I checked 6 multidisciplinary journals on Friday, September 19, 2025 using the Crossref API. For the period September 12 to September 18, I found 11 new paper(s) in 4 journal(s).

Nature

GPT-4o mini: Non-social science research article
A neuronal architecture underlying autonomic dysreflexia
Jan Elaine Soriano, Remi Hudelle, Lois Mahe, Matthieu Gautier, Alan Yue Yang Teo, Michael A. Skinnider, Achilleas Laskaratos, Steven Ceto, Claudia Kathe, Thomas Hutson, Rebecca Charbonneau, Fady Girgis, Steve Casha, Julien Rimok, Marcus Tso, Kelly Larkin-Kaiser, Nicolas Hankov, Aasta Gandhi, Suje Amir, Xiaoyang Kang, Yashwanth Vyza, Eduardo Martin-Moraud, Stephanie Lacour, Robin Demesmaeker, Leonie Asboth, Quentin Barraud, Mark A. Anderson, Jocelyne Bloch, Jordan W. Squair, Aaron A. Phillips, Gregoire Courtine
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Autonomic dysreflexia is a life-threatening medical condition characterized by episodes of uncontrolled hypertension that occur in response to sensory stimuli after spinal cord injury (SCI)1. The fragmented understanding of the mechanisms underlying autonomic dysreflexia hampers the development of therapeutic strategies to manage this condition, leaving people with SCI at daily risk of heart attack and stroke2,3,4,5. Here we expose the neuronal architecture that develops after SCI and causes autonomic dysreflexia. In parallel, we uncover a competing, yet overlapping neuronal architecture activated by epidural electrical stimulation of the spinal cord that safely regulates blood pressure after SCI. The discovery that these adversarial neuronal architectures converge onto a single neuronal subpopulation provided a blueprint for the design of a mechanism-based intervention that reversed autonomic dysreflexia in mice, rats and humans with SCI. These results establish a path towards essential pivotal device clinical trials that will establish the safety and efficacy of epidural electrical stimulation for the effective treatment of autonomic dysreflexia in people with SCI.
GPT-4o mini: Non-social science research article
Addressing the safety of next-generation batteries
Chuanbo Yang, Avtar Singh, Xiaofei Pu, Anudeep Mallarapu, Kandler Smith, Matt Keyser, Michael R. Haberman, Hadi Khani, Pawel Misztal, Ryan Spray, Ofodike A. Ezekoye, Donal P. Finegan
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Owing to increasing demand for low-cost energy storage with secure material supply chains, the battery community is approaching a pivotal shift beyond conventional lithium-ion (Li-ion) towards next-generation cells. Technologies that include alkali-metal anodes, solid electrolytes and earth-abundant materials such as sodium (Na) and sulfur (S) are reaching commercialization in cells. The abuse tolerance and thermal runaway hazards of such technologies diverge from conventional Li-ion cells. Consequently, designing safe batteries with next-generation materials requires a holistic approach to characterize cells and to understand their responses to abuse conditions from the beginning to the end of life. Here we provide a Perspective on how the safety and abuse tolerance of cells are likely to change for up-and-coming technologies; challenges and opportunities for reimagining safe cell and battery designs; gaps in our knowledge; capabilities for understanding the hazards of thermal runaway and how to address them; how standard abuse tests may need to adapt to new challenges; and how research needs to support affected professionals, from pack designers to first responders, to manage hazards and ensure safe roll-out of next-generation cells into applications like electric vehicles (EVs). Finally, given the large number of next-generation technologies being explored, we encourage giving priority to safety-focused research in proportion to the rate of manufacturing scale-up of each specific technology.
GPT-4o mini: Non-social science research article
Stratified wind from a super-Eddington X-ray binary is slower than expected
character(0), Marc Audard, Hisamitsu Awaki, Ralf Ballhausen, Aya Bamba, Ehud Behar, Rozenn Boissay-Malaquin, Laura Brenneman, Gregory V. Brown, Lia Corrales, Elisa Costantini, Renata Cumbee, MarĂ­a DĂ­az Trigo, Chris Done, Tadayasu Dotani, Ken Ebisawa, Megan Eckart, Dominique Eckert, Teruaki Enoto, Satoshi Eguchi, Yuichiro Ezoe, Adam Foster, Ryuichi Fujimoto, Yutaka Fujita, Yasushi Fukazawa, Kotaro Fukushima, Akihiro Furuzawa, Luigi Gallo, Javier A. GarcĂ­a, Liyi Gu, Matteo Guainazzi, Kouichi Hagino, Kenji Hamaguchi, Isamu Hatsukade, Katsuhiro Hayashi, Takayuki Hayashi, Natalie Hell, Edmund Hodges-Kluck, Ann Hornschemeier, Yuto Ichinohe, Manabu Ishida, Kumi Ishikawa, Yoshitaka Ishisaki, Jelle Kaastra, Timothy Kallman, Erin Kara, Satoru Katsuda, Yoshiaki Kanemaru, Richard Kelley, Caroline Kilbourne, Shunji Kitamoto, Shogo Kobayashi, Takayoshi Kohmura, Aya Kubota, Maurice Leutenegger, Michael Loewenstein, Yoshitomo Maeda, Maxim Markevitch, Hironori Matsumoto, Kyoko Matsushita, Dan McCammon, Brian McNamara, François Mernier, Eric D. Miller, Jon M. Miller, Ikuyuki Mitsuishi, Misaki Mizumoto, Tsunefumi Mizuno, Koji Mori, Koji Mukai, Hiroshi Murakami, Richard Mushotzky, Hiroshi Nakajima, Kazuhiro Nakazawa, Jan-Uwe Ness, Kumiko Nobukawa, Masayoshi Nobukawa, Hirofumi Noda, Hirokazu Odaka, Shoji Ogawa, Anna Ogorzalek, Takashi Okajima, Naomi Ota, Stephane Paltani, Robert Petre, Paul Plucinsky, Frederick Scott Porter, Katja Pottschmidt, Kosuke Sato, Toshiki Sato, Makoto Sawada, Hiromi Seta, Megumi Shidatsu, Aurora Simionescu, Randall Smith, Hiromasa Suzuki, Andrew Szymkowiak, Hiromitsu Takahashi, Mai Takeo, Toru Tamagawa, Keisuke Tamura, Takaaki Tanaka, Atsushi Tanimoto, Makoto Tashiro, Yukikatsu Terada, Yuichi Terashima, Yohko Tsuboi, Masahiro Tsujimoto, Hiroshi Tsunemi, Takeshi G. Tsuru, AysegĂŒl TĂŒmer, Hiroyuki Uchida, Nagomi Uchida, Yuusuke Uchida, Hideki Uchiyama, Yoshihiro Ueda, Shinichiro Uno, Jacco Vink, Shin Watanabe, Brian J. Williams, Satoshi Yamada, Shinya Yamada, Hiroya Yamaguchi, Kazutaka Yamaoka, Noriko Yamasaki, Makoto Yamauchi, Shigeo Yamauchi, Tahir Yaqoob, Tomokage Yoneyama, Tessei Yoshida, Mihoko Yukita, Irina Zhuravleva, Joey Neilsen, Ryota Tomaru, Missagh Mehdipour
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Accretion disks in strong gravity ubiquitously produce winds, seen as blueshifted absorption lines in the X-ray band of both stellar mass X-ray binaries (black holes and neutron stars) 1–4 and supermassive black holes 5 . Some of the most powerful winds (termed Eddington winds) are expected to arise from systems in which radiation pressure is sufficient to unbind material from the inner disk ( L ≳ L Edd ). These winds should be extremely fast and carry a large amount of kinetic power, which, when associated with supermassive black holes, would make them a prime contender for the feedback mechanism linking the growth of those black holes with their host galaxies 6 . Here we show the XRISM Resolve spectrum of the galactic neutron star X-ray binary, GX 13+1, which reveals one of the densest winds ever seen in absorption lines. This Compton-thick wind significantly attenuates the flux, making it appear faint, although it is intrinsically more luminous than usual ( L ≳ L Edd ). However, the wind is extremely slow, more consistent with the predictions of thermal-radiative winds launched by X-ray irradiation of the outer disk than with the expected Eddington wind driven by radiation pressure from the inner disk. This puts new constraints on the origin of winds from bright accretion flows in binaries, but also highlights the very different origin required for the ultrafast ( v ~ 0.3 c ) winds seen in recent Resolve observations of a supermassive black hole at a similarly high Eddington ratio 7 .
GPT-4o mini: Non-social science research article
CRISPR activation for SCN2A-related neurodevelopmental disorders
Serena Tamura, Andrew D. Nelson, Perry W. E. Spratt, Elizabeth C. Hamada, Xujia Zhou, Henry Kyoung, Zizheng Li, Coline Arnould, Vladyslav Barskyi, Beniamin Krupkin, Kiana Young, Jingjing Zhao, Stephanie S. Holden, Atehsa Sahagun, Caroline M. Keeshen, Congyi Lu, Roy Ben-Shalom, Sunrae E. Taloma, Selin Schamiloglu, Ying C. Li, Lia Min, Paul M. Jenkins, Jen Q. Pan, Jeanne T. Paz, Stephan J. Sanders, Navneet Matharu, Nadav Ahituv, Kevin J. Bender
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Most neurodevelopmental disorders with single gene diagnoses act via haploinsufficiency, in which only one of the two gene copies is functional1. SCN2A haploinsufficiency is one of the most frequent causes of neurodevelopmental disorder, often presenting with autism spectrum disorder, intellectual disability and, in a subset of children, refractory epilepsy2. Here, using SCN2A haploinsufficiency as a proof-of-concept, we show that upregulation of the existing functional gene copy through CRISPR activation (CRISPRa) can rescue neurological-associated phenotypes in Scn2a haploinsufficient mice. We first show that restoring Scn2a expression in adolescent heterozygous Scn2a conditional knock-in mice rescues electrophysiological deficits associated with Scn2a haploinsufficiency (Scn2a+/−). Next, using an adeno-associated virus CRISPRa-based treatment in adolescent mice, we show that we can correct intrinsic and synaptic deficits in neocortical pyramidal cells, a major cell type that contributes to neurodevelopmental disorders and seizure aetiology in SCN2A haploinsufficiency. Furthermore, we find that systemic delivery of CRISPRa protects Scn2a+/− mice against chemoconvulsant-induced seizures. Finally, we also show that adeno-associated virus CRISPRa treatment rescues excitability in SCN2A haploinsufficient human stem-cell-derived neurons. Our results showcase the potential of this therapeutic approach to rescue SCN2A haploinsufficiency and demonstrates that rescue even at adolescent stages can ameliorate neurodevelopmental phenotypes.
GPT-4o mini: Non-social science research article
Reduced Atlantic reef growth past 2 °C warming amplifies sea-level impacts
Chris T. Perry, Didier M. de Bakker, Alice E. Webb, Steeve Comeau, Ben P. Harvey, Christopher E. Cornwall, Lorenzo Alvarez-Filip, Esmeralda PĂ©rez-Cervantes, John Morris, Ian C. Enochs, Lauren T. Toth, Aaron O’Dea, Erin M. Dillon, Erik H. Meesters, William F. Precht
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Coral reefs form complex physical structures that can help to mitigate coastal flooding risk 1,2 . This function will be reduced by sea-level rise (SLR) and impaired reef growth caused by climate change and local anthropogenic stressors 3 . Water depths above reef surfaces are projected to increase as a result, but the magnitudes and timescales of this increase are poorly constrained, which limits modelling of coastal vulnerability 4,5 . Here we analyse fossil reef deposits to constrain links between reef ecology and growth potential across more than 400 tropical western Atlantic sites, and assess the magnitudes of resultant above-reef increases in water depth through to 2100 under various shared socioeconomic pathway (SSP) emission scenarios. Our analysis predicts that more than 70% of tropical western Atlantic reefs will transition into net erosional states by 2040, but that if warming exceeds 2 °C (SSP2–4.5 and higher), nearly all reefs (at least 99%) will be eroding by 2100. The divergent trajectories of reef growth and SLR will thus magnify the effects of SLR; increases in water depth of around 0.3–0.5 m above the present are projected under all warming scenarios by 2060, but depth increases of 0.7–1.2 m are predicted by 2100 under scenarios in which warming surpasses 2 °C. This would increase the risk of flooding along vulnerable reef-fronted coasts and modify nearshore hydrodynamics and ecosystems. Reef restoration offers one pathway back to higher reef growth 6,7 , but would dampen the effects of SLR in 2100 only by around 0.3–0.4 m, and only when combined with aggressive climate mitigation.
GPT-4o mini: Non-social science research article
Structural basis for mTORC1 activation on the lysosomal membrane
Zhicheng Cui, Alessandra Esposito, Gennaro Napolitano, Andrea Ballabio, James H. Hurley
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The mechanistic target of rapamycin complex 1 (mTORC1) integrates growth factor (GF) and nutrient signals to stimulate anabolic processes connected to cell growth and inhibit catabolic processes such as autophagy 1,2 . GF signalling through the tuberous sclerosis complex regulates the lysosomally localized small GTPase RAS homologue enriched in brain (RHEB) 3 . Direct binding of RHEB–GTP to the mTOR kinase subunit of mTORC1 allosterically activates the kinase by inducing a large-scale conformational change 4 . Here we reconstituted mTORC1 activation on membranes by RHEB, RAGs and Ragulator. Cryo-electron microscopy showed that RAPTOR and mTOR interact directly with the membrane. Full engagement of the membrane anchors is required for optimal alignment of the catalytic residues in the mTOR kinase active site. Converging signals from GFs and nutrients drive mTORC1 recruitment to and activation on lysosomal membrane in a four-step process, consisting of (1) RAG–Ragulator-driven recruitment to within ~100 Å of the lysosomal membrane; (2) RHEB-driven recruitment to within ~40 Å; (3) RAPTOR–membrane engagement and intermediate enzyme activation; and (4) mTOR–membrane engagement and full enzyme activation. RHEB and membrane engagement combined leads to full catalytic activation and structurally explains GF and nutrient signal integration at the lysosome.
GPT-4o mini: Non-social science research article
DeepSeek-R1 incentivizes reasoning in LLMs through reinforcement learning
Daya Guo, Dejian Yang, Haowei Zhang, Junxiao Song, Peiyi Wang, Qihao Zhu, Runxin Xu, Ruoyu Zhang, Shirong Ma, Xiao Bi, Xiaokang Zhang, Xingkai Yu, Yu Wu, Z. F. Wu, Zhibin Gou, Zhihong Shao, Zhuoshu Li, Ziyi Gao, Aixin Liu, Bing Xue, Bingxuan Wang, Bochao Wu, Bei Feng, Chengda Lu, Chenggang Zhao, Chengqi Deng, Chong Ruan, Damai Dai, Deli Chen, Dongjie Ji, Erhang Li, Fangyun Lin, Fucong Dai, Fuli Luo, Guangbo Hao, Guanting Chen, Guowei Li, H. Zhang, Hanwei Xu, Honghui Ding, Huazuo Gao, Hui Qu, Hui Li, Jianzhong Guo, Jiashi Li, Jingchang Chen, Jingyang Yuan, Jinhao Tu, Junjie Qiu, Junlong Li, J. L. Cai, Jiaqi Ni, Jian Liang, Jin Chen, Kai Dong, Kai Hu, Kaichao You, Kaige Gao, Kang Guan, Kexin Huang, Kuai Yu, Lean Wang, Lecong Zhang, Liang Zhao, Litong Wang, Liyue Zhang, Lei Xu, Leyi Xia, Mingchuan Zhang, Minghua Zhang, Minghui Tang, Mingxu Zhou, Meng Li, Miaojun Wang, Mingming Li, Ning Tian, Panpan Huang, Peng Zhang, Qiancheng Wang, Qinyu Chen, Qiushi Du, Ruiqi Ge, Ruisong Zhang, Ruizhe Pan, Runji Wang, R. J. Chen, R. L. Jin, Ruyi Chen, Shanghao Lu, Shangyan Zhou, Shanhuang Chen, Shengfeng Ye, Shiyu Wang, Shuiping Yu, Shunfeng Zhou, Shuting Pan, S. S. Li, Shuang Zhou, Shaoqing Wu, Tao Yun, Tian Pei, Tianyu Sun, T. Wang, Wangding Zeng, Wen Liu, Wenfeng Liang, Wenjun Gao, Wenqin Yu, Wentao Zhang, W. L. Xiao, Wei An, Xiaodong Liu, Xiaohan Wang, Xiaokang Chen, Xiaotao Nie, Xin Cheng, Xin Liu, Xin Xie, Xingchao Liu, Xinyu Yang, Xinyuan Li, Xuecheng Su, Xuheng Lin, X. Q. Li, Xiangyue Jin, Xiaojin Shen, Xiaosha Chen, Xiaowen Sun, Xiaoxiang Wang, Xinnan Song, Xinyi Zhou, Xianzu Wang, Xinxia Shan, Y. K. Li, Y. Q. Wang, Y. X. Wei, Yang Zhang, Yanhong Xu, Yao Li, Yao Zhao, Yaofeng Sun, Yaohui Wang, Yi Yu, Yichao Zhang, Yifan Shi, Yiliang Xiong, Ying He, Yishi Piao, Yisong Wang, Yixuan Tan, Yiyang Ma, Yiyuan Liu, Yongqiang Guo, Yuan Ou, Yuduan Wang, Yue Gong, Yuheng Zou, Yujia He, Yunfan Xiong, Yuxiang Luo, Yuxiang You, Yuxuan Liu, Yuyang Zhou, Y. X. Zhu, Yanping Huang, Yaohui Li, Yi Zheng, Yuchen Zhu, Yunxian Ma, Ying Tang, Yukun Zha, Yuting Yan, Z. Z. Ren, Zehui Ren, Zhangli Sha, Zhe Fu, Zhean Xu, Zhenda Xie, Zhengyan Zhang, Zhewen Hao, Zhicheng Ma, Zhigang Yan, Zhiyu Wu, Zihui Gu, Zijia Zhu, Zijun Liu, Zilin Li, Ziwei Xie, Ziyang Song, Zizheng Pan, Zhen Huang, Zhipeng Xu, Zhongyu Zhang, Zhen Zhang
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General reasoning represents a long-standing and formidable challenge in artificial intelligence (AI). Recent breakthroughs, exemplified by large language models (LLMs) 1,2 and chain-of-thought (CoT) prompting 3 , have achieved considerable success on foundational reasoning tasks. However, this success is heavily contingent on extensive human-annotated demonstrations and the capabilities of models are still insufficient for more complex problems. Here we show that the reasoning abilities of LLMs can be incentivized through pure reinforcement learning (RL), obviating the need for human-labelled reasoning trajectories. The proposed RL framework facilitates the emergent development of advanced reasoning patterns, such as self-reflection, verification and dynamic strategy adaptation. Consequently, the trained model achieves superior performance on verifiable tasks such as mathematics, coding competitions and STEM fields, surpassing its counterparts trained through conventional supervised learning on human demonstrations. Moreover, the emergent reasoning patterns exhibited by these large-scale models can be systematically used to guide and enhance the reasoning capabilities of smaller models.
GPT-4o mini: Non-social science research article
Publisher Correction: Experimental determination of partial charges with electron diffraction
Soheil Mahmoudi, Tim Gruene, Christian Schröder, Khalil D. Ferjaoui, Erik Fröjdh, Aldo Mozzanica, Kiyofumi Takaba, Anatoliy Volkov, Julian Maisriml, Vladimir Paunović, Jeroen A. van Bokhoven, Bernhard K. Keppler
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GPT-4o mini: Non-social science research article
Atomic-scale imaging of frequency-dependent phonon anisotropy
Xingxu Yan, Paul M. Zeiger, Yifeng Huang, Haoying Sun, Jie Li, Chaitanya A. Gadre, Hongbin Yang, Ri He, Toshihiro Aoki, Zhicheng Zhong, Yuefeng Nie, Ruqian Wu, JĂĄn Rusz, Xiaoqing Pan
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Directly visualizing vibrational anisotropy in individual phonon modes is essential for understanding a wide range of intriguing optical, thermal and elastic phenomena in materials1,2,3,4,5. Although conventional optical and diffraction techniques have been used to estimate vibrational anisotropies, they fall short in achieving the spatial and energy resolution necessary to provide detailed information4,5,6,7. Here, we introduce a new form of momentum-selective electron energy-loss spectroscopy, which enables the element-resolved imaging of frequency- and symmetry-dependent vibrational anisotropies with atomic resolution. Vibrational anisotropies manifest in different norms of orthogonal atomic displacements, known as thermal ellipsoids. Using the centrosymmetric strontium titanate as a model system, we observed two distinct types of oxygen vibrations with contrasting anisotropies: oblate thermal ellipsoids below 60 meV and prolate ones above 60 meV. In non-centrosymmetric barium titanate, our approach can detect subtle distortions of the oxygen octahedra by observing the unexpected modulation of q-selective signals between apical and equatorial oxygen sites near 55 meV, which originates from reduced crystal symmetry and may also be linked to ferroelectric polarization. These observations are quantitatively supported by theoretical modelling, which demonstrates the reliability of our approach. The measured frequency-dependent vibrational anisotropies shed new light on the dielectric and thermal behaviours governed by acoustic and optical phonons. The ability to visualize phonon eigenvectors at specific crystallographic sites with unprecedented spatial and energy resolution opens new avenues for exploring dielectric, optical, thermal and superconducting properties.
GPT-4o mini: Non-social science research article
Author Correction: A Ctf4 trimer couples the CMG helicase to DNA polymerase α in the eukaryotic replisome
Aline C. Simon, Jin C. Zhou, Rajika L. Perera, Frederick van Deursen, Cecile Evrin, Marina E. Ivanova, Mairi L. Kilkenny, Ludovic Renault, Svend Kjaer, Dijana Matak-Vinković, Karim Labib, Alessandro Costa, Luca Pellegrini
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GPT-4o mini: Non-social science research article
Wildfire smoke exposure and mortality burden in the US under climate change
Minghao Qiu, Jessica Li, Carlos F. Gould, Renzhi Jing, Makoto Kelp, Marissa L. Childs, Jeff Wen, Yuanyu Xie, Meiyun Lin, Mathew V. Kiang, Sam Heft-Neal, Noah S. Diffenbaugh, Marshall Burke
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Wildfire activity has increased in the US and is projected to accelerate under future climate change 1–3. However, our understanding of the impacts of climate change on wildfire activity, smoke, and health outcomes remains highly uncertain, due to the difficulty of modeling the causal chain from climate to wildfire to air pollution and health. Here we quantify the mortality burden in the US due to wildfire smoke fine particulate matter (PM2.5) under climate change. We construct an ensemble of statistical and machine learning models that link climate to wildfire smoke PM2.5, and empirically estimate smoke PM2.5-mortality relationships using data on all recorded deaths in the US. We project that smoke PM2.5 could result in 71,420 excess deaths (95% CI: 34,930 - 98,430) per year by 2050 under a high warming scenario (SSP3-7.0) – a 73% increase relative to estimated 2011-2020 average annual excess deaths from smoke. Cumulative excess deaths from smoke PM2.5 could reach 1.9 million between 2026-2055. We find evidence for mortality impacts of smoke PM2.5 that last up to three years after exposure. When monetized, climate-driven smoke deaths result in economic damages that exceed existing estimates of climate-driven damages from all other causes combined in the US 4,5. Our research suggests that the health impacts of climate-driven wildfire smoke could be among the most important and costly consequences of a warming climate in the US.
GPT-4o mini: Non-social science research article
Myeloperoxidase transforms chromatin into neutrophil extracellular traps
Garth Lawrence Burn, Tobias Raisch, Sebastian Tacke, Moritz Winkler, Daniel Prumbaum, Stephanie Thee, Niclas Gimber, Stefan Raunser, Arturo Zychlinsky
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Neutrophils, the most abundant and biotoxic immune cells, extrude nuclear DNA into the extracellular space to maintain homeostasis. Termed neutrophil extracellular traps (NETs), these protein-modified and decondensed extracellular DNA scaffolds control infection and are involved in coagulation, autoimmunity and cancer 1,2 . Here we show how myeloperoxidase (MPO), a highly expressed neutrophil protein, disassembles nucleosomes, thereby facilitating NET formation, yet also binds stably to NETs extracellularly. We describe how the oligomeric status of MPO governs both outcomes. MPO dimers interact with nucleosomal DNA using one protomer and concurrently dock into the nucleosome acidic patch with the other protomer. As a consequence, dimeric MPO displaces DNA from the core complex, culminating in nucleosome disassembly. On the other hand, MPO monomers stably interact with the nucleosome acidic patch without making concomitant DNA contacts, explaining how monomeric MPO binds to and licences NETs to confer hypohalous acid production in the extracellular space 3 . Our data demonstrate that the binding of MPO to chromatin is governed by specific molecular interactions that transform chromatin into a non-replicative, non-encoding state that offers new biological functions in a cell-free manner. We propose that MPO is, to our knowledge, the first member of a class of proteins that convert chromatin into an immune effector.
GPT-4o mini: Non-social science research article
Transitions in dynamical regime and neural mode during perceptual decisions
Thomas Zhihao Luo, Timothy Doyeon Kim, Diksha Gupta, Adrian G. Bondy, Charles D. Kopec, Verity A. Elliott, Brian DePasquale, Carlos D. Brody
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Perceptual decision-making is thought to be mediated by neuronal networks with attractor dynamics 1,2 . However, the dynamics underlying the complex neuronal responses during decision-making remain unclear. Here we use simultaneous recordings of hundreds of neurons, combined with an unsupervised, deep-learning-based method, to discover decision-related neural dynamics in the rat frontal cortex and striatum as animals accumulate pulsatile auditory evidence. We found that trajectories evolved along two sequential regimes: an initial phase dominated by sensory inputs, followed by a phase dominated by autonomous dynamics, with the flow direction (that is, neural mode) largely orthogonal to that in the first regime. We propose that this transition marks the moment of decision commitment, that is, the time when the animal makes up its mind. To test this, we developed a simplified model of the dynamics to estimate a putative neurally inferred time of commitment (nTc) for each trial. This model captures diverse single-neuron temporal profiles, such as ramping and stepping 3,4 . The estimated nTc values were not time locked to stimulus or response timing but instead varied broadly across trials. If nTc marks commitment, evidence before this point should affect the decision, whereas evidence afterwards should not. Behavioural analysis aligned to nTc confirmed this prediction. Our findings show that decision commitment involves a rapid, coordinated transition in dynamical regime and neural mode and suggest that nTc offers a useful neural marker for studying rapid changes in internal brain state.
GPT-4o mini: Non-social science research article
Publisher Correction: TCF1 and LEF1 promote B-1a cell homeostasis and regulatory function
Qian Shen, Hao Wang, Jonathan A. Roco, Xiangpeng Meng, Marita Bosticardo, Marie Hodges, Michael Battaglia, Zhi-Ping Feng, Benjamin James Talks, Jason Powell, Vijaya Baskar Mahalingam Shanmugiah, Julia Chu, Najib M. Rahman, Alguili Elsheikh, Probir Chakravarty, Amalie Grenov, Max Emmerich, Ottavia M. Delmonte, Alexandra F. Freeman, Michael D. Keller, Brahim Belaid, Ilenia Papa, James C. Lee, Pablo F. Cañete, Paula Gonzalez-Figueroa, Yaoyuan Zhang, Hai-Hui Xue, Samra Turajlic, Luigi D. Notarangelo, Muzlifah Haniffa, Lee Ann Garrett-Sinha, Helen M. Parry, Nikolaos I. Kanellakis, Carola G. Vinuesa
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GPT-4o mini: Non-social science research article
Continuous operation of a coherent 3,000-qubit system
Neng-Chun Chiu, Elias C. Trapp, Jinen Guo, Mohamed H. Abobeih, Luke M. Stewart, Simon Hollerith, Pavel L. Stroganov, Marcin Kalinowski, Alexandra A. Geim, Simon J. Evered, Sophie H. Li, Xingjian Lyu, Lisa M. Peters, Dolev Bluvstein, Tout T. Wang, Markus Greiner, Vladan Vuletić, Mikhail D. Lukin
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Neutral atoms are a promising platform for quantum science, enabling advances in areas ranging from quantum simulations1−3 and computation4−10 to metrology, atomic clocks11−13 and quantum networking14−16. While atom losses typically limit these systems to a pulsed mode, continuous operation17−22 could significantly enhance cycle rates, remove bottlenecks in metrology23, and enable deep-circuit quantum evolution through quantum error correction24,25. Here we demonstrate an experimental architecture for high-rate reloading and continuous operation of a large-scale atom array system while realizing coherent storage and manipulation of quantum information. Our approach utilizes a series of two optical lattice conveyor belts to transport atom reservoirs into the science region, where atoms are repeatedly extracted into optical tweezers without affecting the coherence of qubits stored nearby. Using a reloading rate of 300,000 atoms in tweezers per second, we create over 30,000 initialized qubits per second, which we leverage to assemble and maintain an array of over 3,000 atoms for more than two hours. Furthermore, we demonstrate persistent refilling of the array with atomic qubits in either a spin-polarized or a coherent superposition state while preserving the quantum state of stored qubits. Our results pave the way for realization of large-scale continuously operated atomic clocks, sensors, and fault-tolerant quantum computers.
GPT-4o mini: Non-social science research article
Delta-type glutamate receptors are ligand-gated ion channels
Haobo Wang, Fairine Ahmed, Jeffrey Khau, Anish Kumar Mondal, Edward C. Twomey
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Delta-type ionotropic glutamate receptors (iGluRs), or GluDs, are members of the iGluR ligand-gated ion channel family, yet their function remains enigmatic1. Although GluDs are widely expressed in the brain, play key roles in synaptic organization, and harbor disease-linked mutations, whether they retain iGluR-like channel function is debated as currents have not been directly observed2,3. Here, we define GluDs as ligand-gated ion channels that are tightly regulated in cellular contexts by purifying human GluD2 (hGluD2) and directly characterizing its structure and function using cryo-electron microscopy (cryoEM) and bilayer recordings. We show that hGluD2 is activated by D-serine and Îł-aminobutyric acid (GABA), with augmented activation at physiological temperatures. We reveal that hGluD2 contains an ion channel directly coupled to clamshell-like ligand-binding domains (LBDs), which are coordinated by the amino terminal domain (ATD) above the ion channel. Ligand binding triggers channel opening via an asymmetric mechanism, and a cerebellar ataxia point mutation in the LBD rearranges the receptor architecture and induces leak currents. Our findings demonstrate that GluDs possess the intrinsic biophysical properties of ligand-gated ion channels, reconciling prior conflicting observations to establish a framework for understanding their cellular regulation and for developing therapies targeting GluD2.
GPT-4o mini: Non-social science research article
Basal cell of origin resolves neuroendocrine–tuft lineage plasticity in cancer
Abbie S. Ireland, Daniel A. Xie, Sarah B. Hawgood, Margaret W. Barbier, Lisa Y. Zuo, Benjamin E. Hanna, Scarlett Lucas-Randolph, Darren R. Tyson, Benjamin L. Witt, Ramaswamy Govindan, Afshin Dowlati, Justin C. Moser, Anish Thomas, Sonam Puri, Charles M. Rudin, Joseph M. Chan, Andrew Elliott, Trudy G. Oliver
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Neuroendocrine and tuft cells are rare chemosensory epithelial lineages defined by the expression of ASCL1 and POU2F3 transcription factors, respectively. Neuroendocrine cancers, including small cell lung cancer (SCLC), frequently display tuft-like subsets, a feature linked to poor patient outcomes1,2,3,4,5,6,7,8,9. The mechanisms driving neuroendocrine–tuft tumour heterogeneity and the origins of tuft-like cancers are unknown. Using multiple genetically engineered animal models of SCLC, we demonstrate that a basal cell of origin (but not the accepted neuroendocrine origin) generates neuroendocrine–tuft-like tumours that highly recapitulate human SCLC. Single-cell clonal analyses of basal-derived SCLC further uncovered unexpected transcriptional states, including an Atoh1+ state, and lineage trajectories underlying neuroendocrine–tuft plasticity. Uniquely in basal cells, the introduction of genetic alterations enriched in human tuft-like SCLC, including high MYC, PTEN loss and ASCL1 suppression, cooperates to promote tuft-like tumours. Transcriptomics of 944 human SCLCs revealed a basal-like subset and a tuft–ionocyte-like state that altogether demonstrate notable conservation between cancer states and normal basal cell injury response mechanisms10,11,12,13. Together, these data indicate that the basal cell is a probable origin for SCLC and other neuroendocrine–tuft cancers that can explain neuroendocrine–tuft heterogeneity, offering new insights for targeting lineage plasticity.
GPT-4o mini: Non-social science research article
A movable long-term implantable soft microfibre for dynamic bioelectronics
Ruijie Xie, Fei Han, Qianhengyuan Yu, Dong Li, Xu Han, Xiaolong Xu, Huan Yu, Jianping Huang, Xiaomeng Zhou, Hang Zhao, Xinping Deng, Qiong Tian, Qingsong Li, Hanfei Li, Yang Zhao, Guoyao Ma, Guanglin Li, Hairong Zheng, Meifang Zhu, Wei Yan, Tiantian Xu, Zhiyuan Liu
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Long-term implantable bioelectronics offer a powerful means to evaluate the function of the nervous system and serve as effective human–machine interfaces1,2,3. Here, inspired by earthworms, we introduce NeuroWorm—a soft, stretchable and movable fibre sensor designed for bioelectronic interface. Our approach involves rolling to transform 2D bioelectronic devices into 1D NeuroWorm, creating a multifunctional microfibre that houses longitudinally distributed electrode arrays for both bioelectrical and biomechanical monitoring. NeuroWorm effectively records high-quality spatio-temporal signals in situ while steerably advancing within the brain or on the muscle as needed. This allows for the dynamic targeting and shifting of desired monitoring sites. Implanted in muscle through a tiny incision, NeuroWorm provides stable bioelectrical monitoring in rats for more than 43 weeks. Even after 54 weeks of implantation in muscle, fibroblast encapsulation around the fibre remains negligible. Our NeuroWorm represents a platform that promotes a substantial advance in bioelectronics—from an immobile probe fixed in place to active, intelligent and living devices for long-term, minimally invasive and mobile evaluation of the nervous system.
GPT-4o mini: Non-social science research article
Co-option of an ancestral cloacal regulatory landscape during digit evolution
Aurélie Hintermann, Christopher C. Bolt, M. Brent Hawkins, Guillaume Valentin, Lucille Lopez-Delisle, Madeline M. Ryan, Sandra Gitto, Paula Barrera Gómez, Bénédicte Mascrez, Thomas A. Mansour, Tetsuya Nakamura, Matthew P. Harris, Neil H. Shubin, Denis Duboule
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The fin-to-limb transition in vertebrate evolution has been central to the study of how development underlies evolutionary change. In this context, the functional analysis of Hox gene regulation to infer evolutionary trajectories has been critical to explain the origin of new features. In tetrapods, the transcription of Hoxd genes in developing digits depends on a set of enhancers forming a large regulatory landscape1,2. The presence of a syntenic counterpart in zebrafish, which lacks digits, suggests deep homology3 or shared developmental foundations underlying distal fin and limbs. However, how this regulatory program evolved has remained unresolved. We genetically evaluated the function of the zebrafish Hoxd regulatory landscapes by comparatively assessing the effects of their full deletions. We show that, unlike in mice, deletion of these regions in fish does not disrupt hoxd gene transcription during distal fin development. By contrast, we found that this deficiency leads to the loss of expression within the cloaca, a structure related by ancestry to the mammalian urogenital sinus, and that distal hox13 genes are essential for correct cloacal formation. Because Hoxd gene regulation in the mouse urogenital sinus relies on enhancers located in this same chromatin domain that controls digit development, we propose that the current regulatory landscape active in distal limbs was co-opted as a whole in tetrapods from a pre-existing cloacal regulatory machinery.
GPT-4o mini: Non-social science research article
Peroxisomal metabolism of branched fatty acids regulates energy homeostasis
Xuejing Liu, Anyuan He, Dongliang Lu, Donghua Hu, Min Tan, Abenezer Abere, Parniyan Goodarzi, Bilal Ahmad, Brian Kleiboeker, Brian N. Finck, Mohamed Zayed, Katsuhiko Funai, Jonathan R. Brestoff, Ali Javaheri, Patricia Weisensee, Bettina Mittendorfer, Fong-Fu Hsu, Paul P. Van Veldhoven, Babak Razani, Clay F. Semenkovich, Irfan J. Lodhi
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Brown and beige adipocytes express uncoupling protein 1 (UCP1), a mitochondrial protein that dissociates respiration from ATP synthesis and promotes heat production and energy expenditure. However, UCP1−/− mice are not obese1,2,3,4,5, consistent with the existence of alternative mechanisms of thermogenesis6,7,8. Here we describe a UCP1-independent mechanism of thermogenesis involving ATP-consuming metabolism of monomethyl branched-chain fatty acids (mmBCFA) in peroxisomes. These fatty acids are synthesized by fatty acid synthase using precursors derived from catabolism of branched-chain amino acids9 and our results indicate that ÎČ-oxidation of mmBCFAs is mediated by the peroxisomal protein acyl-CoA oxidase 2 (ACOX2). Notably, cold exposure upregulated proteins involved in both biosynthesis and ÎČ-oxidation of mmBCFA in thermogenic fat. Acute thermogenic stimuli promoted translocation of fatty acid synthase to peroxisomes. Brown-adipose-tissue-specific fatty acid synthase knockout decreased cold tolerance. Adipose-specific ACOX2 knockout also impaired cold tolerance and promoted diet-induced obesity and insulin resistance. Conversely, ACOX2 overexpression in adipose tissue enhanced thermogenesis independently of UCP1 and improved metabolic homeostasis. Using a peroxisome-localized temperature sensor named Pexo-TEMP, we found that ACOX2-mediated fatty acid ÎČ-oxidation raised intracellular temperature in brown adipocytes. These results identify a previously unrecognized role for peroxisomes in adipose tissue thermogenesis characterized by an mmBCFA synthesis and catabolism cycle.
GPT-4o mini: Non-social science research article
A domed pachycephalosaur from the early Cretaceous of Mongolia
Tsogtbaatar Chinzorig, Ryuji Takasaki, Junki Yoshida, Ryan T. Tucker, Batsaikhan Buyantegsh, Buuvei Mainbayar, Khishigjav Tsogtbaatar, Lindsay E. Zanno
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The dome-headed pachycephalosaurians are among the most enigmatic dinosaurs. Bearing a hypertrophied skull roof and elaborate cranial ornamentation, members of the clade are considered to have evolved complex sociosexual systems1,2,3. Despite their importance in understanding behavioural ecology in Dinosauria, the absence of uncontested early diverging taxa has hindered our ability to reconstruct the origin and early evolution of the clade4,5,6,7. Here we describe Zavacephale rinpoche gen. et sp. nov., from the Lower Cretaceous Khuren Dukh Formation of Mongolia, the most skeletally complete and geologically oldest pachycephalosaurian discovered globally. Z. rinpoche exhibits a well-developed frontoparietal dome and preserves the clade’s first record of manual elements and gastroliths. Phylogenetic analysis recovered Z. rinpoche as one of the earliest diverging pachycephalosaurians, pushing back fossil evidence of the frontoparietal dome by at least 14 Myr and clarifying macroevolutionary trends in its assembly. We found that the earliest stage of dome evolution occurred by means of a frontal-first developmental pattern with retention of open supratemporal fenestra, mirroring proposed ontogenetic trajectories in some Late Cretaceous taxa. Finally, intraskeletal osteohistology of the frontoparietal dome and hindlimb demonstrate decoupling of sociosexual and somatic maturity in early pachycephalosaurians, with advanced dome development preceding terminal body size.
GPT-4o mini: Non-social science research article
Analogue speech recognition based on physical computing
Mohamadreza Zolfagharinejad, Julian BĂŒchel, Lorenzo Cassola, Sachin Kinge, Ghazi Sarwat Syed, Abu Sebastian, Wilfred G. van der Wiel
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With the rise of decentralized computing, such as in the Internet of Things, autonomous driving and personalized healthcare, it is increasingly important to process time-dependent signals ‘at the edge’ efficiently: right at the place where the temporal data are collected, avoiding time-consuming, insecure and costly communication with a centralized computing facility (or ‘cloud’). However, modern-day processors often cannot meet the restrained power and time budgets of edge systems because of intrinsic limitations imposed by their architecture (von Neumann bottleneck) or domain conversions (analogue to digital and time to frequency). Here we propose an edge temporal-signal processor based on two in-materia computing systems for both feature extraction and classification, reaching near-software accuracy for the TI-46-Word1 and Google Speech Commands2 datasets. First, a nonlinear, room-temperature reconfigurable-nonlinear-processing-unit3,4 layer realizes analogue, time-domain feature extraction from the raw audio signals, similar to the human cochlea. Second, an analogue in-memory computing chip5, consisting of memristive crossbar arrays, implements a compact neural network trained on the extracted features for classification. With submillisecond latency, reconfigurable-nonlinear-processing-unit-based feature extraction consuming roughly 300 nJ per inference, and the analogue in-memory computing-based classifier using around 78 ”J (with potential for roughly 10 ”J)6, our findings offer a promising avenue for advancing the compactness, efficiency and performance of heterogeneous smart edge processors through in materia computing hardware.
GPT-4o mini: Non-social science research article
A room temperature rechargeable all-solid-state hydride ion battery
Jirong Cui, Ren Zou, Weijin Zhang, Hong Wen, Jinyao Liu, Shangshang Wang, Shukun Liu, Hetong Chen, Wei Liu, Xiaohua Ju, Weiwei Wang, Tao Gan, Jiong Li, Jianping Guo, Teng He, Hujun Cao, Ping Chen
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As a negative charge carrier, the hydride ion (H−) is more energetic, polarizable and reactive than cations1. An H−-mediated electrochemical process is fundamentally different from existing systems and enables the development of innovative electrochemical devices, such as rechargeable batteries, fuel cells, electrolysis cells and gas separation membranes2. Here we developed a core-shell hydride 3CeH3@BaH2, which exhibits fast H− conduction at ambient temperature and becomes a superionic conductor above 60 °C. This hydride allows us to construct an all-solid-state rechargeable H− battery CeH2|3CeH3@BaH2|NaAlH4, which operates at ambient conditions using NaAlH4 and CeH2 as cathode and anode materials, respectively. This battery has an initial specific capacity of 984 mAh g−1 and retains 402 mAh g−1 after 20 cycles. Using hydrogen as charge carriers can avoid the formation of detrimental metal dendrites, in principle, which creates new research avenues for clean energy storage and conversion.
GPT-4o mini: Non-social science research article
Selective presynaptic inhibition of leg proprioception in behaving Drosophila
Chris J. Dallmann, Yichen Luo, Sweta Agrawal, Akira Mamiya, Grant M. Chou, Andrew Cook, Anne Sustar, Bingni W. Brunton, John C. Tuthill
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Controlling arms and legs requires feedback from the proprioceptive sensory neurons that detect joint position and movement1,2. Proprioceptive feedback must be tuned for different behavioural contexts3,4,5,6, but the underlying circuit mechanisms remain poorly understood. Here, using calcium imaging in behaving Drosophila, we find that the axons of position-encoding leg proprioceptors are active across a range of behaviours, whereas the axons of movement-encoding leg proprioceptors are suppressed during walking and grooming. Using connectomics7,8,9, we identify a specific class of interneurons that provide GABAergic presynaptic inhibition to the axons of movement-encoding proprioceptors. These interneurons receive input from parallel excitatory and inhibitory descending pathways that are positioned to drive the interneurons in a context-specific and leg-specific manner. Calcium imaging from both the interneurons and their descending inputs confirms that their activity is correlated with self-generated but not passive leg movements. Taken together, our findings reveal a neural circuit that suppresses specific proprioceptive feedback signals during self-generated movements.
GPT-4o mini: Non-social science research article
Toughened self-assembled monolayers for durable perovskite solar cells
Wenlin Jiang, Geping Qu, Xiaofeng Huang, Xia Chen, Linyuan Chi, Tonghui Wang, Chun-To Wong, Francis R. Lin, Chunlei Yang, Qing Jiang, Shengfan Wu, Jie Zhang, Alex K.-Y. Jen
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Hole-selective self-assembled monolayers (SAMs)1,2 have played a key role in driving the certified power conversion efficiency (PCE) of inverted perovskite solar cells3,4,5 to 26.7% (ref. 6). However, their instability often compromises the operational performance of devices, strongly hindering their practical applications7,8. Here we employ a cross-linkable co-SAM to enhance the conformational stability of hole-selective SAMs against external stresses, while suppressing the formation of defects and voids in SAM during self-assembly. The azide-containing SAM can be thermally activated to form a cross-linked and densely assembled co-SAM with a thermally stable conformation and preferred orientation. This effectively minimizes substrate surface exposure caused by wiggling of loose SAMs under thermal stress, preventing perovskite decomposition. This enables a certified PCE of 26.92% to be achieved for the best-performing cell, which also possesses excellent thermal stability with negligible decay under maximum-power-point tracking at 85 °C for 1,000 h. It also retains >98% of initial PCE after 700 repetitive thermal cycles between −40 °C and 85 °C, representing the state of the art of the field. This work offers an in-depth understanding of SAM degradation mechanisms to guide the design of a more robust buried interface for SAM-based devices adopting high-roughness substrates to realize highly efficient and durable perovskite solar cells.
GPT-4o mini: Non-social science research article
Covariation MS uncovers a protein that controls cysteine catabolism
Haopeng Xiao, Martha Ordonez, Emma C. Fink, Taylor A. Covington, Hilina B. Woldemichael, Junyi Chen, Mika Sarkin Jain, Milan H. Rohatgi, Shelley M. Wei, Nils Burger, Muneeb A. Sharif, Julius Jan, Yaoyu Wang, Jonathan J. Petrocelli, Katherine Blackmore, Amanda L. Smythers, Bingsen Zhang, Matthew Gilbert, Hakyung Cheong, Sumeet A. Khetarpal, Arianne Smith, Dina Bogoslavski, Yu Lei, Laura Pontano Vaites, Fiona E. McAllister, Nick Van Bruggen, Katherine A. Donovan, Edward L. Huttlin, Evanna L. Mills, Eric S. Fischer, Edward T. Chouchani
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The regulation of metabolic processes by proteins is fundamental to biology and yet is incompletely understood. Here we develop a mass spectrometry (MS)-based approach that leverages genetic diversity to nominate functional relationships between 285 metabolites and 11,868 proteins in living tissues. This method recapitulates protein–metabolite functional relationships mediated by direct physical interactions and local metabolic pathway regulation while nominating 3,542 previously undescribed relationships. With this foundation, we identify a mechanism of regulation over liver cysteine utilization and cholesterol handling, regulated by the poorly characterized protein LRRC58. We show that LRRC58 is the substrate adaptor of an E3 ubiquitin ligase that mediates proteasomal degradation of CDO1, the rate-limiting enzyme of the catabolic shunt of cysteine to taurine1. Cysteine abundance regulates LRRC58-mediated CDO1 degradation, and depletion of LRRC58 is sufficient to stabilize CDO1 to drive consumption of cysteine to produce taurine. Taurine has a central role in cholesterol handling, promoting its excretion from the liver2, and we show that depletion of LRRC58 in hepatocytes increases cysteine flux to taurine and lowers hepatic cholesterol in mice. Uncovering the mechanism of LRRC58 control over cysteine catabolism exemplifies the utility of covariation MS to identify modes of protein regulation of metabolic processes.
GPT-4o mini: Non-social science research article
Engineered prime editors with minimal genomic errors
Vikash P. Chauhan, Phillip A. Sharp, Robert Langer
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Prime editors make programmed genome modifications by writing new sequences into extensions of nicked DNA 3â€Č ends1. These edited 3â€Č new strands must displace competing 5â€Č strands to install edits, yet a bias towards retaining the competing 5â€Č strands hinders efficiency and can cause indel errors2. Here we discover that nicked end degradation, consistent with competing 5â€Č strand destabilization, can be promoted by Cas9-nickase mutations that relax nick positioning. We exploit this mechanism to engineer efficient prime editors with strikingly low indel errors. Combining this error-suppressing strategy with the latest efficiency-boosting architecture, we design a next-generation prime editor (vPE). Compared with previous editors, vPE features comparable efficiency yet up to 60-fold lower indel errors, enabling edit:indel ratios as high as 543:1.
GPT-4o mini: Non-social science research article
Learning the natural history of human disease with generative transformers
Artem Shmatko, Alexander Wolfgang Jung, Kumar Gaurav, SĂžren Brunak, Laust Hvas Mortensen, Ewan Birney, Tom Fitzgerald, Moritz Gerstung
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Decision-making in healthcare relies on understanding patients’ past and current health states to predict and, ultimately, change their future course 1–3 . Artificial intelligence (AI) methods promise to aid this task by learning patterns of disease progression from large corpora of health records 4,5 . However, their potential has not been fully investigated at scale. Here we modify the GPT 6 (generative pretrained transformer) architecture to model the progression and competing nature of human diseases. We train this model, Delphi-2M, on data from 0.4 million UK Biobank participants and validate it using external data from 1.9 million Danish individuals with no change in parameters. Delphi-2M predicts the rates of more than 1,000 diseases, conditional on each individual’s past disease history, with accuracy comparable to that of existing single-disease models. Delphi-2M’s generative nature also enables sampling of synthetic future health trajectories, providing meaningful estimates of potential disease burden for up to 20 years, and enabling the training of AI models that have never seen actual data. Explainable AI methods 7 provide insights into Delphi-2M’s predictions, revealing clusters of co-morbidities within and across disease chapters and their time-dependent consequences on future health, but also highlight biases learnt from training data. In summary, transformer-based models appear to be well suited for predictive and generative health-related tasks, are applicable to population-scale datasets and provide insights into temporal dependencies between disease events, potentially improving the understanding of personalized health risks and informing precision medicine approaches.
GPT-4o mini: Non-social science research article
Repeated head trauma causes neuron loss and inflammation in young athletes
Morgane L. M. D. Butler, Nida Pervaiz, Kerry Breen, Samantha Calderazzo, Petra Ypsilantis, Yichen Wang, Julia Cammasola Breda, Sarah Mazzilli, Raymond Nicks, Elizabeth Spurlock, Marco M. Hefti, Kimberly L. Fiock, Bertrand R. Huber, Victor E. Alvarez, Thor D. Stein, Joshua D. Campbell, Ann C. McKee, Jonathan D. Cherry
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Repetitive head impacts (RHIs) sustained from contact sports are the largest risk factor for chronic traumatic encephalopathy (CTE) 1–4 . Currently, CTE can only be diagnosed after death and the events that trigger initial hyperphosphorylated tau (p-tau) deposition remain unclear 2 . Furthermore, the symptoms endorsed by young individuals are not fully explained by the extent of p-tau deposition 2 , severely hampering therapeutic interventions. Here we observed a multicellular response prior to the onset of CTE p-tau pathology that correlates with number of years of RHI exposure in young people (less than 51 years of age) with RHI exposure, the majority of whom played American football. Leveraging single-nucleus RNA sequencing of tissue from 8 control individuals, 9 RHI-exposed individuals and 11 individuals with low-stage CTE, we identify SPP1-expressing inflammatory microglia, angiogenic and inflamed endothelial cells, astrocytosis and altered synaptic gene expression in those exposed to RHI. We also observe a significant loss of cortical sulcus layer 2/3 neurons independent of p-tau pathology. Finally, we identify TGFÎČ1 as a potential signal that mediates microglia–endothelial cell cross talk. These results provide robust evidence that multiple years of RHI is sufficient to induce lasting cellular alterations that may underlie p-tau deposition and help explain the early pathogenesis in young former contact sport athletes. Furthermore, these data identify specific cellular responses to RHI that may direct future identification of diagnostic and therapeutic strategies for CTE.
GPT-4o mini: Non-social science research article
High-density soft bioelectronic fibres for multimodal sensing and stimulation
Muhammad Khatib, Eric Tianjiao Zhao, Shiyuan Wei, Jaeho Park, Alex Abramson, Estelle Spear Bishop, Anne-Laure Thomas, Chih-Hsin Chen, Pamela Emengo, Chengyi Xu, Ryan Hamnett, Samuel E. Root, Lei Yuan, Matthias J. Wurdack, Tomasz Zaluska, Yeongjun Lee, Kostas Parkatzidis, Weilai Yu, Dorine Chakhtoura, Kyun Kyu Kim, Donglai Zhong, Yuya Nishio, Chuanzhen Zhao, Can Wu, Yuanwen Jiang, Anqi Zhang, Jinxing Li, Weichen Wang, Fereshteh Salimi-Jazi, Talha A. Rafeeqi, Nofar Mintz Hemed, Jeffrey B.-H. Tok, Xiang Qian, Xiaoke Chen, Julia A. Kaltschmidt, James C. Y. Dunn, Zhenan Bao
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There is an increasing demand for multimodal sensing and stimulation bioelectronic fibres for both research and clinical applications1,2. However, existing fibres suffer from high rigidity, low component layout precision, limited functionality and low density of active components. These limitations arise from the challenge of integrating many components into one-dimensional fibre devices, especially owing to the incompatibility of conventional microfabrication methods (for example, photolithography) with curved, thin and long fibre structures2. As a result, limited applications have been demonstrated so far. Here we use ‘spiral transformation’ to convert two-dimensional thin films containing microfabricated devices into one-dimensional soft fibres. This approach allows for the fabrication of high-density multimodal soft bioelectronic fibres, termed Spiral-NeuroString (S-NeuroString), while enabling precise control on the longitudinal, angular and radial positioning and distribution of the functional components. Taking advantage of the biocompatibility of our soft fibres with the dynamic and soft gastrointestinal system, we proceed to show the feasibility of our S-NeuroString for post-operative multimodal continuous motility mapping and tissue stimulation in awake pigs. We further demonstrate multi-channel single-unit electrical recording in mouse brain for up to 4 months, and a fabrication capability to produce 1,280 channels within a 230-ÎŒm-diameter soft fibre. Our soft bioelectronic fibres offer a powerful platform for minimally invasive implantable electronics, where diverse sensing and stimulation functionalities can be effectively integrated.
Nature DOI suffix ≠ "/s...": Not a research article
Equity in science is a beautiful lie — and I’m done pretending
Dolors Armenteras
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For years, I thought equity in science was possible. I believed it in meeting rooms to which I had been invited to speak, until I realized that I had not been invited to shape the discussion. I believed it in working groups that applauded diversity, until I noticed that my ideas only landed when echoed by someone else. And international organizations regularly sought me out, but it was hardly ever for a leadership role. Academia needs a more honest, scientific approach to DEI In 2021, I proposed ways to build healthier collaborations between countries with unequal resources: currently they benefit mainly the wealthier partner (D. Armenteras Nature Ecol. Evol. 5, 1193–1194; 2021). The article resonated with scientists across Latin America, Africa and Asia, who thanked me for exposing these skewed partnerships. But what also stood out to me was that none of the committees and organizations that had so often solicited my input got in touch. Many scholars from historically overexploited countries (often referred to as the global south) expected that exposing the problem would trigger change. Four years on, I see it clearly: the scientific system was never designed for equity. For people whose privilege stems from geography, institutional reputation and inherited networks, the system works perfectly the way it is. That’s why institutions focus only on improved access and optics. They look like they are changing, but the same people retain control. I still believe in science and in justice. But I no longer think that power can be shared equitably in the current system. In 2023, I was invited to contribute to a global map charting the use of controlled fire in ecosystem management. This meant condensing 25 years of research into a 40-minute questionnaire for a chance to win an artwork made by an Indigenous artisan and, perhaps, be invited to a workshop. It was written in Spanish and framed as inclusive. But it exposed how the system works: extract specialist knowledge at low cost and mostly without giving credit, repackage it into global claims and call it collaboration. I declined. Decolonize scientific institutions, don’t just diversify them In 2025, I was invited to contribute to a project developing a global standard for gathering fire data. It used all the right words: co-production, inclusion and diversity. It cited my work. But I wasn’t being invited to co-design or co-lead the project, or even as a peer — only to “contribute regional input”. Time commitment: less than 20 hours. Visibility: none. Influence: symbolic. When I declined, explaining my reasons, I received two replies. One was defensive: “You know I’d never reach out with a symbolic request,” sidestepping my actual concerns. The other was polite, affirming the project’s importance but failing to address its asymmetry. Neither academic offered co-authorship or fresh terms. Nothing changed. These weren’t bad people. That’s the hardest part. They were playing by the rules of a system that rewards extractive collaboration — especially when it’s wrapped in the language of equity. The system doesn’t thrive just because of the people at the top. It holds strong because many scientists in less-privileged positions want to be included. Sometimes we are chosen — not for our ideas or our leadership, but because we tick the right box. A woman from Latin America, visible and qualified. But we don’t become a peer. Our work is not cited as often. Our students become local guides instead of co-authors. Grants continue to be written without us.
Nature DOI suffix ≠ "/s...": Not a research article
A population plunge could help to mitigate the global biodiversity crisis
Matt W. Hayward, Brooke Williams, Bonnie McBain
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Ecologist Paul Ehrlich and conservation biologist Anne Ehrlich might have been wrong in their 1968 prediction that human overpopulation would lead to mass human starvation, as your recent News feature notes (see Nature 644, 594–596; 2025). However, their concerns about the environmental impacts of humanity have mainly been borne out. The global population now takes just over seven months to use the living resources generated by the planet in a year — for instance, by consuming timber and fish, and by converting natural ecosystems to agriculture (see go.nature.com/47zcvty).
Nature DOI suffix ≠ "/s...": Not a research article
The Hidden Link between Racism and Alzheimer’s Risk
Jyoti Madhusoodanan
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Nature DOI suffix ≠ "/s...": Not a research article
My career switch from psychologist to open-science advocate
Esme Hedley
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Working scientist profiles This article is part of an occasional series in which Nature profiles scientists with unusual career histories or outside interests. In 2019, Jenna Keindel came across a research paper that would change her life. The Canadian, then aged 37, found it through a Facebook group of people affected by limb-girdle muscular dystrophy (LGMD), a condition that causes progressive muscle weakness. Keindel was diagnosed with it when she was 16. The paper suggested that another condition, called anti-HMGCR myopathy, a rare autoimmune disease that causes severe muscle weakness, shared some symptoms with specific subtypes of LGMD and was sometimes misdiagnosed as LGMD. Keindel was struck by the similarity with her own symptoms. And because the paper was open access, and so free to view, she could read and digest the findings before sharing them with her clinical team at the Ottawa Hospital. They agreed it was worth testing her for the condition. “Doctors and specialists can’t possibly read every article that’s being published,” she says. “So, as a patient with a rare disease, you kind of have to also be a catalyst and a helper for finding those resources.” Six weeks later, her physician confirmed that Keindel did, in fact, have anti-HMGCR myopathy, not LGMD. Since receiving treatment to fit the new diagnosis, Keindel’s muscle deterioration has slowed considerably. She married in 2023 and now lives and works in Shawville, a small rural community in the northwest of Canada. Kelly Cobey, who directs the Metaresearch and Open Science Program at the University of Ottawa Heart Institute, celebrates Keindel’s story as evidence of the benefits of making research data accessible to everyone. Cobey’s work focuses on implementing open-science practices, promoting responsible research assessment and monitoring the quality of research reporting. Jenna Keindel’s clinical experiences demonstrated to Cobey the life-changing benefits of sharing research with people receiving care.Credit: Jenna Keindel Last year, Cobey’s work in this area, and her focus on advancing awareness of predatory journals, earned her the John Maddox Prize in the early-career category. A joint initiative between Nature and Sense about Science, a London-based charity, the award celebrates scientists who speak up for sound science in the face of challenges, and who inspire others to do the same. “We just cannot underestimate how empowering people with information can literally change the course of their life,” says Cobey of Keindel’s story. “Patients need to be active in decision-making and how they’re cared for." Cobey had first heard Keindel’s story in 2019, when she worked as an investigator and publications officer at the Ottawa Hospital’s Centre for Journalology. There, she spent half her time researching open science, research integrity, transparent research reporting and predatory journals, and the other half providing training and outreach on these topics. The leader of the hospital’s patient–partner network, a link person between individuals interested in taking part in research and researchers looking to engage such people, suggested that Keindel’s story would be a good fit for a series of webinars and blogs that Cobey was developing. The aim of these was to demonstrate the benefits, some of them life-changing, of making information available to people receiving care. Cobey dates her interest in open science and research assessment back to 2011, when she was studying for her PhD in social psychology at the University of Groningen in the Netherlands. That year Diederik Stapel, an acclaimed social psychologist at nearby Tilburg University, was suspended on suspicion of widespread data fabrication. In November of the following year, a report concluded that he had fabricated and manipulated data across 55 publications over 15 years, including in chapters of his PhD dissertation at the University of Amsterdam in 1997. “When this happened, some of my early-career colleagues, postdocs or assistant professors retracted major chunks of their CVs as a consequence,” Cobey recalls. The experience made her question how something like this could persist for so long. “I’m not saying open science will get at every sort of bad actor, but it was like, how was there no record, how was there no openness?” Working Scientist career profiles Cobey decided to look for roles that would allow her to question how research is carried out, incentivized and rewarded. When, in 2015, she came across the role of investigator and publications officer at the journalology centre in Ottawa, she had never heard of meta-research, the practice of applying rigorous methods and analysis to the methods and procedures of research itself. The idea that the role would provide evidence to improve the research ecosystem appealed to her. She was also excited by the chance to teach about how to do and report research — topics that, typically, are not formally taught. Clinical epidemiologist David Moher, who leads the journalology centre, remembers being struck by Cobey’s focus on the importance of evidence when he interviewed her for the role. Six years later, she was appointed to her current position, in which a typical day involves offering informal support to institutions. This includes guiding them on providing feedback on proposed federal-policy consultations on open science. In her research programme, Cobey conducts a lot of audits on science policy. “In Canada, we have some really excellent science policies around open science, but if they’re not audited or monitored in any way, then what gets measured gets done and what doesn’t get measured doesn’t get done,” she says. For example, a 2023 paper1 that she co-authored found that only 3% of clinical trials in Canada met all three of the federally mandated criteria: prospective registration, reporting in the registry and publishing findings. Cobey also produces tools for researchers wanting to implement open-science practices, such as creating data-management-plan templates for study designs commonly used in biomedicine. A predatory problem Cobey’s interest in publishing practices led her to investigate the phenomenon of predatory journals: those that accept articles for publication without performing promised quality checks, such as peer review, and often solicit articles aggressively and indiscriminately. In 2019, she co-authored a Comment article2 for Nature revealing that elite institutions, including Ivy League universities in the United States, were knowingly publishing in predatory journals. It called for researchers to be trained in how to select appropriate journals when submitting their work, and for a declaration on CVs that the individuals’ publication lists are free of predatory publications. Cobey thinks that the discussion around predatory journals has opened the door to making the practices of all journals more transparent. Partnering with the Public Knowledge Project at Simon Fraser University in Burnaby, Canada, Cobey has developed a tool called the Publication Facts Label (PFL). Inspired by food products’ nutrition labels, it lists information about the journal in which an article is published, including its acceptance rate; and about the article itself, such as the number of reviewers, details of the research funders and whether the data are available. The aim is to show whether journals or articles published using Open Journal Systems, a publication software platform used by more than 50,000 journals worldwide, adhere to scholarly standards.. Research assessment toolkit Karim Khan, a physician and medical researcher based in Vancouver, leads the Institute of Musculoskeletal Health and Arthritis at the Canadian Institutes of Health Research, the country’s federal medical research funder. Khan says that Cobey makes organizations take a hard look at their clinical-practice guidelines and their consensus statements. Supporting her Maddox Prize entry, he commended her for “seeing what needs to be done before others do”, highlighting her efforts to define predatory journals and predatory conferences and provide ways for people to avoid them. The two worked together in 2019 with 41 other leading scholars and publishers who met in Ottawa to establish an agreed definition of predatory publishing. Khan says it was impressive to watch Kelly create a mutually supportive group culture and praises her remarkable knowledge of the literature. “It’s like having studied all of Shakespeare versus someone who knows that one of the stories had something to do with star-crossed lovers,” he says. Cobey’s Maddox Prize win also acknowledged her work with the Declaration On Research Assessment (DORA), a global initiative that aims to change the evaluation of scientific research outputs. It began in 2012, when a group of editors and publishers met to develop a set of recommendations to improve scholarly-research assessment. The idea was to encourage funders and institutions to move away from using publication in highly cited journals as the ultimate deciding factor of research merit. Now known as the San Francisco Declaration on Research Assessment, DORA covers all scholarly disciplines and has been signed by more than 26,000 individuals and organizations across 166 countries. Cobey joined the DORA advisory board in 2020, becoming co-chair three years later. In this role, she speaks regularly with policymakers at all levels to change how research is assessed. One of her outputs as co-chair is a guide to responsible research. It outlines steps for individuals to design and execute a responsible research-assessment strategy at their institutions.
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Can Diet and Exercise Really Prevent Alzheimer’s?
Sara Harrison
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Nature DOI suffix ≠ "/s...": Not a research article
Childhood vaccines up for review in the US: what’s at stake
Mariana Lenharo
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A child receives a measles, mumps and rubella vaccine earlier this year in Lubbock, Texas.Credit: Jan Sonnenmair/Getty Update: After this story was published, an updated draft agenda for the ACIP meeting was posted. According to the schedule, the committee will no longer consider the RSV vaccine, but it will vote on the three other shots described in this story: COVID-19, hepatitis B and MMRV. Next week, the panel of top advisers who recommend how vaccines are used in the United States will meet to review jabs that protect against COVID-19, hepatitis B and other diseases. The meeting — the committee’s second since US health secretary and anti-vaccine advocate Robert F. Kennedy Jr abruptly fired all of its previous 17 members and welcomed 7 new ones — has raised eyebrows among public-health specialists, given that the safety and efficacy of some of the vaccines on the agenda have been well established for years. Who is on RFK Jr’s new vaccine panel — and what will they do? “I’m very concerned, given the signalling from the members of this newly reconstituted, hand-picked [committee] that they are going to select targets for further restriction,” says Andrew Pavia, a physician with the Infectious Diseases Society of America, a medical association based in Arlington, Virginia. At their last meeting, the advisers — several of whom have publicly expressed anti-vaccine views — voted to end the use of the preservative thimerosal in influenza vaccines, despite evidence that it is safe at the doses found in jabs. It is unclear exactly what the Advisory Committee on Immunization Practices (ACIP) will vote on at next week’s meeting, to be held on 18 and 19 September, because the agenda lacks detail, increasing researchers’ concern. “It’s very unusual for ACIP to put things on the agenda with only a month’s notice and not discuss who’s going to be presenting data, what data is going to be looked at, and what, if any, questions might come up for a vote,” Pavia says. The US Department of Health and Human Services, which is run by Kennedy and has authority over the ACIP, did not respond to Nature’s request for comment. Nature spoke to public-health specialists about the vaccines up for discussion, what the committee might vote on and the data it should be considering. Scrutiny for COVID-19 jabs Last month, the US Food and Drug Administration (FDA) approved updated COVID-19 vaccines, but it imposed limitations on who can get the shots. Whereas the vaccines were previously authorized for all people aged 6 months and older in the United States, now they are approved only for those older than 65 years, as well as people with health conditions that put them at high risk of severe disease. RFK Jr demanded a vaccine study be retracted — the journal said no The FDA is responsible for authorizing new vaccines, whereas the ACIP, overseen by the US Centers for Disease Control and Prevention (CDC), advises on who should receive them. These recommendations, which are typically adopted by the CDC as official policy, help to inform which vaccines are covered by health insurance. “I assume ACIP could end up mirroring what the FDA has recommended” for COVID-19 shots, says Adam Ratner, a paediatrician at the American Academy of Pediatrics (AAP), an organization based in Itasca, Illinois. In a statement following the FDA’s decision on 27 August, AAP president Susan Kressly called the move “deeply troubling”, especially for children, whose safety Kennedy has focused on when questioning vaccines. The previous week, the AAP issued its own recommendation that all children 6 months and older should be vaccinated and, in particular, kids aged 6–23 months old who are at high risk of severe COVID-19. According to data from the 2022–23 cold and flu season, mRNA-based COVID-19 vaccines were between 46% and 70% effective at preventing COVID-19-related emergencies for children aged 6 months up to 5 years during a 2-month window after the second or third dose. (Flu vaccines, which are also updated seasonally, are typically 40–60% effective.) And such shots elicited no safety concerns in that same age group. However, The Washington Post is reporting that Trump health officials might link COVID-19 vaccines with 25 paediatric deaths reported to a vaccine safety database at next week’s meeting. Anyone can submit reports to the database, but claims must be investigated to confirm a link. Hepatitis B shots no longer for newborns? Anti-vaccine advocates have been questioning whether a hepatitis B vaccine should be given to newborns — the current practice in the United States. Instead, they are suggesting that jabs be administered only to people with certain high-risk behaviours, including unprotected sex and drug use, Pavia says. That’s a problem, he adds, because “the majority of hepatitis B worldwide is transmitted from mother to infant”. Hepatitis B is a liver disease caused by a virus that spreads through contact with infected blood and other body fluids. According to the AAP, babies infected with hepatitis B in their first year of life have a 90% chance of developing chronic disease, and one-quarter of those with chronic hepatitis B die from it. Source: CDC/National Notifiable Diseases Surveillance System Since the United States began recommending hepatitis B vaccines for infants in the 1990s, cases have dropped significantly (see ‘Generational decline in hepatitis B’). Administering “earlier is always better with an incurable virus”, says Peter Chin-Hong, an infectious-disease physician at the University of California, San Francisco.
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The Vexing Promise of New Blood Tests for Alzheimer’s
Cassandra Willyard
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Nature DOI suffix ≠ "/s...": Not a research article
Mysterious changes near Earth’s core revealed by satellites in space
Alexandra Witze
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Material deep inside Earth — thousands of kilometres down, near the planet’s core — has undergone a mysterious shift. Is Earth’s core leaking? Volcanic rocks provide strongest evidence yet Although the change occurred nearly two decades ago, between 2006 and 2008, scientists discovered it only recently, while analysing data from a pair of satellites that once measured variations in Earth’s gravity. The team thinks it might have happened when the structure of some of the rocks near the boundary between Earth’s core and mantle transformed, becoming denser. The discovery — which was possible because the geological shift altered the planet’s gravitational field — is an astonishing testament to Earth-orbiting satellites. “It’s a really new observation,” says Isabelle Panet, a geophysicist at Paris City University. Panet, lead author Charlotte Gaugne Gouranton — also at that university — and their colleagues reported the findings last month in Geophysical Research Letters1. The work will help scientists to better understand the connections between Earth’s various layers, from its brittle crust to its solid mantle to its partially liquid core, Panet says. Connections between these layers affect where large earthquakes originate, how the planet maintains a magnetic field that protects it from solar storms and more. Follow the leader Panet’s team made the discovery using data from a pair of US–German satellites known as the Gravity Recovery and Climate Experiment (GRACE), which orbited Earth between 2002 and 2017. The satellites flew one in front of the other, separated by a set distance. Strange blobs in Earth’s mantle are relics of a massive collision When they encountered a gravitational tug from, for example, the hulking mass of a mountain range, the lead satellite would pull temporarily away from the trailing satellite — a change that could be measured and correlated with the gravitational shift. Researchers have most often used changes in the distance between the GRACE satellites to measure the displacement of masses of water on Earth, such as when groundwater disappears beneath croplands or when glaciers melt. But, as it turns out, GRACE was also able to spot much deeper changes in Earth’s mass. Panet had already used it to look for mass changes happening hundreds of kilometres below the surface ahead of large earthquakes2,3. Then she realized she could probe even farther down, to a depth of nearly 2,900 kilometres, to the complex boundary between the core and mantle. Panet and her colleagues spotted a strange signal in the GRACE data that peaked around 2007 and was centred off Africa’s Atlantic coast. They were unable to attribute it to water shifting around on Earth’s surface, however. “So at least partially, there has to be an origin within the solid Earth,” Panet says. “It has to come from very deep.” In the deep
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Will the public support basic science? A new non-profit aims to find out
Virginia Gewin
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Scientists have launched a crowdfunded initiative for blue-sky research amid federal funding cuts.Credit: Michael Siluk/UCG/Universal Images Group via Getty Amid a backdrop of massive cuts in US federal support for scientific research, a new effort — the Science Foundation — launched last week to raise public funds for transdisciplinary, discovery-based research. The Science Foundation’s initial US$100,000 fundraising goal will support ten $10,000 research grants to advance recipients’ careers, akin to the supplemental grants awarded by the US National Science Foundation to collect proof-of-concept data in pioneering research projects. “We’re calling them ‘What IFS’, or interdisciplinary foundation science,” says Maren Friesen, project director and an evolutionary ecologist at Washington State University in Pullman. Scientists at all career levels will be eligible, and projects will ideally span at least two disciplines. “We want to support cross-fertilization of science based on intellectual curiosity, rather than chasing the latest use for artificial intelligence,” she explains. Friesen and her colleagues are betting that the public will step up to support scientists’ blue-sky endeavours. “In our first request for proposals, we plan to ask: why are you excited about this work?” says Venkatesh Srinivas, deputy project director and a Google software engineer in Seattle, Washington. The non-profit organization has so far raised $20,000, says Srinivas, and secured a pledge to match the next $20,000 in donations, which can be made at science-foundation.org. Solicitations will focus on five disciplines: maths, physics, chemistry, biology and Earth sciences. “We’re not considering biomedical, engineering or computer science, because we feel those already have plenty of investment,” says Friesen. Once Friesen and her team have proposals in hand, they will assemble a review panel of specialists and at least one member of the public. The foundation aims to release its first request for proposals this year. “We need to give young scientists hope that people continue to believe in the value of science,” she adds. A lost generation? Since US President Donald Trump took office in January, his administration has blocked or cancelled billions of dollars of funding through the US National Institutes of Health, the National Science Foundation, the Department of Energy and other sources. Yet even before that, public funding for basic science in the United States had stagnated over the past decade. The federal government’s share of basic-research funding decreased from 52% to 41% between 2012 and 2023, according to a July report by the National Science Board. “We’re not just doing this in response to the Trump-administration cuts or to replace the National Science Foundation,” says Friesen. “We are trying to build something that that we think will have value in addition to government-funded science.” Such support could help to ameliorate one growing concern — a lost generation of scientists. “We are facing a workforce time bomb,” warns David Stern, Science Foundation board member and former president of the Boyce Thompson Institute for Plant Research at Cornell University in Ithaca, New York. “If we don’t have science practitioners, we don’t have science,” he says. Exploratory research is particularly imperilled now, Stern and others argue. “We need alternative models to support basic science,” says Jonathan Eisen, an evolutionary biologist at the University of California, Davis. “I favour this [the Science Foundation] serving as a model for people to experiment with.” But, Stern acknowledges, “Let’s not kid ourselves that this is a solution; it won’t replace federal funding. But it is a need that was already there, and more important now.” Public support is strong
Nature DOI suffix ≠ "/s...": Not a research article
How should ‘mirror life’ research be restricted? Debate heats up
Mark Peplow
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Some researchers are developing biological systems that create mirror-image versions of DNA and other molecules crucial to life.Credit: Ting Zhu Lab This week in Manchester, UK, scientists will be deliberating whether to restrict research that could eventually enable ‘mirror life’ — synthetic cells built from molecules that are mirror images of those found in the natural world. Mirror-image molecules separated using workhorse of chemistry Over the past year, many scientists have voiced concerns over experiments that might lead to the creation of such cells, suggesting that they would pose an enormous risk to human health and the environment. “Pretty much everybody agrees” that mirror-image cells would be “a bad thing”, says John Glass, a synthetic biologist at the J. Craig Venter Institute in La Jolla, California. But there are disagreements about where to draw lines to limit research on mirror-image biology, given the potential benefits of such studies. Many of the molecules in our bodies are ‘chiral’ — that is, they take one of two mirror-image forms, like right-handed and left-handed gloves. Proteins are built from left-handed amino acids, and DNA twists like a right-handed screw, for example. Studying mirror-image versions of such molecules could help to unpick how this handedness emerged, some researchers say. And because the body’s enzymes and immune system might not as readily recognize right-handed amino acids or left-handed DNA, such molecules could resist degradation — making them useful as therapeutic drugs. This approach has already shown clinical success: in 2017, for example, the US Food and Drug Administration approved a small peptide containing mirror-image amino acids, called etelcalcetide, to treat people with chronic kidney disease. Rare ‘ambidextrous’ protein breaks rules of handedness But this ability to evade degradation could be a double-edged sword. If an entire mirror-image cell were ever made, it might proliferate uncontrollably in the body or spread unchecked through the environment, some researchers say. This is why scientists are meeting in Manchester this week. Biochemist Sven Klussmann, founder and chief executive of Aptarion Biotech in Berlin, which is developing short strands of therapeutic mirror-image RNA, agrees that it’s reasonable to consider the potential risks of mirror life. “But we should not panic yet, and we should not restrict research too early,” he says. Yet Kate Adamala, a synthetic biologist at the University of Minnesota, Minneapolis, cautions that the risks of research that could enable mirror life would outweigh any potential benefits. “There is no benefit of mirror biology that couldn’t be achieved other ways with normal biology,” she says. “That’s not a risk I think we should be taking.” Red lines Glass says that several teams, including his own, are close to, for the first time, creating a synthetic cell from molecules with the chirality seen in nature. But nobody is currently building a mirror-image cell, and it could take decades to do so, if it’s even possible at all. Still, researchers are making progress on technologies that could underpin that work; and in 2019, before the potential risks were realized, the US National Science Foundation awarded research grants to ‘boot up’ a mirror cell. Adamala, one of the grant recipients, says her growing concerns convinced her and her colleagues to drop the work. Mirror-image enzyme copies looking-glass DNA Glass and Adamala were among 38 scientists who laid out their worries in Science in December 20241. Since then, the non-profit Mirror Biology Dialogues Fund has sponsored a series of meetings to develop recommendations to avert the threat mirror life could pose. In June, researchers who gathered in Paris called on funders not to support work on a mirror-image cell, and suggested restricting areas of research that could facilitate mirror life. In Manchester this week — and at a US National Academies of Sciences, Engineering, and Medicine meeting at the end of this month — researchers will pick up the conversation and deliberate over where to draw those red lines.
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Can We Fix America’s Dementia Care Crisis before It’s Too Late?
Tara Haelle
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Nature DOI suffix ≠ "/s...": Not a research article
Weird ‘time crystals’ are made visible at last
Elizabeth Gibney
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A time crystal as seen under a microscope.Credit: Zhao & Smalyukh, 2025, Nature Materials A time crystal is a form of matter that shows continuous, repeating patterns over time, much like how atoms in a normal crystal repeat in space. Examples once existed in only complex, quantum matter, but now physicists have found a way to make a time crystal that can be seen, under certain conditions, with the naked eye. The feat, accomplished by physicists at the University of Colorado Boulder, and published in Nature Materials on 4 September1, involved liquid crystals — bar-shaped molecules with properties between those of a liquid and those of a solid. Simply by shining a light on the liquid crystals, the team created ripples of twisting molecules through them. The ripples kept moving for hours, undulating with a distinct beat, even when the researchers changed the conditions. The rhythm was also out of sync with any incoming force — fulfilling the two defining criteria for a time crystal. Although some of this behaviour of liquid crystals was already known, no one had previously considered whether it could be harnessed to make a time crystal, says Young-Ki Kim, a materials scientist at the Pohang University of Science and Technology in South Korea. The macroscopic scale of the time crystal — at millimetres to centimetres across — creates opportunities “to provide deeper understanding” of the phenomena, he says. The distinctive patterns in the crystals could also allow them to be used in anti-counterfeit devices, say the authors. Impossible machines Nobel-prizewinning physicist Frank Wilczek first proposed the idea of a time crystal in 2012. Wilczek’s version was almost like a perpetual-motion machine; something that cycled endlessly while in its natural resting state. A team later published a paper that mathematically proved this concept was impossible2, but researchers soon found that other kinds of time crystal were possible. Ordered time crystals could exist, for example, in bizarre systems that were perpetually in flux, rather than at rest. Time crystals have since been made in a variety of ways, using interacting nanoscale defects in diamonds, trapped ions and simulated on Google’s Sycamore quantum computer. But most examples have been at the microscopic scale. The latest system involves shining a light, even that from a normal light bulb, on a liquid-crystal film trapped between two glass plates. When the light hits photosensitive dye molecules on the glass plates, they switch their orientation, which triggers molecules in the liquid crystal to begin twisting. Intermolecular forces between rod-like liquid crystal molecules mean that they usually all point in the same direction. If some begin twisting, this sets off a domino effect: the molecules reorient themselves in a complex interaction that moves across the sample like a Mexican wave. From this soup of molecules arise stable twisted formations that behave like particles. These particles interact with each other to create observable ripples. “We were surprised and excited to see that such time-crystalline order can be readily observed in soft matter systems,” says Ivan Smalyukh, a physicist at the University of Colorado Boulder, who led the work. To observe the molecular dance in detail, the authors looked at the time-crystal system using a kind of microscope that transmits only polarized light. The amount of light that passes through depends on a molecule’s alignment, revealing the time crystal’s ripples as a series of dark and bright stripes.
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Heroes or hoarders? The strange brains of people who collect
Andrew Robinson
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A Noble Madness: The Dark Side of Collecting from Antiquity to Now James Delbourgo Riverrun (2025) The Galileo Museum, a science museum in Florence, Italy, has astronomer Galileo Galilei’s preserved middle finger on display. Encased in a gilded glass egg, the digit is exhibited “as if it were the relic of a Christian saint”, remarks historian of science James Delbourgo in his illuminating and entertaining history of the ‘dark side’ of humanity’s obsession with collecting things. The finger was severed from Galileo’s corpse in 1737 — long after his death in 1642 — along with an index finger also displayed at the museum and a vertebra held at the University of Padua, Italy. According to a witness to the dismemberment, the Italian nobleman who took the fingers desired them “because Galileo wrote so many beautiful things with them”. How a self-taught biologist transformed nature writing — and inspired Darwin It is an unusual story, but perhaps not entirely atypical. As Delbourgo shows in A Noble Madness, a large driver of the desire to collect artefacts is curiosity — whether scientific, historical, religious or otherwise. But perhaps even more often, it is obsession. Delbourgo focuses on this compulsive aspect, and the varying ways in which society has regarded people who are driven to amass stuff. He offers “a grand portrait gallery that charts the changing image of the collector from the ancient looter and medieval idolater to the decadent of the fin de siùcle and the modern-day hoarder”. Dark desires A compelling example of such obsession is Henry Wellcome. He is known today through the biomedical research-funding organization Wellcome, and the Wellcome Collection museum and library in London. Born in 1853 to an itinerant missionary father in a log cabin in Wisconsin, by his death in 1936, Wellcome had become a highly successful pharmaceutical entrepreneur in the United Kingdom. He also owned a grotesquely overwhelming collection of objects, the variety and sheer number of which the world had never seen — mainly because few were on display. ‘Natural history museums can save the world’: anti-colonialism, conservation and climate change Wellcome obtained many of these objects through highly dubious means, notes Frances Larson in her disturbing 2009 history of his collection, An Infinity of Things. In 1912, for example, Wellcome’s right-hand man wrote to an agent in India, a doctor, that the country must be “completely ransacked as far as we possibly can for literature and other objects of interest connected with ancient medicine”. The agent duly did his best — but there is little evidence that Wellcome ever studied or ‘enjoyed’ what had been collected. He was always too busy acquiring new things, right up to his death. His obsession was rooted in possession. The Wellcome Museum deliberately avoids displaying information about its founder, notes Delbourgo. He regards this stance as “myopic: the Wellcome’s abdication of its duty to educate visitors about its origins denies the public the chance to make up its own mind about its past”. The British Museum, just down the road in London, is less coy about the man who provided its founding collection in 1753. Physician and naturalist Hans Sloane — the subject of Delbourgo’s 2017 book Collecting the World — was an avid collector of curiosities and animal and plant specimens. His motivations were multifarious. He collected manuscripts from astrologers and alchemists to document their ascientific convictions as “disorders of the mind”, delusions that he felt might be cured by bloodletting, his specialism. But when it came to collecting from the natural world, he was explicit about a financial incentive: to “figure out what species were good for, what they cost, and how to make money off them”, in Delbourgo’s words. To his critics, Sloane was an “ignorant arriviste”. Today, his financial links to the slave plantations in Jamaica that part-funded his collecting are openly acknowledged in an exhibit showing a bust of Sloane. Galileo’s elegantly preserved middle finger.Credit: Eric Vandeville/Gamma-Rapho/Getty
Nature DOI suffix ≠ "/s...": Not a research article
The chatbots claiming to be Jesus: spreading gospel or heresy?
Brian Owens
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‘God’s influencer’ Carlo Acutis was canonized on 7 September by Pope Leo XIV. Acutis was known for his use of digital media to promote Catholic devotion.Credit: Vatican Pool/Getty The canonization of Carlo Acutis by Pope Leo XIV on 7 September was a sign of how the Catholic Church is increasingly embracing the digital world. Acutis, who died of leukaemia in 2006 at the age of 15, was known for using the Internet to further his faith, maintaining a website documenting Eucharistic miracles recognized by the church. It earned him the moniker God’s influencer. But the work of a saintly teenage tech-wizard is just one way that new technologies are finding their way into religious practice: artificial intelligence (AI) chatbots and ritual-performing robots are already taking on spiritual roles that are conventionally filled by humans. Worshippers have mixed feelings about them. AI Jesus The rise of generative AI chatbots has led to the creation of tools that purport to offer people the opportunity to speak directly with religious figures, such as Jesus Christ. AnnĂ© Verhoef, a philosopher at North-West University in Potchefstroom, South Africa, analysed five popular Jesus chatbots by asking them questions about themselves and basic theology, and found some worrying trends. None of the chatbots he studied were developed or endorsed by any church, and it is not clear what religious texts they were trained on. Four of the five were created and managed by private companies — with names such as Catloaf Software, a mobile-development company in Los Angeles, California — whereas the fifth is run by a Christian group in South Korea with no official connection to any church. All are free but supported by advertisements, with one offering an ad-free premium subscription. “It’s difficult to know if they are really about religion, or just milking money from the faithful,” says Verhoef. Another concern is that most religious AI bots claim to be Jesus rather than an AI impersonation developed by humans. “If this is really about Christianity and being sincere about faith, they should not be pretending to be God,” he says. “The possibility for abuse is huge” — if people believe a chatbot is actually divine, they might be convinced to follow its instructions for nefarious purposes, Verhoef says. Jesus chatbots are growing in popularity and have hundreds of thousands of users, Verhoef estimates. The AI technology is also being used in more official capacities. Last year, as part of an experiment with a local university, a Catholic church in Lucerne, Switzerland, installed a Jesus chatbot in its confessional booth that could answer theological questions and offer spiritual guidance. In 2023, hundreds of Lutherans in Nuremberg, Germany, attended a church service generated and delivered by chatbot ChatGPT. Both were reasonably well-received, says Verhoef. Many of the functions of a priest could be replaced by AI chatbots in the future, but he sees a problem with it. “If a sermon is prepared by an AI not a person, how seriously can we take that as a spiritually inspired sermon or thought?” asks Verhoef. Religious acceptance Christianity isn’t the only religion using generative AI tools. There are also Buddhist, Hindu, Jewish and Islamic chatbots, but some religions are more open to adopting new technologies than are others, and for different uses. Hinduism and Buddhism, for example, already incorporate some simple forms of automation in their rituals. Some temples in India have begun using robotic arms to perform the Hindu aarti ritual, in which a devotee offers an oil lamp to the deity to symbolize the removal of darkness, and one temple in Kerala has an AI-driven animatronic elephant.
Nature DOI suffix ≠ "/s...": Not a research article
‘Revolutionary’ AI tools rescue old weather data to improve climate models
Davide Castelvecchi
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Thousands of paper documents in the Democratic Republic of the Congo’s meteorological archives are now being digitized.Credit: Derrick Muheki/INERA DRC How can countries find out how climate change will affect them at a regional scale? Can artificial intelligence (AI) help to forecast hurricanes and other extreme weather events? And has the world already blown past the most ambitious target of the Paris climate agreement — to limit global warming to 1.5 °C above pre-industrial levels? The need to address these and other questions is spurring researchers to tap into vast, unused repositories of handwritten weather records that span more than two centuries. These troves of valuable — but in some cases unreadable — data are now becoming easier to access with new, more sophisticated machine-learning tools. “All meteorological services around the world have some basement where they store data from the 1800s that has not been digitized,” says Marlies van der Schee, a climate scientist at the Royal Netherlands Meteorological Institute in De Bilt. “For many institutes, they don’t even know what is in their archives.” Searching for data In the quest to gather missing climate data, climate scientist Derrick Muheki has travelled farther than most. To access the meteorological archives of the Democratic Republic of the Congo (DRC) — which contain records from when the DRC became independent in 1960, collected from 37 weather stations across the country — Muheki had to fly from Kinshasa to Kisangani in the country’s north, travel along the Congo River by boat and then take an unpaved road on a motorcycle to reach the Yangambi branch of the DRC’s National Institute for Agronomic Research (INERA). There, he spent two months earlier this year scanning thousands of pages of weather logs. Muheki had to bring enough batteries to power his digital camera for the duration of the trip, as the remote branch of INERA is not hooked up to the DRC’s national grid. He learnt some of the Bantu language Lingala so that he could communicate with other INERA staff members. He says it helped that many of the words were similar to the language he grew up speaking in his native Uganda. Weather reports from old ships’ logs — such as this eighteenth century document from British vessel HMS Dolphin — contain data that can be fed into climate models. Credit: The History Collection via Alamy After returning to his research group at the Vrije Universiteit in Brussels, Muheki began to extract data from the more than 9,000 scanned images using a machine-learning tool he designed for reading the weather logs, called MeteoSaver1. In initial tests, MeteoSaver could transcribe the data with only 75% accuracy, but further refinements and training of its neural network — on the basis of an open-source package for recognition of handwritten text, called Tesseract — have pushed that to 90%, he says. The resulting data will provide crucial information about how conditions have changed over time in the world’s second largest rainforest. Climate scientist Wim Thiery, Muheki’s adviser at the Vrije Universiteit, says that because of a lack of information about past temperatures, the forested heart of the African continent had a major data gap in the 2021 report from the Intergovernmental Panel on Climate Change, which assessed the severity and speed of global warming in various parts of the world. He hopes that efforts such as Muheki’s will help to rectify this. Forgotten figures Muheki’s logistical hurdles were unusual, but the DRC is not the only country that is yet to fully digitize its weather records. “There are paper records still languishing in archives all over the world,” says Ed Hawkins, a climate scientist at the University of Reading, UK. These include millions of unused rainfall observations in the UK’s National Meteorological Archive. Is it too late to keep global warming below 1.5 °C? The challenge in 7 charts Hawkins has managed several projects that relied on citizen scientists to manually transcribe climate records. Ten years ago or so, machine-learning tools just weren’t up to the task, he says. The hardest part for AI tools is not reading handwritten text, but recognizing the tabular structure in the documents. “When I and colleagues started trying [AI] tools out, they just would not work on tabulated numbers,” says Hawkins. “It wasn’t in their training.” Much of Muheki’s work consisted of developing custom algorithms for doing just that. Now, the tools are finally becoming good enough to match human performance, says Hawkins, who is a co-author on the research paper that describes MeteoSaver. Similar efforts by other teams are showing that machine learning could drastically speed up the rate of recovery of historic records. “It’s really a revolution in our ability to rescue data,” says Thiery.
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Pharmaceutical giants pull out of UK: why it matters for global science
David Adam
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Merck and AstraZeneca have paused research and development investments in the United Kingdom.Credit: Matthew Horwood/Getty A series of statements and funding cuts suggest that the UK pharmaceutical industry and research sector is losing its competitive edge. First, Merck said on 10 September that it was scrapping a plan to develop a £1-billion (US$1.4-billion) research facility in London and cancelling ongoing projects at the nearby Francis Crick Institute. Two days later, it emerged that AstraZeneca was rethinking a £200-million expansion of its research site in Cambridge — a decision that follows a similar U-turn from the company earlier this year on a promised £450-million expansion to its vaccine manufacturing facility in Liverpool. And statements from the US firm Lilly and French company Sanofi have raised doubts about their continued investment in the United Kingdom, too. The pharmaceutical giants have blamed a reduction in government investment in the sector on their decisions to de-invest in pharmaceutical research and development (R&D). At an emergency parliamentary committee in the Houses of Parliament on 16 September, Ben Lucas, managing director of MSD (Merck) UK and Ireland said that “the UK commercial operating environment does need to be addressed”, adding that the UK government should “reflect on how we can avoid these things moving forward”. But the real “crunch issue” is the amount of money the country’s National Health Service (NHS) spends on medicines, according to the UK minister for science, research and innovation, Patrick Vallance, who has also been head of R&D at the drug company GlaxoSmithKline and is a former government chief scientific adviser. Vallance told the committee that Britain would need to spend billions of pounds more on new drugs to convince the pharmaceutical industry to invest in its life-science sector. Britain’s spending on pharmaceuticals has declined from 15% a decade ago to 9% today — a decline that would cost about £12 billion more each year to reverse. “I think industry has been clear that the ongoing investment in the UK is dependent on having a commercial environment which is conducive to them doing business,” said Vallance. UK pharma exodus? The recent announcements come as talks between the UK government and the pharmaceutical industry remain deadlocked over drug-price reform. Under the current scheme, pharma companies agree to repay a proportion of their revenues from drug sales to the NHS. But the industry was unhappy when the government increased the rebate last year from 15% to 24%. Although many attending the committee meeting drew explicit links between the negotiations and the reversal of planned industry investment by pharmaceutical companies, independent specialists are more sceptical, saying it’s really about underlying weaknesses in the global pharmaceutical sector. Richard Sullivan, a cancer-policy researcher at King’s College London, says that the companies are using arguments over drug pricing as an excuse for cuts they needed to make anyway. “This is nothing to do with domestic policy towards our pharmaceutical industry,” he says. “This is smoke and mirrors.” The ‘most favoured nation’ policy of US President Donald Trump, which aims to reduce the high prices the United States pays for medicines relative to other countries, combined with the rise in high-quality cheaper drugs from China and a reduction in health financing in emerging markets have left Merck and other pharmaceutical companies struggling with an obsolete business model and looking to save money, he says. “They don’t want to say they are withdrawing because the competition in China’s too fierce and because they made an upfront strategic mistake of putting it here in the first place,” he adds. What does it mean for other countries? Alexander Schuhmacher, a pharma R&D researcher at Technical University Ingolstadt in Germany says it’s not clear yet how the situation in the United Kingdom might influence or apply to other countries. “Pharma companies operate under long research and production life cycles,” he points out. That means their strategic decisions are typically the result of long-term planning, not short-term reactions to political changes or even to major geopolitical shifts, he says.
Nature DOI suffix ≠ "/s...": Not a research article
New Hope in Alzheimer’s Research
Lauren Gravitz
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Nature DOI suffix ≠ "/s...": Not a research article
Maintenance
Matt Tighe
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The Bot is all long limbs and careful movements, a model designed for small tasks and companionship. Every time it moves, its joints grind very softly. “Don’t you have a maintenance routine?” Hubert asks as he holds up the abstract bookend, a thing of stylized swirls and loops. One of his mother’s friends will think it is the perfect keepsake, no doubt. “Yes,” the Bot replies. It pulls a dark blouse with dusty sequins from the cupboard. Hubert can practically smell the mothballs from across the room. The Bot holds the piece of clothing for a long time without moving. “That can go in the donations,” Hubert says. It is pointless getting the Bot to do something like this. The robot’s central AI is supposed to adapt to a user’s needs, but the thing had been with his mother for so long it probably can’t adjust to what he wants. Clear the place out and go, that is the plan. He needs to remember that. The robot bends to add the blouse to the pile of shoes and coats and other things an older woman accrues over a lifetime. Hubert looks away, trying not to recall that blouse. Those red shoes. His mother, younger, vibrant, smiling down at him. Spin Huey! Spin with me, Huey! So many times. How he had laughed as she had spun, her arms outflung. How she had laughed when he tried. A lifetime ago. Beyond a barrier of hard words, foolish words. The robot moves with that soft grinding noise. “Can you do your maintenance, then? You sound like you need it.” “Yes,” the Bot says as it picks up a vase with a dried flower in it in one hand and a faded Broadway poster in the other. Read more science fiction from Nature Futures “I don’t know what those are,” Hubert says. “Put them in the junk pile.” The Bot does not put the flower or the poster in the discard pile. “Some of these things were valuable to your mother,” the Bot says. “Well, she was wrong!” Hubert snaps. He snatches the poster from the robot and drops it with the other pieces of his mother’s life he knows nothing of. “None of this stuff matters.” An old dance poster. A dried flower, maybe from years ago. She must have left more. Must have cared. The robot stands as still as only a robot can, holding its dead flower. Hubert tries to speak again. His throat is tight. “Did she say anything?” he bursts out finally. “About me?” “You have not visited in three years and two months.” Hubert clenches his fists. “I know that! Tell me something she said!” He wonders if he is about to hit the robot. That would be pointless. As pointless as talking to the thing. As pointless as being here now, too late. He forces his hands to relax. “Tell me 
” he doesn’t know what he wants. Except that is not true. He wants it to be like it was. He wants what he can’t have. He wants her smiling down at him, the years gone. The distance gone. Yay! Spin, Huey! “General conversation is bound by confidentiality,” the Bot says. “Perhaps she left a message during one of the calls she attempted to you.” No, she hadn’t. Mostly hang-ups. Sometimes that deep silence full of ache and sorrow. Once, an indrawn breath like she was about to speak. She could have told him she was sick. Or he could have answered, even just once. He could have called. It hurts. Could have. Should have. But didn’t. “Get out of here,” he tells the Bot. “Go and do your maintenance routine before you seize up completely.” ***** The robot is just standing in the yard. “That can’t be part of your maintenance,” Hubert says from the doorway. “No,” the robot says. “My standard routine is a series of movements designed to rotate and lubricate my joints and expel particles. It increases longevity by a factor of three.” “Did my mother leave a letter for me? Did she write something down?” “Not that I am aware of,” the Bot says. “Maybe she didn’t have time,” Hubert says.
Nature DOI suffix ≠ "/s...": Not a research article
Wired for growth: neuron–tumour signalling in the lung and brain increases growth of a hard-to-treat cancer
Abbie S. Ireland, Trudy G. Oliver
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Some cancers benefit from interacting with the nervous system — either by directly forming functional connections, termed synapses, with neuronal cells or by indirectly receiving signals released from neurons. This phenomenon is most commonly studied in brain cancers, such as gliomas, but tumours located elsewhere can also benefit from interactions with neurons1,2. Writing in Nature, Savchuk et al.3 and Sakthivelu et al.4 reveal that neuron−cancer interactions promote the growth of small-cell lung cancer (SCLC) — a highly aggressive type of lung tumour that often spreads to the brain, and has only limited treatment options5.
Nature DOI suffix ≠ "/s...": Not a research article
The parable of the doors
Alexander B. Joy
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From his spot in the long, orderly queue, Balch could just see the clinic’s large double doors. One intermittently swung open as nurses and national guardsmen ushered the next person inside. The queue then inched forwards like a great lazy caterpillar to fill the vacated space. Balch kneaded his pockets. His turn would be a while yet. Identical clinics had opened worldwide following the parasite’s discovery — a biological oddity colloquially dubbed ‘the Slug’, despite news broadcasts highlighting the microscopic creature’s dendritic shape. How they’d spotted the Slug, Balch couldn’t explain. But he understood why it mattered. Apparently, the Slug had been randomly infecting half the population for centuries. It wasn’t deadly, supposedly. Yet it dulled its host’s every faculty, hampering their ability to do most things — including reasoning cogently, retaining information and even playing sports. How the Slug spread, the World Health Organization couldn’t say. Yet that hadn’t prevented scientists from developing a cure packaged in bubblegum-flavoured oral lozenges. The world’s governments immediately enacted mass screenings among their populations, dosing Slug carriers on detection. Watching nurses shepherd another person through the clinic’s doors, Balch wondered whether he had the Slug. He couldn’t imagine finding himself smarter and more athletic overnight. The thought made his brain itch. He sighed, wishing the affair was over. “Boring wait, huh?” Read more science fiction from Nature Futures Balch turned. Behind him stood a youngish, bespectacled man in a tweed suit and bow tie meant for someone four times older. “If you need entertaining,” he said, “how about a riddle?” “Why not,” said Balch. “Picture a game show,” said the man, “involving three doors. One conceals a million dollars. The others, nothing. You’ll win whatever’s behind the door you choose. With me so far?” “Yup,” said Balch. “Guess correctly, make a bundle.” “Perfect. Suppose you select Door number 1. Before you turn the knob, the host opens Door number 2, revealing empty space. He then invites you to ditch your initial pick for Door number 3. The question is: should you switch?” After a moment, Balch said, “Weirdly enough, you should.” “Interesting. Why?” “Because the original set-up’s a one-in-three chance for the right door, but the second offers a two-in-three chance for Door 2. Much better odds.” “That’s right,” said the man, grinning. Balch smiled back. He’d heard the solution before, but kept that to himself. All of a sudden, the man took Balch’s arm, yanking him out of the queue. “What the 
?” Balch sputtered. “Quiet,” whispered the man. “Nobody must overhear. It’s a matter of vital importance. Most would dismiss me as a crank for what I’m about to say. You, though! You’ve got the right mindset. Because you understand the door puzzle, and how changing circumstances counter-intuitively redefine rational choice.” Balch remained quiet. Interrupting seemed unwise. “You see,” said the man, “I’m an economist. Yes, yes, funny occupation. Correctly predicted seven of the last four recessions, et cetera. Whatever. My friend, the reality is, we’re facing probabilistic questions with existential stakes.” “What?” “Think carefully about the following question: as you await screening 
 do you hope you have the parasite?” “Of course not!” said Balch. “Isn’t that the whole point? To be clean, because it’s better not to have a Slug infection?” The economist’s expression hardened. “You’re mistaken. You should pray you’re infected.” “Nonsense!” “It’s paradoxical,” said the economist, eyes widening. “You’re unaware whether you’re free of the parasite. But you do know what you’re capable of at this moment. You have a handle on your own abilities — your cleverness and strength relative to others, and what that enables you to achieve. If you’re clean, your abilities will remain unchanged after your screening. Yet, if you’re infected, the calculus changes. You’ll become better at everything you’ve ever tried. As will half the world. You should therefore want to number among them.” Balch’s damp hands clenched. “There’s the rub,” the economist continued. “This screening represents a point of no return. You’ll soon learn whether what you are now is all you will be; whether your own mediocrity is mere inconvenience or inescapable fate. Could you live with the results of a clean diagnosis? Could anyone?”
Nature DOI suffix ≠ "/s...": Not a research article
World's most energy-efficient AI supercomputer comes online
Jonathan O’Callaghan
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German Chancellor Friedrich Merz inaugurated the new European supercomputer called JUPITER on 5 September.Credit: Ina Fassbender/AFP via Getty As US and Chinese technology firms have competed in the race to be innovators in artificial intelligence (AI), Europe has fallen behind. But on 5 September, a European supercomputer called JUPITER officially reached the exascale threshold, a milestone in computing power. The device could boost European research. JUPITER is the fourth-fastest computer in the world. Having surpassed one quintillion (1018) operations a second, it joins an exclusive league of exascale supercomputers. According to the European Union, it is also 100% powered by renewable energy, and ranks first in energy efficiency among supercomputers. JUPITER’s computational speed serves its main purpose — to push the capabilities of research in areas such as AI, weather modelling, astrophysics and biomedical research. It gives researchers in Europe access to their own top-level supercomputer, rather than having to rely on machines in the United States and elsewhere. The milestone is “absolutely” a big deal for Europe, says Kirk Cameron, a computer scientist at Virginia Polytechnic Institute and State University (Virginia Tech) in Blacksburg, particularly with regard to AI and large language models (LLMs). “There’s this race going on in the world of who will be the innovators in AI,” he says. “It’s taken a little bit to get [Europe] into the race. So it’s really nice to see them making that progress.” Nature examines what JUPITER can actually do, and what it will be used for. What is JUPITER? JUPITER, which stands for Joint Undertaking Pioneer for Innovative and Transformative Exascale Research, has been in development since 2018, with the explicit aim of giving Europe a foothold in the supercomputer race taking place around the world. Funded by the European Commission and EU member Germany, it is located at the JĂŒlich science research centre in Germany. JUPITER booted up and performed its first computations in July, says Thomas Lippert, the project lead on JUPITER at JĂŒlich. Running on some 24,000 NVIDIA chips, JUPITER is capable of exceeding 1,000 petaflops — one exaflop, or one million trillion operations per second — at its peak performance. For comparison, a typical laptop operates at one teraflop, or one trillion calculations per second. A day in the life of the world’s fastest supercomputer Officially, JUPITER is the fourth-fastest supercomputer in the world, with a benchmark performance of about 800 petaflops, after the United States’ El Capitan (1.7 exaflops), Frontier (1.35 exaflops) and Aurora (1 exaflop). Lippert says that having a supercomputer such as JUPITER will enable Europe to develop the talent necessary to build and operate such machines in the future. “Our economy and welfare depend on these technologies,” he says. The EU says that JUPITER “runs entirely on renewable energy” to limit its impact on the environment. Lippert says that this is achieved by paying to use only renewable energy from Germany’s national grid. When it is running at full load, JUPITER will use 17 megawatts of power, which is equivalent to powering about 11,000 homes. Cameron says such supercomputers can be extremely power-hungry and cause problems. “You’re competing with cities for power,” he says. “These things start to impact the infrastructure of communities around these areas.” How will JUPITER help European research? Researchers will be able to apply to use the supercomputer up to twice a year, and 30 projects have already been selected. These include research on AI applications, such as foundation models and video generation, climate models, particle physics, energy applications and biomedical research for drug development and disease control.
Nature DOI suffix ≠ "/s...": Not a research article
Coordinate to combat Pakistan’s climate-driven disasters
Raees Khan, Jie Liu
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Pakistan is facing a ruthless array of climate-driven disasters — from torrential floods and heatwaves to wildfires and hailstorms. This summer, monsoon floods have already caused more than 900 deaths and roughly 1,000 injuries (see go.nature.com/3vjeuqc). And in 2022, a flood affected at least 33 million people (M. A. Waqas Science 378, 482; 2022) and caused an estimated US$40 billion in economic losses.
Nature DOI suffix ≠ "/s...": Not a research article
Which diseases will you have in 20 years? This AI accurately predicts your risks
Gemma Conroy
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An artificial-intelligence system trained on data from 400,000 people in the United Kingdom can estimate the likelihood that a person will develop cancer and a host of other diseases over the course of 20 years.Credit: Brooks Kraft/Corbis/Getty A new artificial intelligence (AI) tool can forecast a person’s risk of developing more than 1,000 diseases, in some cases providing a prediction decades in advance1. The model, called Delphi-2M, uses health records and lifestyle factors to estimate the likelihood that a person will develop diseases such as cancer, skin diseases and immune conditions up to 20 years ahead of time. Although Delphi-2M was trained only on one data set from the United Kingdom, its multi-disease modelling could one day help clinicians to identify high-risk people, allowing for the early roll-out of preventive measures. The model is described in a study published today in Nature. The tool’s ability to model multiple diseases in one go is “astonishing”, says Stefan Feuerriegel, a computer scientist at the Ludwig Maximilian University of Munich in Germany, who has developed AI models for medical applications. “It can generate entire future health trajectories,” he says. Oracle of health Researchers have already developed AI-based tools to predict a person’s risk of developing certain conditions, including some cancers and cardiovascular disease. But most of these tools estimate the risk of only one disease, says study co-author Moritz Gerstung, a data scientist at the German Cancer Research Center in Heidelberg. “A health-care professional would have to run dozens of them to deliver a comprehensive answer,” he says. To address this, Gerstung and his colleagues modified a type of large language model (LLM) called a generative pre-trained transformer (GPT), that forms the underpinning of AI chatbots such as ChatGPT. When asked a question, GPTs provide outputs that, according to their training on vast volumes of data, are statistically probable. An AI revolution is brewing in medicine. What will it look like? The authors designed their modified LLM to forecast a person’s likelihood of developing 1,258 diseases on the basis of their past medical history. The model also incorporates the person’s age, sex, body mass index and health-related habits, such as tobacco use and alcohol consumption. The researchers trained Delphi-2M on data from 400,000 participants of the UK Biobank, a long-term biomedical monitoring study. For most diseases, Delphi-2M’s predictions matched or exceeded the accuracy of those of current models that estimate the risk of developing a single illness. The tool also performed better than a machine-learning algorithm that uses biomarkers — levels of specific molecules or compounds in the body — to predict the risk of several diseases. “It worked astonishingly well,” says Gerstung.
Nature DOI suffix ≠ "/s...": Not a research article
Why we launched Denmark’s second Young Academy (and what’s different about it)
Jonathan Quinson
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YATSI fellows visiting NKT Photonics in Birkerþd, Denmark.Credit: Tom Jersþ/Danish Academy of Technical Sciences As early-career researchers navigate increasingly complex challenges — from climate change to digital transformation — they need to be empowered to take bold steps, form lasting networks and champion science that serves society. This is where National Young Academies come in. Typically founded by scholars at the beginning of their independent research careers, Young Academies give a voice to and represent the interests of young scientists in academia, helping them to be heard by national governments and wider society. There are now more than 60 Young Academies (and similar networks) worldwide. But in 2023, a different kind of Young Academy launched in Denmark. YATSI, the Young Academy of Technology, Science and Innovation, aims to give a voice to early-career researchers and professionals in STEM (science, technology, engineering and mathematics), with representatives from both academia and industry, and also to strengthen collaboration between the two sectors. YATSI’s three founders (Sandra Wingaard Thrane, Janus Juul Eriksen Andreas Hougaard Laustsen-Kiel and Kirsten Marie Ørnsbjerg Jensen) felt there was a need for a Young Academy that focused exclusively on STEM. Thrane co-founded Bactolife, a biotechnology start-up in Copenhagen, in 2017 and is now its chief scientific officer. Eriksen is a chemistry researcher at the Technical University of Denmark (DTU) in Kongens Lyngby. Laustsen-Kiel leads the Center for Antibody Technologies at DTU, and is also the co-founder of eight companies. Jensen is a researcher in nanomaterials at the University of Copenhagen. Careers advice from scientists in industry YATSI now has four physical meetings a year and several ad hoc meetings across its three committees. Meetings are hosted by universities and companies, and cover topics that range from career development to STEM education and policy. Fellows are selected on the basis of written applications and in-person interviews. To be eligible, applicants must have completed a PhD (or equivalent) within the past seven years. Membership lasts for five years, and the academy is governed by a five-member council. We hope to reach a full capacity of around 40 members by 2027 (the number is capped to optimize communication, networking and teamwork, but also to be representative of early-career STEM professionals in Denmark). Our current fellows come from six universities and nine companies or start-ups across Denmark, and have a variety of STEM backgrounds. Their specialisms encompass physics, chemistry, engineering, food, biology, information technology, cybersecurity and many more fields. There is a balanced and diverse mix of industry and academic profiles, with both Danish people and researchers from other countries who are working in Denmark. For this reason, the lingua franca of YATSI is English. Speaking as a French researcher based in Denmark, joining YATSI is a great opportunity to network with other scientists at a similar career stage. And as a member of YATSI’s Interact committee, I have helped to collate advice around effective industry–academia interactions. Policy, Inspire, Interact YATSI has three committees. Its Policy committee aims to ensure that the voices of early-career professionals are heard in conversations around university education, research funding and personal development. The committee also highlights career opportunities in Denmark and Europe. There is a recognized need for closer collaboration between academic science and industrial commercialization. The Policy committee is gathering support for an academia–industry sabbatical-exchange programme aimed at giving participants a better understanding of the real-world relevance of academic research and helping to ensure that industry practices are informed by state-of-the-art scientific knowledge. Denmark’s Best Science Meme is one example of how YATSI’s Inspire committee strives to engage the public, to illustrate the breadth and diversity of STEM in Denmark and to disseminate knowledge about STEM research and innovation.
Nature DOI suffix ≠ "/s...": Not a research article
How did assaults on science become the norm — and what can we do?
Gretchen T. Goldman
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Science under Siege: How to Fight the Five Most Powerful Forces that Threaten Our World Michael E. Mann & Peter J. Hotez PublicAffairs (2025) Months into President Trump’s second term, science and scientists are under attack as never before in the United States. The administration is forcing devastating cuts to previously stable US research investments, dismantling federal science agencies and programmes, ousting independent scientific officials and blatantly disregarding evidence on issues that affect us all, including vaccines, air pollution and fossil fuels. ‘Now is not the time for despair’ — how scientists can take a stand against political interference The scientific community needs to recognize these trends and fight back in every way possible. The timely release of Science under Siege by paediatrician and vaccine specialist Peter Hotez and climate scientist Michael Mann is a welcome addition to the scientific community’s arsenal. Both authors work to dispel misinformation in the public and political arenas, and both have experienced personal attacks because of it. Mann, known for his ‘hockey stick’ visual representation of soaring global average temperatures owing to climate change, has faced years of public disparagement and threats to his physical safety. Hotez found himself in the crosshairs of the politicization of public-health guidance, on vaccines in particular, during the COVID-19 pandemic — and had to hire private security. Together, they explore the forces that undermine science in the United States and beyond. Five forces to contend with The duo skilfully establishes parallels in the attacks on climate scientists and on public-health professionals. The two fields might seem disparate, but specialists in both share a responsibility to inform the public about the “one-two punch of climate change and pandemics” — the effects of which are mutually reinforcing to “threaten massive loss in human life” — and find solutions. Who is on RFK Jr’s new vaccine panel — and what will they do? In some cases, Mann and Hotez note, the same tactics are used in attempts to discredit their work in both fields — sometimes even by the same people. For example, climate-disinformation messaging morphed over several years from ‘it’s not real’ to ‘it’s actually good for us’. These same tactics were adopted by peddlers of COVID-19 misinformation, who claimed that widespread infection could lead to herd immunity, and caught on much faster, mere months after the virus began spreading. But who’s behind the lies, propaganda and attacks? Mann and Hotez identify five forces — the ‘five Ps’ — that drive threats to science and scientists: plutocrats, petrostates, pros (that is, academics and specialists who use their credentials to promote disingenuous, and lucrative, contrarian views), propagandists and the press. Mann and Hotez detail how bad actors continue to propagate misinformation, persecute scientists, undermine science-based decisions from policymakers and the public and threaten global health and safety. Fighting back As the president of the Union of Concerned Scientists — a science-advocacy non-profit organization that spends its time fighting these known enemies — I found this thorough naming and shaming resonant and indeed cathartic. I imagine that this exploration of just how pervasive and well-funded these forces are might also bring relief to scientists wondering why their commitment to truth-telling isn’t enough.
Nature DOI suffix ≠ "/s...": Not a research article
Fertility declines are no cause for concern, history shows
John MacInnes
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Nature’s News feature asks how problematic the decline in fertility around the world is likely to be (see Nature 644, 594–596; 2025). Comfort can be found by looking to history.
Nature DOI suffix ≠ "/s...": Not a research article
Impoundment of funds endangers US investment in science and medical research
Joshua S. Weitz, Mallory J. Harris, Alyssa H. Sinclair, Jeremy M. Berg
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By the start of August, the National Institutes of Health (NIH) had awarded billions of dollars less in research grants this fiscal year than in previous ones (see go.nature.com/46as8rp). The impoundment of funds that the US Congress designated for support of science and medical research endangers US investments in people, projects and health advances.
Nature DOI suffix ≠ "/s...": Not a research article
Sweet like chocolate: researching in the shade of a cacao tree
Rachel Brazil
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“The seven-year-old cacao tree (Theobroma cacao) that I’m inspecting in this photo is part of the Model Cocoa Orchard established by the University of the West Indies’ Cocoa Research Centre (CRC), where I work as a food-technology researcher. My colleagues and I use this 1,500-tree orchard in Valsayn, a town in the north of the island of Trinidad, to better understand cocoa production. My research focuses on the fermentation of cacao beans, a process that is carried out mainly at a small scale on local farms. Cacao trees produce fruit pods, which are harvested and broken open to release the pulp-covered beans. I’m holding one here. The acidity, sweetness and floral flavour vary from pod to pod. It’s the pulp that acts as the fuel for the microorganisms that drive the beans’ fermentation. The chemical changes that occur over about a week remove the beans’ bitterness and turn them red-brown, but only after roasting do they gain their chocolate flavour. The success of the fermentation process is dependent on climate. And with weather patterns becoming less predictable, the quality of the beans has started to decline. We have started to experiment with manipulating sucrose and water levels at the start of fermentation, and we are also using other techniques to tweak the process.
Nature DOI suffix ≠ "/s...": Not a research article
Controversial New Alzheimer’s Drugs Offer Hope—But at a High Cost
Liz Seegert
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Nature DOI suffix ≠ "/s...": Not a research article
How billions of hacked mosquitoes and a vaccine could beat the deadly dengue virus
Lucila Pinto
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Support for this article was provided by the Pulitzer Center. Last month, a parade of vehicles wound its way through three cities in Brazil, releasing clouds of mosquitoes into the air. The insects all carry a secret weapon — a bacterium called Wolbachia that lowers the odds that the mosquitoes can transmit the dreaded dengue virus to humans. This is the world’s largest ‘mosquito factory’: its goal is to stop dengue These infected mosquitoes are the latest weapon in Brazil’s fight against dengue, which infects millions of people in the country each year and can be fatal. A biofactory that opened in the town of Curitiba in July can produce 100 million mosquito eggs per week — making it the largest such facility in the world. The company that runs it, Wolbito do Brasil, aims to protect about 14 million Brazilians per year through its Wolbachia-infected mosquitoes. That will come as welcome news for the Brazilian health officials battling the rapidly growing threat of dengue. In 2024, the country experienced its worst outbreak yet: with 6.6 million probable cases and more than 6,300 related deaths. This year’s outbreak, although less severe, is also one of the highest on record, with 1.6 million probable cases so far (see ‘Dangerous outbreaks’). And the problem is spreading. Argentina, Colombia and Peru also experienced record-breaking outbreaks in 2024 and have seen a sustained increase in cases in recent years. Across Latin America and the Caribbean, deaths from dengue last year totalled more than 8,400 and the global figure reached more than 12,000 — the highest ever recorded for this disease. SOURCE: Brazilian Ministry of Health As outbreaks grow larger and the crisis becomes more urgent, the Wolbachia method isn’t Brazil’s only bet. A locally produced dengue vaccine is now awaiting approval by the country’s drug-regulatory agency, and its health ministry expects to start administering tens of millions of doses by next year. These twin advances offer some hope to other countries — in the region and beyond. Driven by forces such as climate change, mosquito adaptation, globalized trade and movements of people, dengue is becoming a crisis worldwide, with an estimated 3.9 billion people at risk of infection. As Brazil rolls out its armies of infected mosquitoes and a vaccine in the coming year, the rest of the world will be watching closely. The local approach Currently, there is one main dengue vaccine in use around the world: Qdenga, licensed by the Japanese pharmaceutical company Takeda. The vaccine has been approved in many countries, including Brazil, which was the first nation to include it in its public-health system. However, Qdenga’s roll-out in Brazil is limited. The country bought nine million doses of the two-dose vaccine this year: enough to vaccinate 4.5 million of its population of more than 210 million. So far, Qdenga has been administered to children between the ages of 10 and 14, one of the groups most likely to end up in hospital after contracting dengue, together with older people. Its safety and efficacy have not yet been tested in adults aged over 60. The main reasons for such a limited roll-out in Brazil are availability and cost. Even though Brazil secured Qdenga from Takeda at one of the cheapest prices in the world —around US$19 per dose — the cost is still high compared with other vaccines. And even in the most optimistic scenario, the maximum number of doses Takeda could provide by 2028 is 50 million — enough to vaccinate 25 million people. What’s more, for people who have not had dengue before, clinical trials did not show Qdenga to be effective against all four variants — or serotypes — of the dengue virus. When will dengue strike? Outbreaks sync with heat and rain Brazil is trying to address all of those limitations with its one-dose vaccine candidate, developed at the Butantan Institute, a public biomedical research centre in São Paulo. “Having local production capacity gives us independence on decisions — how many doses we need, and at what speed to vaccinate,” says Esper Kallás, Butantan’s director. “You can practise prices that are more suitable and absorbable by a public-health system such as Brazil’s.” Butantan is also optimistic that its vaccine will be effective against all four forms of dengue. Severe disease usually occurs when a person is infected by a different serotype to their first infection. That means that a successful vaccine needs to generate antibodies for all four serotypes without triggering severe reactions, which makes it a difficult vaccine to develop. “It was indeed a challenge, as each serotype behaves differently,” says Neuza Frazatti Gallina, manager of the viral vaccine development laboratory at Butantan. The vaccine’s development began at the US National Institutes of Health in the late 1990s, where scientists transformed dengue viruses they had isolated from patients into weakened vaccine strains that could trigger the production of protective antibodies without causing disease. In 2009, Butantan extended that research by working to solve the challenges of combining the four strains into a vaccine. Eggs of mosquitoes infected with Wolbachia bacteria. After hatching, the mosquitoes will be released to prevent the spread of dengue.Credit: Xinhua/Shutterstock After testing 30 formulations, Butantan arrived at one that proved highly effective in preventing infections, according to the preliminary results of a phase III trial involving more than 16,000 volunteers in Brazil. The study reported that two years after vaccinations, the formulation was 89% effective in preventing infections in people who had previously been infected with dengue, and 74% effective in those with no previous exposure1. “It was a well-designed trial,” says Annelies Wilder-Smith, who is team lead for vaccine development at the World Health Organization (WHO). But she says one limitation of the trial is that it was conducted in a single country, and therefore runs a risk that all four serotypes were not circulating at the time. In fact, serotypes 3 and 4 were not prevalent during the data-collection period of the clinical trial, although they are now circulating in Brazil. Butantan researchers suggest that the vaccine will be effective against serotypes 3 and 4, pointing to data from a phase II trial2 in 300 adults that showed participants produced neutralizing antibodies to each of the serotypes. That study evaluated safety and immunological response in the short term, rather than looking at the vaccine’s long-term efficacy in preventing infections. The full results of the Brazilian phase III trial — which will provide data on long-term effectiveness — are not yet public and are undergoing peer review. The vaccine is already moving through the country’s regulatory process. And although there’s still no certainty about when Anvisa, Brazil’s regulatory agency, will approve the vaccine, the government is counting on it. In February, President Luiz Inácio Lula da Silva announced that, starting in 2026, the Ministry of Health would be buying 60 million doses annually. To meet that demand, Butantan is now producing the vaccine at its São Paulo facility. On its lush campus, an entire building is dedicated to churning out doses. Regarding the vaccine’s approval, “We are very confident,” says Kallás. “We also anticipate that there is a very prominent need to have this product in the arms of people. So we hit the road running and started producing vaccines late last year.” Although Butantan’s production efforts will focus initially on meeting Brazil’s need for millions of doses, Kallás expects that the vaccine could reach other countries. Butantan has been discussing with its development partner — the pharmaceutical giant Merck — and the Pan American Health Organization (PAHO) how to make the vaccine accessible to other countries. The logical first step, he says, would be to roll it out through PAHO to Latin America and the Caribbean, and then to other regions. In the meantime, Merck is developing a potential vaccine for Asia with an almost identical formulation, which builds on the knowledge that Butantan has developed. In a statement, the drug firm said that Butantan is “sharing clinical data and other learnings”. In June, Merck started enrolling participants for its own phase III trial. “All the data, experiences and insights they have collected with the Butantan vaccine will be helpful,” says Wilder-Smith. Infecting mosquitoes While Butantan awaits news about the vaccine’s approval, the Wolbachia method to control dengue is gaining momentum. The World Mosquito Program (WMP) — a non-profit group of companies owned by Monash University in Melbourne, Australia, where the strategy was developed — has operations in 14 countries, including Vietnam, Indonesia, Mexico and Colombia, but Brazil leads the way in terms of the scale of its expansion. The method’s arrival in the Americas is tied to Brazilian researcher Luciano Moreira, now the chief executive of Wolbito do Brazil. Wolbachia is naturally present in around 50% of insects, but not in the mosquito species Aedes aegypti, which is the main transmitter of dengue and many other viruses.
Nature DOI suffix ≠ "/s...": Not a research article
Alzheimer’s Drugs Are Finally Tackling the Disease Itself. Here’s How
Esther Landhuis
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Nature DOI suffix ≠ "/s...": Not a research article
Bioelectronic implants built from rolled-up stretchy circuits
Hyunjin Lee, Dae-Hyeong Kim
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Flexible, stretchable medical devices called soft bioelectronic implants have the potential to improve both the quality of life and the survival of people with severe, chronic diseases1,2. Now, Xie et al.3 and Khatib et al.4 report the fabrication of soft bioelectronic fibres made by rolling up stretchy sheets that are patterned with 2D electronics. The fabrication techniques developed by the researchers enable the integration of many electronic components into a single device. As well as sensing the properties of the surrounding tissue, the fibres can stimulate cells (Khatib et al.) or navigate in vivo environments (Xie et al.).
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: The most- and least-improved countries for chronic disease
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
People are more likely to cheat when they delegate tasks to AI
Shoko Suzuki
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Artificial intelligence (AI) is permeating daily life at an accelerating pace. From drafting documents and translating text to processing taxes and guiding business decisions, AI is becoming a trusted assistant. But what if that assistant were asked — subtly or explicitly — to break the rules? And what if its actions faithfully mirrored the user’s indirect intentions to cheat, giving the person plausible deniability? Writing in Nature, Köbis et al.1 reveal a troubling dynamic: people are more willing to engage in dishonest behaviour when a large language model (LLM) executes it instead of them, and the LLM is more likely than a human intermediary to comply with prompts that promote cheating.
Nature DOI suffix ≠ "/s...": Not a research article
Caribbean coral reefs are threatened by rising seas
Nicola K. Browne
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Coral reefs provide habitats rich in biodiversity and offer protection against flooding. Climate change threatens their existence if sea-level rise (SLR) outpaces the ability of coral reefs to grow when molecules of calcium carbonate are added to them though a process termed accretion. Writing in Nature, Perry et al.1 present modelling of reef growth and SLR under a variety of global-warming scenarios for more than 400 coral reefs in the tropical western Atlantic (TWA), including reefs in the Florida Keys, the Gulf of Mexico and Mexican Mesoamerica.
Nature DOI suffix ≠ "/s...": Not a research article
AI can learn to show its workings through trial and error
Daphne Ippolito, Yiming Zhang
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When a student encounters a challenging mathematics problem or a programmer needs to write a complex algorithm, they will rarely solve it all in one go. Instead, they will reason through the task, jotting down notes and intermediate steps to arrive at a final solution. Likewise, large language models (LLMs) — artificial intelligence (AI) systems that process and generate human language — perform better at complex tasks when they write down their reasoning process before blurting out an answer than when they do not1. In a paper in Nature, the DeepSeek AI team2 reports that LLMs can be incentivized to learn to reason without ever being shown examples of human reasoning trajectories, using a trial-and-error process called reinforcement learning.
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Heatwaves can be directly linked to emissions from specific companies
Jacob Smith
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Nature DOI suffix ≠ "/s...": Not a research article
LIGO is 10 years old: black-hole breakthroughs will ‘only get better’
Davide Castelvecchi
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The Laser Interferometer Gravitational-wave Observatory (LIGO) facility, in Hanford, Washington.Credit: IMAGO/Xinhua via Alamy Ten years after the historic discovery of gravitational waves, and having spotted hundreds more of these space-time swells since then, physicists say they are only just getting started. On 14 September 2015, the twin facilities of the Laser Interferometer Gravitational-wave Observatory (LIGO), in Hanford, Washington, and Livingston, Louisiana, sensed the passing of ripples in space-time that had originated more than one billion years ago in the cataclysmic merger of two black holes many galaxies away. Clearest gravitational wave detection yet confirms Hawking’s black hole theory That milestone took more than four decades of breakthroughs and heroic improvements in experimental techniques. But seeing such black-hole ‘binaries’ has now become routine. The LIGO detectors — alongside their sister observatories Virgo, near Pisa, Italy, and KAGRA, under Mount Ikenoyama, Japan — have roughly doubled their sensitivities over the past ten years, enabling them to monitor a region of the Universe that is twice as wide and contains about eight times as many galaxies. “We see binary black holes every three days on average now, which is pretty amazing to me,” says David Reitze, a physicist at the California Institute of Technology in Pasadena and long-time director of the LIGO observatories. “It’s only going to get better.” Over the next decade, teams in both the United States and Europe are hoping to build bigger observatories that can spot gravitational waves from anywhere across the observable Universe. Nature takes a look at scientists’ plans for the next generation of gravitational-wave detectors. Cosmic Explorer US-based gravitational-wave researchers want to build the Cosmic Explorer (CE), an interferometer similar to LIGO, but with L-shaped arms that are ten times longer, stretching 40 kilometres. If it is built and works as planned, the CE should collect 100,000 black-hole mergers each year, essentially spotting them wherever they happen in the observable Universe. These will include events that happened more than ten billion years ago, when galaxies were at their busiest creating and destroying stars and making and merging black holes, says Reitze. “You really do want to be able to probe farther back.” Each year, the CE would also pick up more than one million mergers of lighter objects called neutron stars — a rate of or one every several seconds, says Stefan Ballmer, a physicist at Syracuse University in New York. But building it will not be cheap. With its arms stretching far beyond the horizon, the CE will run into the curvature of the Earth. If the endpoints are built at the ground level, the middle points will have to reach some 30 metres below the surface. Physicists have been scouting the United States for remote locations that are naturally bowl-shaped, which could reduce the need for digging. “We are winnowing the candidate sites down to a shortlist,” says Ballmer. LIGO upgrades Meanwhile, a planned set of upgrades called LIGO A# (A-sharp) could more than double the sensitivity of the existing observatory in the early 2030s, and help to test the cutting-edge technology that will eventually go into the CE. Improvements will include raising the power of the lasers that run down the interferometer arms. The LIGO team also plans to install heavier, more stable and more perfectly reflective suspended mirrors at the ends of those arms. (Interferometers detect gravitational waves by measuring tiny changes in the amount of time it takes for laser light to bounce between the mirrors.) However, both the continued funding for maintaining LIGO and that for any upgrades — let alone new US-based facilities — could be at risk if President Donald Trump achieves his target of severely downsizing the US National Science Foundation, the agency that has funded most of LIGO’s construction and operation. Congress has hinted that it might prefer less-drastic cuts, however, and researchers remain hopeful. “I think we just have to wait and see,” Reitze says. An artist’s impression of the Einstein Telescope — an underground gravitational-wave observatory with three 10-kilometre-long arms arranged in a triangle. Credit: Marco Kraan (Nikhef) ‘Einstein’ telescope
Nature DOI suffix ≠ "/s...": Not a research article
Gone with the wind: deciphering how dandelions drive seed dispersal
Mary Abraham
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“You don’t need a weatherman / To know which way the wind blows,” Bob Dylan tells us in his song Subterranean Homesick Blues. One workaround that does not require a meteorologically trained professional is to observe in which direction seeds waft away on the breeze (pictured) from dandelions (Taraxacum officinale). Shields and colleagues delve into the mechanisms that enable this type of plant spread (J. Shields et al. J. R. Soc. Interface 22, 20250227; 2025).
Nature DOI suffix ≠ "/s...": Not a research article
GPS timekeeping is increasingly vulnerable: here’s how to deliver future-proofed time
Leon Lobo, Douglas Paul, Chander Velu
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It might not be apparent, but almost everything people do in this digitally connected world, from sending a text or e-mail to doing an Internet search or paying for something online, depends on accurate, resilient timing. Most electronic communications rely on digital infrastructure that is synchronized to a common time reference, enabling information to flow at a known rate. Accurate timing is also crucial for synchronizing and stabilizing infrastructure such as electricity grids, for helping to ensure the integrity of financial transactions, for steering machinery for precision agriculture, and for managing transport, logistics and postal delivery systems, among a host of other essential functions. Today, the necessary timing signals come overwhelmingly from Global Navigation Satellite Systems (GNSS). These deliver signals from space, with only a radio receiver needed to receive and interpret them. Chief among them is the US-developed Global Positioning System (GPS). GPS is free to use, and the technology is mature: miniature GPS receivers are now embedded in every smartphone, at a cost of a few dollars per unit. This is an easy, low-cost way to reliably synchronize time, certainly compared with the old method of physically calibrating your clock to a reference clock at a national standards agency. Best ever clocks: breakthrough paves way for ultra-precise ‘nuclear’ timekeepers But this success has bred complacency — and led to underappreciated risk. GNSS are far from fail-safe. In many parts of the world, organized-crime syndicates and military authorities are among those increasingly jamming GNSS signals (blocking them entirely) or spoofing them (transmitting false signals to provide misleading time and position coordinates). Disruptions to the signal due to extreme weather events are also on the rise. In some sectors, such as aviation, a multitude of systems would potentially be affected in the event of more-widespread outages. But there is low awareness of the risks — and protections are hugely variable between sectors. The increasing vulnerability of time signals from space necessitates the development of alternative ways of accessing accurate, resilient and secure time. We (the authors) have been involved in varying capacities in technology and economic measures to deliver a nationwide, resilient terrestrial timing solution that is independent of GNSS in the United Kingdom. Here we set out three key steps that we think would help to facilitate the development of alternative time sources worldwide: increasing buy-in from business; linking up existing, heterogeneous local timing systems; and creating entirely new uses for time. Getting buy-in from business Constellations of GNSS satellites disseminate time from the national-standards laboratories that contribute to the formulation of the global time scale, Coordinated Universal Time (UTC). The GPS system was developed by the US Department of Defense during the cold war, initially for the exclusive use of the US military. Each GPS satellite carries multiple atomic clocks, which are ultimately synchronized with a representation of the UTC, known as UTC(USNO), generated by an ensemble of atomic clocks at the US Naval Observatory in Washington DC. The signals these satellites beam down to Earth enable users to determine the time to within an accuracy of 10–7 seconds, or 100 billionths of a second. Recognition in the 1980s of the wider potential societal benefits of GNSS led the United States to make an intentionally degraded, ‘selectively available’ version of the GPS signal accessible to everyone globally, free of charge. The full version was made public in 2000, since when its use has ballooned in a plethora of civilian applications. Other GNSS systems exist, such as GLONASS (operated by Russia), Galileo (the European Union) and BeiDou (China). But GPS remains dominant owing to widespread public confidence in a US-provided infrastructure and to the system’s earlier availability for general use, which means a large number of older receivers are only GPS-compliant. Some 5.6 billion end-user GNSS receiver units were in use in 2023, a number predicted to increase to almost 9 billion units in 2033 (see ‘Sky-high demand’). The economic benefits of using GNSS have been estimated to be around US$300 billion annually for the United States, $81 billion across Europe and from $9 billion to about $18 billion for the United Kingdom (see ‘Productivity plus’). Source: EU Agency for the Space Programme (https://go.nature.com/42AQKJL) The potential costs of disruption to GNSS are similarly considerable: across all sectors, a report for the UK government in 2023 estimated these costs, per day, to be almost $1.9 billion for the United Kingdom alone. But whereas the economic benefits of using GNSS often accrue to individual firms, the economic cost of disturbances to the GPS signal — for example, the failure of the electricity grid due to a GPS outage that might affect transport, financial and communication systems — tends to be borne by all of society. More onus needs to be put on firms and utilities that provide services through GNSS to invest in timing resilience. Regulation to increase the liability of individual firms, and personal accountability of senior managers for ensuring resilience of time, is one way to make this happen. There is also a need to support the development of alternative assured ‘holdover time’ capabilities: accurate, locally based clocks that can continue to provide time for a while if the main GNSS signals are lost. Source: London Economics (https://go.nature.com/4G5NDYM) The cumulative investment costs across every organization in every sector to provide such a holdover system are likely to be significant. Developing national public infrastructures for delivering resilient timekeeping directly from national representations of UTC — in effect, recreating timekeeping as a national public utility — is a way to reduce direct costs for businesses. Such a public utility could instil trust and confidence in users, and cover its costs by offering tiered, paid-for levels of assurance of time. In the United Kingdom, a supporting terrestrial clock system is being designed and developed as a nationwide time infrastructure through the National Timing Centre research and development programme (of which one of us, L.L., is head) at the National Physical Laboratory (NPL) at Teddington. This system is linked to UTC(NPL), the United Kingdom’s real-time realization of UTC. But limited understanding of the need for alternative assured-time capabilities is a barrier to achieving business and political buy-in. A programme of public awareness about the use and importance of GNSS should be rolled out globally, emphasizing both the risks inherent in the current systems and the benefits of alternative timing systems for increased resilience and enhanced performance. Linking up time systems Crucial infrastructures, from financial services to transport and energy systems, are often interdependent. Yet they tend to operate as independent ecosystems, subject to their own legislation and with their own regulatory standards, policies, supply chains and digital ecosystems. Little thought tends to be given to the security of timekeeping in the design and maintenance of the digital systems underpinning this infrastructure. Time’s intangible nature means that it often falls in the gap between cybersecurity and physical-security measures designed to protect digital and physical assets, respectively. When mitigating GNSS loss or disruption is considered at all, it tends to be by individual firms on an ad hoc basis. For example, telecommunications network providers often have atomic clocks distributed across their fibre exchanges to enable synchronization to be maintained for the Internet backbone even if GNSS signals are disrupted. Such mitigation measures are rarely tested robustly for the possibility of GNSS outages across all interconnected sectors. Atomic clock keeps ultra-precise time aboard a rocking naval ship The increasingly interlinked nature of timing infrastructure implies that terrestrial clocks need to be integrated and able to coordinate time in the case of disruption to GNSS. This underlines the desirability of government intervention to provide a base capability that is accessible to all users wherever and whenever they need it. This might take the form of new legislation or regulation and standards to allow interoperability between essential infrastructures. It is part of the rationale behind the UK National Timing Centre’s research programme. A further consideration is that the global supply chain for timing systems — from atomic clocks, time distribution and monitoring systems to user equipment — is currently sparse and lacks diversity. The ubiquity and utility of GNSS for time has resulted in industry investing in and developing receivers that are low in size, weight, power and cost, proliferating dependency on this single solution. (One of us, D.P., is head of the UK Hub for Quantum Enabled Position, Navigation and Timing, led by the University of Glasgow, UK, which runs a programme developing cheaper timing technologies.) A more diverse supply chain needs to be built to provide the enabling technologies to support a national timing infrastructure that can enhance the resilience of time. This needs to be complemented by an upgrade of the skills pipeline. Private-sector investments in building such a resilient supply chain to provide reliable timing will depend on effective, long-term commitment from governments1. Policy initiatives such as direct public investment, or incentives such as tax credits, interest deferrals and loans, must be immune to political winds of change to truly de-risk such investments. This could be achieved by regulating the minimum holdover time — the length of time any backup system can provide accurate timekeeping — across industries to ensure commitment to build and develop such time-based resilience. Such regulation needs to define the requirements for specific clocks with the accuracy needed to enable each national infrastructure to operate effectively. Creating new uses for time The extra revenue-generating opportunity of new timing systems is, on the face of it, limited when compared with the extra costs. A focus solely on managing risk and enhancing the resilience of time systems might not, therefore, be enough to convince firms of the need to invest in supporting the development of terrestrial holdover timing systems. Financial markets require precise, trustable time for transactions to be recorded accurately.Caption: Michael M. Santiago/Getty
Nature DOI suffix ≠ "/s...": Not a research article
This AI tool predicts your risk of 1,000 diseases — by looking at your medical records
Shamini Bundell, Nick Petrić Howe
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Nature DOI suffix ≠ "/s...": Not a research article
‘Lipstick on a pig’: how to fight back against a peer-review bully
Katarina Zimmer
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Nyssa Silbiger still recalls the rude remark that reviewer three made in 2014 about her first paper describing her PhD research. “The phrases I have so far avoided using in this review are, ‘lipstick on a pig’, and ‘bullshit baffles brains’,” they wrote. To Silbiger, a marine biologist at the University of Hawai‘i at Mānoa, the words cut deep. The critique not only made it difficult to work out how she should revise her manuscript on the bioerosion of coral reefs, but also led her to question her abilities and whether she belonged in science at all. “As a twenty-something student, that can have a really big impact on your ability not only to conduct science, but your whole future career,” says Silbiger, who now leads her own marine-ecology group at the university. Can Germany rein in its academic bullying problem? Peer review is supposed to be critical. But too often, Silbiger says, reviewer feedback crosses the line into an unprofessional realm. Such unacceptable behaviours range from outright bullying of other scientists and personal comments about the authors to mean-spirited or unhelpful remarks without constructive, evidence-based criticism. In 2019, Silbiger and Amber Stubler, a marine ecologist at Occidental College in Los Angeles, California, conducted a survey of roughly 1,100 scientists. Some 58% of respondents reported that they had encountered unprofessional peer-review comments1. In particular, women, non-binary scientists and people of colour said that the experience had harmed their confidence and productivity and delayed their career advancement. Attention to the issue has grown ever since and, fortunately, so have ways to address it. Journals, editors and scientific organizations have begun to explore a range of solutions to prevent bullying during the peer-review process and to hold mean-spirited reviewers accountable. Many scientists are also taking matters into their own hands by pushing back on unprofessional reviews. “There is progress being made, just in small increments and in different flavours,” says Emma Dunne, a palaeobiologist at the Friedrich Alexander University of Erlangen–Nuremberg in Germany, and the ethics editor of the journal Historical Biology. “I would like to think that things can only get better.” Why do nasty peer reviews happen? However negatively a referee views a study, there’s always a polite, evidence-based way to express criticism, says Sally Thomas, the Palaeontological Association’s publications officer. During the organization’s peer-review workshop for early-career researchers, she stresses the importance of being careful with language (see ‘Don’t do it’). “Always put yourself in the shoes of the author,” says Thomas, who is based in Cambridge, UK. Start by writing something positive, she says, “and then lay out what is not so good about the work in a totally unemotional and logical way”. Don’t do it As a peer reviewer, avoid harmful and unhelpful comments such as these real examples. ‱ “The writing of this paper was atrocious.”4 ‱ “The result of attending university in a developing country.”4 ‱ “You should look closely at a career outside of science.”1 ‱ “This young lady is lucky to have been mentored by the leading men in the field.”4 ‱ “Utterly disappointed in this submission, it achieves nothing, and was a waste of funding.”4 ‱ “The author’s last name sounds Spanish. I didn’t read the manuscript because I’m sure it’s full of bad English.”1 ‱ “This manuscript was not worth my time so I did not read it and recommend rejection.”4 ‱ “I have rewritten so much of this troubled paper that I should be included as an author.”4 ‱ “The first author is a woman. She should be in the kitchen, not writing papers.”1 ‱ “This paper is, simply, manure.”1 ‱ “What the authors have done is an insult to science.”1 ‱ “The author’s status as a trans person has distorted his view of sex beyond the biological reality.”1 ‱ “The English is not good enough; please have it reviewed by a native speaker.” ‱ “The authors provide us with a nice example [of] what they can, and cannot do, and how they (wrongly) understand nature and ecology.”4 ‱ “This person works for an NGO [non-governmental organization], you shouldn’t believe anything they say.”1 Yet research indicates that some scientists worry that being too nice will allow poor-quality studies to be published or think that authors deserve harsh comments for submitting substandard work2. Other times, overly harsh reviews might be intended to hinder or delay the publication of papers by competing laboratory groups. Personal snipes at study authors are also widespread, including ones targeting early-career scientists, women and people of colour, notes palaeontologist Farid Saleh at the University of Lausanne in Switzerland. He recalls how a reviewer once singled him and a female co-author out on a paper with 12 other authors, “calling us disingenuous, not real scientists, and making other personal attacks”. Remarks that disparage the authors’ English-language skills without constructive feedback are unprofessional and can exacerbate the existing challenges that individuals whose primary language is not English face in scientific publishing, adds Valeria RamĂ­rez Castañeda, a biologist at the University of California, Berkeley, who has studied such challenges3. Not all rude-seeming reviews are intentional, because cultural attitudes to directness vary. A blunt comment from one scientist might be perceived as rude by researchers who are used to more diplomatic language, RamĂ­rez Castañeda says. Reviews by scientists who lack the skills or experience to give nuanced feedback, senior researchers accustomed to the more-adversarial academic cultures of the past and scientists who don’t have the time to thoughtfully consider a paper might seem harsher than intended. What authors can do Avoiding problematic peer reviews starts by considering which journal to submit to and what its peer-review practices are. Specialists agree that the most common form of peer review — single-anonymous, in which referee identities are concealed from the authors but not vice versa — can promote unprofessional comments by giving reviewers anonymity. Valeria RamĂ­rez Castañeda says peer reviewers shouldn’t penalize a lack of English fluency.Credit: Valeria RamĂ­rez Castañeda Fortunately, many journals have begun to offer other kinds of peer review — such as double-anonymous review, in which both author and reviewer identities are concealed. This can help to prevent problematic comments and review-related rejections when reviewers are biased against authors from some demographics or nations. IOP Publishing (IOPP), a publisher of physical-science journals in Bristol, UK, has found few differences in overall rejection rates for papers with double-anonymous reviews compared with single-anonymous ones. However, an internal analysis of 2024 data covering around 28,000 papers suggests that some groups might benefit from double-anonymous reviews. Scientists in Africa were 4% more likely to have their paper accepted when the authors chose to be anonymous during the peer-review stage. But there is no clear trend for women and non-binary authors, says Laura Feetham-Walker, IOPP’s reviewer-engagement manager. And, in some scientific fields, “it’s not that challenging [for a reviewer] to identify who the senior authors are on any paper”, even if they are anonymized, notes Simon Harold, chief editor of Nature Ecology & Evolution in London. (Nature’s Careers team is independent of the journal’s publisher, Springer Nature, which also publishes Nature Ecology & Evolution and other Nature Portfolio journals.) Many journals, including the BMJ, Nature and some of the other Nature Portfolio journals (see go.nature.com/4nvd9zs), also offer open, or transparent, peer review. In this case, the reviews — and sometimes the referees’ identities — are published with the paper. Although this practice can encourage more-considerate behaviour, early-career scientists often worry about retaliation when critically reviewing papers from more-senior or influential authors. The sense of being able to speak freely with anonymity “is why I think the anonymous peer-review system is the default”, Harold adds. Should I tell anyone that I suspect misconduct in a paper I’m reviewing? When biologist Mayank Chugh was pursuing a master’s degree, members of his lab group in India received harsh feedback and demoralizing comments about their written English in some of their papers. So, they decided to submit his first paper to the journal eLife. The journal has both a consultative review process — in which editors and reviewers discuss the manuscript together and share consolidated feedback with the authors — and a policy to publish reviews and encourage reviewers to disclose their names. “We trusted that process over what we had experienced before,” says Chugh, who is now at the University of Maryland, Baltimore County, and a member of eLife’s early-career advisory group. Morteza Mahmoudi, a nanoscientist and anti-bullying researcher at Michigan State University in East Lansing, takes further steps when he anticipates an unproductive peer-review process — something he has often experienced with papers that challenge commercially important assumptions in his field. He now asks editors to exclude certain researchers from reviewing — an option that many journals provide. In these cases, “I don’t get those unnecessary delays in the process or harsh comments”, says Mahmoudi. After receiving a reviewer’s report, if authors aren’t sure whether the language is problematic, Feetham-Walker recommends that the authors ask themselves: “Has this comment helped me to improve my paper, or has it just undermined my confidence?” Importantly, peer review should critique only the science, she adds. “The main defining factor of unprofessional comments is that they are personal.” If still in doubt, Mahmoudi advises authors to consult their colleagues. It’s important to remember that harsh reviews can help authors to improve their paper, notes Mirvat Alasnag, an interventional cardiologist at King Fahad Armed Forces Hospital in Jeddah, Saudi Arabia. “If it’s not what you wanted to hear, leave the noise behind, but try as hard as you can to look at the comments and see if they’re valuable,” she says. However, in the case of especially egregious comments, she and others recommend flagging the problematic behaviour to the manuscript-handling editor (see ‘How to avoid — and push back on — peer review bullying’). Silbiger suggests that authors write an e-mail thanking the editor and reviewer for the critical appraisal and noting that they will take the suggestions into consideration. Then, they should detail the comments they felt were unethical and unprofessional and ask that those comments be removed from the review process — and possibly flagged to the reviewer as being unhelpful. How to avoid — and push back on — peer-review bullying Researchers advise on how to avoid and address problematic comments from reviewers. Choose the right journal. Consider journals that have transparent, open review processes in which reviews are made public, for instance, or that give authors the option to veto certain reviewers. Focus on the science. Try to isolate the scientific critiques in problematic reviews, and if they’re valuable, focus on addressing them. If in doubt, get a second opinion from colleagues on whether a comment is worth addressing. Write to the editor. Thank the editor for their time and politely point out the specific comments you found discriminatory or rude. Consider appealing. If you think that a problematic review has unduly influenced the review process and led to a rejection, consider appealing the editor’s decision. After Silbiger revised her manuscript in 2014 — and reviewer three responded with further unprofessional comments — her PhD supervisor wrote to the journal’s chief editor. After explaining how the team had addressed the valid criticisms and pointing out the unprofessional remarks that couldn’t be addressed, she asked the chief editor to decide whether to accept or reject the paper. The paper was ultimately published and has been cited 88 times. “If you’re junior, sometimes it helps to have your senior author be the one to write the letter,” Silbiger says.
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: What’s next for gravitational-wave detectors?
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Mirror of the unknown: should research on mirror-image molecular biology be stopped?
Ting Zhu
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In theory, all biological structures, functions and even organisms could be recreated in their mirror image, leading to endless possibilities.Credit: Getty This week, experts in synthetic biology and microbiology, among other fields, are gathering in Manchester, UK, to explore the benefits and risks of building synthetic life. One of the topics that will be discussed is how research might be restricted to prevent the creation of organisms made of components that are the mirror image of those that make up life on Earth. Days after the Manchester meeting, the issue will be examined at a workshop organized by the US National Academies of Sciences, Engineering, and Medicine. And other meetings are planned. How should ‘mirror life’ research be restricted? Debate heats up Most of the biological molecules known to make up life on Earth have a specific handedness, or chirality. Amino acids have left-handed chirality, for example, whereas DNA is right-handed. Because mirror-image bacteria or other synthetic life forms would be made of molecules of opposite handedness (so with right-handed amino acids and left-handed DNA), the concern is that such organisms might represent a hazard to known life1–3 (see also go.nature.com/3hshyst and go.nature.com/3vwuytw). For example, some of them might be capable of evading immune systems, confounding medicines, resisting predation and causing harms to humans, non-human animals, plants and ecosystems2,3. Prohibiting the creation of molecules or biological entities of either chirality that could endanger human health or environmental stability should be uncontroversial. And discussions early in the development of a field — as well as efforts to engage the public — can be constructive when it comes to ensuring that research is conducted responsibly and ethically. But in the face of vast unknowns, the noble path of pre-emptively protecting humanity from potential risks in the distant future can be slippery. And we should tread cautiously. The concept of a mirror-image biological world is not new. It was first proposed in 1860 by French chemist and microbiologist Louis Pasteur4. And the potential benefits and risks of mirror-image organisms have been discussed by the research community for more than 30 years1–3 (see also go.nature.com/3hshyst and go.nature.com/3vwuytw). However, in the past few months, the conversation has abruptly shifted to calls for hard limits on basic research and funding2. At this point, there are divergent views (see go.nature.com/46tgjvf and eLetters by R. Derda et al. and D. Perrin in ref. 2) on how soon it might be possible to create mirror-image organisms; the potential benefits and risks of generating mirror-image life and of developing precursor technologies; whether moratoria on research should be imposed; and, if so, what areas of study should be restricted. Given the countless unanswered questions, careful consideration of the scientific facts learnt so far — regarding what it would take to create a mirror-image life form, and the pros and cons of research on mirror-image molecular biology more broadly — is crucial for bridging divergent views and fostering rational and informed debate. On the distant horizon In December 2024, nearly 40 experts, including in synthetic biology, ecology and immunology, co-authored a Policy Forum article in Science2 and released a separate 299-page technical report3. In both, the authors argued that were mirror-image life created, it would be very likely to present unprecedented risks to humans, animals, plants and ecosystems. Multiple meetings have followed the Science publication, including in the United Kingdom, the United States, France and the Netherlands. But how close are scientists to being able to create a mirror-image life form? Scientists have been pondering the idea of a mirror-image world of biology for more than a century.Credit: Jorg Greuel/Getty Dozens of research groups, including those at pharmaceutical companies, have been synthesizing and investigating mirror-image proteins, DNA and RNA for the past three decades to understand fundamental biology and develop therapeutics5–14. My colleagues and I have been exploring various mirror-image molecular processes, too. These include the replication of mirror-image DNA, the transcription of mirror-image DNA into mirror-image RNA and the translation of mirror-image RNA into mirror-image proteins — in other words, a mirror-image version of the central dogma of molecular biology7–11. Research in mirror-image molecular biology is still in its infancy. But scientists working in this field have been humbled by the tremendous challenges of exploring this unknown world5–14. The creation of mirror-image organisms, if it ever became feasible, would face monumental conceptual and technical barriers. Hundreds to thousands of cellular components — including proteins, nucleic acids, membranes, metabolites and complex carbohydrates called glycans — would need to be synthesized chemically or enzymatically in their chirally inverted forms. Some of these are encoded directly by DNA. But many are synthesized or modified by other complex biological machinery, meaning their compositions and structures cannot simply be derived from DNA sequences. And many have not yet been characterized. It took our group nearly four years to chemically synthesize a mirror-image protein fragment of up to around 470 amino acids9 — the longest single-chain mirror-image polypeptide reported so far. Synthesizing longer polypeptides and membrane proteins that are rich in water-repelling (hydrophobic) domains would be even harder. Asilomar conference took courage and foresight — today, inclusivity would also be crucial Likewise, we have been trying to chemically synthesize a highly simplified version of a mirror-image ribosome since 2016, and are still years away from achieving it. Should we succeed, this ribosome will lack protein and RNA modifications and will not have aminoacyl-tRNA synthetases (the enzymes responsible for attaching specific amino acids to their corresponding transfer RNAs during protein biosynthesis)8,11. This means it will be able to produce only short peptides and small proteins (say, of about 300 amino acids)8. Even if all the constituent molecules of the simplest bacterium could be synthesized in their mirror-image forms, these would need to be folded correctly and assembled with spatio-temporal precision to create a mirror-image bacterium that functions as a complex, autonomously replicating cell. Many laboratories have built non-living membrane-bound compartments, in which copies of DNA and RNA molecules can be made or in which RNA molecules can be translated into proteins. Although researchers have been able to isolate biologically derived ribosomes and other cellular machinery with natural chirality for decades, no lab has been able to use this machinery to produce all the essential cellular components in vitro. Researchers don’t yet know how to assemble a natural-chirality self-replicating cell from biologically derived building blocks — let alone how to chemically synthesize a mirror-image one from the ground up. And although other strategies for the creation of mirror-image life have been proposed (such as the stepwise conversion of a natural-chirality cell into a mirror-image cell2,3), there is insufficient evidence to support their feasibility. In short, it is crucial to distinguish mirror-image molecular biology from the creation of mirror-image organisms. A self-replicating cell has molecular diversity, metabolic complexity and structural intricacy that are orders of magnitude greater than what’s found in any currently synthesizable biomolecular system. And the creation of a mirror-image organism lies well beyond the reach of present-day science. Endless possibilities Because all biological structures, functions and even organisms could be recreated in their mirror image, the possibilities — good and bad — in a looking-glass world are endless. As well as considering the risks of hypothetical scenarios, such as the creation of mirror-image life, it is important to keep in mind the realized and potential benefits of the mirror-image molecular biology research that is already under way5–14. When given to animals or humans, mirror-image peptides and nucleic-acid drugs can trigger a much milder immune response compared with their natural-chirality counterparts13. They are also more resistant to biodegradation, which means a dose can stay in the body for much longer. The implications for drug discovery are profound. Mirror-image enzyme copies looking-glass DNA Dozens of mirror-image peptides, DNA and RNA molecules are already being developed as drug candidates for cancer, metabolic diseases, infectious diseases and inflammatory disorders10,13. Indeed, a synthesized mirror-image ribosome would probably drastically accelerate pharmaceutical discovery by enabling the high-throughput production of mirror-image peptides8,11. All sorts of other possible applications of mirror-image molecules or biological entities can be imagined, particularly in medicine and sustainability. Mirror-image glucose tastes as sweet as its natural-chirality counterpart, but does not provide calories because it is not metabolized by the enzymes found in natural-chirality organisms15. This means that mirror-image glucose and other mirror-image sugars could serve as non-caloric sweeteners or other food additives. Mirror-image DNA molecules have the same capacity to hold information as their natural-chirality counterparts do, but they are more resistant to biodegradation and easier to distinguish from contaminant (natural-chirality) DNA. As such, mirror-image DNA molecules can serve as robust information repositories9. Nanoparticles or nanocapsules, built using mirror-image proteins, could enable the safe delivery of drugs by shielding them from the immune system. Mirror-image DNA or RNA molecules designed to detect the presence of certain human proteins and metabolites, such as thrombin10 and guanine11, could be used as diagnostic biosensors in clinical settings. Meanwhile, mirror-image versions of enzymes that are capable of degrading plastics that have no chirality could offer a solution to plastic pollution12. Like their natural-chirality counterparts, such enzymes can break down plastics but are more resistant to biodegradation themselves. In principle, mirror-image versions of enzymes that can capture carbon might similarly be used to help address climate change. Plastic-consuming bacteria, shown in this artist’s impression, contain enzymes that degrade plastics. Biostable mirror-image versions of these proteins could offer a solution to plastic pollution.Credit: Thomas Parsons/Science Photo Library As well as providing solutions for all sorts of practical problems, basic research on biology through the looking glass could offer insights into the structures and functions of biomolecules. It could shed light on the origin of homochirality (the dominance of one set of chiral molecules in known forms of life), and even on the origin of life11. It could guide searches for new life forms, for instance, on Earth as well as on other planets. Of course, the very properties that promise to make mirror-image proteins and nucleic acids so useful in so many contexts — their biostability and tendency to induce only a mild immune response in humans and other organisms — could also make certain mirror-image organisms harmful1–3 (see also go.nature.com/3hshyst and go.nature.com/3vwuytw).
Nature DOI suffix ≠ "/s...": Not a research article
Years of hits to the head prime the brain for decline
Adam Bachstetter, Josh Morganti
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Sustained blows to the head over many years are increasingly being recognized as a serious health risk that affects contact-sport athletes1, military veterans and people who have experienced long-term domestic violence. Writing in Nature, Butler et al.2 investigate the little-understood consequences of repetitive head impacts (RHIs) on the cellular networks that underlie normal brain function.
Nature DOI suffix ≠ "/s...": Not a research article
Ready or not, the digital afterlife is here
Tammy Worth
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Nature DOI suffix ≠ "/s...": Not a research article
AI is helping to decode animals’ speech. Will it also let us talk with them?
Rachel Fieldhouse
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Deep in the rainforests of the Democratic Republic of the Congo, MĂ©lissa Berthet found bonobos doing something thought to be uniquely human. How to detect consciousness in people, animals and maybe even AI During the six months that Berthet observed the primates, they combined calls in several ways to make complex phrases1. In one example, bonobos (Pan paniscus) that were building nests together added a yelp, meaning ‘let’s do this’, to a grunt that says ‘look at me’. “It’s really a way to say: ‘Look at what I’m doing, and let’s do this all together’,” says Berthet, who studies primates and linguistics at the University of Rennes, France. In another case, a peep that means ‘I would like to do this’ was followed by a whistle signalling ‘let’s stay together’. The bonobos combine the two calls in sensitive social contexts, says Berthet. “I think it’s to bring peace.” The study, reported in April, is one of several examples from the past few years that highlight just how sophisticated vocal communication in non-human animals can be. In some species of primate, whale2and bird, researchers have identified features and patterns of vocalization that have long been considered defining characteristics of human language. These results challenge ideas about what makes human language special — and even how ‘language’ should be defined. Perhaps unsurprisingly, many scientists turn to artificial intelligence (AI) tools to speed up the detection and interpretation of animal sounds, and to probe aspects of communication that human listeners might miss. “It’s doing something that just wasn’t possible through traditional means,” says David Robinson, an AI researcher at the Earth Species Project, a non-profit organization based in Berkeley, California, that is developing AI systems to decode communication across the animal kingdom. As the research advances, there is increasing interest in using AI tools not only to listen in on animal speech, but also to potentially talk back. Combining calls Researchers studying animal communication ask some of the same types of question that linguists do. How are speech sounds physically produced (phonetics)? How are sounds combined to make meaningful units (morphology)? What rules determine how phrases and sentences are structured (syntax)? Until about a decade ago, researchers thought that only humans used a feature known in linguistics as compositionality. This is the combining of meaningful words, calls or other noises into expressions that have a meaning derived from those of their parts. A human gene makes mice squeak differently — did it contribute to language? But in 2016, a study of Japanese tits (Parus minor) changed how scientists thought about compositionality. The birds looked for predators when they heard an ‘alert’ call and approached a sound’s source after hearing a ‘recruitment’ call. When they heard the calls in that order, they performed both behaviours3. But they didn’t do so when the order was reversed, suggesting compositionality: the combination of calls had its own meaning. A study in 2023 extended that work. By presenting chimpanzees (Pan troglodytes) with fake snakes in the wild, scientists showed that the primates similarly combine ‘alarm’ and ‘recruitment’ vocalizations into a message that prompts others to gather around the caller to respond to a threat4. However, humans remained the only species known to use compositionality in more than one way. For instance, by ordering words differently to change the meaning of the phrase, adding endings to words to modify meaning and creating metaphors and idioms to produce a figurative expression. Bonobos in the Democratic Republic of the Congo combine calls into phrases in several ways.Credit: Christian Ziegler/Nature Picture Library But the study by Berthet and her colleagues softened that distinction between humans and other animals. They recorded 700 calls by 30 adult bonobos and found that the animals combined a finite number of calls in four ways1. One — a yelp–grunt combination — the authors considered to have ‘trivial’ compositionality, because the meaning of the individual calls had merely been combined. (For instance, ‘the red car’ describes an object that is both red and a car.) In the three other cases, one call modified the other, resulting in ‘non-trivial’ compositionality. (‘A terrible actor’ describes a person who is bad at acting, not someone who is terrible and an actor.) Evolutionary biologist CĂ©dric Girard-Buttoz at the Lyon Neuroscience Research Center, France, and his colleagues reported in May that chimpanzees also combine a finite number of calls in several ways5. For some vocalizations, the meaning of the combined phrase can’t be determined from the meaning of the individual calls, as is the case for some idioms in human languages. For example, a hoot, used when resting on the ground, followed by a pant, which signifies playing and affiliation, prompted the chimpanzees to climb a tree, make a nest and rest together, even though neither call is typically associated with tree climbing, says Girard-Buttoz. Generating meaning in several ways is a building block of language, he adds. Whales, too, have some notable features of human language. Researchers at Project CETI, a non-profit organization in New York City, have been tracking and recording sperm whales (Physeter macrocephalus) off the coast of the Caribbean island of Dominica to compile a large data set of movements and sounds. By finding patterns that link whale sounds and behaviours, the scientists hope to translate ‘whale speak’. CETI linguist GaĆĄper BeguĆĄ has been training generative-AI models to produce sounds and sequences of sounds that mimic those made by sperm whales. Whereas humans create distinct sounds by sending air through vocal folds in the throat, which vibrate at different frequencies, these whales send air through a lip-like structure in their nasal passage, which vibrates and creates clicks. The clicks are grouped into units called codas. Scientists attach sensors that can gather bioacoustic and other data to sperm whales using drones.Credit: Jaime Rojo CETI scientists reported last year that sperm whales have their own ‘phonetic alphabet’, with codas varying in characteristics such as tempo and rhythm6. BeguĆĄ and his colleagues have since found that whale codas can differ in ways analogous to vowels and diphthongs in human language. Vowels in human speech differ on the basis of the tongue’s position and the shape of the lips, such as for the ‘ee’ in cheese versus the ‘o’ in hot. Diphthongs, or gliding vowels, are created by combining two vowels in a single syllable, such as in ‘pout’, resulting in a frequency change as the lips and tongue move. Beguơ’s team identified two codas with distinct sound patterns that the researchers called an a-vowel and i-vowel. They also found that these vowels changed frequency in four ways: they can rise, they can fall, they can fall then rise or they can rise then fall7. The frequency changes could be indicative of diphthongs. What’s in a language Whether the sophistication of animal communication is enough to qualify it as language depends on how a person defines the term and what they think about how animals think. There are two prevailing views, BeguĆĄ says. “One world view says that language and complex thought are intrinsically connected.” According to this view, complex thought came first and language is a way to externalize thoughts. If so, animals can’t have a language unless they are capable of complex thought. The other view holds that language is just one kind of communication, like gestures or facial expressions, and complex thought isn’t required. In this case, animals could have a language with or without complex thought. Experiments that train animals to communicate with humans, such as those with the bonobo Kanzi, who died earlier this year, have hinted that animals might be capable of having a language. But that’s a different question from whether they use language on their own in the wild. “The word is still out on whether we’ll find a full-on language,” says Robinson. For one, some aspects of human language haven’t been found in other species yet. Three of the 16 features — displacement, productivity and duality — on a language checklist created by linguist Charles Hockett haven’t been identified in non-human animals. What do dolphins talk about? One biologist is trying to listen in Displacement is the ability to talk about abstract concepts, such as the past, the future or things that are distant. This feature hasn’t been seen convincingly in animal communication, although there is anecdotal evidence in some instances, such as dolphins calling the names of other dolphins that had disappeared years ago, and orangutans (Pongo spp.) telling others about a predator that was previously in an area, Berthet says. Productivity is the ability to say things that have never been said or heard before, and be understood by another individual. And duality describes meaningful messages made up of smaller meaningful units, which consist of even smaller, meaningless sounds. Although whales use clicks to create longer codas, scientists haven’t yet shown that clicks are meaningless and codas are meaningful. Recursion is another feature that might be unique to human language. This is when sentences or phrases are embedded in each other to create deeper levels of meaning. By training crows (Corvus corone) to peck at open and closed brackets in the appropriate sequence on a touch screen, Diana Liao, who studies vocal communication and cognition at the University of TĂŒbingen in Germany, and her colleagues found evidence that the animals are mentally capable of recursion8. “They do this even better than macaque monkeys and on par with human toddlers”, Liao says. However, it’s not clear whether crows use it in their communication. It’s also unclear whether animals have grammatical rules that define how vocal communication is structured. And, although primates have been shown to mix and match calls to generate meaning, the number of meanings that they can produce is “really far from what humans can do”, says Girard-Buttoz. AI decodes the calls of the wild
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: A ‘time crystal’ made visible to the naked eye
Flora Graham
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Global warming amplifies wildfire health burden and reshapes inequality
Junri Zhao, Bo Zheng, Philippe Ciais, Yang Chen, Thomas Gasser, Josep G. Canadell, Longyi Zhang, Qiang Zhang
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Global warming intensifies wildfires and exacerbates greenhouse gas and pollutant emissions1. However, global projections remain incomplete, hindering effective policy interventions amid uncertain warming futures2. Here, we developed an interpretable machine learning framework to project global burned areas and wildfire emissions. This framework accounts for the impacts of future climate change on fire activity and quantifies associated premature deaths and radiative forcing from fire-induced particulate matter (PM2.5). Here we show that from 2010–2014 to 2095–2099, fire carbon emissions are projected to increase by 23% under the Shared Socioeconomic Pathway (SSP) 2-4.5. Increased fire-related aerosols reduce the 0.06 W m⁻ÂČ cooling effect north of 60°N. Projections show a surge in premature deaths from wildfire smoke, reaching 1.40 (95% Confidence Interval: 0.66–2.25) million annually during 2095–2099, roughly 6 times higher than current levels. Africa is projected to experience the greatest rise in fire-related deaths (11-fold), driven by emission changes and an aging population. Europe and the U.S. would experience a 1–2-fold increase under SSP2-4.5, linked to rising fire occurrences in the mid-latitude Northern Hemisphere. Overall, the health burden would become more evenly distributed across nations of differing development levels than present patterns, underscoring the need for coordinated efforts.
Delegation to artificial intelligence can increase dishonest behaviour
Nils Köbis, Zoe Rahwan, Raluca Rilla, Bramantyo Ibrahim Supriyatno, Clara Bersch, Tamer Ajaj, Jean-François Bonnefon, Iyad Rahwan
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Although artificial intelligence enables productivity gains from delegating tasks to machines 1 , it may facilitate the delegation of unethical behaviour 2 . This risk is highly relevant amid the rapid rise of ‘agentic’ artificial intelligence systems 3,4 . Here we demonstrate this risk by having human principals instruct machine agents to perform tasks with incentives to cheat. Requests for cheating increased when principals could induce machine dishonesty without telling the machine precisely what to do, through supervised learning or high-level goal setting. These effects held whether delegation was voluntary or mandatory. We also examined delegation via natural language to large language models 5 . Although the cheating requests by principals were not always higher for machine agents than for human agents, compliance diverged sharply: machines were far more likely than human agents to carry out fully unethical instructions. This compliance could be curbed, but usually not eliminated, with the injection of prohibitive, task-specific guardrails. Our results highlight ethical risks in the context of increasingly accessible and powerful machine delegation, and suggest design and policy strategies to mitigate them.

Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Probing the connection between chirality and spin through time-resolved EPR spectroscopy
Sunil Saxena, David H. Waldeck
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GPT-4o mini: Non-social science research article
Optimal transitions between nonequilibrium steady states
Samuel Monter, Sarah A. M. Loos, Clemens Bechinger
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The optimal control of finite-time processes on the microscale is of significant theoretical and practical interest, particularly for the energy-efficient operation of nanomachines. While previous studies have primarily focused on transitions between equilibrium states, many biologically and technologically relevant processes occur far from equilibrium. In such nonequilibrium settings, memory, a ubiquitous feature in realistic systems, plays an intricate role, as any driving necessarily excites internal memory modes. This motivates a deeper exploration of optimal control strategies in nonequilibrium regimes. Here, we combine experiments, theory, and computational methods to investigate the transition of a colloidal particle confined in an optical trap between two nonequilibrium steady states (NESS). We identify optimal control protocols that minimize the thermodynamic work during the finite-time transition between two NESS. We compare optimal protocols in viscous and viscoelastic fluid environments, which are common in realistic technical and biological processes and introduce memory due to a delayed response. Regardless of the presence of memory effects, optimal protocols consistently balance energy extraction with dissipation minimization. In the presence of memory, optimal control is achieved if the protocol matches the time response of the environment. These findings offer key insights for designing optimal control strategies for finite-time, nonequilibrium processes in complex environments.
GPT-4o mini: Non-social science research article
An uphill struggle for tropical forest trees
Scott L. Collins
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GPT-4o mini: Non-social science research article
Intercellular propagation of RIPK1/RIPK3 amyloid fibrils
Yeyang Ma, Qiuyuan Zhang, Dekang Li, Kun Zhao, Zefei Li, Yuan Liu, Chu Wang, Bo Sun, Dan Li, Junying Yuan, Cong Liu
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The canonical necrosome formed by receptor-interacting protein kinase 1 (RIPK1) and RIPK3 is a functional amyloid fibril structure critical to intracellularly drive necroptosis. Since necroptosis leads to the release of intracellular content, the fate of RIPK1/RIPK3 fibrils after necroptotic cell death has not been investigated. Here, we tracked RIPK1 and RIPK3 coassemblies and found that these fibrillar aggregates could be released into the culture medium after the membrane rupture in necroptotic cells. Interestingly, these RIPK1/RIPK3 fibrils were capable of infiltrating recipient cells and acting as seeds for the nucleation and formation of the endogenous necrosome. Cryo electron microscopy structural analysis unveiled a distinctive S-shaped conformation common to RHIM fibrils of RIPK1 and RIPK3, which can facilitate the cross-seeding of RIPK3 by RIPK1 or RIPK1/RIPK3 fibrils. Our findings suggest the ability of functional RIPK1/RIPK3 amyloid fibrils in intercellular spreading to induce protein conformation change in recipient cells and provide structural insights into the mechanism of RIPK1 and RIPK3 cross-templating to drive necroptosis.
GPT-4o mini: Non-social science research article
Microbial conservation is essential for sustaining ecosystem functions and services
Robert R. Junker, Nina Farwig
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GPT-4o mini: Non-social science research article
Methionine synthesis and glycine betaine demethylation are intricately intertwined in cosmopolitan marine bacteria
Michaela A. Mausz, Andrew R. J. Murphy, Maria del Mar Aguilo-Ferretjans, Andrew Hitchcock, Mary Ann Moran, David J. Scanlan, Yin Chen, Ian D. E. A. Lidbury
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Across all domains of life, cobalamin-dependent methyltransferases have diversified to perform a range of crucial functions, such as methionine synthesis and the demethylation of various reduced nitrogen and sulfur compounds. These large modular enzymes typically possess three substrate-binding domains, two binding either the methyl donor or methyl acceptor, as well as a cobalamin-binding domain. Here, by challenging the current paradigm of glycine betaine (GBT) catabolism, we have identified a unique methyltransferase in aerobic environmental bacteria that has a dual function both as a methionine synthase and a GBT methyltransferase. Using the marine bacterium Ruegeria pomeroyi DSS-3 as a model, we demonstrate that a core cobalamin-binding domain (MtgC) and a bidirectional methyltransferase (MtgD) are essential for both methionine synthesis and GBT demethylation. MtgC is phylogenetically distinct from the cobalamin-binding domains of either the classical methionine synthase (MetH) or the GBT methyltransferases found in anaerobic bacteria and archaea. Across the global ocean, mtgC expression is frequently greater than previously known GBT catabolic pathways due to its occurrence in abundant cosmopolitan marine bacteria. Thus, we uncover a unique relationship between GBT catabolism and methionine synthesis in nature and identify a major route for N-osmolyte demethylation in the global ocean.
GPT-4o mini: Non-social science research article
A widespread family of molecular chaperones promotes the intracellular stability of type VIIb secretion system–exported toxins
Polyniki Gkragkopoulou, Stephen R. Garrett, Prakhar Y. Shah, Dirk W. Grebenc, Timothy A. Klein, Youngchang Kim, John C. Whitney
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To survive in highly competitive environments, bacteria use specialized secretion systems to deliver antibacterial toxins into neighboring cells, thereby inhibiting their growth. In many Gram-positive bacteria, the export of such toxins requires a membrane-bound molecular apparatus known as the type VIIb secretion system (T7SSb). Recently, it was shown that toxin recruitment to the T7SSb requires a physical interaction between a toxin and two or more so-called targeting factors, which harbor key residues required for T7SS-dependent protein export. However, in addition to these targeting factors, some toxins additionally require a protein belonging to the DUF4176 protein family. Here, by examining two toxin–DUF4176 protein pairs, we demonstrate that DUF4176 constitutes a family of toxin-specific molecular chaperones. In addition to being required for toxin stability in producing cells, we find that DUF4176 proteins facilitate toxin export by specifically interacting with a previously uncharacterized intrinsically disordered region found in many T7SS toxins. Using X-ray crystallography, we determine structures of several DUF4176 chaperones in their unbound state, and of a DUF4176 chaperone in complex with the binding site of its cognate toxin. These structures reveal that this binding site consists of a disordered amphipathic α-helix that requires interaction with its cognate chaperone for proper folding. Overall, we have identified a family of secretion system associated molecular chaperones found throughout T7SSb-containing Gram-positive bacteria.
GPT-4o mini: Non-social science research article
Circular RNA lipid nanoparticle vaccine against SARS-CoV-2
Kelsey L. Swingle, Alex G. Hamilton, Xuexiang Han, Kuo-Chieh Liao, Hannah C. Safford, Ajay S. Thatte, Hannah C. Geisler, Junchao Xu, Tzuen Yih Saw, Yue Wan, Michael J. Mitchell
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With the advent and widespread use of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), RNA vaccines have emerged as an exciting class of vaccine offering low cost, rapid development, and high modularity and manufacturability. Protein-coding circular RNA (circRNA) is an emerging class of RNA cargo that offers increased stability compared to mRNA with potentially reduced immunogenicity, but delivery technologies for intracellular delivery of circRNA remain underexplored. Here, we develop an optimized lipid nanoparticle (LNP) platform for circRNA delivery to immune cells, observing strong and durable transgene expression in vitro and in vivo. We employ a design-of-experiments (DoE) methodology to identify key formulation parameters for enhanced circRNA delivery and, upon intramuscular administration of our optimized circRNA LNPs to mice, observe substantial accumulation within draining lymph nodes and strong dendritic cell (DC) maturation at short time points. Applying this optimized circRNA LNP platform to vaccination against SARS-CoV-2, we demonstrate robust antibody production and enhanced immune responses in mice compared to vaccination with mRNA LNPs, including strong T h 1-biased cellular responses and a 3.8-fold increase in antigen-specific reciprocal endpoint IgG titers. These results provide insights into design criteria for circRNA LNP formulations and support the use of circRNA LNPs for vaccination against infectious diseases.
GPT-4o mini: Non-social science research article
Salmonella produces sulfide to compete with Escherichia coli in the gut lumen
Anaïs B. Larabi, Connor R. Tiffany, Hugo L. P. Masson, Henry Nguyen, Eli J. Bejarano, Megan J. Liou, Lauren C. Radlinski, Aurore M. Demars, Renée M. Tsolis, Andreas J. BÀumler
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Hydrogen sulfide production is a characteristic that distinguishes Salmonella serovars from closely related species, such as Escherichia coli , but its biological significance remains obscure. Here, we show that PhsABC and AsrABC-mediated hydrogen sulfide production by Salmonella enterica serovar ( S. ) Typhimurium was linked to an increased abundance of Deltaproteobacteria and inhibition of cytochrome bd oxidase-mediated aerobic respiration of Escherichia coli in the murine large intestine. Functional phsABC and asrABC operons provided a growth benefit to S. Typhimurium in the cecum of Enterobacterales- free conventional mice only upon inoculation with commensal E. coli. In gnotobiotic mice engrafted with a defined community of 17 human Clostridia isolates, S. Typhimurium infection inhibited cytochrome bd oxidase-mediated aerobic respiration in E. coli only in the presence of Desulfovibrio piger , a sulfide-producing representative of the Deltaproteobacteria. A S. Typhimurium strain deficient for hydrogen sulfide production ( phsA asrA mutant) did not inhibit cytochrome bd oxidase-mediated aerobic respiration in E. coli , even when D. piger was present. Collectively, these data suggest that the phsABC and asrABC operons of Salmonella serovars provide a benefit during competition with closely related bacteria, such as E. coli , by inhibiting cytochrome bd oxidase-mediated aerobic respiration of the commensal.
GPT-4o mini: Non-social science research article
Does AI help humans make better decisions? A statistical evaluation framework for experimental and observational studies
Eli Ben-Michael, D. James Greiner, Melody Huang, Kosuke Imai, Zhichao Jiang, Sooahn Shin
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The use of AI, or more generally data-driven algorithms, has become ubiquitous in today’s society. Yet, in many cases and especially when stakes are high, humans still make final decisions. The critical question, therefore, is whether AI helps humans make better decisions compared to a human-alone or AI-alone system. We introduce a methodological framework to answer this question empirically with minimal assumptions. We measure a decision maker’s ability to make correct decisions using standard classification metrics based on the baseline potential outcome. We consider a single-blinded and unconfounded treatment assignment, in which the provision of AI-generated recommendations is assumed to be randomized across cases, conditional on observed covariates, with final decisions made by humans. Under this study design, we show how to compare the performance of three alternative decision-making systems—human-alone, human-with-AI, and AI-alone. Importantly, the AI-alone system encompasses any individualized treatment assignment, including those not used in the original study. We also show when AI recommendations should be provided to a human-decision maker, and when one should follow such recommendations. We apply the proposed methodology to our own randomized controlled trial evaluating a pretrial risk assessment instrument. We find that the risk assessment recommendations do not improve the classification accuracy of a judge’s decision to impose cash bail. Furthermore, replacing a human judge with algorithms—the risk assessment score and a large language model in particular—yields worse classification performance.
GPT-4o mini: Non-social science research article
Posttranscriptional control of the B cell receptor by HuR is essential for innate B cell maintenance and function
Dunja Capitan-Sobrino, Mailys Mouysset, Orlane Maloudi, Yann Aubert, Ines C. Osma-Garcia, Trang-My M. Nguyen, Greta Dunga, Maia Nestor-Martin, Virginie Mieulet, Manuel D. Diaz-Muñoz
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Innate B-1 cells constitute a self-maintained layer of defense for early detection of bacteria, clearance of apoptotic cell debris, and removal of autoantigens driving autoimmunity. B-1 cells are originated from fetal tissues, but, as opposed to B-2 cells, the molecular mechanisms behind their development and homeostatic maintenance remain largely unknown. Here, we demonstrate that posttranscriptional regulation by the RNA binding protein HuR is essential for the homeostatic self-replenishment of innate B-1a cells, the expansion of B-1 cell clones targeting self-antigens, and the production of natural autoantibodies. HuR KO B-1 cells fail to express the high levels of surface B-cell receptor (BCR), TACI, and BAFFR required for tonic signaling and cell survival. At the molecular level, HuR promotes the translation of messenger RNAs encoding the IgM heavy chain and modules, in a direct or indirect manner, the expression of TACI and BAFFR. In summary, we reveal the need for posttranscriptional regulation in BCR expression, tonic signaling, and homeostatic maintenance of functional innate B-1 cells.
GPT-4o mini: Non-social science research article
Improving the efficacy of anti-SSEA4 antibody in pancreatic cancer immunotherapy with glyco-optimization and immune checkpoint blockade
Po-Kai Chuang, Cinya Chung, Kuo-Shiang Liao, Chi-Huey Wong
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Pancreatic cancer remains one of the most lethal malignancies with limited therapeutic options. Among the alternative targets explored for pancreatic cancer, the glycolipid stage-specific embryonic antigen-4 (SSEA4) has been extensively studied. We have previously demonstrated that the chimeric anti-SSEA4 antibody with alpha-2,6-sialylated complex type biantennary glycan (SCT) or its 3-fluorosialyl derivative (FSCT) attached to the Fc-Asn297 residue exhibited enhanced binding to the Fc-receptors FcÎłRIIIA and FcÎłRIIA which are responsible for antibody-dependent cellular cytotoxicity and phagocytosis as well as vaccinal effect. Here, we found that high-SSEA4 expression correlates with increasing tumor proliferation and sensitivity to the glyco-optimized antibodies (anti-SSEA4-SCT and anti-SSEA4-FSCT) which preferentially recruit NKG2D-expressing natural killer cells and FcÎłRIIA-bearing macrophages with enhanced target killing activity. We also uncovered an immune evasion mechanism involving the interaction of sialoglycans on the cancer cell with Siglec-9 on NK cells or Siglec-10 on macrophages to block the antibody-mediated effector functions, and this immune checkpoint inhibition can be suppressed with the removal of sialic acid on cancer cells or blockade of Siglec recognition. In xenograft models, the glyco-optimized antibodies exhibited superior inhibition of tumor growth with high-SSEA4 expression compared to the wild-type antibody and persistent antitumor activity without additional antibody administration. These findings support anti-SSEA4 antibodies with enhanced effector functions and blockade of Siglec-mediated immune checkpoint as a promising therapeutic strategy for pancreatic cancer.
GPT-4o mini: Non-social science research article
Disentanglement of prosodic meaning: Toward a framework for the analysis of nonverbal information in speech
Tirza Biron, Moshe Barboy, Eran Ben-Artzy, Alona Golubchik, Yanir Marmor, Assaf Marron, Smadar Szekely, Yaron Winter, David Harel
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We propose a theoretical framework and a cost-effective automated method for the interpretation of prosodic messages (e.g., chunking of information, emphasis, conversation action, emotion). At the core of the proposal is a hierarchy of layered prosodic messages that co-occur within the same intonation unit (0.5 to 2 s long). Motivated by this hierarchy, a procedure for the differential detection of three such co-occurring nonverbal messages is then described. In way of implementation, we produce a variant model of the WHISPER automatic speech recognition system that flags intonation unit boundaries, intonation unit prototypes, and emphases therein. The procedure required us to alter WHISPER’s token combinations and significantly adjust its prediction process. The variant model was tested on four datasets that contain spontaneous and read speech, and performs on a par with similar human annotation, and often better, using relatively modest training data. Several insights regarding this implementation, such as model size and encoding methods, are described as well. We believe that the proposed framework, coupled with the results of its application herein, can greatly improve the analysis of speech and language, integrating contextual information and speaker intentions into linguistic descriptions for a large array of purposes with modest means.
GPT-4o mini: Non-social science research article
High-resolution tephrochronology resolves stratigraphic complexities in archaeologically significant Nariokotome tuffs, Turkana Basin
Saini Samim, Hayden Dalton, David Phillips, Janet Hergt
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The Turkana Basin is a renowned paleoanthropological region in Kenya and Ethiopia and is famous for discoveries of numerous hominin fossils and their associated cultural technologies. The Plio-Pleistocene sedimentary sequences hosting these important remains are interbedded with volcanic ash (tuff) beds that provide crucial bracketing age constraints. The Nariokotome Tuff Complex, comprising the Upper, Middle, and Lower Nariokotome Tuffs, preserves deposits that cover an important time interval during the late Early Pleistocene that saw milestone events for Homo erectus and associated technological development. Unfortunately, characterization of these tuffs has been hampered by a) overlapping published eruption ages and b) indistinguishable major element compositions. In addition, fluvial reworking of feldspar-bearing pumice clasts (the target rock for age determinations) from older volcanic deposits into younger tuff layers complicates correct age assignments. Here, we use multiple tephrochronological correlation tools, including high-resolution 40 Ar/ 39 Ar geochronology and grain-specific major- and trace-element geochemistry, to establish a well-characterized geochemical and geochronological framework for the Nariokotome tuffs. Utilizing a modern-generation mass-spectrometer, we report distinct ages for the Upper Nariokotome Tuff at 1,233.1 ± 1.3 ka (± 1.9 ka, 2σ; including external uncertainties), the Middle Nariokotome Tuff at 1,263.4 ± 1.2 ka (± 1.9 ka) and the Lower Nariokotome Tuff at 1,285.8 ± 1.0 ka (± 2.1 ka). In addition, high-spatial resolution Laser Ablation Inductively Coupled Mass Spectrometry trace element compositions provide distinct characterization of each tuff, aiding intrabasin correlation of these units. This combined methodology demonstrates the potential to resolve the stratigraphic complexities associated with assigning ages to key paleoanthropological sites.
GPT-4o mini: Non-social science research article
Engineering a serum response factor superactivator of smooth muscle gene expression with a condensate-forming domain
Peiheng Gan, Xinyi Zhou, Akansha M. Shah, Svetlana Bezprozvannaya, Kenian Chen, Qianqian Ding, Hui Li, Lin Xu, Ning Liu, Eric N. Olson
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Differentiation of smooth muscle cells (SMCs) is driven by the activation of a set of genes controlled by serum response factor (SRF), a ubiquitous transcription factor with limited intrinsic transcriptional activity. Myocardin (MYOCD) is a strong transcriptional coactivator that orchestrates smooth muscle differentiation through its association with SRF. MYOCD forms nuclear condensates via its intrinsically disordered transcription activation domain (TAD), whereas SRF is diffusely distributed in the nucleus. MYOCD recruits SRF into these condensates, thereby activating the smooth muscle gene program. We engineered a “superactivator” of smooth muscle genes by replacing SRF’s weak TAD with that of MYOCD, thereby enabling SRF to form nuclear condensates and reprogram fibroblasts into SMCs. Using protein proximity labeling, quantitative proteomics and superresolution confocal microscopy, we show that condensates formed by the MYOCD TAD aggregate chromatin remodelers, RNA polymerases, and mRNA processing factors to drive smooth muscle gene expression. These findings provide insights into the mechanisms whereby nuclear condensates facilitate tissue-specific gene expression and highlight a strategy for engineering cell fate determinants by coupling condensate-forming domains to heterologous DNA-binding proteins.
GPT-4o mini: Non-social science research article
Action painting under spectroscopic light: Excited-state exchange interactions behind the vibrant blue in Jackson Pollock’s Number 1A, 1948
Alexander J. Heyer, Abed Haddad, Racquel Scott, Glen Kowach, Edward I. Solomon
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Number 1A, 1948 by Jackson Pollock is a quintessential example of his action painting technique where ropes of color, drips of black, and pools of white coalesce into the layered dynamism that defines his style. While past work has identified the red and yellow pigments that form part of his core palette, the vibrant blue in the painting has remained unassigned. In this study resonance Raman spectroscopy is used to assign the blue in the painting as manganese blue. This assignment offers critical context for the conservation of his works. Importantly, assignment of this pigment enables spectroscopic investigation of the electronic structure origin of the pure hue of manganese blue and the chemical phenomena that produce its color. To probe these phenomena, resonance Raman data are coupled to magnetic circular dichroism spectroscopy and density functional theory calculations to assign and analyze the two electronic transitions that create the blue color. This study reveals these bands are split by excited-state exchange interactions; the gap between them contains the reflected light that gives manganese blue its appearance. This sheds light on distinct advantages of molecular inorganic pigments: their ability to leverage ligand field effects in charge transfer states to create multiple intense visible absorption features and the ability to fine-tune pigment color through host lattice electrostatics.
GPT-4o mini: Non-social science research article
Conflicting roles of cell geometry, microtubule deflection, and orientation-dependent dynamic instability in cortical array organization
Tim Y. Y. Tian, Geoffrey O. Wasteneys, Colin B. Macdonald, Eric N. Cytrynbaum
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The self-organization of cortical microtubule (MT) arrays within plant cells is an emergent phenomenon with important consequences for the synthesis of the cell wall, cell shape, and subsequently the structure of plants. Mathematical modeling and experiments have elucidated the underlying processes involved. There has been recent interest in the influence of geometric cues on array orientation, be it direct (cell shape) or indirect (tension in the membrane). However, the mechanical influence of membrane curvature on these elastic filaments has largely been ignored. A previous model was proposed to describe how the anchoring process may control the deflection of individual MTs seeking to minimize bending on a cylindrical cell. We incorporate this process into a model of interacting MTs and find the cell curvature influence to be significant: the array favors orientations parallel to the direction of elongation rather than the expected transverse direction. Even without elasticity, the geometry of large cells hinders robust MT organization. These results suggest the necessity of additional processes to overcome these factors. We propose an orientation-dependent catastrophe rate, hypothetically caused by cellulose microfibrils impeding MT polymerization. We find a combination of anchoring and impedance to be sufficient to generate transverse arrays despite the geometric influences.
GPT-4o mini: Non-social science research article
Fracture of liquid crystal elastomers
Yu Zhou, Chen Wei, Lihua Jin
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Liquid crystal elastomers (LCEs) are anisotropic, viscoelastic materials integrating polymer networks and liquid crystals. While their mechanical responses have been extensively studied, their fracture behavior remains largely unexplored. Specifically, the effect of the deformation-director coupling on LCE fracture paths is unknown, and fracture criteria for LCEs are not yet established. To address this gap, we combine experimental and theoretical approaches to investigate fracture propagation in LCEs. We stretch edge-cracked monodomain LCE samples, recording their stress-stretch responses and crack paths under varying initial directors and stretching rates. Our findings reveal that cracks can change direction during propagation, which are highly dependent on both the initial director and the stretching rate. To further understand LCE fracture behavior, we develop a rate-dependent phase-field fracture model, which is validated through experiments, and demonstrates the ability to predict complex fracture paths. Our study paves the way for designing LCEs with enhanced fracture properties, imperative for their future applications.
GPT-4o mini: Non-social science research article
Humanization of CD47 enables development of functional human neutrophils via postirradiation remodeling of the bone marrow
Esen Sefik, William Philbrick, Fengrui Zhang, Kriti Agrawal, Brian Van Lee, Johannes Sam, Kutay Karatepe, Yunjiang Zheng, Kaixin Liang, Sophia Peng, Haris Mirza, Athreya Rangavajhula, Perrine Simon, Neha Arun, Priyanka Babu, Elizabeth Eynon, Michael Chiorazzi, Liang Shan, Stephanie Halene, Hongbo R. Luo, Anthony Rongvaux, Yuval Kluger, Richard A. Flavell
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Murine and human immune systems differ significantly, particularly within the myeloid lineage. Humanized mice, generated by transplanting human hematopoietic stem, progenitor cells into genetically modified mice, are invaluable to study human immune development and function in vivo. However, a major limitation of current models is suboptimal myelopoiesis, particularly lack of functional human neutrophils, hampering the modeling of human immune responses and chronic diseases. Here, we describe a humanized mouse model, named MaGIC for genes replaced, in the C57Bl/6 N strain, which improves human myelopoiesis and enables development of functional human neutrophils. In MaGIC mice, human cytokines M-CSF/CSF1(M), GM-CSF/CSF2(G) and IL-6(I) are knocked-in replacing mouse genes and murine IL2rg and Rag1 (a) are deleted. Human THPO in these mice supports human hematopoiesis. More importantly, insertion of human CD47 (C) under the control of endogenous mouse CD47 promoter enables xenotransplantation and human neutrophil development. MaGIC mice support all human neutrophil subsets found in human bone marrow and blood, a major improvement. This is achieved by creating a niche postirradiation for human granulocyte–macrophage progenitors via reduced murine CD47 and physiological levels of human CD47. These mice also have mature human monocytes, tissue macrophages, alveolar macrophages, dendritic cells, and NK cells, enabled by humanized M-CSF and GM-CSF. Human neutrophils in MaGIC mice are fully functional in chemotaxis, phagocytosis, reactive oxygen species production, and neutrophil extracellular trap formation in response to inflammation. MaGIC mice address critical gaps in current models and enable incisive translational research on human neutrophils, advancing studies in infectious, autoimmune, and inflammatory diseases.
GPT-4o mini: Non-social science research article
DNA-utilization loci enable exogenous DNA metabolism in gut Bacteroidales
Deepti Sharan, Agnieszka Nurek, Joshua Stemczynski, Kristof Turan, Alexander S. Little, Michael J. Coyne, Mary McMillin, Ashley M. Sidebottom, Laurie E. Comstock, Samuel H. Light
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The human gut microbiome plays a central role in nutrient metabolism, yet the fate of exogenous nucleic acids within this ecosystem remains poorly understood. Here, we show that multiple Bacteroidales species efficiently metabolize exogenous DNA, with Bacteroides thetaiotaomicron converting it into the deaminated nucleobases uracil and xanthine. Using genetic and biochemical approaches, we identify ddbABCDEF , a six-gene locus encoding secreted nucleases and an outer membrane transporter, essential for exogenous DNA metabolism in B. thetaiotaomicron . Colonization of gnotobiotic mice with ddbABCDEF mutants reveals that this pathway significantly alters nucleobase pools in a gnotobiotic mouse model. Comparative genomic analyses demonstrate that ddbABCDEF is evolutionarily related to a natural transformation system present in Bacteroidota and has diversified into four distinct subtypes, each linked to unique DNA-processing activities in closely related gut Bacteroidales strains. These findings thus expand our understanding of DNA metabolism in the gut microbiome and reveal a distinctive pathway for nucleobase production with implications for host–microbe interactions.
GPT-4o mini: Non-social science research article
The power of bridging decision scales: Model coupling for advanced climate policy analysis
Tatiana Filatova, Joos Akkerman, Francesco Bosello, Theodoros Chatzivasileiadis, Ignasi Cortés Arbués, Amineh Ghorbani, Olga Ivanova, Nina Knittel, Jan Kwakkel, Francesco Lamperti, Nicholas R. Magliocca, Giacomo Marangoni, Stefan Nabernegg, Anton Pichler, Adrian Poujon, Karolina Safarzynska, Alessandro Taberna, Mariësse A. E. van Sluisveld, Liz Verbeek, Taoyuan Wei
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Climate policy faces increasingly complex challenges that span multiple human decision scales in nature–society systems. Contemporary climate policy models, while valuable and increasingly versatile in handling spatial and temporal scales, struggle to capture interacting multiscale decisions on the socioeconomic side. This perspective draws attention to the power of coupling among different modeling families, taking integrated assessment models (IAM), computable general equilibrium models (CGE), and agent-based models (ABM) as examples. Recent computational advances, maturity of models, availability of data, and interdisciplinary expertise make model coupling an increasingly feasible, effective, and useful tool for climate policy analysis. We examine the unique contributions of each modeling approach, highlight synergies from uniting their strengths, and discuss alternatives to and conditions for coupling. In addressing methodological challenges, we present examples of effective coupling of IAM–ABM–CGE, emphasizing the importance of maintaining model integrity while enhancing policy relevance. By bridging human decision scales and leveraging complementary strengths, coupled models can provide nuanced insights into climate–economy interactions, ultimately supporting effective and equitable—not just efficient and optimal—climate policies.
GPT-4o mini: Non-social science research article
Employing deep mutational scanning in the Escherichia coli periplasm to decode the thermodynamic landscape for amyloid formation
Conor E. McKay, Miles Deans, Jack Connor, Janet C. Saunders, Christopher Lloyd, Sheena E. Radford, David J. Brockwell
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Deep mutational scanning (DMS) assays provide a powerful method to generate large-scale datasets essential for advancing AI-driven predictions in biology. The tripartite ÎČ-lactamase assay (TPBLA), in which a protein of interest is inserted between two domains of ÎČ-lactamase, has previously been reported as capable of detecting and quantitating the aggregation of proteins and biologics in the oxidizing periplasm of Escherichia coli and used as a platform for identifying small molecule inhibitors of aggregation. Here, we repurpose the TPBLA into a high-throughput DMS platform. We validate this format using a single-site saturation library of the intrinsically disordered peptide AÎČ 42 , linked to Alzheimer’s disease, demonstrating strong agreement between observed variant fitness scores and variant behavior using our previously reported low-throughput TPBLA. The results of DMS revealed variant fitness scores that correlate with known amyloid-promoting regions. An in silico approach using FoldX-derived per-residue thermodynamic stability confirmed that the TPBLA reports on amyloid fibril stability. In vitro experiments support this finding, showing a strong correlation between variant fitness scores and the critical concentration of amyloid formation. Machine learning using the DMS dataset identified ÎČ‐sheet propensity and polarity as primary drivers of variant fitness scores. The derived model is also able to predict thermodynamically stabilizing regions in other amyloid systems, underscoring its generalizability. Collectively, our results demonstrate the TPBLA as a versatile platform for generating robust datasets to advance predictive modeling and to inform the design of aggregation‐resistant proteins.
GPT-4o mini: Non-social science research article
Subtype-specific structural features of the hearing loss–associated human P2X2 receptor
Franka G. Westermann, Adam C. Oken, Philip K. E. Granith, Parthiban Marimuthu, Christa E. MĂŒller, Steven E. Mansoor
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The P2X2 receptor (P2X2R) is a slowly desensitizing adenosine triphosphate (ATP)-gated ion channel that is highly expressed in the cochlea. When mutated, the P2X2R exacerbates age- and noise-related hearing loss, but selective modulators of the receptor are lacking, and the molecular basis of activation and desensitization remains poorly understood. Here, we determine high-resolution cryoelectron microscopy structures of the full-length wild-type human P2X2R in an apo closed state and two distinct ATP-bound desensitized states. In the apo closed state structure, we observe features unique to the P2X2R and locate disease mutations within or near the transmembrane domain. In addition, our ATP-bound structures show how free anionic ATP forms subtype-specific interactions with the orthosteric binding site. We identify and characterize two different ATP-bound desensitized state structures, one similar to published models for other P2XR subtypes, and a second alternate conformation not previously observed. A loop adjacent to the orthosteric binding site between these two ATP-bound desensitized state structures undergoes significant conformational changes. These movements are supported by multireplicate, microsecond-scale molecular dynamics simulation studies and suggest a path by which ATP could enter or leave the orthosteric pocket. Together, our results provide structural insights into the P2X2R, facilitating structure-based drug development for this therapeutically important target.
GPT-4o mini: Non-social science research article
Peritumoral macrophages recruit eosinophils to promote antitumor immune responses in breast cancer
Joseph Saglimbeni, Eduardo Esteva, Josue Canales, Oriana A. Perez, Anna Eichinger, William Huntley, Kamal M. Khanna, Igor Dolgalev, Natalie Klar, Sylvia Adams, Boris Reizis
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Breast tumors harbor dynamic microenvironments, with multiple immune cell types playing opposing roles during tumor progression and/or response to therapy. Tumor-associated macrophages promote mammary tumorigenesis, whereas the role of mammary tissue macrophages (MTMs) remains incompletely understood. High-dimensional immunostaining of murine mammary tumor progression revealed that MTMs were localized in the peritumoral stroma and associated with eosinophils, which were previously shown to facilitate antitumor T cell responses. The depletion of MTMs accelerated tumorigenesis in both spontaneous and orthotopically transplanted mammary tumor models. Upon induction of a productive antitumor response via the depletion of regulatory T cells, MTMs assumed an alternatively activated state and expressed eotaxins, thereby attracting eosinophils to peritumoral regions. MTMs expressed the receptor for the alarmin IL-33, which induced both MTM activation and eosinophil recruitment. These results suggest that MTMs can sense IL-33 and recruit eosinophils to facilitate antitumor immunity, a mechanism that may operate during tumor progression and be further enhanced during productive antitumor responses.
GPT-4o mini: Non-social science research article
Remembering ecologist Margaret Bryan Davis (1931–2024)
Elizabeth A. Lynch, Randy Calcote, Catherine A. Zabinski, Sara C. Hotchkiss
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Margaret Bryan Davis, a prominent ecologist, died on May 22, 2024. She was a Regents Professor at the University of Minnesota and a member of the National Academy of Sciences. Her students remember her as a creative and clear-thinking scientist who combined the tools and perspectives of paleoecology with ideas and problems of ecology in order to understand long-term forest dynamics. She was a champion of diversity and equity in science.
GPT-4o mini: Non-social science research article
More 26S and 30S proteasomes are beneficial in proteinopathy
Youngwon Kim, Namhoon Kim, WonJae Lee, Youbin Kim, Donghyeon Kim, Jisu Park, Yong-Keun Jung
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Despite the many studies on the ubiquitin–proteasome system, our understanding of the proteasome itself is limited. The balance and regulation of 26S and 30S proteasomes are not yet known. Here, we show that among the proteasome base assembly chaperones, only S5b/PSMD5 determines the levels of proteasome holoenzymes, especially the 30S proteasome, in mammals. In a variety of cell lines and mouse tissues, we found that apart from its role in yeast 19S proteasome assembly, loss of S5b/PSMD5 increased assembly toward the 26S and 30S proteasomes. During the process, we identified proteasome complexes that may represent alternative assembly intermediates, including the 19S base complex and 20S complexes harboring 19S subunits, eventually leading to a shift in the overall steady-state level of the 26S and 30S proteasomes. Intriguingly, the addition of the S5b/PSMD5 protein in vitro and its increase in cells efficiently disassembled the 30S proteasome into the 20S and 19S complexes. Increase in the 26S and 30S proteasomes over the 20S proteasome enhances the degradation of the aggregation-prone proteins and ubiquitinated proteins in cells and ameliorates cognitive impairment through the reduction of tau pathology in PS19 mice. These results suggest that 26S and 30S proteasomes are manipulated by S5b/PSMD5 and are beneficial for mitigating proteinopathy in mammals.
GPT-4o mini: Non-social science research article
The glass-ceiling convective regime and the origin and diversity of coronae on Venus
Madeleine C. Kerr, Dave R. Stegman, Suzanne E. Smrekar, Andrea C. Adams
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Venus and Earth are rocky planets of roughly the same size and bulk density, yet their surface volcanic and tectonic features appear substantially different. On Venus, the coexistence of large volcanic highlands—interpreted as the surface expression of long-lived mantle plumes—alongside coronae, smaller features thought to be caused by transient thermal diapirs, remains enigmatic. Using two-dimensional numerical models of mantle convection with sharp and broad mineral phase transitions for pyrolite, we show that both scales of upwellings can be generated in a stagnant lid planet with an interior temperature 250 to 400 K warmer than Earth’s. The smaller plumes originate from a ~600 km deep internal layer that exists as a consequence of the different sequence of mineral phase transitions that occur in warmer mantles less processed and differentiated by partial melting and volcanism. Future models that include melting will provide further tests of our hypothesis.
GPT-4o mini: Non-social science research article
Phonons in electron crystals with Berry curvature
Junkai Dong, Ophelia Evelyn Sommer, Tomohiro Soejima, Daniel E. Parker, Ashvin Vishwanath
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Recent advances in 2D materials featuring nonzero Berry curvature have inspired extensions of the Wigner crystallization paradigm. This paper derives a low-energy effective theory for such quantum crystals, including the anomalous Hall crystal (AHC) with nonzero Chern number. First, we show that the low frequency dispersion of phonons in AHC, despite the presence of Berry curvature, resembles that of the zero field (rather than finite magnetic field) Wigner crystal due to the commutation of translation generators. We explain how key parameters of the phonon theory such as elastic constants and effective mass can be extracted from microscopic models, and apply them to two families of models: the recently introduced λ -jellium model and a model of rhombohedral multilayer graphene (RMG). In the λ -jellium model, we explore the energy landscape as crystal geometry shifts, revealing that AHC can become “soft” under certain conditions. This causes transitions in lattice geometry, although the quantized Hall response remains unchanged. Surprisingly, the Berry curvature seems to enhance the effective mass, leading to a reduction in phonon speed. For the AHC in RMG, we obtain estimates of phonon speed and shear stiffness. We also identify a previously overlooked “kineo-elastic” term in the phonon effective action that is present in the symmetry setting of RMG, and leads to dramatic differences in phonon speeds in opposite directions. We numerically confirm these predictions of the effective actions by time-dependent Hartree–Fock calculations.
GPT-4o mini: Non-social science research article
Intron 1 of the C9orf72 gene: The RNA that RAN
Paul J. Hagerman
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GPT-4o mini: Non-social science research article
An in vitro BRAF activation assay elucidates molecular mechanisms driving disassembly of the autoinhibited BRAF state
Daniel A. Ritt, David E. Durrant, Matthew R. Drew, Suzanne I. Sandin, Juliana A. Martinez Fiesco, Xiaohua Zhang, Fikret Aydin, Timothy S. Carpenter, Grace M. Scheidemantle, Robert A. D’Ippolito, Alexandria L. Sohn, Caroline J. DeHart, Rebika Shrestha, Kelly Snead, Jenna Hull, Jeremy O. B. Tempkin, Yue Yang, Felice C. Lightstone, Frederick H. Streitz, Ping Zhang, Thomas J. Turbyville, Andrew G. Stephen, Dominic Esposito, Helgi I. Ingólfsson, Dwight V. Nissley, Deborah K. Morrison
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The RAF kinases (ARAF, BRAF, and CRAF) are essential components of the RAS-ERK signaling pathway, which controls vital cellular processes and is frequently dysregulated in human disease. Notably, mutations that alter BRAF function are prominent drivers of human cancer and certain RASopathy disorders, making BRAF an important target for therapeutic intervention. Despite extensive research, several aspects of BRAF regulation remain unclear. In this study, we developed an in vitro BRAF activation assay using purified autoinhibited BRAF:14-3-3 2 :MEK complexes. Our results show that fully processed, active-state KRAS alone can promote dimer-dependent BRAF activation. Moreover, we found that phosphatidylserine (PS)-containing liposomes synergized with KRAS to promote BRAF activation, achieving activity levels comparable to those observed with BRAF proteins that constitutively dimerize. In contrast, the SMP phosphatase complex had only a minimal effect on BRAF catalytic activity in this system but mediated the dephosphorylation of the negative regulatory pS365 14-3-3 binding site in a manner that was accelerated by the presence of KRAS alone or KRAS and 30% PS liposomes. Finally, we show that inhibitors blocking the BRAF RBD:KRAS interaction were able to suppress the in vitro activation of BRAF, underscoring the critical role of RAS binding in initiating the disassembly of the BRAF autoinhibited state. Thus, this assay provides valuable insights into the steps required for BRAF activation and can serve as an effective screening tool for identifying compounds that may inhibit this process and have therapeutic potential.
GPT-4o mini: Non-social science research article
SUMO conjugation to promoter-proximal sequence elements–associated proteins impacts on snRNA transcription
Laureano Bragado, Berta Pozzi, Inés Beckerman, Melina Magalnik, Anabella Srebrow
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The noncoding small nuclear RNAs (snRNAs) associate with a large set of proteins to form small nuclear ribonucleoprotein particles (snRNPs). While the function of snRNAs is well characterized, the regulation of their transcription remains poorly understood. Recently, we demonstrated that SUMO conjugation regulates snRNA3â€Č end processing. To further study the connection between SUMOylation and snRNA biogenesis, we generated a CRISPR/dCas9 tool comprising a catalytically inactive Cas9 (dCas9) fused to the catalytic domain of the SUMO protease SENP1 (dCas9-SENP1). Here, we show that snRNA transcription decreases when dCas9-SENP1 is delivered to their promoter-proximal sequence elements (PSE), indicating that SUMO conjugation to proteins associated with snRNA promoters is necessary for proper transcriptional activity. Focusing on SNAPC1, a subunit of the snRNA-specific transcription complex SNAPc, we identified lysine residues 245 and 333 as SUMO acceptor sites and generated a SUMOylation-deficient mutant of this protein (SNAPC1 2KR). To explore the relevance of SNAPC1 SUMOylation on snRNA transcription, we generated a cell line carrying an inducible degron system for depletion of the endogenous SNAPC1 protein. This system led us to demonstrate that SNAPC1 2KR is unable to sustain basal levels of snRNA transcription. By tagging endogenous SNAPC3 and SNAPC4, two other subunits of SNAPc, we show that while SNAPC1 SUMOylation-deficient mutant is able to interact with SNAPC3, its interaction with SNAPC4 is affected, despite the fact it is still recruited to the PSE. Altogether, these results indicate that SNAPC1 SUMOylation is required for proper snRNA transcription and SNAPc complex assembly.
GPT-4o mini: Non-social science research article
PI31 expression is neuroprotective in a mouse model of early-onset parkinsonism
Jose A. Rodriguez, Adi Minis, Rasha Aref, Hieu Hoang Minh Nguyen, Fiona Sun, Hermann Steller
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Neurodegenerative diseases present one of the most significant global health challenges. These disorders are defined by the accumulation of abnormal protein aggregates that impair synaptic function and cause progressive neuronal degeneration. Therefore, stimulating protein clearance mechanisms may be neuro-protective. Variants in FBXO7/PARK15 cause Parkinsonian Pyramidal Syndrome, an early-onset parkinsonian neurodegenerative disorder in humans, and inactivation of this gene in mice recapitulates many phenotypes seen in patients. The proteasome regulator PI31 is a direct binding partner of Fbxo7 and promotes local protein degradation at synapses by mediating fast proteasome transport in neurites. PI31 protein levels are reduced when the function of Fbxo7 is impaired. Here we show that restoring PI31 levels in Fbxo7 mutant fly and mouse strains prevents neuronal degeneration and significantly improves neuronal function, health, and lifespan. Notably, Fbxo7 inactivation in mouse neurons causes hyperphosphorylation of tau, and this was suppressed by transgenic expression of PI31. Our results demonstrate that PI31 is a crucial biological target through which Fbxo7 deficiency drives pathology. Therefore, targeting the PI31-pathway may represent a promising therapeutic approach for treating neurodegenerative disorders.
GPT-4o mini: Non-social science research article
Heterogeneity in the coordination of delta cells with beta cells is driven by both paracrine signals and low-density Cx36 gap junctions
Mohammad S. Pourhosseinzadeh, Jessica L. Huang, Donghan Shin, Ryan G. Hart, Luhaiza Y. Framroze, Jaresley V. Guillen, Joel Sanchez, Ramir V. Tirado, Kelechi Unanwa, Mark O. Huising
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Insulin potently decreases blood glucose; thus, tight control is required to prevent excessive insulin release and hypoglycemia. Central to this inhibition is somatostatin released from delta cells that are clustered with beta cells in pancreatic islets. This communication is of interest because the loss of functional beta cells in diabetes leads to uncontrolled delta cell activity that disrupts islet paracrine crosstalk. While it is established that insulin and somatostatin secretion are coordinated, the specific mechanism is unsettled. We have previously demonstrated that beta cells release the hormone Urocortin 3 to stimulate delta cells at high glucose, demonstrating a paracrine negative feedback loop. Others have proposed direct coordination via gap junctions. To resolve this conundrum, we used the genetically encoded fluorescent Ca 2+ reporter GCaMP6s to simultaneously record the activity of hundreds of beta and delta cells in low (2.8 mM) (LG) and high (16.8 mM) glucose (HG). Surprisingly, while many delta cells exhibit Ca 2+ oscillations in HG that are coordinated with beta cells, the activation of these delta cells precedes beta cells and is more variable than beta cell responses. The selective delta cell knockout of connexin 36 confirmed the involvement of gap junctions. However, blockade of vesicle release with the Rho-GTPase inhibitor ML-141 completely removed coupling between beta and most delta cells in HG. Our data reveal considerable functional heterogeneity among delta cells, where most delta cells are entrained by oscillatory Ca 2+ behaviors of beta cells that are mediated by a combination of paracrine signaling and low-density gap junction coupling.
GPT-4o mini: Non-social science research article
How palytoxin transforms the Na + ,K + pump into a cation channel
Ryuta Kanai, Naoki Tsunekawa, Flemming Cornelius, Bente Vilsen, Chikashi Toyoshima
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Palytoxin (PTX), a potent marine toxin, has long been known to transform Na + ,K + -ATPase (NKA), an indispensable ion pump, into a nonselective cation channel. It has been postulated that PTX takes control of the two gates on either side of a channel-like pore. These gates normally open and close alternately, synchronized with chemical events, never opening simultaneously. A critical question is whether palytoxin takes over the control of the two gates or creates a new pathway. Here, we present structures of NKA with bound palytoxin in three different states. PTX binds to NKA in E2P, occupying the physiological Na + exit pathway, similar to istaroxime, a new-generation cardiotonic steroid. Adding Na + and ATP/ADP to the NKA·PTX complex induces an open channel traversing the entire membrane alongside the physiological ion pathway. As AlF x , a stable transition state analog of phosphate replaces phosphate in the NKA·PTX complex preformed in E2P, the complex appears to undergo the normal reaction cycle from E2P to E1· n Na + . PTX occupies the space between the transmembrane helices M4 and M6, thereby preventing the closure of the extracellular half of the ion pathway. These structures demonstrate that the architecture of NKA is fundamentally different from “a pore with two gates.” Each half of the ion pathway comprises three segments, including a movable component that plays a pivotal role in translocating the bound cations by connecting the constant part to an appropriate inlet. The ion pathway of NKA transforms dynamically, ensuring that the two halves never exist simultaneously.
GPT-4o mini: Non-social science research article
Weighted active space protocol for multireference machine-learned potentials
Aniruddha Seal, Simone Perego, Matthew R. Hennefarth, Umberto Raucci, Luigi Bonati, Andrew L. Ferguson, Michele Parrinello, Laura Gagliardi
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Multireference methods such as multiconfiguration pair-density functional theory accurately capture electronic correlation in systems with strong multiconfigurational character, but their cost precludes direct use in molecular dynamics. Combining these methods with machine-learned interatomic potentials (MLPs) can extend their reach. However, the sensitivity of multireference calculations to the choice of the active space complicates the consistent evaluation of energies and gradients across structurally diverse nuclear configurations. To overcome this limitation, we introduce the weighted active space protocol (WASP), a systematic approach to assign a consistent active space for a given system across uncorrelated configurations. By integrating WASP with MLPs and enhanced sampling techniques, we propose a data-efficient active learning cycle that enables the training of an MLP on multireference data. We demonstrated the approach on the TiC + -catalyzed C–H activation of methane, a reaction that poses challenges for Kohn–Sham density functional theory due to its significant multireference character. This framework enables accurate and efficient modeling of catalytic dynamics, establishing a paradigm for simulating complex reactive processes beyond the limits of conventional electronic-structure methods.
GPT-4o mini: Non-social science research article
Reply to Possenriede et al.: LDLR as a targetable HlyA receptor in Escherichia coli pyelonephritis
Hunter W. Kuhn, Madeleine R. Smither, Christina A. Collins, Joseph P. Gaut, Michael S. Diamond, David A. Hunstad
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GPT-4o mini: Non-social science research article
Structurally diverse viral inhibitors converge on a shared mechanism to stall the antigen transporter TAP
James Lee, Victor Manon, Jue Chen
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In the host–pathogen arms race, herpesviruses and poxviruses encode proteins that sabotage the transporter associated with antigen processing (TAP), thereby suppressing MHC-I antigen presentation and enabling lifelong infection. Of the five known viral TAP inhibitors, only the herpes simplex virus (HSV) protein ICP47 has been structurally resolved. We now report cryoelectron microscopy structures of TAP in complex with the remaining four: BNLF2a (Epstein–Barr virus), hUS6 (human cytomegalovirus), bUL49.5 (bovine herpesvirus 1), and CPXV012 (cowpox virus), assembling a structural atlas of viral TAP evasion. Despite employing divergent sequences, folds, and conformational targets, these viral inhibitors converge on a common strategy: they stall TAP from the alternating access cycle, precluding peptide entry into the ER and shielding infected cells from cytotoxic T cell surveillance. These findings reveal striking functional convergence and provide a structural framework for rational antiviral design.
GPT-4o mini: Non-social science research article
The Arabidopsis TIRome informs the design of artificial TIR (Toll/interleukin-1 receptor) domain proteins
Adam M. Bayless, Lijiang Song, Mitchell Sorbello, Sam C. Ogden, Tyler S. Todd, Alice Flint, Natsumi Maruta, Jedidiah Tulu, Mikhail Drenichev, Vardis Ntoukakis, Thomas Ve, Mehdi Mobli, Li Wan, Qingli Liu, Jeffery L. Dangl, Bostjan Kobe, Murray Grant, Marc T. Nishimura
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The TIR (Toll/interleukin-1 receptor) domain is an ancient protein module that functions in immune and cell death responses across the Tree of Life. TIR domains encoded by plants and prokaryotes function as enzymes to produce diverse small molecule immune signals. Plant genomes can encode hundreds of TIR-domain containing proteins—many of which confer important agricultural disease resistance as TIR-NLR (nucleotide-binding, leucine-rich repeat) immune receptors. Despite their importance, how natural variation influences TIR enzymatic output and immunity-associated cell death is largely unexplored. We assayed a complete collection of the TIR domains of Arabidopsis thaliana Col-0 (the “AtTIRome”) to explore variation in TIR metabolite production and cell death signaling. Roughly half of the AtTIRome triggered cell death in transient assays. Artificial TIR proteins designed based on consensus sequences of the AtTIRome’s cell death phenotypic classes revealed polymorphisms controlling variation in TIR cell death elicitation and metabolite production. Structure–function analyses of artificial TIRs revealed that natural variation in the “BB-loop”, a flexible region overlying the catalytic pocket, determines differences in function across Arabidopsis TIR-containing proteins. We further demonstrate that artificial TIRs are functional on an NLR chassis and that BB-loop variation can tune the activity of a natural TIR-NLR protein. These findings shed light on the diversity of TIR outputs and reveal methods to design and engineer TIR-based immune receptors.
GPT-4o mini: Non-social science research article
Tropical cyclones expand faster at warmer relative sea surface temperature
Danyang Wang, Daniel R. Chavas, Benjamin A. Schenkel
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Tropical cyclones are expected to intensify more rapidly with warming, but relatively little work has examined whether they could expand more rapidly with warming, too. Recent theory predicts that peak expansion rate should increase with sea surface temperature (SST), and physical arguments suggest this dependence should be specifically on the relative SST, i.e. the SST difference from the tropical mean. We test this hypothesis with historical observational data, in which SST variations are primarily variations in relative SST. Both average and peak expansion rates are found to systematically increase with relative SST globally across the Northern Hemisphere (27.2 and 37.5 km/d/K) and within each individual basin. Results are robust across both reanalysis and Best Track observational datasets. Uniform-SST aquaplanet simulations show a much weaker dependence of maximum expansion rate on absolute SST, suggesting that the dominant dependence is on relative SST. Hence, mean global warming is not expected to strongly change storm size dynamics, but patterns of sea surface warming may play an important role in determining how storm size, and hence coastal risk, may change in the future. This work can also help improve forecasting of the wind field and its hazards and impacts at landfall.
GPT-4o mini: Non-social science research article
Ί value analysis underscores strong functional and structural compactness of the GABA A receptor
MichaƂ A. MichaƂowski, Katarzyna Terejko, Michalina Gos, Ilona IĆŒykowska, Marta M. CzyĆŒewska, Karol KƂopotowski, PrzemysƂaw T. Kaczor, Aleksandra BrzĂłstowicz, Estera PƂuĆŒek, Monika MigdaƂek, Jerzy W. Mozrzymas
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Îł-aminobutyric acid type A receptor (GABA A R) is a pentameric ligand-gated ion channel that plays a crucial role in inhibition in the adult brain. Structural and electrophysiological studies have provided numerous insights into the receptor’s functioning but the complete molecular mechanism of GABA A R action remains elusive. Herein, we used high-resolution single-channel recording to analyze point-mutated α 1 ÎČ 2 Îł 2 receptors and applied so called Ί value (REFER, rate-equilibrium free energy relationship) analysis which allows to infer the order of domains engagement during activation, offering a complementary “dynamic” insight into the receptor’s function. As anticipated, point mutations at the orthosteric binding sites reduced GABA binding affinity, with the magnitude of this effect diminishing progressively with increasing distance from the binding site. On the contrary, mutations located all over the macromolecule’s structure, e.g., in “peripheral top position,” extracellular/transmembrane interface, and channel pore, affected the receptor with a clear tendency to influence entire gating including opening/closing, preactivation, and desensitization with no clear correlation with the distance to the channel gate. Interestingly, the calculated Ί values for the GABA A R showed a relatively narrow range (0.42 to 0.81), suggesting that the conformational transitions are highly synchronized and coordinated by a global network of interactions. This prediction is also in agreement with observation that, typically, single GABA A R residue mutation alters the kinetics of not just one but many (often all) conformational transitions. We thus propose a dictum reflecting modus operandi of the GABA A R: Binding is local and gating is global. In conclusion, our analysis indicates that GABA A R shows particularly strong functional compactness manifested as global gating mechanisms and high allostery.
GPT-4o mini: Non-social science research article
In vivo Pirt-Marina voltage sensor imaging detects primary sensory neuron–specific voltage dynamics and neuronal plasticity changes
Yan Zhang, Hyeonwi Son, John Shannonhouse, Ruben Gomez, Eungyung Kim, Chih-Hsuan Ai, Man-Kyo Chung, Jelena Platisa, Vincent A. Pieribone, Yu Shin Kim
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In vivo voltage imaging is a powerful tool for monitoring action potentials and dynamic electrical events in heterogeneous sensory neurons enabling the deciphering of rapid somatosensory information processing. Virus-driven expression of genetically encoded voltage indicator (GEVI) suffers from inconsistent expression levels and offers a limited time window for optimal voltage imaging. Here, we generated and characterized a knock-in mouse line with Pirt-driven expression of Marina, a positively tuned GEVI, in primary sensory neurons. Pirt-Marina mice enable optical reporting of touch, itch, and nociceptive sensations in vivo and distinct action potential patterns in the trigeminal and dorsal root ganglion neurons. Notably, Pirt-Marina mice display robust fluorescence signals in response to mechanical, thermal, or chemical stimuli, allowing visualization of transformations in sensory coding following inflammation and injury. This Pirt-Marina mouse line provides optical access to dynamic neuronal activity and plasticity in the peripheral nervous system (PNS) with high temporal accuracy, fidelity, and reliability.
GPT-4o mini: Non-social science research article
A universal wind–wave–bubble formulation for air–sea gas exchange and its impact on oxygen fluxes
Luc Deike, Xiaohui Zhou, Paridhi Rustogi, Rachel H. R. Stanley, Brandon G. Reichl, Seth M. Bushinsky, Laure Resplandy
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Bubble-mediated gas exchange associated with wave breaking is a critical pathway for ocean–atmosphere exchange of low solubility gases such as oxygen. Yet, ocean and climate models, as well as observation-based products, usually rely on wind-only air–sea flux formulations derived from carbon constraints that ignore the asymmetric nature of the bubble flux, contributing to discrepancies between estimates of oxygen inventories and their response to climate change. Without bubbles, gas exchange is controlled by a symmetric wind-driven exchange, with the ocean–atmosphere gas partial pressure difference controlling whether outgassing or uptake occurs. Bubbles entrained by wave breaking can enhance this symmetric turbulent exchange, and contribute an additional asymmetric flux, always leading to an uptake, as they get squeezed by hydrostatic pressure (large bubbles) or collapse and fully dissolve (small bubbles). We present an observation-constrained theoretical framework of the air–sea flux accounting for air entrainment due to wave breaking and symmetric and asymmetric bubble exchange. The combined evidence from theory, laboratory, and field measurements of carbon dioxide fluxes, oxygen concentration, and noble gas supersaturation yields a universal formulation of gas exchange which we implement into a global ocean biogeochemical model. We discuss the resulting oxygen fluxes and demonstrate that our wind–wave–bubble formulation better reproduces observed in situ oxygen concentrations in water mass formation regions, where air–sea exchange is high, than a commonly used wind-only formulation. We show that the asymmetric bubble flux is essential for evaluating air–sea oxygen fluxes and estimating the magnitude of the ocean oxygen loss associated with global warming.
GPT-4o mini: Non-social science research article
Functional unfolding of the integrin αX transmembrane helix
Han N. Vu, Minhyeong Lee, Alan J. Situ, Woojin An, Klaus Ley, Chungho Kim, Tobias S. Ulmer
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In biological membranes, proteins face a fundamentally different environment than in water. To avoid untenable lipid contacts with polar backbone atoms, they use the continuous hydrogen bonding achieved by α-helices or ÎČ-barrels to traverse membranes. Here, we show that integrin αX, and by homology αM, undermine this paradigm by partially unfolding the N-terminal third of their transmembrane (TM) helix. Unfolding results in a dynamic, frayed helix that weakens the association with its partnering ÎČ2 subunit to lower the activation threshold of integrin αXÎČ2-mediated cell adhesion. The extent of unfolding depends on membrane geometry, thereby establishing a mechanism for sensing membrane properties. The combination of adhesive control with sensory capacity in integrin αXÎČ2 and αMÎČ2 may achieve membrane localization-dependent receptor activation in leukocyte phagocytosis. The unfolding of the αX TM helix arises from a high number of α-helix-destabilizing residues that TM helices in general approach but do not exceed. Accordingly, backbone dynamics of TM helices may disrupt hydrogen bonds, modulate protein function, and optimize TM helix rigidity.
GPT-4o mini: Non-social science research article
Parametrically guided design of beta barrels and transmembrane nanopores using deep learning
David E. Kim, Joseph L. Watson, David Juergens, Sagardip Majumder, Ria Sonigra, Stacey R. Gerben, Alex Kang, Asim K. Bera, Xinting Li, David Baker
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Francis Crick’s global parameterization of coiled coil geometry has been widely useful for guiding design of new protein structures and functions. However, design guided by similar global parameterization of beta barrel structures has been less successful, likely due to the deviations from ideal barrel geometry required to maintain interstrand hydrogen bonding without introducing backbone strain. Instead, beta barrels have been designed using two-dimensional structural blueprints; while this approach has successfully generated new fluorescent proteins, transmembrane nanopores, and other structures, it requires expert knowledge and provides only indirect control over the global shape. Here, we show that the simplicity and control over shape and structure provided by parametric representations can be generalized beyond coiled coils by taking advantage of the rich sequence–structure relationships implicit in RoseTTAFold-based design methods. Starting from parametrically generated barrel backbones, both RFjoint inpainting and RFdiffusion readily incorporate backbone irregularities necessary for proper folding with minimal deviation from the idealized barrel geometries. We show that for beta barrels across a broad range of beta sheet parameterizations, these methods achieve high in silico and experimental success rates, with atomic accuracy confirmed by an X-ray crystal structure of a rare barrel topology, and de novo designed transmembrane nanopores with conductances ranging from 200 to 500 pS. By combining the simplicity and control of parametric generation with the high success rates of deep learning–based protein design methods, our approach makes the design of proteins where global shape confers function, such as beta barrel nanopores, more precisely specifiable and accessible.
GPT-4o mini: Non-social science research article
Endothelial αvÎČ3 integrin induction during hypoxia protects blood–brain barrier integrity
Sebok K. Halder, Violaine D. Delorme-Walker, Richard Milner
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The blood–brain barrier (BBB) is critical for maintaining cerebral homeostasis, and its deterioration with age is an important pathogenic factor in the etiology of vascular dementia. Extracellular matrix–integrin interactions play a central role in regulating vascular stability. The αvÎČ3 integrin is not expressed by brain endothelial cells under stable conditions but is strongly induced by hypoxia. However, it is currently unclear whether αvÎČ3 integrin exerts a destructive or protective influence on BBB integrity. In young (8 to 10 wk) and aged (20 mo) mice, we examined the impact of a function-blocking ÎČ3 integrin antibody as well as the inhibitory peptide cilengitide on BBB disruption during exposure to CMH (8% O 2 ). Hypoxic induction of brain endothelial ÎČ3 integrin was much stronger in aged mice. In both young and aged mice, ÎČ3 integrin inhibition greatly amplified hypoxia-induced BBB disruption, correlating with loss of tight junction proteins and induction of the leaky BBB marker mouse endothelial cell antigen (MECA)-32. Consistent with this, ÎČ3 integrin null mice showed increased levels of hypoxia-induced BBB disruption and MECA-32 expression. Cilengitide also reduced the integrity of a brain endothelial monolayer in vitro, prevented ÎČ3 integrin localization to focal adhesions, and reduced expression of vascular endothelial (VE)-cadherin and tight junction proteins. These observations suggest that hypoxic induction of endothelial αvÎČ3 integrin enhances BBB integrity by stabilizing endothelial adhesion. This raises the interesting possibility that pharmacological upregulation of endothelial αvÎČ3 integrin in the aged brain might hold therapeutic promise for vascular dementia.
GPT-4o mini: Non-social science research article
Designing for cooperative grain boundary segregation in multicomponent alloys
Malik Wagih, Yannick Naunheim, Tianjiao Lei, Christopher A. Schuh
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Tailoring the nanoscale distribution of chemical species at grain boundaries is a powerful method to dramatically influence the properties of polycrystalline materials. However, classical approaches to the problem have tacitly assumed that only competition is possible between solute species. In this paper, we show that solute elements can cooperate in the way they segregate to grain boundaries: In properly targeted alloys, the different chemical species cooperate to each fill complementary grain boundary sites disfavored by the other. By developing a theoretical “spectral” approach to this problem based on quantum-accurate grain boundary site distributions, we show how grain boundaries can be cooperatively alloyed, whether by depletion or enrichment. We provide machine-learned cosegregation information for over 700 ternary aluminum-based alloys and experimentally validate the concept in one ternary alloy where cosegregation is not expected by prior models but is expected based on the cooperative model.
GPT-4o mini: Non-social science research article
Pseudouridine prevalence in Kaposi’s sarcoma–associated herpesvirus transcriptome reveals an essential mechanism for viral replication
Timothy J. Mottram, Katherine L. Harper, Elton J. R. Vasconcelos, Adrian Whitehouse
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Pseudouridylation is a prevalent RNA modification occurring in transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), small non-coding RNAs (snoRNAs), and has been most recently identified in mRNAs and lncRNAs. Emerging evidence suggests that this dynamic RNA modification is implicated in altering gene expression by regulating RNA stability, modulating translation elongation, and modifying amino acid substitution rates. However, the role of pseudouridylation in infection is poorly understood. Herein, we demonstrate that Kaposi’s sarcoma–associated herpesvirus (KSHV) manipulates the pseudouridylation pathway to enhance replication. We show that the pseudouridine synthases (PUS), PUS1, and PUS7 are essential for efficient KSHV lytic replication, supported by their redistribution to viral replication and transcription complexes. We present a comprehensive analysis of KSHV RNA pseudouridylation, revealing hundreds of modified RNAs at single-nucleotide resolution. Notably, we demonstrate that pseudouridylation of the KSHV-encoded polyadenylated nuclear RNA (PAN) plays a significant role in the expression of PAN RNA. These findings reveal an essential role of pseudouridine modification in the KSHV replication cycle.
GPT-4o mini: Non-social science research article
A reanalysis of population dynamics in the Casas Grandes region of Northern Mexico using mitochondrial DNA
Meradeth Snow, Michael T. Searcy, Rachel Summers, Tre Blohm, Lacy Hazelwood, Holli McDonald, Samuel J. Jensen, Jose Luis Punzo-DĂ­az
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The Casas Grandes region in northwest Chihuahua, Mexico, is ideally situated to explore the notion of contact between the US Southwest/Northwest Mexico and Mesoamerica, as it lies geographically in a region where cultural traditions were combined in unique ways. In order to explain these dynamics, past researchers have suggested that the primary catalyst for the flourishing Casas Grandes population in the thirteenth century A.D. was caused by migrants from Mesoamerica or from larger populations to the north. We analyzed mitochondrial genetic data from individuals interred at sites that date to earlier (A.D. 700–1200) and later (A.D. 1200–1450) time periods, which allowed us to examine changes in gene pools over time and to test these migration hypotheses. Comparing the full mitogenomes from 114 individuals, we show that low levels of migration occurred diachronically, although they still may have contributed to hybridized cultural practices. These data counter the long-standing assumption that widescale population replacement was the cause for the rise of PaquimĂ©, the center of the Casas Grandes world in the thirteenth-century A.D.
GPT-4o mini: Non-social science research article
Bacillus subtilis σ A and Escherichia coli σ 70 lacking σ region 1.1 are not released during transcription initiation and elongation
Aniruddha Tewary, Shreya Sengupta, Soumya Mukherjee, Nilanjana Hazra, Yon W. Ebright, Richard H. Ebright, Jayanta Mukhopadhyay
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A “σ cycle” in which the initiation factor σ associates with RNA polymerase (RNAP) core enzyme to permit transcription initiation and dissociates from RNAP core enzyme to permit transcription elongation, has been proposed to occur and to be an essential step for σ-exchange, with all principal σ factors from all bacteria. These proposals were based on studies of the principal σ factor of Escherichia coli , σ 70 , which generally, albeit not obligatorily, is released from RNAP upon the transition from transcription initiation to elongation. Here, we show that, in contrast to E. coli σ 70 , the Bacillus subtilis principal σ factor, σ A , is not released and is retained on RNAP core throughout transcription elongation. We further show that a mutant E. coli σ 70 derivative lacking σ region 1.1 (σ R1.1) is not released and is retained on RNAP core throughout transcription elongation. We also observe that B. subtilis σ A and the mutant E. coli σ 70 derivative lacking σ R1.1 interact much more stably with RNAP than full-length E. coli σ 70 . Our results indicate that the σ cycle is not a universal phenomenon in bacteria.
GPT-4o mini: Non-social science research article
Distinct timescales dissociate spontaneous thought dimensions
Jingyu Hua, Xianliang Ge, Min Dou, Yuqi Zhang, Liezhong Ge, Stuart Fogel, Jianfeng Zhang, Georg Northoff
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Our spontaneous thoughts encompass various dimensions, such as task-relatedness (off vs. on task), and thought orientation (internal vs. external). However, their distinction remains unclear. Our study addresses this issue by focusing on their timescales at both the behavioral level (using fast and slow finger tapping) and the neural level (using EEG) using two independent datasets (N = 84 and 35). Behavioral results revealed a double dissociation: Task-relatedness was linked to fast tapping only, whereas thought orientation was associated with slow tapping only. At the neural level, we assessed topographic similarity in EEG to quantify the temporal influence of past neural activity on current ones. Task-relatedness modulated topographic similarity only during fast tapping, while thought orientation did so only during slow tapping. Critically, topographic similarity was phase-based, as shown by its correlation with phase-locking value and the loss of associations with thought after phase-shuffling. This indicates that the neural signatures of both thought dimensions are strongly phase-dependent. Finally, we demonstrate that nonlinearity plays a distinct role mediating the impact of different timescales (slow and fast finger tapping) on spontaneous thoughts at both behavioral (precision error) and neural levels (topographic similarity). Overall, these results demonstrate that task-relatedness is associated with short timescales, whereas thought orientation is associated with long timescales. This highlights how distinct temporal dynamics shape different spontaneous thought dimensions on both their behavioral and neural features.
GPT-4o mini: Non-social science research article
Tubular ACSM3 deficiency impairs medium-chain fatty acid metabolism and aggravates kidney fibrosis
Jinxi Li, Ting Xiang, Fengping Zhang, Li Feng, Yiting Wu, Fan Guo, Lingzhi Li, Ping Fu, Liang Ma
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Kidney fibrosis is driven by multiple factors, among which impaired fatty acid oxidation has emerged as a critical determinant. Acyl-Coenzyme A (CoA) synthetase medium-chain family member 3 (ACSM3), a key enzyme of medium-chain fatty acid (MCFA) metabolism, has been implicated in metabolic syndrome, but its function in fibrotic kidney remains unexplored. Here, we found that tubular epithelial ACSM3 expression was downregulated in kidney fibrotic mice and patients and inversely correlated with disease severity. Systemic and tubular-specific knockout of ACSM3 both exacerbated renal fibrosis, whereas adeno-associated virus (AAV)-mediated ACSM3 overexpression alleviated fibrotic kidneys in mice. Mechanistically, ACSM3 deficiency disrupted MCFA metabolism and resulted in abnormal mitochondrial homeostasis. Notably, we identified that dodecanoic acid (C12:0) could improve kidney fibrosis, which was primarily utilized via ACSM3 in kidneys. Furthermore, C12:0 oxidation impairment caused by tubular ACSM3 deficiency aggravated fibrotic kidney. Together, ACSM3-regulated MCFA metabolism played a pivotal role in kidney fibrosis, highlighting a potent drug target of ACSM3 and a potential supplementary therapy of MCFA against chronic kidney disease.
GPT-4o mini: Non-social science research article
Reply to Quillien: Intuitive preferences and interpretive humility in intentionality judgments
Will M. Gervais, Ryan T. McKay, Jazmin L. Brown-Iannuzzi, Robert M. Ross, Gordon Pennycook, Jonathan Jong, Jonathan A. Lanman
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GPT-4o mini: Non-social science research article
Discovering neural elastoplasticity from kinematic observations
Georgios Barkoulis Gavris, WaiChing Sun
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Inferring accurate and precise material models necessary for high-fidelity predictions has been a central challenge in constitutive modeling. Both traditional regression methods and modern machine-learning approaches require specialized data labels, which often cannot be sufficiently obtained from experiments. This data demand makes many sophisticated models impractical for real-world problems. Improvements in digital image correlation techniques have enabled accurate measurements of displacement data, providing an alternative kinematics-based approach for model identification. However, for materials undergoing plastic deformation, fracture, and damage, the corresponding inverse problem could be inherently challenging due to the dependence on loading history. We overcome this by formulating an inverse problem to discover interpretable plasticity models parameterized by neural networks (NN) from kinematic observations, leveraging a differentiable simulator with a smooth constitutive update that enables backpropagation for the NN training. The ability to use kinematic observations to infer complex material models may pave the way for a massive generation of material models that can be game-changing for emerging applications such as the design of metamaterials, response surface analyses, and the design of experiments.
GPT-4o mini: Non-social science research article
Earliest evidence of smoke-dried mummification: More than 10,000 years ago in southern China and Southeast Asia
Hsiao-chun Hung, Zhenhua Deng, Yiheng Liu, Zhiyu Ran, Yue Zhang, Zhen Li, Yousuke Kaifu, Qiang Huang, Khanh Trung Kien Nguyen, Hai Dang Le, Guangmao Xie, Anh Tuan Nguyen, Mariko Yamagata, Truman Simanjuntak, Sofwan Noerwidi, Mohammad Ruly Fauzi, Marlin Tolla, Alpius Wetipo, Gang He, Junmei Sawada, Chi Zhang, Peter Bellwood, Hirofumi Matsumura
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In southern China and Southeast Asia (collectively, Southeastern Asia), Terminal Pleistocene and Early to Middle Holocene (ca. 12,000 to 4,000 cal. BP) hunter-gatherer burials feature tightly crouched or squatting postures, sometimes with indications of post-mortem dismemberment. Such burials contrast strongly with the extended supine burial postures typical of subsequent Neolithic inhumations in these regions. Their contorted postures, often with traces of burning, present interpretive challenges. This study uses multiple techniques, including X-ray diffraction and Fourier-transform infrared spectroscopy, to investigate 54 pre-Neolithic burials from 11 archaeological sites located across Southeastern Asia. The findings confirm that many of these pre-Neolithic flexed and squatting burials were treated by an extended period of smoke-drying over fire, a process of mummification similar to that recorded ethnographically in some Australian and Highland New Guinea societies. Some of the analyzed archaeological samples represent the oldest known instances of such artificial mummification in the world.
GPT-4o mini: Non-social science research article
LDL receptor promotes urinary tract infection by α-hemolysin-producing Escherichia coli and long-term histopathologic sequelae in the kidney
Lena Possenriede, Georg W. Sendtner, Peyman Falahat, Julia Miranda, Axel Schmidt, Kerstin U. Ludwig, Sibylle von Vietinghoff
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GPT-4o mini: Non-social science research article
SLC39A8-mediated zinc dyshomeostasis potentiates kidney disease
Zhaoxian Cai, Xiaotian Wu, Tianyi Wang, Zijun Song, Pu Ni, Meijuan Zhong, Yunxing Su, Enjun Xie, Shumin Sun, Yangjun Lin, Junxia Min, Fudi Wang
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While numerous genetic risk loci are linked to kidney disease, a unifying therapeutic target for diverse renal pathologies remains elusive. Here, through large-cohort polymorphic locus screening, we identify the SLC39A8 A391T variant (rs13107325) as a shared modifier of multiple kidney diseases. Functional characterization using Slc39a8 A391T knock-in mice and kidney-specific Slc39a8 knockout mice reveals that loss of SLC39A8 function reduces renal zinc accumulation, thereby mitigating susceptibility to kidney injury and disease progression. Mechanistically, we demonstrate that perturbed zinc homeostasis drives renal damage, and limiting zinc levels—whether via impaired SLC39A8 activity or direct chelation—activates the zinc–AKT–FOXO1–G6PC axis to confer protection. Critically, zinc chelation with EDTA recapitulates this benefit, significantly preventing and ameliorating experimental acute and chronic kidney disease. These findings establish renal zinc homeostasis as a key therapeutic node, with SLC39A8 and zinc-modulating strategies representing promising avenues for treating a broad range of kidney diseases.
GPT-4o mini: Non-social science research article
Characterization of Sr UGT76G4 reveals a key residue for regioselectivity and efficient Reb M synthesis
Yu Wang, Tang Li, Yangjie Zheng, Chenxin Guo, Kuikui Li, Xiaochen Jia, Liping Zhu, Kecai Chen, Heng Yin
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Steviol glycosides (SGs) from Stevia rebaudiana are prized as noncaloric sweeteners, with rebaudioside M (Reb M)—a next-generation SG known for its sucrose-like sweetness and lack of off-tastes—standing out for its superior sensory profile. However, Reb M’s limited natural abundance impedes its commercial production. Here, we report the identification of a glucosyltransferase, UGT76G4 that efficiently catalyzes the conversion of Reb D to Reb M with a strong preference for C19 glycosylation. Structural and functional analyses, including X-ray crystallography, molecular dynamics simulations, and mutagenesis, revealed key residues in UGT76G4 that dictate its regioselectivity, with residue 200 playing a pivotal role. Engineered UGT76G4 variants, including Q199I/G200Y and H155S/Q199I/G200Y, enhanced Reb E and Reb D conversion efficiency by 1.46-fold and 23-fold, respectively, compared to UGT76G1. The engineered variants offer a promising pathway for increasing Reb M production, advancing biotechnological strategies for steviol glycoside biosynthesis and optimizing plant metabolic engineering approaches. Our findings deepen the understanding of SG biosynthesis and provide a basis for sustainable production of high-value sweeteners.
GPT-4o mini: Non-social science research article
Wnt inhibition alleviates resistance to anti-PD1 therapy and improves antitumor immunity in glioblastoma
Shanmugarajan Krishnan, Somin Lee, Zohreh Amoozgar, Sonu Subudhi, Ashwin Srinivasan Kumar, Jessica M. Posada, Neal Lindeman, Pinji Lei, Mark Duquette, Sophie Steinbuch, Marc Charabati, Peigen Huang, Patrik Andersson, Meenal Datta, Lance L. Munn, Dai Fukumura, Rakesh K. Jain
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Wnt signaling plays a crucial role for many developmental processes. It is also pivotal in the generation and limited treatment outcomes of glioblastoma (GBM). Here, we identified Wnt7b, which is markedly upregulated in GBM patients, as a determinant of resistance to immune checkpoint blockers (αPD1; anti-Programmed Cell Death Protein 1) in a clinically relevant, αPD1-resistant GBM murine model with abundant stem cells. We observed that increased levels of Wnt7b and ÎČ-catenin correlated with the resistance to αPD1. Treatment combining a porcupine inhibitor WNT974 with αPD1 reprogrammed the immune suppressive tumor microenvironment (TME) to bolster antitumor immune responses and extended the survival of mice bearing orthotopic GBM, with 25% long-term survivors. Our causal studies revealed that WNT974 potentiated αPD1 therapy by the expansion of antigen presenting DC3-like dendritic cells (DCs). Additionally, WNT974 combination with αPD1 was associated with a reduction in immune suppressive granulocytic myeloid-derived suppressor cells (MDSCs), an increase in the Ki67+CD8/Ki67+regulatory T cells (Treg) ratio, tilting the CD8:Treg balance in the TME toward antitumor immune response, and more pronounced GrzB+CD8+ effector T cells. Conversely, an increase in monocytic MDSCs and phosphorylation of pro-oncogenic proteins was associated with resistance to the combination therapy. Collectively, our preclinical findings provide a strong rationale to test Wnt7b/ÎČ-catenin inhibition with αPD1 therapy in GBM patients with elevated Wnt7b/ÎČ-catenin signaling.
GPT-4o mini: Non-social science research article
Experimental evidence for the continuous transition between elastic and elastoinertial turbulence
Yi-Bao Zhang, Lu Li, Yaning Fan, Jinghong Su, Heng-Dong Xi, Chao Sun
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Elastic turbulence (ET) and elastoinertial turbulence (EIT) of viscoelastic fluids are unique flow states with features distinct from the inertial turbulence of Newtonian fluids. Whether these two states are connected or entirely decoupled remains controversial. We here resolve this controversy by providing experimental evidence of a continuous transition between ET and EIT in Taylor-Couette flow. Through experimentally quantifying the roles of elasticity and inertia in flow stability, we find that elasticity is the primary driving mechanism for both elastic and elastoinertial instabilities, and inertia plays a secondary role in the latter. Remarkably, the critical condition for these instabilities can be described by a unified function derived from stability analysis, revealing that the transition between elastic instability to elastoinertial instability is continuous. Moreover, we show that the flow structures and the energy spectrum evolve seamlessly from ET to elasticity-dominated EIT, transitional EIT, and inertia-modulated EIT, with inertia playing an increasingly important role in the last three regimes. Our results offer insights into the fundamental nature of turbulence in viscoelastic flows and would have implications for applications involving drag reduction and polymer processing.
GPT-4o mini: Non-social science research article
Spatiotemporal mapping of alloy mesostructure dynamics via multimodal coherent X-ray diffraction imaging
Shuntaro Takazawa, Kakeru Ninomiya, Minh-Quyet Ha, Tien-Sinh Vu, Yuhei Sasaki, Masaki Abe, Hideshi Uematsu, Naru Okawa, Nozomu Ishiguro, Kyosuke Ozaki, Takaki Hatsui, Taiki Hoshino, Maiko Nishibori, Hieu-Chi Dam, Yukio Takahashi
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Understanding mesoscale structural dynamics of precipitation-strengthened alloys is essential for optimizing the mechanical performances of these alloys. Herein, we establish a multimodal coherent X-ray diffraction imaging framework for spatiotemporal mapping of mesoscale structural dynamics in precipitation-strengthened alloys. As a demonstrative application, we visualized the structural evolution in Mg 97 Zn 1 Gd 2 during isothermal annealing at 700 K, revealing real-time dynamics of nucleation, growth, and coarsening. Ptychographic reconstruction enabled imaging of microstructural transformations across a wide field of view (~100 ÎŒm 2 ) with temporal resolution spanning several hours. We observed decomposition of (Mg, Zn) 3 Gd and concurrent precipitation and coarsening of long-period stacking ordered phases. To resolve local dynamics at finer spatiotemporal scales, we combined dynamic coherent diffraction imaging with X-ray photon correlation spectroscopy, targeting selected regions (~10 ÎŒm 2 ) with time resolution down to tens of seconds. This approach revealed the rapid formation of nanoscale precipitates within 10 s after heating, followed by coarsening over several hundred seconds. Additionally, we applied optical flow analysis—a computational method to track motion patterns—to visualize and quantify the nucleation, growth, and coarsening kinetics. The abovementioned findings demonstrate the capability of in situ coherent X-ray techniques to acquire the real-time evolutions of mesoscale structures in complex materials. Our methodology offers a robust framework for investigating dynamic phenomena in diverse material systems, including metals, polymers, and functional nanomaterials, under realistic thermal or mechanical conditions.
GPT-4o mini: Non-social science research article
Kupffer cells are essential for platelet-mediated thrombopoietin generation in the liver
Danielle Karakas, June Li, Wenjing Ma, Xun Grace Wu, Christopher J. Khoury, Mina Masoud, Brock Hoard, Yuning Jay Liu, Guangheng Zhu, Junmei Chen, Martha Sim, Chuanbin Shen, José A. López, Sonya A. MacParland, Walter H. A. Kahr, Heyu Ni
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Thrombopoietin (TPO), predominantly produced by the liver, is the key regulator for platelet production and the hematopoietic stem cell niche. Our earlier report demonstrated that platelet GPIbα is required for hepatocellular TPO generation, which is the major resource of TPO in the blood circulation. However, how hepatocytes physically contact circulating sinusoidal platelets across the liver endothelium for this process is unknown. Kupffer cells reside in contact with both sinusoidal blood and underlying hepatocytes, and mediate senescent platelet clearance, but their role in TPO regulation has never been explored. Here, we found Kupffer cell depletion via either clodronate liposomes or specific transgenic models abrogated circulating TPO. Kupffer cell depletion also prevented TPO level increase in GPIbα-deficient mice following wild-type (GPIbα + ) platelet transfusion, signifying an interdependent mechanism for TPO regulation. Mice treated with arsenite had significantly decreased liver endothelial fenestrations and hepatocyte sinusoidal protrusions as well as TPO levels. This effect was exacerbated by Kupffer cell depletion, and Kupffer cells were identified to enhance liver endothelial fenestrations. Electron microscopy and immunofluorescence analysis of the liver revealed platelets arrested on Kupffer cell surface were in contact with hepatocyte protrusions. Thus, we elucidated that Kupffer cells promote endothelial fenestrae and hepatocyte protrusions, accumulate circulating platelets, and facilitate cellular interactions between hepatocytes and platelets, which drive TPO generation. This connection between platelet clearance and thrombopoiesis should have broad implications for hematology and pathologies such as Bernard–Soulier syndrome, thrombocytopenias, as well as liver diseases.
GPT-4o mini: Non-social science research article
Designers join scientists to make living architecture a reality
Carolyn Beans
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GPT-4o mini: Non-social science research article
3D pattern formation of a protein–membrane suspension
Amélie Chardac, Michael M. Norton, Jonathan Touboul, Guillaume Duclos
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Many essential cellular processes, including cell division and the establishment of cell polarity during embryogenesis, are regulated by pattern-forming proteins. These proteins often need to bind to a substrate, such as the cell membrane, onto which they interact and form two-dimensional (2D) patterns. It is unclear how the membrane’s continuity and dimensionality impact pattern formation. Here, we address this gap using the MinDE system, a prototypical example of pattern-forming membrane proteins. We show that when the lipid substrate is fragmented into submicrometer-sized diffusive liposomes, adenosine triphosphate-driven protein–protein interactions generate three-dimensional (3D) spatially extended patterns, despite the complete loss of membrane continuity. Remarkably, these 3D patterns emerge at scales four orders of magnitude larger than the individual liposomes. By systematically varying protein concentration, liposome size, and density, we observed and characterized a variety of 3D dynamical patterns not seen on continuous 2D membranes, including traveling waves, dynamical spirals, and a coexistence phase. Simulations and linear stability analysis of a coarse-grained model revealed that the physical properties of the dispersed membrane effectively rescale both the protein–membrane binding rates and diffusion, two key parameters governing pattern formation and wavelength selection. These findings highlight the robustness of Min’s pattern-forming ability, suggesting that protein–membrane suspensions could serve as an adaptable template for studying out-of-equilibrium self-organization in 3D, beyond in vivo contexts.
GPT-4o mini: Non-social science research article
An open-source photobleacher for fluorescence imaging of large pigment-rich tissues
Tatsuya C. Murakami, Nick Belenko, Griffin Dennis, Cuidong Wang, Maria Esterlita Siantoputri, Yurie Maeda, Christina Pressl, Nathaniel Heintz
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Fluorescence imaging enables visualization of the specific molecules of interest with high contrast, and the use of multiple fluorophores in a single tissue sample allows visualization of complex relationships between biological molecules, cell types, and anatomy. The utility of fluorescence imaging in human tissue has been limited by endogenous pigments that can block the light path or emit an autofluorescence, thereby interfering with the specific imaging of target molecules. Although photobleachers have been developed to quench endogenous pigments, the lack of customizability limits their utility for a broad range of applications. Here, we present a high luminous-intensity photobleacher that is based on rigorous simulations of illumination patterns, along with the framework to maximize bleaching efficiency. This open-source project is designed to help scientists customize and scale the device according to their research goals. The photobleacher is applicable to both thin tissue slices and large-volume cleared tissue samples to enable serial three-dimensional imaging of postmortem human brain using multiplexed antibody or oligonucleotide probes.
GPT-4o mini: Non-social science research article
Amplification of particle collision through contact electrification in isotropic turbulence
Danielle R. Johnson, Adam Bocanski, Emily M. Diorio, James Chen, Hui Meng
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Recent discovery of “extreme clustering” of inertial particles in isotropic turbulent flow suggests a hidden mechanism of particle–particle interaction at sub-Kolmogorov separations unexplained by hydrodynamic interaction. The near-contact radial distribution function (RDF) reaches O ( 10 4 ) , resulting in a collision kernel four orders larger than direct numerical simulation predictions. Statistical stationarity is lost in the particle-laden turbulence, suggesting the particles experience a nonequilibrium process. We hypothesize dielectric particles in isotropic turbulence experience contact electrification through interparticle collisions, creating inhomogeneous mosaic surface charge. These mosaic charges lead to attractive forces and thereby extreme clustering and collision amplification, forming a positive feedback loop. To explore this potential mechanism, we investigated hollow glass spheres dispersed in a high-Reynolds-number homogeneous isotropic air turbulence chamber using high-resolution 3D particle tracking velocimetry and Kelvin Probe Force Microscopy (KPFM). We measured RDF, particle-pair mean-inward radial relative velocity, and mean radial relative acceleration (RA) with time up to 10 min. We sampled particles from the flow chamber through time and evaluated their nanoscopic charge distribution using KPFM. We found that both RDF and mosaic surface charge increase with time; RA at close separations is attractive, intensifies as particles approach, and grows in time; and the turbulence-exposed RA curves collapse when nondimensionalized by the dipole–dipole acceleration calculated from mosaic charge distributions. These results support the proposed mechanism—Inhomogeneous Mosaic Potential Amplified Collisions in Turbulence (IMPACT). Better understanding and modeling of these effects could improve predictions for air pollution, weather patterns, and drug manufacturing—where particle interactions have big impacts.
GPT-4o mini: Non-social science research article
Sizing the largest ocean waves using the SWOT mission
Fabrice Ardhuin, Taina Postec, Mickael Accensi, Jean-François Piolle, Guillaume Dodet, Marcello Passaro, Marine De Carlo, Romain Husson, Gilles Guitton, Fabrice Collard
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Winds generate waves over the oceans with a wide range of properties. The largest wave heights and periods are important parameters in the design of marine structures. Extreme waves also play an outsize role in air–sea fluxes and coastal dynamics, and leave imprints on seismic and sediment records. Rare events have so far escaped measurements, with few wave heights from satellite altimeters exceeding 16 m, and no associated measurement of wave periods. Here, we use swells radiated from storms to reveal long wave periods within the storms, and their generation mechanism. Swells are resolved in the Surface Water and Ocean Topography (SWOT) satellite sea level measurements. Patterns of increasing swell wavelength and decreasing swell height away from storms are consistent with a nonlinear transfer of energy from short to long period waves. We propose an updated parametric shape for wave spectra in storms that aligns with SWOT swell measurements. It reduces energy levels by a factor of 20 at 1.2 to 1.4 times the peak period compared to commonly used spectral shapes and allows estimation of storm wave periods from swell heights. Consistent with less extreme conditions, the peak period generally increases with wave height. This was particularly verified for the largest storm peak period of 20.2 ± 0.6 s, obtained for the event with the largest significant wave height 19.7 ± 0.3 m measured by altimeters. These observations of long period swells should have a wide range of applications from coastal dynamics to seismology.
Circadian-informed modeling predicts regional variation in obesity and stroke outcomes under different permanent US time policies
Lara Weed, Jamie M. Zeitzer
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Seasonal changes in time policy, such as switching between Standard Time (SDT) and Daylight Saving Time (DST), have been adopted by many countries, including the United States. While transitioning between SDT and DST has notable acute negative population health impacts, the chronic impact of these time policies on health has not been well evaluated. To estimate the impact of permanent SDT or DST on health, we modeled the circadian impact of SDT, DST, and Biannual Shifting (BAS) across a year in the contiguous, continental United States. We find that BAS produces a greater burden on the circadian system as compared to either permanent SDT or DST. Chronotype as well as location (latitude and location within time zones) impact this burden. Analyzing these data relative to county-level health data (Centers for Disease Control and Prevention Places dataset), we find that, under idealized light exposure conditions and after controlling for health and socioeconomic factors, there would be a decrease in the prevalence of both obesity [ − 0.78% ( − 0.06% to − 1.49%)] and stroke [ − 0.09% ( − 0.04% to − 0.14%)] under SDT compared with the current policy. The prevalence of both obesity [ − 0.51% ( − 0.09% to − 0.93%)] and stroke [ − 0.07% ( − 0.04% to − 0.09%)] would also decrease under permanent DST, though to a lesser degree. Our data, reflecting the impact of time policy on circadian burden and subsequent health benefits, support the cessation of BAS.
Urban water security and the historical pools of Jerusalem
Guy Bar-Oz, Gideon Avni
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Intention judgments are not a reliable measure of intuitive preferences
Tadeg Quillien
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Did the vilca/tobacco snuff combination at Chavín aim for an “ayahuasca effect”?
Peter Whitridge
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The coherence of US cities
Simone Daniotti, Matté Hartog, Frank Neffke
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Diversified economies are critical for cities to sustain their growth and development, but they are also costly because diversification often requires expanding a city’s capability base. We analyze how cities manage this trade-off by measuring the coherence of the economic activities they support, defined as the technological distance between randomly sampled productive units in a city. We use this framework to study how the US urban system developed over almost two centuries, from 1850 to today. To do so, we rely on historical census data, covering over 600M individual records to describe the economic activities of cities between 1850 and 1940, as well as 8 million patent records and detailed occupational and industrial profiles of cities for more recent decades. Despite massive shifts in the economic geography of the United States over this 170-y period, average coherence in its urban system remains unchanged. Moreover, across different time periods, datasets, and relatedness measures, coherence falls with city size at the exact same rate, pointing to constraints to diversification that are governed by a city’s size in universal ways.
The cost of banning TikTok: Implications for the digital advertising market
Dante Donati, Hortense Fong
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Social media platforms have become vital channels for businesses to reach consumers through advertising. But in the United States, the digital advertising market in which these platforms operate is dominated by a few major players, raising concerns for antitrust regulators. In such a concentrated market, the entry or exit of a single platform can reallocate billions in ad spending, affecting businesses and users. TikTok’s temporary suspension in the United States in January 2025 provides a unique natural experiment to examine how the removal of a major player would shift advertising demand and supply on competitors, specifically Facebook and Instagram, revealing the degree of substitutability across platforms and the intensity of competition. Using a difference-in-differences approach comparing advertising activity in the United States to other countries, we find that Meta ad volume and spend rose by 6.3% and 22.4%, as a result of the outage, without a corresponding increase in ad impressions. Consequently, Meta ad prices, as measured by cost per thousand impressions, jumped by 12.1%. Shifts in demand were three times greater for larger advertisers relative to smaller ones, suggesting that Meta platforms and TikTok are closer substitutes for larger firms and that a TikTok ban would therefore impose greater challenges on smaller businesses.
Life without sex: Large-scale study links sexlessness to physical, cognitive, and personality traits, socioecological factors, and DNA
Abdel Abdellaoui, Laura W. Wesseldijk, Scott D. Gordon, JoĂ«lle A. Pasman, Dirk J. A. Smit, RenĂĄta AndrovičovĂĄ, Nicholas G. Martin, Fredrik UllĂ©n, Miriam A. Mosing, Brendan P. Zietsch, Karin J. H. Verweij
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Romantic (typically sexual) relationships are important to personal, physical, mental, social, and economic well-being, and to human evolution. Yet little is known about factors contributing to long-term lack of intimate relationships. We investigated phenotypic and genetic correlates of never having had sex in ~400,000 UK residents aged 39 to 73 and ~13,500 Australian residents aged 18 to 89. The strongest associations revealed that sexless individuals were more educated, less likely to use alcohol and smoke, more nervous, lonelier, and unhappier. Sexlessness was more strongly associated with physical characteristics (e.g., upper body strength) in men than in women. Sexless men tended to live in regions with fewer women, and sexlessness was more prevalent in regions with more income inequality. Common genetic variants explained 17% (SE = 4%) and 14% (SE = 3%) of variation in sexlessness in men and women, with a genetic correlation between sexes of 0.56 (SE = 0.17). Polygenic scores predicted a range of related outcomes in the Australian dataset. Our findings uncover multifaceted correlates of human intimacy and raise important lines of enquiry in the evolutionary and social sciences.

Science

GPT-4o mini: Non-social science research article
Cumulative impacts to global marine ecosystems projected to more than double by mid-century
Benjamin S. Halpern, Melanie Frazier, Casey C. O’Hara, O. Alejandra Vargas-Fonseca, Amanda T. Lombard
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Pressures from human activities are expected to increase substantially, affecting marine ecosystems globally. To plan for a sustainable future, we need to forecast the distributions of cumulative effects from multiple pressures. Here, we mapped (at 10-kilometer resolution) the future cumulative impacts of 10 climate, land-based, fishing, and other pressures on 20 marine habitats under two climate scenarios at mid-century (around 2050). We found that cumulative impacts are projected to increase 2.2 to 2.6 times globally, with coastal habitats facing higher impacts but offshore regions facing faster increases, especially in equatorial regions. Furthermore, many countries dependent on marine resources will have large increases in impacts. Incorporating these results into strategic policy and management will support more sustainable use and protection of marine ecosystems and the services they provide.

Science Advances

GPT-4o mini: Non-social science research article
A universal oxygen scavenger for oxidase-based biosensors
Huijie Zhang, Mohamed G. Saadeldin, Darren Buesen, Hamzah Elfaitory, Jakob Burger, Vincent M. Friebe, Jonas Honacker, Tobias Vöpel, Alaa A. Oughli, Nicolas Plumeré
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Oxidase-based electrochemical biosensors are widely deployed for point-of-use applications, yet oxygen interference remains a major challenge, substantially reducing sensing accuracy. Here, we developed a universal enzymatic O 2 scavenger composed of alcohol oxidase, catalase, and paraformaldehyde to eliminate O 2 within the sensor by converting it to water. Unlike other oxidases, alcohol oxidase exclusively uses O 2 as an electron acceptor, preventing interference with the electron transfer chain involving the sensing oxidase. We demonstrated the compatibility of this O 2 scavenger for calibration-free sensing of glucose, lactate, and creatinine in the concentration range relevant to human health. Without the O 2 scavenger, sensor readings were less than 50% of those under inert gas conditions. With the O 2 scavenger, the accuracy improved to 99%, even at low substrate concentrations. The general compatibility and performances of this alcohol oxidase-based O 2 scavenger unlock the full potential of oxidase-based biosensors for reliable point-of-use sensing.
GPT-4o mini: Non-social science research article
Repeated climate-driven dispersal and speciation in peripheral populations of Pleistocene mastodons
Emil Karpinski, Sina Baleka, Andrew R. Boehm, Tim Fedak, Chris Widga, Hendrik N. Poinar
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Ancient DNA has been useful in reconciling deep evolutionary relationships and responses to ecological changes in proboscideans. Here, we report the sequencing of a mitochondrial genome from a morphologically distinct Pacific mastodon, as well as from six eastern American mastodons with ages that range through the Middle and Late Pleistocene. We show that Pacific mastodons fall within a deeply divergent mitochondrial clade, extending the range of this species into western Canada and potentially Mexico. We also present evidence for at least three discrete expansion events into northeastern coastal regions and identify two new mastodon clades, which contain temporally distinct but geographically colocalized specimens. We integrate these findings with those of previous work into a comprehensive model of Mammut phylogeography.
GPT-4o mini: Non-social science research article
Transcriptomic diversity of amygdalar subdivisions across humans and nonhuman primates
Michael S. Totty, Rita Cervera Juanes, Svitlana V. Bach, Lamya Ben Ameur, Madeline R. Valentine, Evan Simons, McKenna D. Romac, Hoa Trinh, Krystal Henderson, Ishbel Del Rosario, Madhavi Tippani, Ryan A. Miller, Joel E. Kleinman, Stephanie Cerceo Page, Arpiar Saunders, Thomas M. Hyde, Keri Martinowich, Stephanie C. Hicks, Vincent D. Costa
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The amygdaloid complex mediates learning, memory, and emotions. Understanding cellular and anatomical features specialized in the primate amygdala versus other mammals requires a systematic, anatomically resolved molecular analysis of neuron types. We analyzed five nuclear subdivisions of the primate amygdala with single-nucleus RNA sequencing in macaques, baboons, and humans to examine gene expression profiles for excitatory and inhibitory neurons. Integrated analyses across species identified diverse subtypes of glutamatergic and GABAergic neurons that are highly conserved across primates. Compositional analyses revealed that subdivisions of the primate basolateral complex contain distinct classes of glutamatergic neurons and divergent gene expression profiles for parvalbumin and somatostatin GABAergic neurons. Referencing primate neuron types to transcriptomic atlases of the murine amygdala highlighted primate-specific specializations for glutamatergic neurons and identified which neuron types are conserved across mammals and amygdalar subdivisions. Understanding the molecular heterogeneity of anatomically resolved amygdalar neuron types provides a cellular framework for improving models of how amygdalar circuits contribute to cognition and mental health.
GPT-4o mini: Non-social science research article
Unprecedented accuracy in molecular line-intensity ratios from frequency-based measurements
Jin-Ke Li, Jin Wang, Rui-Heng Yin, Qi Huang, Yan Tan, Chang-Le Hu, Yu R. Sun, Oleg L. Polyansky, Nikolai F. Zobov, Evgenii I. Lebedev, Rainer Stosch, Jonathan Tennyson, Gang Li, Shui-Ming Hu
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Accurate determination of molecular transition intensities is vital to quantum chemistry and metrology, yet even simple diatomic molecules have historically been limited to 0.1% accuracy. Here, we show that frequency-domain measurements of relative intensity ratios outperform absolute methods, achieving 0.003% accuracy using dual-wavelength cavity mode dispersion spectroscopy. Enabled by high-precision frequency metrology, this approach reveals systematic discrepancies with state-of-the-art ab initio calculations, exposing subtle electron correlation effects in the dipole moment curve. Applied to line-intensity ratio thermometry (LRT), our technique determines gas temperatures with 0.5 millikelvin statistical uncertainty, exceeding previous LRT precision by two orders of magnitude. These results redefine the limits of optical gas metrology and enable International System of Units–traceable measurements for applications from combustion diagnostics to isotopic analysis. Discrepancies of up to 0.02% in transition probability ratios challenge theorists to refine models, establishing intensity ratios as a paradigm in precision molecular physics.
GPT-4o mini: Non-social science research article
Nanozyme eye drops for retinal barrier penetration and vasculopathy repair
Bai Xue, Shuyu Wang, Tingting Wu, Lulu Wang, Xuejiao J. Gao, Mengyuan Cao, Ming Tang, Yuxin Wan, Xiyun Yan, Wei Jiang, Bing Jiang
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Retinal neovascularization diseases cause vision impairment due to abnormal blood vessel growth in the retina. Current treatments, including repeated intraocular anti–vascular endothelial growth factor injections, are invasive and often lead to discomfort and complicated hemorrhages. Here, we developed a noninvasive nanozyme eye drop capable of penetrating the fundus to eliminate reactive oxygen species (ROS) and thereby inhibit neovascularization. The nanozyme eye drops consist of liposomes formed by fluorinated and arginine–glycine–aspartic acid–modified phospholipids, which enhance the penetration of ocular barriers. The encapsulated superoxide dismutase–catalase cascade nanozyme within these liposomes allows for efficient ROS scavenging. In vitro and in vivo studies demonstrate that these nanozyme eye drops achieve deep retinal tissue penetration, alleviate oxidative stress, restore mitochondrial function, and suppress aberrant insulin-like growth factor binding protein 6 signaling, thereby inhibiting pathological neovascularization. Enhanced ocular bioavailability and minimal toxicity further underscore its promise as a safe and effective noninvasive treatment for retinal neovascularization diseases.
GPT-4o mini: Non-social science research article
RNA binding protein DDX3X drives pancreatic cancer progression via the TLE2-MYL9 axis
Yuanyang Wang, Qianyi Yang, Feng Lin, Xiaowei Song, Gang Yang, Dahan Wen, Yingyun Yang, Bicheng Wu, Yunmeng Meng, Ning Zhang, Xiaomei Lu, Chunyang Xiong, Wen Zhao, Junbo Liang, Taiping Zhang, Yuying Liu
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Current treatments for pancreatic ductal adenocarcinoma (PDAC) fall short of meeting clinical needs, highlighting the urgent need for a comprehensive understanding of PDAC progression, which involves not only biochemical signals but also essential biomechanical cues. Here, we used a CRISPR-Cas9 screen in an orthotopic xenograft model to explore PDAC dynamics. The RNA binding protein DEAD-box helicase 3X-linked (DDX3X) was identified as a pivotal oncogene and biomechanical checkpoint. Specifically, DDX3X up-regulation in PDAC promoted tumorigenesis and metastasis, primarily through the transcriptional repressor TLE family member 2 (TLE2). Dysregulation of DDX3X in the tumor destabilized TLE2 messenger RNA and therefore disrupted the interaction with KLF4 (KLF transcription factor 4), leading to increased expression of myosin light chain 9 (MYL9). This change remodeled F-actin, enhancing tumor cell traction forces and consequently facilitating tumor metastasis. Targeting the DDX3X-TLE2-MYL9 pathway considerably reduces PDAC progression. This research reveals a promising approach for treating PDAC by focusing on biomechanical cues.
GPT-4o mini: Non-social science research article
Endoplasmic reticulum junctions serve as a platform for endosome-lysosome interactions through their stop-and-go motion switching
Wenjing Li, Yuanhao Guo, Qi Wang, Mengxuan Qiu, Yudong Zhang, Yutong Yang, Junjie Hu, Ge Yang
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Endosomes and lysosomes (collectively termed “endolysosomes”) traverse the cytoplasm in a stop-and-go manner, but the mechanisms underlying this motion remain poorly understood. Using deep learning–based image analyses, including particle tracking, spatial distribution, and endoplasmic reticulum (ER) morphology analysis, we found that ER junctions facilitate stop-and-go motion switching and serve as platforms for endolysosome interactions. Within the ER network, endolysosomes exhibit three dynamic states: fast movement, local slow movement, and pausing. Pauses occur mainly at ER junctions, where transient endosome-lysosome interactions often coincide with organelle fission and are followed by departure. Disruption of ER junctions impairs lysosomal motility and maturation. We further show that actin condensation around endolysosomes mediates motion switching, involving VAP-STARD3 interaction and the actin regulator YWHAH. Other organelles, such as lipid droplets and peroxisomes, also pause near ER junctions. These findings highlight ER junctions as regulatory hubs that orchestrate organelle dynamics, contributing to the spatial coordination of organelle distribution and interactions within the cytoplasm.
GPT-4o mini: Non-social science research article
A misaligned protostellar disk fed by gas streamers in a barred spiral-like massive dense core
Xiaofeng Mai, Tie Liu, Xunchuan Liu, Bo Zhang, Paul F. Goldsmith, Neal J. Evans, Qizhou Zhang, Kee-Tae Kim, Dongting Yang, Mika Juvela, Fengwei Xu, Wenyu Jiao, Hongli Liu, Patricio Sanhueza, Guido Garay, Xi Chen, Shengli Qin, Jakobus M. Vorster, Anandmayee Tej, Zhiyuan Ren, Sami Dib, Shanghuo Li, Qiuyi Luo, Jihye Hwang, Prasanta Gorai, Ariful Hoque, Yichen Zhang, Jeong-Eun Lee, Siju Zhang, Emma Mannfors, Devika Tharakkal, Lokesh Dewangan, Leonardo Bronfman, Pablo García, Xindi Tang, Swagat R. Das, Gang Wu, Chang-Won Lee, James O. Chibueze, Yankun Zhang, Qilao Gu, Ken’ichi Tatematsu, Guangli Wang, Lei Zhu, Zhiqiang Shen
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High-mass stars, born in massive dense cores (MDCs), profoundly affect the cosmic ecosystem through feedback processes and metal enrichment, yet little is known about how MDCs assemble and transfer mass across scales to form high-mass young stellar objects (HMYSOs). Using multiscale [40 to 2500 astronomical units (au)] observations of an MDC hosting an HMYSO, we identify a coherent dynamical structure analogous to barred spiral galaxies: three ~20,000 au spiral arms feed a ~7500 au central bar, which channels gas to a ~2000 au pseudodisk. Further accretion proceeds through the inner structures, including a Keplerian disk and an inner disk (~100 au), which are thought to be driving a collimated bipolar outflow. These multiscale structures (spiral arms, bar, streamers, envelope, disk, and outflow) have been simultaneously observed as a physically coherent structure within an MDC. Our discovery suggests that well-organized hierarchical structures play a crucial role during the gas accretion and angular momentum buildup of a massive disk.
GPT-4o mini: Non-social science research article
A switchable dynamic-static tactile system for augmented haptic secret communication
Huiqi Zhao, Weiqi Qian, Chong Guo, Yaming Zhang, Jiabin Wang, Huiyu Dan, Yan Zhang, Chris R. Bowen, Ya Yang
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Tactility bridges humans and the external world. Although human skin’s tactile receptors provide comprehensive perception, developing a biomimetic tactile system with both dynamic and static functions and rapid conversion remains a challenge. Here, we report a switchable dynamic-static tactile system. It features a rapid 1-millisecond transition between dynamic and static modes via light modulation, an all-in-one structure for simplicity and practicality, a remarkable balance of high sensitivity (198.45 per kilopascal) and wide pressure range (0.0137 to 207 kilopascals), a tunable sensitivity, and a sensing-feedback closed loop. The dynamic mode responds to vibrations, and the static mode responds to static pressure and superposition. In various real-world potential scenarios such as object detection and perception under vibration interference and human-computer interaction, it shows excellent performance. A closed-loop system with feedback and deep learning achieves user-encrypted Morse code haptic secret communication, paving the way for advancements in intelligence and virtual/augmented reality.
GPT-4o mini: Non-social science research article
Observation of Van Hove singularity interband plasmons in the kagome metal CsV 3 Sb 5 for strong light-matter interactions
Xiangkai Meng, Chong Wang, Maoyuan Wang, Jinjin Liu, Pai Zhou, Qiaoxia Xing, Yuqing Zheng, Haochen Zhang, Wenqi Bi, Hanchao Teng, Jianhui Zhou, Jun Li, Zhiwei Wang, Hai Hu, Qing Dai, Hugen Yan, Yugui Yao
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Van Hove singularities (VHSs) play a critical role in determining the properties of topological and correlated electronic states. Their associated excitations offer unique opportunities for exploring light-matter interactions reshaped by these correlated states, although experimental observations remain limited. Here, we studied the interaction between plasmons and VHS-related excitations in kagome metal CsV 3 Sb 5 films via far-field absorption spectroscopy. Notably, an anticrossing phenomenon was observed in the charge density wave states, with coupling strength approaching the strong coupling regime, indicating the formation of dispersive hybrid VHS interband plasmons. These modes are closely correlated to charge ordering states, with both the fitted coupling strength and the universal screening length of interband transitions exhibiting pronounced anomalies at the transition temperature. Our findings offer critical insights into the role of correlated electronic states in modulating plasmon behavior in kagome metals and unveil promising possibilities for tuning light-matter interactions in correlated materials.
GPT-4o mini: Non-social science research article
Entangled measurement for W states
Geobae Park, Holger F. Hofmann, Ryo Okamoto, Shigeki Takeuchi
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Entangled measurements are an indispensable tool for quantum information processing, such as Bell-state measurements in quantum teleportation and entanglement swapping. However, to date, the realization of entangled measurements has mainly focused on bipartite systems or Greenberger-Horne-Zeilinger (GHZ) states. Here, we demonstrate a practical scheme to realize entangled measurements for W states. Thanks to the cyclic shift symmetry in the discrete Fourier transformation (DFT) of bosonic modes, the DFT measurement outcomes can be used to deterministically project multiqubit states onto W states. Experimentally, we show that three-qubit W state discrimination can be achieved by detecting the cyclic shift symmetry with a three-mode DFT optical circuit, yielding a measurement discrimination fidelity of 0.871 ± 0.039. Our experimental demonstration opens the door for the development of new quantum network protocols between multipartite systems.
GPT-4o mini: Non-social science research article
The citrullinating enzyme PADI4 governs progenitor cell proliferation and translation in developing hair follicles
Kim Vikhe Patil, Nil CampamĂ  Sanz, Kylie Hin-Man Mak, Wei Yang, Karl Annusver, Jasson Makkar, David Grommisch, Li Lei, Priyanka Sharma, Ryan R. Driskell, Maria Kasper, Maria Genander
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Posttranslational protein modifications have emerged as a mechanism regulating progenitor cell state transitions during tissue formation. Herein, we exploit the stereotyped hair follicle development to delineate the function of PADI4, an enzyme converting peptidylarginine to citrulline. Single-cell sequencing places Padi4 in both progenitor and differentiated hair lineage cells and indicates that PADI4 acts to repress transcription during hair follicle development. We establish PADI4 as a negative regulator of proliferation, acting on LEF1-positive hair shaft committed progenitor cells. Mechanistically, PADI4 citrullinates proteins associated with mRNA processing and ribosomal biogenesis, and lack of PADI4 promotes protein synthesis and ribosomal RNA transcription in vivo. Characterizing key translational effectors, we demonstrate that PADI4 citrullinates the translational repressor 4E-BP1 and reveal a cross-talk between PADI4 activity and 4E-BP1 phosphorylation. This work sheds light on how posttranslational modifications affect progenitor cell states and tissue formation.
GPT-4o mini: Non-social science research article
A flexible spiking hair sensillum for ultralow power density noncontact perception
Haotian Long, Zhenhua Wan, Mengjiao Pei, Kailu Shi, Lesheng Qiao, Yi Shi, Qing Wan, Changjin Wan
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The ability to recognize targets before physical contact is crucial for organisms’ adaptability to real-world environments. However, current noncontact sensing systems face challenges in power density and biological fidelity. Here, we report a flexible spiking hair sensillum (FISH) with an ultralow power density < 100 nanowatts per square millimeter for achieving noncontact tactile perception (NCTP). This device can transduce proximity or airflow into spike trains with a frequency range of ~500 to 1500 hertz. A spiking NCTP system is developed, achieving high accuracy (>92%) in multidimensional recognition of noncontact targets, mediated by airflow. Furthermore, we show that a spider robot equipped with a FISH matrix outperforms one relying exclusively on machine vision in tasks of predation and evasion, demonstrating high adaptability to complex environments. Our design enriches the perceptual modalities for neuromorphic systems, offering great potential for advancing future robotics and autonomous vehicles.
GPT-4o mini: Non-social science research article
Bi-handed assembly chaperones regulate protein complex assembly through an intramolecular handover mechanism
Jingyi Wu, Chun Wan, Yuan Tian, Yan Ouyang, Harrison Puscher, Suzhao Li, Qian Yin, Jingshi Shen
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A critical yet challenging step in protein complex assembly is the formation of a dimeric intermediate that serves as a seed for incorporating additional subunits. We hypothesized that this step could be facilitated by “bi-handed” chaperones that recognize two different subunits through distinct domains (hands). However, whether such chaperones exist remained unknown. Here, we identify AAGAB as a bona fide bi-handed chaperone. AAGAB uses its C-terminal domain (CTD) to bind the α subunit and its GTPase-like domain (GD) to bind the σ2 subunit of the AP2 adaptor complex, a central player in membrane trafficking. AAGAB first recruits α via its CTD; σ2 then joins through interaction with α, forming a conformationally immature α:σ2 hemicomplex at the CTD. This hemicomplex is subsequently transferred to the GD via a GD:σ2 binding interface, accompanied by conformational maturation. These findings establish AAGAB as the founding member of a bi-handed chaperone family and reveal an intramolecular handover mechanism that underlies their mode of action.
GPT-4o mini: Non-social science research article
Ultrafast and scalable synthesis of enzyme-metal hybrid catalysts in evaporating microdroplets
Yida Qiao, Ruobing Xin, Xiaoyang Li, Jun Ge
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One-pot chemoenzymatic cascade reactions integrate the advantages of enzymatic catalysis and chemical catalysis, offering routes to synthesize enantiopure compounds in an efficient and environmentally friendly manner. The rational design of enzyme-metal hybrid catalysts (EMHCs) is an attractive strategy for operating chemoenzymatic cascade reactions efficiently under mild conditions. In this study, we develop a method for the instantaneous and continuous synthesis of EMHCs in evaporating microdroplets. Compared to traditional wet impregnation methods, the reaction time of the microdroplet-assisted method is shortened from days to seconds, achieving a space-time yield increase by two to five orders of magnitude. The as-prepared Pd/lipase cross-linked enzyme aggregates with ultrasmall Pd nanoclusters and well-preserved structure of enzymes exhibit excellent activity in the dynamic kinetic resolution of chiral amines. The mechanism for the process enhancement in the synthesis of EMHCs in evaporating microdroplets is studied by theoretical calculations, indicating that the fast solvent evaporation and high-heat transfer are the major factors for the instantaneous synthesis of EMHCs.
GPT-4o mini: Non-social science research article
Gangliosides modulate the secretion of extracellular vesicles and their misfolded protein cargo
John Monyror, Vaibhavi Kadam, Luis Carlos Morales, Diego Ordóñez, Jeremies Ibanga, Asifa K. Zaidi, Emily McNamara, Desmond Pink, Magnus Stenlund, Ken Reyes, Aislinn D. Maguire, Jing Huang, Leonardo M. Cortez, Valerie L. Sim, Sue-Ann Mok, Elena Posse de Chaves, Simonetta Sipione
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Gangliosides are glycosphingolipids with important roles in cell signaling and neuroprotection. While present on extracellular vesicles (EVs)—key mediators of intercellular communication—their role in EV biogenesis remains unclear. Here, we identify gangliosides as key modulators of EV biogenesis, with the specific composition of their glycan headgroup and the presence or absence of sialic acid and N -acetyl- d -galactosamine residues dictating whether they promote or inhibit EV biogenesis. GM1 and other complex gangliosides enhance EV secretion, while disruption of ganglioside synthesis impairs it. GM1 supplementation restores EV secretion in Huntington’s disease (HD) fibroblasts and cell models with ganglioside deficiency, including models of neurodegenerative diseases caused by a genetic block of ganglioside synthesis. Notably, GM1 enhances EV-mediated secretion of pathogenic misfolded proteins, including mutant huntingtin (mHTT), α-synuclein, and tau, reducing intracellular burden and providing mechanistic insight into the mHTT-lowering effects of GM1 in HD models. Our findings shed light on the neuroprotective roles of gangliosides and their therapeutic potential in misfolded protein disorders.
GPT-4o mini: Non-social science research article
Increased global subseasonal whiplash by future BSISO behavior
Tat Fan Cheng, Bin Wang, Fei Liu, Guosen Chen, Mengqian Lu
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Propagation patterns of 30- to 90-day boreal summer intraseasonal oscillation (BSISO) markedly affect subseasonal prediction. We show that global warming significantly alters BSISO propagation by Coupled Model Intercomparison Project Phase 6 projections. Under the Shared Socioeconomic Pathway 5-8.5 scenario, the eastward mode’s expansion propagation speed shows a twofold increase from 5.1 ± 1.9 to 10.3 ± 2.0 meters per second by the late 21st century, with a remarkable eastward extension by ~30° longitude compared to the present climate. The accelerated eastward mode frequency is expected to rise by 15%, intensifying subseasonal precipitation whiplash worldwide and shortening disaster preparedness time. This acceleration results from an asymmetric pattern of boundary layer moisture convergence anomalies, driven by weakened Rossby wave westerlies and enhanced Kelvin wave response linked to warming-induced atmospheric stabilization and El Niño–like ocean surface warming pattern. Conversely, a projected weakening of easterly vertical shear over the northern Indian Ocean attenuates the Rossby wave response and favors more eastward expansion events.
GPT-4o mini: Non-social science research article
Molecular and neural basis of vomiting behavior in Drosophila melanogaster
Yanyan Shi, Yinjun Jia, Wei Zhang
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Vomiting is a common yet poorly understood symptom, largely due to the lack of conventional animal models. This study establishes a Drosophila model for vomiting triggered by berberine ingestion. Our findings reveal that this response is mediated by the chemoreceptor TrpA1, which is indirectly activated by berberine via the mAChRs-PLC pathway. Berberine induces acetylcholine release from foregut epithelial cells, which triggers tachykinin secretion from intestinal tracheal cells. Tachykinins contract the visceral muscles, particularly the P4 pump of the foregut, and suppress myosuppressin release from pars intercerebralis neurons, thereby promoting crop motility. We further demonstrate the conservation of key genes involved in mammalian vomiting regulation. Overall, this study provides a molecular and cellular framework for understanding vomiting and introduces Drosophila as a genetic model for mechanistic studies.
GPT-4o mini: Non-social science research article
Label-free and real-time monitoring of photoaging with high spatiotemporal resolution using an nIR fluorescent nanosensor array
Youngwook Cho, Hwira Baek, Damee Koh, Changyu Tian, Minah Choi, Jung Woo, Junoh Kim, Seungchan Baek, Jin Woong Kim, Soo-Yeon Cho
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Reactive oxygen species (ROS) bursts from photoaging cause skin damage and chronic conditions. Understanding spatiotemporal ROS dynamics is critical for developing therapies and cosmetic strategies to enhance skin health. Conventional assays and fluorescence microscopy lack the resolution for real-time ROS quantification due to photobleaching and labeling issues. Here, we developed a label-free, real-time monitoring platform with high spatiotemporal resolution using a near-infrared (nIR) fluorescent single-walled carbon nanotube (SWNT) nanosensor array to quantify ROS bursts from daily photoaging. The SWNT array, dual-functionalized with DNA and poly- l -lysine, achieved selective H 2 O 2 recognition and skin cell compatibility. The skin cell–friendly nanosensor interface (SNI) enabled attomole-level detection of H 2 O 2 bursts in a two-dimensional keratinocyte model under natural ultraviolet exposure, revealing photoadaptation behavior. Distinct oxidative stress wave profiles were identified via nIR data and numerical modeling. Using SNI, we introduced the anti-ROS score to evaluate skin care antioxidants, providing insights into photoaging pathways and cosmetic advancements.
GPT-4o mini: Non-social science research article
Ultrafast reversible photoconductivity in 2D MoTe 2 /Pt van der Waals heterostructure
Ye Tao, Chengyun Hong, Ji-Hee Kim
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Two-dimensional (2D) materials, particularly transition metal dichalcogenides, have exceptional optoelectronic properties, making them highly promising for next-generation photonic integrated circuits. Despite great advancements in 2D optoelectronic devices, achieving ultrafast and controllable photoconductivity polarity inversion with a single device remains a fundamental challenge due to the static nature of built-in electric fields at metal/2D material interfaces. This study demonstrates a transient electric field reversal at the MoTe 2 /Pt Schottky junction, enabling photoconductivity inversion from negative to positive within 100 ps. By applying ultrafast photocurrent detection, a minimal voltage variation (10 mV) precisely controls this transition, and a device with a remarkable photocurrent response time of 3.8 ps is proposed. This work advances the design of ultrafast, tunable photodetectors, offering potential applications in high-speed optical communication, ultrafast imaging, and quantum information processing.
GPT-4o mini: Non-social science research article
Bispecific antibodies cross-link and redirect CD8 + T cells to kill cytomegalovirus-infected cells
Ayub Ali, Arumugam Balamurugan, Francisco J. Ibarrondo, Minh Nguyen, Sara Habibipour, Jaimie M. Lim, Christian Hofmann, Hwee L. Ng, Otto O. Yang
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Adoptive transfer studies of ex vivo–expanded autologous cytomegalovirus (CMV)–specific CD8 + T lymphocytes (CTLs) in immunocompromised hosts demonstrate a central role for viral control, but this therapeutic approach is not generally feasible. We present T cell–redirecting bispecific antibodies (TRBAs) that cross-link CD3Δ on CTLs to gH protein on CMV-infected cells, including versions where a single-chain antibody is appended to the carboxyl terminus of the heavy chain of a regular antibody, or where both light and heavy chains have two tandem variable regions in a crossover ordered design. Both versions bind both antigens and mediate the specific clearance of infected cells with the release of interferon-Îł when added to CTLs with CMV-infected cells. TRBA-mediated clearance is visualized with physical clustering of CTLs with CMV-infected cells. These results illustrate the mechanism and utility of these TRBAs as potential therapeutic candidates for disseminated CMV infection, with potential advantages compared to two prior CMV-specific TRBAs.
GPT-4o mini: Non-social science research article
Dynamically assembled magnetic nanoparticles in a phase transitional matrix for reconfigurable electronics
Min-Gyu Lee, Seong-Yu Choi, HyunJae Yoo, Jae-Man Park, Younghoon Lee, Yun Hyeok Lee, Yong Eun Cho, Sungsoo Lim, Hakjun Lee, Jeong-Yun Sun
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The structure of an electronic device is predetermined at its birth, necessitating new designs and fabrication processes for alternative functions. The advent of reconfigurable electronics, modifying its circuits after manufacture, has unlocked the potential for devices to perform adaptive roles as needed. However, the trade-off between the degree of freedom to reform its structure and electrical stability restricts its potential roles, diminishing the system’s significance. Here, we present a reconfigurable assembly of magnetic nanoparticles in a phase transitional matrix (RAMP) system capable of seamlessly transforming their structure with robust electrical junctions. Nanoparticles form conductive percolation under a precisely patterned magnetic field. Within a phase transitional matrix, junctions between nanoparticles are tightened, enhancing electrical performance during transitions. We demonstrated in situ electrical switching and high-resolution alternating current electroluminescence display using the RAMP system. With enhanced reconfigurability and electrical reliability, we anticipate that the RAMP system will suggest a previously unexplored approach to on-demand electronics.
GPT-4o mini: Non-social science research article
How musicality enhances top-down and bottom-up selective attention: Insights from precise separation of simultaneous neural responses
Cassia Low Manting, Dimitrios Pantazis, John Gabrieli, Daniel Lundqvist
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Natural environments typically contain a blend of simultaneous sounds. A substantial challenge in neuroscience is identifying specific neural signals corresponding to each sound and analyzing them separately. Combining frequency tagging and machine learning, we achieved high-precision separation of neural responses to mixed melodies, classifying them by selective attention toward specific melodies. Across two magnetoencephalography datasets, individual musicality and task performance heavily influenced the attentional recruitment of cortical regions, correlating positively with top-down attention in the left parietal cortex but negatively with bottom-up attention in the right. In prefrontal areas, neural responses indicating higher sustained selective attention reflected better performance and musicality. These results suggest that musical training enhances neural mechanisms in the frontoparietal regions, boosting performance via improving top-down attention, reducing bottom-up distractions, and maintaining selective attention over time. This work establishes the effectiveness of combining frequency tagging with machine learning to capture cognitive and behavioral effects with stimulus precision, applicable to other studies involving simultaneous stimuli.
GPT-4o mini: Non-social science research article
Climate-carbon feedback tradeoff between Arctic and alpine permafrost under warming
Tao Bao, Xiyan Xu, Gensuo Jia, Xingru Zhu, William J. Riley, Yuanhe Yang
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Whether greenhouse gas (GHG) emissions from permafrost will trigger positive climate feedbacks under warming remains unknown. Here, we synthesized the response of growing season carbon dioxide (CO 2 ), methane (CH 4 ), and nitrous oxide (N 2 O) emissions to experimentally manipulated warming of ~2°C for permafrost in alpine and Arctic regions. Warming weakened the GHG sink of alpine permafrost, thereby increasing (13%) its global warming potential, but strengthened the GHG sink of Arctic permafrost and decreased (−10%) its global warming potential. When warming caused drying of alpine permafrost soils, the CO 2 sink weakened but the CH 4 sink increased. In contrast, warming of relatively wet Arctic permafrost increased the CO 2 sink and CH 4 source. Warming led to much stronger increases of the N 2 O source in alpine than Arctic permafrost. Although keeping additional warming below 2°C in permafrost regions can avoid the positive permafrost-climate feedback, measures are needed to maintain fragile carbon sink of alpine permafrost ecosystems.
GPT-4o mini: Non-social science research article
On-chip multi-timescale spatiotemporal optical synchronization
Lida Xu, Mahmoud Jalali Mehrabad, Christopher J. Flower, Gregory Moille, Alessandro Restelli, Daniel G. Suarez-Forero, Yanne Chembo, Sunil Mittal, Kartik Srinivasan, Mohammad Hafezi
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Mode locking is foundational to nonlinear optics, enabling advances in metrology, spectroscopy, and communications. However, it remains unexplored in nonharmonic, multi-timescale regimes. Here, we realize on-chip multi-timescale synchronization using topological photonics. We design a two-dimensional lattice of 261 coupled silicon nitride ring resonators that supports nested mode-locked states with fast ( ≈ 1 terahertz) single-ring and slow ( ≈ 3 gigahertz) topological super-ring timescales. We observe clear signatures of multi-timescale mode locking, including a quadratic distribution of pump noise across both azimuthal mode families, consistent with theory. These findings are supported by near-transform–limited repetition beats and the emergence of periodic temporal patterns on the slow timescale. The edge-confined states show distinct dynamics from bulk and single-ring modes, enabling clear identification. Our results establish topological frequency combs as a robust platform for independently tunable, lattice-scale synchronization, opening new directions for exploring the interplay of nonlinearity and topology in integrated photonics.
GPT-4o mini: Non-social science research article
Neofunctionalized RGF pathways drive haustorial organogenesis in parasitic plants
Maxwell R. Fishman, Anne Greifenhagen, Takanori Wakatake, Anuphon Laohavisit, Ryoko Hiroyama, Sachiko Masuda, Arisa Shibata, Satoko Yoshida, Ken Shirasu
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Parasitic plants will initiate rapid de novo organogenesis of a specialized feeding structure called a haustorium upon contact with their hosts. Currently, little is known about the internal signals regulating haustorium development. Here, we identify root meristem growth factor (RGF) peptides in Phtheirospermum japonicum as endogenous inducers of prehaustorium formation. Treatment with specific RGF peptides in the absence of hosts triggered prehaustoria and induced expression of PjYUC3 , a gene required for auxin biosynthesis and prehaustorium formation. CRISPR-mediated knockouts showed that PjRGFR1 and PjRGFR3, receptors activated by the haustorium-specific RGF peptides PjRGF2 and PjRGF5, are essential for prehaustorium formation, revealing functional redundancy. Phylogenetic analyses indicate that PjRGF2 is broadly conserved among Orobanchaceae, whereas PjRGF5 appears to have recently evolved through segmental tandem multiplication. Our findings establish RGF peptides and their corresponding receptors as critical components of haustorium developmental signaling and provide insights into the evolutionary trajectories that shape plant parasitism.
GPT-4o mini: Non-social science research article
Selective ion transport of nonlinear resistive switching by hierarchical nanometer-to-angstrom channels for nanofluidic transistors
Xiaoyi Hu, Hengyu Xu, Jun Lu, Fenglu Cui, Heng-An Wu, Fengchao Wang, Lei Jiang, Kostya S. Novoselov, Huanting Wang
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Nanoconfined selective ion transport shows promise for achieving biomimetic ion separation and iontronics information transmission. However, exploration of tunable nonlinearity of ion transport is formidable due to the challenge in fabrication of nanochannel devices of exquisite nanoconfined architectures. Here, we report a hierarchical metal-organic framework (MOF)–based nanofluidic device of multiscale heterogeneous channel junctions to achieve unprecedented triode-like nonlinear proton transport, in contrast with diode-like rectifying transport for metal ions. Through experiments and theoretical simulations, we unveil the underlying mechanism for this unique nonlinear proton transport property, i.e., the gating effect from the built-in electric potential across the MOF phase junctions enabled by voltage bias above a threshold. As a proof-of-concept application demonstration, the nanofluidic device exhibits an ionic memory property as a nanofluidic memristor. This finding of proton-specific nonlinear resistive switching and memristive phenomenon can inspire future studies into nanofluidic iontronics and mass transport by rational design of coupled nanometric and angstrom-sized confinement.
GPT-4o mini: Non-social science research article
A 2.7-ÎŒm-thick robust, permeable, and antifreezing hydrogel electrode for long-term ambulatory health monitoring
Yuli Wang, Zonglei Wang, Yujie Zhang, Jiawei Yang, Zongman Zhang, Pengcheng Zhou, Yumiao Xu, Qingyuan Sun, Meiqiong Zheng, Wenqing Yan, Xuezhong He, Jiongyu Chen, Juan Li, Youhua Jiang, Sunghoon Lee, Hossam Haick, Tomoyuki Yokota, Takao Someya, Yan Wang
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Adaptable hydrogel bioelectronics that sustain long-term, uninterrupted operation are critical for early disease diagnosis and personalized health care. However, conventional hydrogel electrodes suffer from mechanical fragility, rapid dehydration, freezing, and poor comfort because of thickness-induced interfacial gaps. We report a 2.7-micrometer-thick robust, permeable, and antifreezing hydrogel electrode for high-quality 8-day electrophysiological monitoring under everyday scenarios. The ultrathin electrode is fabricated using gelatin hydrogels with temperature-controlled phase change properties reinforced by nanomesh while incorporating lithium chloride, and a binary solvent achieves antifreezing and antidehydration characteristics. The design minimizes flexural rigidity, resulting in high interfacial adhesion energy with human skin, and enhances gas (air, oxygen, and carbon dioxide) permeance and water vapor transmission rate. Consequently, the ultrathin hydrogel electrode exhibits high biocompatibility, superior wear comfort, and minimized motion and sweat artifacts, enabling reliable, uninterrupted, wireless health monitoring over eight consecutive days across various real-life activities and adaptation to cold environments.
GPT-4o mini: Non-social science research article
Cell-extrinsic controls over neocortical neuron fate and diversity
Natalia Baumann, Ilaria Morassut, Sergi Roig-Puiggros, Esther Klingler, Giorgia Bartolini, Sabine FiĂšvre, Denis Jabaudon
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Neocortical cellular diversity emerges gradually during development. Cell-extrinsic interactions shape this extended maturation, yet cell type–specific dependence on such cues has not been systematically examined. To address this, we compared how cell identity and diversity unfolds in different conditions during neocortical development. Conditions were modified in vivo using genetically modified mouse models in which position or innervation is altered and in vitro using two-dimensional cultures. This approach revealed a molecular hierarchy in which cell class–distinguishing features emerge first, followed by subclass- and type-related characteristics. Acquisition of cellular identity and diversity remained stable across in vivo models. In contrast, in vitro glutamatergic neurons showed decreased expression of identity-defining genes, reduced diversity, and alterations in connectivity. Cellular identity and diversity were closest to in vivo values in organotypic cultures. These findings reveal population-specific responses to environmental conditions and highlight the role of extracellular context in shaping cell diversity in the maturing neocortex.
GPT-4o mini: Non-social science research article
Superconductivity in compressed quasi−one-dimensional face-sharing hexagonal perovskite chalcogenides
Feng Ke, Shanyuan Niu, Jiajia Feng, Ketao Yin, Minkyung Han, Hong Yang, Bai Yang Wang, Anna Celeste, Chunjing Jia, Bin Chen, Lin Wang, Harold Y. Hwang, Yongjun Tian, Wendy L. Mao, Yu Lin
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Oxide perovskite superconductors typically feature stacks of metal-oxygen octahedra or planar blocks connected through corners, forming three-dimensional (3D) or 2D layered structures. Here, we find a group of quasi-1D superconducting materials among hexagonal perovskite chalcogenides with face-sharing connectivity. Resistance and magnetization measurements demonstrate anisotropic superconductivity in compressed barium titanium trisulfide (BaTiS 3 ) at a low hole carrier concentration of (1.6 ± 0.1) × 10 21 per cubic centimeter, with the highest superconducting temperature ( T c ) reaching ~9.3 kelvin. Synchrotron x-ray diffraction indicates that the superconducting phase retains a hexagonal perovskite structure consisting of quasi-1D infinite titanium hexasulfide chains. Density functional theory calculations, combined with the observed decrease in the maximum T c from ~9.3 to ~6.2 kelvin upon substituting sulfur with selenium, suggest that electron-phonon interactions play a key role in the pairing mechanism of superconducting BaTiX 3 (X = sulfur and selenium). Our study offers a quasi-1D platform with face-sharing metal-chalcogen octahedra for understanding the mechanism of emerging electronic states in perovskite materials.
GPT-4o mini: Non-social science research article
Impact of current and warmer climate conditions on snow cover loss in burned forests
Arielle Koshkin, Adrienne M. Marshall, Karl Rittger
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Wildfires are increasingly burning in snow-dominated watersheds and can alter snowmelt dynamics. However, the spatial variability of snow cover loss in burned forests has been under characterized. Here, we use remotely sensed snow data to show that, under average winter conditions, snow melts earlier in the first year postfire in 99% of the snow zone. Postfire snow cover loss is more extreme in relatively low-elevation, warm environments compared to that in high-elevation, cold regions. Under +2°C of warming, 73% of the snow zone would experience more extreme earlier postfire snowmelt compared to historically average conditions. Regions with the largest shift earlier in postfire snowmelt timing under average climate conditions also have the largest shift earlier in postfire snowmelt under +2°C warming. The spatial variability in postfire snowmelt timing and exacerbated impact in projected warmer winters affect ecosystem water availability, snow albedo feedbacks, and snowmelt runoff forecasting essential to water resource management.
GPT-4o mini: Non-social science research article
Defect passivation and crystallization modulation in methylammonium-free wide-bandgap perovskites for all-perovskite tandem solar cells
Xuefei Jia, Kaicheng Zhang, Xiaofeng Gao, Xufeng Liao, Yujie Yang, Weisheng Li, Xiaojing Lv, Xinyu Zhao, Jiali Liu, Yitong Ji, Zhongliang Yan, Qingguo Du, Fuzhi Huang, Zhiwei Ren, Yaxin Zhai, Wenchao Huang, Yang Bai, Canglang Yao, Qianqian Lin, Yi-Bing Cheng, Jinhui Tong
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Wide-bandgap (WBG; >1.65 electron volts) perovskites based on iodine-bromine (I-Br) mixed halides are critical components of perovskite-based tandem solar cells (TSCs). However, the uncontrolled crystallization dynamics of Br-rich species lead to reduced grain sizes and high defect densities in WBG perovskite films. Herein, a multifunctional additive 3,4,5-trifluorobenzamide (TFBZ) was introduced to enhance the crystallinity and passivate defects of the methylammonium (MA)–free WBG perovskite films. The TFBZ demonstrates superior passivation capability compared to benzamide, effectively mitigating both iodine vacancies and undercoordinated Pb 2+ defects via fluorine-enhanced interactions. In addition, the fluorine substituents in TFBZ could form N–H···F hydrogen bonds with formamidinium iodide to retard the crystallization rate of the perovskite. This proposed method is effective in defect passivation and crystal growth modulation for both 1.67– and 1.79–electron volt MA-free WBG perovskites, enabling the fabrication of MA-free all-perovskite TSCs with an encouraging power conversion efficiency of 29.01% (certified at 28.52%).
GPT-4o mini: Non-social science research article
DeepInMiniscope: Deep learning–powered physics-informed integrated miniscope
Feng Tian, Ben Mattison, Weijian Yang
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Mask-based integrated fluorescence microscopy is a compact imaging technique for biomedical research. It can perform snapshot 3D imaging through a thin optical mask with a scalable field of view (FOV). Integrated microscopy uses computational algorithms for object reconstruction, but efficient reconstruction algorithms for large-scale data have been lacking. Here, we developed DeepInMiniscope, a miniaturized integrated microscope featuring a custom-designed optical mask and an efficient physics-informed deep learning model that markedly reduces computational demand. Parts of the 3D object can be individually reconstructed and combined. Our deep learning algorithm can reconstruct object volumes over 4 millimeters by 6 millimeters by 0.6 millimeters. We demonstrated substantial improvement in both reconstruction quality and speed compared to traditional methods for large-scale data. Notably, we imaged neuronal activity with near-cellular resolution in awake mouse cortex, representing a substantial leap over existing integrated microscopes. DeepInMiniscope holds great promise for scalable, large-FOV, high-speed, 3D imaging applications with compact device footprint.
GPT-4o mini: Non-social science research article
Mapping the genetic landscape of iron metabolism uncovers the SETD2 methyltransferase as a modulator of iron flux
Anthony W. Martinelli, Chun-Pei Wu, Tristan VornbÀumen, Hudson W. Coates, Louise H. Jordon, Niek Wit, Jia J. Sia, Anneliese O. Speak, James A. Nathan
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Cellular iron levels must be tightly regulated to ensure sufficient iron for essential enzymatic functions while avoiding the harmful generation of toxic species. Here, to better understand how iron levels are controlled, we carry out genome-wide mutagenesis screens in human cells. Alongside mapping known components of iron sensing, we determine the relative contributions of iron uptake, iron recycling, ferritin breakdown, and mitochondrial flux in controlling the labile iron pool. We also identify SETD2, a histone methyltransferase, as a chromatin modifying enzyme that controls intracellular iron availability through ferritin breakdown. Functionally, we show that SETD2 inhibition or cancer-associated SETD2 mutations render cells iron deficient, thereby driving resistance to ferroptosis and potentially explaining how some tumors evade antitumoral immunity.
GPT-4o mini: Non-social science research article
Ethanol ingestion via frugivory in wild chimpanzees
Aleksey Maro, Aaron A. Sandel, Bi Z. A. Blaiore, Roman M. Wittig, John C. Mitani, Robert Dudley
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Human attraction to alcohol may derive from an evolutionary association between ethanol and fruits consumed by animals in nature. Fermentative yeasts are widespread in the terrestrial biosphere, and simple carbohydrates underpinning ethanol production are commonplace within fruits. We determined ethanol concentrations within fruits representing a substantial portion of the diet of our closest living relatives, the chimpanzees. Ripe fruit pulp from 20 angiosperm species in CĂŽte d’Ivoire and Uganda contained an average value of 0.31 (± 0.21 SD) and 0.32% (± 0.20) ethanol (weight/weight), respectively, as scaled by annual chimpanzee feeding time per species at each site. Chimpanzees typically eat ~4.5 kilograms of fruit per day, corresponding to an estimated ethanol ingestion of 14 grams (±9), or the equivalent of 1.4 (±0.9) standard drinks by international standards. These findings are consistent with the hypothesis that ethanol is widespread within tropical fruits and that modern predisposition to alcohol consumption derives from ancestral exposure to this psychoactive substance among frugivorous primates.
GPT-4o mini: Non-social science research article
Asymmetrical polyimide membranes with programmable polymer chain architectures for liquid hydrocarbon fractionation
Weilin Feng, Fupeng Li, Jiaqi Li, Zhiyi Li, Lu Xu, Hukang Guo, Nanwen Li, Xinzhong Cao, Chuanjie Fang, Baoku Zhu, Liping Zhu
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Conventional fractionation of liquid hydrocarbons relies on energy-intensive distillation. While organic solvent reverse osmosis provides an energy-efficient alternative, the challenge lies in engineering membranes with accurately tailored molecular differentiation for complex hydrocarbons. Here, we develop diverse fluorinated polyimide membranes featuring programmable polymer chain architectures for efficient hydrocarbon separation. By stoichiometry-controlled polycondensation, the chain packing and microporosity of synthesized polyimides are finely regulated, verified by molecular simulations. The corresponding asymmetrical membranes with defect-free thin layers of 100 to 250 nanometers are prepared via solution casting and thermal annealing steps. Such programmed membranes enable tunable permselectivity for hydrocarbons with less than 40 carbon atoms. The fractionation of kerosene-paraffin mixture in toluene is demonstrated through a two-stage process containing the optimized membranes. The cascade process remarkably enriches the C 10 -C 13 hydrocarbons from 50% up to 97%. The demonstrated polyimide membranes with on-demand molecular discrimination capability provide a potential candidate for the membrane-based hydrocarbon fractionation.
GPT-4o mini: Non-social science research article
Strain-optimized copper dual-atom sites for selective electroreduction of carbon dioxide to ethylene
Xuewei Huang, Xinwei Li, Shuhao Yan, Dawei Wang, Chang Long, Yue Ying, Pengfei An, Zhiyu Guo, Qun Li, Caoyu Yang, Sheng Chen, Jianyu Han, Lin Chang, Siyu Lu, Zhiyong Tang
Full text
Electrocatalytic carbon dioxide (CO 2 ) reduction holds the great potential to convert excess emissions of carbon footprint into high value-added chemicals, but its activity, selectivity, stability, and reproducibility are still far away from satisfactory. The molecular catalysts with precise structures are unique platform to decipher the electrocatalytic mechanism, but they usually suffer from low performance. Herein, we report a strain-optimized dual copper complex immobilized in mesoporous carbon, which exhibits remarkable ethylene (C 2 H 4 ) Faradaic efficiency (FE) up to 49.9% along with a multicarbon (C 2+ ) product’s FE up to 65.2% at −1.19 volts versus reversible hydrogen electrode. Concurrently, the catalyst displays considerable stability for 15 hours at a full cell potential of −3.1 volts. The density functional theory calculation reveals that the strain effect imposed by mesoporous carbon regulates the neighboring dual copper sites in the electrocatalyst to decrease the energy barrier of rate-determining step (*COCO → *COCOH), thus significantly promoting ethylene production.
GPT-4o mini: Non-social science research article
Single-molecule capture, release, and dynamical manipulation via reversible electrokinetic confinement (RECON)
Matheus A. S. PessĂŽa, Piotr Jakuc, Carolina Martins e Queiroz, Naomi Duggan, Ruiyao Liu, Seraphine Kautz, Sarah Ameur, Zezhou Liu, Wangwei Dong, Preethi Ravikumar, Sajad Shiekh, Han Cao, Michael Austin, Sara Mahshid, Deborah Fygenson, Walter Reisner
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We present a nanofluidic device enabling single-molecule confinement through free-energy landscapes created by dynamic electrical gating of embedded nanoelectrodes. Unlike static geometric confinement, this system uses a parallel electrode configuration with nanoelectrodes placed in a dielectric layer. Localized electrokinetic fields at electrode wells form tunable attractive potential wells for bimolecular capture. By modulating the voltage bias waveform, the device allows precise control over confinement dynamics, enabling molecular capture, release, and exposure to periodic or stochastic confinement regimes. This flexibility facilitates the study of biomolecular behavior under dynamically adjustable conditions, including controlled confinement fluctuations. The device can manipulate diverse analytes such as double-stranded DNA, liposomes, and DNA nanotubes and facilitates introducing molecules into confined environments intact from bulk while providing enhanced tunability. With the ability to implement tailored confinement profiles, this platform represents a versatile tool for probing molecular confinement and behavior in complex, dynamically varying environments.
GPT-4o mini: Non-social science research article
Temporal biphasic regulation of photoreceptor degeneration by microglial TREM2: A metabolic-immune nexus in retinitis pigmentosa
Rong Li, Jing Zhang, Jiang-Mei Wu, Jun-Qi Fan, Bin Lin
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Retinitis pigmentosa (RP), the leading cause of inherited blindness, lacks therapies because of undefined photoreceptor degeneration mechanisms. While microglia/myeloid cells drive RP progression, their phenotype-regulating determinants remain unclear. Using rd10 mice, we reveal TREM2 as a biphasic RP regulator via STAT2–mediated microglial reprogramming. Early TREM2 loss amplifies neuroinflammation through STAT2 hyperactivation, while late deficiency triggers NF-ÎșB/STAT2–driven microglial apoptosis, impairing phagocytosis yet preserving photoreceptors. We uncover a photoreceptor-microglia metabolic axis where apoptotic photoreceptors release arachidonic acid, salicylic acid, and creatinine to induce STAT2-dependent apoptosis in TREM2-deficient cells. Crucially, we identify intermicroglia PSAP/GPR37 signaling as a self-propagating apoptotic mechanism—the first evidence of apoptotic transmission in retinal degeneration. This study establishes three advances: (i) TREM2 exhibits stage-dependent neuroprotective/neurotoxic roles, (ii) photoreceptor metabolites dictate microglia/myeloid cell fate via STAT2, and (iii) microglial apoptosis spreads through membrane signaling complexes. Our findings redefine neuroimmune dynamics in retinal degeneration, propose chronotherapeutic TREM2 targeting, and extend to Alzheimer’s and other microglia-associated CNS disorders via metabolic-immune interplay.
GPT-4o mini: Non-social science research article
Active learning for nonparametric multiscale modeling of boundary lubrication
Hannes Holey, Peter Gumbsch, Lars Pastewka
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Lubricated friction is a multiscale problem where molecular processes dictate the macroscopic response of the system. Traditional lubrication models rely on semiempirical constitutive relations, which become unreliable under extreme conditions. Here, we present a simulation framework that seamlessly couples molecular and continuum models for boundary lubrication without fixed-form constitutive laws. We train Gaussian process regression models as surrogates for predicting interfacial shear and normal stress in molecular dynamics simulations. An active learning algorithm ensures that our model adapts in scenarios where common constitutive laws fail, such as at layering transitions. We demonstrate our approach for nanoscale fluid flow over rough and heterogeneous surfaces, paving the way for accurate boundary lubrication simulations at experimental length and timescales.
GPT-4o mini: Non-social science research article
Phase transitions perception in nonreciprocal mechanical metamaterials through electromagnetic resonance
Yun Deng, Xiaoyu Zhao, Zhixin Huang, Ying Li
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Phase transitions of metamaterials are critical in advancing energy conversion efficiency and controlling mechanical performance. However, the design method and localized perception of phase transitions remain challenging. Inspired by the passive coupling mechanisms in ostrich locomotion, this work proposes nonreciprocal metamaterials that can perceive real-time phase transition. These architectures enable the topological solitons to propagate unidirectionally and overcome dispersive and dissipative effects through bistable-to-monostable state switching between adjacent units. The integration of electromagnetic resonators within the metamaterial units enables real-time detection of dynamic phase transitions, as soliton propagation or external loads induce resonance frequency shifts between distinct stable states. By arraying these mechanoreceptive units and the combination of the machine learning, it can encode information and compute programmatically. Furthermore, the mechanoreceptors hold promising applications in robotics. This work provides an approach for integrating phase transition perception and nonlinear wave manipulation and offers insights into dynamic material intelligence and energy management systems.
GPT-4o mini: Non-social science research article
A practical 4.8-V Li||LiCoO 2 battery
Qi Xiong, Dedi Li, Shimei Li, Dechao Zhang, Ruhong Li, Shuoqing Zhang, Shixun Wang, Hu Hong, Daming Zhu, Qi Liu, Xiulin Fan, Chunyi Zhi
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Raising the charging voltage of a lithium||lithium cobalt oxide (Li||LiCoO 2 ) battery is a shortcut to realize high energy density in portable electronics, while the fragile interface of highly delithiated LiCoO 2 (>4.55 volts) can trigger the lattice oxygen release, thus leading to severe interfacial degradation and structural collapse. Here, using lithium pentadecafluorooctanoate as a fluorine source to build robust lithium fluoride–rich electrode-electrolyte interfaces, stable Li||LiCoO 2 batteries at high voltage have been realized, capable of cycling 1500, 600, and 188 times at 4.6, 4.7, and 4.8 volts, respectively. Furthermore, the practicality of Li||LiCoO 2 batteries at an unprecedented cutoff voltage of 4.8 volts has been validated by a 2.7–ampere hour pouch cell, which shows a superior energy density of 544 watt-hours per kilogram and can operate more than 50 cycles. Our exploration of 4.8-volt LiCoO 2 may pave the way to ceaselessly approach its theoretical capacity.
GPT-4o mini: Non-social science research article
Synthesized Kuramoto potential via optomechanical Floquet engineering
Motoki Asano, Hajime Okamoto, Hiroshi Yamaguchi
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Synchronization is a ubiquitous scientific phenomenon in various mesoscopic oscillators. Despite its extensive importance in both nonlinear physics and innovative technologies, their dynamics in laboratory experiments is restricted to a nearly static regime governed by fixed device and system structures. Here, we explore multistable and dynamically tunable synchronization using Floquet engineering technique. Applying a periodically modulated laser light to optomechanical oscillators allows for stable and precise control of oscillator couplings. This enables us to not only explore the physics of quantized integer and fractional phase slips but also synthesize multioctave synchronizations of mechanical oscillators that exhibit tailorable multistability. Furthermore, the dynamically manipulated synchronizations lead to an exotic phase-space trajectory, which has a nontrivial winding number and giant nonreciprocity. This optomechanical Floquet engineering opens up the study of unexplored dynamics in complicated oscillator networks such as biological systems and innovative technology by mimicking their highly efficient information processing.
GPT-4o mini: Non-social science research article
Grin2b -mutant mice exhibit heightened remote fear via suppressed extinction and chronic amygdalar synaptic and neuronal dysfunction
Muwon Kang, Seoyeong Kim, Wangyong Shin, Kyungdeok Kim, Yewon Jung, Woochul Choi, Se-Bum Paik, Eunjoon Kim
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Individuals with autism spectrum disorders (ASD) frequently show long-lasting traumatic fear memory, but the underlying mechanisms remain unclear. Here, we report that Grin2b -mutant mice carrying a human ASD-risk mutation ( Grin2b C456Y/+ mice) show normal acquisition of contextual fear memory but suppressed fear memory extinction and enhanced remote fear memory responses, along with anxiety- and social-related abnormalities. After footshock and fear extinction, these mutants chronically develop occluded neuronal activation in the basal amygdala (BA) detectable at remote fear memory retrieval, which involves suppressed spontaneous excitatory synaptic transmission and neuronal excitability. Chemogenetic activation of mutant BA neurons during fear extinction improves fear memory extinction and remote fear memory responses without affecting anxiety- or social-related phenotypes. This rescue involves normalized spontaneous excitatory synaptic transmission and neuronal excitability. These results suggest that Grin2b C456Y/+ mice, through impaired fear memory extinction, chronically develop suppressed spontaneous excitatory synaptic transmission and neuronal excitability in BA neurons that enhances remote fear memory responses.
GPT-4o mini: Non-social science research article
Oropouche virus efficiently replicates and is immunostimulatory in vivo in nonhuman primate species
Debra S. Yee, Jonathan P. Davies, Laura A. VanBlargan, Andrew R. Rahmberg, Katherine E. Burgomaster, Kelsie Brooks, Jacob K. Flynn, Byron Shue, Alexandra M. Ortiz, Paul Schaughency, Sonja M. Best, Theodore C. Pierson, Jason M. Brenchley
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An Oropouche virus (OROV) outbreak occurred in South America in 2024. The pathogenic potential and host immunological response of this emerging virus are largely unknown, as animal models have been poorly explored. We infected nonhuman primate (NHP) species with OROV and followed viral replication dynamics and subsequent innate and adaptive immunological responses. OROV efficiently replicated in pigtail macaques, rhesus macaques, and vervet African green monkeys. OROV also replicated in sabeus African green monkey, albeit at lower levels than other hosts. OROV RNA was detected in plasma and nasal swabs and infection-induced high levels of innate inflammation, type I interferon gene signatures, immunoglobulin M–positive B cell expansion, high titers of neutralizing antibodies, and detectable frequencies of OROV-specific T cells. Prior infection was protective against reinfection up to 524 days post–initial infection, demonstrating possible protective immunity induction against OROV infection. These data suggest that multiple NHP species are appropriate models for OROV infection and the development of therapeutics and vaccinations.
GPT-4o mini: Non-social science research article
A radiometric timescale challenges the chronology of the iconic 1992 Guliya ice core
Shugui Hou, Theo M. Jenk, Wei Jiang, Wangbin Zhang, Huanting Hu, Xin Feng, Hao Li, Shuang-Ye Wu, Hongxi Pang, Jinhai Yu, Renhui Huang, Zheng-Tian Lu, Guo-Min Yang, Michael Bender, Margit Schwikowski
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The Guliya (Tibet) ice core drilled in 1992 (GP1992) has garnered special interest because of its exceptionally long timescale of ~760 thousand years. This timescale makes GP1992 currently the second oldest ice core in the world, much older than any other extrapolar ice cores. Here, we revisit the GP1992 timescale by dating a Guliya ice core (GP2021) that was drilled close to the GP1992 drilling site in 2021. All our data, including the absolute dates deduced from 210 Pb, 39 Ar, and 14 C, confirmed an age of <3 thousand years at 175.1 meters depth of GP2021, compared with ~100 thousand years previously estimated at the stratigraphically equivalent depth in GP1992. Our results resolved several discrepancies between the GP1992 and other paleoclimate records in the region, leading to different insights in climate history of the Tibetan Plateau.
GPT-4o mini: Non-social science research article
Nonequilibrium quantum dynamics in SrTiO 3 under impulsive THz radiation with machine learning
Francesco Libbi, Anders Johansson, Boris Kozinsky, Lorenzo Monacelli
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Ultrafast spectroscopy paved the way for probing transient states of matter produced through photoexcitation. The microscopic processes governing the formation of these states remain largely unknown, due to the inherent challenges in accessing the microscopic behavior of materials, which is strongly influenced by nuclear quantum effects. Here, we perform simulations of quantum nuclear dynamics in the nonequilibrium regime, extending beyond the current state of the art. By combining first-principles simulations with machine learning, we unveil the complex quantum dynamics of SrTiO 3 emerging after terahertz laser pumping. We disclose the microscopic origin of the phonon upconversion, observed experimentally but not fully understood, and quantify the lifetime of the out-of-equilibrium motion, which is beyond the reach of the state-of-the-art simplified models. Crucially, our simulations predict that terahertz pump pulses can generate persistent out-of-equilibrium stress capable of inducing polar order. This work lays the foundation for systematic explorations of complex quantum materials sensitive to photoexcitation.
GPT-4o mini: Non-social science research article
Specific host-algae relationship, yet flexible bacterial microbiome, in diatom-bearing foraminifera
Elsa B. Girard, Laura del Rio-Hortega, Andi M. A. Pratama, Sophie Volkenandt, Jan-Niklas Macher, Susanne Wilken, Willem Renema
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Whether the adaptive strategies of marine mixotrophs, organisms that combine heterotrophic and autotrophic nutrition, in response to global change are rooted in their symbiotic relationships is debated, especially for larger benthic foraminifera. Despite their importance in the ecosystem, there are controversial findings regarding the specificity of their algal endobionts, preventing a deeper understanding of their adaptive strategies. Using single-cell metabarcoding on 243 diatom-bearing foraminifera specimens from Indonesia, we found one highly dominant diatom strain in each foraminiferal host species bearing at least 90% of the reads in a majority of host species, whereas the bacterial community was very flexible, with only 25% of the variation explained by water depth, substrate type, location, and host species. Our results suggest that the adaptive strategy of the foraminiferal holobiont rather lies within its bacterial endobiome. Its dynamism likely facilitates the adaptive potential of foraminifera, supporting their proliferation across different environmental settings.
GPT-4o mini: Non-social science research article
Cross-dehydrogenative coupling via C(sp 2 )─H bond activation by PSP-pincer rhodium photocatalysis
Kotaro Sakai, Yanzong Lyu, Jun Odake, Naoyuki Toriumi, Nobuharu Iwasawa, Masanobu Uchiyama
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Cross-dehydrogenative coupling (CDC) between two C─H bonds without any oxidant would be an excellent C─C bond-forming reaction, generating H 2 as the only by-product. However, C(sp 2 )─H/C(sp 2 )─H CDC reactions remain rare despite the rapid development of transition metal catalysis, photocatalysis, and electrocatalysis. Here, we describe directing-group- and oxidant-free C(sp 2 )─H/C(sp 2 )─H CDC between arenes and styrenes/furans photocatalyzed by a PSP-pincer Rh complex to afford stilbenes/heterobiaryls under mild conditions (blue light irradiation, near room temperature). The reaction is applicable to a wide range of substrates, and undesired hydrogenation of the styrenes and stilbenes is strongly suppressed. The generated H 2 gas can be used for hydrogenation of alkenes in a connected flask system. Experimental mechanistic studies indicated that the Rh(I)─Ar complex is a key intermediate in the catalytic cycle, and C(sp 2 )─H bond cleavage of the styrenes/furans occurs via oxidative addition in the excited state.
GPT-4o mini: Non-social science research article
Elucidating the mechanism by which HIV-1 nucleocapsid mutations confer resistance to integrase strand transfer inhibitors
Yuta Hikichi, Ryan C. Burdick, Sean C. Patro, Si-Yuan Ding, Brian T. Luke, Erin D. Clark, Sherimay D. Ablan, Xiaolin Wu, Vinay K. Pathak, Eric O. Freed
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Persons with HIV (PWH) receiving integrase (IN) strand transfer inhibitors (INSTIs) have been reported to experience virologic failure (VF) in the absence of resistance mutations in IN. We previously reported that mutations in the viral nucleocapsid (NC) are selected in the presence of the INSTI dolutegravir (DTG). Here, we show that these NC mutations accelerate the kinetics of viral DNA integration, suggesting that they limit the window of time available for INSTIs to block viral DNA integration. We find that in primary peripheral blood mononuclear cells, HIV-1 acquires mutations in the viral envelope glycoprotein, NC, and occasionally IN during selection for INSTI resistance. Notably, the selected NC and IN mutations act in concert to reduce the susceptibility of the virus to INSTIs. These results provide insights into the mechanism by which HIV-1 escapes the inhibitory activity of INSTIs and underscore the importance of genotypic analysis outside IN in PWH experiencing VF on INSTI-containing drug regimens.
GPT-4o mini: Non-social science research article
A space-time holographic metasurface antenna
Geng-Bo Wu, Jun Yan Dai, Yiqing Sun, Kam Man Shum, Ka Fai Chan, Qiang Cheng, Tie Jun Cui, Chi Hou Chan
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Holography is a revolutionary imaging technology capable of storing and recovering full-wave information of the light fields scattered by objects. However, current hologram configurations are based on space-only modulation and can merely record the amplitude and phase information of object lights. Here, we advance the holography concept by transitioning it from a space-only, homodyne, and single-tone approach to a spatiotemporal, heterodyne, and multifrequency methodology. We theoretically propose and experimentally demonstrate a space-time holographic metasurface antenna (HMA) capable of encoding and reconstructing the full amplitude, phase, and frequency contents of object waves. We demonstrate the HMA for frequency conversion and holographic beamforming in the far field, as well as multifrequency two-dimensional (2D) and 3D holographic imaging in the near field. The proposed integrative and multifunctional space-time HMA goes beyond the existing holography technology, with the potential to enable a plethora of applications such as augmented/virtual reality, data storage, metrology, and wireless communications.
GPT-4o mini: Non-social science research article
Color-resolved third harmonic generation microscopy for single-RBC HbA1c measurement and glycemic history assessment
Xuhao Ye, Hui-Yuan Chen, Hao-Cheng Gao, Jin-Ying Lu, Yi-Hua Liao, Tzu-Ming Liu, Yu-Hsiang Cheng, Yajing Wei, Lei-Iat Seng, Youyuan Chen, Tzung-Dau Wang, Chi-Kuang Sun
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The spectral absorption of biomolecules holds immense potential for revealing molecular identity, biological functions, and clinical diagnostics. Here, we present color-resolved third harmonic generation microscopy (cTHGM), a noninvasive method for molecular imaging based on absorption-enhanced THG response. Leveraging one single broadband femtosecond laser beam, cTHGM captures subtle absorption variations, including ~2-nanometer shifts in the Soret band, enabling precise distinction of glycated hemoglobin (HbA1c) from hemoglobin with negligible phototoxicity. We demonstrate that cTHGM measures HbA1c fractions in single red blood cells (RBCs) in vivo and ex vivo, providing noninvasive HbA1c measurement and insights into HbA1c distribution at the cellular level. In addition, cTHGM reconstructs historical glycemic trajectories by decoding single-RBC HbA1c distributions, offering a retrospective view of glycemic variability over months. This innovative method combines label-free imaging, high spatial and spectral resolution, and noninvasive manners, making it a promising tool for diabetes management, glycemic variability monitoring, and broader applications in precision medicine.
GPT-4o mini: Non-social science research article
Ultrahigh-precision analog computing using memory-switching geometric ratio of transistors
Xing-Jian Yangdong, Cong Wang, Yichen Zhao, Zi-Chun Wang, Zaizheng Yang, Zenglin Liu, Wentao Yu, Zhoujie Zeng, Shuang Wang, Wei Wei, Yu Shen, Dehe Kong, Shuo Ding, Xu Wang, Chen Pan, Shi-Jun Liang, Feng Miao
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Analog computing has gained increasing attention for its potential in artificial intelligence hardware. The computation in traditional analog systems relies on use of intrinsic physical quantities (e.g., resistance), which are prone to fluctuations due to environmental changes or repeated programming, leading to compromised precision. Here, we shift the reliance on intrinsic physical quantity of memory devices to geometric ratio of transistors, enabling ultrahigh-precision analog computation. We demonstrate an analog in-memory computing chip based on a standard complementary metal-oxide semiconductor process, achieving the highest precision reported to date. Enhanced by the proposed weight remapping technique, the chip realizes ultrahigh computing accuracy with a root mean square error of only 0.101% across multiple parallel vector-by-matrix multiplication operations. Moreover, our analog in-memory computing chip maintains high precision, with an error of 0.155 and 0.130% under environmental temperatures of −78.5° and 180°C, respectively. This work pushes the boundaries of analog computing precision by leveraging stable geometry feature of devices.
GPT-4o mini: Non-social science research article
Linear ubiquitination prevents lipodystrophy and obesity-associated metabolic syndrome
Ximena Hildebrandt, Önay Veli, Armel Hyoubi, Julia Zinngrebe, Ali T. Abdallah, Julian Rodefeld, Anne Hoffmann, Liane Gardeweg, ÖykĂŒ Kaya, Elena Wagner, Andreas Lindhorst, Matea Poggenberg, Yuan Wang, JoĂ«lle Dimmler, Jutta Schillings, Pegi Koci, Francesca Bonechi, Lucas Valdez Capuccino, Christine Kiefer, Konstantinos Kelepouras, Adhideb Ghosh, Falko NoĂ©, Christian Wolfrum, Michael Singer, Gianmaria Liccardi, Tom Luedde, Aslihan Yavas, Ahmed Ghallab, Jan G. Hengsler, Philipp Antczak, Martin Gericke, Holger Winkels, Matthias BlĂŒher, Henning Walczak, Alessandro Annibaldi, Pamela Fischer-Posovszky, Nieves Peltzer
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Adipocyte hypertrophy during obesity triggers chronic inflammation, leading to metabolic disorders. However, the role of adipocyte-specific inflammatory signaling in metabolic syndrome remains unclear. The linear ubiquitin chain assembly complex, LUBAC, is an E3-ligase that generates nondegradative linear ubiquitination (Lin-Ub). LUBAC regulates NF-ÎșB/MAPK-driven inflammation and prevents cell death triggered by immune receptors like TNF receptor-1. Here, we show that mice lacking HOIP, the Lin-E3 ligase catalytic subunit of LUBAC, in adipocytes ( Hoip A-KO ) display lipodystrophy and heightened susceptibility to obesity-induced metabolic syndrome, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). Mechanistically, loss of HOIP attenuates TNF-induced NF-ÎșB activation and promotes cell death in human adipocytes. Inhibiting caspase-8–mediated cell death is sufficient to prevent lipodystrophy and MASLD in Hoip A-KO obese mice. HOIP expression in adipose tissue positively correlates with metabolic fitness in obese individuals. Overall, our findings reveal a fundamental developmental role for Lin-Ub in adipocytes by mitigating cell death–driven adipose tissue inflammation and protecting against obesity-related metabolic syndrome.
GPT-4o mini: Non-social science research article
Carbonate chemistry fitness landscapes inform diatom resilience to future perturbations
Aaron Ferderer, Kai G. Schulz, Anusuya Willis, Kirralee G. Baker, Zanna Chase, Lennart T. Bach
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Marine diatoms are an abundant and ecologically important phytoplankton group susceptible to changing environmental conditions. Currently available data assessing diatom responses focus on empirical comparisons between present-day and future conditions, rather than exploring the mechanisms driving these responses. Here, we conducted high-resolution growth experiments to map the fitness of diatoms across broad carbonate chemistry landscapes. Our results reveal species-specific carbonate chemistry niches, which can be used to predict ecological shifts between species under changing conditions driven by ocean acidification or ocean alkalinity enhancement. The results demonstrate that changes in diatom fitness are almost exclusively driven by carbon dioxide and proton concentrations, with bicarbonate exerting no discernible effect. Thus, current assumptions regarding the role of bicarbonate as a primary carbon source supporting diatom growth may be overestimated. This study presents a methodological and conceptual framework as a foundation for future studies to collate data capable of predicting species-specific responses and shifts in ecological niches driven by changes in marine carbonate chemistry.
GPT-4o mini: Non-social science research article
CLL to Richter syndrome: Integrating network strategies with experiments elucidating disease drivers and personalized therapies
Julia Maier, Julian D. Schwab, Silke D. Werle, Ralf Marienfeld, Stephan Stilgenbauer, Peter Möller, Nensi Ikonomi, Hans A. Kestler
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Chronic lymphocytic leukemia (CLL) is a common neoplasm that carries the risk of transformation into Richter’s syndrome (RS), a highly aggressive B cell lymphoma with poor prognosis. Limited availability of animal models and cell lines hinders understanding of transformation mechanisms. Addressing this gap, we established the first in silico dynamic model of the disease. Our methodology integrates mathematical logic modeling with experimental data to identify disease drivers, mechanisms, and potential therapeutic targets. We validated the model by comparing the model’s readout with experimental data from different biological levels, such as single-cell RNA sequencing analyses and a CLL/RS patient formalin-fixed paraffin-embedded (FFPE) tissue cohort. Our analyses identified BMI1 proto-oncogene and TP53 loss as key RS progression regulators. In addition, we performed an in silico target screening to identify promising target combinations in a personalized fashion. Through the synergy of mathematical modeling with experimental readouts, our model provides a complementary approach to investigate the process of CLL transformation to RS.
GPT-4o mini: Non-social science research article
Organic electrochemical transceiver: An all-in-one sense-and-release device architecture for physiological modulation
Yuanzhe Li, Mengying Yan, Xie He, Cunman Liang, Heng Liu, Qian Zhu, Mingqiang Wang, Xinhui Lu, Yi Lu, Ni Zhao
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Intelligent wearable devices with integrated sensing and drug-releasing functions are essential for delivering real-time and personalized interventions. Current approaches typically rely on interconnected modules, facing challenges such as large footprint, high energy consumption, and fabrication complexity. To address these limitations, we introduce a modified organic electrochemical transistor structure called the organic electrochemical transceiver (OECTC). The OECTC leverages the electronic wettability switch characteristic of conjugated polymers to convert sensed signals into a valve mechanism for controlling the release of chemical substances (e.g., drugs and neurotransmitters). This provides an all-in-one solution for synchronized signal recording and substance release for physiological modulation. The applications of the OECTC in intelligent wearable devices for managing type II diabetes and as a neural amplifier or inverter for neurotransmitter modulation are demonstrated.
GPT-4o mini: Non-social science research article
Metabolism-driven posttranslational modifications and immune regulation: Emerging targets for immunotherapy
Gujie Wu, Xiaofei Fan, Lin Cheng, Zongwei Chen, Yanjun Yi, Jiaqi Liang, Xiaolong Huang, Na Yang, Jiacheng Yin, Weigang Guo, Yiwei Huang, Shanye Yin
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The interplay between cellular metabolism and immune regulation is central to immune function and disease progression, revealing notable therapeutic opportunities. Upon activation, immune cells undergo metabolic reprogramming to meet heightened demands for energy and biosynthesis, reshaping regulatory networks across epigenomic, transcriptomic, and proteomic layers. Metabolite-derived posttranslational modifications (PTMs) serve as pivotal mechanisms integrating metabolic intermediates with immune signaling pathways. Beyond classical acetylation, diverse nonacetyl PTMs—including lactylation, succinylation, malonylation, palmitoylation, and myristoylation—modify histone and nonhistone proteins, regulating gene expression, protein stability, subcellular localization, enzymatic activity, and protein-protein interactions. Advances in mass spectrometry and bioinformatics now enable precise characterization of these PTMs, uncovering their broad roles in immune regulation. This review summarizes current progress in immunometabolism and explores future directions such as mechanistic studies, combination strategies, and clinical applications. Metabolite-driven PTMs critically connect metabolism to immune regulation, suggesting promising therapeutic approaches for cancer, autoimmune disorders, and inflammatory diseases.
GPT-4o mini: Non-social science research article
Highly efficient coherent amplification of zero-field spin waves in YIG nanowaveguides
Kirill O. Nikolaev, Stephanie R. Lake, Bikash Das Mohapatra, Georg Schmidt, Sergej O. Demokritov, Vladislav E. Demidov
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Transmission and processing of information at the nanoscale using spin waves and their quanta—magnons—offer numerous advantages and opportunities that make it a promising next-generation technology for integrated electronics. The main challenges that still need to be addressed to ensure high competitiveness of magnonic devices include finding ways to efficiently amplify spin waves in nanostructures and developing nanocircuits that can operate without the need for an external bias magnetic field. Here, we demonstrate how these two challenges can be solved using nanowaveguides fabricated from a low-loss magnetic insulator. We show that using local parametric pumping with a power of only a few milliwatts, one can achieve coherent amplification of spin-wave pulses by more than two orders of magnitude at zero bias magnetic field. Our results provide a simple solution to problems that have long prevented the implementation of efficient integrated magnonic circuits.
GPT-4o mini: Non-social science research article
Chemically induced deceleration of nuclear spin relaxation (CIDER) preserves hyperpolarization
Josh P. Peters, Charbel Assaf, Arne Brahms, Kolja Them, Mirco Gerdsen, Rainer Herges, Jan-Bernd Hövener, Andrey N. Pravdivtsev
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Gadolinium-based contrast agents revolutionized magnetic resonance imaging (MRI) by accelerating spin relaxation. In contrast, agents that decelerate relaxation were hitherto unknown. Such agents are highly desirable for metabolic imaging with hyperpolarized tracers such as 15 N-pyridine, 1,4- 13 C 2 -succinate, and 1- 15 N-nicotinamide, where valuable polarization decays rapidly, especially at low fields during transfer between polarizer and scanner. Here, we report on a previously unrecognized effect in which the tracers’ longitudinal and transverse relaxation rates in aqueous solution are substantially reduced by adding nicotinamide, urea, glycerol, or dendrons. The impact on longitudinal relaxation is particularly pronounced at low magnetic fields and near the tracer’s p K a where T 1 can be tripled. This mitigates polarization loss during transfer, so hitherto unsuitable, fast-relaxing molecules can be used now. This way, we achieved the 15 N hyperpolarization of nearly 30% for 1- 15 N-nicotinamide. This chemically induced deceleration of nuclear spin relaxation (CIDER) was confirmed using magnetic field–cycling experiments and offers broad potential for hyperpolarized magnetic resonance and beyond.
GPT-4o mini: Non-social science research article
Biomimetic Janus MXene membrane with bidirectional ion permselectivity for enhanced osmotic effects and iontronic logic control
Han Qian, Hongzhao Fan, Puguang Peng, Yan Du, Xiang Li, Yanhui Liu, Feiyao Yang, Yanguang Zhou, Zhong Lin Wang, Di Wei
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Osmotic efficiency is fundamentally governed by the balance between membrane ion selectivity and permeability, a challenge central to both biological signal transmission and sustainable energy conversion. Conventional membranes are constrained to unidirectional transport of either cations or anions, severely limiting their versatility and performance. Inspired by the chloride voltage-gated channel 5 (ClC-5), we engineered a biomimetic Janus NP-MXene membrane featuring subnanochannels (~6.0 angstrom) and exceptional structural integrity, enabling controlled, simultaneous Na + /Cl − transport with unprecedented permselectivity. Under a 50-fold salinity gradient, the NP-MXene membrane achieved a record power density of 85.1 watts per square meter and an osmotic potential of 181.5 millivolts, the highest reported for a single device. Harnessing ion-specific signals from multi-ion transport, we further demonstrated an iontronic transistor capable of modulating ion flow by salinity gradients, eliminating the need for external gate voltage. This advance enables encoded signals and robotic control for advanced human-machine interfaces. The scalable fabrication of nanofluidic channels facilitates high-performance iontronics for efficient energy-information flow.
GPT-4o mini: Non-social science research article
The BUB1 and BUBR1 paralogs scaffold the kinetochore fibrous corona
Verena Cmentowski, Andrea Musacchio
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The kinetochore corona, a polymeric fibrous structure, facilitates chromosome biorientation and mitotic checkpoint signaling during mitosis. How its main building block, the ROD-Zwilch-ZW10 (RZZ) complex, assembles on the outer kinetochore remains poorly understood. Harnessing corona biochemical reconstitutions and cell biology, we reveal that the paralogous spindle assembly checkpoint (SAC) proteins BUB1 and BUBR1 promote nonredundant branches of corona assembly. MPS1 kinase–dependent kinetochore docking of BUB1 and subsequent recruitment of BUBR1 initiates assembly. Disrupting the first branch by depleting CENP-E, a kinesin that links BUBR1 to RZZ, uncovered a second assembly pathway mediated by a direct interaction between BUB1 and ROD. Discovery of a direct interaction with the RZZ explains how the SAC protein MAD1 fits this corona assembly scheme. Our findings solve the long-standing puzzle of corona assembly and demonstrate the intimate interweaving of chromosome biorientation and checkpoint signaling.
GPT-4o mini: Non-social science research article
Autonomous codesign and fabrication of multistimuli-responsive material systems
Liwei Wang, Alexander L. Evenchik, Jared M. Yang, Ryan L. Truby, Wei Chen
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Responsive materials offer solutions to complex engineering challenges by enabling systems to adapt their shapes or properties in response to external stimuli. To fully harness the potential of responsive materials, inverse design methods that integrate multiple types of stimuli and manufacturing processes are necessary. We present a unified, autonomous codesign framework that simultaneously optimizes structure, manufacturing, materials, and stimuli for responsive material systems, achieving target shape morphing under multiple stimuli without relying on human heuristics or expertise. It integrates generalized topology optimization with hybrid data-physics differentiable simulations to achieve flexible, manufacturing-aware designs for network-like responsive material systems. We showcase our framework with a multimaterial three-dimensional printing process with high material tunability, which we use to fabricate liquid crystal elastomer systems that morph into different forms in response to heat and light. The exceptional flexibility and efficiency of our method will advance shape-morphing applications spanning soft robotics to drug delivery.
GPT-4o mini: Non-social science research article
Frictional strength regulated by roughness alignment
Shaoqi Huang, Shuwen Zhang, Deheng Wei, Hengxu Song, Yifan Li, Jianwei Cheng, Hu Zhao, Siyang Song, Zeqing Li, Liang Li, Shubao Shao, Chongpu Zhai, Minglong Xu
Full text
Rough contacts are ubiquitous, yet the impacts of the roughness matching on frictional behavior remain insufficiently understood. We investigate how slow shear and stick-slip transition depend on the roughness alignment between contacting surfaces. By rotating one surface with respect to the other, we precisely control roughness matching, enabling nearly an order-of-magnitude variation in the maximum static friction coefficient. Both the variation amplitude and the angular range over which the frictional strength varies are governed by roughness alignment. Universal statistical patterns emerge in micromechanical quantities, including the microcontact area, orientation, deformation, and their evolutions under shear, following generalized extreme value distributions. To quantify asperity interactions, we introduce the contact fabric tensor, whose anisotropy provides a unified measure of roughness matching and a predictor for frictional strength and sliding onset. These findings advance our understanding of friction at rough interfaces and inform the design of mechanical systems, adhesives, and fault models.
GPT-4o mini: Non-social science research article
Rational assembly of 3D network materials and electronics through tensile buckling
Xiaonan Hu, Zhi Liu, Zhenjia Tang, Shiwei Xu, Zhangming Shen, Yue Xiao, Youzhou Yang, Renheng Bo, Shuheng Wang, Wenbo Pang, Yihui Zhang
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Bioinspired network designs are widely exploited in biointegrated electronics and tissue engineering because of their high stretchability, imperfection insensitivity, high permeability, and biomimetic J-shaped stress-strain responses. However, the fabrication of three-dimensionally (3D) architected electronic devices with ordered constructions of network microstructures remains challenging. Here, we introduce the tensile buckling of stacked multilayer precursors as a unique route to 3D network materials with regularly distributed 3D microstructures. A data-driven topology optimization framework enables efficient search of the optimal 2D precursor pattern that maximizes out-of-plane dimension of the resulting 3D network material. Computational and experimental results demonstrate rational assembly of optimal multilayer precursor structures into well-architected 3D network materials with an evident interlayer separation. The resulting 3D network materials offer anisotropic, tunable J-shaped stress-strain curves, which can be tailored to reproduce stress-strain responses of biological tissues. Demonstration of reconfigurable volumetric 3D display suggests rich application opportunities in biointegrated electronics and tissue scaffolds.
GPT-4o mini: Non-social science research article
A plant-specific cytochrome b 5 –like protein is essential for phytosterol biosynthesis
Xianhai Zhao, Lijun Qiao, Zhi-Yong Wang, Shou-Ling Xu, John Shanklin, Chang-Jun Liu
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Sterols are essential isoprenoid derivatives that contribute to membrane structure and function. In plants, they also serve as precursors to phytohormones and specialized metabolites important for development, defense, and health. Although the sterol biosynthetic pathway is considered well-characterized, we report the discovery of a plant-specific cytochrome b 5 –like protein, CB5LP, as a critical component of phytosterol biosynthesis. Loss of CB5LP in Arabidopsis causes embryonic defects, seedling lethality, and accumulation of 14α-methyl-sterols, with reduced levels of sitosterol and stigmasterol—indicating a defect in sterol 14α-demethylation. TurboID-based proximity labeling and in vitro assays show that CB5LP physically and functionally interacts with CYP51, a cytochrome P450 enzyme catalyzing this demethylation step. Unlike canonical cytochrome b 5 proteins, CB5LP has a reversed topology and is exclusive to plants, acting as an evolutionarily distinct electron donor. This discovery reveals an uncharacterized redox partnership essential for sterol biosynthesis and highlights a promising target for the development of selective herbicide.
GPT-4o mini: Non-social science research article
Locusts adopt IP 3 as a second messenger for olfactory signal transduction
Jing Yang, Helen He, Shijie Dong, Jing Lv, Lili Cheng, Qiaoqiao Yu, Le Kang, Xiaojiao Guo
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Insects, unlike vertebrates, use heteromeric complexes of odorant receptors and co-receptors for olfactory signal transduction. However, the secondary messengers involved in this process are largely unknown. Here, we use the olfactory signal transduction of the aggregation pheromone 4-vinylanisole (4VA) as a model to address this question. When locusts detect 4VA, the pheromone is transported by OBP10 and OBP13 to the OR35–Orco receptor complex, thereby activating downstream pathways in the antenna. A pivotal downstream molecule, the lipid-binding protein Clvs2, facilitates phosphatidylinositol 4,5-bisphosphate transportation across the cytolemma, providing more substrates for inositol trisphosphate (IP 3 ) production. PLCe1, a biosynthetic enzyme, boosts IP 3 levels in the antennal lobe of the brain. IP 3 is responsible for converting chemical signals from the antenna into neural signals, confirming IP 3 as a secondary messenger in olfaction perception instead of GPCR in locusts. These findings elucidate the universal function of IP 3 in olfactory signal perception, shedding light on the key nodes of insect olfactory signal transduction.
GPT-4o mini: Non-social science research article
The weak land carbon sink hypothesis
James T. Randerson, Yue Li, Weiwei Fu, Francois Primeau, Jinhyuk E. Kim, Mingquan Mu, Forrest M. Hoffman, Anna T. Trugman, Linqing Yang, Chao Wu, Jonathan A. Wang, William R. L. Anderegg, Alessandro Baccini, Mark A. Friedl, Sassan S. Saatchi, A. Scott Denning, Michael L. Goulden
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Over the past three decades, assessments of the contemporary global carbon budget consistently report a strong net land carbon sink. Here, we review evidence supporting this paradigm and quantify the differences in global and Northern Hemisphere estimates of the net land sink derived from atmospheric inversion and satellite-derived vegetation biomass time series. Our analysis, combined with additional synthesis, supports a hypothesis that the net land sink is substantially weaker than commonly reported. At a global scale, our estimate of the net land carbon sink is 0.8 ± 0.7 petagrams of carbon per year from 2000 through 2019, nearly a factor of two lower than the Global Carbon Project estimate. With concurrent adjustments to ocean (+8%) and fossil fuel (−6%) fluxes, we develop a budget that partially reconciles key constraints provided by vegetation carbon, the north-south CO 2 gradient, and O 2 trends. We further outline potential modifications to models to improve agreement with a weaker land sink and describe several approaches for testing the hypothesis.
GPT-4o mini: Non-social science research article
Geospatial patterns in terrestrial organic matter reactivity across four shelf seas spanning the Eurasian Arctic
Junjie Wu, Felipe Matsubara, Gesine Mollenhauer, Ruediger Stein, Bingbing Wei, Kirsten Fahl, Xiaotong Xiao, Örjan Gustafsson
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Organic matter stored in Arctic permafrost represents a key component of the carbon cycle, yet its reactivity across heterogeneous continent-scale permafrost regions remains poorly understood. Here, we leverage the four shelf seas of the Eurasian Arctic as integrative receptor systems to evaluate terrestrial organic matter reactivity, assessed by examining organic carbon preservation as a function of 14 C-constrained cross-shelf transport time. Our findings reveal higher reactivity of terrestrial organic matter released to the Laptev Sea and the eastern East Siberian Sea, lower reactivity in the western East Siberian Sea, and no deducible degradation in the Kara Sea. The reactivity of terrestrial organic matter is primarily determined by the degradation status and composition of its source, alongside potential microbiological controls during transport. This study reveals the heterogeneity of terrestrial organic matter reactivity across the Eurasian Arctic margin and highlights the need for detailed assessments of region-specific carbon release and modeling parameterization.
GPT-4o mini: Non-social science research article
Narrow-linewidth monolithic topological interface state extended laser with optical injection locking
Xiao Sun, Zhibo Li, Yiming Sun, John H. Marsh, David R.S. Cumming, Stephen J. Sweeney, Anthony E. Kelly, Lianping Hou
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Narrow-linewidth lasers are essential for coherent optical applications, including communications, metrology, and sensing. Although compact semiconductor lasers with narrow linewidths have been demonstrated, achieving high spectral purity generally necessitates passive external cavities based on photonic integrated circuits. This study presents a theoretical and experimental demonstration of a monolithic optical injection locking topological interface state extended (MOIL-TISE) laser. By monolithically integrating a TISE laser with a micro-ring resonator on an AlGaInAs multiple quantum-well platform, the proposed device achieves efficient photon injection and linewidth narrowing. Experimental characterization indicates stable single-mode operation over a wide injection current range (65 to 300 milliamperes), exhibiting a side-mode suppression ratio exceeding 50 decibels. The laser’s Voigt linewidth was reduced from 2 megahertz to 4.2 kilohertz, with an intrinsic linewidth of 983 hertz extracted from power spectrum density, underscoring the MOIL-TISE laser’s promise for coherent communications and modulation-free quantum key distribution applications.
GPT-4o mini: Non-social science research article
Somatic mtDNA mutations at intermediate levels of heteroplasmy are a source of functional heterogeneity among primary leukemic cells
Kelly McCastlain, Catherine Welsh, Yonghui Ni, Liang Ding, Ti-Cheng Chang, Robert J. Autry, Besian I. Sejdiu, Qingfei Pan, Melissa Franco, Wenan Chen, Huiyun Wu, Veronica Gonzalez-Pena, Patrick Schreiner, Sasi Arunachalam, Joung Hyuck Joo, Samuel Brady, Jinghui Zhang, Charles Gawad, William E. Evans, M. Madan Babu, Konstantin Khrapko, Jiyang Yu, Gang Wu, Stanley Pounds, Mondira Kundu
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Somatic mitochondrial DNA (mtDNA) mutations are frequently observed in tumors, yet their role in pediatric cancers remains poorly understood. The heteroplasmic nature of mtDNA—where mutant and wild-type mtDNA coexist—complicates efforts to define its contribution to disease progression. In this study, bulk whole-genome sequencing of 637 matched tumor-normal samples from the Pediatric Cancer Genome Project revealed an enrichment of functionally impactful mtDNA variants in specific pediatric leukemia subtypes. Collectively, the results from single-cell sequencing of five diagnostic leukemia samples demonstrated that somatic mtDNA mutations can arise early in leukemogenesis and undergo positive selection during disease progression, achieving intermediate heteroplasmy—a “sweet spot” that balances mitochondrial dysfunction with cellular fitness. Network-based systems biology analyses link specific heteroplasmic mtDNA mutations to metabolic reprogramming and therapy resistance. We reveal somatic mtDNA mutations as a potential source of functional heterogeneity and cellular diversity among leukemic cells, influencing their fitness and shaping disease progression.
GPT-4o mini: Non-social science research article
Acute REM sleep deprivation alleviated depression-like behavior mediated by inhibiting VIP neurons in the mPFC
Yuxuan Zhu, Tongrui Wu, Qingyan Jiao, Haitong Chai, Yuang Wang, Chunxiao Tian, Qiuying Xue, Kai Li, Pu Wang, Zibing Li, Hualin He, Bo Chen, Aili Liu, Hui Shen
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Acute sleep deprivation (SD) rapidly alleviates depression, addressing a critical gap in mood disorder treatment. Rapid eye movement SD (REM SD) modulates the excitability of vasoactive intestinal peptide (VIP) neurons, influencing the synaptic plasticity of pyramidal neurons. However, the precise mechanism remains undefined. To investigate this, we used a modified multiple platform method (MMPM) to induce 12 hours of REM SD, specifically targeting VIP neurons in the medial prefrontal cortex (mPFC). Our results show that REM SD mitigated depression by suppressing VIP neurons activity, which directly increased the excitability of pyramidal neurons and, consequently, promoted synaptic plasticity recovery. In addition, the knockdown of VPAC2 on mPFC pyramidal neurons revealed that VPAC2-mediated AC/cAMP/PKA signaling pathway in these neurons is essential for REM SD to mitigate depression-like behavior. These findings suggest that VIP neurons directly regulate pyramidal neurons and are crucial in alleviating depression by REM SD.
GPT-4o mini: Non-social science research article
North Pacific meridional mode has larger impacts on El Niño evolution than the March Madden-Julian Oscillation
Yu Liang, Shang-Ping Xie, Alexey Fedorov, Stephen G. Yeager
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The El Niño–Southern Oscillation (ENSO) is a key driver of global climate variability. Early-season westerly wind bursts (WWBs) have long been suggested to be important for ENSO evolution and diversity, with the Madden-Julian Oscillation (MJO) among the main sources of WWBs. However, MJO’s contribution to ENSO evolution has been difficult to quantify. Here, using an ensemble hindcast approach specifically designed to isolate internal atmospheric variability, we evaluate the influences of March MJO on subsequent ENSO development. Our results show that the March MJO, under favorable background conditions, by itself has limited impacts on ENSO due to weak equatorial air-sea coupling in spring. In comparison, the North Pacific Oscillation–induced meridional mode exerts a more sustained influence on ENSO evolution. A cyclonic circulation anomaly over Hawaii, associated with the Pacific-North American pattern, also plays a role. These findings suggest that March MJO activity alone may not be a reliable predictor for ENSO evolution, but underscore the importance of North Pacific atmospheric variability.
GPT-4o mini: Non-social science research article
Giant KASH proteins and ribosomes establish distinct cytoplasmic biophysical properties in vivo
Xiangyi Ding, Hongyan Hao, Daniel Elnatan, Patrick Neo Alinaya, Shilpi Kalra, Abby Kaur, Sweta Kumari, Liam J. Holt, G. W. Gant Luxton, Daniel A. Starr
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Understanding how cells control their biophysical properties during development remains a fundamental challenge. While macromolecular crowding affects multiple cellular processes in single cells, its regulation in living animals remains poorly understood. Using genetically encoded multimeric nanoparticles for in vivo rheology, we found that Caenorhabditis elegans tissues maintain mesoscale properties that differ from those observed across diverse systems, including bacteria, yeast species, and cultured mammalian cells. We identified two conserved mechanisms controlling particle mobility: Ribosome concentration, a known regulator of cytoplasmic crowding, works in concert with a previously unknown function for the giant KASH (Klarsicht/ANC-1/SYNE homology) protein ANC-1 in providing structural constraints through associating with the endoplasmic reticulum. These findings reveal mechanisms by which tissues establish and maintain distinct mesoscale properties, with implications for understanding cellular organization across species.
GPT-4o mini: Non-social science research article
The OsbZIP35-COR1-OsTCP19 module modulates cell proliferation to regulate grain length and weight in rice
Penghui Xu, Najeeb Ullah Khan, Haozhen Wang, Yong Zhao, Bingxia Xu, Qianfeng Hu, Yinghua Pan, Danting Li, Junzhou Li, Xingming Sun, Jinjie Li, Hongliang Zhang, Zichao Li, Zhanying Zhang
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Grain size substantially influences rice quality and yield. In this study, we identified CONTROL OF SLENDER RICE 1 ( COR1 ), a quantitative trait locus encoding an F-box protein that enhances grain length by promoting cell proliferation. The transcription factor OsbZIP35 represses COR1 expression, while COR1 interacts with OsTCP19, leading to its degradation. Knockout of either OsbZIP35 or OsTCP19 results in increased grain length, confirming their regulatory roles in grain development. The OsbZIP35-COR1-OsTCP19 module controls the expression of the cell cycle gene OsCycB1;4 , thereby modulating cell proliferation and ultimately determining grain size. Five haplotypes of COR1 were identified, with COR1 -Hap1 and COR1 -Hap3 being elite alleles associated with longer grains. Field plot trials demonstrated that the near-isogenic line NIL- COR1 SLG increased yield by ~6.6% compared to NIL- COR1 Nip . These findings elucidate the genetic mechanisms underlying grain size regulation and offer promising strategies for improving rice yield.
GPT-4o mini: Non-social science research article
CD8 + HLA-DR + CD27 + T cells define a population of naturally occurring regulatory precursors in humans
Huidong Guo, Bixia Wang, Zhigui Wu, Qi Zhang, Xinya Jiang, Fangqing Zhang, Jingrui Zhou, Shuang Fan, Yang Zhou, Zheng-Li Xu, Yu Wang, Xiang-Yu Zhao, Xiao-Jun Huang
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Regulatory T reg cells are essential for immune homeostasis. While CD4 T reg cells are well characterized, CD8 T reg cells remain less understood and are primarily observed in pathological or experimental contexts. Here, we identify a naturally occurring CD8 regulatory precursor T rp cell at the steady state, defined by a CD8 + HLA-DR + CD27 + phenotype and a transcriptome resembling CD4 T reg cells. Multiomics analyses reveal activation of TCF7 and costimulatory and co-inhibitory molecules in CD8 T rp cells. CD8 T rp cells suppress T cell expansion in vitro and in vivo. In a humanized xenogeneic graft-versus-host disease (GVHD) model, they dampen T cell activation, alleviate GVHD pathology, and prolong survival without impairing antileukemia activity. Mechanistically, CD8 T rp cells promote immune regulation by inducing FOXP3 expression in both CD4 T reg cells and themselves. Their expansion also correlates with immune homeostasis restoration post–allogeneic stem cell transplantation. These findings establish CD8 T rp cells as a naturally occurring regulatory precursor population that promotes transplantation tolerance.
GPT-4o mini: Non-social science research article
Differential modulation of movement speed with state-dependent deep brain stimulation in Parkinson’s disease
Alessia Cavallo, Richard M. Köhler, Johannes L. Busch, Jeroen G. V. Habets, Timon Merk, Patricia Zvarova, Jojo Vanhoecke, Thomas S. Binns, Bassam Al-Fatly, Ana Luisa de Almeida Marcelino, Natasha Darcy, Gerd-Helge Schneider, Patricia Krause, Andreas Horn, Katharina Faust, Damian M. Herz, Eric Yttri, Hayriye Cagnan, Andrea A. KĂŒhn, Wolf-Julian Neumann
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Subthalamic deep brain stimulation (STN-DBS) provides unprecedented spatiotemporal precision for the treatment of Parkinson’s disease (PD), allowing for direct real-time state-specific adjustments. Inspired by findings from optogenetic stimulation in mice, we hypothesized that STN-DBS can mimic dopaminergic reinforcement of ongoing movement kinematics during stimulation. To investigate this hypothesis, we delivered DBS bursts during particularly fast and slow movements in 24 patients with PD. Our findings reveal that DBS during fast movements enhanced future movement speed more than DBS during slow movements, raising movement speed to the level of healthy controls. To understand which brain circuits mediate this neurophysiological mechanism, we investigated the behavioral effects using magnetic resonance imaging connectomics and motor cortex electrocorticography. Last, we demonstrate that machine learning–based brain signal decoding can be used to predict continuous movement speed for fully embedded state-dependent closed-loop algorithms. Our findings provide important evidence for reinforcement-based DBS circuit mechanisms that may inspire previously unexplored treatment avenues for dopaminergic disorders.
GPT-4o mini: Non-social science research article
Intermodal microwave-to-optical transduction using silicon-on-sapphire optomechanical ring resonator
I-Tung Chen, Nicholas S. Yama, Haoqin Deng, Qixuan Lin, Yue Yu, Abhi Saxena, Arka Majumdar, Kai-Mei C. Fu, Mo Li
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Optomechanical and electro-optomechanical systems have emerged as one of the most promising approaches for quantum microwave-to-optical transduction to interconnect distributed quantum modalities for scaling the quantum systems. These systems use suspended structures to increase mode overlap and mitigate loss to achieve high efficiency. However, the suspended design’s poor heat dissipation under strong drive limits the ultimate efficiency. Here, we demonstrate an unsuspended optomechanical ring resonator (OMR) based on the silicon-on-sapphire (SOS) platform for microwave-to-optical frequency conversion. The OMR achieves a triply resonant optical-to-optical conversion with an enhanced coupling rate G b  = 3.6 gigahertz per square-root milliwatt at a peak conversion efficiency of 1.2% with 3.6-milliwatt microwave drive power and a microwave-to-optical conversion efficiency of 1.5 × 10 −5 at 10-milliwatt optical drive power. Our results show that the unsuspended SOS platform, which mitigates the thermal effect and is compatible with superconducting qubits, is a promising platform for optomechanical circuitry and quantum transduction.
GPT-4o mini: Non-social science research article
Magnetic field–enhanced vertical integration enables embodied intelligence in untethered soft robots
Xiaosa Li, Xiao Xiao, Xiao Xiao, Zixiao Liu, Junhao Gong, Zenan Lin, Bing Xue, Shibo Liu, Xinru Wu, Wei Zhang, Dongkai Wang, Runze Zhao, Zihan Wang, Xiongwei Zhong, Yiliang Lin, Patrick Chia, Ximin He, John S. Ho, Ghim Wei Ho, Wei Ouyang, Wenbo Ding, Guangmin Zhou, Cecilia Laschi, Changsheng Wu
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Embodied intelligence in soft robotics offers unprecedented capabilities for operating in uncertain, confined, and fragile environments that challenge conventional technologies. However, achieving true embodied intelligence—which requires continuous environmental sensing, real-time control, and autonomous decision-making—faces challenges in energy management and system integration. We developed deformation-resilient flexible batteries with enhanced performance under magnetic fields inherently present in magnetically actuated soft robots, with capacity retention after 200 cycles improved from 31.3 to 57.3%. These compliant batteries enable large-area deployment of 44.9% across the robot body, and their vertical integration with rationally designed flexible hybrid circuits minimizes additional stiffness while maintaining deformability. This actuator-battery-sensor vertical integration methodology maximizes functional area utilization in a manta ray–inspired soft robot, establishing an untethered platform with sensing, communication, and stable power supply. The system demonstrates embodied intelligence in aquatic environments through diverse capabilities including perturbation correction, obstacle avoidance, and temperature monitoring, with proprioceptive and environmental sensing enabling real-time decision-making during magnetically actuated locomotion.
GPT-4o mini: Non-social science research article
Printed sensing human-machine interface with individualized adaptive machine learning
Guohui Wang, Yao Tang, Xinran Luo, Shengdi Lu, Yiru Zhou, Yi Lu, Guangyang Sun, Pei Liu, Jiayu Ning, Hua Jiang, Ke Hu, Hongzhen Liu, Wenqi Song, You Yu
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Developing intelligent robots with integrated sensing capabilities is critical for advanced manufacturing, medical robots, and embodied intelligence. Existing robotic sensing technologies are limited to recording of acceleration, driving torque, pressure feedback, and so on. Expanding and integrating with the multimodal sensors to mimic and even surpass the human feeling is substantially underdeveloped. Here, we introduce a printed soft human-machine interface consisting of an e-skin–enabled gesture recognitions with feedback stimulus and a soft robot with multimodal perception of contact pressure, temperature, thermal conductivity, and electrical conductivity. The sensing e-skin with adaptive machine learning was able to decode and classify the hand gestures with re-wearable convenience and individual’s differences. The soft interface provides the bidirectional communications between robotics and human bodies in the close-loop. This work could substantially extend the robotic intelligence and pave the way for more practical applications.
GPT-4o mini: Non-social science research article
Skin-adaptive focused flexible micromachined ultrasound transducers for wearable cardiovascular health monitoring
Jiawei Yuan, Zhikang Li, Yihe Zhao, Ruiyan Luo, Shaohui Qin, Jie Li, Min Li, Gengyu Han, Zixuan Li, Zilong Zhao, Jiazhu Li, Shiwang Zhang, Zheng Yuan, Xiangguang Han, Lihong Fan, Xiaozhang Wang, Tong Wang, Ping Yang, Libo Zhao, Lirong Yuan, Yi Lv, Rongqian Wu, Tzung K. Hsiai, Zhuangde Jiang
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Continuous monitoring of cardiovascular vital signs can reduce the incidence and mortality of cardiovascular diseases, yet cannot be implemented by current technologies because of device bulkiness and rigidity. Here, we report self-adhesive and skin-conformal ultrasonic transducer arrays that enable wearable monitoring of multiple hemodynamic parameters without interfering with daily activities. A skin-adaptive focused ultrasound method with rational array design is proposed to implement measurement under wide ranges of skin curvatures and depths with improved sensing performances. We introduce a self-adhesive hydrogel layer to enhance the acoustic impedance matching, biocompatibility and contact reliability at device-skin interfaces, and a microelectromechanical systems-compatible process for batch-to-batch and high-consistency manufacturing. The resultant transducer array, with a frequency of 2.4 megacycles per second and a –6 dB bandwidth of 47%, implements accurate and continuous detection of cardiovascular signs, including blood pressure (BP) waveforms of various arteries, heart rate and BP during exercises, and arterial stiffness, validated clinically.
GPT-4o mini: Non-social science research article
Seafloor geodesy unveils seismogenesis of large subduction earthquakes in Mexico
Víctor M. Cruz-Atienza, Josué Tago, Luis A. Domínguez, Vladimir Kostoglodov, Yoshihiro Ito, Efraín Ovando-Shelley, Tonatiuh Rodríguez-Nikl, Renata Gonzålez, Sara Franco, Darío Solano-Rojas, Joel Beltrån-Gracia, Paulina Miranda-García, Frédérick Boudin, Luis Rivera, Anne Bécel, Carlos Villafuerte, Jorge Real, Ekaterina Kazachkina, Arturo Ronquillo
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Based on measurements of near-trench deformations of the oceanic and overriding plates, in this investigation, we elucidate the tectonic and mechanical processes leading to the M w 7.0 (moment magnitude of 7.0) Acapulco, Mexico, earthquake in 2021. We exploit unprecedented ocean-bottom observations using ultralong-period “tilt mechanical amplifiers,” along with hydrostatic pressure, global navigation satellite system, and satellite interferometric synthetic aperture radar data. The joint inversion of these geodetic data, template-matching seismicity, and repeating earthquakes, revealed the first two shallow slow slip events (SSEs) observed in Mexico. The first one migrated from the trench to the earthquake hypocenter before rupture, and the second one occurred following an M w 7.3 long-term SSE induced by the earthquake. Episodic near-trench oceanic-crust deformations (i.e., tilt transients) associated with shallow and deep synchronous decoupling of the plate interface reveal the occurrence of “slab-pull surges” before three regional earthquakes of magnitude 7 or greater, including the Acapulco event, suggesting that they may serve as rupture precursors observable in subduction zones.
GPT-4o mini: Non-social science research article
End-to-end inverse design for programmable acoustic tweezers with simultaneous force and torque control by metasurfaces
Yu Liu, Hao-Wen Dong, Xue Jiang, Han-Jie Xiao, Chuan-Xin Zhang, Yue-Sheng Wang
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Acoustic tweezers leverage acoustic radiation forces for noncontact manipulation. One of the core bottlenecks in multidimensional manipulation is the lack of a systematic design methodology, which prevents the generation of an acoustic field that simultaneously meets the collaborative control requirements of multi-degree-of-freedom forces and torques, making it difficult to achieve precise control under conditions of stable suspension, high-frequency rotation, and complex spatial constraints. To address this challenge, we develop an end-to-end inverse design methodology for acoustic tweezers based on coding metasurfaces, establishing a dual-objective, dual-scale optimization paradigm. At the microscale, the phase modulation and transmission efficiency are co-optimized through coupled physical models. While at the mesoscale, the particle suspension and rotation dynamics are considered. Based on the inverse design framework constructed with a finite-bit element library, we successfully optimized the metasurface configuration with specific acoustic response characteristics and achieved noncontact, multi-degree-of-freedom customized manipulation of individual particles. This approach provides implementation pathways for adaptive multiscale strategies in precision engineering applications.
GPT-4o mini: Non-social science research article
Living with temperature changes: Salicylic acid at the crossroads of plant immunity and temperature resilience
Wei Li, Guoqing Sun, Wentao Yang, Naiyi Lin, Kaihuai Li, Fengquan Liu, Ming Chang (ćžžæ˜Ž)
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Salicylic acid (SA) is a key defense hormone shaped by temperature. High temperatures suppress, while low temperatures enhance, SA biosynthesis and signaling, thereby influencing plant immunity and temperature resilience. This review synthesizes current understanding of how temperature modulates SA pathways and their cross-talk with other hormones to balance growth and defense. We also propose a conceptual model positioning SA as a central integrator of temperature perception, immune regulation, and hormonal signaling. However, key questions remain: How do plants sense temperature shifts to regulate SA dynamics? How do temperature-induced epigenetic changes in SA pathways contribute to long-term adaptation? And how can these insights inform crop improvement? Addressing these gaps is essential for developing climate-resilient crops.
GPT-4o mini: Non-social science research article
Cicada rib-inspired tough films through nanoconfined crystallization for use in acoustic transducers
Jiajun Mao, Jia Yan, Ziyu Wang, Teng Ke, Jingsong Peng, Mingzhu Li, Qunfeng Cheng
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Acoustic transducers require films that demonstrate both toughness and fatigue resistance, presenting notable challenges when achieved through conventional nanoscale reinforcing strategies. Here, we found that the rib structure of a cicada’s tymbal exhibits exceptional toughness and fatigue resistance, attributed to its unique architecture composed of alternating soft and stiff polymer layers. Inspired by this rib structure, we developed a robust artificial rib film (ARF) using a nanoconfined crystallization strategy that involves the deposition of soft polyethylene oxide and stiff phenol formaldehyde. The ARF demonstrates a toughness amplification factor twice that of the cicada’s tymbal rib and exhibits an exceptionally long fatigue life. The nanoconfined crystallization restricts molecular motion and disperses external forces within the crystalline structure, thereby enhancing its mechanical properties. These improvements enable the ARF to outperform commercial polymer films as an acoustic transducer, achieving 2.7 times increase in frequency response and 2.2 times increase in displacement amplitude.
GPT-4o mini: Non-social science research article
Bioadaptive liquid-infused multifunctional fibers for long-term neural recording via BDNF stabilization and enhanced neural interaction
Tae Young Kim, Yeonzu Son, Keun-Young Yook, Dong Gyu Lee, Young Kim, Seo Jung Kim, Kijun Park, Yurim Lee, Tae Kyung Lee, Justin J. Chung, Congqi Yang, Seongjun Park, Jungmok Seo
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Brain-computer interfaces (BCIs) enable direct communication between the brain and computers. However, their long-term functionality remains limited due to signal degradation caused by acute insertion trauma, chronic foreign body reaction (FBR), and biofouling at the device-tissue interface. To address these challenges, we introduce a multifunctional surface modification strategy called targeting-specific interaction and blocking nonspecific adhesion (TAB) coating for flexible fiber, achieving a synergistic integration of mechanical compliance and biochemical stability. The coating combines brain-derived neurotrophic factor (BDNF) conjugation and a lubricant-infused surface. This dual-functional design enables selective interaction with neurons and astrocytes while preventing nonspecific adhesion. Notably, high-quality single-unit neural signals were stably recorded for more than 12 months after implantation, demonstrating exceptional long-term recording performance. Integrating mechanical compatibility, antifouling properties, and selective neural cell interaction, the TAB-coated multifunctional fiber represents a transformative approach for neural implants, bridging biological systems with computational systems.
GPT-4o mini: Non-social science research article
An early surge of norepinephrine along brainstem pathways drives sensory-evoked awakening
Noa Matosevich, Noa Regev, Uddi Kimchy, Noam Zelinger, Sina Kabaha, Noam Gabay, Amit Marmelshtein, Yuval Nir
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The locus coeruleus–norepinephrine (LC-NE) system regulates arousal and awakening; however, it remains unclear whether the LC does this in a global or circuit-specific manner. We hypothesized that sensory-evoked awakenings are predominantly regulated by specific LC-NE efferent pathways. Anatomical, physiological, and functional modularities of LC-NE pathways involving the mouse basal forebrain (BF) and pontine reticular nucleus (PRN) were tested. We found partial anatomical segregation between the LC → PRN and LC → BF circuits. Extracellular NE dynamics in BF and PRN exhibited distinct sound-evoked activation during sleep, including a fast sound-evoked NE peak specific to PRN. Causal optogenetic interrogation of LC efferent pathways, by retro-channelrhodopsin (ChR2) activation or Platynereis dumerilii ciliary opsin (PdCO) silencing of synapses in target regions, revealed a role for early LC → PRN activity in driving arousal and sound-evoked awakenings. Together, our results uncover a role for early LC-NE PRN activity in connecting sensory and arousal pathways and establish LC heterogeneity in regulating arousal.
GPT-4o mini: Non-social science research article
Magnitude uncertainty dominates intermodel spread in zonal-mean precipitation response to anthropogenic aerosol increase
Yu-Fan Geng, Shang-Ping Xie, Xiao-Tong Zheng, Hai Wang, Sarah M. Kang, Xiaopei Lin, Lixin Wu, Fengfei Song
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Anthropogenic aerosols are an important driver of historical climate change but the climate response is not fully understood and the climate model simulations suffer large uncertainties. On the basis of a multimodel ensemble of historical aerosol forcing simulation for a period of global aerosol increase during 1965 to 1989, here, we show that the precipitation response shares a common southward displacement of tropical rain bands but the magnitude differs markedly among models, accounting for 76% of the intermodel uncertainty in zonal-mean precipitation change. Our analysis of atmospheric energetics further reveals key mechanisms for magnitude uncertainty: aerosol radiative forcing drives, cloud radiative feedback amplifies, and ocean circulation damps the intermodel uncertainty in cross-equatorial atmospheric energy transport change and the meridional shift of tropical rain bands. This has important implications for understanding and reducing intermodel uncertainty in anthropogenic climate change.
GPT-4o mini: Non-social science research article
Non-neutralizing antibodies to influenza A matrix-protein-2-ectodomain are broadly effective therapeutics and resistant to viral escape mutations
Teha Kim, Lynn Bimler, Sydney L. Ronzulli, Amber Y. Song, Scott K. Johnson, Cheryl A. Jones, S. Mark Tompkins, Silke Paust
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Influenza A viruses remain a global health threat, yet no universal antibody therapy exists. Clinical programs have centered on neutralizing mAbs, only to be thwarted by strain specificity and rapid viral escape. We instead engineered three non-neutralizing IgG2a mAbs that target distinct, overlapping epitopes within the conserved N terminus of the M2 ectodomain (M2e). Combined at low dose, this “triple M2e-mAb” confers robust prophylactic and therapeutic protection in mice challenged with diverse human and zoonotic IAV strains, including highly pathogenic variants. Therapeutic efficacy depends on Fc-mediated effector activity via FcγRI, FcγRIII, and FcγRIV, rather than in vitro neutralization. Serial passaging in triple M2e-mAb–treated immunocompetent and immunodeficient hosts failed to generate viral escape mutants. Our findings redefine the influenza-specific antibody therapeutic design and support Fc-optimized, non-neutralizing M2e-mAbs as a broadly effective, mutation-resistant, off-the-shelve therapy with direct relevance to human pandemic preparedness.
GPT-4o mini: Non-social science research article
Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti–PD-1 therapy
Jielin Liu, Shelley Herbrich, Sreyashi Basu, Yulong Chen, Ashwat Nagarajan, Swetha Anandhan, Sangeeta Goswami, Liangwen Xiong, Baoxiang Guan, Padmanee Sharma
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PTDSS1 (phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti–PD-1 therapy. Depletion of Ptdss1 in tumor cells increased expression of interferon-γ (IFN-γ)–regulated genes, including B2m , Cxcl9 , Cxcl10 , and Stat1 , even in the absence of IFN-γ stimulation in vitro. Loss of Ptdss1 in tumor cells also led to increased expression of MHC-I, enhanced cytotoxicity of CD8 + T cells, and increased frequency of an iNOS + myeloid subset. A gene signature derived from the iNOS + myeloid cell subset correlated with clinical benefit in patients treated with anti–PD-1 therapy. Moreover, genetic and pharmacological inhibition of Ptdss1 in different tumor models improved anti–PD-1 therapy. Together, our results provide insights on a therapeutic strategy for overcoming immunosuppression by inhibiting PTDSS1 and provide rationale for development of a combination immunotherapy strategy composed of PTDSS1 inhibition plus PD-1 blockade.
GPT-4o mini: Non-social science research article
Rapid moving by liquid-amplified electrostatic rolling
Fei Jia, Shengjun Fan, Jianglong Guo, Yanju Liu, Jinsong Leng
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Mobile robots that simultaneously have fast speeds, sufficient load-carrying capabilities, and multiple locomotive functions have always been challenging to develop. Here, we introduce a liquid-amplified electrostatic rolling (LAER) mechanism, which elegantly integrates actuation and adhesion into a streamline single-degree-of-freedom structure. Based on this, we developed a rigid tethered LAER roller (0.015 grams) that exhibited a rapid moving speed of ~210 body length per second on ceilings and a flexible tethered roller (10.600 grams) that had a load-to-weight ratio of ~121 moving on the ground. Liquid regulating modules were embedded into LAER structures to exhibit controlled moving. We also developed a single-wheeled and two-wheeled untethered LAER robots with onboard power supply. Furthermore, we demonstrate a LAER linear actuator and a camera equipped untethered LAER robot for preliminary environmental monitoring. The lightweight, scalable LAER structure is promising to bring fast electrostatic actuators, motors, and robots with superior load-to-weight ratios and multimodal locomotion capabilities such as turning, circular moving, and plane-to-plane transitioning.
GPT-4o mini: Non-social science research article
A compact cassette tape for DNA-based data storage
Jiankai Li, Cuiping Mao, Shuchen Wang, Xingjian Li, Xueqing Luo, Dou Wang, Shuo Zheng, Jialin Shao, Rui Wang, Chunhai Fan, Xingyu Jiang
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DNA with high storage density can serve as an alternative storage medium to respond to the global explosion of data growth and become a powerful personal storage memory if an integrated compact device can store and handle large-scale data. Here, we incorporate a DNA cassette tape with 5.5 × 10 5 addressable data partitions (addressing rate up to 1570 partitions per second), a DNA loading capacity of 28.6 mg per kilometer, and deposit-many-recover-many (DMRM) features per partition to flexibly manage large-scale storage data and achieve hundreds of years of data preservation. We develop a compact DNA cassette tape drive and verify its functionality by randomly depositing incomplete images into the data partition, demonstrating a completely automated closed-loop operation involving addressing, recovery, removal, subsequent file deposition, and file recovery again, all accomplished within 50 min. Last, the complete image is restored by next-generation sequencing and decoding. DNA cassette tape provides a strategy for fast, compact, large-scale DNA-based cold or warm data storage.
GPT-4o mini: Non-social science research article
Single-cell multiome and spatial profiling reveals pancreas cell type–specific gene regulatory programs of type 1 diabetes progression
Rebecca Melton, Sara Jimenez, Weston Elison, Luca Tucciarone, Abigail Howell, Gaowei Wang, Denise Berti, Elisha Beebe, Michael Miller, Chun Zeng, Carolyn McGrail, Kennedy VanderStel, Katha Korgaonkar, Ruth Elgamal, Hannah Mummey, Joshua Chiou, Emily Griffin, Irina Kusmartseva, Mark Atkinson, Sebastian Preissl, Fabian J. Theis, Maike Sander, Kyle J. Gaulton
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Cell type–specific regulatory programs that drive type 1 diabetes (T1D) in the pancreas are poorly understood. Here, we performed single-nucleus multiomics and spatial transcriptomics in up to 32 nondiabetic (ND), autoantibody-positive (AAB + ), and T1D pancreas donors. Genomic profiles from 853,005 cells mapped to 12 pancreatic cell types, including multiple exocrine subtypes. ÎČ, Acinar, and other cell types, and related cellular niches, had altered abundance and gene activity in T1D progression, including distinct pathways altered in AAB + compared to T1D. We identified epigenomic drivers of gene activity in T1D and AAB + which, combined with genetic association, revealed causal pathways of T1D risk including antigen presentation in ÎČ cells. Last, single-cell and spatial profiles together revealed widespread changes in cell-cell signaling in T1D including signals affecting ÎČ cell regulation. Overall, these results revealed drivers of T1D in the pancreas, which form the basis for therapeutic targets for disease prevention.
GPT-4o mini: Non-social science research article
Genomic characterization of normal and aberrant human milk production
Yarden Golan, Sarah K. Nyquist, Zhe Liu, Dena Ennis, Jingjing Zhao, Emily Blair, Abdur Rahim Khan, Mary Prahl, Stephanie L. Gaw, Moran Yassour, Barbara E. Engelhardt, Valerie J. Flaherman, Nadav Ahituv
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Breastfeeding is essential for reducing infant morbidity and mortality, yet exclusive breastfeeding rates remain low, often because of insufficient milk production. The molecular causes of low milk production are not well understood. Fresh milk samples from 30 lactating individuals, classified by milk production levels across postpartum stages, were analyzed using genomic and microbiome techniques. Bulk RNA sequencing of milk fat globules (MFGs), milk cells, and breast tissue revealed that MFG-derived RNA closely mirrors luminal milk cells. Transcriptomic and single-cell RNA analyses identified changes in gene expression and cellular composition, highlighting key genes ( GLP1R , PLIN4 , and KLF10 ) and cell-type differences between low and high producers. Infant microbiome diversity was influenced by feeding type but not maternal milk production. This study provides a comprehensive human milk transcriptomic catalog and highlights that MFG could serve as a useful biomarker for milk transcriptome analysis, offering insights into the genetic factors influencing milk production.
GPT-4o mini: Non-social science research article
Molecular exaptation by the integrin αI domain
Jeremy A. Hollis, Matthew C. Chan, Harmit S. Malik, Melody G. Campbell
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Integrins bind ligands between their alpha (α) and beta (ÎČ) subunits and transmit signals through conformational changes. Early in chordate evolution, some α subunits acquired an “inserted” (I) domain that expanded integrin’s ligand-binding repertoire but obstructed the ancestral ligand pocket, seemingly blocking conventional integrin activation. Here, we compare cryo–electron microscopy structures of apo and ligand-bound states of the I domain–containing αEÎČ 7 integrin and the I domain–lacking α 4 ÎČ 7 integrin to illuminate how the I domain intrinsically mimics an extrinsic ligand to preserve integrin function. We trace the I domain’s evolutionary origin to an ancestral collagen-collagen interaction domain, identifying an ancient molecular exaptation that facilitated integrin activation immediately upon I domain insertion. Our analyses reveal the evolutionary and biochemical basis of expanded cellular communication in vertebrates.
Investigating the Aliso Canyon gas blowout disaster and adverse birth outcomes: A quasiexperimental approach
Kimberly C. Paul, John Molitor, Yu Yu, Christina Batteate, Massimo Stafoggia, Sanjali Mitra, Qi Meng, Diane Garcia-Gonzales, Myles Cockburn, David Eisenman, Sudipto Banerjee, Honghu Liu, Michael Jerrett, Beate Ritz
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On 23 October 2015, operators at the Aliso Canyon Natural Gas Storage field in Northern Los Angeles reported an uncontrolled natural gas leak. The blowout persisted for 112 days, releasing ~109,000 metric tons of methane into the atmosphere. Elevated air toxics and fine particle pollutant levels were also measured in nearby communities. We used California’s birth records and a quasiexperimental design to assess whether pregnant women living in affected communities during the disaster experienced more adverse birth outcomes than expected. Overall, the prevalence of low birthweight and term low birthweight were 45 to 100% higher than expected among women living in the affected communities whose late pregnancy overlapped with the blowout. The strongest effects were observed among women living directly south and southwest of the facility. Furthermore, we observed a dose-response effect, where the odds of low birthweight were highest among women living closest to the well and attenuated out.
Investigating the know-do gap in antibiotics prescribing: Experimental evidence from India
Zachary Wagner, Manoj Mohanan, Arnab Mukherji, Rushil Zutshi, Sumeet Patil, Jagadish Krishnappa, Somalee Banerjee, Neeraj Sood
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Antimicrobial resistance is largely driven by overuse of antibiotics, which is particularly common in low- and middle-income countries. We combine provider knowledge assessments and over 2000 anonymous standardized patient visits to providers in India to examine why they overprescribe antibiotics for pediatric diarrhea and figure out how to reduce overprescribing. Seventy percent of providers prescribed antibiotics without indication of bacterial infection. Knowledge gaps explain little: 62% of providers who knew antibiotics were inappropriate still prescribed them. Closing this “know-do gap” would reduce prescribing by 30 percentage points, versus only 6 points if all providers had perfect knowledge. Using randomized experiments, we revealed that the know-do gap stems from providers’ beliefs that patients want antibiotics, not from profit motives or lack of alternative treatments. Yet, a discrete choice experiment suggests patients do not prefer providers who give antibiotics. Our findings indicate that addressing provider misperceptions about patient preferences may be more effective than standard information-based interventions in reducing antibiotic overuse.