rheumatoid arthritis

Peishi Rao, Shanzhao Jin, Shibai Xiao, Yinchao Ma, Jing Li, Yuhua Liao, Ziye Wang, Yundi Tang, Xuanlin Cai, Xingyue Zeng, Yixiang Hong, Xiaocheng Wang, Jiaxin He, Shenjie Ma, Junyi Jiang, Wenjuan Zhang, Baozhen Zhang, Ru Li, Liang Zhang, Chuanhui Xu, Qingping Jin, Qingwen Wang, Ming Chu, Xiaolin Sun, Zhanguo Li

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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovitis. Synovial fibroblasts (SF) are the predominant cellular components in the inflamed synovium. Recent studies have shown increased expression of P2X7 receptor (P2X7R) in RA SF. However, its precise expression patterns and its contribution to inflammatory arthritis remain unclear. We demonstrate that P2X7R is robustly expressed in RA synovium, correlating with increased synovitis and systemic inflammation. Single-cell transcriptome analysis indicated that P2X7R was enriched in specific SF associated with refractory RA. Then, we applied a highly selective human P2X7R antagonist, EVT-401, which promoted apoptosis and induced cell cycle arrest in RA SF, reduced the production of proinflammatory and joint-destructive mediators, and mitigated aggressive phenotypes. Furthermore, we demonstrated that EVT-401 markedly reduced synovial inflammation and arthritis severity in a nonhuman primate model of autoimmune arthritis. Together, these findings suggest that P2X7R is involved in synovial inflammation and its inhibition may represent a potential therapeutic strategy for refractory RA.

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

A spin-orbit torque–based key generation system with key concealment and attack detection through irreversible physical changes

Yan Xu, Wei Duan, Hao Wu, Yaoyuan Wang, Tian Qin, Shuai Zhang, Zhe Guo, Meilin Wan, Min Song, Long You

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The confidentiality of key storage devices determines the trustworthiness of cryptographic systems. Existing attack detection methods typically depend on monitoring external variations of devices, which can be circumvented by attackers. This work presents a unified key generation and protection scheme using spin-orbit torque (SOT) devices. By unifying static and dynamic entropy sources within the same devices, the key generation system functions both as physically unclonable functions and as true random number generators. In idle states, devices retain only random numbers and conceal any extractable key. Illegal key access irreversibly destroys stored random numbers, offering a robust attack detection mechanism. A comparator circuit flags illegal key extraction activity, ensuring that the user can promptly detect and revoke compromised keys. This approach merges key generation, concealment, and detection into a single physical platform, providing a hardware-rooted, unforgeable method for key protection.

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

Femtosecond modulation of electron correlations in a Luttinger liquid

Na Li, Umang Mehta, Matin Lebrat, Shunye Gao, Tika Kafle, Richa Sapkota, Henry C. Kapteyn, Oscar Granas, Rahul Nandkishore, Margaret M. Murnane

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Luttinger liquids emerge in one-dimensional metals with strong electron interactions, exhibiting intriguing near-equilibrium properties such as spin-charge separation and power-law correlations. Although these interactions suggest fast, distinctive out-of-equilibrium dynamics, such phenomena remain largely unexplored on ultrashort timescales. Here, we use femtosecond laser excitation to weakly deplete the electron density in the Luttinger band of Li 0.9 Mo 6 O 17 and track the response via time- and angle-resolved photoemission spectroscopy. By fitting the measured electron distributions to a finite-temperature Luttinger liquid model, we observe a fast drop in the Luttinger exponent, quantifying the strength of electron interactions. Subsequently, unlike hot electrons in conventional Fermi liquids that slowly relax within picoseconds via electron-phonon coupling, hot electrons in Li 0.9 Mo 6 O 17 relax within a short time of ~100 femtoseconds, through the excitation of a nonequilibrium collective plasmon. The extremely fast evolution of the Luttinger exponent and electron temperature—including a tens of femtosecond time lag between excitation, recovery, and plasmon-driven modulation—reveals previously unidentified pathways for modulating quantum many-body interactions in low-dimensional materials.

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

On-demand formation of ultrathin liquid metal hydrogel tattoos for conformal and low-impedance bioelectronics

Yichun Ding, Fan Chen, Yizhou Jiang, Yufei Zhang, Xian Song, Jiaheng Liang, Zixuan Zhu, Muzhe Chen, Hong Hu, Chi Zhang, Leni Zhong, Yanhuan Huang, Qingtang Zeng, Xiaoling Hu, Qiyao Huang, Xingyu Jiang, Zijian Zheng

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Ultrathin conductive hydrogels provide conformal and stable contact for flexible bioelectronics, which is critical for achieving the low impedance necessary for high-quality electrophysiological signal acquisition. However, their low modulus has made these hydrogel devices difficult to fabricate and handle. To overcome this, we present an on-demand formation strategy for creating ready-to-use, ultrathin (down to 1 micrometer) hydrogel-based bioelectronics that combine tissue-like softness with ready-to-use functionality. By using cross-linked electrospun polyvinyl alcohol (PVA) fiber mats, we produce liquid metal–patterned hydrogel tattoos (LMHTs). These devices transform from easy-to-handle dry films into adhesive, conformal hydrogel interfaces upon hydration. The resulting LMHTs are ultralight (0.9 milligrams per square centimeter), exhibit ultralow skin contact impedance (1.2 kilohms at 1 kilohertz), and show outstanding biocompatibility. We demonstrate their utility in diverse on-skin and implantable applications, including electrocardiogram recording, multichannel electromyogram mapping, neuromuscular electrical stimulation, and in vivo cardiac monitoring on a beating rat heart. This work offers a scalable and practical approach for generating high-performance, ultrathin hydrogel bioelectronics.

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

PlasmidGPT: A generative framework for plasmid analysis and generation

Bin Shao, Zequan Han, Zeyu Liang, Yi-Xin Huo

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We introduce PlasmidGPT, a generative language model pretrained on 153,208 engineered plasmid sequences from Addgene. PlasmidGPT learns informative sequence embeddings that enable visualization of research topics across laboratories and analysis of plasmid diversity across vector types. Leveraging these embeddings, PlasmidGPT accurately predicts features of engineered plasmids and achieves state-of-the-art performance in lab-of-origin prediction. The learned representations also generalize to natural plasmids, enabling host taxonomy prediction at both the phylum and genus level. Moreover, PlasmidGPT enables controlled generation of functional plasmid sequences by using either a predefined input sequence or specified design constraints, producing outputs that recapitulate the part co-occurrence and synteny of real plasmids.

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

Bioelectric calcium transport and activation in mammalian cells using field-focused DNA-carbon nanotube meshes

Haodong Li, Yuyao Li, Jia Liao, Changming Bao, Xiaodi Cao, Xinping Gao, Wenjian Luo, Tao Ding, Weiming Lin, Xizhi Deng, Hongwu Tang, Mingxing Xie, Sisi Jia, Chunhai Fan, Le Liang

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Electrical signaling in biology is ionic. Safe modulation needs interfaces that couple electrons to ions at soft membranes without injury. We present DNA-FOCUS, a membrane-conformal, DNA-programmed carbon-nanotube biointerface that self-assembles on living cells, weaving DNA-wrapped SWCNTs into an ultraflexible mesh. A subvolt bias is condensed into nanometer hotspots at the membrane, lowering access resistance and engaging endogenous calcium-permeable ion channels. Subvolt stimulation drives sustained Ca 2+ influx across multiple lineages, with voltage-sensitive dye and impedance readouts showing stronger coupling. Responses occur without excess ROS or loss of viability. The focused field also enables gentle electroporation for plasmid delivery, augments mechano-electrical transduction, and modulates neuronal excitability. Transcriptional analysis and functional validation confirm NFAT activation, and in natural killer cells, it boosts perforin and IFN-γ release with higher tumor killing. This programmable, substrate-free interface supports low-voltage electro-modulation for high-throughput analytics and therapeutic augmentation.

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

Understanding the density maximum of water with machine-learned potentials

Yizhi Song, Renxi Liu, Chunyi Zhang, Yifan Li, Biswajit Santra, Mohan Chen, Michael L. Klein, Xifan Wu

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After melting, at ambient pressure, the density of water continues to increase with temperature until it reaches a maximum around 4°C. For nearly a century, this phenomenon has been qualitatively attributed to a mixture of ordered and disordered structures. Here, we use a deep neural network to train a machine-learned (ML) interatomic potential for water using electronic structure data from advanced density functional theory. Notably, molecular dynamics simulations with the ML potential reproduce both the experimental water density anomaly and the thermal expansion coefficient. Detailed structural analysis of the computed hydrogen-bond network reveals that the density anomaly arises from an emergent liquid structure that retains nearly ideal tetrahedral coordination at short range but collapses at intermediate range. Our findings point to a more delicate mechanism causing the density maximum than the conventional picture, emphasizing the collective roles of structural orderings at different length scales.

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

Mesoscale hydrogen-bond network engineering controls quantum-coherent proton transport to suppress aluminum corrosion

Hao Cheng, Zheng Li, Guoxuan Li, Zibo Chen, Jiebin Zheng, Zhengwei Kang, Cong Huang, Wei Zhang, Hui Ying Yang, Zhongliang Tian

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The hydrogen evolution reaction fundamentally constrains the use of aluminum in acidic electrochemical systems. Existing strategies rely on alloying or interfacial passivation and overlook how the electrolyte controls proton transport (PT) to the metal surface. Here, we demonstrate that the Gutmann donor number (DN) provides a quantitative molecular lever to regulate PT through the aqueous medium and suppress hydrogen evolution corrosion of aluminum. High-DN additives reorganize the electrolyte into compartmentalized domains that disrupt long-range PT and force protons onto tortuous, high-barrier pathways. Using water (DN = 18 kilocalories per mole) as a benchmark, additives exceeding this threshold increase the hydrogen evolution overpotential by ~20 to 70 millivolts at 10 milliamperes per square centimeter and reduce the corrosion current density from 7.44 to 2.23 milliamperes per square centimeter, following an approximately inverse linear dependence on DN. These results establish a direct link between a molecular donor descriptor and mesoscale hydrogen-bond networks, revealing a materials-agnostic strategy for corrosion suppression through targeted control of proton dynamics.

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

High-entropy 1D halide perovskite piezoelectrics found by megalibrary synthesis and rapid nonlinear optical screening

Jun Li, Jarod Beights, Tong Cai, Yichen Li, Olivier J. G. L. Chevalier, Yi Xie, Yiming Yang, Chad A. Mirkin

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Piezoelectric molecular crystals offer excellent compositional and structural tunability and sustainable processability. However, their discovery is slow, primarily due to the serial synthesis and screening processes used. Here, we report an approach that combines massively parallel megalibrary synthesis with scanning second harmonic generation (SHG) microscopy for rapid screening of piezoelectric molecular crystals. Megalibraries consisting of more than 1,000,000 compositionally distinct but positionally encoded TMCM x TMA (1–x) Cd y Pb (1–y) Cl z Br (3–z) (TMCM: trimethylchloromethylammonium, TMA: tetramethylammonium; 0 ≤ x ≤ 1, 0 ≤ y ≤ 1, 0 ≤ z ≤ 3) nanocrystals were synthesized. The megalibraries were rapidly screened by SHG microscopy to identify notable noncentrosymmetric structures, which were then tested for piezoelectricity, facilitating discovery of a high-entropy noncentrosymmetric material with a large d 33 (TMCM 0.75 TMA 0.25 Cd 0.75 Pb 0.25 Cl 1.5 Br 1.5, 42.8 picocoulombs per newton). Furthermore, this approach enabled systematic investigation of the Curie temperature ( T C )–composition relationship in the TMCMCdCl z Br (3–z) system, facilitating reverse design of materials with targeted T C . Our work establishes a powerful approach to accelerate the discovery and design of unusual piezoelectrics for next-generation electronics and optics.

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

Perirhinal input to auditory cortex supports memory-guided sensory perception

Luca Godenzini, Ann-Sofie Bjerre, Yi Hu, Lucy M. Palmer

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Through learning and memory, the cortex dynamically forms sensory associations to guide our behavior in an ever-changing environment. How memory-related brain regions, such as the medial-temporal lobe, influence sensory cortex to support this process remains unclear. Here, we used two-photon calcium imaging of axonal projections from the perirhinal (PRh) cortex to the auditory cortex during learning and generalization of an auditory discrimination task. PRh input in the auditory cortex increased during learning and influenced performance in a categorization task. Chemogenetically silencing PRh input selectively disrupted the activity of auditory cortex layer 2/3 pyramidal neurons, and PRh photoactivation drove behavior toward overgeneralization. These findings highlight PRh input as a key modulatory pathway that shapes cortical dynamics underlying auditory learning and memory-guided sensory perception.

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

Symmetry control by Raman-mode excitations via anharmonic couplings with terahertz field–induced infrared modes in ferroaxial PbWO 4

Masaki Yamamoto, Hiroki Sato, Ryohei Ikeda, Tetsushi Kubo, Tatsuya Miyamoto, Kenta Kimura, Takayuki Nagai, Tsuyoshi Kimura, Hiroshi Okamoto

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Ultrafast conversion from a high- to low-symmetry structure is important for optical-switching devices. To realize such a conversion, we used nonlinear phononics. Exciting infrared-active modes with an intense terahertz pulse generates symmetry-reducing Raman modes via anharmonic couplings with the infrared-active modes. A terahertz-pump optical-Kerr-ellipticity-probe method was applied to a ferroaxial material, PbWO 4 , using terahertz pulses with two different bandwidths, revealing that Raman-mode dynamics induced by an anharmonic mode coupling can be distinguished from those due to the stimulated Raman scattering. Our results showed that the anharmonic mode coupling comprises two components. Under terahertz light, forced oscillations of the infrared-active modes drive coherent Raman mode oscillations. After the terahertz light disappears, the square of the infrared-active mode amplitudes induces Raman-mode displacements. By narrowing the bandwidth and broadening the temporal width of the terahertz pulse, the Raman mode displacements are rectified over several picoseconds. This approach is promising for generating a new state with lower symmetry.

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

Autism-like phenotypes and increased NMDAR2D expression in mice with KDM5B histone lysine demethylase deficiency

Leticia Pérez-Sisqués, Shail U. Bhatt, Angela Caruso, Josephine L. Robb, Alex P. A. Donovan, Rosemary Bamford, Alejo Torres-Cano, Shoshana Spring, Eleanor Hendy, Talia E. Gileadi, Martyna Panasiuk, Jed Trengove, Neeru Jindal, Mohi U. Ahmed, Mara Sabbioni, Joyce Taylor-Papadimitriou, Diana Cash, Nicholas Clifton, Jacob Ellegood, Laura C. Andreae, Jason P. Lerch, Maria Luisa Scattoni, K. Peter Giese, Cathy Fernandes, M. Albert Basson

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Loss-of-function mutations in genes encoding lysine demethylases specific for trimethylated lysine 4 of histone 3 (H3K4me3) are associated with neurodevelopmental conditions, including autism spectrum disorder (ASD) and intellectual disability (ID). To study the role of KDM5B (lysine demethylase 5B)–mediated H3K4me3 demethylation, we investigated neurodevelopmental phenotypes in mice without KDM5B demethylase activity. These mice exhibited autism-like behaviors and increased brain size. H3K4me3 levels and the expression of neurodevelopmental genes were increased in the developing Kdm5b mutant neocortex. Increased H3K4me3 levels at the promoter and associated expression of the Grin2d gene were associated with increased levels of N -methyl- d -aspartate receptor subunit 2D (NMDAR2D) protein in synaptosomes isolated from the early postnatal Kdm5b -deficient neocortex. Treating mice with the NMDAR antagonist memantine rescued deficits in ultrasonic vocalizations. These findings suggest that increased H3K4me3 levels and associated Grin2d gene up-regulation disrupt brain development and function, leading to socio-communication deficits and identify a potential therapeutic target for neurodevelopmental disorders associated with KDM5B deficiency.

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

Continuous monitoring of blood–interstitial fluid intercompartmental molecular kinetics in freely moving animals

Yihang Chen, Qitao Hu, Jean Won Kwak, David Zakharian, Jenny Ji, Du Liu, Deepak Gopalan, Caoimhe Lyons, Max Yates, Steven Yee, Han Cui, Michael Eisenstein, Hyongsok Tom Soh

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Accurate health monitoring depends on continuous assessment of biochemical markers across multiple body compartments. While blood remains the clinical gold standard, interstitial fluid (ISF) presents a minimally invasive alternative that reflects local tissue physiology, although its biomarker kinetics often differ from blood. It is currently impossible to achieve simultaneous, continuous monitoring of both compartments, limiting insight into their dynamic relationship. To address this, we present BICEP (blood-ISF continuous-sensing electrochemical probe), a wireless electrochemical platform for continuous dual-compartment monitoring of analytes in blood and ISF. The BICEP system incorporates microfabricated soft sensors with biofouling-resistant aptamer interfaces, paired with a wearable potentiostat for remote configuration and readout. Using this system, we continuously tracked kanamycin signal in both anesthetized and freely moving rats, revealing distinct kinetic profiles and individualized temporal delays between blood and ISF signals. These findings confirm that ISF is not merely a proxy for blood but exhibits unique molecular kinetics influenced by individual variability and physiological state. This platform advances personalized health monitoring by providing integrated, dynamic correlation of blood and ISF biomarkers, deepening understanding of their physiological interplay under real-life conditions and paving the way for broader use of wearable ISF-based biosensors.

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

Schizophrenia risk gene ZNF804A controls ribosome localization and synaptogenesis in developing human neurons

Laura Sichlinger, Maximilian Hausherr, Sara Guerrisi, Lucia Dutan-Polit, George Chennell, Roland Nagy, Rugile Matuleviciute, Fatema Nasser, Szidonia Farkas, Rosemary A. Bamford, Szi Kay Leung, Rodrigo R. R. Duarte, Timothy R. Powell, Jonathan Mill, Katrin Marcus, Anthony C. Vernon, Deepak P. Srivastava

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ZNF804A was among the first genes robustly associated with schizophrenia based on findings from large-scale genomic studies. Previous research has implicated ZNF804A in the regulation of gene expression and synaptic function, but the role of this gene in neurodevelopment and in schizophrenia pathogenesis remains unclear. To study its function during neurodevelopment, we generated isogenic human induced pluripotent stem cells with reduced ZNF804A expression, differentiated them into developing cortical glutamatergic neurons, and studied their transcriptomic, synaptic, and protein signatures. Mutant neurons showed modest evidence for changes in gene expression. However, high-content confocal imaging revealed increased excitatory synapse density in mutant neurons. Cell compartment–specific proteomic analysis further revealed that mutant neurons had higher levels of ribosomal and translational proteins within neurites, and high-content imaging confirmed increased local protein synthesis efficiency. Overall, these results demonstrate that in human developing cortical glutamatergic neurons, ZNF804A regulates excitatory synapse formation potential via increased local protein translation.

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

Improved closure of the global mean sea level budget from observational advances since 1960

Huayi Zheng, Lijing Cheng, Sönke Dangendorf, Benoit Meyssignac, Anne Barnoud, Kevin E. Trenberth, John T. Fasullo, John Abraham

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Balancing the global mean sea level (GMSL) budget is essential for understanding sea level changes. Large uncertainty after 1960 is reduced by accounting for recent observational advances. Budget closure occurs within 0.18 millimeters per year for all periods analyzed (1960–2023, 1993–2023, and 2005–2023). Trends for these three periods are 2.06, 3.41, and 3.94 millimeters per year, revealing an increase in the rate. The annual residual between observed GMSL and the sum of contributions is only between −13 and 10 millimeters since 1960 and ±5 millimeters after 2005. Further, the GMSL acceleration budget is now closed. The principal drivers for the GMSL trend (acceleration) since 1960 are 43% (41%) from thermosteric ocean expansion, 27% (9%) from glacier melting, 15% (16%) from Greenland, 12% (13%) from Antarctic, and 3% (21%) from land water storage. Results highlight the importance of data processing and bias correction techniques in tracking GMSL and its contributions.

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

Cooperativity, entropy, and effective concentration in DNA origami self-replication

Heng Ni, Feng Zhou, Guolong Zhu, Lev Bershadsky, Shen Ai, Kun Wang, Ruojie Sha, Nadrian C. Seeman, Paul M. Chaikin

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Many new structures, machines, active materials, and devices have been produced in the rapidly growing field of DNA nanotechnology. However, the thermodynamics of complex DNA assemblies remains not well understood. Here, we treat the assembly, melting, and activation of more complex structures where interactions are generally cooperative. We abandon a rigorous theory involving a complex landscape in favor of a two-state (open-close) scenario with effective concentration and entropy effects. We test our model with self-replication of DNA origami motifs of increasing sizes and with FRET on a single DNA pair held in proximity, and it predicts melting temperatures to ~2°C where there is a 50°C shift arising from cooperativity. The model is especially useful for designing interactions between large objects programmed to open and close and is readily adaptable to assembly and activation in systems other than DNA.

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

Floodplain slope organizes chute and neck meander cutoffs across rivers in the Amazon basin

Yuan Li, Douglas A. Edmonds, Kory M. Konsoer, José A. Constantine, Ye Jing, Dylan T. Shoemaker, Md Muzahidul Islam

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Channel cutoff is a fundamental mechanism by which meandering rivers of the Amazon reshape their courses, yet it remains unclear how their frequency and type vary across the river basin. Using satellite images from 1984 to 2021, we identified 1132 cutoffs across all single-threaded channels wider than 90 m. We find that cutoff types are unevenly distributed across the basin: Neck cutoffs ( n = 594) dominate low-slope floodplains, while chute cutoffs ( n = 456) are more common in steeper regions. Bimodal distributions of cutoff geometries indicate fundamentally different processes associated with neck and chute cutoffs. Results show that floodplain slope is a first-order control on cutoff type across the river basin, while water discharge and landcover act as secondary controls. The planform geometry of chute cutoffs is more scale-free than necks. This basin-wide perspective illustrates how cutoff type changes systematically across the Amazon, suggesting that floodplain properties control lentic habitat availability.

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

Long-cycling organic flow batteries enabled by electronic-spatial synergistic modulation

Tao Wang, Yuheng Xia, Chenlong Gao, Tianyu Huang, Zhitao Zhao, Miao Chen, Menghao Yang, Mingjin Cui, Yu Ding

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Aqueous organic redox flow batteries (AORFBs) show promise for grid-scale energy storage but are limited by inadequate stability and solubility of active materials. Here we report an electronic-spatial synergistic modulation strategy to simultaneously enhance aqueous dissolution and electrochemical robustness of organic species, demonstrated on 4-aminophenol (PAP)–based molecules. By introducing a piperazine ring and an acetyl group at the amino site, we design 1-(4-(4-hydroxyphenyl)piperazin-1-yl)ethan-1-one (AHPP). This synergistic modulation stabilizes the oxidized state, suppresses side reactions, and boosts solubility to 1.9 molar in aqueous solution (3.8-molar electron concentration). An all-organic flow battery based on AHPP achieves 95.7% capacity retention after 5000 cycles, with stable operation across a wide temperature range. Integrating in situ spectroscopic and electrochemical analysis with computational modeling elucidates the redox chemistry of PAP-based molecules and establishes a link between intermediate stability and functional group effects. Life cycle assessment further reveals the environmental footprint of AHPP-based batteries, demonstrating considerable potential for practical grid-scale storage applications.

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

Probing individual quantum emitters in bulk semiconductors via photonic nanojets

Behrooz Semnani, Sai Sreesh Venuturumilli, Mohammad Soltani, Pratik Adhikary, Abdolreza Pasharavesh, Nikolay Videnov, Paul Anderson, Supratik Sarkar, Vinodh Raj Rajagopal Muthu, Michal Bajcsy

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Solid-state quantum emitters serve as fundamental building blocks for quantum information processing, quantum telecommunication, and quantum-enhanced sensing, particularly at the nanoscale. However, the high refractive index of the emitters’ host materials often result in low-efficiency collection of the photons generated by the emitters. In addition, isolating individual quantum emitters generally requires high-purity samples and precise defect implantation, adding to the fabrication complexity. In this work, we use free-form topology optimization to design broadband monolithic photonic structures within high–refractive index materials hosting a relatively dense ensemble of randomly distributed quantum emitters. Fabricated via standard top-down patterning techniques, these inverse-designed nanostructures generate tightly confined photonic nanojets, which in turn enable selective excitation of individual emitters and improve photon extraction efficiency. The optimized geometries also substantially suppress background photoluminescence from near-surface optically active defects and from randomly distributed emitters in the bulk, boosting the signal-to-noise ratio. We demonstrate this paradigm using negatively charged nitrogen vacancy (NV − ) centers in a low-cost diamond sample at room temperature as a case study, achieving selective single emitter excitation with a 10-fold power enhancement and more than 15-fold improvement in the photon extraction efficiency of photoluminescence collection in confocal microscopy. Beyond NV centers and other diamond-embedded quantum emitters, the use of inverse-designed structures generating subwavelength photonic nanojets is applicable to other semiconductor materials containing emitters and can be seamlessly generalized to fiber-integrated platforms.

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

Tropical basin interactions reduce spring predictability barrier of ENSO in a deep learning model

Lu Zhou, Rong-Hua Zhang

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The El Niño–Southern Oscillation (ENSO) exhibits a pronounced decline in predictability during boreal spring, referred to as spring predictability barrier (SPB). While tropical basin interactions among the Indian, Atlantic, and Pacific Oceans potentially enhance ENSO predictability, their roles in mitigating SPB within deep learning (DL) frameworks remain underutilized. Here, we introduce GL-Geoformer, a DL model for global tropical ocean-atmosphere prediction. GL-Geoformer captures spatiotemporal evolutions of wind and three-dimensional temperature anomalies across the tropical basins. Our modeling demonstrates that incorporating tropical basin interactions substantially reduces SPB, enabling GL-Geoformer to achieve skillful ENSO predictions up to 16 months in advance when initiated in spring. Pacemaker experiments are performed to quantify individual and synergistic contributing nonlinearities of Indian Ocean Dipole and Atlantic Niño via subsurface heat transport and Walker circulation mechanisms, respectively. This study provides a data-driven framework to represent tropical basin interactions and reduce SPB, thereby deepening understanding of ENSO predictability.

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

Computational neural dynamics of goal-directed visual attention in macaques

Jie Zhang, Nuttida Rungratsameetaweemana, Shuo Wang

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Goal-directed visual attention requires the dynamic integration of task goals with perceptual and mnemonic processes across distributed cortical networks. Using large-scale recordings from V4, IT, OFC, and LPFC, we observed that population dynamics robustly represented visual categories during cue presentation, sustained cue information across delay periods, and differentiated both categories and attentional states during search. Cue-related activity predicted subsequent search efficiency, linking presearch processing to behavioral performance. The orthogonal subspace provided a crucial latent representational structure for encoding and maintaining task-relevant information across search stages. Foveal attention enhanced peripheral representations by both increasing pattern separation and reshaping representational geometry in a nonlinear, context-dependent manner. Search dynamics further reflected fixation history and target detection, which modulated both response strength and representational structure. Lastly, V4 and IT encoded the spatial geometry of the search array, preserving its layout. Together, these findings highlight population-level dynamics as critical mechanisms supporting goal-directed visual attention.

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

Integrated perspective on ocean carbon cycle: Untangling facts, fluxes, and fictions

Laure Resplandy, Marina Lévy, Laurent Bopp

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The ocean carbon cycle spans multiple scales and reservoirs, challenging efforts to build a coherent picture and fostering misconceptions or fragmented narratives in science and public discourse. Common examples include the belief that the biological processes control the ocean’s carbon sink (i.e., fraction of human CO 2 emissions absorbed by ocean), that restoring coastal ecosystems is highly effective at mitigating climate change, or that whales substantially contribute to carbon sequestration. We provide a comprehensive review of living and nonliving ocean carbon stocks and fluxes—from plankton to mangroves, whales, fish, and plastics—and an integrated perspective on global ocean carbon cycling, disentangling well-supported insights from misconceptions. This synthesis reaffirms the ocean’s key role as a physics- and chemistry-driven carbon sink, while clarifying the limited contribution of coastal and open-ocean ecosystems to carbon sequestration and climate mitigation. We caution against frameworks that justify marine conservation through climate mitigation—a narrative useful to draw attention, but not always robust and unnecessary, since marine biodiversity is worth preserving regardless of its impact on carbon.

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

Interpreting the dominant signature of inhomogeneous mixing resulting from dry-air entrainment in clouds

Nithin Allwayin, Gregory Roberts, Elise Rosky, Kenny Bala, Aaron Bansemer, Keyvan Ranjbar, Raymond A. Shaw

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How cloud droplets evaporate when mixed with the dry surrounding air is fundamental to cloud optical properties and lifetime. We find from observations in cumulus clouds made during the ESCAPE field campaign that this mixing process appears strongly inhomogeneous-like, where a subset of droplets evaporate completely as mixing proceeds, rather than all droplets partially evaporating. We visualize the microphysical properties in a two-dimensional evaporation-phase-relaxation space and find that a diffusive turbulent-evaporation model is able to capture the dynamic evolution of the entrainment process. The results indicate that the first evaporating droplets humidify the region around the cloud so that the unmixed dry air rarely reaches the core, explaining why most mixing events appear inhomogeneous. A mixing slope parameter also confirms the nature of the mixing process. On the basis of the inhomogeneous mixing model, we propose a simple parameterization of cloud optical properties suitable for coarse-resolution models.

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

Hypoxia-responsive interaction between P-TEFb, BHLHE40, and Tim8-Tim13 regulates hypoxic gene transcription

Shimaa Hassan AbdelAziz Soliman, Simone De Fabritiis, Marta Iwanaszko, Lawrence Austin Lin, Madhurima Das, Sarah Gold, Grant David Andersen, Ram P. Chakrabarty, Navdeep S. Chandel, Ali Shilatifard

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The P-TEFb transcriptional kinase complex regulates the pause release checkpoint step in transcription by RNA polymerase II (RNAPII). We sought to identify hypoxia-specific interactions that could direct P-TEFb activity to hypoxia-responsive genes. Using a biochemical purification approach, we discovered a hypoxia-specific, chromatin-associated interaction between the P-TEFb subunit cyclin T1 (CCNT1), nuclear localized mitochondrial chaperone Tim8-Tim13 complexes, and the hypoxia-inducible, DNA binding transcription factor BHLHE40. This interaction is confirmed across multiple human cell lines. Tim8-Tim13 complex disruption and BHLHE40 silencing both impair the transcriptional response to acute hypoxia. HIF is not involved in the CCNT1/BHLHE40/Tim8-Tim13 interaction, and neither genetic HIF-1β knockout nor pharmacological HIF-2α inhibition (belzutifan) eliminates BHLHE40 expression. Finally, BHLHE40 depletion compromises the proliferation of 786-O clear cell renal carcinoma cells, which constitutively express HIF-2α and hypoxia-responsive genes. Together, these findings reveal a partially HIF-independent regulatory axis, in which Tim8-Tim13 complexes and BHLHE40 modulate P-TEFb activity in the transcriptional response to hypoxia.

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

Serine protease HtrA promotes Campylobacter jejuni intestinal colonization through degrading antimicrobial peptide LL-37

Xiaofei Li, Mengjie Zhang, Zhenzhen Xu, Yunlu Li, Su Bian, Yuanyue Tang, Xinan Jiao, Ozan Gundogdu, Jinlin Huang

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Campylobacter jejuni ( C. jejuni ) is a leading cause of human gastroenteritis worldwide and must overcome intestinal innate immunity, including antimicrobial peptide LL-37. However, how C. jejuni responds to LL-37 remains unclear. Here, we showed that C. jejuni infection stimulates intestinal epithelial cells to secrete LL-37, exhibiting effective antibacterial activity against 86.3% of C. jejuni clinical isolates by disrupting essential processes required for bacterial survival. A subset of isolates displays intrinsic resistance, enabling successful intestinal colonization. We further identified conserved serine protease HtrA as the key determinant of resistance. Mechanistically, LL-37 exposure activates transcriptional regulator NssR, which up-regulates htrA expression. Secreted HtrA cleaves LL-37 at Ile 20 -Val 21 site, abolishing its antimicrobial activity and promoting bacterial survival. In light of this mechanism, we developed a noncleavable LL-37 I20M/V21R that displays enhanced antibacterial activity and promotes bacterial clearance in mice. Together, our findings uncover mechanistic insights into interactions between human enteric pathogens and antimicrobial peptides and provide a potential strategy for combating C. jejuni infection.

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

Ferromagnetic superconductivity with excitonic Cooper pairs: Application to Γ-valley twisted semiconductors

Daniele Guerci, Liang Fu

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We present a theory of ferromagnetic superconductivity that emerges upon doping a correlated ferromagnetic insulator through the condensation of excitonic Cooper pairs, which are charge-2 e bosonic quasiparticles made of Cooper pairs strongly hybridized with excitons. Using a strong-coupling expansion supported by exact diagonalization, we analyze a model of spin-polarized electrons and show that excitonic Cooper pairs form from electron-hole fluctuations upon doping a strongly correlated insulator. We characterize their binding energy, effective mass, and the resulting superconducting transition temperature. We propose possible realization of spin-polarized superconductivity in twisted semiconductors with honeycomb moiré superlattice.

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

Deciphering the ancestral mechanisms of neural regeneration through single-cell analyses of jellyfish rhopalium repair

Yongxue Li, Fanghan Wang, Tingting Sun, Xiaoran Ma, Zhangyi Yu, Ziyue Xu, Wenhui Wang, Yixuan Xing, Saijun Peng, Lei Wang, Jianmin Zhao, Zhijun Dong

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The rhopalium, an early specialized centralized nervous structure in medusozoans, exhibits a remarkable regenerative capacity after removal, offering a unique model for investigating the ancestral regulatory logic of neural regeneration. However, the cellular and molecular mechanisms underlying the process remain unknown. Here, we defined distinct stages of rhopalium regeneration in the jellyfish Aurelia coerulea and constructed a stage-specific cell landscape and gene regulatory networks. Notably, we identified a population of wound-induced cells that emerges rapidly postinjury and activates Wnt signaling to initiate blastema formation; cross-species comparisons revealed that this regulatory mechanism is conserved across metazoans. We further identified that retinoic acid signaling is essential for photoreceptor regeneration and ocelli reconstruction. The findings presented herein uncover the ancestral regulatory mechanisms governing neural regeneration in the early centralized nervous system, providing insights into the common evolutionary origins of neural repair across organisms.

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

Generalizability of an AI-based mammogram risk score (MRS) for breast cancer among diverse populations of women

Shu Jiang, Debbie L. Bennett, Peter Kraft, Graham A. Colditz

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Conventional prediction models incorporating genetic and clinical factors including breast density underperform in non-European populations. We investigated an artificial intelligence–derived mammogram risk score (MRS), a summary of texture features that captures intrinsic breast-tissue characteristics—the substrate for cancer development. This study leveraged data from two North American screening cohorts totaling >226,000 women, including non-Hispanic white, non-Hispanic Black, East Asian, South Asian, and Indigenous women. MRS distributions showed nonsignificant shifts (and similar SDs) between cohorts and across race and ethnic subgroups. MRS increased with age and was significantly associated with breast cancer risk, with hazard ratios per SD ranging from 2.24 [95% confidence interval (CI), 2.03 to 2.46] to 2.32 (95% CI, 2.25 to 2.39) after age adjustment. Associations remained significant within all subgroups. Calibration was excellent across the racial and ethnic groups and across full-field digital mammograms and tomosynthesis. These findings establish MRS as a strong predictor that is independent of race or ethnicity, demonstrating its potential for broader clinical utility.

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

Visualizing the mechanism of quinol oxidation and inhibition of a bd -type oxidase using cryo-EM

Tijn T. van der Velden, Kanwal Kayastha, Famke Pelser, Steffen Brünle, Lars J. C. Jeuken

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Cytochrome bd is a prokaryotic terminal oxidase recognized as an antibiotic target against various pathogens. Despite its critical role in respiration, failure to capture the mechanism of quinol oxidation and inhibition prohibits structure guided drug discovery. Here, we present cryo–electron microscopy structures of Escherichia coli cytochrome bd -I in monomeric and dimeric forms, in several quinone and inhibitor-bound states. We identify a dynamic Q-loop lid that undergoes a disorder-to-order transition upon substrate binding to the dimer, completing the active site and enabling catalysis. Structure-guided mutagenesis confirms Tyr243 CydA and Arg298 CydA as conserved catalytic residues only found in long Q-loop oxidases, highlighting evolutionary divergence from other subfamilies. Inhibition by Aurachin D triggers refolding of the active site, occluding substrate access via an Asp239 CydA -mediated mechanism. The structural and mechanistic insights presented here establish a comprehensive framework, opening paths for drug discovery against bd oxidases.

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

Paleo–salt water dominates coastal aquifer salinization: A continental-scale study in China

Tianyuan Zheng, Bo Guo, Qinpeng Chang, Qiguo Sun, Xiaogang Chen, Xilai Zheng, Jichun Wu, Zhihong Zheng, Shaobo Gao, Chunmiao Zheng, Junguo Liu, Dong Wang, Tao Liu, Xiaolei Liu, Guangquan Chen, Xingyong Xu, Bo Zhang, Lin Zhang, Yajie Wu, Olaf Kolditz, Jian Luo, Alberto Guadagnini

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Seawater intrusion poses a major threat to freshwater resources in coastal aquifers worldwide. In China alone, these types of aquifers provide a vital groundwater source for nearly 400 million people. Whereas modern seawater intrusion is often attributed to human activities and climate change, the role of paleo–salt water remains poorly quantified. This continental-scale investigation of seawater intrusion in China reveals that paleo–salt water, not modern seawater, dominates salinity patterns in large sedimentary basins. Analysis of over 2100 water samples shows a strong correlation between intrusion and tectonic subsidence zones, with paleo–salt water affecting 66% of the observed salinized areas. In northern coastal plains, paleo–salt water trapped in confined aquifers is characterized by salinity levels exceeding 144.6 grams per liter, whereas modern seawater intrusion (34%) occurs in hilly regions with thinner sediments. Isotopic signatures (δ 18 O) trace paleo–salt water intrusion to Quaternary sea level changes. These findings improve seawater intrusion source identification and inform global salinity management.

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

A dual membrane-adsorption evaporator for solar-powered lithium extraction from complex brines

Aydin F. Eskafi, Wenli Jiang, Jeffrey J. Urban, Baoxia Mi

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A reliable supply of lithium is required to meet the increased demand for batteries over the coming decades. In this work, we demonstrated the potential to effectively extract lithium from brines by coupling solar-powered evaporation, adsorption, and membrane technologies together. We first synthesized a three-dimensional adsorptive evaporator by coating a lithium manganese oxide material onto a cotton stick using an easily scalable, one-step method. An osmotic membrane was then installed at the root of the evaporator to enhance the lithium to magnesium selectivity, prevent scaling caused by divalent cations, and thus further increase the water evaporation flux. The operation of the dual membrane-adsorption evaporator is entirely driven by osmosis and capillary force, demanding no extra energy input. The integration of the osmotic membrane was found to increase the lithium to magnesium selectivity over 10-fold to higher than 40. The dual process also produced high lithium to calcium selectivity and proved to sustain long-term stability by self-managing its internal osmotic pressure. Last, a test was done in three simulated brine solutions with varied brine chemistry and the evaporation rate stayed high and consistent throughout the long-term test. This illustrates that this technology can be used in varied brine solutions throughout the world providing efficient lithium capture and separation from competing divalent cations.

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

Identifying menstrual metrics as personal health markers: Age trends and individual footprints in temperature across 5674 cycles

Marie Gombert-Labedens, Alan Taitz, Orsolya Kiss, Fiona C. Baker

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The menstrual cycle is a rich yet underused source of physiological information. To address this, we developed an open-source tool called WAVES (women’s health assessment through variability in endocrine-related signals) that leverages physiological signals to extract menstrual cycle metrics and facilitate biomarker discovery. We tested it on basal body temperature data from 5674 nonconceptive cycles from 753 participants aged 18 to 42 years. We identified multiple associations between aging and menstrual metrics changes, including higher average temperatures, shorter cycles, and decrease in regularity across multiple metrics. In addition, values and cycle-to-cycle regularity of several metrics capturing temperature level and temporal structure of the cycle showed moderate to strong within-individual stability (ICC > 0.5). This work suggests that the WAVES algorithm can be used for advancing digital biomarker discovery and highlights the relevance of a personalized approach in the development of next-generation tools for women’s health.

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

Intestinal obstruction impairs feeding and promotes sleep in Drosophila melanogaster

Cindy Reinger, Laura Blackie, Alexandra M. Medeiros, Hugo Gillet, Carolin Kring, Pedro Gaspar, Dafni Hadjieconomou, Michèle Sickmann, Markus Affolter, Irene Miguel-Aliaga, Martin Müller, Anissa Kempf

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At the onset of life, feeding must be initiated while developmental waste products—the meconium—need to be eliminated. Although these two fundamental physiological processes are interconnected, their mechanistic coupling remains poorly understood. Using Drosophila as a model system, we investigated the coordination of these processes. We show that meconium excretion starts shortly after eclosion and that feeding initiation begins only after partial meconium elimination. We identified a cis-regulatory element associated with the apterous gene that is required for proper hindgut development. Its disruption prevents meconium excretion and leads to intestinal obstruction. As a result, flies with a defective element avoid food and exhibit increased proboscis extension sleep. Experimental inhibition of excretion in freshly eclosed flies recapitulates these phenotypes, indicating that intestinal blockage is sufficient to impair feeding and alter sleep/wake states. The progression of phenotypes parallels hallmarks of mechanical gut obstruction in humans, suggesting that the observed effects may arise from broader physiological consequences of intestinal blockage. Our findings uncover a link between intestinal clearance, feeding, sleep, and survival, with potential implications for understanding similar processes across species.

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

Emergence of unconventional ferroelectric phase in ultrathin Hf 0.5 Zr 0.5 O 2 films

Sangjun Lee, Hyangsook Lee, Hyun Hwi Lee, Han-Koo Lee, Jung-Hwa Kim, Seontae Park, Hyun Jae Lee, Hagyoul Bae, Sanghyun Jo, Musarrat Hasan, Yongho Ha, Bong Jin Kuh, Jinseong Heo, Duk-Hyun Choe, Eunha Lee

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Unlike perovskite-based ferroelectrics, whose polarization typically diminishes at reduced thickness, doped hafnia films retain robust ferroelectricity down to 1-nanometer thickness. Accurate structural determination is crucial for understanding this behavior, as ferroelectricity in ultrathin hafnia-based films has been attributed to enhanced polar distortion in their crystal structures. However, precise identification is challenging because of structural similarities among various polymorphs. Here, we experimentally identify the emergence of an unconventional ferroelectric Pmn2 1 orthorhombic phase in 1.5-nanometer-thick Hf 0.5 Zr 0.5 O 2 films directly grown on silicon substrates. Structural and spectroscopic analyses clearly distinguish the experimentally observed Pmn2 1 phase from the conventional Pca2 1 phase typically reported in thicker hafnia films. Furthermore, we find that substantial expansion of the out-of-plane lattice dimension at ultrathin scales drives the stabilization of the Pmn2 1 structure. The experimental identification of this unconventional phase provides crucial insights into the structural evolution underlying the distinct thickness-dependent ferroelectric properties of ultrathin hafnia films.

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

Adaptive tunneling photodiodes enable visual recognition in high-contrast scenes

Lixin Liu, Fangchen Hu, Jiayue Han, Jun Gou, Peng Zou, Hang Yu, Meiyu He, Lei Guo, Yunlu Lian, Wenjie Deng, Fakun Wang, Jingxuan Wei, Xiaoyang Du, Hongxi Zhou, He Yu, Yadong Jiang, Qi Jie Wang, Jun Wang

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Accurate visual sensing in extreme high-contrast lighting environments is critical for emerging intelligent systems such as autonomous vehicles, smart surveillance, and robotics. These systems rely heavily on high dynamic range (HDR) imaging to capture scenes with wide illumination variations. However, existing HDR solutions primarily depend on computational algorithms or hardware-intensive techniques such as multiexposure fusion or mechanical modulation, which suffers from latency, motion artifacts, high power consumption, and limited adaptability. Here, we present a hardware-centric approach that realizes HDR functionality directly into the photodetectors of a camera image sensor. Our design leverages an engineered tunneling mechanism to achieve bias-controllable, continuously tunable dynamic range covering up to 150 dB. In real-world high-contrast autonomous driving scenarios, this sensor-level HDR capability enables robust object classification confidence score exceeding 91% across the entire exposure scene. By shifting HDR processing to the sensor front-end, our approach substantially reduces the computational load, enabling system-level efficiency, speed, energy consumption, and recognition reliability. This prototype paves the way for the development of next-generation, compact, on-chip visual preprocessing hardware for intelligent vision systems.

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

Erythrocyte patch for enhanced B cell depletion therapy

Jiaqi Liu, Fengju Wang, Lian Li

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Dysregulated B cells are central to many hematologic malignancies and autoimmune diseases, but current B cell–targeted therapies often fail to translate binding into effective signaling. Here, we present CD20 EryPatch, a living dynamic cellular patch that co-opts natural erythrocyte processes of morphological and biological changes, enabling a dual mechanism of micrometer-scale mechanotransduction and phagocytic “tag-and-clear” for enhanced B cell depletion. CD20 EryPatches are designed to adhere to B cells and anchor on CD20 receptors across extensive cell surface areas. Their progressive discocyte-to-echinocyte transition provides deformability-driven traction, enabling localized, large-scale CD20 cross-linking that amplifies downstream apoptosis in target B cells. Concomitant biomarker alteration on CD20 EryPatch converts it into an “eat me” tag attached to the B cell, facilitating further clearance by initiating erythrophagocytosis. This approach proves more effective than standard CD20 monoclonal antibodies in models of B cell disorders, including non-Hodgkin lymphoma, systemic lupus erythematosus, and rheumatoid arthritis.

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

Discovery of spontaneous mesoscopic strain waves in nematic domains using dark-field x-ray microscopy

Kaan A. Yay, William J. Meese, Elliot Kisiel, Matthew J. Krogstad, Anisha G. Singh, Rafael M. Fernandes, Zahir Islam, Ian R. Fisher

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Electronic nematic order arises when correlated electrons spontaneously break the rotational symmetry of a crystal lattice. When electronic nematic order couples bilinearly to symmetry-breaking lattice strain, both appear together at a single ferroelastic phase transition, producing structural twin domains with distinct orientations of the nematic director. While the effects of applied strain on these domains are well established, the intrinsic behavior of spontaneous subdomain strain fields has remained unexplored. Here, we report the discovery of spontaneous mesoscopic strain waves within individual nematic domains of an iron-based superconductor, observed using dark-field x-ray microscopy (DFXM). Using this advanced full-field imaging technique, we visualize subdomain strain modulations emerging concurrently with nematic order. Elastic compatibility relations governing inhomogeneous strains provide a natural mechanism for the strain waves. Our findings reveal a broadly relevant form of strain self-organization and position DFXM as a powerful probe of the local interplay between lattice strain and electronic order.

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

Distinct impacts of tropical North Atlantic warming flavors on cross-basin tropical cyclone activity

Jiuwei Zhao, Luyao Bai, Ruifen Zhan, Yi Liu, Wenju Cai, Yuqing Wang, Jong-Seong Kug, Il-Ju Moon, Xiangbo Feng, Ralf Toumi, Botao Zhou, Leying Zhang, Han-Ching Chen

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Tropical North Atlantic (TNA) warming typically favors tropical cyclone (TC) genesis over the North Atlantic but suppresses TC formation over the Northwest Pacific during boreal summer. The TNA anomaly patterns can be classified into an eastern coastal and a western warm-pool type, but their respective impacts remain unclear. Here, we find a pronounced difference in the impact between the two TNA flavors. The warm-pool TNA warming suppresses Northwest Pacific TC genesis through a remote dynamical control, while the coastal warming promotes North Atlantic TC genesis via a local thermodynamic control. High-resolution modeling reveals that, compared with the canonical TNA warming, the warm-pool TNA warming suppresses Northwest Pacific TC genesis by 65.2%, while the coastal warming enhances North Atlantic TC genesis by 60.1%. Under greenhouse warming, increased coastal TNA warming is projected to intensify North Atlantic TC activity. Therefore, distinguishing TNA flavors is critical for improving seasonal prediction and future projections of cross-basin TC activity.

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

Systemic-to-local nanorobot thrombolysis

Di Zhang, Ouling Zhu, Fangzhi Mou, Xinyi Wang, Chuan Cao, Wei Yi, Manyi Yang, Yun Liu, Xinkang Du, Xiao Wang, Jianfeng Liu, Ding Wang, Wei Luo, Zhi Li, Jianguo Guan

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Magnetic micro/nanorobots hold promise for targeted thrombolysis, yet face challenges of rapid immune clearance and poor degradability, often necessitating invasive localized deployment and retrieval. Here, we present safe and versatile systemic-to-local thrombolysis enabled by magnetic nanorobots constructed from polyvinyl pyrrolidone–shielded porous Fe 3 O 4 colloidal nanocrystal clusters (p-Fe 3 O 4 @PVP CNCs). In this building block design, the PVP coating facilitates efficient tPA (tissue plasminogen activator) loading while ensuring prolonged circulation following systemic injection. The p-Fe 3 O 4 core provides a strong collective magnetic moment necessary for sequential magnetic collection (via gradient field H ) and actuation into navigating nanorobots [via precessing field H p ( t )] for targeted thrombolysis. Following thrombolysis, removal of H p ( t ) disassemble the nanorobots into dispersed CNCs that, owing to their porous structure and ultrasmall primary nanocrystals (<5 nanometers), undergo rapid lysosomal degradation and are cleared primarily via the liver-bile-intestine axis, resulting in no long-term toxicity. This platform overcomes key translational challenges for nanorobotic thrombolytic therapy.

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

COST1 stimulates RHD3 GTPase activity to maintain ER morphology and plant growth in Arabidopsis

Jiaojiao Wang, Jian Jiang, Jie Ren, Yunxi Zhao, Yu Zhang, Deyu Feng, Yanjie Li, Qian Zhang, Yue Niu, Xin Zhang, Kang Xu, Jiaqi Sun, Pengwei Wang, Huanquan Zheng, Diane C. Bassham, Chengyuan Wang, Junjie Hu, Yan Bao

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The endoplasmic reticulum (ER) is essential for cellular homeostasis, yet plant-specific mechanisms regulating its structure remain poorly understood. Here, we uncover a functional partnership between the Arabidopsis dynamin-like GTPase RHD3 and the plant-specific DUF641 protein COST1 in maintaining ER morphology and plant growth. COST1 was previously isolated as a negative regulator of autophagy in the drought response. In this study, by using IP-MS, we identified COST1 as an ER-associated protein that interacts directly with RHD3, a key regulator of ER membrane fusion. COST1, despite lacking transmembrane domains, tightly associates with the ER membrane via RHD3, which recruits COST1 to ER three-way junctions. In addition, recruiting of COST1 to the ER can improve the dimerization of RHD3 and its protein stability. Biochemical assays revealed that COST1 promotes the GTP hydrolysis activity of RHD3 by ~20% and significantly stimulates its membrane fusion capacity. Structural modeling predicts a heterotetrameric complex entangled with each protein’s multiple helix bundles, where COST1’s carboxyl-terminal domain aligns with RHD3’s GTPase region, suggesting a mechanism for GTP hydrolysis regulation. Genetic analyses demonstrated that cost1 rhd3 double mutants exhibit exacerbated ER fragmentation and stunted growth compared with single mutants, underscoring their synergistic roles. Transcriptomic profiling linked these phenotypes to disordered stress responding and growth pathways. Our findings reveal a plant-specific regulatory module in which COST1 partners with RHD3 to govern ER architecture, bridging membrane dynamics with growth and stress adaptation, providing insights into ER maintenance mechanisms with plant innovations and the potential applications in improving crop resilience.

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

Bioinspired ionic thermoreceptors with anisotropic architecture for thermotactile perception in robots

Xuan Cai, Yilin Zeng, Pei Liu, Yifan Zhang, Linfeng Wang, Huaiyu Ke, Xue Long, Hua Jiang, Wendong Yang, Zuoxuan Gan, Shuwen Chen, Jiangjiang Duan

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Emulating human skin’s ability to perceive temperature and identify material through thermotactile perception is critical for human-machine interaction, robotics operation, and prosthetic sensory feedback systems. However, conventional artificial thermal sensors are largely limited to temperature measurement and cannot replicate the thermotactile-mediated material recognition capabilities inherent in biological systems. Here, we present a bioinspired ionic thermoreceptor with anisotropic thermal response characteristics, enabling high-fidelity material recognition and accurate temperature monitoring. The device incorporates spatially specialized sensing elements that encode thermal signals into modality-specific temporal response patterns, allowing the extraction of the thermal contact coefficient for material discrimination and the absolute temperature for precise thermal monitoring. It achieves high-accuracy material recognition (98.9%) and substantial temperature resolution (0.81 millikelvins). Furthermore, robust covalent bonding between functional layers ensures mechanical durability, signal stability, and environmental resilience. This work establishes a physically grounded and energy-autonomous thermotactile sensing platform for safe, intuitive, and intelligent human-machine interaction.

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

Acute temperature effects on cilia beating increase coral deoxygenation

Cesar O. Pacherres, Max S. Dhillon, Mads Bilbo, Mikkel Hansen, Douglas R. Brumley, Manuel Aranda, Soeren Ahmerkamp, Michael Kühl

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Cilia-induced vortical flows are critical for regulating oxygen (O 2 ) and metabolite exchange across coral-water interfaces. While this active ventilation affects the coral tissue microenvironment, its role in thermal stress remains poorly understood. Using high-speed imaging of cilia beating, particle image velocimetry with O 2 -sensitive nanoparticles, and a mechanistic transport model, we quantified how ciliary dynamics in the reef-building coral Porites lutea respond to acute warming in darkness. Moderate warming (~35°C) enhanced ciliary activity and advective transport yet paradoxically thickened the concentration boundary layer with O 2 -depleted water, exposing tissues to transient hypoxia. At higher temperatures, ventilation failed to meet rising metabolic demands and anoxic regions expanded rapidly. Above ~37°C, ciliary coordination collapsed and vortical flows dissipated, shifting transport to a diffusion-limited regime accelerating coral mortality. These results identify ciliary beating as a key regulator of thermal tolerance and early indicator of critical physiological tipping points for reef-building corals in a warming, deoxygenating ocean.

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

The immunoproteome and multimorbidity: A Mendelian randomization study

Nikita Hukerikar, Aroon D. Hingorani, Sandesh Chopade, Arjen J. Cupido, Folkert W. Asselbergs, Chris Finan, A. Floriaan Schmidt

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Multimorbidity presents challenges for research and health care. We investigated how immune-proteins influence multiple diseases to identify shared mechanisms and therapeutic opportunities. Using eight large plasma proteome GWAS, we identified cis-acting variants for 151 immune-proteins and applied cis-Mendelian randomization to assess associations with 64 diseases and biomarkers. Protein-disease communities were derived using a knowledge graph integrating multiplicity-corrected associations, druggability, indications, and tissue-trait associations. Replication was sought in independent pQTLs, with colocalization applied to replicated signals. Immune-proteins were frequently implicated in coronary heart disease, venous thromboembolism, atrial fibrillation, type 2 diabetes, and Parkinson’s disease. Seven protein communities mapped to pathways including ficolin binding and antimicrobial peptides, enriched for proteins influencing multiple diseases. Several associations replicated with colocalization support, including APOE, CD163, and IL-6R across neurodegenerative, cardiometabolic, and inflammatory traits. We found strong genetic support for druggable immune-proteins with pleiotropic effects across common diseases, highlighting opportunities for indication expansion and therapeutic development.

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

Unconventional water and hydrous mineral formation from dry minerals and H 2 fluids

Alberto Vitale Brovarone, Emilie Thomassot, Simone Tumiati, Guillaume Siron, Giulia Consuma, Theodor Alpermann, Jay J. Ague, Fabrizio Nestola, Donato Giovannelli, Dimitri A. Sverjensky, Luca Toffolo

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Water availability in the lithosphere has been crucial to the geological evolution of Earth as well as the emergence and persistence of life. The global geological water cycle associated with plate tectonics has been understood as a system controlled by the presence of oxygen and hydrogen, either in fluids and melts or bound within mineral structures. However, recent work on H 2 production in the lithosphere indicates that a water mass equivalent to about 25 to 50% of global annual water inputs into subduction is converted to H 2 every year. This H 2 can be decoupled from the water cycle and potentially lost to space over geological timescales. Here, we show that the interaction of H 2 -rich fluids with oxygen-bearing minerals results in the formation of unconventional redox water. This influences the residence time of hydrogen in Earth’s interior and offers previously unidentified perspectives on how hydrous fluids, minerals, and melts may form in initially dry geological reservoirs.

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

Ionic liquid–regulated interfacial charge transport and asymmetric device architecture for high-performance electrochemiluminescence

Meilin Liu, Zelong Li, Bee Ru Tan, Jiexin Li, Nannan Li, Suchun Li, Sherwin Chong Li Tan, Jiajia Gao, Keeve Kristen Yiheng Kang, Yun Liu, Xuchen Wang, Le Yang, Yu Jun Tan

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Electrochemiluminescence (ECL) devices are promising alternatives to organic light-emitting diodes (OLEDs) and light-emitting capacitors (LECs) due to their simple structure and lower operating voltage, yet realizing sufficient luminance for practical applications remains challenging. Here, we report a synergistic material-device strategy for ultrabright electrochemiluminescent (UBECL) devices. Decoupling anion and cation effects reveals ion-dependent control of interfacial charge-transfer dynamics and electrochemical stability in annihilation-ECL. An effective electrolyte with favorable photophysical and electrochemical properties, coupled with an asymmetric device architecture, enhances electrochemical reactivity and maximizes ECL brightness. UBECL device turns on at a low alternating voltage (±1.65 V) and operates under high-frequency driving. It achieves a maximum luminance of 1552 cd m −2 and 1.6 cd A −1 current efficiency, a 3.2- and 2-fold improvement over 1-ethyl-3-methylimidazolium bis (trifluoromethylsulfonyl) imide (EMIMTFSI)-based counterparts. Moreover, this flexible UBECL platform enables diverse optoelectronic applications, including multicolor devices with potential for dynamic sensing, real-time digital panels, and robust underwater solid-state devices. This strategy unlocks ultrabright, efficient, high-frequency operation for intuitive visual output.

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

Nereid as a regular satellite of Neptune

Matthew Belyakov, M. Ryleigh Davis, Ian Wong, Konstantin Batygin, Michael E. Brown

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Nereid, Neptune’s third largest moon, is considered to be a captured irregular satellite because of its highly eccentric orbit. However, among irregular satellites, Nereid is an outlier: It is the largest, the closest to its host planet, and the most eccentric. We present James Webb Space Telescope near-infrared spectroscopy of Nereid that demonstrates that its composition is inconsistent with its suggested captured origin. We then simulate Nereid’s early orbital history subsequent to Triton’s capture to demonstrate a plausible dynamical pathway for a regular satellite formed in situ around Neptune to evolve to Nereid’s present-day orbit. On the basis of the available spectroscopic and dynamical evidence, we propose that Nereid is not a body captured from the Kuiper belt but rather the sole surviving intact regular satellite of Neptune.

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

Discovery of White Sea assemblage fossils from Laurentia

Scott D. Evans, Erik A. Sperling, Kimberly V. Lau, Justin V. Strauss

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The dawn of animal life is preserved by fossils of the Ediacara Biota, which have been separated into three biotic assemblages: the Avalon, White Sea, and Nama. Geographic and temporal isolation of these faunas leads to uncertainties regarding patterns of change. We report the discovery of unambiguous fossil communities belonging to the White Sea assemblage from the paleocontinent of Laurentia in the Blueflower Formation, Mackenzie Mountains, Canada. Unlike previous localities, sedimentological and geochronological evidence supports an older origin and deeper-water setting for this assemblage, including the oldest motile bilaterians. Fossil communities overlap temporally with the Avalon assemblage and are recognized in similar deep-water paleoenvironments. These results provide support for a hypothesized pattern of offshore origination followed by habitation of shallower environments through time, potentially unique to the early radiation of animals.

Stress disrupts hippocampal integration of overlapping events and memory inference in humans

Kai A. Schüren, Nicole L. Varga, Hendrik Heinbockel, Alison R. Preston, Benno Roozendaal, Lars Schwabe

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Integrating related events in memory is essential for building knowledge that extends beyond direct observation and enables flexible inference. Here, we show that acute stress impairs inference by both reducing the degree to which past memories are reactivated during new learning and leading to their differentiation, rather than integration, in hippocampus. Adults learned A-B associations on day 1 and underwent a stress or control manipulation before learning overlapping B-C associations on day 2, with A-C inference tested thereafter. We demonstrate that stress reduces hippocampal reactivation of A elements during B-C learning, and lower reactivation was directly correlated with impaired A-C inference. Representational similarity analysis revealed that stress increases neural dissimilarity between overlapping A and C elements in the hippocampus, indicating pattern differentiation and a representation as discrete events. Our findings demonstrate that acute stress hampers a key memory integration mechanism, with broad implications for educational, legal, and clinical settings.

Hierarchies of hostility: Why do citizens prefer certain immigrants?

Judit Kende, Fouad Bou Zeineddine, Jessica Gale, Eva G. T. Green

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A reanalysis of 100 studies examining which immigrants citizens prefer highlights why some immigrants are favored and what creates dichotomies of “good” and “bad” immigrants.

Which immigrants do citizens prefer? A meta-reanalysis of 100 conjoint experiments

Marco Aviña, Taeku Lee, Mashail Malik, Reed Rasband, Marcel F. Roman, Priyanka Sethy

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In the past decade, an important literature in the social sciences has examined public attitudes toward immigrants in host societies. In it, a prominent experimental method—the conjoint design, where participants are tasked with rating or choosing between randomized profiles—has been used reliably to understand how immigrant characteristics shape admission preferences. We collate replication datasets from 100 individual studies spanning 1,475,403 immigrant profiles with 26 randomized attributes evaluated by 142,817 survey respondents from 36 countries. Meta-analyses reinforce well-established findings: Economic, cultural, humanitarian, and procedural factors all influence evaluations. Meta-reanalyses show that preferences are broadly similar across countries and demographic groups. However, they also reveal two additional patterns: Economic considerations have become more influential over time, and evaluations of individual immigrants differ sharply depending on where people stand on the broader immigration debate. These findings shed light on ongoing debates and point to fruitful areas for future research.