We checked 7 multidisciplinary journals on Friday, March 21, 2025 using the Crossref API. For the period March 14 to March 20, we retrieved 12 new paper(s) in 6 journal(s).

Nature

GPT-4o mini: Non-social science research article
Author Correction: B-cell-specific checkpoint molecules that regulate anti-tumour immunity
Lloyd Bod, Yoon-Chul Kye, Jingwen Shi, Elena Torlai Triglia, Alexandra Schnell, Johannes Fessler, Stephen M. Ostrowski, Max Y. Von-Franque, Juhi R. Kuchroo, Rocky M. Barilla, Sarah Zaghouani, Elena Christian, Toni Marie Delorey, Kanishka Mohib, Sheng Xiao, Nadine Slingerland, Christopher J. Giuliano, Orr Ashenberg, Zhaorong Li, David M. Rothstein, David E. Fisher, Orit Rozenblatt-Rosen, Arlene H. Sharpe, Francisco J. Quintana, Lionel Apetoh, Aviv Regev, Vijay K. Kuchroo
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GPT-4o mini: Non-social science research article
Structural dynamics of DNA unwinding by a replicative helicase
Taha Shahid, Ammar U. Danazumi, Muhammad Tehseen, Lubna Alhudhali, Alice R. Clark, Christos G. Savva, Samir M. Hamdan, Alfredo De Biasio
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GPT-4o mini: Non-social science research article
Downscaling micro- and nano-perovskite LEDs
Yaxiao Lian, Yaxin Wang, Yucai Yuan, Zhixiang Ren, Weidong Tang, Zhe Liu, Shiyu Xing, Kangyu Ji, Bo Yuan, Yichen Yang, Yuxiang Gao, Shiang Zhang, Ke Zhou, Gan Zhang, Samuel D. Stranks, Baodan Zhao, Dawei Di
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GPT-4o mini: Non-social science research article
Dynamic cytoskeletal regulation of cell shape supports resilience of lymphatic endothelium
Hans Schoofs, Nina Daubel, Sarah Schnabellehner, Max L. B. Grönloh, SebastiĂĄn Palacios MartĂ­nez, Aleksi Halme, Amanda M. Marks, Marie Jeansson, Sara Barcos, Cord Brakebusch, Rui Benedito, Britta Engelhardt, Dietmar Vestweber, Konstantin Gaengel, Fabian Linsenmeier, Sebastian SchĂŒrmann, Pipsa Saharinen, Jaap D. van Buul, Oliver Friedrich, Richard S. Smith, Mateusz Majda, Taija MĂ€kinen
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Lymphatic capillaries continuously take up interstitial fluid and adapt to resulting changes in vessel calibre 1–3 . The mechanisms by which the permeable monolayer of loosely connected lymphatic endothelial cells (LECs) 4 maintains mechanical stability remain elusive. Here we identify dynamic cytoskeletal regulation of LEC shape, induced by isotropic stretch, as crucial for the integrity and function of dermal lymphatic capillaries. We found that the oak leaf-shaped LECs showed a spectrum of VE-cadherin-based junctional configurations at the lobular intercellular interface and a unique cytoskeletal organization, with microtubules at concave regions and F-actin at convex lobes. Multispectral and longitudinal intravital imaging of capillary LEC shape and actin revealed dynamic remodelling of cellular overlaps in vivo during homeostasis and in response to interstitial fluid volume increase. Akin to puzzle cells of the plant epidermis 5,6 , LEC shape was controlled by Rho GTPase CDC42-regulated cytoskeletal dynamics, enhancing monolayer stability. Moreover, cyclic isotropic stretch increased cellular overlaps and junction curvature in primary LECs. Our findings indicate that capillary LEC shape results from continuous remodelling of cellular overlaps that maintain vessel integrity while preserving permeable cell–cell contacts compatible with vessel expansion and fluid uptake. We propose a bellows-like fluid propulsion mechanism, in which fluid-induced lumen expansion and shrinkage of LEC overlaps are countered by actin-based lamellipodia-like overlap extension to aid vessel constriction.
GPT-4o mini: Non-social science research article
Transient silencing of hypermutation preserves B cell affinity during clonal bursting
Juhee Pae, Niklas Schwan, Bertrand Ottino-Loffler, William S. DeWitt, Amar Garg, Juliana Bortolatto, Ashni A. Vora, Jin-Jie Shen, Alvaro Hobbs, Tiago B. R. Castro, Luka Mesin, Frederick A. Matsen, Michael Meyer-Hermann, Gabriel D. Victora
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In the course of antibody affinity maturation, germinal centre (GC) B cells mutate their immunoglobulin heavy- and light-chain genes in a process known as somatic hypermutation (SHM) 1–4 . Panels of mutant B cells with different binding affinities for antigens are then selected in a Darwinian manner, which leads to a progressive increase in affinity among the population 5 . As with any Darwinian process, rare gain-of-fitness mutations must be identified and common loss-of-fitness mutations avoided 6 . Progressive acquisition of mutations therefore poses a risk during large proliferative bursts 7 , when GC B cells undergo several cell cycles in the absence of affinity-based selection 8–13 . Using a combination of in vivo mouse experiments and mathematical modelling, here we show that GCs achieve this balance by strongly suppressing SHM during clonal-burst-type expansion, so that a large fraction of the progeny generated by these bursts does not deviate from their ancestral genotype. Intravital imaging and image-based cell sorting of a mouse strain carrying a reporter of cyclin-dependent kinase 2 (CDK2) activity showed that B cells that are actively undergoing proliferative bursts lack the transient CDK2 low ‘G0-like’ phase of the cell cycle in which SHM takes place. We propose a model in which inertially cycling B cells mostly delay SHM until the G0-like phase that follows their final round of division in the GC dark zone, thus maintaining affinity as they clonally expand in the absence of selection.
GPT-4o mini: Non-social science research article
Rapid emergence of latent knowledge in the sensory cortex drives learning
CĂ©line Drieu, Ziyi Zhu, Ziyun Wang, Kylie Fuller, Aaron Wang, Sarah Elnozahy, Kishore Kuchibhotla
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GPT-4o mini: Non-social science research article
Sleep pressure accumulates in a voltage-gated lipid peroxidation memory
H. Olof Rorsman, Max A. MĂŒller, Patrick Z. Liu, Laura Garmendia Sanchez, Anissa Kempf, Stefanie Gerbig, Bernhard Spengler, Gero Miesenböck
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Voltage-gated potassium (K V ) channels contain cytoplasmically exposed ÎČ-subunits 1–5 whose aldo-keto reductase activity 6–8 is required for the homeostatic regulation of sleep 9 . Here we show that Hyperkinetic, the ÎČ-subunit of the K V 1 channel Shaker in Drosophila 7 , forms a dynamic lipid peroxidation memory. Information is stored in the oxidation state of Hyperkinetic’s nicotinamide adenine dinucleotide phosphate (NADPH) cofactor, which changes when lipid-derived carbonyls 10–13 , such as 4-oxo-2-nonenal or an endogenous analogue generated by illuminating a membrane-bound photosensitizer 9,14 , abstract an electron pair. NADP + remains locked in the active site of K V ÎČ until membrane depolarization permits its release and replacement with NADPH. Sleep-inducing neurons 15–17 use this voltage-gated oxidoreductase cycle to encode their recent lipid peroxidation history in the collective binary states of their K V ÎČ subunits; this biochemical memory influences—and is erased by—spike discharges driving sleep. The presence of a lipid peroxidation sensor at the core of homeostatic sleep control 16,17 suggests that sleep protects neuronal membranes against oxidative damage. Indeed, brain phospholipids are depleted of vulnerable polyunsaturated fatty acyl chains after enforced waking, and slowing the removal of their carbonylic breakdown products increases the demand for sleep.
GPT-4o mini: Non-social science research article
Global sea-level rise in the early Holocene revealed from North Sea peats
Marc P. Hijma, Sarah L. Bradley, Kim M. Cohen, Wouter van der Wal, Natasha L. M. Barlow, Bas Blank, Manfred Frechen, Rick Hennekam, Sytze van Heteren, Patrick Kiden, Antonis Mavritsakis, Bart M. L. Meijninger, Gert-Jan Reichart, Lutz Reinhardt, Kenneth F. Rijsdijk, Annemiek Vink, Freek S. Busschers
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GPT-4o mini: Non-social science research article
VDAC2 loss elicits tumour destruction and inflammation for cancer therapy
Sujing Yuan, Renqiang Sun, Hao Shi, Nicole M. Chapman, Haoran Hu, Cliff Guy, Sherri Rankin, Anil KC, Gustavo Palacios, Xiaoxi Meng, Xiang Sun, Peipei Zhou, Xiaoyang Yang, Stephen Gottschalk, Hongbo Chi
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GPT-4o mini: Non-social science research article
Optimizing generative AI by backpropagating language model feedback
Mert Yuksekgonul, Federico Bianchi, Joseph Boen, Sheng Liu, Pan Lu, Zhi Huang, Carlos Guestrin, James Zou
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GPT-4o mini: Non-social science research article
Fluctuating magnetism and Pomeranchuk effect in multilayer graphene
Ludwig Holleis, Tian Xie, Siyuan Xu, Haoxin Zhou, Caitlin L. Patterson, Archisman Panigrahi, Takashi Taniguchi, Kenji Watanabe, Leonid S. Levitov, Chenhao Jin, Erez Berg, Andrea F. Young
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GPT-4o mini: Non-social science research article
Drivers of avian genomic change revealed by evolutionary rate decomposition
David A. DuchĂȘne, Al-Aabid Chowdhury, Jingyi Yang, Maider Iglesias-Carrasco, Josefin Stiller, Shaohong Feng, Samir Bhatt, M. Thomas P. Gilbert, Guojie Zhang, Joseph A. Tobias, Simon Y. W. Ho
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GPT-4o mini: Non-social science research article
Oncolytic virus VG161 in refractory hepatocellular carcinoma
Yinan Shen, Xueli Bai, Qi Zhang, Xingmei Liang, Xinyan Jin, Zeda Zhao, Wei Song, Qian Tan, Ronghua Zhao, William Jia, Shanzhi Gu, Guoming Shi, Ziwei Zheng, Guyue Wei, Youlei Wang, Tian Fang, Yuwei Li, Zijun Wang, Zifan Yang, Sida Guo, Danni Lin, Fang Wei, Lei Wang, Xiaoli Sun, Aijun Qin, Longshen Xie, Yeting Qiu, Wenqing Bao, Shah Rahimian, Manu Singh, Yanal Murad, Jianying Shang, Min Chu, Maoliang Huang, Jun Ding, Wei Chen, Yufu Ye, Yiwen Chen, Xiang Li, Tingbo Liang
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GPT-4o mini: Non-social science research article
Author Correction: Spatially resolved multiomics of human cardiac niches
Kazumasa Kanemaru, James Cranley, Daniele Muraro, Antonio M. A. Miranda, Siew Yen Ho, Anna Wilbrey-Clark, Jan Patrick Pett, Krzysztof Polanski, Laura Richardson, Monika Litvinukova, Natsuhiko Kumasaka, Yue Qin, Zuzanna Jablonska, Claudia I. Semprich, Lukas Mach, Monika Dabrowska, Nathan Richoz, Liam Bolt, Lira Mamanova, Rakeshlal Kapuge, Sam N. Barnett, Shani Perera, Carlos Talavera-LĂłpez, Ilaria Mulas, Krishnaa T. Mahbubani, Liz Tuck, Lu Wang, Margaret M. Huang, Martin Prete, Sophie Pritchard, John Dark, Kourosh Saeb-Parsy, Minal Patel, Menna R. Clatworthy, Norbert HĂŒbner, Rasheda A. Chowdhury, Michela Noseda, Sarah A. Teichmann
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GPT-4o mini: Non-social science research article
Structures and mechanism of human mitochondrial pyruvate carrier
Jiaming Liang, Junhui Shi, Ailong Song, Meihua Lu, Kairan Zhang, Meng Xu, Gaoxingyu Huang, Peilong Lu, Xudong Wu, Dan Ma
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GPT-4o mini: Non-social science research article
Matrix-producing neutrophils populate and shield the skin
Tommaso Vicanolo, Alaz Özcan, Jackson LiangYao Li, Carla Huerta-LĂłpez, IvĂĄn Ballesteros, Andrea Rubio-Ponce, Andra C. Dumitru, Jose Ángel NicolĂĄs-Ávila, Miguel Molina-Moreno, Pablo Reyes-Gutierrez, Andrew D. Johnston, Catherine Martone, Eric Greto, Antonio QuĂ­lez-Alvarez, Enrique Calvo, Elena Bonzon-Kulichenko, Rebeca Álvarez-Velez, Ming Yao Chooi, Immanuel Kwok, Blanca GonzĂĄlez-BermĂșdez, Benoit Malleret, Francisco M. Espinosa, Ming Zhang, Yu-Long Wang, Dasheng Sun, Shu Zhen Chong, Ali El-Armouche, Kevin K. Kim, Irina A. Udalova, Valentina Greco, Ricardo Garcia, JesĂșs VĂĄzquez, Ana Dopazo, Gustavo R. Plaza, Jorge Alegre-Cebollada, Stefan Uderhardt, Lai Guan Ng, AndrĂ©s Hidalgo
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GPT-4o mini: Non-social science research article
Regulated somatic hypermutation enhances antibody affinity maturation
Julia Merkenschlager, Andrew G. T. Pyo, Gabriela S. Silva Santos, Dennis Schaefer-Babajew, Melissa Cipolla, Harald Hartweger, Alexander D. Gitlin, Ned S. Wingreen, Michel C. Nussenzweig
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GPT-4o mini: Non-social science research article
Cooper-pair density modulation state in an iron-based superconductor
Lingyuan Kong, MichaƂ Papaj, Hyunjin Kim, Yiran Zhang, Eli Baum, Hui Li, Kenji Watanabe, Takashi Taniguchi, Genda Gu, Patrick A. Lee, Stevan Nadj-Perge
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GPT-4o mini: Non-social science research article
Long-term studies provide unique insights into evolution
James T. Stroud, William C. Ratcliff
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GPT-4o mini: Non-social science research article
Electroluminescence and energy transfer mediated by hyperbolic polaritons
Loubnan Abou-Hamdan, Aurélien Schmitt, Rémi Bretel, Sylvio Rossetti, Marin Tharrault, David Mele, Aurélie Pierret, Michael Rosticher, Takashi Taniguchi, Kenji Watanabe, Camille Maestre, Catherine Journet, BérangÚre Toury, Vincent Garnier, Philippe Steyer, James H. Edgar, Eli Janzen, Jean-Marc Berroir, Gwendal FÚve, Gerbold Ménard, Bernard Plaçais, Christophe Voisin, Jean-Paul Hugonin, Elise Bailly, Benjamin Vest, Jean-Jacques Greffet, Patrick Bouchon, Yannick De Wilde, Emmanuel Baudin
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GPT-4o mini: Non-social science research article
A polyene macrolide targeting phospholipids in the fungal cell membrane
Qisen Deng, Yinchuan Li, Wenyan He, Tao Chen, Nan Liu, Lingman Ma, Zhixia Qiu, Zhuo Shang, Zongqiang Wang
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GPT-4o mini: Non-social science research article
Hyperbolic phonon-polariton electroluminescence in 2D heterostructures
Qiushi Guo, Iliya Esin, Cheng Li, Chen Chen, Guanyu Han, Song Liu, James H. Edgar, Selina Zhou, Eugene Demler, Gil Refael, Fengnian Xia
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GPT-4o mini: Non-social science research article
The somatic mutation landscape of normal gastric epithelium
Tim H. H. Coorens, Grace Collord, Hyungchul Jung, Yichen Wang, Luiza Moore, Yvette Hooks, Krishnaa Mahbubani, Simon Y. K. Law, Helen H. N. Yan, Siu Tsan Yuen, Kourosh Saeb-Parsy, Peter J. Campbell, Iñigo Martincorena, Suet Yi Leung, Michael R. Stratton
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The landscapes of somatic mutation in normal cells inform us about the processes of mutation and selection operative throughout life, providing insight into normal ageing and the earliest stages of cancer development 1 . Here, by whole-genome sequencing of 238 microdissections 2 from 30 individuals, including 18 with gastric cancer, we elucidate the developmental trajectories of normal and malignant gastric epithelium. We find that gastric glands are units of monoclonal cell populations that accrue roughly 28 somatic single-nucleotide variants per year, predominantly attributable to endogenous mutational processes. In individuals with gastric cancer, metaplastic glands often show elevated mutation burdens due to acceleration of mutational processes linked to proliferation and oxidative damage. Unusually for normal cells, gastric epithelial cells often carry recurrent trisomies of specific chromosomes, which are highly enriched in a subset of individuals. Surveying 829 polyclonal gastric microbiopsies by targeted sequencing, we find somatic ‘driver’ mutations in a distinctive repertoire of known cancer genes, including ARID1A , ARID1B , ARID2 , CTNNB1 and KDM6A . The prevalence of mutant clones increases with age to occupy roughly 8% of the gastric epithelial lining by age 60 years and is significantly increased by the presence of severe chronic inflammation. Our findings provide insights into intrinsic and extrinsic influences on somatic evolution in the gastric epithelium in healthy, precancerous and malignant states.
GPT-4o mini: Non-social science research article
Histological signatures map anti-fibrotic factors in mouse and human lungs
Jason L. Guo, Michelle Griffin, Jung-Ki Yoon, David M. Lopez, Yili Zhu, John M. Lu, Georgios Mikos, Jennifer B. L. Parker, Shamik Mascharak, Camille Brenac, Nicholas J. Guardino, Darren B. Abbas, Dayan J. Li, Caleb Valencia, Norah E. Liang, Michael Januszyk, Howard Y. Chang, Derrick C. Wan, Tushar J. Desai, Michael T. Longaker
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GPT-4o mini: Non-social science research article
End-to-end data-driven weather prediction
Anna Allen, Stratis Markou, Will Tebbutt, James Requeima, Wessel P. Bruinsma, Tom R. Andersson, Michael Herzog, Nicholas D. Lane, Matthew Chantry, J. Scott Hosking, Richard E. Turner
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GPT-4o mini: Non-social science research article
GluA2-containing AMPA receptors form a continuum of Ca2+-permeable channels
Federico Miguez-Cabello, Xin-tong Wang, Yuhao Yan, Niklas Brake, Ryan P. D. Alexander, Amanda M. Perozzo, Anmar Khadra, Derek Bowie
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GPT-4o mini: Non-social science research article
Widespread slow growth of acquisitive tree species
L. Augusto, R. Borelle, A. Boča, L. Bon, C. Orazio, A. Arias-GonzĂĄlez, M. R. Bakker, N. Gartzia-Bengoetxea, H. Auge, F. Bernier, A. Cantero, J. Cavender-Bares, A. H. Correia, A. De Schrijver, J. J. Diez-Casero, N. Eisenhauer, M. N. Fotelli, G. GĂąteblĂ©, D. L. Godbold, M. Gomes-Caetano-Ferreira, M. J. Gundale, H. Jactel, J. Koricheva, M. Larsson, V. A. Laudicina, A. Legout, J. MartĂ­n-GarcĂ­a, W. L. Mason, C. Meredieu, S. Mereu, R. A. Montgomery, B. Musch, B. Muys, E. Paillassa, A. Paquette, J. D. Parker, W. C. Parker, Q. Ponette, C. Reynolds, M. J. Rozados-Lorenzo, R. Ruiz-Peinado, X. Santesteban-Insausti, M. Scherer-Lorenzen, F. J. Silva-Pando, A. Smolander, G. Spyroglou, E. B. Teixeira-Barcelos, E. I. Vanguelova, K. Verheyen, L. Vesterdal, M. Charru
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GPT-4o mini: Non-social science research article
Water structure and electric fields at the interface of oil droplets
Lixue Shi, R. Allen LaCour, Naixin Qian, Joseph P. Heindel, Xiaoqi Lang, Ruoqi Zhao, Teresa Head-Gordon, Wei Min
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GPT-4o mini: Non-social science research article
Microsatellite-based real-time quantum key distribution
Yang Li, Wen-Qi Cai, Ji-Gang Ren, Chao-Ze Wang, Meng Yang, Liang Zhang, Hui-Ying Wu, Liang Chang, Jin-Cai Wu, Biao Jin, Hua-Jian Xue, Xue-Jiao Li, Hui Liu, Guang-Wen Yu, Xue-Ying Tao, Ting Chen, Chong-Fei Liu, Wen-Bin Luo, Jie Zhou, Hai-Lin Yong, Yu-Huai Li, Feng-Zhi Li, Cong Jiang, Hao-Ze Chen, Chao Wu, Xin-Hai Tong, Si-Jiang Xie, Fei Zhou, Wei-Yue Liu, Yaseera Ismail, Francesco Petruccione, Nai-Le Liu, Li Li, Feihu Xu, Yuan Cao, Juan Yin, Rong Shu, Xiang-Bin Wang, Qiang Zhang, Jian-Yu Wang, Sheng-Kai Liao, Cheng-Zhi Peng, Jian-Wei Pan
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GPT-4o mini: Non-social science research article
Author Correction: Endocytosis in the axon initial segment maintains neuronal polarity
Kelsie Eichel, Takeshi Uenaka, Vivek Belapurkar, Rui Lu, Shouqiang Cheng, Joseph S. Pak, Caitlin A. Taylor, Thomas C. SĂŒdhof, Robert Malenka, Marius Wernig, Engin Özkan, David Perrais, Kang Shen
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GPT-4o mini: Non-social science research article
Spatially resolved mapping of cells associated with human complex traits
Liyang Song, Wenhao Chen, Junren Hou, Minmin Guo, Jian Yang
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GPT-4o mini: Non-social science research article
Bulk superconductivity near 40 K in hole-doped SmNiO2 at ambient pressure
S. Lin Er Chow, Zhaoyang Luo, A. Ariando
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GPT-4o mini: Non-social science research article
Convergent vocal representations in parrot and human forebrain motor networks
Zetian Yang, Michael A. Long
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GPT-4o mini: Non-social science research article
Down-converted photon pairs in a high-Q silicon nitride microresonator
Bohan Li, Zhiquan Yuan, James Williams, Warren Jin, Adrian Beckert, Tian Xie, Joel Guo, Avi Feshali, Mario Paniccia, Andrei Faraon, John Bowers, Alireza Marandi, Kerry Vahala
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Entangled photon pairs from spontaneous parametric down-conversion (SPDC) 1 are central to many quantum applications 2–6 . SPDC is typically performed in non-centrosymmetric systems 7 with an inherent second-order nonlinearity ( χ (2) ) 8–10 . We demonstrate strong narrowband SPDC with an on-chip rate of 0.8 million pairs per second in Si 3 N 4 . Si 3 N 4 is the pre-eminent material for photonic integration and also exhibits the lowest waveguide loss (which is essential for integrated quantum circuits). However, being amorphous, silicon nitride lacks an intrinsic χ (2) , which limits its role in photonic quantum devices. We enabled SPDC in Si 3 N 4 by combining strong light-field enhancement inside a high optical Q -factor microcavity with an optically induced space-charge field. We present narrowband photon pairs with a high spectral brightness. The quantum nature of the down-converted photon pairs is verified through coincidence measurements. This light source, based on Si 3 N 4 integrated photonics technology, unlocks new avenues for quantum systems on a chip.
GPT-4o mini: Non-social science research article
Overlapping nuclear import and export paths unveiled by two-colour MINFLUX
Abhishek Sau, Sebastian Schnorrenberg, Ziqiang Huang, Debolina Bandyopadhyay, Ankith Sharma, Clara-Marie GĂŒrth, Sandeep Dave, Siegfried M. Musser
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The nuclear pore complex (NPC) mediates nucleocytoplasmic exchange, catalysing a massive flux of protein and nucleic acid material in both directions 1 . Distinct trafficking pathways for import and export would be an elegant solution to avoid unproductive collisions and opposing movements. However, the three-dimensional (3D) nanoscale spatiotemporal dynamics of macromolecules traversing the NPC remains challenging to visualize on the timescale of millisecond-scale transport events. Here we used 3D MINFLUX 2 to identify the nuclear pore scaffold and then to simultaneously monitor both nuclear import and nuclear export, thereby establishing that both transport processes occur in overlapping regions of the central pore. Whereas translocation-arrested import complexes bound at the pore periphery, tracks of translocating complexes within the central pore region revealed a preference for an approximately 40- to 50-nm diameter annulus with minimal circumferential movement, indicating activity-dependent confinement within the permeability barrier. Movement within the pore was approximately 1,000-fold slower than in solution and was interspersed with pauses, indicating a highly restricted environment with structural constraints and/or transient binding events during transport. These results demonstrate that high spatiotemporal precision with reduced photobleaching is a major advantage of MINFLUX tracking, and that the NPC permeability barrier is divided into annular rings with distinct functional properties.
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Daily briefing: Should the Stanford Prison Experiment be retracted?
Jacob Smith
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A century of quantum physics
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‘My career is over’: Columbia University scientists hit hard by Trump team’s cuts
Humberto Basilio
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Dad always mows on summer Saturday mornings
Beth Cato
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Swarms of satellites are harming astronomy. Here’s how researchers are fighting back
Alexandra Witze
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Japan needs a fresh approach to innovation
Peter Gruss
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Why humans have puzzle-shaped cells
Shamini Bundell
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Bird brains help scientists to unveil the secrets of speech
Joshua Neunuebel
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The biggest machine in science: inside the fight to build the next giant particle collider
Davide Castelvecchi
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Asia leads rise in clean-energy research
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Can Earth’s rotation generate power? Physicists divided over controversial claim
Elizabeth Gibney
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Stay safe from online hate with these five tips
Michael Brooks
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Your lab pollutes: here’s how to stop it
Marie Launay
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Don’t wait out four hard years: speak truth to power
Arthur Caplan
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US disruptions to science could transform global research landscape
Chunyu Zhang, Liping Liu
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Food-industry waste finds a second life as bioplastic
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Meeting the energy challenge posed by data centres is central to a green future
Dasom Lee
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What is the best type of tree to use for forest restoration?
Pieter A. Zuidema, Madelon Lohbeck
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New antifungal breaks the mould
Arun Maji, Martin D. Burke
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Is dark energy getting weaker? Fresh data bolster shock finding
Davide Castelvecchi
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An experiment in mass education using satellite TV
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Errors in the Huntington’s disease gene accumulate slowly and then all at once
Veera M. Rajagopal, Sahar Gelfman
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Governments must stop hoarding climate data
Santiago BeguerĂ­a
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Daily briefing: Iguanas from the Americas might have rafted to Fiji
Flora Graham
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Mutations that accrue through life set the stage for stomach cancer
Callum Oddy, Marnix Jansen
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How the US tech industry is shaping the transition to green energy
Mark Peplow
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Could libraries band together to ensure open access for all?
Dalmeet Singh Chawla
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Disconnections
Marissa Lingen
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A textbook assumption about the brain’s most abundant receptors needs to be rewritten
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A radical manifesto for truth
Julia P. G. Jones
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How extreme lethargy can promote healthy ageing
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AI demands a different approach to education
Ziqiang Zeng, Jiuping Xu
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Microsoft quantum computing claim still lacks evidence: physicists are dubious
Dan Garisto
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Vaccines save lives. Leaders must champion them
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I spent two years organizing an international conference. How do I get compensated for my work?
Nikki Forrester
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How I connect Colombia’s remote communities to safer water
Esme Hedley
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‘Science is happening’: Israeli and Palestinian scientists continue collaborations amid conflict
Josie Glausiusz
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Fossilized dinosaur cells that defied the ravages of time — 20 years since a key discovery
Jasmina Wiemann
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Catchy, clear, concise: three-part phrases boost research paper citations
Dalmeet Singh Chawla
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Strong, flexible ‘nylon’ made by engineered bacteria for the first time
Felicity Nelson
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The early origins of bone-tool manufacturing traditions by hominins 1.5 million years ago
Marta MirazĂłn Lahr
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Space debris is falling from the skies. We need to tackle this growing danger
Richard O. Ocaya, Thembinkosi D. Malevu
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Global cooperation is crucial for DeepSeek and broader AI research
Haoyu Liu
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The untamed river and the Moog: Books in brief
Andrew Robinson
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How a PhD travel fellowship enriched an international cell-biology meeting
Rafiou Agoro
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Cleaning up space: how satellites and telescopes can live together
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AI could soon tackle projects that take humans weeks
Garrison Lovely
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Nature DOI suffix ≠ "/s...": Not a research article
What is stopping a complete switch to clean energy?
Benjamin Plackett
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Nature DOI suffix ≠ "/s...": Not a research article
World’s tiniest LED display has pixels smaller than a virus
Davide Castelvecchi
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Nature DOI suffix ≠ "/s...": Not a research article
A practical leap towards secure quantum communication over long distances
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Nature DOI suffix ≠ "/s...": Not a research article
Immune cells ‘bandage’ wounds with bacteria-trapping goo
Miryam Naddaf
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: About 1% of children have genetic paternity other than that recorded by history
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Light pollution threatens fleet of world-class telescopes in Atacama Desert
Humberto Basilio
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How researchers can work fairly with Indigenous and local knowledge
Oscar Allan
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Jurassic mammals had dark fur
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
‘All things that wander in the heavens’: how I swapped my ivory tower for the world of science fiction
Fayth Tan
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Box jellies learn from experience — despite not having a brain
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
What’s in store for US science as funding bill averts government shutdown
Jeff Tollefson
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Nature DOI suffix ≠ "/s...": Not a research article
Ancient peat reveals that sea level surged rapidly twice at the end of the last ice age
Nicole S. Khan
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Nature DOI suffix ≠ "/s...": Not a research article
Measles is surging in the US: how bad could it get?
Julian Nowogrodzki
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Mini-satellite paves the way for quantum messaging anywhere on Earth
Elizabeth Gibney
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Battery researchers strive for standardization
Katharine Sanderson
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Trump’s return puts renewables at a crossroads
Simon Baker
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A guide to the Nature Index
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Babies do make memories — so why can’t we recall our earliest years?
Chris Simms
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Nature DOI suffix ≠ "/s...": Not a research article
Trump team ‘survey’ sent to overseas researchers prompts foreign interference fears
Smriti Mallapaty
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Nature Human Behaviour

GPT-4o mini: Non-social science research article
Publisher Correction: Errors of attention adaptively warp spatial cognition
James A. Brissenden, Yitong Yin, Michael Vesia, Taraz G. Lee
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GPT-4o mini: Non-social science research article
White matter connections of human ventral temporal cortex are organized by cytoarchitecture, eccentricity and category-selectivity from birth
Emily Kubota, Xiaoqian Yan, Sarah Tung, Bella Fascendini, Christina Tyagi, Sophie Duhameau, Danya Ortiz, Mareike Grotheer, Vaidehi S. Natu, Boris Keil, Kalanit Grill-Spector
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Defragmenting psychology
Farid Anvari, Taym Alsalti, Lorenz A. Oehler, Ian Hussey, Malte Elson, Ruben C. Arslan
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Climate resilience in the past was local
Emily Lena Jones
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Understanding when laypeople adopt predictive algorithms
Berkeley J. Dietvorst
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We need Afrocentric datasets for inclusive AI growth
Jerry John Kponyo, Francis Kemausuor, Eric Tutu Tchao, Henry Nunoo-Mensah, Rachel Yayra Adjoe
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When diversity, equity and inclusion fail to globalize
Hye Yun Kang
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Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Integrative spatiotemporal modeling of biomolecular processes: Application to the assembly of the nuclear pore complex
Andrew P. Latham, Wanlu Zhang, Jeremy O. B. Tempkin, Shotaro Otsuka, Jan Ellenberg, Andrej Sali
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Dynamic processes involving biomolecules are essential for the function of the cell. Here, we introduce an integrative method for computing models of these processes based on multiple heterogeneous sources of information, including time-resolved experimental data and physical models of dynamic processes. First, for each time point, a set of coarse models of compositional and structural heterogeneity is computed (heterogeneity models). Second, for each heterogeneity model, a set of static integrative structure models is computed (a snapshot model). Finally, these snapshot models are selected and connected into a series of trajectories that optimize the likelihood of both the snapshot models and transitions between them (a trajectory model). The method is demonstrated by application to the assembly process of the human nuclear pore complex in the context of the reforming nuclear envelope during mitotic cell division, based on live-cell correlated electron tomography, bulk fluorescence correlation spectroscopy–calibrated quantitative live imaging, and a structural model of the fully assembled nuclear pore complex. Modeling of the assembly process improves the model precision over static integrative structure modeling alone. The method is applicable to a wide range of time-dependent systems in cell biology and is available to the broader scientific community through an implementation in the open source Integrative Modeling Platform (IMP) software.
GPT-4o mini: Non-social science research article
Correction for Kharrat et al., The antimicrobial activity of ETD151 defensin is dictated by the presence of glycosphingolipids in the targeted organisms
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GPT-4o mini: Non-social science research article
Reply to Ahmed and Lu: Cluster signals depend on how samples are made and measured
Gang Chen, Guangxin Lv, James H. Zhang, Yaodong Tu
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GPT-4o mini: Non-social science research article
Avian cranial kinesis is the result of increased encephalization during the origin of birds
Alec T. Wilken, Kaleb C. Sellers, Ian N. Cost, Julian Davis, Kevin M. Middleton, Lawrence M. Witmer, Casey M. Holliday
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The origin of birds represents a pivotal transition in vertebrate evolution, marked by significant changes in both brain size and feeding biomechanics. The evolution of the avian skull involved dramatic modifications, such as a segmented palate and the development of powered cranial kinesis in neognath birds. Powered kinesis, the ability to move parts of the skull independently, is considered a key innovation behind the dietary diversity and evolutionary success of birds. However, the processes driving the emergence of avian kinesis have remained unclear until recently. By analyzing data from Mesozoic birds, including reinterpretations of palate homology, 3D jaw muscle biomechanics, and linkage analysis, researchers have quantified changes in muscle forces and their effects on palate mechanics during the transition from theropods to birds. As the neurocranium expanded in non-avian theropods, temporal muscles shifted to more rostrocaudal positions in birds, aiding in the segmentation of the pterygoid. This musculoskeletal transformation increased fore-aft muscle force in neognaths, enabling powered cranial kinesis. A critical change was the separation of the epipterygoid ossification from the braincase, leading to the breakdown of primitive kinematic linkages and the development of a new basicranial joint, which allowed for greater cranial flexibility. These findings shed light on how the neurosensory and feeding systems coevolved during bird origins and offer new methods for identifying cranial kinesis in extinct vertebrates.
GPT-4o mini: Non-social science research article
Electric spiking activity in epithelial cells
Sun-Min Yu, Steve Granick
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Epithelial cells (human keratinocyte cells and the canine MDCK cell line), traditionally viewed as electrically non-self-excitable and involved primarily in physiological functions such as barrier presentation, absorption, secretion, and protection, are shown here to exhibit traveling extracellular electric charge when they recover from spatially focused, laser-induced wounding of confluent monolayers cultured on a multielectrode array chip. Voltage spikes measured on these electrodes display depolarization, repolarization, and hyperpolarization phases with amplitudes similar to the action potentials of neurons but with the markedly slower duration of 1 to 2 s. Some propagate distances up to hundreds of ÎŒm from the wound with a mean speed of around 10 mm s −1 . Generation and transmission of bioelectric signals are significantly influenced by the perturbation of mechanosensitive cationic ion channels. These direct measurements confirm bioelectric signaling that previous work has hypothesized to regulate epithelial cell development and may have relevance to the frequency parameter selection of bioelectric devices.
GPT-4o mini: Non-social science research article
Connectional axis of individual functional variability: Patterns, structural correlates, and relevance for development and cognition
Hang Yang, Guowei Wu, Yaoxin Li, Xiaoyu Xu, Jing Cong, Haoshu Xu, Yiyao Ma, Yang Li, Runsen Chen, Adam Pines, Ting Xu, Valerie J. Sydnor, Theodore D. Satterthwaite, Zaixu Cui
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The human cerebral cortex exhibits intricate interareal functional synchronization at the macroscale, with substantial individual variability in these functional connections. However, the spatial organization of functional connectivity (FC) variability across the human connectome edges and its significance in cognitive development remain unclear. Here, we identified a connectional axis in the edge-level FC variability. The variability declined continuously along this axis from within-network to between-network connections and from the edges linking association networks to those linking the sensorimotor and association networks. This connectional axis of functional variability is associated with spatial pattern of structural connectivity variability. Moreover, the connectional variability axis evolves in youth with an flatter axis slope. We also observed that the slope of the connectional variability axis was positively related to the performance in the higher-order cognition. Together, our results reveal a connectional axis in functional variability that is linked with structural connectome variability, refines during development, and is relevant to cognition.
GPT-4o mini: Non-social science research article
Polymorphic transposable elements contribute to variation in recombination landscapes
Yuheng Huang, Zita Y. Gao, Kayla Ly, Leila Lin, Jan-Paul Lambooij, Elizabeth G. King, Aniek Janssen, Kevin H.-C. Wei, Yuh Chwen G. Lee
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Meiotic recombination is a prominent force shaping genome evolution, and understanding why recombination rates vary within and between species has remained a central, though challenging, question. Variation in recombination is widely thought to influence the efficacy of selection in purging transposable elements (TEs), prevalent selfish genetic elements, leading to widely observed negative correlations between TE abundance and recombination rates across taxa. However, accumulating evidence suggests that TEs could instead be the cause rather than the consequence of this relationship. To test this prediction, we formally investigated the influence of polymorphic, putatively active TEs on recombination rates. We developed and benchmarked an approach that uses PacBio long-read sequencing to efficiently, accurately, and cost-effectively identify crossovers (COs), a key recombination product, among large numbers of pooled recombinant individuals. By applying this approach to Drosophila strains with distinct TE insertion profiles, we found that polymorphic TEs, especially RNA-based TEs and TEs with local enrichment of repressive marks, reduce the occurrence of COs. Such an effect leads to different CO frequencies between homologous sequences with and without TEs, contributing to varying CO maps between individuals. The suppressive effect of TEs on CO is further supported by two orthogonal approaches–analyzing the distributions of COs in panels of recombinant inbred lines in relation to TE polymorphism and applying marker-assisted estimations of CO frequencies to isogenic strains with and without transgenically inserted TEs. Our investigations reveal how the constantly changing TE landscape can actively modify recombination, shaping genome evolution within and between species.
GPT-4o mini: Non-social science research article
Conserved leucine-rich repeat proteins in the adhesive projectile slime of velvet worms
Zhaolong Hu, Alexander Baer, Lars Hering, Ivo de Sena Oliveira, Alexandre Poulhazan, Darren C. Browne, Xue Guo, Quentin Moana Perrin, Radoslaw M. Sobota, Shawn Hoon, Georg Mayer, Srinivasaraghavan Kannan, Chandra S. Verma, Matthew J. Harrington, Ali Miserez
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The slime of velvet worms (Onychophora) is a protein-based bioadhesive that undergoes rapid, yet reversible transition from a fluid into stiff fibers used for prey capture and defense, but the mechanism by which this phase transition functions is largely unknown. Here, integrating transcriptomic and proteomic approaches with AI-guided structure predictions, we discover a group of evolutionarily conserved leucine-rich repeat (LRR) proteins in velvet worm slime that readily adopt a receptor-like, protein-binding “horseshoe” structure. Our structural predictions suggest dimerization of LRR proteins and support their interactions with conserved ÎČ-sheet-rich domains of high-molecular-weight proteins, the primary building blocks of velvet worm slime fibers. This suggests that LRR proteins might be involved in reversible, receptor-based supramolecular interactions in these biofibers, providing potential avenues for fabricating fully recyclable (bio)polymeric materials.
GPT-4o mini: Non-social science research article
Cell–matrix feedback controls stretch-induced cellular memory and fibroblast activation
Yuan Hong, Xiangjun Peng, Haomin Yu, Mohammad Jafari, Delaram Shakiba, Yuxuan Huang, Chengqing Qu, Ermia E. Melika, Andrew K. Tawadros, Aliza Mujahid, Yin-Yuan Huang, Jacob A. Sandler, Kenneth M. Pryse, Justin M. Sacks, Elliot L. Elson, Guy M. Genin, Farid Alisafaei
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Mechanical stretch can activate long-lived changes in fibroblasts, increasing their contractility and initiating phenotypic transformations. This activation, critical to wound healing and procedures such as skin grafting, increases with mechanical stimulus for cells cultured in two-dimensional but is highly variable in cells in three-dimensional (3D) tissue. Here, we show that static mechanical stretch of cells in 3D tissues can either increase or decrease fibroblast activation depending upon recursive cell–extracellular matrix (ECM) feedback and demonstrate control of this activation through integrated in vitro and mathematical models. ECM viscoelasticity, signaling dynamics, and cell mechanics combine to yield a predictable, but nonmonotonic, relationship between mechanical stretch and long-term cell activation. Results demonstrate that feedback between cells and ECM determine how cells retain memory of mechanical stretch and have direct implications for improving outcomes in skin grafting procedures.
GPT-4o mini: Non-social science research article
Reinforcement learning–based adaptive strategies for climate change adaptation: An application for coastal flood risk management
Kairui Feng, Ning Lin, Robert E. Kopp, Siyuan Xian, Michael Oppenheimer
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Conventional computational models of climate adaptation frameworks inadequately consider decision-makers’ capacity to learn, update, and improve decisions. Here, we investigate the potential of reinforcement learning (RL), a machine learning technique that efficaciously acquires knowledge from the environment and systematically optimizes dynamic decisions, in modeling and informing adaptive climate decision-making. We consider coastal flood risk mitigations for Manhattan, New York City, USA (NYC), illustrating the benefit of continuously incorporating observations of sea-level rise into systematic designs of adaptive strategies. We find that when designing adaptive seawalls to protect NYC, the RL-derived strategy significantly reduces the expected net cost by 6 to 36% under the moderate emissions scenario SSP2-4.5 (9 to 77% under the high emissions scenario SSP5-8.5), compared to conventional methods. When considering multiple adaptive policies, including accomodation and retreat as well as protection, the RL approach leads to a further 5% (15%) cost reduction, showing RL’s flexibility in coordinatively addressing complex policy design problems. RL also outperforms conventional methods in controlling tail risk (i.e., low probability, high impact outcomes) and in avoiding losses induced by misinformation about the climate state (e.g., deep uncertainty), demonstrating the importance of systematic learning and updating in addressing extremes and uncertainties related to climate adaptation.
GPT-4o mini: Non-social science research article
Hair cell apoptosis and deafness in Tmc1 mutations
Maryline Beurg, Dakota Elle Konrad, Robert Fettiplace
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Transmembrane channel-like protein 1 (TMC1), a pore-forming component of the mechano-electrical transducer (MET) channel in cochlear outer hair cells, is subject to numerous mutations causing deafness and hair cell death. We studied mice harboring semidominant mutations Tmc1 p.T416K, p.M412K, and p.D569N, which all display functional MET channels at postnatal day (P)6 but become deaf by P21. Early signs of concomitant hair cell apoptosis were assayed in neonatal Tmc1 mutants by labeling with Calcein-acetomethyl ester (AM), MitoTracker, and Annexin V, the latter labeling scramblase externalization of phosphatidyl serine. Reduced labeling with Calcein-AM was correlated with reduced MitoTracker, the targeting of mitochondria being confirmed with the uncoupling agent carbonylcyanide p -trifluoromethoxyphenylhydrazone, and use of MitoLight to monitor mitochondrial membrane potential. These markers demonstrated mitochondrial dysfunction in Tmc1 mutants, even at P6 when MET currents were still present. Acoustic brainstem responses established that Tmc1 p.D569N and Tmc1 p.M412K mice were deaf by P15 and Tmc1 p.T416K by P21. Two methods of blocking the stereociliary PMCA2 Ca 2+ pump both elicited scramblase activity, suggesting that apoptosis is promoted by elevation of hair bundle [Ca 2+ ]. Reduced PMCA2 density was found in the stereocilia of Tmc1 mutants and was correlated with a decrease in MET channel Ca 2+ permeability. Cre-Lox excision of the mutant M412K exon at P1 fully preserved hearing across all frequencies by P19 and promoted recovery to wild type of PMCA2 density. These results demonstrate that hair cells in Tmc1 mutants have embarked on apoptosis at P6 and argue for connections between stereociliary PMCA2 density, hair cell apoptosis, and deafness.
GPT-4o mini: Non-social science research article
John Brauman (1937–2024): Physical organic chemist, sage, and servant of science
Stephen L. Craig
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GPT-4o mini: Non-social science research article
Rippled metamaterials with scale-dependent tailorable elasticity
Jian Zhou, Richard Huang, Nicolaie Moldovan, Liliana Stan, Jianguo Wen, Dafei Jin, David R. Nelson, Andrej KoĆĄmrlj, David A. Czaplewski, Daniel LĂłpez
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Thermally induced ripples are intrinsic features of nanometer-thick films, atomically thin materials, and cell membranes, significantly affecting their elastic properties. Despite decades of theoretical studies on the mechanics of suspended thermalized sheets, controversy still exists over the impact of these ripples, with conflicting predictions about whether elasticity is scale-dependent or scale-independent. Experimental progress has been hindered so far by the inability to have a platform capable of fully isolating and characterizing the effects of ripples. This knowledge gap limits the fundamental understanding of thin materials and their practical applications. Here, we show that thermal-like static ripples shape thin films into a class of metamaterials with scale-dependent, customizable elasticity. Utilizing a scalable semiconductor manufacturing process, we engineered nanometer-thick films with precisely controlled frozen random ripples, resembling snapshots of thermally fluctuating membranes. Resonant frequency measurements of rippled cantilevers reveal that random ripples effectively renormalize and enhance the average bending rigidity and sample-to-sample variations in a scale-dependent manner, consistent with recent theoretical estimations. The predictive power of the theoretical model, combined with the scalability of the fabrication process, was further exploited to create kirigami architectures with tailored bending rigidity and mechanical metamaterials with delayed buckling instability.
GPT-4o mini: Non-social science research article
Laser imaging of ancient tattoos: New tools illuminate established knowledge
Aaron Deter-Wolf, BenoĂźt Robitaille, Lars Krutak
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GPT-4o mini: Non-social science research article
Red-light signaling pathway activates desert cyanobacteria to prepare for desiccation tolerance
Hai-Feng Xu, Guo-Zheng Dai, Ren-Han Li, Yang Bai, Ai-Wei Zuo, Lei Zhao, Shu-Ren Cui, Jin-Long Shang, Chao Cheng, Yu-Jie Wang, Gui-Fang Feng, Deqiang Duanmu, Aaron Kaplan, Bao-Sheng Qiu
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Desiccation-tolerant cyanobacteria are able to survive frequent cycles of hydration and dehydration, which are closely linked to diurnal light oscillations. Previous studies have shown that light serves as a crucial anticipatory cue, activating desert cyanobacteria to prepare for desiccation. However, the mechanisms underlying their light-coupled desiccation tolerance remain largely unknown. Here, we demonstrate that red-light-induced photosynthetic genes are positively regulated by a LuxR family transcription factor NfSrr1. We further identified the cyanobacteriochrome NfPixJ as interacting with NfSrr1 and functioning as a red light sensor. Phenotypic analysis revealed that the red-light signaling module NfPixJ-NfSrr1 plays a key role in preparing cyanobacteria for desiccation tolerance. This module also regulates the synthesis of protective compatible solutes, suggesting that red light functions as a global regulatory signal for the broader stress response. Phylogenetic analysis indicates that the presence of this red-light signaling pathway, mediated by NfPixJ-NfSrr1 module, correlates with the ability of cyanobacteria to thrive in water-deficit habitats. Overall, our findings uncover a red-light signaling pathway that enhances desiccation tolerance as desert cyanobacteria encounter red light at dawn, before water limitation. These results provide insights into the mechanisms behind light-induced anticipatory stress tolerance in photosynthetic organisms.
GPT-4o mini: Non-social science research article
Correction for Sauciuc et al., Blobs form during the single-file transport of proteins across nanopores
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GPT-4o mini: Non-social science research article
Agriculture’s impact on water–energy balance varies across climates
Masoud Zaerpour, Shadi Hatami, André S. Ballarin, Simon Michael Papalexiou, Alain Pietroniro, Ali Nazemi
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Agriculture is a cornerstone of global food production, accounting for a substantial portion of water withdrawals worldwide. As the world’s population grows, so does the demand for water in agriculture, leading to alterations in regional water–energy balances. We present an approach to identify the influence of agriculture on the water–energy balance using empirical data. We explore the departure from the Budyko curve for catchments with agricultural expansion and their associations with changes in the water–energy balance using a causal discovery algorithm. Analyzing data from 1,342 catchments across three Köppen-Geiger climate classes—temperate, snowy, and others—from 1980 to 2014, we show that temperate and snowy catchments, which account for over 90% of stations, exhibit distinct patterns. Cropland percentage (CL%) emerges as the dominant factor, explaining 47 and 37% of the variance in deviations from the Budyko curve in temperate and snowy catchments, respectively. In temperate catchments, CL% shows a strong negative correlation with precipitation-streamflow (P-Q) causal strength (Spearman ρ = − 0.75 ), suggesting that cropland exacerbates precipitation-driven deviations. A moderate negative correlation with aridity-streamflow (AR-Q) causal strength ( ρ = − 0.42 ) indicates additional influences of cropland through aridity-driven interactions. In snowy catchments, CL% is similarly influential, with a positive correlation with P-Q causal strength ( ρ = 0.51 ). However, the negative correlation with AR-Q causal strength ( ρ = − 0.45 ) underscores the role of aridity as a secondary driver. While vegetation and precipitation seasonality also contribute to the deviations, their impacts are comparatively lower. These findings underscore the need for inclusion of agricultural activities in changing water–energy balance to secure future water supplies.
GPT-4o mini: Non-social science research article
Spatially resolved charge-transfer kinetics at the quantum dot–microbe interface using fluorescence lifetime imaging microscopy
Mokshin Suri, Farshid Salimi Jazi, Jack C. Crowley, Youngchan Park, Bing Fu, Peng Chen, Warren R. Zipfel, Buz Barstow, Tobias Hanrath
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Integrating the optoelectronic properties of quantum dots (QDs) with biological enzymatic systems to form microbe-semiconductor biohybrids offers promising prospects for both solar-to-chemical conversion and light-modulated biochemical processes. Developing these nano–bio hybrid systems necessitates a deep understanding of charge-transfer dynamics at the nano–bio interface. Photoexcited carrier transfer from QDs to microbes is driven by complex interactions, with emerging insights into the relevant thermodynamic and kinetic factors. The heterogeneities of both microbes and QD ensembles pose significant challenges in mechanistic understanding, which is critical for designing advanced nano–bio hybrids. We used fluorescence lifetime imaging microscopy to analyze charge transfer between a CdSe QD film and Shewanella oneidensis microbes. We correlated the spatiotemporal fluorescence data with an analytical model. Our analysis revealed two distinct distributions of QD de-excitation pathways. The characteristics of these distributions: 1) a faster transfer rate ( k ¯ E T 1 = 1.5   10 9   s - 1 ), with a lower acceptor number ( N ¯ a 1 = 0.03 ) and 2) a slower transfer rate ( k ¯ E T 2 = 4.1   10 8   s - 1 ) with a higher acceptor number ( N ¯ a 2 = 0.18 ). We assign these distributions to the indirect and direct electron transfer mechanisms, respectively. Our findings demonstrate how spectroscopic imaging can uncover fundamental electron transfer mechanisms at complex interfaces, offering valuable design principles for future nano–bio hybrids.
GPT-4o mini: Non-social science research article
Predicting nature-based coastal protection by mangroves under extreme waves
Zhan Hu, Stijn Temmerman, Qin Zhu, Xinran Wang, Jinwei Wu, Tianping Xu, Ken Schoutens, Tomohiro Suzuki, Zhifeng Yang, Tjeerd J. Bouma
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Forested wetlands such as mangroves are considered highly valuable for nature-based mitigation of coastal flooding. However, their wave attenuation capacity during extreme storms, when risks are highest, is rarely measured and remains challenging to predict. Here, we compile a unique dataset on the largest incident wave heights (0.39 to 1.44 m) ever recorded in forested wetlands, including our own measurements and literature data. Our analysis reveals that forested wetlands can significantly attenuate storm waves (35% over 3 wavelengths) except in rare near-submerged cases. Notably, 19 of the 20 existing formulations for vegetation drag coefficient, a key parameter for wave attenuation modeling, are inapplicable in storm conditions. Hence, we introduce an new approach to reliably predict wave attenuation during storms, without the need for drag coefficient determination nor modeling expertise. This approach offers coastal practitioners a new user-friendly tool to assess the effectiveness of nature-based solutions for storm hazard mitigation.
GPT-4o mini: Non-social science research article
Functional morphology of gliding motility in benthic diatoms
Karen Grace Bondoc-Naumovitz, Emanuele Crosato, Kirsty Y. Wan
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Diatoms, a highly successful group of photosynthetic algae, contribute to a quarter of global primary production. Many species are motile, despite having no appendages and a completely rigid cell body. Cells move to seek out nutrients, locate mating partners, and undergo vertical migration. To explore the natural diversity of diatom motility, we perform a comparative study across five common biofilm-forming species. Combining morphological measurements with high-resolution cell tracking, we establish how gliding movements relate to the morphology of the raphe—a specialized slit in the cell wall responsible for motility generation. Our detailed analyses reveal that cells exhibit a rich but species-dependent phenotype, switching stochastically between four stereotyped motility states. We model this behavior and use stochastic simulations to predict how heterogeneity in microscale navigation patterns leads to differences in long-time diffusivity and dispersal. In a representative species, we extend these findings to quantify diatom gliding in complex, naturalistic 3D environments, suggesting that cells may exploit these distinct motility signatures to achieve niche segregation in nature.
GPT-4o mini: Non-social science research article
Spiral spin liquid noise
Hiroto Takahashi, Chun-Chih Hsu, Fabian Jerzembeck, Jack Murphy, Jonathan Ward, Jack D. Enright, Jan Knapp, Pascal Puphal, Masahiko Isobe, Yosuke Matsumoto, Hidenori Takagi, J. C. SĂ©amus Davis, Stephen J. Blundell
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An emerging concept for identification of different types of spin liquids [C. Broholm et al. , Science 367 , eaay0668 (2020)] is through the use of spontaneous spin noise [S. Chatterjee, J. F. Rodriguez-Nieva, E. Demler, Phys. Rev. B 99 , 104425 (2019)]. Here, we develop spin noise spectroscopy for spin liquid studies by considering Ca 10 Cr 7 O 28 , a material hypothesized to be either a quantum or a spiral spin liquid (SSL). By enhancing techniques introduced for magnetic monopole noise studies [R. Dusad et al. , Nature 571 , 234–239 (2019)], we measure the time and temperature dependence of spontaneous flux Ί ( t , T ) and thus magnetization M ( t , T ) of Ca 10 Cr 7 O 28 samples. The resulting power spectral density of magnetization noise S M ω , T reveals intense spin fluctuations with S M ω , T ∝ ω - α ( T ) and 0.84 < α T < 1.04 . Both the variance σ M 2 T and the correlation function C M t , T of this spin noise undergo crossovers at a temperature T ∗ ≈ 450   mK . While predictions for quantum spin liquids are inconsistent with this phenomenology, those from Monte–Carlo simulations of a two-dimensional (2D) SSL state in Ca 10 Cr 7 O 28 yield overall quantitative correspondence with the measured frequency and temperature dependences of S M ω , T ,   C M t , T , and σ M 2 T , thus indicating that Ca 10 Cr 7 O 28 is an SSL.
GPT-4o mini: Non-social science research article
Absence of water clusters in visible light interactions with the air–water interface
Musahid Ahmed, Wenchao Lu
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GPT-4o mini: Non-social science research article
Molecular mechanisms underlying the evolution of a color polyphenism by genetic accommodation in the tobacco hornworm, Manduca sexta
Yuichiro Suzuki, Stephanie Amaya, Paula Gonzalez, Daniela Becerril, Surisadai Aquit, Maya Davis, Madeline Hoesel, Elizabeth Chou, Hesper Khong, Kathryn Zaia, Heidi S. Park, H. Frederik Nijhout, Brian Tjaden
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How organisms evolve under extreme environmental changes is a critical question in the face of global climate change. Genetic accommodation is an evolutionary process by which natural selection acts on novel phenotypes generated through repeated encounters with extreme environments. In this study, polyphenic and monophenic strains of the black mutant tobacco hornworm, Manduca sexta , were evolved via genetic accommodation of heat stress-induced phenotypes, and the molecular differences between the two strains were explored. Transcriptomic analyses showed that epigenetic and hormonal differences underlie the differences between the two strains and their distinct responses to temperature. DNA methylation had diverged between the two strains potentially mediating genetic assimilation. Juvenile hormone (JH) signaling in the polyphenic strain was temperature sensitive, whereas in the monophenic strain, JH signaling remained low at all temperatures. Although 20-hydroxyecdysone titers were elevated under heat shock conditions in both strains, the strains did not differ in the titers. Tyrosine hydroxylase was also found to differ between the two strains at different temperatures, and its expression could be modulated by topical application of a JH analog. Finally, heat shock of unselected black mutants demonstrated that the expression of the JH-response gene, KrĂŒppel-homolog 1 ( Kr-h1 ), increased within the first 30 min of heat shock, suggesting that JH levels respond readily to thermal stress. Our study highlights the critical role that hormones and epigenetics play during genetic accommodation and potentially in the evolution of populations in the face of climate change.
GPT-4o mini: Non-social science research article
The origin of sulfur in Canary Island magmas and its implications for Earth’s deep sulfur cycle
Zoltån Taracsåk, Margaret E. Hartley, Ray Burgess, Marie Edmonds, Marc-Antoine Longpré, Brian D. Monteleone, Romain TartÚse, Alexandra V. Turchyn
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The global sulfur cycle plays a critical role in the redox evolution of Earth’s surface and upper mantle, yet the distribution and origin of sulfur in the mantle remains largely unconstrained. El Hierro is a volcanic island in the Canary archipelago that is fed by sulfur-rich magmas. To constrain the origin of sulfur in these melts, we combine in situ sulfur isotope analyses with regression modeling. We calculate that undegassed El Hierro melts have ÎŽ 34 S values of 0 ± 2‰. The average ÎŽ 34 S of undegassed El Hierro melts is 0.3‰ to 1‰ higher than magmas erupting at mid-ocean ridges. Mass balance calculations reveal that El Hierro’s mantle source contains 310 ± 120 ÎŒg/g sulfur and that on average 60% of sulfur in the source is of recycled origin. This recycled material should contain >1,800 ÎŒg/g sulfur to satisfy isotopic constraints on its mass fraction in the mantle source. The sulfur and oxygen isotopic signature in serpentinites and sediments deviate significantly from the upper mantle, making them unsuitable candidates for the recycled material. An oxidized partial melt of recycled oceanic crust that retained one third of its sulfur budget after subduction zone processing can explain excess sulfur in the Canary Island mantle. Recycled oceanic crust is expected to contain sulfur as sulfide, which is not capable of oxidizing the mantle. The presence of ferric iron in the recycled component is necessary to produce metasomatic melts that are oxidizing enough to carry sufficient sulfur into the mantle source of ocean island basalts.
GPT-4o mini: Non-social science research article
Ectopic germinal centers in the nasal turbinates contribute to B cell immunity to intranasal viral infection and vaccination
Romain Gailleton, Nimitha R. Mathew, Laura Reusch, Karin Schön, Lydia Scharf, Anneli Strömberg, Andrea Cvjetkovic, Luaay Aziz, Johan Hellgren, Ka-Wei Tang, Mats Bemark, Davide Angeletti
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The nasal mucosa is the first immunologically active site that respiratory viruses encounter and establishing immunity at the initial point of pathogen contact is essential for preventing viral spread. Influenza A virus (IAV) in humans preferentially replicates in the upper respiratory tract (URT) but mouse models of infection result in lower respiratory tract infection. Here, we optimize IAV inoculation to enhance replication in the nasal turbinate (NT) and study local B cell immunity. We demonstrate that URT-targeted IAV infection stimulates robust local B cell responses, including germinal center (GC) B cell formation in the NT, outside of classical nasal-associated lymphoid tissues. NT GC contributes to local tissue-resident B cell generation and enhances local antibody production. Furthermore, URT-focused immunization also induces significant GC formation in the NT. Finally, we detect steady-state GC in the NT of both mice and healthy humans, suggesting continuous immune surveillance triggered by environmental stimuli. These findings highlight the pivotal role of the NT in local and systemic immunity, with important implications for future mucosal vaccines targeting the upper airways.
GPT-4o mini: Non-social science research article
Wdr5-mediated H3K4 methylation facilitates HSPC development via maintenance of genomic stability in zebrafish
Xiaohan Wang, Mengyao Liu, Yifan Zhang, Dongyuan Ma, Lu Wang, Feng Liu
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During fetal stage, hematopoietic stem and progenitor cells (HSPCs) undergo rapid proliferation with a tight control of genomic stability. Although histone H3 lysine 4 (H3K4) methylation has been reported to stabilize the genome in proliferating cells, its specific role in HSPC development remains elusive. In this study, we demonstrated that tryptophan-aspartic acid (WD) repeat protein 5 (Wdr5)-mediated H3K4 methylation is crucial for maintaining genomic stability of proliferating HSPCs in zebrafish embryos. Loss of wdr5 led to a severe reduction of HSPC pool in the caudal hematopoietic tissue, accompanied with attenuated H3K4 methylation level and evident p53 -dependent apoptosis in the HSPCs. Mechanistically, Wdr5-mediated H3K4 methylation maintains genomic stability by inhibiting the formation of abnormal R-loops in the HSPCs, whereas accumulation of R-loops exacerbates DNA damage. Moreover, the absence of H3K4 trimethylation leads to an inactivated DNA damage response (DDR) pathway, which is deleterious to DNA damage repair and genomic stability. Subsequently, we found that DDR-associated genes, mutL homolog 1 and breast and ovarian cancer interacting helicase 1 , are important to ensure HSPC survival, likely by stabilizing their genome. In summary, these findings reveal that Wdr5-mediated H3K4 methylation is essential for HSPC development through tight control of R-loop accumulation and DDR-associated program to ensure genomic stability and survival of proliferating HSPCs.
GPT-4o mini: Non-social science research article
Tumor immune evasion: Systemic immunosuppressive networks beyond the local microenvironment
Chengsong Yan, Xiao-Fan Wang
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GPT-4o mini: Non-social science research article
Realizing a topological diode effect on the surface of a topological Kondo insulator
Jiawen Zhang, Zhenqi Hua, Chengwei Wang, Michael Smidman, David Graf, Sean Thomas, Priscila F. S. Rosa, Steffen Wirth, Xi Dai, Peng Xiong, Huiqiu Yuan, Xiaoyu Wang, Lin Jiao
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Introducing the concept of topology into material science has sparked a revolution from classic electronic and optoelectronic devices to topological quantum devices. The latter has potential for transferring energy and information with unprecedented efficiency. Here, we demonstrate a topological diode effect on the surface of a three-dimensional material, SmB 6 , a candidate topological Kondo insulator. The diode effect is evidenced by pronounced rectification and photogalvanic effects under electromagnetic modulation and radiation at radio frequency. Our experimental results and modeling suggest that these prominent effects are intimately tied to the spatially inhomogeneous formation of topological surface states (TSS) at the intermediate temperature. This work provides a manner of breaking the mirror symmetry (in addition to the inversion symmetry), resulting in the formation of pn -junctions between puddles of metallic TSS. This effect paves the way for efficient current rectifiers or energy-harvesting devices working down to radio frequency range at low temperature, which could be extended to high temperatures using other topological insulators with large bulk gap.
GPT-4o mini: Non-social science research article
Combining exchangeable P -values
Matteo Gasparin, Ruodu Wang, Aaditya Ramdas
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The problem of combining P -values is an old and fundamental one, and the classic assumption of independence is often violated or unverifiable in many applications. There are many well-known rules that can combine a set of arbitrarily dependent P -values (for the same hypothesis) into a single P -value. We show that essentially all these existing rules can be strictly improved when the P -values are exchangeable, or when external randomization is allowed (or both). For example, we derive randomized and/or exchangeable improvements of well-known rules like “twice the median” and “twice the average,” as well as geometric and harmonic means. Exchangeable P -values are often produced one at a time (for example, under repeated tests involving data splitting), and our rules can combine them sequentially as they are produced, stopping when the combined P -values stabilize. Our work also improves rules for combining arbitrarily dependent P -values, since the latter becomes exchangeable if they are presented to the analyst in a random order. The main technical advance is to show that all existing combination rules can be obtained by calibrating the P -values to e-values (using an α -dependent calibrator), averaging those e-values, converting to a level- α test using Markov’s inequality, and finally obtaining P -values by combining this family of tests; the improvements are delivered via recent randomized and exchangeable variants of Markov’s inequality.
GPT-4o mini: Non-social science research article
The reuniens thalamus recruits recurrent excitation in the medial prefrontal cortex
Gil Vantomme, Gabrielle Devienne, Jacob M. Hull, John R. Huguenard
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The medial prefrontal cortex (mPFC) and hippocampus are critical for memory retrieval, decision making, and emotional regulation. While ventral CA1 (vCA1) shows direct and reciprocal connections with mPFC, dorsal CA1 (dCA1) forms indirect pathways to mPFC, notably via the thalamic reuniens nucleus (Re). Neuroanatomical tracing has documented structural connectivity of this indirect pathway through Re however, its functional operation is largely unexplored. Here, we used in vivo and in vitro electrophysiology along with optogenetics to address this question. Whole-cell patch-clamp recordings in acute mouse brain slices revealed both monosynaptic excitatory responses and disynaptic feedforward inhibition at Re–mPFC synapses. However, we also identified a prolonged excitation of mPFC by Re. These early monosynaptic and late recurrent components are in marked contrast to the primarily feedforward inhibition characteristic of thalamic inputs to the neocortex. Local field potential recordings in mPFC brain slices revealed prolonged synaptic activity throughout all cortical lamina upon Re activation, with the late excitation enhanced by blockade of parvalbumin neurons and GABA A Rs. In vivo Neuropixels recordings in head-fixed awake mice revealed a similar prolonged excitation of mPFC units by Re activation. In summary, Re output produces recurrent feedforward excitation within mPFC suggesting a potent amplification system in the Re–mPFC network. This may facilitate amplification of dCA1->mPFC signals for which Re acts as the primary conduit, as there is little direct connectivity. In addition, the capacity of mPFC neurons to fire bursts of action potentials in response to Re input suggests that these synapses have a high gain.
GPT-4o mini: Non-social science research article
Iguanas rafted more than 8,000 km from North America to Fiji
Simon G. Scarpetta, Robert N. Fisher, Benjamin R. Karin, Jone B. Niukula, Ammon Corl, Todd R. Jackman, Jimmy A. McGuire
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Founder-event speciation can occur when one or more organisms colonize a distant, unoccupied area via long-distance dispersal, leading to the evolution of a new species lineage. Species radiations established by long-distance, and especially transoceanic, dispersal can cause substantial shifts in regional biodiversity. Here, we investigate the occurrence and timing of the greatest known long-distance oceanic dispersal event in the history of terrestrial vertebrates—the rafting of iguanas from North America to Fiji. Iguanas are large-bodied herbivores that are well-known overwater dispersers, including species that colonized the Caribbean and the Galápagos islands. However, the origin of Fijian iguanas had not been comprehensively tested. We estimated the phylogenetic relationships and evolutionary timescale of the iguanid lizard radiation using genome-wide exons and ultraconserved elements (UCEs). Those data indicate that the closest living relative of extant Fijian iguanas is the North American desert iguana and that the two taxa likely diverged during the late Paleogene near or after the onset of volcanism that produced the Fijian archipelago. Biogeographic models estimate North America as the most probable ancestral range of Fijian iguanas. Our analyses support the hypothesis that iguanas reached Fiji via an extraordinary oceanic dispersal event from western North America, and which spanned a fifth of the earth’s circumference (>8,000 km). Overwater rafting of iguanas from North America to Fiji strengthens the importance of founder-event speciation in the diversification of iguanids and elucidates the scope of long-distance dispersal across terrestrial vertebrates.
GPT-4o mini: Non-social science research article
Deficiency in platelet 12-lipoxygenase exacerbates inflammation and disease severity during SARS-CoV-2 infection
Ana Claudia dos S. P. Andrade, Emile Lacasse, Isabelle Dubuc, Leslie Gudimard, Annie Gravel, Florian Puhm, Gabriel Campolina-Silva, Celso Queiroz-Junior, Isabelle Allaeys, Julien Prunier, Oumaima Azeggouar Wallen, Élizabeth Dumais, ClĂ©mence BelleannĂ©e, Arnaud Droit, Nicolas Flamand, Éric Boilard, Louis Flamand
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Platelets, known for maintaining blood balance, also participate in antimicrobial defense. Upon severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, platelets become hyperactivated, releasing molecules such as cytokines, granule contents, and bioactive lipids. The key effector biolipids produced by platelets include 12-hydroxyeicosatetraenoic acid (12-HETE) and 12-hydroxyeicosatrienoic acid (12-HETrE), produced by 12-lipoxygenase (12-LOX), and prostaglandins and thromboxane, produced by cyclooxygenase-1. While prostaglandin E2 and thromboxane B2 were previously associated with lung inflammation in severe COVID-19, the role of platelet 12-LOX in SARS-CoV-2 infection remains unclear. Using mice deficient for platelets’ 12-LOX, we report that SARS-CoV-2 infection resulted in higher lung inflammation characterized by histopathological tissue analysis, increased leukocyte infiltrates, and cytokine production relative to wild-type mice. In addition, distinct platelet and lung transcriptomic changes, including alterations in NOD-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) inflammasome-related gene expression, were observed. Mass spectrometry lipidomic analysis in 12-LOX-deficient-infected mice revealed significant changes in bioactive lipid content, including reduced levels of 12-HETrE that inversely correlated with disease severity. Finally, platelet 12-LOX deficiency was associated with increased morbidity and lower survival rates relative to wild type (WT) mice. Overall, this study highlights the complex interplay between 12-LOX-related lipid metabolism and inflammatory responses during SARS-CoV-2 infection. The findings provide valuable insights into potential therapeutic targets aimed at mitigating severe outcomes, emphasizing the pivotal role of platelet enzymes in the host response to viral infections.
GPT-4o mini: Non-social science research article
Cryo-EM structures reveal the acetylation process of piccolo NuA4
Lin Wang, Haonan Zhang, Qi Jia, Wenyan Li, Chenguang Yang, Lijuan Ma, Ming Li, Ying Lu, Hongtao Zhu, Ping Zhu
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NuA4 is the only essential acetyltransferase in yeast that can catalyze the acetylation of the histones H2A, H2A.Z, and H4, thereby affecting gene transcription. However, the acetylation process of NuA4, such as how NuA4 acetylates H4 and H2A.Z differently, remains largely elusive. Here, using cryoelectron microscopy (cryo-EM) single particle analysis, we present seven cryo-EM structures of piccolo NuA4 (pNuA4) in complex with wild-type H2A.Z or H2A.Z-mutant-containing nucleosomes in the absence or presence of acetyl coenzyme A (Ac-CoA). We revealed that, in the absence of Ac-CoA, pNuA4 adopts multiple conformations to search for its substrates. After adding Ac-CoA, the single-molecule Förster resonance energy transfer (smFRET) and cryo-EM data indicated that pNuA4 prefers to bind H4 and undergoes a dynamic conformational change to complete the acetylation. We also obtained previously unseen structures in states associated with the acetylation of H2A.Z. These cryo-EM structures and smFRET results suggest a complex acetylation process on H4 and H2A.Z by pNuA4. The results provide a comprehensive picture of the mechanism by which pNuA4 acetylates its substrates within an H2A.Z-containing nucleosome.
GPT-4o mini: Non-social science research article
A splendid molecular factory: De- and reconstruction of the mammalian respiratory chain
Lukas Rimle, Ben P. Phillips, Isabela M. Codo Costa Barra, Noëlle Arnold, Charlie Hennebert, Thomas Meier, Christoph von Ballmoos
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Mitochondrial respiratory complexes I to IV and the F 1 F o -ATP synthase (complex V) are large protein assemblies producing the universal cellular energy currency adenosine triphosphate (ATP). Individual complexes have been extensively studied in vitro, but functional co-reconstitution of several mammalian complexes into proteoliposomes, in particular, the combination of a primary pump with the ATP synthase, is less well understood. Here, we present a generic and scalable strategy to purify mammalian respiratory complexes I, III and the ATP synthase from enriched mitochondria in enzymatically fully active form, and procedures to reassemble the complexes into liposomes. A robust functionality can be shown by in situ monitoring of ATP synthesis rates and by using selected inhibitors of the respiratory chain complexes. By inclusion of cytochrome c oxidase, our procedures allowed us to reconstruct the entire mitochondrial respiratory chain (complexes I, III, IV, and V) in ubiquinone Q 10 containing liposomes, demonstrating oxidative phosphorylation by nicotinamide adenine dinucleotide hydrogen driven ATP synthesis. The system was fully coupled at all levels and was used to probe cardiolipin as an essential component to activate the mammalian respiratory chain. Structural characterization using electron cryomicroscopy allowed us to resolve apo-state complex III and complex V at high and medium resolution, respectively, using in silico particle sorting, confirming the presence of all protein subunits and cofactors in native stoichiometry and conformation. The reported findings will facilitate future endeavors to characterize or modulate these key bioenergetic processes.
GPT-4o mini: Non-social science research article
US grass-fed beef is as carbon intensive as industrial beef and ≈10-fold more intensive than common protein-dense alternatives
Gidon Eshel, Avi I. Flamholz, Alon Alon Shepon, Ron Milo
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The high resource intensity of industrial beef in high-income economies has prompted growing interest in alternative, potentially lower environmental impact beef production pathways. Of those, grass feeding is promoted by some as one such alternative, but rigorous quantification of this claim is required. Motivated to bridge this knowledge gap, we integrate empirical evidence with a model based on authoritative equations governing beef cattle performance to quantify the greenhouse gas emissions of producing grass-fed beef. Because geographical specificity and dependence on agricultural intensity are key, we model widely varied herds, from extensive operations on semiarid, marginal rangelands to partially industrial, intensive ones in lusher, more accommodating settings. We find that emissions per kg protein of even the most efficient grass-fed beef are 10 to 25% higher than those of industrial US beef and 3- to over 40-fold higher than a wide range of plant and animal alternatives. Soil sequestration enhancement by rangeland grazing reduces these emissions from 280–390 to 180–290 kg CO 2eq (kg protein) −1 , still somewhat above industrial beef’s 180 to 220 kg CO 2eq (kg protein) −1 , and well above nonbeef alternatives’ 10 to 70 kg CO 2eq (kg protein) −1 . These differences prove robust across a broad set of combinations of grass-fed beef operation types, management practices, and ration qualities. Consequently, even with maximal credit for putative sequestration enhancement, grass-fed beef is still no less carbon intensive than industrial beef, and severalfold more intensive than nonbeef alternatives.
GPT-4o mini: Non-social science research article
Bringing pressure-induced superconductivity back to ambient pressure
Yuhang Deng, M. Brian Maple
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GPT-4o mini: Non-social science research article
Chlamydomonas FBB18 is a ubiquitin-like protein essential for the cytoplasmic preassembly of various ciliary dyneins
Ryosuke Yamamoto, Yui Sahashi, Rieko Shimo-Kon, Miho Sakato-Antoku, Miyuka Suzuki, Leo Luo, Hideaki Tanaka, Takashi Ishikawa, Toshiki Yagi, Stephen M. King, Genji Kurisu, Takahide Kon
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Motile cilia are organelles found on many eukaryotic cells that play critical roles in development and fertility. Human CFAP298 has been implicated in the transport/assembly of ciliary dyneins, and defects in this protein cause primary ciliary dyskinesia. However, neither the exact function nor the structure of CFAP298 have been elucidated. Here, we took advantage of Chlamydomonas , a ciliated alga, to study the structure and function of FBB18, an ortholog of CFAP298. Multiple ciliary dyneins were greatly reduced in cilia of Chlamydomonas fbb18 mutants. In addition, we found that both the stability of ciliary dynein heavy chains (HCs) and the association between HCs and intermediate/light chains (IC/LCs) are greatly reduced in fbb18 cytoplasm, strongly suggesting that FBB18 functions in the cytoplasmic assembly (the so-called “preassembly”) of dynein complexes from HC/IC/LCs. Furthermore, X-ray crystallography revealed that FBB18 forms a bilobed structure with globular domains at both ends of the molecule, connected by an α-helical bundle. Unexpectedly, one globular domain shows high similarity to ubiquitin, a small protein critical for the modification of a variety of protein complexes, and this ubiquitin-like domain is indispensable for the molecular function of FBB18. Our results demonstrate that FBB18, a specialized member of the ubiquitin-like protein family, plays a critical role in dynein preassembly, most likely by mediating diverse interactions between dynein HCs, molecular chaperone(s), and other preassembly factor(s) using the ubiquitin-like domain as well as other regions, and by facilitating the proper folding of dynein HCs.
GPT-4o mini: Non-social science research article
Androgen receptors in corticotropin-releasing hormone neurons mediate the sexual dimorphism in restraint-induced thymic atrophy
Yutong Meng, Yaning Li, Huating Gu, Ziyao Chen, Xiaoyang Cui, Xiaodong Wang
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Sexual dimorphism in immune responses is well documented, but the underlying mechanisms remain incompletely understood. Here, we identified a subset of corticotropin-releasing hormone (CRH) neurons that express androgen receptors (ARs) as key mediators of sex differences in restraint-induced immunosuppression. Mechanistically, androgens directly activate AR-positive CRH neurons, enhancing the hypothalamic–pituitary–adrenal axis activation. This results in elevated corticosterone levels in response to restraint stress, leading to increased immune cell apoptosis and immune organ atrophy in male mice. Conditional knockout of ARs in CRH neurons eliminated this sexual dimorphism, highlighting ARs in CRH neurons as pivotal regulators of sex-specific immune responses to stress.
GPT-4o mini: Non-social science research article
MITD1 is a brain-specific interferon-inducible factor that inhibits flavivirus replication
Jim Zoladek, Marion Cannac, Maël Seite, Emma Davies, Jordan Quellec, Jonathan Barthelemy, Kamila Gorna, Sophie Desgraupes, Ines Bribes, Sara Salinas, Muriel Coulpier, Nathalie J. Arhel, Massimo Palmarini, Yannick Simonin, Sam J. Wilson, Sébastien Nisole
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West Nile virus (WNV) and Usutu virus (USUV) are closely related mosquito-borne neurotropic flaviviruses that share common transmission cycle and can infect humans. However, while human infections by WNV are widespread, infections by USUV are comparatively less frequent, less severe, and currently limited to Africa and Europe. To identify human host factors that contribute to the pathogenic signatures of these two flaviviruses, we carried out an arrayed expression screen of over 1,300 interferon-stimulated genes (ISGs). Several ISGs known to target flaviviruses, including IFI6, SHFL, and RTP4 were among the strongest hits. Interestingly, we also found MITD1, an ISG with no previously reported antiviral activity, among the strongest hits. We demonstrated that the antiviral activity of MITD1 was not limited to USUV and WNV, since it also inhibited Zika and dengue virus replication. We found MITD1 to interfere with viral RNA replication by sequestering specific endosomal sorting complexes required for transport-III (ESCRT-III) proteins involved in the formation of viral replication factories. MITD1 expression was not increased by type I interferon (IFN-I) in most human cells and mouse tissues that we examined, although WNV and USUV replication was strongly inhibited by IFN-I. Strikingly, MITD1 was induced in the brain of USUV-infected mice and importantly, in human monocyte-derived microglia. Using human microglial-like cells, we confirmed that MITD1 is an essential mediator of the anti-flavivirus activity of IFN-I in these cells. We conclude that MITD1 plays a key role in the cellular defenses against neurotropic flaviviruses.
GPT-4o mini: Non-social science research article
Correction to Supporting Information for Struve et al., Systematic changes in circumpolar dust transport to the Subantarctic Pacific Ocean over the last two glacial cycles
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GPT-4o mini: Non-social science research article
Epidemic evolutionarily stable strategies within an age-structured host population
Andreas Eilersen, Ottar N. BjĂžrnstad, Ruiyun Li, Sebastian J. Schreiber, Zeyuan Pei, Nils Chr. Stenseth
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To understand infectious disease dynamics, we need to understand the inextricably intertwined nature of the ecology and evolution of pathogens and hosts. Epidemiological dynamics of many infectious diseases have highlighted the importance of considering the demographics of the societies in which they spread, particularly with respect to age structure. In addition, the waves of the recent COVID-19 pandemic driven by variant replacements at an unprecedented speed show that it is vital to consider the evolutionary aspects. The classic trade-off theory of virulence addresses aspects of pathogen evolution, but here we explore in more detail the possibility of society-specific evolutionarily stable strategies (ESS) during an unfolding pandemic. Theory posits the existence under some conditions of an ESS representing the evolutionary endpoint of change. By using a demographically realistic model incorporating infection rates that vary with age, we outline which evolutionary scenarios are plausible. Focusing on the rate of infection and duration of infectivity, we ask whether an ESS exists, what characterizes it, and as a result which long-term public-health consequences may be expected. We demonstrate that the ESS of an evolving pathogen depends upon the background age-dependent frailty and mortality rates. Our findings shed important light on the plausible long-term trajectories of highly evolvable novel pathogens.
GPT-4o mini: Non-social science research article
Genomics highlight an underestimation of phenology sensitivity to the urban heat island effect
Meghan Blumstein, Sophie Webster, Robin Hopkins, David Basler, Jie Yun, David Lee Des Marais
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The phenological timing of leaf out in temperate forests is a critical transition point each year that alters the global climate system, which in turn, feeds back to plants, driving leaf out to occur nearly 3 d earlier per decade as temperatures rise. To improve predictions of leaf out timing, urban heat islands (UHIs) or densely developed areas that are hotter than surrounding undeveloped regions are often used to approximate warming via space-for-time substitutions (i.e., rural-to-urban temperature gradients). However, more than just environment changes along these gradients—urban regions are highly managed systems with limited-to-no within species diversity. We demonstrate here that recent observations that UHI gradients underpredict leaf out response to temperature when compared to temperature gradients through time is likely because both genetics and environment are changing across rural-to-urban gradients, whereas only environment is changing through time. We tested this hypothesis using genomic, phenological, and temperature data of northern red oak ( Quercus rubra ) over several years between an urban and rural site. Across our gradient, models that included just temperature predicted moderate advancement of leaf out. However, if we account for the genetic diversity of our trees in our model, leaf out phenology is predicted to advance significantly more in response to temperature. We demonstrate that this stronger relationship between phenological timing and climate is because urban trees have reduced genetic diversity as they are planted from limited stock by humans and, moreover, are most closely related to individuals at the rural site that leaf out later on average.
GPT-4o mini: Non-social science research article
Staphylococcus aureus uses a GGDEF protein to recruit diacylglycerol kinase to the membrane for lipid recycling
Aaron Mychack, Dwayne Evans, Tarah Gilles, Michael J. James, Suzanne Walker
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Staphylococcus aureus is a Gram-positive pathogen responsible for numerous antibiotic-resistant infections. Identifying vulnerabilities in S. aureus is crucial for developing new antibiotics to treat these infections. With this in mind, we probed the function of GdpS, a conserved Staphylococcal membrane protein containing a cytoplasmic GGDEF domain. These domains are canonically involved in cyclic-di-GMP signaling processes, but S. aureus is not known to make cyclic-di-GMP. Using a transposon screen, we found that loss of GdpS is lethal when combined with disruption in synthesis of the glycolipid anchor of a cell surface polymer called lipoteichoic acid (LTA) or with deletion of genes important in cell division. Taking advantage of a small molecule that inhibits LTA glycolipid anchor synthesis, we selected for suppressors of Δ gdpS lethality. The most prevalent suppressors were hypermorphic alleles of dgkB , which encodes a soluble diacylglycerol (DAG) kinase required to recycle DAG to phosphatidylglycerol. By following up on these suppressors, we found that the GGDEF domain of GdpS interacts directly with DgkB, orienting its active site at the membrane to promote DAG recycling. DAG kinase hypermorphs also suppressed the lethality caused by combined loss of gdpS and cell division factors, highlighting the importance of lipid homeostasis for cell division. GdpS’ positive regulation of DAG kinase function was dependent on the GGDEF domain but not its catalytic residues. As the sole conserved GGDEF-domain protein in Staphylococci, GdpS promotes an enzymatic process independent of cyclic-di-GMP signaling, revealing a new function for the ubiquitously conserved GGDEF domain.
GPT-4o mini: Non-social science research article
Correction for Colen et al., Machine learning active-nematic hydrodynamics
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GPT-4o mini: Non-social science research article
Flycodes enable simultaneous preclinical analysis for dozens of antibodies in single cassette–dosed mice
Justin D. Walter, Michal Beffinger, Pascal Egloff, Iwan Zimmermann, Lea M. HĂŒrlimann, Fabian Ackle, Matthias Seifert, Sebastian Kobold, Johannes vom Berg, Markus A. Seeger
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Protein therapeutics such as antibodies require in-depth in vivo characterization during development and consequently account for a large proportion of laboratory animal consumption in the pharmaceutical industry. Currently, antibody candidates are exhaustively tested one-by-one in animal models to determine pharmacokinetic and pharmacodynamic (PK/PD) profiles. The simultaneous analysis of antibody mixtures in single animals, called cassette-dosing, could in principle overcome this bottleneck, but is currently limited to small cassette sizes. Here, we demonstrate how the use of genetically encoded peptide tags (flycodes), designed for maximal detectability in liquid chromatography-mass spectrometry, can allow for the simultaneous characterization of large pools of drug candidates, from single cassette–dosed mice. We demonstrate the simultaneous assessment of PK parameters for a group of >20 marketed/development-stage antibodies. Biodistribution experiments in mice bearing EGFR-expressing tumors correctly identified the two pool members recognizing EGFR, while organ analysis registered liver accumulation of an antibody targeting glucagon receptor, a protein profoundly expressed in that organ. In analogy to an early-phase drug development campaign, we performed biophysical and PK analysis for a cassette of 80 unique bispecific DARPin-sybody molecules. The data shown in this study originate from only 18 cassette-dosed mice, thereby demonstrating how flycode technology efficiently advances preclinical discovery pipelines allowing a direct comparison of drug candidates under identical experimental conditions.
GPT-4o mini: Non-social science research article
Systemic signals control infection plasticity in parasitic plants
Hannes Ruwe, Thomas Spallek
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GPT-4o mini: Non-social science research article
Building better biochronology: New fossils and 40 Ar/ 39 Ar radioisotopic dates from Central Anatolia
Andrew Tholt, OkƟan BaƟoğlu, Yener BektaƟ, Raymond Bernor, Joshua P. Carlson, Ömer Dağ, Uğur Doğan, Ahmet Cem Erkman, Ferhat Kaya, Nuretdin Kaymakçı, Pınar GözlĂŒk Kırmızıoğlu, Maud J. M. Meijers, Özge Kahya Parıldar, Cesur Pehlevan, Emrah ƞimƟek, Tim White, Paul Renne
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TĂŒrkiye’s geographic position between Europe, Asia, and Africa gives it pivotal importance for understanding the local, interregional, and intercontinental dynamics of Neogene vertebrate evolution. Although rich in vertebrate fossil deposits spanning the Middle and Late Miocene, associated geochronology has been limited by the lack of available volcanic materials that allow radioisotopic dating and geochemical correlation. As a result, calibrating mammalian evolution has been largely restricted to the semicircular application of paleomagnetic inferences combined with temporally ill-constrained and geographically remote biochronological deductions. For example, fossils from three Greek localities and one Anatolian locality assigned to the primate genus Ouranopithecus lack datable samples, leaving its ages poorly constrained. Chronological calibration based on the 40 Ar/ 39 Ar results reported here demonstrates how a fauna-focused, precision geochronology can enhance a better understanding of evolving species lineages and the ecosystems they comprise.
GPT-4o mini: Non-social science research article
Jellyfish shape as a mechanical balance
Mengsha Gong, Minakshi Ashok, Ariane Helou, Lea Goentoro
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Why are jellyfish round? Animals get their shapes as they develop. After development, however, how animals keep their shapes is less understood. Moon jellies respond to perturbations to body shape, such as being halved or quartered, by reorganizing existing body parts and regaining radial symmetry, i.e., their round shape. The robust recovery of radial symmetry led us to investigate, in this study, how being round is encoded. We tested perturbing shape by grafting body sections in varying configurations. Testing these perturbations confirms the moon jellies’ ability to recover their round shape from many perturbations. However, in response to some perturbations, the jellies can also adopt other stable body shapes, such as oval, quadrilateral, and triangular. Thus, although the jellies are characterized by a radially symmetrical body plan, perturbations can lead to them recovering to bilateral shapes. Employing mathematical modeling, we find that interactions between forces from muscle contractions and viscoelastic tissues can explain the recovery to different shapes. A stable body shape is achieved when the mechanical forces are locally balanced, regardless of symmetry. Consistent with the model prediction that stable shape is the outcome of balancing mechanical forces, modulating the mechanical parameter in the system, i.e., the muscle contraction rate, can produce shape-shifting. Maintaining shapes dynamically as the balance of mechanical forces may enable the animals to readily adapt to changing physical environments.
GPT-4o mini: Non-social science research article
Diel partitioning in microbial phosphorus acquisition in the Sargasso Sea
Daniel Muratore, Naomi E. Gilbert, Gary R. LeCleir, Steven W. Wilhelm, Joshua S. Weitz
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The daily cycle of photosynthetic primary production at the base of marine food webs is often limited by the availability of scarce nutrients. Microbial competition for these scarce resources can be alleviated insofar as the intensity of nutrient uptake and assimilation activities are distributed heterogeneously across organisms over periodic input cycles. Recent analysis of community transcriptional dynamics in the nitrogen-limited subtropical North Pacific gyre revealed evidence of temporal partitioning of nitrogen uptake and assimilation between eukaryotic phytoplankton, cyanobacteria, and heterotrophic bacteria over day-night cycles. Here, we present results from a Lagrangian metatranscriptomic time series survey in the Sargasso Sea and demonstrate temporally partitioned phosphorus uptake in this phosphorus-limited environment. In the Sargasso, heterotrophic bacteria, eukaryotic phytoplankton, and cyanobacteria express genes for phosphorus assimilation during the morning, day, and dusk, respectively. These results support the generality of temporal niche partitioning as an emergent mechanism that can structure uptake of limiting nutrients and facilitate coexistence of diverse microbes in open ocean ecosystems.
GPT-4o mini: Non-social science research article
Vortex reversal is a precursor of confined bacterial turbulence
Daiki Nishiguchi, Sora Shiratani, Kazumasa A. Takeuchi, Igor S. Aranson
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Active turbulence, or chaotic self-organized collective motion, is often observed in concentrated suspensions of motile bacteria and other systems of self-propelled interacting agents. To date, there is no fundamental understanding of how geometrical confinement orchestrates active turbulence and alters its physical properties. Here, by combining large-scale experiments, computer modeling, and analytical theory, we have identified a generic sequence of transitions occurring in bacterial suspensions confined in cylindrical wells of varying radii. With increasing the well’s radius, we observed that persistent vortex motion gives way to periodic vortex reversals, four-vortex pulsations, and then well-developed active turbulence. Using computational modeling and analytical theory, we have shown that vortex reversal results from the nonlinear interaction of the first three azimuthal modes that become unstable with the radius increase. The analytical results account for our key experimental findings. To further validate our approach, we reconstructed equations of motion from experimental data. Our findings shed light on the universal properties of confined bacterial active matter and can be applied to various biological and synthetic active systems.
GPT-4o mini: Non-social science research article
Correction to Supporting Information for Wang et al., Metabolomic insights into pathogenesis and therapeutic potential in adult acute lymphoblastic leukemia
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GPT-4o mini: Non-social science research article
Reply to Deter-Wolf et al.: Laser-stimulated fluorescence of Chancay tattoos
Thomas G. Kaye, Judyta Bąk, Henry William Marcelo, Michael Pittman
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GPT-4o mini: Non-social science research article
Correction to Supporting Information for Stransky et al., Toward a CRISPR-based mouse model of Vhl -deficient clear cell kidney cancer: Initial experience and lessons learned
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GPT-4o mini: Non-social science research article
Correction to Supporting Information for Utzschneider et al., Force balance of opposing diffusive motors generates polarity-sorted microtubule patterns
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GPT-4o mini: Non-social science research article
Audible enclaves crafted by nonlinear self-bending ultrasonic beams
Jia-Xin Zhong, Jun Ji, Xiaoxing Xia, Hyeonu Heo, Yun Jing
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Delivering audible content to a targeted listener without disturbing others is paramount in audio engineering. However, achieving this goal has long been challenging due to the diffraction of low-frequency (long-wavelength) audio waves in linear acoustics. Here, we introduce an approach for creating remote audio spots, dubbed audible enclaves, by harnessing the local nonlinear interaction of two self-bending ultrasonic beams with distinct spectra. The self-bending ultrasonic beams created by acoustic metasurfaces, though inaudible, can bypass obstacles such as human heads. At their intersection behind obstacles, highly localized audible enclaves are formed due to the local nonlinear interactions. Additionally, we demonstrate the ultrabroadband capabilities of our metasurface-based implementation both numerically and experimentally, spanning from 125 Hz to 4 kHz (6 octave bands), covering the majority of the audible frequency range. The practicality of our proposed technique is underscored by its compact implementation size (0.16 m, equivalent to 0.06 wavelengths at 125 Hz), as well as its robust performance under wideband transient audio signal excitation and in a common room with reverberations. Our proposed audible enclaves hold significant potential for various applications in advanced audio engineering, including private speech communications, immersive spatial audio reproduction, and high-resolution sound/quiet zone control.
GPT-4o mini: Non-social science research article
An atlas of early human mandibular endochondral and osteogenic paracrine signaling regions of Meckel’s cartilage
Zongshan Shen, Ran Zhang, Xinyue Chen, Guan Yang, Yuanchun Si, Tianxing Yan, Suwen Chen, Bin Cheng, Xiaoshan Wu, Di Chen, Dong Zhang, Guozhi Xiao, Jian-Kang Zhu, Songlin Wang
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The mandible, also known as the lower jaw, is the only bone in the skull that can move and is essential for speaking and chewing. Meckel’s cartilage (MC) is a temporary structure that supports the formation of the mandible, but how MC is involved in the ossification of the mandible is poorly understood. Through the use of single-cell RNA sequencing and single-cell spatial transcriptomics analyses, a spatiotemporal atlas of MC in human fetuses from 7 to 15 wk postconception was established, highlighting the role of MC in the ossification of the mandible. Importantly, we revealed that two populations of MC contributed to mandibular ossification through different mechanisms. The anterior MC can differentiate into osteolineage cells, as shown in an in vivo lineage tracing mouse model. The intermediate MC facilitates intramembranous ossification through cell–cell communications, possibly through signaling ligands like BMP5 , BMP7 , SEMA3A , PDGFC , and FGF7 . This study suggests that MC plays a crucial role in mediating mandibular ossification through distinct mechanisms, providing valuable insights for understanding oral and craniofacial diseases and disorders in the future.
GPT-4o mini: Non-social science research article
A solvable model for strongly interacting nonequilibrium excitons
Zhenhao Song, Tessa Cookmeyer, Leon Balents
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We study the driven-dissipative Bose-Hubbard model with an all-to-all hopping term in the system Hamiltonian, while subject to incoherent pumping and decay from the environment. This system is naturally probed in several recent experiments on excitons in WS 2 /WSe 2 moiré systems, as well as quantum simulators. By positing a particular form of coupling to the environment, we derive the Lindblad jump operators and show that, in certain limits, the system admits a closed-form expression for the steady-state density matrix. Away from the exactly solvable regions, the steady state can be obtained numerically for 100s to 1,000s of sites. We study the nonequilibrium phase diagram and phase transitions, which qualitatively matches the equilibrium phase diagram, agreeing with the intuition that increasing the intensity of the light is equivalent to changing the bosonic chemical potential. However, the steady states are far from thermal states, and the nature of the phase transitions is changed.
GPT-4o mini: Non-social science research article
Triggering and modulation of a complex behavior by a single peptidergic command neuron in Drosophila
Magdalena Fernandez-Acosta, Rebeca Zanini, Fabiana Heredia, Yanel A. VolontĂ©, Juliane Menezes, Katja PrĂŒger, Julieta Ibarra, Maite Arana, MarĂ­a S. PĂ©rez, Jan A. Veenstra, Christian Wegener, Alisson M. Gontijo, AndrĂ©s Garelli
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At the end of their growth phase, Drosophila larvae remodel their bodies, glue themselves to a substrate, and harden their cuticle in preparation for metamorphosis. This process—termed pupariation—is triggered by a surge in the hormone ecdysone. Substrate attachment is achieved by a pupariation subprogram called glue expulsion and spreading behavior (GSB). An epidermis-to-CNS Dilp8-Lgr3 relaxin signaling event that occurs downstream of ecdysone is critical for unlocking progression of the pupariation motor program toward GSB, but the factors and circuits acting downstream of Lgr3 signaling remain unknown. Here, using cell-type-specific RNA interference and behavioral monitoring, we identify Myoinhibiting peptide (Mip) as a neuromodulator of multiple GSB action components, such as tetanic contraction, peristaltic contraction alternation, and head-waving. Mip is required in a pair of brain descending neurons, which act temporally downstream of Dilp8-Lgr3 signaling. Mip modulates GSB via ventral nerve cord neurons expressing its conserved receptor, sex peptide receptor (SPR). Silencing of Mip descending neurons by hyperpolarization completely abrogates GSB, while their optogenetic activation at a restricted competence time window triggers GSB-like behavior. Hence, Mip descending neurons have at least two functions: to act as GSB command neurons and to secrete Mip to modulate GSB action components. Our results provide insight into conserved aspects of Mip-SPR signaling in animals, reveal the complexity of GSB control, and contribute to the understanding of how multistep innate behaviors are coordinated in time and with other developmental processes through command neurons and neuropeptidergic signaling.
GPT-4o mini: Non-social science research article
Constructed languages are processed by the same brain mechanisms as natural languages
Saima Malik-Moraleda, Maya Taliaferro, Steve Shannon, Niharika Jhingan, Sara Swords, David J. Peterson, Paul Frommer, Marc Okrand, Jessie Sams, Ramsey Cardwell, Cassie Freeman, Evelina Fedorenko
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What constitutes a language? Natural languages share features with other domains: from math, to music, to gesture. However, the brain mechanisms that process linguistic input are highly specialized, showing little response to diverse nonlinguistic tasks. Here, we examine constructed languages (conlangs) to ask whether they draw on the same neural mechanisms as natural languages or whether they instead pattern with domains like math and programming languages. Using individual-subject fMRI analyses, we show that understanding conlangs recruits the same brain areas as natural language comprehension. This result holds for Esperanto (n = 19 speakers) and four fictional conlangs [Klingon (n = 10), Na’vi (n = 9), High Valyrian (n = 3), and Dothraki (n = 3)]. These findings suggest that conlangs and natural languages share critical features that allow them to draw on the same representations and computations, implemented in the left-lateralized network of brain areas. The features of conlangs that differentiate them from natural languages—including recent creation by a single individual, often for an esoteric purpose, the small number of speakers, and the fact that these languages are typically learned in adulthood—appear to not be consequential for the reliance on the same cognitive and neural mechanisms. We argue that the critical shared feature of conlangs and natural languages is that they are symbolic systems capable of expressing an open-ended range of meanings about our outer and inner worlds.
GPT-4o mini: Non-social science research article
Dynamics of an algae–bacteria microcosm: Photosynthesis, chemotaxis, and expulsion in inhomogeneous active matter
Praneet Prakash, Yasa Baig, François J. Peaudecerf, Raymond E. Goldstein
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In nature, there are significant relationships known between microorganisms from two kingdoms of life, as in the supply of vitamin B 12 by bacteria to algae. Such interactions motivate general investigations into the spatiotemporal dynamics of metabolite exchanges. Here we study by experiment and theory a model system: a coculture of the bacterium Bacillus subtilis , an obligate aerobe that is chemotactic to oxygen, and a nonmotile mutant of the alga Chlamydomonas reinhardtii , which photosynthetically produces oxygen when illuminated. Strikingly, when a shaft of light illuminates a thin, initially uniform suspension of the two, the chemotactic influx of bacteria to the photosynthetically active region leads to expulsion of the algae from that area. We propose that this effect arises from advection by the inhomogeneous bacterial concentration. The resulting generalization of Fick’s law has been proposed in the context of chemotaxis and is mathematically related to the “turbulent pumping” in magnetohydrodynamics.
GPT-4o mini: Non-social science research article
The TEA domain transcription factors TEAD1 and TEAD3 and WNT signaling determine HLA-G expression in human extravillous trophoblasts
Bowen Gu, Leonardo M. R. Ferreira, Sebastian Herrera, Lara Brown, Judy Lieberman, Richard I. Sherwood, Torsten B. Meissner, Jack L. Strominger
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Maternal–fetal immune tolerance guarantees a successful pregnancy throughout gestation. HLA-G, a nonclassical human leukocyte antigen (HLA) molecule exclusively expressed in extravillous trophoblasts (EVT), is a crucial factor in establishing maternal–fetal immune tolerance by interacting with inhibitory receptors on various maternal immune cells residing in the uterus. While trophoblast-specific cis-regulatory elements impacting HLA-G transcription have been described, the identity of trans-acting factors controlling HLA-G expression in EVT remains poorly understood. Utilizing a genome-wide CRISPR-Cas9 knockout screen, we find that the WNT signaling pathway negatively regulates HLA-G expression in EVT. In addition, we identified two trophoblast-specific transcription factors, TEAD1 and TEAD3, required for HLA-G transcription in EVT in a Yes-associated protein-independent manner. Altogether, we systematically elucidated essential genes and pathways underlying HLA-G expression in EVT, shedding light on the mechanisms of maternal–fetal tolerance and potentially providing insights into controlling HLA-G expression beyond EVT to protect allogeneic cells from immune rejection.
GPT-4o mini: Non-social science research article
Correction for Bednarek et al., How and why funders support engaged research
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GPT-4o mini: Non-social science research article
Reply to Grossman et al.: The case for a time-varying oxygen isotopic composition of seawater and cooler Ordovician oceans
Nivedita Thiagarajan, Aivo Lepland, Uri Ryb, Trond H. Torsvik, Leho Ainsaar, Olle Hints, John Eiler
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GPT-4o mini: Non-social science research article
Substrate recognition by a peptide-aminoacyl-tRNA ligase
Josseline Ramos-Figueroa, Haoqian Liang, Wilfred A. van der Donk
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The continuing discovery of new peptide-aminoacyl-tRNA ligases (PEARLs) has unveiled a diverse array of enzymes with the unique potential to append amino acids to the C terminus of substrate peptides in an aminoacyl-tRNA-dependent manner. To date, PEARLs have been reported that can conjugate Cys, Ala, Trp, Gly, Leu, Asn, and Thr residues, but the basis of peptide substrate and aminoacyl-tRNA recognition is not known. Cell-free expression (CFE) has emerged as a powerful tool to rapidly assay activity of substrate variants, and we used the technique in this study to investigate the peptide substrate specificity of the PEARL B h a B C T r p . This enzyme that adds Trp was discovered previously during genome mining for ribosomally synthesized and posttranslational modified peptides (RiPPs). The enzyme is remarkably tolerant of changes to the C-terminal amino acid of the peptide substrate, and truncation and replacement experiments suggest a minimal sequence requirement. An AlphaFold3 model provided insights into binding interactions of the substrate peptide BhaA-Ala to B h a B C T r p and also generated predictions for tRNA, ATP, and Mg 2+ binding modes that were tested by site-directed mutagenesis. The data suggest that several highly conserved residues in PEARLs recognize the 3â€Č-CCA sequence present in all tRNAs. The minimal sequence required for Trp incorporation by B h a B C T r p was employed as a protein tag for C-terminal labeling of eGFP, lysozyme, and MBP with Trp and 5-Br-Trp.
GPT-4o mini: Non-social science research article
Structural assembly of the PAS domain drives the catalytic activation of metazoan PASK
Sajina Dhungel, Michael Xiao, Rajesh Rajaian Pushpabai, Chintan K. Kikani
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PAS domains are ubiquitous sensory modules that transduce environmental signals into cellular responses through tandem PAS folds and PAS-associated C-terminal (PAC) motifs. While this conserved architecture underpins their regulatory roles, here we uncover a structural divergence in the metazoan PAS domain–regulated kinase (PASK). By integrating evolutionary-scale domain mapping with deep learning-based structural models, we identified two PAS domains in PASK, namely PAS-B and PAS-C, in addition to the previously known PAS-A domain. Unlike canonical PAS domains, the PAS fold and PAC motif in the PAS-C domain are spatially segregated by an unstructured linker, yet a functional PAS module is assembled through intramolecular interactions. We demonstrate that this assembly is nutrient responsive and serves to remodel the quaternary structure of PASK that positions the PAS-A domain near the kinase activation loop. This nutrient-sensitive spatial arrangement stabilizes the activation loop, enabling catalytic activation of PASK. These findings revealed an alternative mode of regulatory control in PAS sensory proteins, where the structural assembly of PAS domains links environmental sensing to enzymatic activity. By demonstrating that PAS domains integrate signals through dynamic structural rearrangements, this study broadens the understanding of their functional and regulatory roles and highlights potential opportunities for targeting PAS domain–mediated pathways in therapeutic applications.
GPT-4o mini: Non-social science research article
Hardware-optimal quantum algorithms
Stefanie Muroya, Krishnendu Chatterjee, Thomas A. Henzinger
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Quantum hardware is inherently fragile and noisy. We find that the accuracy of traditional quantum error correction algorithms can be improved depending on the hardware. Given different hardware specifications, we automatically synthesize hardware-optimal algorithms for parity correction, qubit resetting, and GHZ (Greenberger–Horne–Zeilinger) state preparation. Using stochastic techniques from computer science, our method presents a computational tool to compute exact accuracy guarantees and synthesize optimal algorithms that are often different from traditional ones. We also show that improvements can be gained with respect to the Qiskit transpiler as we compute the hardware-optimal qubit mapping for the GHZ state-preparation problem.
GPT-4o mini: Non-social science research article
Energy landscape analysis of the development of the chromosome structure across the cell cycle
Vinícius G. Contessoto, Antonio B. Oliveira Jr., Sumitabha Brahmachari, Peter G. Wolynes, Michele Di Pierro, José N. Onuchic
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During mitosis, there are significant structural changes in chromosomes. We used a maximum entropy approach to invert experimental Hi-C data to generate effective energy landscapes for chromosomal structures at different stages during the cell cycle. Modeled mitotic structures show a hierarchical organization of helices of helices. High-periodicity loops span hundreds of kilobases or less, while the other low-periodicity ones are larger in genomic separation, spanning several megabases. The structural ensembles reveal a progressive decrease in compartmentalization from interphase to mitosis, accompanied by the appearance of a second diagonal in prometaphase, indicating an organized array of loops. While there is a local tendency to form chiral helices, overall, no preferential left-handed or right-handed chirality appears to develop on the time scale of the cell cycle. Chromatin thus appears to be a liquid crystal containing numerous defects that anneal rather slowly.
GPT-4o mini: Non-social science research article
Diversification, niche adaptation, and evolution of a candidate phylum thriving in the deep Critical Zone
Wenlu Feng, Xiaonan Wan, Yiran Zhang, John Quensen, Tom A. Williams, Michael Thompson, Matthew Streeter, Yang Zhang, Shuo Jiao, Gehong Wei, Yuanjun Zhu, Jie Gu, James M. Tiedje, Xun Qian
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The deep subsurface soil microbiome encompasses a vast amount of understudied phylogenetic diversity and metabolic novelty, and the metabolic capabilities and ecological roles of these communities remain largely unknown. We observed a widespread and relatively abundant bacterial phylum (CSP1-3) in deep soils and evaluated its phylogeny, ecology, metabolism, and evolutionary history. Genome analysis indicated that members of CSP1-3 were actively replicating in situ and were widely involved in the carbon, nitrogen, and sulfur cycles. We identified potential adaptive traits of CSP1-3 members for the oligotrophic deep soil environments, including a mixotrophic lifestyle, flexible energy metabolisms, and conservation pathways. The ancestor of CSP1-3 likely originated in an aquatic environment, subsequently colonizing topsoil and, later, deep soil environments, with major CSP1-3 clades adapted to each of these distinct niches. The transition into the terrestrial environment was associated with genome expansion, including the horizontal acquisition of a range of genes for carbohydrate and energy metabolism and, in one lineage, high-affinity terminal oxidases to support a microaerophilic lifestyle. Our results highlight the ecology and genome evolution of microbes in the deep Critical Zone.
GPT-4o mini: Non-social science research article
ACOD1-mediated lysosomal membrane permeabilization contributes to Mycobacterium tuberculosis –induced macrophage death
Ziwei Yang, Li Zhang, Samantha Ottavi, Jacob B. Geri, Andrew Perkowski, Xiuju Jiang, Daniel Pfau, Ruslana Bryk, Jeffrey Aubé, Matthew Zimmerman, Véronique Dartois, Carl Nathan
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Mycobacterium tuberculosis (Mtb) primarily infects macrophages. In vitro without antibiotics, wild-type Mtb hastens death of the macrophages, but the processes leading to rapid cell death are not well understood. Our earlier work indicated that the death of Mtb-infected mouse macrophages in vitro is markedly exacerbated by induction of interferon-ÎČ (IFN-ÎČ) [L. Zhang et al., J. Exp. Med. 18 , e20200887 (2021)]. Here, we identified a key downstream response to IFN-ÎČ in the context of Mtb infection as the massive induction of cis-aconitate decarboxylase (ACOD1), not only in its canonical subcellular localization in mitochondria but also in the cytosol, where it bound to the lysosome-stabilizing protein HSP70. ACOD1’s product, itaconate, protected Mtb-infected macrophages. However, the contrasting and predominant effect of high-level ACOD1 expression was to act in a noncatalytic manner to promote HSP70’s degradation, leading to lysosomal membrane permeabilization (LMP). Mtb-induced macrophage death was markedly diminished by inhibitors of cysteine proteases, consistent with lysosome-mediated cell death. Neither ACOD1 inhibitors nor cysteine protease inhibitors are suitable for potential host-directed therapy (HDT) of tuberculosis. Instead, this work directs attention to how ACOD1 acts nonenzymatically to promote the degradation of HSP70.
GPT-4o mini: Non-social science research article
In This Issue
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GPT-4o mini: Non-social science research article
Embryonic reprogramming of the tumor vasculature reveals targets for cancer therapy
Elisabeth J. M. Huijbers, Judy R. van Beijnum, Karlijn van Loon, Christian J. Griffioen, Richard Volckmann, Ayse Bassez, Diether Lambrechts, Madalena Nunes Monteiro, Connie R. Jimenez, Pancras C. W. Hogendoorn, Jan Koster, Arjan W. Griffioen
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A sustained blood supply is critical for tumor growth, as it delivers the nutrients and oxygen required for development. Targeting of blood vessel formation via immunotherapies is an area of great importance. Knowing that certain embryonic genes, such as carcinoembryonic antigens (CEA) and oncofetal fibronectin, become reexpressed in malignant transformation, we hypothesized that a similar phenomenon holds true for tumor endothelial cells (TECs) as well. An approach for identification of highly selective tumor endothelial markers was conducted to develop targeted antiangiogenic immunotherapies. We first queried the transcriptome that is present during embryo development. We then performed a systematic search for genes selectively expressed in the mouse embryo at days E11 and E18, as compared to the transcriptome of the adult mouse. Subsequently, we queried for expression of these embryonic genes in sorted murine TECs. This approach identified among others the tumor endothelial antigens fibrillin-2 (Fbn2), elastin microfibril interface-located protein 2 (Emilin2) as well as the tumor endothelial antigens lysyl oxidase (Lox) and serine/cysteine protease inhibitor, clade E, member 1 (Serpine1; Pai-1). For these selected genes, functional involvement in angiogenesis was confirmed in in vitro bioassays. We subsequently used iBoost conjugate vaccine technology to develop vaccines against the selected targets. For all four targets, vaccination readily induced target-specific antibody responses in mice, resulting in inhibition of tumor growth. Access to highly specific tumor endothelial markers provides opportunities for direct targeting of the tumor vasculature with high specificity, without affecting healthy vasculature.
GPT-4o mini: Non-social science research article
Archaeogenomic insights into commensalism and regional variation in pig management in Neolithic northwest Europe
Jolijn A. M. Erven, Valeria Mattiangeli, Merita Dreshaj, Victoria E. Mullin, Conor Rossi, Kevin G. Daly, Iseult Jackson, Mike Parker Pearson, Daniel G. Bradley, Laurent A. F. Frantz, Ole Madsen, Daan Raemaekers, Canan Çakirlar
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The relationship between humans and pigs has changed dramatically since their domestication in southwest Asia and subsequent human-induced introduction into Europe. Introgression between incoming southwest Asian pigs and European boar resulted in the gradual replacement of southwest Asian ancestry in European pigs. However, we currently lack genomic data required to explore the regional trajectories, nature, and extent of contact between European boar and pigs that led to this turnover, and how this process was facilitated by human activity. We addressed this deficit by sequencing four Mesolithic boar and seven Neolithic pig samples from six archaeological sites in the Netherlands and Britain ranging from the Mesolithic (5500 BCE) to Neolithic (2500 BCE). Our data show that despite continuous gene flow with European boar, Neolithic European pigs show varying levels of southwest Asian ancestry. The low and varying southwest Asian ancestry in pigs from the Early Neolithic Dutch settlement Swifterbant indicates a high contribution of wild ancestry. The genetic profile, enriched ÎŽ 15 N values, on-site presence, and wide size distribution of Swifterbant Sus scrofa suggest a commensal relationship. Runs of homozygosity (ROH) imply that both closed-breeding and free-ranging management occurred in Neolithic communities, where the former showed an extreme burden of long segments of ROH. We further show selection signatures, associated with coat color and behavior, in Neolithic herds despite recurrent wild gene flow. Altogether, our results show distinct husbandry practices through space and time in Neolithic Europe, with heavy reliance on boar recruitment via the commensal pathway in northwest Europe.
GPT-4o mini: Non-social science research article
Entropy is an important design principle in the photosystem II supercomplex
Johanna L. Hall, Shiun-Jr Yang, David T. Limmer, Graham R. Fleming
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Photosystem II (PSII) can achieve near-unity quantum efficiency of light harvesting in ideal conditions and can dissipate excess light energy as heat to prevent the formation of reactive oxygen species (ROS) under light stress. Understanding how this pigment–protein complex accomplishes these opposing goals is a topic of great interest that has so far been explored primarily through the lens of the system energetics. Despite PSII’s known flat energy landscape, a thorough consideration of the entropic effects on energy transfer in PSII is lacking. In this work, we aim to discern the free energetic design principles underlying the PSII energy transfer network. To accomplish this goal, we employ a structure-based rate matrix and compute the free energy terms in time following a specific initial excitation to discern how entropy and enthalpy drive ensemble system dynamics. We find that the interplay between the entropy and enthalpy components differ among each protein subunit, which allows each subunit to fulfill a unique role in the energy transfer network. This individuality ensures that PSII can accomplish efficient energy trapping in the reaction center (RC), effective nonphotochemical quenching (NPQ) in the periphery, and robust energy trapping in the other-monomer RC if the same-monomer RC is closed. We also show that entropy, in particular, is a dynamically tunable feature of the PSII free energy landscape accomplished through regulation of LHCII binding. These findings help rationalize natural photosynthesis and provide design principles for more efficient solar energy harvesting technologies.
GPT-4o mini: Non-social science research article
Comprehensive mutant chemotyping reveals embedding of a lineage-specific biosynthetic gene cluster in wider plant metabolism
Xue Qiao, Alan Houghton, James Reed, Burkhard Steuernagel, Jiahe Zhang, Charlotte Owen, Aymeric Leveau, Anastasia Orme, Thomas Louveau, Rachel Melton, Brande B. H. Wulff, Anne Osbourn
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Plants produce diverse specialized metabolites with important ecological functions. It has recently become apparent that the genes for many of these pathways are not dispersed in plant genomes, but rather are arranged like beads on a string in biosynthetic gene clusters (BGCs). Pathways encoded by BGCs are as a rule dedicated linear pathways that do not form parts of wider metabolic networks. In contrast, the genes for the biosynthesis of widely distributed more ancestral metabolites such as carotenoids and anthocyanins are not clustered. Little is known about how these more recently evolved clustered pathways interact with general plant metabolism. We recently characterized a 12-gene BGC for the biosynthesis of the antimicrobial defense compound avenacin A-1, a triterpene glycoside produced by oats. Avenacin A-1 is acylated with the fluorophore N -methyl anthranilate and confers bright blue fluorescence of oat root tips under ultraviolet light. Here, we exploit a suite of >100 avenacin-deficient mutants identified by screening for reduced root fluorescence to identify genes required for the function of this paradigm BGC. Using a combination of mutant chemotyping, biochemical and molecular analysis, and genome resequencing, we identify two nonclustered genes ( Sad4 and Pal2 ) encoding enzymes that synthesize the donors required for avenacin glycosylation and acylation (recruited from the phenylpropanoid and tryptophan pathways). Our finding of these Cluster Auxiliary Enzymes (CAEs) provides insights into the interplay between general plant metabolism and a newly evolved lineage-specific BGC.
GPT-4o mini: Non-social science research article
TAOK1 promotes filament formation in HR repair through phosphorylating USP7
Tian-Chen Zhu, Zhang-Ping He, Shu-Ting Li, Lin Zheng, Xue-Yi Zheng, Xia-Lu Lan, Chun-Hua Qu, Run-Cong Nie, Chao Gu, Li-Ning Huang, Xiao-Xia Cai, Zhi-Cheng Xiang, Dan Xie, Mu-Yan Cai
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Poly-ADP-ribose polymerase (PARP) inhibitors are vital therapeutic agents that exploit synthetic lethality, particularly effective in tumors with homologous recombination (HR) defects. However, broadening their clinical utility remains a significant challenge. In this study, we conducted a high-throughput kinase inhibitor screen to identify potential targets exhibiting synthetical lethality with PARP inhibitors. Our results show that thousand and one amino acid protein kinase 1 (TAOK1) plays a pivotal role in the DNA damage response by phosphorylating ubiquitin specific peptidase 7 (USP7), thereby promoting its enzymatic activity and preventing the ubiquitylation and subsequent degradation of RAD51, a crucial protein in the filament formation of HR repair. Notably, genetic depletion or pharmacological inhibition of TAOK1, as well as blocking peptide targeting the USP7 phosphorylation site, impaired USP7 function, leading to RAD51 degradation, disruption of HR repair, and increased tumor cell and sensitivity to PARP inhibition. This study highlights TAOK1 as a critical regulator of HR repair pathway in human cancer cells and presents a therapeutic strategy overcoming resistance to PARPi inhibitors. These findings support the potential clinical application of combining PARP inhibitors with TAOK1 inhibition or peptide treatment to improve therapeutic outcomes.
GPT-4o mini: Non-social science research article
Dnmt3a-mediated hypermethylation of FoxO3 promotes redox imbalance during osteoclastogenesis
Wei Zhang, Wenming Li, Jun Du, Chen Yang, Lei Yu, Peng Yang, Haifeng Zhang, Zebin Wu, Gaoran Ge, Huilin Yang, Dechun Geng
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Redox imbalance contributes to aberrant osteoclastogenesis and osteoporotic bone loss. In this study, we observed lower Forkhead box protein O3 (FoxO3), a transcription factor associated with cellular oxidative stress, enhanced osteoclastogenesis in osteoporosis (OP). Single-cell RNA sequencing (scRNA-seq) analysis on the human femoral head indicated that FoxO3 is widely expressed in macrophages. Furthermore, Lysm-Cre;FoxO3 f/f OVX mice showed increased reactive oxygen species (ROS), enhanced osteoclastogenesis, and more bone loss than normal OVX mice. Mechanistically, we identified FoxO3 promoter methylation as a crucial factor contributing to decreased FoxO3, thereby influencing osteoclastogenesis and OC function. Intriguingly, we observed that Dnmt3a, highly expressed during osteoclastogenesis, played a pivotal role in regulating the methylation of the FoxO3 promoter. Knockdown of Dnmt3a promoted FoxO3 expression, inhibiting osteoclastogenesis and mitigating OP. Interestingly, we observed that Dnmt3a alleviated osteoclastogenesis by suppressing ROS via upregulating FoxO3 rather than inducing the dissociation of RANK and TRAF6. Collectively, this study elucidates the role and mechanism of FoxO3 in osteoclastogenesis and OP, providing a epigenetic target for the treatment of OP.
GPT-4o mini: Non-social science research article
Trans-synaptic modulation of cholinergic circuits tunes opioid reinforcement
Stefano Zucca, Gloria Brunori, Henry A. Dunn, Colten K. Lankford, Laurie P. Sutton, Beatriz Algibez Flores, Nycole A. Maza, Omar Sial, Gogce Crynen, Rafael LujĂĄn, Kirill A. Martemyanov
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Opioids trigger structural and functional neural adaptations of the reward circuit that lead to dependence. Synaptic cell adhesion molecules (CAMs) play a pivotal role in circuit organization and present prime candidates for orchestrating remodeling of neural connections in response to drug exposure. However, the contribution of CAMs to opioid-induced rewiring of the reward circuit has not been explored. Here, we used unbiased molecular profiling to identify CAMs in the nucleus accumbens (NAc) modulated by morphine administration. We found that opioid exposure induces the expression of ELFN1, a CAM selectively expressed in cholinergic interneurons in the NAc. We determined that ELFN1 acts trans-synaptically to modulate the strength and plasticity of the glutamatergic inputs onto cholinergic neurons via the recruitment of presynaptic metabotropic glutamate receptor 4 (mGlu4). Disruption of Elfn1 diminished morphine reward and intake in self-administering mice. Together, our findings identify a key molecular factor responsible for adjusting the strength of opioid effects by modulating the configuration of striatal circuitry in an experience-dependent fashion and unveil potential therapeutic target for combating opioid abuse.
Maintaining cooperation through vertical communication of trust when removing sanctions
Ann-Christin Posten, Pınar Uğurlar, Sebastian Kube, Joris Lammers
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An effective way to foster cooperation is to monitor behavior and sanction freeriding. Yet, previous studies have shown that cooperation quickly declines when sanctioning mechanisms are removed. We test whether explicitly expressing trust in players’ capability to maintain cooperation after the removal of sanctions, i.e., vertical communication of trust, has the potential to alleviate this drop in compliance. Four incentivized public-goods experiments ( N = 2,823) find that the vertical communication of trust maintains cooperation upon the removal of centralized (Study 1), third-party (Study 2a, 2b), and peer punishment (Study 3), and this effect extends beyond single interactions (Study 4). In all studies, vertical trust communication increases mutual trust among players, providing support to the idea that vertically communicating trust can be a self-fulfilling prophecy. Extrapolating our findings to natural environments, they suggest that authorities should carefully consider how they communicate the lifting of rules and sanctions.
Reply to Wang: Improving large language model approaches for identifying social determinants of health from clinical notes
Rodney A. Gabriel
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Poverty alleviation resettlement in China reduces deforestation
Feifei Chen, Wei Chen, Huanguang Qiu
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Deforestation frequently accompanies poverty, yet various antipoverty programs in many countries have exhibited mixed results in addressing deforestation. Poverty Alleviation Resettlement (PAR) stands out as one of the few government-led resettlement programs designed to alleviate poverty, offering comprehensive follow-up support for quality of life and employment after relocation. Our study uncovered empirical evidence of the PAR program’s impact on forest quality. Through a multiperiod difference-in-differences analysis of remote sensing and household survey data, we found that the PAR program significantly curbed deforestation in the participating counties and reduced forest-clearing activities among the resettled households, even those relocating to rural villages. Mechanism analysis revealed that the program discouraged deforestation by enhancing market accessibility, fostering nonfarm employment opportunities, and elevating income levels. The study underscores that altering livelihood strategies and lifestyles is essential for resettlement programs to effectively mitigate ecological degradation.
Day-to-day fluctuations in motivation drive effort-based decision-making
Samuel R. C. Hewitt, Agnes Norbury, Quentin J. M. Huys, Tobias U. Hauser
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Internal states like motivation fluctuate substantially over time. However, studies of the neurocomputational mechanims of motivated behavior have failed to capture this. Here, we examined how naturalistic ups and downs in state motivation influence the subjective value of reward and effort. In a microlongitudinal design (N = 155, state timepoints = 3,344, decision-making tasks = 845), we captured fluctuations in state and effort-based decision-making using smartphone-based momentary assessments as people went about their daily lives. We found that both state and trait have independent and multiplicative effects on decision-making. State–behavior coupling was particularly pronounced in individuals with higher trait apathy, meaning that their choices were even more state dependent. Using computational modeling, we demonstrate that state motivation prospectively boosted reward sensitivity, making people more willing to exert effort in future. Our results show that day-to-day fluctuations in state and cognition are tightly linked and critical for understanding fundamental human behaviors and mental ill-health.
The file drawer problem in social science survey experiments
Philip Moniz, James N. Druckman, Jeremy Freese
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The file drawer problem—often operationalized in terms of statistically significant results being published and statistically insignificant not being published—is widely documented in the social sciences. We extend Franco’s et al. [ Science 345 , 1502–1505(2014)] seminal study of the file drawer problem in survey experiments submitted to the Time-sharing Experiments for the Social Sciences (TESS) data collection program. We examine projects begun after Franco et al. The updated period coincides with the contemporary open science movement. We find evidence of the problem, stemming from scholars opting to not write up insignificant results. However, that tendency is substantially smaller than it was in the prior decade. This suggests increased recognition of the importance of null results, even if the problem remains in the domain of survey experiments.

Science

GPT-4o mini: Non-social science research article
Direct effects of mountain uplift and topography on biodiversity
Eyal Marder, Tara M. Smiley, Brian J. Yanites, Katherine Kravitz
Full text
Biodiversity hotspots in Earth’s mountain ranges suggest a strong connection between topographic development and biological processes. However, it remains unclear whether high biodiversity in mountain ranges is an evolutionary response to the rate of relief generation during mountain building. Focusing on small mammals, such as rodents, we used coupled landscape-biological simulations to show that biodiversity increases with the magnitude and rate of tectonic uplift. This relationship, visible in depositional lowlands over millions of years, underscores the considerable role of mountain building in shaping past and present terrestrial biodiversity. Our results provide insights into the influence of topographic changes on evolutionary processes, offering a potential link between mountain formation and paleodiversity records.
GPT-4o mini: Non-social science research article
Recent gains in global terrestrial carbon stocks are mostly stored in nonliving pools
Yinon M. Bar-On, Xiaojun Li, Michael O’Sullivan, Jean-Pierre Wigneron, Stephen Sitch, Philippe Ciais, Christian Frankenberg, Woodward W. Fischer
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Terrestrial sequestration of carbon has mitigated ≈30% of anthropogenic carbon emissions. However, its distribution across different pools, live or dead biomass and soil and sedimentary organic carbon, remains uncertain. Analyzing global observational datasets of changes in terrestrial carbon pools, we found that ≈35 ± 14 gigatons of carbon (GtC) have been sequestered on land between 1992 and 2019, whereas live biomass changed by ≈1 ± 7 GtC. Global vegetation models instead imply that sequestration has been mostly in live biomass. We identify key processes not included in most models that can explain this discrepancy. Most terrestrial carbon gains are sequestered as nonliving matter and thus are more persistent than previously appreciated, with a substantial fraction linked to human activities such as river damming, wood harvest, and garbage disposal in landfills.
GPT-4o mini: Non-social science research article
In-cell architecture of the mitochondrial respiratory chain
Florent Waltz, Ricardo D. Righetto, Lorenz Lamm, Thalia Salinas-Giegé, Ron Kelley, Xianjun Zhang, Martin Obr, Sagar Khavnekar, Abhay Kotecha, Benjamin D. Engel
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Mitochondria regenerate adenosine triphosphate (ATP) through oxidative phosphorylation. This process is carried out by five membrane-bound complexes collectively known as the respiratory chain, working in concert to transfer electrons and pump protons. The precise organization of these complexes in native cells is debated. We used in situ cryo–electron tomography to visualize the native structures and organization of several major mitochondrial complexes in Chlamydomonas reinhardtii cells. ATP synthases and respiratory complexes segregate into curved and flat crista membrane domains, respectively. Respiratory complexes I, III, and IV assemble into a respirasome supercomplex, from which we determined a native 5-angstrom (Å) resolution structure showing binding of electron carrier cytochrome c . Combined with single-particle cryo–electron microscopy at 2.4-Å resolution, we model how the respiratory complexes organize inside native mitochondria.
GPT-4o mini: Non-social science research article
COP 30: Brazilian policies must change
Philip M. Fearnside, Walter Leal Filho
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The 30th Conference of the Parties (COP 30) of the United Nations Framework Convention on Climate Change will be held in November 2025 in Belém, in the Brazilian Amazon. For COP 30 to be effective in leading the world to reverse its disastrous course toward a climate tipping point, it will be necessary not only to halt deforestation but also to facilitate a rapid worldwide phaseout of fossil-fuel combustion. Yet as host of the conference, Brazil is not leading by example. As participants prepare for COP 30 over the months ahead, it is important that the meeting be used not only to agree on further global measures to combat climate change, but also to encourage the host country to change current practices.
GPT-4o mini: Non-social science research article
Unifying spatial scaling laws of biodiversity and ecosystem stability
Maowei Liang, Qi Yang, Jonathan M. Chase, Forest Isbell, Michel Loreau, Bernhard Schmid, Eric W. Seabloom, David Tilman, Shaopeng Wang
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While both species richness and ecosystem stability increase with area, how these scaling patterns are linked remains unclear. Our theoretical and empirical analyses of plant and fish communities show that the spatial scaling of ecosystem stability is determined primarily by the scaling of species asynchrony, which is in turn driven by the scaling of species richness. In wetter regions, plant species richness and ecosystem stability both exhibit faster accumulation with area, implying potentially greater declines in biodiversity and stability following habitat loss. The decline in ecosystem stability after habitat loss can be delayed, creating a stability debt mirroring the extinction debt of species. By unifying two foundational scaling laws in ecology, our work underscores that ongoing biodiversity loss may destabilize ecosystems across spatial scales.
GPT-4o mini: Non-social science research article
Synaptic architecture of a memory engram in the mouse hippocampus
Marco Uytiepo, Yongchuan Zhu, Eric Bushong, Katherine Chou, Filip Souza Polli, Elise Zhao, Keun-Young Kim, Danielle Luu, Lyanne Chang, Dong Yang, Tsz Ching Ma, Mingi Kim, Yuting Zhang, Grant Walton, Tom Quach, Matthias Haberl, Luca Patapoutian, Arya Shahbazi, Yuxuan Zhang, Elizabeth Beutter, Weiheng Zhang, Brian Dong, Aureliano Khoury, Alton Gu, Elle McCue, Lisa Stowers, Mark Ellisman, Anton Maximov
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Memory engrams are formed through experience-dependent plasticity of neural circuits, but their detailed architectures remain unresolved. Using three-dimensional electron microscopy, we performed nanoscale reconstructions of the hippocampal CA3-CA1 pathway after chemogenetic labeling of cellular ensembles recruited during associative learning. Neurons with a remote history of activity coinciding with memory acquisition showed no strong preference for wiring with each other. Instead, their connectomes expanded through multisynaptic boutons independently of the coactivation state of postsynaptic partners. The rewiring of ensembles representing an initial engram was accompanied by input-specific, spatially restricted upscaling of individual synapses, as well as remodeling of mitochondria, smooth endoplasmic reticulum, and interactions with astrocytes. Our findings elucidate the physical hallmarks of long-term memory and offer a structural basis for the cellular flexibility of information coding.
GPT-4o mini: Non-social science research article
Error-detected quantum operations with neutral atoms mediated by an optical cavity
Brandon Grinkemeyer, Elmer Guardado-Sanchez, Ivana Dimitrova, Danilo Shchepanovich, G. Eirini Mandopoulou, Johannes Borregaard, Vladan Vuletić, Mikhail D. Lukin
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Neutral-atom quantum processors are a promising platform for large-scale quantum computing. Integrating them with optical cavities enables fast nondestructive qubit readout and access to fast remote entanglement generation for quantum networking. In this work, we introduce a platform for coupling single atoms in optical tweezers to a Fabry-Perot fiber cavity. Leveraging the strong atom-cavity coupling, we demonstrated fast qubit-state readout with 99.960 − 24 + 14 % fidelity and two methods for cavity-mediated entanglement generation with integrated error detection. First, we used cavity-carving to generate a Bell state with 91(4)% fidelity and a 32(1)% success rate (the number in parentheses is the standard deviation). Second, we performed a cavity-mediated gate with a deterministic entanglement fidelity of 52.5(18)%, increased to 76(2)% with error detection. Our approach provides a route toward modular quantum computing and networking.
GPT-4o mini: Non-social science research article
Apoplastic barriers are essential for nodule formation and nitrogen fixation in Lotus japonicus
Defeng Shen, Nikola Micic, Rafael E. Venado, Nanna Bjarnholt, Christoph Crocoll, Daniel Pergament Persson, Sebastian Samwald, Stanislav Kopriva, Philip Westhoff, Sabine Metzger, Ulla Neumann, Ryohei Thomas Nakano, Macarena MarĂ­n Arancibia, Tonni Grube Andersen
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Establishment of the apoplastic root barrier known as the Casparian strip occurs early in root development. In legumes, this area overlaps with nitrogen-fixing nodule formation, which raises the possibility that nodulation and barrier formation are connected. Nodules also contain Casparian strips, yet, in this case, their role is unknown. We established mutants with defective barriers in Lotus japonicus . This revealed that effective apoplastic blockage in the endodermis is important for root-to-shoot signals underlying nodulation. Our findings further revealed that in nodules, the genetic machinery for Casparian strip formation is shared with roots. Apoplastic blockage controls the metabolic source-sink status required for nitrogen fixation. This identifies Casparian strips as a model system to study spatially constrained symbiotic plant-microbe relationships.
GPT-4o mini: Non-social science research article
Cognitive perception of circulating oxygen in seals is the reason they don’t drown
J. Chris McKnight, Eva-Maria BĂžnnelycke, Steve Balfour, Ryan Milne, Simon E. W. Moss, Holly C. Armstrong, Caitlin Downie, Ailsa J. Hall, Joanna L. Kershaw
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Marine mammals rely on maintaining sufficient blood oxygen levels while diving to prevent drowning. Generally, oxygen is cognitively imperceptible to mammals that instead sense rising carbon dioxide as a proxy for low oxygen. Not perceiving oxygen, however, is risky for diving mammals. We argue that any ability to alter dives based upon direct perception of oxygen should have been strongly selected for. We exposed diving seals to inhaled gas mixes that were experimentally altered to affect circulating levels of oxygen and carbon dioxide. Dive duration was positively correlated with circulating oxygen levels but unaffected by carbon dioxide levels and pH. These results suggest that seals do cognitively perceive circulating oxygen and use this to alter dive behavior.
GPT-4o mini: Non-social science research article
Artificial intelligence learns to reason
Melanie Mitchell
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Julia has two sisters and one brother. How many sisters does her brother Martin have? Solving this tiny puzzle requires a bit of thinking. You might mentally picture the family of three girls and one boy and then realize that the boy has three sisters. Or you might figure out a more general rule: Any boy in the family will have one more sister than any girl. In other words, the answer to such a puzzle isn’t something you immediately know, like Paris is the capital of France; it requires reasoning, a central feature of human intelligence, and one that large language models (LLMs) like GPT-4, for all their impressive behavior, struggle with.
GPT-4o mini: Non-social science research article
Macroecological rules predict how biomass scales with species richness in nature
Alex L. Pigot, Laura E. Dee, Anthony J. Richardson, Declan L. M. Cooper, Nico Eisenhauer, Richard D. Gregory, Simon L. Lewis, Callum J. Macgregor, Dario Massimino, Daniel S. Maynard, Helen R. P. Phillips, Marina Rillo, Michel Loreau, Bart Haegeman
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Despite advances in theory and experiments, how biodiversity influences the structure and functioning of natural ecosystems remains debated. By applying new theory to data on 84,695 plant, animal, and protist assemblages, we show that the general positive effect of species richness on stocks of biomass, as well as much of the variation in the strength and sign of this effect, is predicted by a fundamental macroecological quantity: the scaling of species abundance with body mass. Standing biomass increases with richness when large-bodied species are numerically rare but is independent of richness when species size and abundance are uncoupled. These results suggest a new fundamental law in the structure of ecological communities and show that the impacts of changes in species richness on biomass are predictable.
GPT-4o mini: Non-social science research article
Deep learning the flow law of Antarctic ice shelves
Yongji Wang, Ching-Yao Lai, David J. Prior, Charlie Cowen-Breen
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Antarctic ice shelves buttress the grounded ice sheet, mitigating global sea level rise. However, fundamental mechanical properties, such as the ice flow law and viscosity structure, remain under debate. In this work, by leveraging remote-sensing data and physics-informed deep learning, we provide evidence over several ice shelves that the flow law follows a grain size–sensitive composite rheology in the compression zone. In the extension zone, we found that ice exhibits anisotropic properties. We constructed ice shelf–wide anisotropic viscosity maps that capture the suture zones, which inhibit rift propagation. The inferred stress exponent near the grounding zone dictates the grounding-line ice flux and grounding line stability, whereas the inferred viscosity maps inform the prediction of rifts. Both are essential for predicting the future mass loss of the Antarctic Ice Sheet.
GPT-4o mini: Non-social science research article
Circularly polarized electroluminescence from chiral supramolecular semiconductor thin films
Rituparno Chowdhury, Marco D. Preuss, Hwan-Hee Cho, Joshua J. P. Thompson, Samarpita Sen, Tomi K. Baikie, Pratyush Ghosh, Yorrick Boeije, Xian Wei Chua, Kai-Wei Chang, Erjuan Guo, Joost van der Tol, Bart W. L. van den Bersselaar, Andrea Taddeucci, Nicolas Daub, Daphne M. Dekker, Scott T. Keene, Ghislaine Vantomme, Bruno Ehrler, Stefan C. J. Meskers, Akshay Rao, Bartomeu Monserrat, E. W. Meijer, Richard H. Friend
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Current organic light-emitting diode (OLED) technology uses light-emitting molecules in a molecular host. We report green circularly polarized luminescence (CPL) in a chirally ordered supramolecular assembly, with 24% dissymmetry in a triazatruxene (TAT) system. We found that TAT assembled into helices with a pitch of six molecules, associating angular momentum to the valence and conduction bands and obtaining the observed CPL. Cosublimation of TAT as the “guest” in a structurally mismatched “host” enabled fabrication of thin films in which chiral crystallization was achieved in situ by thermally triggered nanophase segregation of dopant and host while preserving film integrity. The OLEDs showed external quantum efficiencies of up to 16% and electroluminescence dissymmetries ≄10%. Vacuum deposition of chiral superstructures opens new opportunities to explore chiral-driven optical and transport phenomena.
GPT-4o mini: Non-social science research article
Sunlight drives the abiotic formation of nitrous oxide in fresh and marine waters
Elizabeth Leon-Palmero, Rafael Morales-Baquero, Bo Thamdrup, Carolin Löscher, Isabel Reche
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Nitrous oxide (N 2 O) is a potent greenhouse gas and the main stratospheric ozone-depleting agent, yet its sources are not well resolved. In this work, we experimentally show a N 2 O production pathway not previously considered in greenhouse gas budgets, which we name photochemodenitrification. Sunlight induces substantial and consistent N 2 O production under oxic abiotic conditions in fresh and marine waters. We measured photochemical N 2 O production rates using isotope tracers and determined that nitrite is the main substrate and that nitrate can also contribute after being photoreduced to nitrite. Additionally, this N 2 O production was strongly correlated to the radiation dose. Photochemodenitrification exceeded biological N 2 O production in surface waters. Although previously overlooked, this process may contribute considerably to global N 2 O emissions through its occurrence in fresh and marine surface waters.
GPT-4o mini: Non-social science research article
Trypanosome doublet microtubule structures reveal flagellum assembly and motility mechanisms
Xian Xia, Michelle M. Shimogawa, Hui Wang, Samuel Liu, Angeline Wijono, Gerasimos Langousis, Ahmad M. Kassem, James A. Wohlschlegel, Kent L. Hill, Z. Hong Zhou
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The flagellum of Trypanosoma brucei drives the parasite’s characteristic screw-like motion and is essential for its replication, transmission, and pathogenesis. However, the molecular details of this process remain unclear. Here, we present high-resolution (up to 2.8 angstrom) cryo–electron microscopy structures of T. brucei flagellar doublet microtubules (DMTs). Integrated modeling identified 154 different axonemal proteins inside and outside the DMT and, together with genetic and proteomic interrogation, revealed conserved and trypanosome-specific foundations of flagellum assembly and motility. We captured axonemal dynein motors in their pre–power stroke state. Comparing atomic models between pre– and post–power strokes defined how dynein structural changes drive sliding of adjacent DMTs during flagellar beating. This study illuminates structural dynamics underlying flagellar motility and identifies pathogen-specific proteins to consider for therapeutic interventions targeting neglected diseases.
GPT-4o mini: Non-social science research article
Mesozoic mammaliaforms illuminate the origins of pelage coloration
Ruoshuang Li, Liliana D’Alba, Gerben Debruyn, Jessica L. Dobson, Chang-Fu Zhou, Julia A. Clarke, Jakob Vinther, Quanguo Li, Matthew D. Shawkey
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Pelage coloration, which serves numerous functions, is crucial to the evolution of behavior, physiology, and habitat preferences of mammals. However, little is known about the coloration of Mesozoic mammaliaforms that coevolved with dinosaurs. In this study, we used a dataset of melanosome (melanin-containing organelle) morphology and quantitatively measured hair colors from 116 extant mammals to reliably reconstruct the coloration of six Mesozoic mammaliaforms, including a previously undescribed euharamiyidan. Unlike the highly diverse melanosomes discovered in feathered dinosaurs, hairs in six mammaliaforms of different lineages and diverse ecomorphotypes showed uniform melanosome geometry, corresponding to dark-brown coloration consistent with crypsis and nocturnality. Our results suggest that the melanosome variation and color expansion seen in extant mammals may have occurred during their rapid radiation and diversification after the Cretaceous-Paleogene extinction.
GPT-4o mini: Non-social science research article
Three-dimensional maps of the interstellar dust extinction curve within the Milky Way galaxy
Xiangyu Zhang, Gregory M. Green
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Interstellar dust grains cause extinction (absorption and scattering) of light from background astronomical sources. The spectral shape of the extinction curve depends on the dust composition. We used low-resolution optical spectra to measure the extinction curve of 130 million stars. By inverting these data, we mapped the extinction curve parameter R ( V ) within the Milky Way in three dimensions and within the Magellanic Clouds in two dimensions. These maps provide improved extinction corrections for astronomical observations. We find that R ( V ) varies with extinction, consistent with dust grains growing by accretion in low-extinction regions and by coagulation in higher-extinction regions. Star-forming regions have high R ( V ) values, indicating either preferential destruction of small dust grains or additional supply of large dust grains in those regions.
GPT-4o mini: Non-social science research article
Identification of antigen-presenting cell–T cell interactions driving immune responses to food
Maria Cecilia Campos Canesso, Tiago Bruno Rezende de Castro, Sandra Nakandakari-Higa, Ainsley Lockhart, Julia Luehr, Juliana Bortolatto, Roham Parsa, Daria EsterhĂĄzy, Mengze Lyu, Tian-Tian Liu, Kenneth M. Murphy, Gregory F. Sonnenberg, Bernardo S. Reis, Gabriel D. Victora, Daniel Mucida
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The intestinal immune system must concomitantly tolerate food and commensals and protect against pathogens. Antigen-presenting cells (APCs) orchestrate these immune responses by presenting luminal antigens to CD4 + T cells and inducing their differentiation into regulatory (peripheral regulatory T cell) or inflammatory [T helper (Th) cell] subsets. We used a proximity labeling method (LIPSTIC) to identify APCs that presented dietary antigens under tolerizing and inflammatory conditions and to understand cellular mechanisms by which tolerance to food is induced and can be disrupted by infection. Helminth infections disrupted tolerance induction proportionally to the reduction in the ratio between tolerogenic APCs—including migratory dendritic cells (cDC1s) and Rorγt + APCs—and inflammatory APCs, which were primarily cDC2s. These inflammatory cDC2s expanded by helminth infection did not present dietary antigens, thus avoiding diet-specific Th2 responses.
GPT-4o mini: Non-social science research article
Tunneling nanotube–like structures regulate distant cellular interactions during heart formation
Lianjie Miao, Yangyang Lu, Anika Nusrat, Guizhen Fan, Shaohua Zhang, Luqi Zhao, Chia-Ling Wu, Hongyan Guo, Trang Le Nu Huyen, Yi Zheng, Zhen-Chuan Fan, Weinian Shou, Robert J. Schwartz, Yu Liu, Ashok Kumar, Haixin Sui, Irina I. Serysheva, Alan R. Burns, Leo Q. Wan, Bin Zhou, Sylvia M. Evans, Mingfu Wu
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In the developing mammalian heart, the endocardium and the myocardium are separated by so-called cardiac jelly. Communication between the endocardium and the myocardium is essential for cardiac morphogenesis. How membrane-localized receptors and ligands achieve interaction across the cardiac jelly is not understood. Working in developing mouse cardiac morphogenesis models, we used a variety of cellular, imaging, and genetic approaches to elucidate this question. We found that myocardium and endocardium interacted directly through microstructures termed tunneling nanotube–like structures (TNTLs). TNTLs extended from cardiomyocytes (CMs) to contact endocardial cells (ECs) directly. TNTLs transported cytoplasmic proteins, transduced signals between CMs and ECs, and initiated myocardial growth toward the heart lumen to form ventricular trabeculae-like structures. Loss of TNTLs disturbed signaling interactions and, subsequently, ventricular patterning.
GPT-4o mini: Non-social science research article
Environmental effects of the Kakhovka Dam destruction by warfare in Ukraine
O. Shumilova, A. Sukhodolov, N. Osadcha, A. Oreshchenko, G. Constantinescu, S. Afanasyev, M. Koken, V. Osadchyi, B. Rhoads, K. Tockner, M. T. Monaghan, B. Schröder, J. Nabyvanets, C. Wolter, O. Lietytska, J. van de Koppel, N. Magas, S. C. JÀhnig, V. Lakisova, G. Trokhymenko, M. Venohr, V. Komorin, S. Stepanenko, V. Khilchevskyi, S. Domisch, M. Blettler, P. Gleick, L. De Meester, H.-P. Grossart
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The use of water as a weapon in highly industrialized areas in the Russo-Ukrainian war has resulted in catastrophic economic and environmental damages. We analyze environmental effects caused by the military destruction of the Kakhovka Dam. We link field, remote sensing, and modeling data to demarcate the disaster’s spatial-temporal scales and outline trends in reestablishment of damaged ecosystems. Although media attention has focused on the immediate impacts of flooding on society, politics, and the economy, our results show that toxic contamination within newly exposed sediments of the former reservoir bed poses a largely overlooked long-term threat to freshwater, estuarine, and marine ecosystems. The continued use of water as a weapon may lead to even greater risks for people and the environment.
GPT-4o mini: Non-social science research article
Uphold US-Canada science
RĂ©mi Quirion
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A partnership can be demanding, and as with any couple, can have good days and bad. The United States–Canada relationship is most definitely having a bad one. It’s difficult to fully comprehend all the dimensions of the current threats to one of the world’s strongest, longest, and multifaceted alliances. From contemptuous musings on annexation to a tariff war that could wreak economic havoc on both sides of the border, the insults and aggravations are stoking uncertainty about a relationship that has flourished for decades. This includes a strongly intertwined connection between Canadian and American science—one that must continue in these challenging times.
GPT-4o mini: Non-social science research article
Piezoelectricity in half-Heusler narrow-bandgap semiconductors
Yi Huang, Fu Lv, Shen Han, Mengzhao Chen, Yuechu Wang, Qianhui Lou, Chenguang Fu, Yuhui Huang, Di Wu, Fei Li, Tiejun Zhu
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Piezoelectricity is primarily observed in noncentrosymmetric insulators or wide bandgap semiconductors. We report the observation of the piezoelectric (PE) effect in half-Heusler (HH) narrow-bandgap semiconductors TiNiSn, ZrNiSn, and TiCoSb. These materials exhibit shear PE strain coefficients that reach ~38 and 33 picocoulombs per newton in ZrNiSn and TiCoSb, respectively, which are high values for noncentrosymmetric nonpolar materials. We demonstrated a TiCoSb-based PE sensor with a large voltage response and capable of charging a capacitor. The PE effect in HHs remains thermally stable up to 1173 kelvin, underscoring their potential for high-temperature applications. Our observations suggest that these HH narrow-bandgap semiconductors may find promising applications for advanced multifunctional technologies.
GPT-4o mini: Non-social science research article
Evolutionary adaptations of doublet microtubules in trypanosomatid parasites
Matthew H. Doran, Qingwei Niu, Jianwei Zeng, Tom Beneke, James Smith, Peter Ren, Sophia Fochler, Adrian Coscia, Johanna L. Höög, Shimi Meleppattu, Polina V. Lishko, Richard J. Wheeler, Eva Gluenz, Rui Zhang, Alan Brown
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The movement and pathogenicity of trypanosomatid species, the causative agents of trypanosomiasis and leishmaniasis, are dependent on a flagellum that contains an axoneme of dynein-bound doublet microtubules (DMTs). In this work, we present cryo–electron microscopy structures of DMTs from two trypanosomatid species, Leishmania tarentolae and Crithidia fasciculata , at resolutions up to 2.7 angstrom. The structures revealed 27 trypanosomatid-specific microtubule inner proteins, a specialized dynein-docking complex, and the presence of paralogous proteins that enable higher-order periodicities or proximal-distal patterning. Leveraging the genetic tractability of trypanosomatid species, we quantified the location and contribution of each structure-identified protein to swimming behavior. Our study shows that proper B-tubule closure is critical for flagellar motility, exemplifying how integrating structural identification with systematic gene deletion can dissect individual protein contributions to flagellar motility.
GPT-4o mini: Non-social science research article
Excited-state configuration of nitroarenes enables oxidative cleavage of aromatics over alkenes
Wesley J. Olivier, Piotr BƂyszczyk, Enrique M. Arpa, Kenshiro Hitoshio, Miguel Gomez-Mendoza, VĂ­ctor de la Peña O’Shea, Isabelle Marchand, Thomas Poisson, Alessandro Ruffoni, Daniele Leonori
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The ozonolytic deconstruction of aromatics remains a challenge in organic chemistry. Ozone preferentially reacts with alkenes over arenes, meaning that once the initial aromatic cleavage occurs, the dearomatized products are inherently more reactive than the starting materials. Consequently, the process cannot be halted, resulting in full oxidation. Addressing this challenge requires subverting intrinsic rules of chemoselectivity to transform a less reactive substrate in the presence of a more reactive one. We demonstrate that this concept can be achieved by using photoexcited nitroarenes. Crucial to the success of this chemoselective process is the use of a nitroarene that is preferentially excitable to a triplet π,π* state over the n,π* state. This switch in excited-state configuration provides an otherwise inaccessible manifold, in which oxidative cleavage is diverted toward aromatics in the presence of alkenes.
Science abstract < 200 char.: Not a research article
Overseas universities see opportunity in U.S. ‘brain drain’
Catherine Offord
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But scientists seeking to leave the U.S. may struggle to find roles in countries grappling with their own funding issues
Science abstract < 200 char.: Not a research article
Did dark energy’s cosmic push vary with time?
Daniel Clery
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New galaxy mapping data add to idea that cosmological constant wasn’t so constant
Science abstract < 200 char.: Not a research article
Securing education’s future
William F. Tate
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Science abstract < 200 char.: Not a research article
Erratum for the Report “A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging” by W. Zhang et al .
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Science abstract < 200 char.: Not a research article
U.S. study of Scandinavian prison model expands
Jennifer Couzin-Frankel
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Project tests effects of a homier environment and more social interaction
Science abstract < 200 char.: Not a research article
Babies form fleeting memories
Adam I. Ramsaran, Paul W. Frankland
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The human hippocampus constructs short-lived memories from around 1 year of age
Science abstract < 200 char.: Not a research article
In Science Journals
Bianca Lopez, Keith T. Smith, Phil Szuromi, Stella M. Hurtley, Madeleine Seale, Courtney Malo, Hannah Isles, Mattia Maroso, Sarah H. Ross, Ian S. Osborne, Jake S. Yeston, Jesse Smith, Sacha Vignieri, Leslie K. Ferrarelli
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
A deep dive into oxygen sensing
Lucy Hawkes, Jessica Kendall-Bar
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Seals directly detect blood oxygen to adjust time underwater
Science abstract < 200 char.: Not a research article
Looking beyond the trees for carbon storage
Josep G. Canadell
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Nonliving organic matter could create more stable carbon reservoirs
Science abstract < 200 char.: Not a research article
Conservation in Sudan’s conflict zones
Piotr Tryjanowski, Andrzej Węgiel
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Science abstract < 200 char.: Not a research article
The animal apothecaries Doctors by Nature: How Ants, Apes, and Other Animals Heal Themselves Jaap de Roode Princeton University Press, 2025. 264 pp.
John M. Drake
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An evolutionary biologist finds lessons in how animals use plants as medicine
Science abstract < 200 char.: Not a research article
Columbia University reels as federal grants killed
Jocelyn Kaiser
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Other universities face similar threats to end research funding over alleged antisemitism
Science abstract < 200 char.: Not a research article
In Other Journals
Keith T. Smith, Sarah H. Ross, Stella M. Hurtley, Bianca Lopez, Sarah LempriĂšre, Phil Szuromi, Melissa McCartney
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
Clash on monkey island
Refael Kubersky
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Mauritius has become the world’s leading exporter of research primates, pitting conservationists, politicians, and neighbors against one another
Science abstract < 200 char.: Not a research article
Social and environmental impacts of war in Syria
Abd Al Karim Jaafar, Andrés Rodríguez-Seijo
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Science abstract < 200 char.: Not a research article
The problem with AI dialogue at scale
Ehsan Nabavi, Faranak Hardcastle, Joan Leach, Fabien Medvecky, Merryn McKinnon, Sujatha Raman, Dan Santos
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Science abstract < 200 char.: Not a research article
Tunneling through cardiac jelly
José Luis de la Pompa
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Membrane projections from muscle cells enable signaling in the developing mouse heart
Science abstract < 200 char.: Not a research article
Reading palms to characterize islands
Anna J. Holmquist, Rosemary G. Gillespie
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Rattan palms illuminate the drivers of biodiversity in tropical Asia
Science abstract < 200 char.: Not a research article
Making sense of fat in cancer
Estela Jacinto
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A lipid chaperone enables sensing of an essential fatty acid to drive tumor growth
Science abstract < 200 char.: Not a research article
News at a glance
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Science abstract < 200 char.: Not a research article
NIH kills existing grants on transgender issues
Sara Reardon
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Some termination letters cite “biological realities” to dismiss usefulness of such research
Science abstract < 200 char.: Not a research article
Large AI models are cultural and social technologies
Henry Farrell, Alison Gopnik, Cosma Shalizi, James Evans
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Implications draw on the history of transformative information systems from the past
Science abstract < 200 char.: Not a research article
In Ukraine, dam’s destruction sets off a ‘toxic time bomb’
Richard Stone
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Floods threaten to spread sediments laden with toxicants
Science abstract < 200 char.: Not a research article
Oceans’ trenches are home to ‘incredible’ diversity
Phie Jacobs
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In trio of studies, scientists explore life in the mysterious hadal zone
Science abstract < 200 char.: Not a research article
H5N1 avian flu is spreading rapidly in Antarctica
Sofia Moutinho
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Expedition finds the virus in 13 bird and seal species around the Antarctic Peninsula
Science abstract < 200 char.: Not a research article
Imperfect sounds
Cathleen O’Grady
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Cochlear implants give deaf kids unprecedented access to sound. But insisting they avoid using sign language may be risky
Science abstract < 200 char.: Not a research article
No sign that vaccine advisers are beholden to industry
Meredith Wadman
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RFK Jr. has claimed conflicts of interest must be rooted out of key CDC panel
Science abstract < 200 char.: Not a research article
Face to face with the first known Western European
Ann Gibbons
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At least 1.1 million years old, a fossil face suggests more than one type of early human inhabited Europe
Science abstract < 200 char.: Not a research article
Support PhDs building deep-tech ventures
Theo Diamandis, Josué J. López, Fiona Murray
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Science abstract < 200 char.: Not a research article
How does Antarctic ice deform?
Bryan Riel
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A deep-learning model infers large-scale dynamics of Antarctic ice shelves
Science abstract < 200 char.: Not a research article
Studies seek signs of consciousness before birth
Kelly Servick
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Fetal and infant brains offer clues to when human experience begins

Science Advances

GPT-4o mini: Non-social science research article
Tissue stiffness mapping by light sheet elastography
Min Zhu, Kaiwen Zhang, Evan C. Thomas, Ran Xu, Brian Ciruna, Sevan Hopyan, Yu Sun
Full text
Tissue stiffness plays a crucial role in regulating morphogenesis. The ability to measure and monitor the dynamic progression of tissue stiffness is important for generating and testing mechanistic hypotheses. Methods to measure tissue properties in vivo have been emerging but present challenges with spatial and temporal resolution especially in 3D, by their reliance on highly specialized equipment, and/or due to their invasive nature. Here, we introduce light sheet elastography, a noninvasive method that couples low-frequency shear waves with light sheet fluorescence microscopy by adapting commercially available instruments. With this method, we achieved in toto stiffness mapping of organ-stage mouse and zebrafish embryos at cellular resolution. Versatility of the method enabled time-lapse stiffness mapping during tissue remodeling and of the beating embryonic heart. This method expands the spectrum of tools available to biologists and presents opportunities for uncovering the mechanical basis of morphogenesis.
GPT-4o mini: Non-social science research article
An annually resolved 5700-year storm archive reveals drivers of Caribbean cyclone frequency
Dominik Schmitt, Eberhard Gischler, Martin Melles, Volker Wennrich, Hermann Behling, Lyudmila Shumilovskikh, Flavio S. Anselmetti, Hendrik Vogel, Jörn Peckmann, Daniel Birgel
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Predictions of tropical cyclone (TC) frequencies are hampered by insufficient knowledge of their natural variability in the past. A 30-m-long sediment core from the Great Blue Hole, a marine sinkhole offshore Belize, provides the longest available, continuous, and annually resolved TC-frequency record. This record expands our understanding, derived from instrumental monitoring (73 years), historical documentations (173 years), and paleotempestological records (2000 years), to the past 5700 years. A total of 694 event layers were identified. They display a distinct regional trend of increasing storminess in the southwestern Caribbean, which follows an orbitally driven shift in the Intertropical Convergence Zone. Superimposed short-term variations match Holocene climate intervals and originate from solar irradiance–controlled sea-surface temperature anomalies and climate phenomena modes. A 21st-century extrapolation suggests an unprecedented increase in TC frequency, attributable to the Industrial Age warming.
GPT-4o mini: Non-social science research article
Affinity selection–mass spectrometry with linearizable macrocyclic peptide libraries
Michael A. Lee, Joseph S. Brown, Charlotte E. Farquhar, Andrei Loas, Bradley L. Pentelute
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Despite their potential, the preparation of large synthetic macrocyclic libraries for ligand discovery and development has been limited. Here, we produce 100-million-membered macrocyclic libraries containing natural and nonnatural amino acids. Near-quantitative intramolecular disulfide formation is facilitated by rapid oxidation with iodine in solution. After use in affinity selection, treatment with dithiothreitol enables near-quantitative reduction, rendering linear peptide analogs for standard tandem mass spectrometry. We use these libraries to discover macrocyclic binders to cadherin-2 and anti-hemagglutinin antibody clone 12ca5. Structure-activity relationship studies of an initial cadherin-binding peptide [ CBP ; apparent dissociation constant ( K d ) = 53 nanomolar] reveal residues responsible for driving affinity (hotspots) and mutation-tolerant residues (coldspots). Two original macrocyclic libraries are prepared in which these hotspots and coldspots are derivatized with nonnatural amino acids. Following discovery and validation, high-affinity ligands are discovered from the coldspot library, with NCBP-4 demonstrating improved affinity ( K d = 29 nanomolar). Overall, we expect that this work will improve the use of macrocyclic libraries in therapeutic peptide development.
GPT-4o mini: Non-social science research article
Special delivery of proteinaceous matter to deep-sea microbes
Yuan Shen, Ronald Benner, Taylor A. B. Broek, Brett D. Walker, Matthew D. McCarthy
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Earth’s deep ocean holds a vast reservoir of dissolved organic carbon, traditionally considered old and resistant to microbial degradation. Radiocarbon analyses indicate the hidden occurrence of younger dissolved organic carbon components, assumed to be accessible to deep-sea microorganisms but not yet demonstrated. Using compound-class radiocarbon analysis, molecular characterization, and bioassay experiments, we provide direct evidence for rapid microbial utilization of young, labile, high–molecular weight proteinaceous material in bathypelagic waters. The abundance of labile proteinaceous material diminishes from epipelagic to mesopelagic waters but notably increases in bathypelagic waters, where it exhibits a short turnover time (days) and resembles surface plankton in molecular composition. This observation coincides with peak zooplankton biomass recorded over the year. The nonmonotonic depth trend suggests a deep-sea replenishment of organic particles from mesopelagic migrating zooplankton. Our results indicate the presence of labile organic molecules at bathypelagic depths and reveal a nonlinear supply of plankton-derived substrates that support microbial metabolism and carbon sequestration in the deep ocean.
GPT-4o mini: Non-social science research article
Microfluidic-derived montmorillonite composite microparticles for oral codelivery of probiotic biofilm and postbiotics
Zhonglin Fang, Xinyuan Yang, Luoran Shang
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Oral delivery of probiotics has shown promising effects in modulating the gut microbiota and treating ulcerative colitis (UC). However, the therapeutic efficacy is restricted by gastrointestinal assaults, poor mucosal adhesion, and single therapeutic modality. Here, we developed acid-resistant, gut-environment–responsive composite microparticles based on microfluidic electrospray for the oral codelivery of probiotic [ Lactobacillus acidophilus (LA)] biofilm and postbiotics (indole-3-propionic acid). Montmorillonite was selected for supporting biofilm formation due to its cation-exchange capability and clearly defined biosafety. The montmorillonite-LA biofilm was effectively protected by the microparticles and markedly improved the intestinal retention. Upon oral administration, the composite microparticles notably alleviated colitis in mice, including reducing the inflammatory response, improving intestinal barrier function, and modulating the gut microbiota. Consequently, the composite microparticles show high potential for enhancing probiotic delivery efficacy and present a promising strategy for UC treatment.
GPT-4o mini: Non-social science research article
USP8 and Hsp70 regulate endoreplication by synergistically promoting Fzr deubiquitination and stabilization
Wenliang Qian, Xing Zhang, Dongqin Yuan, Yuting Wu, Hao Li, Ling Wei, Zheng Li, Zongcai Dai, Pei Song, Qiaoling Sun, Zizhang Zhou, Qingyou Xia, Daojun Cheng
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Endoreplication is characterized by multiple rounds of DNA replication without cell division and determines the growth and final size of endoreplicating cells and tissues in eukaryotes. The cyclic ubiquitination and degradation of several cell cycle regulators are required for endoreplication progression. However, the deubiquitinase that deubiquitinates and stabilizes key factors to modulate endoreplication remains unknown. Here, we found in the endoreplicating Drosophila salivary gland and Bombyx silk gland that the depletion of ubiquitin-specific peptidase 8 (USP8) led to endoreplication arrest and a decrease in gland size. Mechanistically, we showed that USP8 interacted with the Fizzy-related (Fzr) protein, a conserved master regulator of endoreplication, thereby deubiquitinating and stabilizing Fzr to modulate endoreplication. Moreover, the molecular chaperone heat shock protein 70 (Hsp70) mediated proper folding of Fzr and increased the interaction between Fzr and USP8, thereby promoting the deubiquitination and stabilization of Fzr. Together, our study demonstrates that USP8 and Hsp70 regulate endoreplication by synergistically maintaining Fzr stability though deubiquitination.
GPT-4o mini: Non-social science research article
Enantioselective electrochemical nickel-catalyzed vinylogous radical reactions
Jiayin Zhang, Minghao Liu, Wenyuan Zhang, Chang Guo
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Highly functionalized structural motifs with extended chiral carbon chains are prevalent in a wide range of bioactive compounds and play critical roles in the production of various functionalized molecules. Here, we describe a nickel-catalyzed asymmetric radical-based electrochemical functionalization of silyl polyenolates at α-, γ-, Δ-, and η-positions. Driven by electric current, this methodology provides a sustainable route to access enantioenriched dicarbonyls via vinylogous radical pathways. It demonstrates excellent functional groups tolerance, mild reaction conditions, broad substrate compatibility, formation of quaternary stereocenters at remote positions, and high levels of regio- and enantioselectivity (up to 98% enantiomeric excess). Mechanistic investigations indicate that ferrocene-based electron transfer mediators are pivotal in the anodic oxidation process, facilitating the generation of nickel-bound α-carbonyl radicals while suppressing the undesired oxidation of silyl polyenolates, thus guiding the selection of mediators for electrocatalytic systems. The versatility of catalytic asymmetric electrosynthesis is highlighted by the preparation of valuable enantioenriched building blocks and the total synthesis of (-)-ethosuximide.
GPT-4o mini: Non-social science research article
Structure and dynamics determine G protein coupling specificity at a class A GPCR
Marina Casiraghi, Haoqing Wang, Patrick C. Brennan, Chris Habrian, Harald HĂŒbner, Maximilian F. Schmidt, Luis Maul, Biswaranjan Pani, Sherif M. F. M. Bahriz, Bing Xu, Nico Staffen, Tufa E. Assafa, Bohan Chen, Elizabeth White, Roger K. Sunahara, Asuka Inoue, Yang K. Xiang, Robert J. Lefkowitz, Ehud Y. Isacoff, Nathaniel Nucci, Peter Gmeiner, Michael T. Lerch, Brian K. Kobilka
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G protein–coupled receptors (GPCRs) exhibit varying degrees of selectivity for different G protein isoforms. Despite the abundant structures of GPCR–G protein complexes, little is known about the mechanism of G protein coupling specificity. The ÎČ 2 -adrenergic receptor is an example of GPCR with high selectivity for Gαs, the stimulatory G protein for adenylyl cyclase, and much weaker for the Gαi family of G proteins inhibiting adenylyl cyclase. By developing a Gαi-biased agonist (LM189), we provide structural and biophysical evidence supporting that distinct conformations at ICL2 and TM6 are required for coupling of the different G protein subtypes Gαs and Gαi. These results deepen our understanding of G protein specificity and bias and can accelerate the design of ligands that select for preferred signaling pathways.
GPT-4o mini: Non-social science research article
Low-intensity pulsed ultrasound elevates blood pressure for shock
Chenrui Wu, Yu Tian, Tao Liu, Shuo An, Yu Qian, Chuang Gao, Jiangyuan Yuan, Mingqi Liu, Meng Nie, Weiwei Jiang, Zhuang Sha, Chuanxiang Lv, Qiang Liu, Xiaochun Wang, Sheng Zhou, Rongcai Jiang
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Fluid replacement is the primary treatment for life-threatening shock but is challenging in harsh environments. This study explores low-intensity pulsed ultrasound (LIPUS) as a resuscitation strategy. Cervical LIPUS stimulation effectively elevated blood pressure in shocked rats. It also improved cerebral and multiorgan perfusion. Mechanistically, LIPUS activated pathways related to sympathetic nerve excitation and vascular smooth muscle contraction, increasing plasma catecholamines and stimulating blood pressure–regulating neural nuclei. Partial sympathetic nerve transection reduced LIPUS efficacy, while complete inhibition of these nuclei abolished the response. Preliminary clinical trials demonstrated LIPUS’s ability to raise blood pressure in shock patients. The findings suggest that LIPUS enhances sympathetic nerve activity and activates blood pressure–regulating nuclei, offering a noninvasive, neuromodulation-based approach to shock treatment. This method holds potential for improving blood pressure and organ perfusion in shock patients, especially in resource-limited environments.
GPT-4o mini: Non-social science research article
Structural basis for the substrate recognition and transport mechanism of the human y + LAT1-4F2hc transporter complex
Lu Dai, Qian Zeng, Ting Zhang, Yuanyuan Zhang, Yi Shi, Yaning Li, Kangtai Xu, Jing Huang, Zilong Wang, Qiang Zhou, Renhong Yan
Full text
Heteromeric amino acid transporters (HATs), including y + LAT1-4F2hc complex, are responsible for transporting amino acids across membranes, and mutations in y + LAT1 cause lysinuric protein intolerance (LPI), a hereditary disorder characterized by defective cationic amino acid transport. The relationship between LPI and specific mutations in y + LAT1 has yet to be fully understood. In this study, we characterized the function of y + LAT1-4F2hc complex in mammalian cells and determined the cryo-EM structures of the human y + LAT1-4F2hc complex in two distinct conformations: the apo state in an inward-open conformation and the native substrate-bound state in an outward-open conformation. Structural analysis suggests that Asp 243 in y + LAT1 plays a crucial role in coordination with sodium ion and substrate selectivity. Molecular dynamic (MD) simulations further revealed the different transport mechanism of cationic amino acids and neutral amino acids. These results provide important insights into the mechanisms of the substrate binding and working cycle of HATs.
GPT-4o mini: Non-social science research article
Ectopic expression of testis-specific transcription elongation factor in driving cancer
Bin Zheng, Marta Iwanaszko, Shimaa Hassan AbdelAziz Soliman, Yukitomo Ishi, Sarah Gold, Ruxuan Qiu, Benjamin Charles Howard, Madhurima Das, Zibo Zhao, Rintaro Hashizume, Lu Wang, Ali Shilatifard
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The testis-specific BET protein BRDT structurally resembles the ubiquitous BRD4 and is misexpressed in cancer, and we show that BRDT misexpression may affect lung cancer progression. BRDT knockdown in lung cancer cells slowed tumor growth and prolonged survival in a xenograft model. Comparative characterization of PTEFb complex participation and chromatin binding indicates BRD4-redundant and BRD4-distinct BRDT functions. Unlike dual depletion, individual BRD4 or BRDT knockdown did not impair transcriptional responses to hypoxia in BRDT-expressing cells, consistent with redundant function. However, BRD4 depletion/BRDT complementation revealed that BRDT can also release paused RNA polymerase II independently of its bromodomains as we previously demonstrated not to be required for Pol II pause/release function of BRD4, underscoring the functional importance of the C-terminal domains in both BRD4 and BRDT and their potential as therapeutic targets in solid tumors. Based on this study, future investigations should explore BRD4-distinct BRDT functions and BRDT misexpression driving cancer pathogenesis.
GPT-4o mini: Non-social science research article
Inhibiting EZH2 complements steroid effects in Duchenne muscular dystrophy
Eun Young Jeon, Yejin Kwak, Hyeji Kang, Hanbyeol Kim, Se Young Jin, Soojin Park, Ryeo Gyeong Kim, Dayoung Ko, Jae-Kyung Won, Anna Cho, Inkyung Jung, Chul-Hwan Lee, Jeongbin Park, Hyun-Young Kim, Jong-Hee Chae, Murim Choi
Full text
Duchenne muscular dystrophy (DMD) is a devastating X-linked disorder caused by dystrophin gene mutations. Despite recent advances in understanding the disease etiology and applying emerging treatment methodologies, glucocorticoid derivatives remain the only general therapeutic option that can slow disease development. However, the precise molecular mechanism of glucocorticoid action remains unclear, and there is still need for additional remedies to complement the treatment. Here, using single-nucleus RNA sequencing and spatial transcriptome analyses of human and mouse muscles, we investigated pathogenic features in patients with DMD and palliative effects of glucocorticoids. Our approach further illuminated the importance of proliferating satellite cells and revealed increased activity of a signal transduction pathway involving EZH2 in the patient cells. Subsequent administration of EZH2 inhibitors to Dmd mutant mice resulted in improved muscle phenotype through maintaining the immune-suppressing effect but overriding the muscle weakness and fibrogenic effects exerted by glucocorticoids. Our analysis reveals pathogenic mechanisms that can be readily targeted by extant therapeutic options for DMD.
GPT-4o mini: Non-social science research article
Biological age prediction using a DNN model based on pathways of steroidogenesis
Qiuyi Wang, Zi Wang, Kenji Mizuguchi, Toshifumi Takao
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Aging involves the progressive accumulation of cellular damage, leading to systemic decline and age-related diseases. Despite advances in medicine, accurately predicting biological age (BA) remains challenging due to the complexity of aging processes and the limitations of current models. This study introduces a method for predicting BA using a deep neural network (DNN) based on pathways of steroidogenesis. We analyzed 22 steroids from 148 serum samples of individuals aged 20 to 73, using 98 samples for model training and 50 for validation. Our model reflects the often-overlooked fact that aging heterogeneity expands over time and uncovers sex-specific variations in steroidogenesis. This study leveraged key markers, including cortisol (COL), which underscore the role of stress-related and sex-specific steroids in aging. The resulting model establishes a biologically meaningful and robust framework for predicting BA across diverse datasets, offering fresh insights and supporting more targeted strategies in aging research and disease management.
GPT-4o mini: Non-social science research article
An enzymatic cleavage-triggered minimally invasive nanosensor for urine-based detection of early atherosclerosis
Zhina Wu, Rui Liu, Jianai Chen, Xueying Cai, Jingzheng Yi, Jiasi Wang, Di Wang, Min Hu
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Timely detection of early atherosclerosis (AS) is crucial for improving cardiovascular outcomes, creating a growing demand for diagnostic tools that are simple, sensitive, and cost-effective. Here, we introduce a synthetic nanosensor for early AS detection that leverages the fluorescence and renal clearance properties of carbon quantum dots (CQDs). This nanosensor, designed to respond to the proteolytic activity of AS-associated dysregulated enzymes, entails CQDs as signal reporters to convert AS-associated proteolytic activity to fluorometric readings enabling a sensitive and cost-effective urine-based assay for early AS detection. Our findings demonstrated that the nanosensor provided distinct signals in atherosclerotic versus healthy mice at early AS stages, indicating its diagnostic potential. Moreover, toxicity tests showed no notable adverse effects, supporting its safety for diagnostic applications. This minimally invasive diagnostic approach could facilitate personalized therapy design and continuous efficacy assessment. It is expected that such a modular nanosensor platform can be integrated with simple urine tests to offer cost-effective detection of various diseases.
GPT-4o mini: Non-social science research article
Interfering with proton and electron transfer enables antibacterial starvation therapy
Ji Tan, Haifeng Zhang, Yisi Liu, Zhenhao Hou, Donghui Wang, Junjie Zhou, Yuanming Cao, Shi Qian, Bowen Zheng, JingJun Nie, Yuanyuan Cui, Yun Du, Kai Huang, Shengbing Yang, Dafu Chen, Xuanyong Liu
Full text
Implant-associated infections are urgently addressed; however, existing materials are difficult to kill bacteria without damaging cells. Here, we propose an innovative concept of selective antibacterial starvation therapy based on interfering with proton and electron transfer on the bacterial membrane. As a proof-of-principle demonstration, a special Schottky heterojunction film composed of gold and alkaline magnesium-iron mixed metal oxides (Au/MgFe-MMO) was constructed on the titanium implant. Once bacteria contacted this implant, the Au/MgFe-MMO film continuously captured the proton and electron participated in respiratory chain of bacteria to impede their energy metabolism, leading to the deficit of adenosine 5â€Č-triphosphate. Prolonged exposure to this starvation state inhibited numerous biosynthesis processes and triggered severe oxidative stress in bacteria, ultimately leading to their death due to DNA and membrane damage. In addition, this heterojunction film was comfortable for mammalian cells, without inhibiting mitochondrial function. This proposed starvation antibacterial therapy gives a notable perspective in designing biosafe smart antibacterial biomaterials.
GPT-4o mini: Non-social science research article
PPDPF preserves integrity of proximal tubule by modulating NMNAT activity in chronic kidney diseases
Xiaoliang Fang, Yi Zhong, Rui Zheng, Qihui Wu, Yu Liu, Dexin Zhang, Yuwei Wang, Wubing Ding, Kaiyuan Wang, Fengbo Zhong, Kai Lin, Xiaohui Yao, Qingxun Hu, Xiaofei Li, Guofeng Xu, Na Liu, Jing Nie, Dali Li, Hongquan Geng, Yuting Guan
Full text
Genome-wide association studies (GWAS) have identified loci associated with kidney diseases, but the causal variants, genes, and pathways involved remain elusive. Here, we identified a kidney disease gene called pancreatic progenitor cell differentiation and proliferation factor (PPDPF) through integrating GWAS on kidney function and multiomic analysis. PPDPF was predominantly expressed in healthy proximal tubules of human and mouse kidneys via single-cell analysis. Further investigations revealed that PPDPF functioned as a thiol-disulfide oxidoreductase to maintain cellular NAD + levels. Deficiency in PPDPF disrupted NAD + and mitochondrial homeostasis by impairing the activities of nicotinamide mononucleotide adenylyl transferases (NMNATs), thereby compromising the function of proximal tubules during injuries. Consequently, knockout of PPDPF notably accelerated the progression of chronic kidney disease (CKD) in mouse models induced by aging, chemical exposure, and obstruction. These findings strongly support targeting PPDPF as a potential therapy for kidney fibrosis, offering possibilities for future CKD interventions.
GPT-4o mini: Non-social science research article
A nucleus-encoded dynamin-like protein controls endosymbiont division in the trypanosomatid Angomonas deanei
Anay K. Maurya, Lena Kröninger, Georg Ehret, Miriam BÀumers, Marcel Marson, Stefanie Scheu, Eva C. M. Nowack
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Angomonas deanei is a trypanosomatid of the Strigomonadinae. All members of this subfamily contain a single ÎČ-proteobacterial endosymbiont. Intriguingly, cell cycles of host and endosymbiont are synchronized. The molecular mechanisms underlying this notable level of integration are unknown. Previously, we identified a nucleus-encoded dynamin-like protein, called ETP9, that localizes at the endosymbiont division site of A. deanei . Here, we found by comparative genomics that endosymbionts throughout the Strigomonadinae lost the capacity to autonomously form a division septum. We describe the cell cycle–dependent subcellular localization of ETP9 that follows accumulation of the bacterium-encoded division protein FtsZ at the endosymbiont division site. Furthermore, we found that ETP9 is essential in symbiotic but dispensable in aposymbiotic A. deanei that lost the endosymbiont. In the symbiotic strain, ETP9 knockdowns resulted in filamentous, division-impaired endosymbionts. Our work unveiled that in A. deanei an endosymbiont division machinery of dual genetic origin evolved in which a neo-functionalized host protein compensates for losses of endosymbiont division genes.
GPT-4o mini: Non-social science research article
A KNOTTED1-LIKE HOMEOBOX PROTEIN1–interacting transcription factor SlGATA6 maintains the auxin-response gradient to inhibit abscission
Xianfeng Liu, Lina Cheng, Yue Cai, Yang Liu, Xuemei Yan, Jiayun Liu, Ruizhen Li, Siqi Ge, Sai Wang, Xingan Liu, Sida Meng, Mingfang Qi, Cai-Zhong Jiang, Tianlai Li, Tao Xu
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The KNOTTED1-LIKE HOMEOBOX PROTEIN1 (SlKD1) is a master abscission regulator in tomato ( Solanum lycopersicum ). Here, we identified an SlKD1-interacting transcription factor GATA transcription factor 6 (SlGATA6), which is required for maintaining the auxin-response gradient and preventing abscission. SlGATA6 up-regulates the expression of SlLAX2 and SlIAA3 . The AUXIN RESISTANT/LIKE AUXIN RESISTANT (AUX/LAX) proteins SlLAX2-dependent asymmetric auxin distribution causes differential accumulation of Auxin/Indole-3-Acetic Acid 3 (SlIAA3) and its homolog SlIAA32 across different abscission zone cells. It is also required for SUMOylation of AUXIN RESPONSE FACTOR 2a (SlARF2a), a key suppressor of auxin signaling and abscission initiator. Moreover, SlIAA3 and SlIAA32 depress SUMOylated SlARF2a, thus suppressing SlARF2a function. The interaction between SlKD1 and SlGATA6 suppresses SlGATA6 binding to the promoters of SlLAX2 and SlIAA3 , thereby disrupting the auxin-response gradient and triggering abscission. This regulatory mechanism is conserved under low light–induced abscission in diverse Solanaceae plants. Our findings reveal a critical role of SlKD1 in modulating the auxin-response gradient and abscission initiation.
GPT-4o mini: Non-social science research article
The oral drug obeldesivir protects nonhuman primates against lethal Ebola virus infection
Courtney Woolsey, Robert W. Cross, Victor C. Chu, Abhishek N. Prasad, Krystle N. Agans, Viktoriya Borisevich, Daniel J. Deer, Mack B. Harrison, Jasmine K. Martinez, Natalie S. Dobias, Karla A. Fenton, Tomas Cihlar, Anh-Quan Nguyen, Darius Babusis, Roy Bannister, Meghan S. Vermillion, Thomas W. Geisbert
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Obeldesivir (ODV; GS-5245) is an orally administered ester prodrug of the parent nucleoside GS-441524 that has broad spectrum antiviral activity inhibiting viral RNA–dependent RNA polymerases. We recently showed that ODV completely protects cynomolgus macaques against lethal infection with Sudan virus when given 24 hours after parenteral exposure. Here, we report that once daily oral ODV treatment of cynomolgus and rhesus macaques for 10 days confers 80 and 100% protection, respectively, against lethal Ebola virus infection when treatment is initiated 24 hours after mucosal (conjunctival) exposure. ODV treatment delayed viral replication to abate excessive inflammation and promote adaptive immunity. For outbreak response, oral antivirals might present substantial advantages over now approved intravenous drugs, such as easy supply, storage, distribution, and administration. Furthermore, these results support the potential of ODV as an oral postexposure prophylaxis with broad spectrum activity across filoviruses.
GPT-4o mini: Non-social science research article
Disproportionately large impacts of wildland-urban interface fire emissions on global air quality and human health
Wenfu Tang, Louisa K. Emmons, Christine Wiedinmyer, Debatosh B. Partha, Yaoxian Huang, Cenlin He, Junzhe Zhang, Kelley C. Barsanti, Benjamin Gaubert, Duseong S. Jo, Jun Zhang, Rebecca Buchholz, Simone Tilmes, Francis Vitt, Claire Granier, Helen M. Worden, Pieternel F. Levelt
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Fires in the wildland-urban interface (WUI) are a global issue with growing importance. However, the impact of WUI fires on air quality and health is less understood compared to that of fires in wildland. We analyze WUI fire impacts on air quality and health at the global scale using a multi-scale atmospheric chemistry model—the Multi-Scale Infrastructure for Chemistry and Aerosols model (MUSICA). WUI fires have notable impacts on key air pollutants [e.g., carbon monoxide (CO), nitrogen dioxide (NO 2 ), fine particulate matter (PM 2.5 ), and ozone (O 3 )]. The health impact of WUI fire emission is disproportionately large compared to wildland fires primarily because WUI fires are closer to human settlement. Globally, the fraction of WUI fire–caused annual premature deaths (APDs) to all fire–caused APDs is about three times of the fraction of WUI fire emissions to all fire emissions. The developed model framework can be applied to address critical needs in understanding and mitigating WUI fires and their impacts.
GPT-4o mini: Non-social science research article
Molecule-induced ripening control in perovskite quantum dots for efficient and stable light-emitting diodes
Jiawei Chen, Shulin Chen, Xiangyu Liu, Danlei Zhu, Bo Cai, Xiyu Luo, Wenjing Feng, Yuanzhuang Cheng, Yaonan Xiong, Jiuyao Du, Zhou Li, Dongdong Zhang, Lian Duan, Dongxin Ma
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Perovskite quantum dots (QDs) show an excellent application perspective in semiconductor optoelectronic devices. However, problems of ligand loss during the growth, purification, film formation, and storage process always induce the aggregation and ripening of QDs, adversely affecting QDs’ and QD-based devices’ performance. Here, we use a bidentate molecule to control ripening toward a notable performance boost in CsPbI 3 QDs. The strong interaction between QDs and the bidentate molecules maintains stable surface states of QDs, inhibiting QDs’ undesirable ripening and generation of defects. We fabricate QD-based light-emitting diodes (LEDs) with a maximum external quantum efficiency (EQE) of 26.0% at 686 nm and an operating half-life of 10,587 hours at an initial radiance of 190 mW sr −1 m −2 (equivalent to a luminance of 100 cd m −2 for green perovskite LEDs). Benefiting from the high storability of the target QDs, the as-fabricated devices based on the QD solution storing for 1 month show a maximum EQE of 21.7% (20.3% for 3 months).
GPT-4o mini: Non-social science research article
Pigment removal from reverse-printed laminated flexible films by solvent-targeted recovery and precipitation
Tianwei Yan, Charles Granger, Kevin L. SĂĄnchez-Rivera, Panzheng Zhou, Steven Grey, Kevin Nelson, Fei Long, Ezra Bar-Ziv, Reid C. Van Lehn, Styliani Avraamidou, George W. Huber
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The solvent-targeted recovery and precipitation (STRAP) process separates and recovers the constituent resins in multilayer plastic packaging films by selective polymer dissolution. In this work, the cause of coloring in the STRAP-recycled polyethylene (PE) resins from postindustrial printed films was identified as decomposed diarylide pigments. Two different approaches are needed to completely remove the dissolved colorants during the STRAP process including (i) adding an activated carbon (AC) adsorbent to the solvent after polymer dissolution and (ii) proper mechanical filtration of the polymer-solvent cake to remove as much solvent from the cake as possible. Colorless recycled PE can be produced by a combination of the proposed approaches (choosing the proper solvent, adding an AC adsorbent, and doing proper mechanical filtration) with minimal accumulation of colorants in the recycled STRAP solvents. This study demonstrated that high-quality STRAP low-density PE can be obtained from printed plastic films, enhancing the potential circularity of these packaging materials.
GPT-4o mini: Non-social science research article
A polyvalent vaccine for selectively killing tumor-associated bacteria to prevent cancer metastasis
Zheyu Kang, Linfu Chen, Pengxing Li, Zixuan Zheng, Jingjing Shen, Zhisheng Xiao, Yu Miao, Yang Yang, Qian Chen
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Specific bacteria, including Fusobacterium nucleatum , Streptococcus sanguis , Enterococcus faecalis , and Staphylococcus xylosus , have been identified as contributors to breast cancer metastasis. Due to limitations such as lack of selectivity, traditional antibiotic therapies face obstacles in eliminating intratumoral bacteria. Herein, this work proposes the use of therapeutic vaccines to selectively target and eliminate harmful bacteria within tumors. A multivalent vaccine encapsulating both insoluble and soluble bacterial antigens was developed, addressing the shortcomings of traditional antibacterial vaccines by balancing broad antigen coverage with effective immune activation. This vaccine induces robust downstream immune responses to eliminate F. nucleatum , S. sanguis , E. faecalis , and S. xylosus , demonstrating notable therapeutic and preventive efficacy in bacteria-induced cancer metastasis models. Unexpectedly, vaccinated infected mice showed even slower tumor metastasis than uninfected mice. Overall, this study validates the potential of nanovaccines in modulating the intratumoral microbiome for tumor therapy and highlights tumor-associated bacterial infections as potential promising antitumor targets.
GPT-4o mini: Non-social science research article
Observation of vortex-pair dance and oscillation
Dadong Liu, Lai Chen, Li-Gang Wang
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Vortex dynamics, which encompass the motion, evolution, and propagation of vortices, elicit both fascination and challenges across various domains such as fluid dynamics, atmospheric science, and physics. This study focuses on the fundamental dynamics of vortex-pair fields, specifically known as vortex-pair beams (VPBs) in optics. VPBs have gained increasing attention due to their unique properties, including vortex attraction and repulsion. Here, we explore the dynamics of pure-phase VPBs (PPVPBs) and observe intriguing helical and intertwined behaviors of vortices, resembling a vortex-pair dance. We uncover the oscillation property of the intervortex distance for PPVPBs in free space. The observed dancing and oscillation phenomena are intricately tied to the initial intervortex distance and can be explained well in the hydrodynamic picture. Notably, the vortex dancing and oscillation alter the process of vortex-pair annihilation, extending the survival range for opposite vortices. This discovery enhances our understanding of vortex interactions and sheds light on the intricate dynamics of both vortex-vortex and vortex-antivortex interactions.
GPT-4o mini: Non-social science research article
Broadband uniform-efficiency OAM-mode detector
Suman Karan, Martin P. Van Exter, Anand K. Jha
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The high-dimensional basis of orbital angular momentum (OAM) has several added and unique advantages for photonic quantum technologies compared to the polarization basis, which is only two-dimensional. However, one of the major roadblocks in implementing OAM-based applications with their full potentials is the absence of an ideal OAM-mode detector. Despite the plethora of efforts in the last three decades, currently, there is no OAM detector that can detect a broad OAM-mode spectrum, has uniform detection-efficiency over all the modes, measures the true spectrum, and works for an arbitrary quantum state without the need for any previous information. Here, we experimentally demonstrate just such an OAM detector. We report detection of pure and mixed OAM states with fidelities more than 98% and with measurement times of only a few minutes for dimensionalities up to 100. We expect our work to substantially boost the OAM-based photonic quantum technology efforts.
GPT-4o mini: Non-social science research article
A multimodal defect-rich nanoreactor triggers sono-piezoelectric tandem catalysis and iron metabolism disruption for implant infections
Fuyuan Zheng, Xufeng Wan, Yangming Zhang, Yan Yue, Qiaochu Li, Zhuang Zhang, Shuoyuan Li, Hong Xu, Qiang Su, Xiaoting Chen, Le Tong, Long Zhao, Jian Cao, Xin Tang, Xiao Yang, Jiagang Wu, Jian Li, Xiang Lv, Zongke Zhou, Duan Wang
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Tracking and eradicating drug-resistant bacteria are critical for combating implant-associated infections, yet effective antibacterial therapies remain elusive. Herein, we propose an oxygen vacancy–rich (BiFe) 0.9 (BaTi) 0.1 O 3− x nanoreactor as a piezoelectric sonosensitizer by spatiotemporal ultrasound–driven sono- and chemodynamic tandem catalysis to amplify antibacterial efficacy. The piezoelectric charge carriers under a built-in electric field synchronize the reaction of O 2 and H 2 O, efficiently generating H 2 O 2 . The electron-rich oxygen vacancies modulate the local electronic structure of an Fe site. It facilitates reactive oxygen species generation by piezoelectric electrons and accelerates valence state cycles of Fe(III)/Fe(II) to achieve the sustained maintenance of hydroxyl radicals via H 2 O 2 /Fe(II)–catalyzed chemodynamic reactions, which lead to bacterial membrane damage. Transcriptomics analysis revealed that intracellular Fe overload induced by excessive Fe(II)-mediated dysregulation of the two-component system disrupts bacterial metabolism, triggering bacterial ferroptosis-like death. Thus, the porous titanium scaffold, engineered with a piezoelectric nanoreactor, demonstrates superior antibacterial efficacy under ultrasound and facilitates osteogenesis via piezoelectric immunomodulation–activated therapy.
GPT-4o mini: Non-social science research article
Assessing E. coli levels in surface soils of informal settlements using boot sock and standard grab methods
Lamiya Bata, Rebekah Henry, S. Fiona Barker, John Boyce, Fiona Lynch, Silvia Rosovoa Vilsoni, Autiko Tela, Revoni Vamosi, Ruzka R. Taruc, Andi Zulkifli Agussalim, Maghfira Saifuddaolah, Zainal Handis, David McCarthy, Karin Leder, character(0)
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Rapid urbanization leads to the growth of informal settlements, where inadequate sanitation infrastructure is common, thus promoting environmental contamination and risk of gastrointestinal infection. Soil contamination contributes to the transmission of enteropathogens, but traditional sampling approaches may poorly indicate public health risks due to limited spatial representation. This study compares traditional grab sampling of soil with a boot sock method, a composite technique designed to better reflect human-pathogen interactions. The boot sock method provided more sensitive detection of E. coli and lower inter-replicate variation compared to grab samples. Post hoc power analyses indicated that the boot sock technique required fewer samples to achieve adequate spatial representation across a sampling area than grab samples, potentially improving time and cost efficiency in pathogen exposure risk estimation.
GPT-4o mini: Non-social science research article
Long-term adhesion durability revealed through a rheological paradigm
Changhong Linghu, Rui Wu, Yuqing Chen, Yulin Huang, Young-Jae Seo, Hua Li, Guannan Wang, Huajian Gao, K. Jimmy Hsia
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The question of how long an object can adhere to a surface has intrigued scientists for centuries. Traditional studies focus on rapid crack-propagation detachment and account only for short-term adhesion governed by interfacial-viscoelastic dissipation, failing to explain long-term phenomena like sudden detachment after prolonged adherence and to predict corresponding adhesion lifetimes. Here, we investigate the long-term adhesion through a rheological paradigm using both theory and experiment. By considering both the bulk rheology and interfacial viscoelasticity mechanisms, we show that long-term adhesion durability is governed by the competition between them. This understanding leads to accurate lifetime predictions, which we validate through experiments. In addition, our study reveals a previously undocumented, counterintuitive phenomenon unique to long-term adhesion: the expansion of the contact area under tensile forces, in contrast to short-term adhesion in which the contact area always shrinks during detachment. This research fills a critical gap in adhesion physics.
GPT-4o mini: Non-social science research article
Senolytic treatment for low back pain
Matthew Mannarino, Hosni Cherif, Saber Ghazizadeh, Oliver Wu Martinez, Kai Sheng, Elsa Cousineau, Seunghwan Lee, Magali Millecamps, Chan Gao, Alice Gilbert, Cedric Peirs, Reza Sharif Naeini, Jean A. Ouellet, Laura S. Stone, Lisbet Haglund
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Senescent cells (SnCs) accumulate because of aging and external cellular stress throughout the body. They adopt a senescence-associated secretory phenotype (SASP) and release inflammatory and degenerative factors that actively contribute to age-related diseases, such as low back pain (LBP). The senolytics, o -vanillin and RG-7112, remove SnCs in human intervertebral discs (IVDs) and reduce SASP release, but it is unknown whether they can treat LBP. sparc −/− mice, with LBP, were treated orally with o -vanillin and RG-7112 as single or combination treatments. Treatment reduced LBP and SASP factor release and removed SnCs from the IVD and spinal cord. Treatment also lowered degeneration scores in the IVDs, improved vertebral bone quality, and reduced the expression of pain markers in the spinal cord. Together, our data suggest RG-7112 and o -vanillin as potential disease-modifying drugs for LBP and other painful disorders linked to cell senescence.
GPT-4o mini: Non-social science research article
Short-lived reactive components substantially contribute to particulate matter oxidative potential
Steven J. Campbell, Battist Utinger, Alexandre Barth, Zaira Leni, Zhi-Hui Zhang, Julian Resch, Kangwei Li, Sarah S. Steimer, Catherine Banach, Benjamin Gfeller, Francis P. H. Wragg, Joe Westwood, Kate Wolfer, Nicolas Bukowiecki, Mika Ihalainen, Pasi Yli-PirilĂ€, Markus Somero, Miika Kortelainen, Juho Louhisalmi, Martin Sklorz, Hendryk Czech, Sebastiano di Bucchianico, Thorsten Streibel, Mathilde N. Delaval, Christopher Ruger, Nathalie Baumlin, Matthias Salathe, Zheng Fang, Michal Pardo, Sara D’Aronco, Chiara Giorio, Zongbo Shi, Roy M. Harrison, David C. Green, Frank J. Kelly, Yinon Rudich, Suzanne E. Paulson, Olli Sippula, Ralf Zimmermann, Marianne Geiser, Markus Kalberer
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Exposure to airborne particulate matter (PM) has been attributed to millions of deaths annually. However, the PM components responsible for observed health effects remain unclear. Oxidative potential (OP) has gained increasing attention as a key property that may explain PM toxicity. Using online measurement methods that impinge particles for OP quantification within seconds, we reveal that 60 to 99% of reactive oxygen species (ROS) and OP in secondary organic aerosol and combustion-generated PM have a lifetime of minutes to hours and that the ROS activity of ambient PM decays substantially before offline analysis. This implies that current offline measurement methods substantially underestimate the true OP of PM. We demonstrate that short-lived OP components activate different toxicity pathways upon direct deposition onto reconstituted human bronchial epithelia. Therefore, we suggest that future air pollution and health studies should include online OP quantification, allowing more accurate assessments of links between OP and health effects.
GPT-4o mini: Non-social science research article
Skin-attached haptic patch for versatile and augmented tactile interaction
Jung-Hwan Youn, Seung-Yeon Jang, Inwook Hwang, Qibing Pei, Sungryul Yun, Ki-Uk Kyung
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Wearable tactile interfaces can enhance immersive experiences in virtual/augmented reality systems by adding tactile stimulation to the skin along with the visual and auditory information delivered to the user. We introduce a flat cone dielectric elastomer actuator (FCDEA) array that is thin, soft, and capable of producing spatiotemporally adjustable and large static-to-dynamic force in response to electric voltage signals on large areas of the skin. Integration of the FCDEA array into a photomicrosensor array enables the implementation of a wearable wireless communication haptic patch. We demonstrate that the developed haptic patch allows users to communicate tactile information in real time while maintaining conformal contact with the skin. The haptic patch can also express the topology of 3D structures and render textures of virtual objects in response to localized vibration of the FCDEA array. We expect that the developed haptic patch will provide an immersive touching experience in virtual reality and facilitate tactile communication between users in various applications.
GPT-4o mini: Non-social science research article
Bcl-xL overexpression in T cells preserves muscle mitochondrial structure and function and prevents frailty in old mice
Cristina Mas-Bargues, Aurora Romån-Domínguez, Jorge Sanz-Ros, Nekane Romero-García, Javier Huete-Acevedo, Mar Dromant, Ana María Cuervo, Consuelo Borrås, José Viña
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Our previous transcriptomic analysis revealed an up-regulation of the antiapoptotic protein B cell lymphoma-extra large (Bcl-xL) in centenarians relative to octogenarians or younger cohorts. In this study, we used Bcl-xL–overexpressing mice to assess its impact on successful aging. Our findings indicate that Bcl-xL overexpression modifies T cell subsets and improves their metabolism, apoptosis resistance, macroautophagy, and cytokine production during aging. This more resilient immune system reduces inflammation and preserves mitochondrial integrity and function in muscle tissue, thereby retarding the onset of frailty. These results underscore the important contribution of Bcl-xL to healthy aging, a phenomenon that is conserved across mammalian species.
GPT-4o mini: Non-social science research article
An ICU-grade breathable cardiac electronic skin for health, diagnostics, and intraoperative and postoperative monitoring
Qiuna Zhuang, Kuanming Yao, Xian Song, Qiang Zhang, Chi Zhang, Huiming Wang, Ruofan Yang, Guangyao Zhao, Shanghang Li, Haihua Shu, Qiyao Huang, Yunfei Chai, Xinge Yu, Zijian Zheng
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Cardiovascular digital health technologies potentially outperform traditional clinical equipment through their noninvasive, on-body, and portable monitoring with mass cardiac data beyond the confines of inpatient settings. However, existing cardiovascular wearables have difficulty with providing medical-grade accuracy with a chronically comfortable and stable patient/consumer device interface for reliable clinical decision-making. Here, we develop an intensive care unit (ICU)–grade breathable cardiac electronic skin system (BreaCARES) for real-time, wireless, continuous, and comfortable cardiac care. BreaCARES enables a novel digital cardiac care platform for health care, outpatient diagnostics, stable intraoperative monitoring during heart surgery, and continuous and comfortable inpatient postoperative cardiac care, exhibiting ICU-grade accuracy while having superior anti-interference stability, portability, and long-term on-skin biocompatibility to the clinically and commercially available cardiac monitors in cardiovascular ICUs.
GPT-4o mini: Non-social science research article
Bio-inspired organic electrosense transistor for impalpable perception
Cong Wang, Jiaofu Li, Xufan Li, Wenlong Li, Yanzhen Li, Yinan Huang, Changxian Wang, Zhihua Liu, Ming Wang, Nuan Chen, Mingxi Chen, Liang Pan, Feilong Zhang, Jinshun Bi, Liqiang Li, Wenping Hu, Xiaodong Chen
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Artificial sense technologies predominantly rely on visual and tactile input, which often prove inadequate in obscured or opaque environments. Inspired by the natural electrosensory capabilities of electrogenic fishes, we introduce an organic electrosense transistor designed to detect electric fields generated by nearby objects, facilitating the creation of impalpable perception systems. Unlike traditional sensors, our electrosense transistor perceives bipolar electric fields with high sensitivity and stability. We use compact models and device simulations to elucidate the mechanisms of charge induction and transport within organic electrosense transistors when exposed to spatial electric fields. Demonstrating its practical utility, we show that robots equipped with our electrosense transistor can successfully navigate and detect concealed objects without requiring direct contact. This work not only advances the understanding of charge dynamics in electrosensory systems but also establishes a platform for developing highly sensitive, noninvasive artificial sensing technologies applicable in surveillance, search and rescue, and other challenging environments.
GPT-4o mini: Non-social science research article
Protein misfolding involving entanglements provides a structural explanation for the origin of stretched-exponential refolding kinetics
Yang Jiang, Yingzi Xia, Ian Sitarik, Piyoosh Sharma, Hyebin Song, Stephen D. Fried, Edward P. O’Brien
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Stretched-exponential protein refolding kinetics, first observed decades ago, were attributed to a nonnative ensemble of structures with parallel, non-interconverting folding pathways. However, the structural origin of the large energy barriers preventing interconversion between these folding pathways is unknown. Here, we combine simulations with limited proteolysis (LiP) and cross-linking (XL) mass spectrometry (MS) to study the protein phosphoglycerate kinase (PGK). Simulations recapitulate its stretched-exponential folding kinetics and reveal that misfolded states involving changes of entanglement underlie this behavior: either formation of a nonnative, noncovalent lasso entanglement or failure to form a native entanglement. These misfolded states act as kinetic traps, requiring extensive unfolding to escape, which results in a distribution of free energy barriers and pathway partitioning. Using LiP-MS and XL-MS, we propose heterogeneous structural ensembles consistent with these data that represent the potential long-lived misfolded states PGK populates. This structural and energetic heterogeneity creates a hierarchy of refolding timescales, explaining stretched-exponential kinetics.
GPT-4o mini: Non-social science research article
Interlayer confinement toward short hydrogen bond network construction for fast hydroxide transport
Ruixiang Guo, Yecheng Zhou, Wei Wang, Yeming Zhai, Xiaofen Liu, Weijun He, Wen Ou, Rui Ding, Hao-Li Zhang, Meiling Wu, Zhongyi Jiang, Kai-Ge Zhou
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Driven by boosting demands for sustainable energy, highly conductive hydroxide exchange membranes (HEMs) are urgently required in electrochemical conversion devices. The hydrogen bonds shorter than 2.5 angstrom are expected to accelerate the ion transport. However, short hydrogen bonds (SHBs) can hardly form naturally because of the electron-withdrawing capability of O atom, which impedes its applications in water-mediated ion transport. This work develops an interlayer confinement strategy to construct SHB networks in a two-dimensional (2D) nanocapillary assembled by bismuth oxyiodide (BiOI) nanosheets and boost the ionic conductivity of HEMs. With confined nanochannels and adjustable hydrophilic groups in BiOI-based HEMs, the number of SHBs increases by 12 times, creating a shortcut for the Grotthuss-type anion transport, which in turn affords a high ionic conductivity of 168 millisiemens per centimeter at 90°C, higher than polymeric HEM and 2D-based HEM. This work demonstrates the facile approach to generating SHB networks in 2D capillaries and opens a promising avenue to developing advanced HEMs.
GPT-4o mini: Non-social science research article
The sodium leak channel NALCN is regulated by neuronal SNARE complex proteins
Samuel Usher, Estelle Toulmé, Roberta Florea, Stanislau Yatskevich, Christine C. Jao, Luuk R. H. Dijkhof, Janne M. Colding, Prajakta Joshi, Inna Zilberleyb, Thorsten Trimbuch, Bettina Brokowski, Alexander S. Hauser, Alexander Leitner, Christian Rosenmund, Marc Kschonsak, Stephan A. Pless
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NALCN (sodium leak channel, nonselective) is vital for regulating electrical activity in neurons and other excitable cells, and mutations in the channel or its auxiliary proteins lead to severe neurodevelopmental disorders. Here, we show that the neuronal SNARE (soluble N -ethylmaleimide–sensitive factor attachment protein receptors) complex proteins syntaxin and SNAP25 (synaptosome-associated protein 25), which enable synaptic transmission in the nervous system, inhibit the activity of the NALCN channel complex in both heterologous systems and primary neurons. The existence of this interaction suggests that the neurotransmitter release machinery can regulate electrical signaling directly and therefore modulate the threshold for its own activity. We further find that reduction of NALCN currents is sufficient to promote cell survival in syntaxin-depleted cells. This suggests that disinhibited NALCN may cause the puzzling phenomenon of rapid neuronal cell death in the absence of syntaxin. This interaction could offer opportunities for future drug development against genetic diseases linked to both NALCN- and SNARE protein–containing complexes.
GPT-4o mini: Non-social science research article
Polyelectrolyte-based wireless and drift-free iontronic sensors for orthodontic sensing
Jia Song, Rusong Yang, Junli Shi, Xingxing Chen, Sai Xie, Zelong Liao, Ruijie Zou, Yupeng Feng, Terry Tao Ye, Chuan Fei Guo
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The real-time monitoring of health conditions of humans is a long-lasting topic, but there are two major challenges. First, many biomedical applications accept only implanted sensors. Second, tissue-like soft sensors often suffer from viscoelasticity-induced signal drift, causing inaccurate measurements. Here, we report a wireless and drift-free sensory system enabled by a low-creep polyelectrolyte elastomer. The system consists of the iontronic pressure sensors incorporating inductance-capacitance (LC) oscillators, exhibiting combined low drift ratio, high Q factor, high robustness to interferences, and wide-range measurement, superior to other capacitive sensors using regular dielectrics or ionogels. We have recorded 14-day orthodontic loads of two subjects using the system, showing pressure decreasing from 300 to 50 kPa and torque from 12.5 to 0.5 N·mm. The wireless, drift-free sensory system may be extended to other implants for long-term and accurate sensing.
GPT-4o mini: Non-social science research article
PseudoSorter: A self-supervised spike sorting approach applied to reveal Tau-induced reductions in neuronal activity
Marius Brockhoff, Jakob TrÀuble, Sagnik Middya, Tanja Fuchsberger, Ana Fernandez-Villegas, Amberley Stephens, Miranda Robbins, Wenyue Dai, Belquis Haider, Sulay Vora, Nino F. LÀubli, Clemens F. Kaminski, George G. Malliaras, Ole Paulsen, Gabriele S. Kaminski Schierle
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Microelectrode arrays (MEAs) permit recordings with high electrode counts, thus generating complex datasets that would benefit from precise neuronal spike sorting for meaningful data extraction. Nevertheless, conventional spike sorting methods face limitations in recognizing diverse spike shapes. Here, we introduce PseudoSorter, which uses self-supervised learning techniques, a density-based pseudolabeling strategy, and an iterative fine-tuning process to enhance spike sorting accuracy. Through benchmarking, we demonstrate the superior performance of PseudoSorter compared to other spike sorting algorithms before applying PseudoSorter on MEA recordings from hippocampal neurons exposed to subneuronal concentrations of monomeric Tau as a model for Alzheimer’s disease. Our results unveil that Tau diminishes the firing rate of a subset of neurons, which complement our findings observed using conventional electrophysiology analysis, and demonstrate that PseudoSorter’s high accuracy and throughput make it a valuable tool for studying neurodegenerative diseases, enhancing our understanding of their underlying mechanisms, as well as for therapeutic drug screening.
GPT-4o mini: Non-social science research article
Multiple B-site doping suppresses ion migration in halide perovskites
Yuhang Liang, Feng Li, Xiangyuan Cui, Catherine Stampfl, Simon P. Ringer, Xudong Yang, Jun Huang, Rongkun Zheng
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Lead halide perovskites hold great promise for photovoltaics and optoelectronics, yet ion migration continues to challenge their long-term stability. Here, combining first-principles calculations and machine learning molecular dynamics, we unravel the interplay between perovskite octahedral lattice dynamics and energy barrier associated with ion migration. Our results show that B-site substitution, particularly with alkaline-earth and lanthanide elements, notably strengthens lattice interactions, restrains octahedral oscillation, and increases iodine-migration barriers, outperforming the commonly used A-site and X-site substitutions and interstitial doping. Moreover, the enhanced barrier aligns with the geometric factor of Ότ (tolerance-octahedral product), underlining the superior effectiveness of co- and multiple-element B-site doping in lattice stabilization and ion migration suppression. Experimental validation with exemplary hysteresis-free Eu-Ca–doped perovskite single crystals demonstrates remarkable improvements in ambient stability and transport properties. These findings highlight B-site engineering as an effective microstructural strategy for controlling ion migration, with important implications for stable and lead-reduced perovskite devices.
GPT-4o mini: Non-social science research article
Gene-specific transcript buffering revealed by perturbation of coactivator complexes
Faezeh Forouzanfar, David F. Moreno, Damien Plassard, Audrey Furst, Karen A. Oliveira, Bernardo Reina-San-Martin, LĂĄszlĂł Tora, Nacho Molina, Manuel Mendoza
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Transcript buffering entails reciprocal modulation of mRNA synthesis and degradation to maintain stable RNA levels under varying cellular conditions. Current models depict a global connection between mRNA synthesis and degradation, but underlying mechanisms remain unclear. Here, we show that changes in RNA metabolism following depletion of TIP60/KAT5, the acetyltransferase subunit of the NuA4 transcriptional coactivator complex, reveal that transcript buffering occurs at a gene-specific level. By combining RNA sequencing of nuclear, cytoplasmic, and newly synthesized transcript fractions with biophysical modeling in mouse embryonic stem cells, we demonstrate that transcriptional changes caused by TIP60 depletion are offset by corresponding changes in RNA nuclear export and cytoplasmic stability, indicating gene-specific buffering. Disruption of the unrelated ATAC coactivator complex also causes gene-specific transcript buffering. We propose that cells dynamically adjust RNA splicing, export, and degradation in response to individual RNA synthesis alterations, thereby sustaining cellular homeostasis.
GPT-4o mini: Non-social science research article
Reducing hepatitis C diagnostic disparities with a fully automated deep learning–enabled microfluidic system for HCV antigen detection
Hui Chen, Yuxin Gao, Gaojian Li, Manasvi Alam, Srisruthi Udayakumar, Qazi Noorul Mateen, Sahar Rostamian, Katherine Cilley, Sungwan Kim, Giwon Cho, Juyong Gwak, Yixuan Song, Joseph Michael Hardie, Manoj Kumar Kanakasabapathy, Hemanth Kandula, Prudhvi Thirumalaraju, Younseong Song, Azim Parandakh, Arafeh Bigdeli, Gregory P. Fricker, Jenna Gustafson, Raymond T. Chung, Jorge Mera, Hadi Shafiee
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Viral hepatitis remains a major global health issue, with chronic hepatitis B (HBV) and hepatitis C (HCV) causing approximately 1 million deaths annually, primarily due to liver cancer and cirrhosis. More than 1.5 million people contract HCV each year, disproportionately affecting vulnerable populations, including American Indians and Alaska Natives (AI/AN). While direct-acting antivirals (DAAs) are highly effective, timely and accurate HCV diagnosis remains a challenge, particularly in resource-limited settings. The current two-step HCV testing process is costly and time-intensive, often leading to patient loss before treatment. Point-of-care (POC) HCV antigen (Ag) testing offers a promising alternative, but no FDA-approved test meets the required sensitivity and specificity. To address this, we developed a fully automated, smartphone-based POC HCV Ag assay using platinum nanoparticles, deep learning image processing, and microfluidics. With an overall accuracy of 94.59%, this cost-effective, portable device has the potential to reduce HCV-related health disparities, particularly among AI/AN populations, improving accessibility and equity in care.
GPT-4o mini: Non-social science research article
Amplified wintertime Arctic warming causes Eurasian cooling via nonlinear feedback of suppressed synoptic eddy activities
Manman Yin, Xiu-Qun Yang, Linyuan Sun, Lingfeng Tao, Noel Keenlyside
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The amplified wintertime Arctic warming has accelerated in recent decades. However, whether and how the warming can cause Eurasian cooling remains debated. By identifying daily Arctic warming events, we find direct observational evidence that the Arctic warming tends to cause substantial Eurasian cooling and an increase in occurrence frequency of Eurasian cooling events with a roughly 2-day lag. We propose a mechanism explaining the causality. We find that the Arctic warming causes a large suppression in activities of daily weather disturbances (referred to as synoptic eddies) over high-latitude Eurasia. This produces a meridional dipole in geopotential height anomalies characterized by an equivalent-barotropic anomalous low (high) and a lower-level cooling (warming) over mid-latitude Eurasia (the Arctic) via a nonlinear eddy–to–mean flow feedback. The feedback induces near-surface northeasterly anomalies that enlarge the Eurasian cooling via cold advection. Thus, we conclude that the warm Arctic versus cold Eurasia is essentially an intrinsic dipole determined by synoptic eddy–mean flow interaction.
GPT-4o mini: Non-social science research article
Random encounters dominate water-water interactions at supercritical conditions
Katja Mauelshagen, Philipp Schienbein, Inga Kolling, Gerhard Schwaab, Dominik Marx, Martina Havenith
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Supercritical water is widely present in Earth’s crust and has a great potential as an environmentally friendly solvent. Water also serves as the prototype for directional hydrogen bonding at ambient conditions. However, the question of whether supercritical water is still hydrogen-bonded or how water molecules interact en route to the supercritical regime is a matter of controversial discussions. We present terahertz (THz) spectra, which directly probe the intermolecular interactions of water under these extreme conditions. While we spectroscopically detect the liquid-gas phase transition just below the critical point, THz spectra of the high-temperature gas phase are indistinguishable from those of supercritical water at the same density. The accompanying ab initio simulations provide the molecular underpinnings: The water-water contacts at supercritical conditions are essentially orientationally random.
GPT-4o mini: Non-social science research article
Fast and reliable probabilistic reflectometry inversion with prior-amortized neural posterior estimation
Vladimir Starostin, Maximilian Dax, Alexander Gerlach, Alexander Hinderhofer, Álvaro Tejero-Cantero, Frank Schreiber
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Reconstructing the structure of thin films and multilayers from measurements of scattered x-rays or neutrons is key to progress in physics, chemistry, and biology. However, finding all structures compatible with reflectometry data is computationally prohibitive for standard algorithms, which typically results in unreliable analysis with only a single potential solution identified. We address this lack of reliability with a probabilistic deep learning method that identifies all realistic structures in seconds, redefining standards in reflectometry. Our method, prior-amortized neural posterior estimation (PANPE), combines simulation-based inference with adaptive priors that inform the inference network about known structural properties and controllable experimental conditions. PANPE networks support key scenarios such as high-throughput sample characterization, real-time monitoring of evolving structures, or the corefinement of several experimental datasets and can be adapted to provide fast, reliable, and flexible inference across many other inverse problems.
GPT-4o mini: Non-social science research article
Elevated methylmercury in Arctic rain and aerosol linked to air-sea exchange of dimethylmercury
Yipeng He, Hannah Inman, David C. Kadko, Mark P. Stephens, Douglas E. Hammond, William M. Landing, Robert P. Mason
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Mercury (Hg) is a global pollutant with substantial human health impacts. While most studies focus on atmospheric total Hg (THg) deposition, contributions of methylated Hg (MeHg), including monomethylmercury (MMHg) and dimethylmercury (DMHg), remain poorly understood. To examine this, we use rain and aerosol Hg speciation data and high-resolution surface DMHg measurements, collected on a transect from Alaskan coastal waters to the Bering and Chukchi Seas. We observed a significant fivefold increase in the MeHg:THg fraction in rain and a 10-fold increase for aerosols, closely linked to elevated surface DMHg and the highest DMHg evasion (~9.4 picomoles per square meter per hour) found in upwelling waters near the Aleutian Islands. These data highlight a previously underexplored aspect of MeHg air-sea exchange and its importance to Hg cycling and human health concerns. Our findings emphasize the importance of DMHg evasion by demonstrating that atmospheric MeHg can be transported long distances (~1700 kilometers) in the Arctic, posing risks to human health and ecosystems.
GPT-4o mini: Non-social science research article
PPDPF: Preventing kidney disease through NAD + regulation
Shin-ichiro Imai
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Researchers have discovered PPDPF, a critical cellular factor that controls NAD + biosynthesis, whose function is important to prevent kidney diseases.
GPT-4o mini: Non-social science research article
Genome-wide CRISPR screen identifies IRF1 and TFAP4 as transcriptional regulators of Galectin-9 in T cell acute lymphoblastic leukemia
Caroline R. M. Wiggers, Burak YĂŒzĂŒgĂŒldĂŒ, Nathanial G. Tadros, Tayla B. Heavican-Foral, Eugene Y. Cho, Zachary C. Eisenbies, Merve Ozdemir, Steffen B. Kulp, Yun-Cheol Chae, Alejandro Gutierrez, Jens G. Lohr, Birgit Knoechel
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Galectin-9 is overexpressed in a variety of cancers and associated with worse clinical outcome in some cancers. However, the regulators driving Galectin-9 expression are unknown. Here, we defined the transcriptional regulators and epigenetic circuitry of Galectin-9 in pediatric T cell acute lymphoblastic leukemia (T-ALL), as an example of a disease with strong Galectin-9 expression, in which higher expression was associated with lower overall survival. By performing a genome-wide CRISPR screen, we identified the transcription factors IRF1 and TFAP4 as key regulators for Galectin-9 expression by binding its regulatory elements. Whereas IRF1 was observed exclusively on the promoter, TFAP4 binding was detected at an enhancer solely in T-ALL cells associated with higher Galectin-9 levels. Together, our results show that IRF1 is responsible and indispensable for Galectin-9 expression and TFAP4 further fine-tunes its expression. Our approach, a flow-based genome-wide CRISPR screen complemented by transcription factor binding and enhancer mapping, creates innovative opportunities for understanding and manipulating epigenetic transcriptional regulation in cancer.
GPT-4o mini: Non-social science research article
Dynamic cross-linked topological network reconciles the longstanding contradictory properties of polymers
Zekai Wu, Chengzhen Chu, Yuhui Jin, Lei Yang, Bo Qian, Yuepeng Wang, Yihan Wang, Jiani Wu, Yujie Jia, Wenwen Zhang, Zhengwei You
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There is usually a trade-off between high-tensile properties and processability in polymers because the mechanisms of these properties are mutually exclusive. Here, we design a chemically coupled four-arm dynamic polymer cross-link site to overcome this challenge. By concurrently increasing cross-link sites and dynamic bond contents, this approach fabricates polymer networks with high cross-link density yet low processing temperature, challenging the conventional structure-property relationship where cross-linking inherently limits plasticity. Notably, the material demonstrates remarkable processability, evidenced by the ratio of G â€Č max to G â€Č min with a temperature differential (Δ T ) of 120°C (which signifies the soft-to-hard transition capability). This ratio reaches 153.3, higher than all reported cross-linked polyurethanes. This work represents a molecular strategy that combines electronic effect and topology network design to modulate materials’ properties, and it will be useful for developing next-generation materials.
GPT-4o mini: Non-social science research article
The conserved Spd-2/CEP192 domain adopts a unique protein fold to promote centrosome scaffold assembly
Liuyi Hu, Alan Wainman, Antonina Andreeva, Muladili Apizi, Ines Alvarez-Rodrigo, Siu-Shing Wong, Saroj Saurya, Devon Sheppard, Matthew Cottee, Steven Johnson, Susan M. Lea, Jordan W. Raff, Mark van Breugel, Zhe Feng
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Centrosomes form when centrioles assemble pericentriolar material (PCM) around themselves. Spd-2/CEP192 proteins, defined by a conserved “Spd-2 domain” (SP2D) comprising two closely spaced AspM-Spd-2-Hydin (ASH) domains, play a critical role in centrosome assembly. Here, we show that the SP2D does not target Drosophila Spd-2 to centrosomes but rather promotes PCM scaffold assembly. Crystal structures of the human and honeybee SP2D reveal an unusual “extended cradle” structure mediated by a conserved interaction interface between the two ASH domains. Mutations predicted to perturb this interface, including a human mutation associated with male infertility and Mosaic Variegated Aneuploidy, disrupt PCM scaffold assembly in flies. The SP2D is monomeric in solution, but the Drosophila SP2D can form higher-order oligomers upon phosphorylation by PLK1 (Polo-like kinase 1). Crystal-packing interactions and AlphaFold predictions suggest how SP2Ds might self-assemble, and mutations associated with one such potential dimerization interface markedly perturb SP2D oligomerization in vitro and PCM scaffold assembly in vivo.
GPT-4o mini: Non-social science research article
A plant peptide with dual activity against multidrug-resistant bacterial and fungal pathogens
Xueyan Chen, Meirong Song, Lei Tian, Xinxin Shan, Changsi Mao, Minghui Chen, Jiaqi Zhao, Abdul Sami, Haoqiang Yin, Usman Ali, Jiawei Shi, Hehuan Li, Yuqian Zhang, Jinghua Zhang, Shunxi Wang, Chun-Lin Shi, Yanhui Chen, Xiang-Dang Du, Kui Zhu, Liuji Wu
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Multidrug-resistant (MDR) bacteria pose a major threat to public health, and additional sources of antibacterial candidates are urgently needed. Noncanonical peptides (NCPs), derived from noncanonical small open reading frames, represent small biological molecules with important roles in biology. However, the antibacterial activity of NCPs remains largely unknown. Here, we discovered a plant-derived noncanonical antibacterial peptide (NCBP1) against both Gram-positive and Gram-negative bacteria. NCBP1 is composed of 11 amino acid residues with cationic surface potential and favorable safety and stability. Mechanistic studies revealed that NCBP1 displayed antibacterial activity by targeting phosphatidylglycerol and cardiolipin in bacterial membrane, resulting in membrane damage and dysfunction. Notably, NCBP1 showed promising efficacy in mice. Furthermore, NCBP1 effectively inhibited the growth of plant fungal pathogens and enhanced disease resistance in maize. Our results demonstrate the unexplored antimicrobial potential of plant-derived NCPs and provide an accessible source for the discovery of antimicrobial substances against MDR bacterial and fungal pathogens.
GPT-4o mini: Non-social science research article
Wetting-induced interfacial instability: A mechanism for droplet emission at air-liquid interfaces
Yao-Yao Su, Da-Wei Pan, Tao-Xian Zhang, Rui Xie, Xiao-Jie Ju, Zhuang Liu, Nan-Nan Deng, Wei Wang, Liang-Yin Chu
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High-throughput production of monodisperse microdroplets has revolutionized many fields, typically relying on shear-induced emulsification in intricate microfluidic channels to induce the Rayleigh-Plateau instability. This mechanism exhibits low robustness due to its high dependence on the physical properties and flow conditions of fluids. Here, we report a robust emulsification mechanism—wetting-induced interfacial instability—for droplet emission. We find that, when pendant microdroplets in the air contact with an immiscible wetting bulk phase, it triggers interfacial instability in the hanging droplets and then their rapid breakup into the bulk phase. This simplifies the monodisperse microdroplet production using a nozzle positioned above an air-liquid interface, requiring no complex microchannels. We demonstrate that this method exhibits highly scalable production and exceptional robustness against variations in physical properties and flow conditions of fluids, including highly viscous non-Newtonian fluid (56,600 millipascal-seconds). This mechanism provides a simpler alternative to the traditional Rayleigh-Plateau instability for emulsification, offering opportunities for industrial applications and insights into microscale interfacial science.
GPT-4o mini: Non-social science research article
Deep tissue sensing of chiral molecules using polarization-enhanced photoacoustics
Swathi Padmanabhan, Jaya Prakash
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Chiral molecule sensing is typically performed using techniques like chromatography, electrophoresis, enzymatic assays, mass spectrometry, and chiroptical methods. While polarimetry allows for in vivo sensing up to 1 mm depth using ultraviolet-visible light, it is limited by dominant light scattering beyond this depth. We propose that photoacoustic sensing in the near-infrared II (NIR-II) window can enable deep tissue sensing as acoustic waves scatter less than light. To achieve this, we developed a photoacoustic polarization–enhanced optical rotation sensing (PAPEORS) system, capable of estimating optical rotation from photoacoustic signals and correlating it with chiral molecular concentration for depths up to 3.5 mm. Experiments were conducted using aqueous glucose solutions, naproxen, serum-based glucose samples, and ex vivo chicken tissue. PAPEORS achieved a detection limit of 80 mg/dl while using circularly polarized light with serum samples, demonstrating the potential for deep-tissue chiral molecular sensing. PAPEORS holds promise for in vivo sensing and easy miniaturization using single wavelength.
GPT-4o mini: Non-social science research article
SARS-related coronavirus S-protein structures reveal synergistic RBM interactions underpinning high-affinity human ACE2 binding
Jingjing Wang, Yong Ma, Zimu Li, Hang Yuan, Banghui Liu, Zexuan Li, Mengzhen Su, Gul Habib, Yutong Liu, Lutang Fu, Peiyi Wang, Mei Li, Jun He, Jing Chen, Peng Zhou, Zhengli Shi, Xinwen Chen, Xiaoli Xiong
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High-affinity and specific binding toward the human angiotensin-converting enzyme 2 (hACE2) receptor by severe acute respiratory syndrome coronavirus (SARS)–related coronaviruses (SARSr-CoVs) remains incompletely understood. We report cryo–electron microscopy structures of eight different S-proteins from SARSr-CoVs found across Asia, Europe, and Africa. These S-proteins all adopt tightly packed, locked, prefusion conformations. These structures enable the classification of SARSr-CoV S-proteins into three types, based on their receptor-binding motif (RBM) structures and ACE2 binding characteristics. Type-2 S-proteins often preferentially bind bat ACE2 (bACE2) over hACE2. We report a structure of a type-2 BtKY72-RBD in complex with bACE2 to understand ACE2 specificity. Structure-guided mutagenesis of BtKY72-RBD reveals that multiple synergistic mutations in four different regions of RBM are required to achieve high-affinity hACE2 binding. Similar RBM changes can also confer hACE2 binding to another type-2 BM48-31 S-protein, which is primarily non-ACE2 binding. These results provide an understanding of how high-affinity hACE2 binding may be acquired by SARSr-CoV S-proteins.
GPT-4o mini: Non-social science research article
Spraying of water microdroplets forms luminescence and causes chemical reactions in surrounding gas
Yifan Meng, Yu Xia, Jinheng Xu, Richard N. Zare
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When neutral water is sprayed, oppositely charged microdroplets are formed. The close approach of oppositely charged microdroplets causes an electrical discharge and leads to luminescent emission. The light emission happens without any external voltage applied, and the electrical discharge is sufficiently energetic to excite, dissociate, or ionize surrounding neutral gas molecules. Thus, sprayed water microdroplets cause chemical reactions to occur. Similar findings to the Urey-Miller experiment were observed by spraying room temperature water microdroplets into a gas mixture containing nitrogen, methane, carbon dioxide, and ammonia, which leads to the synthesis of organic molecules containing carbon-nitrogen (C─N) bonds. These observations provide another explanation for unique reactivity at the gas-water interface, as well as a possible mechanism for making the building blocks of life on early Earth.
GPT-4o mini: Non-social science research article
Monolithically integrated solid-state vertical organic electrochemical transistors switching between neuromorphic and logic functions
Tianming Li, Zhe Qu, Jiansong Si, Yeji Lee, Vineeth Kumar Bandari, Oliver G. Schmidt
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Manipulating the ionic-electronic coupling in organic electrochemical transistors (OECTs) offers opportunities for interesting phenomena and advanced applications but has not been systematically exploited. Here, we develop monolithically integrated solid-state vertical OECTs to fully explore polyelectrolyte’s strengths, enabling the OECTs to switch between neuromorphic and logic functions. This transition capability is achieved by mastering the complex transport of large-size polycations within the channel through well-designed drain electrodes. Frame drains positioned atop the organic channel act as ion barriers, regulating the penetration and relaxation of polycations. This regulation allows our multilevel synaptic OECTs to transform from short-term depression (STD) to STD-based long-term memory, and eventually to long-term depression (LTD). Conversely, placing frame drains beneath the channel exposes the polyelectrolyte fully, hence yielding high-density logic OECTs, which have been successfully used to construct unipolar integrated circuits such as NOT, NAND, and NOR gates. These achievements represent a substantial advancement in manipulating polyelectrolyte-based ionic-electronic interactions, introducing more possibilities beyond small ion-based OECTs.
GPT-4o mini: Non-social science research article
Calcium-activated ion channels drive atypical inhibition in medial habenula neurons
Takafumi Kawai, Ping Dong, Konstantin Bakhurin, Henry H. Yin, Huanghe Yang
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Nicotine is an addictive substance that poses substantial health and societal challenges. Despite the known links between the medial habenula (MHb) and nicotine avoidance, the ionic mechanisms underlying MHb neuronal responses to nicotine remain unclear. Here, we report that MHb neurons use a long-lasting refractory period (LLRP) as an unconventional inhibitory mechanism to curb hyperexcitability. This process is initiated by nicotine-induced calcium influx through nicotinic acetylcholine receptors, which activates a calcium-activated chloride channel (CaCC). Owing to high intracellular chloride levels in MHb neurons, chloride efflux through CaCC, coupled with high-threshold voltage-gated calcium channels, sustains MHb depolarization near the chloride equilibrium potential of −30 millivolts, thereby enabling LLRP. Concurrently, calcium-activated BK potassium channels counteract this depolarization, promoting LLRP termination. Our findings reveal an atypical inhibitory mechanism, orchestrated by synergistic actions between calcium-permeable and calcium-activated channels. This discovery advances our understanding of neuronal excitability control and nicotine addiction.
GPT-4o mini: Non-social science research article
Electrically switchable ON-OFF spin-orbit torque in an ionic-gated metallic trilayer
Soobeom Lee, Suhyeok An, Eunchong Baek, Dongryul Kim, Jaeyong Cho, Chun-Yeol You
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With the advancement of magnetization-based spintronic applications, there has been considerable interest in spin-orbit torque as an electric technique to dynamically manipulate magnetization. In this study, gate-induced ON-OFF switchable spin-orbit torque in Pt/Co/Pt spin-orbit device using the ionic gating technique is reported. By canceling the spin currents from Pt layers, the OFF state is attained in Pt/Co/Pt spin-orbit device. Notably, under a strong negative gate electric field applied to the Pt/Co/Pt spin-orbit device, the damping-like spin-orbit torque is markedly enhanced over sixfold compared with the applied positive gate electric field. We show that the gate modulation of the spin-orbit torque in the Pt/Co/Pt spin-orbit device can be explained by considering the change of the spin-charge interconversion by electric gating. This research serves as a promising avenue for electrically programmable spintronic devices.
GPT-4o mini: Non-social science research article
Immunoengineered mitochondria for efficient therapy of acute organ injuries via modulation of inflammation and cell repair
Qing Zhang, Yan Shen, Chengyuan Zhang, Hanyi Zhang, Xuemei Li, Shengqian Yang, Chen Dai, Xiuyan Yu, Jie Lou, Jinwei Feng, Chenglu Hu, Zhihua Lin, Xiaohui Li, Xing Zhou
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Acute organ injuries represent a major public health concern, driven by inflammation and mitochondrial dysfunction, leading to cell damage and organ failure. In this study, we engineered neutrophil membrane–fused mitochondria (nMITO), which combine the injury-targeting and anti-inflammatory properties of neutrophil membrane proteins with the cell repairing function of mitochondria. nMITO effectively blocked inflammatory cascades and restored mitochondrial function, targeting both key mechanisms in acute organ injuries. In addition, nMITO selectively targeted damaged endothelial cells via ÎČ-integrins and were delivered to injured tissues through tunneling nanotubes, enhancing their regulatory effects on inflammation and cell damage. In mouse models of acute myocardial injury, liver injury, and pancreatitis, nMITO notably reduced inflammatory responses and repaired tissue damage. These findings suggest that nMITO is a promising therapeutic strategy for managing acute organ injuries.
GPT-4o mini: Non-social science research article
Cascaded-mode interferometers: Spectral shape and linewidth engineering
Jinsheng Lu, Ileana-Cristina Benea-Chelmus, Vincent Ginis, Marcus Ossiander, Federico Capasso
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Interferometers are essential tools for measuring and shaping optical fields, widely used in optical metrology, sensing, laser physics, and quantum mechanics. They superimpose waves with a mutual phase delay, modifying light intensity. A frequency-dependent phase delay enables spectral shaping for filtering, routing, wave shaping, or multiplexing. Conventional Mach-Zehnder interferometers generate sinusoidal output intensities, limiting spectral engineering capabilities. Here, we propose a framework that uses interference of multiple transverse modes within a single multimode waveguide to achieve arbitrary spectral shapes in a compact geometry. Designed corrugated gratings couple these modes, enabling energy exchange akin to a beam splitter for easy multimode handling. We theoretically and experimentally demonstrate spectra with independently tunable linewidth and free spectral range, along with distinct spectral shapes for various transverse modes. Our method applies to orthogonal modes of different orders, polarization, and angular momentum, offering potential for sensing, calibration, metrology, and computing.
GPT-4o mini: Non-social science research article
Teleconnection from Arctic warming suppresses long-term warming in central Eurasia
Hainan Gong, Lin Wang, James A. Screen, Wen Chen, Judah Cohen, Renguang Wu
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Whether the rapid warming of the Arctic, particularly the Barents-Kara Sea (BKS), substantially affects the Eurasian winter climate has been debated for over a decade. Here, we use an extended dynamical adjustment method to separate the effects of internal dynamics and thermodynamically forced BKS warming on atmospheric circulation, relying solely on observations. Evidence shows that the observed link between BKS warming and Eurasian cooling is influenced by both atmospheric internal variability and forced BKS warming. Internal variability, particularly the Arctic Oscillation, predominantly contributed to the observed Eurasian cooling from 1991 to 2012. While BKS warming has a weaker impact on Eurasian cooling on interannual to interdecadal timescales, it notably affects multidecadal scales, contributing to the observed “warming hole” in central Eurasia during 1980–2022. Our findings suggest a weak but non-negligible Eurasian cooling response to BKS warming on multidecadal timescales. These findings advance the understanding of the complex causal relationships between Arctic and mid-latitude climates.
GPT-4o mini: Non-social science research article
Phi29 assembly intermediates reveal how scaffold interactions with capsid protein drive capsid construction and maturation
Michael Woodson, Nikolai S. Prokhorov, Seth D. Scott, Wei Zhao, Wei Zhang, Kyung H. Choi, Paul J. Jardine, Marc C. Morais
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The self-assembly of bacteriophage capsids from major capsid proteins (MCPs) and scaffolding proteins (SPs) and the subsequent expansion of these capsids are essential steps in bacteriophage life cycles. However, the mechanism by which assembly occurs remains poorly understood, and few intermediate states are available to illuminate the expansion of meta-stable procapsids into robust mature capsids. Here, we present the structure of a partially expanded phi29 procapsid that reveals distinct conformations of MCPs and allows visualization of SPs in multiple oligomeric states. These results suggest that formation of SP dimers, tetramers, and higher-order oligomers drives dissociation of SP from MCP to actuate capsid expansion. Hexons expand first, and we propose penton maturation is delayed by a symmetry match with SP oligomers. We further show that the prolate shape of phi29’s capsid is possible due to concave hexons in the equatorial region of the capsid that may alter interactions with SP and explain the observed dependence of the prolate shape on SP.
GPT-4o mini: Non-social science research article
Using waste CO 2 to produce essential amino acids for humans: An efficient photoelectrochemical route
Xiaoran Zhang, Yanhong Lyu, Jingjing Ding, Xin Wang, Bernt Johannessen, San Ping Jiang, Jianyun Zheng
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l -phenylalanine ( l -Phe), an essential amino acid for humans, is widely used as building blocks. Currently, l -Phe is obtained via biosynthetic methods including microbial and enzymatic processes, but their tightly complex feedback regulation and lengthy reaction steps lead to a low practical yield of l -Phe. Here, we have designed a hierarchical Si-based photocathode for l -Phe synthesis by photoelectrochemical coupling of waste CO 2 and nitrophenyl ethane, achieving a high yield rate of 37.5 ÎŒg·hour −1 ·cm −2 and a remarkable Faradaic efficiency of 21.2% at low applied potential under 1 sun illumination. The hierarchical structure with CuO-TiO 2 -C mixtures dispersed in amorphous TiO 2 layer/n + p-Si creates an internal built-in electric field and forms plentiful conducting channels to efficiently realize the injection of electrons into Cu and Ti sites. These Cu and Ti sites adsorb and activate the CO 2 and nitrophenyl ethane, respectively, cooperatively facilitating the l -Phe synthesis. This work introduces an environmentally friendly and highly efficient approach for converting solar energy into valuable amino acid products.
GPT-4o mini: Non-social science research article
Transfer RNA acetylation regulates in vivo mammalian stress signaling
Supuni Thalalla Gamage, Roxane Khoogar, Shereen Howpay Manage, Judey T. DaRos, McKenna C. Crawford, Joe Georgeson, Bogdan V. Polevoda, Chelsea Sanders, Kendall A. Lee, Kellie D. Nance, Vinithra Iyer, Anatoly Kustanovich, Minervo Perez, Chu T. Thu, Sam R. Nance, Ruhul Amin, Christine N. Miller, Ronald J. Holewinski, Sudipto Das, Thomas J. Meyer, Vishal Koparde, Acong Yang, Parthav Jailwala, Joe T. Nguyen, Thorkell Andresson, Kent Hunter, Shuo Gu, Beverly A. Mock, Elijah F. Edmondson, Simone Difilippantonio, Raj Chari, Schraga Schwartz, Mitchell R. O’Connell, Colin Chih-Chien Wu, Jordan L. Meier
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Transfer RNA (tRNA) modifications are crucial for protein synthesis, but their position-specific physiological roles remain poorly understood. Here, we investigate the impact of N 4 -acetylcytidine (ac 4 C), a highly conserved tRNA modification catalyzed by the essential acetyltransferase Nat10. By targeting Thumpd1, a nonessential adapter protein required for Nat10-catalyzed tRNA acetylation, we determine that loss of tRNA acetylation leads to reduced levels of tRNA Leu , increased ribosome stalling, and activation of eIF2α phosphorylation. Thumpd1 knockout mice exhibit growth defects and sterility. Concurrent knockout of Thumpd1 and the stress-sensing kinase Gcn2 causes penetrant postnatal lethality in mice, indicating a critical genetic interaction. Our findings demonstrate that a modification restricted to a single position within type II cytosolic tRNAs can regulate ribosome-mediated stress signaling in mammalian organisms, with implications for our understanding of translational control and therapeutic interventions.

Socio-Economic Review

A cohabitation wealth premium for women and men: considering the regulatory framework and normative acceptance in France and Germany
Nicole Kapelle, Nicolas Frémeaux, Philipp M Lersch, Marion Leturcq
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We examine the association between cohabitation and women’s and men’s wealth, closely considering the distinct regulatory and normative contexts in France and Eastern and Western Germany. Using longitudinal data from the German Socio-Economic Panel Study (2002–2017) and the French wealth survey Histoire de Vie et Patrimoine (2014/15-2020/21), we apply fixed-effects regression models to examine potential wealth advantages associated with cohabitation, including the relevance of gender and contextual differences. We find that cohabitation is positively associated with women’s and men’s wealth across contexts, without meaningful gender differences. For France, entering a Pacs (i.e. registered cohabitation) is associated with an additional premium beyond the (unregistered) cohabitation premium—though these effects may not be causal. Overall, our results suggest that the regulatory treatment of cohabitation plays a more significant role in shaping the wealth accumulation of cohabiting women and men than normative acceptance, while gender has little impact on the associated benefits.
On Jana Costas’, Dramas of dignity: cleaners in the corporate underworld of Berlin . Cambridge: Cambridge University Press, 2022
Karen A Shire, Sumrin Kalia, Matt Vidal
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