We checked 7 multidisciplinary journals on Friday, November 07, 2025 using the Crossref API. For the period October 31 to November 06, we retrieved 9 new paper(s) in 4 journal(s).

Nature

GPT-4o mini: Non-social science research article
A probabilistic histological atlas of the human brain for MRI segmentation
Adrià Casamitjana, Matteo Mancini, Eleanor Robinson, Loïc Peter, Roberto Annunziata, Juri Althonayan, Shauna Crampsie, Emily Blackburn, Benjamin Billot, Alessia Atzeni, Oula Puonti, Yaël Balbastre, Peter Schmidt, James Hughes, Jean C. Augustinack, Brian L. Edlow, Lilla Zöllei, David L. Thomas, Dorit Kliemann, Martina Bocchetta, Catherine Strand, Janice L. Holton, Zane Jaunmuktane, Juan Eugenio Iglesias
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GPT-4o mini: Non-social science research article
An ATP-gated molecular switch orchestrates human messenger RNA export
Ulrich Hohmann, Max Graf, LĂĄszlĂł TiriĂĄn, BelĂ©n Pacheco-Fiallos, Ulla Schellhaas, Laura Fin, Dominik Handler, Alex W. Philipps, Daria Riabov-Bassat, Rupert W. Faraway, Thomas PĂŒhringer, Michael-Florian Szalay, Elisabeth Roitinger, Julius Brennecke, Clemens Plaschka
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GPT-4o mini: Non-social science research article
The new frontier in understanding human and mammalian brain development
Tomasz J. Nowakowski, Patricia R. Nano, Katherine S. Matho, Xiaoyin Chen, Emily K. Corrigan, Wubin Ding, Yuan Gao, Matthew Heffel, Jaikishan Jayakumar, Harris S. Kaplan, Fae N. Kronman, Rothem Kovner, Camiel C. A. Mannens, Mengyi Song, Marilyn R. Steyert, Sridevi Venkatesan, Jenelle L. Wallace, Li Wang, Jonathan M. Werner, Di Zhang, Guohua Yuan, Guolong Zuo, Seth A. Ament, Carlo Colantuoni, Catherine Dulac, Rong Fan, Jesse Gillis, Arnold R. Kriegstein, Fenna M. Krienen, Yongsoo Kim, Sten Linnarsson, Partha P. Mitra, Alex A. Pollen, Nenad Sestan, Daniel J. Tward, Cindy T. J. van Velthoven, Zizhen Yao, Aparna Bhaduri, Hongkui Zeng
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GPT-4o mini: Non-social science research article
Millisecond lifetimes and coherence times in 2D transmon qubits
Matthew P. Bland, Faranak Bahrami, Jeronimo G. C. Martinez, Paal H. Prestegaard, Basil M. Smitham, Atharv Joshi, Elizabeth Hedrick, Shashwat Kumar, Ambrose Yang, Alexander C. Pakpour-Tabrizi, Apoorv Jindal, Ray D. Chang, Guangming Cheng, Nan Yao, Robert J. Cava, Nathalie P. de Leon, Andrew A. Houck
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GPT-4o mini: Non-social science research article
Author Correction: The emergence of transcriptional identity in somatosensory neurons
Nikhil Sharma, Kali Flaherty, Karina Lezgiyeva, Daniel E. Wagner, Allon M. Klein, David D. Ginty
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GPT-4o mini: Non-social science research article
Myriad Aryne Derivatives from Carboxylic Acids
Chris M. Seong, Sallu S. Kargbo, Chia-Ling Yu, Daniel Gibney, Jan-Niklas Boyn, Courtney C. Roberts
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GPT-4o mini: Non-social science research article
Assessing phylogenetic confidence at pandemic scales
Nicola De Maio, Nhan Ly-Trong, Samuel Martin, Bui Quang Minh, Nick Goldman
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Phylogenetics has a central role in evolutionary biology and genomic epidemiology 1 . Assessing phylogenetic confidence and reliability is therefore crucial and the methods that do this, such as those derived from Felsenstein’s bootstrap 2 , are among the most widely used in modern science. However, these methods require enormous computational capacity, and are unsuitable for large datasets. Furthermore, most of these methods emerge from a focus on the membership of clades (groupings of taxa), which makes their results difficult to interpret in the context of genomic epidemiology. Here we propose subtree pruning and regrafting-based tree assessment (SPRTA), an efficient and interpretable approach to assess confidence in phylogenetic trees. SPRTA shifts the paradigm of phylogenetic support measurement from evaluating the confidence in clades to evolution histories and phylogenetic placement—for example, assessing whether a lineage evolved from another considered lineage, which is particularly valuable in genomic epidemiology. We use SPRTA to investigate a global public SARS-CoV-2 phylogenetic tree relating more than two million genomes, highlighting plausible alternative evolutionary origins of many SARS-CoV-2 variants, assessing reliability in the Pango outbreak lineage classification system 3 , and demonstrating the effect of phylogenetic uncertainty on inferred mutation rates. Our results show that SPRTA enables pandemic-scale and detailed probabilistic assessment of transmission and mutational histories. Our method introduces a new approach to assessing phylogenetic confidence, enhancing the interpretability of pandemic-scale phylogenetic analyses and improving our ability to prepare for and respond to future pandemics.
GPT-4o mini: Non-social science research article
Spatial dynamics of brain development and neuroinflammation
Di Zhang, Leslie A. Rubio Rodríguez-Kirby, Yingxin Lin, Wenqi Wang, Mengyi Song, Li Wang, Lijun Wang, Shigeaki Kanatani, Tony Jimenez-Beristain, Yonglong Dang, Mei Zhong, Petra Kukanja, Shuozhen Bao, Shaohui Wang, Xinyi Lisa Chen, Fu Gao, Dejiang Wang, Hang Xu, Cong Ma, Xing Lou, Yang Liu, Jinmiao Chen, Nenad Sestan, Per Uhlén, Arnold Kriegstein, Hongyu Zhao, Gonçalo Castelo-Branco, Rong Fan
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GPT-4o mini: Non-social science research article
Lineage-resolved atlas of the developing human cortex
Matthew G. Keefe, Marilyn R. Steyert, Tomasz J. Nowakowski
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GPT-4o mini: Non-social science research article
Accelerating the discovery of multicatalytic cooperativity
Marcus H. Sak, Richard Y. Liu, Eugene E. Kwan, Eric N. Jacobsen
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GPT-4o mini: Non-social science research article
Lymphoid gene expression supports neuroprotective microglia function
Pinar Ayata, Jessica M. Crowley, Matthew F. Challman, Vinaya Sahasrabuddhe, Maud Gratuze, Sebastian Werneburg, Diogo Ribeiro, Emma C. Hays, Violeta DurĂĄn-Laforet, Travis E. Faust, Philip Hwang, Francisco Mendes Lopes, Chrysa Nikopoulou, Sarah Buchholz, Robert E. Murphy, Taoyu Mei, Anna A. Pimenova, Carmen Romero-Molina, Francesca Garretti, Tulsi A. Patel, Claudia De Sanctis, Angie V. Ramirez Jimenez, Megan Crow, Felix D. Weiss, Jason D. Ulrich, Edoardo Marcora, John W. Murray, Felix Meissner, Andreas Beyer, Dan Hasson, John F. Crary, Dorothy P. Schafer, David M. Holtzman, Alison M. Goate, Alexander Tarakhovsky, Anne Schaefer
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Microglia, the innate immune cells of the brain, play a defining role in the progression of Alzheimer’s disease (AD) 1 . The microglial response to amyloid plaques in AD can range from neuroprotective to neurotoxic 2 . Here we show that the protective function of microglia is governed by the transcription factor PU.1, which becomes downregulated following microglial contact with plaques. Lowering PU.1 expression in microglia reduces the severity of amyloid disease pathology in mice and is linked to the expression of immunoregulatory lymphoid receptor proteins, particularly CD28, a surface receptor that is critical for T cell activation 3,4 . Microglia-specific deficiency in CD28, which is expressed by a small subset of plaque-associated PU.1 low microglia, promotes a broad inflammatory microglial state that is associated with increased amyloid plaque load. Our findings indicate that PU.1 low CD28-expressing microglia may operate as suppressive microglia that mitigate the progression of AD by reducing the severity of neuroinflammation. This role of CD28 and potentially other lymphoid co-stimulatory and co-inhibitory receptor proteins in governing microglial responses in AD points to possible immunotherapy approaches for treating the disease by promoting protective microglial functions.
GPT-4o mini: Non-social science research article
Atomically accurate de novo design of antibodies with RFdiffusion
Nathaniel R. Bennett, Joseph L. Watson, Robert J. Ragotte, Andrew J. Borst, DĂ©JenaĂ© L. See, Connor Weidle, Riti Biswas, Yutong Yu, Ellen L. Shrock, Russell Ault, Philip J. Y. Leung, Buwei Huang, Inna Goreshnik, John Tam, Kenneth D. Carr, Benedikt Singer, Cameron Criswell, Basile I. M. Wicky, Dionne Vafeados, Mariana Garcia Sanchez, Ho Min Kim, Susana VĂĄzquez Torres, Sidney Chan, Shirley M. Sun, Timothy T. Spear, Yi Sun, Keelan O’Reilly, John M. Maris, Nikolaos G. Sgourakis, Roman A. Melnyk, Chang C. Liu, David Baker
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GPT-4o mini: Non-social science research article
Fair human-centric image dataset for ethical AI benchmarking
Alice Xiang, Jerone T. A. Andrews, Rebecca L. Bourke, William Thong, Julienne M. LaChance, Tiffany Georgievski, Apostolos Modas, Aida Rahmattalabbi, Yunhao Ba, Shruti Nagpal, Orestis Papakyriakopoulos, Dora Zhao, Jinru Xue, Victoria Matthews, Linxia Gong, Austin T. Hoag, Mircea Cimpoi, Swami Sankaranarayanan, Wiebke Hutiri, Morgan K. Scheuerman, Albert S. Abedi, Peter Stone, Peter R. Wurman, Hiroaki Kitano, Michael Spranger
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Computer vision is central to many artificial intelligence (AI) applications, from autonomous vehicles to consumer devices. However, the data behind such technical innovations are often collected with insufficient consideration of ethical concerns 1–3 . This has led to a reliance on datasets that lack diversity, perpetuate biases and are collected without the consent of data rights holders. These datasets compromise the fairness and accuracy of AI models and disenfranchise stakeholders 4–8 . Although awareness of the problems of bias in computer vision technologies, particularly facial recognition, has become widespread 9 , the field lacks publicly available, consensually collected datasets for evaluating bias for most tasks 3,10,11 . In response, we introduce the Fair Human-Centric Image Benchmark (FHIBE, pronounced ‘Feebee’), a publicly available human image dataset implementing best practices for consent, privacy, compensation, safety, diversity and utility. FHIBE can be used responsibly as a fairness evaluation dataset for many human-centric computer vision tasks, including pose estimation, person segmentation, face detection and verification, and visual question answering. By leveraging comprehensive annotations capturing demographic and physical attributes, environmental factors, instrument and pixel-level annotations, FHIBE can identify a wide variety of biases. The annotations also enable more nuanced and granular bias diagnoses, enabling practitioners to better understand sources of bias and mitigate potential downstream harms. FHIBE therefore represents an important step forward towards trustworthy AI, raising the bar for fairness benchmarks and providing a road map for responsible data curation in AI.
GPT-4o mini: Non-social science research article
Adenosine signalling drives antidepressant actions of ketamine and ECT
Chenyu Yue, Na Wang, Haojiang Zhai, Zhengwei Yuan, Yuting Cui, Jing Quan, Yu Zhou, Xiaofeng Fan, Hongshuang Wang, Zhaofa Wu, Huijie Mi, Wooping Ge, Yulong Li, Xiaohui Wang, Minmin Luo
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GPT-4o mini: Non-social science research article
Conservation and alteration of mammalian striatal interneurons
Emily K. Corrigan, Michael DeBerardine, Aunoy Poddar, Miguel Turrero GarcĂ­a, Sean de la O, Siting He, Harsha Sen, Mariana Duhne, Shanti Lindberg, Menygi Song, Matthew T. Schmitz, Karen E. Sears, Ricardo Mallarino, Joshua D. Berke, Corey C. Harwell, Mercedes F. Paredes, Fenna M. Krienen, Alex A. Pollen
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GPT-4o mini: Non-social science research article
Structural snapshots capture nucleotide release at the Ό-opioid receptor
Saif Khan, Aaliyah S. Tyson, Mohsen Ranjbar, Zixin Zhang, Jaskaran Singh, Gye Won Han, Cornelius Gati
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GPT-4o mini: Non-social science research article
Global satellite survey reveals uncertainty in landfill methane emissions
Matthieu Dogniaux, Joannes D. Maasakkers, Marianne Girard, Dylan Jervis, Jason McKeever, Berend J. Schuit, Shubham Sharma, Ana Lopez-Noreña, Daniel J. Varon, Ilse Aben
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Methane is a potent but short-lived greenhouse gas and rapid reductions of its anthropogenic emissions could help decrease near-term warming 1 . Solid waste emits methane through the decay of organic material, which amounts to about 10% of total anthropogenic methane emissions 2 . Satellite instruments 3 enable monitoring of strong methane hotspots 4 , including many strongly emitting urban areas that include solid waste disposal sites as most prominent sources 5 . Here we present a survey of methane emissions from 151 individual waste disposal sites across six continents using high-resolution satellite observations that can detect localized methane emissions above 100 kg h –1 . Within this dataset, we find that our satellite-based estimates generally show no correlation with reported or modelled emission estimates at facility scale. This reveals major uncertainties in the current understanding of methane emissions from waste disposal sites, warranting further investigations to reconcile bottom-up and top-down approaches. We also observe that managed landfills show lower emission per area than dumping sites, and that detected emission sources often align with the open non-covered parts of the facility where waste is added. Our results highlight the potential of high-resolution satellite observations to detect and monitor methane emissions from the waste sector globally, providing actionable insights to help improve emission estimates and focus mitigation efforts.
GPT-4o mini: Non-social science research article
Specificity, length and luck drive gene rankings in association studies
Jeffrey P. Spence, Hakhamanesh Mostafavi, Mineto Ota, Nikhil Milind, Tamara Gjorgjieva, Courtney J. Smith, Yuval B. Simons, Guy Sella, Jonathan K. Pritchard
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Standard genome-wide association studies (GWAS) and rare variant burden tests are essential tools for identifying trait-relevant genes 1 . Although these methods are conceptually similar, by analysing association studies of 209 quantitative traits in the UK Biobank 2–4 , we show that they systematically prioritize different genes. This raises the question of how genes should ideally be prioritized. We propose two prioritization criteria: (1) trait importance — how much a gene quantitatively affects a trait; and (2) trait specificity — the importance of a gene for the trait under study relative to its importance across all traits. We find that GWAS prioritize genes near trait-specific variants, whereas burden tests prioritize trait-specific genes. Because non-coding variants can be context specific, GWAS can prioritize highly pleiotropic genes, whereas burden tests generally cannot. Both study designs are also affected by distinct trait-irrelevant factors, complicating their interpretation. Our results illustrate that burden tests and GWAS reveal different aspects of trait biology and suggest ways to improve their interpretation and usage.
GPT-4o mini: Non-social science research article
Anti-progestin therapy targets hallmarks of breast cancer risk
Bruno M. SimĂ”es, Robert Pedley, Curtis W. McCloskey, Matthew Roberts, Austin D. Reed, Alecia-Jane Twigger, Pirashaanthy Tharmapalan, Amanda Caruso, Sara Cabral, Anthony J. Wilby, Hannah Harrison, Yuxi Zhou, Alice Greenhalgh, Suad A. Alghamdi, Martina Forestiero, Jesica Lopez-Muñoz, Jasmin Roche, Ren Jie Tuieng, Muhammad A. Khan, Steven Squires, Susan M. Astley, Elaine F. Harkness, AngĂ©lica Santiago-GĂłmez, Katherine Spence, Jessica Ritchie, Susan Pritchard, Yit Lim, Michael J. Sherratt, Sebastiano AndĂČ, Anthony Howell, D. Gareth Evans, Andrew P. Gilmore, Walid T. Khaled, Rama Khokha, Robert B. Clarke, Sacha J. Howell
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Breast cancer is the leading cause of cancer-related death in women worldwide 1 . Here, in the Breast Cancer-Anti-Progestin Prevention Study 1 (BC-APPS1; NCT02408770 ), we assessed whether progesterone receptor antagonism with ulipristal acetate for 12 weeks reduces surrogate markers of breast cancer risk in 24 premenopausal women. We used multilayered OMICs and live-cell approaches as readouts for molecular features alongside clinical imaging and tissue micromechanics correlates. Ulipristal acetate reduced epithelial proliferation (Ki67) and the proportion, proliferation and colony formation capacity of luminal progenitor cells, the putative cell of origin of aggressive breast cancers 2 . MRI scans showed reduction in fibroglandular volume with treatment, whereas single-cell RNA sequencing, proteomics, histology and atomic force microscopy identified extracellular matrix remodelling with reduced collagen organization and tissue stiffness. Collagen VI was the most significantly downregulated protein after ulipristal acetate treatment, and we uncovered an unanticipated spatial association between collagen VI and SOX9 high luminal progenitor cell localization, establishing a link between collagen organization and luminal progenitor activity. Culture of primary human breast epithelial cells in a stiff environment increased luminal progenitor activity, which was antagonized by anti-progestin therapy, strengthening this mechanistic link. This study offers a template for biologically informed early-phase therapeutic cancer prevention trials and demonstrates the potential for premenopausal breast cancer prevention with progesterone receptor antagonists through stromal remodelling and luminal progenitor suppression.
GPT-4o mini: Non-social science research article
Synthetic α-synuclein fibrils replicate in mice causing MSA-like pathology
Domenic Burger, Marianna Kashyrina, Lukas van den Heuvel, Hortense de La SeigliÚre, Amanda J. Lewis, Francesco De Nuccio, Inayathulla Mohammed, Jérémy VerchÚre, Cécile Feuillie, Mélanie Berbon, Marie-Laure Arotcarena, Aude Retailleau, Erwan Bezard, Marie-HélÚne Canron, Wassilios G. Meissner, Antoine Loquet, Luc Bousset, Christel Poujol, K. Peter R. Nilsson, Florent LaferriÚre, Thierry Baron, Dario Domenico Lofrumento, Francesca De Giorgi, Henning Stahlberg, François Ichas
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GPT-4o mini: Non-social science research article
Dispersion-engineered multipass optical parametric amplification
Jan H. NĂ€gele, Tobias Steinle, Johann Thannheimer, Philipp Flad, Harald Giessen
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GPT-4o mini: Non-social science research article
Vector-stimuli-responsive magnetorheological fibrous materials
Junhong Pu, Haiqiong Li, Jin Liu, Ke Li, Xiaoming Tao
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Fibrous materials that provide reversible actuation 1,2 or adapt mechanical properties 3,4 in response to external stimuli hold great promise for smart textiles 5 , soft robotics 6 and wearable technologies 7 . Although considerable progress has been made in creating fibrous materials responsive to scalar stimuli such as voltage 8 , temperature 6 , humidity 2 and ion concentration 9 , these technologies often lack directional controllability and functional diversity 10–14 . Here we report a class of vector-stimuli-responsive magnetorheological fibrous materials, guided by our engineering model integrating the structural mechanics of textiles with the magnetics of soft magnetic materials. We mass-produced soft magnetic polymer composite fibres with optimized mechanical and magnetic properties, which we then assembled into concentric helical yarns. These yarns exhibited pronounced bending and stiffening properties controlled by the direction and magnitude of magnetic fields, allowing for customized fabrics with various actuation and stiffening functionalities. We demonstrated innovative smart textiles derived from those fabrics, including an active ventilation fabric for personal moisture management, an integrated conformable gripper for handling objects of varying shapes and stiffness, and a compact remote-controllable haptic finger glove that replicates the sensation of fabric hardness and smoothness. Our work provides insights into stimuli-responsive fibrous materials, elevating them from scalar to sophisticated vector control, heralding an era of smart textile innovation.
GPT-4o mini: Non-social science research article
Two residues reprogram immunity receptors for nitrogen-fixing symbiosis
Magdalini Tsitsikli, Bine Simonsen, Thi-Bich Luu, Maria M. Larsen, Camilla G. Andersen, Kira Gysel, Damiano Lironi, Christina Krönauer, Henriette RĂŒbsam, Simon B. Hansen, RenĂ© BĂŠrentsen, Jesper Lundsgaard Wulff, Sarah Holt Johansen, GĂŒlendam Sezer, Jens Stougaard, Kasper RĂžjkjĂŠr Andersen, Simona Radutoiu
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GPT-4o mini: Non-social science research article
Independent mechanisms of inflammation and myeloid bias in VEXAS syndrome
Varun K. Narendra, Tandrila Das, Linsey J. Wierciszewski, Rebecca J. Londoner, Joshua K. Morrison, Pia Martindale, Tessa Devine, Kevin Chen, Michael Trombetta, Yuzuka Kanno, Alejandro E. Casiano, Elisa de Stanchina, Caleb A. Lareau, Scott W. Lowe, Alexander D. Gitlin
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GPT-4o mini: Non-social science research article
Author Correction: TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2
Manolis Pasparakis, Gilles Courtois, Martin Hafner, Marc Schmidt-Supprian, Arianna Nenci, Atiye Toksoy, Monika Krampert, Matthias Goebeler, Reinhard Gillitzer, Alain Israel, Thomas Krieg, Klaus Rajewsky, Ingo Haase
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GPT-4o mini: Non-social science research article
Transcriptomic and spatial organization of telencephalic GABAergic neurons
Cindy T. J. van Velthoven, Yuan Gao, Michael Kunst, Changkyu Lee, Delissa McMillen, Anish Bhaswanth Chakka, Tamara Casper, Michael Clark, Rushil Chakrabarty, Scott Daniel, Tim Dolbeare, Rebecca Ferrer, Jessica Gloe, Jeff Goldy, Junitta Guzman, Carliana Halterman, Windy Ho, Mike J. Huang, Katelyn James, Rachel McCue, Beagan Nguy, Trangthanh Cardenas, Kara Ronellenfitch, Emma D. Thomas, Amy Torkelson, Chelsea M. Pagan, Lauren Kruse, Nick Dee, Lydia Ng, Jack Waters, Kimberly A. Smith, Bosiljka Tasic, Zizhen Yao, Hongkui Zeng
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GPT-4o mini: Non-social science research article
Secretome translation shaped by lysosomes and lunapark-marked ER junctions
Heejun Choi, Ya-Cheng Liao, Young J. Yoon, Jonathan Grimm, Nan Wang, Luke D. Lavis, Robert H. Singer, Jennifer Lippincott-Schwartz
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GPT-4o mini: Non-social science research article
Targeting FSP1 triggers ferroptosis in lung cancer
Katherine Wu, Alec J. Vaughan, Jozef P. Bossowski, Yuan Hao, Aikaterini Ziogou, Seon Min Kim, Tae Ha Kim, Mari N. Nakamura, Ray Pillai, Mariana Mancini, Sahith Rajalingam, Mingqi Han, Toshitaka Nakamura, Lidong Wang, Suckwoo Chung, Diane Simeone, David Shackelford, Yun Pyo Kang, Marcus Conrad, Thales Papagiannakopoulos
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GPT-4o mini: Non-social science research article
Continuous cell-type diversification in mouse visual cortex development
Yuan Gao, Cindy T. J. van Velthoven, Changkyu Lee, Emma D. Thomas, Rémi Mathieu, Angela P. Ayala, Stuard Barta, Darren Bertagnolli, Jazmin Campos, Trangthanh Cardenas, Daniel Carey, Tamara Casper, Anish Bhaswanth Chakka, Rushil Chakrabarty, Megan Chiang, Lindsey Ching, Michael Clark, Marie J. Desierto, Rebecca Ferrer, Jessica Gloe, Jeff Goldy, Nathan Guilford, Junitta Guzman, Carliana R. Halterman, Samantha D. Hastings, Daniel Hirschstein, Windy Ho, Katelyn James, Zoe Juneau, Naomi Martin, Rachel McCue, Emma Meyerdierks, Amanda C. Mitchell, Josh S. Nagra, Beagan Nguy, Thuc Nghi Nguyen, Paul Olsen, Alana A. Oyama, Nick Pena, Jacob Quon, Qingzhong Ren, Augustin Ruiz, Nadiya V. Shapovalova, Josef Sulc, Amy Torkelson, Alex Tran, Herman Tung, Nasmil Valera Cuevas, Justin Wang, Jeanelle Ariza, Delissa A. M. McMillen, Jack Waters, Michael Kunst, Kara Ronellenfitch, Boaz Levi, Michael J. Hawrylycz, Chelsea Pagan, Nick Dee, Kimberly A. Smith, Bosiljka Tasic, Zizhen Yao, Hongkui Zeng
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GPT-4o mini: Non-social science research article
The importance of past rifting in large igneous province development
R. Kounoudis, I. D. Bastow, C. J. Ebinger, S. Goes, P. Zhou, M. Musila, C. S. Ogden, A. Ayele
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Lithospheric thin zones, such as recently failed rifts, are generally assumed to be weak spots where magmatism and deformation can concentrate during rifting and large igneous province development 1–3 . Yet, the Turkana Depression in East Africa, the site of the failed 66-million-year-old Anza Rift, did not experience the widespread flood magmatism seen on the adjacent Ethiopian Plateau, despite being a lithospheric thin spot when the region encountered hot plume material around 45 million years ago 4 . Here we jointly invert surface-wave and receiver function data to constrain crustal and upper-mantle seismic structure below the Depression to evaluate lithospheric thermo-mechanical modification. Evidence for thick lower crustal intrusions, ubiquitous below the uplifted Ethiopian Plateau 5,6 , is comparatively lacking below the Depression’s failed Anza Rift system, which ongoing East African rifting is circumnavigating, not exploiting. The mantle lithosphere below the Depression has also retained its cool, fast-wavespeed ‘lid’ character, contrasting the Ethiopian Plateau. Volatile depletion during failed Anza rifting probably rendered the thinned lithosphere refractory without later rejuvenation. Subsequent rifting and magmatism thus initiated away from the still-thin Anza Rift, in regions where fertile lithosphere enabled melting and the sufficient lowering of plate yield strength. Areas of thinned lithosphere are thus not necessarily persistent weak zones where significant extension and magmatic provinces will develop.
GPT-4o mini: Non-social science research article
Lymph node environment drives FSP1 targetability in metastasizing melanoma
Mario Palma, Milena Chaufan, Cort B. Breuer, Sebastian MĂŒller, Marie Sabatier, Cameron S. Fraser, Krystina J. Szylo, Mahsa Yavari, Alanis Carmona, Mayher Kaur, Luiza Martins Nascentes Melo, Feyza Cansiz, June Monge-Lorenzo, Midori Flores, Eikan Mishima, Toshitaka Nakamura, Bettina Proneth, Marcos Labrado, Yanshan Liang, Nicole Cayting, Lan Zheng, Tatiana Cañeque, Ludovic Colombeau, Adam Wahida, JosĂ© Pedro Friedmann Angeli, Alpaslan Tasdogan, Sheng Hui, RaphaĂ«l Rodriguez, Marcus Conrad, Nathan E. Reticker-Flynn, Jessalyn M. Ubellacker
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GPT-4o mini: Non-social science research article
Eight millennia of continuity of a previously unknown lineage in Argentina
Javier Maravall-LĂłpez, Josefina M. B. Motti, NicolĂĄs Pastor, MarĂ­a PĂ­a Tavella, Mariana Fabra, Pilar Babot, Mariano Bonomo, Silvia E. Cornero, Guillermo N. Lamenza, Diego Catriel Leon, Paula C. Miranda de Zela, Gustavo G. Politis, SofĂ­a C. Angeletti, G. Roxana CattĂĄneo, Mariana Dantas, Hilton Drube, Lucia G. Gonzalez Baroni, SalomĂłn Hocsman, AndrĂ©s D. Izeta, Reinaldo A. Moralejo, VerĂłnica Aldazabal, Diego M. Basso, Cristina BayĂłn, MarĂ­a Guillermina Couso, Ulises D’Andrea, Paula Del RĂ­o, GermĂĄn G. Figueroa, Romina Frontini, Mariela Edith Gonzalez, AndrĂ©s G. Laguens, Jorge G. MartĂ­nez, Pablo G. Messineo, Beatriz Nores, Daniel E. Olivera, Gisela M. Sario, AnalĂ­a Sbattella, Clara Scabuzzo, Aldana M. Tavarone, Rodrigo Vecchi, Kim Callan, Ella Caughran, Oscar Estrada, Trudi Frost, Lora Iliev, Aisling Kearns, Jack Kellogg, Kim-Louise Krettek, Ann Marie Lawson, Matthew Mah, Nihal Manjila, Adam Micco, Iris Patterson, Lijun Qiu, Xavier Roca-Rada, Gregory Soos, Peter A. Webb, J. Noah Workman, Nadin Rohland, Nick Patterson, Iosif Lazaridis, Lars Fehren-Schmitz, Cosimo Posth, Bastien Llamas, Swapan Mallick, DarĂ­o A. Demarchi, Graciela S. Cabana, David Reich, Rodrigo Nores
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Ultrashort laser pulse amplified by back-and-forth propagation
Christoph Heyl, Marc Hanna
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Nature DOI suffix ≠ "/s...": Not a research article
By the time you hear these bats, it’s too late
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Daily briefing: How the plastics-treaty breakdown could pave the way for something better
Flora Graham
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Personalized gene editing helped one baby: can it be rolled out widely?
Heidi Ledford
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From pangolins to primates: how I use zoo facilities to treat wild animals
Jack Leeming
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Developmental maps of the brain trace when cell types emerge
Emily Sylwestrak
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How the rush for critical minerals is neglecting human needs
Daniel M. Franks, Paul Rogers, Fitsum Weldegiorgis, Lynda Lawson, Louise Gallagher, Natalie Gardner, Bora Aska, Johanna H. Linus, Shrey Varshney
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COVID-19 is spreading again — how serious is it and what are the symptoms?
Katie Kavanagh
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Longer walks beat shorter strolls for heart health
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Anosophoros
Christine Lucas
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How to fight climate change without the US: a guide to global action
Xiaoying You, Mariana Lenharo, Mohana Basu, Davide Castelvecchi, Jeff Tollefson
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How I’m helping to cultivate science entrepreneurship in Brazil
Emma Ulker
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Secret route to warm cosmic ‘inflation’: the nuclear force
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Climate change is devastating mining of minerals needed to fight it
Tom Savige, Mark Quigley, Tim T. Werner
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: A guide to global climate change action
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Wildlife wonders and a Super Heavy — the month’s best science images
Flora Graham
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When will Africa have a Nobel prize in medicine?
Nicholas Aderinto
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Too much social media gives AI chatbots ‘brain rot’
Rachel Fieldhouse
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Japan’s first female prime minister doesn’t call herself a feminist — but the country needs her to tackle sexism in science
Misa Shimuta
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‘Teenage T. rex’ fossil is actually a different species
Katie Kavanagh
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Forests’ misty breath sustains crops in distant lands
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PhD training needs a reboot in an AI world
Alex Sen Gupta
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Safeguards for virology must be designed in partnership with the public
Caesar Alimsinya Atuire, Jonathan Ewbank
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‘Memory foam’ skeleton in cells helps them to navigate
Joseph d’Alessandro, MĂ©lina L. HeuzĂ©
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Google claims ‘quantum advantage’ again — but researchers are sceptical
Elizabeth Gibney
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Most Antarctic ice shelves are set to disappear if greenhouse-gas emissions remain high
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Images for AI use can be sourced responsibly
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‘Google Maps’ for Roman roads reveals vast extent of ancient network
Katie Kavanagh
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Chinese scientists increasingly lead joint projects with the UK, US and Europe
Mohana Basu
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Powerful new antibiotic that can kill superbugs discovered in soil bacteria
Miryam Naddaf
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Insiders warn how dismantling federal agencies could put science at risk
Virginia Gewin
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Does gravity produce quantum weirdness? Proposal divides physicists
Davide Castelvecchi
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‘Biotech Barbie’ says the time has come to consider CRISPR babies. Do scientists agree?
Heidi Ledford
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The ‘implementation COP’: why the BelĂ©m summit must ratchet up climate action
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Sex, drugs and the conscious brain: Francis Crick beyond the double helix
Georgina Ferry
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Antibody drugs show promise for treating bird flu and HIV
Rachel Fieldhouse
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Shadow scholars: inside Kenya’s multibillion-dollar fake-essay industry
Anna McKie
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Can AI predict and limit online hate?
Chirantan Chatterjee
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Alzheimer’s decline slows with just a few thousand steps a day
Mariana Lenharo
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Why India’s controversial ‘cloud seeding’ trial failed to make it rain
Mohana Basu
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Single video camera tells the story of deadly Myanmar quake
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‘Mind-captioning’ AI decodes brain activity to turn thoughts into text
Max Kozlov
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Meet the ‘Wee-rex’. Tiny tyrannosaur is its own species
Benjamin Thompson, Shamini Bundell
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China should undertake more risky research to close the Nobel gap
Alex J. Yang, Sanhong Deng, Richard B. Freeman
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My funding applications are taking up too much time. How can I stay focused on my research?
Xiaoying You
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Artificial brains with less drain
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From the archive: Do sunspots affect the price of corn?
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Daily briefing: The bowhead whale’s secret to living to 200
Jacob Smith
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Daily briefing: Custom-made gene-editing therapy for children to enter clinical trial
Flora Graham
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Please stay out of the abandoned buildings
Amanda Dier
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Biggest black-hole outburst ever seen records death throes of a star
Jenna Ahart
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First ever atlas of brain development shows how stem cells turn into neurons
Miryam Naddaf
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Can AI be truly creative?
Jo Marchant
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Daily briefing: UK science is ‘bleeding to death’, says report
Flora Graham
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Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Eliminating intercrystalline side effects for stable lithium metal batteries
Xingwei Sun, Yang Feng, Jiangtao Yu, Yong Lu, Shuo Xu, Ying Jiang, Haixia Li, Zhenhua Yan, Kai Zhang, Jun Chen
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Lithium metal is widely recognized as the ultimate anode material for next-generation lithium batteries due to its superior specific capacity. However, microscopic crystallographic heterogeneity caused by crystal faces and grain boundaries leads to nonuniform lithium deposition, thereby undermining the stability of lithium metal anode. This study systematically investigates the intricate impact of grain boundaries on the structural characteristics, deposition behavior, and electrochemical properties of lithium metal. We demonstrate that grain boundaries serve as preferential nucleation sites, exacerbating morphological heterogeneity. Although eliminating preexisting grain boundaries from substrate facilitates homogeneous lithium nucleation and enhances electrochemical performance, this approach does not address the deposition issues originating from the intercrystalline regions of newly deposited grains. Furthermore, the continuous expansion of the intercrystalline network disrupts single-crystal structure and accelerates anode degradation, imposing a critical constraint on performance enhancement. This work unveils a previously overlooked intercrystalline-driven failure mechanism and provides insights for realizing dendrite-free lithium batteries.
GPT-4o mini: Non-social science research article
Loss of calcium-dependent protein kinases OsCPK5 and OsCPK13 leads to NLR-dependent resistance in rice
Zhanchun Wang, Shibo Yu, Wencai Xu, Han Peng, Xuan Zhou, Anja Liese, Lilan Chen, Guitao Zhong, Chen Zhong, Xianya Deng, Libo Han, Na Liu, Justin Lee, Tina Romeis, Dingzhong Tang, Wei Wang
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Calcium (Ca 2+ ) signaling plays a crucial role in plant immunity, regulating both pattern-triggered immunity (PTI) through cell-surface receptors and effector-triggered immunity (ETI) via intracellular nucleotide-binding, leucine-rich repeat receptors (NLRs). Calcium-dependent protein kinases (CPKs/CDPKs) serve as key Ca 2+ sensors and signal transducers in these processes. In this study, we demonstrate the relevance of two rice CPKs, OsCPK5 and OsCPK13, for rice blast resistance. Both are Ca 2+ -responsive kinases, with potential in planta heteromer formation enhancing their phosphorylation/signaling functions. Single oscpk5 and oscpk13 mutants exhibit impaired early PTI responses and enhanced susceptibility to rice blast fungus, suggesting that these kinases are essential for effective immunity. Surprisingly, although it is also defective in PTI, the oscpk5 / 13 double mutant displays enhanced resistance to rice blast. An NLR protein OsCPK5/13-ASSOCIATING RESISTANCE PROTEIN 1 (OsCARP1), which is physically associated with both OsCPK5 and OsCPK13, is genetically required for the heightened resistance of oscpk5 / 13. Furthermore, OsCARP1-induced cell death in Nicotiana benthamiana can be suppressed by the expression of OsCPK5 and OsCPK13. Based on these findings, we postulate that the positive blast resistance roles of OsCPK5 and OsCPK13 are guarded by OsCARP1, thus leading to OsCARP1-dependent ETI resistance in the oscpk5 / 13 double mutant or upon manipulation by still unknown pathogen effectors during infection. Our results offer insights into how plants counteract potential pathogen attack on key Ca 2+ signaling immune components.
GPT-4o mini: Non-social science research article
Nanofluidic logic based on chiral skyrmion flows
Xichao Zhang, Jing Xia, Yan Zhou, Guoping Zhao, Xiaoxi Liu, Yongbing Xu, Masahito Mochizuki
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Particle-like chiral magnetic skyrmions can flow in nanotracks and behave like chiral fluids. Using interacting flows to perform logical operations is an important topic in microfluidics and nanofluidics. Here, we report a basic nanofluidic logic computing system based on chiral magnetic skyrmions flowing in parallel pipelines connected by an H-shaped junction. The flow behaviors could be manipulated by adjusting the spin polarization angle, which controls the intrinsic skyrmion Hall angle. We demonstrate that within certain range of the spin polarization angle, fully developed skyrmion flows could lead to fluidic logical operations, which significantly reduce the complexity of skyrmion logic as there is no need for deterministic creation, precise control, and detection of a single isolated skyrmion. Our results suggest that the chiral flow behaviors of magnetic quasiparticles may offer possibilities for spintronic and nanofluidic functions.
GPT-4o mini: Non-social science research article
Energetically expensive dynamo action in Earth’s basal magma ocean
Nathanaël Schaeffer, Stéphane Labrosse, Jonathan M. Aurnou
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Previous studies focusing on the electrical conductivity and thermal evolution of an early magma ocean at the base of Earth’s mantle have found that basal magma ocean (BMO) convection could have produced the ancient geomagnetic field. By advances in high-resolution dynamo modeling, we find that convection in a thin BMO-like spherical shell is able to sustain strong magnetic fields, including axial dipolar fields similar to current day field structure. However, integrating our dynamo results with improved thermal evolution models and taking the planet’s rapid rotation into account using rotating convective turbulence models implies that an Earth-like magnetic field was unlikely to have been generated in the BMO, a finding relevant to the interpretation of ancient paleomagnetic signatures, Earth’s global-scale dynamics, and long-term planetary evolution. Large uncertainties still remain, calling for refined models of deep Earth thermal and mineralogical processes, accurate determination of prefactors in convective scaling laws, and fully coupled core-BMO dynamo simulations. Nonetheless, our work highlights that BMO-type dynamos intrinsically require a larger product of electrical conductivity and velocity than core-type dynamos, and that they are similarly rotationally constrained, so that velocities are significantly reduced compared to nonrotating estimates.
GPT-4o mini: Non-social science research article
From sequence to scaffold: Computational design of protein nanoparticle vaccines from AlphaFold2-predicted building blocks
Cyrus M. Haas, Naveen Jasti, Annie Dosey, Joel D. Allen, Rebecca Gillespie, Jackson McGowan, Elizabeth M. Leaf, Max Crispin, Cole A. DeForest, Masaru Kanekiyo, Neil P. King
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Self-assembling protein nanoparticles are being increasingly utilized in the design of next-generation vaccines due to their ability to induce antibody responses of superior magnitude, breadth, and durability. Computational protein design offers a route to nanoparticle scaffolds with structural and biochemical features tailored to specific vaccine applications. Although strategies for designing self-assembling proteins have been established, the recent development of powerful machine learning (ML)–based tools for protein structure prediction and design provides an opportunity to overcome several of their limitations. Here, we leveraged these tools to develop a generalizable method for designing self-assembling proteins starting from AlphaFold2 predictions of oligomeric protein building blocks. We used the method to generate six 60-subunit protein nanoparticles with icosahedral symmetry, and single-particle cryoelectron microscopy reconstructions of three of them revealed that they were designed with atomic-level accuracy. To transform one of these nanoparticles into a functional immunogen, we reoriented its termini through circular permutation, added a genetically encoded oligomannose-type glycan, and displayed a stabilized trimeric variant of the influenza hemagglutinin receptor-binding domain through a rigid de novo linker. The resultant immunogen elicited potent receptor-blocking and neutralizing antibody responses in mice. Our results demonstrate the practical utility of ML–based protein modeling tools in the design of nanoparticle vaccines. More broadly, by eliminating the requirement for experimentally determined structures of protein building blocks, our method dramatically expands the number of starting points available for designing self-assembling proteins.
GPT-4o mini: Non-social science research article
Peptide vaccine formulations with structurally distinct STING agonist drugamers induce discrete, efficacious antitumor responses
Kefan Song, Dinh Chuong Nguyen, Yonghui Wang, Simbarashe Jokonya, Omeed Yazdani, Drew L. Sellers, Patrick S. Stayton, Suzie H. Pun
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Peptide therapeutic cancer vaccines are an attractive treatment modality for their safety and manufacturability but have been hindered in clinical translation by low immunogenicity and insufficient CD8 + T cell activation. We developed virus-inspired polymers for endosomal release (VIPER) to address systemic and intracellular delivery obstacles, but durable antitumor immunity remained elusive. Adjuvants stimulating innate immunity, such as stimulator of interferon genes (STING) agonists, can enhance vaccine potency but risks systemic toxicity and improper immune activation. We developed STING “drugamers” with cathepsin-cleavable linkers and dendritic cell (DC)-targeting moieties for intracellular delivery of STING agonists to DCs. We explored two different STING drugamer structures: a hydrophilic statistical polymer “polySTING” and a diblock polymer “NPSTING” that forms into nanoparticles. PolySTING achieved higher systemic STING agonist delivery, whereas NPSTING is more efficient in delivering STING agonists into inguinal lymph nodes (LNs). Both drugamer platforms enhanced STING activation and DC maturation compared to the free drug. When combined with VIPER, NPSTING generated more antigen-presenting DCs in the LNs and more antigen-responsive CD8 + T cells in the spleens, whereas polySTING generated more tumor-infiltrating CD8 + T cells and CD8 + DCs. Both VIPER–STING drugamer platforms demonstrated efficacy in a B16-OVA melanoma model and a MC38 colon cancer model. Combination treatment with anti-PD-1 immune checkpoint inhibitor results in tumor remission and tumor immunity in a subset of mice. This study highlights how an endosomolytic peptide vaccine platform combined with two structurally different drugamers induce superior antitumor responses through distinctive mechanisms.
GPT-4o mini: Non-social science research article
Correction for Young-Brun et al., Within-country inequality and the shaping of a just global climate policy
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GPT-4o mini: Non-social science research article
Reply to Uzoigwe: DLW is safe and validated
Amanda McGrosky, Amy Luke, Jennifer Rood, Hiroyuki Sagayama, Klaas R. Westerterp, William W. Wong, Yosuke Yamada, John R. Speakman, Herman Pontzer
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GPT-4o mini: Non-social science research article
Mobile species’ responses to surrounding land use generate trade-offs and synergies among nature’s contributions to people
Sophie A. O’Brien, Jason M. Tylianakis, Dean P. Anderson, Andrea Larissa Boesing, Hao Ran Lai, GaĂ«tane Le Provost, Peter Manning, Margot Neyret, Nico BlĂŒthgen, Kirsten Jung, Paul Magdon, Sandra MĂŒller, NoĂ«lle V. Schenk, Michael Scherer-Lorenzen, Sandra Lavorel
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Agricultural landscapes provide material, nonmaterial, and regulating contributions that affect human well-being (nature’s contributions to people, NCP). The responses of these NCP to land-use patterns depend on supporting biota with different habitat requirements, generating trade-offs and synergies. Predictions from spatially explicit modeling of NCP trade-offs and synergies could inform land-use decisions, but these do not typically account for the effects of land-use patterns on the movement of NCP-providing species, nor for interactions among NCP providers. To explore spatial trade-offs and synergies in eight indicators of NCP, we used Bayesian models that allow for interactions among land uses and among NCP using data from 150 grassland sites across rural Germany. We found that spatial arrangements of forest and open habitat influenced many beneficial NCP: acoustic diversity, birdwatching potential, natural enemy abundance, and pollination. In particular, the amount and proximity of land uses in the surrounding landscape, especially forest and open habitat, drove the supply of most NCP. However, detrimental NCP provided by smaller-bodied taxa (herbivory and pathogen infection) responded weakly to landscape factors. Multiple NCP provided by a given taxon responded differently to their surrounding landscape (e.g., bird-provided beneficial caterpillar predation and detrimental seed predation), leading to trade-offs and synergies among NCP over short distances. These were caused by different rates and directions of response to amount and location of land uses. Resulting spatial predictions revealed that the ratio of beneficial to detrimental NCP was maximized in areas with a high (≄95%) area of grassland or mixed forest-grassland (70:30%), rather than purely forest-dominated areas. This suggests promoting seminatural vegetation in agricultural landscapes to provide greater-than-additive benefits to net NCP supply.
GPT-4o mini: Non-social science research article
Molecular drivers of RNA phase separation
Vysakh Ramachandran, Davit A. Potoyan
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RNA molecules play central roles in the assembly and regulation of biomolecular condensates, often in concert with proteins containing low complexity RNA-binding domains. Recently, it has been shown that RNA can phase-separate in the absence of any proteins. Unlike protein-based condensates, RNAs condensates are strongly influenced by magnesium ions which play crucial roles in their dynamics and thermodynamics, giving rise to base-specific lower critical solution temperatures (LCSTs). The molecular basis and functional significance of sequence and ion-dependent LCST behavior RNA condensates have yet to be elucidated. Here, we use atomistic simulations to systematically dissect the driving forces underlying the sequence-, ion-, and temperature-dependent phase behaviors of RNA condensates. By choosing RNA tetranucleotides alongside their ssDNA counterpart and chemically modified analogs, we map equilibrium thermodynamic profiles and structural ensembles across various external conditions. Our results show that magnesium ions promote LCST behavior by inducing local disorder-order transitions within RNA structures. Additionally, the base chemistry and the 2’hydroxyl group of the ribose sugar further modulate this LCST response. In agreement with experiments, we find that the thermal stability of RNA condensates follows the order G n > A n > C n > U n , governed by the balance of base stacking and hydrogen bonding interactions. Moreover, our simulations reveal that posttranslational nucleotide modifications can fine-tune the threshold of RNA self-assembly and the resulting condensate structures.
GPT-4o mini: Non-social science research article
Mapping the placental galectin-3 interactome identifies CD9 and ITGB1 as functional glycoprotein counterreceptors during syncytialization
Abigail E. Reeves, Gil-Suk Yang, Sabyasachi Baboo, Jolene K. Diedrich, Pranali Bedekar, Shaheen A. Farhadi, Arun Wanchoo, Christopher Bratcher, Gregory A. Hudalla, John R. Yates, Mia L. Huang
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The fetomaternal interface is replete with glycan-binding proteins (GBPs) that can interact with cell surface glycoprotein counterreceptors to regulate placental function. Here, we interrogate the role of galectin-3, a GBP that controls placental trophoblast syncytialization, an important differentiation process where progenitor cytotrophoblast cells fuse to produce the multinucleated syncytiotrophoblast. The molecular mechanism of galectin-3-mediated fusion has not yet been elucidated in part due to the difficulty of studying glycan-GBP binding events in live cells. To overcome these challenges, we employ a proximity labeling strategy to identify the galectin-3 interactome. From this interactome dataset, we selected and validated CD9 and integrin beta 1 as functional counterreceptors of galectin-3 and showed that CD9 is glycosylated with an N-linked glycan at a rare noncanonical sequon. Furthermore, we present evidence that galectin-3 acts to physically alter the fluidity of the cellular membrane, and it does not activate canonical syncytialization signaling pathways. Overall, we report that galectin-mediated binding events and their corresponding functions in cell biology can be precisely regulated by select glycoproteins at specific glycosites.
GPT-4o mini: Non-social science research article
Predicted molecules followed by experimental validation for protecting human neurons from oxidative stress–induced cytotoxicity
Xuyu Yang, Joo-Youn Lee, Farbod Moghadam, Joseph Steiner, Soo-Kyung Kim, Neha Ganjur, Adrian J. de Almenara, Brian M. Stoltz, Y. Peng Loh, William A. Goddard
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Alzheimer neurodegenerative disease (AD) has had a major impact worldwide, with no effective drugs for treatment. We discovered and reported earlier that neurotrophic factor-α1 (NF-α1)/carboxypeptidase E (CPE) reversed neurodegeneration and cognitive dysfunction in AD mouse models. We then predicted computationally and validated experimentally that CPE interacts with a pharmacophore of six residues on the 5-HT1E receptor (HTR1E) to activate the ERK-BCL2 signaling pathway leading to protection of human neurons against oxidative stress–induced cell death. We now report using this pharmacophore for in silico virtual screening of ~6 million small molecules to discover candidates with similar binding and neuroprotective properties as CPE. This in silico search identified a molecule (Z124) that was verified experimentally to bind to HTR1E with protective efficacy comparable to NF-α1/CPE but requiring a higher concentration. Next, we carried out R-group design optimization based on Z124 to identify 4 compounds predicted to have much better efficacy than Z124. These compounds were synthesized and tested for neuroprotective activity. All four compounds showed binding to HTLA-HTR1E cells comparable to CPE. We determined the Kd for two of these compounds: R9, 1.38 ± 0.2 nM, and R10, 2.1 ± 0.2 nM, to be over 15 times better than CPE. Furthermore, all four new compounds showed protective activity against oxidative stress–induced cytotoxicity in human HEK293 cells stably transfected with HTR1E, as well as human primary neurons. Mechanistically, R9 and R10 activated ERK phosphorylation and increased the mitochondria prosurvival protein, BCL2, making them excellent candidates for further development as a drug to treat neurodegenerative diseases.
GPT-4o mini: Non-social science research article
The temporal dynamics of self-control
Paul E. Stillman, James D. Wilson, David A. Kalkstein, Melissa J. Ferguson
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Self-control—the ability to pursue long-term goals over short-term temptations—is a critical faculty of human cognition, but the cognitive processes enabling self-control are not well understood. Traditional models have focused on impulse inhibition: effortfully inhibiting prepotent motor responses toward a temptation, yielding a stage-based evolution of choice. Other models emphasize dynamic competition between goal and temptation, yielding a more integrative evolution of choice. Although these models represent fundamentally different conceptions of self-control, current methods are inadequate for investigating real-time dynamics, leaving the question of which model best describes self-control unresolved. We investigate these models using mouse-tracking: a dynamic, real-time measure of decision-making in which we measure participants’ computer mouse movements as they navigate tradeoffs between immediate and delayed gratification (e.g., $5 today vs. $20 in 3 mo). We develop a quantitative approach that integrates the rich spatial and temporal information contained in mouse trajectories, and find evidence for both impulse inhibition and dynamic competition. Notably, impulse inhibition is less frequent, occurring in only one-quarter of choices favoring larger later rewards over smaller sooner ones. We further find substantial individual variability on who relies on impulse inhibition, with more present-biased individuals more likely to use impulse inhibition to choose larger-later options. Finally, our approach reveals the diverse variability within impulse inhibition and dynamic competition, and accounting for this variability greatly strengthened models predicting out-of-sample choices. Our findings clarify the mechanisms underlying self-control and introduce a robust tool for quantifying real-time decision-making dynamics.
GPT-4o mini: Non-social science research article
Correction for Zhou et al., 9,000-year-old barley consumption in the foothills of central Asia
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GPT-4o mini: Non-social science research article
LHFPL5 is required for maximal activation of the mechanotransduction channel in cochlear hair cells
Xufeng Qiu, Jose P. Llongueras, Lili Yin, Christopher Cunningham, Ulrich MĂŒller
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Mechanoelectrical transduction (MET) channels in cochlear hair cells are gated by tip links through a mechanism that is poorly defined. LHFPL5 interacts with the tip-link component PCDH15 and the MET-channel component TMC1, suggesting that LHFPL5 regulates channel activation by mechanical force. To test this hypothesis, we analyzed MET in hair cells from mice expressing an LHFPL5 mutant protein lacking three N-terminal amino acids. These mutant mice suffer from recessive deafness, and MET is drastically impaired in cochlear hair cells. The resting open probability of the MET channels is increased in the mutants, while unitary channel conductance, adaptation, and tonotopic channel properties remain unaltered. Unlike in other LHFPL5 mutants, MET channel proteins are still present at normal levels in stereocilia of mutant mice. We conclude that LHFPL5 is required for maximal mechanical activation of MET channels in cochlear hair cells thereby affecting the hair bundle sensitivity to mechanical stimulation and thus the sound sensitivity of the auditory sense organ.
GPT-4o mini: Non-social science research article
Stimuli-responsive STING nanovaccine for systemic therapy of HPV-induced cancers
Shuang Chen, Shuyue Ye, Gang Huang, Zhichen Sun, Qiang Feng, Maggie Wang, Raymundo Pantoja, Baran D. Sumer, Jinming Gao
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In recent years, therapeutic cancer vaccines have been extensively investigated, aiming to boost cancer-specific T cells crucial for antitumor activity. The effectiveness of these vaccines is often limited by insufficient immune activation and suboptimal antigen delivery. Stimulator of interferon genes (STING) is an important immune signaling protein that activates host defense genes against infection and cancer. Clinical evaluation of small-molecule STING agonists has shown tepid antitumor responses with immune-related toxicities, particularly when they are administered systemically. To overcome these limitations, we report a stimuli-responsive STING nanovaccine for treating human papillomavirus (HPV)-induced cancers. The nanovaccine consists of di-amidobenzimidazoles (diABZI) conjugated to a STING-activating polymer, PSC7A, through an azobenzene linker as an adjuvant, and HPV16 E7 protein as an antigen. The nanovaccine is responsive to acidic pH and NAD(P)H quinone oxidoreductase 1 (NQO1), which enhances antitumor immunity with reduced systemic toxicity. Upon intravenous injection, the STING nanovaccine (25 to 30 nm in diameter) achieved efficient codelivery of E7 protein and STING agonists to the myeloid cell populations in the secondary lymphoid organs and tumors. Interestingly, PSC7A uptake induces NQO1 expression in dendritic cells and macrophages for accelerated diABZI cleavage and STING activation. This results in efficient production of E7-specific CD8 + T cells and robust antitumor response in late-stage TC-1 and metastatic MLM3 tumor models. This study illustrates a systemic STING nanovaccine design that allowed not only tumor regression but also markedly reduced systemic toxicity for innate activation to achieve cancer-specific T cell immunity.
GPT-4o mini: Non-social science research article
Mechanism of controlled radical initiation in radical SAM GTP 3’,8-cyclase
Haoran Pang, Di Li, Qinglin Wu, Pan Zhang, Weitao Yang, Alexey Silakov, Pei Zhou, Kenichi Yokoyama
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Metalloenzymes couple substrate binding and formation of oxidative intermediates to minimize unwanted side reactions. However, the molecular details of such coupling frequently remain ambiguous. Radical S -adenosyl-L-methionine (SAM) enzymes constitute one of the largest groups of metalloenzymes and catalyze various radical-mediated reactions. While radical SAM enzymes significantly accelerate the conserved radical initiation reaction, the reductive cleavage of SAM into 5â€Č-deoxyadenosyl radical (5â€Č-dA‱), the molecular mechanism of this rate acceleration is largely unexplored. Here, using MoaA, aradical SAM enzyme in the molybdenum cofactor (Moco) biosynthesis, as a model, we reveal the mechanism of substrate-triggered radical initiation. We first elucidated the intact active site structure of MoaA using solution NMR characterization of the C-terminal tail, which was disordered in the reported crystal structures, and its computational docking into the MoaA structure. Together with the comprehensive functional validation, we show that MoaA uses its conformationally flexible C-terminal tail with two conserved Gly residues (GG motif) at the C-terminus as a sensor to detect substrate guanosine 5â€Č-triphosphate (GTP) binding and trigger reductive SAM cleavage. Importantly, mutations that disrupt this regulatory mechanism cause Moco deficiency disease in humans. Comparison of these observations with other radical SAM enzymes provides insight into the general mechanism of substrate-triggered radical initiation in radical SAM enzymes.
GPT-4o mini: Non-social science research article
eATP sensing by the purinergic receptor PA2072 for allosteric modulation in intracellular c-di-GMP signaling
Yan Zhang, Xiaojing Gao, Yunjie Xiao, Yajing Duan, Wangxin Xiao, Yangyang Xu, Tingting Yang, Huimin Zhang, Cheng Chen, Shuo Shi, Xun-Cheng Su, Xinghua Jin, Jiaqing Zhao, Haitao Yang, Guowei Yin, Wensu Yuan, Zefang Wang, Weidong Huang, Zhi Lin
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Extracellular ATP (eATP) has emerged as a crucial signaling molecule across eukaryotic and prokaryotic domains, modulating diverse cellular functions by activating purinergic receptors to initiate intracellular signaling cascades. However, the structural and molecular mechanisms underlying eATP sensing and signaling by prokaryotic receptors remain largely unknown. Here, we demonstrate that the receptor PA2072 in Pseudomonas aeruginosa is responsible for recognizing eATP to down-regulate intracellular cyclic di-GMP levels. The periplasmic CHASE4 domain of PA2072 specifically binds and hydrolyzes eATP, exhibiting ATPase activity both in the presence and absence of a divalent cation cofactor. Structural elucidation of the PA2072 CHASE4 domain in its monomeric and complex states unveils an exquisite molecular switch governed by the oligomeric state. ATP hydrolysis by the catalytically active monomeric form is coupled to homodimerization, concomitantly deactivating its ATPase activity and initiating intracellular phosphodiesterase activity. These findings open avenues for understanding interkingdom eATP signaling and developing targeted therapeutic interventions.
GPT-4o mini: Non-social science research article
Correction for Bellis et al., Genomics of sorghum local adaptation to a parasitic plant
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GPT-4o mini: Non-social science research article
Correction for Lu and Kang, Efficient acquisition of dual metastasis organotropism to bone and lung through stable spontaneous fusion between MDA-MB-231 variants
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GPT-4o mini: Non-social science research article
Dynamic changes of dopamine neuron activity and plasticity at different stages of negative reinforcement learning
Qiangqiang Cheng, Wenqing Liu, Li Yao, Shuyuan Xu, Chunling Wei, Qiaohua Zheng, Meilin Wu, Jing Han, Zhiqiang Liu, Wei Ren, Zongpeng Sun
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Research indicates that midbrain dopaminergic neurons encode reward prediction error (RPE) signals involved in positive reinforcement learning. However, studies on dopamine’s role in negative reinforcement learning (NRL) are scarce. Learning to escape aversive stimuli is vital for survival and may differ significantly from positive reinforcement in behavior and neural mechanisms. This study employs footshocks as aversive stimuli to investigate neural activity, synaptic transmission, and intrinsic excitability in a NRL paradigm using fiber photometry and ex vivo electrophysiology. Results show that inescapable footshocks initially increase activity in substantia nigra pars compacta (SNc) dopaminergic neurons, which later shifts to reflect shock termination as exposure increases. Electrophysiological observations reveal increased intrinsic excitability and excitatory synaptic transmission in SNc neurons, with decreased inhibitory transmission. After mice learn to escape the shock by nose-poking, dopaminergic activity shifts from shock termination to shock onset. Furthermore, inhibitory input increases, while excitatory input decreases after learning, with intrinsic excitability returning to baseline levels. This indicates that SNc dopaminergic neurons exhibit RPE-like signals in response to aversive stimuli, with their intrinsic excitability adjusting according to expectations of shock termination. These findings enhance our understanding of RPE encoding in negative reinforcement learning and may inform therapeutic strategies for disorders caused by environmental factors such as aversive stimuli.
GPT-4o mini: Non-social science research article
An all-sky light pollution model for global-scale applications that embraces a full range of cloud distributions
Miroslav Kocifaj, Fabio Falchi, FrantiĆĄek Kundracik
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Light pollution has been traditionally modeled using clear or completely overcast conditions. Usually, atmospheric conditions are more complex and involve variable cloudiness. To predict light pollution in a realistic atmosphere, we developed a model for computing the artificial night sky brightness over the sky hemisphere, considering the presence of different types of clouds and the cloud fraction. The model is applied to the city of Ćœilina, Slovakia, which has moderate levels of light pollution and a population of approximately 80,000. We performed simulations for various aerosol optical depths, distances from the city, cloud types, and cloud coverages (from clear to completely overcast). Results show that above the simulated city, the clouds can amplify the zenith artificial radiance by more than 15 times and the irradiance incident at ground level by more than 4 times compared to clear-sky conditions. Outside the city, however, the presence of clouds can have a screening effect, lowering the artificial zenith radiance. Additionally, an analysis performed in photopic units demonstrated that over the urban area, amplification caused by low clouds can generate amplification factors of up to 27 in zenith luminance and 17 in horizontal illuminance. These amplification factors are obtained for a moderately urbanized environment; in highly urbanized areas, even stronger amplification effects might be expected. The model can be used to explain observational data collected by light pollution monitoring networks, particularly at sites where the combination of amplifying and darkening effects of clouds generates ambiguous brightness outcomes.
GPT-4o mini: Non-social science research article
Revisiting the high-dimensional geometry of population responses in the visual cortex
Dean A. Pospisil, Jonathan W. Pillow
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Recent advances in large-scale recording technology have spurred inquiries into the high-dimensional geometry of the neural code. However, characterizing this geometry from noisy neural responses, particularly in datasets with more neurons than trials, poses major statistical challenges. We address this problem by developing tools for the accurate estimation of high-dimensional signal geometry. We apply these tools to investigate the geometry of representations in the mouse primary visual cortex. Previous work has argued that these representations exhibit a power law, in which the i th principal component falls off as 1 / i . Here, we show that response geometry in V1 is better described by a broken power law, in which two different exponents govern the falloff of early and late eigenmodes of population activity. Our analysis reveals that later modes decay more rapidly than previously suggested, resulting in a substantially lower-dimensional representation that is concentrated in early modes. We thus characterize the stimulus encoding of these dominant population modes. We find properties of population coding in the mouse primary visual cortex that underscore its greater tractability relative to single-neuron characterization. Specifically, we find these modes encode visual features with far higher fidelity than single neurons, and these features are easier to characterize than the tuning of single neurons: both classical and deep network models of V1 achieve more than 25 % better predictive performance for eigenmodes than single neurons. Overall, our approach overturns prior results and reveals emergent structure in a population sensory representation.
GPT-4o mini: Non-social science research article
Correction for Hvid et al., Relationship dynamics and behavioral adaptations in the control of the 2022 mpox epidemic
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GPT-4o mini: Non-social science research article
Microfluidic networks using isotachophoresis
Alexandre S. Avaro, Shahab Mirjalili, Andrew D. Griffiths, Juan G. Santiago
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The development of microfluidic technologies has enabled chemical and biological analysis systems with increased functionality, complexity, and parallelization. These functionalities often drive the creation and control of complex and dynamic fluidic architectures. Introduced here is a class of microfluidic network based on isotachophoresis (ITP), an electrokinetic process that can extract and purify samples, selectively transport, mix, and aliquot (split) samples in a system with no moving parts. Presented is a theoretical framework to describe these networks. The framework relies on the coupling between a one-dimensional description of ITP and two-dimensional, transient graphs to describe the dynamic evolution of ITP networks. We leverage this framework to create numerical simulations of branched ITP circuits. We build, control, and experimentally study a variety of ITP networks. These systems automatically split and merge ITP zones, enabling complex sample manipulation with minimal external control. The model captures the experimentally observed sample dynamics. We demonstrate an example system where an ITP network is used to control and quantify parallel CRISPR-Cas enzymatic reactions. The methods described here are generally applicable to highly complex topologies and may offer a basis for easily reconfigurable, electric field-driven microfluidic systems. Networks generally offer broad potential for automated chemical and biochemical analysis and lab-on-a-chip integration.
GPT-4o mini: Non-social science research article
Correction for Reva et al., Higher-order interactions in neuronal function: From genes to ionic currents in biophysical models
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GPT-4o mini: Non-social science research article
Choosing structure over complexity: POMDPs for emerging diseases and invasive species
Iadine Chades
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GPT-4o mini: Non-social science research article
Neuronal normalization in monkey MT is an intensity-weighted average
Chery Cherian, John H. R. Maunsell
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Normalization is a fundamental and ubiquitous neuronal computation that stabilizes activity across populations of neurons and preserves stimulus selectivity. While it is observed throughout the visual system, normalization may be particularly important in higher visual areas, where neurons have large receptive fields (RFs) that are frequently presented with multiple stimuli under natural viewing conditions. Yet it remains unclear how a population of neurons, with diverse selectivities and offset RFs, responds to complex scenes in which given stimuli engage different RFs more effectively than others. Here, we investigated how normalization varies with the spatial offset of stimuli from the centers of neurons’ RFs in the macaque monkey middle temporal area. We found that existing models of normalization perform poorly when stimuli appear in arbitrary RF locations. Instead, an intensity-weighted normalization model, in which intensity is defined as the product of stimulus contrast and a location-specific RF weight, is required to closely account for normalization. Intensity-weighted normalization furthermore explains a systematic increase in contrast sensitivity at sites closer to the field center. Finally, intensity-weighted normalization reveals that spontaneous activity contributes to normalization in a manner indistinguishable from experimental stimuli.
GPT-4o mini: Non-social science research article
Glycolipid nanoparticles target the spleen and detarget the liver without charge
Kara Gentry, Liming Lian, Hyejin Kim, Ozgenur Celik, Camille Jones, Ananda R. Podilapu, Avraham Shakked, David Loughrey, Ryan Zenhausern, Bora Jang, Jessie Doan, Sebastian Rudden, James E. Dahlman
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Lipid nanoparticles (LNPs) formulated with a neutral helper lipid can deliver RNA to the liver in humans. However, clinically relevant delivery to other tissues has remained challenging. To avoid the liver, scientists often add antibodies or helper lipids with a permanent charge. Here, we report an alternative approach: antibody- and charge-independent liver detargeting. Using DNA barcoding to test 109 chemically distinct LNPs in vivo, we found that replacing a neutral helper lipid with a neutral glycolipid reduced liver delivery and increased splenic delivery. Consistent with this differential tropism, these glycolipid nanoparticles caused differences in downstream cellular signaling in vivo compared to traditional LNPs. These data suggest that extrahepatic LNPs can be designed without the imposition of a net negative or positive charge.
GPT-4o mini: Non-social science research article
HIV-1 Vif and Vpr cooperatively modulate the cell cycle to maximize per-cell virion production
Madison Bandini, Dhaval Ghone, Edward L. Evans, Aussie Suzuki, Nathan M. Sherer
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The HIV type 1 (HIV-1) accessory proteins Virion Infectivity Factor (Vif) and Viral Protein R (Vpr) are essential for efficient virus replication in vivo. Vif mediates degradation of host restriction factor APOBEC3G, while Vpr modulates the host cell proteome in ways that promote virion infectivity and viral gene expression. In cycling cells including CD4+ T cells, Vif and Vpr also severely impact cell cycle progression for reasons that remain unknown. Here, we combined live-cell imaging with virological assays to define the relative impacts of Vif and Vpr on the cell cycle and single-cell virion production. We demonstrate that Vif and Vpr’s effects on the cell cycle are markedly distinct, with Vif arresting cells in mitosis, while Vpr causes a G2 phase delay followed by endoreplication and reversion of cells into a “pseudo-G1” cell state lacking G2 markers. When coexpressed, Vpr’s capacity to bypass mitosis acts to suppress cytotoxicity associated with Vif-mediated cell cycle arrest, with the two proteins cooperating to extend the infected cell’s time in interphase as much as fivefold. Vpr-driven endoreplication also caused duplication of transcriptionally active proviral genomes, yielding a correlative ~twofold increase in per-cell viral gene expression. Based on these findings, we propose that Vif and Vpr coordinately regulate the cell cycle to prolong the infected cell’s lifespan and maximize single-cell virion output.
GPT-4o mini: Non-social science research article
Glycosylated cannabinoids meet computational enzyme design
Joseph M. Jez
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GPT-4o mini: Non-social science research article
Sticking around: σ factor dynamics and implications for transcription elongation
Rachel A. Mooney, Robert Landick
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GPT-4o mini: Non-social science research article
Two exceptionally preserved biotas from North Dakota reveal cryptic Ordovician shelf ecologies
Giovanni Mussini, Nicholas J. Butterfield
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The Ordovician saw one of the greatest evolutionary radiations in the Earth’s history, precipitating the assembly of modern animal-dominated ecologies in the aftermath of the Cambrian Explosion. However, Ordovician nonmineralized faunas are rare and mostly sample ecologically marginal settings. We describe small carbonaceous fossils (SCFs), including semiarticulated elements preserving submicrometric detail, from epicratonic deposits of the Deadwood and Winnipeg formations (ND). The Osterberg SCFs, associated with biostratigraphically informative conodonts and graptolites, record two successive biotas of Cambrian-Tremadocian (the “lower Osterberg” biota) and Darriwilian (the “upper Osterberg” biota) ages, demonstrating a long-term persistence of high-quality, Burgess Shale-type microfossil preservation after the end of the Cambrian. Their components open a window on normal marine, well-oxygenated Ordovician shelf habitats, revealing taxa and functional morphologies unrecorded by coeval macrofossils. These include specialized grazing and predatory molluskan radulae, triturative crustaceomorph molars, the oldest known eurypterid-type cuticles, and microphagous priapulid worms. The Osterberg fossils attest to an Ordovician co-occurrence of cryptic taxa and feeding adaptations, reminiscent of the most ecologically modern Cambrian biotas, alongside classic later-Paleozoic forms like colonial zooplankton and biomineralized early vertebrates. By contrast, they do not record classic Burgess Shale-style taxa typical of marginal or deeper-water Ordovician assemblages. These results demonstrate a lasting presence of cryptic, modern-style shelf faunas throughout the earliest Paleozoic, suggesting that exceptional Ordovician macrofossil sites are unrepresentative of the broader state of their coeval biosphere.
GPT-4o mini: Non-social science research article
Beyond reweighting: On the predictive role of covariate shift in effect generalization
Ying Jin, Naoki Egami, Dominik RothenhÀusler
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Many existing approaches to generalizing statistical inference amid distribution shift operate under the covariate shift assumption, which posits that the conditional distribution of unobserved variables given observable ones is invariant across populations. However, recent empirical investigations have demonstrated that adjusting for shifts in observed variables (covariate shift) is often insufficient for generalization. In other words, covariate shift does not typically “explain away” the distribution shift between populations. As such, addressing the unknown yet nonnegligible shift in the unobserved variables given observed ones (conditional shift) is crucial for generalizable inference. In this paper, we present empirical evidence from two large-scale multisite replication studies indicating that covariate shift can help predict the strength of unknown conditional shift. Analyzing 680 studies across 65 sites, we find that even though the conditional shift is nonnegligible, its strength can often be bounded by that of the observable covariate shift. This pattern only emerges when the two sources of shifts are quantified by our proposed standardized, pivotal measures. We then interpret this phenomenon by connecting it to similar patterns that can be theoretically derived from a random distribution shift model. Finally, we demonstrate that exploiting the predictive role of covariate shift leads to reliable and efficient uncertainty quantification for target estimates in generalization tasks with partially observed data. Overall, our empirical and theoretical analyses highlight an alternative perspective on the problem of distributional shift, generalizability, and external validity.
GPT-4o mini: Non-social science research article
Reprogramming tumor microenvironment via systemic delivery of TLR3 agonist and manganese nanoparticle
Young Seok Cho, Xingwu Zhou, Xiaoqi Sun, Ziye Wan, Julia Crowther, Mariko Takahashi, Swetha Kodamasimham, Qi Wu, May Thazin Phoo, Youngseo Na, Kai Han, Zaiye Li, Anna Schwendeman, Steven P. Schwendeman, Yu Leo Lei, James J. Moon
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Toll-like receptor (TLR) agonists, as potent immunostimulatory adjuvants, play a critical role in linking the innate and adaptive immune responses. However, their antitumor effects as cancer immunotherapeutic agents have been limited. Here, we report our finding that manganese ion (Mn 2+ ) potentiates various TLR agonists, leading to robust activation of the TLR pathway and the stimulator of interferon genes (STING) pathway among innate immune cells. In particular, we have observed robust antitumor efficacy after intratumoral administration of a TLR3 agonist and Mn 2+ . To achieve systemic codelivery of TLR3 agonist and Mn 2+ , we have developed a low-molecular-weight poly(inosinic:cytidylic acid)-Mn 2+ coordination lipid nanoparticle (PLCMP). When administered intravenously in tumor-bearing mice, PLCMP successfully accumulated in tumor, induced innate immune activation, generated tumor-specific T cells, and exerted antitumor efficacy in TLR3- and STING-dependent manner without triggering overt toxicity. Moreover, PLCMP in combination with α-PD-1 therapy achieved long-lasting antitumor efficacy in multiple murine tumor models. Furthermore, vaccination with PLCMP carrying TC-1 tumor antigen peptide elicited strong antigen-specific CD8 + T cell responses and remodeled the tumor microenvironment, resulting in robust therapeutic efficacy. Overall, these results show that simultaneous activation of the TLR3 and STING pathways via PLCMP provides a promising strategy for immunotherapy and vaccination against cancer.
GPT-4o mini: Non-social science research article
Parental investment and body temperature explain encephalization in vertebrates
Zitan Song, Michael Griesser, Carel P. van Schaik
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The systematic variation in relative brain size among vertebrate classes remains poorly understood. Here, based on the expensive brain hypothesis, we propose that two broad constraints explain much of the variation: 1) the ability to produce large offspring, and so provide them with the energy required for constructing larger brains, and 2) the ability to sustain continuously high body temperatures, because cooler and varying brain temperatures reduce brain performance and thus fitness. We therefore predicted that encephalization (major evolutionary increases in brain size) only happened where changes in physiology or natural history created these abilities. First, comparative analyses across all major vertebrate classes (n = 2600 species) revealed that protecting or provisioning eggs or embryos is associated with larger newborns. Subsequent analyses at the class level confirmed that newborn size and adult brain size underwent correlated evolution in birds, mammals, and cartilaginous fishes, but not in other fishes, amphibians, and reptiles. Second, we found a positive relationship between mean body temperature and brain size within each class (albeit sometimes insignificant). Third, a combined analysis across all vertebrates revealed a positive interaction between the effects of body temperature and newborn size. In conclusion, encephalization became most pronounced in vertebrate lineages that can both produce large offspring, reflecting internal fertilization with matrotrophy, and sustain high body temperature, partly linked to endothermy.
GPT-4o mini: Non-social science research article
Genomic and transcriptomic landscape of carcinogenesis in patients with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS)
Chihiro Matsumoto, Kazuki K. Takahashi, Masaaki Iwatsuki, Noriko Yasuda-Yoshihara, Atsushi Niida, Kohei Yamashita, Takeshi Morinaga, Kojiro Eto, Shiro Iwagami, Satoshi Ida, Hiromu Yano, Yoshihiro Komohara, Yuji Miyamoto, Takaaki Masuda, Yasuhito Tanaka, Koshi Mimori, Hideo Baba
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Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal dominant syndrome characterized by polyposis localized in the gastric body and fundus with a strong tendency for adenocarcinoma. The genetic mutations that accumulate during the progression from normal mucosa through polyp to carcinoma in GAPPS remain unclear. We investigated the evolutionary process from normal mucosa to polyp and carcinoma in GAPPS. Through comprehensive mutational and transcriptome analyses, we aimed to provide insights into the biology of this disease. Whole-exome sequencing and RNA sequencing were performed on carcinoma, polyp, and normal mucosa samples from multiple sites from seven patients with GAPPS (n = 54 samples). We comprehensively investigated genomic alterations (including copy number alterations and somatic mutations), clonal architecture, and transcriptome dynamics during carcinogenesis. Genomic evolutionary analysis showed that in GAPPS, somatic mutations of APC occur in carcinoma and polyp while mutations of KRAS additionally occur in carcinoma. We also found the co-occurrence of APC and KRAS mutations in carcinoma recurrently both across cases and within subclones of the same case. The co-occurrence of APC/KRAS mutations may contribute to the carcinogenesis of GAPPS. Our study provides detailed information on the genomic and transcriptomic landscape in GAPPS carcinogenesis, conferring valuable insights into its underlying mechanisms.
GPT-4o mini: Non-social science research article
Local control of T cell fate in lymph nodes safely and durably reverses myelin-driven autoimmunity
Senta M. Kapnick, Emily A. Gosselin, Shannon J. Tsai, Robert S. Oakes, Zahra A. Habibabady, Marian A. Ackun-Farmmer, Sean T. Carey, Shrey A. Shah, Ruochen Shen, Eugene Froimchuk, Haleigh B. Eppler, Christopher J. Bridgeman, Alexis A. Yanes, Ryan A. McIlvaine, Maeesha Noshin, Lisa H. Tostanoski, Sheneil K. Black, Xiangbin Zeng, Agnes Azimzadeh, Richard N. Pierson, Jonathan S. Bromberg, Christopher M. Jewell
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Development of tolerogenic, antigen-specific immunotherapies could overcome limitations of existing treatments for inflammatory autoimmune diseases by achieving potent, durable remission without impacting healthy immune surveillance. Here, we deliver diffusion-limited polymer depots to lymph nodes to locally guide T cell fates for the treatment of multiple sclerosis (MS), an autoimmune disease that occurs when the immune system mistakenly attacks myelin. In preclinical MS models, depots loaded with myelin self-antigen and tolerizing cues mediate localized retention of activated CD4 T cells, promote myelin-specific regulatory T cells, and reshape inflammation in the central nervous system (CNS) to eliminate lesions. Selective disease reversal is achieved with a single treatment that induces long-lasting remission without hindering healthy responses to vaccine challenge with foreign antigen. Furthermore, depots offer favorable chemistry and manufacturing control features and are well tolerated in non-human primates. This work supports a clinically feasible concept for inducing safe, effective, antigen-specific tolerance without systemic or repeated dosing.
GPT-4o mini: Non-social science research article
cGAS-agonistic spherical nucleic acids reprogram the glioblastoma immune microenvironment and promote antitumor immunity
Akanksha S. Mahajan, Corey Dussold, Seunghyun Kim, Rachel Jarvis, Lisa A. Hurley, Serena Tommasini-Ghelfi, Jungsoo Park, Connor M. Forsyth, Bin Zhang, Jason Miska, Amy B. Heimberger, Chad A. Mirkin, Alexander H. Stegh
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The cyclic GMP-AMP synthase-Stimulator of Interferon Genes (cGAS–STING) pathway is an important DNA-sensing mechanism that increases T cell trafficking and activation in tumors and reverses the immunosuppressive phenotype of myeloid cells. Therefore, direct STING targeting using synthetic cyclic dinucleotides (CDNs) is an attractive strategy for treating lymphocyte-depleted and myeloid cell–enriched tumors, such as glioblastoma (GBM). However, inadequate bioavailability and poor cellular accumulation limit the clinical development of CDNs, particularly for noninvasive administration strategies. Spherical nucleic acids (SNAs) have emerged as promising modular constructs for creating therapeutic lead compounds for many diseases, including different forms of cancer. Here, we report the development of cGAS-activating SNAs that consist of gold nanoparticle cores functionalized with a shell of densely packed interferon-stimulatory DNA oligonucleotides (ISD 45 -SNAs). These nanostructures bind to cGAS, the sensor of cytosolic dsDNA upstream of STING, promoting the catalytic production of endogenous CDNs and downstream STING activation more potently than clinically tested CDNs. When administered intranasally or intratumorally to poorly immunogenic syngeneic GBM mouse models, ISD 45 -SNAs inhibit tumor growth more effectively than CDNs and promote long-term animal subject survival through specific cGAS–STING pathway activation. ISD 45 -SNAs induce a proinflammatory immune microenvironment enriched with effector T cells and proinflammatory macrophages. When coadministered with immune checkpoint inhibitors (ICI), they abolish GBM tumor development and induce long-term antiglioma immunity. These studies establish ISD 45 -SNAs as an immune-stimulatory modality for triggering innate and adaptive immune responses and increasing ICI efficacy for GBM treatment.
GPT-4o mini: Non-social science research article
Underestimated input of terrestrial dissolved organic carbon to the ocean
Yuanbi Yi, Andrew J. Tanentzap, Chen He, Julian Merder, Helena Osterholz, Hongyan Bao, Jeffrey A. Hawkes, Ruanhong Cai, Si-Liang Li, Quan Shi, Sheng Xu, Chuanlun Zhang, Cong-Qiang Liu, Meixun Zhao, Ding He
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The contribution of terrestrial dissolved organic matter (DOM) to the ocean has been an enigma for decades. Tracking terrestrial DOM in the ocean has proven challenging due to factors such as the instability of terrestrial biomarkers, indistinguishable carbon isotopes from biogeochemical fractionation, and similar chemical composition between terrestrial and oceanic DOM. Here, we show that the terrestrial contribution to oceanic organic carbon pools is 1.7 to 2.5 times higher than previously assumed, highlighting the need to adjust global carbon cycle models. We derive these estimates by bridging high-performance liquid chromatography with ultra-high resolution mass spectrometry to investigate the presence of terrestrial molecules that are transported from rivers to the ocean and estimate their contribution to oceanic DOM. We identified 269 molecular formulae (MF) that are likely transported from land to the ocean. These formulae exhibited resistance to biological and photochemical degradation in incubation experiments, and were widely distributed in global rivers, marginal seas, and open oceans, suggesting that they are ubiquitous in inland and ocean waters and have a similar source. By relating the abundances of terrestrially derived MF to dissolved organic carbon concentrations, and radiocarbon measurements, we estimated that 16.7 to 25.0% of oceanic DOM is likely derived from rivers.
GPT-4o mini: Non-social science research article
An ADAR2-mimic base editor for efficient C-to-U RNA editing in vivo
Chenhui Hao, Niubing Zhang, Ouyang Mo, Ping Chen, Qian Liu, Xiang Cheng, Xuan Li, Pei Hao
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RNA base editing has the capability to rewrite genetic codes while offering improved safety due to its reversibility and temporal-spatial tunability. The development of cytosine-to-uridine editors faces issues of DNA mutagenic activity of APOBECs and the large-size anchoring domains associated with immunogenicity due to their microbial origin. To address these issues, we took an approach by returning to the original formula of adenosine deaminase acting on RNA (ADAR), i.e., to convert ADAR2 to a cytosine deaminase acting on RNA by introducing 17 mutant substitutions derived from RESCUE-S—it is named ADAR2-mimic base editor for C-to-U RNA editing (AMBER). AMBER displays similar sequence contexts preference to that of RESCUE, and exhibits robust performance across various tested cell lines. By applying AMBER to correct several pathogenic transcript mutations, we achieved substantial editing with efficiency ranging from 8 to 38%. For example, for the Pah mutant (c.788T>C) that caused phenylketonuria in mice, AMBER had an editing efficiency of 19.7% in HEK293T cells. Additionally, concurrent bystander editing of target transcripts was mitigated by two alternate strategies. To demonstrate its effectiveness in vivo, we applied AMBER in C57BL/6 mice, and observed gRNA-dependent editing with ~21% on-target efficiencies at 72 h post injection, which remained detectable up to 1 wk. RNA-sequencing analysis of the mouse liver transcriptome revealed minimal off-target effects and no significant changes to endogenous RNA editing events. These results highlight AMBER as a promising therapeutic tool for repairing T-to-C mutations, offering great potential for the treatment of genetic diseases.
GPT-4o mini: Non-social science research article
Unveiling FERONIA receptor kinase–mediated cellular mechanisms with a small-molecule inhibitor
Mengze Sun, Baiyan Lu, Ying Yang, Junping Fan, Weiwei Ren, Xiaonan Chu, Yihui Gao, Jun Wu, Jue Wang, Han Ke, Zhiwen Liu, Shaojun Dai, Xiaoguang Lei, Chao Li
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Since its initial identification as the receptor for Rapid Alkalinization Factor 1 (RALF1), FERONIA (FER) receptor kinase has emerged as a central signaling hub coordinating plant development, stress adaptation, and immune responses. Nevertheless, fundamental questions persist regarding the precise mechanisms of FER-mediated signal transduction and its context-dependent functional specialization in multicellular processes. Here, we develop Ferovicin (FRV), a small-molecule inhibitor that specifically disrupts FER kinase activity, thereby enabling mechanistic dissection of FER. Cocrystallization and mutational analysis show that FRV selectively binds to the ATP-binding pocket of the kinase domain of FER and inhibits its kinase activity. Assisted by the FRV tool and quantitative phosphoproteomics, we characterized a series of signaling pathways and networks regulated by RALF1 and FER. Notably, our analysis reveals that RALF1 activates FER through phosphorylation at Ser695, which subsequently inhibits H + -ATPase1/2 via phosphorylation at Ser899. This mechanism leads to apoplastic alkalinization and regulates cell expansion in the root meristem. Given the conservation of FRV binding sites in FER proteins across land plant species, FRV will serve as a valuable tool for dissecting FER signaling mechanisms as well as facilitating agricultural applications.
GPT-4o mini: Non-social science research article
The geometry of jamming algorithms in the random Lorentz gas
Giampaolo Folena, Patrick Charbonneau, Peter K. Morse, Rafael DĂ­az HernĂĄndez Rojas, Federico Ricci-Tersenghi
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Deterministic optimization algorithms unequivocally partition a complex energy landscape into inherent structures (ISs) and their respective basins of attraction. Can these basins be defined solely through geometric principles? This question is paramount to understanding hard sphere jamming, a key model of disordered matter. We here address the issue by proposing a geometric class of gradient descent–like algorithms, which we use to study a system in the hard-sphere universality class, the random Lorentz gas. The statistics of the resulting ISs is found to be strictly inherited from those of Poisson–Voronoi tessellations. The landscape roughness is further found to give rise to a hierarchical organization of ISs, which various algorithms explore differently. In particular, greedy and reluctant schemes tend to favor ISs of markedly different densities. The resulting ISs nevertheless robustly exhibit a universal force distribution, thus confirming the geometric nature of the jamming universality class. Along the way, the physical origin of a dynamical Gardner transition is identified.
GPT-4o mini: Non-social science research article
Two-factor synaptic consolidation reconciles robustness with pruning and homeostatic scaling
Georgios Iatropoulos, Wulfram Gerstner, Johanni Brea
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Memory consolidation refers to a process of engram reorganization and stabilization that is thought to occur primarily during sleep through a combination of neural replay, homeostatic plasticity, synaptic maturation, and pruning. From a computational perspective, however, this process remains puzzling, as it is unclear how to incorporate the underlying mechanisms into a common mathematical model of learning and memory. Here, we propose a solution by deriving a self-supervised consolidation model that uses replay and two-factor synapses to encode memories in neural networks in a way that maximizes the robustness of cued recall with respect to intrinsic synaptic noise. We show that the dynamics of this optimization make the connectivity sparse and offer a unified account of several experimentally observed signs of consolidation, such as multiplicative homeostatic scaling, task-driven synaptic pruning, increased neural stimulus selectivity, and preferential strengthening of weak memories. The model also reproduces developmental trends in connectivity and stimulus selectivity better than previous models. Finally, it predicts that intrinsic synaptic noise fluctuations should scale sublinearly with synaptic strength; we find support for this in a meta-analysis of published synaptic imaging datasets.
GPT-4o mini: Non-social science research article
Conformational regulation of two essential activators of bacterial cell elongation
Morgan S. A. Gilman, Irina Shlosman, Daniel D. Samé Guerra, Masy Domecillo, Elayne M. Fivenson, Claire Bourett, Thomas G. Bernhardt, Nicholas F. Polizzi, Joseph J. Loparo, Andrew C. Kruse
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The peptidoglycan (PG) cell wall is critical for bacterial growth and survival and is a primary antibiotic target. MreD is an essential accessory factor of the Rod complex, which carries out PG synthesis during elongation, yet little is known about how MreD facilitates this process. Here, we present the cryoelectron microscopy structure of Thermus thermophilus MreD in complex with another essential Rod complex component, MreC. The structure reveals that a periplasmic-facing pocket of MreD interacts with multiple membrane-proximal regions of MreC. We use single-molecule FRET to show that MreD controls the conformation of MreC through these contacts, inducing a state primed for Rod complex activation. Using Escherichia coli as a model, we demonstrate that disrupting these interactions abolishes Rod complex activity in vivo. Our findings reveal the role of MreD in bacterial cell shape determination and highlight its potential as an antibiotic target.
GPT-4o mini: Non-social science research article
Methanogenic archaea encoding Pyrrolysine maintain ambiguous amber codon usage
Katie E. Shalvarjian, Grayson L. Chadwick, Paloma I. Pérez, Philip H. Woods, Victoria J. Orphan, Dipti D. Nayak
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Natural genetic code expansion is a phenomenon wherein an additional amino acid is encoded by a stop codon. These nonstandard amino acids are beneficial as they facilitate novel biochemical reactions. However, code expansion leads to ambiguity at the recoded stop codon, which can either be read-through or terminated. Pyrrolysine (Pyl) is encoded by the amber codon (TAG/UAG) and is widespread in archaea, where it is required for methylamine-mediated methanogenesis, an environmentally important metabolism. Mechanisms to conditionally suppress the amber stop codon for Pyl installation during protein synthesis have not been identified. In the model methanogen, Methanosarcina acetivorans, we demonstrate that the UAG codon encodes dual meaning as stop and Pyl. Our data suggest that expression of Pyl biosynthesis and incorporation genes is tuned to the cellular demand for Pyl, which might allow these archaea to navigate ambiguous stop decoding in response to environmental cues.
GPT-4o mini: Non-social science research article
Changing minds epigenetically: Germline genes in neurons disrupt animal behavior
Emily Teets, Aakanksha Singhvi
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GPT-4o mini: Non-social science research article
Doubting doubly labeled water
Chika Edward Uzoigwe
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GPT-4o mini: Non-social science research article
Abscisic acid regulates iron accumulation in plant seeds via the PYLs–bHLH IVc–YSLs module
Hongyun Zhao, Juntao Jiang, Cun Wang, Yuan Zheng
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Abscisic acid (ABA) is pivotal in seed development, yet its role in iron (Fe) homeostasis remains unclear. Here, we reveal a PYLs–bHLH IVc–YSLs module that mediates ABA-dependent suppression of seed Fe accumulation in Arabidopsis . During seed maturation, ABA receptors PYLs directly interact with bHLH34/104/115 transcription factors, blocking their binding to YSL1/3 promoters to inhibit Fe transport. Conversely, Fe deficiency triggers bHLH104/115 to repress ABA2 , reducing ABA biosynthesis and PYL expression to derepress YSL1/3 expression—a feedback loop balancing Fe and ABA levels. Genetic analyses confirm that this module governs Fe loading, as ABA-deficient mutants ( aba2-1 , nced6-1 ) and pyr1 pyl124 quadruple mutants accumulate higher Fe, while bhlh34 104 115 phenocopies ysl1 ysl3 Fe deficiency. Our findings establish ABA as a dual regulator that safeguards Fe homeostasis by preventing toxicity during maturation while enabling adaptive Fe storage under deficiency. This mechanistic insight opens avenues for bioengineering crops with enhanced seed Fe content, addressing global nutritional challenges.
GPT-4o mini: Non-social science research article
Global profiling of polyketide synthases in facultative multicellular eukaryotes
Markus GĂŒnther, Rosa Herbst, Nico Ueberschaar, Daniela Hildebrandt, Lisa Reimer, Pierre Stallforth
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Polyketides represent a structurally diverse class of natural products with a wide range of biological functions, including antimicrobial activity, defense responses, developmental regulation, pigmentation, and intercellular and intracellular communication signals. The social amoeba Dictyostelium discoideum harbors 40 polyketide synthase (PKS) genes, yet the specific and collective functions remain poorly understood. PKSs require activation by the phosphopantetheinyl transferase DiSfp, which converts inactive apoenzymes into functional holo forms. Disruption of the DiSfp gene abolished the production of PKS-derived metabolites across all developmental stages. Integrated phenotypic, transcriptomic, and metabolomic analyses revealed impaired growth in liquid culture, defects in macropinocytosis, aberrant chemotaxis, and diminished spore formation, associated with altered expression of genes regulating these processes. Comparative metabolomic profiling of the mutant identified candidate polyketide metabolites across different developmental stages, providing a valuable resource for targeted identification and isolation of previously undescribed compounds. This study establishes a functional link between the PKS machinery and the metabolic and developmental networks of D. discoideum , highlighting the essential roles of polyketides in cellular physiology and offering a framework for future polyketide discovery.
GPT-4o mini: Non-social science research article
Gene drives, species complexes, and the risks of collateral damage
Christophe Boëte
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GPT-4o mini: Non-social science research article
Modulating antigen processing through metal–organic frameworks to bias adaptive immunity
Ezra Cho, Meredith A. Davis, Julia A. Nowak, Mayayi Izzo, Anna Maria Ferrante, Fanrui Sha, Julian S. Magdalenski, Omar K. Farha, Michelle H. Teplensky
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Vaccines induce specific immunity through antigen uptake and processing. However, while nanoparticle vaccines have elevated uptake, the impact of intracellular protein release and how this affects processing and downstream responses are not fully understood. Herein, we reveal how tuning unmodified antigen release rate, specifically through modulation of metal–organic framework (MOF) pore size, influences the type and extent of raised adaptive immunity. We use two MOFs in the NU-100x series with 1.4 nm difference in pore diameter, employ facile postsynthesis loading to achieve significant internalization of model protein antigen ovalbumin ( ca. 1.4 mg/mg), and observe distinct antigen release and intracellular processing profiles influenced by MOF pore size. We investigate how this difference in release biases downstream CD8 + , T H 1, and T H 2 T cell responses. Ovalbumin-loaded NU-1003 induced 1.8-fold higher CD8 + :CD4 + T cell proliferation ratio and displayed 2.2-fold greater ratio of CD4 + T H 1:T H 2 cytokines compared to ovalbumin-loaded NU-1000. Antigen released from NU-1000 in vivo exhibited stronger antigen-specific IgG responses, which is dependent on CD4 + T cells (up to ninefold stronger long-term antibody production and 5.9-fold higher IgG1:IgG2a ratio), compared to NU-1003. When translated to wild-type SARS-CoV-2 receptor-binding domain (RBD) protein, RBD-loaded NU-1000 induced 60.5-fold higher IgG1:IgG2a compared to NU-1003. Wild-type RBD-loaded NU-1000 immunization also induced a greater breadth of epitope recognition compared to NU-1003, as evidenced by increased binding antibodies to the Omicron RBD variant. Overall, this work highlights how antigen release significantly influences immunity induced by vaccines and offers a path to employ unmodified antigen release kinetics to drive personalized protective responses.
GPT-4o mini: Non-social science research article
Scaffold vaccination for prevention of orthopedic device infection
Alexander M. Tatara, Shanda Lightbown, Shawn Kang, Wei-Hung Jung, Hamza Ijaz, Jean C. Lee, Sandra B. Nelson, Michael Super, David J. Mooney
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Staphylococcus aureus is the leading cause of global bacterial mortality. While S. aureus can cause a variety of diseases, orthopedic device infections are particularly challenging due to the need for additional surgeries with associated morbidity. Conventional vaccine technology has failed to prevent S. aureus orthopedic device infection in animal models and clinical trials. In this study, injectable scaffold vaccines are presented as a modality to augment host immunity and mitigate orthopedic device infection. These scaffold vaccines increased cytokine production, antigen-specific cell-mediated immune responses, and humoral responses. When loaded with a pool of antigens collected via an engineered human opsonin, these scaffold vaccines decreased the bacterial burden against methicillin-susceptible and methicillin-resistant S. aureus (MRSA) strains in a murine model of orthopedic device infection. Scaffold vaccination was ~100× more effective in decreasing S. aureus burden compared to prior published immunotherapy attempts in murine models of orthopedic device infection. Scaffold vaccination was also effective when using a monovalent protein-based antigen. Scaffold vaccination is an alternative strategy to facilitate more robust immunity in scenarios where conventional bolus vaccines have not been effective.
GPT-4o mini: Non-social science research article
Divergent evolutionary dynamics of benign and malignant tumors
George Butler, Joanna Baker, Sarah R. Amend, Kenneth J. Pienta, Chris Venditti
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Benign and malignant (cancerous) tumors differ markedly in their impact on organismal fitness, yet studies in comparative oncology rarely distinguish between them. Using a Bayesian phylogenetic framework across birds and mammals, we show that while both tumor types increase in prevalence with body mass, only the prevalence of malignant tumors is negatively associated with the rate of body size evolution—suggesting that adaptive mechanisms of cancer defense are associated with rapidly evolving lineages. Additionally, the rate of lineage diversification is positively associated with the prevalence of both tumor types in birds but not mammals, potentially reflecting differences in genome architecture and speciation dynamics. Together, these results highlight distinct macroevolutionary drivers of benign versus malignant tumor prevalence and underscore the value of treating tumor types separately in comparative oncology.
GPT-4o mini: Non-social science research article
Impact of biomanufacturing protein fibers on achieving sustainable development
Benjamin D. Allen, Baljit Ghotra, Birgit Kosan, Philipp Köhler, Marcus Krieg, Christoph Kindler, Michael Sturm, Melik C. Demirel
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Biomanufactured fibers produced through fermentation processes provide a promising pathway to decouple textile production from agricultural land. This would free up arable land for food cultivation and contribute to the United Nations Sustainable Development Goal 2: Zero Hunger. Protein fibers from natural sources such as cocoon silk, collagen, and soy have attracted attention since the last century. However, commercial production declined with the rise of cheaper synthetic fibers and competition for food crops. Recently, renewed interest in protein fibers has emerged as a means to minimize plastic pollution, fueled by advances in fermentation, even though challenges related to yield, costs, and industrial spinning persist. Here, we studied a lyocell-based technique for spinning protein fibers using yeast biomass purified through an enzymatic method. We demonstrated that the enzymatic approach produces insoluble proteins that can be continuously spun for over 100 h of production time. Pilot-scale production exhibited stable spinning behavior with high viscosity and consistency quality. We achieved fiber fineness between 1.7 and 2.2 dtex, with strength values reaching 23 cN/tex, which is 50% higher than those of natural protein fibers such as wool. Life cycle assessment indicates that fermentation-based protein fibers require significantly less land and water than natural fibers while providing a reduced environmental footprint. Techno-economic analysis indicates a cost of $6 per kilogram at a production rate of 6,750 t annually. Adopting biomanufacturing-based protein fibers marks a significant advancement toward a future where fiber needs are fulfilled without compromising the planet’s capacity to nourish its growing population.
GPT-4o mini: Non-social science research article
Chemokine/cytokine-releasing biomaterials induce in situ tertiary lymphoid–like structures and enhance antitumor immunity
Rana Falahat, James J. Mulé
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Despite the growing recognition of tertiary lymphoid structures (TLSs) as valuable prognostic markers in certain cancer types, detailed studies on their development and therapeutic function remain limited. This is partially due to the lack of appropriate preclinical animal models. In this study and based on our earlier work [D. Coppola et al., Am. J. Pathol. 179 , 37–45 (2011); J. L. Messina et al., Sci. Rep. 2 , 765 (2012)], we hypothesized that encapsulating lymphoid chemokines and cytokines in controlled-release biomaterials would allow for their sustained delivery to the local tissue microenvironment, promote immune T-cell and B-cell accumulation, and lead to the in situ formation of TLS-like structures. To test this hypothesis, we encapsulated CCL19, CCL21, CXCL13, and lymphotoxin-α1ÎČ2 in lipid-coated microparticles (MPs) and embedded them in a biodegradable thermosensitive hydrogel designed to gel rapidly and release encapsulated payloads at injection sites over several days. In mice, subcutaneous injections of chemokine/cytokine-releasing MPs in hydrogel led to a substantial increase in CD45 + immune cell accumulation within newly developed structures surrounding the residual hydrogel after 3 wk. This influx was accompanied by a marked increase in the numbers of CD19 + B cells and CD3 + T cells. Using a mouse model of melanoma, we further show these induced structures can suppress tumor growth by promoting tumor antigen-specific T-cell responses. These findings indicate that chemokine/cytokine-releasing MPs in hydrogel can induce lymphoid structures resembling TLSs, highlighting their potential both as preclinical models for elucidating mechanisms regulating TLS formation and as platforms for therapeutic interventions against tumors.
GPT-4o mini: Non-social science research article
Drug-loaded bispecific T cell nanoengager overcomes T cell exhaustion for potent cancer immunotherapy
Jinjin Wang, Xisha Huang, Qiangqiang Shi, Kelsey L. Swingle, Alex G. Hamilton, Ningqiang Gong, Michael J. Mitchell
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Bispecific T cell engager (BiTE) therapeutics that link T cells and tumor cells to induce tumor cell lysis have demonstrated great success in the clinic for the treatment of many cancers. However, T cell exhaustion in the tumor microenvironment leads to tumor cell escape and BiTE therapy resistance. Herein, we developed a drug-loaded bispecific T cell nanoengager (NanoBiTE) to overcome this obstacle. NanoBiTE is composed of a mesoporous silica nanoparticle encapsulating the adenosine A2A receptor antagonist PBF-509 as a core, with a lipid layer surface coating as a shell and modification with anti-CD19 and anti-CD3 antibodies for tumor and T cell binding, respectively. Like the traditional BiTE blinatumomab, NanoBiTE can engage T cells with CD19 + tumor cells to promote tumor cell lysis. However, unlike blinatumomab, which tends to induce T cell exhaustion, we showed that the release of PBF-509 from NanoBiTE suppressed the A2AR pathway and substantially improved tumor cell killing induced by NanoBiTE. Moreover, NanoBiTE treatment led to substantially reduced tumor burden in vivo in a humanized mouse model. Our results demonstrate that NanoBiTE is a safe and potent bispecific therapy that can also reduce T cell exhaustion for cancer immunotherapy.
GPT-4o mini: Non-social science research article
In This Issue
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GPT-4o mini: Non-social science research article
Exploring evolutionary trajectories of drug resistance
Linfeng Hu, Aoxuan Zhang, Arieh Warshel
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Drug resistance poses a major global health challenge, necessitating the development of effective therapeutic strategies. The main challenge is to predict drug-resistant mutations and design drugs that retain efficacy against such evolving targets. Our previous effort in computing the vitality value has provided a framework in assessing drug resistance. While promising, the approach lacked accuracy due to insufficient information about mutation tendencies and protein stability. In this study, we used the Stanford University HIV Drug Resistance Database and observed that drug resistance, usually quantified as K i mutant / K i WT , exhibits a positive correlation with the Maximum Entropy energy, E M a x E n t . However, both drug resistance and vitality are also correlated with the number of mutations, indicating that the virus cannot easily gain resistance through specific mutational pathways and must sacrifice stability and function to escape inhibition. To overcome this number dependence, we looked for a system with less extensive mutagenesis and chose HCV protease. In this case, resistance substitutions cluster at low E M a x E n t values, reflecting a limited mutational space. This restricted landscape enables E M a x E n t to predict evolutionary pathways of resistance and to guide the identification of robust therapeutic candidates.
GPT-4o mini: Non-social science research article
Switching the strict substrate specificities of the ÎČ-ketoacyl-acyl carrier protein synthases, FabH and BioZ
Xudong Hang, Lin Zhang, Yanqiang Huang, Yuanyuan Hu, Qi Zeng, John E. Cronan, Liang Zhang, Hongkai Bi
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The ÎČ-ketoacyl-acyl carrier protein (ACP) synthases are pivotal elongation enzymes that catalyze the condensation of acyl-CoA or acyl-ACP with malonyl-ACP to produce ÎČ-ketoacyl-ACP. Among these, the homologous enzymes FabH (ÎČ-ketoacyl-ACP synthase III) and the recently characterized BioZ play crucial roles, initiating the biosynthetic pathways for fatty acids and biotin, respectively. FabH primarily utilizes acetyl-CoA as the primer substrate, whereas BioZ exclusively condenses the longer glutaryl-CoA, which contains a charged ω-carboxyl group. Despite their similar catalytic mechanisms, the molecular bases for the strict substrate specificities remain undetermined. Here, we report crystal structures of the BioZ: glutaryl-CoA cocrystalized complexes and demonstrate the ability to swap the physiological functions and substrate specificities between FabH and BioZ. This functional interchange was achieved by grafting the ÎČ8-α9 loop plus residue Ala317 of Agrobacterium tumefaciens BioZ to Escherichia coli FabH, resulting in a shift in substrate preference from acetyl-CoA to glutaryl-CoA. The reverse manipulations of BioZ resulted in FabH activity. These data identify the structural elements as the minimal determinants of substrate specificity and enzyme function. These findings provide valuable insights into the molecular mechanisms of substrate recognition and catalysis by FabH and BioZ and offer a foundation for the development of targeted therapeutic strategies against these enzymes.
GPT-4o mini: Non-social science research article
Receptive fields from single-neuron recording and MRI reveal similar information coding for binocular depth
Andrew J. Parker, Ivan Alvarez, Alessandro Mancari, I. Betina Ip, Kristine Krug, Holly Bridge
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The population receptive field (pRF) approach to functional measurement of the sensory properties of magnetic resonance (MR)-identified locations in the human brain was extended to include the third dimension of binocular depth. In total, pRFs were extracted from nine different visual areas (V1, V2, V3, V3AB, V4, V5, V7, Ventral Occipital Cortex: VOC, Lateral Occipital Cortex: LOC) of the human cortex and, where possible, comparisons were made with electrophysiological recordings from homologous areas in the macaque cortex. Human and macaque V1 showed strikingly similar information profiles for the encoding of binocular depth. Further, both human and macaque V5 showed consistent changes in preferred binocular depth of the stimulus, dependent on whether the stimuli were binocularly correlated or anticorrelated. Across the nine areas of the visual cortex explored, the population profiles of pRFs for binocular depth showed evidence of a greater responsiveness to relative depth in higher visual cortical areas, again consistent with the findings from macaque electrophysiology. Overall, the pRF measures of cortical response were more sensitive to fine-scale differences of binocular depth, compared with many existing electrophysiological measures of tuning for binocular depth. Our results show that the pRF method can be extended beyond the characterization of RFs in retinotopic coordinates to reveal higher-order, derived visual properties. The parallels between noninvasive, MR-based measures of pRFs in humans and the electrophysiological recordings of single neurons in experimental animals make a further step toward validation of the pRF methodology.
GPT-4o mini: Non-social science research article
The RANK/RANKL axis controls vascular dynamics in the bone marrow
Takeshi Kaneko, Shinya Yari, Junichi Kikuta, Yoshiki Omatsu, Shigeto Seno, Sumire Kikuchi, Kazuma Sato, Kentaro Fujii, Takao Sudo, Tetsuo Hasegawa, Kunimaro Furuta, Qianqian Guo, Samar H. Ibrahim, Kosuke Muraoka, Yoshiaki Okada, Yoshiaki Kubota, Daisuke Okuzaki, Yasuhiro Kobayashi, Atsushi Kumanogoh, Nobuyuki Udagawa, Takashi Nagasawa, Josef M. Penninger, Masaru Ishii
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Receptor activator of nuclear factor kappa B ligand (RANKL) is an essential cytokine that induces osteoclastic differentiation by monocyte-macrophage lineage precursors. Here, we showed that in addition to its conventional action, RANKL controls vascular permeability in the bone marrow, where it facilitates the mobilization of hematopoietic monocytic cells, including osteoclast precursors, and resultantly regulates bone metabolism. RANK, a cognate receptor for RANKL, is abundantly expressed in sinusoidal endothelial cells and controls vascular permeability by regulating the expression patterns of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1. High RANKL expression was detected in perivascular C–X–C motif chemokine ligand 12-abundant reticular (CAR) stromal cells. Specific deletion of RANKL expression in CAR cells abrogated the vascular leakage, suggesting that perivascular RANKL is responsible for controlling permeability. In summary, our study revealed a role for RANK/RANKL signaling as a gatekeeper of bone marrow sinusoids in vivo.
GPT-4o mini: Non-social science research article
Controlling intracellular processing to enhance spherical nucleic acid immune stimulation
Janice Kang, Michelle H. Teplensky, Jasper W. Dittmar, Michael Evangelopoulos, Jeongmin Hwang, Chad A. Mirkin
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To mount a robust and durable immune response, the antigen in a vaccine must be processed efficiently in the appropriate intracellular compartment. Here, we report an approach for optimizing the antigen processing pathway and efficiency by using the modular design of spherical nucleic acid (SNA) nanostructures. We utilized the substrate specificity of endoplasmic reticulum aminopeptidase1 (ERAP1), a protease known to generate major histocompatibility complex class I (MHC I) epitopes in the endoplasmic reticulum, to design two ERAP1-responsive peptide linkers (EPLs). The peptide linkers append the peptide antigen onto the SNAs to bias the processing pathway toward ERAP1 and to vary the antigen processing efficiency. The two EPLs varied ERAP1 antigen processing efficiency by 10-fold. Subsequently, the EPLs increased colocalization of the antigen with ERAP1 by up to ca. 58% when compared to an SNA that did not employ this linker. The EPL that drove more efficient cleavage, augmented antigen surface presentation by 30%, ex vivo CD8 + T cell proliferation by fivefold, and in vivo generation of proinflammatory and effector memory CD8 + T cells by 5% and 18%, respectively. Furthermore, the more efficiently processed EPL-containing SNA resulted in a 2.5-fold more effective inhibition of E.G7-OVA lymphoma tumors in vivo. Taken together, these findings underscore the importance of the deliberate and rational design of vaccine structures to spatially bias antigen processing and elevate its processing efficiency to augment immune stimulation.
GPT-4o mini: Non-social science research article
On the absence of the ultimate regime in turbulent thermal convection
Harshit Tiwari, Lekha Sharma, Mahendra K. Verma
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Quantifying heat transport in turbulent convection remains a challenge. The two competing models of heat transport predict that the nondimensional heat flux, known as the Nusselt number (Nu), is proportional to Ra 1 / 3 (classical scaling) and Ra 1 / 2 (ultimate-regime scaling), where Ra is the Rayleigh number. Some experiments and simulations report that the Nusselt number transitions from near classical scaling, Ra 0.30 , to a larger power law when the boundary layer turns turbulent near Ra ≈ 10 14 . However, others find Ra 0.30 scaling to continue for larger Ra. In this work, we perform a comparative study of Rayleigh-BĂ©nard, compressible, and periodic convection in two and three dimensions using direct numerical simulations. We show that up to Ra = 10 16 in two dimensions and up to Ra = 10 13 in three dimensions, the positive and negative energy fluxes in Rayleigh-BĂ©nard and compressible convection are nearly equal. However, in the distribution function, the positive fluxes have longer tails than the negative ones, and the differences between the positive and negative fluxes scale as Ra − 0.20 , which leads to Nu ∌ Ra 0.30 . The above robust and universal properties, even in the presence of a logarithmic layer in compressible convection, indicate a likely absence of the ultimate regime in turbulent thermal convection. In contrast, periodic convection, which is related to the ultimate regime, exhibits a predominantly positive heat flux.
GPT-4o mini: Non-social science research article
The role of active mRNA–ribosome dynamics and closing constriction in daughter chromosome separation in Escherichia coli
Chathuddasie I. Amarasinghe, Mu-Hung Chang, Jaana MĂ€nnik, Scott T. Retterer, Maxim O. Lavrentovich, Jaan MĂ€nnik
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The mechanisms by which two sister chromosomes separate and partition into daughter cells in bacteria remain poorly understood. A recent theoretical model has proposed that out-of-equilibrium central dogma reactions involving mRNA and ribosomes play a significant role in this process. Here, we test this idea in the Escherichia coli model system using high-throughput fluorescence microscopy in microfluidic devices. We compare our experimental observations with predictions from a reaction–diffusion model that includes central dogma-related reactions and excluded volume interactions between ribosomal subunits, polysomes, and chromosomal DNA. Our results show that the nonequilibrium reactions of ribosomes cause them to aggregate at the midcell, and this process facilitates the separation of the two daughter chromosomes. However, the observed effects are weaker in live cells than our one-dimensional reaction–diffusion model predicts. Rather than relying solely on active mRNA–ribosome dynamics, our data suggest that the closing division septum via steric interactions and potentially entropic forces between two DNA strands coupled to cell elongation act as additional mechanisms to ensure faithful partitioning of the nucleoids to two daughter cells.
GPT-4o mini: Non-social science research article
Extracellular nanobody screening using conformationally stable GPCR variants
Xin Zhang, Kaixuan Gao, Jia Nie, Hengyu Meng, Xiaoou Sun, Jiawei Zhao, Xiangyu Liu
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G protein–coupled receptors (GPCRs) are prominent drug targets that have attracted intensive efforts in drug screening. Binding-based screening methods for GPCR ligands often require conformationally stable, purified receptors. However, obtaining large quantities of GPCRs in stable states, particularly with unoccupied extracellular ligand-binding pockets and especially in their active conformations, remains challenging due to the inherent dynamic nature of these receptors. To address this challenge, we propose a universal approach for stabilizing GPCRs in specific conformations. Using the M1 muscarinic acetylcholine receptor (M1R) as a model, we successfully stabilized M1R in its active conformation through de novo design of a fusion protein, and further demonstrated the generalizability of this strategy by applying it to other GPCRs. We screened a synthetic yeast display library of nanobodies against both the stabilized active-state and previously reported inactive-state M1R, identifying several nanobodies that specifically recognize each conformation. This method not only facilitates the stabilization of GPCRs in desired states but also provides valuable tools for developing more selective therapeutic agents, enhancing drug discovery efficiency and specificity.
GPT-4o mini: Non-social science research article
BRAF inhibition increases TGFÎČ2 production and stimulates metastasis in mice with endogenous BRAF V600E -induced hepatocellular carcinoma
Jaroslaw Cisowski, Ahmed Ezat El Zowalaty, Sama I. Sayin, Piotr Czarnota, Tomasz Gromowski, Ella A. Eklund, Muhammad Kashif, Angana A. H. Patel, Antonio Molinaro, Per Lindahl, Clotilde Wiel, Volkan I. Sayin, Martin O. Bergo
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The MEK–ERK pathway is a key driver of hepatocellular carcinoma (HCC) pathogenesis, and BRAF mutations, particularly BRAF V600E , can contribute to its activation. Although BRAF V600E mutations are rare in human HCC, they do occur, yet their physiologic impact in liver cells, especially when combined with frequent comutations in tumor suppressor genes, remains poorly understood. Moreover, the effect of BRAF inhibitors on HCC progression and metastasis is not well-defined. Therefore, we developed mouse models with hepatocyte-specific BRAF V600E expression and Trp53 or Cdkn2a deletion to assess tumor development, subtypes, and metastatic patterns. We found that BRAF V600E expression caused hepatomegaly, vascular congestion, and ductal reactions, and led to reduced liver function and early mortality. Codeletion of Trp53 or Cdkn2a markedly increased primary liver tumor incidence and enabled sarcomatoid metastasis. While the BRAF inhibitor PLX4720 effectively reduced primary tumors and extended survival, it paradoxically increased sarcomatoid metastases. Mechanistically, PLX4720 and other RAF inhibitors induced TGFÎČ2 expression which promoted epithelial-to-mesenchymal transition (EMT) and enhanced tumorigenicity. The effects of RAF inhibitors on TGFÎČ2 expression were validated in BRAF V600E -mutant human melanoma cells. We conclude that BRAF V600E drives diverse primary tumors but only one type of metastasis and that RAF inhibition, while effective against primary tumors, may promote metastasis through TGFÎČ2-mediated EMT. Although RAF inhibitors remain promising therapies, their unintended role in enhancing metastasis raises concerns that may extend beyond liver cancer to other BRAF V600E -driven malignancies.
GPT-4o mini: Non-social science research article
Restoration of cGAS in cancer cells promotes antitumor immunity via transfer of cancer cell–generated cGAMP
Alexander M. Cryer, Pere Dosta, Michelle Z. Dion, Leonardo de la Parra Soto, Eliz Amar-Lewis, Gabriela Garcia de Leon Carmona, Alejandro Abraham Espinosa Pérez, Diego Fernando Ruiz Aguilar, Triana Huerta, Beatriz Nicolås Ruiz, Nathalie Nicole Casteele Hernandez, Yael Soria, Natalie Artzi
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Cancer cells comprise a significant proportion of the tumor microenvironment (TME) and often have compromised expression or repression of cyclic GMP-AMP (cGAMP) synthase (cGAS), which prevents effective stimulation of interferon genes (STING) signaling. Here, we leverage the cancer cells and hijack their cellular machinery for increased production of cGAMP, differing from conventional strategies whereby synthetic STING agonists are delivered to immune cells in the TME as a bolus dose, are rapidly cleared and can cause systemic toxicity. Increasing evidence suggests that cGAMP derived from cancer cells can act on proximal immune cells, activating STING, contributing to an antitumor immune response. We used lipid nanoparticles (LNPs) to deliver mRNA coding for cGAS which catalyzes the production of cGAMP. We observed dramatic increases in extracellular and intracellular cGAMP when cancer cells were transfected with cGAS mRNA and genomic DNA, the substrate for cGAS. We confirmed that cGAS and cGAMP are functional due to activation of immune cells, through a combination of extracellular transfer and cell–cell contact mechanisms. Treatment of syngeneic murine melanoma with cGAS LNPs reduced tumor growth significantly and further benefit was observed upon combination with immune checkpoint blockade (anti-PD-1). Moreover, we found increased activation in CD8 + T cells, NK cells, macrophages, and dendritic cells in the TME post treatment with cGAS LNPs. These findings highlight how cancer cells can be used to actively contribute to their own elimination and may be a broadly applicable strategy for delivery of other reprogramming molecules to cancer cells and wider therapeutic combinations.
GPT-4o mini: Non-social science research article
The synergy of methylphenidate- and reconsolidation-based extinction normalizes ventromedial prefrontal function in drug addiction
Ahmet O. Ceceli, Sarah G. King, K. Rachel Drury, Natalie McClain, John Gray, Priyanthi S. Dassanayake, Jeffrey H. Newcorn, Daniela Schiller, Nelly Alia-Klein, Rita Z. Goldstein
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Drug-related memories can hinder abstinence goals in drug addiction. Promoting nondrugmemories via ventromedial prefrontal cortex (vmPFC)- and amygdala-guided extinctionyields mixed success. Postretrieval extinction (RE) destabilizes and updates memoriesduring reconsolidation, improving extinction. Supplementing RE, we tested methylphenidate(MPH), a dopamine agonist that promotes PFC-dependent learning and memory in cocaineuse disorder (CUD). In a proof-of-concept double-blind randomized clinical trialusing a within-subjects design, participants received oral MPH (20 mg) or placebobefore the retrieval of some of the conditioned stimuli (CS) (i.e., reminded CS+ vs.nonreminded CS+) followed by extinction; lab-simulated drug-seeking was measuredthe following day. Lower vmPFC activity following nonreminded CS+ (standardextinction) under placebo replicated the putative impairments in CUD; separately, RE (trend) and MPH conditions recruited the vmPFC, and RE’s vmPFC-reliance correlatedwith drug-seeking only under placebo. Crucially, MPH-combined RE normalized cortico-limbicprocessing, bypassing the vmPFC and its amygdala connectivity. Pharmacologically-enhanced drug memory modulation may inform intervention development for addictionrecovery.
GPT-4o mini: Non-social science research article
Direct and in situ examination of Li + transport kinetics in an isotope-labeled solid–electrolyte interphase
Xiaofei Yu, Stefany Angarita-Gomez, Yaobin Xu, Peiyuan Gao, Jun-Gang Wang, Xin Zhang, Minyung Song, Hao Jia, Wu Xu, Xiaolin Li, Hsin-Mei Kao, Yingge Du, Zhijie Xu, Janet S. Ho, Kang Xu, Perla B. Balbuena, Chongmin Wang, Zihua Zhu
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Solid–electrolyte interphase (SEI) is the critical component in all advanced battery chemistries, whose ionic transport and electron leakage behaviors remain least understood among all battery components. Here, using unique in situ liquid secondary ion mass spectroscopy on isotope-labeled SEI, assisted by cryogenic transmission electron microscopy and constrained ab initio molecular dynamics simulation, we answer the question regarding the Li + transport mechanism across SEI and quantitatively determine the Li + mobility therein. We unequivocally unveil that Li + transport in SEI mainly follows a mechanism of successive displacement. We further reveal that in accordance with the spatial dependence of SEI structure across the thickness, the apparent Li + self-diffusivity continuously drops from the SEI–electrolyte side to the SEI–electrode side (6.7 × 10 −19 m 2 /s to 1.0 × 10 −20 m 2 /s), setting a quantitative gauging of both ionic transport behavior of the SEI layer against the underlying electrode and the rate-limiting step of battery operation. This direct study on Li + kinetics in SEI fills part of the decade-long knowledge gap about the most important component in advanced batteries and provides more precise guidelines for the tailoring of interphasial chemistries for future battery chemistries.
GPT-4o mini: Non-social science research article
Amino acid insufficiency impairs hepatic vitamin A mobilization in mice
Chintan T. Bhavsar, Youn-Kyung Kim, Flavio C. Rodriguez-Polanco, Brian A. Zalma, Esther M. Lopez, Saad A. Farooq, Maria Ibrahim, Eileen White, Tracy G. Anthony, Loredana Quadro
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Retinol-binding protein 4 (RBP4) is the sole specific serum carrier of vitamin A, delivering it from the hepatic stores to the peripheral organs in a complex with retinol (ROH) and transthyretin (TTR). Regulators of hepatic mobilization aside from vitamin A status itself are ill-defined. Here, we show that amino acid (AA) insufficiency by diet (low-protein, leucine-devoid diet) or drug (asparaginase, ASNase) elevated liver RBP4 without depleting hepatic retinoid stores. In addition, ASNase reduced liver TTR protein. Furthermore, circulating ROH–RBP4–TTR levels were attenuated, and retinoid levels in peripheral organs were perturbed. To understand the basis for elevated RBP4 in the liver, we isolated total and polysomal mRNA to assess gene-specific translation. ASNase significantly reduced Rbp4 mRNA translation, indicating that elevated hepatic RBP4 protein was not due to increased protein synthesis. In contrast, ASNase reduced Ttr mRNA abundance but not its translation. Global deletion of the AA insufficiency sensor, general control nonderepressible 2 (GCN2), lessened ASNase-induced RBP4 protein accumulation in the liver but did not rescue circulating ROH–RBP4 levels. These effects were replicated by chemical inhibition of GCN2 in ASNase-exposed primary hepatocytes. Finally, hepatocyte-specific knockout of autophagy-related 7, an enzyme involved in autophagy and protein secretion, fully rescued circulating ROH–RBP4–TTR and normalized liver RBP4 and TTR during ASNase. Overall, our findings identify AA insufficiency to modulate hepatic ROH–RBP4 mobilization independent of vitamin A status.
GPT-4o mini: Non-social science research article
Robert Haselkorn (1934–2025): Pioneer in molecular biology and microbiology
Susan S. Golden, David J. DeRosier, James E. Dahlberg, Louis A. Sherman, Bianca Brahamsha
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Robert Haselkorn (1934–2025) began a long and impactful career during the early years of nucleic acids research when the foundations of molecular biology were being laid. Focusing first on plant viruses, and then also bacteriophage, he hit upon a cyanophage—a cyanobacterial virus—that led his group to establish cyanobacterial strains as model organisms for fundamental bacterial research. He established that the specialized cells called heterocysts that are differentiated by multicellular Anabaena ( Nostoc ) are the sites of biological nitrogen fixation, and went on to reveal mechanisms of prokaryotic development. The Haselkorn lab became a leader more broadly in prokaryotic gene, and later genome, sequencing and annotation. Appreciated for his generosity and unwavering support of his lab members, and his contributions to creating a field of cyanobacterial molecular genetics, his impact continues across molecular biology and microbiology through those whose creativity he encouraged.
GPT-4o mini: Non-social science research article
A viral Cyclin D homolog protein hijacks the metabolic stress sensor SESN2 to promote primary effusion lymphoma growth
Mingjun Lin, Guanya Li, Xinyu Tang, Ru Li, Yinan Li, Lijie Wang, Zeyu Xu, Liansheng Liu, Enguo Ju, Jian Shang, Shanping He, Tingting Li
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Metabolic pathways are typically dysregulated in cancer to support critical cellular processes. In response to metabolic disturbances, cancer cells preferentially manipulate stress sensors to enhance their adaptability. Sestrin 2 (SESN2), a highly conserved protein induced by various stressors, is implicated in this adaptation. Mutations and alterations of SESN2 are prevalent among cancer patients, suggesting a potential role in tumor progression. However, the functions and regulation of SESN2 in cancer, particularly in virus-induced cancer, remain largely unknown. In this study, we demonstrate that latent infection with Kaposi’s sarcoma–associated herpesvirus (KSHV) stabilizes and upregulates SESN2 by inhibiting its proteasomal degradation across multiple cell lines. Notably, KSHV-encoded vCyclin, a homolog of cellular Cyclin D, directly interacts with SESN2 and promotes its stabilization by recruiting the deubiquitinase OTUB1, thereby blocking SESN2 polyubiquitination and proteasomal degradation. Moreover, vCyclin- and OTUB1-mediated stabilization of SESN2 activates AMP-activated protein kinase (AMPK), which supports the survival and growth of KSHV-driven primary effusion lymphoma cells. Importantly, the lysine at residue 74 of vCyclin is crucial for its cytosolic localization, OTUB1 recruitment, and subsequent SESN2 upregulation and AMPK activation. These findings unveil a regulatory mechanism for SESN2 involving vCyclin and OTUB1, positioning them as potential therapeutic targets for diseases associated with AMPK dysregulation.
GPT-4o mini: Non-social science research article
Correction for Hazime et al., Nanoscale restructuring of the immune synapse with an engager enhances NK cell function
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GPT-4o mini: Non-social science research article
Correction for Younis et al., CFTR dictates monocyte adhesion by facilitating integrin clustering but not activation
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GPT-4o mini: Non-social science research article
Structural basis for a potent human neutralizing antibody targeting a conserved epitope on the H7 hemagglutinin head
Junxin Li, Min Wang, Yang Yang, Limin Zhang, Lvyan Liu, Wei Yang, Yun Peng, Xu Zhang, Bin Yuan, Qi Peng, Xiaolu Yang, Yixin Chen, George F. Gao, Yi Shi, Xiaochun Wan
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Zoonotic H7N9 avian influenza virus infection remains a global concern because of its pandemic potential. Therefore, developing effective antibodies and vaccines against H7N9 is vital for preventing and controlling major outbreaks. Here, we isolated a human VH3-30 gene-encoded antibody, designated 6Y13, from a survivor of H7N9 infection. This antibody recognized the hemagglutinins (HAs) of the representative H7 subtype zoonotic viruses spanning two decades of antigenic evolution and potently neutralized epidemic H7N9 viruses in vitro. Moreover, 6Y13 conferred complete protection in mice against lethal H7N9 challenge in both prophylactic and therapeutic experiments. Structural analysis by cryoelectron microscopy indicated that 6Y13 binds to a unique conserved site on the HA head, distinct from the receptor-binding site and lateral patch. Nevertheless, 6Y13 efficiently blocked viral receptor binding without interfering with HA receptor binding, independent of Fc-mediated steric hindrance. Our findings provide a promising therapeutic candidate against pan-H7 subtype viruses and are beneficial for the design of H7 subtype influenza vaccine immunogens.
GPT-4o mini: Non-social science research article
Revealing emergent human-like conceptual representations from language prediction
Ningyu Xu, Qi Zhang, Chao Du, Qiang Luo, Xipeng Qiu, Xuanjing Huang, Menghan Zhang
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People acquire concepts through rich physical and social experiences and use them to understand and navigate the world. In contrast, large language models (LLMs), trained solely through next-token prediction on text, exhibit strikingly human-like behaviors. Are these models developing concepts akin to those of humans? If so, how are such concepts represented, organized, and related to behavior? Here, we address these questions by investigating the representations formed by LLMs during an in-context concept inference task. We found that LLMs can flexibly derive concepts from linguistic descriptions in relation to contextual cues about other concepts. The derived representations converge toward a shared, context-independent structure, and alignment with this structure reliably predicts model performance across various understanding and reasoning tasks. Moreover, the convergent representations effectively capture human behavioral judgments and closely align with neural activity patterns in the human brain, providing evidence for biological plausibility. Together, these findings establish that structured, human-like conceptual representations can emerge purely from language prediction without real-world grounding, highlighting the role of conceptual structure in understanding intelligent behavior. More broadly, our work suggests that LLMs offer a tangible window into the nature of human concepts and lays the groundwork for advancing alignment between artificial and human intelligence.
GPT-4o mini: Non-social science research article
A conductive folding metamaterial via laser-induced biomimetic electrospinning
Kangze Dong, Guangtao Zan, Xiaoge Mao, Hongmin Zhou, Huasen Wang, Qingsheng Wu, Tong Wu
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Conductive folding metamaterials (CFMs) represent a class of cross-physical-domain new-type metamaterials. However, the inherently nonfoldable nature of intrinsic conductive materials and the incompatibility between conductivity and extreme foldability have posed formidable challenges for their design and fabrication. To overcome these limitations, we developed a laser–electric-field coupled biomimetic spinning (LECBS) technique, which couples laser induction with cocoon/lotus-root-inspired biomimicry in a fast electrospinning Taylor cone reaction. Using this approach, we report the fabrication of CFMs composed of hierarchically adaptive carbon nanofiber networks. The CFMs constitute a new class of artificially microstructured composites with extraordinary physical properties absent in nature, filling a critical gap in the metamaterials family. The resulting CFMs endure up to 10 7 cycles, and potentially unlimited cycles, of true folding without damage, in arbitrary directions and with unrestricted 360° flexibility. Simultaneously, they achieve electrical conductivities on the order of 10 3 S·m − 1 , nearly one order of magnitude higher than comparable systems without carbon nanotubes. Mechanistic studies reveal that LECBS can effectively modulate Taylor cone hydrodynamics and jet behavior through photo-electro-matter interactions, which yields thinner nanofibers, enhanced sliding freedom of nanofibers, and axial alignment of CNTs in carbon nanofibers. Real-time SEM observations demonstrate the formation of characteristic M-shaped creases with “separated layers–smooth arcs–slidable grooves” during folding, which successfully disperse stress, in excellent agreement with finite element simulations. This work not only represents a breakthrough in metamaterials but also a technological revolution, opening new opportunities for flexible and foldable electronics fields.
GPT-4o mini: Non-social science research article
Modeling protein–small molecule conformational ensembles with PLACER
Ivan Anishchenko, Yakov Kipnis, Indrek Kalvet, Guangfeng Zhou, Rohith Krishna, Samuel J. Pellock, Anna Lauko, Gyu Rie Lee, Linna An, Justas Dauparas, Frank DiMaio, David Baker
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Modeling the conformational heterogeneity of protein–small molecule interactions is important for understanding natural systems and evaluating designed systems but remains an outstanding challenge. We reasoned that while residue-level descriptions of biomolecules are efficient for de novo structure prediction, for probing heterogeneity of interactions with small molecules in the folded state, an entirely atomic-level description could have advantages in speed and generality. We developed a graph neural network called PLACER (protein-ligand atomistic conformational ensemble resolver) trained to recapitulate correct atomic positions from partially corrupted input structures from the Cambridge Structural Database and the Protein Data Bank; the nodes of the graph are the atoms in the system. PLACER accurately generates structures of diverse organic small molecules given knowledge of their atom composition and bonding. When given a description of the larger protein context, it builds up structures of small molecules and protein side chains for protein–small molecule docking. Because PLACER is rapid and stochastic, ensembles of predictions can be readily generated to map conformational heterogeneity. In enzyme design efforts described here and elsewhere, we find that using PLACER to assess the accuracy and preorganization of the designed active sites results in higher success rates and higher activities; we obtain a preorganized retroaldolase with a k cat / K M of 11,000 M −1 min −1 , considerably higher than any pre–deep learning design for this reaction. We anticipate that PLACER will be widely useful for rapidly generating conformational ensembles of small molecule and small molecule–protein systems and for designing higher activity preorganized enzymes.
GPT-4o mini: Non-social science research article
Electromechanically induced membrane restructuring enables learning and memory
Peter T. Podar, Dima Bolmatov, Teshani Kumarage, Rana Ashkar, Ariana Adkisson, Olivia Ziemer, Victoria Sullivan, Ahmed S. Mohamed, Joseph. S. Najem, C. Patrick Collier, John Katsaras
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Human neural networks of interconnected neurons have evolved to be remarkably efficient and are capable of learning and memory through the brain’s synaptic plasticity, including short-term plasticity (STP), and long-term potentiation (LTP) and depression (LTD). These activity-dependent mechanisms induce changes in synaptic efficiency over both transient and extended timescales. Understanding the molecular basis of learning and memory is central to deciphering brain function and advancing therapeutics for neurodegenerative diseases. Here, we report that lipid bilayers with embedded gramicidin A ion channels can structurally reorganize when interrogated using a neurologically inspired electrical stimulation protocol, adopting metastable structures with enhanced STP response and emergent LTP or LTD. Specifically, voltage-induced electrocompression is found to restructure membranes, driving them into nonequilibrium steady states with enhanced stability and increased ionic conductivity, leading to stronger and persistent membrane ion conductance. These results show how membrane restructuring and emergent complexity may regulate synaptic plasticity at the molecular level.
GPT-4o mini: Non-social science research article
ENKD1 attenuates antibacterial immunity by facilitating TRIM21-mediated RUBCN degradation to suppress LC3-associated phagocytosis
Caimeng Song, Lulu Sun, Jie Wang, Shujun Liu, Wenqing Xu, Cai Zhang, Jun Zhou, Tianliang Li, Yan Li
Full text
Microtubule-associated protein 1A/1B-light chain 3 (LC3)-associated phagocytosis (LAP) plays a critical role in host defense against invading pathogens, including Listeria monocytogenes ( Listeria. monocytogenes ) , Salmonella typhimurium ( S. typhimurium ) , and Francisella novicida ( F. novicida ) . However, the precise regulatory mechanisms controlling LAP remain poorly understood. Here, we identify enkurin domain-containing protein 1 (ENKD1) as a key negative regulator of LAP during infection with these pathogens. Macrophages infected with L. monocytogenes (10403S), S. typhimurium (ATCC14028), or F. novicida (U112) exhibit significant ENKD1 downregulation. ENKD1-deficient macrophages display enhanced antibacterial activity, characterized by increased LAP, higher reactive oxygen species production, enhanced LC3 lipidation on phagosomes, and improved phagosome-lysosome fusion. In vivo, ENKD1 - deficient mice ex hibited improved bacterial clearance in the liver and spleen, with notable survival benefits. Mechanistically, ENKD1 interacts with the E3 ubiquitin ligase tripartite motif-containing protein 21 (TRIM21), which mediates degradation of Run domain Beclin-1-interacting and cysteine-rich domain-containing protein (RUBCN) through K48-linked polyubiquitination, thereby dampening RUBCN’s role in LAP. Our findings reveal an ENKD1–TRIM21–RUBCN axis that suppresses LAP, providing insights into antibacterial immune regulation and suggesting potential therapeutic strategies to enhance host defense against intracellular pathogens.
GPT-4o mini: Non-social science research article
Hund’s flat band in a frustrated spinel oxide
Dongjin Oh, Alexander Hampel, Joshua P. Wakefield, Peter C. Moen, Steef Smit, Xiangyu Luo, Marta Zonno, Sergey Gorovikov, Mats Leandersson, Craig Polley, Asish K. Kundu, Anil Rajapitamahuni, Elio Vescovo, Chris Jozwiak, Aaron Bostwick, Eli Rotenberg, Masahiko Isobe, Manish Verma, Matteo Crispino, Martin Grundner, Fabian B. Kugler, Olivier Parcollet, Ulrich Schollwöck, Hidenori Takagi, Andrea Damascelli, Giorgio Sangiovanni, Joseph G. Checkelsky, Antoine Georges, Riccardo Comin
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Electronic flat bands associated with quenched kinetic energy and heavy electron mass have attracted great interest for promoting strong electronic correlations and emergent phenomena such as high-temperature charge fractionalization and superconductivity. Intense experimental and theoretical research has been devoted to establishing the rich nontrivial metallic and heavy fermion phases intertwined with such localized electronic states. Here, we investigate the transition metal oxide spinel LiV 2 O 4 , an enigmatic heavy fermion compound lacking localized f orbital states. We use angle-resolved photoemission spectroscopy and dynamical mean-field theory to reveal a kind of correlation-induced flat band with suppressed interatomic electron hopping arising from intra-atomic Hund’s coupling. The appearance of heavy quasiparticles is ascribed to a proximate orbital-selective Mott state characterized by fluctuating local moments as evidenced by complementary magnetotransport measurements. The spectroscopic fingerprints of long-lived quasiparticles and their disappearance with increasing temperature further support the emergence of a high-temperature “bad” metal state observed in transport data. This work resolves a long-standing puzzle on the origin of heavy fermion behavior and unconventional transport in LiV 2 O 4 . Simultaneously, it opens a path to achieving flat bands through electronic interactions in d -orbital systems with geometrical frustration, potentially enabling the realization of exotic phases of matter such as the fractionalized Fermi liquids.
GPT-4o mini: Non-social science research article
A multivalent nanobody–drug conjugate to prevent and treat influenza virus infections
Thibault J. Harmand, Laura Pietrok, Helen Rich, Rhogerry Deshycka, Laney Flanagan, Aaron Accardo, Novalia Pishesha, Hidde L. Ploegh
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We describe the production and use of nanobody drug conjugates that comprise of VHH kappa , a nanobody that recognizes mouse immunoglobulin kappa light chains, and one or more copies of the small molecule influenza virus neuraminidase (NA) inhibitor, zanamivir. Such compounds achieve half-life extension of zanamivir, while recruiting polyclonal immunoglobulins of all isotypes regardless of specificity to infected cells for antibody-dependent cell-mediated cytotoxicity and complement-dependent cellular cytotoxicity. Since the influenza A virus (IAV) NA is a tetramer, we produced VHH kappa adducts with 1, 2, or 4 zanamivir molecules attached in a site-specific manner, to allow multivalent engagement of NA. Administration of a VHH kappa adduct modified with 4 zanamivir molecules (VHH kappa –Zan 4 ) was ~10-fold more potent in protection against infection with IAV than VHH kappa –Zan carrying only a single zanamivir molecule. VHH kappa –Zan 4 can be given intranasally to confer full protection against a lethal IAV challenge. The neutralizing antibody titers in the respiratory mucosa and in the circulation, as well as the serum IgG antibody response against the hemagglutinin and nucleoprotein, are higher in VHH kappa –Zan 4 treated mice that survived the lethal challenge than in controls infected with a sublethal dose of virus. VHH kappa –Zan 4 affords protection even when given intranasally weeks prior to a challenge with a lethal dose of IAV. This type of adduct can therefore be applied prophylactically and therapeutically and does not require prior immunization for protection against a lethal dose of IAV.
GPT-4o mini: Non-social science research article
Structural immunotherapy: Harnessing chemical design to build powerful next-generation therapeutics
Michelle H. Teplensky, Julianna N. Bourgeois, Sergej Kudruk, Sarah Hurst Petrosko, Chad A. Mirkin
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Structural immunotherapy relies on the structural features of immunotherapeutics in addition to component identity to influence biodistribution, intra- or extracellular localization, target engagement, and processing kinetics. This strategy is poised to redefine how immunotherapeutics mobilize immunity against disease and transform our ability to harness structure–function relationships to enhance clinical outcomes.
GPT-4o mini: Non-social science research article
Secreting salt glands constrain cuticle fracture to enhance desalination efficiency
Melissa H. Mai, Fulton E. Rockwell, Juan M. Losada, Nya Nicholson, Zhigang Suo, N. Michele Holbrook
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Plants responding to excessive soil salinity by discharging brine onto their leaf surface risk dehydration through the osmotic continuity between the living tissue and the surface brine, which further enriches with evaporation. Cuticle cracks have long been identified as essential for salt to reach the leaf surface but enable a potentially desiccating continuity between the brine and the gland interior. Using the secreting salt gland of Nolana mollis as a model system, we integrate mathematical modeling, imaging, and physiological measurements to examine the mechanical and biochemical processes required for efficient salt removal. We find that the subcuticular space between the concentrated surface brine and the more dilute secreting cell eases the energetic limits of active salt secretion by reducing the concentration gradient of salt across the cell membrane. We show that crack size plays a critical role in balancing the osmotic and pressure gradients required for salt removal without runaway foliar desiccation.
Strategic analysis of dissent and self-censorship
Joshua J. Daymude, Robert Axelrod, Stephanie Forrest
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Expressions of dissent against authority are an important feature of most societies, and efforts to suppress such expressions are common. Modern digital communications, social media, and Internet surveillance and censorship technologies are changing the landscape of public speech and dissent. Especially in authoritarian settings, individuals must assess the risk of voicing their true opinions or choose self-censorship, voluntarily moderating their behavior to comply with authority. We present a model in which individuals strategically manage the tradeoff between expressing dissent and avoiding punishment through self-censorship while an authority adapts its policies to minimize both total expressed dissent and punishment costs. We study the model analytically and in simulation to derive conditions separating defiant individuals who express their desired dissent in spite of punishment from self-censoring individuals who fully or partially limit their expression. We find that for any population, there exists an authority policy that leads to total self-censorship. However, the probability and time for an initially moderate, locally adaptive authority to suppress dissent depend critically on the population’s willingness to withstand punishment early on, which can deter the authority from adopting more extreme policies.
Why more social interactions lead to more polarization in societies
Stefan Thurner, Markus Hofer, Jan Korbel
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Over the past two decades, the number of close social connections increased substantially, at least by a factor of two. At the same time, societal opinions have become increasingly polarized in many Western countries. To explore whether these trends could be connected, we employ a simple computational model of society, where people—within their social networks—continuously compare and update their opinions. Here, we show that the model that is known to realistically capture both homophily and social balance exhibits a phase transition phenomenon where, above a critical social connectivity, an explosive transition toward strong polarization must occur. The model allows us to understand the empirical inflation of polarization during the last decades as a function of the observed increased values of social connectivity. In the presence of a small fraction of synchronized influencers, the transition becomes continuous; however, polarization then appears at lower connectivities. We discuss the implications of the presence of a phase transition in social polarization.
Recent immigration raids increased student absences
Thomas S. Dee
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Local immigration raids expanded dramatically across the United States during the first 2 mo of 2025. Anecdotal accounts suggest that these raids increased student absences from schools because parents fear being separated from their children. This study evaluates this claim using a daily time series of school absences spanning the current and two prior school years from five school districts serving communities subject to recent and unexpected raids in California’s Central Valley. The results indicate that recent raids coincided with a 22 percent increase in daily student absences with particularly large increases among the youngest students. These increased absences underscore the broader policy relevance of this immigration enforcement in terms of their impact on schools, childhood stress, and opportunities to learn.
The 2020 US Decennial Census is more private than you (might) think
Buxin Su, Weijie J. Su, Chendi Wang
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The US Decennial Census serves as the foundation for many high-profile policy decision-making processes, including federal funding allocation and redistricting. In 2020, the Census Bureau adopted differential privacy to protect the confidentiality of individual responses through a disclosure avoidance system that injects noise into census data tabulations. The Bureau subsequently posed an open question: Could stronger privacy guarantees be obtained for the 2020 US Census compared to their published guarantees, or equivalently, had the privacy budgets been fully utilized? In this paper, we address this question affirmatively by demonstrating that the 2020 US Census provides significantly stronger privacy protections than the officially published guarantees suggest at each of the eight geographical levels, from the national level down to the block level. This finding is enabled by our precise tracking of privacy losses using f -differential privacy, applied to the composition of private queries across these geographical levels. Our analysis reveals that the Census Bureau introduced unnecessarily high levels of noise to meet the specified privacy guarantees for the 2020 Census. Consequently, we show that noise variances could be reduced by 15.08% to 24.82% while maintaining nearly the same level of privacy protection for each geographical level, thereby improving the accuracy of privatized census statistics. We empirically demonstrate that reducing noise injection into census statistics mitigates distortion caused by privacy constraints in downstream applications of private census data, illustrated through a study examining the relationship between earnings and education.
The lower boundary of workplace mistreatment: Do small slights matter?
Michal Hodor, Liat Eldor, Peter Cappelli
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Recent research in psychology, management, and more recently in economics, highlights the role of individual managers and their behavior in shaping employee performance. While emerging literature on harmful managerial behavior has focused primarily on severe forms of workplace mistreatment, especially various types of harassment, much less is known about its boundary conditions: How minor can a manager’s bad behavior be and still negatively affect employee performance? We study what appears to be a very minor workplace mistreatment—failing to deliver an expected birthday gift and greeting card on time—and examine its effect on subsequent employee performance. Using a dynamic difference-in-differences approach with detailed data from a national retail chain, we find that this small slight leads to over a 50% increase in employee absenteeism and a reduction of more than two working hours per month. Our analysis suggests that emotional responses to perceived workplace mistreatment drive the results. These findings indicate that even modest slights can meaningfully harm employee performance.

Science

GPT-4o mini: Non-social science research article
Direct targeting and regulation of RNA polymerase II by cell signaling kinases
Preeti Dabas, Meritxell B. Cutrona, Wojciech Rosikiewicz, Ryan P. Kempen, Patrick Rodrigues, John Bowling, Mollie S. Prater, Walter H. Lang, Adithi Danda, Zhi Yuan, Beisi Xu, Shondra M. Pruett-Miller, Gang Wu, Taosheng Chen, Aseem Z. Ansari
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Distinct phosphorylation marks are placed on the carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) during different stages of gene transcription. These phospho-CTD marks function as a molecular recognition code for the recruitment of stage-specific effector proteins. Querying ~80% of the human kinome, we identified 117 kinases that phosphorylate the CTD with a high degree of positional selectivity. The unifying characteristic linking these diverse kinases is that they selectively regulate Pol II at signal-responsive genes. An example of such “direct-at-gene” Pol II regulation is displayed by epidermal growth factor receptor (EGFR), a cell surface receptor tyrosine kinase. More broadly, our atlas of CTD kinases implicates Pol II as a direct regulatory end point for signal-transducing kinases that govern cellular physiology and contribute to the etiology of numerous diseases.
GPT-4o mini: Non-social science research article
Repair of DNA double-strand breaks leaves heritable impairment to genome function
Susanne Bantele, Irene Mordini, Alva Biran, Nicolas Alcaraz, Gijs Zonderland, Alice Wenger, Nils Krietenstein, Anja Groth, Jiri Lukas
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Upon DNA breakage, a genomic locus undergoes alterations in three-dimensional chromatin architecture to facilitate signaling and repair. Although cells possess mechanisms to repair damaged DNA, it is unknown whether the surrounding chromatin is restored to its naĂŻve state. We show that a single DNA double-strand break (DSB) within a topologically associated domain (TAD) harboring conformation-sensitive genes causes lasting chromatin alterations, which persist after completion of DNA repair and feature topological rearrangements and loss of local RNA species. These newly acquired features of postrepair chromatin are transmitted to daughter cells and manifest as heritable impairments of gene expression. These findings uncover a hitherto concealed dimension of DNA breakage, which we term postrepair chromatin fatigue and which confers heritable impairment of gene function beyond DNA repair.
GPT-4o mini: Non-social science research article
Shear-induced bubble nucleation in magmas
Olivier Roche, Jean-Michel Andanson, Alain Dequidt, Christian Huber, Olivier Bachmann, David Pinel
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The nucleation of gas bubbles in magmas is fundamental to controlling the dynamics of volcanic eruptions. In this study, we addressed nucleation in a volatile-saturated liquid triggered by viscous shear, which is ubiquitous in volcanic environments. By combining laboratory experiments, theoretical analysis, and numerical simulations, we investigated the conditions under which the mechanical energy associated with shearing favors the formation and growth of gas molecule nuclei in a liquid supersaturated with volatiles. Our results reveal that the critical shear stress for nucleation decreases as the volatile supersaturation increases. Dimensional analysis applied to natural systems shows that shear-induced nucleation is likely to occur in volcanic conduits, which has implications for magma degassing processes and eruptive styles.
GPT-4o mini: Non-social science research article
Probing critical phenomena in open quantum systems using atom arrays
Fang Fang, Kenneth Wang, Vincent S. Liu, Yu Wang, Ryan Cimmino, Julia Wei, Marcus Bintz, Avery Parr, Jack Kemp, Kang-Kuen Ni, Norman Y. Yao
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At continuous phase transitions, quantum many-body systems exhibit complex, emergent behavior. Most notably, at a quantum critical point, correlations decay as a power law, with exponents determined by a set of universal scaling dimensions. Experimentally probing such power law correlations is extremely challenging, owing to the interplay between decoherence, the vanishing energy gap, and boundary effects. In this work, we used a Rydberg quantum simulator to adiabatically prepare critical ground states of both a one-dimensional ring and a two-dimensional square lattice. By accounting for and tuning the openness of our quantum system, which is well-captured by a single phenomenological length scale, we directly observed power law correlations and extracted the corresponding scaling dimensions. Our work complements recent studies of quantum criticality that use the Kibble-Zurek mechanism and digital quantum circuits.
GPT-4o mini: Non-social science research article
Multi-timescale frequency-phase matching for high-yield nonlinear photonics
Mahmoud Jalali Mehrabad, Lida Xu, Gregory Moille, Christopher J. Flower, Supratik Sarkar, Apurva Padhye, Shao-Chien Ou, Daniel G. SuĂĄrez-Forero, Mahdi Ghafariasl, Yanne Chembo, Kartik Srinivasan, Mohammad Hafezi
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Integrated nonlinear photonics struggles to deliver wafer-scale functional device yields: Nanometer-level fabrication variations compromise the strict frequency-phase matching mandated by energy- and momentum-conserving nonlinear processes. We introduce nested frequency-phase matching, a passive scheme that relaxes these constraints, and implement it in a two-timescale lattice of commercially available silicon nitride (SiN) coupled ring resonators for harmonic generation. The nested lattice simultaneously generates ultrabroad bandwidth light in the fundamental-, second-, third-, and fourth-harmonic bands and achieves 100% multifunctional wafer-scale device yield, all passively and without geometry fine-tuning. Distinct spatial and spectral signatures confirm the predicted relaxation of frequency-phase matching, establishing a scalable route for chip-scale nonlinear optics. Our approach provides possibilities for integrated frequency conversion and synchronization, self-referencing, precision metrology, squeezed-light sources, and nonlinear optical computing.
GPT-4o mini: Non-social science research article
River metabolism in the contiguous United States: A West of extremes
Taylor Maavara, Zimin Yuan, Andrew M. Johnson, Shuang Zhang, Kelly S. Aho, Craig B. Brinkerhoff, Laura A. Logozzo, Peter Raymond
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River metabolism is among the most uncertain fluxes in the global carbon cycle. We present estimates for gross primary productivity (GPP) and ecosystem respiration (ER) for more than 175,000 rivers across the contiguous United States (CONUS), including metabolic responses to extreme hydrological conditions. Our model predicts an annual GPP in CONUS rivers of 10.1 teragrams of carbon per year and an ER of 18.7 teragrams of carbon per year, which implies that net ecosystem productivity (NEP; where NEP = GPP – ER) is a small contributor to river carbon dioxide emissions. More than 70% of river metabolism occurs in the West, where regions of both extreme heterotrophy and autotrophy exist. Autotrophy is prominent across the West and is sensitive to drought, particularly in understudied biomes such as arid desert shrublands, which may indicate that global riverine uptake of carbon dioxide is higher than hypothesized.
GPT-4o mini: Non-social science research article
Unlocking the potential of brassinosteroids: A path to precision plant engineering
Nemanja Vukaơinović, Trevor M. Nolan, Eugenia Russinova
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Brassinosteroids are essential plant hormones that play a central role in regulating growth, development, and stress responses. Their impact on plant architecture and productivity makes them attractive targets for crop improvement. Recent findings reveal that brassinosteroid signaling is more complex than previously thought, involving multiple layers of regulation and cross-talk with other pathways. Cutting-edge technologies, such as single-cell analysis, proteomics, and advanced imaging in model plants, are beginning to uncover this complexity at cellular resolution. Applying these tools to crop species could reveal previously unknown signaling components and enable precise plant engineering. Because mutations in this pathway often cause widespread, unintended effects, future strategies must focus on fine-tuned tissue- or organ-specific modulation. This Review highlights how new insights could drive innovative, targeted crop enhancement.
GPT-4o mini: Non-social science research article
Extreme warming of Amazon waters in a changing climate
Ayan Santos Fleischmann, Fabrice Papa, Stephen K. Hamilton, John Melack, Bruce Forsberg, Adalberto Val, Walter Collischonn, Leonardo Laipelt, JĂșlia Brusso Rossi, Bruno Comini de Andrade, Bruna Mendel, Priscila Alves, Maiby Bandeira, Lady CustĂłdio, Maria CecĂ­lia Gomes, DĂ©bora Hymans, Isabela Keppe, Raize Mendes, Renan Nascimento, Paula dos Santos Silva, Camila Vieira, Rodrigo Xavier, AndrĂ© Zumak, Anderson Ruhoff, Wencai Zhou, Sally MacIntyre, Eduardo G. Martins, Naziano Filizola, RogĂ©rio Marinho, Ednaldo Bras Severo, Mariana Frias, Renata D. Alquezar, Lucas Lauretto, Waleska Gravena, AndrĂ© Coelho, Hilda ChĂĄvez-PĂ©rez, Susana Braz-Mota, Michel Chamy, Daniel Medeiros Moreira, Leandro Guedes Santos, JosĂ© R. Pacheco Peleja, Miriam Marmontel
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In 2023, an unprecedented drought and heat wave severely affected Amazon waters, leading to high mortality of fishes and river dolphins. Five of 10 lakes monitored had exceptionally high daytime water temperatures (over 37°C), with one large lake reaching up to 41°C in the entire approximately 2-meter-deep water column and up to 13°C of diel variation. Modeling showed that high solar radiation, reduced water depth and wind speed, and turbid waters were the main drivers of the high temperatures. This extreme heating of Amazon waters follows a long-term increase of 0.6°C/decade revealed by satellite estimates across the region’s lakes between 1990 and 2023. With ongoing climate change, temperatures that approach or exceed thermal tolerances for aquatic life are likely to become more common in tropical aquatic systems.
GPT-4o mini: Non-social science research article
Cosmic dust reveals dynamic shifts in central Arctic sea-ice coverage over the past 30,000 years
Frank J. Pavia, Jesse R. Farmer, Laura Gemery, Thomas M. Cronin, Jonathan Treffkorn, Kenneth A. Farley
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Arctic sea-ice loss affects biological productivity, sustenance in coastal communities, and geopolitics. Forecasting these impacts requires mechanistic understanding of how Arctic sea ice responds to climate change, but this is limited by scarce long-term records. We present continuous 30,000-year reconstructions of sea-ice coverage from the Arctic Ocean based on measurements of two isotopes, thorium-230 and extraterrestrial helium-3, whose burial ratio changes with sea-ice coverage. We found that the central Arctic was perennially covered by sea ice during the last glaciation. Sea-ice cover retreated during the deglaciation approximately 15,000 years ago, culminating in seasonal sea-ice coverage in the warm early Holocene, before ice coverage increased into the late Holocene. Sea-ice changes closely correlate with biological nutrient consumption, supporting projections of a nutrient-starved central Arctic Ocean with continued sea-ice loss.
GPT-4o mini: Non-social science research article
The anti-inflammatory activity of IgG is enhanced by co-engagement of type I and II Fc receptors
Andrew T. Jones, Alessandra E. Marino, Tetyana Martynyuk, Stylianos Bournazos, Jeffrey V. Ravetch
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Intravenous immunoglobulin (IVIG) administered at high doses is used to treat a wide array of autoimmune diseases. Studies in murine models have identified that the anti-inflammatory activity of IVIG is dependent on sialylation of the N-linked glycan on the CH2 domain of immunoglobulin G (IgG), the type I IgG inhibitory Fc receptor FcγRIIB, and the type II Fc receptor dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). We hypothesized that DC-SIGN, a C-type lectin, may directly interact with glycans on FcγRIIB, augmenting its ability to bind sialylated IgG. We found that Fc-engineering sialylated IgG1 to enhance its affinity for FcγRIIB resulted in a molecule that was more potent than IVIG in reducing the inflammatory sequelae of antibody or T cell–mediated autoimmune diseases, providing the basis for a class of potent anti-inflammatory therapeutics.
GPT-4o mini: Non-social science research article
NUDT5 regulates purine metabolism and thiopurine sensitivity by interacting with PPAT
Zheng Wu, Phong T Nguyen, Varun Sondhi, Run-Wen Yao, Zhifang Lu, Tao Dai, Jui-Chung Chiang, Feng Cai, Imani M Williams, Eliot B Blatt, Zengfu Shang, Ling Cai, Jing Zhang, Mya D Moore, Islam Alshamleh, Xiangyi Li, Tamaratare Ogu, Lauren G Zacharias, Rainah Winston, Joao S Patricio, Xandria Johnson, Wei-Min Chen, Qian Cong, Thomas P Mathews, Yuanyuan Zhang, Limei Zhang, Ralph J DeBerardinis
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Cells generate purine nucleotides through de novo purine biosynthesis (DNPB) and purine salvage. Purine salvage represses DNPB to prevent excessive purine nucleotide synthesis through mechanisms that are incompletely understood. We identified Nudix hydrolase 5 (NUDT5) as a DNPB regulator. During purine salvage, NUDT5 suppresses DNPB independently of its catalytic function but through interaction with phosphoribosyl pyrophosphate amidotransferase (PPAT), the rate-limiting enzyme in the DNPB pathway. The NUDT5-PPAT interaction promoted PPAT oligomerization, suppressed PPAT’s enzymatic activity, and facilitated disassembly of the purinosome, a metabolon that functions in DNPB. Disrupting the NUDT5-PPAT interaction overcame DNPB suppression during purine salvage, permitting excessive DNPB and inducing thiopurine resistance. Therefore, NUDT5 governs the balance between DNPB and salvage to maintain appropriate cellular purine nucleotide concentrations.
GPT-4o mini: Non-social science research article
A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis
Tuan-Anh Nguyen, Jung-Ming G. Lin, Anne-Sophie M. C. Marques, Maximilian Fottner, Ludwig G. Bauer, Andreas Reicher, Diana Daum, Lorenzo Scrofani, Yusi Liu, Carol Cheng, Luna D’Angelo L.d.D., Juan Sanchez, Christoph Bueschl, Nara Marella, Pisanu Buphamalai, Florian Traversi, MaĆĄa BereĆĄ, Herwig P. Moll, Marton Siklos, Jakob-Wendelin Genger, Gerald Hofstaetter, Ludovica Villanti, Monika Malik, Christoph Klimek, Kathrin Runggatscher, Bettina Guertl, Jesper S. Hansen, Sarah Dobner, Olga Babosova, Tina Becirovic, Laura P. M. H. de Rooij, Emilio Casanova, Anna Koren, D. Sean Froese, David S. Rosenblatt, Kristaps Klavins, Andreas Bergthaler, Jörg Menche, J. Thomas Hannich, Miriam Abele, Sara Sdelci, Kathrin Lang, Kilian V. M. Huber, Stefan Kubicek
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Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic dependencies caused by mutations in methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (MTHFD1), we discovered a key role for Nudix hydrolase 5 (NUDT5) in regulating purine de novo synthesis. Genetic depletion and selective chemical degradation showed that a scaffolding role, rather than NUDT5 enzymatic activity, was causing this phenotype. NUDT5 interacted with phosphoribosyl pyrophosphate amidotransferase (PPAT), the rate-limiting enzyme of purine de novo synthesis, to repress the pathway in response to increased purine abundance. Through this mechanism, loss of NUDT5 mediates resistance to purine analogs in cancer treatment and prevents adenosine toxicity in MTHFD1 deficiency.
GPT-4o mini: Non-social science research article
Experimental evidence for nodal superconducting gap in moiré graphene
Jeong Min Park, Shuwen Sun, Kenji Watanabe, Takashi Taniguchi, Pablo Jarillo-Herrero
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Understanding the nature of superconductivity in magic-angle graphene remains challenging. A key difficulty lies in discerning the different energy scales in this strongly interacting system, particularly the superconducting gap. Here, we report simultaneous tunneling spectroscopy and transport measurements of magic-angle twisted trilayer graphene. This approach allows us to identify two coexisting V-shaped tunneling gaps with different energy scales: a distinct low-energy superconducting gap that vanishes at the superconducting critical temperature and magnetic field, and a higher-energy pseudogap. The superconducting tunneling spectra display a linear gap-filling behavior with temperature and magnetic field and exhibit the Volovik effect, consistent with a nodal order parameter. Our work suggests an unconventional nature of the superconducting gap and establishes an experimental framework for multidimensional investigation of tunable quantum materials.
GPT-4o mini: Non-social science research article
Postdomestication selection of MKK3 shaped seed dormancy and end-use traits in barley
Morten E. JĂžrgensen, Dominique Vequaud, Yucheng Wang, Christian B. Andersen, Micha Bayer, Amanda Box, Katarzyna B. Braune, Yuanyang Cai, Fahu Chen, Jose A. Cuesta-Seijo, Haoran Dong, Geoffrey B. Fincher, Zoran Gojkovic, Zihao Huang, Benjamin Jaegle, Sandip M. Kale, Flavia Krsticevic, Pierre-Marie Le Roux, Antoine Lozier, Qiongxian Lu, Martin Mascher, Emiko Murozuka, Shingo Nakamura, Martin Ude Simmelsgaard, Pai R. Pedas, Pierre A. Pin, Dagmara Podzimska-Sroka, Kazuhiro Sato, Manuel Spannagl, Magnus W. Rasmussen, Joanne Russell, Miriam Schreiber, Hanne C. Thomsen, Nina W. Thomsen, Sophia Tulloch, Cynthia Voss, Birgitte Skadhauge, Nils Stein, Eske Willerslev, Robbie Waugh, Christoph Dockter
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Anthropogenic selection of grain traits such as dormancy has shaped the developmental trajectories of crops. In cereals, shortening dormancy provides rapid and even post-harvest germination, but increases the risk of weather-induced pre-harvest sprouting (PHS) with yearly harvest losses beyond 1 billion USD. Our understanding of how, why, when and where cereal dormancy diversification arose is fragmentary. Here, we show in the founder crop barley ( Hordeum vulgare ) that dormancy is primarily regulated through a mosaic of locus haplotypes comprising copy-number variation and inherent kinase activity of Mitogen-activated protein kinase kinase 3 ( MKK3 ). We provide evidence supporting the historical selection of specific MKK3 haplotypes that shape dormancy levels according to changing climatic pressures and outline a genetic framework for breeders to balance grain dormancy and PHS-avoidance.
GPT-4o mini: Non-social science research article
Adipogenin promotes the development of lipid droplets by binding a dodecameric seipin complex
Chao Li, Xue-Nan Sun, Jan-Bernd Funcke, Lauri Vanharanta, Xavier Prasanna, Kaitlynn Gov, Yan Li, Megan Virostek, Chanmin Joung, Nolwenn Joffin, Kristiina Kanerva, Abel Szkalisity, Waldemar Kulig, Leon Straub, Shiuhwei Chen, Joselin Velasco, Ayanna Cobb, Davide La Padula, May-Yun Wang, Toshiharu Onodera, Csaba Vörös, Dae-Seok Kim, Min Kim, Oleg Varlamov, Yang Li, Chen Liu, Andrea R. Nawrocki, Shangang Zhao, Da Young Oh, Zhao V. Wang, Ruth Gordillo, Joel M. Goodman, R. Max Wynn, W. Mike Henne, Ilpo Vattulainen, Yan Han, Elina Ikonen, Philipp E. Scherer
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The microprotein adipogenin (Adig) is predominantly expressed in adipose tissues. Here, we found that Adig interacts with seipin to form a stable, rigid complex. We present the structure of the seipin-Adig complex at an overall resolution of ~3.0 angstroms. The structure revealed that mammalian seipin assembles into two distinct oligomeric forms: undecamers and dodecamers. Adig selectively bound to the dodecameric form and enhanced seipin assembly by bridging and stabilizing adjacent subunits. Functionally, this complex promoted lipid droplet development at both early and late stages. In transgenic mice, adipocyte-specific overexpression of Adig increased fat mass and enlarged lipid droplets, whereas Adig deletion disrupted triglyceride accumulation in brown adipose tissues. Thus, Adig can modulate lipid storage through its structural and functional interactions with seipin.
GPT-4o mini: Non-social science research article
Strengthening Ni alloys with nanoscale interfaces of negative excess energy
J. X. Li, Z. H. Jin, X. Y. Li, K. Lu
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The strength of nanograined and nanotwinned metals is limited by the inherent instability of grain or twin boundaries below a length scale of typically about 10 nanometers. From experimental and density functional theory calculations, we found that the coherent interfaces between face-centered-cubic and hexagonal-close-packing lattices with a negative excess energy were more stable than twin boundaries in supersaturated Ni(Mo) solution. The negative excess-energy interface can be produced at extremely high density in Ni(Mo) solution with average spacing as small as about 1 nanometer, which inhibits plastic deformation and elevates the strength close to the theoretical value of the alloys. The measured Young’s modulus of the Ni(Mo) alloys increases obviously with the interface density, reaching 254.5 gigapascals, well above that of the same compositional metallic glass and intermetallic compound (Ni 3 Mo).
GPT-4o mini: Non-social science research article
Ultrafast inverse chirality-induced spin selectivity observed by THz emission
Yifan Dong, Aeron McConnell, Matthew P. Hautzinger, Md Azimul Haque, Andrew H. Comstock, Pius M. Theiler, Joseph M. Luther, Peter C. Sercel, Dali Sun, Matthew C. Beard
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Chirality-induced spin selectivity (CISS) phenomena arise from an interplay among structural chirality, electron spin orientation, and charge current. Steady-state observations such as magnetoresistance offer little insight into the timescales that govern the spin-charge interconversion and often conflate interfacial and bulk phenomena. By contrast, inverse CISS involves the conversion of spin to a charge current. Using terahertz (THz) emission spectroscopy, we directly measured an ultrafast charge current due to inverse CISS with picosecond time resolution. Polarity and polarization analysis of the THz emission map the induced charge current direction upon spin injection. We found that a charge current is generated along the spin orientation that changes direction with stereochemical configuration. These observations directly demonstrate the inherent coupling between spin and charge currents in chiral systems, offering key insights into their fundamental dynamics.
GPT-4o mini: Non-social science research article
The origin of hepatocellular carcinoma depends on metabolic zonation
Jason Guo, Roger Liang, Andrew Chung, Zhijie Li, Boyuan Li, Eric Chen, Lin Li, Jingjing Wang, Meng-Hsiung Hsieh, Ivy Xiangyi Fang, Benjamin Kroger, Yunguan Wang, Min Zhu, Xiongzhao Ren, Greg Mannino, Yuemeng Jia, Yonglong Wei, Stephen Moore, Daniel J. Siegwart, Stephen S. Chung, Zixi Wang, Tripti Sharma, Suman Komjeti, Yi Han, Purva Gopal, Guanghua Xiao, Tao Wang, Hao Zhu
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The origin of cancer is poorly understood because premalignant cells are rarely followed in their native environments. While the spatial compartmentalization of metabolic functions is critical for proper liver function, it is unknown if cancers arise from some zones but not others, and if there are metabolic determinants of cancer risk. Zone-specific, mosaic introduction of Ctnnb1 and Arid2 mutations, commonly co-mutated genes in hepatocellular carcinoma (HCC), showed that position and metabolic context determine clone fates. Ctnnb1/Arid2 -driven cancers were much more likely to arise in zone 3. The zone 3 genes Gstm2 and Gstm3 were required for efficient HCC initiation, in part through inhibition of ferroptosis. In the liver, the zonal determinants of HCC development can reveal metabolic vulnerabilities of cancer.
GPT-4o mini: Non-social science research article
Cryo–electron microscopy visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2
Luke A. Greenhough, Lorenzo Galanti, Chih-Chao Liang, Simon J. Boulton, Stephen C. West
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Homologous recombination repairs DNA double strand breaks and protects stalled replication forks, but how the five RAD51 paralogs contribute to these processes remains unclear. Mutations in the RAD51 paralogs are linked to heritable breast and ovarian cancers and the cancer-prone disease Fanconi anemia. In this work, we show that the RAD51 paralogs assemble into two distinct heterotetrameric complexes, RAD51B-RAD51C-RAD51D-XRCC2 (RAD51B complex) and XRCC3-RAD51C-RAD51D-XRCC2 (XRCC3 complex). The RAD51B complex promotes dynamic adenosine triphosphate hydrolysis–dependent assembly of RAD51 filaments, whereas the XRCC3 complex stably caps the 5â€Č-termini of RAD51 filaments to promote homologous pairing, as visualized by cryo–electron microscopy. Highly conserved across evolution, these complexes reveal insights into RAD51 filament formation and capping during DNA repair and replication fork stabilization.
GPT-4o mini: Non-social science research article
Homogenized chlorine distribution for >27% power conversion efficiency in perovskite solar cells
Zhuang Xiong, Qian Zhang, Kai Cai, Haitao Zhou, Qi Song, Zhaoyang Han, Shuaiqing Kang, Yaowen Li, Qi Jiang, Xingwang Zhang, Jingbi You
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The spatial heterogeneity of halogen distribution in perovskite thin films represents a critical factor currently limiting both the power conversion efficiency and stability of solar cells. We identified pronounced through-film inhomogeneity in chlorine distribution in formamidinium lead iodide films, with the generally used additive methylammonium chloride. We demonstrated that incorporating alkali metal oxalates could effectively homogenize the chlorine distribution. These compounds underwent thermal dissociation, releasing alkali metal cations that selectively bound chloride ions, which considerably suppressed surface defects and eliminated interfacial barriers. A certified steady-state power conversion efficiency (PCE) of 27.2% (device area and measured mask area: 0.108 square cm and 0.074 square cm, respectively) in perovskite solar cells was achieved, and devices retained 86.3% of their initial PCE after 1529 hours of continuous maximum power point tracking (MPPT) under 1 Sun condition. Moreover, the unpassivated device maintained 82.8% of its original PCE under MPPT at 85°C aging under 1 Sun illumination after 1000 hours.
Science abstract < 200 char.: Not a research article
Protect Iraq’s Mesopotamian Marshes
Sarmad Dashti Latif
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Science abstract < 200 char.: Not a research article
Britain must step up on AI policy
George Breckenridge
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Science abstract < 200 char.: Not a research article
A foundation of trust
Sofia Moutinho
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A 3-decade partnership between archaeologists and the Kuikuro people offers a model of collaboration—and documents the complexity of early Amazonian societies
Science abstract < 200 char.: Not a research article
New Products
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A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.
Science abstract < 200 char.: Not a research article
Thinning of DOE advisory bodies dismays researchers
Adrian Cho
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Department of Energy scraps committees that served as conduits to distinct research communities
Science abstract < 200 char.: Not a research article
Cell signaling meets gene transcription
Richard Young
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Receptor tyrosine kinases directly regulate RNA polymerase II in the nucleus
Science abstract < 200 char.: Not a research article
In Science Journals
Rachel Wood, Jake S. Yeston, Jesse Smith, Ian S. Osborne, Jelena Stajic, Angela Hessler, Christiana N. Fogg, Dorothy Hallberg, Madeleine Seale, Di Jiang, Yevgeniya Nusinovich, Sarah H. Ross, Stella M. Hurtley, Phil Szuromi, Marc S. Lavine, Leslie Ferrarelli, Mark Aldenderfer
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
Unbiased discovery of neuronal architectures
Jordan W. Squair, Michael A. Skinnider, Gregoire Courtine
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Comparative whole-brain and single-cell analyses identify neurons orchestrating neurological functions
Science abstract < 200 char.: Not a research article
Tree rings from ancient coffins offer clues to Earth’s past
Taylor Mitchell Brown
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Wood from gravesites can help reconstruct historic temperatures, droughts, and floods
Science abstract < 200 char.: Not a research article
Frankenstein and the problem of abandonment Frankenstein; or, The Modern Prometheus Mary Shelley Lackington, Hughes, Harding, Mavor, & Jones, 1818. 280 pp.
Dov Greenbaum
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A new adaptation of the cautionary tale is an opportunity to reflect on scientific stewardship
Science abstract < 200 char.: Not a research article
The role of organizations in fostering innovation
Imran Rasul
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Science abstract < 200 char.: Not a research article
FDA export restrictions threaten collaboration
Kaili Zhang, Jingyi Niu, Zhiyong Li
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Science abstract < 200 char.: Not a research article
The normalization of (almost) everything: Our minds can get used to anything, and even crises start feeling normal
Rachit Dubey
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Our minds can get used to anything, and even crises start feeling normal
Science abstract < 200 char.: Not a research article
Understanding nature and nurture: Statistical and AI innovations uncover how genes and environment shape human health
Jiacheng Miao
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Statistical and AI innovations uncover how genes and environment shape human health
Science abstract < 200 char.: Not a research article
Seipin-adipogenin controls lipid storage in fat cells
Jin Wu, Hongyuan Yang
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A protein complex promotes the expansion of lipid droplets during the formation of mature adipocytes
Science abstract < 200 char.: Not a research article
The need for a global effort to attend to human neural organoid and assembloid research
Sergiu P. Pașca, Paola Arlotta, Philip Campbell, Alta Charo, John H. Evans, Nita Farahany, Fred H. Gage, Peter Godfrey-Smith, Insoo Hyun, Arnold R. Kriegstein, Lucia Melloni, Guo-Li Ming, Jonathan D. Moreno, Jeremy Sugarman, Sally Temple, Giuseppe Testa, Henry T. Greely
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A continuing international process is needed to monitor and advise this rapidly progressing field
Science abstract < 200 char.: Not a research article
When ‘we’ turns wicked
Sorin M. S. Krammer
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Science abstract < 200 char.: Not a research article
Platforms of power The Age of Extraction: How Tech Platforms Conquered the Economy and Threaten Our Future Prosperity Tim Wu Knopf, 2025. 224 pp.
Simson L. Garfinkel
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A legal scholar pushes for net neutrality and other actions to rein in tech monopolies
Science abstract < 200 char.: Not a research article
Antarctic glacier’s retreat is fastest in modern history
Hannah Richter
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Tides and glacial earthquakes caused record ice loss at Hektoria Glacier
Science abstract < 200 char.: Not a research article
AI hallucinates because it’s trained to fake it till it makes it
Celina Zhao
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Teaching chatbots to say “I don’t know” could curb falsehoods but harm business model
Science abstract < 200 char.: Not a research article
Biomedical philanthropy promises dramatic expansion and AI focus
Jon Cohen
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Entering its second decade, the Chan Zuckerberg Initiative will make science the core mission for its founders’ billions
Science abstract < 200 char.: Not a research article
In Other Journals
Madeleine Seale, Marc S. Lavine, Jesse Smith, Corinne Simonti, Stella M. Hurtley, Mattia Maroso, Phil Szuromi
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
Shrinking interconnects beyond copper
Mehrdad T. Kiani, Judy J. Cha
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Quantum materials can speed up the information processing in a computer chip
Advancing research on financial stability and climate-related financial risk
William Pizer, James Stock
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Climate change–related natural disasters such as floods, fires, and storms devastate communities, and their massive costs continue to grow. But as climate risks increase, financial risk management infrastructure is not keeping pace. Analytical tools on which investors, regulators, central banks, and governments depend were largely built for a 20th-century climate and a fossil fuel–dominated economy. Policy-makers need a sounder understanding of which climate-related risks pose a threat to the financial system and macroeconomy, as well as the potential channels through which those risks operate. Although the US government recently disbanded its main efforts to understand and address these risks, it is vital that such work continues. Climate change is not a distant environmental issue, but a present financial and macroeconomic concern that will affect all of us, whether we accept it or not.

Science Advances

GPT-4o mini: Non-social science research article
Efficient launching of shear phonons in photostrictive halide perovskites
Dmytro O. Horiachyi, Mikhail O. Nestoklon, Ilya A. Akimov, Artur V. Trifonov, Nikita V. Siverin, Nataliia E. Kopteva, Alexander N. Kosarev, Dmitri R. Yakovlev, Vitalyi E. Gusev, Melina Fries, Olga Trukhina, Vladimir Dyakonov, Manfred Bayer
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Optical generation of coherent transverse phonons by femtosecond light pulses is appealing for sub-terahertz high-speed active control of material properties. Lead-free double-perovskite semiconductors, such as Cs 2 AgBiBr 6 , attract particular interest in this respect due to their structural phase transition and strong carrier-lattice coupling. Here, we reveal that the giant anisotropic photostriction in halide perovskites with tetragonal crystal structure provides an efficient nonthermal tool for generating coherent transverse phonons. Using time-domain Brillouin spectroscopy, we observe transverse and longitudinal acoustic phonons with comparable amplitudes in the tetragonal phase of Cs 2 AgBiBr 6 below the temperature of 122 kelvins, while, in the cubic phase, only longitudinal phonons are generated. The polarization of the transverse phonons is dictated by the projection of the crystal c axis on the surface plane, which leads to a prominent anisotropic polarization response in the detection. The generated strain pulses correspond to soft transverse acoustic eigenmodes with a strong temperature dependence of dispersion, providing an additional degree of freedom for hypersonic manipulation.
GPT-4o mini: Non-social science research article
Decoding paradoxical BOLD responses to transcranial ultrasound stimulation with concurrent optoacoustic magnetic resonance imaging
Yi Chen, Zhenyue Chen, Hector Estrada, Irmak Gezginer, Hikari A. I. Yoshihara, Diana Kindler, Chunqi Qian, David C. Zhu, Shy Shoham, Daniel Razansky
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Focused transcranial ultrasound stimulation (TUS) can affect neural activity with high spatial precision, advancing noninvasive neuromodulation toward targeted treatment of brain disorders. Direct monitoring of TUS responses is crucial for ensuring optimal outcomes. Blood-oxygenation-level–dependent (BOLD) functional magnetic resonance imaging has primarily been used for studying TUS effects in both human and nonhuman primate brains. However, the physiology and mechanisms underlying BOLD remain largely unknown due to its highly convoluted nature. To address these limitations, we developed a hybrid system for concurrent optoacoustic and magnetic resonance imaging of TUS (OMRITUS) to comprehensively characterize the hemodynamic changes in murine brains. Our findings reveal paradoxical negative BOLD signals in the activated cortical regions, coupled with increased total hemoglobin levels simultaneously monitored with optoacoustic tomography. Multispectral optoacoustic readings further demonstrated a stronger increase in deoxygenated versus oxygenated hemoglobin, suggesting a potential molecular basis for the negative BOLD responses. OMRITUS enables the study of complex TUS-hemodynamic interactions, paving the way for precise neuromodulatory interventions.
GPT-4o mini: Non-social science research article
Substantially underestimated winter CO 2 sources of the Southern Ocean
Siqi Zhang, Peng Chen, Kelsey Bisson, Cédric Jamet, Paolo Di Girolamo, Davide Dionisi, Yongxiang Hu, Zhenhua Zhang, Kun Shi, Delu Pan
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The size and control mechanism of the Southern Ocean’s carbon fluxes remain highly uncertain due to sparse winter observations. Here, we integrate satellite light detection and ranging (LIDAR) measurements with machine learning to assess the Southern Ocean air-sea CO 2 fluxes between 2007 and 2020. We reveal that CO 2 outgassing south of 50°S was underestimated by up to 40% in previous studies. While the midlatitude Southern Ocean (30° to 50°S) strengthens as a carbon sink, the high-latitude region (50° to 90°S) shows Southern Annular Mode (SAM)–modulated alternation between uptake and outgassing. The air-sea CO 2 partial pressure difference (Δ p CO 2 ) increasingly dominates flux variability over wind-driven transfer velocity. We propose a framework involving three latitudinal loops with differing p CO 2 controls: (i) Antarctic (salinity/sea ice), (ii) polar front (atmospheric CO 2 /chlorophyll), and (iii) subpolar (sea surface temperature/CO 2 ). The findings underscore the winter processes’ critical role and necessitate year-round observations to understand Southern Ocean’s global carbon cycle impact.
GPT-4o mini: Non-social science research article
Curved graphite precursors enable cubic-hexagonal diamond heterostructures with unprecedented toughness-hardness synergy
Xiaoci Ma, Di Wang, Min Lian, Xinglin Wang, Cun You, Yufei Ge, Guiqian Sun, Hetian Liu, Yutong Hou, Qiang Tao, Quan Li, Pinwen Zhu, Tian Cui
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The intrinsic trade-off between hardness and toughness presents a long-standing challenge for diamond-based materials, limiting their use in extreme environments. Here, we report a bioinspired strategy to overcome this limitation by engineering graphite precursors with mimosa-like microscale curvature. Under high-pressure and high-temperature conditions (15 gigapascals and 2300 kelvin), these precursors concentrate local stress, promoting nucleation of hexagonal diamond within a cubic diamond matrix and forming cubic-hexagonal heterostructures. The resulting composites exhibit exceptional hardness (169 gigapascals) and toughness (15.7 megapascals multiplied by square root of meter), representing 36 and 104% improvements over single-phase nanopolycrystalline diamond, respectively. This dual enhancement arises from stacking fault interlocking and semi/coherent boundaries that resist deformation, coupled with phase transformation and crack deflection that dissipate fracture energy. Our results demonstrate a microstructural design paradigm for mitigating the property trade-off in superhard materials and offer a scalable strategy for engineering robust diamond-based systems.
GPT-4o mini: Non-social science research article
Functional landscape of mechanistic diversity in 27 claudin family members at tight junctions
Hiroka Kashihara, Hiroo Tanaka, Manabu Kitamata, Gen Shiratsuchi, Tatsuya Katsuno, Kazuto Tsukita, Tomoki Nishida, Mayumi Hamasaki, Fabian Eisenstein, Hiroshi Suzuki, Shun Nakamura, Koji Aoyama, Takeshi Yagi, Radostin Danev, Yoshinori Fujiyoshi, Atsushi Tamura, Sachiko Tsukita
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The diversity of epithelial paracellular barriers, essential for various biological functions, is primarily determined by the combination of 27 claudins (Cldns) that form tight junctions (TJs). However, the basis of their functional diversity remains largely unexplored. Here, we generated complete Cldn -null mouse epithelial cells to reconstitute the TJ paracellular barrier (TJ barrier) with individual Cldns. Each Cldn establishes its respective TJ barrier, either autonomously or nonautonomously, exhibiting distinct ion conductivity and selectivity. Clustering algorithms revealed a previously unidentified classification of Cldns into four main classes with well-defined subclasses, moving beyond the conventional paracellular barrier–versus–channel-forming dichotomy. Our findings, including the in vivo Cldn dynamics, provide a framework for understanding TJ barrier diversity and plasticity, offering insights into organ-specific homeostasis and guiding therapeutic strategies targeting TJ barriers in health and disease.
GPT-4o mini: Non-social science research article
A multi-agentic framework for real-time, autonomous freeform metasurface design
Robert Lupoiu, Yixuan Shao, Tianxiang Dai, Chenkai Mao, Kofi Edée, Jonathan A. Fan
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Innovation in nanophotonics currently relies on human experts who synergize specialized knowledge in photonics and coding with simulation and optimization algorithms, entailing design cycles that are time-consuming, computationally demanding, and frequently suboptimal. We introduce MetaChat, a multi-agentic design framework that can translate semantically described photonic design goals into high-performance, freeform device layouts in an automated, nearly real-time manner. Multistep reasoning is enabled by our Agentic Iterative Monologue paradigm, which coherently interfaces agents with code-based tools, other specialized agents, and human designers. Design acceleration is facilitated by Feature-wise Linear Modulation–conditioned Maxwell surrogate solvers that support the generalized evaluation of metasurface structures. We use freeform dielectric metasurfaces as a model system and demonstrate with MetaChat the design of multiobjective, multiwavelength metasurfaces orders of magnitude faster than conventional methods. These concepts present a scientific computing blueprint for using specialist design agents, surrogate solvers, and human interactions to drive multiphysics innovation and discovery.
GPT-4o mini: Non-social science research article
The editable landscape of the yeast genome reveals hotspots of structural variant formation
Shengdi Li, Sibylle C. Vonesch, Kevin R. Roy, Chelsea Szu Tu, Friederike Steudle, Michelle Nguyen, Cosimo Jann, Lars M. Steinmetz
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It is unclear how CRISPR editing outcomes vary across the genome and whether undesirable events such as structural variants (SVs) are predictable or preventable. To define a genome-wide map of editability, we performed whole-genome sequencing on 1875 budding yeast clones edited across 16 chromosomes by CRISPR-Cas9 and donor-templated repair. We found that unintended edits, including short indels and SVs, were enriched in specific genomic and sequence contexts. We developed a predictive model, SCORE (System for CRISPR Outcome and Risk Evaluation), which revealed 4.8% of the genome as SV prone, consisting of 562 SV hotspots. Donor repair-enhancing strategies suppressed SV formation in regions with moderate, but not high, predicted risk. Applying SCORE to the Sc2.0 synthetic yeast genome revealed a markedly altered SV landscape due to the removal of endogenous repetitive elements and the insertion of loxP sites. Our study provides the genome-scale map of SV hotspots after CRISPR editing and predictive and experimental tools to mitigate their formation.
GPT-4o mini: Non-social science research article
A network of basolateral amygdala projection neurons contributes to stress-induced activation of the hypothalamic-pituitary-adrenal axis
Robert J. Aukema, Gavin N. Petrie, Benjamin K. Lau, Lauren T. Seabrook, Samantha L. Baglot, John P. Christianson, Jaideep S. Bains, Maria Morena, Stephanie L. Borgland, Matthew N. Hill
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The basolateral amygdala (BLA) is reliably activated by psychological stress in both humans and rodents and influences diverse behavioral and physiological processes involved in stress adaptation. However, functional organization of distinct BLA circuits and their contribution to stress-induced activation of the neuroendocrine response is unclear. We establish four major findings in adult male rats: (i) BLA projection neurons are necessary and sufficient for stress-induced neuroendocrine activation; (ii) projection populations have a heterogeneous spatial distribution across the BLA; (iii) diverse BLA populations targeting the prelimbic cortex, nucleus accumbens, bed nucleus of stria terminalis, central amygdala, lateral hypothalamus, and ventral hippocampus are activated by acute stress, with the location of activated populations biased toward the medial basal amygdala; and (iv) inhibition of singular projections does not recapitulate global inhibition of BLA projection neurons. Together, this suggests that a network of BLA projection populations is broadly activated by acute stress and collectively contribute to neuroendocrine regulation.
GPT-4o mini: Non-social science research article
Real-time decoding of full-spectrum Chinese using brain-computer interface
Youkun Qian, Changjiang Liu, Peixi Yu, Xingchen Ran, Shurui Li, Qinrong Yang, Yang Liu, Lei Xia, Yijie Wang, Jianxuan Qi, Erda Zhou, Junfeng Lu, Yuanning Li, Tiger H. Tao, Zhitao Zhou, Jinsong Wu
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Speech brain-computer interfaces (BCIs) offer a promising means to provide functional communication capacity for patients with anarthria caused by neurological conditions such as amyotrophic lateral sclerosis (ALS) or brainstem stroke. Current speech decoding research has predominantly focused on English using phoneme-driven architectures, whereas real-time decoding of tonal monosyllabic languages such as Mandarin Chinese remains a major challenge. This study demonstrates a real-time Mandarin speech BCI that decodes monosyllabic units directly from neural signals. Using the 256-channel microelectrocorticographic BCI, we achieved robust decoding of a comprehensive set of 394 distinct syllables based purely on neural signals, yielding median syllable identification accuracy of 71.2% in a single-character reading task. Leveraging this high-performing syllable decoder, we further demonstrated real-time sentence decoding. Our findings demonstrate the efficacy of a tonally integrated, direct syllable neural decoding approach for Mandarin Chinese, paving the way for full-coverage systems in tonal monosyllabic languages.
GPT-4o mini: Non-social science research article
Surface reconstructions govern ice nucleation on silver iodide
Johanna I. HĂŒtner, Andrea Conti, David Kugler, Franziska Sabath, Kim Noelle Dreier, Hans-Georg Stammler, Florian Mittendorfer, Angelika KĂŒhnle, Michael Schmid, Ulrike Diebold, Jan Balajka
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Silver iodide (AgI) is among the most effective ice-nucleating agents, attributed to its close lattice match with hexagonal ice. However, the atomic-level mechanism behind its efficiency remains unclear. The basal surfaces of AgI are polar and inherently unstable, necessitating a compensation mechanism, such as surface reconstruction, which may disrupt the favorable lattice match with ice. We combine noncontact atomic force microscopy with advanced computational modeling to determine the atomic structure of basal AgI surfaces in ultrahigh vacuum. The Ag-terminated (0001) surface exhibits a (2 × 2) reconstruction with ordered Ag vacancies, preserving a hexagonal arrangement of surface atoms that facilitates epitaxial ice growth. In contrast, the I-terminated (000 1 ¯ ) surface adopts a complex rectangular reconstruction, incompatible with continuous ice layer formation. These findings highlight the decisive role of surface atomic structure and indicate that the Ag-terminated basal plane is primarily responsible for efficient ice nucleation on AgI.
GPT-4o mini: Non-social science research article
Unlocking the therapeutic potential of cellular mechanobiology
Yohalie Kalukula, Giuseppe Ciccone, Danahe Mohammed, Anthony ProcÚs, Marie Versaevel, Amandine Deridoux, Lucie Ergot, Zoé Barbier, Maxime Mansy, Roxane Aucouturier, Rémi Tranzer, Mathieu Surin, Sylvain Gabriele, Marine Luciano
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Mechanobiology is a rapidly advancing field at the intersection of biology, physics, and engineering that reveals how mechanical forces shape cellular behavior, tissue architecture, and disease progression. By elucidating how cells sense and transduce mechanical cues, mechanobiology has fundamentally advanced our understanding of processes ranging from migration and differentiation to immune responses and tissue remodeling. These advances have driven the development of innovative biophysical tools and engineered biomaterials that enable precise modulation of the cellular microenvironment. Translating mechanobiological principles into clinical practice is giving rise to mechanomedicine, a previously unrecognized paradigm that integrates mechanical forces as key modulators of health and disease. This review highlights how mechanobiology informs therapeutic strategies across diverse domains, including cancer immunotherapy, cardiovascular and neurodegenerative disorders, and regenerative medicine. By bridging fundamental discoveries with translational applications, this review positions mechanobiology as a cornerstone of next-generation medical innovation, translating mechanistic insights into impactful clinical applications.
GPT-4o mini: Non-social science research article
BrainSTEM: A single-cell multiresolution fetal brain atlas reveals transcriptomic fidelity of human midbrain cultures
Hilary S. Y. Toh, Lisheng Xu, Carissa Chen, Pengyi Yang, Alfred X. Sun, John F. Ouyang
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Protocols for deriving midbrain dopaminergic (mDA) neurons for Parkinson’s disease (PD) modeling and therapy remain incompletely benchmarked against in vivo references. To establish transcriptomic standards, we generated an integrated human fetal whole-brain atlas and a midbrain subatlas. Whole-brain analysis revealed strong region-specific signatures, underscoring the need for global mapping before refined midbrain annotation. We implemented this two-tier strategy, BrainSTEM (Brain Single-cell Two tiEr Mapping), to systematically reassess published single-cell datasets of human midbrain culture models. BrainSTEM confirmed the presence of bona fide midbrain cell types (“on-target”), but also revealed substantial populations aligning with nonmidbrain regions (“off-target”), inflating reported mDA yields across protocols. This unbiased framework enables rigorous evaluation of differentiation outcomes, clarifies current limitations of midbrain-directed models, and provides a foundation for refining protocols toward more faithful in vitro systems for PD research and regenerative applications.
GPT-4o mini: Non-social science research article
KDM4A serves as an α-tubulin demethylase regulating microtubule polymerization and cell mitosis
Suhao Cao, Shaogang Wang, Xuan Xie, Xinyi Tan, Xinyu Hu, Fengxia Shao, Yanling Liu, Xu Zhang, Hong Cheng, Lei Diao, Lan Bao
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Posttranslational modifications of tubulin give microtubule distinct properties to support diverse cellular functions. Trimethylation on lysine-40 of α-tubulin (α-TubK40me3) is involved in cell division and neuronal development. The “writer” (SETD2) and “reader” (PBRM1) of α-TubK40me3 have been identified. However, the “eraser” of α-TubK40me3 and the impact of α-TubK40me3 dynamic balance on cells are still unclear. Here, we report that KDM4A, a member of the histone demethylase family, binds α-tubulin through its catalytic core domain and demethylates α-tubulin. KDM4A knockout significantly enhances α-TubK40me3, inducing microtubule polymerization and mitotic defects. Furthermore, the overpolymerized microtubules and cell mitotic defects caused by KDM4A knockout are rescued by reducing α-TubK40me3 with overexpression of an α-tubulin mutant α-tubulin K40A or depolymerizing microtubules with nocodazole treatment in cells. Together, our study identifies KDM4A as an α-tubulin demethylase, and this demethylation is important for regulating microtubule polymerization and cell mitosis.
GPT-4o mini: Non-social science research article
Thalamo-hippocampal pathway determines aggression and self-harm
Jane Jung, In-Jee You, Sora Shin
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Aggression and self-harm are maladaptive coping strategies that often occur in individuals with a history of early life trauma (ELT), yet their underlying neural mechanisms remain unclear. Here, we identify L-type calcium channel (LTCC)–expressing thalamic nucleus reuniens (RE) as a critical component regulating both behaviors. ELT-induced excessive LTCC activity in vesicular glutamate transporter 2 (vGlut2) RE neurons and its corresponding effects on persistent neuronal activation contribute to increasing susceptibility to aggression and self-harm. Activation of vGlut2 RE neurons projecting to ventral hippocampus (vCA1), but not medial prefrontal cortex, promotes these behaviors in control mice. Furthermore, we found that RE neurons modulate two distinct subsets of vCA1 neurons, with one projecting to the hypothalamus to drive aggression and another to the basal amygdala to mediate self-harm. Our findings uncover how LTCC functions in the RE-to-vCA1 neural pathway increase the risk of aggression and self-harm, highlighting potential therapeutic targets for mitigating destructive behaviors following early adversity.
GPT-4o mini: Non-social science research article
Direct evidence of natal homing in an Atlantic herring metapopulation
Dorothee Moll, Patrick Polte, Klaus Peter Jochum, Tomas Gröhsler, Dorte Bekkevold, Ian McQuinn, Christian Möllmann, Christopher Zimmermann, Paul Kotterba
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In times of increased human interventions, knowledge on animal breeding-site fidelity is crucial for the conservation of important reproduction areas vital to the resilience of populations. In particular, in the marine environment, dependency of ocean-going fish on specific coastal locations are rarely implemented in spatial planning. However, when essential nursery habitats are threatened, the resilience of fish populations is jeopardized. For technical reasons, former studies on Atlantic herring could not specify if fish, returning to spawning grounds, returned to sites of their own natal origin. Combining otolith microchemistry with genetics, we show that Atlantic herring perform natal homing with rates between 56 and 73%. The implicit number of strays adopted along migration maintain the gene flow between subpopulations, supporting the hypothesized “metapopulation” concept. With respect to increasing anthropogenic impacts, this study demonstrates the need for a goal-oriented coastal zone management to ensure productive ecosystems and a sustainable fishery in the future.
GPT-4o mini: Non-social science research article
Ni-catalyzed enantioselective synthesis of ÎČ-aminoboronates via spin-center shift and proton transfer
Yahao Wang, Guozhen Wu, Wei Zhu, Xiaotian Qi, Qiuling Song
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The spin-center shift (SCS) process, involving 1,2-radical migrations, plays a pivotal role in both biological transformations and organic synthesis. While the potential of combining SCS with transition metal–catalyzed enantioselective reductive coupling of electrophiles to construct Csp 3 -Csp 3 bonds at remote positions is highly attractive, this strategy has remained unexplored to date. Here, we report an enantioselective Ni-catalyzed reductive cross-coupling for the synthesis of ÎČ-aminoboronates. Our catalytic system operates under mild conditions, achieving excellent enantioselectivity while maintaining broad functional group compatibility. Mechanistic studies, including detailed density functional theory (DFT) calculations, demonstrate the synergistic involvement of both SCS and proton transfer (P.T.) processes in the reaction pathway.
GPT-4o mini: Non-social science research article
Intrinsically charge-generating polymers with long-lived free carriers for efficient photon-to-hydrogen conversion
Yunzhi Wang, Partha Maity, Yinglu Jia, Baiqiao Liu, Lingyun Zhao, Yanru Li, Weiwei Li, Zhuping Fei, Martin Heeney, Suzana P. Nunes, Wan-Lu Li, Omar F. Mohammed, Huabin Zhang
Full text
A single organic semiconductor typically struggles with inefficient intrinsic charge generation due to large binding energy ( E B  ≈ 0.5 electron volts) of Frenkel excitons, particularly in narrow-bandgap organic semiconductors that exhibit near-infrared (NIR) absorption. Here, we develop double-cable polymer–based nanoparticles (NPs), enabling single-component organic photocatalysts to achieve NIR photon absorption and generate long-lived free charges simultaneously. as -DCPIC, a double-cable polymer with donor polymer (PBDB-T) as electron-donating conjugated backbones and pendent NIR acceptor (TPDIC) as the electron-deficient side chains, offers potential for self-sustained photoelectric conversion. Consequently, as -DCPIC NPs exhibit significantly enhanced hydrogen evolution performance (11.88 mmol per hour per gram) compared to pristine PBDB-T or TPDIC NPs. Transient absorption spectroscopy elucidates the effective electron-hole separation inside as -DCPIC NPs, whereas decay kinetics monitor the long-lived free carriers (109 nanoseconds) in as -DCPIC NPs. Our findings demonstrate that double-cable polymers provide a powerful platform for establishing efficient single-component organic photocatalysts to generate long-lived reactive charges.
GPT-4o mini: Non-social science research article
Neural correlates of phosphene perception in blind individuals: A step toward a bidirectional cortical visual prosthesis
Fabrizio Grani, Cristina Soto-SĂĄnchez, Alfonso Rodil Doblado, Rocio Lopez Peco, Pablo Gonzalez-Lopez, Eduardo Fernandez
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Blindness is one of the most impactful disabilities in human lives. Cortical prostheses could one day restore functional vision in some blind subjects, but their success will depend on integrating advanced technologies to realize the therapeutic benefits they promise. Most previous studies in humans used electrodes only for stimulation, which has made it challenging to precisely control the appearance of individual phosphenes. Herein, we implanted an intracortical microelectrode array of 100 electrodes in the visual cortex of two blind volunteers. We recorded the neural activity around the electrodes while performing electrical stimulation to induce visual perceptions. Besides showing how stimulation parameters influence perceptual thresholds, perceived brightness, and the minimum interval required to distinguish separate stimuli, our results indicate that subjective visual experience can be accurately predicted from the recorded neural activity. These results highlight the potential for using the neural activity of neighboring electrodes to accurately infer and control visual perceptions in cortical visual prostheses.
GPT-4o mini: Non-social science research article
Nonfluorinated membrane with a decentralized ion-transport network enables efficient and sustainable polysulfide redox flow batteries
Feiran Wang, Shuang Luo, Jiafeng Lei, Fei Ai, Ka Lok Leung, Jun Fan, Yi-Chun Lu
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Polysulfide-based redox flow batteries are promising for long-duration energy storage, owing to ultralow-cost/earth-abundant active materials and full decoupling of power and energy. However, their practical application has been prevented by poor cycle life resulting from polysulfide crossover and a heavy reliance on costly fluorinated membranes (Nafion 117, USD $800 to $3500 per square meter), along with the environmental concerns. Here, we develop a nonfluorinated sulfonated polyethersulfone (SPES)–based membrane with decentralized ion-transport channels, achieving a 20 times higher ionic selectivity at a markedly reduced cost (USD $12 to $66 per square meter) compared to the commercial Nafion membrane. The low-cost SPES-based membrane enabled stable cycling of polysulfide-ferrocyanide redox flow batteries with a high coulombic efficiency (>99.9%) and energy efficiency (average >75%) for 1600 cycles (>6 months). This strategy demonstrated polysulfide-based redox flow batteries with a record longevity using a low-cost and sustainable membrane, paving the way for their practical commercialization.
GPT-4o mini: Non-social science research article
Mind captioning: Evolving descriptive text of mental content from human brain activity
Tomoyasu Horikawa
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A central challenge in neuroscience is decoding brain activity to uncover mental content comprising multiple components and their interactions. Despite progress in decoding language-related information from human brain activity, generating comprehensive descriptions of complex mental content associated with structured visual semantics remains challenging. We present a method that generates descriptive text mirroring brain representations via semantic features computed by a deep language model. Constructing linear decoding models to translate brain activity induced by videos into semantic features of corresponding captions, we optimized candidate descriptions by aligning their features with brain-decoded features through word replacement and interpolation. This process yielded well-structured descriptions that accurately capture viewed content, even without relying on the canonical language network. The method also generalized to verbalize recalled content, functioning as an interpretive interface between mental representations and text and simultaneously demonstrating the potential for nonverbal thought–based brain-to-text communication, which could provide an alternative communication pathway for individuals with language expression difficulties, such as aphasia.
GPT-4o mini: Non-social science research article
The two-component nuclease-active KELShedu system confers broad antiphage activity via abortive infection
Hengwei Zhang, Jiajia You, Hanwen Zhou, Zan Zhang, Hongxuan Wu, Di Zhang, Xuewei Pan, Weiguo Zhang, Xian Zhang, Zhiming Rao
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Bacteriophages and bacteria engage in a continuous evolutionary arms race, driving the development of intricate bacterial defense systems such as CRISPR-Cas, BREX (Bacteriophage Exclusion), Gabija, and Shedu. Here, we characterize a two-component KELShedu system in Escherichia coli that confers resistance to phages via abortive infection. The KELShedu system comprises KELA, a double-stranded DNA–binding protein, and KELB, a metal ion-dependent nuclease harboring the DUF4263 domain. In addition, we find that physiological levels of nucleotide triphosphates (NTPs) inhibit the DNA cleavage activity of the KELShedu system, suggesting that KELShedu’s activation depends on reduced intracellular NTP levels during phage invasion. Our research demonstrates that the KELShedu system responds to nucleotide depletion triggered by phage replication, leading to nonspecific degradation of cellular DNA and ultimately inducing abortive infection. These insights into the KELShedu system expand the repertoire of bacterial antiphage mechanisms and lay the groundwork for applications in microbial engineering and therapeutic development.
GPT-4o mini: Non-social science research article
Quantum twin interferometers
Wei Du, Shuhe Wu, Dong Zhang, Jun Chen, Yiquan Yang, Peiyu Yang, Jinxian Guo, Guzhi Bao, Weiping Zhang
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Quantum-correlated interferometer is an emerging tool in quantum technology that offers classical-limit-breaking phase sensitivity. However, to date, there exists a configurational bottleneck for its practicability due to the low phase-sensing power limited by the current detection strategies. Here, we establish an innovative development termed as “quantum twin interferometer” with dual pairs of entangled twin beams arranged in the parallel configuration, allowing full exploitation of the quantum resource through the configuration of entangled detection. We observe the distributed phase sensing with 3-decibel quantum noise reduction in phase-sensing power at the level of milliwatts, which advances the record of signal-to-noise ratio so far achieved in photon-correlated interferometers by three orders of magnitude. The developed techniques in this work can be used to revolutionize a diversity of quantum devices requiring phase measurement.
GPT-4o mini: Non-social science research article
Charting the nanotopography of inner hair cell synapses using MINFLUX nanoscopy
Rohan Kapoor, Hyojin Kim, Evelyn Garlick, Maria Augusta do R. B. F. Lima, Klara Esch, Torben Ruhwedel, Wiebke Möbius, Fred Wolf, Tobias Moser
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The cochlea encodes sounds into neural signals at the synapses of inner hair cells (IHCs) and spiral ganglion neurons (SGNs) with remarkable fidelity. To achieve high rates of precise synaptic transmission over long periods, IHCs use ribbon-type active zones (AZs). To understand synaptic sound encoding, we need to decipher the underlying molecular topography of these synapses, which has remained challenging because of technological limitations. Here, we applied three-dimensional minimal flux optical nanoscopy to mouse IHC-SGN synapses to chart the positions of key pre- and postsynaptic proteins with single-digit nanometer resolution. We demonstrate that nanoclusters of ion channels and their interacting proteins govern the topography of AZs and postsynaptic densities (PSDs). We count synaptic proteins and their nanoclusters and determine their spatial organization, feeding into computational modeling of AZ function. In conclusion, this study reveals a nanocluster-based molecular AZ and PSD topography, likely serving as functional modules in synaptic sound encoding.
GPT-4o mini: Non-social science research article
Adhesive nonfibrotic bioelectronic interfaces on diverse peripheral nerves for long-term functional neuromodulation
Hyunmin Moon, Bastien F. G. Aymon, Jue Deng, Tao Zhou, Vincent Prevosto, Fan Wang, Jingjing Wu, Xuanhe Zhao
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Bioelectronic devices implanted on peripheral nerves offer potential for the treatment and rehabilitation of clinical diseases. However, the foreign body reaction and the subsequent fibrous capsule formation at the device–peripheral nerve interface severely limit their efficacy and longevity in vivo. Here, we describe a robust bioadhesive strategy that can establish nonfibrotic bioelectronic interfaces on diverse peripheral nerves—occipital, vagus, deep peroneal, sciatic, tibial, and common peroneal nerves—for up to 12 weeks. Our approach inhibits the infiltration of immune cells into the interface, thereby preventing the formation of fibrous capsules in the inflammatory microenvironment. We demonstrate that our adhesive bioelectronic device with nonfibrotic interfaces maintains long-term blood pressure regulation in a spontaneously hypertensive rat model over 4 weeks. Furthermore, we confirm minimal accumulation of macrophages, smooth muscle actin, and collagen at nonfibrotic bioelectronic interfaces after 12 weeks of device implantation with nerve stimulation, supporting long-lasting neuromodulation without fibrosis.
GPT-4o mini: Non-social science research article
In situ structure of a gap junction–stomatin complex
Nils Rosenkranz, Alexandra N. Birtasu, Konstantin Wieland, Lisa Rehm, Rachita Sharma, Atal Vats, Sina Manger, Aayush Srivastava, Abhishek Bhattacharya, Gerhard Hummer, Achilleas S. Frangakis, Alexander Gottschalk
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Gap junctions (GJs) are intercellular channels that mediate electrical signals and transfer of small molecules. They are crucial for brain, heart, and other organ functions. While molecular structures of purified homomeric GJs are available, information of in situ structures is lacking. In vivo, GJs can form heteromers with different functionalities and may associate with other proteins. Here, we analyzed Caenorhabditis elegans GJs by cryo–electron tomography and subtomogram averaging. We observed hexagonal arrays of GJs at cellular junctions in primary embryonal cells that displayed distinct wide and narrow conformations. Moreover, we found a cap-like, cytosolic protein assembly enclosing the channel pore. We propose that the cap is formed by the stomatin UNC-1, known to interact with UNC-9 innexins. This is corroborated by matching AlphaFold3 models of UNC-1 multimers with our subtomogram average structure; by expressing GFP-tagged UNC-1, leading to cap structures with additional density; and by coarse-grained MD simulations. UNC-1/stomatin rings may affect GJ formation or functions, possibly beyond nematodes.
GPT-4o mini: Non-social science research article
Salicylic acid and ROS signaling modulate hypocotyl elongation in darkness via NPR1 and EX1
Mengshuang Li, Mengping Li, Shan Qi, Liangsheng Wang, Chanhong Kim
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During early seedling growth in darkness, germinating seeds must balance growth and defense to ensure a successful transition from a heterotrophic to a photoautotrophic state. However, the molecular mechanisms regulating this process in etiolated seedlings remain poorly understood. Here, we investigate the role of salicylic acid (SA), a key defense hormone, in controlling hypocotyl elongation under dark conditions. SA inhibited hypocotyl growth in a dose-dependent manner, with a more substantial effect in the Arabidopsis npr1 mutant, revealing NPR1’s role in maintaining growth under SA-accumulating conditions. In etiolated npr1 seedlings, auxin-responsive genes, including multiple SMALL AUXIN UP-REGULATED RNA ( SAUR ) and EXPANSIN genes, were down-regulated. Overexpression of SAUR19 or SAUR63 fully rescued SA-induced growth inhibition. We also identified EXECUTER1 (EX1), a mediator of singlet oxygen ( 1 O 2 ) signaling, as a contributor to this process. SA-driven lipid peroxidation increased 1 O 2 levels in darkness, triggering EX1-mediated retrograde signaling that represses auxin-related genes.
GPT-4o mini: Non-social science research article
Implementation of multiparticle quantum speed limits on observables
Rui-Heng Miao, Zhao-Di Liu, Chen-Xi Ning, Yu-Cong Hu, Hao Zhang, Chuan-Feng Li, Guang-Can Guo
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The energy-time uncertainty relation limits the maximum speed of quantum system evolution and is crucial for determining whether quantum tasks can be accelerated. However, multiparticle quantum speed limits have not been experimentally explored. In this work, we experimentally verify that both multiparticles and entanglement can accelerate the quantum speed on observables in two-particle systems based on ultrahigh precision control of quantum evolution time. Furthermore, we experimentally prove that the initial quantum state plays a critical role in the quantum speed limits of the entangled systems. In addition, we experimentally demonstrate that the upper bound and lower bound of the quantum speed are workable even in a nonunitary Markovian open system with two photons. The results obtained based on two-photon experiments have been shown to be generalizable to more particles. Our work facilitates the characterization of the dynamic transient properties of complex quantum systems and the control of the quantum speed of large-scale quantum systems.
GPT-4o mini: Non-social science research article
International trade regulations take a limited bite out of the shark fin trade
Diego Cardeñosa, Elizabeth A. Babcock, Stanley K. Shea, Huarong Zhang, Kevin A. Feldheim, Feng Yang, Stephan W. Gale, Daniel Fernando, Akshay Tanna, Luke Warwick, Demian D. Chapman
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International trade is a major driver of shark overexploitation. In 2013, five threatened shark species were listed on Appendix II of the Convention on International Trade of Endangered Species to regulate global trade and promote recovery. Once listed, any uncertified, unreported export of these species became illegal. Minimal trade was reported from 2015 to 2021, yet fins from four of these species were common in the world’s largest shark fin hub (Hong Kong) throughout this period, indicating substantial and sustained illegal trade. Seventy three of 90 shark fin–exporting nations (81%) have never reported any trade of these species. Mixed stock analysis of a market sample of fins from one listed species revealed six populations of origin but only three were from regions where trade was reported. Broader application of CITES compliance mechanisms is necessary to combat widespread illegal trade of shark fins and realize the conservation potential of these trade regulations.
GPT-4o mini: Non-social science research article
Spatially confined hydration for robust underwater adhesion
Gang Lu, Rui Ma, Jian Lu, Yuanhao Chang, Ming Li, Eduardo Saiz
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Underwater adhesion has long been limited by interfacial water’s paradoxical role as both bonding mediator and failure initiator. We present a confined hydration adhesive tape (CHAT) that harnesses water as a molecular architect through spatial hydration management. By confining water penetration to sub–8-micrometer depths, we create a dynamic interface where hydration-activated hydrogen bonds enable adaptive, high-density interfacial connections, and hydrophobic nanodomains maintain bulk integrity via entropic water exclusion. This orchestrated hydration yields an interfacial toughness of 6 kilojoules per square meter (>1.8× literature benchmarks; 1.4 to 3.8× commercial tapes), while preserving stability across harsh conditions (pH 1 and 13, 3.5% saline). Multiscale experiments and simulations reveal water’s triple role as a hydrogen bond catalyst at the interface, a dynamical reorganizer of supramolecular networks, and a mechanical decoupler of interfacial adhesion/bulk cohesion. By establishing interfacial water as a design variable rather than a compromise, CHAT opens avenues for marine, biomedical, and industrial applications where water-resistant adhesion is critical.
GPT-4o mini: Non-social science research article
Determining the cause of inconsistent onset-season trends in the Northern Hemisphere snow cover extent record
Aleksandra Elias Chereque, Paul J. Kushner, Lawrence Mudryk, Chris Derksen
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While seasonal snow cover extent (SCE), an essential climate variable, has broadly declined as a response to global warming, notable inconsistencies remain among long-term satellite-based estimates of SCE change during the Northern Hemisphere snow onset season. SCE datasets from a reanalysis-driven simple snow model serve as benchmarks and allow us to reconcile the trends from one prominent snow cover record with other recent studies. In particular, artificial increasing snow cover trends in the National Oceanic and Atmospheric Administration’s Snow Cover Extent Climate Data Record (CDR) during the onset season are related to changes in snow detection sensitivity. This artificial drift primarily affects September, October, and November snow cover but is detectible through February. Revised trends produced by merging the last decade’s CDR estimates with the offline model datasets reveal decreasing Northern Hemisphere trends in all months but January. This approach shows that offline snow models produce useful benchmarks that can expose biases in observational snow cover datasets with other cross-validation.
GPT-4o mini: Non-social science research article
FuXi-ENS: A machine learning model for efficient and accurate ensemble weather prediction
Xiaohui Zhong, Lei Chen, Hao Li, Roberto Buizza, Jun Liu, Jie Feng, Zijian Zhu, Xu Fan, Kan Dai, Jing-jia Luo, Jie Wu, Bo Lu
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Ensemble forecasting is essential for quantifying forecast uncertainty and providing probabilistic weather predictions. However, the substantial computational demands of current global ensemble prediction systems based on conventional models limit ensemble sizes, hindering the representation of diverse weather scenarios. Recent advances in machine learning (ML) have greatly reduced computational costs and improved deterministic forecasting. Nonetheless, applying ML to ensemble forecasting poses challenges in addressing uncertainties in initial conditions and models, which are the major sources of forecasting errors. To address these challenges, we introduce FuXi-ENS, an advanced ML model that generates 6-hourly global ensemble weather forecasts up to 15 days ahead at a spatial resolution of 0.25°. Using a variational autoencoder framework, FuXi-ENS optimizes a loss function that combines the continuous ranked probability score (CRPS) with the Kullback-Leibler divergence, enabling flow-dependent perturbations. Comprehensive evaluations demonstrate that FuXi-ENS outperforms the ECMWF ensemble in key forecast metrics such as CRPS and Brier score.
GPT-4o mini: Non-social science research article
Creation of a black hole bomb instability in an electromagnetic system
M. Cromb, M.C. Braidotti, A. Vinante, D. Faccio, H. Ulbricht
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The amplification and generation of electromagnetic radiation by a rotating metallic or lossy cylinder, first proposed by Zel’dovich in the 1970s, is closely linked to quantum friction, energy extraction from rotating black holes, and runaway mechanisms such as black hole bombs. Although advances such as acoustic analogs of the Zel’dovich effect and the observation of negative resistance in low-frequency electromagnetic models have been reported, genuine positive signal gain, spontaneous emission of electromagnetic waves, and runaway amplification have not previously been verified. Here, we provide the first experimental demonstration that a mechanically rotating metallic cylinder acts as an amplifier of a rotating electromagnetic field mode. Moreover, when combined with a low-loss resonator, the system becomes unstable and operates as a generator seeded only by noise. The exponential runaway amplification of spontaneously generated electromagnetic modes is observed, establishing the electromagnetic analog of the Press-Teukolsky black hole bomb and paving the way to experimental tests of quantum friction from vacuum fluctuations.
GPT-4o mini: Non-social science research article
Mechanism-based peroxiredoxin 3 inhibitors exploit a covalent warhead for cancer therapy
Kimberly J. Nelson, Terrence L. Smalley, Terri Messier, Rajesh Gumpena, Uma Gandhi, Stephanie Milczarek, Aida Habibovic, Hattie Hoffman, Victoria Gibson, Robert J. Hondal, W. Todd Lowther, Brian Cunniff
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Covalent inhibitors that are approved and marketed drugs exploit a wide array of warheads and reactions with amino acid side chain–based nucleophiles. Thiostrepton (TS) inhibits the peroxidase activity of the mitochondrial antioxidant protein peroxiredoxin 3 by forming a covalent crosslink between the two active site cysteine residues. Peroxiredoxin 3 inactivation increases reactive oxygen species levels, induces cancer cell death in preclinical models, and shows promise in an ongoing clinical trial for malignant mesothelioma using direct pleural infusion. We report the identification of the minimal fragment of TS that contains tandem dehydro-alanine (DHA) moieties and maintains anticancer activity while losing interactions with three alternative targets of intact TS. Biochemical, kinetic, cellular, and structural studies demonstrate that this fragment is a mechanism-based peroxiredoxin inhibitor. These findings represent a promising start toward a pro-oxidant approach for cancer therapy. Moreover, the data support that the DHA moiety should be added to the covalent warhead arsenal.
GPT-4o mini: Non-social science research article
Homogenizing hole-selective contacts for centimeter-square flexible perovskite/Cu(In,Ga)Se 2 tandems
Jingjing Zhou, Enbing Bi, Weizhong Tian, Shaochen Zhang, Caner Değer, Ilhan Yavuz, Jiahui Shen, Libing Yao, Xuechun Sun, Jichuang Shen, Ke Zhao, Runda Li, Jiazhe Xu, Qingqing Liu, Xiaonan Wang, Qinggui Li, Yixin Luo, Pengju Shi, Xu Zhang, Yuan Tian, Donger Jin, Lu Jin, Sisi Wang, Jingyi Sun, Chongyan Lian, Tie Guo, Jingjing Xue, Rui Wang
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Flexible perovskite/Cu(In,Ga)Se 2 (CIGS) tandems offer a path to high-efficiency and lightweight photovoltaics. However, simultaneously achieving high efficiency and mechanical durability remains a challenge. A contributing factor is the interfacial inhomogeneity arising from molecular aggregation in planar carbazole-based hole-selective contacts (HSCs) on flexible substrates. Here, we develop a strategy of spatial steric hindrance that transforms planar carbazole core into a three-dimensional π-conjugated skeleton. This molecular reconfiguration suppresses intermolecular π-π stacking, yielding homogenized selective contacts and high-quality perovskite films. When integrated into flexible monolithic perovskite/CIGS tandem devices, this strategy enabled a champion stabilized power conversion efficiency (PCE) of 26.2% (certified 25.5%) for a 0.091–square centimeter device and 25.3% (certified 24.3%) for a centimeter-scale device, both representing high certified efficiencies reported to date for flexible two-terminal tandems. These devices demonstrated remarkable mechanical robustness, retaining their initial PCE after 10,000 bending cycles at a 10-millimeter radius, highlighting the potential of molecular-level interfacial engineering to realize high-efficiency, stable, and scalable flexible photovoltaics.
GPT-4o mini: Non-social science research article
Dorsomedial striatum monitors unreliability of current action policy and probes alternative one via the indirect pathway
Alain Rios, Satoshi Nonomura, Yutaka Sakai, Kazuto Kobayashi, Shigeki Kato, Masahiko Takada, Yoshikazu Isomura, Minoru Kimura
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Previous studies revealed critical involvement of the striatum in adapting to the environment by actions that anticipate rewards from experiences as a policy. However, it remains unclear how current policy is evaluated to explore more advantageous alternatives. Here, we show that during policy-based sequential actions in a rat reversal task, the dorsomedial striatum plays an essential role in pathway-specific manner. Recording and optical manipulation of the indirect pathway showed that late-onset activity following unrewarded suboptimal action represents a lowered valuation of the current action policy and a heightened bias to try the suboptimal action. The early-onset activity complementarily mediated policy-based suppression of unrewarded action. These results demonstrate the indirect pathway’s role in monitoring unreliability of current action policy and probing alternative one. This study extends conventional understanding of consequence-guided persistence with reward-oriented action policy and provides key insights regarding how the dorsomedial striatum enables proactive and flexible adaptation to environmental changes.
GPT-4o mini: Non-social science research article
Cascade-targeting pH/ROS microneedles promote scarless diabetic wound healing by macrophage metaboimmune reprogramming
Ganghua Yang, Jianqiu Yang, Zhaoping Diao, Jiajun Long, Zhiwen Shu, Chengkang Liu, Wenbing Wan
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Precise macrophage modulation is essential for diabetic wound treatment, yet mitochondrial dysfunction often sustains proinflammatory states. We developed cascade-targeting nanoparticles [epigallocatechin-3-gallate and metformin nanoparticles modified with mannose (EM/Man NPs)] to regulate macrophage mitochondria, integrated into a detachable core-shell microneedle patch (EM/Man MNs) made of quaternary ammonium chitosan and reactive oxygen species (ROS)–degradable polymer. The patch offered high penetration and antibacterial activity, while its ROS-sensitive core released EM/Man NPs to scavenge ROS, restore adenosine 5â€Č-triphosphate production, and reestablish redox balance. The NPs further activated the adenosine 5â€Č-monophosphate–activated protein kinase/Sirtuin 1/peroxisome proliferator–activated receptor gamma coactivator 1α axis to promote mitochondrial biogenesis and oxidative phosphorylation, repolarizing macrophages to an anti-inflammatory phenotype. In diabetic mice, EM/Man MNs accelerated healing via bacterial clearance, immune reprogramming, angiogenesis, and collagen deposition while inhibiting scar formation through interleukin-17 and phosphatidylinositol 3-kinase–Akt suppression. This cascade-targeting strategy for modulating macrophage mitochondria to regulate immunity and redox homeostasis provides a previously unidentified approach for designing tissue engineering materials.
GPT-4o mini: Non-social science research article
Discovering sensorimotor agency in cellular automata using diversity search
Gautier Hamon, Mayalen Etcheverry, Bert Wang-Chak Chan, Clément Moulin-Frier, Pierre-Yves Oudeyer
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The field of artificial life studies how life-like phenomena such as agency and self-regulation can self-organize in computer simulations. In cellular automata (CA), a key open question is whether it is possible to find environment rules that self-organize robust “individuals” from an initial state with no prior existence of things like “bodies,” “brain,” “perception,” or “action.” Here, we leverage recent advances in machine learning, combining algorithms for diversity search, curriculum learning, and gradient descent, to automate the search of such “individuals.” We show that this approach enables us to systematically find environmental conditions in CA leading to self-organization of basic forms of agency, i.e., localized structures that move around and react in a coherent and highly robust manner to external obstacles, maintain their integrity, and have strong capabilities to generalize to new environments. We discuss how this approach opens new perspectives in artificial intelligence and synthetic bioengineering.
GPT-4o mini: Non-social science research article
Computational discovery and experimental validation of high–refractive index HfS 2 nanoresonators
Xavier Zambrana-Puyalto, Mark Kamper Svendsen, Amalie H. SĂžndersted, Avishek Sarbajna, Joakim P. Sandberg, Albert L. Riber, Georgy Ermolaev, Tara Maria Boland, Gleb Tselikov, Valentyn S. Volkov, Kristian S. Thygesen, SĂžren Raza
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High–refractive index dielectric materials can enhance many optical technologies by enabling efficient light manipulation in waveguides, metasurfaces, and nanoscale resonators. Van der Waals materials, which are anisotropic semiconductor materials, are particularly promising due to their excitonic response and strong in-plane polarizability. Here, we perform ab initio calculations to determine the refractive index of over a hundred anisotropic semiconductor materials, many of them van der Waals in nature. Our computational screening reveals both established and less-explored promising materials, including hafnium disulfide (HfS 2 ), which exhibits an in-plane refractive index above 3 and large anisotropy in the visible range. We confirm these properties through ellipsometry and develop a nanofabrication process for HfS 2 , demonstrating Mie-resonant nanodisks. This is achieved by mitigating the air sensitivity of HfS 2 through storage in controlled environment or encapsulation. Our work provides a comparative overview of high-index van der Waals materials and establishes HfS 2 as a promising material for visible-range photonics.
GPT-4o mini: Non-social science research article
Structural insights into the divergent evolution of a photosystem I supercomplex in Euglena gracilis
Koji Kato, Yoshiki Nakajima, Runa Sakamoto, Minoru Kumazawa, Kentaro Ifuku, Takahiro Ishikawa, Jian-Ren Shen, Atsushi Takabayashi, Ryo Nagao
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Photosystem I (PSI) forms supercomplexes with light-harvesting complexes (LHCs) to perform oxygenic photosynthesis. Here, we report a 2.82-angstrom cryo–electron microscopy structure of the PSI-LHCI supercomplex from Euglena gracilis , a eukaryotic alga with secondary green alga-derived plastids. The structure reveals a PSI monomer core with eight subunits and 13 asymmetrically arranged LHCI proteins. Euglena LHCIs bind diadinoxanthin, which is one of the carotenoids typically associated with red-lineage LHCs and is not present in the canonical LHCI belt found in green-lineage PSI-LHCI structures. Phylogenetic analysis shows that the Euglena LHCIs originated from LHCII-related clades rather than from the green-lineage LHCI group and that the nuclear-encoded PSI subunit PsaD likely originated from cyanobacteria via horizontal gene transfer. These observations indicate a mosaic origin of the Euglena PSI-LHCI. Our findings uncover a noncanonical light-harvesting architecture and highlight the structural and evolutionary plasticity of photosynthetic systems, illustrating how endosymbiotic acquisition and lineage-specific adaptation shape divergent light-harvesting strategies.
GPT-4o mini: Non-social science research article
Records of mantle geodynamics and atmospheric escape in Archean quartz
Félix Vayrac, Guillaume Avice, Xinmu J. Zhang, Rita Parai, Pascal Philippot
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Early planetary degassing and atmospheric escape are two major, yet unconstrained, processes that shaped early Earth. Modeling predicts that the atmospheric 20 Ne/ 22 Ne ratio is sensitive to solar-Ne mantle degassing over geological time. Until the Great Oxidation Event, atmospheric escape progressively depletes the atmosphere in Xe, leaving an isotopic imprint. However, the quantity of xenon in the ancient atmosphere remains largely unknown. In this study, we analyzed noble gases in Archean hydrothermal quartz fluid inclusions and show that a modern atmospheric 20 Ne/ 22 Ne ratio was almost reached 2.7 Ga ago, implying intense mantle degassing during the first 1.7 billion years of Earth’s history, three orders of magnitude higher than today. Furthermore, we determine an Archean atmospheric Xe/Kr ratio, 2.3 times higher than today, consistent with models of Xe depletion over time through atmospheric escape.
GPT-4o mini: Non-social science research article
Landscape-wide cosmogram built by the early community of Aguada Fénix in southeastern Mesoamerica
Takeshi Inomata, Daniela Triadan, VerĂłnica A. VĂĄzquez LĂłpez, Melina GarcĂ­a HernĂĄndez, Juan Carlos Fernandez-Diaz, Ashley E. Sharpe, Claudia Alvarado, Atasta Flores, Xanti Ceballos, Kelsey E. Hanson, Ran Chen, Timothy Beach, Takayuki Omori, Hiroo Nasu, Kazuo Aoyama, Keitaro Yamada, Ikuko Kitaba, Takeshi Nakagawa
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There is growing recognition that societies without prominent hierarchies could build large constructions. Scholars are debating what motivated many people to participate in these construction projects. We investigated the site of Aguada Fénix, Mexico, which features the oldest and largest monumental architecture in the Maya area. Using light detection and ranging (LiDAR) and excavations, we documented a site plan composed of nested cross forms built between 1050 and 700 BCE. Its center was marked by a large cruciform cache containing the earliest known directional color symbols in Mesoamerica. The overall pattern consisted of 9- and 7.5-kilometer-long axes delineated by canals and corridors. The builders constructed canals, measuring up to 35 meters wide and 5 meters deep, and a dam to supply them with lake water. Although the canals appear unfinished, this site plan exceeded or rivaled the extents of later Mesoamerican cities. Aguada Fénix was probably designed as a cosmogram, which likely attracted people from a broad area.
GPT-4o mini: Non-social science research article
Universality in the small scales of turbulent Taylor-Couette flow
Julio M. Barros, Christian Butcher, Pinaki Chakraborty
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From a humble kitchen blender to the vast galactic disks, rotating turbulent flows exhibit remarkable diversity. They are also replete with puzzling features. A notable example is the energy spectrum of a widely studied rotating flow—the turbulent Taylor-Couette (TC) flow. Previous studies have shown that, unlike other canonical turbulent flows, it does not obey Kolmogorov’s universal power law or any other power law. Here, we report measurements of the energy spectra in turbulent TC flow from unique “flying-wire” experiments where a rotating probe sweeps through the flow. In contrast with previous studies, which focused primarily on spectral power laws, we analyze spectral data collapse. Through this broader approach, we show that, contrary to the prevailing understanding, the spectral structure of small scales in turbulent TC flow is in excellent accord with the potent paradigm of Kolmogorov’s small-scale universality.
GPT-4o mini: Non-social science research article
T H 1 effector CD4 T cells rely on IFN-Îł production to induce alopecia areata
Samuel J. Connell, Sydney Crotts, Ryan Reis, Maddison M. Lensing, Payton Kahl, Nicholas Henderson, Otgonzaya Ayush, Zhaowen Zhu, Luana S. Ortolan, Audrey C. Ko, Erin M. Shriver, Keith D. Carter, John T. Harty, Joan M. Goverman, Ali Jabbari
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Alopecia areata (AA) is an autoimmune disease defined by hair loss and peribulbar infiltrate of CD8 and CD4 T cells. Prior studies have focused on the role of CD8 T cells in the development of AA. Multiple roles for CD4 T cell help have been demonstrated for support of CD8 T cell responses; however, the role of CD4 T cells in AA remains unclear. Here, we demonstrate that CD4 T cells from the skin-draining lymph nodes (SDLNs) of AA mice transferred disease to recipient mice. These cells exhibited a T helper type 1 (T H 1) effector transcriptional and phenotypic profile, and their pathogenic activity required endogenous CD8 T cells and host IFN-γ responsiveness. Targeted deletion of CD4 T cell–mediated production of IFN-γ abrogated the ability of this cell population to transfer disease. Together, these data provide mechanistic insights into pathways driving AA development, strengthening our understanding of the disease and inviting studies into exploring alternative therapeutic strategies for human patients.
GPT-4o mini: Non-social science research article
Reefal regions were biodiversity hotspots throughout the Phanerozoic
Roger A. Close, Roger B. J. Benson, Wolfgang Kiessling, Erin E. Saupe
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Reefs are important hotspots of marine biodiversity today and have acted as cradles of diversification in the geological past. However, we know little about how the diversity of reef-supporting regions varied through deep time, and how this differed from other regions. We quantified regional diversity patterns in reef-supporting and non–reef-supporting regions in the fossil record of Phanerozoic marine invertebrates. Diversity in reef-supporting regions is on average two- to threefold higher than in non–reef-supporting regions and has been remarkably stable over timescales of tens to hundreds of millions of years. This signal is present in both reefal and non-reefal facies within reef-supporting regions, suggesting that reefs enriched diversity in surrounding environments. Sepkoski’s “Modern Fauna,” an assemblage of higher taxa that includes gastropods, bivalves, and echinoids, has been a key component of reef-supporting regions since the Paleozoic, contrasting with its later rise to dominance in non–reef-supporting regions during the later Mesozoic-Cenozoic.
GPT-4o mini: Non-social science research article
Drivers of canyon incision in the Peruvian Andes: Tectonics, precipitation, and drainage basin capture
Jennie Plasterr, Nadine McQuarrie, Eitan Shelef, Sarah Falkowski, Paul R. Eizenhöfer, Todd A. Ehlers
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The drivers behind the marked 2- to 3-km relief canyons carved into the ca. 3.7-km-high Andean Plateau remain debated, with proposed triggers ranging from plateau surface uplift to precipitation-enhanced erosion. We integrate a surface processes model with published cross-section–derived estimates of structural geometry, kinematics, and shortening rates, as well as precipitation estimates from global atmospheric circulation models, to assess whether the geometry, sequential fault motion, and resulting surface uplift can reproduce plateau morphology. Endorheic basins form where uplift on faults exceeds incision. A decrease in shortening after ~10 Ma allows rivers to compete with uplift and incise into endorheic basins at the plateau edge. Two modeled basin capture events at ~7 to 5 Ma and ~3.5 to 0.5 Ma, coupled with climate-driven discharge fluctuations, markedly increase rivers’ discharge, erosion, and sediment transport, facilitating canyon incision and highlighting the importance of basin captures in canyon formation along the northeastern edge of the Andean Plateau.
GPT-4o mini: Non-social science research article
Dopamine and serotonin cotransmission filters striatonigral synaptic activity via 5-HT1B receptor activation
Maya Molinari, Alina Aaltonen, Ori J. Lieberman, David Sulzer, Emanuela Santini, Anders Borgkvist
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The substantia nigra pars reticulata (SNr), a key basal ganglia output nucleus, is modulated by dopamine (DA) believed to be released locally from midbrain DA neurons. Although DA has been proposed to regulate γ-aminobutyric acid (GABA) release from medium spiny neuron (MSN) terminals via presynaptic D1 receptors, the precise mechanisms remain unclear. Using presynaptic optical recordings of synaptic vesicle fusion, calcium influx in D1-MSN synapses together with postsynaptic patch-clamp recordings from SNr neurons, we found that DA inhibits D1-MSN GABA release in a frequency-dependent manner. Unexpectedly, this effect was independent of DA receptors and instead required 5-HT1B receptor activation. Using two-photon serotonin biosensor imaging in slices and fiber photometry in vivo, we demonstrate that DA enhances extracellular serotonin in the SNr via inhibition of serotonin reuptake. Our results suggest that serotonin mediates DAergic control of basal ganglia output and contributes to the therapeutic actions of dopaminergic medications for Parkinson’s disease and psychostimulant-related disorders.
GPT-4o mini: Non-social science research article
Speciation atlas of polyoxometalates in aqueous solution (Part II): Molybdenum browns
Ingrid Gregorovic, Nadiia I. Gumerova, Annette Rompel
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We present a validated, openly accessible workflow and spectral database charting the solution speciation of molybdenum browns. These redox-active polyoxometalates are central to catalysis and increasingly explored for bioinspired transformations and nanomedicine, making their solution behavior critical for both mechanistic understanding and practical use. Two archetypal Keplerate-type polyoxometalates, {Mo 72 V 30 } and {W 72 V 30 }, were investigated under 69 systematically varied aqueous conditions. Complementary 51 V/ 31 P nuclear magnetic resonance, resonance Raman, electrospray ionization mass spectrometry, and ultraviolet-visible spectroscopy interrogate the effects of pH, buffer identity, temperature, and incubation time on Keplerate integrity. Substituting Mo with W changes redox potential and hard/soft metal balance, yielding distinct stability patterns: {Mo 72 V 30 } breaks into fragments under all tested conditions whereas {W 72 V 30 } remains intact in fresh solutions and retains structural integrity up to pH 4 after 24 hours. All raw spectra, processed data, and stepwise protocols are deposited in a FAIR (findable, accessible, interoperable, reusable) repository, providing an open resource to accelerate catalytic and biological applications of polyoxometalates.
GPT-4o mini: Non-social science research article
The mechanical response of vinculin
Xuyao Liu, Jingzhun Liu, Yinan Wang, Mingxi Yao, Karen B. Baker, Benjamin Klapholz, Nicholas H. Brown, Benjamin T. Goult, Jie Yan
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Vinculin is a mechanosensitive adaptor that links actin to cell-matrix and cell-cell adhesions. Known as a mechanoeffector, it is recruited to adhesion sites under force via mechanotransducers talin and α-catenin. Here, we examine vinculin’s mechanical properties to assess its role as a mechanotransducer. We find that at physiological loading rates, vinculin domains unfold at forces of 5 to 15 pN and refold rapidly when forces drop to 1 pN. This behavior is reminiscent of force-dependent switches in talin and α-catenin, suggesting vinculin domains also function as molecular switches. Unfolding induces large extension changes up to 150 nm in steps of 20 to 30 nm. These findings reveal that vinculin exhibits a previously unrecognized mechanical response, with dynamic folding/unfolding under force acting as a buffering mechanism. Given its role as a scaffold for many proteins, this mechanosensitive behavior supports a model where vinculin functions directly as a mechanotransducer, recruiting binding partners in a force-dependent manner.
GPT-4o mini: Non-social science research article
A gastric retentive robotic capsule enables emergency-prepared and responsive oral drug delivery in canine models
Hao Huang, Yunlong Fan, Zhenlin Chen, Huihui Hu, Yidan Lyu, Jia Xu, Jiahang Xu, Di Wu, Yuelong Liang, Qijiang Mao, Jun Wang, Haoyu Zhang, Haoran Fu, Yixin Guan, Jian Chen, Kaichen Xu, Ha Uk Chung, Xinge Yu, Kewang Nan
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Existing oral drug delivery modalities often fall short in medical emergencies due to the absence of readily deployable, internalized drug storage and delivery mechanisms that combine long-term standby with rapid activation. To address this challenge, we develop and validate a gastric retentive robotic capsule capable of autonomously prepositioning multiple drug doses within the stomach upon oral administration. This system maintains quiescence for extended periods while enabling on-demand, remote-triggered drug release within seconds during emergencies. In a canine (beagle) model, we demonstrate safe gastric residence and functionality for at least 10 weeks, including closed-loop emergency drug delivery modulated by external or onboard biometric sensors for unsupervised symptom detection. At the end of its service life, the capsule can be safely excreted on-demand through the administration of an alkaline solution. These findings establish such a system as a paradigm for emergency-prepared and responsive drug delivery, particularly in vulnerable patient populations.
GPT-4o mini: Non-social science research article
Mie-enhanced microfocused Brillouin light scattering for full wave vector resolution of nanoscale spin waves
Jakub Krčma, Ondƙej Wojewoda, Martin Hrtoƈ, Jakub Holobrádek, Jon Ander Arregi, Jaganandha Panda, Ekaterina Pribytova, Michal Urbánek
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Magnons, the quanta of spin waves, are magnetic excitations of matter spanning through the entire crystal’s Brillouin zone and covering a wide range of frequencies ranging from subgigahertz to terahertz. Magnons play a crucial role in many phenomena, such as the reduction of saturation magnetization with increasing temperature or the Bose-Einstein condensation. However, established experimental techniques cannot resolve magnons with wave vectors between 30 and 300 rad ÎŒm −1 . We address this gap by tailoring the Brillouin light scattering process with dielectric periodic nanostripes hosting Mie resonances. This approach enables access to the previously unmeasurable wave vector range while providing at the same time full wave vector resolution, all within a tabletop setup. Filling this gap can stimulate further experimental investigations of the fundamental phenomena associated with magnons as well as applications in computational and microwave devices. In addition, the same methodology can be applied to other excitations of matter, such as phonons, opening up possibilities in, e.g., mechanobiological studies.
GPT-4o mini: Non-social science research article
New magnetic topological materials from high-throughput search
Iñigo Robredo, Yuanfeng Xu, Yi Jiang, Claudia Felser, B. Andrei Bernevig, Luis Elcoro, Nicolas Regnault, Maia G. Vergniory
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We conducted a high-throughput search for topological magnetic materials across 522 new, experimentally reported commensurate magnetic structures from MAGNDATA, doubling the number of available materials on the Topological Magnetic Materials database. This brings up to date the previous studies. For each material, we performed first-principles electronic calculations and diagnosed the topology as a function of the Hubbard U parameter. Our high-throughput calculation led us to the prediction of 250 experimentally relevant topologically nontrivial materials, which represent 47.89% of the newly analyzed materials. We present five remarkable examples of these materials, each showcasing a different topological phase: Mn 2 AlB 2 (BCSID 1.508), which exhibits a nodal line semimetal to topological insulator transition as a function of SOC; CaMnSi (BCSID 0.599), a narrow gap axion insulator; UAsS (BCSID 0.594), a 5 f -orbital Weyl semimetal; CsMnF 4 (BCSID 0.327), a material presenting a new type of quasi-symmetry protected closed nodal surface; and FeCr 2 S 4 (BCSID 0.613), a symmetry-enforced semimetal with double Weyls and spin-polarized surface states.
GPT-4o mini: Non-social science research article
Strain release through hydrogen bond–mediated layer twisting
Qi Zheng, Boyang Li, Sizhan Liu, Chuntian Cao, Jessica M. Rimsza, Qiubo Zhang, Jianming Bai, Chun Chang, Jiawei Wang, Chengyao Liang, Haiyan Mao, Matthew R. Carbone, Deyu Lu, Tatiana Pyatina, Haimei Zheng
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Strain engineering, enabling the precise control over structure and functional properties, is a key strategy for the design of advanced materials. However, the mechanisms governing strain evolution and release at the nanoscale remain largely unexplored. In this study, we leverage in situ heating transmission electron microscopy and synchrotron x-ray spectroscopy to investigate the strain relaxation pathways of boehmite (γ-AlOOH) at 575 kelvin by revealing real-time structural dynamics. Through tracking the moiré pattern evolution, we identify distinct strain release mechanisms, including layer twisting, defect formation, and domain restructuring. Our neural network potential calculations reveal that energy fluctuations at small twist angles are dominated by an interference-like interaction modulation of hydrogen bonds between boehmite interlayers, with metastable twisted structures corresponding to local minima of the potential energy landscape. This work establishes a previously unidentified paradigm of two-dimensional layer twisting mediated by hydrogen bonding, offering insights into strain-driven transformation mechanisms, and thus may have broad implications for strain in material and earth sciences.
GPT-4o mini: Non-social science research article
Tardigrade Dsup extends C. elegans life span by impeding mitochondrial respiration and promoting oxidative stress resistance
Myriam Richaud, Rohit Shrivastava, Dimitris Xirodimas, Simon Galas, Aymeric Bailly
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Tardigrades survive extreme environments partly through the damage suppressor (Dsup) protein, which protects DNA from ionizing radiation and oxidative stress. Dsup is largely unstructured but binds nucleosomes to shield DNA from damage. To investigate its protective role in a whole organism, we expressed the Ramazzottius varieornatus Dsup gene in the nematode Caenorhabditis elegans . Transgenic worms tolerated x-ray exposure and oxidative stress without apparent toxicity and exhibited a notable extension of life span. This effect was independent of the canonical DAF-2/DAF-16 longevity pathway and mitochondrial dynamics. Instead, Dsup expression markedly reduced mitochondrial respiration, providing a plausible mechanism for enhanced oxidative stress resistance and extended longevity. Our findings demonstrate that Dsup can confer stress resistance and longevity benefits across species, highlighting a unique protective strategy with potential implications for understanding aging and developing stress-resilient organisms.
GPT-4o mini: Non-social science research article
Single-nucleus profiling highlights the all-brain echinoderm nervous system
Periklis Paganos, Jack Ullrich-LĂŒter, Alba AlmazĂĄn, Danila Voronov, Jil Carl, Anne-C. Zakrzewski, Berit Zemann, Maria Lorenza Rusciano, Tiphaine Sancerni, Maria Schauer, Oğuz Akar, Filomena Caccavale, Maria Cocurullo, Giovanna Benvenuto, Jenifer Carol Croce, Carsten LĂŒter, Maria Ina Arnone
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Metazoans comprise diverse tissues and cell types, each essential for the organismal survival. Most of these types are established early in embryogenesis and persist into adulthood. In indirectly developing sea urchins, however, the continuity between embryonic and adult stages is interrupted by a planktonic larval stage that undergoes complete metamorphosis. While gene regulatory networks controlling embryonic and larval lineages are well studied, the molecular and morphological identities of postmetamorphic cell types remain poorly understood. Here, we reconstructed the cell atlas of postmetamorphic Paracentrotus lividus juveniles using single-nucleus transcriptomics, revealing conservation of regulatory mechanisms. We identified signatures of eight distinct cell type groups and analyzed 29 neuronal families, including 15 unique photoreceptor types. By combining transcriptomics, spatial analysis, and ultrastructure, we identified vertebrate neuronal and opsin homologs expressed across the juvenile. These findings show that the echinoderm body plan is predominantly head-like and exhibits an “all-brain” organization.
GPT-4o mini: Non-social science research article
Xenopus IgX informs engineering strategies of IgM and IgG hexamers
Ruixue Zhang, Chenggong Ji, Shuhan Li, Ningning Li, Ning Gao, Junyu Xiao
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Polymeric immunoglobulins are essential components of the immune system in jawed vertebrates. While mammalian immunoglobulin M (IgM) typically forms a pentamer linked by the joining chain (J-chain), Xenopus laevis IgX can assemble into a J-chain–independent polymer. Here, we present the cryo–electron microscopy (cryo-EM) structure of IgX, revealing its hexameric configuration. By incorporating the IgX tailpiece into human IgM, we achieved efficient IgM hexamer formation. Truncating IgM’s natural tailpiece to a range of 11 to 16 residues also substantially enhanced hexamerization efficiency. Furthermore, introducing a shortened IgM tailpiece to IgG resulted in effective IgG hexamer formation. We further show that the engineered IgM and IgG hexamers targeting CD20 demonstrated robust complement-dependent cytotoxicity (CDC) against several B lymphoma cells. In addition, the IgG-Fc hexamer functioned as a decoy, attenuating CDC in cell cultures. These findings deepen our understanding of polymeric immunoglobulin evolution and introduce innovative strategies for the development of IgM- and IgG-based biologics.
GPT-4o mini: Non-social science research article
Sea surface warming and ocean-to-atmosphere feedback driven by large-scale offshore wind farms under seasonally stratified conditions
Hyodae Seo, César Sauvage, Christoph Renkl, Julie K. Lundquist, Anthony Kirincich
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Offshore wind farms may induce changes in the upper ocean and near-surface atmosphere through coupled ocean-atmosphere feedbacks. Yet, the role of air-sea interactions mediated by offshore wind farms remains poorly understood. Using fully coupled ocean-atmosphere-wave model simulations for seasonally stratified conditions along the US East Coast, we show that simulated cumulative reductions in wind stress due to large-scale wind farm clusters lead to sea surface warming of 0.3° to 0.4°C and a shallower mixed layer. This warming drives upward heat fluxes, destabilizing the atmospheric boundary layer and enhancing wind stress, which partially offsets wake-induced wind deficits. These wake-ocean interactions influence near-surface meteorology and air-sea fluxes, suggesting that a coupled modeling approach may be necessary for assessing potential oceanographic impacts of offshore wind developments. However, ocean coupling exerts limited influence on winds at turbine-relevant heights or within downstream wakes, resulting in minimal impact on long-term energy. These findings suggest that models without ocean coupling may be adequate for wind energy applications.
GPT-4o mini: Non-social science research article
Regiocontrolled hydrobromination of unactivated alkenes via direct and chain-walking pathways
Minseok Kim, Seunghoon Han, Changseok Lee, Sungwoo Hong
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The development of regioselective methods for C(sp 3 )─Br bond formation in unactivated alkenes remains a fundamental challenge in organic synthesis. Herein, we report a nickel hydride–catalyzed method that enables regiocontrolled hydrobromination of both terminal and internal alkenes through strategic deployment of an N -fluoropyridinium oxidant. The method features two complementary approaches: direct hydrobromination of alkenes with high proximal selectivity and a chain-walking strategy that enables switchable site-selective functionalization in extended alkyl chains. Notably, temperature-controlled reaction parameters enable regiodivergent access to ÎČ- or Îł-brominated products from identical alkenes with excellent selectivity. The protocol demonstrates broad functional group tolerance and enables late-stage functionalization of pharmaceuticals. Mechanistic studies, including deuterium labeling, radical clock experiments, and density functional theory calculations, revealed a radical-mediated pathway featuring temperature-dependent regioselectivity in the chain-walking process. This unified method provides a versatile platform to access diverse alkyl bromides and offers fundamental insights into selective C─Br bond construction through direct and chain-walking pathways.
GPT-4o mini: Non-social science research article
From breaking rules to making rules in materials science
Bharat Jalan
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Intersectional inequalities in social ties
Samuel Martin-Gutierrez, Mauritz N. Cartier van Dissel, Fariba Karimi
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Social networks are shaped by complex, intersecting identities that drive our connection preferences. These preferences create tie inequalities: Systematic differences in the number of links members of different groups accumulate. Understanding tie inequalities is critical because they contribute to disparities in social capital, with downstream consequences for access to opportunities and resources. Previous research has examined the impact of single-dimensional identities on tie disparities, but when multiple identities intersect, network disadvantages accumulate nonlinearly, disproportionately harming individuals belonging to several disadvantaged groups. However, how multidimensional connection preferences affect network dynamics and amplify or mitigate differences in ties remains unknown. Using a network model, we characterize the effects of multidimensional preferences and attribute correlation. We find that correlation creates counterintuitive tie inequalities unobservable in one-dimensional systems. We calibrate the model with high school friendship data and derive closed-form expressions for tie inequalities, which reproduce the empirical patterns with remarkable accuracy. Our findings have substantial implications for addressing intersectional inequalities in social networks.
The direct financial costs of having a family member incarcerated
Garrett Baker, Sarah Jobe, Sarah Sernaker, Christopher Wildeman
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Using original data from the Family Incarceration Costs Survey, we present national estimates of the direct financial costs of family member incarceration. We find that most Americans with an incarcerated family member provide them direct financial support. The median monthly direct expense among those who contribute is $172, which represents 6% of their household income. On average, Blacks and Hispanics incur higher direct expenses than whites despite their lower household incomes. Men and women contribute similar amounts, but these direct expenses reflect a larger share of women’s household income. Poor families’ direct expenses are comparable to those of affluent families and are similar to their spending on health care, utilities, and car-related costs. Together, these results suggest that familial incarceration is a prominent line item that strains marginalized families’ already-tight household budgets and is a substantial yet underappreciated mechanism through which mass incarceration has reshaped the texture of American poverty in recent decades.
Focusing on family finances reveals actual cost of incarceration
Karin Martin
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An estimate of incarceration’s financial burden reveals that families contribute 6% of household income for an incarcerated family member’s food, calls, and direct support.