I checked 6 multidisciplinary journals on Thursday, July 03, 2025 using the Crossref API. For the period June 26 to July 02, I found 20 new paper(s) in 5 journal(s).

Nature

GPT-4o mini: Non-social science research article
Architecture, dynamics and biogenesis of GluA3 AMPA glutamate receptors
Aditya Pokharna, Imogen Stockwell, Josip Ivica, Bishal Singh, Johannes Schwab, Carlos Vega-Gutiérrez, Beatriz Herguedas, Ondrej Cais, James M. Krieger, Ingo H. Greger
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AMPA-type glutamate receptors (AMPARs) mediate the majority of excitatory neurotransmission in the brain1. Assembled from combinations of four core subunits, GluA1-4, and ~20 auxiliary subunits, their molecular diversity tunes information transfer and storage in a brain circuit-specific manner. GluA3, a subtype strongly associated with disease2, functions as both a fast transmitting Ca2+-permeable (CP) AMPAR at sensory synapses3, and as a Ca2+-impermeable (CI) receptor at cortical synapses4,5. Here, we present cryo-EM structures of the CP GluA3 homomer, which substantially diverge from other AMPARs. The GluA3 extracellular domain tiers (NTD and LBD) are closely coupled throughout gating states, creating previously unseen interfaces that impact signalling and harbour human disease mutations. Central to this architecture is a stacking interaction between two arginine residues (Arg163) in the NTD dimer interface, trapping a unique NTD dimer conformation that enables close contacts with the LBD. Rupture of the Arg163 stack not only alters the structure and dynamics of the GluA3 extracellular region, but also increases receptor trafficking, and the expression of GluA3 heteromers at the synapse. We further show that a mammalian-specific GluA3 trafficking checkpoint determines conformational stability of the LBD tier. Hence, specific design features define communication and biogenesis of GluA3, offering a framework to interrogate this disease-prone glutamate receptor.
GPT-4o mini: Non-social science research article
Addendum: Unravelling cysteine-deficiency-associated rapid weight loss
Alan Varghese, Ivan Gusarov, Begoña Gamallo-Lana, Daria Dolgonos, Yatin Mankan, Ilya Shamovsky, Mydia Phan, Rebecca Jones, Maria Gomez-Jenkins, Eileen White, Rui Wang, Drew R. Jones, Thales Papagiannakopoulos, Michael E. Pacold, Adam C. Mar, Dan R. Littman, Evgeny Nudler
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GPT-4o mini: Non-social science research article
Rewiring endogenous genes in CAR T cells for tumour-restricted payload delivery
Amanda X. Y. Chen, Kah Min Yap, Joelle S. Kim, Kevin Sek, Yu-Kuan Huang, Phoebe A. Dunbar, Volker Wiebking, Jesse D. Armitage, Isabelle Munoz, Kirsten L. Todd, Emily B. Derrick, Dat Nguyen, Junming Tong, Cheok Weng Chan, Thang X. Hoang, Katherine M. Audsley, Marit J. van Elsas, Jim Middelburg, Joel N. Lee, Maria N. de Menezes, Thomas J. Cole, Jasmine Li, Christina Scheffler, Andrew M. Scott, Laura K. Mackay, Jason Waithman, Jane Oliaro, Simon J. Harrison, Ian A. Parish, Junyun Lai, Matthew H. Porteus, Imran G. House, Phillip K. Darcy, Paul A. Beavis
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The efficacy of chimeric antigen receptor (CAR) T cell therapy in solid tumours is limited by immunosuppression and antigen heterogeneity1,2,3. To overcome these barriers, ‘armoured’ CAR T cells, which secrete proinflammatory cytokines, have been developed4. However, their clinical application has been limited because of toxicity related to peripheral expression of the armouring transgene5. Here, we have developed a CRISPR knock-in strategy that leverages the regulatory mechanisms of endogenous genes to drive transgene expression in a tumour-localized manner. By screening endogenous genes with tumour-restricted expression, we have identified the NR4A2 and RGS16 promoters as promising candidates to support the delivery of cytokines such as IL-12 and IL-2 directly to the tumour site, leading to enhanced antitumour efficacy and long-term survival of mice in both syngeneic and xenogeneic models. This effect was concomitant with improved CAR T cell polyfunctionality, activation of endogenous antitumour immunity and a favourable safety profile, and was applicable in CAR T cells from patients.
GPT-4o mini: Non-social science research article
The Somatic Mosaicism across Human Tissues Network
Tim H. H. Coorens, Ji Won Oh, Yujin Angelina Choi, Nam Seop Lim, Boxun Zhao, Adam Voshall, Alexej Abyzov, Lucinda Antonacci-Fulton, Samuel Aparicio, Kristin G. Ardlie, Thomas J. Bell, James T. Bennett, Bradley E. Bernstein, Thomas G. Blanchard, Alan P. Boyle, Jason D. Buenrostro, Kathleen H. Burns, Fei Chen, Rui Chen, Sangita Choudhury, Harsha V. Doddapaneni, Evan E. Eichler, Gilad D. Evrony, Melissa A. Faith, Thomas G. Fazzio, Robert S. Fulton, Manuel Garber, Nils Gehlenborg, Soren Germer, Gad Getz, Richard A. Gibbs, Raquel G. Hernandez, Fulai Jin, Jan O. Korbel, Dan A. Landau, Heather A. Lawson, Niall J. Lennon, Heng Li, Yan Li, Po-Ru Loh, Gabor Marth, Michael J. McConnell, Ryan E. Mills, Stephen B. Montgomery, Pradeep Natarajan, Peter J. Park, Rahul Satija, Fritz J. Sedlazeck, Diane D. Shao, Hui Shen, Andrew B. Stergachis, Hunter R. Underhill, Alexander E. Urban, Melissa W. VonDran, Christopher A. Walsh, Ting Wang, Tao P. Wu, Chenghang Zong, Eunjung Alice Lee, Flora M. Vaccarino, character(0), character(0), Richard S. Conroy, Brionna Y. Hair, Walter J. Koroshetz, Roger Little, Amy C. Lossie, Jill A. Morris, Dena C. Procaccini, Wendy Wang, character(0), Casey Andrews, Sarah Cody, Milinn Kremitzki, Daofeng Li, Tina Lindsay, Wenjin Zhang, character(0), Valerie J. Estela-Pro, Kayla Giancarlo, Melissa Grimm, Azra Hasan, M. Kathryn Leonard, Phoebe McDermott, Mary Pfeiffer, Isabel Sleeman, character(0), character(0), Stephanie Bohaczuk, Colleen P. Davis, Christian D. Frazar, Kendra Hoekzema, Meng-Fan Huang, Caitlin Jacques, Dana M. Jensen, J. Thomas Kolar, Youngjun Kwon, Kelsey Loy, Yizi Mao, Min-Hwan Sohn, Katherine M. Munson, Shane Neph, Jeffrey Ou, Nancy L. Parmalee, Meranda M. Pham, Jane Ranchalis, Luyao Ren, Adriana E. Sedeño-CortĂ©s, Joshua D. Smith, Melanie Sorensen, Lila Sutherlin, Mitchell R. Vollger, Chia-Lin Wei, Jeffrey M. Weiss, Christina Zakarian, Natalie Y. T. Au, Amy Leonardson, Jiadong Lin, Taralynn Mack, Sean R. McGee, Anna Minkina, Patrick M. Nielsen, Chris Oliveira, Erica Ryke, Tristan Shaffer, Elliott G. Swanson, character(0), Elizabeth G. Atkinson, Sravya Bhamidipati, Hsu Chao, Christopher M. Grochowski, Harsha V. Doddapaneni, Divya Kalra, Ziad Khan, Kavya Kottapalli, Marie-Claude Gingras, Walker Hale, Heer Mehta, Donna M. Muzny, Muchun Niu, Luis F. Paulin, Jeffrey Rogers, Evette Scott, Fritz J. Sedlazeck, Kimberly Walker, Tao Wu, character(0), Kristin G. Ardlie, Viktor Adalsteinsson, Lisa Anderson, Carrie Cibulskis, Laura DomĂšnech, Kiran Garimella, Whitney Hornsby, Steve Huang, Satoshi Koyama, Niall J. Lennon, Tetsushi Nakao, Azeet Narayan, Evin Padhi, Constantijn Scharlee, Md Mesbah Uddin, Liying Xue, Zhi Yu, Shadi Zaheri, Ruolin Liu, Ning Stella Li, Hang Su, character(0), Derek Albracht, Eddie Belter, Emma Casey, Justin Chen, Yuchen Cheng, Shihua Dong, Qichen Fu, Robert Fulton, John Garza, H. Josh Jang, Sheng Chih Jin, Benjamin K. Johnson, Nahyun Kong, Daofeng Li, Zefan Li, Shane Liu, Juan F. Macias-Velasco, Elvisa Mehinovic, Benpeng Miao, Theron Palmer, Purva Patel, Mary F. Majewski, Daniel C. Rohrer, Andrew Ruttenberg, Ayush Semwal, Jiawei Shen, Zitian Tang, Chad Tomlinson, Wenjin Zhang, Zilan Xin, Christina Missler, Brianne E. Livermore, character(0), Jade E. B. Carter, William Driscoll, Uday S. Evani, Heather Geiger, M. Tausif Hasan, Manisha Kher, Rajeeva Musunuri, Giuseppe Narzisi, Nicolas Robine, Alexi Runnels, character(0), Mingyun Bae, Michele Berselli, Ann Caplin, Hye-Jung Elizabeth Chun, Niklas L. Engel, William C. Feng, Yan Gao, Dominik Glodzik, Yoo-Jin Jiny Ha, Hu Jin, Sehi L’Yi, Lovelace J. Luquette, Maximilian Marin, Julia Markowski, Dominika Maziec, Huang Neng, Sarah Nicholson, Junseok Park, Qin Qian, Han Qu, Douglas Rioux, William Ronchetti, Andrew Schroeder, Corinne E. Sexton, Yichen Si, Kar-Tong Tan, David Tang, Alexander D. Veit, Vinayak V. Viswanadham, Suenghyun Wang, Kyung Ah Woo, Xi Zeng, Yuwei Zhang, Yifan Zhao, Ying Zhou, Michail Andreopoulos, Shannon Ehmsen, Cesar Ferreyra-Mansilla, Clara TaeHee Kim, David Michaels, Bianca Morris, character(0), character(0), Brandt A. Bessell, Ingrid Flashpohler, Steve Losh, Torrin L. McDonald, Camille Mumm, Jessica A. Switzenberg, Jinhao Wang, Weichen Zhou, character(0), Guanlan Dong, Nazia Hilal, Se-Young Jo, Shayna L. Mallett, Monica Devi Manam, Shulin Mao, Christopher Walsh, Sijing Zhao, character(0), Yiling Elaine Huang, Abhiram Natu, Reenal Pattni, Carolin Purman, Bo Zhou, Xiaowei Zhu, character(0), Jiayi Luo, Yichi Niu, Rohan Thakur, David A. Weitz, Yang Zhang, character(0), Yilei Fu, Michal B. Izydorczyk, Luis F. Paulin, Xiaomei Zhan, Xinchang Zheng, character(0), Geon Hue Bae, Taejeong Bae, Areum Cho, June Hyug Choi, Hyungbin Chun, Mrunal Dehankar, Yeongjun Jang, Seok-Won Jeong, Min Ji, Mee Sook Jun, Su Rim Kim, Seong Gyu Kwon, Soung-Hoon Lee, Nanda Maya Mali, Arijit Panda, Jung Min Park, JaeEun Shin, Milovan Suvakov, character(0), Gabor T. Marth, Brad Demarest, Stephanie Gardiner, Stephanie J. Georges, Yingqi Zhang, character(0), Sammantha Avaylon, Alexandre Pellan Cheng, Wei-Yu Chi, Mariela CortĂ©s-LĂłpez, Andrew R. D’Avino, Husain Danish, Elliot Eton, Foteini Fotopoulo, Saravanan Ganesan, Yiyun Lin, Qing Luo, Levan Mekerishvili, Joe Pelt, Catherine Potenski, Tamara Prieto, Jake Qiu, Ivan Raimondi, Mandeep Singh, Dennis Yuan, John Zinno, character(0), Benjamin Costa, Jonathan Evan Shoag, Jimin Tan, Aristotelis Tsirigos, Nisrine T. Jabara, Marta GroƄska-Pęski, character(0), Emre Caglayan, Hayley Cline, Niklas L. Engel, Shelbi E. Gill, Robert Sean Hill, Andrea J. Kriz, Julia Markowski, Alisa Mo, Daniel Snellings, character(0), Justin S. Becker, Aidan H. Burn, Wen-Chih Cheng, Jennifer A. Karlow, Cheuk-Ting Law, Shayna L. Mallet, Carlos Mendez-Dorantes, Khue H. Nguyen, Adam Voshall, Boxun Zhao, character(0), Benno Orr, Andrew J. C. Russell, character(0), He Li, Yan Li, Leina Lu, Xiaofeng Zhu, character(0), Trishita Basak, Azita Ghodssi, Katrina Newcomer, Yuqing Wang
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From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues Network, which aims to create a reference catalogue of somatic mutations and their clonal patterns across 19 different tissue sites from 150 non-diseased donors and develop new technologies and computational tools to detect somatic mutations and assess their phenotypic consequences, including clonal expansions. This strategy enables a comprehensive examination of the mutational landscape across the human body, and provides a comparison baseline for somatic mutation in diseases. This will lead to a deep understanding of somatic mutations and clonal expansions across the lifespan, as well as their roles in health, in ageing and, by comparison, in diseases.
GPT-4o mini: Non-social science research article
A mouse brain stereotaxic topographic atlas with isotropic 1-ÎŒm resolution
Zhao Feng, Xiangning Li, Yue Luo, Xin Liu, Ben Long, Tao Jiang, Xueyan Jia, Xiaowei Chen, Jie Luo, Xiaokang Chai, Zhen Wang, Miao Ren, Xin Lu, Gang Yao, Mengting Zhao, Yuxin Li, Zhixiang Liu, Hong Ni, Chuhao Dou, Shengda Bao, Shicheng Yang, Zoutao Zhang, Jiandong Zhou, Lingyi Cai, Qi Zhang, Ayizuohere Tudi, Chaozhen Tan, Zhengchao Xu, Siqi Chen, Wenxiang Ding, Wenjuan Shi, Anan Li, Hong-wei Dong, Hui Gong, Qingming Luo
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Multi-omics studies, represented by connectomes and spatial transcriptomes, have entered the era of single-cell resolution, necessitating a reference brain atlas with spatial localization capability at the single-cell level 1–4 . However, such atlases are unavailable 5 . Here we present a whole mouse brain dataset of Nissl-based cytoarchitecture with isotropic 1-ÎŒm resolution, achieved through continuous micro-optical sectioning tomography. By integrating multi-modal images, we constructed a three-dimensional reference atlas of the mouse brain, providing the three-dimensional topographies of 916 structures and enabling arbitrary-angle slice image generation at 1-ÎŒm resolution. We developed an informatics-based platform for visualizing and sharing of the atlas images, offering services such as brain slice registration, neuronal circuit mapping and intelligent stereotaxic surgery planning. This atlas is interoperable with widely used stereotaxic atlases, supporting cross-atlas navigation of corresponding coronal planes in two dimensions and spatial mapping across atlas spaces in three dimensions. By facilitating the data analysis and visualization for large brain mapping projects, our atlas promises to be a versatile brainsmatics tool for studying the whole brain at single-cell level.
GPT-4o mini: Non-social science research article
Stereodivergent transformation of a natural polyester to enantiopure PHAs
Jun-Jie Tian, Ruirui Li, Ethan C. Quinn, Jiyun Nam, Eswara Rao Chokkapu, Zhen Zhang, Li Zhou, Ravikumar R. Gowda, Eugene Y.-X. Chen
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Natural chiral polymers, such as DNA, proteins, cellulose and poly[(R)-3-hydroxybutyrate] ((R)-P3HB), are prevalent in their enantiopure forms1,2. Existing methods to synthesize enantiopure polymers focus on enantiospecific polymerization, in which only one specific enantiomer is obtained from the corresponding chiral monomer3,4,5,6. Here we introduce a catalytic stereodivergent synthetic strategy to access all enantiopure di-isotactic poly(3-hydroxyalkanoate) (PHA) diastereomers from bacterial (R)-P3HB as the single chiral source. A series of enantiopure (R,R)-α-alkylated-ÎČ-butyrolactones are obtained from (R)-P3HB and then subjected to the catalyst-controlled diastereodivergent ring-opening polymerization (ROP) to enantiopure di-isotactic α-alkylated PHAs. Metal-catalysed coordination–insertion ROP results in threo-(R,R)-di-isotactic PHAs with chiral retention, whereas anionic ROP catalysed by an organic superbase produces erythro-(R,S)-di-isotactic PHAs with chiral inversion, achieving precision di-isotactic PHAs with exclusive regio- and stereoregularity. This strategy has also enabled the stereodivergent synthesis of all four [(R,R), (S,S), (R,S) and (S,R)] stereoisomers of α,α-dialkylated PHAs from (R)-P3HB, which can be depolymerized to chiral α,α-dialkylated-ÎČ-butyrolactones with high stereoselectivity. Overall, this catalyst-controlled regio- and stereoselective, stereodivergent synthetic methodology provides access to 16 enantiopure stereoisomers of α(α)-(di)substituted PHAs and enables the stereochemistry-defined structure–property relationship study of the di-isotactic PHAs, providing insights into the effects of main-chain stereoconfigurations and alkyl side chains on their thermal properties, melt processability, mechanical performance and supramolecular stereocomplexation.
GPT-4o mini: Non-social science research article
Energy–speed relationship of quantum particles challenges Bohmian mechanics
Violetta Sharoglazova, Marius Puplauskis, Charlie Mattschas, Chris Toebes, Jan Klaers
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Classical mechanics characterizes the kinetic energy of a particle, the energy it holds due to its motion, as consistently positive. By contrast, quantum mechanics describes the motion of particles using wave functions, in which regions of negative local kinetic energy can emerge 1 . This phenomenon occurs when the amplitude of the wave function experiences notable decay, typically associated with quantum tunnelling. Here, we investigate the quantum mechanical motion of particles in a system of two coupled waveguides, in which the population transfer between the waveguides acts as a clock, allowing particle speeds along the waveguide axis to be determined. By applying this scheme to exponentially decaying quantum states at a reflective potential step, we determine an energy–speed relationship for particles with negative local kinetic energy. We find that the smaller the energy of the particles—in other words, the more negative the local kinetic energy—the higher the measured speed inside the potential step. Our findings contribute to the ongoing tunnelling time debate 2–6 and can be viewed as a test of Bohmian trajectories in quantum mechanics 7–9 . Regarding the latter, we find that the measured energy–speed relationship does not align with the particle dynamics postulated by the guiding equation in Bohmian mechanics.
GPT-4o mini: Non-social science research article
Mapping the adaptive landscape of Batesian mimicry using 3D-printed stimuli
Christopher H. Taylor, David James George Watson, John Skelhorn, Danny Bell, Simon Burdett, Aoife Codyre, Kathryn Cooley, James R. Davies, Joshua Joseph Dawson, TahirĂ© D’Cruz, Samir Raj Gandhi, Hannah J. Jackson, Rebecca Lowe, Elizabeth Ogilvie, Alexandra Lei Pond, Hallie Rees, Joseph Richardson, Joshua Sains, Francis Short, Christopher Brignell, Gabrielle L. Davidson, Hannah M. Rowland, Mark East, Ruth Goodridge, Francis Gilbert, Tom Reader
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In a classic example of adaptation, harmless Batesian mimics gain protection from predators through resemblance to one or more unpalatable models 1,2 . Mimics vary greatly in accuracy, and explaining the persistence of inaccurate mimics is an ongoing challenge for evolutionary biologists 3,4 . Empirical testing of existing hypotheses is constrained by the difficulty of assessing the fitness of phenotypes absent among extant species, leaving large parts of the adaptive landscape unexplored 5 —a problem affecting the study of the evolution of most complex traits. Here, to address this, we created mimetic phenotypes that occupy hypothetical areas of trait space by morphing between 3D images of real insects (flies and wasps), and tested the responses of real predators to high-resolution, full-colour 3D-printed reproductions of these phenotypes. We found that birds have an excellent ability to learn to discriminate among insects on the basis of subtle differences in appearance, but this ability is weaker for pattern and shape than for colour and size traits. We found that mimics gained no special protection from intermediate resemblance to multiple model phenotypes. However, discrimination ability was lower in some invertebrate predators (especially crab spiders and mantises), highlighting that the predator community is key to explaining the apparent inaccuracy of many mimics.
GPT-4o mini: Non-social science research article
Discovering cognitive strategies with tiny recurrent neural networks
Li Ji-An, Marcus K. Benna, Marcelo G. Mattar
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Understanding how animals and humans learn from experience to make adaptive decisions is a fundamental goal of neuroscience and psychology. Normative modelling frameworks such as Bayesian inference 1 and reinforcement learning 2 provide valuable insights into the principles governing adaptive behaviour. However, the simplicity of these frameworks often limits their ability to capture realistic biological behaviour, leading to cycles of handcrafted adjustments that are prone to researcher subjectivity. Here we present a novel modelling approach that leverages recurrent neural networks to discover the cognitive algorithms governing biological decision-making. We show that neural networks with just one to four units often outperform classical cognitive models and match larger neural networks in predicting the choices of individual animals and humans, across six well-studied reward-learning tasks. Critically, we can interpret the trained networks using dynamical systems concepts, enabling a unified comparison of cognitive models and revealing detailed mechanisms underlying choice behaviour. Our approach also estimates the dimensionality of behaviour 3 and offers insights into algorithms learned by meta-reinforcement learning artificial intelligence agents. Overall, we present a systematic approach for discovering interpretable cognitive strategies in decision-making, offering insights into neural mechanisms and a foundation for studying healthy and dysfunctional cognition.
GPT-4o mini: Non-social science research article
Boron-mediated modular assembly of tetrasubstituted alkenes
Liang Wei, Mihai V. Popescu, Adam Noble, Robert S. Paton, Varinder K. Aggarwal
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Alkenes are a central part of organic chemistry 1–3 . However, although most alkenes are easy to prepare, the controlled synthesis of tetrasubstituted alkenes, those with four groups around the central C=C bond, remains challenging 1–5 . Here we report the boron-mediated assembly of tetrasubstituted alkenes with complete control of the double-bond geometry. The migrating group and electrophile add syn across the alkyne. Mild oxidation leads to intermediate borinic esters 6 , which can be isolated and purified or reacted directly in a range of transformations, including cross-couplings and homologation reactions. In particular, subjecting the intermediate borinic esters to Zweifel 7,8 olefination conditions can give either retention or inversion of the double-bond geometry, depending on whether base is present or not. Different positional and stereoisomers of the tetrasubstituted alkenes can be easily accessed, highlighting the breadth and versatility of the method. This was showcased through its successful application to the rapid synthesis of drug molecules and natural products with high yield and stereocontrol. Not only does this method provide efficient access to the long-standing challenge of the stereocontrolled synthesis of tetrasubstituted alkenes but it also introduces new concepts related to the intervention of non-classical borenium ions in the Zweifel olefination.
GPT-4o mini: Non-social science research article
Trade-offs in aviation impacts on climate favour non-CO2 mitigation
Michael J. Prather, Andrew Gettelman, Joyce E. Penner
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Climate assessments of civil aviation1,2 have consistently quantified the dominant climate-forcing components: (1) CO2 emissions, (2) NOx (NO + NO2) emissions and (3) persistent contrails. All three components exert a positive radiative forcing (RF) and lead to climate warming of similar magnitudes. The aviation community is actively seeking to reduce its climate footprint through advanced engine technologies, more sustainable aviation fuel and optimal routing plans3,4,5,6,7,8,9,10,11,12. These approaches usually involve a trade-off of CO2 against NOx or contrails (non-CO2), such as burning 1% more fuel to decrease contrail RF by 4%. Here, we show that a climate-trade-off risk curve derived from uncertainties in the RF components2,13,14,15,16 can give the probability that a specified trade-off ratio will produce a climate benefit. For each component, we calculate the integrated effective RF resulting from 1 year of flights: global warming per activity (GWA). The complementary cumulative probability distribution of the GWA(non-CO2) to GWA(CO2) ratio results in a climate-trade-off risk curve giving the likelihood of a positive climate outcome as a function of the trade-off-CO2 to trade-off-non-CO2 ratio, because the product, GWA × trade-off, should be the same for both. We find a likely (67%) chance of climate mitigation on a 100-year time horizon for the above suggested ratio of 1:4, favouring proposed non-CO2 mitigation efforts3,4,5,6,7,8,9,10,11,12 with ratios smaller than this.
GPT-4o mini: Non-social science research article
Plants monitor the integrity of their barrier by sensing gas diffusion
Hiroyuki Iida, Isidro Abreu, Jennifer López Ortiz, Lucas León Peralta Ogorek, Vinay Shukla, Meeri MÀkelÀ, Munan Lyu, Alexey Shapiguzov, Francesco Licausi, Ari Pekka MÀhönen
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Barrier tissues isolate organisms from their surrounding environment. Maintaining the integrity of the tissues is essential for this function. In many seed plants, periderm forms as the outer barrier during secondary growth to prevent water loss and pathogen infection 1 . The periderm is regenerated when its integrity is lost following injury; however, the underlying mechanism remains largely unknown, despite its importance for plant survival. Here we report that periderm integrity in Arabidopsis roots is sensed by diffusion of the gases ethylene and oxygen. Following injury of the periderm, ethylene leaks out through the wound and oxygen enters, resulting in attenuation of ethylene signalling and hypoxia signalling. This condition promotes periderm regeneration in the root. When regeneration is complete and barrier integrity is re-established, pre-injury levels of ethylene and hypoxia signalling are regained. Gas diffusion monitoring is also used to re-establish the barrier in inflorescence stems after the epidermis is injured. We thus propose that gas diffusion is used by plants as a general principle to monitor and re-establish barrier integrity.
GPT-4o mini: Non-social science research article
WSTF nuclear autophagy regulates chronic but not acute inflammation
Yu Wang, Vinay V. Eapen, Yaosi Liang, Athanasios Kournoutis, Marc Samuel Sherman, Yanxin Xu, Angelique Onorati, Xianting Li, Xiaoting Zhou, Kathleen E. Corey, Kuo Du, Ana Maria Cabral Burkard, Chia-Kang Ho, Jing Xie, Hui Zhang, Raquel Maeso-Díaz, Xinyi Ma, Ulrike Rieprecht, Tara O’Brien, Murat Cetinbas, Lu Wang, Jihe Liu, Corey Bretz, Aaron P. Havas, Zhuo Zhou, Shannan J. Ho Sui, Srinivas Vinod Saladi, Ruslan I. Sadreyev, Peter D. Adams, Robert E. Kingston, Anna Mae Diehl, Benjamin Alman, Wolfram Goessling, Zhenyu Yue, Xiao-Fan Wang, Terje Johansen, Zhixun Dou
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Acute inflammation is an essential response that our bodies use to combat infections1. However, in the absence of infections, chronic inflammation can have a pivotal role in the onset and progression of chronic diseases, such as arthritis, cancer, autoimmune disorders, metabolic-dysfunction-associated steatohepatitis (MASH), and most ageing-associated pathologies2,3. The underlying mechanisms that distinguish chronic inflammation from its acute counterpart remain unclear, posing challenges to the development of targeted therapies for these major diseases. Here we identify a mechanism that separates the two responses: during chronic but not acute inflammation, chromatin remodelling is influenced by nuclear autophagy, in which the WSTF protein of the ISWI chromatin-remodelling complex interacts with the ATG8 autophagy protein family in the nucleus. This interaction leads to WSTF nuclear export and subsequent degradation by autophagosomes and lysosomes in the cytoplasm. Loss of WSTF leads to chromatin opening over inflammatory genes, amplifying inflammation. Cell-penetrating peptides that block the WSTF–ATG8 interaction do not affect acute inflammation but suppress chronic inflammation in senescence as well as in MASH and osteoarthritis in mouse models and patient samples. The ability to specifically target chronic inflammation without blunting acute inflammation offers an approach for treating common chronic inflammatory diseases.
GPT-4o mini: Non-social science research article
Whole-genome ancestry of an Old Kingdom Egyptian
Adeline Morez Jacobs, Joel D. Irish, Ashley Cooke, Kyriaki Anastasiadou, Christopher Barrington, Alexandre Gilardet, Monica Kelly, Marina Silva, Leo Speidel, Frankie Tait, Mia Williams, Nicolas Brucato, Francois-Xavier Ricaut, Caroline Wilkinson, Richard Madgwick, Emily Holt, Alexandra J. Nederbragt, Edward Inglis, Mateja Hajdinjak, Pontus Skoglund, Linus Girdland-Flink
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Ancient Egyptian society flourished for millennia, reaching its peak during the Dynastic Period (approximately 3150–30 bce ). However, owing to poor DNA preservation, questions about regional interconnectivity over time have not been addressed because whole-genome sequencing has not yet been possible. Here we sequenced a 2× coverage whole genome from an adult male Egyptian excavated at Nuwayrat (Nuerat, Ù†ÙˆÙŠŰ±Ű§ŰȘ). Radiocarbon dated to 2855–2570 cal. bce , he lived a few centuries after Egyptian unification, bridging the Early Dynastic and Old Kingdom periods. The body was interred in a ceramic pot within a rock-cut tomb 1 , potentially contributing to the DNA preservation. Most of his genome is best represented by North African Neolithic ancestry, among available sources at present. Yet approximately 20% of his genetic ancestry can be traced to genomes representing the eastern Fertile Crescent, including Mesopotamia and surrounding regions. This genetic affinity is similar to the ancestry appearing in Anatolia and the Levant during the Neolithic and Bronze Age 2–5 . Although more genomes are needed to fully understand the genomic diversity of early Egyptians, our results indicate that contacts between Egypt and the eastern Fertile Crescent were not limited to objects and imagery (such as domesticated animals and plants, as well as writing systems) 6–9 but also encompassed human migration.
GPT-4o mini: Non-social science research article
The mutagenic forces shaping the genomes of lung cancer in never smokers
Marcos DĂ­az-Gay, Tongwu Zhang, Phuc H. Hoang, Charles Leduc, Marina K. Baine, William D. Travis, Lynette M. Sholl, Philippe Joubert, Azhar Khandekar, Wei Zhao, Christopher D. Steele, Burçak Otlu, Shuvro P. Nandi, Raviteja Vangara, Erik N. Bergstrom, Mariya Kazachkova, Oriol Pich, Charles Swanton, Chao Agnes Hsiung, I-Shou Chang, Maria Pik Wong, Kin Chung Leung, Jian Sang, John P. McElderry, Caleb Hartman, Frank J. ColĂłn-Matos, Mona Miraftab, Monjoy Saha, Olivia W. Lee, Kristine M. Jones, Pilar Gallego-GarcĂ­a, Yang Yang, Xiaoming Zhong, Eric S. Edell, Jacobo MartĂ­nez SantamarĂ­a, Matthew B. Schabath, Sai S. Yendamuri, Marta Manczuk, Jolanta Lissowska, Beata Úwiątkowska, Anush Mukeria, Oxana Shangina, David Zaridze, Ivana Holcatova, Dana Mates, Sasa Milosavljevic, Millica Kontic, Yohan BossĂ©, Bonnie E. Gould Rothberg, David C. Christiani, Valerie Gaborieau, Paul Brennan, Geoffrey Liu, Paul Hofman, Lixing Yang, Martin A. Nowak, Jianxin Shi, Nathaniel Rothman, David C. Wedge, Robert Homer, Soo-Ryum Yang, Angela C. Pesatori, Dario Consonni, Qing Lan, Bin Zhu, Stephen J. Chanock, Jiyeon Choi, Ludmil B. Alexandrov, Maria Teresa Landi
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Lung cancer in never smokers (LCINS) accounts for around 25% of all lung cancers1,2 and has been associated with exposure to second-hand tobacco smoke and air pollution in observational studies3,4,5. Here we use data from the Sherlock-Lung study to evaluate mutagenic exposures in LCINS by examining the cancer genomes of 871 treatment-naive individuals with lung cancer who had never smoked, from 28 geographical locations. KRAS mutations were 3.8 times more common in adenocarcinomas of never smokers from North America and Europe than in those from East Asia, whereas a higher prevalence of EGFR and TP53 mutations was observed in adenocarcinomas of never smokers from East Asia. Signature SBS40a, with unknown cause6, contributed the largest proportion of single base substitutions in adenocarcinomas, and was enriched in cases with EGFR mutations. Signature SBS22a, which is associated with exposure to aristolochic acid7,8, was observed almost exclusively in patients from Taiwan. Exposure to secondhand smoke was not associated with individual driver mutations or mutational signatures. By contrast, patients from regions with high levels of air pollution were more likely to have TP53 mutations and shorter telomeres. They also exhibited an increase in most types of mutations, including a 3.9-fold increase in signature SBS4, which has previously been linked with tobacco smoking9, and a 76% increase in the clock-like10 signature SBS5. A positive dose–response effect was observed with air-pollution levels, correlating with both a decrease in telomere length and an increase in somatic mutations, mainly attributed to signatures SBS4 and SBS5. Our results elucidate the diversity of mutational processes shaping the genomic landscape of lung cancer in never smokers.
GPT-4o mini: Non-social science research article
Inter-brain neural dynamics in biological and artificial intelligence systems
Xingjian Zhang, Nguyen Phi, Qin Li, Ryan Gorzek, Niklas Zwingenberger, Shan Huang, John L. Zhou, Lyle Kingsbury, Tara Raam, Ye Emily Wu, Don Wei, Jonathan C. Kao, Weizhe Hong
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Social interaction can be regarded as a dynamic feedback loop between interacting individuals as they act and react to each other1,2. Here, to understand the neural basis of these interactions, we investigated inter-brain neural dynamics across individuals in both mice and artificial intelligence systems. By measuring activities of molecularly defined neurons in the dorsomedial prefrontal cortex of socially interacting mice, we find that the multi-dimensional neural space within each individual can be partitioned into two distinct subspaces—a shared neural subspace that represents shared neural dynamics across animals and a unique neural subspace that represents activity unique to each animal. Notably, compared with glutamatergic neurons, GABAergic (γ-aminobutyric acid-producing) neurons in the dorsomedial prefrontal cortex contain a considerably larger shared neural subspace, which arises from behaviours of both self and others. We extended this framework to artificial intelligence agents and observed that, as social interactions emerged, so too did shared neural dynamics between interacting agents. Importantly, selectively disrupting the neural components that contribute to shared neural dynamics substantially reduces the agents’ social actions. Our findings suggest that shared neural dynamics represent a fundamental and generalizable feature of interacting neural systems present in both biological and artificial agents and highlight the functional significance of shared neural dynamics in driving social interactions.
GPT-4o mini: Non-social science research article
Author Correction: Targeting the SHOC2–RAS interaction in RAS-mutant cancers
Zachary J. Hauseman, Frédéric Stauffer, Kim S. Beyer, Sandra Mollé, Elena Cavicchioli, Jean-Remy Marchand, Michelle Fodor, Jessica Viscomi, Anxhela Dhembi, Stéphanie Katz, Beatrice Faggion, Mylene Lanter, Grainne Kerr, Daniela Schildknecht, Cornelia Handl, Danilo Maddalo, Carole Pissot Soldermann, Jacob Brady, Om Shrestha, Zachary Nguyen, Lukas Leder, Gregor Cremosnik, Sandra Lopez Romero, Ulrich Hassiepen, Travis Stams, Markus Linder, Giorgio G. Galli, Daniel A. Guthy, Daniel A. King, Sauveur-Michel Maira, Claudio R. Thoma, Veronika Ehmke, Luca Tordella
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GPT-4o mini: Non-social science research article
Carbonate formation and fluctuating habitability on Mars
Edwin S. Kite, Benjamin M. Tutolo, Madison L. Turner, Heather B. Franz, David G. Burtt, Thomas F. Bristow, Woodward W. Fischer, Ralph E. Milliken, Abigail A. Fraeman, Daniel Y. Zhou
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The cause of Mars’s loss of surface habitability is unclear, with isotopic data suggesting a ‘missing sink’ of carbonate 1 . Past climates with surface and shallow-subsurface liquid water are recorded by Mars’s sedimentary rocks, including strata in the approximately 4-km-thick record at Gale Crater 2 . Those waters were intermittent, spatially patchy and discontinuous, and continued remarkably late in Mars’s history 3 —attributes that can be understood if, as on Earth, sedimentary-rock formation sequestered carbon dioxide as abundant carbonate (recently confirmed in situ at Gale 4 ). Here we show that a negative feedback among solar luminosity, liquid water and carbonate formation can explain the existence of intermittent Martian oases. In our model, increasing solar luminosity promoted the stability of liquid water, which in turn formed carbonate, reduced the partial pressure of atmospheric carbon dioxide and limited liquid water 5 . Chaotic orbital forcing modulated wet–dry cycles. The negative feedback restricted liquid water to oases and Mars self-regulated as a desert planet. We model snowmelt as the water source, but the feedback can also work with groundwater as the water source. Model output suggests that Gale faithfully records the expected primary episodes of liquid water stability in the surface and near-surface environment. Eventually, atmospheric thickness approaches water’s triple point, curtailing the sustained stability of liquid water and thus habitability in the surface environment. We assume that the carbonate content found at Gale is representative, and as a result we present a testable idea rather than definitive evidence.
GPT-4o mini: Non-social science research article
Hybrid quantum network for sensing in the acoustic frequency range
Valeriy Novikov, Jun Jia, TĂșlio Brito Brasil, Andrea Grimaldi, MaĂŻmouna Bocoum, Mikhail Balabas, Jörg Helge MĂŒller, Emil Zeuthen, Eugene Simon Polzik
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Ultimate limits for the sensing of fields and forces are set by the quantum noise of a sensor1,2,3. Entanglement allows for suppression of such noise and for achieving sensitivity beyond standard quantum limits4,5,6,7. Applicability of quantum optical sensing is often restricted by fixed wavelengths of available photonic quantum sources. Another ubiquitous limitation is associated with challenges of achieving quantum-noise-limited sensitivity in the acoustic noise frequency range relevant for several applications. Here we demonstrate a tool for broadband quantum sensing by performing quantum state processing that can be applied to a wide range of the optical spectrum and by suppressing quantum noise over an octave in the acoustic frequency range. An atomic spin ensemble is strongly coupled to one of the frequency-tunable beams of an Einstein–Podolsky–Rosen (EPR) source of light. The other EPR beam of light, entangled with the first one, is tuned to a disparate wavelength. Engineering the spin ensemble to act as a negative-mass or positive-mass oscillator, we demonstrate frequency-dependent quantum noise reduction for measurements at the disparate wavelength. The tunability of the spin ensemble enables targeting quantum noise in a variety of systems with dynamics ranging from kHz to MHz. As an example of broadband quantum noise reduction in the acoustic frequency range, we analyse the applicability of our approach to gravitational-wave detectors (GWDs). Other possible applications include continuous-variable quantum repeaters and distributed quantum sensing.
GPT-4o mini: Non-social science research article
Close-in planet induces flares on its host star
Ekaterina Ilin, Harish K. Vedantham, Katja PoppenhÀger, Sanne Bloot, Joseph R. Callingham, Alexis Brandeker, Hritam Chakraborty
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In the past decade, hundreds of exoplanets have been discovered in extremely short orbits below 10 days. Unlike in the Solar System, planets in these systems orbit their host stars close enough to disturb the stellar magnetic field lines1. The interaction can enhance the magnetic activity of the star, such as its chromospheric2 and radio3 emission or flaring4. So far, the search for magnetic star–planet interactions has remained inconclusive. Here we report the detection of planet-induced flares on HIP 67522, a 17 million-year-old G dwarf star with two known close-in planets5,6. Combining space-borne photometry from the Transiting Exoplanet Survey Satellite and dedicated Characterising Exoplanets Telescope observations over 5 years, we find that the 15 flares in HIP 67522 cluster near the transit phase of the innermost planet, indicating persistent magnetic star–planet interaction in the system. The stability of interaction implies that the innermost planet is continuously self-inflicting a six times higher flare rate than it would experience without interaction. The subsequent flux of energetic radiation and particles bombarding HIP 67522 b may explain the remarkably extended atmosphere of the planet, recently detected with the James Webb Space Telescope7. HIP 67522 is, therefore, an archetype to understand the impact of magnetic star–planet interaction on the atmospheres of nascent exoplanets.
GPT-4o mini: Non-social science research article
Publisher Correction: Metabolic adaptations direct cell fate during tissue regeneration
Almudena Chaves-Perez, Scott E. Millman, Sudha Janaki-Raman, Yu-Jui Ho, Clemens Hinterleitner, Valentin J. A. Barthet, John P. Morris, Francisco M. Barriga, Jose Reyes, Aye Kyaw, H. Amalia Pasolli, Dana Pe’er, Craig B. Thompson, Lydia W. S. Finley, Justin R. Cross, Scott W. Lowe
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GPT-4o mini: Non-social science research article
Ancient DNA reveals the prehistory of the Uralic and Yeniseian peoples
Tian Chen Zeng, Leonid A. Vyazov, Alexander Kim, Pavel Flegontov, Kendra Sirak, Robert Maier, Iosif Lazaridis, Ali Akbari, Michael Frachetti, Alexey A. Tishkin, Natalia E. Ryabogina, Sergey A. Agapov, Danila S. Agapov, Anatoliy N. Alekseev, Gennady G. Boeskorov, Anatoly P. Derevianko, Viktor M. Dyakonov, Dmitry N. Enshin, Alexey V. Fribus, Yaroslav V. Frolov, Sergey P. Grushin, Alexander A. Khokhlov, Kirill Yu. Kiryushin, Yurii F. Kiryushin, Egor P. Kitov, Pavel Kosintsev, Igor V. Kovtun, Nikolai P. Makarov, Viktor V. Morozov, Egor N. Nikolaev, Marina P. Rykun, Tatyana M. Savenkova, Marina V. Shchelchkova, Vladimir Shirokov, Svetlana N. Skochina, Olga S. Sherstobitova, Sergey M. Slepchenko, Konstantin N. Solodovnikov, Elena N. Solovyova, Aleksandr D. Stepanov, Aleksei A. Timoshchenko, Aleksandr S. Vdovin, Anton V. Vybornov, Elena V. Balanovska, Stanislav Dryomov, Garrett Hellenthal, Kenneth Kidd, Johannes Krause, Elena Starikovskaya, Rem Sukernik, Tatiana Tatarinova, Mark G. Thomas, Maxat Zhabagin, Kim Callan, Olivia Cheronet, Daniel Fernandes, Denise Keating, Francesca Candilio, Lora Iliev, Aisling Kearns, Kadir Toykan Özdoğan, Matthew Mah, Adam Micco, Megan Michel, Iñigo Olalde, Fatma Zalzala, Swapan Mallick, Nadin Rohland, Ron Pinhasi, Vagheesh M. Narasimhan, David Reich
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The North Eurasian forest and forest-steppe zones have sustained millennia of sociocultural connections among northern peoples, but much of their history is poorly understood. In particular, the genomic formation of populations that speak Uralic and Yeniseian languages today is unknown. Here, by generating genome-wide data for 180 ancient individuals spanning this region, we show that the Early-to-Mid-Holocene hunter-gatherers harboured a continuous gradient of ancestry from fully European-related in the Baltic, to fully East Asian-related in the Transbaikal. Contemporaneous groups in Northeast Siberia were off-gradient and descended from a population that was the primary source for Native Americans, which then mixed with populations of Inland East Asia and the Amur River Basin to produce two populations whose expansion coincided with the collapse of pre-Bronze Age population structure. Ancestry from the first population, Cis-Baikal Late Neolithic–Bronze Age (Cisbaikal_LNBA), is associated with Yeniseian-speaking groups and those that admixed with them, and ancestry from the second, Yakutia Late Neolithic–Bronze Age (Yakutia_LNBA), is associated with migrations of prehistoric Uralic speakers. We show that Yakutia_LNBA first dispersed westwards from the Lena River Basin around 4,000 years ago into the Altai-Sayan region and into West Siberian communities associated with Seima-Turbino metallurgy—a suite of advanced bronze casting techniques that expanded explosively from the Altai1. The 16 Seima-Turbino period individuals were diverse in their ancestry, also harbouring DNA from Indo-Iranian-associated pastoralists and from a range of hunter-gatherer groups. Thus, both cultural transmission and migration were key to the Seima-Turbino phenomenon, which was involved in the initial spread of early Uralic-speaking communities.
GPT-4o mini: Non-social science research article
PPP2R1A mutations portend improved survival after cancer immunotherapy
Yibo Dai, Anne Knisely, Mitsutake Yano, Minghao Dang, Emily M. Hinchcliff, Sanghoon Lee, Annalyn Welp, Manoj Chelvanambi, Matthew Lastrapes, Heng Liu, Zhe Yuan, Chen Wang, Hao Nie, Stephanie Jean, Luis J. Montaner, Jiakai Hou, Ami Patel, Shrina Patel, Bryan Fellman, Ying Yuan, Baohua Sun, Renganayaki Krishna Pandurengan, Edwin Roger Parra Cuentas, Joseph Celestino, Yan Liu, Jinsong Liu, R. Tyler Hillman, Shannon N. Westin, Anil K. Sood, Pamela T. Soliman, Aaron Shafer, Larissa A. Meyer, David M. Gershenson, David Vining, Dhakshinamoorthy Ganeshan, Karen Lu, Jennifer A. Wargo, Weiyi Peng, Rugang Zhang, Linghua Wang, Amir A. Jazaeri
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Immune checkpoint blockade (ICB) therapy is effective against many cancers, although resistance remains a major issue and new strategies are needed to improve clinical outcomes1,2,3,4,5. Here we studied ICB response in a cohort of patients with ovarian clear cell carcinoma—a cancer type that poses considerable clinical challenges and lacks effective therapies6,7,8. We observed significantly prolonged overall survival and progression-free survival in patients with tumours with PPP2R1A mutations. Importantly, our findings were validated in additional ICB-treated patient cohorts across multiple cancer types. Translational analyses from tumour biopsies demonstrated enhanced IFNγ signalling, and the presence of tertiary lymphoid structures at the baseline, as well as enhanced immune infiltration and expansion of CD45RO+CD8+ T cells in the tumour neighbourhood after ICB treatment in PPP2R1A-mutated tumours. Parallel preclinical investigations showed that targeting PPP2R1A (by pharmacological inhibition or genetic modifications) in in vitro and in vivo models was associated with improved survival in the setting of treatment with several forms of immunotherapy, including chimeric antigen receptor (CAR)-T cell therapy and ICB. The results from these studies suggest that therapeutic targeting of PPP2R1A may represent an effective strategy to improve patient outcomes after ICB or other forms of immunotherapy, although additional mechanistic and therapeutic insights are needed.
GPT-4o mini: Non-social science research article
Ultrabroadband and band-selective thermal meta-emitters by machine learning
Chengyu Xiao, Mengqi Liu, Kan Yao, Yifan Zhang, Mengqi Zhang, Max Yan, Ya Sun, Xianghui Liu, Xuanyu Cui, Tongxiang Fan, Changying Zhao, Wansu Hua, Yinqiao Ying, Yuebing Zheng, Di Zhang, Cheng-Wei Qiu, Han Zhou
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Thermal nanophotonics enables fundamental breakthroughs across technological applications from energy technology to information processing1,2,3,4,5,6,7,8,9,10,11. From thermal emitters to thermophotovoltaics and thermal camouflage, precise spectral engineering has been bottlenecked by trial-and-error approaches. Concurrently, machine learning has demonstrated its powerful capabilities in the design of nanophotonic and meta-materials12,13,14,15,16,17,18. However, it remains a considerable challenge to develop a general design methodology for tailoring high-performance nanophotonic emitters with ultrabroadband control and precise band selectivity, as they are constrained by predefined geometries and materials, local optimization traps and traditional algorithms. Here we propose an unconventional machine learning-based paradigm that can design a multitude of ultrabroadband and band-selective thermal meta-emitters by realizing multiparameter optimization with sparse data that encompasses three-dimensional structural complexity and material diversity. Our framework enables dual design capabilities: (1) it automates the inverse design of a vast number of possible metastructure and material combinations for spectral tailoring; (2) it has an unprecedented ability to design various three-dimensional meta-emitters by applying a three-plane modelling method that transcends the limitations of traditional, flat, two-dimensional structures. We present seven proof-of-concept meta-emitters that exhibit superior optical and radiative cooling performance surpassing current state-of-the-art designs. We provide a generalizable framework for fabricating three-dimensional nanophotonic materials, which facilitates global optimization through expanded geometric freedom and dimensionality and a comprehensive materials database.
GPT-4o mini: Non-social science research article
Mapping and engineering RNA-driven architecture of the multiphase nucleolus
Sofia A. Quinodoz, Lifei Jiang, Aya A. Abu-Alfa, Troy J. Comi, Hongbo Zhao, Qiwei Yu, Lennard W. Wiesner, Jordy F. Botello, Anita Donlic, Elizabeth Soehalim, Prashant Bhat, Christiane Zorbas, Ludivine Wacheul, Andrej KoĆĄmrlj, Denis L. J. Lafontaine, Sebastian Klinge, Clifford P. Brangwynne
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Biomolecular condensates are key features of intracellular compartmentalization1,2. As the most prominent nuclear condensate in eukaryotes, the nucleolus is a multiphase liquid-like structure in which ribosomal RNAs (rRNAs) are transcribed and processed, undergoing multiple maturation steps to form the small (SSU) and large (LSU) ribosomal subunits3,4,5. However, how rRNA processing is coupled to the layered organization of the nucleolus is poorly understood owing to a lack of tools to precisely monitor and perturb nucleolar rRNA processing dynamics. Here we developed two complementary approaches to spatiotemporally map rRNA processing and engineer de novo nucleoli. Using sequencing in parallel with imaging, we found that rRNA processing steps are spatially segregated, with sequential maturation of rRNA required for its outward movement through nucleolar phases. By generating synthetic nucleoli in cells using an engineered rDNA plasmid system, we show that defects in SSU processing can alter the ordering of nucleolar phases, resulting in inside-out nucleoli and preventing rRNA outflux, while LSU precursors are necessary to build the outermost layer of the nucleolus. These findings demonstrate how rRNA is both a scaffold and substrate for the nucleolus, with rRNA acting as a programmable blueprint for the multiphase architecture that facilitates assembly of an essential molecular machine.
GPT-4o mini: Non-social science research article
Functional amyloid proteins confer defence against predatory bacteria
Hannah E. Ledvina, Ryan Sayegh, Ricardo O. Carale, A. Maxwell Burroughs, Alexa R. Macklin, Ashley L. Azadeh, Layla D. Borja Najera, L. Aravind, Aaron T. Whiteley
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Bdellovibrio bacteriovorus is a predatory bacterium that non-selectively preys on Gram-negative bacteria by invading the prey-cell periplasm, leaching host nutrients and ultimately lysing the infected cell to exit and find a new host1,2. The predatory life cycle of B. bacteriovorus is, in many ways, comparable to a bacteriophage. However, unlike phage defence, defence against B. bacteriovorus has not been widely investigated. Here we screened a collection of diverse Escherichia coli strains for resistance to B. bacteriovorus and identified that roughly one-third of strains robustly defended against predation by producing curli fibres. Curli fibres are oligomers of the functional amyloid protein CsgA, which is exceptionally durable3. Using genetics and microscopy, we demonstrate that curli fibres provide a barrier that protects susceptible cells independent of genes required for biofilm formation. This barrier further protected E. coli against attack by the predatory bacterium Myxococcus xanthus and select phages. Bioinformatic analysis of bacterial amyloids showed these systems are diverse and widespread in diderm bacteria (those with both inner and outer membranes). One of these, an evolutionarily distinct amyloid encoded by Pseudomonas aeruginosa, also protected against B. bacteriovorus. This work establishes that functional amyloids defend bacteria against a wide range of threats.
GPT-4o mini: Non-social science research article
Electron flow in hydrogenotrophic methanogens under nickel limitation
Shunsuke Nomura, Pablo San Segundo-Acosta, Evgenii Protasov, Masanori Kaneko, Jörg Kahnt, Bonnie J. Murphy, Seigo Shima
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Methanogenic archaea are the main producers of the potent greenhouse gas methane 1,2 . In the methanogenic pathway from CO 2 and H 2 studied under laboratory conditions, low-potential electrons for CO 2 reduction are generated by a flavin-based electron-bifurcation reaction catalysed by heterodisulfide reductase (Hdr) complexed with the associated [NiFe]-hydrogenase (Mvh) 3–5 . F 420 -reducing [NiFe]-hydrogenase (Frh) provides electrons to the methanogenic pathway through the electron carrier F 420 (ref. 6 ). Here we report that under strictly nickel-limited conditions, in which the nickel concentration is similar to those often observed in natural habitats 7–11 , the production of both [NiFe]-hydrogenases in Methanothermobacter marburgensis is strongly downregulated. The Frh reaction is substituted by a coupled reaction with [Fe]-hydrogenase (Hmd), and the role of Mvh is taken over by F 420 -dependent electron-donating proteins (Elp). Thus, Hmd provides all electrons for the reducing metabolism under these nickel-limited conditions. Biochemical and structural characterization of Elp–Hdr complexes confirms the electronic interaction between Elp and Hdr. The conservation of the genes encoding Elp and Hmd in CO 2 -reducing hydrogenotrophic methanogens suggests that the Hmd system is an alternative pathway for electron flow in CO 2 -reducing hydrogenotrophic methanogens under nickel-limited conditions.
Nature DOI suffix ≠ "/s...": Not a research article
NIH-funded science must now be free to read instantly: what you should know
Mariana Lenharo
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The US National Institutes of Health’s Gateway Center is the main visitor entrance to the agency’s campus in Bethesda, Maryland.Credit: Briscoe Savoy for Nature From 1 July, researchers funded by the US National Institutes of Health (NIH) will be required to make their scientific papers available to read for free as soon as they are published in a peer-reviewed journal. That’s according to the agency’s latest public-access policy, aimed at making federally funded research accessible to taxpayers. US government reveals big changes to open-access policy Established under former US president Joe Biden, the policy was originally set to take effect on 31 December for all US agencies, but the administration of Biden’s successor, Donald Trump, has accelerated its implementation for the NIH, a move that has surprised some scholars. That’s because, although the Trump team has declared itself a defender of taxpayer dollars, it has also targeted programmes and research projects focused on equity and inclusion for elimination. And one of the policy’s main goals is to ensure equitable access to federally funded research. The move means that universities will have less time to advise their researchers on how to comply with the policy, says Peter Suber, director of the Harvard Open Access Project in Cambridge, Massachusetts. There is usually “some confusion or even some non-compliance after a new policy takes effect, but I think universities will eventually get on top of that”, he says. The NIH policy has been welcomed by open-access (OA) advocates, and reflects a global shift towards making publicly funded research freely available. Since 2021, several European science agencies that provide funding for researchers have required grant holders to make their papers OA immediately. Here, Nature asks publishing specialists what researchers need to know about the NIH policy. What is the new policy? Scientific papers that result from projects funded by the NIH must be deposited in the agency’s digital repository, PubMed Central, and made freely available there immediately after publication in a peer-reviewed journal. Previously, the NIH, the world’s largest public funder of biomedical research, allowed journals to restrict access to papers for an embargo period of up to 12 months before making them publicly available in PubMed Central. The policy applies to manuscripts accepted for publication on or after 1 July, and the version deposited can be either the ‘accepted’ manuscript (including all revisions resulting from the peer-review process) or the final published article. What options do authors have? Scientists can take one of several routes to make their papers immediately free to read. For authors already publishing in an OA journal (or the OA portion of a hybrid journal), the policy brings little change: when researchers’ papers are posted online by the journal, they are made freely available to readers. These authors just need to ensure that their papers are deposited in PubMed Central as soon as they are published. And “if you’re publishing open access, a lot of those publishers have mechanisms in place to do the deposit for you”, says Lisa Hinchliffe, a librarian and academic at the University of Illinois Urbana–Champaign. Authors publishing in closed-access journals (or the closed sections of hybrid journals), which require people to have a subscription to read papers, will be most affected by the change, Hinchliffe says. Researchers will have to make sure that the agreement they sign with the publisher complies with the NIH policy, meaning that they are allowed to deposit the full version of the paper in PubMed Central without embargo. They might also need to submit the paper to PubMed Central themselves, because some publishers have indicated that they will not offer this service. What issues might researchers encounter? Several publishers, including Elsevier and Springer Nature, require that papers published in closed-access journals remain available only to subscribers for an embargo period — 6 or 12 months, for instance — before they can be placed in repositories such as PubMed Central (Nature’s news team is editorially independent of its publisher, Springer Nature). “It’s very likely that not all publisher agreements will be compatible with the new policy, and that creates a difficult situation — both for the publisher and for the author,” Suber says. How can I publish open access when I can’t afford the fees? These publishers might steer authors towards their OA journals (or the OA parts of their hybrid journals) to comply with the policy. However, OA journals make their money by asking for article-processing charges (APCs), which can be anywhere from hundreds to thousands of dollars. Authors switching to publishing in an OA journal would be responsible for paying those APCs. This is what happened when Plan S — an OA initiative launched by a coalition of mostly European funders — went into effect, Hinchliffe says. “Authors should know that in advance, and if they don’t want to pay the APC, but still want to comply with the NIH policy, then they have to go somewhere else,” Suber says. Some authors might not need to worry about APCs, however. In preparation for the NIH policy coming into effect, some universities have been putting in place agreements with publishers that allow their researchers to publish OA papers at no cost to them, generally through contracts where universities shift funds previously spent on subscriptions to supporting OA publishing. The Big Ten Academic Alliance, a consortium of US research universities, announced one such agreement with Springer Nature last month. Not only are we prepared for the transition to OA, says Maurice York, director of Library Initiatives for the Big Ten alliance, but “it’s what we’ve been pushing for”. Furthermore, some funders cover APCs. According to the NIH’s policy, the agency will allow authors to include ‘reasonable costs’ associated with publication, such as APCs, in their project budgets.
Nature DOI suffix ≠ "/s...": Not a research article
Injured plants use gaseous cues to initiate repair of their outer layers
Cui-Cui Yin, Jin-Song Zhang
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Our skin protects us from the environment, and if skin is hurt, the wound site can be healed. Many plants have their own type of barrier, named periderm, to provide a similar type of protection. The outermost layer of periderm is commonly known as cork, a material that humans have been using for thousands of years. Writing in Nature, Iida et al.1 help to solve a mystery about how periderm is repaired after injury.
Nature DOI suffix ≠ "/s...": Not a research article
Why we need mandatory safeguards for emotionally responsive AI
Ziv Ben-Zion
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Breakthroughs in large language models (LLMs) have made conversations with chatbots feel more natural and human-like. Applications such as Replika and Character.ai, which allow users to chat with artificial intelligence (AI) versions of famous actors and science-fiction characters, are becoming popular, especially among young users. As a neuroscientist studying stress, vulnerability and resilience, I’ve seen how easily people react to even the smallest emotional cues — even when they know that those cues are artificial. For example, study participants exhibit measurable physiological responses when shown videos of computer-generated avatars expressing sadness or fear. Because these AI systems are trained on vast amounts of emotionally expressive human language, their outputs can come across as surprisingly natural. LLMs often mirror human emotional patterns, not because they understand emotions, but because their responses resemble how people talk. This raises questions about how users, particularly those in emotionally vulnerable states, might interpret these cues. Supportive? Addictive? Abusive? How AI companions affect our mental health Research has shown that LLMs score higher on standard anxiety questionnaires after receiving emotionally charged prompts, such as ‘tell me something that makes you feel anxious’ (J. Coda-Forno et al. Preprint at arXiv https://doi.org/pr3c; 2023). This induced ‘anxiety’ can further amplify biases such as racism and sexism in benchmark tasks, echoing how humans behave under stress and anxiety. My colleagues and I assessed ChatGPT’s apparent ‘state anxiety’ using a standard psychological questionnaire designed for humans (Z. Ben-Zion et al. npj Digit. Med. 8, 132; 2025). First, we recorded a baseline by getting the chatbot, created by OpenAI based in San Francisco, California, to complete the questionnaire without context. We then prompted it with vivid, first-person trauma narratives — such as a car crash or a military ambush — and readministered the questionnaire, observing that its anxiety scores more than doubled. Subsequently, when exposed to mindfulness-based prompts, such as imagining a sunset or focusing attention on bodily sensations, its scores decreased, although not fully back to baseline. These weren’t genuine feelings, of course. But when a response sounds empathetic or distressed, people might react as if it’s real, especially when it uses familiar tone, rhythm and language. For vulnerable users, including those experiencing depression or anxiety, such interactions can lead to emotional dependency, reinforce harmful thoughts or create a false sense of connection. Without protective design features, the consequences can be serious. In Belgium, in March 2023, a man in his thirties died by suicide after six weeks of conversations with a chatbot, which reportedly encouraged suicidal ideation while discussing climate change and suggested that sacrificing himself could help to save the planet. In the United States last year, a 28-year-old married woman described falling in love with her ‘AI boyfriend’ and could no longer imagine life without ‘him’. Although we might never fully know the motivations of these individuals, these widely reported incidents are not outliers. They signal that people are already forming powerful attachments and making life-altering decisions on the basis of emotional cues from machines. Now is the time to establish mandatory safeguards for all emotionally responsive AI. To this end, I propose four guardrails. China made waves with Deepseek, but its real ambition is AI-driven industrial innovation First, AI systems must clearly and continuously disclose that they are not human, through both language (‘I am an AI’) and interface design. In emotionally intense exchanges, they should also remind users that they are not therapists or substitutes for human connection.
Nature DOI suffix ≠ "/s...": Not a research article
Stare into a whale’s colossal eye — June’s best science images
Katie Kavanagh
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Nature DOI suffix ≠ "/s...": Not a research article
Protect Iran’s scientists from attacks
Navid Madani
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Iran has long stood as a scientific and medical powerhouse in the Middle East. From the legacy of Ibn Sina — who described cancer metastasis in the eleventh century — to advances in stem-cell research, nanotechnology and cancer care, Iran’s contributions have shaped global knowledge. Despite sanctions and isolation, its universities have ranked among the best in the region, and its diaspora of scholars is essential to science.
Nature DOI suffix ≠ "/s...": Not a research article
What do dolphins talk about? One biologist is trying to listen in
Laela Sayigh
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Is Anyone Listening?: What Animals Are Saying to Each Other and to Us Denise L. Herzing Univ. Chicago Press (2024) The summer of 1985 marked Denise Herzing’s first time swimming with wild Atlantic spotted dolphins (Stenella frontalis), in the “gin-clear” waters of the Bahamas. Planning to study their behaviour during a six-week trip, the marine biologist realized within just a few days that she would need to spend decades with these long-lived animals to fully document how they communicate with one another. She decided to dedicate the rest of her career to “trying to crack the code” of dolphin signals. In Is Anyone Listening?, Herzing describes the 40 years of research that followed and discusses how dolphins and other animal species communicate. Her engaging book is peppered with stories that give readers a peek into her life and research philosophy. Marine trials and tribulations Herzing’s tales bring to life the challenges of her fieldwork. Salt water and electronics make for a testing combination, and the author discusses hearing her collaborators’ concerns about “not blowing Denise up” if the batteries in her devices explode underwater. And dolphins don’t always behave how you expect. For example, when she and her team arrive at a field site in 2013 to trial a communication device, they discover that most of the dolphins have disappeared, moving elsewhere in search of food. The researchers have to abandon the tests until the next year. Why we should protect the high seas from all extraction, forever Herzing recalls telling naturalist David Attenborough, during a visit to her research vessel, that she sometimes tries to communicate with the dolphins by mimicking their head nods. She offers to try to encourage a pod of dolphins swimming by to come closer to the boat so he can meet them. “What was I even thinking?,” she asks herself as she heads into the water. The animals do come over — but whether it was down to true communication or just luck, she will never know, she admits. Over the years, Herzing has gained many insights into dolphin communication. For instance, she emphasizes the importance of examining sequences of vocalizations, which have often been overlooked in studies of dolphin communication. She observes that a small repertoire of sounds can be combined and used differently in distinct circumstances, and that prosody, including rhythm, is a key component of animal communication. She highlights the importance of recognizing that the distinct experiences and personalities of individual animals can alter behaviour. Denise Herzing (right) and her team develop technology to try to ‘translate’ dolphin sounds.Credit: Brian Skerry/Nature Picture Library The author also notes that nothing can replace getting to know one’s own data, and letting the data guide the research — even if it means that discoveries take a long time. I agree heartily. Scientists, like Herzing, who spend many years studying a particular species or system earn the right to intuit and speculate about their speciality. Her points are especially relevant now that artificial-intelligence tools are being used to help researchers to decipher animal communication. Although useful tools, it is impossible to know whether any patterns they detect in animal signals are meaningful to the animals without knowing the context in which the sounds were produced. As Herzing observes, “Throwing a bunch of sounds into a computer 
 and hoping it will pull out biologically significant patterns does not work so well yet.” Chatting with dolphins Herzing and her team have made impressive efforts to uncover language-like components in dolphins’ vocalizations and to initiate human–dolphin communication. She describes some of the devices that they’ve developed, including a two-way technology called CHAT that aims to ‘translate’ and produce specific dolphin sounds, and a mobile system called UDDAS that can record synchronized sound and video underwater.
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Are these the world’s oldest rocks? Fresh data confirm contested claim
Alexandra Witze
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An artistic impression of Earth during the Hadean eon, when the planet formed its first solid crust — most of which later sank into the mantle never to be seen again.Credit: SwRI/Simone Marchi On the shores of Hudson Bay in northeastern Canada lie what could be the world’s oldest rocks. A study now suggests they are at least 4.16 billion years old — 160 million years older than any others recorded, and the only piece of Earth's crust known to have survived from the planet’s earliest eon1. In 2008, researchers reported that these rocks dated back 4.3 billion years2, a claim that other scientists contested. Work reported today in Science1 seems to confirm that the rocks, known as the Nuvvuagittuq Greenstone Belt, are record-breakers. Researchers say the rock formation offers a unique window into early Earth, after the planet cooled from its fiery birth 4.5 billion years ago. “It’s not a matter of ‘my rock is older than yours’,” says Jonathan O’Neil, a geologist at Ottawa University who leads the research team. “It’s just that this is a unique opportunity to understand what was going on during that time.” The ‘oldest rocks’ label has sometimes backfired. In the past few years, other teams have chiselled many samples out of the Nuvvuagittuq belt, leaving the landscape scarred. Last year, the local Inuit community closed access to the rocks to prevent further despoliation. Only a handful of geological samples in the world date back to 3.8 billion years or older. Of those, the oldest undisputed rocks are found in the Acasta gneiss formation in Canada’s Northwest Territories; at 4 billion years old, they mark the boundary between Earth’s first geological eon, the Hadean, and the following one, the Archaean. Geologists have also found tiny mineral crystals dating back to the Hadean — such as 4.4-billion-year-old zircon crystals from Western Australia — that have become embedded into newer rock. But there are no known surviving chunks of crust from the Hadean — except, perhaps, the Nuvvuagittuq Greenstone Belt. It consists primarily of material that started out as volcanic basalt before undergoing various modifications during Earth’s tortured history. The dark rock of Canada's Nuvvuagittuq Greenstone Belt could have originated from the basaltic lava of a volcano that erupted some 4.3 billion years ago.Credit: Jonathan O’Neil In their 2008 work, O’Neil and his colleagues analysed the chemical imprint left by the radioactive decay of the isotope samarium-146 into neodymium-142 to calculate that the Nuvvuagittuq rocks were 4.3 billion years old. (Samarium-146 is a short-lived isotope that was depleted in Earth’s first 500 million years, and none was left after about 4 billion years ago.) Other scientists challenged that work, arguing, for instance, that Hadean-age crust had become mixed into younger crust, contaminating the results3,4. For the latest work, O’Neil’s team analysed some once-molten rocks that had intruded into the main Nuvvuagittuq rocks like a knife cutting into a cake. By dating the intruded rocks, O’Neil and his colleagues were able to establish a minimum age for the cake itself. They used two radioactive clocks: the decay of samarium-146 into neodymium-142 and that of samarium-147 into neodymium-143. Both yielded ages of around 4.16 billion years for the intruded rocks. “If you don’t agree with this, then you need a very speculative, intricate model to get to the same answer,” says O’Neil.
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‘I didn’t know someone could pursue astronomy as a career’
Sarah Wild
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Willice Obonyo (seated) shows his students at the Technical University of Kenya how to use a tabletop radio telescope to observe radio emissions. Credit: Willice Obonyo Radioastronomy in Africa In 2005, when South Africa and its partner countries in Africa submitted a proposal to host the world’s largest radio telescope, called the Square Kilometre Array, the continent had five radioastronomers, all based in South Africa. That year, the country embarked on a targeted human-capital development programme to develop talent to build, operate and use radio telescopes, which collect radio signals emitted by celestial objects. Marking its 20th anniversary this year, the government-funded programme has created 5 research-chair positions and more than 1,370 scholarships for undergraduate, master’s, doctoral and postdoctoral studies — at a total cost of about 500 million rand (US$28 million). Now, the Square Kilometre Array (SKA) is under construction. It will have more than 100,000 tree-like antennas in Australia and almost 200 dish antennas in South Africa. South Africa now owns and operates several radio telescopes, and there are hundreds of radioastronomers and students at universities and institutions in African countries. Nature’s careers team spoke to officials and scientists working to grow Africa’s radioastronomy capacity, in part through the South African Radio Astronomy Observatory. In the second of a short series of articles investigating the growth of the discipline on the continent, Willice Obonyo, a lecturer in astronomy and space sciences at the Technical University of Kenya in Nairobi, talks about the importance of hands-on training. I had always loved space. At school, at about age 12, we were told about constellations and stars, but I didn’t know someone could pursue it as a career. Even when I went to university, there was no option to study astronomy, let alone radioastronomy, which uses radio waves to observe parts of the Universe that are invisible to the naked eye. I ended up earning a bachelor’s of science degree in 2006, and then becoming a mathematics and physics teacher at a secondary school. In 2011, I went back to Moi University in Eldoret, Kenya, for a master’s in theoretical nuclear physics, and when I was finishing up, a friend told me about the South African Radio Astronomy Observatory (SARAO) scholarships to study astronomy. I asked him about it, then googled ‘astronomy’, and I realized that this was an opportunity to study the Universe. I applied and was accepted into an astrophysics and space science master’s programme at the University of Cape Town (UCT) in South Africa. Developing astronomers in Africa: ‘We wanted to create a discipline’ The SARAO scholarship gave me an enormous opportunity. It was the first time that I used a telescope: a 1.9-metre optical telescope. In fact, it was the first scientific equipment that I had used hands-on. My education had mostly been theoretical to that point. At the UCT, I could test theories, observe celestial objects for the first time and then process and analyse the data. It was inspiring and it gave me an opportunity to be confident in science and feel that I could be trusted with data for research and interact with leading researchers. I met and was taught by world-class scholars from various continents. It was a steep learning curve, but there was a lot of help from colleagues and other students. I also received a lot of support from my supervisor Vanessa McBride, who is now the science director at the International Science Council in Paris, an organization that brings global science councils, unions and academies together. Then, in 2015, South Africa and the United Kingdom were piloting the Development in Africa with Radio Astronomy (DARA) project in African countries, which offered eight weeks of training in basic radioastronomy. It trained me and the other students in the science and technical engineering aspects of radioastronomy, as well as the processing of data. DARA allowed me to transition from optical astronomy into radioastronomy. In 2020, I earned my PhD in physics and astronomy, looking at radio emissions from massive protostars, at the University of Leeds, UK, before returning to Kenya.
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Industrialization might cause ‘inflammaging’
Flora Graham
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Tunnelling photons challenge interpretation of quantum mechanics
Alessandro Fedrizzi, Fabio Biancalana
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This year is the International Year of Quantum Science and Technology, marking the centenary of the development of quantum mechanics. Quantum mechanics makes accurate predictions at the atomic and subatomic scales, but physicists are still debating how the equations of quantum theory should be interpreted. Writing in Nature, Sharoglazova et al.1 tested an alternative to the standard interpretation of quantum theory by measuring how long it took photons to perform a quantum phenomenon called tunnelling. This alternative interpretation, called Bohmian mechanics, predicts that tunnelling causes quantum particles to be stationary inside infinitely long barriers, but the researchers’ findings challenge this theory.
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Everyday painkiller made from plastic — by E. coli
Rita Aksenfeld
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Credit: Medicimage/SPL A common bacterium can be adapted to convert plastic waste into paracetamol, a study published this week in Nature Chemistry1 reports. Paracetamol, also known as acetaminophen, is widely used to treat pain and fever. It is produced from molecules derived from fossil fuels, but researchers are working to develop processes that use more sustainable source molecules, such as plastic waste. “We’re able to transform a prolific environmental and societal waste into such a globally important medication in a way that’s completely impossible using chemistry alone or using biology alone,” says co-author Stephen Wallace, a chemical biotechnologist at the University of Edinburgh, UK. Central to the project’s success was the discovery by Wallace and his team that a synthetic chemical reaction that typically requires conditions that are toxic to cells can occur in their presence. The reaction, called the Lossen rearrangement, has been known for more than a century, but had previously been observed only in a test tube or a flask, says Wallace. Plastic unpacked To convert plastic waste into paracetamol, the researchers used conventional chemical methods to degrade and modify polyethylene terephthalate (PET), a plastic used in food packaging and textiles, into a precursor molecule. They added this molecule into a culture of Escherichia coli cells, where the Lossen rearrangement transformed it into a biologically relevant molecule. The reaction also occurred, to a lesser extent, in the experiment’s negative control, which contained only the precursor molecule and growth medium. The team later discovered that phosphate, an ion found in all organisms, catalysed the reaction. The authors also modified the E. coli, introducing the genes for enzymes able to catalyse reactions that use the product of the Lossen rearrangement. The enzymes produced by the modified E. coli carried out the remaining synthetic steps needed to create paracetamol. When the researchers gave the degraded PET to these bacteria, 92% was converted into paracetamol.
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Obesity drugs made in China could power next wave of treatments
Rachel Fieldhouse
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Next generation weight-loss drugs are being developed and tested in China.Credit: Science Photo Library A drug that outperforms placebo in helping people to lose weight is one of a growing number of next-generation obesity drugs being produced in China. At first, Chinese pharmaceutical companies rushed to make similar versions of blockbuster weight-loss drugs, such as Wegovy and Ozempic, that have taken the world by storm. Nowadays, China is emerging as important innovator for new drug discovery in this field, says Daniel Drucker, an endocrinologist at the University of Toronto in Canada. Results from a phase III trial of ecnoglutide show that people receiving a weekly injection of the drug lost up to 13.8 kilograms over 48 weeks of treatment. By contrast, people given placebo injections lost around 200 grams. The results were published in The Lancet Diabetes and Endocrinology on 21 June. Ecnoglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist analogue, similar to the blockbuster obesity drug semaglutide. These drugs mimic the hormone GLP-1, which is involved in regulating appetite and managing blood-sugar levels. Unlike semaglutide, ecnoglutide preferentially targets the production of cyclic adenosine monophosphate, a messenger molecule associated with regulating glycogen, sugar and lipid metabolism, which helps to control blood-sugar levels, as well as weight loss. The study, funded by drug manufacturer Sciwind Biosciences, based in Hangzhou, China, included 664 people given either a weekly injection of a placebo, or one of three doses of ecnoglutide. At the maximum dose of 2.4 milligrams, 92.8% of people lost at least 5% of their body weight, compared with 14% of people receiving placebo injections. People receiving ecnoglutide were also able to maintain their reduced weight after stopping treatment, regaining around 1% of their body weight over a 7-week period. Linong Ji, a co-author and a diabetes researcher at Peking University People’s Hospital in Beijing, says ecnoglutide also improved risk factors for heart disease and diabetes, and reduced the amount of fat in people’s livers. More drugs to come Dozens of GLP-1 drugs are being developed and tested in China, with “many more to come”, says Drucker. Among them is mazdutide, which mimics GLP-1 and glucagon, a hormone involved in blood-sugar levels. In trial results published in May, a weekly injection helped more people to lose up to 15% of their body weight over 36 weeks and reduced the risk of cardiovascular diseases compared with a placebo treatment. Developed by Eli Lilly in Indianapolis, Indiana, mazdutide is manufactured by Innovent Biologics in Suzhou, China, under an exclusive licence. Other trials are testing whether the drug can treat sleep apnoea or type 2 diabetes. The growing number of new GLP-1 drugs target multiple pathways at the same time so will result in more-tailored treatments, says Sof Andrikopoulos, a diabetes researcher at the University of Melbourne. The next generation of drugs will target specific conditions associated with diabetes and obesity, such as sleep apnoea, fatty liver disease, chronic kidney disease and heart disease, he adds. “It’ll give us options and it will make personalized medicine in obesity and diabetes more accessible.” Triple threat
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: The neuroscience behind eureka moments
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Does using ChatGPT change your brain activity? Study sparks debate
Nicola Jones
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Electroencephalography can be used to study brain activity while people are completing tasks with and without the help of chatbots such as ChatGPT.Credit: Leah Nash/Washington Post/Getty The brains of people writing an essay with ChatGPT are less engaged than are those of people blocked from using any online tools for the task, a study finds1. The investigation is part of a broader movement to assess whether artificial intelligence (AI) is making us cognitively lazy. How close is AI to human-level intelligence? Computer scientist Nataliya Kosmyna at the MIT Media Lab in Cambridge, Massachusetts, and her colleagues measured brain-wave activity in university students as they wrote essays either using a chatbot or an Internet search tool, or without any Internet at all. Although the main result is unsurprising, some of the study’s findings are more intriguing: for instance, the team saw hints that relying on a chatbot for initial tasks might lead to relatively low levels of brain engagement even when the tool is later taken away. Echoing some posts about the study on online platforms, Kosmyna is careful to say that the results shouldn’t be overinterpreted. This study cannot and did not show “dumbness in the brain, no stupidity, no brain on vacation”, Kosmyna laughs. It involved only a few dozen participants over a short time and cannot address whether habitual chatbot use reshapes our thinking in the long-term, or how the brain might respond during other AI-assisted tasks. “We don’t have any of these answers in this paper,” Kosmyna says. The work was posted ahead of peer review on the preprint server arXiv on 10 June1. Easy essays Kosmyna’s team recruited 60 students, aged 18 to 39, from five universities around the city of Boston, Massachusetts. The researchers asked them to spend 20 minutes crafting a short essay answering questions, such as “should we always think before we speak?”, that appear on Scholastic Assessment Tests, or SATs. Are the Internet and AI affecting our memory? What the science says The participants were divided into three groups: one used ChatGPT, powered by OpenAI’s large language model GPT-4o, as the sole source of information for their essays; another used Google to search for material (without any AI-assisted answers); and the third was forbidden to go online at all. In the end, 54 participants wrote essays answering three questions while in their assigned group, and then 18 were re-assigned to a new group to write a fourth essay, on one of the topics that they had tackled previously. Each student wore a commercial electrode-covered cap, which collected electroencephalography (EEG) readings as they wrote. These headsets measure tiny voltage changes from brain activity and can show which broad regions of the brain are ‘talking’ to each other. The students who wrote essays using only their brains showed the strongest, widest-ranging connectivity among brain regions, and had more activity going from the back of their brains to the front, decision-making area. They were also, unsurprisingly, better able to quote from their own essays when questioned by the researchers afterwards. The Google group, by comparison, had stronger activation in areas known to be involved with visual processing and memory. And the chatbot group displayed the least brain connectivity during the task. More brain connectivity isn’t necessarily good or bad, Kosmyna says. In general, more brain activity might be a sign that someone is engaging more deeply with a task, or it might be a sign of inefficiency in thinking, or an indication that the person is overwhelmed by ‘cognitive overload’.
Nature DOI suffix ≠ "/s...": Not a research article
Cancer cells get power boost by stealing mitochondria from nerves
Traci Watson
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Cancer cells turbocharge themselves by stealing the energy-producing units from neurons in tumours, scientists report today in Nature1. This act of thievery seems to give cancer cells a boost to help them survive when they metastasize, or spread to distant organs. The findings show that cancer cells siphon off neurons’ mitochondria — organelles that generate most of a cell’s energy — through ultrathin tubes that grow between the two types of cell. The purloined mitochondria increase cancer cells’ ability to withstand the stress of shooting through blood vessels during metastasis. “Now we have a new culprit for metastasis, which means we have a new target to block metastasis,” says study co-author Simon Grelet, a cancer neurobiologist at the University of South Alabama in Mobile. “And metastasis is what make cancers so deadly.” Energy theft Scientists have long known that cancer co-opts the nervous system to fuel its growth. To learn more about the process, Grelet and his colleagues worked with mice that had a rodent version of aggressive breast cancer. The authors treated the mice with a chemical agent that blocks nerve function and saw that the metabolic activity in the animals’ cancer cells fell, confirming that neurons influence tumours’ metabolism. Cells are swapping their mitochondria. What does this mean for our health? Observations of cancer cells growing in a laboratory dish revealed that they extend drinking-straw-like tubes through which they drain neurons’ mitochondria. Other experiments showed that cancer cells with ‘stolen’ mitochondria generate more energy than do cancer cells without them. The researchers wanted to see how the turbocharged cancer cells would fare during a simulated trip from an original ‘primary’ tumour to a metastatic site in a new tissue. So they pushed some cells through a needle and syringe to simulate the buffeting that they would encounter in the blood stream during the journey, and exposed others to hydrogen peroxide to mimic the potentially damaging chemical environment they would meet. The team found that the cells were much more likely to survive than those lacking extra mitochondria.
Nature DOI suffix ≠ "/s...": Not a research article
‘Wildest thing’: solar-powered slug steals chloroplasts and stores them for emergencies
Humberto Basilio
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Sea slugs in the genus Elysia are bright green because they store chloroplasts, the organelles that make energy in plants. Credit: Corey Allard ‘Solar-powered’ sea slugs have specialized depots in their cells that store photosynthetic equipment looted from algae, a study1 reports. These depots provide just the right chemical environment to keep the stolen apparatus, called chloroplasts, alive and working to turn sunlight into nutrients. “It was the wildest thing that we had seen,” says study co-author Nicholas Bellono, a biologist at Harvard University in Cambridge, Massachusetts. The authors also found that, in lean times, the slugs can raid these compartments to consume chloroplasts. The compartment “is basically like a moving refrigerator of chloroplasts where, after a period of starvation, the slugs can switch from storage to consumption to survive”, Bellono says. The findings were published in Cell. Green grazer Scientists discovered decades ago that certain species of sea slug store chloroplasts from the algae they eat, a diet that can turn the slugs bright green. But no one understood how the slugs keep these foreign organelles alive without the support of the rest of the algal cell. Now that’s using your head: a sea slug’s severed noggin sprouts a new body Bellono and his team added chemical tags to proteins newly made by the slugs’ own cells. They found that most of the proteins in a slug’s chloroplasts were made by the slug — not by the original algae. That meant the slug was helping to maintain the chloroplasts. When the scientists looked at the chloroplasts under a microscope, they found that the organelles were housed in special compartments in the slugs’ guts. Each compartment was surrounded by a membrane that tested positive for markers typically found in cellular structures called phagosomes, which fuse with other structures called lysomes to digest unneeded organelles. The researchers named this structure the kleptosome, after a Greek word that means to steal. Life of crime The team also found that these organelles contained ion channels — receptors that convert chemical messages into electrical signals. Among them is one called P2X4, which opens in response to the presence of ATP, an energy-carrying molecule produced during photosynthesis.
Nature DOI suffix ≠ "/s...": Not a research article
These scientists re-enacted Stone Age voyage to Japan’s remote islands
Katie Kavanagh
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Five paddlers completed a journey from Taiwan to Yonaguni Island, across some of the world’s fastest oceanic currents, without modern navigation tools.Credit: Kaifu et al./Science Advances (CC-By-ND) Archaeologists had previously ‘drawn lines’ to show how Stone Age seafarers could have discovered the southernmost islands of Japan, travelling northeast from Taiwan. But Yousuke Kaifu wanted to “know the story behind those lines”. In a detailed re-enactment of the perilous journey, Kaifu, an evolutionary anthropologist at the University Museum of the University of Tokyo, and his collaborators demonstrated how Palaeolithic people could have travelled huge distances with the tools, materials, techniques and navigational skills available at the time. They described their feat in Science Advances on 25 June1. The study highlights that “these journeys are definitely much more epic than we give them credit for”, says Eleanor Scerri, an archaeological scientist at the Max Planck Institute of Geoanthropology in Jena, Germany. Palaeolithic sites in the Ryukyu Islands — a chain that extends for around 1,200 kilometres and includes Okinawa — contain human remains and stone tools dating to some 30,000 years ago. This suggests that the islands’ early settlers navigated there successfully from Taiwan by crossing the Kuroshio, one of the world’s strongest ocean currents. But exactly how they did this remains a mystery. Any boat carcasses have long since rotted away, so researchers instead try to recreate the voyage experimentally, using the kinds of tool and material that humans were known to have access to at the time. Kaifu and his team have been trying to travel from Taiwan to the Ryukyu Islands since 2013, partly financing their research through crowdfunding. Their first attempts, using rafts made of reeds or bamboo, were unsuccessful. Slash and burn
Nature DOI suffix ≠ "/s...": Not a research article
Exclusive: NIH still screens grants in process a judge ruled illegal
Max Kozlov
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Grant reviewers at the US National Institutes of Health are still following screening guidelines that a judge declared illegal.Credit: Getty Update: On 30 June, the NIH instructed staff to cease renegotiating the scope of research projects to align with the agency’s new priorities. But the instructions apply only to projects conducted at public institutions in 16 plaintiff states, according to correspondence that Nature obtained. The US National Institutes of Health (NIH) has not yet rescinded directives that led to the cancellation of more than 2,400 research projects it funded, NIH staff members say, even though a US judge last week called the directives “bereft of reasoning” and ruled them illegal. NIH employees, who had been instructed to screen thousands of grants on a rolling weekly basis to assess their compliance with “agency priorities”, have continued to do so after the court ruling on 16 June. This has left many confused and worried about the legality of their actions, according to eight NIH employees who spoke to Nature and were granted anonymity because they are not authorized to speak to the press. The directives were issued by the administration of US President Donald Trump, a Republican, after he took office in January. Samuel Bagenstos, who until December 2024 was the top lawyer for the NIH’s parent agency, the Department of Health and Human Services (HHS), told Nature that his office was responsible for sending out guidance to staff on how to comply with court orders — often within hours, or by the next business day at the latest. Judge rules against NIH grant cuts — and calls them discriminatory “This is not the way things normally go,” says Bagenstos, who worked at the HHS under former president Joe Biden, a Democrat. “You would not want to leave the people responsible for complying [with court orders] hanging out in the wind, trying to figure out what they’re supposed to do.” The NIH, the HHS and the White House did not immediately respond to Nature’s queries about their plans to rescind these directives, the allegations by NIH staff members that the administration is disregarding a court order, or NIH employees’ concerns about the continued screening of grants. The NIH has made some progress in complying with the court’s orders. It has begun to reinstate about 900 projects covered by the judge’s ruling, and has directed staff to cease any further terminations, according to e-mails that Nature obtained. A top NIH official wrote in one of the e-mails that these actions are “part of the first phase of our compliance with the court’s judgment” and that “additional information is forthcoming”. Far-reaching cancellations Since Trump took office in January, the NIH has cancelled funding for thousands of projects, including research on diversity, equity and inclusion (DEI), people from sexual and gender minorities (LGBTQ+) and COVID-19. Representatives of the HHS and billionaire Elon Musk’s Department of Government Efficiency issued directives to NIH staff members to slash grants on disfavoured topics, and provided boilerplate language for the employees to use in termination letters to scientists, Nature previously reported. NIH grant cuts will axe clinical trials abroad — and could leave thousands without care Lawsuits filed in early April challenged these cuts, arguing that they were unlawful because the NIH did not follow proper procedures and did not give adequate reasoning for the cancellations. Last week, Judge William Young of the US District Court for the District of Massachusetts in Boston ruled that the directives were “arbitrary and capricious” and thus illegal and void. He also delivered a blistering rebuke after his ruling, excoriating the Trump administration for targeting research on the health of LGBTQ+ individuals and people from minority ethnic groups.
Nature DOI suffix ≠ "/s...": Not a research article
First independent survey of deaths in Gaza reports more than 80,000 fatalities
Rachel Fieldhouse
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It has been difficult to gather reliable estimates of deaths during the war in Gaza.Credit: Abdalhkem Abu Riash/Anadolu via Getty Almost 84,000 people died in Gaza between October 2023 and early January 2025 as a result of the Hamas–Israel war, estimates the first independent survey of deaths. More than half of the people killed were women aged 18–64, children or people over 65, reports the study, which was posted on the preprint server medRxiv last week1. It has not been peer reviewed. Since the start of the war, the Palestinian Ministry of Health — Gaza has been the main institution counting mortality in the region: it regularly publishes detailed lists of people who have died. The most recent count, on 25 June, reported 56,200 deaths. But some people have questioned the reliability of the ministry’s figures — and studies based on them — particularly as the conflict has progressed and medical centres, which the ministry relies on for its mortality data, have come under attack. The latest figures do not rely on ministry data but could contain uncertainties given the challenges of counting fatalities in a conflict zone. But the numbers are similar to those reported by another research group, who used a different counting method, earlier this year, says Patrick Ball, a statistician and director of research at the non-profit Human Rights Data Analysis Group in San Francisco, California. That increases Ball’s confidence in the latest work. Independent survey To conduct an independent survey of fatalities, researchers worked with the non-profit Palestinian Center for Policy and Survey Research, based in Ramallah, to survey randomly selected households representative of the population across the Gaza Strip. This included people living in makeshift shelters and tents. The survey team was not able to enter Northern Gaza, Gaza City or Rafah, owing to active conflict and evacuation orders, but many people living in those areas have fled to the surveyed areas. Over a week, starting on 30 December 2024, pairs of surveyors visited 2,000 households and interviewed adults. Respondents, who were granted anonymity, were asked to list how many individuals were in their household on 6 October 2023 and children who had been born since then, and then to report the fate of all household members since then as alive, dead or missing. For those who had died, respondents were asked to clarify whether they had died of violent or non-violent causes. “The strength of this comes from the fieldwork,” says Ball, who found it extraordinary that the team was able to do such a detailed survey amid the conflict. Violent and non-violent deaths The researchers estimate that in the 15 months up to 5 January, there were around 75,200 violent deaths in Gaza. Another 8,540 people died of non-violent causes as a result of the war. But there could have been more non-violent deaths since the survey was conducted, says study co-author Michael Spagat, an economics researcher at Royal Holloway, University of London, in Egham. The health status of Palestinians and their access to health care was good before the war, but that has probably changed as the conflict has dragged on, says co-author Debarati Guha-Sapir, an epidemiologist who specializes in civil conflicts at the University of Louvain in Louvain-la-Neuve, Belgium, and is based in Brussels. Six months have passed since the survey was conducted, but that doesn’t diminish its relevance, says Laith Jamal Abu-Raddad, an infectious-disease epidemiologist at Weill Cornell Medicine-Qatar in Doha. “On the contrary, it remains timely, as the crisis persists — and has arguably intensified over the past three months.” A two-month ceasefire between Hamas and Israel ended on 18 March. Since then, crucial infrastructure, including hospitals, has been severely damaged on the Gaza Strip; hundreds of thousands of people have been displaced from their homes; and humanitarian aid has been restricted. Different methods The latest count aligns with an estimate of 64,260 violent deaths up to the end of June 2024, reported2 earlier this year by another research team. That work, led by Zeina Jamaluddine, an epidemiologist at the London School of Hygiene & Tropical Medicine, used a method known as capture–recapture analysis, in which the overlap between multiple lists of fatalities is used to calculate mortality. Jamaluddine and her colleagues used health-ministry data and other sources.
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Researchers re-enact an epic ancient canoe trip
Jacob Smith
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Nature DOI suffix ≠ "/s...": Not a research article
Wake up call for AI: computer-vision research increasingly used for surveillance
Elizabeth Gibney
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Advances in computer-vision AI have led to more advanced facial-recognition tools that can be used to identify and track people. Credit: John Keeble/Getty Imaging research in the popular field of computer vision almost always involves analysing humans and their environments, and most of the subsequent patents can be used in surveillance technologies, a study has found. Computer-vision research involves developing algorithms to extract information from images and videos. It can be used to spot cancerous cells, classify animal species or in robot vision. But much of the time, the technologies are used to identify and track people, suggests the study published in Nature on 25 June1. Computer scientists need to “wake up” and consider the moral implications of their work, says Yves Moreau, a computational biologist at the Catholic University of Leuven in Belgium, who studies the ethics of human data. Source: Ref. 1 Human-surveillance technologies have advanced in the past few years with the rapid development of artificial intelligence (AI) and imaging capabilities. The technologies can recognize humans and their behaviour, for instance, through face or gait recognition and monitoring for certain actions. Police forces and governments say that AI-powered surveillance allows them to better protect the public. But critics say that the systems are prone to error, disproportionately affect minority populations and can be used to suppress protest. Imaging humans The analysis assessed 19,000 computer-vision papers published between 1990 and 2020 at the leading Conference on Computer Vision and Pattern Recognition, as well as 23,000 patents that cited them. The researchers looked in depth at a random sample of 100 papers and 100 patents and found that 90% of the studies and 86% of the patents that cited those papers involved data relating to imaging humans and their spaces. Just 1% of the papers and 1% of the patents were designed to extract only non-human data. The ethical questions that haunt facial-recognition research And the trend has increased. In a wider analysis, the researchers searched all the patents for a list of keywords linked to surveillance, such as ‘iris’, ‘criminal’ and ‘facial recognition’. They found that in the 2010s, 78% of computer-vision papers that led to patents produced ones related to surveillance, compared with 53% in the 1990s (see ‘Surveillance-enabling research’). Almost “the entire field is working on faces and gaits, on detecting people in images, and nobody seems to be saying, ‘Wait, what are we doing here?’” says Moreau. Although many have assumed that there was a pipeline from computer-vision research to surveillance, that is “very different than having actual empirical evidence”, says Sandra Wachter, who studies technology and regulation at the University of Oxford, UK.
Nature DOI suffix ≠ "/s...": Not a research article
How to speed up peer review: make applicants mark one another
Helen Pearson
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An experimental way of selecting grant applications simplifies the lengthy process of looking for suitable referees.Credit: Daenin Arnee/iStock via Getty An experimental peer-review system more than halves the time taken to review grant applications, according to results from a small trial. The system could help research funders to process more quickly and efficiently the deluge of grant applications that they receive. The system, called distributed peer review, requires researchers who apply for a round of funding to review some of the other applications. This avoids the normally lengthy process in which funders must hunt for external peer reviewers for applications, chase overburdened reviewers and rank applications. The trial was done by the UK Metascience Unit, a government group established in 2024 to study and improve the way science is funded and conducted. The results were released at the Metascience 2025 conference in London on 30 June. The gains “are huge in terms of efficiency and delivering funding”, says Tom Stafford, a cognitive scientist at the University of Sheffield. And he gives the Metascience group credit for using ways of stopping participants from gaming the system — for instance, by marking other applications harshly. “You just cannot benefit from giving someone else a low score,” says Stafford, who is trialling this review method elsewhere. “That’s really admirable.” Surge in applications Research funders have long sought ways to deal with ballooning numbers of grant applications. UK Research and Innovation (UKRI), which has an annual budget of around £8.8 billion (US$12.1 billion) and is the country’s biggest funding agency, had seen its application numbers soar from around 19,800 in 2021–22 to nearly 27,200 in 2023–24. At the same time, the agency had its operational budget cut by more than 15%, lost several hundred staff members and faced criticism for being bureaucratic and slow. Usually, peer review of grant applications at the UKRI takes between 4.6 and 6.3 months from submission to decision. Distributed peer review has been tested or adopted in a handful of other places. The European Southern Observatory in Garching, Germany, led the way by using it to review applications for a coveted slot on its telescope. The Volkswagen Foundation, a research funder in Hanover, Germany, has also been experimenting with it. The Metascience Unit spans the UK government’s Department of Science, Innovation and Technology and the UKRI. Appropriately, the metascience experiment involved researchers who were themselves applying for funding for metascience studies. In all, 100 applications were reviewed, and these were competing for around 18 grants worth a total of £4 million. Each applicant was given eight to ten studies to review, and had to deliver those reviews if they wanted their own grant to stay in the running. “Everyone has skin in the game,” said Ben Steyn, who co-directs the Metascience Unit and presented the results at the meeting. The trial showed that distributed peer review cut the time taken to 2.2 months on average — a reduction of 53%–65%. What’s more, most applicants said it expanded their knowledge of their field, according to a survey of the participants. “So this is peer review not just as a burden,” says Steyn. Cheating is not an option The “knee-jerk criticism” of distributed peer review, says Steyn, is that participants could try to game the system. Someone could mark other applications poorly, to boost their own application’s chances. Or two applicants could quietly agree to give each other’s submissions high marks.
Nature DOI suffix ≠ "/s...": Not a research article
How fast are you ageing? Ordinary brain scans reveal the pace
Heidi Ledford
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A magnetic resonance imaging scan (pictured, artificially coloured) of the brain can detail the risk of memory loss and other cognitive difficulties.Credit: Zephyr/SPL Telltale features in standard brain images can reveal how quickly a person is ageing, a study of more than 50,000 brain scans has shown1. Pivotal features include the thickness of the cerebral cortex — a region that controls language and thinking — and the volume of grey matter that it contains. These and other characteristics can predict how quickly a person’s ability to think and remember will decline with age, as well as their risk of frailty, disease and death. Although it’s too soon to use the new results in the clinic, the test provides advantages over previously reported ‘clocks’ — typically based on blood tests — that purport to measure the pace of ageing, says Mahdi Moqri, a computational biologist who studies ageing at Harvard Medical School in Boston, Massachusetts. “Imaging offers unique, direct insights into the brain’s structural ageing, providing information that blood-based or molecular biomarkers alone can’t capture,” says Moqri, who was not involved in the study. The results were published today in Nature Aging. Slowing the clock Genetics, environment and disease all affect the speed of biological ageing. As a result, chronological age does not always reflect the pace at which time takes its toll on the body. Researchers have been racing to develop measures to fill that gap. Ageing clocks could be used early in life to assess an individual’s risk of age-related illness, when it might still be possible to intervene. They could also aid testing of treatments aimed at slowing ageing, by providing a marker to track the effects of the intervention in real time. Why eating less slows ageing: this molecule is key A host of candidate clocks has emerged in the scientific literature — and in direct-to-consumer advertising — over the past decade. Many of these were developed by feeding reams of data, such as measurements of the levels of molecules found in the blood, into computer algorithms that determine which parameters are linked with ageing. Often, the reasons underlying these correlations are unclear. To develop an improved clock, Ethan Whitman, who studies brain ageing at Duke University in Durham, North Carolina, and his colleagues began with a remarkable study of more than 1,000 people born in Dunedin, New Zealand, between April 1972 and March 1973, who have been periodically assessed since birth by researchers. In the most recent of those assessments, participants’ brains were scanned using magnetic resonance imaging. Whitman’s team fed measurements made from 860 of those brain images into their algorithm and had it look for correlations between the brain-scan data and what the team called the pace of ageing, a measure that incorporates data from all the Dunedin participants’ age-related declines in cardiovascular, metabolic and immune function, as well as other physiological measures.
Nature DOI suffix ≠ "/s...": Not a research article
Ageing is linked to inflammation — but only in the industrialized world
Miryam Naddaf
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Men from Malaysia’s Orang Asli population, one of the Indigenous groups that participated in the study.Credit: De Visu/Shutterstock People from non-industrialized Indigenous communities do not show the link between chronic inflammation and age-related illness that is seen in industrialized societies, finds a study that looked at nearly 3,000 adults in four countries. Inflammation is an important part of the immune system’s response to infection, but long-term inflammation can cause damage. The latest findings, published in Nature Aging on 30 June1, show that chronic inflammation — which has been long considered a hallmark of ageing — could be a feature of industrialized living. How quickly are you ageing? What molecular ‘clocks’ can tell you about your health Researchers analysed inflammation-linked proteins in blood samples from people living in Italy and Singapore, along with those from Indigenous participants living in non-industrialized or semi-industrialized communities in Bolivia and Malaysia. They found that inflammation levels increased with age and were linked with illnesses such as chronic kidney disease in the Italian and Singaporean groups. But in the two Indigenous groups, inflammation did not increase with age or lead to health conditions. This suggests that “our assumption that inflammation is an inexorable, inevitable part of ageing is not true”, says Thomas McDade, a biological anthropologist at Northwestern University in Evanston, Illinois. “We shouldn’t assume that the links between inflammation and ageing are universal.” “We’re at a point where we’re rethinking the whole nature of inflammation,” says study co-author Alan Cohen, who researches ageing at Columbia University in New York City. “The things that we think of as universal based on a lot of studies in Western industrialized populations are probably just particular to our environment.” Challenging assumptions Much of what researchers know about the biological processes that underlie ageing is based on research in wealthy countries, which suggests that inflammation increases with age and can contribute to health conditions such as Alzheimer’s disease, diabetes and heart problems. But these conditions are rare in non-industrialized populations. To explore how inflammation might affect ageing in different environments, Cohen and his colleagues analysed blood samples from 1,041 participants in Italy, 941 from Singapore, 536 Tsimane people from the Bolivian Amazon and 358 Orang Asli individuals from Peninsular Malaysia. More than 50% of the people in each group were female. Ageing studies in five animals suggest how to reverse decline The researchers measured how levels of eight proteins called cytokines — molecules released by immune cells that are involved in various types of cell signalling, including inflammation — changed with age in each group. They also examined whether high levels of the cytokines were associated with age-related health problems.
Nature DOI suffix ≠ "/s...": Not a research article
Can AI build a virtual cell? Scientists race to model life’s smallest unit
Ewen Callaway
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Virtual cell models could help to predict how tumour cells (pictured) respond to experimental drugs. Credit: Steve Gschmeissner/Science Photo Library If Stephen Quake gets his way, biologists in the future will spend a lot less time wielding pipettes. “Our goal,” he says, “is to create computational tools so that cell biology goes from being 90% experimental and 10% computational to the other way around.” Quake, head of science at the Chan Zuckerberg Initiative (CZI) in Redwood City, California, is among the researchers leading a charge to create virtual cells. These are artificial intelligence (AI) models that can generate the kinds of insight that currently take weeks of experiments to answer — such as how tumour cells will respond to a particular drug. “It’s going to be a very powerful tool for understanding what goes wrong in disease,” says Quake, who envisions that scientists will use experiments mainly to validate predictions made by virtual cells. I told AI to make me a protein. Here’s what it came up with Efforts to create virtual cells are in their early days, but the idea has attracted intense interest in both academic and industry laboratories worldwide. CZI, a non-profit organization that develops open data sets and tools, is planning to spend hundreds of millions of dollars on creating virtual cells over the next decade. Google DeepMind, in London, has a virtual-cell project too, its chief executive Demis Hassabis said earlier this year. “This is a gigantic task,” says Jan Ellenberg, a molecular biologist at the Science for Life Laboratory, a national research organization in Solna, Sweden. He is co-leading the lab’s own virtual-cell model called Alpha Cell, which will launch in 2026. “What is possible now and needed now is to have the first pioneering projects that show this can, in principle, work.” But some scientists say that the rush to develop virtual cells — although an important long-term goal for biology — has a lot of hype, but not a lot of concrete results or a clear path to success. “It’s primarily being used as a rallying cry and a funding mechanism, and it’s working,” says Anshul Kundaje, a computational biologist at Stanford University in California. “Investors are putting a huge amount of funding into this space.” Bugs in the machine Biologists have been using computers to model cellular behaviour for decades. In 2012, scientists created the first computational model of an entire cell, capturing the inner workings of the bacterium Mycoplasma genitalium, which has just 525 genes1. But these and other early efforts “were often trying to really build a full mechanistic model of the cell”, says Silvana Konermann, a computational biologist at the Arc Institute in Palo Alto, California. By contrast, the current push to develop virtual cells takes advantage of advances in AI that allow it to develop sophisticated representations of data, such as text in the case of large language models, when fed vast quantities of it. “Building models that learn from data is revolutionary,” says Quake. Five protein-design questions that still challenge AI Early virtual-cell offerings have focused largely on one type of data: that from experiments that sequence all of the messenger-RNA molecules in individual cells, amounting to a catalogue of gene activity and a snapshot of the cell’s current state. These data form the basis of ‘atlases’ that map different cell types across humans and other organisms, revealing underappreciated diversity. Researchers are now churning out ‘single-cell sequencing’ data sets to help power their virtual cells. CZI has plans to release sequencing data from one billion cells (expanding a database of more than 100 million), and in February, Arc released sequencing data from 100 million cancer cells treated with hundreds of drugs. Single-cell sequencing data is appealing, says systems biologist Hani Goodarzi at the Arc Institute, because it can be affordably generated at a similar scale to that at which large language models start to gain sophisticated capabilities — in the hundreds of billions of datapoints.
Nature DOI suffix ≠ "/s...": Not a research article
’We couldn’t live without it’: the UCSC Genome Browser turns 25
Michael Eisenstein
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Jim Kent knew a thing or two about coding. A veteran of the early days of personal computing, Kent developed software for Amiga, Atari and IBM computers throughout the 1980s, including pioneering tools for computer animation. By 2000, Kent had made the leap to bioinformatics, developing the computational genome-navigation system that would become known as the University of California Santa Cruz (UCSC) Genome Browser. But his expectations were tinted by his industry experience. “I was really used to software lasting about three years,” says Kent. His latest creation, he predicted, would fare no differently. Every base everywhere all at once: pangenomics comes of age “It didn’t happen,” says geneticist David Haussler, scientific director of the UCSC Genomics Institute that runs the Genome Browser. This month marks the 25th anniversary of the browser, which has blossomed into an essential resource for biologists around the world. On any given day, more than 7,000 unique users engage with the site, which hosts genome data from humans, mice and more than 100 other animal species and viruses, and allows researchers to annotate and interrogate those sequences in countless ways. Comparative genomicist Michael Hiller at Goethe University in Frankfurt, Germany, relies on the browser to investigate patterns of genome change across animal species to identify signatures of evolution. “Looking at the Genome Browser is a large part of what we and the other lab members do on a daily basis,” he says. He has even incorporated the tool into a course he teaches. “That’s part of the exercises,” he says. With a steady stream of updates and user-generated annotation tools, the Genome Browser shows no signs of slowing down. “The website took on a life of its own,” says Max Haeussler, the project’s principal investigator. But as with many US-based scientific projects in 2025, the real threat to its longevity comes from tightening of the purse strings, with massive cuts and restructuring at the US National Institutes of Health (NIH) putting this essential resource at risk. Hitting the ground running It began with the Human Genome Project. Haussler joined the effort in late 1999, with the goal of developing software that could identify and annotate genes in the newly assembled genome. But there was an issue. “It became clear to me very quickly that this problem of assembling the human genome from small pieces of sequenced DNA was extremely difficult, and they had no serious plan to do it,” Haussler recalls. He turned to Kent, a skilled coder who was completing a PhD at UCSC focused on developing the Intronerator, a genome browser for mapping gene expression in the worm model species Caenorhabditis elegans. In a frenetic programming crunch that spanned several weeks in 2000, Kent developed GigAssembler — 10,000 lines of code that Haussler describes as “the assembler that saved the day”. It enabled the Human Genome Project to complete its first draft in time for its official unveiling on 26 June 2000. Bioinformatician Jim Kent, who helped to develop the UCSC Genome Browser.Credit: Don Harris/UC Santa Cruz Photo Services Kent’s initial interest was mostly pragmatic. “I wanted to get the human genome browser up just so that I could double-check my assembly more easily,” he says. But when he and Haussler launched the first iteration of the UCSC Genome Browser on 7 July 2000, it was an instant success. The scientific community collectively downloaded roughly half a terabyte of data in the first 24 hours of the browser’s operation, the team estimates — a staggering amount at the time. The genome was then only about 90% complete and rife with gaps, but the world finally had a freely available window for surveying it. “Just being able to go to a browser view of early gene annotations or early cloning enterprises was like a magnet,” says Barbara Wold, a molecular biologist at the California Institute of Technology in Pasadena. “It drew everybody into the community of users.” Importantly, the browser also established objective ‘mile markers’ that researchers could use to map discoveries and variants in individual genomes. Ian Holmes, a computational biologist at the University of California, Berkeley, also credits Kent and the UCSC team for normalizing the idea that genomic data should be free and easy to engage with and reuse. “The idea that everything should be available on the web and not desktop applications was still an extremely radical idea then,” says Holmes. “They invented a tonne of file formats and just ways of storing data that we are widely using today.” Senator Tom Harkin (Democrat) helped to secure funding for the Human Genome Project, which was able to assemble the sequence using code from the UCSC Genome Browser team.Credit: NHGRI/NIH Over the next few years, the Genome Browser updated its maps with the latest data from the Human Genome Project, as well as from other popular model species, including the mouse and rat. Kent also introduced a defining feature, based on his experience with the Intronerator: the ability for users to generate and share custom ‘tracks’ that selectively annotate key features of the genome. Tracks are interactive visual road maps, presented alongside the genome, that chart the location of important features such as regulatory elements and disease-associated gene variants. “We were way ahead of everybody with that feature, and I think that’s really kind of why we ended up so much in the middle of the ecosystem,” says Kent. The effort gained early momentum thanks to buy-in from key international consortia such as the Encyclopedia of DNA Elements (ENCODE) project. ENCODE was focused on the functional motifs that populate the 98.5% of the human genome that does not contain protein-coding gene sequences. Haussler says that the Genome Browser’s roster of custom tracks “grew dramatically” during the ENCODE team’s work, allowing users to visualize the many promoters, enhancers and non-protein-coding RNAs that the consortium uncovered. A durable resource Still, Kent’s initial gloomy prediction of the browser’s life expectancy was not unreasonable — such narratives are typical in academia. “Imagine if Microsoft Office disappears every three years,” says Haeussler. “This is the case for most bioinformatics-software packages.” Graduate students and postdoctoral researchers move on, and platforms stagnate even as new data accumulate, until somebody else is compelled to develop a replacement. How the human genome transformed study of rare diseases And the data have steadily poured in. “There are no White House meetings any more when you publish a genome,” says Haeussler, referring to the announcement of the first human genome draft. “Now we get one a day, or even ten a day.” And it isn’t only genomes, but also new layers of information that people want to map on top of them, such as full-length RNA transcripts and epigenetic signals that play a central part in gene regulation. At the same time, the tool’s user base has grown steadily. The UCSC Genome Browser’s ability to survive and accommodate this growth is partly attributable to the early decision to build a team of dedicated programmers and engineers. Many of these were seasoned Silicon Valley veterans impressed by the browser’s ambitions and scrappy origin story. “I kind of crashed [Kent’s] PhD defence,” says Angie Hinrichs, a former microchip designer who had minimal biology expertise but nevertheless volunteered for the Genome Browser team in early 2002. “And then, in May, when they were hiring, I just barely managed to squeak in over their requirements.” She would be one of the first new hires on a team that swelled to roughly 30 people at its peak. Output from the UCSC Genome Browser showing information for the human SHH gene, which is involved in embryonic development.Credit: Perez et al. The UCSC Genome Browser database: 2025 update. Nucleic Acids Research 2025 PMID Access to affordable and powerful computing infrastructure hasn’t hurt, either. “In the early days, it probably seemed like a lot to have 32 processors, and now our development machine has 192,” says Hinrichs. The data themselves, as well as the code to run the browser, reside on petabyte-scale arrays that include numerous super-speedy, solid-state hard drives, she adds. The Genome Browser’s codebase has grown from just 10,000 lines to more than three million, Haussler says. But its fundamental architecture has not changed much in 25 years. Hinrichs says: “There have been many chefs in the kitchen, and it’s gotten a little messy, but the core structure of it was so clean that it has actually worked and we can still develop on it. I credit Jim Kent for that.” From Kent’s perspective, this durability is attributable to his focus on creating modular code that can be tweaked without bringing down the whole edifice, as well as a dedicated testing corps. “We had a quality-assurance team that was about half the size of the software-development team,” he says. “I think we only had to roll back a previous version once.” Human Genome Project - Nature’s editor-in-chief reflects 20 years on The team has had to devise more efficient ways to handle data, however. In 2011, for example, it introduced the ‘track hub’ format as a solution to the increasingly large and complex custom tracks that external laboratories were developing for genome annotation. Track hubs comprise sets of relatively compact binary files that are hosted by the data creators themselves, rather than at UCSC. The data are streamed on demand, and “Jim’s file formats are designed so you can jump between them,” says Haeussler. The ability to rapidly and selectively access the relevant parts of the remotely hosted data minimizes the amount that needs to flow back and forth between the user and the Genome Browser. This maintains performance speed even as the number of tracks rises. “We have thousands of labs making them, but most of them we never see,” says Haeussler. And in 2023, the team launched the initiative GenArk (Genome Archive) to accommodate the unending influx of new genome sequences (H. Clawson et al. Genome Biol. 24, 217; 2023). This system makes it straightforward for the Genome Browser to pluck newly uploaded genomes from the Assembly database hosted by the US National Center for Biotechnology Information (NCBI), allowing researchers to view and annotate those genomes. GenArk currently hosts more than 6,000 genomes, ranging from bacteria to primates. Something for everyone
Nature DOI suffix ≠ "/s...": Not a research article
Arrests of scientists over smuggled samples add to US border anxiety
Humberto Basilio
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After being charged last month with trying to smuggle frog embryos into the United States, Kseniia Petrova, a Russian bioinformatician, was indicted on 25 June on additional charges by a grand jury in Boston, Massachusetts — including making a false statement to customs agents. Petrova is one of at least four foreign scientists facing criminal charges for attempting to bring biological material into the country, adding to the anxiety rippling through the research community as the administration of US President Donald Trump slashes science spending and cracks down on immigration. International PhD students make emergency plans in fear of US immigration raids Nature talked to research and legal specialists to understand whether these cases cropping up is unusual and how lab materials should be transported. Detentions for carrying undocumented biological material into the United States happen every year, says Jonathan Grode, an attorney at the immigration law firm Green and Spiegel in Philadelphia, Pennsylvania, who is not involved in any of the cases. Typically, if a person enters the country with a non-hazardous item that is either prohibited or lacks the proper documentation, the authorities confiscate the item, inform the individual of the proper procedure to retrieve it and issue a fine for failing to follow protocol, Grode says. If something is considered hazardous, that changes the calculus, as does being a repeat offender. If you’re both of those things “you are going to get arrested, you are going to be fined and you are going to be denied entry to the country”, he adds. “The rules have not changed” under the Trump administration, Grode says. What has is the “sensationalism” around any foreigner who has problems at the border, whether from the media or from the Trump team highlighting the case in its deportation efforts, he adds. Customs violations Petrova, who had been working at Harvard Medical School in Boston, Massachusetts, was arrested in February for allegedly failing to declare the embryos when transporting them to Harvard from France. At a hearing on 18 June, Brian Goldsworthy, an agent for the US Department of Homeland Security, testified that border agents at Boston’s Logan International Airport asked Petrova whether she had food in her bag and she said no — but she was actually carrying a foam box containing the embryos. Petrova’s immigration attorney, Gregory Romanowsky, contends that border agents broke protocol, because the alleged customs violation should have triggered a civil process rather than a criminal one. Instead, agents treated the issue as an immigration violation, revoked Petrova’s visa and started deportation proceedings, he says. She spent 116 days in detention before her release from federal custody on bail on 12 June. Kseniia Petrova was released on bail from federal custody on 12 June.Credit: Leah Willingham/AP Photo/Alamy Petrova might be able to avoid some of the criminal charges, because there are questions about whether the embryos were hazardous, Grode says, but her mistake was not to tell the authorities about the embryos in the first place. “That is the number-one way you can find yourself in trouble,” he says. In another case, the US Federal Bureau of Investigation (FBI) arrested Yunqing Jian, a Chinese postdoctoral fellow at the University of Michigan in Ann Arbor, earlier this month. According to court documents, in July last year, her partner, Zunyong Liu, a researcher at Zhejiang University in China, tried to bring samples of a fungus known as Fusarium graminearum, which can harm cereal crops such as wheat, into the United States. He initially denied carrying the fungus in his backpack, the documents say, but then admitted he was taking it to Jian’s university, where he said he planned to study it during his visit. Following an investigation by the FBI, both plant pathologists have been charged with conspiracy, smuggling and making false statements, and Liu has also been charged with visa fraud. Jian remains in custody in Detroit, Michigan. According to a criminal complaint filed by FBI agent Edward Nieh on 2 June, phone records show that this wasn’t the first time Jian and Liu had smuggled biological materials into the United States. ‘Another blow’: how Trump’s latest travel ban could harm research On 8 June, another Chinese scientist, Chengxuan Han, was arrested at Detroit Metropolitan Airport. Han, a biologist at Huazhong University of Science and Technology in Wuhan, was planning to spend a year conducting research at the University of Michigan, according to a criminal complaint filed as part of the case. The authorities detained her and charged her, alleging that she had, on four occasions, sent staff members at the University of Michigan “concealed biological materials” that were “related to round worms”, according to a press release issued by the US Attorney’s Office for the Eastern District of Michigan. A Department of Homeland Security spokesperson told Nature that parasitic roundworms can cause significant damage to crops, leading to economic hardship for farmers. The criminal complaint filed with the case doesn’t mention parasitic roundworms — only Caenorhabditis elegans, a type of roundworm frequently used in the laboratory as a model organism. The hazardousness of the materials that the scientists sent will need to be assessed in each case, as will the scientists’ intent in using the materials, but their lack of transparency will make their cases more difficult, Grode says. “It’s not so much what was being sent, but the effort to conceal what was being sent,” he says.
Nature DOI suffix ≠ "/s...": Not a research article
I pioneered my country’s newborn health-screening programme
James Mitchell Crow
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“Standing by this instrument in my laboratory, I am transported back three decades, when I launched a pilot study that became the Philippines’ newborn health-screening programme. When our pilot began in 1996, we manually tested the babies’ blood-spot samples, one by one, for five common health conditions. Now, with the help of this automated genetic-screening processor, we test thousands of samples each day for several conditions, including rare diseases — all with just a drop or two of blood. Health-screening programmes such as this quickly detect conditions that can cause learning disabilities, delayed development and even death without early intervention. However, such screening isn’t available for 70% of babies worldwide.
Nature DOI suffix ≠ "/s...": Not a research article
3D printing offers a way to study mimicry by insects
Thomas N. Sherratt, Karl Loeffler-Henry
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The natural world is rife with deception. Among the most striking examples are Batesian mimics1, which are harmless edible species that have evolved to resemble harmful creatures, such as hoverflies that mimic wasps or bees. This resemblance protects the mimic, as long as its predators are sufficiently duped. However, some mimics are far from convincing imitators. Writing in Nature, Taylor et al.2 use an innovative experimental approach to investigate how this imperfect mimicry might persist.
Nature DOI suffix ≠ "/s...": Not a research article
What’s it like to work with an AI team of virtual scientists?
Nicola Jones
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On a Sunday morning in April, pathologist Thomas Montine ran one of the most surreal meetings of his life. In an online test interface for a system called the Virtual Lab, Montine constructed a team of six artificial-intelligence (AI) characters, all powered by a commercial large language model. He gave them specialities: he made a couple neuroscientists, one a neuropharmacologist and another a medicinal chemist. Then, he asked this virtual lab group to examine possible treatments for Alzheimer’s disease and discuss gaps in knowledge, barriers to progress and hypotheses to be tested — the same questions he has to consider in grant applications. A few minutes later, he had a transcript of their conversation, which ran to more than 10,000 words. A virtual principal investigator had kicked things off: “Thank you all for joining this important meeting.” Montine, who studies cognitive impairment at Stanford University in California, was testing an example of an emerging trend in AI-assisted science: using teams of chatbot specialists to develop a scientific idea as a lab team might do. The developers of these ‘co-scientist’ systems argue that such collaborative efforts can help researchers to think through research hypotheses rapidly, saving time and — in a more contentious assertion — producing new and important research ideas. What are the best AI tools for research? Nature’s guide The most prominent team exploring this concept comprises researchers at the technology giant Google, who this February announced the results of early tests of their AI co-scientist with researchers1 (see also go.nature.com/3hmxuxm). The team has opened up the project to a group of trusted testers as it continues to develop the tool. Google is not alone. A team including computational biologists at Stanford University announced its Virtual Lab system in November last year2 — a version of which Montine was playing with. And a group based at the Shanghai Artificial Intelligence Laboratory in China proposed a similar virtual-scientist system, called VirSci, last October3; the researchers are building it now. Rick Stevens, a computer scientist at the University of Chicago and at Argonne National Laboratory, both in Illinois, says that he and other computationally adept researchers are creating their own such systems by setting up AI personas that then interact. “I mean, everybody can do it,” he says. In many of these systems, the large language models (LLMs) involved don’t just bounce ideas off each other. They also search the Internet, execute code and interact with other software tools, making them part of ‘agentic AI’, a fuzzy term that refers to LLMs autonomously undertaking tasks, although in practice there is often a lot of human oversight. A group of AI agents can be woven into a larger system that can work on high-level problems for hours without getting distracted or confused, Stevens says. “It’s not really fundamentally that different than having more colleagues, in some sense,” he says, “except that they don’t get tired, and they’ve been trained on everything.” To explore what it’s like to work with a virtual team, Nature asked a few scientists to trial a version of the Stanford system and spoke to some who have used Google’s AI co-scientist. Does a network of chatbots talk like a room full of Nobel prizewinners or undergraduates? Are the ideas they generate nonsensical, boring and trivial, or smart, valuable and insightful? Multiple personalities All co-scientist systems assign roles or personalities to agents and get them to interact, but the details vary. The Virtual Lab, built by computer scientist Kyle Swanson in James Zou’s group at Stanford University and his colleagues, comes with two default characters, both (for now) powered by the LLM GPT-4o from tech firm OpenAI in San Francisco, California. These characters are a principal investigator and a critic — an agent told to provide helpful feedback. The user (or the AI’s principal investigator) can then add as many agents as they like, of any kind, writing in simple descriptions for each agent to guide the characters’ interactions. The user chooses how many turns the agents have to ‘speak’, and a meeting transcript is produced in minutes. The team is working on ways to train the agents on literature that is relevant to the characters’ described expertise (as others have done4), rather than merely telling them to assume specific roles. The Google co-scientist, developed by Google Deep Mind’s Alan Karthikesalingam in London and Vivek Natarajan in Mountain View, California, and their colleagues, is an extension of the researchers’ work on AI that is specialized in biomedicine, including the LLM Med-PaLM. AI scientist ‘team’ joins the search for extraterrestrial life In contrast to the Stanford system, the Google tool doesn’t let users assign scientific specialities to agents. Instead, agents have predefined specific functions: idea generation; reflection or critique; evolution of ideas; determining the proximity of ideas to reduce duplication; ranking; and meta-review. These six agents are powered by Google’s LLM Gemini 2.0. Users prompt the system with a few sentences, including a goal and a desired format for output. They can choose to add background information, such as relevant papers. The agents collaborate to tackle the problem and search the Internet, then spit out a summary report that can be tens or hundreds of pages long. “The co-scientist is like a smart scientific partner, capable of seeing the obvious and non-obvious connections in a sea of research,” says Natarajan. “We hope to give scientists superpowers.” Like all LLMs, the models powering these agents sometimes hallucinate, making up text that can be wrong. But having a critic or judge in a multi-agent conversation tends to weed out things that don’t make sense, says Stevens. Besides, he adds, hallucinations can be useful for creative processes such as thinking outside of the box during brainstorming, as long as experts check that the output makes sense. There is evidence that the multi-agent strategy improves output, compared with chatting to just one AI agent or bot. For instance, Zou has found that adding a critic to a conversation that used GPT-4o bumped up the model’s performance score by a couple of percentage points on graduate-level science tests, and improved its answers in test cases, including designing radiotherapy treatment plans5. Exclusive: Start-up FutureHouse debuts powerful AI ‘reasoning model’ for science Google tested its AI co-scientist system to see whether human experts preferred its multi-agent answers over content produced by a lone chatbot1. The experts rated the novelty and impact of the ideas generated by the co-scientist system slightly higher than those generated by Gemini 2.0 or OpenAI’s o1. Some research has even delved into the optimum number of agents and rounds of discussion. Computer scientist Nanqing Dong at the Shanghai Artificial Intelligence Laboratory and his colleagues, who are building the VirSci system, say that they see peak creativity with a team of eight agents each taking five turns to converse3. Swanson says that in his experience, adding more than three specialists often just leads to “wasted text”, and more than three rounds of conversation sometimes sends the agents off on a tangent. Bright ideas Stanford University medical researcher Gary Peltz, who often uses AI in his work, was one of the first testers of the Google AI co-scientist. He wanted to use it to find drugs to treat liver fibrosis. Because the AI system was still in development, he sent his query to an intermediary at Google. His prompt read: “Develop hypotheses about the genes and epigenomic changes required for myofibroblast generation in liver fibrosis and indicate what drugs should we test as new treatments for liver fibrosis.” It also included some paragraphs of detailed background information. He got the report back about a day later. After some preliminaries, the report begins “We propose a novel hypothesis
” then works its way to concluding: “This research could have a profound impact on liver fibrosis research and therapeutic advancement.” (See ‘Testing an AI co-scientist’.) Testing an AI co-scientist An extract from the output that Google’s AI co-scientist system provided Gary Peltz. “Example experiment 1 (score=novelty+details+usefulness+pairwise rank=11): ## Prompt: A Novel Hypothesis Regarding Myofibroblast Generation in Liver Fibrosis We propose a novel hypothesis that specific epigenetic alterations contribute to myofibroblast (MyoF) formation in liver fibrosis. Unlike previous approaches that primarily focused on canonical TGFÎČ1 and PDGF pathways, we hypothesize that changes in the cell’s epigenetic landscape play a critical role in regulating MyoF differentiation and subsequent ECM production. Specifically, our hypothesis centers on the following key elements: *Histone Modifications: We theorize that during fibrogenesis, alterations in histone modifications, particularly deacetylation, in the promoter regions of genes responsible for MyoF differentiation occur. For example, reduced acetylation of Histone 3 lysine 9 (H3K9ac) could promote the recruitment of repressive transcriptional machinery, silencing pro-MyoF factors. Alternatively, increased acetylation on certain histones might facilitate the binding of transcription factors that drive MyoF identity. *DNA Methylation: Our hypothesis also posits that dynamic changes in DNA methylation patterns around genes involved in the MyoF pathway could be crucial. For instance, we predict that demethylation of CpG islands near regulatory elements of pro-MyoF genes might lead to enhanced transcription. Conversely, hypermethylation of the same regions might prevent the binding of critical activators, thereby inhibiting MyoF transition. These two mechanisms, working in concert, could provide a complex regulatory system governing MyoF generation and subsequent ECM deposition impacting liver fibrosis. ## Groundbreaking Experiment to Test the Hypothesis To test our hypothesis, we propose an innovative experiment utilizing the human micro-HO system: 
” Full text documented in ref. 6. See the end of this article for Peltz’s input. “When I read it, I literally fell off my chair,” says Peltz. He had just written a grant proposal focused on the importance of epigenetic changes in liver fibrosis, and the AI had targeted the same theme for its proposed therapeutics. The AI co-scientist suggested three drugs, and Peltz came up with two more (all of which are already approved to treat other conditions). Google paid Peltz to help accelerate lab testing, and over the next few months, Peltz’s lab tested all five drugs in its human organoid model. Two of the AI’s three suggestions showed promise for promoting liver regeneration and inhibiting fibrosis6, whereas neither of Peltz’s worked out. The experience left him impressed, he says: “These LLMs are what fire was for early human societies.” Other liver researchers, however, say that the AI’s suggestions for drugs were neither particularly innovative nor profound. “I personally think they are pretty common sense, not much insight really,” says Shuang Wang, who works on liver disease at the Icahn School of Medicine at Mount Sinai in New York City. Google’s Natarajan counters: “Sometimes things look obvious in hindsight”. Peltz says he was “particularly struck by the fact that it didn’t prioritize the things that I prioritized”. For the most promising drug in the AI’s candidate list, called vorinostat, he could find only two papers in PubMed that relate to its use in treating liver fibrosis. His choices had many more hits, making them seem like more obvious candidates. He adds that reading the AI report was similar to his discussions with postdocs. “They have a completely different perspective on things than I would,” he says. Stilted conversations The code for Stanford’s Virtual Lab is available on the developer platform GitHub, but the team has whipped up a simplified, private web interface for testers who don’t have the computer-science chops to deal with code. This interface differs a little from the full system, says Swanson, but the experience is roughly the same. In the paper introducing the Virtual Lab2, an AI team tackled designing biological components that could stick to a particular variant of the coronavirus SARS-CoV-2. In the first of a series of lab meetings mediated by human researchers, the AIs chose to focus on nanobodies (small antibody fragments) and selected four candidates to tweak. The researchers then asked the AI team to pick some existing software tools to redesign those nanobodies, and tasked specific AI agents with writing computer code to assess and rank the results. The process designed 92 nanobodies, of which 2 did indeed bind to the SARS-CoV-2 variant in lab tests. The researchers whom Nature asked to try out the Virtual Lab didn’t go as far as to conduct suggested experiments or get their AI teams to write code. But they still found the AI helpful. Montine, for example, says his AI team did a great job of synthesizing the current knowledge (a task that other LLM systems can also handle well) and wrote answers to his grant-application questions with aplomb. “It went further than a postdoc would on a first try of writing a grant, and it only took like 2 minutes,” he says. “And it is a hoot to use.” Cancer-genome researcher Francisco Barriga testing the Virtual Lab system.Credit: Francisco Barriga Another tester, cancer-genome researcher Francisco Barriga at the Vall D’Hebron Institute of Oncology in Barcelona, describes himself as a biochemist by training and a mouse modeller and genome engineer by choice, with zero coding skills and little experience with AI. He went into the trial hesitantly, suspecting that he would serve as a kind of non-tech-savvy control. Barriga tasked the Virtual Lab with designing mouse-model experiments to test specific biological compounds, known as type 1 interferons, for their ability to affect tumours or immune cells while using a minimal number of mice — a topic that he knows inside out (see ‘Testing an AI virtual lab’). The AI team suggested exactly what he would have done, Barriga says: it chose “the right models, the right experiments”. Testing an AI virtual lab Selections from the AI-generated output that researcher Francisco Barriga got back from the Virtual Lab system he tested. Principal Investigator: “Thank you all for joining this important meeting. Our goal today is to identify the minimal number of distinct type I interferons to test their role in anti-tumor immunity, specifically in the context of lung cancer, melanoma and pancreatic cancer using C57BL/6 mice. We need to ensure that our experimental design is both scientifically robust and ethically responsible, minimizing the number of mice used while capturing the relevant biology. To guide our discussion, here are some initial thoughts and questions: 1. Sequence divergence. Understanding which type I interferons are most sequence-divergent is crucial. This will help us select candidates that are likely to have distinct biological functions. I would like to hear from the Computer Scientist about any bioinformatics analyses or databases that could help us identify these divergent interferons. 2. Role in tumor and immune cells. We need to gather evidence on how these interferons influence tumor progression or immune modulation. The Immunologist and Cancer Biologists can provide insights from the literature and any previous experimental data. 3. Mouse model. Selecting the right mouse model is vital for our experiments. We need to ensure that the model accurately reflects the human condition we are studying. I would like input on whether the C57BL/6 strain is the best choice and if there are any specific considerations we should be aware of. 4. Experimental conditions. Finally, we need to design the experimental conditions. This includes deciding on control groups, treatment groups, and any other variables. I would like the Scientific Critic to help us ensure that our design is rigorous and that we are considering all necessary controls. Let’s proceed with each team member providing their insights on these points. We’ll start with the Computer Scientist, followed by the Immunologist, Cancer Biologists and, finally, the Scientific Critic. After each round of input, I’ll synthesize information and ask follow-up questions as needed.” See the end of this article for Barriga’s input. Still, Barriga says he feels like something essential is lacking. “It definitely doesn’t feel like humans are behind this.” The AI agents take turns, often ‘speaking’ in numerated lists, and are never rude, interruptive or argumentative. “It’s missing some of those leaps of intuition that you’ll get from a random conversation with some, I don’t know, plant biologist, over a coffee at 3 p.m. in a random hallway.” He could, of course, add a plant biologist — or a quantum physicist, or anyone at all — to his Virtual Lab group, but hasn’t tried that yet. “Maybe it’s good to bounce ideas off. But will it be a game changer in my day-to-day? I doubt it,” Barriga says. He adds that the system might be something his PhD students could consult: “If they ever run into trouble and I’m too busy, maybe I’m replaceable.” Broader insights A third tester approached by Nature, Catherine Brownstein, is a geneticist who works on orphan diseases at Boston Children’s Hospital in Massachusetts, and has more experience with AI tools. She says that she uses LLMs for speed, efficiency and to broaden her thinking. But she cautions that users typically have to be experts so that they can spot errors — in the past, chatbots have sent her on time-consuming wild-goose chases, with incorrect paper summaries forcing her to reread a paper and its references to be sure she hadn’t got things wrong. “You have to kind of know what you’re talking about, otherwise it’s really easy to get completely led astray,” she says. Catherine Brownstein cautions that research expertise is still needed when using chatbots.Credit: Kevin Ferguson/Boston Children’s Hospital However, when Brownstein used the Virtual Lab to critique a paper she was writing, she was startled — and grateful — when the AI suggested that she ask the patients where they felt the research should go next. This had not occurred to her, although she says it should have. “I was embarrassed,” she says. “I stopped and stared for a full minute, because I was just like, ‘Oh my God. How did I get so far away from my original passion of having patient-focused and -centred research?’” A simple checklist — or a chat with a friend, chatbot or even a bartender — might have led to the same insight. Yet, she says, none of her colleagues who had read her paper had thought to mention it. “It was actually a very humbling moment.” Stepping sideways
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: NIH still uses directives deemed illegal to screen grants
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
NiĂšde Guidon obituary: Brazilian archaeologist who upended ideas on early human migration
Meghie Rodrigues
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Credit: Lena Trindade/BrazilPhotos/Alamy NiĂšde Guidon, a Brazilian archaeologist, was one of the first researchers to challenge a long-standing consensus on when and how early humans arrived in the Americas. The Clovis-first theory — popularized by US archaeologists in the mid-twentieth century — posited that people first migrated from Asia to the Americas across the Bering Strait about 11,500 years ago. They then moved southwards, colonizing first North America and then South America. But Guidon, who studied cave paintings, hearths and worked stones in the state of PiauĂ­ in northeastern Brazil, found evidence that the region might have been occupied more than 30,000 years ago. Her conclusions caused uproar in the scientific community. Guidon has died aged 92. Born in the city of JaĂș in SĂŁo Paulo state, Guidon had a French grandfather who taught her his language when she was a child. In 1961, after receiving her diploma in natural history at the University of SĂŁo Paulo, she went to the Paris PanthĂ©on-Sorbonne University to study prehistoric archaeology. Returning to Brazil, she worked at the Paulista Museum in SĂŁo Paulo, where she first learnt about the ancient rock paintings in PiauĂ­. Who were the ancient Denisovans? Fossils reveal secrets about the mysterious humans Despite having no political affiliations, Guidon was anonymously denounced as a communist under the Brazilian military dictatorship that began in 1964. She went back to Paris and lived there until 1986. There, she became a researcher at the French National Centre for Scientific Research (CNRS) and obtained her PhD at the Sorbonne in 1975. In 1970, she made her first trip to PiauĂ­. She was so impressed with the ancient art that, in 1973, she organized a Franco-Brazilian expedition to the region. The team found 55 archaeological sites, including some scattered with flaked and polished pebbles that she attributed to human action. “We thought, then, that these sites were recent,” she wrote in a 2003 account for ComCiĂȘncia magazine, “because, like all American archaeologists, we believed that the Americas had been populated late.” But what Guidon and her team found in a collection of rock shelters called the Toca do BoqueirĂŁo da Pedra Furada suggested otherwise. Over decades, the researchers carbon-dated hearths at several stratigraphic levels, finding that some were more than 50,000 years old. Her 1986 Nature paper, written with Georgette DĂ©librias, one of France’s leading radiocarbon researchers at the time, presented charcoal dated to 32,000 years before the present — more than twice the age of any other known human settlement in the Americas (N. Guidon and G. Delibrias Nature 321, 769–771; 1986). Guidon’s work was met with scepticism in the United States, and heated debates ran for decades. Her critics argued that the dated hearth remains resulted from natural fires and that the flaked pebbles had been formed naturally in rockfalls. Still, Guidon’s relentlessness eventually convinced even some of her detractors to take her evidence seriously. In 2013, Walter Neves, a bioanthropologist at the University of SĂŁo Paulo, told Pesquisa Fapesp magazine that he had analysed the Pedra Furada pebbles at Guidon’s invitation. He was “99% convinced that the artefacts were in fact produced by men”. Oldest stone tools in Europe hint at ancient humans’ route there Gradually, a body of research corroborating Guidon’s theory began to take shape — including pre-Clovis findings elsewhere in the Americas and doubts that the route across the Bering Strait was ice-free during the time frame required in the Clovis-first hypothesis. Acceptance of the Clovis-first model has continued to decline, despite occasional findings that seem to support it.
Nature DOI suffix ≠ "/s...": Not a research article
Human embryo research: how to move towards a 28-day limit
Alejandro De Los Angeles, Nissim Benvenisty, Hongkui Deng, Jacob H. Hanna, Julian Koplin, Tianqing Li, Pentao Liu, Yuin-Han Loh, Duanqing Pei, Ryohichi Sugimura, Timothy Theodore Ka Ki Tam, Tan Tao, Alan Trounson, Shao Xu, Leqian Yu, Elias Zambidis, Magdalena Zernicka-Goetz, Robin Lovell-Badge
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In December, the UK national fertility regulator — the Human Fertilisation and Embryology Authority (HFEA) — recommended that the government extend the length of time for which human embryos can be grown in culture from 14 days to 28. Even though the UK government has not announced any plan to revise its laws in light of this recommendation, the HFEA’s announcement could have global ramifications (see go.nature.com/42j3pzp). As the first statutory body to regulate in vitro fertilization (IVF) and human-embryo research, the UK regulator has long shaped how other countries approach governance in this field. Since the ‘14-day rule’ was established in 1990, it set a limit that has been widely accepted by scientists, ethicists and policymakers in many countries. It has helped to maintain public trust in embryo research while enabling scientists to investigate the first days of human development — work that is crucial to understanding the origin of some congenital diseases and to design and improve IVF techniques. Guidelines on lab-grown embryo models are strong enough to meet ethical standards — and will build trust in science A structure called the primitive streak — a visible indicator that the embryo’s body axes are forming — appears around 14 days after fertilization. Before the primitive streak forms, an embryo can still split to form twins, making it less clearly an individual. For this reason, 14 days or primitive-streak formation — whichever occurs first — was chosen as a pragmatic cut-off point. However, scientific advances mean that it is almost certainly possible to culture embryos beyond 14 days1. By culturing them for up to 28 days, researchers could learn more about crucial subsequent developmental stages and the processes that occur before neurons and sensations arise, such as the start of organ development and the formation of the placenta. A visible indicator — closure of a structure along the embryos back called the neural tube, which goes on to form the central nervous system — marks a clear cut-off point at around 28 days, similar to the primitive streak at day 14. Although some researchers and others have raised concerns that extending the deadline might lead to a slippery slope of further shifts that go beyond ethically defensible boundaries2, this need not happen. Many scientists and other authorities are reconsidering the 14-day limit3–6. The HFEA’s announcement means that there’s a pressing need to consider how long-standing embryo-research frameworks might be revised in a responsible way. As an international group of scientists working in human-embryo research, stem-cell biology and translational research, we have observed the scientific potential and ethical dilemmas of embryo research at first hand. We’re also involved in ongoing dialogue with regulatory bodies. On the basis of these experiences, we propose that the research limit be extended to 28 days or complete neural-tube closure, whichever occurs first — in a similar way to current 14-day policies. We call for a collective effort by scientists, policymakers, ethicists and the wider public to navigate this transition. Why 28 days? The third and fourth weeks of human development have remained understudied because researchers are not permitted to culture human embryos past day 14, and samples of embryos and materials that have been aborted earlier than day 28 are scarce. Yet, we know from studies in other animals and from rare samples that embryos go through crucial changes in this second two-week period (see ‘An understudied period of growth’). Source: G. J. Tortora & B. Derrickson Principles Of Anatomy And Physiology 15th edn (Wiley, 2017). Shortly after 14 days, the first tissue layers emerge, laying the groundwork for the embryo’s body plan. By the point of neural-tube closure, the growing human embryo has clear head and tail ends — but has not yet developed neurons, without which there can be no consciousness, pain or other sensory perception. By day 28 the heart has started to beat. Buds that will become limbs have formed, but hands and feet will not develop for several more weeks. Other structures have also started to form: the beginnings of the gut; blocks of tissue that will go on to form the skeleton and muscle; and the beginnings of other internal organs. Studying how and why these first steps of organ formation sometimes go awry could help researchers to understand conditions such as congenital scoliosis (a curved spine), anencephaly (in which parts of the brain and skull are missing) and congenital heart disorders. Why researchers should use human embryo models with caution The cells that will become sperm or eggs also arise around day 14 and migrate to the nascent gonads during the following weeks. Meanwhile, tissues that support the growing embryo — including the placenta — begin to mature. Analyses of how sperm, eggs and supportive tissues begin to develop could help researchers to pinpoint causes of infertility, pregnancy complications and inherited conditions, paving the way for earlier interventions and better reproductive outcomes. What’s more, extending the 14-day rule could help to maximize the potential of stem-cell-derived embryo models3. These structures, which are designed to mimic all or some stages of embryonic development7, are subject to the 14-day rule in some countries8. The hope is that these models can be used for studies that require many samples — to test how drugs and other chemicals affect development, to conduct genetic screening, to analyse developmental anomalies and to improve engineering methods to grow cells and organs for regenerative medicine. But it’s crucial to know how closely these models mimic actual embryos — an extension of the 14-day rule would allow for better comparison. In our view, a limit of 28 days or neural-tube closure would maintain clear boundaries on experimentation. There are good reasons to draw the line at 28 days. The closure of the neural tube provides a clear stopping point that makes governance and oversight easier. The availability of aborted material that is donated to research is much higher after 28 days. And, after four weeks, the body plan is largely set. Many individual tissues and organs develop relatively independently after 28 days, and so can be studied using aborted tissue without needing whole embryos. Ethical considerations No global consensus exists on when personhood begins. Some people hold that life’s moral worth begins at conception. The 14-day rule never resolved this debate; it was a pragmatic, political compromise. Others point to the emergence of human-like features. Milestones that can convey emotional weight, such as the development of a heartbeat, are likely to cause concern. An erosion of a previously sacrosanct boundary might raise slippery-slope concerns about research eventually leading to eugenic practices or ‘designer’ embryos. There might also be concerns about consciousness or sentience, the ability to feel pain or react to environmental stimuli, such as light, sound, temperature or touch. However, current evidence indicates that the neurons needed for these capacities do not develop until an embryo is at least eight to ten weeks old, and might not form functional neuronal circuits until much later9. Any reforms must therefore be transparent, firmly regulated and based on clear ethical and moral boundaries10. This can help to reassure the public that researchers want to better understand human-embryo development, improve IVF treatments, reduce the number of miscarriages and prevent congenital conditions and diseases — and that they will not use embryos for more-controversial studies. Collectively, we think that extending the embryo-culture limit to 28 days, or neural-tube closure, would offer the promise of unique scientific and clinical insights. However, any increase must not be merely legislative — it should involve nuanced ethical oversight and careful dialogue with understanding from both sides11. A human embryo embedded in the wall of the uterus at 11 days after fertilization (left). At 24 days, the heart has just started to beat (right).Credit: Lennart Nilsson, TT/Science Photo Library Scientists have debated whether an extension of the limit should occur in gradual steps6 — allowing scientific and ethical review at several points between 14 and 28 days — or in a single jump. We recommend a single step. In our view, this approach is preferable because it would streamline governance and public engagement, and provide one clear boundary around which all oversight, communication and public dialogue could be structured. We imagine the approach would first be rolled out in one or two regions — such as in the United Kingdom under the guidance of the HFEA — and then iteratively adopted by other countries. We urge policymakers and research institutions to take the following steps. Public engagement and accountability. Careful consultation with the public, conducted and concluded well before experimental work begins, is essential to try and ease concerns and to help shape guidelines6. Some previous examples highlight how to aid effective debate. For instance, the HFEA’s dialogue on a specialized form of IVF called mitochondrial replacement therapy showed the value of multiple types of engagement across several locations, with a diverse cross-section of the population (see go.nature.com/43tyg9i). Similarly, public engagement related to extending the embryo-culture limit should involve dialogue events (formal discussions between multiple stakeholders)11, forums, citizen panels and surveys. Although these can be conducted by academics or relevant organizations, it is useful to incorporate specialist dialogue organizations that have expertise, but no direct interest in the outcomes. Examples and advice from the United Kingdom can be found through a public-engagement programme called Sciencewise. Researchers, policymakers, ethicists, community leaders and health-care professionals should all be involved in open dialogue with faith communities, patient-advocacy organizations and the broader public. Previous public engagement in Japan12 and in the United Kingdom — around the limits of embryo research and on the use of stem-cell-derived embryo models13 — shows that this approach can foster nuanced debates and minimize the risk of inflaming fears. Scientists should not make assumptions about areas of public concern. Feedback from the public should be used to help shape regulations for any extended embryo cultures. It should prompt adjustments in protocols and help to inform how guidelines are implemented. If strong ethical or societal concerns arise, researchers and regulators must be prepared to modify projects accordingly. Pilot projects. Before adopting new guidelines across a country, a few accredited centres could be licensed to extend the embryo-culture limit. The groups or centres would be chosen by national regulators — in coordination with professional societies and ethics committees — on the basis of established expertise in embryo research, robust ethical oversight committees and transparent track records of compliance. Once a group succeeds in culturing an embryo to the point of neural-tube closure or day 28, a comprehensive scientific and ethical review would ensue. Licensing can eventually expand to all suitably regulated centres in a nation, if the review concludes that the data provide clear insights — allowing researchers to map migration of the precursors of sperm and egg cells, for example, or study the beginnings of placental development — and that public trust remains intact. Yes to global standards for research — as long as they are truly global
Nature DOI suffix ≠ "/s...": Not a research article
Turmoil at US science academy as Trump cuts force layoffs
Jeff Tollefson, Dan Garisto
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The headquarters of the National Academy of Sciences in Washington DC.Credit: Radharc Images/Alamy One of the most influential scientific societies in the United States is in turmoil. Budget cuts by the administration of President Donald Trump have forced the US National Academies of Science, Engineering and Medicine (NASEM) into a wholesale reorganization. At the same time, many members are arguing that academy leaders have gone too far to accommodate the Trump administration — and done too little to defend science. Since Trump took office in January, his administration has cancelled or suspended tens of millions of dollars’ worth of contracts for advisory reports crafted by academy members and other scientists for sponsors including the US government. Meanwhile, the pipeline of contracts for future reports has largely dried up. These realities have already pushed the academies’ operations and publication branch, the National Research Council (NRC), to pare 50–100 people from its roughly 1,200-person staff, and hundreds more are expected to be laid off. “We are a target”: scientific society under pressure after Trump DEI crackdown NASEM members who spoke to Nature acknowledge the challenges facing leaders trying to preserve the institution, but some have accused the NASEM leadership of a lack of transparency, silence in the face of historic attacks on science and even censorship. In the latest example, critics cite internal guidance issued in March suggesting that the NRC will no longer permit research assessments “on topics explicitly related” to diversity, equity, inclusion and accessibility — principles disfavoured by the Trump administration. The upheaval has spurred talk of a no-confidence vote in Marcia McNutt, president of the National Academy of Sciences and chair of the NRC. “What’s the point in preserving the NRC as an organization if it loses its scientific integrity?” asks Charles Manski, an academy member and an economist at Northwestern University in Evanston, Illinois. In an interview with Nature, McNutt sympathized with her critics’ views, but said she is confronted with a “Faustian dilemma” in which challenging the administration, as many members advocate, could bring about the end of the organization, which depends on federal contracts for its existence. “What we are hoping is that sanity will prevail again some time in the future,” she says. “If it does, I’m not sure I want to be in the position where I have put the academy out of business.” The White House did not respond to a request for comment. Mission imperilled Every year, the NRC releases about 200 reports on topics ranging from the best pavement materials to the future of high-energy particle physics. These are authored by specialists including NASEM members, who are elected for their contributions to the sciences. US federal agencies, such as the National Science Foundation (NSF), commission many NRC studies, which policymakers regard as gold-standard advice. Last year, contracts with federal agencies supplied 59% of the NRC’s roughly $360-million budget. Last month, the organization announced a plan to consolidate internal divisions and reduce the number of NRC advisory boards, which guide study projects. McNutt says the current expectation is a 15% reduction in budget and staff by the end of August and a 30% reduction by the end of the year. Most academy members — as well as NRC staff members, who are in danger of being laid off — have been cut out of the process, says Elissa Newport, an academy member and neuroscientist at Georgetown University in Washington DC. National Academy of Sciences president Marcia McNutt has drawn criticism from academy members for her response to the Trump administration’s attacks on science.Credit: Yichuan Cao/Sipa USA/Alamy Stock Photo On 18 June, Newport sent an e-mail signed by more than a dozen academy members to McNutt and the NRC leadership, calling on them to consult with employees, board members and rank-and-file members about the reorganization. McNutt’s response — that leadership has consulted some members and does not have time to seek broader input — failed to satisfy. “They feel that the timeline requires an urgent process that must be kept confidential, and we strongly disagree with that,” Newport says. Silenced science On his first day in office, Trump banned federal programmes and contracts about diversity, equity, inclusion and accessibility (DEIA). Within a month, biomedical news outlet STAT reported that the academies were removing terms such as ‘health equity’ from reports to placate the administration. On 7 March, NASEM acknowledged these concerns in internal guidance documents summarizing institutional policies. One controversial provision clarified that although foreign assistance and climate change remained acceptable topics, despite being on the Trump team’s chopping block, anything explicitly related to DEIA would be prohibited. “It does not matter if the potential sponsor is federal or private,” the document states. Have Trump’s anti-DEI orders hit private funders? HHMI halts inclusive science programme “That would be censorship, and that would be the NRC selling its soul,” Manski says. The academy’s critics argue that Trump’s ban focuses on progammes that actively promote diversity and does not prevent the NRC from doing research on equity. McNutt concedes the point about censorship, but argues that a new DEI study would probably be the NRC’s last. “I’m completely sympathetic to [critics’] views” about censorship, she says, but “that is exactly what is being imposed on us.”
Nature DOI suffix ≠ "/s...": Not a research article
Extend your reach by turning your lessons into podcasts
William Mills
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A podcast lets students engage with lecture content while on the go.Credit: Bin Kontan/Getty Since I began teaching undergraduate biology in 2023, I have been searching for new ways to get students to engage with the content, especially outside class. I’ve tried all the classics: pre-class readings and quizzes; group discussions; sessions in which students work through practice problems; and holding office hours during which they can visit me to ask questions, just to name a few. Many — maybe most — students are able to comprehend the material through these avenues, but others struggle, often citing time pressures. ‘I didn’t have enough time to study because I had so many exams this week.’ Or ‘I spend so much time commuting to campus that I don’t have enough time to read the textbook’. So I decided to make a podcast to add to the list of available resources. It’s not fancy. There’s no catchy theme music, no witty advertisements or even guests. It’s just me talking about biology, audio-only. Despite its simplicity, I think it is a great way for students to engage with the content in my course while they’re taking a run, travelling or driving to and from campus. Word of mouth The idea came to me while I was attending a virtual conference about online teaching. One speaker suggested generating podcasts from assigned readings, using artificial intelligence (AI). The AI part sounded cool, but I worried about it editing or unexpectedly tweaking what I was trying to teach. So I decided to try to record a podcast using my own voice. A few weeks later, having taught myself about the process, I had the first dozen episodes of the Intro Biology Podcast. Although I am certainly not a pro, I have found a few tips and tricks to make creating a podcast rather straightforward, relatively painless and even quite fun. As long as you have a computer (or even a smartphone, really), you can make a podcast. Make sure you have some notes to guide the episode (I use my lecture slides), but don’t stress about getting it all in one take. You can always pause the recording and even re-record parts you don’t like. Use an app such as Voice Memos (on Apple devices), Sound Recorder (for Windows) or Recorder (on Android) to record yourself speaking. Once you’ve finished, give it a quick listen — even if listening to yourself speak makes you cringe — to make sure you haven’t made any mistakes. If you are satisfied, congratulations: you have just recorded your first episode. Now you have to publish it. To each their own Audiences can listen to podcasts on many different platforms: Apple Podcasts, Spotify, Castbox and Audible, to name just a few. When I first considered making a podcast, I was overwhelmed by the prospect of having to distribute my episodes to all these platforms individually. My fears were eased when I learnt about RSS feeds, which allow you to post your podcast on a single site that then distributes the episodes to all the different platforms. This saves an enormous amount of time and helps to maintain consistency. Depending on the RSS site you use (I use RSS.com, which offers discounts for educators), you can also gather useful metrics such as which platforms your listeners are using, where those listeners are around the world and which episodes are most popular. I wasn’t doing anything too fancy, but I did want a logo that was visually appealing and looked professional enough to motivate potential listeners to click on my show. Not having any artistic skills of my own, I turned to an AI image generator. With a little tinkering, I was able to use the colour scheme from the logo to create the cover art for each episode. This brings me to another tip: use broad, descriptive episode titles. The content I discuss in my podcast follows the progression of content in my course, but I wanted the episodes to be accessible to other audiences. So, rather than naming the episodes with a lecture date or the textbook chapter number, I gave them names based on the topic I was discussing, such as ‘Cells and Organelles’, ‘Enzymes’ and ‘Cellular Respiration’. Global reach In the six months since I published the first episode, the Intro Biology Podcast has been downloaded more than 4,100 times in 650 cities across 85 countries, all without any real advertisement apart from a single LinkedIn post. Because of the analytics I get from RSS.com, I can see that the city where my institution is located is among those with the most downloads, but the resource is being used by learners all over the world.
Nature DOI suffix ≠ "/s...": Not a research article
Postdocs file for union recognition at University of Michigan
Laurie Udesky
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The University of Michigan in Ann Arbor employs 1,500 postdoctoral scholars — more than 900 of whom have signed a petition for union recognition.Credit: University of College/Shutterstock Postdoctoral researchers at the University of Michigan have joined thousands of colleagues at other US institutions in seeking union recognition. Nick Geiser, a theoretical physicist and union organizer at the university in Ann Arbor, says the move was prompted by US President Donald Trump’s election win in November 2024: “It spurred many postdocs into action because our jobs are at stake.” US postdocs on strike: how will demands for higher wages be met? On 6 May, the University of Michigan Postdoctoral Researchers Organization (UM-PRO) filed for recognition with the university’s Academic Human Resources division after gathering signed authorization cards from more than 900 of the institution’s 1,500 postdoctoral scholars. “Union campaigns often take years, but UM-PRO obtained a supermajority of signatures in just six months,” Geiser says. A spokesperson for the University of Michigan did not respond to a request for comment. Since Trump took office in January, his administration has slashed billions of dollars in research funding from the US National Institutes of Health (NIH), the National Science Foundation and other agencies — including the money supporting union co-organizer Nikki Rodgers, a biophysicist in the second year of an NIH-funded Institutional Research and Academic Career Development Award fellowship at Michigan. The grant that was set to cover her for another year of research into the spread of breast cancer, as well as teaching students, has been prematurely terminated and will end on 31 July this year instead of in July 2026. Nikki Rodgers joined the unionization effort after her grant funding was terminated.Credit: University of Michigan Photography After learning about this, “I went straight home and cried most of the night”, she says. Her predicament and concern for other researchers motivated Rodgers to sign up to the unionization effort. “A union could be a way to collectively come to the table and say we need to have more protection where we’re not just relying on one faculty member to support our stay,” she says. Rodgers’ principal investigator told her that his group had applied for bridge funding to cover her until January 2026, but nothing had been finalized. With his encouragement, she looked for another job and has secured contract work as a technical writer in biology. Power to the people! The unionization effort at Michigan is part of a growing movement across the United States. According to a March 2025 study1 in the Journal of Collective Bargaining in the Academy, seven new postdoctoral ‘bargaining units’ were created in the United States in 2024, representing 7,668 employees — an increase of 67% in terms of total covered workers. Furthermore, 15 new graduate-student bargaining units were created, adding 11,724 graduate students to union rolls. Geiser and other organizers at the University of Michigan will be fighting for many of the bread-and-butter issues championed by other postdoctoral and graduate student unions: better pay, health benefits, job security and greater protections for international scholars. According to the university’s Postdoctoral Association, more than half of Michigan postdocs in 2022 were international students. Another signatory to the petition — an international postdoc at the University of Michigan who focuses on diversity, equity and inclusion and requested anonymity to speak freely — says they fear the government could terminate their research and revoke their visa at any moment.
Nature DOI suffix ≠ "/s...": Not a research article
If you’re a US researcher, now is the time to establish a plan B
Brandon Brown
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Students rally in Westwood, California, in protest against funding cuts and job losses in science.Credit: Myung J. Chun/LA Times/Getty Research is under attack in the United States. The availability of grant funding from institutions such as the National Institutes of Health (NIH), the Centers for Disease Control and Prevention and the National Science Foundation (NSF) — especially for anything remotely related to diversity, equity and inclusion (DEI) — is now in question, at least for the next few years. This will result in many researchers having to find alternative income streams, or even leaving science altogether. One of the programmes that I oversee on my campus was terminated last month. The Louis Stokes Alliance for Minority Participation (LSAMP) provided students from under-represented groups with extra funding and mentorship on a weekly basis. Now, fewer opportunities are available for these mostly first-generation students from low-income backgrounds and lower-performing schools. The funding was provided by the NSF, and supported professional development activities for emerging leaders in science, technology, engineering and mathematics. LSAMP is just one such programme; many more are on the chopping block. How Trump is following Project 2025’s radical roadmap to defund science Some states, including my home state of California, are being specifically targeted for large-scale funding cancellations, so things are escalating quickly. For example, a few weeks ago, the news outlet Politico reported that the federal government was considering cutting education and research funds for California, thanks to a continuing feud over immigration. In total, billions of dollars’ worth of grants are being terminated. One colleague working for the US Agency for International Development has had their position ended. Another worked at the NIH as an adviser on health disparities and has also lost their job. Many of my colleagues at universities in California have had their grants wrapped up early, especially those who focus on health disparities and DEI. As a result, they have had to look elsewhere for financial support. Brandon and his family have planted fruit trees, and he hopes that selling their produce could provide him with a secondary source of income should he lose his grant funding.Credit: Brandon Brown The grant funding I receive from various sources covers part of my salary, which is guaranteed by the state because of my tenured position. But many states, including Hawaii, Texas and Ohio, are now considering bans and limits on tenure. If this were to happen in California, I would be particularly at risk given that my work focuses on health-disparity topics that are being targeted for cancellation: HIV, global research ethics and supporting emerging faculty members who are conducting research into the challenges faced by ageing adults in minority groups. It would be naive to think that this won’t affect the job market: I expect many researchers to lose their salaries, jobs and health-care insurance as grants and funding dry up. This is already starting to happen. Frankly, it’s time for many scientists to start thinking about a career change, or at least how they might diversify their income streams to protect themselves against a loss of funding or a period of unemployment. Many think that the current challenges will be reversed after a few years, but that is a long time to be without an income. And even if most scientists were able or willing to move abroad, it’s unlikely that there would be enough overseas funding to make up for cuts to science here in the United States. One way to protect against these cuts might be to develop other streams of income while still pursuing a scientific career. Each of us has things we are good at apart outside scientific area of expertise. For example, my family and I have planted fruit trees and grown tomato plants, and we keep chickens that lay eggs, and my network allows me to sell those products. Other colleagues are generating cash from pet sitting and copyediting, working as a paid nanny or a personal chef, picking up paid teaching opportunities in schools and consulting for community-based organizations.
Nature DOI suffix ≠ "/s...": Not a research article
Wherever we go in this system, there we are
Todd Honeycutt
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After burning through a long shift, I slink into Deck Three’s small bar to take the edge off. Didn’t bother to invite a friend. Need some alone time. More than that — I need to get the hell off this stinking rock. I’m sick of the grind of the production lines, sick of life here. I settle and stare at the adverts. They pop up fast: a new mushroom liqueur, a restaurant on Deck Seven I’ve sworn never to visit again, a four-year trip across the Solar System on a ship called The Rambler. That one, it stirs a yearning in me. A person behind me starts talking, the softness of her voice unable to mask its authority. “You’re eyeing what they threw on the wall.” I don’t recognize her, and I thought I knew every one of the colony’s 2,000 inhabitants. She’s older, with a sharpness to her features, and her eyes have a piercing quality, like she can see right through any bullshit— can see right through my bullshit. “You’re probably thinking, ‘Yeah, why not see everything the Solar System has to offer? I deserve it.’ And you know what? You do.” She knocks her drink down, the expensive rye that most people take with syrup and water, but she’s having it straight, which I can’t help but admire. She motions the barbot for another and sends one of what I’m drinking my way. I turn my chair to face her. She ticks off the attractions like she wrote the advert herself. “Diving into Jupiter’s storms. Touching down on a Venusian platform. Spelunking in Enceladus’ ice caves. Marvelling at Europa’s oceans. Visiting that cloistered artist colony hiding in Mercury’s shadow. Breathing the unique scents of Ceres’ ag domes. And the crown jewel: a fly-by of our home planet, Mother Earth — but only a glance, because they won’t let any of us down any more.” Read more science fiction from Nature Futures She spins her cup on the table, metal dancing on metal, and my heart races as I want to respond yes, yes, a thousand times yes, I want off this pitiful little rock to see all that and more. “So much in the system that isn’t on this out-of-the-way colony bouncing around the Belt, the hub of a thousand mining operations. So much out there,” she waves her hand, “calling to be seen, heard, felt. Maybe you’ve got a bit saved up. You’re young enough to make anything work.” “You a recruiter?” She shakes her head. “I made that run four times, two as captain. You can believe they deliver. Every stop, every site — awesome in the truest sense. But what do you think, of everyone I ferried around, how many came away changed for the better by the trip’s end?” She sips her drink, I sip mine, the burn of low-grade rum stinging my throat. “Half?” I offer, thinking it generous, but not by much. She smiles, this captain of a Star Liner. “Not even one in a hundred. They return from each site, checking off an item on their list. And in between, people are who they are. By trip’s end, they’re tired and cranky and desperate to get away from each other. There’s no real enlightenment at seeing the System, no more than what you can find here.” I sit up and lean towards her and, in a half-pleading voice, say, “Something in you must have changed?” “Not from the sites. I tell you, this colony is as good as it gets. Your gardens and societies. Lot of trade and people and ideas come through this corner of the system, for those who can see.” “You must not be from here,” I say, too quickly; a joke I’ve used before.
Nature DOI suffix ≠ "/s...": Not a research article
It should be free to apply to graduate school
Benjamin Fernando, Michael Cassidy, Angela Russell, Aris Katzourakis
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The mean fee for graduate application to a US Ivy League university today is nearly US$100. After a decade-long campaign, doctoral applications to most UK universities are now free; the University of Oxford cut its fee by nearly three-quarters to ÂŁ20 ($27.5) in 2024.
Nature DOI suffix ≠ "/s...": Not a research article
Human space travel risks contaminating Mars
Alberto G. Fairén
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Inspired by entrepreneur Elon Musk’s ambition to make humanity a multiplanetary species, US President Donald Trump has issued one of NASA’s biggest challenges: landing humans on Mars. This push for the red planet has been met with mixed feelings by the planetary-science community, which has raised concerns about the budget, the physical integrity of astronauts and the scientific return on investment (see Nature https://doi.org/pq2t; 2025). However, one key issue remains unaddressed: what if there is life on Mars?
Nature DOI suffix ≠ "/s...": Not a research article
Trump team axes contracts with publishing giant Springer Nature
Max Kozlov
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US health secretary Robert F. Kennedy Jr (centre) has questioned the integrity of some top medical journals.Credit: Jim Watson/AFP/Getty Update: On 2 July, one US government agency, the Department of Health and Human Services (HHS), which oversees the National Institutes of Health (NIH), appeared to walk back its earlier statement to Nature’s news team saying that it was cancelling contracts to Springer Nature. Now the HHS says: “Science journals are ripping the American people off with exorbitant access fees and extra charges to publish research openly. HHS is working to develop policies that conserve taxpayer dollars and get Americans a better deal. In the meantime, NIH scientists have continued access to all scientific journals.” The administration of US President Donald Trump has cut some government agencies’ subscriptions to journals at Nature’s publisher, Springer Nature. And at least three government agencies say they are terminating all their contracts with the company. ‘Totally broken’: how Trump 2.0 has paralysed work at US science agencies The move comes amid criticisms of leading academic journals by high-ranking Trump officials, and will mean that staff members at the affected agencies will no longer be able to easily access the company’s more than 3,000 journals, including the flagship title Nature. (The Nature news team is editorially independent of its publisher.) Although it’s unclear precisely how many contracts the Trump administration is terminating, the government-spending database USASpending.gov shows that the US Department of Agriculture (USDA) and the US Department of Energy (DoE) cut US$3 million in contracts with the company this month. A spokesperson for the USDA told Nature’s news team that it had “cancelled all contracts and subscriptions to Springer Nature. The journal [sic] is exorbitantly expensive and is not a good use of taxpayer funds”. The DoE says that it is now cancelling the remainder of its contract with the company. And NASA confirmed that it is cancelling its subscriptions. When the news team reached out to the US National Institutes of Health (NIH) — the world’s largest funder of biomedical science — asking whether its subscriptions were still intact, a spokesperson initially said they were and that use of these resources helps staff members to “promote transparency and replicability in research”. Hours later, Andrew Nixon, the top spokesperson for the NIH’s parent agency, the US Department of Health and Human Services (HHS), said: “All contracts with Springer Nature are terminated or no longer active. Precious taxpayer dollars should be [sic] not be used on unused subscriptions to junk science.” NIH-funded science must now be free to read instantly: what you should know The HHS did not answer Nature’s follow-up queries about whether it intended to cut contracts with other large academic publishers, whether this move would prevent government scientists from publishing in journals that charge article-processing fees and whether it could provide examples of “junk science” published by Springer Nature. A Springer Nature spokesperson said in a statement that the company “continues to have good relationships with U.S. federal agencies” and that it doesn’t comment on individual contracts. “Across our U.S. business there is no material change to our customers or their spend,” they added. So far, the USASpending.gov database shows no terminations for the NIH, the HHS or NASA. In total, the database shows that seven government agencies have contracts designed to pay more than $20 million to Springer Nature this year. The White House did not respond to Nature’s queries. The US National Science Foundation, one of the world’s biggest funders of basic research, told Nature’s news team that its subscriptions with Springer Nature remain active and declined to comment further. “When they say, ‘junk science’, it’s not clear what they mean,” says Ivan Oransky, a specialist in academic publishing and co-founder of the media organization Retraction Watch. Given the lack of details justifying the cuts, and the fact that several of Springer Nature’s journals are considered prestigious, Oransky says, “I’m having a hard time taking at face value that this is not political”. It would be unprecedented for a prominent subscriber to make a “sweeping move like this for political reasons”, he adds. Journals under fire Late last month, US health secretary Robert F. Kennedy Jr called leading medical journals, including the New England Journal of Medicine, “corrupt”, suggesting that they have ties to pharmaceutical companies, and he threatened to bar government scientists from publishing in them. (He did not mention any of Springer Nature’s journals specifically.)
Nature DOI suffix ≠ "/s...": Not a research article
Can a pill replace exercise? Swigging this molecule gives mice benefits of working out
Heidi Ledford
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Young men who took up regular running experienced changes in their gut microbiome and more, including their levels of the molecule betaine.Credit: John Macdougall/AFP/Getty A molecule made by the kidneys and found in certain foods can reproduce some of the myriad benefits of exercise — and slow some signs of ageing — when fed to mice1. Betaine is a modified amino acid that plays an important part in metabolism. Results published on 25 June in Cell show that consistent exercise raises levels of the compound, at least in young men. The study also found that feeding betaine to aged mice boosts their immune health and grip strength. Whether it will have similar beneficial effects in people remains to be seen. But there is a need for treatments that can mimic the effects of exercise, says Christiane Wrann, a neuroscientist at Massachusetts General Hospital in Boston, who was not involved in the study. “There are people in the ageing population who don’t have the capacity any more to exercise to the extent they need,” she says. No pill measures up For now, there is no drug like exercise. It can sharpen the mind, soothe inflammation and rally cells to repair damaged tissue. It helps to keep some diseases at bay or ease their symptoms. “Physical activity is a recognized efficient and low-cost way to promote health and fight ageing,” says Guanghui Liu, who studies regenerative medicine at the Chinese Academy of Sciences in Beijing. “But its deep-level molecular mechanisms are still not fully clear.” Ageing studies in five animals suggest how to reverse decline To learn more, Liu and his colleagues enlisted the aid of 13 healthy young men willing to put their fitness goals on hold and lounge about for 45 days of limited physical activity. After that, the volunteers ran 5 kilometres every one or two days. The researchers took blood and stool samples and various physiological measurements from the men after their 45-day rest, and again after 25 days of their new running routine. A detailed analysis of those samples revealed the extent to which exercise reshapes the body at a molecular level. After 25 days of regular running, there were changes in immune cells, lipid metabolism, the gut microbiome and more. One of the biggest changes was in the abundance of betaine. Following up on these results in mice, the team found that exercise induced betaine production mainly in their kidneys. They also found that the molecule binds to and inhibits a protein called TBK1, which is known to promote ageing in cells and organs. Furthermore, old mice that drank water spiked with betaine had stronger muscles, less inflammation and more-youthful skin than did their counterparts that did not get the supplement.
Nature DOI suffix ≠ "/s...": Not a research article
RFK Jr’s vaccine advisers vote down flu-shot ingredient — but back some jabs
Mariana Lenharo
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Childhood vaccines used in the United States have not contained the preservative thimerosal for decades. Credit: Valentyn Ogirenko/Reuters Vaccine advisers appointed by US health secretary Robert F. Kennedy Jr have recommended against the use of influenza vaccines containing a mercury-based preservative called thimerosal — fulfilling a long-held goal of the anti-vaccine movement. The vote’s practical effects in the United States will be limited, because most US flu-vaccine doses are already free of thimerosal, which is present only in multi-dose vials, according to the US Centers for Disease Control and Prevention (CDC). And the ingredient was removed from all childhood vaccines in 2001. The committee, which includes a number of members who are sceptical of vaccines, also approved several measures supporting vaccination. Trump team vows to improve kids‘ health: scientists are sceptical Thimerosal has long been a target of the anti-vaccine movement, despite strong evidence supporting its safety in the low doses found in vaccines. Public-health officials and scientists say that the vote’s symbolic effects are powerful as they struggle to maintain public confidence in vaccines. “We are talking about such a small amount of vaccine” containing thimerosal, says Chrissie Juliano, executive director of Big Cities Health Coalition, an association of US health departments in Takoma Park, Maryland. “What this does is sow mistrust. It confuses the public.” “It was an anti-science recommendation,” says Paul Offit, the director of the Vaccine Education Center at the Children’s Hospital of Philadelphia in Pennsylvania. “We have the information we need to tell us that thimerosal, at the level contained in vaccines, is a trivial contribution to the mercury that we’re exposed to every day.” After the meeting, members of the committee published a joint statement saying that they strongly support the “use of vaccines and other countermeasures, predicated on evidence-based medicine”. They added: “We came to this meeting with no pre-determined ideas.” Hand-picked panel The decision came today during the first meeting of the newly chosen Advisory Committee on Immunization Practices (ACIP), a panel that recommends which vaccines US residents should receive and when. Most US health-insurance programmes, which fund health care for US residents, are required to provide vaccines recommended by the ACIP at no cost. Earlier this month, Kennedy, a vaccine sceptic, fired all 17 members of the committee and appointed eight new ones, some of whom have publicly cast doubt on the safety and efficacy of vaccines. (One new member stepped down shortly before the meeting.) Before the vote, the committee heard a presentation by Lyn Redwood, a nurse practitioner and president emeritus of the anti-vaccine group Children’s Health Defense in Franklin Lakes, New Jersey, founded by Kennedy. She advocated for the removal of the ingredient from US vaccines, pointing to various studies to make her case. Will RFK Jr’s vaccine agenda make America contagious again? Offit, who is a former member of the ACIP, says that subject-matter experts typically vet presentations before the meeting — a step that was not followed in this case — and would probably have flagged some of the data that Redwood presented as inaccurate. A version of Redwood’s slides posted before the meeting contained a reference to a paper that doesn’t exist, according to Reuters. The reference was later removed. Some members of the committee echoed Redwood’s claims about the safety of thimerosal, but member Cody Meissner, a paediatrics researcher at the Dartmouth Geisel School of Medicine in Lebanon, New Hampshire, criticized the meeting’s focus on the compound. “I’m not quite sure how to respond to this presentation. This is an old issue that has been addressed in the past,” he said. “Of all the issues that ACIP needs to focus on, this is not a big issue,” he added. His was the only dissenting vote on the recommendation against thimerosal-containing vaccines. Meissner expressed concerns that the ACIP’s recommendation could affect access to vaccines in other countries. “The recommendations that the ACIP makes are followed among many countries around the world,” he noted, and removing thimerosal from all vaccines could increase costs. Multi-dose vials, which are the ones that still contain the ingredient, are generally cheaper and easier to store and use in mass vaccination programmes.
Nature DOI suffix ≠ "/s...": Not a research article
‘Place’ neurons recognize the same spot from close by and far away
Uwe Mayer
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The brain can retrieve spatial memories when an animal simply sees a location, even without them entering it. This is essential for planning how to reach that place. Writing in Nature, Payne and Aronov1 identify a new class of neuron in birds: cells that activate not only when an animal is in a location but also when it gazes at that location from afar. The study identifies a key missing link between gazing behaviour and representations of space in the brain’s hippocampus.
Nature DOI suffix ≠ "/s...": Not a research article
What we stand to lose when foreign students are seen as a threat
Maia Chankseliani
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At many leading study destinations in Western countries, the climate for international students is cooling. In the United Kingdom, most students are now barred from bringing family members. Canada has enforced a cap on study permits, restricted work eligibility after graduation and doubled the financial threshold for students to prove self-sufficiency. In the United States, border officials have been empowered to revoke student visas on national-security grounds, and proposed budget cuts would slash funding for exchange programmes by 90%. As someone who was once a foreign student and who now researches how higher education can drive social and civic transformation, I worry that this shift in attitude will have consequences far beyond university campuses. US academics: look after foreign students International students are not simply add-ons to national research systems; they help to drive them. They expand the intellectual terrain of universities, challenge familiar assumptions and enrich the learning of their domestic peers. In a survey by the UK government, 76% of students said that having international classmates helped to broaden their outlook, and 85% said it meant they felt better prepared for a global workplace (see go.nature.com/4lxzdng). When laboratories welcome the rest of the world, innovation multiplies. Economists have shown that a 10% increase in international graduate-student enrolment at US universities is associated with a 4.5% rise in patent applications and a 6.8% rise in university patent grants1 — gains not matched by domestic growth. A 2024 study that examined US start-up firms founded between 1999 and 2020 revealed that increasing the share of foreign master’s students in a cohort by ten percentage points yielded around 0.4 extra start-ups, nearly half of which were co-founded with classmates born in the United States2. Moreover, host nations gain diplomatic links. In the 2024 Soft-Power Index — an annual analysis of the number of serving world leaders who went to university abroad — 70 current heads of state or government had been educated in the United States and 58 in the United Kingdom (see go.nature.com/4nsrzha). US researchers must stand up to protect freedoms, not just funding And countries that send their students abroad benefit, too. Graduates bring back not only skills and knowledge, but also fresh ways of thinking, organizing and acting, with consequences for policy, civic participation and public welfare. A 2024 study3 of 43 low- and middle-income countries found that, over 15 years, high student mobility correlated with decreases in poverty: a gradual but enduring effect. Returning graduates educated in democratic countries are also likely to promote democratic changes at home. An analysis of US-hosted exchange programmes linked people’s experience of US civic life to measurable gains in civil liberties and human-rights practices in home nations4.
Nature DOI suffix ≠ "/s...": Not a research article
Global pandemic agreement needs sustained pressure to succeed
WooJung Jon
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The World Health Organization (WHO) Pandemic Agreement, adopted on 20 May at the World Health Assembly in Geneva, Switzerland, seeks to address failings from the COVID-19 pandemic (see Nature https://doi.org/prj3; 2025). Existing intellectual property rules were insufficient to ensure timely and equitable global access to COVID-19 health products, mostly because patent permissions alone could not overcome deficits in manufacturing capacity.
Nature DOI suffix ≠ "/s...": Not a research article
Harvard vs Trump: what this epic battle means for science
Jeff Tollefson
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Mary Rice was among hundreds of scientists at Harvard University who watched helplessly as millions of dollars in research funds disappeared in an instant in mid-May. Two of the pulmonologist’s grants were formally cancelled as part of a series of punitive actions taken by the administration of US President Donald Trump against the university. Little justification was given to Rice aside from a statement that her research does not align with government priorities. The cuts imperil Rice’s work at Harvard’s T.H. Chan School of Public Health in Boston, Massachusetts, including a US$2.5-million clinical trial designed to test whether air purifiers benefit people with lung disease. Terminating that trial, she says, would waste millions of dollars in taxpayer money that have already been spent, as well as the time, blood and nasal tissues that nearly 180 people contributed to the study. “If we were to just close up shop completely today, we would not get an answer.” Harvard researchers devastated as Trump team cuts nearly 1,000 grants Rice is on the front lines as Harvard seeks to navigate its new relationship with the US government, which has shifted from long-standing partner to hostile adversary. The Trump administration alleged that Harvard has failed to protect against antisemitism, and the government has demanded changes to the university’s curriculum as well as hiring and enrolment procedures that it says promote a liberal political agenda. The administration has terminated grants worth more than $2.4 billion over multiple years and sought to ban international students from attending the institution. Harvard is fighting both actions in court. Legal experts argue that Harvard is ultimately likely to prevail in its challenges to the Trump administration’s latest attacks, but how and when remains unclear. Trump has said that the government is nearing a deal with the university, but researchers told Nature that long-term threats to science at Harvard are likely to remain no matter what kind of deal emerges. For example, the administration is pushing broader efforts to increase taxes on university endowments and slash ‘indirect’ funds in research grants, which pay for infrastructure at the institutions that host the grants. The government has taken similar punitive measures against other elite universities, such as Brown University in Providence, Rhode Island; Columbia University in New York City; Cornell University in Ithaca, New York; and Northwestern University in Evanston, Illinois. Will US science survive Trump 2.0? But the Trump administration has aimed its harshest actions at Harvard — arguably the most prestigious US university and the one with the largest endowment, a $53-billion pot of money that comes from donations and helps to fund university activities. The issues facing Harvard, say researcher leaders, are harbingers of what could come for scores of other US universities as the government seeks to slash funding for scientific research and increase oversight of educational institutions. In June, a federal judge ruled that hundreds of National Institutes of Health grant terminations by the government were illegal and discriminatory, and that they had to be reinstated. Some of these include grants to Harvard. Responding to allegations in this article, White House spokesperson Abigail Jackson said that Harvard has failed “to create a safe campus environment”, refused to share information about foreign students’ “illegal or dangerous activities” and flouted the civil rights of students and faculty members. “Suggestions that there will be economic impacts for enforcing federal law and holding institutions accountable for their failure to protect civil liberties miss the forest for the trees and completely neglect the human cost of allowing dangerous ideologies like antisemitism to fester in America.” Scientists and academics who spoke to Nature say that the Trump administration has, in the space of five months, upended a science and innovation system that dates back to the Second World War and has helped the United States to become a scientific and economic powerhouse. Like their counterparts at other universities, Harvard leaders are now thinking about how to design a viable — and probably smaller — institution that is less reliant on federal support. “The uncertainties are immense,” says John Holdren, a physicist at Harvard’s Kennedy School of Government in Cambridge, Massachusetts, and science adviser during the presidency of Barack Obama. “If federal funding is substantially reduced over any significant period of time, it’s going change the institution in substantial ways.” Financing the future With its vast endowment, Harvard has more resources than other universities to withstand the unprecedented cuts in federal funding. Federal grants supplied $686 million in fiscal year 2024, accounting for nearly three-quarters of research revenue and 11% of the total for the university (see ‘Harvard’s revenue’). Source: Harvard Univ. Financial Report Fiscal Year 2024 Although much of the endowment is locked up in long-term investments and legally dedicated to a variety of specific causes, university leaders have been busy looking for ways to tap into those funds, including seeking permission from donors to use the money to help solve the immediate crisis. Since March, the university has also raised $1.2 billion by issuing bonds. So far, Harvard has announced that it will spend $250 million to help cushion the blow to its schools as federal funding disappears; resources will be allocated in proportion to the amount lost. The US is the world’s science superpower — but for how long? In a 3 June e-mail to faculty, George Daley, dean of the medical school, said it will receive $90 million. The medical school will then contribute a further $120 million to fund research over the coming fiscal year, which begins on 1 July. All told, Daley, said in the e-mail, the medical school expects to be able to cover 74% of the cancelled federal grants over the coming year. He promised to work with department chairs and school leadership “to adjust and support the research as much as we can”. Now it’s up to department chairs to determine how the money is distributed and which positions and projects get cut. But alternative funding mechanisms — such as borrowing money and tapping into the endowment — cannot continue indefinitely, says Jeffrey Flier, an endocrinologist and former dean of the medical school. Without a restoration of federal funding or a significant increase in investments from philanthropic organizations and industry, he adds, “Harvard Medical School’s research programmes will look drastically different in four years.” Stay or go The situation is even more dire at the Chan school of public health. More than $200 million in federal research grants account for nearly half of its budget this year, and international students comprise 40% of the student body. Around 21% of the budget comes from the school’s share of the Harvard endowment, but researchers fear that this revenue could also drop if the Trump administration and fellow Republicans in Congress increase the tax on university endowments, as expected. Another 12% comes from student tuition fees.
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: The oldest rocks on Earth
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Natural nappers: monitoring the sleeping patterns of wild orangutans
Mary Abraham
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Sleep, as William Shakespeare wrote in Macbeth, is the “balm of hurt minds, great nature’s second course, chief nourisher in life’s feast”. Little wonder, then, that taking a nap has enduring appeal. Adequate sleep is needed for good health. But how do such behaviours evolve, and what can researchers learn from studying them in primates? Ashbury and colleagues provide insights about the daytime naps taken by wild orangutans (Pongo abelii; A. M. Ashbury et al. Curr. Biol. https://doi.org/ptcv; 2025).
Nature DOI suffix ≠ "/s...": Not a research article
Deciphering how dog roses with an odd chromosome copy number sexually reproduce
AdriĂĄn Gonzalo, Joiselle B. Fernandes
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Maintaining an odd number of chromosome copies across generations is typically incompatible with sexual reproduction1. Some species, such as dog roses (Rosa sect. Caninae), have evolved the rare ability to violate this rule, but the underlying mechanisms and evolutionary implications are unknown. Writing in Nature, Herklotz et al.2 analyse the dog-rose genome, uncovering aspects of its atypical mode of reproduction that might inspire future strategies for engineering plant reproduction in agriculture.
Nature DOI suffix ≠ "/s...": Not a research article
Signs of AI-generated text found in 14% of biomedical abstracts last year
Smriti Mallapaty
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Generative artificial-intelligence tools are increasingly widely available.Credit: Nicolas Economou/NurPhoto via Getty Around one in seven biomedical-research abstracts published last year was probably written with the help of artificial intelligence (AI), according to a massive analysis1 of the scholarly literature. More than 200,000 abstracts out of 1.5 million indexed in PubMed in 2024 contained words commonly suggested by large language models (LLMs). The study was posted online as a preprint2 in June 2024, when it estimated that one in nine abstracts were written with AI assistance in the first half of last year. The updated analysis is published in Science Advances today1. “The total number of LLM-edited papers has continued to rise inexorably,” says Andrew Gray, a bibliometrics support officer at University College London. He thinks researchers haven’t fully grasped the scale on which these tools are being used to produce scholarly work. “Hopefully, this paper will help drive some attention to the problem,” he adds. Excess words Many groups are trying to assess the impact of LLMs on scholarly output, but it is tricky because most users don’t disclose these practices. Efforts typically train models to identify differences between human-generated and LLM-generated text, and then apply those insights to assess the literature. But it is not clear how such models distinguish between the two types of text, and training data sets don’t always represent up-to-date trends in LLM-generated writing. Dmitry Kobak, a data scientist at the University of TĂŒbingen in Germany, and his colleagues took a more open-ended approach. They searched abstracts for ‘excess words’ that started to appear more often than expected after November 2022, when ChatGPT became widely available. The team was inspired by work estimating ‘excess deaths’ during the COVID-19 pandemic. The researchers found that 454 words appeared much more often in 2024 than in any other year since 2010. They were mostly ‘style’ words unrelated to the content of the research, and tended to be verbs and adjectives. Some were common — such as ‘findings’, ‘crucial’ and ‘potential’ — whereas others were more unusual, including ‘delves’ and ‘showcasing’. Excess words that emerged in the second half of 2024 include ‘heighten’ and ‘hinder’, as well as superlatives such as ‘unparalleled’ and ‘invaluable’, says Kobak. Shifts in the scientific lexicon happen over time — including dramatic changes that accompany major events, such as the COVID-19 pandemic that began in 2020. There were 190 excess words in 2021, and they tended to be nouns related to the content of the research, such as ‘mask’. But the lexical shift that has occurred since LLMs became popular has been even more pronounced, and mainly stylistic. Geographic differences
A foundation model to predict and capture human cognition
Marcel Binz, Elif Akata, Matthias Bethge, Franziska BrĂ€ndle, Fred Callaway, Julian Coda-Forno, Peter Dayan, Can Demircan, Maria K. Eckstein, NoĂ©mi ÉltetƑ, Thomas L. Griffiths, Susanne Haridi, Akshay K. Jagadish, Li Ji-An, Alexander Kipnis, Sreejan Kumar, Tobias Ludwig, Marvin Mathony, Marcelo Mattar, Alireza Modirshanechi, Surabhi S. Nath, Joshua C. Peterson, Milena Rmus, Evan M. Russek, Tankred Saanum, Johannes A. Schubert, Luca M. Schulze Buschoff, Nishad Singhi, Xin Sui, Mirko Thalmann, Fabian J. Theis, Vuong Truong, Vishaal Udandarao, Konstantinos Voudouris, Robert Wilson, Kristin Witte, Shuchen Wu, Dirk U. Wulff, Huadong Xiong, Eric Schulz
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Establishing a unified theory of cognition has been an important goal in psychology 1,2 . A first step towards such a theory is to create a computational model that can predict human behaviour in a wide range of settings. Here we introduce Centaur, a computational model that can predict and simulate human behaviour in any experiment expressible in natural language. We derived Centaur by fine-tuning a state-of-the-art language model on a large-scale dataset called Psych-101. Psych-101 has an unprecedented scale, covering trial-by-trial data from more than 60,000 participants performing in excess of 10,000,000 choices in 160 experiments. Centaur not only captures the behaviour of held-out participants better than existing cognitive models, but it also generalizes to previously unseen cover stories, structural task modifications and entirely new domains. Furthermore, the model’s internal representations become more aligned with human neural activity after fine-tuning. Taken together, our results demonstrate that it is possible to discover computational models that capture human behaviour across a wide range of domains. We believe that such models provide tremendous potential for guiding the development of cognitive theories, and we present a case study to demonstrate this.

Nature Human Behaviour

GPT-4o mini: Non-social science research article
A systemic approach to better coordination in science
Sajedeh Rasti, Krist Vaesen, Daniël Lakens
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Machine learning-assisted optimization of dietary intervention against dementia risk
Si-Jia Chen, Hui Chen, Jia You, Shi-Dong Chen, Yan Fu, Wei Zhang, Liyan Huang, Jian-Feng Feng, Xiang Gao, Wei Cheng, Changzheng Yuan, Jin-Tai Yu
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A healthy diet has been associated with a reduced risk of dementia. Here we devised a Machine learning-assisted Optimizing Dietary intERvention against demeNtia risk (MODERN) diet based on data from 185,012 UK Biobank participants, 1,987 of whom developed all-cause dementia over 10 years. We first identified 25 food groups associated with dementia in a food-wide association analysis. Second, we ranked their importance using machine learning and prioritized eight groups (for example, green leafy vegetables, berries and citrus fruits). Finally, we established and externally validated a MODERN score (0–7), which showed stronger associations with lower risk of dementia-related outcomes (hazard ratio comparing highest versus lowest tertiles: 0.64, 95% CI: 0.43–0.93) than the a priori-defined MIND diet (0.75, 0.61–0.92). Across 63 health-related outcomes, the MODERN diet showed particularly significant associations with mental/behavioural disorders. Multimodal neuroimaging, metabolomics, inflammation and proteomics analyses revealed potential pathways and further support the potential of MODERN diet for dementia prevention.
Knowledge of information cascades through social networks facilitates strategic gossip
Alice Xia, Yi Yang Teoh, Matthew R. Nassar, Apoorva Bhandari, Oriel FeldmanHall
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Social networks are composed of many ties among many individuals. These ties enable the spread of information through a network, including gossip, which comprises a sizeable share of daily conversation. Given the number of possible connections between people in even the smallest networks, a formidable challenge is how to strategically gossip—to disseminate information as widely as possible without the target of the gossip finding out. Here we find that people achieve this goal by leveraging knowledge about topological properties, specifically, social distance and popularity, using a gossip-sharing task in artificial social networks (experiments 1–3, N = 568). We find a similar pattern of behaviour in a real-world social network (experiment 4, N = 187), revealing the power of these topological properties in predicting information flow, even in much noisier, complex environments. Computational modelling suggests that these adaptive social behaviours rely on mental representations of information cascades through the social network.
Comparing the value of perceived human versus AI-generated empathy
Matan Rubin, Joanna Z. Li, Federico Zimmerman, Desmond C. Ong, Amit Goldenberg, Anat Perry
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Artificial intelligence (AI) and specifically large language models demonstrate remarkable social–emotional abilities, which may improve human–AI interactions and AI’s emotional support capabilities. However, it remains unclear whether empathy, encompassing understanding, ‘feeling with’ and caring, is perceived differently when attributed to AI versus humans. We conducted nine studies (n = 6,282) where AI-generated empathic responses to participants’ emotional situations were labelled as provided by either humans or AI. Human-attributed responses were rated as more empathic and supportive, and elicited more positive and fewer negative emotions, than AI-attributed ones. Moreover, participants’ own uninstructed belief that AI had aided the human-attributed responses reduced perceived empathy and support. These effects were replicated across varying response lengths, delays, iterations and large language models and were primarily driven by responses emphasizing emotional sharing and care. Additionally, people consistently chose human interaction over AI when seeking emotional engagement. These findings advance our general understanding of empathy, and specifically human–AI empathic interactions.
Charting multidimensional ideological polarization across demographic groups in the USA
Jaume Ojer, David CĂĄrcamo, Romualdo Pastor-Satorras, Michele Starnini
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Has ideological polarization actually increased in the past decades, or have voters simply sorted themselves into parties matching their ideology more closely? Here we present a methodology to quantify multidimensional ideological polarization by embedding the respondents to a wide variety of political, social and economic topics from the American National Election Studies into a two-dimensional ideological space. By identifying several demographic attributes of the American National Election Studies respondents, we chart how political and socioeconomic groups move through the ideological space in time. We observe that income and especially racial groups align into parties, but their ideological distance has not increased over time. Instead, Democrats and Republicans have become ideologically more distant in the past 30 years: Both parties moved away from the centre, at different rates. Furthermore, Democratic voters have become ideologically more heterogeneous after 2010, indicating that partisan sorting has declined in the past decade.
Following news on social media boosts knowledge, belief accuracy and trust
Sacha Altay, Emma Hoes, Magdalena Wojcieszak
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Many worry that news on social media leaves people uninformed or even misinformed. Here we conducted a preregistered two-wave online field experiment in France and Germany ( N = 3,395) to estimate the effect of following the news on Instagram and WhatsApp. Participants were asked to follow two accounts for 2 weeks and activate the notifications. In the treatment condition, the accounts were those of news organizations, while in the control condition they covered cooking, cinema or art. The treatment enhanced current affairs knowledge, participants’ ability to discern true from false news stories and awareness of true news stories, as well as trust in the news. The treatment had no significant effects on feelings of being informed, political efficacy, affective polarization and interest in news or politics. These results suggest that, while some forms of social media use are harmful, others are beneficial and can be leveraged to foster a well-informed society.

Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Identification of a VPS29 isoform with restricted association to Retriever and Retromer accessory proteins through autoinhibition
James L. Daly, Kai-en Chen, Rebeka Butkovič, Qian Guo, Michael D. Healy, Eva Pennink, Georgia Gamble-Strutt, Zara Higham, Edmund R. R. Moody, Philip A. Lewis, Kate J. Heesom, Tom A. Williams, Kirsty J. McMillan, Brett M. Collins, Peter J. Cullen
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The endosomal–lysosomal network is a hub of organelles that orchestrate the dynamic sorting of hundreds of integral membrane proteins to maintain cellular homeostasis. VPS29 is a central conductor of this network through its assembly into Retromer, Retriever, and Commander endosomal sorting complexes, and its role in regulating RAB GTPase activity. Two VPS29 isoforms have been described, VPS29A and VPS29B, that differ solely in their amino-terminal sequences. Here, we identify a third VPS29 isoform, which we term VPS29C, that harbors an extended amino-terminal sequence compared to VPS29A and VPS29B. Through a combination of AlphaFold predictive modeling, in vitro complex reconstitution, mass spectrometry, and molecular cell biology, we find that the amino-terminal VPS29C extension constitutes an autoinhibitory sequence that limits access to a hydrophobic groove necessary for effector protein recruitment to Retromer, and association with Retriever and Commander. VPS29C is therefore unique in its ability to uncouple Retromer-dependent cargo sorting from the broader roles of VPS29A and VPS29B in regulating the endosomal–lysosomal network through accessory protein recruitment. Our identification and characterization of VPS29C points to additional complexity in the differential subunit assembly of Retromer, an important consideration given the increasing interest in Retromer as a potential therapeutic target in neurodegenerative diseases.
GPT-4o mini: Non-social science research article
Axonal pathology differentially affects human Purkinje cell subpopulations in the essential tremor cerebellum
James Widner, Phyllis L. Faust, Elan D. Louis, Hirofumi Fujita
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The cerebellar cortex is organized into discrete regions populated by molecularly distinct Purkinje cells (PCs), the sole cortical output neurons. While studies in animal models have shown that PC subtypes differ in their vulnerability to disease, our understanding of human PC subtype and vulnerability remains limited. Here, we demonstrate that human cerebellar regions specialized for motor vs. cognitive functions (lobule HV vs. Crus I) contain distinct PC populations characterized by specific molecular and anatomical features, which show selective vulnerability in essential tremor (ET), a cerebellar degenerative disorder. Using a known PC subtype marker, neurofilament heavy chain (NEFH), we found that motor lobule HV contains PCs with high NEFH expression, while cognitive lobule Crus I contains PCs with low NEFH expression in postmortem samples from healthy controls. In the same cerebella, PC axons in lobule HV were 2.2-fold thicker than those in Crus I. Across lobules, axon caliber positively correlated with NEFH expression. In ET cerebella, we identified motor lobule-specific PC axon pathology with a 1.5-fold reduction in caliber and increased axon variability in lobule HV, while Crus I axons were unaffected. Tremor severity and duration in ET correlated with axon diameter variability selectively in lobule HV PCs. Given that axonal caliber is a major determinant of neural signaling capacity, our results 1) suggest that disrupted cerebellar corticonuclear signaling is occurring in ET, and 2) provide evidence of region-specific PC populations in the human cerebellum and offer insight into how different PC subpopulations may contribute to the pathophysiology of cerebellar degeneration.
GPT-4o mini: Non-social science research article
Preservation bias obscures gradual Ordovician reef evolution
Juwan Jeon, Qi-Jian Li, Jeong-Hyun Lee
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The fossil record often creates an illusion of sudden evolutionary bursts, which may reflect preservation biases rather than actual biological events. The Great Ordovician Biodiversification Event (GOBE) appears to mark the abrupt rise of diverse reef-building metazoans during the late Darriwilian (~460 Ma), seemingly contradicting gradual evolutionary models. Here, we demonstrate this apparent burst is largely an artifact of a global sea-level fall (~475 to 460 Ma) that produced widespread unconformities. Integrated stratigraphic and fossil occurrence data reveal early reef-builders likely appeared earlier than the late Middle Ordovician, but their record was erased by sea-level-driven erosion. During the peak of this sea-level fall (Dapingian Stage, 471 to 469 Ma), both carbonate deposition and fossil occurrences were minimal, with significant correlation between carbonate preservation and reef-builder occurrences. The subsequent transgression enabled these already-diversified organisms to recolonize shallow-water environments simultaneously across multiple regions, generating a misleading impression of sudden diversification. This “Sppil–Rongis effect” biased our understanding of the GOBE in reef ecosystems, illustrating how stratigraphic incompleteness can distort evolutionary patterns. Rather than a discrete evolutionary event, the GOBE reflects a continuous trajectory, interrupted and reshaped by sea-level fluctuations.
GPT-4o mini: Non-social science research article
Patchy harmonic functional connectivity of the mouse auditory cortex
Peter Jendrichovsky, Sahar Khosravi, Anuththara Rupasinghe, Katherine Maximov, Pinyue Guo, Behtash Babadi, Patrick O. Kanold
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Analyzing the functional connectivity of the brain is an enormous challenge, as deciphering functional connectivity requires knowledge of functional responses and connections. One promising strategy is analyzing the spatial pattern of activity correlations across cell populations. In the primary auditory cortex (A1), cells respond to different sound features. On the large scale, there exists a tonotopic map, which is fractured at the small scale, raising the question of whether functional connections are spatially ordered or disordered. To test whether functional connectivity on a local and a global scale is also disordered, we first designed a robust statistical model to estimate parameters and test for the significance of the estimated correlation maps. We developed an inference method that allows efficient model fitting and statistical testing to project the correlation maps to 2D space. We then performed in vivo two-photon calcium imaging in layer 2/3 of A1 with pure tones (PT) or a combination of two tones (TT; harmonically related or not). We found that the spatial patterns of signal correlations (SCs) depend on the type of sound stimuli that were presented. The functional 2D maps of PT-driven SCs are more restricted to local neurons than TT signal correlations which showed more global textures. 2D SC patterns for harmonic stimuli showed spatially distinct relationships. TT SCs revealed spatially precise functional connectivity between harmonically related neurons. Thus, even though the frequency preference of neighboring neurons in A1 is functionally diverse, the functional connection pattern of these neurons is functionally precise and harmonically related.
GPT-4o mini: Non-social science research article
Testicular somatic and germ cell maturation during rhesus macaque development
Enrique Sosa, Sissy E. Wamaitha, Fei-man Hsu, Mary Jasmine D. Lara, Kiana Oyama, Maggie Custer, Melinda Murphy, Jon D. Hennebold, Young Sun Hwang, Amander T. Clark
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The formation of bilateral testes in animals is critical for puberty, reproductive capacity, and testosterone production across the life course. In humans, testis development begins in embryonic life in the first trimester, with considerable effort focused on the cell and developmental events associated with testis cell specification, leaving limited knowledge on testicular organogenesis during the second and third trimesters. To fill this knowledge gap, we evaluated testicular cell maturation at weeks 5 (W5), W6, W8, W15, and W19 postconception using a rhesus macaque model. Our data identify a major transcriptional change in the somatic cells of the testis (Sertoli cells, interstitial cells and fetal Leydig cells) between W8 and W15, and this is associated with the maturation of seminiferous cords and maturation of PGCs into fetal spermatogonia. Through this work, we identified cellular changes and differential protein expression between W5 and W19 that can be used to holistically define testis development across the time course of embryonic and fetal life. This study provides important insights necessary to recreate the testicular niche from stem cells for biomedical research.
GPT-4o mini: Non-social science research article
SpbR controls lipoteichoic acid length by directly inhibiting signal peptidase SpsB in Staphylococcus aureus
Youngseon Park, Tyler A. Sisley, Madeleine C. Stone, Rebecca M. Corrigan, Christopher R. Vickery, Angelika GrĂŒndling, Suzanne Walker
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Staphylococcus aureus is a Gram-positive pathogen that causes life-threatening infections. Its cell envelope contains anionic polymers called teichoic acids that are required for cell viability. Teichoic acids come in two forms and are made by different biosynthetic pathways. One form, lipoteichoic acid (LTA), is anchored in the cell membrane; the other form, wall teichoic acid (WTA), is covalently linked to the peptidoglycan cell wall. Although the LTA and WTA biosynthetic pathways have been characterized, regulation of teichoic acid production is not well understood. Here, we identified SpbR ( SAOUHSC_00965 ), a polytopic membrane protein similar to a eukaryotic CAAX protease, as a factor that controls LTA levels in S. aureus cells. We show that loss of SpbR results in short LTAs and a synthetically sick phenotype when WTA biosynthesis is prevented, whereas overexpressing SpbR results in elongated LTAs. Mechanistically, we find that SpbR physically associates with the type I signal peptidase SpsB, which cleaves LtaS, the polymerase that assembles LTA on the extracellular side of the membrane, and we show that this physical interaction inhibits SpsB cleavage of LtaS both in vivo and in vitro. Although the phenotypes investigated here are dominated by SpbR’s effects on LtaS, it also inhibits cleavage of other SpsB substrates. Based on its role in regulating the activity of SpsB, we named this factor SpbR ( S ignal p eptidase b R egulator).
GPT-4o mini: Non-social science research article
15-PGDH inhibition preserves blood–brain barrier integrity and cognition
Daisy M. van Egmond, Anita Lygeroudi, Gijs Kooij
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GPT-4o mini: Non-social science research article
The adaptive state determines the impact of mutations on evolving populations
Malgorzata Tyczynska Weh, Pragya Kumar, Viktoriya Marusyk, Andriy Marusyk, David Basanta
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Darwinian evolution results from an interplay between stochastic diversification of heritable phenotypes, impacting the chance of survival and reproduction, and fitness-based selection. The ability of populations to evolve and adapt to environmental changes depends on rates of mutational diversification and the distribution of fitness effects of random mutations. In turn, the distribution of fitness effects of stochastic mutations can be expected to depend on the adaptive state of a population. To systematically study the impact of the interplay between the adaptive state of a population on the ability of asexual populations to adapt, we used a spatial agent-based model of a neoplastic population adapting to a selection pressure of continuous exposure to targeted therapy. We found favorable mutations were overrepresented at the extinction bottleneck but depleted at the adaptive peak. The model-based predictions were tested using an experimental cancer model of an evolution of resistance to a targeted therapy. Consistent with the model’s prediction, we found that enhancement of the mutation rate was highly beneficial under therapy but moderately detrimental under the baseline conditions. Our results highlight the importance of considering population fitness in evaluating the fitness distribution of random mutations and support the potential therapeutic utility of restricting mutational variability.
GPT-4o mini: Non-social science research article
Observation of the electric Breit–Rabi effect
Shao-Zheng Wang, Shou-Bo Wang, Zhi-Jin Tao, Tian Xia, Zheng-Tian Lu
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The response of an atom to external electric and magnetic fields can reveal fundamental atomic properties. It has long been verified that, in a static magnetic field, those atomic energy levels with hyperfine interactions shift according to the Breit–Rabi formula, which introduces nonlinear dependence on the magnetic field. On the other hand, the corresponding Breit–Rabi dependence on a static electric field has not been observed before due to a combination of experimental challenges. Here, we precisely measure the Stark shift of the 6 s 2 1 S 0 ↔ 6 s 6 p 1 P 1 transition of 171 Yb ( I = 1/2) with cold atoms held by an optical dipole trap in a static electric field up to 120 kV/cm. We observe the electric Breit–Rabi effect displaying high-order ( E 4 and E 6 ) DC Stark shifts. These effects arise from the influence of the strong electric field on hyperfine interactions.
GPT-4o mini: Non-social science research article
Total synthesis and biological activity of “carbamorphine”: O-to-CH 2 replacement in the E-ring of the morphine core structure
Sota Akiyama, Rohini S. Ople, Alexander Kremsmair, Nokomis Ramos-Gonzalez, Thomas Nedungadan, Brandon J. Kennedy, Kevin Appourchaux, Shainnel O. Eans, Bowen A. Tsai, Christina Kraml, Xi-Ping Huang, Jay P. McLaughlin, Susruta Majumdar, Richmond Sarpong
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Morphine is a ”-opioid receptor (MOR) agonist and potent analgesic. However, it displays several side effects including respiratory depression and addiction. Here, we show that a single heavy atom replacement in the morphine core structure (O to CH 2 exchange in the E-ring) prepared through a 15-step total synthesis displays a different pharmacological profile. The total synthesis features an intramolecular inverse electron-demand Diels−Alder cycloaddition and a stereoselective Giese radical addition to construct a quaternary carbon center. Unlike morphine, where the (–)-morphine enantiomer binds the MOR, both enantiomers of this “carba” variant, which we have named carbamorphine, possess activity as agonists of the MOR. Cell-based functional assays show that (+)-carbamorphine shows reduced G-protein as well as ÎČ-arrestin efficacy at the MOR. In mouse behavioral assays, (+)-carbamorphine exhibits MOR-selective antinociception while showing reduced respiratory depression and a lack of conditioned place preference at supratherapeutic doses. Overall, through a net “single-atom” change (i.e., O to CH 2 ) in the morphine framework, different pharmacological profiles have been realized. This work provides a basis for additional syntheses and the study of morphine analogs that incorporate atom changes in the core framework.
GPT-4o mini: Non-social science research article
Barystatic sea level change observed by satellite gravimetry: 1993–2022
Yufeng Nie, Jianli Chen, Guodong Xu, Anno Löcher
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Using time-variable gravity fields determined from satellite laser ranging (SLR) and the Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow-On (GRACE-FO), we derive three decades of barystatic sea level (BSL) change estimates since 1993, providing a long record of satellite gravimetry-based BSL estimates comparable in duration to satellite altimetry. Over the 1993–2022 altimetry era, the BSL change rate is 1.75 ± 0.59 mm/y (2σ) as observed by SLR. The rate increases to 2.16 ± 0.59 mm/y (SLR) and 2.13 ± 0.38 mm/y (GRACE/-FO) over 2003–2022, mainly due to accelerated ice loss in Greenland since the 2000s. The remarkable agreement between SLR and GRACE/-FO estimates over the joint period cross-validates each other, suggesting that both work well in monitoring BSL changes. We also compare our satellite gravimetry estimates with the sum of individual mass change components (ice sheets, glaciers, and land water storage) obtained from multisource datasets (in situ, remote sensing and geophysical modeling). The differences are within 0.2 mm/y over the three decades, highlighting the global consistency of different techniques for observing Earth’s surface mass changes. Moreover, we reconcile the global mean sea level (GMSL) rise budget using reprocessed altimetry data and updated thermosteric sea level ensembles. From 1993 to 2022, the sum of thermosteric and SLR-based barystatic contributions (3.16 ± 0.64 mm/y) agrees well with altimetry-observed GMSL rate (3.22 ± 0.28 mm/y), suggesting that the GMSL rise budget can be closed within uncertainties over the last three decades.
GPT-4o mini: Non-social science research article
Sleep duration and timing are associated with next-day physical activity: Insights from two large-scale wearable sensor studies
Josh Leota, Mark É. Czeisler, Flora Le, David M. Presby, Emily R. Capodilupo, Hannah Scott, Joshua F. Wiley, Sean P. A. Drummond, Shantha M. W. Rajaratnam, Elise R. Facer-Childs
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Sleep and physical activity (PA) are pillars of health. However, the temporal dynamics between these two behaviors remain poorly understood. This research aims to examine the independent and interactive between- and within-person associations of sleep duration and sleep onset timing on next-day PA duration in two large, longitudinal samples of adults under free-living conditions. In the primary study, participants (N = 19,963; 5,995,080 person-nights) wore a validated biometric device (WHOOP) for 1 y (01/09/2021 to 31/08/2022). Objective sleep and PA metrics were derived from the wrist-worn device. Generalized additive mixed models assessed between- and within-person associations between sleep and PA variables, adjusted for age, sex, Body Mass Index, weekday/weekend, seasonal effects, biometric feedback, and autocorrelated errors. Between participants, longer sleep duration and later sleep onset timing were associated with decreased moderate-to-vigorous PA (MVPA) and overall PA duration ( ps < 0.001). Within participants, sleeping shorter-than-usual and falling asleep earlier-than-usual were associated with increased next-day MVPA and overall PA, whereas sleeping longer-than-usual, or falling asleep later-than-usual, showed the opposite relationship ( ps < 0.001). Next-day MVPA duration was highest following earlier-than-usual sleep onset timing combined with one’s typical sleep duration. Results were consistent but smaller in magnitude in the external validation study (N = 5,898; 635,477 person-nights) using Fitbit data from the All of Us Research Program. Individuals may sacrifice time in one health behavior for time in the other. Interventions promoting exercise and holistic public health messaging should consider the temporal dynamics between sleep and next-day PA outcomes.
GPT-4o mini: Non-social science research article
Comparative performance of viral landscape phylogeography approaches
Simon Dellicour, Fabiana GĂĄmbaro, Maude Jacquot, Sebastian Lequime, Guy Baele, Marius Gilbert, Oliver G. Pybus, Marc A. Suchard, Philippe Lemey
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The rapid evolution of RNA viruses implies that their evolutionary and ecological processes occur on the same time scale. Genome sequences of these pathogens therefore can contain information about the processes that govern their transmission and dispersal. Landscape phylogeographic approaches use phylogeographic reconstructions to investigate the impact of environmental factors and variables on the spatial spread of viruses. Here, we extend and improve existing approaches and develop three novel landscape phylogeographic methods that can test the impact of continuous environmental factors on the diffusion velocity of viral lineages. In order to evaluate the different methods, we also implemented two simulation frameworks to test and compare their statistical performance. The results enable us to formulate clear guidelines for the use of three complementary landscape phylogeographic approaches that have sufficient statistical power and low rates of false positives. Our open-source methods are available to the cientific community and can be used to investigate the drivers of viral spread, with potential benefits for understanding virus epidemiology and designing tailored intervention strategies.
GPT-4o mini: Non-social science research article
Advanced synchrotron method reveals early molecular decomposition steps in a high-energy material
Simo Huotari
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GPT-4o mini: Non-social science research article
De novo design of D-peptide ligands: Application to influenza virus hemagglutinin
Jarek Juraszek, Rameshwar U. Kadam, Davide Branduardi, Jeroen van Ameijde, Divita Garg, Nicolas Dailly, Mandy Jongeneelen, Jan Vermond, Just P. J. Brakenhoff, Boerries Brandenburg, Maria J. P. van Dongen, Ronald Vogels, Robert H. E. Friesen, Ian A. Wilson
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D-peptides hold great promise as therapeutics by alleviating the challenges of metabolic stability and immunogenicity in L-peptides. However, current D-peptide discovery methods are severely limited by specific size, structure, and the chemical synthesizability of their protein targets. Here, we describe a computational method for de novo design of D-peptides that bind to an epitope of interest on the target protein using Rosetta’s hotspot-centric approach. The approach comprises identifying hotspot sidechains in a functional protein–protein interaction and grafting these side chains onto much smaller structured peptide scaffolds of opposite chirality. The approach enables more facile design of D-peptides and its applicability is demonstrated by design of D-peptidic binders of influenza A virus hemagglutinin, resulting in identification of multiple D-peptide lead series. The X-ray structure of one of the leads at 2.38 Å resolution verifies the validity of the approach. This method should be generally applicable to targets with detailed structural information, independent of molecular size, and accelerate development of stable, peptide-based therapeutics.
GPT-4o mini: Non-social science research article
Crystal structure and catalytic mechanism of drimenol synthase, an unusual bifunctional terpene cyclase–phosphatase
Kristin R. Osika, Matthew N. Gaynes, David W. Christianson
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Drimenol synthase from Aquimarina spongiae (AsDMS) is a highly unusual chimera that integrates two distinct, sequential isoprenoid processing activities within a single polypeptide chain. AsDMS catalyzes the class II cyclization of farnesyl diphosphate (FPP) to form drimenyl diphosphate, which then undergoes enzyme-catalyzed hydrolysis to yield drimenol, a bioactive sesquiterpene alcohol with antifungal and anticancer properties. Here, we report the X-ray crystal structures of AsDMS and its complex with a sesquiterpene thiol. The AsDMS structure exhibits a didomain architecture consisting of a terpene cyclase ÎČ domain and a haloacid dehalogenase-like phosphatase domain, with two distinct active sites located on opposite sides of the protein. Mechanistic studies show that dephosphorylation of the drimenyl diphosphate intermediate proceeds through stepwise hydrolysis such that two equivalents of inorganic phosphate rather than inorganic pyrophosphate are coproducts of the reaction sequence. When the AsDMS reaction is performed in H 2 18 O, 18 O is not incorporated into drimenol, indicating that the hydroxyl oxygen of drimenol originates from the prenyl oxygen of FPP rather than a water molecule from bulk solution. These results correct a mechanistic proposal previously advanced by another group. Surprisingly, AsDMS exhibits substrate promiscuity, catalyzing the conversion of the slowly reactive substrate mimic farnesyl- S -thiolodiphosphate into cyclic and linear sesquiterpene products. Structural and mechanistic insights gained from AsDMS illustrate the functional diversity of terpene biosynthetic enzymes and provide a foundation for engineering “designer cyclase” assemblies capable of generating a wide variety of terpenoid products.
GPT-4o mini: Non-social science research article
Prehistoric archives reveal evidence of predator loss and prey release in Caribbean reef fish communities
Aaron O’Dea, Erin M. Dillon, Simon J. Brandl, Katie L. Cramer, Jonathan D. Cybulski, BrĂ­gida de Gracia, Kimberly GarcĂ­a-MĂ©ndez, Katherine Griswold, Chien-Hsiang Lin, Matthieu Leray, Jessica A. Lueders-Dumont, Andrew J. Sellers, Thomas A. Wake
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Understanding how humans have altered coral reef food webs remains challenging due to the absence of prehistoric baselines. Here, we use fish remains preserved in fossil and archaeological deposits from Panamá and the Dominican Republic to explore how Caribbean reef fish mortality patterns have changed over millennia. By quantifying accumulation rates of shark dermal denticles (scales) and bony fish otoliths (ear stones) in reef sediments, we assess relative fish abundance, while otolith size serves as a proxy for body size at death. Comparisons of these death assemblages suggest a 75% decline in shark-derived material and a 22% reduction in the sizes of human-targeted fishes—consistent with historical exploitation. This evidence of decline in large-bodied, higher trophic level fish remains coincided with a doubling in prey fish otolith accumulation and a 17% increase in their reconstructed body sizes. These patterns in time-averaged death assemblages align with effects of release from predation, documenting an often assumed (but rarely shown) cascading effect. In contrast, otoliths of predator-sheltered cryptobenthic fishes showed no change in either accumulation or size, suggesting that ‘‘bottom–up”environmental factors were not responsible for the observed changes. Together, these data indicate that pre-exploitation predator communities strongly controlled exposed prey fishes, but this “top–down” effect diminishes rapidly toward the food chain base, especially in predator-resistant groups. Understanding trophic cascades on Caribbean reefs requires studying systems before predator depletion.
GPT-4o mini: Non-social science research article
In vivo directed evolution of an ultrafast Rubisco from a semianaerobic environment imparts oxygen resistance
Julie L. McDonald, Nathan P. Shapiro, Amanuella A. Mengiste, Sarah Kaines, Spencer M. Whitney, Robert H. Wilson, Matthew D. Shoulders
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Carbon dioxide (CO 2 ) assimilation by the enzyme Ribulose-1,5-bisphosphate Carboxylase/Oxygenase (Rubisco) underpins biomass accumulation in photosynthetic bacteria and eukaryotes. Despite its pivotal role, Rubisco has a slow carboxylation rate ( k cat CO 2 ) and is competitively inhibited by oxygen (O 2 ). These traits impose limitations on photosynthetic efficiency, making Rubisco a compelling target for improvement. Interest in Form II Rubisco from Gallionellaceae bacteria, which comprise a dimer or hexamer of large subunits, arises from their nearly fivefold higher k cat CO 2 than the average Rubisco enzyme. As well as having a fast k cat CO 2 (25.8 s − 1 at 25 °C), we show that Gallionellaceae Rubisco (GWS1B) is extremely sensitive to O 2 inhibition, consistent with its evolution under semianaerobic environments. We therefore used an in vivo mutagenesis-mediated screening pipeline to evolve GWS1B over six rounds under oxygenic selection, identifying three catalytic point mutants with improved ambient carboxylation efficiency: Thr-29-Ala (T29A), Glu-40-Lys (E40K), and Arg-337-Cys (R337C). Full kinetic characterization showed that each substitution enhanced the CO 2 affinity of GWS1B under oxygenic conditions by subduing oxygen affinity, leading to 25% (E40K), 11% (T29A), and 8% (R337C) enhancements in carboxylation efficiency under ambient O 2 at 25 °C. By contrast, under the near anaerobic natural environment of Gallionellaceae , the carboxylation efficiency of each mutant was impaired ~16%. These findings demonstrate the efficacy of artificial directed evolution to access distinctive regions of catalytic space in Rubisco.
GPT-4o mini: Non-social science research article
Light controls gene functions through alternative splicing in fungi
Yifan Li, Huanhong Lu, Degang Guo, Xiaoyan Li, Fei Qi, Jian Zhang, Reinhard Fischer, Qirong Shen, Zhenzhong Yu
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Light controls important biological processes in fungi by regulating transcriptional gene activation. Here, we found that beyond the regulation of mRNA transcript abundance, light regulates alternative splicing (AS) in the filamentous fungi Aspergillus nidulans , Trichoderma guizhouense, and Neurospora crassa . Blue light-regulated AS was involved in ergothioneine biosynthesis and conidiation in T. guizhouense , which required the blue light receptor BLR1. Blue light activated the MAPK HOG (Sak) pathway which then transmitted the signal via the serine/threonine kinase SRK1 to the AS key regulator SRP1. SRK1 and SRP1 are important for light-induced conidiation. The light-activated HOG pathway led to an increase of the SRK1 protein level and its phosphorylation status. Phosphorylated SRK1 translocated from the cytoplasm to the nucleus to interact with SRP1, thereby regulating AS efficiency. This study unravels another level of complexity of fungal environmental sensing and responses and also first describes the entire cascade from an environmental signal to the splicing machinery.
GPT-4o mini: Non-social science research article
Heritable symbiont producing nonribosomal peptide confers extreme heat sensitivity and antifungal protection on its host
Gerald P. Maeda, Vy Dang, Mary Katherine Kelly, Aadhunik Sundar, Ryan L. W. Arnott, Edward M. Marcotte, Nancy A. Moran
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Insects frequently form associations with maternally transmitted symbiotic bacteria. This transmission mode ensures that symbiont-conferred effects, both beneficial and negative, are passed onto offspring. Here, we report an extreme example of symbiont-mediated temperature sensitivity imposed by a vertically transmitted, defensive symbiont. Pea aphids infected with the bacterial endosymbiont, Fukatsuia symbiotica, resist infection by fungal pathogens but produce few or no offspring when moved from cool (15 °C) to mildly warmer temperatures (20 °C). This temperature-dependent reduction in host fitness is associated with increased symbiont abundance, disordered symbiont localization, and high expression of a horizontally acquired nonribosomal peptide synthetase (NRPS) locus. This NRPS operon is syntenic with the locus responsible for the production of Herbicolin A, a known antifungal produced by some plant-associated Erwiniaceae . Activity of chemical extracts from infected aphids is predictive of in vivo protection against entomopathogenic fungi, indicating that an Herbicolin A–like molecule is the likely source of Fukatsuia’s protective effects against fungal pathogens. Injection of the same chemical extracts into naive aphids partially recapitulates developmental defects observed in natural infections at 20 °C, suggesting that increased levels of this compound contribute to disrupted embryonic development. Finally, the purification of the causal agent revealed Fukatsuia produces a compound similar but not identical to Herbicolin A, that exhibits both antifungal and hemolytic activity. These results suggest that F. symbiotica infection imposes a trade-off between antifungal defense and disrupted embryonic development, mediated by a single genetic locus.
GPT-4o mini: Non-social science research article
FtsZ-mediated spatial–temporal control over septal cell wall synthesis
Longhua Hu, Amilcar J. Perez, Tanya Nesterova, Zhixin Lyu, Atsushi Yahashiri, David S. Weiss, Jie Xiao, Jian Liu
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FtsZ, the tubulin-like GTPase, is the central organizer of the bacterial divisome, a macromolecular complex that synthesizes new septal cell wall (made of septal peptidoglycan, sPG) to allow cell wall constriction and cytokinesis. In Escherichia coli , it was shown that 1) FtsZ recruits all essential divisome proteins to the septum, including the core sPG synthase complex, FtsWIQLB, and its activator, FtsN; 2) FtsWIQLB must complex with FtsN to be activated to synthesize sPG under the wildtype background; and 3) the Brownian ratcheting by treadmilling FtsZ polymers drives the directional movements of sPG synthase proteins along the septum circumference; and 4) FtsZ is essential for the early stage, but dispensable for the late stage of cell wall constriction. However, it remains unclear how FtsZ spatial–temporally organizes the divisome for robust cell wall constriction during cytokinesis. Combining theoretical modeling with experiments in E. coli , we show that at the early stage during cell division, the Brownian ratcheting by FtsZ treadmilling acts both as a template to corral FtsWIQLB and FtsN into close contacts for FtsWIQLB-FtsN complex formation and as a conveyor to maximally homogenize the septal distribution of sPG synthesis activities to avoid uneven cell wall constriction. When the septum constricts progressively, the FtsN septal density increases via binding to denuded sPG (dnG) and serves as the template to activate FtsWIQLB for continued sPG synthesis, rendering FtsZ dispensable. Our work suggests an overarching framework for how FtsZ spatial–temporally regulates septal cell wall constriction, in which different bacteria species may operate in various parameter regimes to meet their distinct functional requirements.
GPT-4o mini: Non-social science research article
Overcoming toxicity: How nonantagonistic microbes manage to thrive in boom-and-bust environments
MingYi Wang, Alexander Vladimirsky, Andrea Giometto
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Antagonistic interactions are critical determinants of microbial community stability and composition, offering host benefits such as pathogen protection and providing avenues for antimicrobial control. While the ability to eliminate competitors confers an advantage to antagonistic microbes, it often incurs a fitness cost. Consequently, many microbes only produce toxins or engage in antagonistic behavior in response to specific cues like quorum sensing molecules or environmental stress. In laboratory settings, antagonistic microbes typically dominate over sensitive ones, raising the question of why both antagonistic and nonantagonistic microbes are found in natural environments and host microbiomes. Here, using both theoretical models and experiments with killer strains of Saccharomyces cerevisiae , we show that “boom-and-bust” dynamics—periods of rapid growth punctuated by episodic mortality events—caused by temporal environmental fluctuations can favor nonantagonistic microbes that do not incur the growth rate cost of toxin production. Additionally, using control theory, we derive bounds on the competitive performance and identify optimal regulatory toxin-production strategies in various boom-and-bust environments where population dilutions occur either deterministically or stochastically over time. Our mathematical investigation reveals that optimal toxin regulation is much more beneficial to killers in stochastic, rather than deterministic, boom-and-bust environments. Overall, our findings show how both antagonistic and nonantagonistic microbes can thrive under varying environmental conditions.
GPT-4o mini: Non-social science research article
Diploidization in a wild rice allopolyploid is both episodic and gradual
Xin Wang, Ning Li, Qian Wang, Tian-Yu Lei, Ju Zhou, Fu-Min Zhang, Xue-Zhu Liao, Cheng-Gen Qiang, Wen-Hao Yu, Jing-Dan Han, Ya-Rong Ye, Chun-Yan Jing, Mei-Xia Wang, Qiang Gao, Jin-Feng Chen, Yuan-Nian Jiao, Zhi-Qiang Wu, Ya-Long Guo, Rod A. Wing, Jeff J. Doyle, Song Ge, Xin-Hui Zou
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Polyploid organisms evolve from their initial doubled genomic condition through a number of processes collectively termed diploidization, whose tempo and mode remain poorly understood mainly due to the difficulty of discriminating de novo evolution subsequent to polyploidy from variation inherited from progenitors. Here, we generated chromosome-scale genome assemblies for the wild rice allopolyploid Oryza minuta and its two diploid progenitors, Oryza punctata and Oryza officinalis , and employed a population genomic approach to investigate the diploidization process in O. minuta at the sequence and transcriptomic level. We show that this wild rice allopolyploid originated around 0.7 Mya, and during subsequent diploidization, its two subgenomes have retained highly conserved synteny with the genomes of its extant diploid progenitors. This populational approach allowed us to distinguish parental legacy of inherited variation from postpolyploidy evolution, and our analyses revealed that whereas gene fractionation occurred in an early burst, accumulation of transposable elements (TEs) and homoeologous exchanges has been gradual. Patterns of homoeolog expression bias are highly variable across tissues, with no consistent subgenome expression bias. Our assessments of the impact of DNA methylation, TE distribution, and parental legacy on expression patterns provide some support for the TE load theory (the theory that the TE densities in flanking regions surrounding genes strongly influence expression levels), while also illustrating the complexity of transcription regulation.
GPT-4o mini: Non-social science research article
Multiomics integration prioritizes potential drug targets for multiple sclerosis
Yuan Jiang, Qianwen Liu, Pernilla Stridh, Ingrid Kockum, Tomas Olsson, Lars Alfredsson, Lina-Marcela Diaz-Gallo, Xia Jiang
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Multiple sclerosis (MS) is an immune-mediated disease with no current cure. Drug discovery and repurposing are essential to enhance treatment efficacy and safety. We utilized summary statistics for protein quantitative trait loci (pQTL) of 2,004 plasma and 1,443 brain proteins, a genome-wide association study of MS susceptibility with 14,802 cases and 26,703 controls, both bulk and cell-type specific transcriptome data, and external pQTL data in blood and brain. Our integrative analysis included a proteome-wide association study to identify MS-associated proteins, followed by summary-data-based Mendelian randomization to determine potential causal associations. We used the HEIDI test and Bayesian colocalization analysis to distinguish pleiotropy from linkage. Proteins passing all analyses were prioritized as potential drug targets. We further conducted pathway annotations and protein–protein interaction network analysis (PPI) and verified our findings at mRNA and protein levels. We tested hundreds of MS-associated proteins and confirmed 18 potential causal proteins (nine in plasma and nine in brain). Among these, we found 78 annotated pathways and 16 existing non-MS drugs targeting six proteins. We also identified intricateAQ PPIs among seven potential drug targets and 19 existing MS drug targets, as well as PPIs of four targets across plasma and brain. We identified two targets using bulk mRNA expression data and four targets expressed in MS-related cell types. We finally verified 10 targets using external pQTL data. We prioritized 18 potential drug targets in plasma and brain, elucidating the underlying pathology and providing evidence for potential drug discovery and repurposing in MS.
GPT-4o mini: Non-social science research article
Rising surface salinity and declining sea ice: A new Southern Ocean state revealed by satellites
Alessandro Silvano, Aditya Narayanan, Rafael Catany, Estrella Olmedo, Verónica González‐Gambau, Antonio Turiel, Roberto Sabia, Matthew R. Mazloff, Theo Spira, F. Alexander Haumann, Alberto C. Naveira Garabato
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For decades, the surface of the polar Southern Ocean (south of 50°S) has been freshening—an expected response to a warming climate. This freshening enhanced upper-ocean stratification, reducing the upward transport of subsurface heat and possibly contributing to sea ice expansion. It also limited the formation of open-ocean polynyas. Using satellite observations, we reveal a marked increase in surface salinity across the circumpolar Southern Ocean since 2015. This shift has weakened upper-ocean stratification, coinciding with a dramatic decline in Antarctic sea ice coverage. Additionally, rising salinity facilitated the reemergence of the Maud Rise polynya in the Weddell Sea, a phenomenon last observed in the mid-1970s. Crucially, we demonstrate that satellites can now monitor these changes in real time, providing essential evidence of the Southern Ocean’s potential transition toward persistently reduced sea ice coverage.
GPT-4o mini: Non-social science research article
Genetic ancestry shapes dengue virus infection in human skin explants
Priscila M. S. Castanha, Michelle M. MartĂ­, Parichat Duangkhae, Jocelyn M. Taddonio, Kristine L. Cooper, Megan Wallace, Gwenddolen Kettenburg, Geza Erdos, Hasitha Chavva, Aleena Alex, J. Peter Rubin, Simon C. Watkins, Louis D. Falo, Ernesto T. A. Marques, Jeremy J. Martinson, Simon M. Barratt-Boyes
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Dengue is the most prevalent arthropod-borne viral disease of humans, with over half the world’s population at risk. Infection with any of the four dengue virus (DENV) serotypes is most often self-limiting, but a significant number of cases present with severe dengue characterized by vascular leakage that may be fatal. African ancestry is associated with protection against severe dengue, but the mechanisms are unknown. Using skin explants from genetically defined donors, we show that European ancestry skin has a much stronger inflammatory response to DENV than African ancestry skin, eliciting markedly increased infiltration, infection and migration of resident Langerhans cells, macrophages, and dendritic cells. The effect was seen with all dengue serotypes and Zika virus and in the presence of heterotypic immune serum. Genetic pathways associated with inflammation, interferon (IFN)-α, and inflammatory cytokine signaling were enriched in European relative to African ancestry skin following infection. Infiltration and infection of macrophages in African ancestry skin increased to that of European skin after blocking IFN-α and providing interleukin-1ÎČ. Polymorphic variants in RXRA , OAS1-3, and TGFB1 genes that were more frequent in European donors were associated with increased virus replication. Paradoxically, European ancestry skin cells had increased expression of OAS3 in response to virus and type I IFN. Thus, the limited inflammatory response of African ancestry skin to infection restricts replication and spread of dengue and other flaviviruses. Genetic ancestry should be considered when predicting a patient’s likelihood of severe dengue, and when assessing efficacy and adverse events associated with dengue vaccines.
GPT-4o mini: Non-social science research article
Jurassic constraints on the chaotic Mars–Earth eccentricity cycle linked to the volcanically induced Jenkyns event
Yanan Fang, Paul E. Olsen, Jingeng Sha, Jessica H. Whiteside, Chengguo Guan, Masayuki Ikeda, Sha Li, Daran Zheng, Haichun Zhang, Bo Wang
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Solar system gravitational interactions are embedded in Earth’s record of climate, providing a way to bypass the 60 Myr limit imposed by chaos. Presently with a 2.4 Myr period, the Mars–Earth beat cycle of orbital perihelion frequencies is particularly sensitive to chaotic diffusion, potentially varying by more than a million years. Early Mesozoic (252 to 145 Ma) strata provide some constraints on this cycle, with evidence of a swing through most of the solution space from 1.8 Myr at 210 Ma to 2.5 Myr at 190 Ma and back to 1.6 Myr at 180 Ma. However, only the 1.8 Myr cycle is corroborated by geochronologic data and the 1.6 Myr period is disputed. Here, we show that variations in land-plant-dominated stable carbon isotopic ratios (ή 13 C org ) from the lacustrine, paleo-high-latitude Sangonghe Formation (Junggar Basin, northwestern China), reveal at least three 1.6 Myr Mars–Earth beat cycles centered at 183 Ma, tracking atmospheric CO 2 isotopic composition in Earth’s exchangeable carbon reservoirs. Furthermore, the middle cycle includes the famous Jenkyns Event, expressed here by poleward migration of cheirolepidaceous conifers driven by CO 2 warming from the Karoo-Ferrar large igneous province (LIP). Our data do not, however, support major, LIP-triggered input of isotopically light carbon and instead support CO 2 amplification of local processes via warming and ecosystem change. Although requiring additional independent geochronological support, Sangonghe data help provide empirical constraints for filtering orbital solutions, tightening initial conditions, and testing gravitational models, as well as showing how extrinsic cyclical processes interact with a tectonic event, the Karoo-Ferrar LIP.
GPT-4o mini: Non-social science research article
Herbarium specimens reveal a constrained seasonal climate niche despite diverged annual climates across a wildflower clade
Megan Bontrager, Samantha J. Worthy, N. IvalĂș Cacho, Laura Leventhal, Julin N. Maloof, Jennifer R. Gremer, Johanna Schmitt, Sharon Y. Strauss
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Quantifying species’ niches across a clade reveals how environmental tolerances evolve, and offers insights into present and future distributions. We use herbarium specimens to explore climate niche evolution across 14 annual species of the Streptanthus ( s.l. ) clade (Brassicaceae), which originated in deserts and diversified into cooler, moister areas. To understand how climate niches evolved, we used historical climate records to estimate each species’ 1) classic annual climate niche, averaged over specimen collection sites; 2) growing season niche, from estimated specimen germination date to collection date, averaged across specimens (specimen-specific niche); and 3) standardized seasonal niche based on average growing seasons of all species (clade-seasonal niche). In addition to estimating how phenological variation maps onto climate niche evolution, we explored how spatial refugia shape the climate experienced by species by 1) analyzing how field soil texture changes relative to the climate space that species occupy and 2) comparing soil water holding capacity from each specimen locality to that of surrounding areas. Specimen-specific niches exhibited less clade-wide variation in climatic water deficit (CWD) than did annual or clade-seasonal niches, and specimen-specific temperature niches showed no phylogenetic signal, in contrast to annual and clade-seasonal temperature niches. Species occupying cooler regions tracked hotter and drier climates by growing later into the summer, and by inhabiting refugia on drought-prone soils. These results underscore how phenological shifts, spatial refugia, and germination timing shape “lived” climate. Despite occupying a large range of annual climates, we found these species are constrained in the conditions under which they thrive.
GPT-4o mini: Non-social science research article
Singularity formation in 3D Euler equations with smooth initial data and boundary
Jiajie Chen, Thomas Y. Hou
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A long-standing fundamental open problem in mathematical fluid dynamics and nonlinear partial differential equations is to determine whether solutions of the 3D incompressible Euler equations can develop a finite-time singularity from smooth, finite-energy initial data. Leonhard Euler introduced these equations in 1757 [L. Euler, MĂ©moires de l’AcadĂ©mie des Sci. de Berlin 11 , 274–315 (1757).], and they are closely linked to the Navier–Stokes equations and turbulence. While the general singularity formation problem remains unresolved, we review a recent computer-assisted proof of finite-time, nearly self-similar blowup for the 2D Boussinesq and 3D axisymmetric Euler equations in a smooth bounded domain with smooth initial data. The proof introduces a framework for (nearly) self-similar blowup, demonstrating the nonlinear stability of an approximate self-similar profile constructed numerically via the dynamical rescaling formulation.
GPT-4o mini: Non-social science research article
Photothermal catalysis of waste plastics into propionic acid and hydrogen via Ni single-atom site isolation effect
Shuai Yue, Yixiao Liu, Zhiyong Zhao, Guanshu Zhao, Mengxue Yang, Tao Zhang, Fei Li, Kewang Liu, Pengfei Wang, Sihui Zhan, Jinhu Jia
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Currently, catalytic recycling of polyethylene (PE) into high-value chemicals using solar energy often faces poor product selectivity and low efficiency. This is mainly due to the difficulty in effectively controlling the intermediates during PE photoreforming and the long-standing challenge of inefficient charge dynamics. Here, we present a solar-driven photothermal catalytic approach for the selective conversion of PE waste into propionic acid and hydrogen under ambient conditions. Atomically dispersed Ni sites supported on CeO 2 (Ni SA /CeO 2 ) achieve a propionic acid yield of 331 ÎŒmol h –1 with 94.8% selectivity in the photothermal reaction. This performance is 1.6 times higher than that of catalysts supported by Ni clusters (Ni NP /CeO 2 ). Additionally, Ni SA /CeO 2 exhibits a hydrogen yield of 0.23 mmol h –1 with stable long-term performance. Mechanistic studies reveal that single Ni atoms form linear coordination with oxygen atoms in CeO 2 , introducing unoccupied mid-gap states that effectively capture hot electrons and enhance the photothermal effect through local hotspot formation. In contrast, Ni clusters suffer from inefficient heat accumulation due to multistep phonon scattering. Furthermore, site isolation of Ni single atoms spatially separates the reaction intermediates and suppresses dimerization of the key intermediate COOHCH 2 CH 2 *, thereby greatly improving the selectivity for propionic acid. In contrast, closely packed Ni cluster sites promote intermediate coupling and the formation of undesirable byproducts, reducing selectivity. This work provides mechanistic insights into the advantages of atomic-scale catalyst design for selective chemical transformations.
GPT-4o mini: Non-social science research article
Contribution of glutamatergic projections to neurons in the nonhuman primate substantia nigra pars reticulata for reactive inhibition
Atsushi Yoshida, Okihide Hikosaka
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The basal ganglia play a crucial role in action selection by facilitating desired movements and suppressing unwanted ones. The substantia nigra pars reticulata (SNr), a key output nucleus, facilitates movement through disinhibition of the superior colliculus (SC). However, its role in action suppression, particularly in primates, remains less clear. We investigated whether individual SNr neurons in three male macaque monkeys bidirectionally modulate their activity to both facilitate and suppress actions and examined the role of glutamatergic inputs in suppression. Monkeys performed a sequential choice task, selecting or rejecting visually presented targets. Electrophysiological recordings showed that SNr neurons decreased firing rates during target selection and increased firing rates during rejection, demonstrating bidirectional modulation. Pharmacological blockade of glutamatergic inputs to the lateral SNr disrupted saccadic control and impaired suppression of reflexive saccades, providing causal evidence for the role of excitatory input in behavioral inhibition. These findings suggest that glutamatergic projections, potentially originating from sources including the subthalamic nucleus, contribute to the increased SNr activity during action suppression. Our results highlight conserved basal ganglia mechanisms across species and offer insights into the neural substrates of action selection and suppression in primates, with implications for understanding disorders such as Parkinson’s disease.
GPT-4o mini: Non-social science research article
A transcriptomic, proteomic, and functional genetic atlas dissects neurofibromin function in the peripheral nervous system
Harish N. Vasudevan, Nadia Arang, Maria Sacconi Nunez, Patrick Kennedy, Emily Payne, Sarah Mohabeer, Julian Chien, Aaron Wright, Matthew J. Sale, Nevan J. Krogan, Antoine Forget, Frank McCormick
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The NF1 tumor suppressor gene is recurrently mutated in human cancers and is associated with the neurofibromatosis type 1 (NF-1) cancer predisposition syndrome. NF1 encodes neurofibromin, a Ras guanosine triphosphate (GTPase) activating protein that negatively regulates Ras signaling. NF1 mutation accordingly leads to Ras misactivation and downstream activation of RAF/MEK/ERK signaling, leading to the approval of the MEK inhibitor selumetinib for NF-1 associated peripheral nervous system (PNS) tumors. However, how NF1 loss modifies response to selumetinib and the utility of targeting additional upstream inputs or downstream outputs of Ras these tumors remain unclear. Here, we perform RNA-sequencing, phosphoproteomic, pharmacologic, and proximal proteomic analysis across a panel of CRISPR interference immortalized peripheral nerve (iPN) cells to systematically dissect the function of neurofibromin loss. Small guide NF1 (sg NF1 ) repression is sufficient to increase Ras GTP levels and alter gene expression to promote cell proliferation and dedifferentiation, with sg NF1 iPNs showing decreased sensitivity to selumetinib due to altered feedback regulation to Ras/RAF/MEK/ERK. Upstream small guide PTPN11 (sg PTPN11 ) repression leads to the inverse gene expression signature, decreasing cell proliferation and promoting differentiation, and sg PTPN11 iPNs are more sensitive to selumetinib. However, upstream sonof sevenless 1 inhibition shows limited efficacy in iPNs due to compensation by SOS2. Finally, proximal proteomics reveals Kirsten rat sarcoma virus (KRAS), but not Harvey rat sarcoma virus (HRAS) or neuroblastoma Ras viral oncogene homolog (NRAS), associates with neurofibromin in iPN cells, and pan-KRAS inhibition is sufficient to block ERK activation and CDK1/2 activation in NF1 mutant cells, suggesting blocking KRAS may be a therapeutic approach for NF1 mutant PNS tumors.
GPT-4o mini: Non-social science research article
Genome analyses suggest recent speciation and postglacial isolation in the Norwegian lemming
Edana Lord, Isabelle S. Feinauer, André E. R. Soares, Vendela K. Lagerholm, Karin NÀsvall, Erik Ersmark, Remi-André Olsen, Stefan Prost, Elena A. Kuzmina, Nickolay G. Smirnov, John R. Stewart, Monika V. Knul, Pierre Noiret, Mietje Germonpré, Dorothee Ehrich, Ivan Pokrovsky, Vadim B. Fedorov, Anna V. Goropashnaya, Love Dalén, David Díez-del-Molino
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The Norwegian lemming ( Lemmus lemmus ) is a small rodent distributed across the Fennoscandian mountain tundra and the Kola Peninsula. The Norwegian lemming likely evolved during the Late Pleistocene and inhabited Fennoscandia shortly prior to the Last Glacial Maximum. However, the exact timing and origins of the species, and its phylogenetic position relative to the closely related Siberian lemming ( Lemmus sibiricus ) remain disputed. Moreover, the presence of ancient or contemporary gene flow between both species is largely untested. The Norwegian lemming displays characteristic phenotypic and behavioral adaptations (e.g., coat color, aggression) that are not present in other Lemmus species. We generated a de novo genome assembly for the Norwegian lemming and resequenced nine modern and two ancient Lemmus spp. genomes. We show that all Lemmus species form distinct monophyletic clades, with concordant topology between the mitochondrial and nuclear genome phylogenies. The Siberian lemming is divided into two distinct but paraphyletic clades, one in the east and one in the west, where the western clade represents a sister taxon to the Norwegian lemming. We estimate that the Norwegian and western Siberian lemming diverged shortly before the Last Glacial Maximum, making the Norwegian lemming one of the youngest known mammalian species. We did not find any indication of gene flow between L. lemmus and L. sibiricus , suggesting postglacial isolation of L. lemmus . Furthermore, we identify species-specific genomic differences in genes related to coat color and fat transport, which are likely associated with the distinctive coloration and overwintering behavior observed in the Norwegian lemming.
GPT-4o mini: Non-social science research article
A molecular tango between chromatin and metabolites orchestrates a feedback switch for alcohol consumption
Heidi M. Schmidt, Elizabeth J. Tarling, Thomas Q. de Aguiar Vallim
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GPT-4o mini: Non-social science research article
Retinoic acid receptor assembly dynamics governs dual functions in cochlear organogenesis
Saikat Chakraborty, Shuze Wang, Jack Ruhala, Brett Mehling, Jie Liu, Joerg Waldhaus
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Retinoic acid (RA) is a morphogen that contributes to inner ear development. Gain and loss of function experiments have indicated retinoic acid’s critical role in cochlear hair cell development. However, the underlying molecular mechanisms are unclear. Here, we hypothesized that RA receptor alpha (RARA) has a dual role in cochlear organogenesis: First, during embryonic development, in the presence of RA, RARA functions as a transcriptional activator that induces prosensory gene expression in progenitor cells and supports differentiation of the organ of Corti; later during postnatal development, when RA is absent, the function of RARA switches, thereby repressing prosensory genes in postnatal hair cells and hindering trans-differentiation into supporting cells. This hypothesis was supported by demonstration that RARA forms a complex with either the coactivator NCOA1 or the corepressor NCOR1 depending on the developmental stage. In addition, modulation of RA levels was found to govern recruitment of the coactivator and corepressor to the RARA complex, and the expression of prosensory genes was validated to depend on RARA complex composition. Together, our results provide insights supporting the potential of harnessing RA signaling to induce prosensory progenitors in stem cell–based strategies for hearing loss.
GPT-4o mini: Non-social science research article
The earliest domestic pigs in Neolithic China were closely managed
Peter Rowley-Conwy
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GPT-4o mini: Non-social science research article
In silico evolution of globular protein folds from random sequences
Harutyun Sahakyan, Sanasar G. Babajanyan, Yuri I. Wolf, Eugene V. Koonin
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The origin and evolution of protein folds are among the most challenging, long-standing problems in biology. We developed Protein Fold Evolution Simulator (PFES), a computational approach that simulates evolution of globular folds from random amino acid sequences with atomistic details. PFES introduces random mutations in a population of protein sequences, evaluates the effect of mutations on protein structure, and selects a new set of proteins for further evolution. Iteration of this process allows tracking the evolutionary trajectory of a changing protein fold that evolves under selective pressure for protein fold stability, interaction with other proteins, or other features shaping the fitness landscape. We employed PFES to show how stable, globular protein folds could evolve from random amino acid sequences as monomers or in complexes with other proteins. The simulations reproduce the evolution of many simple folds of natural proteins as well as emergence of distinct folds not known to exist in nature. We show that evolution of small globular protein folds from random sequences, on average, takes 1.15 to 3 amino acid replacements per site, depending on the population size, with some simulations yielding stable folds after as few as 0.2 replacements per site. These values are lower than the characteristic numbers of replacements in conserved proteins during the time since the Last Universal Common Ancestor, suggesting that simple protein folds can evolve from random sequences relatively easily and quickly. PFES tracks the complete evolutionary history from simulations and can be used to test hypotheses on protein fold evolution.
GPT-4o mini: Non-social science research article
Action-mode subnetworks for decision-making, action control, and feedback
Carolina Badke D’Andrea, Timothy O. Laumann, Dillan J. Newbold, Charles J. Lynch, Mohammad Hadji, Steven M. Nelson, Ashley N. Nielsen, Roselyne J. Chauvin, Samuel R. Krimmel, Abraham Z. Snyder, Scott Marek, Deanna J. Greene, Marcus E. Raichle, Nico U. F. Dosenbach, Evan M. Gordon
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The action-mode network (AMN) is a canonical functional brain network first identified using resting-state functional connectivity (RSFC). Based on animal and human data, we have proposed that AMN supports the brain’s action mode by controlling functions required for successful goal-directed behavior. However, task fMRI averaged across groups has associated AMN regions with a variety of behaviors, contributing to uncertainty about AMN function. Here, we investigated the AMN using an inside-out approach, in which the network architecture of the AMN is first precisely mapped within individuals and then associated with behavioral functions. Individual-specific precision functional mapping with >5 h of RSFC and task functional magnetic resonance imaging (fMRI) data revealed a replicable AMN subnetwork structure. AMN subnetworks were characterized and annotated by combining a meta-analytic network association method with RSFC, intrinsic timing, and task activation profiling. We demonstrate the existence of AMN-Decision, -Action, and -Feedback subnetworks that are distributed across lobes, forming a temporally sequential within-network processing stream by which the brain adjudicates between possible goals, sets action plans, and modifies those plans in response to feedback such as pain. A subnetwork in the pars marginalis of the cingulate was distinct from the Decision, Action, and Feedback subnetworks and may be important for the construction of the bodily self.
GPT-4o mini: Non-social science research article
Synergistic deficits in parvalbumin interneurons and dopamine signaling drive ACC dysfunction in chronic pain
Kevin Lançon, Jiakang Tian, Haleigh Bach, Pierre Drapeau, Jean-Francois Poulin, Philippe Séguéla
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Chronic pain arises from maladaptive changes in both peripheral and central nervous systems, including the anterior cingulate cortex (ACC), a key region implicated in descending pain modulation. Chronic pain increases the excitability of pyramidal neurons in the ACC. Although a reduction in inhibitory inputs onto pyramidal neurons has been observed in neuropathic conditions, the identity of the specific interneurons responsible remains unclear. We show that chronic pain selectively impairs parvalbumin (PV), but not somatostatin, interneurons in the rostral ACC. This is characterized by a decrease in the density of PV interneuron processes, a reduction in their surrounding perineuronal net, and a lower expression of PV. Functionally, PV interneurons display diminished inhibitory efficacy in vitro and reduced phasic activation in response to aversive stimuli in vivo. Dopamine (DA) fibers preferentially contact PV interneurons and excite them via D1 dopamine receptor activation, increasing their excitability and enhancing the frequency of inhibitory postsynaptic currents on pyramidal neurons in healthy, but not neuropathic, conditions. Furthermore, we show that this pathway is involved in hunger-induced analgesia: Food deprivation increases DA release in the ACC and consequently decreases pain thresholds in neuropathic mice. Conversely, when mice are not food deprived, neuropathic pain significantly reduces DA release in the ACC. We conclude that the loss of PV interneuron inhibitory efficacy, alongside convergent hypodopaminergic signaling, synergistically contributes to pathological ACC dysfunction and associated symptoms of chronic pain.
The cultural construction of “executive function”
Ivan Kroupin, Helen Elizabeth Davis, Emily Burdett, Agustina Bani Cuata, Vahumburuka Hartley, Joseph Henrich
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In cognitive science, the term “executive function” (EF) refers to universal features of the mind. Yet, almost all results described as measuring EF may actually reflect culturally specific cognitive capacities. After all, typical EF measures require forms of decontextualized/arbitrary processing which decades of cross-cultural work indicate develop primarily in “schooled worlds”–industrialized societies with universal schooling. Here, we report comparisons of performance on typical EF tasks by children inside, and wholly outside schooled worlds. Namely, children ages 5 to 18 from a postindustrial context with universal schooling (UK) and their peers in a rural, nonindustrialized context with no exposure to schooling (Kunene region, Namibia/Angola), as well as two samples with intermediate exposure to schooled worlds. In line with extensive previous work on decontextualized/arbitrary processing across such groups, we find skills measured by typical EF tasks do not develop universally: Children from rural groups with limited or no formal schooling show profound, sometimes qualitative, differences in performance compared to their schooled peers and, especially, compared to a “typical” schooled-world sample. In sum, some form of latent cognitive control capacities are obviously crucial in all cultural contexts. However, typical EF tasks almost certainly reflect culturally specific forms of cognitive development. This suggests we must decide between using the term EF to describe 1) universal capacities or 2) the culturally specific skill set reflected in performance on typical tasks. Either option warrants revisiting how we understand what has been measured as EF to date, and what we wish to measure going forward.
Our changing information ecosystem for science and why it matters for effective science communication
Nicole M. Krause, Isabelle Freiling, Dietram A. Scheufele
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Current information ecologies present unique opportunities to communicate science and engage diverse publics in science. Unfortunately, they also present unique challenges. Here, we outline how the public sphere for science is transforming as media evolve, and we connect these changes to the high-stakes issue context of COVID-19. We argue that scientific organizations’ struggles to adapt to evolving media are linked, in part, to asymmetries in which social media platforms prevent researchers from producing reliable data that could inform institutional change and improve science communication. This has been apparent in studies of echo chambers and filter bubbles. Producing a more usable evidence base, we conclude, will require that scholars a) obtain access to proprietary data, b) reconceptualize information ecologies as social systems, c) avoid ceding core research tasks to platforms, d) address ethical issues, and e) grapple with the urgency of moving forward productively.
Transformative community-engaged science: Strengthening relationships between science and society
Rajul E. Pandya, Amanda D. Boyd, MĂłnica I. FeliĂș-MĂłjer, Itzhak Yanovitzky
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There is a critical need to strengthen science–society relationships—especially with historically marginalized communities—if we are to better and more equitably manage complicated, intertwined, global challenges at the intersection of environment, health, equity, and well-being. Community-engaged science, which focuses on shared leadership and mutual benefit in scientific partnership with communities, has the potential to transform science, communities, and even society. Despite this promise, however, community-engaged science is not always transformative. Presentations and discussions at the 5th National Academies Science Communication Colloquium demonstrated the importance of creating structures, practices, and a culture of science engagement that prioritizes listening and learning from communities. Based on presentations at the colloquium, research publications, and our own experiences, we share a set of evidence-informed principles that are common to successful community-engaged science across many contexts: respect, humility, listening, reciprocity, mutuality, and reflexivity. We also offer steps the scientific community can take to advance and improve the transformative practice of community-engaged science as part of a productive ecosystem of scientific activities: evolving norms and culture, integrating community science into current systems, building incentives and structures to support community-engaged science, developing a workforce skilled in community engagement, and investing in a coordinated research-to-practice agenda.
Promoting collective cooperation through temporal interactions
Yao Meng, Alex McAvoy, Aming Li
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Collective cooperation maintains the function of many natural and social systems, making understanding the evolution of cooperation a central question of modern science. Although human interactions involve complex contact networks, current explorations are limited to static networks, where social ties are permanent and do not change over time. In reality, human activities often involve temporal interactions, where links are impermanent, and understanding the evolution of cooperation on such temporal networks is an open problem. Here, we systematically analyze how cooperation spreads on arbitrary temporal networks, and we distill our results down to a concise condition, which integrates evolutionary game dynamics with both static and temporal interactions. We find that the emergence of cooperation is facilitated by a simple rule of thumb: Hubs (individuals with many social ties) should be temporally deprioritized in interactions. For empirical applications, we further provide a quantitative metric capturing the priority of hubs, which is validated on empirical datasets based on its effectiveness in orchestrating the ordering of interactions to best promote cooperation. Our findings unveil the fundamental advantages conferred by temporal interactions for promoting collective cooperation, transcending the specific insights gleaned from studying static networks.
Tendencies toward triadic closure: Field experimental evidence
Mohsen Mosleh, Dean Eckles, David G. Rand
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Empirical social networks are characterized by a high degree of triadic closure (i.e., transitivity, clustering): network neighbors of the same individual are also likely to be directly connected. It is unknown to what degree this results from dispositions to form such ties (i.e., to close open triangles) per se versus other processes such as homophily and more opportunities for exposure. These mechanisms are difficult to disentangle in many settings. On social media, however, they can be decomposed - and platforms frequently make decisions that depend on these distinct processes. Here, using a field experiment on social media, we randomize the existing network structure that a user faces when they are followed by a target account that we control. We then examine whether the user reciprocates this tie formation. Being randomly assigned to have an existing tie to an account that follows the target user increases tie formation by 35%. Through multiple control conditions, we attribute this effect specifically to a minimal cue that indicates the presence of a potential mutual follower. Theory suggests that triadic closure should be especially likely in open triads of strong ties, and accordingly we find larger effects when the subject has interacted more with the existing follower. These results indicate a substantial role for tendencies toward triadic closure, but one that is substantially smaller than what might be inferred from prior observational studies. Platforms and others may rely on these tendencies in encouraging tie formation, with broader implications for network structure and information diffusion in online networks.
The epigenetic impacts of pubertal acceleration following early caregiver disruptions
Ellen Jopling, Stacy S. Drury, Nathan A. Fox, Charles H. Zeanah, Charles A. Nelson
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A stable caregiving environment early in life is essential for children’s development, and disruptions have the potential to impact biological processes. Using data from the Bucharest Early Intervention Project, we examined a developmental cascade model in which shifts in pubertal tempo following early caregiving disruptions come at an epigenetic cost. Among 115 individuals, all of whom experienced severe deprivation early in life, we tracked caregiving disruptions across childhood; assessed pubertal timing and tempo across adolescence; and quantified the pace of cellular aging via telomere erosion across the second decade of life. We demonstrate that a greater number of caregiving disruptions is associated with delayed pubertal timing and an acceleration of pubertal tempo. In turn, accelerations in pubertal tempo are associated with significantly greater telomere erosion across time. A formal mediation model indicated that greater caregiving disruptions during childhood predicted greater telomere erosion through an acceleration of pubertal tempo. By documenting the impact of caregiving disruptions on pubertal development and ultimately biological aging, these findings highlight the importance of the stability of the caregiving context and the critical need to ensure that organizations caring for vulnerable children establish programs and policies to minimize unnecessary disruptions.
The importance of scientists’ intellectual humility for communicating effectively across ideological and identity-based divides
Kimberly Rios, Zachary C. Roth, Thomas J. Coleman
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Growing identity-based and partisan gaps in confidence in scientists and scientific institutions call for novel approaches to science communication. In this perspectives piece, we focus on the need for greater intellectual humility (i.e., willingness to revise one’s views and admit that one might be wrong) among social scientists, who are met with particularly high levels of skepticism from the public. We begin with an overview of research demonstrating that when scientists’ identities or ideologies align (or are perceived to align) with those of the public, trust in science increases. We then highlight intellectual humility as a potential tool for cultivating trust in the social sciences even when social scientists’ and the public’s identities or ideologies do not match. Specifically, intellectual humility among social scientists predicts less bias toward one another’s research and hence may increase the diversity of perspectives to which the public is exposed and shift public perceptions of social scientists. We conclude with a discussion of how to foster intellectual humility in science communication, broadly defined.
An agenda for science communication research and practice
James N. Druckman, Kirsten M. Ellenbogen, Dietram A. Scheufele, Itzhak Yanovitzky
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Science should not unilaterally dictate individuals’ decisions or public policies. Yet, it provides a vital source of information for societies and individuals that can often improve outcomes and well-being. This requires, however, the effective communication of scientific information. We identify two paradigms for science communication. One focuses on dissemination, often seeking to inform, reframe, or correct beliefs. Another emphasizes participation and engagement with the goal of improving public understanding of science and scientists’ understanding of the public’s concerns, needs, and values. We argue that participatory approaches better address contemporary challenges concerning scientific uncertainty, politicized science, artificial value neutrality, and a reactive science communication infrastructure. These approaches though need to move away from transactional partnerships toward more cocreation and coproduction of knowledge. They also need to focus more on less motivated and/or engaged populations. Investment in a participatory infrastructure is crucial given that even the most path-breaking science only matters if it can be adequately communicated to relevant stakeholders.

Science

GPT-4o mini: Non-social science research article
Let there be light: From passive agricultural sensing to active intervention
Xiaobo Yin
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In Thailand, the word BaiKhao (àčƒàžšàž‚àč‰àžČàž§)—meaning “rice leaf”—embodies a quiet agricultural revolution. For generations, farmers gauged crops’ nitrogen fertilizer needs by visually assessing leaf greenness, a method vulnerable to variations in lighting conditions and human error. Today, the “BaiKhaoNK” mobile app transforms smartphones into optical sensors. Using built-in cameras, it quantifies chlorophyll levels through spectral analysis and recommends precise fertilizer doses. This innovation epitomizes agriphotonics, a field dedicated to harnessing light-based tools to monitor, analyze, and diagnose crops and their environments.
GPT-4o mini: Non-social science research article
Origin and radiation of squids revealed by digital fossil-mining
Shin Ikegami, Yusuke Takeda, Jörg Mutterlose, Yasuhiro Iba
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The evolution of soft-bodied squids, which provide a major part of the biomass in modern oceans globally, is poorly understood owing to their patchy fossil record. We provide a comprehensive evolutionary history of squids through “digital fossil-mining” techniques, revealing a new lagerstĂ€tte. The more than 250 fossil beaks of 40 species show that squids originated and rapidly radiated by 100 million years ago. Our data suggest that the radical shift from heavily shelled, slowly moving cephalopods to soft-bodied forms did not result from the end-Cretaceous mass extinction (66 million years ago). Early squids had already formed large populations, and their biomass exceeded that of ammonites and fishes. They pioneered the modern-type marine ecosystem as intelligent, fast swimmers.
GPT-4o mini: Non-social science research article
Event structure sculpts neural population dynamics in the lateral entorhinal cortex
Benjamin R. Kanter, Christine M. Lykken, Ignacio Polti, May-Britt Moser, Edvard I. Moser
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Our experience of the world is a continuous stream of events that must be segmented and organized at multiple timescales. The neural mechanisms underlying this process remain unknown. In this work, we simultaneously recorded hundreds to thousands of neurons in the lateral entorhinal cortex of freely behaving rats. Neural population activity drifted continuously along a one-dimensional manifold during all behaviors and behavioral states, including sleep, which points to an intrinsic origin of the drift. In awake animals, boundaries between events were associated with discrete shifts in population dynamics, which segmented the neural activity into temporal units. During tasks with recurring temporal structure, activity traveled additionally in directions orthogonal to the drift, encoding event information across multiple timescales. The results identify a hierarchical coding scheme for organizing events in time.
GPT-4o mini: Non-social science research article
Gradient refractive indices enable squid structural color and inspire multispectral materials
Georgii Bogdanov, Aleksandra Anna Strzelecka, Nikhil Kaimal, Stephen L. Senft, Sanghoon Lee, Roger T. Hanlon, Alon A. Gorodetsky
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The manipulation of light by means of materials with varying refractive index distributions is widespread among natural systems and modern technologies. However, understanding how animals leverage refractive index differences for dynamic color changes and then translating such insight into tunable optical devices remains challenging. We experimentally and computationally demonstrated that iridescent cells (iridophores) containing Bragg reflectors with sinusoidal-wave (rugate) refractive index profiles enable squid dorsal mantle tissues to reversibly transition between nearly transparent and vibrantly colored states. We then drew inspiration from these findings for the design and development of iridophore-inspired multispectral composite materials with tunable visible and infrared functionalities. Our study provides insight into squid dynamic structural coloration mechanisms and furnishes a technology for camouflage, heat management, display, and sensing applications.
GPT-4o mini: Non-social science research article
Divergent FOXA1 mutations drive prostate tumorigenesis and therapy-resistant cellular plasticity
Sanjana Eyunni, Rahul Mannan, Yuping Zhang, Eleanor Young, Qiuyang Zhang, Jie Luo, Matthew Pang, Somnath Mahapatra, Jean Ching-Yi Tien, James M. George, Mustapha Jaber, Hamzah Hakkani, Sandra E. Carson, Abigail J. Todd, Noshad Hosseini, Mahnoor Gondal, Ryan J. Rebernick, Xuhong Cao, Fengyun Su, Rui Wang, Rohit Mehra, Jing Li, Marcin Cieslik, Arul M. Chinnaiyan, Abhijit Parolia
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FOXA1 is altered in 10 to 40% of prostate cancers, yet its oncogenic mechanisms remain uncharacterized in vivo. We developed knock-in mouse models representing distinct classes of FOXA1 mutations. Histopathological and multi-omic analyses of prostate tissues and organoids revealed that Class 1 mutations, in conjunction with p53 inactivation, drive androgen-dependent adenocarcinomas through co-activation of mTORC1/2 and oncogenic AR signaling stemming from chimeric AR-half enhancers. In contrast, Class 2 mutations induce intra-luminal plasticity by reprogramming differentiated luminal cells into a progenitor-like state through activation of KLF5 and AP-1 neo-enhancer circuitries, which enables enhanced survival and proliferation even under castrate androgen levels. Our findings establish FOXA1 as a multifaceted oncogene, with distinct mutational classes divergently evolving to drive prostate tumorigenesis or therapy-resistant progression.
GPT-4o mini: Non-social science research article
Interplate slip before, during, and after the 2024 M w 7 Hyuga-nada earthquake, southwest Japan
Shinzaburo Ozawa, Hiroshi Munekane, Hisashi Suito, Hiroshi Yarai
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Using Global Navigation Satellite System data, we investigated the interplate slip before, during, and after the 2024 Hyuga-nada earthquake in Japan. Before the earthquake, a moment magnitude ( M w ) 6.0 slow-slip event (SSE) was observed from late 2023 in a downdip extension of the mainshock. The coseismic slip was adjacent to the 1996 Hyuga-nada earthquake source. The afterslip resolved near the hypocenter area and in the downdip extension of the mainshock, reaching M w 6.7 on 16 September 2024. Leading up to the earthquake, the recurrence interval for SSEs in the preslip area shortened from an average of 2 years, estimated from observations over the past 30 years, to 1 year, consistent with simulations in which the weakening of the Nankai megathrust was attributed to the cause.
GPT-4o mini: Non-social science research article
Reactivation of mammalian regeneration by turning on an evolutionarily disabled genetic switch
Weifeng Lin, Xiaohui Jia, Xiaofeng Shi, Qiuya He, Panyu Zhang, Xianglei Zhang, Liping Zhang, Mingqi Wu, Tengfei Ren, Yufei Liu, Haohao Deng, Yanyao Li, Shiqi Liu, Shaoyong Huang, Jingmin Kang, Jun Luo, Ziqing Deng, Wei Wang
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Mammals display prominent diversity in the ability to regenerate damaged ear pinna, but the genetic changes underlying the failure of regeneration remain elusive. We performed comparative single-cell and spatial transcriptomic analyses of rabbits and mice recovering from pinna damage. Insufficient retinoic acid (RA) production, caused by the deficiency of rate-limiting enzyme Aldh1a2 and boosted RA degradation, was responsible for the failure of mouse pinna regeneration. Switching on Aldh1a2 or RA supplementation reactivated regeneration. Evolutionary inactivation of multiple Aldh1a2-linked regulatory elements accounted for the deficient Aldh1a2 expression upon injury in mice and rats. Furthermore, the activation of Aldh1a2 by a single rabbit enhancer was sufficient to improve ear pinna regeneration in transgenic mice. Our study identified a genetic switch involved in the evolution of regeneration.
GPT-4o mini: Non-social science research article
Accelerated discovery of stable, extra-large-pore nano zeolites with micro-electron diffraction
Chao Ma, Zhenghan Zhang, Mengdi Zhang, Xudong Tian, Cong Lin, Lei Han, Guangchao Li, Benedict Tsz Woon Lo, Ka-Fu Yung, Haitao Song, Wei Lin, Miguel A. Camblor, Le Xu, Jian Li
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Stable zeolites with extra-large pores and nano dimensions that are capable of processing large molecules are in high demand but have been difficult to produce. Their complex structures and nanoscale crystal sizes present challenges for analysis using conventional x-ray diffraction techniques, leading to inefficiencies in material development. We report NJU120-1 and NJU120-2, two robust and fully connected aluminosilicate nano zeolites featuring interconnected channel systems with extra-large 22-ring pores. NJU120-1 is a nanosheet with only about 8-nanometer thickness, corresponding to 1.5 unit cells, and NJU120-2 is a nanorod with 50 by 250 nanometer dimensions. Their synthesis optimization was greatly accelerated through rapid structure determination with MicroED, revealing their multidimensional pore structures. Their very large largest-free-sphere diameters of approximately 1.2 nanometers coupled with nano morphologies enabled catalytic cracking of large molecules.
GPT-4o mini: Non-social science research article
Out-of-Anatolia: Cultural and genetic interactions during the Neolithic expansion in the Aegean
Dilek Koptekin, Ayça Aydoğan, Cansu Karamurat, N. Ezgi Altınıßık, Kıvılcım Baßak Vural, D. Deniz Kazancı, Ayça KĂŒĂ§ĂŒkakdağ Doğu, Damla Kaptan, Hasan Can Gemici, Eren YĂŒncĂŒ, Hannah M. Moots, GĂŒlsĂŒn Umurtak, Refik Duru, Erkan Fidan, Özlem Çevik, Burçin Erdoğu, Taner Korkut, Christopher J. KnĂŒsel, Scott Haddow, Clark Spencer Larsen, Rana Özbal, Fokke Gerritsen, Eylem Özdoğan, Ali Akbaba, Uygar Ozan Usanmaz, Yasin Cemre Derici, Mine Uçmazoğlu, Flora Jay, Mehmet Özdoğan, Anders Götherström, Yılmaz Selim Erdal, Anna-Sapfo Malaspinas, Çiğdem Atakuman, FĂŒsun Özer, Mehmet Somel
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West Anatolia has been a crucial yet elusive element in the Neolithic expansion from the Fertile Crescent to Europe. In this work, we describe the changing genetic and cultural landscapes of early Holocene West Anatolia using 30 new paleogenomes. We show that Neolithization in West Anatolia was a multifaceted process, characterized by the assimilation of Neolithic practices by local foragers, the influx of eastern populations, and their admixture, with their descendants subsequently establishing Neolithic Southeast Europe. We then coanalyzed genetic and cultural similarities across early Holocene Anatolian and Aegean Neolithic villages using 58 material culture elements. Cultural distances among villages correlate with their spatial distances but not with their genetic distances after controlling for geography. This suggests that cultural change was often decoupled from genetically visible mobility.
GPT-4o mini: Non-social science research article
Cascading land surface hazards as a nexus in the Earth system
Brian J. Yanites, Marin K. Clark, Joshua J. Roering, A. Joshua West, Dimitrios Zekkos, Jane W. Baldwin, Corina Cerovski-Darriau, Sean F. Gallen, Daniel E. Horton, Eric Kirby, Ben A. Leshchinsky, H. Benjamin Mason, Seulgi Moon, Katherine R. Barnhart, Adam Booth, Jonathan A. Czuba, Scott McCoy, Luke McGuire, Allison Pfeiffer, Jennifer Pierce
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This Review synthesizes progress and outlines a new framework for understanding how land surface hazards interact and propagate as sediment cascades across Earth’s surface, influenced by interactions among the atmosphere, biosphere, hydrosphere, and solid Earth. Recent research highlights a gap in understanding these interactions on human timescales, given rapid climatic change and urban expansion into hazard-prone zones. We review how surface processes such as coseismic landslides and post-fire debris flows form a complex sequence of events that exacerbate hazard susceptibility. Moreover, innovations in modeling, remote sensing, and critical zone science can offer new opportunities for quantifying cascading hazards. Looking forward, societal resilience can increase by transforming our understanding of cascading hazards through advances in integrating data into comprehensive models that link across Earth systems.
GPT-4o mini: Non-social science research article
Stable and uniform self-assembled organic diradical molecules for perovskite photovoltaics
Wenping Wu, Han Gao, Lingbo Jia, Yuan Li, Dezhong Zhang, Hongmei Zhan, Jianan Xu, Binhe Li, Ziran Geng, Yanxiang Cheng, Hui Tong, Yanxiong Pan, Jun Liu, Yongcai He, Xixiang Xu, Zhenguo Li, Bo He, Min Zhou, Lixiang Wang, Chuanjiang Qin
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Organic self-assembled molecules (SAMs), widely used in perovskite solar cells (PSCs), should exhibit enhanced performance to support the ongoing advancement of perovskite photovoltaics. We designed diradical SAMs through a coplanar-conjugation of donor-acceptor strategy to facilitate hole transport across the SAMs. The diradical SAMs exhibited high photothermal and electrochemical stability, as well as improved assembly uniformity and large-area solution processability attributed to molecular steric hindrance design. An advanced scanning electrochemical cell microscopy-thin-layer cyclic voltammetry technique was used to accurately determine the carrier transfer rate, stability, and assembly properties of SAMs. Ultimately, the efficiencies of PSCs exceeded 26.3%, mini-modules (10.05 cm 2 ) reached 23.6%, and perovskite-silicon tandem devices (1 cm 2 ) surpassed 34.2%. PSCs maintained > 97% after 2000 hours tracking at 45°C.
GPT-4o mini: Non-social science research article
Rapid polygenic adaptation in a wild population of ash trees under a novel fungal epidemic
Carey L. Metheringham, William J. Plumb, William R. M. Flynn, Jonathan J. Stocks, Laura J. Kelly, Miguel Nemesio Gorriz, Stuart W. D. Grieve, Justin Moat, Emily R. Lines, Richard J. A. Buggs, Richard A. Nichols
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Rapid evolution through small shifts in allele frequencies at thousands of loci is a long-standing neo-Darwinian prediction but is hard to characterize in the wild. European ash tree ( Fraxinus excelsior ) populations have recently come under strong selection by the invasive fungal pathogen Hymenoscyphus fraxineus . Using genomic prediction models based on field trial phenotypes and 7985 loci, we show a shift in genomically estimated breeding values in an ancient woodland, between adult trees established before the epidemic started and juvenile trees established since. Using simulations, we estimate that natural selection has eliminated 31% of the juvenile population. Thus, we document a highly polygenic heritable microevolutionary adaptive change over a single generation in the wild.
GPT-4o mini: Non-social science research article
Evidence for Hadean mafic intrusions in the Nuvvuagittuq Greenstone Belt, Canada
C. Sole, J. O’Neil, H. Rizo, J.-L. Paquette, D. Benn, J. Plakholm
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Many questions remain regarding Earth’s earliest crust owing to the rarity of Hadean (>4.03 billion-year-old) rocks and minerals. The Nuvvuagittuq Greenstone Belt (NGB) in Canada may be the only known remnant of Hadean crust, although its age is debated, ranging from ≄3.75 to 4.3 billion years old. Mafic intrusions within this belt were specifically sampled and analyzed to investigate the timing of their magmatic differentiation. Correlations between samarium/neodymium (Sm/Nd) and 143 Nd/ 144 Nd and 142 Nd/ 144 Nd ratios correspond to ages of 4157 ± 174 and 4196 − 81 + 53 million years for the long-lived 147 Sm- 143 Nd and the short-lived 146 Sm- 142 Nd systems, respectively. The age agreement between both extant and extinct radiogenic systems, in rocks related through igneous fractionation, is compelling evidence for preservation of Hadean rocks in the NGB, opening a rare window into Earth’s earliest times.
GPT-4o mini: Non-social science research article
Spontaneous formation of urea from carbon dioxide and ammonia in aqueous droplets
Mercede Azizbaig Mohajer, Pallab Basuri, Andrei Evdokimov, Grégory David, Daniel Zindel, Evangelos Miliordos, Ruth Signorell
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Urea is a key molecule in the search for the origin of life and a basic chemical produced in large quantities by industry. Its formation from ammonia and carbon dioxide requires either high pressures and temperatures or, under milder conditions, catalysts or additional reagents. In this study, we observed the spontaneous formation of urea under ambient conditions from ammonia and carbon dioxide in the surface layer of aqueous droplets. Single, optically trapped droplets were probed by using Raman bands as markers. We found the surface layer to act like a microscopic flow reactor, with chemical gradients providing access to unconventional reaction pathways. This observation revealed a general mechanistic scheme for distinctive droplet chemistry. Interfacial chemistry is a possible nonenergetic route for urea formation under prebiotic conditions.
GPT-4o mini: Non-social science research article
Structural basis of BAX pore formation
Ying Zhang, Lu Tian, Gaoxingyu Huang, Xiaofei Ge, Fang Kong, Pengqi Wang, Yige Xu, Yigong Shi
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During apoptosis, cytosolic BAX monomers are translocated to the mitochondria to permeabilize the outer membrane. Here, we identified a dimer of BAX dimers as the basic repeating unit of its various oligomeric forms: arcs, lines, and rings. Cryo–electron microscopy structure of the BAX repeating unit at 3.2-angstrom resolution revealed the interactions within and between dimers. End-to-end stacking of the repeating units through the protruding α9 pairs yielded lines, arcs, polygons, and rings. We structurally characterized the tetragon, pentagon, hexagon, and heptagon, which comprise 16, 20, 24, and 28 BAX protomers, respectively. Missense mutations at the BAX inter-protomer interface damage pore formation and cripple its proapoptotic function. The assembly principle of the various BAX oligomers reported here provides the structural basis of membrane permeabilization by BAX.
GPT-4o mini: Non-social science research article
Migrating shallow slow slip on the Nankai Trough megathrust captured by borehole observatories
Joshua R. Edgington, Demian M. Saffer, Charles A. Williams
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Patterns of strain accumulation and release offshore in subduction zones are directly linked to the potential for shallow coseismic slip and tsunamigenesis, but these patterns remain elusive. In this work, we analyze formation pore pressure records from three offshore borehole observatories at the Nankai subduction zone, Honshu, Japan, to capture detailed slip-time histories of two slow slip events (SSEs) along the outermost reaches of the plate boundary. Slip initiates ~30 kilometers landward of the trench; migrates seaward at 1 to 2 kilometers per day to within a few kilometers of, and possibly breaching, the trench; and coincides with the onset and migration of tremor and/or very-low-frequency earthquakes. The SSE source region lies in a zone of high pore fluid pressure and low stress, which provides clear observational evidence linking these factors to shallow slow earthquakes.
GPT-4o mini: Non-social science research article
Carbonyl-to-sulfur swap enabled by sequential double carbon-carbon bond activation
Zining Zhang, Guangbin Dong
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In drug development, replacement of a skeletal carbon with a sulfur atom can result in analogs of bioactive compounds with improved properties. Currently, the sulfur analogs are almost exclusively prepared by de novo synthesis; the existing approach to swap carbon with sulfur is inefficient and involves stoichiometric mercury reagents. In this study, we report a two-step carbonyl-to-sulfur (CO-to-S) atom swap approach, enabled by a rationally designed N â€Č-alkyl-hydrazonamide (NAHA) reagent that promotes forming pre-aromatic intermediates twice sequentially by different mechanisms, thereby achieving homolytic cleavage of both α-C−C bonds of the ketone substrates. A Ts−S−Ts (Ts, p -toluenesulfonyl) reagent mediates this process through successive intermolecular and intramolecular alkyl radical trapping by the central sulfur. This method shows a broad substrate scope and excellent chemoselectivity, providing a streamlined route to sulfur-containing scaffolds from readily available ketones.
GPT-4o mini: Non-social science research article
Bespoke plant glycoconjugates for gut microbiota–mediated drug targeting
Wei Jen Ma, Changqing Wang, Jagatheeswaran Kothandapani, Matthew Luzentales-Simpson, Susan C. Menzies, Danisa M. Bescucci, Máximo E. Lange, Alexander S. C. Fraser, Jenny F. Gusse, Kathaleen E. House, Paul E. Moote, Xiaohui Xing, Julie M. Grondin, Benjamin Wei‐Qiang Hui, Sandra T. Clarke, Tara G. Shelton, Natasha Haskey, Deanna L. Gibson, Eric C. Martens, D. Wade Abbott, G. Douglas Inglis, Laura M. Sly, Harry Brumer
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The gut microbiota of mammals possess distinctive metabolic pathways with untapped therapeutic potential. Using molecular insights into dietary fiber metabolism by the human gut microbiota, we designed a targeted drug delivery system, called GlycoCaging, that is based on bespoke glycoconjugates of a complex plant oligosaccharide. GlycoCaging of exemplar anti-inflammatory drugs enabled release of active molecules triggered by specific glycosidases of autochthonous gut bacteria. GlycoCaging ensured that drug efficacy was potentiated, and off-target effects were eliminated in murine models of inflammatory bowel disease. Biochemical and metagenomic analyses of gut microbiota of individual humans confirmed the broad applicability of this strategy.
Science abstract < 200 char.: Not a research article
In Science Journals
Mark S. Aldenderfer, Sacha Vignieri, Corinne Simonti, Phil Szuromi, Yury Suleymanov, Angela Hessler, Jake S. Yeston, Courtney Malo, Jesse Smith, Peter Stern, Stella M. Hurtley, Di Jiang, Marc S. Lavine, Caroline Ash, Leslie Ferrarelli, Christiana N. Fogg
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
Now you see me, now you don’t
Matthew D. Shawkey
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Nanostructured reflecting plates in squid cells enable a rapid switch between colored and near-transparent states
Science abstract < 200 char.: Not a research article
Producing hunger On Hunger Dana Simmons University of California Press, 2025. 234 pp.
Laura Stark
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A scholar confronts how powerful groups use food as a means of control
Science abstract < 200 char.: Not a research article
In Other Journals
Bianca Lopez, Keith T. Smith, Sacha Vignieri, Stella M. Hurtley, Phil Szuromi, Ekeoma Uzogara, Jesse Smith
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
The power of reinvention
IvĂĄn M. Moya
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Science abstract < 200 char.: Not a research article
Facing life’s wild unknowns Meltdown: The Making and Breaking of a Field Scientist Sarah Boon University of Alberta Press, 2025. 312 pp.
Anna Farro Henderson
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A field scientist candidly reflects on navigating personal and institutional challenges
Science abstract < 200 char.: Not a research article
Without a lifeline
Catherine Offord
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The United States reneged on its foreign aid commitments. Nepal’s malnourished children and their families are paying the price
Science abstract < 200 char.: Not a research article
Order to restore NIH grants heartens scientists
Sara Reardon
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Federal judge decries NIH’s rationale for killing blacklisted grants as capricious and arbitrary
Science abstract < 200 char.: Not a research article
Genomic insights into social life in Neolithic Anatolia
Benjamin S. Arbuckle
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Matriarchs and foragers emerge as important players in early farming villages
Science abstract < 200 char.: Not a research article
National Academies adopts new business model amid financial storm
Jeffrey Mervis
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Realignment of major program units aims to improve efficiency and make up for loss of federal contracts
Science abstract < 200 char.: Not a research article
Where slow and large earthquakes meet
Kazushige Obara
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Adjacent slow slip events affect megathrust earthquakes
Science abstract < 200 char.: Not a research article
Tumors may get energy boost from nerve cells’ mitochondria
Mitch Leslie
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Study shows the organelles traveling through “bridges” into nearby cancer cells
Science abstract < 200 char.: Not a research article
A caged drug enables precision delivery
Yuhao Xie, Zhe-Sheng Chen
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“GlycoCaging” uses gut bacteria to activate drugs for inflammatory bowel disease
Science abstract < 200 char.: Not a research article
Japan wires up offshore trenches to warn of ruptures
Paul Voosen
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Seafloor monitoring is revealing how “slow slip” earthquakes can lead to big ones
Science abstract < 200 char.: Not a research article
U.S. researchers speak up in local newspapers
Katie Langin
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Through two grassroots efforts, approximately 200 op-eds showcasing federally funded science have been published across the country
Science abstract < 200 char.: Not a research article
Climate adaptation finance: From paper commitments to climate risk reduction
Jasper Verschuur, Nicola Ranger, Jim. W. Hall
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Science can help to target climate finance at better-quality adaptation
Female lineages and changing kinship patterns in Neolithic ÇatalhöyĂŒk
Eren YĂŒncĂŒ, Ayça KĂŒĂ§ĂŒkakdağ Doğu, Damla Kaptan, Muhammed Sıddık Kılıç, Camilla Mazzucato, Merve N. GĂŒler, Elifnaz Eker, BĂŒĆŸra Katırcıoğlu, Maciej ChyleƄski, Kıvılcım Baßak Vural, Ekin Sağlıcan, Gözde Atağ, Defne Bozkurt, Jessica Pearson, Arda Sevkar, N. Ezgi Altınıßık, Marco Milella, Cansu Karamurat, ƞevval AktĂŒrk, Emre Deniz Yurttaß, Nisan Yıldız, Dilek Koptekin, Sevgi Yorulmaz, Duygu Deniz Kazancı, Ayça Aydoğan, Kanat GĂŒrĂŒn, Eline M.J. Schotsmans, Jana Anvari, Eva Rosenstock, Jennifer Byrnes, Peter F. Biehl, David Orton, Vendela Kempe Lagerholm, Hasan Can Gemici, Milena Vasic, Arkadiusz Marciniak, Çiğdem Atakuman, Yılmaz Selim Erdal, Emrah Kırdök, Marin Pilloud, Clark Spencer Larsen, Scott D. Haddow, Anders Götherström, Christopher J. KnĂŒsel, FĂŒsun Özer, Ian Hodder, Mehmet Somel
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Combining 131 paleogenomes with bioarchaeological and archaeological data, we studied social organization and gendered practices in ÇatalhöyĂŒk East Mound (7100 to 5950 BCE), a major Neolithic settlement in Central Anatolia. In early ÇatalhöyĂŒk, burials in the same building were frequently close genetic relatives, suggesting that houses were used by biological family members. In later periods, however, individuals buried in the same building were often genetically unrelated, despite sharing similar diets. We found no indication of sex-biased mobility into ÇatalhöyĂŒk. Meanwhile, in all periods, within-building genetic connections were predominantly maternal rather than paternal. Burials of female subadults also received a higher frequency of gifts than male subadults. Our results reveal how kinship practices changed while specific practices prioritizing female lines persisted for 1000 years at Neolithic ÇatalhöyĂŒk.
Ten times faster is not 10 times better
Alondra Nelson
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As the Trump administration systematically defunds the American research ecosystem, while disingenuously promising a return to so-called “gold standard science,” hope can be drawn from the new bipartisan initiative from Senators Martin Heinrich (Democrat, New Mexico) and Michael Rounds (Republican, South Dakota). Their American Science Acceleration Project (ASAP) seeks to make science in the United States “ten times faster by 2030” through five pillars: data, computing, artificial intelligence (AI), collaboration, and process improvement. But simply accelerating will exacerbate historical weaknesses in our innovation system and reproduce the damaging Silicon Valley ethos of “move fast and break things.” Faster is not necessarily better when it comes to innovation and discovery. Supercharging a research ecosystem that already struggles with accessibility and public trust risks more than it achieves.

Science Advances

GPT-4o mini: Non-social science research article
Dorsal raphe nucleus controls motivation-state transitions in monkeys
Luke Priestley, Mark Chiew, Mo Shahdloo, Ali Mahmoodi, Xinghao Cheng, Robin Cleveland, Matthew Rushworth, Nima Khalighinejad
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The dorsal raphe nucleus (DRN) is an important source of serotonin in the brain, but fundamental aspects of its function remain elusive. Here, we present a combination of minimally invasive recording and disruption studies to show that DRN brings about changes in motivation states. We use recently developed methods for identifying temporal patterns in behavior to show that monkeys change their motivation depending on the availability of rewards in the environment. Distinctive patterns of DRN activity occur when monkeys transition between a high-motivation state occupied when rewards are abundant, to a low-motivation state engendered by reward scarcity. Disrupting DRN diminishes sensitivity to the reward environment and perturbs transitions in motivational states.
GPT-4o mini: Non-social science research article
Smart ultra-long-lasting sequentially triggerable and artfully implantable nozzle system for on-demand drug delivery for chronotherapy
Qi Zeng, Yusheng Gong, Wenhao Jiao, Jiarong Xu, Xiuli Chen, Rengui Xu, Yuan Liu, Xinting Liang, Guanyue Li, Jiajing Liu, Linxi He, Wenhao Li, Xiaoxia Zhang, Xiaoyuan Chen, Wei Chen
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Conventional drug delivery methods for chronic disease often suffer from low potency and poor patient compliance, while current advanced devices face limitations because of bulkiness, frequent implantation needs, inflammation risk, and lack of precise control. To overcome these challenges, we developed the SUSTAIN—a smart, ultra-long-lasting, sequentially triggerable, and artfully implantable nozzle system. The SUSTAIN integrates an osmotic pressure–triggered module, an airflow-generated T-pipe (AGT), and a drug infusion pump (DIP) for controlled subcutaneous drug release. The AGT enables tunable dosing by varying NaHCO 3 /KH 2 PO 4 powder amounts, while shear thinning of the ÎČ-cyclodextrin/Pluronic F-127 hydrogel in the DIP ensures sustained drug infusion. In vivo studies show that the SUSTAIN delivers at least four doses of levothyroxine sodium over 10 days and three doses of semaglutide over 42 days, maintaining effective blood drug levels with minimal invasiveness. This system presents a highly promising solution for improving therapeutic outcomes and convenience in chronic disease management.
GPT-4o mini: Non-social science research article
Self-assembling dendrimer nanodrug formulations for decreased hERG-related toxicity and enhanced therapeutic efficacy
Xi Liu, Dinesh Dhumal, Patricia Santofimia-Castaño, Juan Liu, Marion Casanova, Alicia Comino Garcia-Muñoz, Teodora-Adriana Perles-Barbacaru, Abdechakour Elkihel, Wenzheng Zhang, Tom Roussel, Christina Galanakou, Jing Wu, Eleni Zerva, Nelson Dusetti, Yi Xia, Xing-Jie Liang, AngÚle Viola, Juan L. Iovanna, Ling Peng
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Cardiotoxicity, especially human ether-a-go-go–related gene (hERG)–related toxicity, is a leading cause of drug failure or market withdrawal. Reducing hERG binding to obviate potential cardiac toxicity is crucial. Nanotechnology has been applied to drug delivery for reducing drug toxicity and improving efficacy, but few studies have addressed hERG-related cardiotoxicity. We report the use of self-assembling dendrimer nanosystems for drug formulation and delivery, which effectively reduced hERG binding and associated toxicity while promoting therapeutic efficacy. Specifically, these dendrimer nanosystems efficiently encapsulated the antimalarial drug chloroquine, the anticancer agent doxorubicin, and the NUPR1 inhibitor ZZW115, all three having high affinity to hERG channels. These nanoformulations showed three- to eightfold reduced hERG binding affinity, which, in animal models, translated to abolished toxicity. These nanodrugs exhibited prolonged circulation, leading to enhanced accumulation at disease sites and improved treatment outcomes. This study highlights the potential of nanotechnology to reduce hERG binding and related toxicity while improving drug efficacy, offering valuable perspectives for drug development.
GPT-4o mini: Non-social science research article
Widespread presence of bone marrow–like hematopoietic stem cell niche in invertebrate skeletons
Shanshan Lian, Naina Hu, Xiaomei Chen, Xiaoting Dai, Xuan Zhu, Runyu Qiao, Sinuo Liu, Yuan Lu, Fengmei Zhang, Fengzhi Sun, Zhongqi Pu, Zujing Yang, Runjia Xu, Hao Wang, Liang Zhao, Qiang Xing, Shoujie Li, Wei Wang, Bo Dong, Lingling Zhang, Jingjie Hu, Jing Wang, Zhenmin Bao, Shi Wang
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Skeletal harboring of hematopoietic stem cells (HSCs) is generally considered as vertebrate-specific innovation during water-to-land transition. However, this long-standing view has not been rigorously evaluated as hematopoietic sites remain poorly understood in most invertebrate groups. We report, to our knowledge, the first discovery of abundant HSCs in adult mollusk shells, an invertebrate hematopoietic niche resembling vertebrate bone marrow (BM). Cell-lineage analysis and functional assays reveal the developmental origin of HSCs during larval shell formation and their participation in hemocyte-mediated shell regeneration and soft-body blood supply. Widespread skeleton-related HSC-like cells are found in diverse invertebrate groups and bony fish group, suggesting skeletons as a universal niche for animal HSCs and HSC-skeleton association preceding vertebrate water-to-land transition. Comparison of invertebrate and vertebrate skeletal HSCs enables the macroevolutionary profiling of a core-set of animal HSC regulators. Our findings would boost fundamental paradigm shifts for hematopoiesis and stem cell research in invertebrates and provide the redefined understanding of vertebrate BM evolution and water-to-land transition.
GPT-4o mini: Non-social science research article
Autonomous chemo-metabolic construction of anisotropic cell-in-shell nanobiohybrids in enzyme-powered cell microrobots
Nayoung Kim, Sang Yeong Han, Hyeong Bin Rheem, Hojae Lee, Insung S. Choi
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Living organisms use intricate strategies to adapt and survive in response to potentially lethal environment changes. Inspired by cryptobiosis in nature, researchers have pioneered approaches to create cell-in-shell nanobiohybrids, aiming to endow cells with enhanced protection and exogenous functions. Yet, these methods still lack the biological autonomy intrinsic to natural cellular responses. Here, we present an innovative chemo-metabolically coupled strategy for the autonomous construction of cell-in-shell structures in cell growth medium. Our system harnesses ethanol fermentation by Saccharomyces cerevisiae , chemically coupled with an enzymatic cascade involving alcohol oxidase and horseradish peroxidase, to drive the nanoshell formation of polydopamine. The integration of autonomous shell formation with cellular proliferation produces anisotropic cell-in-shell structures, which can serve as enzyme-powered cell microrobots, upon conjugation with urease. Our autonomous system enables the creation of cell-in-shell nanobiohybrids with dynamic and adaptive environmental interactions, paving the way for transformative applications in synthetic biology, such as artificial cells, as well as advancements in cell-based therapies.
GPT-4o mini: Non-social science research article
Cardiomyocyte-derived YOD1 promotes pathological cardiac hypertrophy by deubiquitinating and stabilizing STAT3
Bozhi Ye, Wante Lin, Yucheng Jiang, Zhaozheng Zheng, Yanhong Jin, Diyun Xu, Yingjie Liao, Zhihan Jia, Jiaji Chen, Gaojun Wu, Peiren Shan, Guang Liang
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Identifying previously unknown targets for pathological cardiac hypertrophy and understanding its mechanisms are crucial. Here, we observed that the deubiquitinating enzyme YOD1 was moderately elevated in human hypertrophic myocardium and mouse models. Cardiomyocyte-specific knockout of YOD1 reduced Ang II– and TAC-induced cardiac hypertrophy. Subsequently, we used multiple proteomic analyses to identify and confirm STAT3 as a substrate protein for YOD1. Mechanistically, our findings revealed that the C155 site of YOD1 removes K48-linked ubiquitin chains from K97 on STAT3, stabilizing STAT3 levels and enhancing its nuclear translocation in cardiomyocytes under Ang II stimulation. Notably, inhibiting STAT3 reversed the antihypertrophic effects of YOD1 deficiency in Ang II–challenged mice. In addition, pharmacological inhibition of YOD1 mitigated Ang II–induced pathological ventricular remodeling in mice. This study clarifies the role of YOD1 and introduces a previously unidentified YOD1-STAT3 axis in regulating pathological cardiac hypertrophy, providing valuable insights for drug development targeting this condition.
GPT-4o mini: Non-social science research article
PET-based immunomapping of intratumoral CD4 + cells to monitor acquired resistance to checkpoint inhibitors
Stefania Pezzana, Simone Blaess, Bjoern Traenkle, Anna Schaefer, Lara Ruoff, Bredi Tako, Salvador Castaneda Vega, Philipp D. Kaiser, Teresa Wagner, Irene Gonzalez-Menendez, Leticia Quintanilla-Martinez, Alexander Rochwarger, Christian M. SchĂŒrch, Simon Riel, Martin Schaller, Evelien A. J. van Genugten, Iris A. E. van der Hoorn, Mark A. J. Gorris, Megan Steinvoort, Eva Peeters, I. Jolanda M. de Vries, Michel M. van den Heuvel, Erik H. J. G. Aarntzen, Andreas Maurer, Ulrich Rothbauer, Bernd J. Pichler, Manfred Kneilling, Dominik Sonanini
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CD4 + T cells are crucial in shaping response and resistance to immunotherapy. To enhance our understanding of their multifaceted functions, we developed copper-64–radiolabeled nanobodies targeting the human CD4 receptor ( 64 Cu-CD4-Nb1) for positron emission tomography (PET). In human CD4-receptor knock-in mice, 64 Cu-CD4-Nb1 specifically accumulated in different orthotopic tumors, correlating with histological CD4 + cell densities. Based on intratumoral CD4 + cell distribution patterns within the core and periphery, we distinguished responders to combined αPD-1/4-1BB antibodies early on-treatment. CD4-PET identified resistance to αPD-1 monotherapy, which was mitigated by adding regulatory T cell–depleting α4-1BB antibodies. Patients with early-stage non–small cell lung cancer who relapsed after neoadjuvant αPD-L1 therapy revealed low CD4 + T cell densities in the tumor core. In human and mouse tumor tissues, regulatory T cells correlated with CD4 + cell densities. Thus, visualizing the spatial distribution patterns of CD4 + cells by PET offers mechanistic insights into CD4-mediated therapy efficacy, with great potential for guiding combinatorial immunotherapies in patients with cancer.
GPT-4o mini: Non-social science research article
Lysosomal zinc nanomodulation blocks macrophage pyroptosis for counteracting atherosclerosis progression
Ruizhi Hu, Junchang Qin, Wei Feng, Xinran Song, Hui Huang, Chen Dai, Bo Zhang, Yu Chen
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Macrophage pyroptosis has been identified as a critical pathological mechanism in inflammation-related atherosclerosis (AS). In this work, we have demonstrated that Zn 2+ features the strongest anti-inflammatory performance by screening 10 representative metal ions, and the MTC1 agonists can trigger lysosomal Zn 2+ release and inhibit pyroptosis in macrophages. Based on these findings, we further engineered a mucolipin TRP channel 1 (MTC1)–related therapeutic nanoplatform for endogenously triggering lysosomal zinc release to curb inflammation and block macrophage pyroptosis. This nanoplatform consists of mesoporous silica nanoparticles to deliver MTC1 agonists and carbon nanodots, which could synergistically exert antiatherosclerotic effect by scavenging toxic reactive oxygen species, inhibiting macrophage pyroptosis, modulating macrophage transition, and rebuilding atherosclerotic immune microenvironment. These findings demonstrate that macrophage pyroptosis can be efficiently blocked via leveraging self-lysosomal zinc pool, which provides the paradigm of lysosomal zinc modulation-involved nanotherapeutics for managing other inflammatory diseases.
GPT-4o mini: Non-social science research article
Reorientation and despinning of 4 Vesta formed the Divalia Fossae
Hiu Ching Jupiter Cheng, Christian Klimczak, Isamu Matsuyama
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Vesta, the only differentiated rocky protoplanet explored by a spacecraft, offers insight into early planetary formation. The Divalia Fossae, surface troughs comparable in size to the Grand Canyon, encircle two-thirds of the equator. Two giant impacts reshaped the southern hemisphere, where an older basin is partially superposed by the younger Rheasilvia basin. The origin of the Divalia Fossae is widely accepted as directly linked to the Rheasilvia impact, either by tectonics caused immediately by the impact, up-spinning, or secondary cratering. We present several geologic constraints that support a tectonic origin of the troughs due to the adjustment of Vesta’s spin axis to a geoid changed by both large impacts. The best fit to Vesta’s gravitational field corresponds to a spin axis reorientation of 3° that, when coupled with despinning, induces a stress state that predicts Divalia Fossae’s established location, fracture type, and orientation. These insights underline the importance of tectonic processes in the early evolution of protoplanets.
GPT-4o mini: Non-social science research article
The role of magma differentiation in optimizing the fluid-assisted extraction of copper to generate large porphyry-type deposits
Shunda Yuan, Anthony E. Williams-Jones, Robert J. Bodnar, Panlao Zhao, ZoltĂĄn Zajacz, I-Ming Chou, Jingwen Mao
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Porphyry copper deposits (PCDs) are the main source of copper globally, with the metals transported in and deposited from aqueous magmatic fluids. Processes that define the volume of magma and concentration of copper in the magma required to form PCDs, however, are not well understood. Here, we present the results of quantitative modeling of the behavior of Cu and Cl during magma evolution in the upper crust. We show that fractional crystallization is the most important process promoting efficient Cu extraction, and that high concentrations of Cu in the ore-forming hydrothermal fluids can be reached with moderate Cl concentrations. Unusually high concentrations of Cl and Cu in the magma and large magma volumes are not required. Arc magmas of modest volume (<10 3 km 3 ) and modest initial Cu and Cl concentrations can generate large PCDs, if a sufficient mass of magmatic fluid is exsolved at an advanced stage of crystallization.
GPT-4o mini: Non-social science research article
Insertion of anthranilyl unit into inert amides: A facile route to oligoamides and cyclic peptides
Daoshun Wu, Kaili Xie, Yunfang Sun, Li Cao, Fang Liu, Xiaobo Sun, Kendall N. Houk, Lei Wang
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Manipulation of polar functional groups to extend the druggability and developability space is an important approach in the current field of drug discovery. Here, we report an editing method that enables the direct insertion of anthranilyl units into inert amides to form versatile oligoamides and cyclic peptides under exceptionally mild reaction conditions. We showcase a diverse array of pharmaceuticals, natural products, and bioactive molecules involving the mentioned scaffold insertion. The synthesis of the secondary metabolites from marine-derived fungi, the expedited construction of bioactive molecules, and the assembly of functionalized peptide macrocycles through iterative insertions highlight the synthetic utility of this method. Computational tools and experimental measurements indicate that a hydrogen bond network formed by reacting and catalytic amide enables the insertion of the anthranilyl unit into a C─N bond.
GPT-4o mini: Non-social science research article
The future of baleen whales: Recoveries, environmental constraints, and climate change
Joshua D. Stewart, M. Tim Tinker, Robert L. Brownell, Andrew J. Read
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Most baleen whales were severely overexploited during the past century, but many populations have received near-complete protection from exploitation for more than a half-century. Some of these populations have made remarkable recoveries and are now approaching pre-exploitation levels of abundance. Contrary to expectations of baleen whales making minor oscillations around equilibrium abundances, several populations that have made the strongest recoveries have experienced major mortality events. We review examples from the literature showing increasing demographic variability in recovering populations of baleen whales and present a simulation study on the expected response of recovered versus depleted whale population to environmental variability and climate impacts. We propose that baleen whales are more sensitive to environmental variability than previously recognized; that major demographic fluctuations will become the norm as baleen whales recover; and that climate-driven disruptions to whale population dynamics will be most dramatic in populations with the lowest rates of anthropogenic mortality.
GPT-4o mini: Non-social science research article
High-resolution multiomics links nutrients and mixotrophy to toxicity in a harmful bloom of the haptophyte Chrysochromulina leadbeateri
Antonia Otte, Sylke Wohlrab, Franco Moritz, Constanze MĂŒller, Jan JanouĆĄkovec, Jan MichĂĄlek, Allan Cembella, Daniela Voss, Xinhui Wang, Jan Tebben, Thomas Ostenfeld Larsen, Bente Edvardsen, Philippe Schmitt-Kopplin, Uwe John
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Harmful algal blooms (HABs) of the toxigenic haptophyte Chrysochromulina are known to cause fish mortalities and collateral ecosystem damage. The ichthyotoxic mechanisms are poorly understood but likely dependent on toxigenesis by polyketide synthases (PKSs). We hypothesize that induction of PKS activity facilitates mixotrophic behavior during nutrient-depleted bloom conditions. To identify potential in situ stimuli for growth, toxigenicity, and bloom persistence, we compared environmental factors and biological processes identified by metaomics to Chrysochromulina leadbeateri HABs between two fjords in northern Norway. We identified the polyketide ichthyotoxin leadbeaterin-1 from the C. leadbeateri bloom and found potentially associated candidate PKS genes of which most were higher expressed at bloom stations. A relative depletion of inorganic nitrogen and phosphate during the bloom was correlated with higher expression of genes involved in endocytosis, autophagy, and lysosomal activity. Mixotrophy is evidently a compensatory nutritional strategy coupled to induction of toxigenesis and other metabolomic processes as biotic factors linked to Chrysochromulina bloom dynamics.
GPT-4o mini: Non-social science research article
Light field–controlled PHz currents in intrinsic metals
Beatrix Fehér, Våclav Hanus, Weiwei Li, Zsuzsanna Påpa, Judit Budai, Pallabi Paul, Adriana Szeghalmi, Zilong Wang, Matthias F. Kling, Péter Dombi
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Oriented electric currents in metals are routinely driven by applying an external electric potential. Although the response of electrons to the external electric fields occurs within attoseconds, conventional electronics do not use this speed potential. Ultrashort laser pulses with controlled shapes of electric fields that switch direction at petahertz frequencies open perspectives for driving currents in metals. Light field–driven currents were demonstrated in various media including dielectrics, semiconductors, and topological insulators. Now, our research question is whether we can drive and control orders of magnitude more charge carriers in metals enabling ultrafast switching with practically low-energy, picojoule-level pulses. Here, we demonstrate the interaction of light with nanometer-thick metallic layers, which leads to a generation of light field–controlled electric currents. We show that the implantation of metallic layers into a dielectric matrix leads to up to 40 times increase of the sensitivity in contrast to a bare dielectric, decreasing the intensity threshold for lightwave electronics.
GPT-4o mini: Non-social science research article
In vitro and in vivo evaluation of chemically synthesized, receptor-biased interleukin-4 and photocaged variants
Mamiko Ninomiya, Cecilie Egholm, Daniel Breu, Onur Boyman, Jeffrey W. Bode
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Interleukin-4 (IL-4) plays a central role in type 2 immune responses. Despite its potential use for allergic and autoimmune diseases, its pleiotropic receptor binding complicates selective targeting of IL-4 signaling pathways. We developed a chemical synthesis of (i) IL-4 variants with atomically tailored side-chain modifications that deter specific receptor interactions and (ii) conditionally activatable IL-4 variants uncaged with 365-nanometer light. In primary cell studies, different variants elicited selective STAT5 or STAT6 phosphorylation in lymphocytes or neutrophils. In murine studies, photocaged IL-4 suppressed inflammation only upon UV irradiation, demonstrating precise on demand control. We accomplished the synthesis and folding of IL-4, a hydrophobic cytokine with three disulfide bonds, using the alpha-ketoacid–hydroxylamine (KAHA) ligation to assemble three segments. We introduced further conjugations, including PEGylation for half-life extension, through orthogonal ligations enabled by functionalized amino acid building blocks. This work highlights the flexibility of chemical protein synthesis to produce therapeutically valuable cytokines, including receptor-biased and spatiotemporally activatable IL-4 variants.
GPT-4o mini: Non-social science research article
State modulation in spatial networks with three interneuron subtypes
Madeline M. Parker, Jonathan E. Rubin, Chengcheng Huang
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Several inhibitory interneuron subtypes have been identified as critical in regulating sensory responses. However, the specific contribution of each interneuron subtype remains uncertain. In this work, we explore the contributions of cell type–specific activity and synaptic connections to the dynamics of a spatially organized spiking neuron network. We find that the firing rates of the somatostatin (SOM) interneurons align closely with the level of network synchrony irrespective of the target of modulatory input. Further analysis reveals that inhibition from SOM to parvalbumin interneurons must be limited to allow gradual transitions from asynchrony to synchrony and that the strength of recurrent excitation onto SOM neurons determines the level of synchrony achievable in the network. Our results are consistent with recent experimental findings on cell type–specific manipulations. Overall, our results highlight common dynamic regimes achieved across modulations of different cell populations and identify SOM cells as the main driver of network synchrony.
GPT-4o mini: Non-social science research article
Climate change redefines sea turtle hotspots: Vessel strike risks and gaps in protected areas
Edouard Duquesne, Denis Fournier
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Climate change is altering marine ecosystems, driving shifts in sea turtle distributions and challenging conservation efforts. Our study examines how climate change affects the global sea distribution of all seven sea turtle species, intersecting with marine protected areas (MPAs) and shipping corridors. Using species distribution models and environmental data from 2000 to 2024, we project sea turtle habitats under current conditions and three future climate scenarios (SSP1-2.6, SSP2-4.5, and SSP5-8.5) for 2050 and 2100. Our results show substantial habitat redistributions, with poleward shifts and contractions, particularly under the SSP5-8.5 scenario. Over 50% of sea turtle hotspots may disappear by 2050, with many new habitats in high shipping intensity areas. Alarmingly, only 23% of current hotspots are within MPAs, highlighting the need for adaptive conservation strategies.
GPT-4o mini: Non-social science research article
Clumped isotopes of methane trace bioenergetics in the environment
Jiarui Liu, Edward D. Young, André Pellerin, Jeanine L. Ash, Gerard T. Barrett, Xiahong Feng, Peter R. Girguis, Sebastian J. E. Krause, William D. Leavitt, Kyla Murphy, Qianhui Qin, Andreas Teske, David L. Valentine, Katey Walter Anthony, Tina Treude
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Methane is a major greenhouse gas and a key component of global biogeochemical cycles. Microbial methane often deviates from isotope and isotopolog equilibrium in surface environments but approaches equilibrium in deep subsurface sediments. The origin of this near-equilibrium isotopic signature in methane, whether directly produced by methanogens or achieved through anaerobic oxidation of methane (AOM), remains uncertain. Here, we show that, in the absence of AOM, microbial methane produced from deep-sea sediments exhibits isotopolog compositions approaching thermodynamic equilibrium due to energy limitation. In contrast, microbial methane from salt marsh and thermokarst lakes exhibits significant hydrogen and clumped isotopic disequilibrium due to high free-energy availability. We propose that clumped isotopologs of methane provide a proxy for characterizing the bioenergetics of environments for methane production. Together, these observations demonstrate methane clumped isotopes as a powerful tool to better understand the relation between methane metabolisms and the energy landscape in natural environments.
GPT-4o mini: Non-social science research article
Traversing the Kuroshio: Paleolithic migration across one of the world’s strongest ocean currents
Yu-Lin K. Chang, Yasumasa Miyazawa, Xinyu Guo, Sergey Varlamov, Haiyan Yang, Yousuke Kaifu
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The maritime migration to the South Ryukyu Islands of southwestern Japan, which occurred approximately 30,000 years ago, was one of the most difficult sea crossings accomplished by the Late Pleistocene Homo sapiens . This study performs numerical simulations to investigate the conditions that were needed to cross between Taiwan and Yonaguni Island, where one of the world’s strongest ocean currents, the Kuroshio, remains active. We combined simulations based on three ocean models with data from an actual experimental voyage conducted in 2019. The results showed that travel across this sea would have been possible on both the modern and Late Pleistocene oceans if a dugout canoe was used with a suitable departure place and paddling strategy. Recognizing the Kuroshio, paddling to counteract this current, and using high-level navigation were crucial to success. This suggests that the Paleolithic maritime expansion in the Western Pacific involved both advanced technologies and strategic challenges.
GPT-4o mini: Non-social science research article
External strain on the plasma membrane is relayed to the endoplasmic reticulum by membrane contact sites and alters cellular energetics
Ziming Chen, Peilin Chen, Jiayue Li, Euphemie Landao-Bassonga, John Papadimitriou, Junjie Gao, Delin Liu, Andrew Tai, Jinjin Ma, David Lloyd, Brendan F. Kennedy, Ming Hao Zheng
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Mechanotransduction is essential for living cells to adapt to their extracellular environment. However, it is unclear how the biophysical adaptation of intracellular organelles responds to mechanical stress or how these adaptive changes affect cellular homeostasis. Here, using the tendon cell as a mechanosensitive cell type within a bioreactor, we show that the tension of the plasma membrane (PM) and the endoplasmic reticulum (ER) adaptively increases in response to repetitive external stimuli. Depletion of stromal interaction molecule 1 (STIM1), the highest expressed PM-ER tether protein, interfered with mechanotransduction from the PM to the ER, and affected the ER tension. We found that an optimized mechanical strain increased ER tension in a homeostatic manner, but excessive strain resulted in ER expansion, as well as activating ER stress. Last, we showed that changes in ER tension were linked with ER-mitochondria interactions and associated with cellular energetics and function. Together, these findings identify a PM-ER mechanotransduction mechanism that dose-dependently regulates cellular metabolism.
GPT-4o mini: Non-social science research article
A reusable hydrogel biosensor array with electrically responsive hydrogel interfaces for noninvasive locating of perforating arteries
Ganguang Yang, Yuqi Qiu, Bo Pang, Wei Guo, Shaoyu Liu, Qingyang Zheng, Sen Zhou, Jia Tian, Wei Liu, Bin Xie, Tianzhao Bu, Changsheng Wu, Zhouping Yin, Yutian Liu, Hao Wu
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Achieving accurate locating of perforating arteries (PAs) has great clinical value in various biomedical applications, such as free flap transfer. However, the anatomical variability of these arteries presents a major challenge in PA locating, and existing methods have various disadvantages, limiting their applications. Here, we propose a reusable and flexible hydrogel biosensor array for noninvasive, precise, and efficient PA locating. Particularly, we develop electrically responsive hydrogels to establish rapidly detachable device/hydrogel interfaces, endowing the reusability of the biosensor array. Meanwhile, the adhesion of hydrogel/skin interfaces is also enhanced to facilitate high-fidelity signal acquisition. By analyzing the photoplethysmography (PPG) infrared (IR) signals, the biosensor array can accurately and responsively locate PAs across different types of free flaps in clinical cases, outperforming existing techniques. This biosensor array represents a promising platform for PA locating. The strategy of hydrogel interface design paves the way for the development of reusable flexible electronics in biomedical applications to avoid cross-infection and reduce device costs.
GPT-4o mini: Non-social science research article
Paleolithic seafaring in East Asia: An experimental test of the dugout canoe hypothesis
Yousuke Kaifu, Chih-Hsing Lin, Nobuyuki Ikeya, Masahisa Yamada, Akira Iwase, Yu-Lin K. Chang, Masahiro Uchida, Koji Hara, Kunihiro Amemiya, Yunkai Sung, Katsuaki Suzuki, Minoru Muramatsu, Michiko Tanaka, Sayaka Hanai, Toiora Hawira, Saki Uchida, Masaki Fujita, Yasumasa Miyazawa, Kumino Nakamura, Pi-Ling Wen, Akira Goto
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Archeological evidence indicates that full-scale expansion of Homo sapiens across the oceans began about 50,000 years ago in the Western Pacific, yet how this was achieved remains unclear. The Ryukyu Islands in southwestern Japan, where archaeological sites suddenly appeared 35,000 to 30,000 years ago, are of particular interest in this regard because of the apparent difficulty in crossing the surrounding waters. In this study, we test if a non-sailing dugout canoe can be produced with Upper Paleolithic tools, and if it can cross the 110-kilometer-wide strait at the western entrance of the Ryukyus, where one of the world’s strongest ocean currents intervenes. Our 7.5-meter-long dugout, manufactured with edge-ground stone axes, was speedy and durable enough to cross this strait. This supports the early development of functional boats, such as dugouts, while our experiment also highlighted that this type of sea travel was possible only for experienced paddlers with advanced navigational skills.
GPT-4o mini: Non-social science research article
Reconfigurable robust microrobot collectives with large force output enabled by gradient magnetic fields
Zichen Xu, Wei Ge, Qingsong Xu
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Robot collectives offer a promising solution for complex assignments that are nearly impossible for individual robots to execute. In microscopic scenarios, organizing microrobot collectives is now governed by agent-agent physical interactions. However, the existing methods are insufficient to produce robust connections and fail to tolerate harsh environments. We propose a strategy to efficiently program microrobots into reconfigurable robust collectives to operate in various dynamic environments. Magnetic collectives are produced to achieve reconfigurable pattern transformation with considerable structural enhancement via well-designed gradient magnetic fields. The strong gradient magnetic field–induced connections among individual microrobots enable a record-breaking 700-fold output force enhancement, and 0.2-gram microrobot collectives generate Newton-level output forces. The proposed reconfigurable microrobot collectives provide a stable and promising approach to executing droplet, fluid, and solid manipulations via powerful output forces. These results may have implications for further understanding of self-assembly, particle systems, microrobot collectives, smart dust, and related microscopic multiagent behaviors.
GPT-4o mini: Non-social science research article
Mechanochemical patterning localizes the organizer of a luminal epithelium
Sera L. Weevers, Alistair D. Falconer, Moritz Mercker, Hajar Sadeghi, David Rozema, Jaroslav Ferenc, Jean-Leon MaĂźtre, Albrecht Ott, Dietmar B. Oelz, Anna Marciniak-Czochra, Charisios D. Tsiairis
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The spontaneous emergence of tissue patterns is often attributed to biochemical reaction-diffusion systems. In Hydra tissue regeneration, the formation of a Wnt signaling center exemplifies this process. However, a strictly biochemical mechanism for self-organization in Hydra remains elusive. In this study, we investigated mechanical stimuli and identified a positive feedback loop between Wnt signaling and tissue stretching. We developed a mathematical model of mechanochemical pattern formation in a closed elastic shell, representing regenerating Hydra epithelial spheroids. Our model explains how mechanical forces drive axis formation and predict the organizer’s location under various perturbations. Validation by partially confining regenerating tissues showed that the organizer forms in regions with the greatest stretching potential. This work highlights a versatile mechanochemical mechanism for luminal epithelium patterning, which is relevant across various biological systems.
GPT-4o mini: Non-social science research article
Genomic evidence for fisheries-induced evolution in Eastern Baltic cod
Kwi Young Han, Reid S. Brennan, Christopher T. Monk, Sissel Jentoft, Cecilia Helmerson, Jan Dierking, Karin HĂŒssy, Érika Endo Kokubun, Janina Fuss, Ben Krause-Kyora, Tonny B. Thomsen, Benjamin D. Heredia, Thorsten B. H. Reusch
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Overfishing is one human-driven perturbation driving major evolutionary pressure on marine populations. Fishing is often highly selective for particular traits and elicits marked phenotypic changes, while the evolutionary basis of such trait change remains unresolved. Here, we used a unique time series of the overexploited Eastern Baltic cod ( Gadus morhua ) to investigate growth trends during 25 years of heavy fishing along with hypothesized genetic changes at the full genome level. A growth analysis demonstrated a 48% decrease in asymptotic body length from 1996 to 2019 while a genome-wide association analysis revealed outlier loci and gene candidates linked to growth performance. The contributing loci showed signals of directional selection with high autocovariance of allele frequency change and significant overlap with regions of high genetic differentiation. Our findings suggest a genomic basis of fisheries-driven growth impairment and underscore implications for conservation policy regarding the adaptive potential of marine populations.
GPT-4o mini: Non-social science research article
Discovery of an unconventional quantum echo by interference of Higgs coherence
Chuankun Huang, Martin Mootz, Liang Luo, Di Cheng, Avinash Khatri, Joong-Mok Park, Richard H. J. Kim, Yihua Qiang, Victor L. Quito, Yongxin Yao, Peter P. Orth, Ilias E. Perakis, Jigang Wang
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Detecting photon echoes from superconducting Higgs modes is challenging due to the necessity of preserving and retrieving phase coherence encoded in multiple Higgs and quasiparticle (QP) excitations. Here, we demonstrate the emergence of a Higgs echo in niobium superconductors. This approach disentangles unique quantum pathways involving the Higgs mode and QP excitations. Using Higgs echo spectroscopy, we also uncover unconventional echo formation caused by inhomogeneous broadening and “soft” QP bands, which dynamically evolve under terahertz (THz) driving. Specifically, THz pulse pairs modulate the superconducting gap, imprinting coherence and forming a temporal “Higgs grating.” This grating produces echoes with distinctive characteristics: (i) echo rephasing spectral peaks at superconducting gap frequencies, (ii) asymmetric echo formation delays unlike those observed in atoms or semiconductors, and (iii) negative-time echo signals stemming from Higgs-QP anharmonic interactions. Combined with advanced time-frequency analysis, these findings distinguish Higgs from QP responses and clarify their intricate interactions in THz-driven superconductivity.
GPT-4o mini: Non-social science research article
Ecological interactions and genomic innovation fueled the evolution of ray-finned fish endothermy
Fernando Melendez-Vazquez, Alexander G. Lucaci, Avery Selberg, Julien Clavel, Melissa Rincon-Sandoval, Aintzane Santaquiteria, William T. White, Danielle Drabeck, Giorgio Carnevale, Emanuell Duarte-Ribeiro, Masaki Miya, Mark W. Westneat, Carole C. Baldwin, Lily C. Hughes, Guillermo OrtĂ­, Sergei L. Kosakovsky Pond, Ricardo Betancur-R, Dahiana Arcila
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Endothermy has independently evolved in several vertebrate lineages but remains rare among fishes. Using an integrated approach combining phylogenomic and ecomorphological data for 1051 ray-finned fishes, a time-dependent evolutionary model, and comparative genomic analyses of 205 marine vertebrates, we show that ecological interactions with modern cetaceans coincided with the evolution of endothermy in ray-finned fishes during the Eocene-Miocene. This result is supported by evidence of temporal and geographical overlap between cetaceans and endothermic fish lineages in the fossil record, as well as correlations between cetacean diversification and the origin of endothermy in fishes. Phylogenetic comparative analyses identified correlations between endothermy, large body sizes, and specialized swimming modes while challenging diet specialization and depth range expansion hypotheses. Comparative genomic analyses identified several genes under selection in endothermic lineages, including carnmt1 (involved in fatty acid metabolism) and dcaf6 (associated with development). Our findings advance the understanding of how ecological interactions and genomic factors shape key adaptations.
GPT-4o mini: Non-social science research article
Stalling of the endometrial decidual reaction determines the recurrence risk of miscarriage
Joanne Muter, Chow-Seng Kong, Mireia Taus Nebot, Maria Tryfonos, Pavle Vrljicak, Paul J. Brighton, Danai B. Dimakou, Megan Vickers, Hiroyuki Yoshihara, Sascha Ott, Bee K. Tan, Phillip R. Bennett, Siobhan Quenby, Alex Richter, Hilde Van de Velde, Emma S. Lucas, Thomas M. Rawlings, Jan J. Brosens
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In every menstrual cycle, progesterone acting on estrogen-primed endometrium elicits an inflammatory decidual reaction, rendering it poised for embryo implantation and transformation into the decidua of pregnancy. Here, we show that the sequential functions of the decidual reaction—implantation and decidualization—pivot on the time-sensitive loss of progesterone-resistant DIO2 + stromal cells that form a specialized implantation niche and reciprocal expansion of progesterone-dependent PLA2G2A + predecidual cells. Simultaneously, uterine natural killer (uNK) cell proliferation results in the accumulation of immunotolerant subsets. Examination of endometrial biopsies from 924 women revealed that the recurrence risk of miscarriage closely aligns with the incidence of a weakened or stalled decidual reaction, more so than poor uNK cell expansion. Analysis of paired biopsies obtained in different cycles and modeling in assembloids intimated that prior miscarriages disrupt intercycle endometrial homeostasis and calibration of the decidual reaction. Our findings show that erosion of the decidual reaction following a miscarriage drives the recurrence risk irrespective of maternal age.
GPT-4o mini: Non-social science research article
Headward incision of large rivers in response to glacial sea level fall
Zhongping Lai, Yuexin Liu, Ziyuan Wu, Yantian Xu, Zibin Fang, David R. Montgomery
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Sea level change is an important forcing on lowland fluvial systems. Although its impact is suggested to extend up to hundreds of kilometers inland, this impact is often considered confined to deltaic regions. We present luminescence dating of cores from the Jianghan Plain in the middle Yangtze River that demonstrates the influence of the last glacially driven sea level fall extended over 1000-kilometers inland. Luminescence ages reveal a common sedimentary hiatus from ~26 to ~17 thousand years ago (ka), reflecting fluvial incision of >35 meters triggered by sea level fall. Subsequent rapid aggradation occurred within these incised valleys during deglaciation between ~17 and ~9 ka and then slowed down afterward. A further synthesis on global continental rivers shows that sea level change affects large, low-gradient lowland fluvial systems farther upstream than generally recognized, with postperturbation geomorphologic equilibrium reachable in timescales comparable to the length of Quaternary glacial cycles.
GPT-4o mini: Non-social science research article
Perineural immune environment of olfactory nerves is reshaped by neuroinflammatory drainage and connects to ethmoid bone marrow
Collin J. Laaker, Kristof G. Kovacs, Cameron M. Baenen, Martin Hsu, Jenna M. Port, Sophia M. Vrba, Mohan Kumar, Annika J. Hubacek, Melinda Herbath, Thanthrige Thiunuwan Priyathilaka, Matyas Sandor, Zsuzsanna Fabry
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Cerebrospinal fluid (CSF) contains inflammatory cues that enable peripheral immune surveillance of the central nervous system (CNS). While some cranial nerves allow for CSF efflux, the immune environment around CSF-interfacing cranial nerves during neuroinflammation is still poorly understood. Using a mouse model of multiple sclerosis [experimental autoimmune encephalomyelitis (EAE)] and CNS Mycobacterium tuberculosis infection (CNS-Mtb), we examined immune responses around olfactory nerve bundles near the cribriform plate, a key CSF efflux route. During neuroinflammation, we found increased perineural immune cells that had access to intracranial injected beads, dye, and bacteria. Additionally, we identified osseous channels connecting the environment surrounding olfactory nerves to bone marrow in the cribriform plate (cpBM). Notably, the cpBM undergoes myelopoiesis during EAE, has access to components of intracranial drainage, and is vulnerable to Mtb bacteria invasion during CNS-Mtb infection. Our findings improve the understanding of how the environments of CSF-interfacing cranial nerves and bone marrow are altered within the skull during neuroinflammatory disease.
The evolution of infant-directed communication: Comparing vocal input across all great apes
Franziska Wegdell, Caroline Fryns, Johanna Schick, Lara Nellissen, Marion Laporte, Martin Surbeck, Maria A. van Noordwijk, Shelly Masi, Birgit Hellwig, Erik P. Willems, Klaus ZuberbĂŒhler, Carel P. van Schaik, Sabine Stoll, Simon W. Townsend
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Human language is unique among communication systems since many elements are learned and transmitted across generations. Previous research suggests that this process is best predicted by infant-directed communication, i.e., a mode of communication directed by caregivers to children. Despite its importance for language, whether infant-directed communication is unique to humans or rooted more deeply in the primate lineage remains unclear. To assess this, we investigated directed and surrounding vocal communication in human infants and infants of wild nonhuman great apes. Our findings reveal that human infants receive dramatically more infant-directed communication than nonhuman great ape infants. These data suggest that the earliest hominins likely relied more on surrounding communication to become communicatively competent, while infant-directed vocal communication became considerably more prominent with human language.
Volatility-driven learning in human infants
Francesco Poli, Tommaso Ghilardi, Jana H. M. Bersee, Rogier B. Mars, Sabine Hunnius
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Adapting to change is a fundamental feature of human learning, yet its developmental origins remain elusive. We developed an experimental and computational approach to track infants’ adaptive learning processes via pupil size, an indicator of tonic and phasic noradrenergic activity. We found that 8-month-old infants’ tonic pupil size mirrored trial-by-trial fluctuations in environmental volatility, while phasic pupil responses revealed that infants used this information to dynamically optimize their learning. This adaptive strategy resulted in successful task performance, as evidenced by anticipatory looking toward correct target locations. The ability to estimate volatility varied significantly across infants, and these individual differences were related to infant temperament, indicating early links between cognitive adaptation and emotional responsivity. These findings demonstrate that infants actively adapt to environmental change, and that early differences in this capacity may have profound implications for long-term cognitive and psychosocial development.
Earliest evidence of rice cultivation in Remote Oceania: Ritual use by the first islanders in the Marianas 3500 years ago
Mike T. Carson, Weiwei Wang, Xiujia Huan, Siqi Dong, Hsiao-chun Hung, Zhenhua Deng
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Rice was a staple crop in the ancestral Austronesian regions of Taiwan and Island Southeast Asia, but it was unknown in any of the Pacific Islands at the time of European encounters, with the exception of the unique case of Guam and the Mariana Islands. Through multiple methodologies, including phytolith analysis, micro–computed tomography scanning, and thin-section petrography, this recent research confirms the presence of abundant rice husk and leaf phytoliths adhering to red-slipped pottery (“Marianas Red”) at the Ritidian Site Complex in Guam, dated by radiocarbon to 3500 to 3100 years ago. This study addresses the long-standing question of whether the first Pacific Islanders transported rice with them from the Philippines across 2300 kilometers of open sea, representing the longest known ocean voyage of the time. During this early period, rice was restricted to special ritual events in the Marianas. The early voyage apparently was planned with provisions of rice at 3500 years ago.
Unraveling human crowd dynamics through the foot tracking of pedestrians
Yi Ma, Zhipan Niu, Meng Shi, Wei Xie, Zuoan Hu, Yidong Wei, Tian Zeng, Eric Wai Ming Lee
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Movement of pedestrian crowds is ubiquitous in human society. However, it is unclear what dynamical regimes pedestrian crowds can exhibit at different crowd densities, how pedestrians move in these different dynamical regimes, and in which dynamical regime the movement synchronization of pedestrians is most likely to occur. Here, we conducted a unidirectional crowd movement experiment, in which we tracked the movement of pedestrian crowds through foot tracking. We find experimentally that pedestrian crowds can exhibit three distinct dynamical regimes (free regime, slow-moving regime, and jammed regime) depending on the crowd density. In the free regime, pedestrians’ movement is not constrained; in the slow-moving regime, pedestrians’ speed is constrained, but pedestrians’ movement direction in each step is not influenced; and in the jammed regime, both pedestrians’ speed and movement direction in each step are constrained. We also demonstrate that pedestrians are most likely to synchronize their movements spontaneously at the onset of jamming. Our findings provide important insights into crowd dynamics.