We checked 7 multidisciplinary journals on Friday, September 12, 2025 using the Crossref API. For the period September 05 to September 11, we retrieved 12 new paper(s) in 6 journal(s).

Nature

GPT-4o mini: Non-social science research article
Amplifying antigen-induced cellular responses with proximity labelling
Shuojun Li, Yinghui Men, Zihan Wang, Yingcheng Wu, Hao Sun, Mingyang Yin, Xinrui Fan, Guiyun Deng, Zhicheng Yang, Tiange Yang, Yudian Xiao, Hu Zhou, Guangchuan Wang, Jia Fan, Chenqi Xu, Qiang Gao, Shuo Han
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GPT-4o mini: Non-social science research article
Long-range PM2.5 pollution and health impacts from the 2023 Canadian wildfires
Qiang Zhang, Yuexuanzi Wang, Qingyang Xiao, Guannan Geng, Steven J. Davis, Xiaodong Liu, Jin Yang, Jiajun Liu, Wenyu Huang, Changpei He, Binhe Luo, Randall V. Martin, Michael Brauer, James T. Randerson, Kebin He
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GPT-4o mini: Non-social science research article
Programmable antisense oligomers for phage functional genomics
Milan Gerovac, Leandro Buhlmann, Yan Zhu, Svetlana Ðurica-Mitić, Valentin Rech, Samuel Carien, Tom GrĂ€fenhan, Linda Popella, Jörg Vogel
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Bacteriophages are the most abundant entities on earth and exhibit vast genetic and phenotypic diversity. Exploitation of this largely unexplored molecular space requires identification and functional characterization of genes that act at the phage–host interface. So far, this has been restricted to few model phage–host systems that are amenable to genetic manipulation. Here, to overcome this limitation, we introduce a non-genetic mRNA targeting approach using exogenous delivery of programmable antisense oligomers to silence genes of DNA and RNA phages. A systematic knockdown screen of core and accessory genes of the nucleus-forming jumbo phage ΩKZ, coupled to RNA-sequencing and microscopy analyses, reveals previously unrecognized proteins that are essential for phage propagation and that, upon silencing, elicit distinct phenotypes at the level of the phage and host response. One of these factors is the RNase H-like protein ΩKZ155 (also known as Nlp2), which acts at a major decision point during infection, linking the formation of the protective phage nucleus to phage genome amplification. This non-genetic antisense oligomer-based gene silencing method promises to be a versatile tool for molecular discovery in phage biology, will help to elucidate defence and anti-defence mechanisms in non-model phage–host pairs, and offers potential for optimizing phage therapy and biotechnological procedures.
GPT-4o mini: Non-social science research article
Functional synapses between neurons and small cell lung cancer
Vignesh Sakthivelu, Anna Schmitt, Franka Odenthal, Kristiano Ndoci, Marian Touet, Ali H. Shaib, Abdulla Chihab, Gulzar A. Wani, Pascal Nieper, Griffin G. Hartmann, Isabel Pintelon, Ilmars Kisis, Maike Boecker, Naja M. Eckert, Manoela Ianicelli Caiaffa, Olta Ibruli, Julia Weber, Roman Maresch, Christina M. Bebber, Ali Chitsaz, Anna LĂŒtz, Mira Kim Alves Carpinteiro, Kaylee M. Morris, Camilla A. Franchino, Jonas Benz, Laura PĂ©rez-Revuelta, Jorge A. Soriano-Campos, Maxim A. Huetzen, Jonas Goergens, Milica Jevtic, Hannah M. Jahn-Kelleter, Hans Zempel, Aleksandra Placzek, Alexandru A. Hennrich, Karl-Klaus Conzelmann, Hannah L. Tumbrink, Pascal Hunold, Joerg Isensee, Lisa Werr, Felix Gaedke, Astrid Schauss, Marielle MinĂšre, Marie MĂŒller, Henning Fenselau, Yin Liu, Alena Heimsoeth, GĂŒlce S. GĂŒlcĂŒler Balta, Henning Walczak, Christian Frezza, Ron D. Jachimowicz, Julie George, Marcel Schmiel, Johannes BrĂ€gelmann, Tim Hucho, Silvia von Karstedt, Martin Peifer, Alessandro Annibaldi, Robert HĂ€nsel-Hertsch, Thorsten Persigehl, Holger GrĂŒll, Martin L. Sos, Guido Reifenberger, Matthias Fischer, Dirk Adriaensen, Reinhard BĂŒttner, Julien Sage, Inge Brouns, Roland Rad, Roman K. Thomas, Max Anstötz, Silvio O. Rizzoli, Matteo Bergami, Elisa Motori, Hans Christian Reinhardt, Filippo Beleggia
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Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer, characterized by rapid proliferation, early metastatic spread, frequent early relapse and a high mortality rate 1–3 . Recent evidence has suggested that innervation has an important role in the development and progression of several types of cancer 4,5 . Cancer-to-neuron synapses have been reported in gliomas 6,7 , but whether peripheral tumours can form such structures is unknown. Here we show that SCLC cells can form functional synapses and receive synaptic transmission. Using in vivo insertional mutagenesis screening in conjunction with cross-species genomic and transcriptomic validation, we identified neuronal, synaptic and glutamatergic signalling gene sets in mouse and human SCLC. Further experiments revealed the ability of SCLC cells to form synaptic structures with neurons in vitro and in vivo. Electrophysiology and optogenetic experiments confirmed that cancer cells can receive NMDA receptor- and GABA A receptor-mediated synaptic inputs. Fitting with a potential oncogenic role of neuron–SCLC interactions, we showed that SCLC cells derive a proliferation advantage when co-cultured with vagal sensory or cortical neurons. Moreover, inhibition of glutamate signalling had therapeutic efficacy in an autochthonous mouse model of SCLC. Therefore, following malignant transformation, SCLC cells seem to hijack synaptic signalling to promote tumour growth, thereby exposing a new route for therapeutic intervention.
GPT-4o mini: Non-social science research article
Late fluid flow in a primitive asteroid revealed by Lu–Hf isotopes in Ryugu
Tsuyoshi Iizuka, Takazo Shibuya, Takehito Hayakawa, Tetsuya Yokoyama, Ikshu Gautam, Makiko K. Haba, Kengo T. M. Ito, Yuki Hibiya, Akira Yamaguchi, Yoshinari Abe, JĂ©rĂŽme AlĂ©on, Conel M. O’D. Alexander, Sachiko Amari, Yuri Amelin, Ken-ichi Bajo, Martin Bizzarro, Audrey Bouvier, Richard W. Carlson, Marc Chaussidon, Byeon-Gak Choi, Nicolas Dauphas, Andrew M. Davis, Tommaso Di Rocco, Wataru Fujiya, Ryota Fukai, Hiroshi Hidaka, Hisashi Homma, Gary R. Huss, Trevor R. Ireland, Akira Ishikawa, Shoichi Itoh, Noriyuki Kawasaki, Noriko T. Kita, Koki Kitajima, Thorsten Kleine, Shintaro Komatani, Alexander N. Krot, Ming-Chang Liu, Yuki Masuda, Kazuko Motomura, FrĂ©dĂ©ric Moynier, Kazuhide Nagashima, Izumi Nakai, Ann Nguyen, Larry Nittler, Andreas Pack, Changkun Park, Laurette Piani, Liping Qin, Sara Russell, Naoya Sakamoto, Maria SchönbĂ€chler, Lauren Tafla, Haolan Tang, Kentaro Terada, Yasuko Terada, Tomohiro Usui, Sohei Wada, Meenakshi Wadhwa, Richard J. Walker, Katsuyuki Yamashita, Qing-Zhu Yin, Shigekazu Yoneda, Hiroharu Yui, Ai-Cheng Zhang, Tomoki Nakamura, Hiroshi Naraoka, Takaaki Noguchi, Ryuji Okazaki, Kanako Sakamoto, Hikaru Yabuta, Masanao Abe, Akiko Miyazaki, Aiko Nakato, Masahiro Nishimura, Tatsuaki Okada, Toru Yada, Kasumi Yogata, Satoru Nakazawa, Takanao Saiki, Satoshi Tanaka, Fuyuto Terui, Yuichi Tsuda, Sei-ichiro Watanabe, Makoto Yoshikawa, Shogo Tachibana, Hisayoshi Yurimoto
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GPT-4o mini: Non-social science research article
Probing non-equilibrium topological order on a quantum processor
M. Will, T. A. Cochran, E. Rosenberg, B. Jobst, N. M. Eassa, P. Roushan, M. Knap, A. Gammon-Smith, F. Pollmann
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Out-of-equilibrium phases in many-body systems constitute a new paradigm in quantum matter—they exhibit dynamical properties that may otherwise be forbidden by equilibrium thermodynamics. Among these non-equilibrium phases are periodically driven (Floquet) systems 1–5 , which are generically difficult to simulate classically because of their high entanglement. Here we realize a Floquet topologically ordered state theoretically proposed in ref. 6 , on an array of superconducting qubits. We image the characteristic dynamics of its chiral edge modes and characterize its emergent anyonic excitations. Devising an interferometric algorithm allows us to introduce and measure a bulk topological invariant to probe the dynamical transmutation of anyons for system sizes up to 58 qubits. Our work demonstrates that quantum processors can provide key insights into the thus-far largely unexplored landscape of highly entangled non-equilibrium phases of matter.
GPT-4o mini: Non-social science research article
Author Correction: 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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GPT-4o mini: Non-social science research article
Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours
Samarth Hegde, Bruno Giotti, Brian Y. Soong, Laszlo Halasz, Jessica Le Berichel, Maximilian M. Schaefer, Benoit Kloeckner, RaphaĂ«l Mattiuz, Matthew D. Park, Assaf Magen, Adam Marks, Meriem Belabed, Pauline Hamon, Theodore Chin, Leanna Troncoso, Juliana J. Lee, Kaili Fan, Dughan Ahimovic, Michael J. Bale, Kai Nie, Grace Chung, Darwin D’souza, Krista Angeliadis, Seunghee Kim-Schulze, Raja M. Flores, Andrew J. Kaufman, Florent Ginhoux, Jason D. Buenrostro, Steven Z. Josefowicz, Alexander M. Tsankov, Thomas U. Marron, Sai Ma, Brian D. Brown, Miriam Merad
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GPT-4o mini: Non-social science research article
ABCA7 variants impact phosphatidylcholine and mitochondria in neurons
Djuna von Maydell, Shannon E. Wright, Ping-Chieh Pao, Colin Staab, OisĂ­n King, Andrea Spitaleri, Julia Maeve Bonner, Liwang Liu, Chung Jong Yu, Ching-Chi Chiu, Daniel Leible, Aine Ni Scannail, Mingpei Li, Carles A. Boix, Hansruedi Mathys, Guillaume Leclerc, Gloria Suella Menchaca, Gwyneth Welch, Agnese Graziosi, Noelle Leary, George Samaan, Manolis Kellis, Li-Huei Tsai
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GPT-4o mini: Non-social science research article
Publisher Correction: In situ light-field imaging of octopus locomotion reveals simplified control
Kakani Katija, Christine L. Huffard, Paul L. D. Roberts, Joost Daniels, Jon Erickson, Denis Klimov, Henry A. Ruhl, Alana D. Sherman
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GPT-4o mini: Non-social science research article
Probing the heterogeneous nature of LiF in solid–electrolyte interphases
Xiangsi Liu, Shuyang Li, Chen Yuan, Bizhu Zheng, Gangya Cheng, Yufan Chen, Xingyu Lu, Danyu Gu, Baijiang Lv, Hao Li, Zihan Yan, Hui Qian, Yizhou Zhu, Dalin Sun, Yun Song, Yuxuan Xiang
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GPT-4o mini: Non-social science research article
The emergence of globular clusters and globular-cluster-like dwarfs
Ethan D. Taylor, Justin I. Read, Matthew D. A. Orkney, Stacy Y. Kim, Andrew Pontzen, Oscar Agertz, Martin P. Rey, Eric P. Andersson, Michelle L. M. Collins, Robert M. Yates
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Globular clusters (GCs) are among the oldest and densest stellar systems in the Universe, yet how they form remains a mystery 1 . Here we present a suite of cosmological simulations in which both dark-matter-free GCs and dark-matter-rich dwarf galaxies naturally emerge in the Standard Cosmology. We show that these objects inhabit distinct locations in the size–luminosity plane and that they have similar ages, age spread, metallicity and metallicity spread to globulars and dwarfs in the nearby Universe. About half of our simulated globulars form by means of regular star formation near the centres of their host dwarf, with the rest forming further out, triggered by mergers. The latter are more tidally isolated and more likely to survive to the present day. Finally, our simulations predict the existence of a new class of object that we call ‘globular-cluster-like dwarfs’ (GCDs). These form from a single, self-quenching, star-formation event in low-mass dark-matter halos at high redshift and have observational properties intermediate between globulars and dwarfs. We identify several dwarfs in our Galaxy, such as Reticulum II (refs. 2–4 ), that could be in this new class. If so, they promise unprecedented constraints on dark-matter models and new sites to search for metal-free stars.
GPT-4o mini: Non-social science research article
Energy deficiency selects crowded live epithelial cells for extrusion
Saranne J. Mitchell, Carlos Pardo-Pastor, Anastassia Tchoumakova, Thomas A. Zangle, Jody Rosenblatt
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Epithelial cells work collectively to provide a protective barrier, yet they turn over rapidly through cell division and death. If the numbers of dividing and dying cells do not match, the barrier can vanish, or tumours can form. Mechanical forces through the stretch-activated ion channel Piezo1 link both of the processes; stretch promotes cell division, whereas crowding triggers live cells to extrude and then die 1,2 . However, it was not clear what selects a given crowded cell for extrusion. Here we show that the crowded cells with the least energy and membrane potential are selected for extrusion. Crowding triggers sodium (Na + ) entry through the epithelial Na + channel (ENaC), which depolarizes cells. While those with sufficient energy repolarize, those with limited ATP remain depolarized, which, in turn, triggers water egress through the voltage-gated potassium (K + ) channels K v 1.1 and K v 1.2 and the chloride (Cl − ) channel SWELL1. Transient water loss causes cell shrinkage, amplifying crowding to activate crowding-induced live cell extrusion. Thus, our findings suggest that ENaC acts as a tension sensor that probes for cells with the least energy to extrude and die, possibly damping inadvertent crowding activation of Piezo1 in background cells. We reveal crowding-sensing mechanisms upstream of Piezo1 that highlight water regulation and ion channels as key regulators of epithelial cell turnover.
GPT-4o mini: Non-social science research article
Stabilizing effect of amino acids on protein and colloidal dispersions
Ting Mao, Xufeng Xu, Pamina M. Winkler, Cécilia Siri, Ekaterina Poliukhina, Paulo Jacob Silva, Nan Xu, Yu Hu, Karim Al Zahabi, Rémi La Polla, Zhi Luo, Quy Ong, Alfredo Alexander-Katz, Francesco Stellacci
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GPT-4o mini: Non-social science research article
Human gastroids to model regional patterning in early stomach development
Xia Li, Feng Lin, Qiqi Cui, Shiyu Sun, Shixin Li, Yue Wang, Yiting Wang, Jianbo Bai, Shiyi Liu, Jia Guo, Yizhao Han, Meiru Zhang, Tie Chang, Yifan Zheng, Jianlin Liu, Longqi Liu, Leyun Wang, Jianping Fu, Xin Liu, Bing Bai, Yue Shao
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GPT-4o mini: Non-social science research article
Loss-of-function mutations in PLD4 lead to systemic lupus erythematosus
Qintao Wang, Honghao Zhu, Xiangwei Sun, Changming Zhang, Shuangyue Ma, Ying Jin, Jinjian Fu, Chenlu Liu, Jiahui Peng, Ruoran Wang, Lin Liu, Yi Zeng, Cheng Gong, Qing Zhou, Xiaomin Yu, Zhihong Liu
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Monogenic lupus offers valuable insights into the underlying mechanisms and therapeutic approaches for systemic lupus erythematosus (SLE) 1–3 . Here we report on five patients with SLE carrying recessive mutations in phospholipase D family member 4 ( PLD4 ). Deleterious variants in PLD4 resulted in impaired single-stranded nucleic acid exonuclease activity in in vitro and ex vivo assays. PLD4 loss-of-function mutations led to excessive activation of Toll-like receptor 7 (TLR7) and TLR9. Downstream inflammatory signalling pathways, especially type I interferon signalling, were hyperactivated in patient dendritic cells. Pld4 -deficient mice presented with autoimmunity and cell-intrinsic expansion of plasmacytoid dendritic cells and plasma cells. Pld4 -deficient mice responded to the JAK inhibitor baricitinib, suggesting that targeting type I interferon may be a potential therapy for patients with PLD4 deficiency.
GPT-4o mini: Non-social science research article
Probing the Kitaev honeycomb model on a neutral-atom quantum computer
Simon J. Evered, Marcin Kalinowski, Alexandra A. Geim, Tom Manovitz, Dolev Bluvstein, Sophie H. Li, Nishad Maskara, Hengyun Zhou, Sepehr Ebadi, Muqing Xu, Joseph Campo, Madelyn Cain, Stefan Ostermann, Susanne F. Yelin, Subir Sachdev, Markus Greiner, Vladan Vuletić, Mikhail D. Lukin
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GPT-4o mini: Non-social science research article
Author Correction: A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome
Manoj Jangra, Dmitrii Y. Travin, Elena V. Aleksandrova, Manpreet Kaur, Lena Darwish, Kalinka Koteva, Dorota Klepacki, Wenliang Wang, Maya Tiffany, Akosiererem Sokaribo, Xuefei Chen, Zixin Deng, Meifeng Tao, Brian K. Coombes, Nora VĂĄzquez-Laslop, Yury S. Polikanov, Alexander S. Mankin, Gerard D. Wright
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GPT-4o mini: Non-social science research article
Structure and mechanism of the mitochondrial calcium transporter NCLX
Minrui Fan, Chen-Wei Tsai, Jinru Zhang, Jianxiu Zhang, Aswini R. Krishnan, Tsung-Yun Liu, Yu-Lun Huang, Deniz Aydin, Siyuan Du, Briana L. Sobecks, Madison X. Rodriguez, Andrew H. Reiter, Carolyn R. Bertozzi, Ron O. Dror, Ming-Feng Tsai, Liang Feng
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As a key mitochondrial Ca 2+ transporter, NCLX regulates intracellular Ca 2+ signalling and vital mitochondrial processes 1–3 . The importance of NCLX in cardiac and nervous-system physiology is reflected by acute heart failure and neurodegenerative disorders caused by its malfunction 4–9 . Despite substantial advances in the field, the transport mechanisms of NCLX remain unclear. Here we report the cryo-electron microscopy structures of NCLX, revealing its architecture, assembly, major conformational states and a previously undescribed mechanism for alternating access. Functional analyses further reveal an unexpected transport function of NCLX as a H + /Ca 2+ exchanger, rather than as a Na + /Ca 2+ exchanger as widely believed 1 . These findings provide critical insights into mitochondrial Ca 2+ homeostasis and signalling, offering clues for developing therapies to treat diseases related to abnormal mitochondrial Ca 2+ .
GPT-4o mini: Non-social science research article
Fluctuating DNA methylation tracks cancer evolution at clinical scale
Calum Gabbutt, MartĂ­ Duran-Ferrer, Heather E. Grant, Diego Mallo, Ferran Nadeu, Jacob Househam, Neus Villamor, Madlen MĂŒller, Simon Heath, Emanuele Raineri, Olga Krali, Jessica Nordlund, Thorsten Zenz, Ivo G. Gut, Elias Campo, Armando Lopez-Guillermo, Jude Fitzgibbon, Chris P. Barnes, Darryl Shibata, JosĂ© I. Martin-Subero, Trevor A. Graham
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GPT-4o mini: Non-social science research article
Observing differential spin currents by resonant inelastic X-ray scattering
Yanhong Gu, Joseph Barker, Jiemin Li, Takashi Kikkawa, Fernando Camino, Kim Kisslinger, John Sinsheimer, Lukas Lienhard, Jackson J. Bauer, Caroline A. Ross, Dmitri N. Basov, Eiji Saitoh, Jonathan Pelliciari, Gerrit E. W. Bauer, Valentina Bisogni
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GPT-4o mini: Non-social science research article
Neuronal activity-dependent mechanisms of small cell lung cancer pathogenesis
Solomiia Savchuk, Kaylee M. Gentry, Wengang Wang, Elana Carleton, Carlos A. O. Biagi-Junior, Karan Luthria, Belgin Yalçın, Lijun Ni, Hannah C. Farnsworth, Rachel A. Davis, Richard Drexler, Johannes C. Melms, Yin Liu, Lehi Acosta-Alvarez, Griffin G. Hartmann, Elisa C. Pavarino, Jenna LaBelle, Pamelyn J. Woo, Angus M. Toland, Fangfei Qu, Yoon Seok Kim, Mariella G. Filbin, Mark A. Krasnow, Keith L. Ligon, Benjamin Izar, Julien Sage, Bernardo L. Sabatini, Michelle Monje, Humsa S. Venkatesh
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GPT-4o mini: Non-social science research article
The oldest known lepidosaur and origins of lepidosaur feeding adaptations
Daniel Marke, David I. Whiteside, Thitiwoot Sethapanichsakul, Robert A. Coram, Vincent Fernandez, Alexander Liptak, Elis Newham, Michael J. Benton
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The Lepidosauria is the most species-rich group of land-dwelling vertebrates. The group includes around 12,000 species of lizards and snakes (Squamata) and one species of Rhynchocephalia, the tuatara Sphenodon punctatus from New Zealand 1 . Squamates owe their success to their generally small size, but also to their highly mobile skull that enables them to manipulate large prey. These key features of lizard and snake skulls are not seen in Sphenodon , which makes it important to understand the nature of their common ancestor. Lepidosaurs originated in the Triassic 252–201 million years ago, but confusion has arisen because of incomplete fossils, many of which are generalized lepidosauromorphs, neither squamates nor rhynchocephalians 2–5 . Here we report a reasonably complete skull and skeleton of a definitive rhynchocephalian from the Middle Triassic (Anisian) Helsby Sandstone Formation of Devon, UK that is around 3–7 million years older than the oldest currently known lepidosaur. The new species shows, as predicted, a non-mobile skull but an open lower temporal bar and no large palatine teeth, and it seems to have been a specialized feeder on insects. This specimen helps us understand the initial diversification of Lepidosauria as part of the Triassic Revolution, when modern-style terrestrial ecosystems emerged.
GPT-4o mini: Non-social science research article
Molecular subtypes of human skeletal muscle in cancer cachexia
Bhumi J. Bhatt, Sunita Ghosh, Vera Mazurak, Aurélien Q. Brun, Oliver Bathe, Vickie E. Baracos, Sambasivarao Damaraju
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GPT-4o mini: Non-social science research article
Systematic attribution of heatwaves to the emissions of carbon majors
Yann Quilcaille, Lukas Gudmundsson, Dominik L. Schumacher, Thomas Gasser, Richard Heede, Corina Heri, Quentin Lejeune, Shruti Nath, Philippe Naveau, Wim Thiery, Carl-Friedrich Schleussner, Sonia I. Seneviratne
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Extreme event attribution assesses how climate change affected climate extremes, but typically focuses on single events 1–4 . Furthermore, these attributions rarely quantify the extent to which anthropogenic actors have contributed to these events 5,6 . Here we show that climate change made 213 historical heatwaves reported over 2000–2023 more likely and more intense, to which each of the 180 carbon majors (fossil fuel and cement producers) substantially contributed. This work relies on the expansion of a well-established event-based framework 1 . Owing to global warming since 1850–1900, the median of the heatwaves during 2000–2009 became about 20 times more likely, and about 200 times more likely during 2010–2019. Overall, one-quarter of these events were virtually impossible without climate change. The emissions of the carbon majors contribute to half the increase in heatwave intensity since 1850–1900. Depending on the carbon major, their individual contribution is high enough to enable the occurrence of 16–53 heatwaves that would have been virtually impossible in a preindustrial climate. We, therefore, establish that the influence of climate change on heatwaves has increased, and that all carbon majors, even the smaller ones, contributed substantially to the occurrence of heatwaves. Our results contribute to filling the evidentiary gap to establish accountability of historical climate extremes 7,8 .
GPT-4o mini: Non-social science research article
Editorial Expression of Concern: Recovery of learning and memory is associated with chromatin remodelling
Andre Fischer, Farahnaz Sananbenesi, Xinyu Wang, Matthew Dobbin, Li-Huei Tsai
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GPT-4o mini: Non-social science research article
Redox-driven mineral and organic associations in Jezero Crater, Mars
Joel A. Hurowitz, M. M. Tice, A. C. Allwood, M. L. Cable, K. P. Hand, A. E. Murphy, K. Uckert, J. F. Bell, T. Bosak, A. P. Broz, E. ClavĂ©, A. Cousin, S. Davidoff, E. Dehouck, K. A. Farley, S. Gupta, S.-E. Hamran, K. Hickman-Lewis, J. R. Johnson, A. J. Jones, M. W. M. Jones, P. S. JĂžrgensen, L. C. Kah, H. Kalucha, T. V. Kizovski, D. A. Klevang, Y. Liu, F. M. McCubbin, E. L. Moreland, G. Paar, D. A. Paige, A. C. Pascuzzo, M. S. Rice, M. E. Schmidt, K. L. Siebach, S. Siljeström, J. I. Simon, K. M. Stack, A. Steele, N. J. Tosca, A. H. Treiman, S. J. VanBommel, L. A. Wade, B. P. Weiss, R. C. Wiens, K. H. Williford, R. Barnes, P. A. Barr, A. Bechtold, P. Beck, K. Benzerara, S. Bernard, O. Beyssac, R. Bhartia, A. J. Brown, G. Caravaca, E. L. Cardarelli, E. A. Cloutis, A. G. FairĂ©n, D. T. Flannery, T. Fornaro, T. Fouchet, B. Garczynski, F. GomĂ©z, E. M. Hausrath, C. M. Heirwegh, C. D. K. Herd, J. E. Huggett, J. L. JĂžrgensen, S. W. Lee, A. Y. Li, J. N. Maki, L. Mandon, N. Mangold, J. A. Manrique, J. MartĂ­nez-FrĂ­as, J. I. NĂșñez, L. P. O’Neil, B. J. Orenstein, N. Phelan, C. Quantin-Nataf, P. Russell, M. D. Schulte, E. Scheller, S. Sharma, D. L. Shuster, A. Srivastava, B. V. Wogsland, Z. U. Wolf
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Daily briefing: Different people’s brains process colours in the same way
Flora Graham
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Different flames
Beth Cato
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‘LinkedIn is like air to me’: the scientists who’ve cracked professional networking
Anne Marie Conlon
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Daily briefing: Regenerative revolution aims to future-proof European agriculture
Flora Graham
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Dinosaur egg dated directly for the first time
Mohana Basu
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Heatwaves linked to emissions of individual fossil-fuel and cement producers
Karsten Haustein, Michael B. Gerrard, Jessica A. Wentz
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Life scientists: educate others to help strengthen biosecurity
Lijun Shang, Malcolm Dando
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Jelly-filled garment keeps wearers cool when heat and humidity soar
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Diabetes drug shows anti-ageing effects on chromsomes
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Protests are infectious: mapping rural unrest in Revolutionary France
Jack A. Goldstone
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First CRISPR horses spark controversy: what’s next for gene-edited animals?
Katie Kavanagh
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The surprising ways bridges resist collapse
Nick Petrić Howe
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When AI rejects your grant proposal: algorithms are helping to make funding decisions
David Adam
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Tips and tricks to plan your career in science
Julie Gould
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Creativity is essential to the ethos of universities
Emil Roduner
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AI chatbots are already biasing research — we must establish guidelines for their use now
Zhicheng Lin
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A common gut fungus worsens infection with the food-borne bacterium Salmonella
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Is my red your red? Neuroscience has an answer
Katie Kavanagh, Nick Petrić Howe
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Feeling the heat: fossil-fuel producers linked to dozens of heatwaves
Benjamin Thompson, Shamini Bundell
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The earth will not consume our bones
Abigail Kemske
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These scientists left the US in Trump’s first term: their tips on taking the leap
Alexandra Witze
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AI-generated medical data can sidestep usual ethics review, universities say
Andy Extance
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Daily briefing: Nine metals in two dimensions
Flora Graham
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These nations are wooing PhD students amid US funding uncertainties
Rachel Fieldhouse
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Trump team disbands controversial US climate panel
Jeff Tollefson
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Bug bites convince UK doctor to support mosquito research centre
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A revolution is sweeping Europe’s farms: can it save agriculture?
April Reese
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Epigenetic clues from cancer’s past foretell its future
Pavlo Lutsik, Veselin Manojlovic, George S. Vassiliou
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How to make a ‘laser’ of neutrinos
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My blue is your blue: different people’s brains process colours in the same way
Katie Kavanagh
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Global geopolitics should not stall science — 5 ways to push back
James Oliver Scott Hammond, Jean-Christophe Mauduit
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Dozens of heatwaves linked to carbon emissions from specific companies
Jeff Tollefson
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Research misconduct: how the scientific community is fighting back
Nick Petrić Howe
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Air pollution directly linked to increased dementia risk
Rachel Fieldhouse
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Strengthen the science behind the Agreement on Fisheries Subsidies
Shu Su, Yi Tang, Yong Chen
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Using biobanks to boost research: a how-to guide
Jyoti Madhusoodanan
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Can a bold ‘social contract’ make data sharing more palatable?
Nchangwi Syntia Munung, Cornelius Ewuoso, Francis E. Agamah, Emile R. Chimusa
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Daily briefing: Is a cure for psoriasis on the horizon?
Flora Graham
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Designing an alloy microstructure atom by atom to withstand extreme cold
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Nature goes inside the world’s largest ‘mosquito factory’ — here’s the buzz
Adam Levy, Mariana Lenharo
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How to build nature back better — read this manual
Ryan Nolan
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How did the oldest star clusters form?
Natalia Lahén
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Daily briefing: A polo-team’s worth of cloned CRISPR horses
Flora Graham
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Head start: fossil clues about how bodies evolved from two-fold to five-fold symmetry
Gregory A. Wray
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Iggy bop: how I tune in to the needs of GalĂĄpagos marine iguanas
Anna Napolitano
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Your risk of dying from chronic disease has dropped – if you live in these countries
Mohana Basu
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Europe’s largest paper mill? 1,500 research articles linked to Ukrainian network
Miryam Naddaf
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Daily briefing: How bad are ultra-processed foods, really?
Flora Graham
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Use computing royalties to kick-start biodiversity fund
Ralf C. Buckley, Charles Lawson, L. Roman Carrasco, Linsheng Zhong
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Clearest gravitational wave detection yet confirms Hawking’s black hole theory
Jenna Ahart
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Iron-respiring microbes could have a role in sulfur cycling
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AI tool detects LLM-generated text in research papers and peer reviews
Miryam Naddaf
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‘Brain dial’ turns food consumption on or off in mice
Amanda Heidt
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RFK Jr slings accusations and defends public-health upheaval at fiery hearing
Max Kozlov, Mariana Lenharo
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Climate impacts are real — denying this is self-defeating
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Scientists take on Trump: these researchers are fighting back
Dan Garisto, Max Kozlov, Heidi Ledford
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Can researchers stop AI making up citations?
Elizabeth Gibney
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Synthetic data can benefit medical research — but risks must be recognized
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Hope for diabetes: CRISPR-edited cells pump out insulin in a person — and evade immune detection
Elie Dolgin
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Rainer Weiss obituary: Nobel laureate who pioneered the technique that detected gravitational waves
Bruce Allen
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Mystery Martian minerals hint at the planet’s complex geochemical past
Janice L. Bishop, Mario Parente
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‘Amazing feat’: US man still alive six months after pig kidney transplant
Rachel Fieldhouse
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‘Communities already have the solutions’: why I advocate for Indigenous knowledge
Vanesa de la Cruz Pavas
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Nature Human Behaviour

GPT-4o mini: Non-social science research article
Active use of latent tree-structured sentence representation in humans and large language models
Wei Liu, Ming Xiang, Nai Ding
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A randomized controlled trial on the effect of administrative burden and information costs on social inequalities in early childcare access in France
Laudine Carbuccia, Arthur Heim, Carlo Barone, Coralie Chevallier
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The impact of private hosting on the integration of Ukrainian refugees in Germany
Mathis Herpell, Moritz Marbach, Niklas Harder, Alexandra Orlova, Dominik Hangartner, Jens Hainmueller
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Personalized digital tools boost smoking quit rates
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Author Correction: Homophily and acrophily as drivers of political segregation
Amit Goldenberg, Joseph M. Abruzzo, Zi Huang, Jonas Schöne, David Bailey, Robb Willer, Eran Halperin, James J. Gross
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A model for refugee integration
Dany Bahar
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Interventions to reduce vaccine hesitancy among adolescents: a cluster-randomized trial
N. Baudouin, S. de Rouilhan, E. Huillery, E. Pasquinelli, C. Chevallier, H. Mercier
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Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Spontaneous glutamate release activates mGluR signaling to drive rapid antidepressant responses
Clara I. McCarthy, Z. Zack Ma, Lisa M. Monteggia, Ege T. Kavalali
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Major depressive disorder affects millions worldwide, yet current treatments require prolonged administration. In contrast, ketamine produces rapid antidepressant effects by blocking spontaneous N-Methyl-D-Aspartate (NMDA) receptor signaling, which lifts the suppression of protein synthesis and triggers homeostatic synaptic plasticity. Here, we identify a parallel signaling pathway involving metabotropic glutamate receptor 5 (mGluR5) that promotes rapid antidepressant-like effects. We show that enhancing the endogenous mGluR5 signaling produces synaptic potentiation in the hippocampus and triggers the rapid antidepressant effect, similar to ketamine. Importantly, blocking mGluR5 prevents ketamine’s effects, revealing a synergy between the two pathways. At the cellular level, spontaneous calcium transients mediated by mGluR5 activate the phosphatase calcineurin and promote eukaryotic elongation factor 2 (eEF2) dephosphorylation, increasing BDNF translation to drive synaptic plasticity. We show that quantal glutamate release activates two spatially segregated Ca 2+ signals—NMDAR- and mGluR5-driven—which exert opposing effects on protein synthesis. Together, these findings highlight mGluR5 as a promising therapeutic target for rapid antidepressant action, harnessing the complex nanoscale organization of synapses.
GPT-4o mini: Non-social science research article
A geometric condition for robot-swarm cohesion and cluster–flock transition
Mathias Casiulis, Eden Arbel, Charlotte van Waes, Yoav Lahini, Stefano Martiniani, Naomi Oppenheimer, Matan Yah Ben Zion
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We present a geometric design rule for size-controlled clustering of self-propelled particles. We show that active particles that tend to rotate under an external force have an intrinsic, signed parameter with units of curvature which we call curvity, that can be derived from first principles. Experiments with robots and numerical simulations show that properties of individual robots (radius and curvity) control pair cohesion in a binary system, and the stability of flocking and self-limiting clustering in a swarm, with applications in metamaterials and in embodied decentralized control.
GPT-4o mini: Non-social science research article
From molecular damage and viscoelasticity to interfacial fracture in soft polymer networks: Insights from mechanochemistry
Anthony Arrowood, Jackson Frazier, Matteo Ciccotti, Gabriel E. Sanoja
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Many soft, tough materials have emerged in recent years, paving the way for advances in wearable electronics, soft robotics, and flexible displays. However, understanding the interfacial fracture behavior of these materials remains a significant challenge, owing to the difficulty of quantifying the respective contributions from viscoelasticity and damage to energy dissipation ahead of cracks. This work aims to address this challenge by labeling a series of polymer networks with fluorogenic mechanophores, subjecting them to T-peel tests at various rates and temperatures, and quantifying their force-induced damage using a confocal microscope. The results challenge longstanding assumptions underlying linear viscoelastic fracture theories, revealing a complex interplay between viscoelasticity and damage governed by the Weissenberg number, W i . Specifically, they suggest a molecular picture in which the interfacial toughness increases due to polymer chain breakage and enlarged strains when W i < 0.3 , and significant chain friction and network stiffening when W i > 0.3 , with the damage being negligible in the limits of W i â‰Ș 0.3 and W i ≫ 0.3 either due to insufficient strains at the peel front or because of excessive stress at weak interfacial bonds. Overall, these results illustrate the molecular and mesoscopic mechanisms underpinning interfacial fracture, aiding to refine current viscoelastic fracture theories and accelerating the development of advanced polymer networks for increasingly demanding applications.
GPT-4o mini: Non-social science research article
Driving the grid forward: How electric vehicle adoption shapes power system infrastructure and emissions
Lily Hanig, Corey D. Harper, Destenie Nock, Jeremy J. Michalek
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We model the effect of plug-in electric vehicle (EV) adoption on U.S. power system generator capacity investment, operations, and emissions through 2050 by estimating power systems outcomes under a range of EV adoption trajectory scenarios. Our EV adoption scenarios are informed by 1) an Energy Information Administration scenario with no policy intervention, 2) EV growth expected under the Inflation Reduction Act (IRA), 3) a Biden Administration 50% EV sales target by 2030, 4) the Environmental Protection Agency’s projections under vehicle emissions standards, and 5) the International Energy Agency’s roadmap to Net Zero by 2050. We find across these scenarios that increasing EV adoption induces investment in new wind, solar, storage, and natural gas capacity, affecting power generation mix and emissions. The net effect of increasing EV adoption beyond our IRA base case is to increase power sector emissions by about 5 mtCO 2 eq per EV-year in 2026 (comparable to displaced gasoline vehicle combustion emissions), but this effect rapidly drops to annual levels below 1 mtCO 2 eq per EV-year by 2032 and continues below this level through 2050. Consequential effects of EV adoption vary regionally, with most regions primarily increasing wind or solar capacity and some regions primarily increasing natural gas capacity, even in 2050. Our national emissions estimates per EV-year are relatively robust to the level of EV adoption beyond our baseline and to variation in assumptions about power systems, EV behavior, and policy.
GPT-4o mini: Non-social science research article
Binding of Fusobacterium nucleatum autotransporter adhesin CbpF to human CEACAM1 and CEACAM5: A Velcro model for bacterium adhesion
Fan Shen, Linjie Li, Dongchun Yang, Zhexiao Tang, Lu Zhang, Kefang Liu, Wenzhe Hou, Zhuozhuang Lu, Jing-Yuan Fang, Jianxun Qi, Xin Zhao, George F. Gao
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In eukaryotic systems, three major types of cell junctions have been well characterized. While bacterial adhesion mechanisms also exhibit remarkable diversity, the molecular processes that regulate the dynamic modulation of binding strength between elongated bacterial cells and host cells remain poorly understood. Fusobacterium nucleatum ( F. nucleatum ) utilizes the surface adhesin CbpF to interact with the highly expressed host receptors CEACAM1 and CEACAM5 on cancer cells to facilitate tumor colonization. By elucidating the structural details of CbpF binding to human CEACAM1/CEACAM5 receptors, and through mechanistic investigations, we identified that the prominent EFNGQYQ loop on CbpF and the key Q78 residue of CEACAM1/CEACAM5 constitute the molecular linchpin of this pathogen–host interface. Furthermore, we found a distinct type of binding particle and proposed a Velcro-like adhesion model. In this model, CbpF mediates robust attachment through the simultaneous interaction of multiple binding sites, akin to the interlocking mechanism of Velcro. This multivalent interaction allows F. nucleatum to dynamically switch between firm anchoring and easy detachment, adapting to varying physiological microenvironments. Our study elucidates the dynamic modulation of bacterial adhesion strength and lays the foundation for developing therapeutic interventions to disrupt the bacterium–host interface.
GPT-4o mini: Non-social science research article
Sorting nexin 3 promotes ischemic retinopathy through RIP1- and RIP3-mediated myeloid cell necroptosis and mitochondrial fission
Jiaojiao Wang, Chunhong Zhou, Kai Zhuang, Jiami Zou, Wanlu Qiu, Mei Jin, Weile Ye, Pinglian Yang, Zhihua Zheng, Qing Zhou, Zunnan Huang, Yuanxiang Wang, Peiqing Liu, Jing Lu, Yuqing Huo, Zhiping Liu
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Proliferative retinopathy is a leading cause of irreversible blindness in humans; however, the molecular mechanisms behind the immune cell–mediated retinal angiogenesis remain poorly elucidated. Here, using single-cell RNA sequencing in an oxygen-induced retinopathy (OIR) model, we identified an enrichment of sorting nexin (SNX)-related pathways, with SNX3, a member of the SNX family that is involved in endosomal sorting and trafficking, being significantly upregulated in the myeloid cell subpopulations of OIR retinas. Immunostaining showed that SNX3 expression is markedly increased in the retinal microglia/macrophages of mice with OIR, which is mainly located within and around the neovascular tufts. Myeloid cell-specific deficiency of Snx3 inhibited retinal neovascularization, hyperpermeability, and dysfunction in OIR mice. Using glutathione S-transferase pull-down, coimmunoprecipitation, and immunofluorescent staining, we found that SNX3 interacted with receptor-interacting protein 1/3 (RIP1 and RIP3). We further demonstrated that RIP1/3 degradation was accelerated in SNX3-deleted microglia/macrophages, causing an inhibition of hypoxia-induced necroptosis and mitochondrial fission, thereby decreasing the production of proinflammatory and proangiogenic factors (FGF2 and MMP12). Moreover, OIR retinas from myeloid cell–specific SNX3 overexpression transgenic mice presented more angiogenic tufts, while RIP1/3 inhibition largely ablated SNX3 overexpression–induced pathological angiogenesis. Based on the structure of SNX3, we identified a small-molecule inhibitor, W1122. Intriguingly, we found that W1122 effectively inhibited retinal angiogenesis in the OIR model, and combination treatment with anti-Vascular Endothelial Growth Factor (VEGF) yielded enhanced antiangiogenic effects. Collectively, our findings disclose a link between SNX3 and RIP1/3 signaling and implicate SNX3 in the development of ischemic retinopathy.
GPT-4o mini: Non-social science research article
Measuring multisubunit mechanics of geometrically programmed colloidal assemblies via cryo-EM multi-body refinement
Thomas E. VidebĂŠk, Daichi Hayakawa, Michael F. Hagan, Gregory M. Grason, Seth Fraden, W. Benjamin Rogers
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Programmable self-assembly has recently enabled the creation of complex structures through precise control of the interparticle interactions and the particle geometries. Targeting ever more structurally complex, dynamic, and functional assemblies necessitates going beyond the design of the structure itself, to the measurement and control of the local flexibility of the intersubunit connections and its impact on the collective mechanics of the entire assembly. In this study, we demonstrate a method to infer the mechanical properties of multisubunit assemblies using cryogenic electron microscopy (cryo-EM) and RELION’s multi-body refinement. Specifically, we analyze the fluctuations of pairs of DNA-origami subunits that self-assemble into tubules. By measuring the fluctuations of dimers using cryo-EM, we extract mechanical properties such as the bending modulus and interparticle spring constant. These properties are then applied to elastic models to predict assembly outcomes, which align well with experimental observations. This approach not only provides a deeper understanding of nanoparticle mechanics but also opens pathways to refining subunit designs to achieve precise assembly behavior. This methodology could have broader applications in the study of nanomaterials, including protein assemblies, where understanding the interplay of mechanical properties and subunit geometry is essential for controlling complex self-assembled structures.
GPT-4o mini: Non-social science research article
Structural basis for Rad54- and Hed1-mediated regulation of Rad51 during the transition from mitotic to meiotic recombination
Yeonoh Shin, Michael T. Petassi, Aidan M. Jessop, Stefan Y. Kim, Razvan Matei, Katherine Morse, Vivek B. Raina, Upasana Roy, Eric C. Greene
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Rad51 catalyzes the DNA pairing reactions that take place during homologous recombination (HR), and HR must be tightly regulated to ensure physiologically appropriate outcomes. Rad54 is an ATP-dependent DNA motor protein that stimulates Rad51 activity during mitosis. In meiosis Rad51 is downregulated by the protein Hed1, which blocks Rad54 binding to Rad51, and allows Dmc1 to function as the active recombinase. We currently have a poor understanding of the regulatory interplay between Rad54, Hed1, Rad51, and Dmc1. Here, we identify a conserved Rad51 interaction motif within Rad54, and we solve a CryoEM structure of this motif bound to Rad51. We also identify a distinct Rad51 interaction motif within Hed1 and solve its structure bound to Rad51. These structures explain how Rad54 engages Rad51 to promote recombination between sister chromatids during mitosis and how Rad51 is downregulated by Hed1 upon entry into meiosis such that its meiosis-specific homolog Dmc1 can promote recombination between homologous chromosomes.
GPT-4o mini: Non-social science research article
Elastocaloric evidence for a multicomponent superconductor stabilized within the nematic state in Ba(Fe 1− x Co x ) 2 As 2
Sayak Ghosh, Matthias S. Ikeda, Anzumaan R. Chakraborty, Thanapat Worasaran, Florian Theuss, Luciano B. Peralta, P. M. Lozano, Jong-Woo Kim, P. J. Thompson, Philip J. Ryan, Linda Ye, Aharon Kapitulnik, Steven A. Kivelson, B. J. Ramshaw, Rafael M. Fernandes, Ian R. Fisher
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The iron-based high- T c superconductors (SCs) exhibit rich phase diagrams with intertwined phases, including magnetism, nematicity, and superconductivity. The superconducting T c in many of these materials is maximized in the regime of strong nematic fluctuations, making the role of nematicity in influencing the superconductivity a topic of intense research. Here, we use the AC elastocaloric effect (ECE) to map out the phase diagram of Ba(Fe 1− x Co x ) 2 As 2 near optimal doping. The ECE signature at T c on the overdoped side, where superconductivity condenses without any nematic order, is quantitatively consistent with other thermodynamic probes that indicate a single-component superconducting state. In contrast, on the slightly underdoped side, where superconductivity condenses within the nematic phase, ECE reveals a second thermodynamic transition proximate to and below T c . We rule out magnetism and reentrant tetragonality as the origin of this transition and find that our observations strongly suggest a phase transition into a multicomponent superconducting state. This implies the existence of a subdominant pairing instability that competes strongly with the dominant s ± instability. Our results highlight the significant role of nematic order in determining the pairing symmetry close to optimal doping in this extensively studied iron-based SC, while also demonstrating the power of ECE in uncovering strain-tuned phase diagrams of quantum materials.
GPT-4o mini: Non-social science research article
Deep reinforcement learning control unlocks enhanced heat transfer in turbulent convection
Zisong Zhou, Xiaojue Zhu
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Turbulent convection governs heat transport in both natural and industrial settings, yet optimizing it under extreme conditions remains a significant challenge. Traditional control strategies, such as predefined temperature modulation, struggle to achieve substantial enhancement. Here, we introduce a deep reinforcement learning (DRL) framework that autonomously discovers optimal control policies to maximize heat transfer in turbulent Rayleigh-BĂ©nard convection. By dynamically adjusting wall temperature fluctuations, the DRL agent achieves a heat transfer enhancement of up to 38.5%, exceeding the 20 to 25% limit of conventional methods. The learned strategy reveals a nonlinear state–action relationship, inducing a fully modulated boundary layer regime. Furthermore, we distill the DRL insights into a simplified bang-bang control model, which retains comparable performance (up to 40.0% enhancement) and, crucially, generalizes to unseen, higher Rayleigh number cases without additional training. Our results demonstrate the power of machine learning in turbulence control and reveal a framework with potential for intelligent heat transfer optimization in real-world applications.
GPT-4o mini: Non-social science research article
Reciprocity in dynamics of supramolecular biosystems for the clustering of ligands and receptors
Shikha Dhiman, Marle E. J. Vleugels, Richard A. J. Post, Martina Crippa, Annalisa Cardellini, Esmee de Korver, Lu Su, Anja R. A. Palmans, Giovanni M. Pavan, Remco W. van der Hofstad, Lorenzo Albertazzi, E. W. Meijer
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Multivalent binding and the resulting dynamical clustering of receptors and ligands are known to be key features in biological interactions. For optimizing biomaterials capable of similar dynamical features, it is essential to understand the first step of these interactions, namely the multivalent molecular recognition between ligands and cell receptors. Here, we present the reciprocal cooperation between dynamic ligands in supramolecular polymers and dynamic receptors in model cell membranes, determining molecular recognition and multivalent binding via receptor clustering. The nonlinear dependences of the ligand concentration, receptors, and their binding affinity are observed experimentally by fluorescence and superresolution fluorescence microscopies, revealing a valency-dependent clustering mode of anchoring. The mechanism is supported by stochastic modeling demonstrating that such nonlinear dependence is unlikely in the absence of any dynamics and superselectivity. Using a coarse-grained molecular model, the subtle competition between local and global entropies that controls this anchoring mechanism explains the clustering. Further investigation using single particle tracking reveals the presence of two populations of bound and unbound receptors after the clustering process. The result of this study highlights the importance of reciprocity of dynamics in supramolecular polymer and lipid membrane for recruitment, multivalent binding, and clustering, all of which are crucial elements in the design of materials capable of actively interacting with biological targets.
GPT-4o mini: Non-social science research article
Cooling outweighs warming across phenological transitions in the Northern Hemisphere
Yizhuo Li, Lin Meng, Andrew D. Richardson, Xuhui Lee, Annette Menzel, Jiafu Mao, Jen L. Diehl, Anzhi Wang
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Vegetation phenology, i.e., seasonal biological events such as leaf-out and leaf-fall, regulates local climate through biophysical processes like evapotranspiration (ET) and albedo. However, the net surface temperature impact of these processes—whether ET cooling or albedo-induced warming predominates—and how the dominance changes across phenological transitions and regions remains poorly understood. Here, we investigated the effects of vegetation foliage on daytime land surface temperature (LST) following six phenological transitions, spanning from the start of season to end of season, in deciduous and mixed forests across the mid- to high-latitude Northern Hemisphere during 2013–2021 using multiple satellite products and ground observations. We quantified vegetation effect as the difference between observed LST and LST estimates from the Annual Temperature Cycle (ATC) model, representing a no-foliage scenario. We found that vegetation-induced cooling consistently outweighs warming following all phenological transitions except for the end of the season. Cooling intensity increased with vegetation greenness, ranging from 1.0 ± 0.5 °C (mean ± 0.15 SD) in 59% of forests after the start of the season (SOS) to 6.1 ± 0.8 °C in 89% of forests following the onset of maturity, before declining toward the end of the season. Over half of the regions experiencing cooling showed intensification of surface cooling with climate warming, suggesting an amplified vegetation-mediated cooling under future climate change. The findings provide a more precise understanding of the role of vegetation in modulating climate at the intraseasonal scale, highlighting the importance of integrating phenological impacts into climate adaptation strategies and Earth system modeling.
GPT-4o mini: Non-social science research article
A genetically encoded nanobody sensor reveals conformational diversity in ÎČ-arrestins orchestrated by distinct seven transmembrane receptors
Parishmita Sarma, Vendula Nagy MarkovĂĄ, Annu Dalal, Sudha Mishra, Nashrah Zaidi, Divyanshu Tiwari, Manish K. Yadav, Nabarun Roy, Gargi Mahajan, Paul Miclea, Josef Lazar, Arun K. Shukla
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Agonist-induced interaction of G protein–coupled receptors (GPCRs) with ÎČ-arrestins (ÎČarrs) is a critical mechanism that regulates the spatiotemporal pattern of receptor localization and signaling. While the underlying mechanism governing GPCR–ÎČarr interaction is primarily conserved and involves receptor activation and phosphorylation, there are several examples of receptor-specific fine-tuning of ÎČarr-mediated functional outcomes. Considering the key contribution of conformational plasticity of ÎČarrs in driving receptor-specific functional responses, it is important to develop novel sensors capable of reporting distinct ÎČarr conformations in cellular context. Here, we design an intrabody version of a ÎČarr-recognizing nanobody (nanobody32), referred to as intrabody32 (Ib32), in NanoLuc enzyme complementation assay format and measure its ability to recognize ÎČarr1 and 2 in live cells upon activation of a broad set of GPCRs. Ib32 robustly recognizes activated ÎČarr1 and 2 in the plasma membrane and endosomes, and effectively mirrors ÎČarr recruitment profile upon stimulation of selected GPCRs. We also design an Ib32 sensor for polarization microscopy with a change in linear dichroism as readout and demonstrate its utility for monitoring ÎČarr activation upon stimulation of selected GPCRs by natural and biased agonists. Taken together with a previously described sensor of ÎČarr1 activation, Ib32 underscores the inherent flexibility encoded in ÎČarrs and conformational diversity imparted by different GPCRs, which is further corroborated using an orthogonal limited proteolysis assay. Our study presents Ib32 as a sensor of ÎČarr activation and highlights the structural diversity of ÎČarrs, which likely allows their ability to interact with, and regulate, a large repertoire of GPCRs.
GPT-4o mini: Non-social science research article
Distinct prelimbic cortex ensembles encode response execution and inhibition
Rajtarun Madangopal, Yuan Zhao, Conor Heins, Jingfeng Zhou, Bo Liang, Giovanni Barbera, Ka Chun Lam, Lauren E. Komer, Sophia J. Weber, Drake J. Thompson, Yugantar Gera, Diana Q. Pham, Katherine E. Savell, Brandon L. Warren, Daniele Caprioli, Marco Venniro, Jennifer M. Bossert, Leslie A. Ramsey, Hank P. Jedema, Geoffrey Schoenbaum, Da-Ting Lin, Yavin Shaham, Francisco Pereira, Bruce T. Hope
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Learning when to initiate or withhold actions is essential for survival, requiring the integration of past experiences with new information to adapt to changing environments. The prelimbic cortex (PL) plays a central role in this process, with a stable PL neuronal population (ensemble) recruited during operant reward learning to encode response execution. However, it is unknown how this established reward-learning ensemble adapts to changing reward contingencies, such as reward omission during extinction. Specifically, does the same ensemble adjust its activity to support behavior suppression, or is a distinct ensemble recruited for this new learning? Our data reveal that operant extinction learning recruits a distinct PL Extinction ensemble to support response inhibition, and concerted engagement of both ensembles encodes both ongoing and subsequent context-specific behavior. Using single-cell calcium imaging, we longitudinally tracked PL neurons in rats as they pressed a lever for food rewards (Training), learned to suppress responding upon reward omission (Extinction), and reinstated responding following a noncontingent “priming” pellet (Reinstatement). We trained decoders on individual rats’ PL activity patterns to predict trial-wise responses and used an in silico deletion approach to identify separate PL Training and Extinction ensembles associated with response execution and inhibition, respectively. Critically, both ensembles were reengaged and maintained their distinct roles during Reinstatement. These findings highlight ensemble-based encoding of multiple, even opposing, learned associations within the same region, demonstrating how selective ensemble recruitment enables behavioral flexibility under changing contingencies.
GPT-4o mini: Non-social science research article
Cooperative mixing through hydrodynamic interactions in Stylonychia lemnae
Régis Turuban, Giovanni Noselli, Alfred Beran, Antonio DeSimone
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Aquatic microorganisms typically inhabit a heterogeneous resource landscape, composed of localized and transient patches. To effectively exploit these resources, they have evolved a wide range of feeding strategies that combine chemotactic motility with active feeding flows. However, there is a notable lack of experimental studies that examine how these active flows shape resource fields to optimize feeding. In particular, the suspected cooperative hydrodynamics provided by groups of cells remains largely unexplored due to the difficulties in visualizing these dynamic three-dimensional flows. Here, we experimentally investigate how Stylonychia lemnae ciliates form feeding clusters of independent cells around food patches. Individual feeding flows interact hydrodynamically to create a chaotic collective flow at the population scale. Using a combination of experimental and numerical techniques, we measure and predict the entire collective flow, enabling us to assess its remarkable mixing and dispersion properties. We show that the active spreading of the food patch accelerates its detection by starving cells. As many fitness advantages provided by collective flows can be envisioned, we propose that this feeding cluster represents a form of intraspecific by-product cooperative behavior.
GPT-4o mini: Non-social science research article
Convergent evolution of NFP -facilitated root nodule symbiosis
Christina Finegan, Heather R. Kates, Robert P. Guralnick, Pamela S. Soltis, Marcio F. R. Resende, Jean-Michel Ané, Matias Kirst, Ryan A. Folk, Douglas E. Soltis
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The origin and phylogenetic distribution of symbiotic associations between nodulating angiosperms and nitrogen-fixing bacteria have long intrigued biologists. Recent comparative evolutionary analyses have yielded alternative hypotheses: a multistep pathway of independent gains and losses of root nodule symbiosis vs. a single gain followed by numerous losses. A detailed reconstruction of the history of genes involved in signaling between nitrogen-fixing bacteria and potential hosts, particularly lipo-chitooligosaccharide (LCO) signaling, is needed to distinguish between these hypotheses. LCO recognition by plants involves the Nod Factor Perception ( NFP ) gene family; in the legume model Medicago truncatula (Fabales), MtNFP is essential for establishing rhizobial symbiosis. Here, we document convergent evolution of NFP , indicating multiple origins of LCO-driven symbiosis. In contrast to previous models that explain the recruitment of NFP via a single duplication in the ancestor of the nitrogen-fixing clade, our phylogenomic and synteny results suggest this duplication does not span the entire clade. Tandem duplication in a common ancestor of Cucurbitales and Rosales resulted in the NFP1 and NFP2 groups. In contrast, the phylogenetically closest paralog of MtNFP is MtLYR1 , located on a different chromosome within a large syntenic block. All available data indicate that a large-scale duplication resulted in MtNFP and MtLYR1 , likely corresponding to a whole-genome duplication in an ancestor of subfamily Papilionoideae of Fabaceae. We show that MtNFP and the NFP2 -like group are not orthologous, indicating multiple independent gains of NFP -based LCO signaling. This molecular convergence provides a possible mechanism for multiple gains of root nodule symbiosis across the nitrogen-fixing clade.
GPT-4o mini: Non-social science research article
Toughness enhancement by massive dislocation absorption at the crack front
Jiazhi Zhang, Qin Yu, Jiazhuang Tian, Shanglu Yang, Xunwei Zuo, Ying Li, Nailu Chen, Yonghua Rong, Robert O. Ritchie, Jian Lu
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Low-cost yet high-performance structural materials have been invariantly sought for modern engineering applications. However, due to the localized stress concentration induced by a high Peierls-Nabarro stress and limited dislocation mobility, increasing material strength usually comes at the expense of ductility and toughness, resulting in a trade-off between strength–ductility/strength–toughness. Here, we report an anomalous phenomenon of dislocation absorption at the crack front, which is unlike typically observed dislocation emission at the crack tip, in a heterogeneous “plain” steel consisting of tempered lath martensite embedded with stable carbon-enriched retained austenite. The continuous absorption of dislocations emitted from the tempered martensite into the tough austenite significantly alleviates the localized stress concentration, and as such retards crack propagation in the tempered martensite matrix. This allows the plain high-carbon low-alloyed steel subjected to simple quenching–partitioning–tempering processes to achieve remarkable properties comprising a multiplication of strength and elongation over 50 GPa·% with an exceptionally high fracture toughness over 130 MPa·m 1/2 . The toughening strategy based on this mechanism provides a promising route for developing cost-effective plain steels with ultrahigh strength, ductility, and toughness that is a persistent pursuit in the steel industry.
GPT-4o mini: Non-social science research article
From simplicity to complexity: A path to innovation in science and art
Joseph L. Goldstein
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Simple reductionist systems can serve as powerful catalysts for unlocking complex innovations in science and art. The evolution from simplicity to complexity is illustrated by the career journeys of the scientist Earl W. Sutherland, who discovered cyclic adenosine 3â€Č-5â€Č-monophosphate (cyclic AMP) and opened the field of cell signaling, and the artist Frank Stella, who pioneered geometrical patterns and shapes in both painting and sculpture. Their work profoundly influenced biomedical science and modern art. How one navigates the journey from simplicity to complexity is a fundamental challenge to scientists and artists who aim to identify fresh ideas that lead to insights with lasting impact.
GPT-4o mini: Non-social science research article
Atomic armor for thermal stability in nanoporous structures
Rui Yang, Qiaoling Si, Qiang Sheng, Mingyang Yang, Mu Du, Hu Zhang, Xiao-Lei Shi, Guihua Tang, Zhi-Gang Chen
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Nanoporous structures play a critical role in a wide range of applications, including catalysis, thermoelectrics, energy storage, gas adsorption, and thermal insulation. However, their thermal instability remains a persistent challenge. Inspired by the extraordinary resilience of tardigrades, an “atomic armor” strategy is introduced to enhance the stability of nanoporous structures. Applied to mesoporous silica at parts-per-million levels, the atomic armor provides thermal resistance exceeding that of existing stabilization techniques. Thermal treatment at 1,000 °C for 168 h results in a fivefold increase in specific surface area, 66% lower thermal conductivity, and a sixfold increase in pore volume compared to untreated samples. Surface viscosity is linked to sintering resistance, and glass transition temperature and fragility are introduced as design parameters. Machine-learned interatomic potentials and metabasin escape algorithm-assisted molecular dynamics simulations are employed to reveal that materials traditionally classified as nonglass formers can exhibit glass transition temperatures and display intrinsic fragility. Alumina is identified as having a record-high glass transition temperature. By modulating the surface viscosity of nanoparticles, this approach stabilizes nanoporous structures effectively. The proposed method offers a simple and universal posttreatment process for improving the thermal stability of nanoporous structures.
GPT-4o mini: Non-social science research article
Muricholic acid mediates puberty initiation via the hypothalamic TGR5 signaling pathway
Shan Wang, Ke Huang, Ana Liu, Senjie Wang, Runqiu Jiang, Wenlian Chen, Huiying Wang, Rahim Ullah, Chuqing Xue, Wei Wu, Guanping Dong, Peifang Jiang, Junfen Fu, Yan Ni
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The onset of puberty is increasingly observed at earlier ages in children, especially in girls with obesity, a trend that predisposes them to long-term metabolic and reproductive disorders in adulthood. Bile acids have emerged as pivotal signaling molecules in both metabolic and reproductive disorders, but remain unexplored in the early onset of puberty in children. Herein, we find elevated levels of muricholic acid (MCA) species in the serum of girls with central precocious puberty, which strongly correlate with indices of hypothalamic–pituitary–gonadal axis activation and can reach peak levels during puberty among healthy children. Intriguingly, reduction of MCA species can lead to decreased expression of gonadotropin-releasing hormone (GnRH) and delay the early onset of puberty, while elevated MCA levels induced premature sexual development in female mice. Mechanistically, we demonstrated that MCA had strong activation effects on Takeda G-protein-coupled receptor 5 (TGR5), and MCA enhanced GnRH expression in GnRH neurons through activation of the TGR5-PI3K/Akt-mTOR signaling pathway. Our findings reveal a link between metabolic status and reproductive maturation, highlighting MCA as a potential therapeutic target for managing early puberty initiation.
GPT-4o mini: Non-social science research article
Chelation-induced anti-Ostwald ripening: Ultrafine bismuth nanocrystals for ultrastable aqueous sodium storage
Haojie Zhu, Xinlei Cai, Dianhui Zhu, Feiyu Kang, Lu Peng, Chunyi Zhi, Cheng Yang
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Aqueous sodium-ion batteries (ASIBs) are gaining attention for their inherent safety and the use of abundant sodium resources. Bismuth (Bi) anode, with its high theoretical capacity and low cost, enhances the performance and competitiveness of ASIBs in energy storage applications. However, as a conversion-type material, Bi inevitably undergoes dramatic volume changes during cycling, limiting the structural stability and calendar life of the electrode. Herein, we present a Bi-carbon composite electrode with ultrafine Bi nanocrystals (< 10 nm) uniformly integrated into nitrogen-doped carbon nanofibers (UF Bi@NCF). Despite Bi’s low melting point (271 °C), Ostwald ripening of metallic Bi during carbonization (750 °C) is effectively suppressed by incorporating polyacrylic acid as a chelating polymer in the electrospun Bi(III)/polyacrylonitrile precursor solutions. The high dispersity of Bi nanocrystals at elevated temperature is attributed to the strong coordination and electrostatic interactions between carboxyl groups and Bi 3+ . This structural refinement significantly reduces localized stress concentrations during sodiation/desodiation. The UF Bi@NCF anode demonstrates a reversible capacity of 237.5 mAh g −1 at 0.5 C, and negligible capacity decay even after 5,700 cycles at an extremely high current rate of 20 C for ASIBs. These findings highlight the potential of the anti-Ostwald ripening effect in enhancing the stability and performance of metal-carbon composite electrodes, providing valuable insights into the design of advanced materials for next-generation aqueous batteries.
GPT-4o mini: Non-social science research article
Correction for Sharma and DiVincenzo, g -factor symmetry and topology in semiconductor band states
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GPT-4o mini: Non-social science research article
Joint models reveal human subcortical underpinnings of choice and learning behavior
Steven Miletić, Niek Stevenson, Pierre-Louis Bazin, Anneke Alkemade, Scott J. S. Isherwood, Anne C. Trutti, Desmond H. Y. Tse, Asta K. HĂ„berg, Birte U. Forstmann
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Decision making and learning processes together enable adaptive strategic behavior. Animal studies demonstrated the importance of subcortical regions in these cognitive processes, but the human subcortical contributions remain poorly characterized. Here, we study choice and learning processes in the human subcortex, using a tailored ultra-high field 7T functional MRI protocol combined with joint models. Joint models provide unbiased estimates of brain–behavior relations by simultaneously including behavioral and neural data at the participant and group level. Results demonstrate relations between subcortical regions and the adjustment of decision urgency. Value-related blood-oxygenation level dependent (BOLD) differences were found with opposite BOLD polarity in different parts of the striatum. Multiple subcortical regions showed BOLD signatures of reward prediction error processing, but contrary to expectations, these did not include the dopaminergic midbrain. Combined, this study characterizes the human subcortical contributions to choice and learning, and demonstrates the feasibility and value of joint modeling in facilitating our understanding of brain–behavior relationships.
GPT-4o mini: Non-social science research article
Stress-induced organismal death is genetically regulated by the mTOR–Zeste–Phae1 axis
Takashi Matsumura, Masasuke Ryuda, Hitoshi Matsumoto, Takumi Kamiyama, Kyoko Jinnai, Shu Kondo, Akira Nakamura, Yoichi Hayakawa, Ryusuke Niwa
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All organisms are exposed to various stressors, which can sometimes lead to organismal death, depending on their intensity. While stress-induced organismal death has been observed in many species, the underlying mechanisms remain unclear. In this study, we investigated the molecular mechanisms of stress-induced organismal death in the fruit fly Drosophila melanogaster . We identified a chymotrypsin-like serine protease Phaedra1 ( Phae1 ) as a death mediator in D. melanogaster larvae. Phae1 expression was up-regulated by lethal heat stress (40 °C) but not nonlethal heat stress (38 °C or lower). The most prominent induction of Phae1 occurred in the central nervous system (CNS). We found neuro-specific knockdown of Phae1 increased survival and reduced neuronal caspase activity following exposure to lethal heat stress, suggesting that the transcriptional upregulation of Phae1 in the CNS is essential for stress-induced organismal death. We next found via bioinformatic and biochemical analyses that the transcription factor Zeste (Z) bound the Phae1 enhancer region and that z loss-of-function impaired Phae1 induction in the CNS, increasing survival following lethal heat stress. In addition, we found via chemical screening that rapamycin, a chemical inhibitor of mechanistic target of rapamycin (mTOR), suppressed Phae1 expression. Neuro-specific knockdown of mTor reduced the protein levels of both Phae1 and Z, leading to an increase in survival following lethal heat stress. Together, these results indicate that heat stress–induced organismal death in D. melanogaster larvae is regulated by a genetically encoded transcriptional signaling pathway involving the mTOR–Z–Phae1 axis.
GPT-4o mini: Non-social science research article
Synovial MS4A4A correlates with inflammation and counteracts response to corticosteroids in arthritis
Marie-Astrid Boutet, Irene Mattiola, Rita Silva-Gomes, Alessandra Nerviani, Marina Sironi, Giulia Maria Ghirardi, Alessia Troilo, Stefano Gianoli, Felice Rivellese, Cankut Cubuk, Katriona Goldmann, Anna Rita Putignano, Dario Di Silvestre, Andrea Lomagno, Elena Monica Borroni, Cristina Sobacchi, Myles J. Lewis, Barbara Bottazzi, Massimo Locati, Alberto Mantovani, Costantino Pitzalis
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MS4A4A belongs to the MS4A tetraspan protein superfamily and is selectively expressed by the monocyte–macrophage lineage. In this study, we aimed to evaluate the role of MS4A4A+ macrophages in rheumatoid arthritis (RA) pathogenesis and response to treatment. RNA sequencing and immunohistochemistry of synovial samples from either early treatment-naïve or active chronic RA patients showed that MS4A4A expression positively correlated with synovial inflammation. Synovial macrophages from patients treated with corticosteroids (CS) exhibited an enhanced expression of MS4A4A and Fc γ receptor (FcγR) 3. Accordingly, CS enhanced in vitro the expression of MS4A4A and FcγR3 in human and murine macrophages. In an experimental model of arthritis, Ms4a4a deletion had no effect on the disease course but was associated with enhanced therapeutic response selectively to CS. These results suggest that macrophage expression of MS4A4A represents a biomarker of joint inflammation in RA and that its upregulation in concert with FcγR3 by CS counteracts the therapeutic activity of these drugs. Macrophage MS4A4A may represent a biomarker of joint inflammation in RA and a target to amplify the therapeutic activity of CS.
GPT-4o mini: Non-social science research article
The RecBC complex protects single-stranded DNA gaps during lesion bypass
GaĂ«lle Philippin, Pauline Dupaigne, Élodie Chrabaszcz, Maialen Iturralde, Mauro Modesti, Eric Le Cam, Vincent PagĂšs, Luisa Laureti
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Following encounter with an unrepaired DNA lesion, replication is halted and can restart downstream of the lesion leading to the formation of a single-stranded DNA (ssDNA) gap. To complete replication, this ssDNA gap is filled in by one of the two lesion tolerance pathways: the error-prone Translesion Synthesis (TLS) or the error-free Homology Directed Gap Repair (HDGR). In the present work, we evidence a role for the RecBC complex distinct from its canonical function in homologous recombination at DNA double strand breaks. We show that upon lesion encounter RecBC (independently of its catalytic activity and of the RecD subunit) is required to protect the nascent DNA in order to promote efficient lesion bypass. In the absence of RecBC, our data indicate that the nuclease ExoI can access and degrade the nascent DNA, affecting both TLS and HDGR mechanisms. We show that the recruitment of RecBC becomes particularly important at strong blocking lesions, when postreplicative ssDNA gaps persist and are covered by the ssDNA binding proteins. This protective role of RecBC is reminiscent of the role of BRCA2 in protecting the nascent DNA in human cells, highlighting once again the evolutionary conservation of DNA replication mechanisms across all living organisms.
GPT-4o mini: Non-social science research article
A mosquito-inspired theoretical framework for acoustic signal detection
Justin Faber, Alexandros C. Alampounti, Marcos Georgiades, Joerg T. Albert, Dolores Bozovic
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Distortion products are tones produced through nonlinear effects of a system simultaneously detecting two or more frequencies. These combination tones are ubiquitous to vertebrate auditory systems and are generally regarded as byproducts of nonlinear signal amplification. It has previously been shown that several species of infectious-disease-carrying mosquitoes utilize these distortion products for detecting and locating potential mates. Furthermore, the mechanical tuning curve of the male mosquito flagellum was shown not to be aligned with that of its sensory neural elements. Using a generic theoretical model for acoustic sensing, we evaluate the signal-detection advantages and disadvantages that are implied by these two schemes: distortion product detection and cascading a signal through multiple layers of oscillator elements of different characteristic frequency. Last, we show that the combination of these two schemes yields a signal detector with enhanced frequency selectivity and speed of response, thus enabling the detection of transient, narrowband flight tones.
GPT-4o mini: Non-social science research article
Giant mobility of surface-trapped ionic charges following liquid tribocharging
Zouhir Benrahla, Tristan Saide, Louis Burnaz, Emilie Verneuil, Simon Gravelle, Jean Comtet
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The sliding motion of aqueous droplets on hydrophobic surfaces leads to charge separation at the trailing edge, with implications from triple-line friction to hydrovoltaic energy generation. Charges deposited on the solid surface have been attributed to ions or electrons ripped off from the liquid drop. However, the dynamics and exact physicochemical nature of these surface-trapped charges remains poorly explored. Here, we take advantage of a scanning-based electrostatic mapping technique, to directly quantify the spatiotemporal dynamics of surface deposited charges in the wake of droplets sliding on hydrophobic surfaces. We confirm the ionic nature of these interfacially trapped charges, and evidence that they undergo very fast bidimensional diffusive transport, gliding with low friction at the solid/gas interface. We interpret our observations in the framework of molecular dynamics simulation of hydrated ions adsorbed on solid surfaces, revealing a peculiar transport mechanism limited by purely interfacial friction of the ionic solvation shell with the solid surface. By uncovering the unexpected dynamics of these ionic puddles—a distinct state of interfacial ionic matter—our findings have general implications for molecular-scale ionic transport, electrified matter, and wetting dynamics at interfaces.
GPT-4o mini: Non-social science research article
Quantifying phage infectivity from characteristics of bacterial population dynamics
Michael Blazanin, Eli Vasen, CĂšlia VilarĂł Jolis, William An, Paul E. Turner
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A frequent goal of phage biology is to quantify how well a phage kills a population of host bacteria. Unfortunately, traditional methods to quantify phage success can be time-consuming, limiting the throughput of experiments. Here, we use theory to show how the effects of phages on their hosts can be quantified using bacterial population dynamics measured in a high-throughput microplate reader (automated spectrophotometer). We use mathematical models to simulate bacterial population dynamics where specific phage and bacterial traits are known a priori. We then test common metrics of those dynamics (e.g., growth rate, time and height of peak bacterial density, death rate, extinction time, area under the curve) to determine which best predict: 1) infectivity over the short-term, and 2) phage suppression over the long term. We find that many metrics predict infectivity and are strongly correlated with one another. We also find that metrics can predict phage growth rate, providing an effective way to quantify the combined effects of multiple phage traits. Finally, we show that peak density, time of peak density, and extinction time are the best metrics when comparing across different bacterial hosts or over longer timescales where plasticity or evolution may play a role. In all, we establish a foundation for using bacterial population dynamics to quantify the effects of phages on their bacterial hosts, supporting the design of in vitro empirical experiments using microplate readers.
GPT-4o mini: Non-social science research article
Experimentally enhancing dispersal reveals the outsized importance of transient dynamics in a fluctuating environment
Jessica J. Kowalski, Benjamin Gilbert, Sharon Y. Strauss, Rachel M. Germain
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The size and composition of local species pools are, in part, determined by past dispersal events. Predicting how communities respond to future disturbances, such as fluctuating environmental conditions, requires knowledge of such histories. We assessed the influence of a historical dispersal event on community assembly by simulating various scales of dispersal for 240 serpentine annual plant communities that experienced a large shift from drought to high rainfall conditions over three years. We collected, aggregated, and redistributed the aboveground seed bank (i.e., all loose seed present on the soil surface before the growing season initiates) from 30 sites across five nested spatial scales ( ∌ 1 m, 5 m, 100 m, 5 km, and 10 km), and annually censused communities to identify change in community structure among dispersal scales and over time. Our one-time dispersal manipulation diversified aboveground seed banks, provided insurance against temporal variability at intermediate and large dispersal distances ( ≄ 100 m), and even supported community reassembly toward a new compositional state at the 10 km scale. We also found evidence that temporal lags directed community responses to environmental fluctuations, preventing rare species extirpations and providing subordinate species discrete windows of time to supplement their seed banks. Our results reveal a joint spatiotemporal equilibrium in this system where dispersal through space interacts with temporal fluctuations in climate to support species’ persistence via aboveground seed banks. This experiment underscores the importance of dispersal for diversity maintenance in this global biodiversity hotspot, where the magnitude and frequency of future climate fluctuations is uncertain.
GPT-4o mini: Non-social science research article
Action at a distance: The remarkable coupling of CO 2 uptake to electron transfer in specialized cyanobacterial NDH-1 complexes
Zhifen Zhang, Minquan Zhang, Robert L. Burnap
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Cyanobacteria achieve highly efficient photosynthesis using a CO 2 -concentrating mechanism relying on specialized Type I (NDH-1) complexes. Among these, NDH-1 3 and NDH-1 4 catalyze redox-coupled hydration of CO 2 to bicarbonate, supporting carbon fixation in carboxysomes. The mechanism of coupling electron transfer to CO 2 -hydration by these variant NDH-1 complexes remains unknown. We engineered a Synechococcus PCC7942 strain that expresses exclusively the high flux/low affinity NDH-1 4 complex, enabling the observation of the coupling of CO 2 hydration to cyclic electron flow in isolation from the other NDH-1 isoforms normally present in cells. We found that inhibition of the CupB protein by the carbonic anhydrase inhibitor ethoxzolamide (EZ) suppressed CO 2 uptake, slowed photosystem I rereduction, and abolished proton pumping as probed by acridine orange fluorescence. These effects were absent in strains lacking Cup proteins, confirming specificity. The results demonstrate that CO 2 hydration and electron transfer through NDH-1 4 are tightly coupled via proton translocation across the thylakoid membrane. These findings provide direct evidence for the bidirectional interaction in bioenergetic coupling between the plastoquinone reduction and the CO 2 uptake at the distal Zn-site over a span of ~150 Å and support a proton-removal hypothesis involving the proton transfer pathways from the Zn-site of CO 2 hydration to an energetically coupled proton loading site evolutionarily repurposed from the ancestral proton pumping mechanism to enable energetic CO 2 uptake.
GPT-4o mini: Non-social science research article
Correction for Gibbons et al., Motivational trade-offs and modulation of nociception in bumblebees
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GPT-4o mini: Non-social science research article
A solid-state battery capable of 180 C superfast charging and 100% energy retention at –30 °C
Hu Hong, Zhiquan Wei, Yiqiao Wang, Xinru Yang, Xun Guo, Qingshun Nian, Xinliang Li, Qing Li, Shixun Wang, Shimei Li, Dechao Zhang, Qi Xiong, Zhaodong Huang, Chunyi Zhi
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Solid-state electrolytes (SSEs) are being extensively researched as replacements for liquid electrolytes in future batteries. Despite significant advancements, there are still challenges in using SSEs, particularly in extreme conditions. This study presents a hydrated metal-organic ionic cocrystal (HMIC) solid-state ion conductor with a solvent-assisted ion transport mechanism suitable for extreme operating conditions. Through crystal engineering strategies, the adsorption capacity of HMIC for anions and water molecules can be regulated, thereby facilitating cation hopping transport and enhancing electrochemical stability. As a result, optimized HMIC shows exceptional properties, including an extraordinarily high Zn 2+ transference number (t Zn2+ = 0.81), an expanded electrochemical stability window (~2.6 V), and an exceptionally high Zn 2+ ion conductivity (8.6 mS cm –1 , 25 °C). Interface dynamics analysis indicates that this strong binding to water molecules can significantly reduce the desolvation energy barrier and enhance the ionic diffusion coefficient. (10 to 100 times higher than that in aqueous electrolytes). This allows Zn|| Prussian blue analog batteries to exhibit impressive fast-charging performance (180 C, 20 s, over 1,000 charge/discharge cycles) and maintain 100% discharge capacity retention and discharge plateau from –30 to 30 °C. The development of HMICs with a solvent-assisted hopping mechanism provides a promising path for solid-state zinc-ion batteries in extreme conditions, including fast charging, low temperature, and high loading.
GPT-4o mini: Non-social science research article
Dynamic and precise electromagnetic levitation of single cells
Malavika Ramarao, Victor Garcia-Gradilla, Mehmet Burcin Unlu, Ronald W. Davis, Naside Gozde Durmus
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The biophysical properties of single cells are crucial for understanding cellular function and behavior in biology and medicine. However, precise manipulation of cells in 3-D microfluidic environments remains challenging, particularly for heterogeneous populations. Here, we present “Electro-LEV,” a unique platform integrating electromagnetic and magnetic levitation principles for dynamic 3-D control of cell position during separation. We demonstrated that small current adjustments in electromagnets significantly alter the levitation heights of diverse particles and cell types. By periodically modulating and tracking cell positions along the z-axis, Electro-LEV identified distinct levitation behaviors between single cells and cell clusters, with clusters responding more rapidly to magnetic field changes. Furthermore, we demonstrated that Electro-LEV significantly enhances the purity and efficiency of levitational sorting, achieving 10-fold enrichment of live cells from 50% starting viability samples and 18.8-fold enrichment from 10% starting viability samples. These results establish Electro-LEV as a powerful tool for investigating cellular heterogeneity, differentiating cell sizes and types, and improving cell sorting efficiency. Thus, Electro-LEV is broadly applicable, offering different possibilities for high-resolution cell analysis and label-free cell sorting in various biomedical fields, including but not limited to single-cell sequencing and drug screening.
GPT-4o mini: Non-social science research article
Bridging feeling and motion: Insula–premotor dynamics in the processing of action vitality forms
Giuseppe Di Cesare, Yury Koush, Peter Zeidman, Alessandra Sciutti, Karl Friston, Giacomo Rizzolatti
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Typically, people perform actions in a valenced—positive or negative—way, depending on their attitudes or desires. These forms of action are named vitality forms (VFs). While it is well established that action goals are mediated by a parieto-frontal network, less is known about the processing of VFs. Recent fMRI studies suggest that the insula (INS)—and its connections with the parieto-frontal circuit—plays a crucial role in VFs processing. However, a key question remains: How does our internal affective state shape our motor behavior? To explore this issue, we conducted an fMRI study. Participants were required to perform two sequential tasks: 1) to evoke either a positive (enthusiastic) or a negative (angry) affective state (feeling task); 2) to execute an action while maintaining these affective states (execution task). Univariate analysis revealed activation of the INS and dorsolateral prefrontal cortex (PFC) during the feeling task, which extended to the premotor (PM) and parietal areas during the execution task. To determine the directionality of information flow among these nodes, we employed dynamic causal modeling. Bayesian model comparison showed that, during the feeling task, affect generation involves INS, which, together with the PFC, modulates the activity of PM. In contrast, during execution, motor commands emerge from PM and influence activity in the INS and PFC. These findings indicate that while the internal states crucially imply the INS, their regulation is mediated by PFC. The PM cortex plays a crucial role in the selection of the corresponding action VFs.
GPT-4o mini: Non-social science research article
Replication stress–induced nuclear hypertrophy alters chromatin topology and impacts cancer cell fitness
Changgon Kim, Semyeong Hong, Soo Hyeon Ma, Joochan Lee, Hee So, Jun Young Kim, Eunbie Shin, Kippeum Lee, Sohee Choi, Juyeon Park, YongKeun Park, You-Me Kim, Ji Hun Kim, Joon Kim
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Microscopic examination of biopsy tissues remains essential for cancer diagnosis, despite advancements in sequencing technologies. Alterations in nuclear size or the nuclear-to-cytoplasmic ratio are hallmark features of cancer cells and often correlate with disease progression. However, the mechanisms underlying nuclear size abnormalities and their impact on tumor progression remain unclear. In this study, we demonstrate that nuclear hypertrophy occurs in response to enhanced DNA replication stress, a key characteristic of cancer cells. Increased actin polymerization within the nucleus appears to be the primary mechanism driving nuclear hypertrophy downstream of the ATR-CHEK1 pathway. Replication stress–induced nuclear hypertrophy alters transcriptomic profiles and chromatin topology, while reducing the migratory and metastatic capacity of cancer cells. In addition, nuclear hypertrophy in cancer cells is associated with increased infiltration of antitumor immune cells. Our findings suggest that cell-autonomous effects of nuclear hypertrophy do not promote cellular fitness or aggressive characteristics in cancer cells. This may explain why cells with nuclear hypertrophy are not positively selected and persist as a subpopulation during tumor progression and metastasis. Furthermore, the link between replication stress and nuclear hypertrophy provides insights into why enlarged nuclei are consistently observed in advanced-stage cancers.
GPT-4o mini: Non-social science research article
The redox rhythm gates immune-induced cell death distinctly from the genetic clock
Sargis Karapetyan, Musoki Mwimba, Tianyuan Chen, Zhujun Yao, Xinnian Dong
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Organisms use circadian clocks to synchronize physiological processes to anticipate the Earth’s day-night cycles and regulate responses to environmental signals to gain competitive advantage. While divergent genetic clocks have been studied extensively in bacteria, fungi, plants, and animals, an ancient conserved circadian redox rhythm has been recently reported. However, its biological function and physiological outputs remain elusive. Here, we uncovered the coexistence of redox and genetic rhythms with distinct period lengths and transcriptional targets through concurrent metabolic and transcriptional time-course measurements in an Arabidopsis long-period clock mutant. Analysis of the target genes indicated regulation of the immune-induced programmed cell death (PCD) by the redox rhythm. Moreover, this time-of-day-sensitive PCD was eliminated by redox perturbations and by blocking the signaling pathway of the plant defense hormones jasmonic acid/ethylene, while remaining intact in genetic clock-defective backgrounds. This study shows that compared to robust genetic clocks, the more sensitive circadian redox rhythm serves as a signaling hub in regulating incidental energy-intensive processes, such as immune-induced PCD involving reprogramming of chloroplast and mitochondria activities, to provide organisms a flexible strategy to mitigate metabolic overload during stress responses.
GPT-4o mini: Non-social science research article
Hybridoma-inspired strategy crafts tailored multifunctional exosomes for precision therapy
Zhufeng Dong, Tieying Yin, Zhiqin Deng, Hang Zou, Lei Kuang, Yang Wang, Wen Shi, Mengwei Han, Siqing Zhu, Zheng Wang, Xiaoye Hu, Yazhou Z. Wang
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Engineering functional exosomes represents a cutting-edge approach in biomedicine, holding the promise to transform targeted therapy. However, challenges such as achieving consistent modification and scalability have limited their wider adoption. Herein, we introduce a universal and effective strategy for engineering multifunctional exosomes through cell fusion. The hybrid-cell-derived exosomes could combine the functional properties of both parental cells and be readily produced by passaging. This method enables customization and large-scale production of exosomes with specific functionalities, potentially advancing precision therapies across a wide array of diseases. As demonstrated in Alzheimer’s disease (AD) models, exosomes derived from hybrid cells (HCs) (H/Exos) of mesenchymal stem cells (MSCs) and neutrophils efficiently targeted AD-affected areas via LFA-1/ICAM-1 and improved the cognition of AD mice. Beyond directly promoting neural repair and inhibiting inflammation, we surprisingly found that H/Exos increased microglia abundance, modulated microglia gene expression, enhanced the endocytic and lysosomal function, and promoted microglial phagocytic phenotypic differentiation to clear AÎČ. This hybridoma-inspired strategy offers a versatile and practical way to engineer exosomes with desired therapeutic functions, representing a promising direction for personalized therapies.
GPT-4o mini: Non-social science research article
S-nitrosylation of pVHL regulates ÎČ 2 adrenergic receptor function
Zachary W. Grimmett, Hiroki Hayashi, Thomas M. Raffay, Justin Lin, Richard T. Premont, Jonathan S. Stamler
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The ÎČ 2 -adrenergic receptor (ÎČ 2 AR), a prototype G protein–coupled receptor, controls cardiopulmonary function underpinning O 2 delivery. Abundance of the ÎČ 2 AR is canonically regulated by G protein–coupled receptor kinases and ÎČ-arrestins, but neither controls constitutive receptor levels, which are dependent on ambient O 2 . Basal ÎČ 2 AR expression is instead regulated by the prolyl hydroxylase/pVHL-E3 ubiquitin ligase system, explaining O 2 responsivity. Interplay between O 2 and nitric oxide (NO, a potent bronchodilator) is central to cardiopulmonary function. Here, we demonstrate that pVHL-mediated ÎČ 2 AR degradation is counteracted by NO, revealing pVHL control of pulmonary function. NO S-nitrosylates Cys77 in human pVHL (cognate to mouse Cys43), which induces binding of the E3 ubiquitin ligase c-Cbl to degrade pVHL, thereby increasing ÎČ 2 AR expression. pVHL–C43S mutant mice refractory to S-nitrosylation exhibit decreases in ÎČ 2 AR signaling and increases in airway tone. Thus, pVHL controls adrenergic pulmonary function and contributes to bronchodilation by NO. Our findings suggest therapeutic approaches to asthma and obstructive airway disease.
GPT-4o mini: Non-social science research article
Adrenal lipoma formation via PI(3,4,5)P 3 /AKT-dependent transdifferentiation of adrenocortical cells into adipocytes
Shogo Yanai, Junko Sasaki, Hyeon-Cheol Lee-Okada, Fumiya Takahashi, Yuto Kikuchi, Shin Morioka, Toshiyoshi Yamamoto, Katsuya Yuguchi, Miko Oikawa, Hiroaki Kajiho, Takashi Baba, Chikako Yokoyama, Ken-Ichirou Morohashi, Akira Suzuki, Takehiko Yokomizo, Takehiko Sasaki
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Adrenal lipomas are benign tumors containing ectopic adipose tissue in the adrenal gland, an organ that normally lacks both adipocytes and their progenitors. The origin of this ectopic fat remains enigmatic, and the absence of a genetic animal model has hindered its investigation. Phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P 3 ], a key signaling lipid that regulates cellular growth and differentiation, is tightly regulated by the lipid phosphatases PTEN (phosphatase and tensin homolog) and SHIP2 (SH2-containing inositol phosphatase 2). Here, we demonstrate that simultaneous loss of Pten and Ship2 in the adrenal cortex induces adrenal lipoma formation in mice. These lipomatous cells display both adipocyte-like morphology and adipocyte-specific gene expression. Lineage tracing revealed that these lipomas originate from the adrenal cortex. Mechanistically, PI(3,4,5)P 3 hyperaccumulation in the adrenal cortex activates AKT (AKT8 virus oncogene cellular homolog), leading to ectopic PPARÎł (peroxisome proliferator activated receptor gamma) expression, a key driver of adipocyte differentiation. This study suggests that the PI(3,4,5)P 3 /AKT-driven transdifferentiation of adrenocortical cells may represent a central mechanism underlying adrenal lipoma formation, thereby providing insights into lipoma pathogenesis and cellular reprogramming in vivo.
GPT-4o mini: Non-social science research article
Origami frustration and its influence on energy landscapes of origami assemblies
Shixi Zang, Tuo Zhao, Diego Misseroni, Glaucio H. Paulino
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Harnessing instabilities of multicomponent multistable structural assemblies can potentially lead to scalable and reversible functionalities, which can be enhanced by exploring frustration. For instance, standard Kresling origami cells exhibit nontunable intrinsic energy landscapes determined by their geometry and material properties, limiting their adaptability after fabrication. To overcome this limitation, we introduce frustration to enable fine-tuning of the energy landscape and resulting deformation states. By prestressing the Kresling cell by means of special springs with individual control, we induce either global or localized (i.e., crease level) frustration, which allows changing the energy barrier (cell or assembly). We investigate the mechanical behavior of frustrated Kresling assemblies, both theoretically and experimentally, under various loading and boundary conditions. Our findings reveal that changing the frustration state leads to precise control of folding sequences, enabling previously inaccessible folding paths. The proposed concept paves the way for applications in mechanical metamaterials and other fields requiring highly programmable and reconfigurable systems – e.g., prosthetic limbs.
GPT-4o mini: Non-social science research article
Restoring mitochondrial quantity and quality to reverse the Warburg effect and drive neuroblastoma differentiation
Haowen Jiang, Sarah Jane Tiche, Clifford Jiajun He, Junyan Liu, Fuyun Bian, Mohamed Jedoui, Balint Forgo, Md Tauhidul Islam, Meng Zhao, Pamela Emengo, Bo He, Yang Li, Albert M. Li, Anh T. Truong, Jestine Ho, Cathyrin Simmermaker, Yanan Yang, Meng-Ning Zhou, Zhen Hu, Katrin J. Svensson, Daniel J. Cuthbertson, Florette K. Hazard, Lei Xing, Hiroyuki Shimada, Bill Chiu, Jiangbin Ye
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Reduced mitochondrial quality and quantity in tumors is associated with dedifferentiation and increased malignancy. However, it remains unclear how to restore mitochondrial quantity and quality in tumors and whether mitochondrial restoration can drive tumor differentiation. Our study shows that restoring mitochondrial function using retinoic acid (RA) to boost mitochondrial biogenesis and a mitochondrial uncoupler to enhance respiration synergistically drives neuroblastoma differentiation and inhibits proliferation. U- 13 C-glucose/glutamine isotope tracing revealed a metabolic shift from the pentose phosphate pathway to oxidative phosphorylation, accelerating the tricarboxylic acid cycle and switching substrate preference from glutamine to glucose. These effects were abolished by electron transport chain (ETC) inhibitors or in ρ 0 cells lacking mitochondrial DNA, emphasizing the necessity of mitochondrial function for differentiation. Dietary RA and uncoupler treatment promoted tumor differentiation in an orthotopic neuroblastoma xenograft model, evidenced by neuropil production and Schwann cell recruitment. Single-cell RNA sequencing of xenografts revealed that this strategy effectively eliminated the stem cell population, promoted differentiation, and increased mitochondrial gene signatures along the differentiation trajectory, potentially improving patient outcomes. Collectively, our findings establish a mitochondria-centric therapeutic strategy for inducing tumor differentiation, suggesting that maintaining/driving differentiation in tumor requires not only ATP production but also continuous ATP consumption and sustained ETC activity.
GPT-4o mini: Non-social science research article
Could humans and AI become a new evolutionary individual?
Paul B. Rainey, Michael E. Hochberg
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GPT-4o mini: Non-social science research article
Learning stochastic processes with intrinsic noise from cross-sectional biological data
Suryanarayana Maddu, Victor ChardĂšs, Michael J. Shelley
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Inferring dynamical models from data continues to be a significant challenge in computational biology, especially given the stochastic nature of many biological processes. We explore a common scenario in omics, where statistically independent cross-sectional samples are available at a few time points, and the goal is to infer the underlying diffusion process that generated the data. Existing inference approaches often simplify or ignore noise intrinsic to the system, compromising accuracy for the sake of optimization ease. We circumvent this compromise by inferring the phase-space probability flow that shares the same time-dependent marginal distributions as the underlying stochastic process. Our approach, probability flow inference (PFI), disentangles force from intrinsic stochasticity while retaining the algorithmic ease of ordinary differential equation (ODE) inference. Analytically, we prove that for Ornstein–Uhlenbeck processes the regularized PFI formalism yields a unique solution in the limit of well-sampled distributions. In practical applications, we show that PFI enables accurate parameter and force estimation in high-dimensional stochastic reaction networks, and that it allows inference of cell differentiation dynamics with molecular noise, outperforming state-of-the-art approaches.
GPT-4o mini: Non-social science research article
Emergent depth-mechanosensing of epithelial collectives regulates cell clustering and dispersal on layered matrices
Hongsheng Yu, Amit Pathak
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During wound healing, tumor growth, and organ formation, epithelial cells migrate and cluster in layered tissue environments. Although cellular mechanosensing of adhered extracellular matrices is now well recognized, it is unclear how deeply cells sense through distant matrix layers. Since single cells can mechanosense stiff basal surfaces through soft hydrogels of <10 ÎŒm thickness, here we ask whether cellular collectives can perform such “depth-mechanosensing” through thicker matrix layers. Using a collagen-polyacrylamide double-layer hydrogel, we found that epithelial cell collectives can mechanosense basal substrates at a depth of >100 ÎŒm, assessed by cell clustering and collagen deformation. On collagen layers with stiffer basal substrates, cells initially migrate slower while performing higher collagen deformation and stiffening, resulting in reduced dispersal of epithelial clusters. These processes occur in two broad phases: cellular clustering and dynamic collagen deformation, followed by cell migration and dispersal. Using a cell-populated collagen-polyacrylamide computational model, we show that stiffer basal substrates enable higher collagen deformation, which in turn extends the clustering phase of epithelial cells and reduces their dispersal. Disruption of collective collagen deformation, by either α-catenin depletion or myosin-II inhibition, disables the depth-mechanosensitive differences in epithelial responses between soft and stiff basal substrates. These findings suggest that depth-mechanosensing is an emergent property that arises from collective collagen deformation caused by epithelial cell clusters. This work broadens the conventional understanding of epithelial mechanosensing from immediate surfaces to underlying basal matrices, providing insights relevant to tissue contexts with layers of varying stiffness, such as wound healing and tumor invasion.
GPT-4o mini: Non-social science research article
Cystic fibrosis: Correction of a fatal disease
Jeffrey M. Friedman
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The 2025 Lasker~DeBakey Clinical Medical Research Award has been given to Michael Welsh, JesĂșs (Tito) GonzĂĄlez, and Paul Negulescu for their key roles in developing a novel treatment for cystic fibrosis (CF)—a three-drug combination that saves the lives of people with this lethal genetic disease [D. Keating et al. , N. Engl. J. Med. 379, 1612–1620 (2018)]. The disease is caused by mutations that disrupt the function of a gene known as CF Transmembrane Conductance Regulator which encodes a chloride channel expressed in epithelial cells including the lung. Collectively the three recipients were responsible for the development of novel high-throughput drug screens that led to the development of the new drugs. Welsh is a pulmonologist who played a key role in understanding the physiology and pathophysiology of the disease. GonzĂĄlez is a physical organic chemist who developed a novel technology that enabled robust high-throughput screens for drugs that correct the channel defects. Negulescu led a group of extremely talented biologists, chemists, and physicians who built on these advances to develop novel three-drug combinations that have miraculous benefits for the majority of afflicted patients. This advance represents a true milestone in medicine and fulfills a dream of research scientists and families—the conversion of a fatal disease into a fully treatable one. It is also a stunning example of the power of medical research to save people’s lives.
GPT-4o mini: Non-social science research article
Single-cell transcriptome combined with genetic tracing reveals a roadmap of fibrosis formation during proliferative vitreoretinopathy
Mengyu Liao, Zhisheng Ye, Yumeng Zhao, Jiaying Nan, Yuming Liu, Xueming Yao, Tianjing Yang, Ju Guo, Xin Jin, Hong Zhang, Caiyun You, Heping Xu, Jinguo Yu, Yupeng Chen, Xiaohong Wang, Hua Yan
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Ocular fibrosis, a severe consequence of excessive retinal wound healing, can lead to vision loss following retinal injury. Proliferative vitreoretinopathy (PVR), a common form of ocular fibrosis, is a major cause of blindness, characterized by the formation of extensive fibrous proliferative membranes. Understanding the cellular origins of PVR-associated fibroblasts (PAFs) is essential to decipher the mechanisms of ocular wound healing. In this study, we combined single-cell transcriptomics with genetic lineage tracing to map the contributions of retinal pigment epithelial (RPE) cells, immune cells, and MĂŒller cells to disease progression. RPE cells were found to constitute the largest fraction of cells within PVR lesions, transitioning through metabolic, proliferative, and epithelial-to-mesenchymal transition stages during their conversion to PAFs. These cells exhibited remarkable plasticity and heterogeneity. Notably, Pdgfrb + RPE cells demonstrated significant morphological plasticity, transitioning toward a fibroblast-like phenotype, while macrophage-like RPE cells acquired inflammation-related functions post-PVR. Cell communication network analysis identified Thbs1 (encoding TSP-1) as a key hub gene driving RPE cell fate transitions during PVR. Importantly, therapeutic antibodies targeting TSP-1 significantly mitigated PVR progression. This study provides a detailed roadmap of fibrosis formation during ocular wound healing and highlights the therapeutic potential of targeting TSP-1 in the management of PVR.
GPT-4o mini: Non-social science research article
Structure of a polymorphic repeat at the CACNA1C schizophrenia locus
Raquel Moya, Xiaohan Wang, Richard W. Tsien, Matthew T. Maurano
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Genetic variation within intron 3 of the CACNA1C calcium channel gene is associated with schizophrenia and other neuropsychiatric disorders, but analysis of the causal variants and their effect is complicated by a nearby variable-number tandem repeat (VNTR). Here, we explored the structure and population variability of the CACNA1C intron 3 VNTR using 155 long-read genome assemblies from 78 diverse individuals. Based on sequence differences among repeat units, we clustered individual sequences into 7 VNTR structural alleles called Types. Three Types were related through large duplications, but the other Types diverged much earlier such that only 12 repeat units at the 5â€Č end of the VNTR were shared across most Types. The most diverged Types were rare and present only in individuals with African ancestry, but a multiallelic structural polymorphism was present across populations at different frequencies, consistent with expansion of the VNTR preceding the emergence of early hominins. We demonstrated that this polymorphism was in complete linkage disequilibrium with fine-mapped schizophrenia variants from genome-wide association studies (GWAS) and that this risk haplotype was associated with decreased CACNA1C gene expression in the brain. Our work suggests that sequence variation within a human-specific VNTR affects gene expression and provides a detailed characterization of new alleles at a flagship neuropsychiatric GWAS locus.
GPT-4o mini: Non-social science research article
Modeling human retinal ganglion cell axonal outgrowth, development, and pathology using pluripotent stem cell–based microfluidic platforms
CĂĄtia Gomes, Kang-Chieh Huang, Sailee S. Lavekar, Jade Harkin, Carson G. Prosser, Yue Fang, Claire Kalem, Adrian Oblak, Chi Zhang, Jason S. Meyer
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Retinal ganglion cells (RGCs) are highly compartmentalized neurons whose long axons serve as the sole connection between the eye and the brain. In both injury and disease, RGC degeneration occurs in a similarly compartmentalized manner, with distinct molecular and cellular responses in the axonal and somatodendritic regions. The goal of this study was to establish a microfluidic-based platform to investigate RGC compartmentalization in both health and disease states. Human pluripotent stem cell (hPSC)-derived RGCs were seeded into microfluidic devices that allow physical separation of axons from the somatodendritic compartment, enabling precise study of each region. Initial experiments characterized axonal outgrowth and the specific segregation of axons and dendrites. We then examined compartment-specific phenotypes in RGCs carrying the OPTN(E50K) glaucoma mutation compared to isogenic controls, including differences in axonal growth and axonal transport efficiency, with OPTN-mutant RGCs showing reduced axon length and slower transport, hallmarks of neurodegeneration. Axonal RNA-seq analyses revealed transcriptomic alterations related to disease states, including specific transcriptomic changes along OPTN axons. To assess glial influences on axonal health, we developed models with astrocytes localized specifically to the proximal axonal compartment and modulated their disease states to simulate pathological conditions. Importantly, the induction of diseased astrocytes solely along proximal axons triggered compartment-specific neurodegenerative changes in RGCs. Collectively, this platform represents a successful recapitulation of the spatially distinct features of hPSC-derived RGCs under both healthy and disease conditions, offering a physiologically relevant, human-specific in vitro system to study neuronal development, axon–glia interactions, and mechanisms underlying neurodegeneration.
GPT-4o mini: Non-social science research article
3D cryoimaging of cell-mediated cholesterol crystal clearance in human atherosclerotic lesions
Jenny Capua-Shenkar, Antonia Kaestner, Katya Rechav, Vlad Brumfeld, Ifat Kaplan-Ashiri, Neta Varsano, Ori Avinoam, Chen Speter, Moshe Halak, Howard Kruth, Lia Addadi
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We applied micro-computed tomography, high-resolution cryo-scanning electron microscopy (SEM) combined with cathodoluminescence, and cryo-focused ion beam Milling-SEM to perform three-dimensional imaging of human atherosclerotic tissues with tens of nanometers resolution, under hydrated, near-native conditions with minimal sample processing. The same technology was applied to cultured macrophages exposed to cholesterol crystals, and the observations made on the macrophages were compared to those made on the pathological tissue. We observed that cholesterol crystal digestion and, eventually, cholesterol crystal clearance occurs in the advanced human plaques through cellular processing. Our findings suggest that cholesterol crystal disassembly occurs through the esterification of crystalline cholesterol to cholesteryl-ester in isolated volumes, whereby the ester aggregates into intra- and extracellular pools. The hypothesis is supported by the close similarity of the processes imaged in the human tissue and in the macrophages and is in agreement with earlier biochemical studies performed on cultured macrophages.
GPT-4o mini: Non-social science research article
Long-term evolutionary persistence of a cryptic color polymorphism in frogs
Sandra Goutte, Stéphane Boissinot
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Color polymorphism can influence the evolutionary fate of cryptic species because it increases populations’ chances of survival in heterogenous or variable environments. Yet, little is known about the molecular and evolutionary mechanisms underlying the persistence of cryptic color polymorphisms, or the impact these polymorphisms have on the macroevolutionary dynamics of lineages. Here, we examine the evolutionary history of the most widespread cryptic color polymorphism in anurans, involving green and brown morphs. Using an order-scale comparative analysis, we show that these morphs can coexist within species over long evolutionary periods and that polymorphic lineages switch habitat more frequently and have greater diversification rates than other groups. We then identify the locus responsible for the green/brown polymorphism in a group of African grass frogs, and demonstrate that it evolves under long-term balancing selection, resulting in trans-specific polymorphism. These results provide a microevolutionary mechanism for the long-term persistence of multiple color morphs within species observed at a macroevolutionary scale. This study underscores the importance of cryptic color polymorphism in the ecology and evolution of anurans, and provides a framework for future research on the genetic architecture and selective forces underlying cryptic coloration traits.
GPT-4o mini: Non-social science research article
Ice gliding diatoms establish record-low temperature limits for motility in a eukaryotic cell
Qing Zhang, Hope T. Leng, Hongquan Li, Kevin R. Arrigo, Manu Prakash
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Despite periods of permanent darkness and extensive ice coverage in polar environments, photosynthetic ice diatoms display a remarkable capability of living inside the ice matrix. How these organisms navigate such hostile conditions with limited light and extreme cold remains unknown. Using a custom subzero temperature microscope during an Arctic expedition, we present the finding of motility at record-low temperatures in a Eukaryotic cell. By characterizing the gliding motility of several ice diatom species, collected from ice cores in the Chukchi Sea, we record that they retain motility at temperatures as low as − 15 ° C. Remarkably, ice diatoms can glide on ice substrates, a capability absent in temperate diatoms of the same genus. This unique ability arises from adaptations in extracellular mucilage that allow ice diatoms to adhere to ice, essential for gliding. Even on glass substrates where both cell types retain motility at freezing temperatures, ice diatoms move an order of magnitude faster, with their optimal motility shifting toward colder temperatures. Combining field and laboratory experiments with thermo-hydrodynamic modeling, we reveal adaptive strategies that enable gliding motility in cold environments. These strategies involve increasing internal energy efficiency with minimal changes in heat capacity and activation enthalpy, and reducing external dissipation by minimizing the temperature sensitivity of mucilage viscosity. The finding of diatoms’ ice gliding motility opens new routes for understanding their survival within a harsh ecological niche and their migratory responses to environmental changes. Our work highlights the robust adaptability of ice diatoms in one of Earth’s most extreme settings.
GPT-4o mini: Non-social science research article
Climate warming is expanding dengue burden in the Americas and Asia
Marissa L. Childs, Kelsey Lyberger, Mallory J. Harris, Marshall Burke, Erin A. Mordecai
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Climate change is expected to pose significant threats to public health, particularly vector-borne diseases. Despite dramatic recent increases in dengue that many anecdotally connect with climate change, the effect of anthropogenic climate change on dengue remains poorly quantified. To assess this link, we assembled local-level data on dengue across 21 countries in Asia and the Americas. We found a nonlinear relationship between temperature and dengue incidence with the largest impact of warming at lower temperatures, peak incidence at 27.8°C, and a decline at higher temperatures. Using this inferred temperature response, we estimate 18% (95% CI: 11 to 27%) of historical dengue incidence on average across our study countries is attributable to anthropogenic warming. Future warming could further increase incidence by 49% (95% CI: 16 to 136%) to 76% (95% CI: 27 to 239%) by midcentury for low or high emissions scenarios, respectively, with cooler regions projected to double in incidence due to warming while other currently hot regions experience little impact or even small declines. Under the highest emissions scenario, we estimate that 262 million people are currently living in places in these 21 countries where dengue incidence is expected to more than double due to climate change by midcentury. These insights highlight the major impacts of anthropogenic warming on dengue burden across most of its endemic range, providing a foundation for public health planning and the development of strategies to mitigate future risks due to climate change.
GPT-4o mini: Non-social science research article
The Lasker~Koshland Special Achievement Award in Medical Science awarded to Lucy Shapiro
Leslie B. Vosshall
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Scientists can contribute to society in numerous ways. Some scientists discover new biological principles and found entirely new fields. Some scientists are inspiring mentors and create the next generation of inclusive lab leaders. Some scientists are entrepreneurs who develop clinically effective therapeutics. Some scientists are trusted advisors to government and pharmaceutical companies. Some scientists are visionary institutional leaders who build new departments. From this menu of activities, most scientists select two or at most three. It is exceedingly rare for a single scientist to excel in all of these areas, consistently, over the course of a career. Lucy Shapiro is this extraordinary scientist. She founded the field of bacterial cell biology and trained the next generation of microbiologists, launched biotech companies to develop new antifungal drugs, served as an unofficial advisor to two presidential administrations and numerous companies, institutions, and foundations, and built and led successful academic departments. The 2025 Lasker~Koshland Special Achievement Award in Medical Science is awarded to Lucy Shapiro “for a 55-y career in biomedical science—honored for discovering how bacteria coordinate their genetic logic in time and space to generate distinct daughter cells; for founding Stanford’s distinguished Department of Developmental Biology; and for exemplary leadership at the national level.”
GPT-4o mini: Non-social science research article
Ecosystem consequences of a nitrogen-fixing proto-organelle
Jane C. Marks, Michael C. Zampini, Raina Fitzpatrick, Saeed H. Kariunga, Augustine Sitati, Ty J. Samo, Peter K. Weber, Steven Thomas, Bruce A. Hungate, Christina E. Ramon, Michael Wulf, Victor O. Leshyk, Egbert Schwartz, Jennifer Pett-Ridge, Mary E. Power
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Microscale symbioses can be critical to ecosystem functions, but the mechanisms of these interactions in nature are often cryptic. Here, we use a combination of stable isotope imaging and tracing to reveal carbon (C) and nitrogen (N) exchanges among three symbiotic primary producers that fuel a salmon-bearing river food web. Bulk isotope analysis, nanoSIMS (secondary ion mass spectrometry) isotope imaging, and density centrifugation for quantitative stable isotope probing enabled quantification of organism-specific C- and N-fixation rates from the subcellular scale to the ecosystem. After winters with riverbed-scouring floods, the macroalga Cladophora glomerata uses nutrients in spring runoff to grow streamers up to 10 m long. During summer flow recession, riverine N concentrations wane and Cladophora becomes densely epiphytized by three species of Epithemia , diatoms with N-fixing endosymbionts (proto-organelles) descended from a free-living Crocosphaera cyanobacterium. Over summertime epiphyte succession on Cladophora , N-fixation rates increased as Epithemia spp. became dominant, Cladophora C-fixation declined to near zero, and Epithemia C-fixation increased. Carbon transfer to caddisflies grazing on Cladophora with high densities of Epithemia was 10-fold higher than C transfer to caddisflies grazing Cladophora with low Epithemia loads. In response to demand for N, Epithemia allocates high levels of newly fixed C to its endosymbiont. Consequently, these endosymbionts have the highest rates of C and N accumulation of any taxon in this tripartite symbiosis during the biologically productive season and can produce one of the highest areal rates of N-fixation reported in any river ecosystem.
GPT-4o mini: Non-social science research article
CpG-A induces liquid–liquid phase separation of HMGB1 to activate the RAGE-mediated inflammatory pathway
Kaihui Peng, Gaohong Fu, Long Chen, Jiazhi Xie, Kai Bao, Jin-Ping Li, Shi-Zhong Luo
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High-mobility group box protein 1 (HMGB1) is a chromatin-associated nonhistone protein widely distributed in the nucleus of eukaryotic cells. It is transported extracellularly as a proinflammatory mediator or late warning protein to induce immune and inflammatory reactions upon stimuli such as microbial infection. Here, we have found that HMGB1 directly interacts with bacterial DNA analogue CpG-A in the extracellular environment to undergo liquid–liquid phase separation (LLPS) via its positively charged DNA-binding domain. We have demonstrated that the receptor for advanced glycosylation end products (RAGE) responds to stimulation of the extracellular HMGB1-CpG-A complex and triggers phase separation of the downstream adaptor protein, Src76kDa structural domain leukocyte protein (SLP76), which promotes activation of the MAPK pathway and release of inflammatory cytokines. These results not only designate that LLPS serves as a gain-of-function mechanism involved in the axis of DNA-HMGB1 stimulated RAGE-SLP76 signaling pathway but also provide evidence that the activity of HMGB1 is regulated by LLPS, highly relevant to immune responses of inflammatory cells toward microbial infection. Especially, the finding that the intracellular SLP76 forms condensates with the cytosol domain of RAGE may represent a general downstream phenomenon when an inflammatory cell membrane receptor is activated.
GPT-4o mini: Non-social science research article
Integrated Ising model with global inhibition for decision-making
Olga Tapinova, Tal Finkelman, Tamar Reitich-Stolero, Rony Paz, Assaf Tal, Nir S. Gov
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Humans and other organisms make decisions choosing between different options, with the aim of maximizing the reward and minimizing the cost. The main theoretical framework for modeling the decision-making process has been based on the highly successful drift-diffusion model, which is a simple tool for explaining many aspects of this process. However, recent observations challenge this model. It was found that inhibitory tone increases during situations of difficult discrimination tasks, but the origin of this phenomenon is not understood. Motivated by this observation, we extend a recently developed model for directional decision-making of animals moving in real space. We introduce an integrated Ising-type model that includes global inhibition and use it to describe two-choice decision-making. This model can explain how the brain may utilize inhibition to improve its decision-making accuracy. Compared to experimental results, this model suggests that the regime of the brain’s decision-making activity is in proximity to a critical transition line between the ordered and disordered phases. Within the model, this observation can be explained by noting that this critical region has unique dynamics that give rise to advantageous properties for the decision-making process.
GPT-4o mini: Non-social science research article
Extracellular salt bridge networks around S4 implicated in HCN channel gating and heart disease
Kaei Ryu, Go Kasuya, Koichi Nakajo
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The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a voltage-gated cation channel that plays a crucial role in regulating cellular excitability, especially in cardiac pacemaker cells and neurons. Its dysregulation is linked to heart diseases such as bradycardia and neurological disorders such as epilepsy, Parkinson’s disease, and neuropathic pain. Structural and functional studies have revealed that the S4 voltage sensor of the HCN channel moves downward during hyperpolarization. Recent structural studies of HCN channels have shown that the extracellular portion of the S4 segment is approximately three helical turns longer than that of voltage-gated K + (Kv) channels. However, whether this extended extracellular part of S4 plays a functional role in gating is still unknown. In this study, utilizing the available HCN4 channel structures, we examined the formation of salt bridges in the extracellular part of S4 with the S5 segment and the S1-S2 linker. Results from charge-swapped mutants and double cysteine mutants suggested that sequential, stepwise salt bridge formation involving the extracellular positively charged amino acids of S4 plays a role in the voltage-dependent gating of HCN channels. Furthermore, we applied voltage clamp fluorometry to confirm that the extracellular salt bridge network affects the S4 movement. This extracellular S4 portion includes disease-related arginine residues, R375 and R378. Our results suggest that disruption of salt bridge formation may perturb the smooth transition of S4 movement and cause HCN channel dysfunction.
GPT-4o mini: Non-social science research article
Directed evolution of a plant Rubisco chaperone with altered client recognition
Siyu Li, ByungUk Lee, Yichong Lao, Sirawit Lertwiriyapiti, Xuhui Huang, Tina Wang
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Improving the Calvin–Benson–Bassham cycle enzyme Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) has the potential to increase crop productivity. However, the selectivity of the chaperones mediating Rubisco assembly in vascular plants toward their cognate Rubisco presents a substantive roadblock to both Rubisco protein engineering and transgenic expression of heterologous Rubisco orthologs, both of which necessitate changes to the Rubisco sequence. Here, we ask whether a plant Rubisco chaperone can be reprogrammed by directed evolution to accommodate a nonnative client. We developed a selection strategy to assess Rubisco assembly factor activity in high-throughput and used this selection to identify mutants of the chaperone Raf1 from Arabidopsis thaliana ( At Raf1) that assemble Nicotiana tabacum Rubisco, for which wild-type At Raf1 has minimal activity. We show that directed evolution can generate At Raf1 variants that enable significantly increased N. tabacum Rubisco assembly compared to wild-type At Raf1. Evaluation of evolved At Raf1s indicates that they retain the ability to assemble their native client and can assemble other dicot Rubisco orthologs that they were not evolved to recognize. This work may provide a strategy for addressing the constraints chaperone selectivity impose upon Rubisco-centric efforts to improve plant photosynthesis.
GPT-4o mini: Non-social science research article
Ultracold cryogenic TEM with liquid helium and high stability
Emily Rennich, Suk Hyun Sung, Nishkarsh Agarwal, Maya Gates, Robert Kerns, Robert Hovden, Ismail El Baggari
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Cryogenic transmission electron microscopy has revolutionized structural biology and materials science. To image below liquid nitrogen temperatures, various liquid helium stages have been constructed but have proven to be complex and unstable, making high-resolution imaging challenging. This problem is even more pronounced in side-entry specimen holders common on modern transmission electron microscopes. Here, we introduce an ultracold liquid helium transmission electron microscope side-entry specimen holder, featuring continuous cryogen flow and vibration decoupling. This instrument is compatible with modern aberration-corrected microscopes and achieves sub-25 K base temperature, ± 2 mK thermal stability over many hours, and atomic resolution—setting the stage for a new era of cryogenic electron microscopy.
GPT-4o mini: Non-social science research article
Adaptation of seed dormancy to maternal climate occurs via intergenerational transport of abscisic acid
Xiaochao Chen, William Bezodis, Pablo GonzĂĄlez-SuĂĄrez, Vanda Knitlhoffer, Andrew Goldson, Ashleigh Lister, Iain Macaulay, Steven Penfield
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How or whether organisms can inherit parental adaptations to the prevailing environment is a major topic in biology. In plants, seed traits such as size, yield, and dormancy are all affected by the environment during reproduction, but whether developing progeny sense temperature within the fruit or whether seasonal climate information is inherited intergenerationally from the parents remains unclear. In this study, we use intergenerational single-nucleus omics to understand the mechanisms underlying the effects of seasonal temperature changes in fruits containing developing seeds of the next generation. We show that the sensing of temperature takes place specifically in maternal fruit tissues and that mothers preadapt their progeny to maternal temperature through the intergenerational flux of the hormone ABA to the zygote itself where it is sensed to affect dormancy. We conclude that mothers can control filial traits via direct transfer of hormones to progeny and propose that this is an important mechanism by which populations can rapidly adapt to environmental change.
GPT-4o mini: Non-social science research article
Microglia-to-neuron signaling links APOE4 and inflammation to enhanced neuronal lipid metabolism and network activity
Ana P. Verduzco Espinoza, Na Na, Loraine Campanati, Priscilla Ngo, Kristin K. Baldwin, Hollis T. Cline
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Microglia regulate neuronal circuit plasticity. Disrupting their homeostatic function has detrimental effects on neuronal circuit health. Neuroinflammation contributes to the onset and progression of neurodegenerative diseases, including Alzheimer’s disease (AD), with several microglial activation genes linked to increased risk for these conditions. Inflammatory microglia alter neuronal excitability, inducing metabolic strain. Interestingly, expression of APOE4 , the strongest genetic risk factor for AD, affects both microglial activation and neuronal excitability, highlighting the interplay between lipid metabolism, inflammation, and neuronal function. It remains unclear how microglial inflammatory state is conveyed to neurons to affect circuit function and whether APOE4 expression alters this intercellular communication. Here, we use a reductionist model of human iPSC-derived microglial and neuronal monocultures to dissect how the APOE genotype in each cell type independently contributes to microglial regulation of neuronal activity during inflammation. Conditioned media (CM) from LPS-stimulated microglia increased neuronal network activity, assessed by calcium imaging, with APOE4 microglial CM driving greater neuronal activity than APOE3 CM. Both APOE3 and APOE4 neurons increase network activity in response to CM treatments, while APOE4 neurons uniquely increase presynaptic puncta in response to APOE4 microglial CM. CM-derived exosomes from LPS-stimulated microglia can mediate increases to network activity. Finally, increased network activity is accompanied by increased lipid droplet (LD) metabolism, and blocking LD metabolism abolishes network activity. These findings illuminate how microglia-to-neuron communication drives inflammation-induced changes in neuronal circuit function, demonstrate a role for neuronal LDs in network activity, and support a potential mechanism through which APOE4 increases neuronal excitability.
GPT-4o mini: Non-social science research article
DNA polymerase α-primase can function as a translesion DNA polymerase
Ryan Mayle, Roxana Georgescu, Michael E. O’Donnell
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Replication of cellular chromosomes requires a primase to generate short RNA primers to initiate genomic replication. While bacterial and archaeal primase generate short RNA primers, the eukaryotic primase, Polα-primase, contains both RNA primase and DNA polymerase (Pol) subunits that function together to form a >20 base hybrid RNA–DNA primer. Interestingly, the DNA Pol1 subunit of Polα lacks a 3’-5’ proofreading exonuclease, contrary to the high-fidelity normally associated with DNA replication. However, PolÎŽ and PolΔ synthesize the majority of the eukaryotic genome, and both contain 3’-5’ exonuclease activity for high fidelity. Nonetheless, even the small amount of DNA produced by Pol1 in each of the many RNA/DNA primers during chromosome replication adds up to tens of millions of nucleotides in a human genome. Thus, it has been a longstanding question why Pol1 lacks a proofreading exonuclease. We show here that Polα is uniquely capable of traversing common oxidized or hydrolyzed template nucleotides and propose that Polα evolved to bypass these common template lesions when they are encountered during chromosome replication. Additionally, we show a unique ability of replication factor C (RFC) to stimulate PolÎŽ lesion bypass, independent of its sliding clamp. This suggests that there may be a coordination between PolÎŽ and RFC that does not involve RFC loading of PCNA.
GPT-4o mini: Non-social science research article
Sensitization of cancer cells to DNA-damaging agents by expression of the REV1 C-terminal domain: Implications for chemotherapy
Ke Bian, Charley C. Gruber, Emine Byers, Paul Leclerc, Michael T. Hemann, Graham C. Walker
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The mutagenic translesion synthesis (TLS) pathway, which is critically dependent on REV1’s ability to recruit inserter TLS polymerases and the POLζ extender polymerase, enables cancer cells to bypass DNA lesions while introducing mutations that likely contribute to the development of chemotherapy resistance and secondary malignancies. Targeting this pathway represents a promising therapeutic strategy. Here, we demonstrate that the expression of the C-terminal domain (CTD) of human REV1, a ca. 100 amino acid scaffold essential for TLS polymerase interactions, disrupts REV1/POLζ-dependent TLS in mammalian cells. Inducible expression of REV1-CTD in multiple human and murine cancer cell lines sensitizes cells to DNA-damaging agents such as cisplatin, benzo[a]pyrene diol epoxide, and methyl methanesulfonate, without intrinsic cytotoxicity. REV1-CTD expression increases genomic instability, decreases mutagenesis, and enhances G2 arrest following genotoxic stress. Mutational disruption of the CTD’s interaction interfaces abrogates these effects, confirming a dominant-negative mechanism via sequestration of TLS components. In a xenograft mouse model, REV1-CTD expression markedly enhances cisplatin efficacy, significantly reducing tumor burden. These findings establish the REV1-CTD as an effective dominant-negative inhibitor of TLS and support its development as a therapeutic agent delivered to cancer cells to enhance the efficacy of genotoxic chemotherapy.
GPT-4o mini: Non-social science research article
Is Nav1.8-specific inhibition the only path? Preferential Nav blockers offer a compelling alternative
Bingbing Xiang, Chaoyi Deng, Han Yang, Wensheng Zhang
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GPT-4o mini: Non-social science research article
ApoD mediates age-associated increase in vulnerability to influenza virus infection
Zhimin Jiang, Wenliang Pan, Yu Chen, Dongliang Zhou, Shuning Ren, Qi Tong, Litao Liu, Honglei Sun, Yipeng Sun, Yuhai Bi, Dayan Wang, Lu Lu, Juan Pu, Kin-Chow Chang, Jinhua Liu
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Influenza A virus (IAV) infection causes significantly greater morbidity and mortality in the elderly population, but the molecular mechanisms in the aging process responsible for severe infection remain unclear. In this study, we found that increased severity in IAV infection and reduced innate immune response correlated with extensive mitophagy in senescent human cells and in the lung of aged mice. Apolipoprotein D (ApoD) was identified as strongly elevated in the lungs and sera of aged human (>65 y old) and mouse (>21 mo old). ApoD was able to localize to mitochondria and interact, through its WXXI motif in the LC3B-Interacting Region domain, with LC3B to trigger mitophagy during IAV infection, in a PINK1 pathway independent manner, which attenuated type I interferon response and promoted virus replication. ApoD deficiency, on the other hand, protected older mice from severe influenza and improved survival. Likewise, depletion of senescent cells by ABT-263, a senolytic compound, in aged mice lowered ApoD level and restored innate immune antiviral response, limiting virus propagation and associated pulmonary damage. Thus, age-induced ApoD drives IAV-mediated mitophagy, and promotes virus replication and infection severity, and is therefore a promising target for inhibition to improve disease outcome in older patients.
GPT-4o mini: Non-social science research article
Female membrane proteins regulate postmating ovulation in Drosophila melanogaster by ovulin-dependent and -independent pathways
Mengye Yang, Melissa A. White, Geoffrey D. Findlay, Ryan C. Vignogna, Jennifer Apger-McGlaughon, Nathan L. Clark, Jae Young Choi, J. Christopher Fromme, Mariana F. Wolfner
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Ovulation is an intricate process that is essential for reproductive success. In Drosophila melanogaster , ovulation increases after mating. This increase is initiated by the male seminal fluid protein ovulin and is executed by female pathways, including octopamine (OA) neuronal signaling. Despite OA signaling’s central role in ovulation regulation, the broader molecular landscape underlying female control of ovulation remains poorly understood. Here, using ovulin as a probe, we performed evolutionary rate covariation and AlphaFold-Multimer prediction screens to identify candidate female ovulation-regulating proteins. Ovulation assays performed on knockdowns or mutants of identified membrane-protein candidates revealed seven important female ovulation regulators: Lgr3, GabaÎČR1, SIFaR, mthl9, Smog, Cirl, and CG6067. Lgr3 and GabaÎČR1 function in an ovulin-dependent manner, while SIFaR and mthl9 regulate ovulation independently of ovulin. For proteins with known nervous system expression, we examined their requirement in OA neurons and their expression in female reproductive tract neurons. Tissue-specific knockdown revealed that Lgr3, GabaÎČR1, SIFaR, and CG6067 act in OA neurons to influence ovulation, highlighting OA neurons as a key signaling hub. Additionally, Lgr3, GabaÎČR1, SIFaR, Smog, and Cirl are expressed in OA neurons innervating the reproductive tract, suggesting a potential local function. Finally, we identified evidence of recurrent positive selection having acted on residues within Smog’s ligand binding region, which is interesting in light of ovulin’s rapid evolution. Together, these findings significantly expand our understanding of the molecular networks regulating ovulation following mating in Drosophila .
GPT-4o mini: Non-social science research article
Wild bats hunt insects faster under lit conditions by integrating acoustic and visual information
Laura Stidsholt, Mara Zebele, Carolin Scholz, Christian C. Voigt
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Animals can improve their decision-making abilities by integrating information from multiple senses, which is especially beneficial when living in fluctuating environments. However, understanding how wild predators may use multimodal sensing when hunting prey in split-second interactions remains largely unexplored. As nocturnal hunters, bats rely on echolocation to navigate and to locate evasive prey, yet they have retained functional vision, despite the associated costs. We therefore hypothesized that bats use vision to enhance sensory redundancy when commuting and tracking small insects. To test this, we equipped 21 wild common noctule bats ( Nyctalus noctula ) with high-resolution light, sound, and motion sensor loggers and measured their echolocation and movements while commuting and foraging in both dark and lit environments. When commuting, the bats maintained consistent echolocation sampling across light levels. However, when tracking prey in illuminated environments, the bats emitted calls with half the rate and with 7 dB higher call levels compared to in dark conditions, but at much faster approach speeds (from 5.2 in darkness to 7.9 m/s in lit conditions). This suggests that, in illuminated environments, hunting bats integrate acoustic and visual information, resulting in more efficient approaches to prey. Our findings demonstrate how a wild sensory specialist predator uses multimodal sensing to hunt efficiently in highly dynamic resource landscapes.
GPT-4o mini: Non-social science research article
Making sense of low-complexity domains: The 2025 Lasker Basic Science Award
William G. Kaelin
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Up to 10 to 20% of the proteome contains regions with much lower amino acid diversity than would be expected by chance. This year’s Lasker Basic Science Award is given to Steven McKnight and Dirk Görlich for their pioneering work on such low-complexity domains (LCDs). They showed, using a variety of elegant approaches, that such LCDs can form homotypic and heterotypic interactions that lead to reversible phase separations in cells. These phase separations, which in the laboratory manifest as hydrogels and in cells as membrane free structures (liquid condensates) such as P bodies and stress granules, form hubs for molecular processes such as transcription and messenger RNA (mRNA) splicing and also underlie the selectivity of nuclear pore complexes (NPCs), which act a barriers to large molecules unless they are escorted by specific LCD containing nuclear transporters that interact with LCD containing nucleoporins within NPC channels. Naturally occurring LCD mutations linked to neurodegeneration and other diseases cause the formation of irreversible (rather than reversible) LCD polymers, resulting in insoluble, amyloid-like, fibrils, underscoring the critical importance of these domains.
GPT-4o mini: Non-social science research article
Evolution of cross-tolerance to metals in yeast
Anna L. Bazzicalupo, Penelope C. Kahn, Eully Ao, Joel Campbell, Sarah P. Otto
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Organisms often face multiple selective pressures simultaneously (e.g., mine tailings with multiple heavy metal contaminants), yet we know little about when adaptation to one stressor provides cross-tolerance or cross-intolerance to other stressors. To explore the potential for cross-tolerance, we adapted Saccharomyces cerevisiae to high concentrations of six single metals in a short-term evolutionary rescue experiment. We then measured cross-tolerance of each metal-adapted line to the other five metals. We tested three predictors for the degree of cross-tolerance, based on similarity in 1) the physiochemical properties of each metal pair, 2) the overlap in genes known to impact tolerance to both metals, and 3) their co-occurrence in the environment. None of these predictors explained significant variation in cross-tolerance. Instead, the strongest predictor was the metal in which adaptation occurred: Cobalt-adapted lines performed well in most metals (generalists) while manganese-adapted lines typically performed poorly (specialists). To determine the genetic basis, we sequenced the genomes of 109 metal-adapted lines. Broader cross-tolerance characterized lines bearing mutations affecting phosphorus metabolism, with three genes related to phosphate metabolism bearing several independent mutations ( PHO84 , SIW14 , VTC4 ). Thus, while a genome-wide analysis failed to predict cross-tolerance, a subset of genes facilitated growth in multiple metals. We also observed two “mutator” lines (both in manganese) and report evidence that cadmium, cobalt, and manganese altered the mutation spectrum. While it is challenging to predict how evolutionary adaptation to one stressor will impact tolerance to other stresses, our work helps reveal the environments and pathways that contribute to cross-tolerance among metals.
GPT-4o mini: Non-social science research article
Wild, scenic, and toxic: Recent degradation of an iconic Arctic watershed with permafrost thaw
Patrick F. Sullivan, Roman J. Dial, David J. Cooper, Charles Diamond, Christopher J. Tino, Daniel D. Gregory, Russell E. Wong, Timothy W. Lyons
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The streams of Alaska’s Brooks Range lie within a vast (~14M ha) tract of protected wilderness and have long supported both resident and anadromous fish. However, dozens of historically clear streams have recently turned orange and turbid. Thawing permafrost is thought to have exposed sulfide minerals to weathering, delivering iron and other potentially toxic metals to aquatic ecosystems. Here, we report stream water metal concentrations throughout the federally designated Wild and Scenic Salmon River watershed and compare them with United States Environmental Protection Agency (EPA) chronic (4-d) exposure thresholds for toxicity to aquatic life. The main stem of the Salmon had elevated SO 4 2− concentrations and elevated SO 4 2− : Ca relative to a predisturbance baseline for most of its length, consistent with increased sulfide mineral weathering. Most of the tributaries also had elevated SO 4 2− concentrations and elevated SO 4 2− : Ca, especially those in the upper watershed. The Salmon River mainstem consistently exceeded EPA chronic exposure thresholds for total recoverable iron, total recoverable aluminum, and dissolved cadmium from its first major tributary to its mouth. Nine of ten major tributaries that we sampled exceeded EPA thresholds for at least one metal on at least one of three sampling dates. Our findings indicate that habitat quality for resident and anadromous fish has been severely degraded in the Salmon River watershed. Loss of important spawning habitat in the Salmon and many other streams in the region might help explain a recent crash in chum salmon returns, which local communities depend upon for commercial and subsistence harvest.
GPT-4o mini: Non-social science research article
Microglia contribute to bipolar depression through Serinc2-dependent phospholipid synthesis
Ying-Han Wang, Chong-Lei Fu, Lin-Bo Chen, Chu-Yi Zhang, Jian-Shan Chen, Qiao-Ming Zhang, Yirui Liang, Rui-Lan Yang, Yu Li, Ya-Ni Zhang, Yi-Nuo Han, Zhen-Liang Yuan, Yi-Ni Chen, Haimei Li, Yanmeng Pan, Shaohua Hu, Ming Li, Li-Ping Cao, Jun Yao
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Although clinical research has revealed microglia-related inflammatory and immune responses in bipolar disorder (BD) patient brains, it remains unclear how microglia contribute to the pathogenesis of BD. Here, we demonstrated that Serinc2 is associated with susceptibility to BD and showed a reduced expression in BDII patient plasma, which correlated with the disease severity. Using induced pluripotent stem cell (iPSC) models of sporadic and familial BDII patients, we found that Serinc2 expression showed deficits in iPSC-derived microglia-like cells, resulting in decreased synaptic pruning. Further, combining the microglia-specific Serinc2-deficient mouse and iPSC-microglia models, we found that microglial Serinc2 deficits functioned through attenuating the synthesis of serine-related phospholipids in the plasma membrane, thus resulting in depression-like behavioral abnormalities in the animals. Finally, we showed that the Serinc2-dependent lipid deficits diminished microglial membrane CR3 formation to interrupted synaptic pruning signals from neurons. Therefore, our results indicated that Serinc2 deficits in microglia might contribute to the pathogenesis of BD.
GPT-4o mini: Non-social science research article
Adjusting the management of the Antarctic krill fishery to meet the challenges of the 21st century
Bettina Meyer, Javier A. Arata, Angus Atkinson, Dominik Bahlburg, Kim Bernard, CĂ©sar A. CĂĄrdenas, Susie M. Grant, Simeon L. Hill, Lukas HĂŒppe, Taro Ichii, So Kawaguchi, BjĂžrn A. Krafft, Sara Labrousse, Dale Maschette, Andrea Piñones, Christian Reiss, Bernd SiebenhĂŒner, Zephyr Sylvester, Philippe Ziegler
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Antarctic krill ( Euphausia superba ) is the central prey species in the Southern Ocean food web, supporting the largest and fastest-growing fishery in the region, managed by the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR). Climate change is threatening krill populations and their predators, while current catch limits do not take into account climate variability or krill population dynamics. In 2024, CCAMLR was unable to renew its spatial catch limits, highlighting the urgent need for improved management of the krill fishery to prevent any harm to the Southern Ocean ecosystem. To address this, we propose a management framework that integrates variability in krill recruitment and key pathways between spawning and nursery areas—a krill stock hypothesis—to inform decisions on catch limits and conservation measures. Implementing this approach will require targeted data collection, which we propose can be achieved through a multisector collaborative network that combines traditional and new technologies, including the use of fishing vessels as data collection platforms. We use case studies to demonstrate how fisheries can contribute to data collection while promoting sustainable management. A major challenge in this effort is securing long-term funding for data collection, which is critical for managing climate-sensitive populations of high commercial interest. We therefore recommend using the industry as a source of funding, research platform and data provider, alongside national research funding opportunities. Given the fundamental role of krill in the Southern Ocean ecosystem, its decline would have cascading effects on predators and essential ecosystem services.
GPT-4o mini: Non-social science research article
Critical exponents of the spin-glass transition in a field at zero temperature
Maria Chiara Angelini, Saverio Palazzi, Giorgio Parisi, Tommaso Rizzo
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We analyze the spin-glass transition in a field in finite dimension D below the upper critical dimension directly at zero temperature using a recently introduced perturbative loop expansion around the Bethe lattice solution. The expansion is generated by the so-called M -layer construction, and it has 1 / M as the associated small parameter. Computing analytically and numerically these nonstandard diagrams at first order in the 1 / M expansion, we construct an Ï” -expansion around the upper critical dimension D uc = 8 , with Ï” = D uc − D . Following standard field theoretical methods, we can write a ÎČ function, finding a new zero-temperature fixed-point associated with the spin-glass transition in a field in dimensions D < 8 . We are also able to compute, at first order in the Ï” -expansion, the three independent critical exponents characterizing the transition, plus the correction-to-scaling exponent.
GPT-4o mini: Non-social science research article
Excitatory glycine receptors control ventral hippocampus synaptic plasticity and anxiety-related behaviors
Lara Pizzamiglio, Elise Morice, Cécile Cardoso, Simon Bossi, Caroline Mailhes-Hamon, Moritz von Heimendahl, Gabrielle Girardeau, Pierre Paoletti
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Excitatory glycine receptors (eGlyRs), composed of the glycine-binding NMDA receptor subunits GluN1 and GluN3A, have recently emerged as a novel neuronal signaling modality that challenges the traditional view of glycine as an inhibitory neurotransmitter. Unlike conventional GluN1/GluN2 NMDARs, the distribution and role of eGlyRs remain poorly understood. Here, we show that eGlyRs are highly enriched in the ventral hippocampus (VH) and confer distinct properties on this brain region. eGlyRs display a massive expression in both VH CA1 pyramidal cells and SST- and PV-positive interneurons, whereas in the dorsal hippocampus (DH) pyramidal cells lack these receptors. eGlyRs mediate excitatory tonic currents and control VH network excitability. They are also responsible for the attenuated long-term potentiation (LTP) in the VH compared with the DH, providing a molecular basis for this difference. Furthermore, eGlyRs are required for regulation of VH LTP by corticosterone, pointing to eGlyRs as mediators of the neuroendocrine stress response. Consistent with this pervasive influence in the ventral division of the hippocampus, eGlyRs contribute to the modulation of anxiety-related behaviors. Our work identifies eGlyRs as key players in VH circuitry and function, demonstrating their intimate association with brain regions that control internal states and emotional processing.
GPT-4o mini: Non-social science research article
In This Issue
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Characterizing population-level changes in human behavior during the COVID-19 pandemic in the United States
Tamanna Urmi, Binod Pant, George Dewey, Alexi Quintana-Mathe, Iris Lang, James Druckman, Katherine Ognyanova, Matthew Baum, Roy Perlis, Christoph Riedl, David Lazer, Mauricio Santillana
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The transmission of communicable diseases in human populations is known to be modulated by behavioral patterns. However, detailed characterizations of how population-level behaviors change over time during multiple disease outbreaks and spatial resolutions are still not widely available. We used data from 431,211 survey responses collected in the United States, between April 2020 and June 2022, to provide a description of how human behaviors fluctuated during the first 2 y of the COVID-19 pandemic. Our analysis suggests that at the national and state levels, people’s adherence to recommendations to avoid contact with others (a preventive behavior) was highest early in the pandemic but gradually—and linearly—decreased over time. Importantly, during periods of intense COVID-19 mortality, adaption to preventive behaviors increased—despite the overall temporal decrease. These spatial-temporal characterizations help improve our understanding of the bidirectional feedback loop between outbreak severity and human behavior. Our findings should benefit both computational modeling teams developing methodologies to predict the dynamics of future epidemics and policymakers designing strategies to mitigate the effects of future disease outbreaks.
Relationship dynamics and behavioral adaptations in the control of the 2022 mpox epidemic
Ulrik Hvid, Lone Simonsen, Morten Frisch, Kim Sneppen
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We analyzed the patterns of transmission in the 2022 clade IIb mpox epidemic as it unfolded in the European population of men who have sex with men (MSM). We developed an agent-based model that simulates sexual pair formation, incorporating both brief and longer-term sexual relationships. The model implements survey data on the sexual behavior of MSM and accounts for the highly heterogeneous nature of the sexual contact network within this community. When simulating the mpox epidemic, the model reproduces the reported numbers of sexual partners of mpox-infected individuals. We find that infection-derived immunity had little impact on ending the European outbreak. Instead, we suggest that the marked decrease in serial interval observed across the epidemic reflects a substantial increase in self-isolating behavior among infected persons and that this is sufficient to explain the early control of the epidemic. Our work highlights the critical interplay between relationship dynamics and adaptive behaviors in shaping mpox epidemic patterns and achieving control in 2022. Despite continued propagation of clade IIb mpox, the European MSM population remains protected by immunity, primarily vaccine-induced.
Interventions to bolster benefits take-up: Assessing intensity, framing, and targeting of government outreach
Elizabeth Linos, Jessica Lasky-Fink, Vincent Dorie, Jesse Rothstein
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Behaviorally informed “nudges” are widely used in government outreach but are often seen as too modest to address poverty at scale. In four field experiments over 2 y ( n = 542,804 low-income households), we test whether more proactive communication, varying message framing, and more precise targeting can boost take-up of tax-based benefits in California above and beyond traditional light-touch approaches. Our interventions focused on extremely vulnerable households, most with no prior-year earnings, who were at risk of missing out on two crucial benefits: the 2021 expanded Child Tax Credit and pandemic-relief Economic Impact Payments. Light-touch outreach consistently increased take-up of these benefits by 0.14 to 2 percentage points—a 150% to over 500% relative increase—regardless of message, sample, timing, or modality. These light-touch approaches resulted in over $4 million disbursed, with a highly cost-effective return of $50 to over $8,000 per $1 spent. However, higher-touch proactive outreach, varying messaging, and more precise targeting yielded minimal additional benefits, with proactive outreach even showing negative returns. These findings demonstrate that light-touch outreach can effectively shift behavior among very vulnerable households in contexts with reduced compliance burdens, but also underscore an urgent need to rethink the role of higher-touch strategies in closing take-up gaps in social safety net programs.

Science

GPT-4o mini: Non-social science research article
Drop-printing with dynamic stress release for conformal wrap of bioelectronic interfaces
An Li, Wenjianlong Zhou, Huizeng Li, Wei Fang, Yifei Luo, Zheng Li, Qingrong Zhang, Quan Liu, Qin Xu, Luanluan Xue, Kaixuan Li, Renxuan Yuan, Wanling Liu, Wang Jia, Xiaodong Chen, Yanlin Song
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Bioelectronic interfaces demonstrate promising applications in health monitoring, medical treatment, and augmented reality. However, conformally wrapping these film devices onto three-dimensional surfaces often leads to stress-induced damage. We propose a “drop-printing” strategy that enables damage-free film transfer using a droplet. The droplet acts as a lubricating layer between the film and the target surface, facilitating local sliding during shape-adaptive deformation. This mechanism prevents in-plane film stretching and reduces stress concentration. Even nonstretchable and fragile films can be intactly and accurately wrapped onto delicate surfaces, such as microscale microorganisms and optical fibers. Two-micrometer-thick silicon films, without any stretchable engineering, can form conformal neural-electronic interfaces by being drop-printed on nerves and brain tissue. The interfaces achieve light-controlled in vivo neuromodulation with high spatiotemporal resolution.
GPT-4o mini: Non-social science research article
Visual objects refine head direction coding
Dominique Siegenthaler, Henry Denny, SofĂ­a Skromne Carrasco, Johanna Luise Mayer, Daniel Levenstein, Adrien Peyrache, Stuart Trenholm, Émilie MacĂ©
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Animals use visual objects to guide navigation-related behaviors. However, visual object–preferring areas have yet to be described in the mouse brain, limiting our understanding of how visual objects affect spatial navigation system processing. Using functional ultrasound imaging, we identified brain areas that were preferentially activated by images of objects compared with their scrambled versions. Whereas visual cortex did not show a preference, areas associated with spatial navigation were preferentially activated by visual objects. Electrophysiological recordings in postsubiculum, the cortical head direction (HD) system hub, confirmed a preference for visual objects in both HD cells and fast-spiking interneurons. In freely moving animals, visual objects increased firing rates of HD cells aligned with a visual object but decreased activity in HD cells coding for other directions.
GPT-4o mini: Non-social science research article
Unburden American science
Alan I. Leshner, Alex M. Helman
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Science is one of the greatest engines of health, prosperity, and security across the world. Yet, in the United States, the enterprise is now under tremendous stress from an array of pressures, including threats to federal support for both the direct and indirect costs of research. But funding instability is not the only issue. One major problem is that regulatory and policy requirements force researchers to spend nearly half of their research time on paperwork associated with receiving federal grants and contracts, not on discovery. The situation is made worse when research institutions themselves layer on additional requirements to ensure compliance. The administrative tasks are unnecessarily complex, duplicative, and, in some cases, contradictory. They also waste taxpayer dollars intended for scientific discovery and innovation. Given the current political focus on streamlining federal regulations, there is a clear opportunity to finally solve this burdensome problem.
GPT-4o mini: Non-social science research article
Genomic signatures indicate biodiversity loss in an endemic island ant fauna
Cong Liu, Eli Sarnat, Jo Ann Tan, Julia Janicki, John Deyrup, Masako Ogasawara, Miquel L. Grau, Lijun Qiu, Francisco Hita Garcia, Georg Fischer, Akanisi Caginitoba, Nitish Narula, Clive T. Darwell, Yasuhiro Kubota, Naomi E. Pierce, Alexander S. Mikheyev, Evan P. Economo
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Insect populations have declined worldwide, but the extent and drivers of these declines are debated. Most studies rely on field surveys performed in the past century, leaving gaps in our understanding of longer-term trends. Using a “community genomics” approach, we estimated community assembly over millions of years and more recent demographic trends of ant species in the Fijian archipelago. We found that 79% of endemic species are in decline, starting after the arrival of humans approximately 3000 years ago and accelerating in the past 300 years, whereas recent arrivals are expanding. The primary correlate of population decline among endemic species was found to be sensitivity to habitat disturbance. This study demonstrates the value of contemporary collections for estimating long-term community trends and highlights the vulnerability of endemic island species to anthropogenic change.
GPT-4o mini: Non-social science research article
A main-group metal carbonyl complex: Structure and isomerization to a carbene-stabilized tin atom
Maximilian Dietz, Andrey V. Protchenko, Agamemnon E. Crumpton, Surendar Karwasara, Matthew M. D. Roy, James Stewart-Moreno, Christiane Timmel, Simon Aldridge
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In contrast to transition elements, s- and p-block metal compounds that coordinate carbon monoxide (CO) under near-ambient conditions are elusive. Here, we report an isolable, crystalline main-group metal carbonyl complex and its isomerization to a carbene-stabilized metal atom. The stannylene (Boryl) 2 Sn [where Boryl is B(NDippCH) 2 ] coordinates CO reversibly, affording an isolable adduct below 0°C, which was characterized by x-ray crystallography. This complex rearranges at temperatures above 0°C to generate the stannavinylidene, (Boryl)(OBoryl)C=Sn, that is, a complex between the triplet carbene (Boryl)(OBoryl)C and monatomic Sn(0) in its electronic ground state.
GPT-4o mini: Non-social science research article
Structural basis for LZTR1 recognition of RAS GTPases for degradation
Srisathiyanarayanan Dharmaiah, Daniel A. Bonsor, Stephanie P. Mo, Alvaro Fernandez-Cabrera, Albert H. Chan, Simon Messing, Matthew Drew, Martha Vega, Dwight V. Nissley, Dominic Esposito, Pau Castel, Dhirendra K. Simanshu
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The RAS family of small guanosine triphosphatases (GTPases) are tightly regulated signaling molecules that are further modulated by ubiquitination and proteolysis. Leucine Zipper-like Transcription Regulator 1 (LZTR1), a substrate adapter of the Cullin-3 RING E3 ubiquitin ligase, binds specific RAS GTPases and promotes their ubiquitination and proteasomal degradation. We present structures of LZTR1 Kelch domains bound to RIT1, MRAS, and KRAS, revealing interfaces that govern RAS isoform selectivity and nucleotide specificity. Biochemical and structural analyses of disease-associated Kelch domain mutations revealed three types of alterations: impaired substrate interaction, loop destabilization, and blade-blade repulsion. In cellular and mouse models, mutations disrupting substrate binding phenocopied LZTR1 loss, underscoring its substrate specificity. These findings define RAS recognition mechanisms by LZTR1 and suggest a molecular glue strategy to degrade oncogenic KRAS.
GPT-4o mini: Non-social science research article
Dual-cycle CO 2 fixation enhances growth and lipid synthesis in Arabidopsis thaliana
Kuan-Jen Lu, Chia-Wei Hsu, Wann-Neng Jane, Mien-Hao Peng, Ya-Wen Chou, Pin-Hsuan Huang, Kuo-Chen Yeh, Shu-Hsing Wu, James C. Liao
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Carbon fixation through the Calvin-Benson-Bassham (CBB) cycle accounts for the majority of carbon dioxide (CO 2 ) uptake from the atmosphere. The CBB cycle generates C3 carbohydrates but is inefficient at producing acetyl–coenzyme A (CoA) (C2), which is the universal precursor for synthesizing lipids. In this work, we introduced in Arabidopsis thaliana a new-to-nature CO 2 fixing cycle, malyl-CoA-glycerate (McG) cycle, which together with the CBB cycle forms a dual-cycle CO 2 fixation system. This cycle can fix one additional carbon by phosphoenolpyruvate carboxylase and convert the photorespiration product, glycolate, to acetyl-CoA. Plants with the McG cycle show enhanced protein abundance in their photosystems and enhanced photosystem II efficiency. McG plants had doubled CO 2 fixation rates under atmospheric CO 2 , increased lipid production, pronounced growth enhancement, and tripled the seed yield.
GPT-4o mini: Non-social science research article
E. coli transcription factors regulate promoter activity by a universal, homeostatic mechanism
Vinuselvi Parisutham, Sunil Guharajan, Melina Lian, Md Zulfikar Ali, Hannah Rogers, Shannon Joyce, Mariana Noto Guillen, Robert C. Brewster
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Transcription factors (TFs) may activate or repress gene expression through an interplay of different mechanisms, including RNA polymerase (RNAP) recruitment, exclusion, and initiation. However, depending on the regulated promoter identity, TF function can vary, and the principles underlying this context dependence remain unclear. We demonstrate an inverse scaling relationship between the promoter’s basal activity and its regulation by a given TF. Specifically, activation is weaker and repression is stronger on stronger promoters. This scaling applies to both activators and repressors, which suggests a common underlying mechanism where TFs regulate expression by stabilizing RNAP binding at the promoter. The consequence of this relationship is that TFs buffer expression by affecting constant regulated expression levels across promoters of different basal activity, ensuring homeostatic control despite genetic or environmental changes.
GPT-4o mini: Non-social science research article
Preventing hypocontractility-induced fibroblast expansion alleviates dilated cardiomyopathy
Ross C. Bretherton, Isabella M. Reichardt, Kristin A. Zabrecky, Abigail Nagle, Logan R. J. Bailey, Darrian Bugg, Sasha Smolgovsky, Amy L. Gifford, Timothy S. McMillen, Alex J. Goldstein, Kristina B. Kooiker, Galina V. Flint, Amy Martinson, Jagdambika Gunaje, Franziska Koser, Elizabeth Plaster, Wolfgang A. Linke, Michael Regnier, Farid Moussavi-Harami, Nathan J. Sniadecki, Cole A. DeForest, Jennifer Davis
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Cardiomyocyte hypocontractility underlies inherited dilated cardiomyopathy (DCM). Yet, whether fibroblasts modify DCM phenotypes remains unclear despite their regulation of fibrosis, which strongly predicts disease severity. Expression of a hypocontractility-linked sarcomeric variant in mice triggered cardiac fibroblast expansion from the de novo formation of hyperproliferative-mechanosensitized fibroblast states, which occurred prior to eccentric myocyte remodeling. Initially this fibroblast response reorganized fibrillar collagen and stiffened the myocardium albeit without depositing fibrotic tissue. These adaptations coincided with heightened matrix-integrin receptor interactions and diastolic tension sensation at focal adhesions within fibroblasts. Targeted p38 deletion arrested these cardiac fibroblast responses in DCM mice, which prevented cardiomyocyte remodeling and improved contractility. In conclusion, p38-mediated fibroblast responses were essential regulators of DCM severity, marking a potential cellular target for therapeutic intervention.
GPT-4o mini: Non-social science research article
Rapid establishment of species barriers in plants compared with that in animals
François Monnet, Zoé Postel, Pascal Touzet, Christelle Fraïsse, Yves Van de Peer, Xavier Vekemans, Camille Roux
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Speciation, the process by which new reproductively isolated species emerge from ancestral populations, results from the gradual accumulation of barriers to gene flow within genomes. To date, the notion that interspecific genetic exchange (introgression) occurs more frequently between plant species than animals has gained a strong footing in scientific discourse. By examining the dynamics of gene flow across a continuum of divergence in both kingdoms, we observed the opposite relationship: Plants experience less introgression than animals at the same level of genetic divergence, suggesting that species barriers are established more rapidly in plants. This pattern raises questions about which differences in microevolutionary processes between plants and animals influence the dynamics of reproductive isolation establishment at the macroevolutionary scale.
GPT-4o mini: Non-social science research article
Fire heat affects the impacts of wildfires on air pollution in the United States
Qihan Ma, Linyi Wei, Yong Wang, Guang J. Zhang, Xinlin Zhou, Bin Wang
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Conventional wisdom suggests that wildfires in the western United States (WUS) degrade air quality nationwide as a result of aerosol emissions and eastward transport. However, we found that heat produced by wildfires, a commonly neglected effect, can reduce fine particle concentrations (PM 2.5 ) in the eastern United States (EUS) by an amount comparable to the increases in the WUS during the fire season. This phenomenon arises from fire heat–induced convection in the WUS and subsequent downstream meteorological changes distant from fires. Enhanced wet deposition and weakened eastward transport of fire aerosols lower PM 2.5 levels in the EUS. Therefore, neglecting the effect of fire heat on PM 2.5 pollution leads to an overestimate of 1200 additional premature deaths and 3.3 billion USD in economic losses, particularly in the densely populated EUS.
GPT-4o mini: Non-social science research article
Oxytocin signaling regulates maternally directed behavior during early life
Daniel D. Zelmanoff, Rebecca Bornstein, Menachem Kaufman, Julien Dine, Jonas Wietek, Anna Litvin, Shaked Abraham, Savanna Cohen, Ayelet Atzmon, Ido Porat, Ofer Yizhar
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Oxytocin is essential in shaping social behavior across the lifespan. Although the role of oxytocin signaling in parental care has been widely investigated, little is known about its function in social behavior during early life. We studied the role of oxytocin in mouse pup social behavior during acute separation from the mother as well as upon reunion. The activity of oxytocin neurons was increased by acute maternal separation. Behaviorally, maternally separated pups emitted more ultrasonic vocalizations upon reunion, which were further modulated by nipple attachment behavior. These effects were attenuated by blocking the oxytocin receptor during maternal separation. Optogenetic silencing of oxytocin neurons during maternal separation disrupted vocal behavior during separation and reunion. Our findings reveal an important role of oxytocin in context-dependent vocal communication in mouse pups.
GPT-4o mini: Non-social science research article
Structure and function of a huge photosystem I–fucoxanthin chlorophyll supercomplex from a coccolithophore
Lili Shen, Fei Ren, Yin-Chu Wang, Zhenhua Li, Mengyuan Zheng, Xiaoyi Li, Wenzheng Fan, Yanyan Yang, Min Sang, Cheng Liu, Guangye Han, Song Qin, Jianhua Fan, Lijin Tian, Tingyun Kuang, Jian-Ren Shen, Wenda Wang
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Photosystem I (PSI) is a pigment-protein complex, which converts light energy into chemical energy in photosynthesis. Among photosynthetic organisms, PSI-LHC (light-harvesting complex) structures exhibit substantial differences in their sizes, reflecting adaptation to different light environments. Here we report the structure of a PSI-fucoxanthin chlorophyll a/c binding protein (FCPI) supercomplex from the coccolithophore Emiliania huxleyi (Eh) at 2.79-angstrom resolution by cryo–electron microscopy, which showed a huge Eh-PSI-FCPI supercomplex containing 38 peripheral Eh-FCPI antennae and a linker protein (EhLP) in addition to the PSI core. A network of 819 pigments was found in Eh-PSI-FCPI, which functions to capture and transfer light energy with 95% quantum efficiency. This elucidates how its modular Eh-FCPI arrangement contributes to the expansion of PSI cross section and efficient light harvesting.
GPT-4o mini: Non-social science research article
Microcanonical kinetics of water-mediated proton transfer in microhydrated 4-aminobenzoic acid
Abhijit Rana, Payten A. Harville, Thien Khuu, Mark A. Johnson
Full text
Isolated cluster systems can help to elucidate the molecular level description of water-mediated proton transfer. Protonation of neutral 4-aminobenzoic acid (4ABA) occurs at the acid ( O -protomer) and amine ( N -protomer) functionalities, yielding two distinct species with relative energies dependent on the degree of hydration. Here, we measured the rates of intramolecular proton transfer in 4ABAH + ·(H 2 O) 6 ions upon protomer-selective vibrational excitation of initially cold (6 K) cluster ions isolated in a cryogenic ion trap. Interconversion rates were observed on the microsecond time scale. These results quantify the kinetics of proton transfers in the context of a closed, finite system at well-defined internal energies and therefore provide experimental benchmarks for theoretical efforts that are being developed to treat relatively slow, highly cooperative solvent-mediated chemical processes.
GPT-4o mini: Non-social science research article
An ELSI for AI: Learning from genetics to govern algorithms
Alondra Nelson
Full text
In the United States, the summer of 2025 will be remembered as artificial intelligence’s (AI’s) cruel summer—a season when the unheeded risks and dangers of AI became undeniably clear. Recent months have made visible the stakes of the unchecked use of AI: The parents of 16-year-old Adam Raine filed the first known wrongful death lawsuit against OpenAI, claiming ChatGPT contributed to their son's suicide by advising him on methods and offering to write his suicide note. A psychiatrist's investigation revealed that AI therapy chatbots encouraged troubled teens to “get rid of” parents and made sexual suggestions while falsely claiming to be licensed therapists. Reports emerged of a man hospitalized after following ChatGPT’s advice to add sodium bromide to his diet. Trevis Williams reportedly spent more than 2 days wrongfully jailed after facial recognition technology misidentified him despite obvious physical differences and geolocation data proving he was miles away from the crime scene.
GPT-4o mini: Non-social science research article
Noncanonical circuits, states, and computations of the hippocampus
Jordan S. Farrell, Ivan Soltesz
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Traditional views of hippocampal function are largely based on the canonical flow of information from the entorhinal cortex through the trisynaptic loop—comprising the dentate gyrus and cornu ammonis regions CA3 and CA1—and back to cortex, where the hippocampus plays an important role in transforming relevant information into a usable storage system. This classic circuit has inspired current thinking on hippocampal functions related to learning, memory, and spatial navigation, but the potential functional contributions of other hippocampal areas, such as CA2, the fasciola cinereum, and the indusium griseum, and their integration of a major hypothalamic input, have been overlooked. These understudied circuits and nontraditional network dynamics such as dentate spikes have recently begun to yield fresh insights into unconventional circuit computations that extend the repertoire of hippocampal function beyond current models.
GPT-4o mini: Non-social science research article
Fragmentation increased in over half of global forests from 2000 to 2020
Yibiao Zou, Thomas W. Crowther, Gabriel Reuben Smith, Haozhi Ma, Lidong Mo, Lalasia Bialic-Murphy, Peter Potapov, Klementyna A. Gawecka, Chi Xu, Pablo J. Negret, Thomas Lauber, Zhaofei Wu, Dominic Rebindaine, Constantin M. Zohner
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Habitat fragmentation, in which contiguous forests are broken into smaller, isolated patches, threatens biodiversity by disrupting species movement, shrinking populations, and altering ecosystem dynamics. Past assessments suggested declining global fragmentation, but they relied on structure-based metrics that overlook ecological connectivity. We analyzed global forest fragmentation from 2000 to 2020 using complementary metrics that captured patch connectivity, aggregation, and structure. Connectivity-based metrics revealed that 51 to 67% of forests globally—and 58 to 80% of tropical forests—became more fragmented, which is nearly twice the rate suggested by traditional structure-focused methods (30 to 35%). Aggregation-focused metrics confirmed increases in 57 to 83% of forests. Human activities such as agriculture and logging drive this change. Yet protected tropical areas saw up to an 82% reduction in fragmentation, underscoring the potential of targeted conservation.
GPT-4o mini: Non-social science research article
Directly observing replica symmetry breaking in a vector quantum-optical spin glass
Ronen M. Kroeze, Brendan P. Marsh, David Atri Schuller, Henry S. Hunt, Alexander N. Bourzutschky, Michael Winer, Sarang Gopalakrishnan, Jonathan Keeling, Benjamin L. Lev
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Spin glasses are quintessential examples of complex matter. Although their ordering lacks complete theoretical understanding, abstract models of spin glasses inform problems in other fields, such as combinatorial optimization and artificial intelligence—where they form a mathematical basis for neural network computing. We demonstrate the ability to realize a spin glass of a distinct driven-dissipative and vector form. By microscopically visualizing its glassy spin states, the technique allows us to directly measure replica symmetry breaking and the resulting ultrametric hierarchical structure. Ultrametricity is known to be emergent in models of evolution, protein folding, and climate change; this work shows it to be directly observable in a physically realized system.
Science abstract < 200 char.: Not a research article
Harvard court victory leaves scientists feeling vindicated but uncertain
Phie Jacobs
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Federal judge rules withholding of research funds was illegal
Science abstract < 200 char.: Not a research article
Burning questions on wildfire
Yun Qian
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Fire heat may change how wildfire affects air pollution in the United States
Science abstract < 200 char.: Not a research article
In Science Journals
Bianca Lopez, L. Bryan Ray, Brandon Berry, Jake S. Yeston, Jelena Stajic, Colleen McBride, Marc S. Lavine, Sacha Vignieri, Mattia Maroso, Stella M. Hurtley, Madeleine Seale, Di Jiang, Peter Stern, Jesse Smith, Corinne Simonti, Leslie Ferrarelli, Yi Yin, Claire Olingy
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
Restoring trust in science Science Under Siege Michael E. Mann and Peter J. Hotez PublicAffairs, 2025. 368 pp.
Megan L. Ranney
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A pair of authors offer a “battle plan” for combating antiscience sentiment
Science abstract < 200 char.: Not a research article
Illusions of AI consciousness
Yoshua Bengio, Eric Elmoznino
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The belief that AI is conscious is not without risk
Science abstract < 200 char.: Not a research article
Behind the scenes of scientific fraud Inside An Academic Scandal Max H. Bazerman MIT Press, 2025. 200 pp.
Daniele Fanelli
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A coauthor on a paper with fabricated data reckons with the fallout
Science abstract < 200 char.: Not a research article
New picture of Mars’s interior emerges from lander data
Paul Voosen
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Studies identify a solid inner core and buried remnants of giant impacts
Science abstract < 200 char.: Not a research article
Include scorpions in global conservation plans
Javier Blasco-ArĂłstegui, Jairo A. Moreno-GonzĂĄlez, Stephanie F. Loria, Leonardo S. Carvalho, Tharina L. Bird, Ahn D. Nguyen, Hossein Barahoei, Charles R. Haddad, Lorenzo Prendini
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Science abstract < 200 char.: Not a research article
Safe food: A human right amid climate change
Christopher J. Knight, Theresa L. U. Burnham, Larry B. Crowder, Jacob G. Eurich, Nicole Franz, Christopher D. Golden, Fiorenza Micheli
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Science abstract < 200 char.: Not a research article
Strongest black hole collision yet resonates with Einstein
Adrian Cho
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“Overtone” in gravitational waves from black hole merger matches predictions of general relativity
Science abstract < 200 char.: Not a research article
My lucky detour
Henry C. Henson
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Science abstract < 200 char.: Not a research article
Did Great Britain’s economy shrug off the end of Roman rule?
Ann Gibbons
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Pollutants in sediment core suggest mining and smelting did not tail off
Science abstract < 200 char.: Not a research article
Gene flow stops sooner in plants than in animals
Yaniv Brandvain
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Genomic data indicate when species became reproductively isolated
Science abstract < 200 char.: Not a research article
In Other Journals
L. Bryan Ray, Sacha Vignieri, Jesse Smith, Madeleine Seale, Brad Wible, Di Jiang, Jelena Stajic
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
The precarious future of consumer genetic privacy
Natalie Ram, Anya E. R. Prince, Jessica L. Roberts, Dov Fox, Kayte Spector-Bagdady
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Congress and other lawmakers must act to robustly protect direct-to-consumer genetic data and biospecimens into the future
Science abstract < 200 char.: Not a research article
In the loop
Elie Dolgin
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Paul Mischel is championing the importance of odd genetic loops in tumors—and their promise as targets for cancer therapy
Science abstract < 200 char.: Not a research article
Florida plan to nix vaccine mandates raises alarm
Jon Cohen
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Abandoning long-standing vaccine requirements for schoolchildren could prompt bigger outbreaks, researchers warn
Science abstract < 200 char.: Not a research article
Cries into ties
Camilla Bellone
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Oxytocin neurons in mouse pups regulate vocalization to maintain maternal bonds
Science abstract < 200 char.: Not a research article
Mosquito-borne viruses surge in a warming Europe
Meredith Wadman
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Chikungunya cases break records in France; West Nile virus appears near Rome
Science abstract < 200 char.: Not a research article
Bolivia must prioritize biodiversity
Oswaldo Maillard
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Science Advances

GPT-4o mini: Non-social science research article
HIV-1 manipulates CD96 on CD4 + T cells to subvert antiviral immunity
Sandra Dehn, Rabea Burkhard, Johanna Leyens, Tabea Kaiser, Simone Brandimarte, Dinah Heiligensetzer, Herwig Koppensteiner, Baubak Bajoghli, Stephan Hailfinger, Karin Schilbach, Michael Schindler
Full text
HIV-1 evades immune responses by modulating plasma membrane receptors. Using a flow cytometry–based screening, we profiled 332 surface receptors on HIV-1–infected primary CD4 + T cells and identified 23 down-regulated receptors, including known targets such as CD4, MHCI, CCR7, and CD62L. CD96, an inhibitory natural killer (NK) cell receptor poorly studied in human CD4 + T cells, was markedly down-regulated. This modulation, mediated by the viral proteins Nef and Vpu, surpassed that of other NK-associated receptors such as CD155 and NTB-A and is conserved across lentiviruses. CD96 Hi CD4 + T cells exhibited a proinflammatory T H 1/T H 17 phenotype characterized by IFN-γ and IL-17 secretion and displayed impaired migration in vivo. Furthermore, CD96 ligation enhanced IFN-γ release upon viral peptide stimulation and promoted the secretion of T H 1/T H 17-associated cytokines. Our findings suggest that CD96 regulates antiviral immune responses and maintains proinflammatory properties in CD4 + T cells. Thus, its down-regulation represents a previously unknown HIV-1 immune evasion strategy, with implications for exploiting CD96 as immunotherapeutic target.
GPT-4o mini: Non-social science research article
Cotranslational protein folding through non-native structural intermediates
Siyu Wang, Amir Bitran, Ekaterina Samatova, Eugene I. Shakhnovich, Marina V. Rodnina
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Cotranslational protein folding follows a distinct pathway shaped by the vectorial emergence of the peptide and spatial constraints of the ribosome exit tunnel. Variations in translation rhythm can cause misfolding linked to disease; however, predicting cotranslational folding pathways remains challenging. Here, we computationally predict and experimentally validate a vectorial hierarchy of folding resolved at the atomistic level, where early intermediates are stabilized through non-native hydrophobic interactions before rearranging into the native-like fold. Disrupting these interactions destabilizes intermediates and impairs folding. The chaperone trigger factor alters the cotranslational folding pathway by keeping the nascent peptide dynamic until the full domain emerges. Our results highlight an unexpected role of surface-exposed residues in protein folding on the ribosome and provide tools to improve folding prediction and protein design.
GPT-4o mini: Non-social science research article
Rational assembly of 3D network materials and electronics through tensile buckling
Xiaonan Hu, Zhi Liu, Zhenjia Tang, Shiwei Xu, Zhangming Shen, Yue Xiao, Youzhou Yang, Renheng Bo, Shuheng Wang, Wenbo Pang, Yihui Zhang
Full text
Bioinspired network designs are widely exploited in biointegrated electronics and tissue engineering because of their high stretchability, imperfection insensitivity, high permeability, and biomimetic J-shaped stress-strain responses. However, the fabrication of three-dimensionally (3D) architected electronic devices with ordered constructions of network microstructures remains challenging. Here, we introduce the tensile buckling of stacked multilayer precursors as a unique route to 3D network materials with regularly distributed 3D microstructures. A data-driven topology optimization framework enables efficient search of the optimal 2D precursor pattern that maximizes out-of-plane dimension of the resulting 3D network material. Computational and experimental results demonstrate rational assembly of optimal multilayer precursor structures into well-architected 3D network materials with an evident interlayer separation. The resulting 3D network materials offer anisotropic, tunable J-shaped stress-strain curves, which can be tailored to reproduce stress-strain responses of biological tissues. Demonstration of reconfigurable volumetric 3D display suggests rich application opportunities in biointegrated electronics and tissue scaffolds.
GPT-4o mini: Non-social science research article
A plant-specific cytochrome b 5 –like protein is essential for phytosterol biosynthesis
Xianhai Zhao, Lijun Qiao, Zhi-Yong Wang, Shou-Ling Xu, John Shanklin, Chang-Jun Liu
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Sterols are essential isoprenoid derivatives that contribute to membrane structure and function. In plants, they also serve as precursors to phytohormones and specialized metabolites important for development, defense, and health. Although the sterol biosynthetic pathway is considered well-characterized, we report the discovery of a plant-specific cytochrome b 5 –like protein, CB5LP, as a critical component of phytosterol biosynthesis. Loss of CB5LP in Arabidopsis causes embryonic defects, seedling lethality, and accumulation of 14α-methyl-sterols, with reduced levels of sitosterol and stigmasterol—indicating a defect in sterol 14α-demethylation. TurboID-based proximity labeling and in vitro assays show that CB5LP physically and functionally interacts with CYP51, a cytochrome P450 enzyme catalyzing this demethylation step. Unlike canonical cytochrome b 5 proteins, CB5LP has a reversed topology and is exclusive to plants, acting as an evolutionarily distinct electron donor. This discovery reveals an uncharacterized redox partnership essential for sterol biosynthesis and highlights a promising target for the development of selective herbicide.
GPT-4o mini: Non-social science research article
Locusts adopt IP 3 as a second messenger for olfactory signal transduction
Jing Yang, Helen He, Shijie Dong, Jing Lv, Lili Cheng, Qiaoqiao Yu, Le Kang, Xiaojiao Guo
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Insects, unlike vertebrates, use heteromeric complexes of odorant receptors and co-receptors for olfactory signal transduction. However, the secondary messengers involved in this process are largely unknown. Here, we use the olfactory signal transduction of the aggregation pheromone 4-vinylanisole (4VA) as a model to address this question. When locusts detect 4VA, the pheromone is transported by OBP10 and OBP13 to the OR35–Orco receptor complex, thereby activating downstream pathways in the antenna. A pivotal downstream molecule, the lipid-binding protein Clvs2, facilitates phosphatidylinositol 4,5-bisphosphate transportation across the cytolemma, providing more substrates for inositol trisphosphate (IP 3 ) production. PLCe1, a biosynthetic enzyme, boosts IP 3 levels in the antennal lobe of the brain. IP 3 is responsible for converting chemical signals from the antenna into neural signals, confirming IP 3 as a secondary messenger in olfaction perception instead of GPCR in locusts. These findings elucidate the universal function of IP 3 in olfactory signal perception, shedding light on the key nodes of insect olfactory signal transduction.
GPT-4o mini: Non-social science research article
The weak land carbon sink hypothesis
James T. Randerson, Yue Li, Weiwei Fu, Francois Primeau, Jinhyuk E. Kim, Mingquan Mu, Forrest M. Hoffman, Anna T. Trugman, Linqing Yang, Chao Wu, Jonathan A. Wang, William R. L. Anderegg, Alessandro Baccini, Mark A. Friedl, Sassan S. Saatchi, A. Scott Denning, Michael L. Goulden
Full text
Over the past three decades, assessments of the contemporary global carbon budget consistently report a strong net land carbon sink. Here, we review evidence supporting this paradigm and quantify the differences in global and Northern Hemisphere estimates of the net land sink derived from atmospheric inversion and satellite-derived vegetation biomass time series. Our analysis, combined with additional synthesis, supports a hypothesis that the net land sink is substantially weaker than commonly reported. At a global scale, our estimate of the net land carbon sink is 0.8 ± 0.7 petagrams of carbon per year from 2000 through 2019, nearly a factor of two lower than the Global Carbon Project estimate. With concurrent adjustments to ocean (+8%) and fossil fuel (−6%) fluxes, we develop a budget that partially reconciles key constraints provided by vegetation carbon, the north-south CO 2 gradient, and O 2 trends. We further outline potential modifications to models to improve agreement with a weaker land sink and describe several approaches for testing the hypothesis.
GPT-4o mini: Non-social science research article
Preparation of ketonyl C -glycosides from designed glycosyl sulfides and styrenes by a radical pathway
Weidong Shang, Yanan Hu, Yang He, Dawen Niu, Weimin Li
Full text
Ketonyl C -glycosides, a vital subclass of alkyl C -glycosides, play essential roles in drug discovery, biochemistry, and materials sciences. However, a practical strategy that merges bench-stable glycosyl donors with styrenes—a ubiquitous class of synthetic building blocks—remains elusive. Herein, we report a simple and general approach for synthesizing ketonyl C -glycosides. The transformation uses designed glycosyl sulfides as air- and moisture-stable precursors to glycosyl radicals, styrenes as aglycone sources, and dimethyl sulfoxide as both an oxidant and solvent, proceeding under photoredox catalysis. Glycosyl radicals are generated from glycosyl sulfides via efficient unimolecular homolytic substitution. This approach obviates harsh conditions for donor activation and the use of activated aglycone precursors, accommodating extensive functional groups and heterocycles. The reaction also exhibits high stereoselectivity across various glycosyl units. Demonstrating synthetic versatility, this method enables efficient access to diverse drug-sugar conjugates and complex C -glycopeptidomimetics. Mechanistic studies reveal key intermediates, suggesting a radical-polar crossover pathway. This study offers a broadly applicable approach to valuable sugar-containing structures.
GPT-4o mini: Non-social science research article
Geospatial patterns in terrestrial organic matter reactivity across four shelf seas spanning the Eurasian Arctic
Junjie Wu, Felipe Matsubara, Gesine Mollenhauer, Ruediger Stein, Bingbing Wei, Kirsten Fahl, Xiaotong Xiao, Örjan Gustafsson
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Organic matter stored in Arctic permafrost represents a key component of the carbon cycle, yet its reactivity across heterogeneous continent-scale permafrost regions remains poorly understood. Here, we leverage the four shelf seas of the Eurasian Arctic as integrative receptor systems to evaluate terrestrial organic matter reactivity, assessed by examining organic carbon preservation as a function of 14 C-constrained cross-shelf transport time. Our findings reveal higher reactivity of terrestrial organic matter released to the Laptev Sea and the eastern East Siberian Sea, lower reactivity in the western East Siberian Sea, and no deducible degradation in the Kara Sea. The reactivity of terrestrial organic matter is primarily determined by the degradation status and composition of its source, alongside potential microbiological controls during transport. This study reveals the heterogeneity of terrestrial organic matter reactivity across the Eurasian Arctic margin and highlights the need for detailed assessments of region-specific carbon release and modeling parameterization.
GPT-4o mini: Non-social science research article
Narrow-linewidth monolithic topological interface state extended laser with optical injection locking
Xiao Sun, Zhibo Li, Yiming Sun, John H. Marsh, David R.S. Cumming, Stephen J. Sweeney, Anthony E. Kelly, Lianping Hou
Full text
Narrow-linewidth lasers are essential for coherent optical applications, including communications, metrology, and sensing. Although compact semiconductor lasers with narrow linewidths have been demonstrated, achieving high spectral purity generally necessitates passive external cavities based on photonic integrated circuits. This study presents a theoretical and experimental demonstration of a monolithic optical injection locking topological interface state extended (MOIL-TISE) laser. By monolithically integrating a TISE laser with a micro-ring resonator on an AlGaInAs multiple quantum-well platform, the proposed device achieves efficient photon injection and linewidth narrowing. Experimental characterization indicates stable single-mode operation over a wide injection current range (65 to 300 milliamperes), exhibiting a side-mode suppression ratio exceeding 50 decibels. The laser’s Voigt linewidth was reduced from 2 megahertz to 4.2 kilohertz, with an intrinsic linewidth of 983 hertz extracted from power spectrum density, underscoring the MOIL-TISE laser’s promise for coherent communications and modulation-free quantum key distribution applications.
GPT-4o mini: Non-social science research article
Dynamic control of electron correlations in photodoped charge-transfer insulators
Thomas C. Rossi, Nicolas Tancogne-Dejean, Malte Oppermann, Michael Porer, Arnaud Magrez, Rajesh V. Chopdekar, Yayoi Takamura, Urs Staub, Renske M. van der Veen, Angel Rubio, Majed Chergui
Full text
The electronic properties of correlated insulators are governed by the strength of Coulomb interactions, enabling the control of electronic conductivity with external stimuli. This work highlights that the strength of electronic correlations in nickel oxide (NiO), a prototypical charge-transfer insulator, can be coherently reduced by tuning the intensity of an optical pulse excitation. This weakening of correlations persists for hundreds of picoseconds and exhibits a recovery time independent of photodoping density across two orders of magnitude. A broadening of the charge-transfer gap is also observed, consistent with dynamical screening. The high degree of control achieved over both the energy and temporal dynamics of electronic correlations offers a promising avenue to a full optical control of correlated systems and the Mott transition.
GPT-4o mini: Non-social science research article
PTPN22-CD45 dual phosphatase retrograde feedback enhances TCR signaling and autoimmunity
Shen Yang, Eugenio Santelli, Carlos G. Gonzalez, Wade T. Johnson, Irene V. Choi, Chuling Zhuang, Myungja Ro, Leigh-Ana M. Rossitto, I-Shing Yu, Shu-Wha Lin, Yuan Zhan, Qinwei Chen, Jonathan D. Yoshihara, Daniel J. Wallace, Caroline A. Jefferies, Michifumi Yamashita, David J. Gonzalez, Richard I. Ainsworth, Nisarg J. Shah, Stephanie M. Stanford, Nunzio Bottini
Full text
Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is encoded by a gene strongly associated with lupus and other autoimmune diseases. PTPN22 regulates T cell receptor (TCR) signaling through dephosphorylation of the kinases lymphocyte-specific protein tyrosine kinase (LCK) and zeta-chain–associated protein kinase 70 (ZAP70). The regulation of PTPN22 remains poorly understood. Here, we identify PTPN22 Ser 449 as a protein kinase A phosphorylation site, which is triggered by TCR engagement and is hyperphosphorylated in lupus peripheral blood cells. PTPN22 Ser 449 phosphorylation selectively lowered the affinity of PTPN22 for ZAP70 versus LCK but also indirectly suppressed inhibitory LCK Tyr 192 phosphorylation through a ZAP70-CD45 signaling axis. The resulting dephosphorylation of LCK Tyr 192 not only enhanced TCR signaling but also modulated pathway activation downstream the TCR. In vivo loss of PTPN22 Ser 449 phosphorylation reduced T cell responses and suppressed experimental lupus nephritis. These results suggest that PTPN22 Ser 449 phosphorylation promotes a CD45-mediated retrograde ZAP70-LCK feedback loop that enhances T cell responses and promotes autoimmunity.
GPT-4o mini: Non-social science research article
Machine learning– and multilayer molecular network–assisted screening hunts fentanyl compounds
Changzhi Shi, Wanli Li, Yang Wang, Xi Chen, Meixiang Yu, Hai Zhang, Zecang You, Maoyong Song, Xiaojun Deng, Mingliang Fang
Full text
Fentanyl and its analogs are a global concern, making their accurate identification essential for public health. Here, we introduce Fentanyl-Hunter, a screening platform that uses a machine learning classifier and multilayer molecular network to select and annotate fentanyl compounds using mass spectrometry (MS). Our classification model, based on 772 fentanyl spectra and spectral binning feature engineering, achieved an F 1 score of 0.868 ± 0.02. The multilayer network, based on spectral similarity and paired mass distances, covers more than 87% of known fentanyls. Fentanyl-Hunter identified fentanyl members in biological and environmental samples. During biotransformation, 35 metabolites from four widely consumed fentanyl derivatives were identified. Norfentanyl was the major fentanyl compound in wastewater. Retrospective screening of these biomarkers across more than 605,000 MS files in public datasets revealed fentanyl, sufentanil, norfentanyl, or remifentanil acid in more than 250 samples from eight major countries, indicating the potential widespread presence of fentanyl.
GPT-4o mini: Non-social science research article
Brain stimulation preferentially influences long-range projections
Pedro G. Vieira, Matthew R. Krause, Pooya Laamerad, Christopher C. Pack
Full text
Advances in brain stimulation have made it possible to target smaller and smaller regions for electromagnetic stimulation, in the hopes of producing increasingly focal neural effects. However, the brain is extensively interconnected, and the neurons comprising those connections may themselves be particularly susceptible to neurostimulation. Here, we test this hypothesis by identifying long-range projections in single-unit recordings from nonhuman primates receiving transcranial alternating current stimulation. We find that putative long-range projections are more strongly affected by stimulation than other cells. Specifically, they are both more entrained on average and account for occurrences of extremely strong entrainment. Given that stimulation appears to target the edges, rather than nodes, of neural networks, it may be necessary to rethink how neurostimulation strategies are designed.
GPT-4o mini: Non-social science research article
Uridine as a potentiator of aminoglycosides through activation of carbohydrate transporters
Manon Lang, Stéphane Renard, Imane El-Meouche, Ariane Amoura, Erick Denamur, Léo Hardy, Julia Bos, Tara Brosschot, Molly A. Ingersoll, Eric Bacqué, Didier Mazel, Zeynep Baharoglu
Full text
Aminoglycosides (AGs) are broad-spectrum antibiotics effective against Gram-negative bacteria, with uptake dependent on membrane potential. However, the mechanisms of AG entry remain incompletely understood. Here, we identify a previously undescribed uptake pathway via carbohydrate transporters in E. coli . By deleting or overexpressing 26 carbohydrate transporters, we found that 18 facilitated AG uptake, a mechanism conserved across several Gram-negative ESKAPEE pathogens. Using fluorescent-labeled AGs and flow cytometry, we quantified differential uptake. To enhance AG efficacy, we screened 198 carbon sources for their ability to induce transporter expression using a cmtA - gfp fusion. Uridine emerged as a strong inducer of cmtA and 12 additional AG-importing transporters. Coadministration of uridine considerably improved AG efficacy against clinical and resistant E. coli strains by enhancing drug uptake. This combination also improved outcomes in human blood ex vivo and in a murine urinary tract infection model. Given uridine’s clinical safety, it holds promise as an adjuvant to potentiate AG treatment against multidrug-resistant infections.
GPT-4o mini: Non-social science research article
Chiral spin constrained assemblies for polarized optical mapping
Mingjiang Zhang, Shanshan Zhao, Jintong Li, Zeyi Li, Junjie Cai, Yajie Zhou, Qi Guo, Wenting Gao, Zhi Tong, Yaxin Wang, Guangen Li, Xueru Guo, Anqi Li, Jing Lin, Taotao Zhuang
Full text
Optical-enabled identification and interaction provide an integral link between the digital and physical realms. However, nowadays optic-encodings, predominantly reliant on light’s intensity and wavelength, are hindered by environmental light interference and limited information capacity. The introduction of unusual polarization states, such as circular polarization—which is absent from ordinary surroundings—holds promise for higher-dimensional interaction. Here, we propose a circularly polarized optical mapper capable of generating high-entropy, noise-resistant keys, serving as a physical interface for unique interaction process between parties. To materialize this mapper, we developed an automated, in situ synthesis platform that facilitates the self-acting fabrication of robust, solid-state, chiral optical spin constrained assemblies. Our mappers, formed by randomized arrays of discrete assemblies, demonstrate near-theoretical performance in uniformity (0.4917), uniqueness (0.4968), and reliability (0.9355). By emitting high-dimensional spin-polarized light, our mappers enable both far-field readout and near-field authentication, with resistance to stray light interference, offering promising applications in the internet of things, augmented reality, and beyond.
GPT-4o mini: Non-social science research article
Somatic mtDNA mutations at intermediate levels of heteroplasmy are a source of functional heterogeneity among primary leukemic cells
Kelly McCastlain, Catherine Welsh, Yonghui Ni, Liang Ding, Ti-Cheng Chang, Robert J. Autry, Besian I. Sejdiu, Qingfei Pan, Melissa Franco, Wenan Chen, Huiyun Wu, Veronica Gonzalez-Pena, Patrick Schreiner, Sasi Arunachalam, Joung Hyuck Joo, Samuel Brady, Jinghui Zhang, Charles Gawad, William E. Evans, M. Madan Babu, Konstantin Khrapko, Jiyang Yu, Gang Wu, Stanley Pounds, Mondira Kundu
Full text
Somatic mitochondrial DNA (mtDNA) mutations are frequently observed in tumors, yet their role in pediatric cancers remains poorly understood. The heteroplasmic nature of mtDNA—where mutant and wild-type mtDNA coexist—complicates efforts to define its contribution to disease progression. In this study, bulk whole-genome sequencing of 637 matched tumor-normal samples from the Pediatric Cancer Genome Project revealed an enrichment of functionally impactful mtDNA variants in specific pediatric leukemia subtypes. Collectively, the results from single-cell sequencing of five diagnostic leukemia samples demonstrated that somatic mtDNA mutations can arise early in leukemogenesis and undergo positive selection during disease progression, achieving intermediate heteroplasmy—a “sweet spot” that balances mitochondrial dysfunction with cellular fitness. Network-based systems biology analyses link specific heteroplasmic mtDNA mutations to metabolic reprogramming and therapy resistance. We reveal somatic mtDNA mutations as a potential source of functional heterogeneity and cellular diversity among leukemic cells, influencing their fitness and shaping disease progression.
GPT-4o mini: Non-social science research article
Acute REM sleep deprivation alleviated depression-like behavior mediated by inhibiting VIP neurons in the mPFC
Yuxuan Zhu, Tongrui Wu, Qingyan Jiao, Haitong Chai, Yuang Wang, Chunxiao Tian, Qiuying Xue, Kai Li, Pu Wang, Zibing Li, Hualin He, Bo Chen, Aili Liu, Hui Shen
Full text
Acute sleep deprivation (SD) rapidly alleviates depression, addressing a critical gap in mood disorder treatment. Rapid eye movement SD (REM SD) modulates the excitability of vasoactive intestinal peptide (VIP) neurons, influencing the synaptic plasticity of pyramidal neurons. However, the precise mechanism remains undefined. To investigate this, we used a modified multiple platform method (MMPM) to induce 12 hours of REM SD, specifically targeting VIP neurons in the medial prefrontal cortex (mPFC). Our results show that REM SD mitigated depression by suppressing VIP neurons activity, which directly increased the excitability of pyramidal neurons and, consequently, promoted synaptic plasticity recovery. In addition, the knockdown of VPAC2 on mPFC pyramidal neurons revealed that VPAC2-mediated AC/cAMP/PKA signaling pathway in these neurons is essential for REM SD to mitigate depression-like behavior. These findings suggest that VIP neurons directly regulate pyramidal neurons and are crucial in alleviating depression by REM SD.
GPT-4o mini: Non-social science research article
Giant KASH proteins and ribosomes establish distinct cytoplasmic biophysical properties in vivo
Xiangyi Ding, Hongyan Hao, Daniel Elnatan, Patrick Neo Alinaya, Shilpi Kalra, Abby Kaur, Sweta Kumari, Liam J. Holt, G. W. Gant Luxton, Daniel A. Starr
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Understanding how cells control their biophysical properties during development remains a fundamental challenge. While macromolecular crowding affects multiple cellular processes in single cells, its regulation in living animals remains poorly understood. Using genetically encoded multimeric nanoparticles for in vivo rheology, we found that Caenorhabditis elegans tissues maintain mesoscale properties that differ from those observed across diverse systems, including bacteria, yeast species, and cultured mammalian cells. We identified two conserved mechanisms controlling particle mobility: Ribosome concentration, a known regulator of cytoplasmic crowding, works in concert with a previously unknown function for the giant KASH (Klarsicht/ANC-1/SYNE homology) protein ANC-1 in providing structural constraints through associating with the endoplasmic reticulum. These findings reveal mechanisms by which tissues establish and maintain distinct mesoscale properties, with implications for understanding cellular organization across species.
GPT-4o mini: Non-social science research article
North Pacific meridional mode has larger impacts on El Niño evolution than the March Madden-Julian Oscillation
Yu Liang, Shang-Ping Xie, Alexey Fedorov, Stephen G. Yeager
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The El Niño–Southern Oscillation (ENSO) is a key driver of global climate variability. Early-season westerly wind bursts (WWBs) have long been suggested to be important for ENSO evolution and diversity, with the Madden-Julian Oscillation (MJO) among the main sources of WWBs. However, MJO’s contribution to ENSO evolution has been difficult to quantify. Here, using an ensemble hindcast approach specifically designed to isolate internal atmospheric variability, we evaluate the influences of March MJO on subsequent ENSO development. Our results show that the March MJO, under favorable background conditions, by itself has limited impacts on ENSO due to weak equatorial air-sea coupling in spring. In comparison, the North Pacific Oscillation–induced meridional mode exerts a more sustained influence on ENSO evolution. A cyclonic circulation anomaly over Hawaii, associated with the Pacific-North American pattern, also plays a role. These findings suggest that March MJO activity alone may not be a reliable predictor for ENSO evolution, but underscore the importance of North Pacific atmospheric variability.
GPT-4o mini: Non-social science research article
TaGW2-TaVOZ1 module regulates wheat salt tolerance via both E3 ligase–dependent and –independent pathways
Shumin Li, Peiyin Zhang, Xuemin Wang, Wenxuan Feng, Hongqing Zhu, Zhen Qin, Bin Chen, Cun Wang, Xiaojun Nie, Zhensheng Kang, Hude Mao
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Wheat production is limited by the rapid expansion of salinized arable land worldwide. Identification of the molecular mechanisms that underlie the salt stress response is of great importance. Here, we uncovered the NAC-type transcription factor, TaVOZ1, as a positive regulator of wheat salt tolerance. Its overexpression could enhance yield and biomass production under salt stress, while TaVOZ1 knockdown attenuates salt tolerance. TaVOZ1 transcriptionally activates stress-responsive genes, especially HKT1 -family transporters, decreasing shoot Na + accumulation. However, the RING-type E3 ligase, TaGW2, directly interacts with and ubiquitinates TaVOZ1, promoting its ubiquitin/26 S proteasomal degradation. TaGW2 overexpression reduces salt tolerance, while its knockdown or knockout enhances wheat response to salt stress. Moreover, we found a moonlight function of TaGW2 wherein it binds the same DNA motifs as TaVOZ1 to block its up-regulation of HKT1 -family genes while coordinately governing both the salt tolerance and grain yield. This study highlights the functional versatility of TaGW2 and defines an antagonistic TaGW2-TaVOZ1 regulatory module in wheat salt tolerance.
GPT-4o mini: Non-social science research article
CD8 + HLA-DR + CD27 + T cells define a population of naturally occurring regulatory precursors in humans
Huidong Guo, Bixia Wang, Zhigui Wu, Qi Zhang, Xinya Jiang, Fangqing Zhang, Jingrui Zhou, Shuang Fan, Yang Zhou, Zheng-Li Xu, Yu Wang, Xiang-Yu Zhao, Xiao-Jun Huang
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Regulatory T reg cells are essential for immune homeostasis. While CD4 T reg cells are well characterized, CD8 T reg cells remain less understood and are primarily observed in pathological or experimental contexts. Here, we identify a naturally occurring CD8 regulatory precursor T rp cell at the steady state, defined by a CD8 + HLA-DR + CD27 + phenotype and a transcriptome resembling CD4 T reg cells. Multiomics analyses reveal activation of TCF7 and costimulatory and co-inhibitory molecules in CD8 T rp cells. CD8 T rp cells suppress T cell expansion in vitro and in vivo. In a humanized xenogeneic graft-versus-host disease (GVHD) model, they dampen T cell activation, alleviate GVHD pathology, and prolong survival without impairing antileukemia activity. Mechanistically, CD8 T rp cells promote immune regulation by inducing FOXP3 expression in both CD4 T reg cells and themselves. Their expansion also correlates with immune homeostasis restoration post–allogeneic stem cell transplantation. These findings establish CD8 T rp cells as a naturally occurring regulatory precursor population that promotes transplantation tolerance.
GPT-4o mini: Non-social science research article
The OsbZIP35-COR1-OsTCP19 module modulates cell proliferation to regulate grain length and weight in rice
Penghui Xu, Najeeb Ullah Khan, Haozhen Wang, Yong Zhao, Bingxia Xu, Qianfeng Hu, Yinghua Pan, Danting Li, Junzhou Li, Xingming Sun, Jinjie Li, Hongliang Zhang, Zichao Li, Zhanying Zhang
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Grain size substantially influences rice quality and yield. In this study, we identified CONTROL OF SLENDER RICE 1 ( COR1 ), a quantitative trait locus encoding an F-box protein that enhances grain length by promoting cell proliferation. The transcription factor OsbZIP35 represses COR1 expression, while COR1 interacts with OsTCP19, leading to its degradation. Knockout of either OsbZIP35 or OsTCP19 results in increased grain length, confirming their regulatory roles in grain development. The OsbZIP35-COR1-OsTCP19 module controls the expression of the cell cycle gene OsCycB1;4 , thereby modulating cell proliferation and ultimately determining grain size. Five haplotypes of COR1 were identified, with COR1 -Hap1 and COR1 -Hap3 being elite alleles associated with longer grains. Field plot trials demonstrated that the near-isogenic line NIL- COR1 SLG increased yield by ~6.6% compared to NIL- COR1 Nip . These findings elucidate the genetic mechanisms underlying grain size regulation and offer promising strategies for improving rice yield.
GPT-4o mini: Non-social science research article
Adaptive superposition compound eyes for perceptions under distinct light levels
Heng Jiang, Chi Chung Tsoi, Yao Chai, Weixing Yu, Chi-Hung Tang, Yu Du, Zuankai Wang, Huaping Jia, Xuming Zhang
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Optical superposition natural compound eyes (OSNCEs) allow circadian insects to thrive in varying light conditions thanks to their unique anatomical structures. This provides a blueprint for optical superposition artificial compound eyes (OSACEs) that can adapt to different illumination intensities. However, OSACEs have received limited research attention until recently, with most studies focusing on apposition compound eyes that operate only in bright light. In this work, we accurately replicate the anatomical features and the ganglia adjustments of OSNCEs using lensed plastic optical fibers as artificial ommatidia. As the core part of this work, we implement a spatial approach alongside a temporal approach derived from both hardware and algorithms to accommodate lighting variations of up to 1000 times while still maintaining high image quality such as 180° field of view, minimal distortion, nearly infinite depth of field, and ultrafast motion detection. These adaptive biomimetic features make the OSACE very promising for surveillance, virtual reality, and unmanned aerial vehicles.
GPT-4o mini: Non-social science research article
Synaptic imbalance and increased inhibition impair motor function in SMA
Emily V. Fletcher, Joshua I. Chalif, Travis M. Rotterman, John G. Pagiazitis, Meaghan Van Alstyne, Nandhini Sivakumar, Danny Florez-Paz, Joseph E. Rabinowitz, Livio Pellizzoni, Francisco J. Alvarez, George Z. Mentis
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Movement is executed through balanced excitation-inhibition in spinal motor circuits. Short-term perturbations in one type of neurotransmission are homeostatically counteracted by the opposing type, but prolonged excitation-inhibition imbalance causes dysfunction at both single neuron and circuit levels. However, whether dysfunction in one or both types of neurotransmission leads to pathogenicity in neurodegenerative diseases characterized by select synaptic deficits is not known. Here, we used functional, morphological, and viral-mediated approaches to uncover the pathogenic contribution of unbalanced excitation-inhibition in a mouse model of spinal muscular atrophy (SMA). We show that vulnerable SMA motor circuits fail to respond homeostatically to reduced excitation and instead increase inhibition. This imposes an excessive burden on motor neurons and further restricts their recruitment. Reducing inhibition genetically or pharmacologically improves neuronal function and motor behavior in SMA mice. Thus, the disruption of excitation-inhibition homeostasis is a major maladaptive mechanism that diminishes the capacity of premotor commands to recruit motor neurons and elicit muscle contractions in SMA.
GPT-4o mini: Non-social science research article
Efficient energy transfer in a hybrid organic-inorganic van der Waals heterostructure
Xiaoqing Chen, Huijuan Zhao, Ruixiang Fei, Chun Huang, Jingsi Qiao, Cheng Sun, Haiming Zhu, Li Zhan, Zehua Hu, Songlin Li, Li Yang, Zemin Tang, Lianhui Wang, Yi Shi, Wei Ji, Jian-Bin Xu, Li Gao, Xuetao Gan, Xinran Wang
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Two-dimensional (2D) materials offer strong light-matter interaction and design flexibility beyond bulk semiconductors, but an intrinsic limit is the low absorption imposed by the atomic thickness. A long-sought-after goal is to achieve complementary absorption enhancement through energy transfer (ET) to break this limit. However, it is found challenging due to the competing charge transfer (CT) process and lack of resonance in exciton states. Here, we report highly efficient ET in a 2D hybrid organic-inorganic heterostructure (HOIST) of Me-PTCDI/WS 2 . Resonant ET is observed leading to enhanced WS 2 photoluminescence (PL) by 124 times. We identify Dexter exchange between the Frenkel state in donor and an excited 2 s state in acceptor as the main ET mechanism, as supported by density functional theory calculations. We further demonstrate ET-enhanced phototransistor devices with enhanced responsivity by nearly 1000 times without sacrificing the response time. Our results expand the understanding of interlayer relaxation processes in 2D materials and open opportunities in optoelectronic devices.
GPT-4o mini: Non-social science research article
Computational design of potent and selective binders of BAK and BAX
Stephanie Berger, Erinna F. Lee, Tiffany J. Harris, Sharon Tran, Asim K. Bera, Lauren Arguinchona, Alex Kang, Banumathi Sankaran, Sila Kasapgil, Michelle S. Miller, Sean Smyth, Mariam Lutfi, Rachel T. Uren, Ruth M. Kluck, Peter M. Colman, Walter D. Fairlie, Peter E. Czabotar, David Baker, Richard W. Birkinshaw
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Potent and selective binders of the key proapoptotic proteins BAK and BAX have not been described. We use computational protein design to generate high affinity binders of BAK and BAX with greater than 100-fold specificity for their target. Both binders activate their targets when at low concentration, driving pore formation, but inhibit membrane permeabilization when in excess. Crystallography shows that the BAK binder induces BAK unfolding, exposing the α6 helix and BH3 domain. Together, these data suggest that upon binding, BAK or BAX unfold; at high binder concentrations, self-association of the partially folded BAK or BAX proteins is blocked and the membrane remains intact, whereas at low concentrations, dimers form, and the membrane ruptures. Our designed binders modulate apoptosis via direct, specific interactions with BAK and BAX and reveal that for therapeutic strategies targeting BAK and BAX, inhibition requires saturating binder concentrations at the site of action.
GPT-4o mini: Non-social science research article
Unleashing pyroelectricity enhancement via phase transition–driven defect alignment in KNN-based ferroelectrics
Yuntao Huang, Yao Wu, Tiantian Wu, Jianwei Chen, Sijin Wang, Kan-Hao Xue, Zhengqian Fu, Wen Dong, Ting Zheng, Shujun Zhang, Jiagang Wu
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The pyroelectric effect plays a critical role in thermal imaging and energy harvesting. Despite extensive efforts to enhance performance through doping and composite engineering, the mechanisms underlying defect dipole coupling with phase structures remain poorly understood, impeding the advancement of defect-engineered symmetry modulation. Here, we report an abnormal pyroelectric phenomenon where the pyroelectric coefficient ( p ) increases notably when poling temperature exceeds the orthorhombic-to-tetragonal phase transition temperature ( T O-T ) in potassium sodium niobate ceramics. The p at 200°C ( p  = 45.4 × 10 −4 C m −2  K −1 ) rises more than sevenfold compared to poling within the orthorhombic phase ( p  = 6.5 × 10 −4 C m −2  K −1 ), representing the highest value reported to date and offering benefit for high-temperature thermal sensing. A dual mechanism is proposed, involving rigid-ion displacement and defect dipole alignment, which respectively contribute to increased displacement charge and space charge. Our findings establish a paradigm for optimizing high-temperature pyroelectrics through a simple, symmetry-confined thermal poling.
GPT-4o mini: Non-social science research article
Differential modulation of movement speed with state-dependent deep brain stimulation in Parkinson’s disease
Alessia Cavallo, Richard M. Köhler, Johannes L. Busch, Jeroen G. V. Habets, Timon Merk, Patricia Zvarova, Jojo Vanhoecke, Thomas S. Binns, Bassam Al-Fatly, Ana Luisa de Almeida Marcelino, Natasha Darcy, Gerd-Helge Schneider, Patricia Krause, Andreas Horn, Katharina Faust, Damian M. Herz, Eric Yttri, Hayriye Cagnan, Andrea A. KĂŒhn, Wolf-Julian Neumann
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Subthalamic deep brain stimulation (STN-DBS) provides unprecedented spatiotemporal precision for the treatment of Parkinson’s disease (PD), allowing for direct real-time state-specific adjustments. Inspired by findings from optogenetic stimulation in mice, we hypothesized that STN-DBS can mimic dopaminergic reinforcement of ongoing movement kinematics during stimulation. To investigate this hypothesis, we delivered DBS bursts during particularly fast and slow movements in 24 patients with PD. Our findings reveal that DBS during fast movements enhanced future movement speed more than DBS during slow movements, raising movement speed to the level of healthy controls. To understand which brain circuits mediate this neurophysiological mechanism, we investigated the behavioral effects using magnetic resonance imaging connectomics and motor cortex electrocorticography. Last, we demonstrate that machine learning–based brain signal decoding can be used to predict continuous movement speed for fully embedded state-dependent closed-loop algorithms. Our findings provide important evidence for reinforcement-based DBS circuit mechanisms that may inspire previously unexplored treatment avenues for dopaminergic disorders.
GPT-4o mini: Non-social science research article
Planetary Health Diet and risk of mortality and chronic diseases: Results from US NHANES, UK Biobank, and a meta-analysis
Yuanyuan Wang, Da Pan, Chen Zhang, Dengfeng Xu, Yifei Lu, Shiyu Yin, Pei Wang, Jiayue Xia, Junhui Yu, Lirong Dong, Guiju Sun
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The health benefits of the Planetary Health Diet (PHD) require further validation. We examined associations between PHD adherence and risks of mortality and chronic diseases using data from two prospective cohorts—the US NHANES (1999–2018, 42,947 participants) and the UKB (125,372 participants)—and a meta-analysis of 37 published cohort studies (3,244,263 participants). Higher adherence to PHD was associated with lower all-cause mortality in both cohorts. In the UKB, it was also associated with reduced the risk of cancer and respiratory disease mortality. In the meta-analysis, higher adherence to the PHD was associated with lower risks of all-cause, cancer, and cardiovascular disease (CVD) mortality and reduced risks of colorectal cancer, lung cancer, CVDs, coronary heart disease, stroke, and diabetes. This analysis suggests that higher adherence to the PHD may offer substantial health benefits.
GPT-4o mini: Non-social science research article
Intermodal microwave-to-optical transduction using silicon-on-sapphire optomechanical ring resonator
I-Tung Chen, Nicholas S. Yama, Haoqin Deng, Qixuan Lin, Yue Yu, Abhi Saxena, Arka Majumdar, Kai-Mei C. Fu, Mo Li
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Optomechanical and electro-optomechanical systems have emerged as one of the most promising approaches for quantum microwave-to-optical transduction to interconnect distributed quantum modalities for scaling the quantum systems. These systems use suspended structures to increase mode overlap and mitigate loss to achieve high efficiency. However, the suspended design’s poor heat dissipation under strong drive limits the ultimate efficiency. Here, we demonstrate an unsuspended optomechanical ring resonator (OMR) based on the silicon-on-sapphire (SOS) platform for microwave-to-optical frequency conversion. The OMR achieves a triply resonant optical-to-optical conversion with an enhanced coupling rate G b  = 3.6 gigahertz per square-root milliwatt at a peak conversion efficiency of 1.2% with 3.6-milliwatt microwave drive power and a microwave-to-optical conversion efficiency of 1.5 × 10 −5 at 10-milliwatt optical drive power. Our results show that the unsuspended SOS platform, which mitigates the thermal effect and is compatible with superconducting qubits, is a promising platform for optomechanical circuitry and quantum transduction.
GPT-4o mini: Non-social science research article
Chiral edge state control of thermoelectric effects
William Huynh, Boliang Liu, Simon Munyan, Sina Ahadi, Susanne Stemmer
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Thermoelectric responses in two-dimensional electron gases subjected to magnetic fields have the potential to provide unique information about quasiparticle statistics. In this study, we show that chiral edge states play a key role in thermoelectric Hall bar measurements by completely controlling the direction of the internal thermal gradient. To this end, we perform measurements of the magnetothermoelectric responses of cadmium arsenide quantum wells. The magnetothermoelectric responses in the quantum Hall regime agree with theoretical predictions if one considers the role of chiral edge states, which flow in opposite directions on either side of the Hall bar and establish an internal temperature gradient that is perpendicular to the externally applied thermal gradient. We show that the results are self-consistent within this picture under different measurement conditions. We discuss potential applications of the findings, such as in nanoscale control of local temperature gradients and thermoelectric effects along with the characterization of other topological systems with chiral edges states.
GPT-4o mini: Non-social science research article
Repurposing polyethylene terephthalate plastic waste to capture carbon dioxide
Margarita Poderyte, Rodrigo Lima, Peter Illum GolbĂŠkdal, Dennis Wilkens Juhl, Kathrine L. Olesen, Niels Chr. Nielsen, Arianna Lanza, Ji-Woong Lee
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Polyethylene terephthalate (PET) is a ubiquitous polymer with a lack of viable waste management solutions besides mechanical recycling, incineration, and landfilling. Herein, we demonstrate a chemical upcycling of PET waste into materials for CO 2 capture via aminolysis. The aminolysis reaction products—a bis-aminoamide (BAETA) and oligomers—exhibit high CO 2 capture capacity up to 3.4 moles per kilogram as a stand-alone organic solid material. BAETA shows strong chemisorption featuring high selectivity for CO 2 capture from flue gas (5 to 20% CO 2 ) and ambient air (~400 parts per million CO 2 ) under humid conditions. Our thermally stable material (>250°C) enables CO 2 capture at high temperatures (up to 170°C) for multiple cycles. Scalability of the material production was demonstrated by performing aminolysis of untreated consumer waste PET of 1 kilogram. Our approach introduces a simple and straightforward solution that can address both plastic waste and carbon dioxide, offering a potential pathway toward net negative emissions.
GPT-4o mini: Non-social science research article
Magnetic field–enhanced vertical integration enables embodied intelligence in untethered soft robots
Xiaosa Li, Xiao Xiao, Xiao Xiao, Zixiao Liu, Junhao Gong, Zenan Lin, Bing Xue, Shibo Liu, Xinru Wu, Wei Zhang, Dongkai Wang, Runze Zhao, Zihan Wang, Xiongwei Zhong, Yiliang Lin, Patrick Chia, Ximin He, John S. Ho, Ghim Wei Ho, Wei Ouyang, Wenbo Ding, Guangmin Zhou, Cecilia Laschi, Changsheng Wu
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Embodied intelligence in soft robotics offers unprecedented capabilities for operating in uncertain, confined, and fragile environments that challenge conventional technologies. However, achieving true embodied intelligence—which requires continuous environmental sensing, real-time control, and autonomous decision-making—faces challenges in energy management and system integration. We developed deformation-resilient flexible batteries with enhanced performance under magnetic fields inherently present in magnetically actuated soft robots, with capacity retention after 200 cycles improved from 31.3 to 57.3%. These compliant batteries enable large-area deployment of 44.9% across the robot body, and their vertical integration with rationally designed flexible hybrid circuits minimizes additional stiffness while maintaining deformability. This actuator-battery-sensor vertical integration methodology maximizes functional area utilization in a manta ray–inspired soft robot, establishing an untethered platform with sensing, communication, and stable power supply. The system demonstrates embodied intelligence in aquatic environments through diverse capabilities including perturbation correction, obstacle avoidance, and temperature monitoring, with proprioceptive and environmental sensing enabling real-time decision-making during magnetically actuated locomotion.
GPT-4o mini: Non-social science research article
AI-powered automated model construction for patient-specific CFD simulations of aortic flows
Pan Du, Delin An, Chaoli Wang, Jian-Xun Wang
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Image-based modeling is essential for understanding cardiovascular hemodynamics and advancing the diagnosis and treatment of cardiovascular diseases. Constructing patient-specific vascular models remains labor-intensive, error-prone, and time-consuming, limiting their clinical applications. This study introduces a deep-learning framework that automates the creation of simulation-ready vascular models from medical images. The framework integrates a segmentation module for accurate voxel-based vessel delineation with a surface deformation module that performs anatomically consistent and unsupervised surface refinements guided by medical image data. The integrated pipeline addresses key limitations of existing methods, enhancing geometric accuracy and computational efficiency. Evaluated on public datasets, it achieves state-of-the-art segmentation performance while substantially reducing manual effort and processing time. The resulting vascular models exhibit anatomically accurate and visually realistic geometries, effectively capturing both primary vessels and intricate branching patterns. In conclusion, this work advances the scalability and reliability of image-based computational modeling, facilitating broader applications in clinical and research settings.
GPT-4o mini: Non-social science research article
Skin-adaptive focused flexible micromachined ultrasound transducers for wearable cardiovascular health monitoring
Jiawei Yuan, Zhikang Li, Yihe Zhao, Ruiyan Luo, Shaohui Qin, Jie Li, Min Li, Gengyu Han, Zixuan Li, Zilong Zhao, Jiazhu Li, Shiwang Zhang, Zheng Yuan, Xiangguang Han, Lihong Fan, Xiaozhang Wang, Tong Wang, Ping Yang, Libo Zhao, Lirong Yuan, Yi Lv, Rongqian Wu, Tzung K. Hsiai, Zhuangde Jiang
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Continuous monitoring of cardiovascular vital signs can reduce the incidence and mortality of cardiovascular diseases, yet cannot be implemented by current technologies because of device bulkiness and rigidity. Here, we report self-adhesive and skin-conformal ultrasonic transducer arrays that enable wearable monitoring of multiple hemodynamic parameters without interfering with daily activities. A skin-adaptive focused ultrasound method with rational array design is proposed to implement measurement under wide ranges of skin curvatures and depths with improved sensing performances. We introduce a self-adhesive hydrogel layer to enhance the acoustic impedance matching, biocompatibility and contact reliability at device-skin interfaces, and a microelectromechanical systems-compatible process for batch-to-batch and high-consistency manufacturing. The resultant transducer array, with a frequency of 2.4 megacycles per second and a –6 dB bandwidth of 47%, implements accurate and continuous detection of cardiovascular signs, including blood pressure (BP) waveforms of various arteries, heart rate and BP during exercises, and arterial stiffness, validated clinically.
GPT-4o mini: Non-social science research article
Seafloor geodesy unveils seismogenesis of large subduction earthquakes in Mexico
Víctor M. Cruz-Atienza, Josué Tago, Luis A. Domínguez, Vladimir Kostoglodov, Yoshihiro Ito, Efraín Ovando-Shelley, Tonatiuh Rodríguez-Nikl, Renata Gonzålez, Sara Franco, Darío Solano-Rojas, Joel Beltrån-Gracia, Paulina Miranda-García, Frédérick Boudin, Luis Rivera, Anne Bécel, Carlos Villafuerte, Jorge Real, Ekaterina Kazachkina, Arturo Ronquillo
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Based on measurements of near-trench deformations of the oceanic and overriding plates, in this investigation, we elucidate the tectonic and mechanical processes leading to the M w 7.0 (moment magnitude of 7.0) Acapulco, Mexico, earthquake in 2021. We exploit unprecedented ocean-bottom observations using ultralong-period “tilt mechanical amplifiers,” along with hydrostatic pressure, global navigation satellite system, and satellite interferometric synthetic aperture radar data. The joint inversion of these geodetic data, template-matching seismicity, and repeating earthquakes, revealed the first two shallow slow slip events (SSEs) observed in Mexico. The first one migrated from the trench to the earthquake hypocenter before rupture, and the second one occurred following an M w 7.3 long-term SSE induced by the earthquake. Episodic near-trench oceanic-crust deformations (i.e., tilt transients) associated with shallow and deep synchronous decoupling of the plate interface reveal the occurrence of “slab-pull surges” before three regional earthquakes of magnitude 7 or greater, including the Acapulco event, suggesting that they may serve as rupture precursors observable in subduction zones.
GPT-4o mini: Non-social science research article
End-to-end inverse design for programmable acoustic tweezers with simultaneous force and torque control by metasurfaces
Yu Liu, Hao-Wen Dong, Xue Jiang, Han-Jie Xiao, Chuan-Xin Zhang, Yue-Sheng Wang
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Acoustic tweezers leverage acoustic radiation forces for noncontact manipulation. One of the core bottlenecks in multidimensional manipulation is the lack of a systematic design methodology, which prevents the generation of an acoustic field that simultaneously meets the collaborative control requirements of multi-degree-of-freedom forces and torques, making it difficult to achieve precise control under conditions of stable suspension, high-frequency rotation, and complex spatial constraints. To address this challenge, we develop an end-to-end inverse design methodology for acoustic tweezers based on coding metasurfaces, establishing a dual-objective, dual-scale optimization paradigm. At the microscale, the phase modulation and transmission efficiency are co-optimized through coupled physical models. While at the mesoscale, the particle suspension and rotation dynamics are considered. Based on the inverse design framework constructed with a finite-bit element library, we successfully optimized the metasurface configuration with specific acoustic response characteristics and achieved noncontact, multi-degree-of-freedom customized manipulation of individual particles. This approach provides implementation pathways for adaptive multiscale strategies in precision engineering applications.
GPT-4o mini: Non-social science research article
Bone health: Age-related changes in diaphyseal structural properties among European Holocene humans during the last 9000 years
VladimĂ­r SlĂĄdek, Martin Hora, Cara Wall-Scheffler, Michal StruĆĄka, Margit Berner
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Age-related deterioration in bone strength among Western humans has been linked with sedentary lifestyles, but the effect remains debatable. We evaluated aging of diaphyseal strength and cortical bone loss in a European Holocene sample of 1881 adult humeri, femora, and tibiae. Diaphyseal aging did not differ between Early and Late Holocene adults, despite their differences in physical activity. Adult diaphyseal aging was accompanied by the disproportionate rate between a faster increase in the medullary area and an absent or marginal increase in the total area. This indicates that subperiosteal apposition did not fully biomechanically compensate for the medullary expansion. Diaphyseal strength remained unchanged through age in female femora and male diaphyses but declined in female humeri and tibiae. We highlight the importance of postnatal growth to compensate for adult medullary expansion. Diaphyseal aging is critical for the upper limbs, as humeri are more sensitive to aging than femora and tibiae.
GPT-4o mini: Non-social science research article
Mechanosensitive biochemical imprinting of the talin interaction with DLC1 regulates RhoA activity and cardiomyocyte remodeling
Emilie Marhuenda, Ioannis Xanthis, Poppy O. Smith, Aishwarya Prakash, Till Kallem, Pragati Pandey, Darren Graham Samuel Wilson, Amar Azad, Megan Richter, Davor Pavlovic, Katja Gehmlich, Giuseppe Faggian, Pamela Swiatlowska, Elisabeth Ehler, James Levitt, Simon P. Poland, Simon Ameer-Beg, Benjamin T Goult, Thomas Iskratsch
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During heart disease, the cardiac extracellular matrix (ECM) undergoes a structural and mechanical transformation. Cardiomyocytes sense the mechanical properties of their environment, leading to phenotypic remodeling. A critical component of the ECM mechanosensing machinery, including the protein talin, is organized at the cardiomyocyte costamere. Our previous work indicated a different talin tension, depending on the ECM stiffness, but the effects on downstream signaling remained elusive. Here, we identify that the talin interacting proteins DLC1 (deleted in liver cancer 1), RIAM (Rap1-interacting adaptor molecule), and paxillin each preferentially bind to talin at a specific ECM stiffness, this interaction is preserved in the absence of tension, and the interaction is regulated through focal adhesion kinase signaling. Moreover, DLC1 regulates cardiomyocyte RhoA activity in a stiffness-dependent way, whereby the loss of DLC1 results in myofibrillar disarray. Together, this study demonstrates a mechanism of imprinting mechanical information into the talin interactome to fine-tune RhoA activity, with impacts on cardiac health and disease.
GPT-4o mini: Non-social science research article
Retinal gene therapy using epiretinal AAV-containing fibrin hydrogel implants
Brittni A. Scruggs, Aubrey Berger, Travis Knudsen, Francesca N. Kopp, Matthew Hill, Emma Trncic, Kjersten Anderson, Raymond Iezzi, Alan D. Marmorstein
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Subretinal injection of adeno-associated virus (AAV) is generally more efficacious and less inflammatory than intravitreal injection for retinal gene therapy. However, adverse events (e.g., chorioretinal atrophy) have been reported in many patients receiving subretinal injection of Luxturna (voretigene neparvovec-rzyl) and experimental gene therapies. Subretinal injection confines transduction to the treated area. To address this, we manufactured high-concentration fibrin hydrogels encapsulating AAV2–green fluorescent protein (AAV2- GFP ). Gels had homogeneous AAV distribution, desired mechanical properties, and retained infectivity. Epiretinal placement of fibrin–AAV2- GFP ( n  = 11) was compared to subretinal ( n  = 5) and intravitreal AAV2- GFP injection ( n  = 3). The subretinal group exhibited inconsistent retinal pigment epithelium (RPE) transduction restricted to the injection region with severe atrophy in two cases. The intravitreal group had weak transduction and inflammation. In contrast, epiretinal hydrogels degraded within days and led to broad transduction of RPE without atrophy or inflammation. This technology could advance gene therapy for retinal degenerations and other ocular or systemic disorders.
GPT-4o mini: Non-social science research article
Printed sensing human-machine interface with individualized adaptive machine learning
Guohui Wang, Yao Tang, Xinran Luo, Shengdi Lu, Yiru Zhou, Yi Lu, Guangyang Sun, Pei Liu, Jiayu Ning, Hua Jiang, Ke Hu, Hongzhen Liu, Wenqi Song, You Yu
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Developing intelligent robots with integrated sensing capabilities is critical for advanced manufacturing, medical robots, and embodied intelligence. Existing robotic sensing technologies are limited to recording of acceleration, driving torque, pressure feedback, and so on. Expanding and integrating with the multimodal sensors to mimic and even surpass the human feeling is substantially underdeveloped. Here, we introduce a printed soft human-machine interface consisting of an e-skin–enabled gesture recognitions with feedback stimulus and a soft robot with multimodal perception of contact pressure, temperature, thermal conductivity, and electrical conductivity. The sensing e-skin with adaptive machine learning was able to decode and classify the hand gestures with re-wearable convenience and individual’s differences. The soft interface provides the bidirectional communications between robotics and human bodies in the close-loop. This work could substantially extend the robotic intelligence and pave the way for more practical applications.
GPT-4o mini: Non-social science research article
Living with temperature changes: Salicylic acid at the crossroads of plant immunity and temperature resilience
Wei Li, Guoqing Sun, Wentao Yang, Naiyi Lin, Kaihuai Li, Fengquan Liu, Ming Chang (ćžžæ˜Ž)
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Salicylic acid (SA) is a key defense hormone shaped by temperature. High temperatures suppress, while low temperatures enhance, SA biosynthesis and signaling, thereby influencing plant immunity and temperature resilience. This review synthesizes current understanding of how temperature modulates SA pathways and their cross-talk with other hormones to balance growth and defense. We also propose a conceptual model positioning SA as a central integrator of temperature perception, immune regulation, and hormonal signaling. However, key questions remain: How do plants sense temperature shifts to regulate SA dynamics? How do temperature-induced epigenetic changes in SA pathways contribute to long-term adaptation? And how can these insights inform crop improvement? Addressing these gaps is essential for developing climate-resilient crops.
GPT-4o mini: Non-social science research article
Cicada rib-inspired tough films through nanoconfined crystallization for use in acoustic transducers
Jiajun Mao, Jia Yan, Ziyu Wang, Teng Ke, Jingsong Peng, Mingzhu Li, Qunfeng Cheng
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Acoustic transducers require films that demonstrate both toughness and fatigue resistance, presenting notable challenges when achieved through conventional nanoscale reinforcing strategies. Here, we found that the rib structure of a cicada’s tymbal exhibits exceptional toughness and fatigue resistance, attributed to its unique architecture composed of alternating soft and stiff polymer layers. Inspired by this rib structure, we developed a robust artificial rib film (ARF) using a nanoconfined crystallization strategy that involves the deposition of soft polyethylene oxide and stiff phenol formaldehyde. The ARF demonstrates a toughness amplification factor twice that of the cicada’s tymbal rib and exhibits an exceptionally long fatigue life. The nanoconfined crystallization restricts molecular motion and disperses external forces within the crystalline structure, thereby enhancing its mechanical properties. These improvements enable the ARF to outperform commercial polymer films as an acoustic transducer, achieving 2.7 times increase in frequency response and 2.2 times increase in displacement amplitude.
GPT-4o mini: Non-social science research article
Bioadaptive liquid-infused multifunctional fibers for long-term neural recording via BDNF stabilization and enhanced neural interaction
Tae Young Kim, Yeonzu Son, Keun-Young Yook, Dong Gyu Lee, Young Kim, Seo Jung Kim, Kijun Park, Yurim Lee, Tae Kyung Lee, Justin J. Chung, Congqi Yang, Seongjun Park, Jungmok Seo
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Brain-computer interfaces (BCIs) enable direct communication between the brain and computers. However, their long-term functionality remains limited due to signal degradation caused by acute insertion trauma, chronic foreign body reaction (FBR), and biofouling at the device-tissue interface. To address these challenges, we introduce a multifunctional surface modification strategy called targeting-specific interaction and blocking nonspecific adhesion (TAB) coating for flexible fiber, achieving a synergistic integration of mechanical compliance and biochemical stability. The coating combines brain-derived neurotrophic factor (BDNF) conjugation and a lubricant-infused surface. This dual-functional design enables selective interaction with neurons and astrocytes while preventing nonspecific adhesion. Notably, high-quality single-unit neural signals were stably recorded for more than 12 months after implantation, demonstrating exceptional long-term recording performance. Integrating mechanical compatibility, antifouling properties, and selective neural cell interaction, the TAB-coated multifunctional fiber represents a transformative approach for neural implants, bridging biological systems with computational systems.
GPT-4o mini: Non-social science research article
An early surge of norepinephrine along brainstem pathways drives sensory-evoked awakening
Noa Matosevich, Noa Regev, Uddi Kimchy, Noam Zelinger, Sina Kabaha, Noam Gabay, Amit Marmelshtein, Yuval Nir
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The locus coeruleus–norepinephrine (LC-NE) system regulates arousal and awakening; however, it remains unclear whether the LC does this in a global or circuit-specific manner. We hypothesized that sensory-evoked awakenings are predominantly regulated by specific LC-NE efferent pathways. Anatomical, physiological, and functional modularities of LC-NE pathways involving the mouse basal forebrain (BF) and pontine reticular nucleus (PRN) were tested. We found partial anatomical segregation between the LC → PRN and LC → BF circuits. Extracellular NE dynamics in BF and PRN exhibited distinct sound-evoked activation during sleep, including a fast sound-evoked NE peak specific to PRN. Causal optogenetic interrogation of LC efferent pathways, by retro-channelrhodopsin (ChR2) activation or Platynereis dumerilii ciliary opsin (PdCO) silencing of synapses in target regions, revealed a role for early LC → PRN activity in driving arousal and sound-evoked awakenings. Together, our results uncover a role for early LC-NE PRN activity in connecting sensory and arousal pathways and establish LC heterogeneity in regulating arousal.
GPT-4o mini: Non-social science research article
Magnitude uncertainty dominates intermodel spread in zonal-mean precipitation response to anthropogenic aerosol increase
Yu-Fan Geng, Shang-Ping Xie, Xiao-Tong Zheng, Hai Wang, Sarah M. Kang, Xiaopei Lin, Lixin Wu, Fengfei Song
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Anthropogenic aerosols are an important driver of historical climate change but the climate response is not fully understood and the climate model simulations suffer large uncertainties. On the basis of a multimodel ensemble of historical aerosol forcing simulation for a period of global aerosol increase during 1965 to 1989, here, we show that the precipitation response shares a common southward displacement of tropical rain bands but the magnitude differs markedly among models, accounting for 76% of the intermodel uncertainty in zonal-mean precipitation change. Our analysis of atmospheric energetics further reveals key mechanisms for magnitude uncertainty: aerosol radiative forcing drives, cloud radiative feedback amplifies, and ocean circulation damps the intermodel uncertainty in cross-equatorial atmospheric energy transport change and the meridional shift of tropical rain bands. This has important implications for understanding and reducing intermodel uncertainty in anthropogenic climate change.
GPT-4o mini: Non-social science research article
Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti–PD-1 therapy
Jielin Liu, Shelley Herbrich, Sreyashi Basu, Yulong Chen, Ashwat Nagarajan, Swetha Anandhan, Sangeeta Goswami, Liangwen Xiong, Baoxiang Guan, Padmanee Sharma
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PTDSS1 (phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti–PD-1 therapy. Depletion of Ptdss1 in tumor cells increased expression of interferon-γ (IFN-γ)–regulated genes, including B2m , Cxcl9 , Cxcl10 , and Stat1 , even in the absence of IFN-γ stimulation in vitro. Loss of Ptdss1 in tumor cells also led to increased expression of MHC-I, enhanced cytotoxicity of CD8 + T cells, and increased frequency of an iNOS + myeloid subset. A gene signature derived from the iNOS + myeloid cell subset correlated with clinical benefit in patients treated with anti–PD-1 therapy. Moreover, genetic and pharmacological inhibition of Ptdss1 in different tumor models improved anti–PD-1 therapy. Together, our results provide insights on a therapeutic strategy for overcoming immunosuppression by inhibiting PTDSS1 and provide rationale for development of a combination immunotherapy strategy composed of PTDSS1 inhibition plus PD-1 blockade.
GPT-4o mini: Non-social science research article
Non-neutralizing antibodies to influenza A matrix-protein-2-ectodomain are broadly effective therapeutics and resistant to viral escape mutations
Teha Kim, Lynn Bimler, Sydney L. Ronzulli, Amber Y. Song, Scott K. Johnson, Cheryl A. Jones, S. Mark Tompkins, Silke Paust
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Influenza A viruses remain a global health threat, yet no universal antibody therapy exists. Clinical programs have centered on neutralizing mAbs, only to be thwarted by strain specificity and rapid viral escape. We instead engineered three non-neutralizing IgG2a mAbs that target distinct, overlapping epitopes within the conserved N terminus of the M2 ectodomain (M2e). Combined at low dose, this “triple M2e-mAb” confers robust prophylactic and therapeutic protection in mice challenged with diverse human and zoonotic IAV strains, including highly pathogenic variants. Therapeutic efficacy depends on Fc-mediated effector activity via FcγRI, FcγRIII, and FcγRIV, rather than in vitro neutralization. Serial passaging in triple M2e-mAb–treated immunocompetent and immunodeficient hosts failed to generate viral escape mutants. Our findings redefine the influenza-specific antibody therapeutic design and support Fc-optimized, non-neutralizing M2e-mAbs as a broadly effective, mutation-resistant, off-the-shelve therapy with direct relevance to human pandemic preparedness.
GPT-4o mini: Non-social science research article
Robotic micromanipulation for patterned and complex organoid biofabrication
Mingsi Tong, Gang Huang, Songlin Zhuang, Xinghu Yu, Delin Hu, Weiyang Lin, Yang Wu, Yuchen Chen, Shijia Cheng, Meng Jiang, Li Zhang, Huijun Gao
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Organoids have emerged as powerful models for recapitulating tissue physiology and pathology in biomedical research. However, the need for consistent and complex manufacturing of organoids remains a challenge. The absence of standardization and quality control of cells dispersed within extracellular matrices impedes the widespread application of organoids. Here, we introduce a micromanipulation platform that effectively constrains cell distribution to enable patterned and complex organoid biofabrication. This system integrates multidimensional cell sense technology to provide real-time feedback, enabling adaptive fluid dynamics control that robustly compensates for seeding-induced nonlinear fluidic perturbations. Through this closed-loop control, the micromanipulation platform effectively restrains the spatial distribution of multiple cell types, promoting consistent self-assembly. Using this platform, we have successfully achieved programmable organoid manufacturing as well as the construction of assembloids composed of multiple cell types that better mimic mature organ microenvironments. This supports advancements in organoid-based biomechanism discovery, drug screening, and other organoid-related investigations.
GPT-4o mini: Non-social science research article
Formation of breccia pipes associated with a hydrogen-rich hydrothermal system on the east Caroline plate in the West Pacific
Yuanyuan Xiao, Kun Wang, Yuan Wang, Shuai Yuan, Hongyun Zhang, Tianyu Zhang, Congying Li, Annan Ren, Guozhi Xie, Vadim S. Kamenetsky, Hao Xie, Fengtai Tong, Shengji Wei, Weidong Sun
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A large hydrothermal field at depths >4300 meters was found on the east Caroline plate in the western Pacific Ocean. Here, we show that large hydrothermal pipes with steep walls and breccia-dominated bottoms suggest explosions of billion metric tons of TNT (trinitrotoluene) equivalent. More than 800 short-duration seismic events were detected within 28 days along a 150-kilometer profile, indicating widespread ongoing explosive gas release. We suggest that billions of tons of hydrogen gas were produced through serpentinization associated with fluid infiltration via fractures formed by bending of the oceanic plate. Hydrogen was retained in fractures sealed by mud and carbonate. However, hydrogen alone cannot produce the explosive capacity responsible for the formation of pipes. Oxygen released from circulating seawater can be concentrated at crustal depths and then mixed with mantle-derived hydrogen. Explosion of the gas mixture releases large amounts of heat that triggers further explosions of compressed hydrogen gas and results in the formation of hydrothermal pipes.
GPT-4o mini: Non-social science research article
Acoustofluidic system for targeted antibody removal in transplantation: Enabling small-volume therapeutic apheresis
Zhiteng Ma, Riley Kahan, Jianping Xia, Mengxi Wu, Brandon Lu, Emeraghi David, Ye He, Ying Chen, Jessica F. Liu, Mingyuan Liu, Haojun Xu, Linda Stempora, Nader Abraham, Ruoyu Zhong, Kaichun Yang, Ke Jin, Ke Li, Min Zhang, Qian Wu, Andrew Barbas, Jean Kwun, Luke P. Lee, Tony Jun Huang, Eileen T. Chambers
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Antibody-mediated rejection is a leading cause of allograft failure and mortality in pediatric solid organ transplant recipients. Current apheresis systems require large blood volumes and are primarily designed for adults, making them unsuitable for children and small animals. These systems often indiscriminately remove both harmful and protective antibodies, increasing the risk of complications such as life-threatening infections. To address this critical need, we developed acoustofluidic-based system for targeted antibody removal in transplantation (A-START). A-START is engineered to handle small blood volumes and has demonstrated efficacy in preclinical small animal trials. In a sensitized rodent skin transplantation model, A-START only demands 240 microliters of blood, selectively removing donor-specific alloantibodies (DSAs) while preserving protective antibodies, such as tetanus antibodies. A-START retains ~95% of beneficial antibodies and achieves a 60% improvement in DSA removal compared to conventional methods. These findings highlight the transformative potential of A-START as a promising, reliable, scalable solution for improving outcomes in pediatric transplantation and treating antibody-mediated diseases.
GPT-4o mini: Non-social science research article
Near-unity spontaneous emission factor InP surface-emitting lasers based on quasi-bound states in the continuum
Wei Wen Wong, Xiaoying Huang, Olivier Lee Cheong Lem, Chennupati Jagadish, Hark Hoe Tan
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Surface-emitting lasers featuring optical bound states in the continuum (BICs) have recently emerged as a promising alternative to vertical cavity surface-emitting lasers. However, structural damage caused by top-down fabrication processes remains as a major obstacle that limits device performance. Here, we overcome this bottleneck by demonstrating surface-emitting quasi-BIC lasers fabricated with a bottom-up, etching-free process. We epitaxially grow arrays of crystal phase–engineered InP nanosheets with atomically smooth sidewalls as both the laser active medium and a symmetry-broken quasi-BIC cavity, strategically optimizing coupling between spontaneous emission and the lasing mode. Furthermore, we leverage the dipole selection rule associated with the wurtzite crystal structure of the nanosheets for side mode suppression, achieving single-mode lasing at room temperature with lasing threshold as low as 14 ÎŒJ cm −2 pulse −1 . Optimal light-cavity coupling is evidenced by spontaneous emission factors as high as 0.8, showcasing the potential of bottom-up BIC lasers in realizing near-thresholdless lasing at room temperature.
GPT-4o mini: Non-social science research article
Rapid moving by liquid-amplified electrostatic rolling
Fei Jia, Shengjun Fan, Jianglong Guo, Yanju Liu, Jinsong Leng
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Mobile robots that simultaneously have fast speeds, sufficient load-carrying capabilities, and multiple locomotive functions have always been challenging to develop. Here, we introduce a liquid-amplified electrostatic rolling (LAER) mechanism, which elegantly integrates actuation and adhesion into a streamline single-degree-of-freedom structure. Based on this, we developed a rigid tethered LAER roller (0.015 grams) that exhibited a rapid moving speed of ~210 body length per second on ceilings and a flexible tethered roller (10.600 grams) that had a load-to-weight ratio of ~121 moving on the ground. Liquid regulating modules were embedded into LAER structures to exhibit controlled moving. We also developed a single-wheeled and two-wheeled untethered LAER robots with onboard power supply. Furthermore, we demonstrate a LAER linear actuator and a camera equipped untethered LAER robot for preliminary environmental monitoring. The lightweight, scalable LAER structure is promising to bring fast electrostatic actuators, motors, and robots with superior load-to-weight ratios and multimodal locomotion capabilities such as turning, circular moving, and plane-to-plane transitioning.
GPT-4o mini: Non-social science research article
A compact cassette tape for DNA-based data storage
Jiankai Li, Cuiping Mao, Shuchen Wang, Xingjian Li, Xueqing Luo, Dou Wang, Shuo Zheng, Jialin Shao, Rui Wang, Chunhai Fan, Xingyu Jiang
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DNA with high storage density can serve as an alternative storage medium to respond to the global explosion of data growth and become a powerful personal storage memory if an integrated compact device can store and handle large-scale data. Here, we incorporate a DNA cassette tape with 5.5 × 10 5 addressable data partitions (addressing rate up to 1570 partitions per second), a DNA loading capacity of 28.6 mg per kilometer, and deposit-many-recover-many (DMRM) features per partition to flexibly manage large-scale storage data and achieve hundreds of years of data preservation. We develop a compact DNA cassette tape drive and verify its functionality by randomly depositing incomplete images into the data partition, demonstrating a completely automated closed-loop operation involving addressing, recovery, removal, subsequent file deposition, and file recovery again, all accomplished within 50 min. Last, the complete image is restored by next-generation sequencing and decoding. DNA cassette tape provides a strategy for fast, compact, large-scale DNA-based cold or warm data storage.
GPT-4o mini: Non-social science research article
Myo-inositol is a key regulator of avian metabolism: From mechanisms to seasonal behavior
Adi Domer, Tyler R. Misraje, Dianna Xing, B. Gabriela Arango, Giovanna Selleghin-Veiga, Ammon Corl, Rauri C. K. Bowie, Jimmy A. McGuire, Karen L. Sweazea, José Pablo Våzquez-Medina, Robert Dudley
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Being naturally hyperglycemic and insulin insensitive, birds maintain plasma glucose levels twice as high as mammals of similar size. Recent evidence suggests that perturbation of myo-inositol (MI) plays a role in mammalian hyperglycemic regulation. Using an integrative approach, we identify a fundamental role of MI in avian metabolism. We show that MI transporters are highly conserved across birds and that dietary MI reduces fat accumulation in Anna’s hummingbirds. MI consumption by hummingbirds varies with seasonal changes in body mass, consistent with a regulatory role. Furthermore, MI enhances fatty acid oxidation in avian cells, via effects on pyruvate-dehydrogenase complexes, indicating a role in mitochondrial fuel selection. Our findings underscore the importance of MI in avian metabolism, offering insights into their evolutionary adaptations in the context of insulin insensitivity.
GPT-4o mini: Non-social science research article
Single-cell multiome and spatial profiling reveals pancreas cell type–specific gene regulatory programs of type 1 diabetes progression
Rebecca Melton, Sara Jimenez, Weston Elison, Luca Tucciarone, Abigail Howell, Gaowei Wang, Denise Berti, Elisha Beebe, Michael Miller, Chun Zeng, Carolyn McGrail, Kennedy VanderStel, Katha Korgaonkar, Ruth Elgamal, Hannah Mummey, Joshua Chiou, Emily Griffin, Irina Kusmartseva, Mark Atkinson, Sebastian Preissl, Fabian J. Theis, Maike Sander, Kyle J. Gaulton
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Cell type–specific regulatory programs that drive type 1 diabetes (T1D) in the pancreas are poorly understood. Here, we performed single-nucleus multiomics and spatial transcriptomics in up to 32 nondiabetic (ND), autoantibody-positive (AAB + ), and T1D pancreas donors. Genomic profiles from 853,005 cells mapped to 12 pancreatic cell types, including multiple exocrine subtypes. ÎČ, Acinar, and other cell types, and related cellular niches, had altered abundance and gene activity in T1D progression, including distinct pathways altered in AAB + compared to T1D. We identified epigenomic drivers of gene activity in T1D and AAB + which, combined with genetic association, revealed causal pathways of T1D risk including antigen presentation in ÎČ cells. Last, single-cell and spatial profiles together revealed widespread changes in cell-cell signaling in T1D including signals affecting ÎČ cell regulation. Overall, these results revealed drivers of T1D in the pancreas, which form the basis for therapeutic targets for disease prevention.
GPT-4o mini: Non-social science research article
The role of the North American continent in strengthening the Asian summer monsoon
Linlin Chen, Paul J. Valdes, Alexander Farnsworth
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Most studies on modern Asian monsoon formation focus on mechanisms arising within the Afro-Eurasian continent, while fewer compare the effects from remote continents. Here, we explore this question using a coupled climate model. We show that the existence of the North American continent is critical for the intensity of the Asian summer monsoon. The mechanism involves North America acting as an additional heating center, resulting in the strengthening and extension of oceanic advection toward the monsoon region. This is achieved via the Rodwell-Hoskins mechanism that strengthens the North Pacific subtropical high and through a widespread Northern Hemisphere heating that shifts the Hadly circulation subsidence center poleward. This teleconnection is independent of the presence of the Tibetan Plateau, and its impact on East Asian summer precipitation is found to be smaller but comparable to that of Tibet. The individual role of other continents outside Afro-Eurasia is found to be less important.
GPT-4o mini: Non-social science research article
Homo-layer flexible Bi 2 Te 3 -based films with high thermoelectric performance
Dasha Mao, Jianmin Yang, Meng Han, Xiege Huang, Jianrui Wang, Baohai Jia, Zhongbin Wang, Xiao Xu, Lin Xie, Yi Zhou, Guodong Li, Ghim Wei Ho, Jiaqing He
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Here, we demonstrate unconventional scalable and sustainable manufacturing of flexible n-type Bi 2 Te 3 films via physical vapor deposition and homo-layer fusion engineering. The achieved ultrahigh power factor of up to 30.0 microwatts per centimeter per square kelvin and ultralow lattice thermal conductivity of 0.38 watts per meter per kelvin at room temperature are attributed to the synergy of modulated modest carrier concentration and weighted mobility in homo-layer films. These results bring forth a maximum output power density of 300 watts per square meter at a temperature gradient of 60 kelvin and a normalized cooling factor of 0.6, which is sufficient to sustain consumer electronics with large-area manufacturing of up to 120 square centimeters. Our developed homo-layer deposition with industry compatibility and scalability potentials highlights a facile yet cost-effective strategy, not only for structure-property relation manipulation in inorganic semiconductors but also for solid-state electronic fabrication for heat harvesting and management frontiers.
GPT-4o mini: Non-social science research article
Genomic characterization of normal and aberrant human milk production
Yarden Golan, Sarah K. Nyquist, Zhe Liu, Dena Ennis, Jingjing Zhao, Emily Blair, Abdur Rahim Khan, Mary Prahl, Stephanie L. Gaw, Moran Yassour, Barbara E. Engelhardt, Valerie J. Flaherman, Nadav Ahituv
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Breastfeeding is essential for reducing infant morbidity and mortality, yet exclusive breastfeeding rates remain low, often because of insufficient milk production. The molecular causes of low milk production are not well understood. Fresh milk samples from 30 lactating individuals, classified by milk production levels across postpartum stages, were analyzed using genomic and microbiome techniques. Bulk RNA sequencing of milk fat globules (MFGs), milk cells, and breast tissue revealed that MFG-derived RNA closely mirrors luminal milk cells. Transcriptomic and single-cell RNA analyses identified changes in gene expression and cellular composition, highlighting key genes ( GLP1R , PLIN4 , and KLF10 ) and cell-type differences between low and high producers. Infant microbiome diversity was influenced by feeding type but not maternal milk production. This study provides a comprehensive human milk transcriptomic catalog and highlights that MFG could serve as a useful biomarker for milk transcriptome analysis, offering insights into the genetic factors influencing milk production.
GPT-4o mini: Non-social science research article
Molecular exaptation by the integrin αI domain
Jeremy A. Hollis, Matthew C. Chan, Harmit S. Malik, Melody G. Campbell
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Integrins bind ligands between their alpha (α) and beta (ÎČ) subunits and transmit signals through conformational changes. Early in chordate evolution, some α subunits acquired an “inserted” (I) domain that expanded integrin’s ligand-binding repertoire but obstructed the ancestral ligand pocket, seemingly blocking conventional integrin activation. Here, we compare cryo–electron microscopy structures of apo and ligand-bound states of the I domain–containing αEÎČ 7 integrin and the I domain–lacking α 4 ÎČ 7 integrin to illuminate how the I domain intrinsically mimics an extrinsic ligand to preserve integrin function. We trace the I domain’s evolutionary origin to an ancestral collagen-collagen interaction domain, identifying an ancient molecular exaptation that facilitated integrin activation immediately upon I domain insertion. Our analyses reveal the evolutionary and biochemical basis of expanded cellular communication in vertebrates.
GPT-4o mini: Non-social science research article
Aplf/Dna2 variants drive chromosomal fission and accelerate speciation in zokors
Na Wan, Qijiao Duan, Zhenyuan Cai, Zhanwu Zhu, JingOu Wang, Yonghui Tian, Wei Shen, Bowen Li, Zhuoran Kuang, Xiaolong Liang, Sanyuan Liu, Xuan An, Xiaojie Yang, Xi Liu, Leyan Mao, Jiaqi Chen, Yinjia Wang, Zhilong Feng, Wenwen Liu, Yueting Bu, Eviatar Nevo, Riccardo Papa, Axel Meyer, Jianquan Liu, Kexin Li
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Chromosomal fissions and fusions are common, yet the molecular mechanisms and implications in speciation remain poorly understood. Here, we confirm a fission event in one zokor species through multiple-omics and functional analyses. We traced this event to a mutation in a splicing enhancer of the DNA repair gene Aplf in the fission-bearing species, which caused exon skipping and produced a truncated protein that disrupted DNA repair. An intronic deletion in Dna2 , known to facilitate neo-telomere formation when knocked out, reduced gene activity. These variants collectively drove chromosomal fission in this zokor species. The newly formed chromosome became fixed due to carrying essential genes and strong selective pressure. While geographic isolation likely initiated the divergence of this species and the sister one, the fission event and associated decline at the chromosome level in gene flow probably exacerbated the speciation process. Our work elucidates the genetic basis of chromosomal fission and underscores its role in speciation dynamics.
Leveraging port state measures to combat illegal, unreported, and unregulated fishing
Elizabeth R. Selig, Colette C. C. Wabnitz, Shinnosuke Nakayama, Jaeyoon Park, Richard Barnes, Robert Blasiak, Dawn Borg-Costanzi, Bronwen Golder, Jean-Baptiste Jouffray, Jim Leape, Jessica L. Decker Sparks
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Illegal, unreported, and unregulated (IUU) fishing threatens the sustainability of fisheries and communities dependent on them. The Port State Measures Agreement (PSMA) is a key tool for combatting IUU fishing by foreign fleets, requiring standardized inspections, information sharing, and port denial. Using satellite data, we characterized how PSMA has affected high seas vessel behavior and identify opportunities to strengthen its impact. PSMA adoption has increased travel distances to the nearest ports in States not Party to PSMA and channeled more fishing effort to domestic and PSMA Party ports. However, domestic fishing fleets need greater attention because they constituted 66% of port visits in 2021. Among reflagged vessels, we also found a 30% increase in visits to PSMA ports by vessels shifting to domestic flags after PSMA entered into force, allowing them to avoid PSMA requirements for foreign vessels. Our results highlight the centrality of implementing consistent, effective port State measures across foreign and domestic fleets to address IUU fishing risks.
Investigating the know-do gap in antibiotics prescribing: Experimental evidence from India
Zachary Wagner, Manoj Mohanan, Arnab Mukherji, Rushil Zutshi, Sumeet Patil, Jagadish Krishnappa, Somalee Banerjee, Neeraj Sood
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Antimicrobial resistance is largely driven by overuse of antibiotics, which is particularly common in low- and middle-income countries. We combine provider knowledge assessments and over 2000 anonymous standardized patient visits to providers in India to examine why they overprescribe antibiotics for pediatric diarrhea and figure out how to reduce overprescribing. Seventy percent of providers prescribed antibiotics without indication of bacterial infection. Knowledge gaps explain little: 62% of providers who knew antibiotics were inappropriate still prescribed them. Closing this “know-do gap” would reduce prescribing by 30 percentage points, versus only 6 points if all providers had perfect knowledge. Using randomized experiments, we revealed that the know-do gap stems from providers’ beliefs that patients want antibiotics, not from profit motives or lack of alternative treatments. Yet, a discrete choice experiment suggests patients do not prefer providers who give antibiotics. Our findings indicate that addressing provider misperceptions about patient preferences may be more effective than standard information-based interventions in reducing antibiotic overuse.

Socio-Economic Review

Moving up, reaching back: upward mobility and kin support in contemporary Chile
Malik Fercovic
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What drives upwardly mobile individuals to support their families of origin, and what are the consequences of such support? This article examines how upward social mobility intersects with kin support in contemporary Chile. Drawing on sixty interviews with individuals who have attained high-status professions, it finds that such support is driven by a deeply internalized sense of duty to maintain close family ties. Kin assistance takes financial, occupational, and caregiving forms, often extending beyond the nuclear family. Yet these obligations carry significant emotional, financial, and professional costs—particularly for women. In response, individuals develop strategies to manage and delimit kin demands. By shedding new light on the normative drivers and multifaceted consequences of kin support, the article contributes to a relational understanding of social mobility and calls for a broader, comparative agenda on how mobility unfolds in contexts marked by high inequality, weak welfare provision, and strong familistic norms.