We checked 7 multidisciplinary journals on Friday, October 24, 2025 using the Crossref API. For the period October 17 to October 23, we retrieved 4 new paper(s) in 5 journal(s).

Nature

GPT-4o mini: Non-social science research article
Uncertain climate effects of anthropogenic reactive nitrogen
Øivind Hodnebrog, Caroline Jouan, Didier A. Hauglustaine, Fabien Paulot, Susanne E. Bauer, Maureen Beaudor, Michael J. Prather, Marit Sandstad, Ragnhild B. Skeie, Gunnar Myhre
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GPT-4o mini: Non-social science research article
Classical theories of gravity produce entanglement
Joseph Aziz, Richard Howl
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The unification of gravity and quantum mechanics remains one of the most profound open questions in science. With recent advances in quantum technology, an experimental idea first proposed by Richard Feynman 1 is now regarded as a promising route to testing this unification for the first time. The experiment involves placing a massive object in a quantum superposition of two locations and letting it gravitationally interact with another mass. If the two objects subsequently become entangled, this is considered unambiguous evidence that gravity obeys the laws of quantum mechanics. This conclusion derives from theorems that treat a classical gravitational interaction as a local interaction capable of transmitting only classical, not quantum, information 2–8 . Here we extend the description of matter used in these theorems to the full framework of quantum field theory, finding that theories with classical gravity can then transmit quantum information and, thus, generate entanglement through physical, local processes. The effect scales differently to that predicted by theories of quantum gravity, and so it gives information on the parameters and form of the experiment required to robustly provide evidence for the quantum nature of gravity.
GPT-4o mini: Non-social science research article
Joint neutrino oscillation analysis from the T2K and NOvA experiments
character(0), S. Abubakar, M. A. Acero, B. Acharya, P. Adamson, N. Anfimov, A. Antoshkin, E. Arrieta-Diaz, L. Asquith, A. Aurisano, D. Azevedo, A. Back, N. Balashov, P. Baldi, B. A. Bambah, E. F. Bannister, A. Barros, A. Bat, K. Bays, R. Bernstein, T. J. C. Bezerra, V. Bhatnagar, B. Bhuyan, J. Bian, A. C. Booth, R. Bowles, B. Brahma, C. Bromberg, N. Buchanan, A. Butkevich, S. Calvez, J. M. Carceller, T. J. Carroll, E. Catano-Mur, J. P. Cesar, R. Chirco, B. C. Choudhary, A. Christensen, M. F. Cicala, T. E. Coan, T. Contreras, A. Cooleybeck, D. Coveyou, L. Cremonesi, G. S. Davies, P. F. Derwent, P. Ding, Z. Djurcic, K. Dobbs, M. Dolce, D. Dueñas Tonguino, E. C. Dukes, A. Dye, R. Ehrlich, E. Ewart, P. Filip, M. J. Frank, H. R. Gallagher, A. Giri, R. A. Gomes, M. C. Goodman, R. Group, A. Habig, F. Hakl, J. Hartnell, R. Hatcher, J. M. Hays, M. He, K. Heller, V. Hewes, A. Himmel, T. Horoho, A. Ivanova, B. Jargowsky, I. Kakorin, A. Kalitkina, D. M. Kaplan, A. Khanam, B. Kirezli, J. Kleykamp, O. Klimov, L. W. Koerner, L. Kolupaeva, R. Kralik, A. Kumar, C. D. Kuruppu, V. Kus, T. Lackey, K. Lang, P. Lasorak, J. Lesmeister, A. Lister, J. Liu, J. A. Lock, M. MacMahon, S. Magill, W. A. Mann, M. T. Manoharan, M. Manrique Plata, M. L. Marshak, M. Martinez-Casales, V. Matveev, B. Mehta, M. D. Messier, H. Meyer, T. Miao, W. H. Miller, S. R. Mishra, R. Mohanta, A. Moren, A. Morozova, W. Mu, L. Mualem, M. Muether, K. Mulder, D. Myers, D. Naples, S. Nelleri, J. K. Nelson, R. Nichol, E. Niner, A. Norman, A. Norrick, H. Oh, A. Olshevskiy, T. Olson, M. Ozkaynak, A. Pal, J. Paley, L. Panda, R. B. Patterson, G. Pawloski, R. Petti, R. K. Plunkett, J. C. C. Porter, L. R. Prais, A. Rafique, V. Raj, M. Rajaoalisoa, B. Ramson, B. Rebel, E. Robles, P. Roy, O. Samoylov, M. C. Sanchez, S. SĂĄnchez Falero, P. Shanahan, P. Sharma, A. Sheshukov, Shivam, A. Shmakov, W. Shorrock, S. Shukla, I. Singh, P. Singh, V. Singh, S. Singh Chhibra, D. K. Singha, A. Smith, J. Smolik, P. Snopok, N. Solomey, A. Sousa, K. Soustruznik, M. Strait, L. Suter, A. Sutton, S. Swain, C. Sweeney, A. Sztuc, N. Talukdar, P. Tas, T. Thakore, J. Thomas, E. Tiras, M. Titus, Y. Torun, D. Tran, J. Trokan-Tenorio, J. Urheim, P. Vahle, Z. Vallari, K. J. Vockerodt, A. V. Waldron, M. Wallbank, T. K. Warburton, C. Weber, M. Wetstein, D. Whittington, D. A. Wickremasinghe, J. Wolcott, S. Wu, W. Wu, W. Wu, Y. Xiao, B. Yaeggy, A. Yahaya, A. Yankelevich, K. Yonehara, S. Zadorozhnyy, J. Zalesak, R. Zwaska, character(0), K. Abe, S. Abe, H. Adhkary, R. Akutsu, H. Alarakia-Charles, Y. I. Alj Hakim, S. Alonso Monsalve, L. Anthony, S. Aoki, K. A. Apte, T. Arai, T. Arihara, S. Arimoto, Y. Ashida, E. T. Atkin, N. Babu, V. Baranov, G. J. Barker, G. Barr, D. Barrow, P. Bates, L. Bathe-Peters, M. Batkiewicz-Kwasniak, N. Baudis, V. Berardi, L. Berns, S. Bhattacharjee, A. Blanchet, A. Blondel, P. M. M. Boistier, S. Bolognesi, S. Bordoni, S. B. Boyd, C. Bronner, A. Bubak, M. Buizza Avanzini, J. A. Caballero, F. Cadoux, N. F. Calabria, S. Cao, S. Cap, D. Carabadjac, S. L. Cartwright, M. P. Casado, M. G. Catanesi, J. Chakrani, A. Chalumeau, D. Cherdack, A. Chvirova, J. Coleman, G. Collazuol, F. Cormier, A. A. L. Craplet, A. Cudd, D. D’ago, C. Dalmazzone, T. Daret, P. Dasgupta, C. Davis, Yu. I. Davydov, P. de Perio, G. De Rosa, T. Dealtry, C. Densham, A. Dergacheva, R. Dharmapal Banerjee, F. Di Lodovico, G. Diaz Lopez, S. Dolan, D. Douqa, T. A. Doyle, O. Drapier, K. E. Duffy, J. Dumarchez, P. Dunne, K. Dygnarowicz, A. Eguchi, J. Elias, S. Emery-Schrenk, G. Erofeev, A. Ershova, G. Eurin, D. Fedorova, S. Fedotov, M. Feltre, L. Feng, D. Ferlewicz, A. J. Finch, M. D. Fitton, C. Forza, M. Friend, Y. Fujii, Y. Fukuda, Y. Furui, J. GarcĂ­a-Marcos, A. C. Germer, L. Giannessi, C. Giganti, M. Girgus, V. Glagolev, M. Gonin, R. GonzĂĄlez JimĂ©nez, J. GonzĂĄlez Rosa, E. A. G. Goodman, K. Gorshanov, P. Govindaraj, M. Grassi, M. Guigue, F. Y. Guo, D. R. Hadley, S. Han, D. A. Harris, R. J. Harris, T. Hasegawa, C. M. Hasnip, S. Hassani, N. C. Hastings, Y. Hayato, I. Heitkamp, D. Henaff, Y. Hino, J. Holeczek, A. Holin, T. Holvey, N. T. Hong Van, T. Honjo, M. C. F. Hooft, K. Hosokawa, J. Hu, A. K. Ichikawa, K. Ieki, M. Ikeda, T. Ishida, M. Ishitsuka, A. Izmaylov, N. Jachowicz, S. J. Jenkins, C. JesĂșs-Valls, M. Jia, J. J. Jiang, J. Y. Ji, T. P. Jones, P. Jonsson, S. Joshi, C. K. Jung, M. Kabirnezhad, A. C. Kaboth, H. Kakuno, J. Kameda, S. Karpova, V. S. Kasturi, Y. Kataoka, T. Katori, Y. Kawamura, M. Kawaue, E. Kearns, M. Khabibullin, A. Khotjantsev, T. Kikawa, S. King, V. Kiseeva, J. Kisiel, A. KlustovĂĄ, L. Kneale, H. Kobayashi, L. Koch, S. Kodama, M. Kolupanova, A. Konaka, L. L. Kormos, Y. Koshio, K. Kowalik, Y. Kudenko, Y. Kudo, A. Kumar Jha, R. Kurjata, V. Kurochka, T. Kutter, L. Labarga, M. Lachat, K. Lachner, J. Lagoda, S. M. Lakshmi, M. Lamers James, A. Langella, D. H. Langridge, J.-F. Laporte, D. Last, N. Latham, M. Laveder, L. Lavitola, M. Lawe, D. Leon Silverio, S. Levorato, S. V. Lewis, B. Li, C. Lin, R. P. Litchfield, S. L. Liu, W. Li, A. Longhin, A. Lopez Moreno, L. Ludovici, X. Lu, T. Lux, L. N. Machado, L. Magaletti, K. Mahn, K. K. Mahtani, M. Mandal, S. Manly, A. D. Marino, D. G. R. Martin, D. A. Martinez Caicedo, L. Martinez, M. Martini, T. Matsubara, R. Matsumoto, V. Matveev, C. Mauger, K. Mavrokoridis, N. McCauley, K. S. McFarland, C. McGrew, J. McKean, A. Mefodiev, G. D. Megias, L. Mellet, C. Metelko, M. Mezzetto, S. Miki, V. Mikola, E. W. Miller, A. Minamino, O. Mineev, S. Mine, J. Mirabito, M. Miura, S. Moriyama, S. Moriyama, P. Morrison, Th. A. Mueller, D. Munford, A. Muñoz, L. Munteanu, Y. Nagai, T. Nakadaira, K. Nakagiri, M. Nakahata, Y. Nakajima, K. D. Nakamura, Y. Nakano, S. Nakayama, T. Nakaya, K. Nakayoshi, C. E. R. Naseby, D. T. Nguyen, V. Q. Nguyen, K. Niewczas, S. Nishimori, Y. Nishimura, Y. Noguchi, T. Nosek, F. Nova, J. C. Nugent, H. M. O’Keeffe, L. O’Sullivan, R. Okazaki, W. Okinaga, K. Okumura, T. Okusawa, N. Onda, N. Ospina, L. Osu, Y. Oyama, V. Paolone, J. Pasternak, D. Payne, T. Peacock, M. Pfaff, L. Pickering, B. Popov, A. J. Portocarrero Yrey, M. Posiadala-Zezula, Y. S. Prabhu, H. Prasad, F. Pupilli, B. Quilain, P. T. Quyen, E. Radicioni, B. Radics, M. A. Ramirez, R. Ramsden, P. N. Ratoff, M. Reh, G. Reina, C. Riccio, D. W. Riley, E. Rondio, S. Roth, N. Roy, A. Rubbia, L. Russo, A. Rychter, W. Saenz, K. Sakashita, S. Samani, F. SĂĄnchez, E. M. Sandford, Y. Sato, T. Schefke, C. M. Schloesser, K. Scholberg, M. Scott, Y. Seiya, T. Sekiguchi, H. Sekiya, T. Sekiya, D. Seppala, D. Sgalaberna, A. Shaikhiev, M. Shiozawa, Y. Shiraishi, A. Shvartsman, N. Skrobova, K. Skwarczynski, D. Smyczek, M. Smy, J. T. Sobczyk, H. Sobel, F. J. P. Soler, A. J. Speers, R. Spina, A. Srivastava, P. Stowell, Y. Stroke, I. A. Suslov, A. Suzuki, S. Y. Suzuki, M. Tada, S. Tairafune, A. Takeda, A. Teklu, Y. Takeuchi, H. K. Tanaka, H. Tanigawa, V. V. Tereshchenko, N. Thamm, C. Touramanis, N. Tran, T. Tsukamoto, M. Tzanov, Y. Uchida, M. Vagins, M. Varghese, I. Vasilyev, G. Vasseur, E. Villa, U. Virginet, T. Vladisavljevic, T. Wachala, D. Wakabayashi, H. T. Wallace, J. G. Walsh, L. Wan, D. Wark, M. O. Wascko, A. Weber, R. Wendell, M. J. Wilking, C. Wilkinson, J. R. Wilson, K. Wood, C. Wret, J. Xia, K. Yamamoto, T. Yamamoto, C. Yanagisawa, Y. Yang, T. Yano, N. Yershov, U. Yevarouskaya, M. Yokoyama, Y. Yoshimoto, N. Yoshimura, R. Zaki, A. Zalewska, J. Zalipska, G. Zarnecki, J. Zhang, X. Y. Zhao, H. Zheng, H. Zhong, T. Zhu, M. Ziembicki, E. D. Zimmerman, M. Zito, S. Zsoldos
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The landmark discovery that neutrinos have mass and can change type (or flavour) as they propagate—a process called neutrino oscillation 1–6 —has opened up a rich array of theoretical and experimental questions being actively pursued today. Neutrino oscillation remains the most powerful experimental tool for addressing many of these questions, including whether neutrinos violate charge-parity (CP) symmetry, which has possible connections to the unexplained preponderance of matter over antimatter in the Universe 7–11 . Oscillation measurements also probe the mass-squared differences between the different neutrino mass states (Δ m 2 ), whether there are two light states and a heavier one (normal ordering) or vice versa (inverted ordering), and the structure of neutrino mass and flavour mixing 12 . Here we carry out the first joint analysis of datasets from NOvA 13 and T2K 14 , the two currently operating long-baseline neutrino oscillation experiments (hundreds of kilometres of neutrino travel distance), taking advantage of our complementary experimental designs and setting new constraints on several neutrino sector parameters. This analysis provides new precision on the $$\Delta {m}_{32}^{2}$$ Δ m 32 2 mass difference, finding $$2.4{3}_{-0.03}^{+0.04}\times 1{0}^{-3}\,{{\rm{eV}}}^{2}$$ 2.4 3 − 0.03 + 0.04 × 1 0 − 3 eV 2 in the normal ordering and $$-2.4{8}_{-0.04}^{+0.03}\times 1{0}^{-3}\,{{\rm{eV}}}^{2}$$ − 2.4 8 − 0.04 + 0.03 × 1 0 − 3 eV 2 in the inverted ordering, as well as a 3 σ interval on ÎŽ CP of [−1.38π, 0.30π] in the normal ordering and [−0.92π, −0.04π] in the inverted ordering. The data show no strong preference for either mass ordering, but notably, if inverted ordering were assumed true within the three-flavour mixing model, then our results would provide evidence of CP symmetry violation in the lepton sector.
GPT-4o mini: Non-social science research article
Discovering state-of-the-art reinforcement learning algorithms
Junhyuk Oh, Greg Farquhar, Iurii Kemaev, Dan A. Calian, Matteo Hessel, Luisa Zintgraf, Satinder Singh, Hado van Hasselt, David Silver
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GPT-4o mini: Non-social science research article
A circular economy approach for the global lithium-ion battery supply chain
Mengyu Zhai, Yufeng Wu, Shaonan Tian, Haoran Yuan, Bin Li, Xubiao Luo, Guohe Huang, Yupeng Fu, Mengye Zhu, Yifan Gu, Wei Huan, Yu Dai, Huaidong Wang, Liming Yang, Xiaofei Yin, Gongqi Liu, Zhi Li, Jing Gu, Yazhuo Wang, Yong Chen, Tieyong Zuo
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GPT-4o mini: Non-social science research article
Mapping Plasmodium transitions and interactions in the Anopheles female
Yan Yan, Lisa H. Verzier, Elaine Cheung, Federico Appetecchia, Sandra March, Ailsa R. Craven, Esrah Du, Alexandra S. Probst, Tasneem A. Rinvee, Laura E. de Vries, Jamie Kauffman, Sangeeta N. Bhatia, Elisabeth Nelson, Naresh Singh, Duo Peng, W. Robert Shaw, Flaminia Catteruccia
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The human malaria parasite, Plasmodium falciparum , relies exclusively on Anopheles mosquitoes for transmission. Once ingested during blood feeding, most parasites die in the mosquito midgut lumen or during epithelium traversal 1 . How surviving ookinetes interact with midgut cells and form oocysts remains poorly understood, yet these steps are essential to initiate a remarkable growth process culminating in the production of thousands of infectious sporozoites 2 . Here, using single-cell RNA sequencing of both parasites and mosquito cells across different developmental stages and metabolic conditions, we unveil key transitions and mosquito–parasite interactions that occur in the midgut. Functional analyses uncover processes that regulate oocyst growth and identify the Plasmodium transcription factor PfSIP2 as essential for sporozoite infection of human hepatocytes. Combining shared mosquito–parasite barcode analysis with confocal microscopy, we reveal that parasites preferentially interact with midgut progenitor cells during epithelial crossing, potentially using their basal location as an exit landmark. Additionally, we show tight connections between extracellular late oocysts and surrounding muscle cells that may ensure parasite adherence to the midgut. We confirm our major findings in several mosquito–parasite combinations, including field-derived parasites. Our study provides fundamental insight into the molecular events that characterize previously inaccessible biological transitions and mosquito–parasite interactions, and identifies candidates for transmission-blocking strategies.
GPT-4o mini: Non-social science research article
Bottom-up design of Ca2+ channels from defined selectivity filter geometry
Yulai Liu, Connor Weidle, Ljubica Mihaljević, Joseph L. Watson, Zhe Li, Le Tracy Yu, Sagardip Majumder, Andrew J. Borst, Kenneth D. Carr, Ryan D. Kibler, Tamer M. Gamal El-Din, William A. Catterall, David Baker
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GPT-4o mini: Non-social science research article
Cryogenic X-ray photoelectron spectroscopy for battery interfaces
Sanzeeda Baig Shuchi, Giulio D’Acunto, Philaphon Sayavong, Solomon T. Oyakhire, Kenzie M. Sanroman Gutierrez, Juliet Risner-Jamtgaard, Il Rok Choi, Yi Cui, Stacey F. Bent
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GPT-4o mini: Non-social science research article
Author Correction: A room temperature rechargeable all-solid-state hydride ion battery
Jirong Cui, Ren Zou, Weijin Zhang, Hong Wen, Jingyao Liu, Shangshang Wang, Shukun Liu, Hetong Chen, Wei Liu, Xiaohua Ju, Weiwei Wang, Tao Gan, Jiong Li, Jianping Guo, Teng He, Hujun Cao, Ping Chen
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GPT-4o mini: Non-social science research article
Observation of constructive interference at the edge of quantum ergodicity
character(0), Dmitry A. Abanin, Rajeev Acharya, Laleh Aghababaie-Beni, Georg Aigeldinger, Ashok Ajoy, Ross Alcaraz, Igor Aleiner, Trond I. Andersen, Markus Ansmann, Frank Arute, Kunal Arya, Abraham Asfaw, Nikita Astrakhantsev, Juan Atalaya, Ryan Babbush, Dave Bacon, Brian Ballard, Joseph C. Bardin, Christian Bengs, Andreas Bengtsson, Alexander Bilmes, Sergio Boixo, Gina Bortoli, Alexandre Bourassa, Jenna Bovaird, Dylan Bowers, Leon Brill, Michael Broughton, David A. Browne, Brett Buchea, Bob B. Buckley, David A. Buell, Tim Burger, Brian Burkett, Nicholas Bushnell, Anthony Cabrera, Juan Campero, Hung-Shen Chang, Yu Chen, Zijun Chen, Ben Chiaro, Liang-Ying Chih, Desmond Chik, Charina Chou, Jahan Claes, Agnetta Y. Cleland, Josh Cogan, Saul Cohen, Roberto Collins, Paul Conner, William Courtney, Alexander L. Crook, Ben Curtin, Sayan Das, Laura De Lorenzo, Dripto M. Debroy, Sean Demura, Michel Devoret, Agustin Di Paolo, Paul Donohoe, Ilya Drozdov, Andrew Dunsworth, Clint Earle, Alec Eickbusch, Aviv Moshe Elbag, Mahmoud Elzouka, Catherine Erickson, Lara Faoro, Edward Farhi, Vinicius S. Ferreira, Leslie Flores Burgos, Ebrahim Forati, Austin G. Fowler, Brooks Foxen, Suhas Ganjam, Gonzalo Garcia, Robert Gasca, Élie Genois, William Giang, Craig Gidney, Dar Gilboa, Raja Gosula, Alejandro Grajales Dau, Dietrich Graumann, Alex Greene, Jonathan A. Gross, Hanfeng Gu, Steve Habegger, John Hall, Ikko Hamamura, Michael C. Hamilton, Monica Hansen, Matthew P. Harrigan, Sean D. Harrington, Stephen Heslin, Paula Heu, Oscar Higgott, Gordon Hill, Jeremy Hilton, Sabrina Hong, Hsin-Yuan Huang, Ashley Huff, William J. Huggins, Lev B. Ioffe, Sergei V. Isakov, Justin Iveland, Evan Jeffrey, Zhang Jiang, Xiaoxuan Jin, Cody Jones, Stephen Jordan, Chaitali Joshi, Pavol Juhas, Andreas Kabel, Dvir Kafri, Hui Kang, Amir H. Karamlou, Kostyantyn Kechedzhi, Julian Kelly, Trupti Khaire, Tanuj Khattar, Mostafa Khezri, Seon Kim, Robbie King, Paul V. Klimov, Andrey R. Klots, Bryce Kobrin, Alexander N. Korotkov, Fedor Kostritsa, Robin Kothari, John Mark Kreikebaum, Vladislav D. Kurilovich, Elica Kyoseva, David Landhuis, Tiano Lange-Dei, Brandon W. Langley, Pavel Laptev, Kim-Ming Lau, Loïck Le Guevel, Justin Ledford, Joonho Lee, Kenny Lee, Yuri D. Lensky, Shannon Leon, Brian J. Lester, Wing Yan Li, Alexander T. Lill, Wayne Liu, William P. Livingston, Aditya Locharla, Erik Lucero, Daniel Lundahl, Aaron Lunt, Sid Madhuk, Fionn D. Malone, Ashley Maloney, Salvatore Mandrà, James M. Manyika, Leigh S. Martin, Orion Martin, Steven Martin, Yossi Matias, Cameron Maxfield, Jarrod R. McClean, Matt McEwen, Seneca Meeks, Anthony Megrant, Xiao Mi, Kevin C. Miao, Amanda Mieszala, Zlatko Minev, Reza Molavi, Sebastian Molina, Shirin Montazeri, Alexis Morvan, Ramis Movassagh, Wojciech Mruczkiewicz, Ofer Naaman, Matthew Neeley, Charles Neill, Ani Nersisyan, Hartmut Neven, Michael Newman, Jiun How Ng, Anthony Nguyen, Murray Nguyen, Chia-Hung Ni, Murphy Yuezhen Niu, Logan Oas, Thomas E. O’Brien, William D. Oliver, Alex Opremcak, Kristoffer Ottosson, Andre Petukhov, Alex Pizzuto, John Platt, Rebecca Potter, Orion Pritchard, Leonid P. Pryadko, Chris Quintana, Ganesh Ramachandran, Chandrasekhar Ramanathan, Matthew J. Reagor, John Redding, David M. Rhodes, Gabrielle Roberts, Eliott Rosenberg, Emma Rosenfeld, Pedram Roushan, Nicholas C. Rubin, Negar Saei, Daniel Sank, Kannan Sankaragomathi, Kevin J. Satzinger, Alexander Schmidhuber, Henry F. Schurkus, Christopher Schuster, Thomas Schuster, Michael J. Shearn, Aaron Shorter, Noah Shutty, Vladimir Shvarts, Volodymyr Sivak, Jindra Skruzny, Spencer Small, Vadim Smelyanskiy, W. Clarke Smith, Rolando D. Somma, Sofia Springer, George Sterling, Doug Strain, Jordan Suchard, Philippe Suchsland, Aaron Szasz, Alex Sztein, Douglas Thor, Eifu Tomita, Alfredo Torres, M. Mert Torunbalci, Abeer Vaishnav, Justin Vargas, Sergey Vdovichev, Guifre Vidal, Benjamin Villalonga, Catherine Vollgraff Heidweiller, Steven Waltman, Shannon X. Wang, Brayden Ware, Kate Weber, Travis Weidel, Tom Westerhout, Theodore White, Kristi Wong, Bryan W. K. Woo, Cheng Xing, Z. Jamie Yao, Ping Yeh, Bicheng Ying, Juhwan Yoo, Noureldin Yosri, Grayson Young, Adam Zalcman, Chongwei Zhang, Yaxing Zhang, Ningfeng Zhu, Nicholas Zobrist
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GPT-4o mini: Non-social science research article
Neuroendocrine control of calcium mobilization in the fruit fly
Naoki Okamoto, Yosuke Mizuno, Akira Watanabe, Hiroshi Kohsaka, Ryusuke Niwa
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GPT-4o mini: Non-social science research article
Video‐rate tunable colour electronic paper with human resolution
Ade Satria Saloka Santosa, Yu-Wei Chang, Andreas B. Dahlin, Lars Österlund, Giovanni Volpe, Kunli Xiong
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As demand for immersive experiences grows, displays with smaller sizes and higher resolutions are being viewed increasingly closer to the human eye 1 . As the size of emitting pixels shrinks, the intensity and uniformity of their emission are degraded while colour cross-talk and fabrication complexity increase, making ultra-high-resolution imaging challenging 2–4 . By contrast, electronic paper, which uses ambient light for visibility, can maintain high optical contrast regardless of pixel size, but cannot achieve high resolution 5,6 . Here we demonstrate electronic paper with electrically tunable metapixels down to ~560 nm in size (>25,000 pixels per inch) consisting of WO 3 nanodisks, which undergo a reversible insulator-to-metal transition on electrochemical reduction. This transition enables dynamic modulation of the refractive index and optical absorption, allowing precise control over reflectance and contrast at the nanoscale. By using this effect, the metapixels can achieve pixel densities approaching the visual resolution limit when the display size matches the pupil diameter, which we refer to as retina electronic paper. Our technology also demonstrates full-colour video capability (>25 Hz), high reflectance (~80%), strong optical contrast (~50%), low energy consumption (~0.5–1.7 mW cm – 2 ) and support for anaglyph 3D display, highlighting its potential as a next-generation solution for immersive virtual reality systems.
GPT-4o mini: Non-social science research article
Deterministic soliton microcombs in Cu-free photonic integrated circuits
Xinru Ji, Xurong Li, Zheru Qiu, Rui Ning Wang, Marta Divall, Andrey Gelash, Grigory Lihachev, Tobias J. Kippenberg
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GPT-4o mini: Non-social science research article
Integration of hunger and hormonal state gates infant-directed aggression
Mingran Cao, Rachida Ammari, Maxwell X. Chen, Patty Wai, Bradley B. Jamieson, Swang Liang, Basma F. A. Husain, Aashna Sahni, Nathalie Legrave, Irene Salgarella, James MacRae, Molly Strom, Johannes Kohl
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Social behaviour is substantially shaped by internal physiological states. Although progress has been made in understanding how individual states such as hunger, stress or arousal modulate behaviour 1–9 , animals experience multiple states at any given time 10 . The neural mechanisms that integrate such orthogonal states—and how this integration affects behaviour—remain poorly understood. Here we report how hunger and oestrous state converge on neurons in the medial preoptic area (MPOA) to shape infant-directed behaviour. We find that hunger promotes pup-directed aggression in normally non-aggressive virgin female mice. This behavioural switch occurs through the inhibition of MPOA neurons, driven by the release of neuropeptide Y from Agouti-related peptide-expressing neurons in the arcuate nucleus (Arc AgRP neurons). The propensity for hunger-induced aggression is set by reproductive state, with MPOA neurons detecting changes in the progesterone to oestradiol ratio across the oestrous cycle. Hunger and oestrous state converge on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which sets the baseline activity and excitability of MPOA neurons. Using microendoscopy imaging, we confirm these findings in vivo, revealing that MPOA neurons encode a state for pup-directed aggression. This work provides a mechanistic understanding of how multiple physiological states are integrated to flexibly control social behaviour.
GPT-4o mini: Non-social science research article
Enteropathogenic bacteria evade ROCK-driven epithelial cell extrusion
Giovanni Luchetti, Marin V. Miner, Rachael M. Peterson, William P. Scott, Praveen Krishnamoorthy, Eric M. Kofoed, Angel G. Jimenez, Hua Zhang, Man Wah Tan, Rohit Reja, Tommy K. Cheung, Elizabeth Skippington, Yuxin Liang, Christopher M. Rose, Nobuhiko Kayagaki, Kim Newton, Isabella Rauch, Vishva M. Dixit
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GPT-4o mini: Non-social science research article
Author Correction: Structures of α-synuclein filaments from multiple system atrophy
Manuel Schweighauser, Yang Shi, Airi Tarutani, Fuyuki Kametani, Alexey G. Murzin, Bernardino Ghetti, Tomoyasu Matsubara, Taisuke Tomita, Takashi Ando, Kazuko Hasegawa, Shigeo Murayama, Mari Yoshida, Masato Hasegawa, Sjors H. W. Scheres, Michel Goedert
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GPT-4o mini: Non-social science research article
Transcriptional interferences ensure one olfactory receptor per ant neuron
Bogdan Sieriebriennikov, Olena Kolumba, Aurore de Beaurepaire, Jennifer Wu, Valentina Fambri, Eva Bardol, Yuwei Zhong, Ildar Gainetdinov, Danny Reinberg, Hua Yan, Claude Desplan
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GPT-4o mini: Non-social science research article
Myocardial reprogramming by HMGN1 underlies heart defects in trisomy 21
Sanjeev S. Ranade, Feiya Li, Sean Whalen, Angelo Pelonero, Lin Ye, Yu Huang, Abigail Brand, Tomohiro Nishino, Rahul Mital, Ryan M. Boileau, Frances Koback, Arun Padmanabhan, Victoria Yu, Bastien Cimarosti, Diana Presas-Ramos, Alexander F. Merriman, Langley Grace Wallace, Annie Nguyen, Nikolaos Poulis, Mauro W. Costa, Casey A. Gifford, Katherine S. Pollard, Deepak Srivastava
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GPT-4o mini: Non-social science research article
Optimization by decoded quantum interferometry
Stephen P. Jordan, Noah Shutty, Mary Wootters, Adam Zalcman, Alexander Schmidhuber, Robbie King, Sergei V. Isakov, Tanuj Khattar, Ryan Babbush
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GPT-4o mini: Non-social science research article
A global coral phylogeny reveals resilience and vulnerability through deep time
Claudia Francesca Vaga, Andrea M. Quattrini, Isabela Galvão de Lossio e Seiblitz, Danwei Huang, Zheng Bin Randolph Quek, JarosƂaw Stolarski, Stephen Douglas Cairns, Marcelo Visentini Kitahara
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GPT-4o mini: Non-social science research article
A metallic p-wave magnet with commensurate spin helix
Rinsuke Yamada, Max T. Birch, Priya R. Baral, Shun Okumura, Ryota Nakano, Shang Gao, Motohiko Ezawa, Takuya Nomoto, Jan Masell, Yuki Ishihara, Kamil K. Kolincio, Ilya Belopolski, Hajime Sagayama, Hironori Nakao, Kazuki Ohishi, Takashi Ohhara, Ryoji Kiyanagi, Taro Nakajima, Yoshinori Tokura, Taka-hisa Arima, Yukitoshi Motome, Moritz M. Hirschmann, Max Hirschberger
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GPT-4o mini: Non-social science research article
Neoadjuvant immunotherapy in mismatch-repair-proficient colon cancers
Pedro B. Tan, Yara L. Verschoor, José G. van den Berg, Sara Balduzzi, Niels F. M. Kok, Marieke E. Ijsselsteijn, Kat Moore, Adham Jurdi, Antony Tin, Paulien Kaptein, Monique E. van Leerdam, John B. A. G. Haanen, Emile E. Voest, Noel F. C. C. de Miranda, Ton N. Schumacher, Lodewyk F. A. Wessels, Myriam Chalabi
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GPT-4o mini: Non-social science research article
Parity and lactation induce T cell mediated breast cancer protection
Balaji Virassamy, Franco Caramia, Peter Savas, Michael A. Harris, Jia-Wern Pan, Jianan Wang, Emmaline Brown, Megan M. R. O’Malley, Courtney T. van Geelen, Michael Hun, Thomas N. Burn, Sneha Sant, Jamieson D. Ballan, Jasmine Kay, Luis E. Lara Gonzalez, Kylie Clarke, Han Xian Aw Yeang, Rejhan Idrizi, Metta Jana, Damon J. Challice, Roberto Salgado, Heather Thorne, character(0), David Amor, Lesley Andrews, Yoland Antill, Rosemary Balleine, Jonathan Beesley, Ian Bennett, Michael Bogwitz, Simon Bodek, Leon Botes, Meagan Brennan, Melissa Brown, Michael Buckley, Jo Burke, Phyllis Butow, Liz Caldon, Ian Campbell, Michelle Cao, Anannya Chakrabarti, Deepa Chauhan, Manisha Chauhan, Georgia Chenevix-Trench, Alice Christian, Paul Cohen, Alison Colley, Ashley Crook, James Cui, Eliza Courtney, Margaret Cummings, Sarah-Jane Dawson, Anna deFazio, Martin Delatycki, Rebecca Dickson, Joanne Dixon, Stacey Edwards, Gelareh Farshid, Andrew Fellows, Georgina Fenton, Michael Field, James Flanagan, Peter Fong, Laura Forrest, Stephen Fox, Juliet French, Michael Friedlander, Clara Gaff, Mike Gattas, Peter George, Sian Greening, Marion Harris, Stewart Hart, Philip Harraka, Nick Hayward, John Hopper, Cass Hoskins, Clare Hunt, Paul James, Mark Jenkins, Alexa Kidd, Judy Kirk, Jessica Koehler, James Kollias, Sunil Lakhani, Mitchell Lawrence, Jason Lee, Shuai Li, Geoff Lindeman, Jocelyn Lippey, Lara Lipton, Liz Lobb, Sherene Loi, Graham Mann, Deborah Marsh, Sue-Anne McLachlan, Bettina Meiser, Roger Milne, Shona O’Connell, Sarah O’Sullivan, David Gallego-Ortega, Nick Pachter, Jia-Min Pang, Gargi Pathak, Briony Patterson, Amy Pearn, Kelly Phillips, Ellen Pieper, Susan Ramus, Edwina Rickard, Abi Ragunathan, Bridget Robinson, Mona Saleh, Anita Skandarajah, Elizabeth Salisbury, Christobel Saunders, Jodi Saunus, Peter Savas, Rodney Scott, Clare Scott, Adrienne Sexton, Joanne Shaw, Andrew Shelling, Shweta Srinivasa, Peter Simpson, Melissa Southey, Amanda Spurdle, Jessica Taylor, Renea Taylor, Heather Thorne, Alison Trainer, Kathy Tucker, Jane Visvader, Logan Walker, Rachael Williams, Ingrid Winship, Mary-Ann Young, Milita Zaheed, Cathie Poliness, Sophie Nightingale, Soo-Hwang Teo, Terence P. Speed, Jane Visvader, Paul J. Neeson, Phillip K. Darcy, Laura K. Mackay, Sherene Loi
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GPT-4o mini: Non-social science research article
Selective Methylene Oxidation in α,ÎČ-Unsaturated Carbonyl Natural Products
Chiyoung Ahn, Alexander Gomez, Marc A. Hartmann, M. Christina White
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GPT-4o mini: Non-social science research article
Oxidative potential of atmospheric particles in Europe and exposure scenarios
CĂ©cile Tassel, Jean-Luc Jaffrezo, Pamela Dominutti, Kaspar R. Daellenbach, Sophie Darfeuil, Rhabira Elazzouzi, Paolo Laj, Anouk Marsal, Takoua Mhadhbi, Vy Ngoc Thuy Dinh, CĂ©line Voiron, Stephan Houdier, Marc Durif, MĂ©lodie Chatain, Florie Francony, Julie Cozic, Guillaume Salque Moreton, Meryll Le Quilleuc, VĂ©ronique Ghersi, GrĂ©gory Gille, Boualem Mesbah, Evdokia Stratigou, Manuela Zublena, Henri DiĂ©moz, AndrĂ©s Alastuey, Barbara D’Anna, Nicolas Marchand, SĂ©bastien Conil, ValĂ©rie Gros, Marloes F. van Os, Imre Salma, Nikolaos Mihalopoulos, GriĆĄa Močnik, Katja DĆŸepina, Katarzyna Styszko, Christoph HĂŒglin, Xavier Querol, AndrĂ© S. H. PrĂ©vĂŽt, Olivier Favez, ValĂ©rie Siroux, GaĂ«lle Uzu
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GPT-4o mini: Non-social science research article
Reply to: Uncertain climate effects of anthropogenic reactive nitrogen
Cheng Gong, Hanqin Tian, Hong Liao, Naiqing Pan, Shufen Pan, Akihiko Ito, Atul K. Jain, Sian Kou-Giesbrecht, Fortunat Joos, Qing Sun, Hao Shi, Nicolas Vuichard, Qing Zhu, Changhui Peng, Federico Maggi, Fiona H. M. Tang, Sönke Zaehle
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GPT-4o mini: Non-social science research article
Non-van der Waals superlattices of carbides and carbonitrides
Qi Zhao, Zhiguo Du, Kunpeng Si, Zian Xu, Ziming Wang, Qi Zhu, Yuxuan Ye, Xinping Wu, Genqing Wang, Guanhui Gao, Yongji Gong, Li Song, Peizhe Tang, Shubin Yang
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GPT-4o mini: Non-social science research article
Designing allosteric modulators to change GPCR G protein subtype selectivity
Madelyn N. Moore, Kelsey L. Person, Valeria L. Robleto, Abigail R. Alwin, Campbell L. Krusemark, Noah Foster, Caroline Ray, Asuka Inoue, Michael R. Jackson, Michael J. Sheedlo, Lawrence S. Barak, Ezequiel Marron Fernandez de Velasco, Steven H. Olson, Lauren M. Slosky
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GPT-4o mini: Non-social science research article
SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade
Adam J. Grippin, Christiano Marconi, Sage Copling, Nan Li, Chen Braun, Cole Woody, Elliana Young, Priti Gupta, Min Wang, Annette Wu, Seong Dong Jeong, Dhruvkumar Soni, Frances Weidert, Chao Xie, Eden Goldenberg, Andrew Kim, Chong Zhao, Anna DeVries, Paul Castillo, Rishabh Lohray, Michael K. Rooney, Benjamin R. Schrank, Yifan Wang, Yifan Ma, Enoch Chang, Ramez Kouzy, Kyle Dyson, Jordan Jafarnia, Nina Nariman, Gregory Gladish, Jacob New, Ada Argueta, Diana Amaya, Nagheme Thomas, Andria Doty, Joe Chen, Nikhil Copling, Gabriel Alatrash, Julie Simon, Alicia Bea Davies, William Dennis, Richard Liang, Jeff Lewis, Xiong Wei, Waree Rinsurongkawong, Ara A. Vaporciyan, Andrew Johns, character(0), Ashley Aaroe, Sanu Abraham, Lee Andrews, Kiran K. Badami, Janna A. Baganz, Pratibha Bajwa, Gregory R. Barbosa, Hannah C. Beird, Kristy Brock, Elizabeth M. Burton, Juan Cata, Caroline Chung, Catherine Claussen, John Crommett, Michael Cutherell, Bouthaina Dabaja, Hiba Dagher, Kevin M. Daniels, Mary Domask, Giulio Draetta, Paul Edelkamp, Sarah Fisher, Katy Elizabeth French, Andrew Futreal, Maria Gaeta, Myrna Godoy, Drew Goldstein, Jillian Gunther, Kate Hutcheson, David Jaffray, Jeff Jin, Teny Matthew John, Trey Kell, Mark Knafl, Rayson C. Kwan, J. Jack Lee, Jennifer Litton, Kevin W. McEnery, Mary McGuire, Benjamin Mescher, Tejo Musunuru, Mayoora Muthu, Joseph Nates, Craig S. Owen, Priyadharshini Padmakumar, Nicholas Palaskas, Jay J. Patel, Sabitha Prabhakaran, Lucas Ramsey, Vinod Ravi, Cristhiam Rojas Hernandez, Bilja Sajith, Paul A. Scheet, Stephanie Schmidt, Kenna R. Shaw, Sanjay Shete, Daniel P. Shoenthal, Lessley J. Stoltenberg, Hussein Tawbi, Anastasia Turin, Samir Unni, Benju Vicknamparampil, Max C. Weber, John Weinstein, Scott Eric Woodman, Mark C. Wozny, Carol Wu, Jia Wu, James C. Yao, Chingyi Young, Emily Yu, Steven Zatorski, Thomas A. Aloia, John Cuenca Trujillo, Christopher Gibbons, Anai Kothari, Ishwaria Subbiah, Phillip Thompson, Jack Lee, Ji-Hyun Lee, Ryan Sun, Padmanee Sharma, Hai Tran, Jianjun Zhang, Don L. Gibbons, Jennifer Wargo, Betty Y. S. Kim, John V. Heymach, Hector R. Mendez-Gomez, Wen Jiang, Elias J. Sayour, Steven H. Lin
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Nature DOI suffix ≠ "/s...": Not a research article
Google Scholar tool gives extra credit to first and last authors
Dalmeet Singh Chawla
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Nature DOI suffix ≠ "/s...": Not a research article
Mysterious cosmic ‘dots’ are baffling astronomers. What are they?
Jenna Ahart
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Nature DOI suffix ≠ "/s...": Not a research article
Evolutionary history of stony corals suggests that some could be resilient to climate change
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Nature DOI suffix ≠ "/s...": Not a research article
Are these the happiest PhD students in the world?
Linda Nordling
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Nature DOI suffix ≠ "/s...": Not a research article
People with some cancers live longer after a COVID vaccine
Max Kozlov
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Nature DOI suffix ≠ "/s...": Not a research article
Copper-free chips generate robust ‘combs’ of multicoloured light
Mher Ghulinyan, Martino Bernard
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Time to retire the Turing test?
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Honey, I ate the kids: how hunger and hormones make mice aggressive
Shamini Bundell, Nick Petrić Howe
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Nature DOI suffix ≠ "/s...": Not a research article
This AI method could turbocharge the hunt for new medicines
Heidi Ledford
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Nature DOI suffix ≠ "/s...": Not a research article
The TrumpRx website won’t slash drug prices — but this will
Beth Woods
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Nature DOI suffix ≠ "/s...": Not a research article
This luxury ‘cat poo’ coffee has a unique flavour: what’s behind it?
Nicola Jones
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Nature DOI suffix ≠ "/s...": Not a research article
AI language models killed the Turing test: do we even need a replacement?
Elizabeth Gibney
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Nature DOI suffix ≠ "/s...": Not a research article
Cake to the rescue: how these PhD students are cooking up a sense of community
Sarah Wells
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Nature DOI suffix ≠ "/s...": Not a research article
Global health is in crisis — who will step in to fix it?
Fred Schwaller
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Nature DOI suffix ≠ "/s...": Not a research article
Is there a ‘smoking gun’ test for quantum gravity?
Zachary Weller-Davies
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Stinkbugs nurture fungi in a newly discovered organ
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
US PhD admissions shrink as fears over Trump’s cuts take hold
Alexandra Witze
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Nature DOI suffix ≠ "/s...": Not a research article
Blood tests are now approved for Alzheimer’s: how accurate are they?
Katie Kavanagh
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Nature DOI suffix ≠ "/s...": Not a research article
What makes PhD students happy? Good supervision
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Nature DOI suffix ≠ "/s...": Not a research article
Four game-changing immunology tools to watch
Gemma Conroy
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Nature DOI suffix ≠ "/s...": Not a research article
AI discovers learning algorithm that outperforms those designed by humans
Joel Lehman
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Nature DOI suffix ≠ "/s...": Not a research article
‘Gland-in-a-dish’ secretes stress hormone like the real thing
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: How the brain locks in long-term memories
Jacob Smith
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Nature DOI suffix ≠ "/s...": Not a research article
How emotional memories are engraved on the brain, with surprising helper cells
Katie Kavanagh
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Nature DOI suffix ≠ "/s...": Not a research article
Universities are embracing AI: will students get smarter or stop thinking?
Helen Pearson
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Nature DOI suffix ≠ "/s...": Not a research article
Why we still don’t understand the Universe — even after a century of dispute
Helge Kragh
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Nature DOI suffix ≠ "/s...": Not a research article
Measles, polio, tuberculosis: what’s causing spikes in infectious diseases?
Rachel Nuwer
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Nature DOI suffix ≠ "/s...": Not a research article
Google AI aims to make best-in-class scientific software even better
Matthew Hutson
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Nature DOI suffix ≠ "/s...": Not a research article
Genetics can give evolving societies a leg up
Andrew J. Doig
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Gene that causes obesity also shields against heart disease
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
The search for mutations that sperm acquire as men age
Caroline Watson
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Nature DOI suffix ≠ "/s...": Not a research article
Sex differences in depression revealed by large genetics study
Na Cai
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Here there be
Carl Goodman
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Nature DOI suffix ≠ "/s...": Not a research article
Disconnecting part of the brain sends it into a deep sleep
Rachel Fieldhouse
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: People with macular degeneration can read again after retinal implant
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Stinkbug ‘ear’ actually hosts parasite-fighting fungi
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Nature DOI suffix ≠ "/s...": Not a research article
Surprise meteorite debris uncovered on Moon’s far side
Jenna Ahart
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Nature DOI suffix ≠ "/s...": Not a research article
Pancreatic cancer relies on opposing signalling pathways to drive its cellular diversity
Marc P. Stemmler
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Is academic research becoming too competitive? Nature examines the data
Miryam Naddaf
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Why simply ending animal testing isn’t the answer in biomedical research
K. C. Kent Lloyd
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How to spot fake scientists and stop them from publishing papers
Miryam Naddaf
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John Gurdon obituary: Biologist who made cloning possible
Ron Laskey
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People with blindness can read again after retinal implant
Liam Drew
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Nature DOI suffix ≠ "/s...": Not a research article
Would ChatGPT hire you? Your age and gender matter
Shamini Bundell
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Breastfeeding boosts immune cells that protect against breast cancer
Starre Vartan
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Take the time to ensure that AI is safe
Sam Illingworth
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Nature DOI suffix ≠ "/s...": Not a research article
Alternatives to animal testing are the future — it’s time that journals, funders and scientists embrace them
Todd J. Herron, Anke BrĂŒning-Richardson, Julie E. Gough, Aline F. Miller, Geoffrey J. Pilkington, John Greenman, Valerie Speirs, Joseph C. Wu
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Hopes of realizing a dream ‘city of health’
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Tumours might be sensitized to immune therapy by COVID mRNA vaccines
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What’s the cap on human energy expenditure? Elite athletes reveal ‘metabolic ceiling’
Mohana Basu
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Warning signs
Alan Dove
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A guide to the Nature Index
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Brazil must beef up its COP30 scheme to preserve tropical forests
James D. Langston, Daniel S. Mendham, Ali Yansyah Abdurrahim, Jatna Supriatna
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Time-resolved fluorescent proteins expand the microscopy palette
Stephanie Melchor
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Cold plunge: how I gained hands-on experience in marine biology
Nikki Forrester
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How scientists are pushing back against Trump’s funding ‘deal’ for universities
Dan Garisto, Alexandra Witze, Jenna Ahart
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Nature DOI suffix ≠ "/s...": Not a research article
Gene implicated in the heart defects associated with Down’s syndrome
Beverly A. Rothermel
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This gene causes obesity — and shields against heart disease
Heidi Ledford
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We need more than good science to fight infectious disease
Bec Crew
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Nature DOI suffix ≠ "/s...": Not a research article
The race for deep-sea minerals could cause geopolitical and ecological harm
Milad Haghani, Abbas Rajabifard, Thomas Wiedmann, David A. Hensher
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Nature Human Behaviour

Attention on social media depends more on how you express yourself than on who you are
Yizhang Zhao, Tianyu Qiao, Yirao Chen, Meiying Kuang, Wei Bai, Yankun Yi, Xinxin Huang, Wen Li, Weidong Wang
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Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Linker histone regulates the myeloid versus lymphoid bifurcation of multipotent hematopoietic stem and progenitors
Kutay Karatepe, Bruna Mafra de Faria, Jian Zhang, Xinyue Chen, Hugo Pinto, Dmitry Fyodorov, Esen Sefik, Michael A. Willcockson, Richard A. Flavell, Arthur I. Skoultchi, Shangqin Guo
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Myeloid-biased differentiation of multipotent hematopoietic stem and progenitor cells (HSPCs) occurs with aging or exhaustion. The molecular mechanism(s) responsible for this fate bias remain unclear. Here, we report that linker histone regulates HSPC fate choice at the lymphoid versus myeloid bifurcation. Linker histones package nucleosomes and compact chromatin. HSPCs expressing a doxycycline (dox)-inducible H1.0 transgene favor the lymphoid fate, display strengthened nucleosome organization, and reduced chromatin accessibility at subsets of genomic regions. The genomic regions showing reduced chromatin accessibility host many known marker genes of myeloid-biased HSCs. The transcription factor Hlf is located in one of the most differentially closed regions, whose chromatin accessibility and gene expression are reduced in H1.0 high HSPCs. Failure to reduce Hlf expression in multipotential HSPCs abrogates the H1.0-endowed lymphoid potential. Furthermore, HSPCs display aspartyl protease–dependent H1.0 decreases, especially in response to interferon alpha (IFNα). Aspartyl protease inhibitors preserve endogenous H1.0 levels and promote the lymphoid fate of wild type HSPCs. Thus, our work elucidates a molecular scenario of how myeloid bias arises and uncovers a point of intervention for correcting myeloid skewed hematopoiesis.
GPT-4o mini: Non-social science research article
Exceptional diversity of allorecognition receptors in a nonvertebrate chordate reveals principles of innate allelic discrimination
Henry Rodriguez-Valbuena, Jorge Salcedo, Olivier De Thier, Jean Francois Flot, Stefano Tiozzo, Anthony W. De Tomaso
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Highly polymorphic allorecognition systems have been characterized in numerous invertebrate species, and exhibit discriminatory capabilities reminiscent of vertebrate adaptive immunity. As these systems utilize germline encoded receptors, the mechanisms underlying allelic discrimination are unknown. The invertebrate chordate, Botryllus schlosseri, undergoes a natural transplantation reaction controlled by a highly polymorphic, polygenic locus (called the fuhc) with over 1,000 allelic haplotypes found worldwide. Two individuals are compatible if they share one or both fuhc alleles, and we had found that polymorphic discrimination is due to the integration of signals from two allorecognition receptors encoded within the fuhc locus, called fester and uncle fester. Here we show that these two receptors are members of an extended family consisting of >35 genes, now called the Fester family ( FF ), and coexpressed with members of another diverse gene family, the fester coreceptors ( FcoR ). Both FF and FcoR are Immunoglobulin superfamily members and each FcoR encodes conserved tyrosine signal transduction motifs, including ITIMs or hemITAMs. FF and FcoR are expressed and encoded as cognate pairs in two polymorphic haplotypes: one within the fuhc locus, and another on a separate chromosome, and remarkably, copy number variation between haplotypes is of gene pairs. Furthermore, two FcoR genes can swap ITIMs and hemITAMs by alternative splicing, suggesting that dynamic tuning of activating and inhibitory signaling is required for allelic discrimination. These results indicate that conserved signal processing mechanisms are the foundation of both allelic discrimination in Botryllus , and recurring convergent evolution of allorecognition receptors observed from invertebrates to mammals.
GPT-4o mini: Non-social science research article
Reconfiguration of brain-wide neural activity after early life adversity
Taylor W. Uselman, Russell E. Jacobs, Elaine L. Bearer
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Early life adversity (ELA) predisposes individuals to physical and mental disorders lifelong. How ELA affects brain functions, leading to these vulnerabilities, is a mystery. To understand ELA’s impacts, investigations into neural activity affected by ELA must go beyond localized areas toward simultaneous recordings from multiple widely distributed regions over time. Such studies will expose relative activity between regions and discover shifts in regional activity in response to different experiences. Here, we performed longitudinal manganese-enhanced MRI (MEMRI) to measure degrees of brain-wide neural activity in ELA-exposed mice across a series of experiences in adulthood. To ascertain whether ELA resulted in atypical brain activity, results were compared to those of the standard mouse (Std). MEMRI captured activity in the freely moving home cage condition, and short- and long-term after exposure to TMT, a naturalistic predator threat. Images were normalized and aligned then analyzed with statistical mapping and automated segmentation. We found that neural activity in the home cage was greater in ELA compared to Std in multiple striatal-pallidal and hypothalamic regions. Upon acute threat, neural activity in Std increased in these regions to become more similar to that in ELA, while new hyperactive responses in ELA emerged in the midbrain and hindbrain. Nine days after acute threat, heightened neural activity in ELA persisted within locus coeruleus and increased within the posterior amygdala, ventral hippocampus, and dorsomedial and ventromedial hypothalamus. These results reveal functional imbalances that arise between multiple brain-systems after ELA, which are dependent upon context and cumulative experiences into adulthood.
GPT-4o mini: Non-social science research article
Dual-site cooperation for synergistic optimization of the band structure and spin state to facilitate C–N coupling reaction
Qizhu Qian, Qilong Liu, Mengxiang Wang, Jingjing Yang, Huiyi Li, Wei Bai, Wentao Wang, Changzheng Wu, Chong Xiao, Yi Xie
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The emerging electrocatalytic C–N coupling reaction provides an attractive route toward green urea synthesis, but a lack of in-depth insight into the catalytic mechanism and the geometric/electronic configurations that determine the key C- and N-coupling intermediates formation hampers the exploration of efficient catalysts. Herein, we design a bimetallic oxide (Fe-Mo-O) with dual active sites of Fe and Mo for the adsorption and activation of NO 2 − and CO 2 , respectively. Constructing dual-metal catalyst leads to an upshift of the d-band center and the generation of an intermediate-spin Fe center, which not only favors the selective conversion of *CO 2 into the key intermediate *CO on Mo sites, but also facilitates the adsorption and reduction of NO 2 − on Fe sites. Operando characterizations and theoretical calculations together elucidate that urea generation is associated with the formation of *CONH 2 intermediate by coupling *CO and *NH 2 on the alternating Mo and intermediate-spin Fe active sites, ultimately synergistically lowering the C–N coupling energy barrier. Specifically, the Fe-Mo-O catalyst delivers a high urea yield rate of 681.8 ÎŒg h −1 mg −1 cat. and an excellent Faradaic efficiency of 60% at −0.5 V (vs. RHE). Furthermore, a C–N coupling paired with a glycerol oxidation system allows for energy-saving electrochemical coproduction of urea and formic acid. Our findings offer a feasible strategy to develop cutting-edge electrocatalysts for urea synthesis by active site design and electronic structure regulation.
GPT-4o mini: Non-social science research article
A universal thermal performance curve arises in biology and ecology
Jean-François Arnoldi, Andrew L. Jackson, Ignacio Peralta-Maraver, Nicholas L. Payne
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Temperature has strong impacts on all biological and ecological processes, and thermal performance curves (TPCs) have been employed recurrently to assess them. TPCs almost always take a particular asymmetric shape across the biological hierarchy, with many different competing mechanisms and models doing a similarly good job of trying to explain the TPC phenomenon. Here, we reveal that the ubiquitous exponential scaling of biological processes with temperature creates a mechanistic tendency for TPC data and models to collapse onto a single curve (which we call the Universal TPC, UTPC), explaining mathematically why biological systems respond to temperature in such a consistent way. We illustrate that many seemingly different TPCs actually approximate rescaled versions of the same curve, even when thermal performance estimates vary widely across organisms, systems, and contexts. We demonstrate remarkable UTPC collapse across the tree of life, with diverse datasets spanning microbes to vertebrates, and individual physiology to population growth. UTPC phenomena also provide a strong theoretical basis for predicting performance of warm-adapted organisms will be more sensitive to- and less tolerant of- temperature fluctuations; an important consideration in the context of climate change.
GPT-4o mini: Non-social science research article
Full interhemispheric integration sustained by a fraction of posterior callosal fibers
Tyler Santander, Selin Bekir, Theresa Paul, Jessica M. Simonson, Valerie M. Wiemer, Henri Etel Skinner, Johanna L. Hopf, Anna Rada, Friedrich G. Woermann, Thilo Kalbhenn, Barry Giesbrecht, Christian G. Bien, Olaf Sporns, Michael S. Gazzaniga, Lukas J. Volz, Michael B. Miller
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The dynamic integration of the lateralized and specialized capacities of the two cerebral hemispheres constitutes a hallmark feature of human brain function. This interhemispheric exchange of information critically depends upon the corpus callosum. Classical anatomical descriptions of callosal organization outline a topographic gradient from front to back, such that specific transcallosal fibers support distinct aspects of integrated brain function. Here, we present a challenge to this conventional model. Using neuroimaging data obtained from a new cohort of adult corpus callosotomy patients, we leverage modern network neuroscience techniques to show that full interhemispheric integration can be achieved via a small proportion of posterior callosal fibers. Partial callosotomy patients with spared callosal fibers retained widespread patterns of interhemispheric functional connectivity and showed no signs of behavioral disconnection, even with only 1 cm of the splenium intact. Conversely, only complete callosotomy patients demonstrated sweeping disruptions of interhemispheric network architectures, aligning with disconnection syndromes long-thought to reflect diminished information propagation and communication across the brain. These findings motivate an evolving mechanistic understanding of synchronized interhemispheric neural activity for large-scale human brain function and behavior.
GPT-4o mini: Non-social science research article
Outrunning protein diffusion to the air–water interface in cryoEM
Anastasiia Gusach, Kasim Sader, Christopher J. Russo
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Here, we report a series of measurements indicating that it is physically possible to thin and vitrify a specimen for electron cryomicroscopy (cryoEM) faster than proteins diffuse to the air–water interface. We achieved this by spraying picoliter volume droplets at speeds of hundreds of meters per second into a thin layer of liquid ethane coating the surface of a precooled specimen support. The droplets simultaneously collapsed and froze in microseconds into the amorphous phase as they landed on the surface. The atomic structure of the proteins was preserved and tomographic reconstructions of the vitrified specimens indicated adhesion to the interfaces was eliminated. Improved control of the final thickness of the specimen and the orientation distribution of the particles are now the limiting factors. This demonstration provides a basis for the development of specimen preparation methods and instruments that eliminate the detrimental effects of the air–water interface in cryoEM.
GPT-4o mini: Non-social science research article
Impact of baleen whales on ocean primary production across space and time
Carla Freitas, Morten D. Skogen, Guðjón M. Sigurðsson, Martin Biuw, Tore Haug, Lotta Lindblom, Kjell Gundersen
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Primary production in the ocean is a fundamental process that supports marine food webs and global carbon sequestration. This process depends on nutrients that are often limited in surface waters. Whales are known to release essential elements such as nitrogen, phosphorus, and iron, yet the extent of their contribution to ocean primary production remains unclear. Here, we present daily estimates of nutrient input by baleen whales in high-latitude feeding grounds (Nordic and Barents Seas), based on multielement analyses of feces and urine. We then used end-to-end ecosystem models to assess the impact of these nutrients on primary production. We found that nitrogen is primarily excreted via urine, whereas phosphorus and trace elements are mainly released through feces. Ecosystem models indicate that baleen whales, including minke, fin, sei, humpback, blue, and bowhead whales, support annual and seasonal net primary production, with varying impacts across space and time. While the annual effects are modest (<2%) in most areas, the greatest impacts (up to 10%) occur during summer stratification and in offshore areas far from other nutrient sources. These increases in primary production have cascading effects on the food web, driving rises in mesozooplankton biomass. This study highlights the ecological significance of nutrient cycling by whales and underscores the value of integrating whale nutrient data into ecosystem modeling to assess the broader impacts of whales on marine productivity.
GPT-4o mini: Non-social science research article
Descattering and image restoration with a transformer-based neural network in deep tissue imaging
Xiangcong Xu, Renlong Zhang, Chenggui Luo, Chi Zhang, Yanping Li, Danying Lin, Bin Yu, Liwei Liu, Xiaoyu Weng, Yiping Wang, Lingjie Kong, Jia Li, Junle Qu
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Imaging biological structures deep inside tissues is crucial but challenging due to common light scattering. This study proposes a multiattention network that directly maps degraded scattering two-photon excitation fluorescence (TPEF) images to high-quality scattering-free images, thereby computationally extending the imaging depth for TPEF without requiring complex optical additions. The model relies solely on simulated data rather than well-registered real data pairs, and is trained to descatter and restore hidden spatial information at greater depths. Quantitative evaluations on simulated fluorescent beads and vasculature show significant performance improvements in peak signal-to-noise ratio (23 to 29 dB) and structural similarity index (23×) compared to the raw data. We also apply the framework to various ex vivo and in vivo experiments, achieving clear visualization of lipid droplets up to a depth of 1,300 ÎŒm and of vascular structure and astrocytes up to 950 ÎŒm and 500 ÎŒm, respectively, in live mouse brains at lower excitation powers.
GPT-4o mini: Non-social science research article
Therapeutic IgG- and IgM-specific proteases disarm the acetylcholine receptor autoantibodies that drive myasthenia gravis pathology
Alexandra C. Bayer, Liliana M. Sanmarco, Alex Pellerin, Gianvito Masi, Agustin Plasencia, Jordan M. Anderson, Richard J. Nowak, Valentina Damato, Luca Massacesi, Minh C. Pham, Fatemeh Khani-Habibabadi, Heather Vital, Nathan Higginson-Scott, Kevin L. Otipoby, Yi Xing, Ivan D. Mascanfroni, Kevin C. O’Connor
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Myasthenia gravis (MG) is an autoimmune disorder caused mainly by autoantibodies against the acetylcholine receptor (AChR), leading to muscle weakness. While treatments targeting AChR autoantibodies benefit many, some patients remain refractory, highlighting the need for personalized therapies. This study evaluates the therapeutic potential of S-1117, a pan-IgG-specific protease, in AChR autoantibody-mediated pathology. Using live cell-based assays, we examined AChR-specific monoclonal IgG autoantibodies (mAbs) and patient-derived serum samples for their effects on receptor binding, blockade, internalization, and complement activation, before and after treatment with S-1117. S-1117 effectively removed the crystallizable fragment (Fc)Îł from both mAbs and serum IgG, impairing FcÎł-mediated complement activation in both soluble and antigen-bound forms. In cases with partial complement reduction, AChR-specific IgM contributed to complement deposition. AChR-IgM acted in concert with IgG in some patients to enhance complement deposition, while acting as main complement driver in others. An IgM-specific protease completely suppressed the pathogenic effects of AChR-IgM in two independent patient cohorts. These findings highlight the therapeutic potential of S-1117 in neutralizing AChR-IgG FcÎł-mediated effector functions and reveal an MG subset driven by IgM pathology. Our study shows that targeting both IgG- and IgM-mediated mechanisms with therapeutic proteases provides an approach to MG treatment and establishes a framework for patient stratification based on disease mechanisms, advancing precision medicine in MG.
GPT-4o mini: Non-social science research article
Aberrant X chromosome dosage compensation causes hybrid male inviability in Caenorhabditis
Yongbin Li, Yimeng Gao, Jiaonv Ma, Yifan Gao, Jiemei Tang, Rui Yang, Jiajia Wang, Wangyan Zhou, Hantang Zhang, Wenhua Shao, Zhijin Liu, Zhongying Zhao, Xiao Liu
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Zygotic reproductive isolation frequently initiates with hybrid incompatibility in the heterogametic sex, such as males in XX/XY systems. The genetic basis of hybrid male incompatibility has long remained elusive. Here, we show that crosses of Caenorhabditis nigoni males with C. briggsae females result in insufficient expression of Cbr-xol-1 , an X-linked master switch responsible for intimately linked sex determination and dosage compensation pathways, consequently triggering aberrant X-chromosome repression in males, and ultimately leading to embryonic inviability. In contrast, male embryos from the reciprocal cross maintain normal expression level of C. nigoni xol-1 genes, consistent with their viability. We further demonstrate that the cis-regulatory regions of Cbr-xol-1 and Cni-xol-1 have functionally diverged. Finally, X transcription is also aberrantly repressed in lethal hybrid male embryos from crosses between gonochoristic species C. latens and C. remanei . Our results suggest an evolutionary scenario in which incompatibility of the dosage compensation system leads to reproductive isolation.
GPT-4o mini: Non-social science research article
Joint disruption of Ret and Ednrb transcription shifts cell fate trajectories in the enteric nervous system in Hirschsprung disease
Ryan D. Fine, Rebecca Chubaryov, Mingzhou Fu, Gabriel Grullon, Aravinda Chakravarti
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Despite extensive genetic heterogeneity, 72% of pathogenic alleles for Hirschsprung disease (HSCR) arise from coding and regulatory variants in genes of the RET and EDNRB gene regulatory network (GRN) in the enteric nervous system (ENS). To elucidate the mechanisms leading to enteric neuronal loss from these genetic defects, we generated four strains of mice carrying reduced function alleles at Ret or Ednrb or both, along with their wild-type alleles. ENS tissue- and single-cell gene expression profiling of the developing and postnatal gastrointestinal tract in these five mouse models revealed three major insights: i) Ret and Ednrb deficiency, rather than complete loss, is sufficient to induce HSCR, ii) Ret and Ednrb demonstrate strong trans interactions, and iii) disruption of this interaction leads to cellular fate changes to compensate for neuronal loss. Critically, we show the combined reduction of signaling of these two receptors below a threshold in enteric neural crest-derived cells (ENCDCs) leads to a molecular tipping point at which otherwise lesser cellular defects result in aganglionosis. This study of targeted mouse models of a multifactorial disorder reveals how increasing dosage of genetic defects within a GRN leads to quantifiably increasing dysregulation from genotype to gene expression to cellular identity to function. Importantly, our studies establish that aganglionosis results only with severely reduced gene expression at both receptor genes and their consequent disruption of normal and compensatory cell fate trajectories.
GPT-4o mini: Non-social science research article
The moving mantle beneath Hawaii: A new look at an old bend
R. Dietmar MĂŒller
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GPT-4o mini: Non-social science research article
HIF2α negatively regulates MYCN protein levels and promotes a low-risk noradrenergic phenotype in neuroblastoma
Juan Yuan, Subhamita Maitra, Eirini Antoniou, Jiacheng Zhu, Wenyu Li, Ilknur Safak Demirel, Kostantinos Toskas, Iria Laura Martinez, Lacin Ozcimen, Henrik Lindehell, Jonas Muhr, Jakob Stenman, Per Kogner, Oscar C. Bedoya-Reina, Susanne Schlisio, Johan Holmberg
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The role of HIF2α, encoded by EPAS1 , in neuroblastoma remains controversial. Here, we demonstrate that induction of high levels of HIF2α in MYCN-amplified neuroblastoma cells results in a rapid and profound reduction of the oncoprotein MYCN. This is followed by an upregulation of genes characteristic of noradrenergic cells in the adrenal medulla. Additionally, upon induction of HIF2α, the proliferation rate drops substantially, and cells develop elongated neurite-like protrusions, indicative of differentiation. In vivo HIF2α induction in established xenografts significantly attenuates tumor growth. Notably, analysis of sequenced neuroblastoma patient samples, revealed a negative correlation between EPAS1 and MYCN expression and a strong positive correlation between EPAS1 expression, high expression levels of noradrenergic markers, and improved patient outcome. This was paralleled by analysis of human developing adrenal medulla datasets wherein EPAS1 expression was prominent in populations with high expression levels of genes characteristic of noradrenergic chromaffin cells. Our findings show that high levels of HIF2α in neuroblastoma, leads to drastically reduced MYCN protein levels, cell cycle exit, and noradrenergic cell differentiation. Taken together, our results challenge the dogma that HIF2α acts as an oncogene in neuroblastoma.
GPT-4o mini: Non-social science research article
Genetic regulation of the estrogen receptor and inherited predisposition to breast cancer
Sarah B. Pierce, Hannah Kortbawi, Suleyman Gulsuner, Jessica B. Mandell, Ming K. Lee, Tom Walsh, Mary-Claire King
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For many families severely affected with breast cancer, no inherited causal allele has been detected in any tumor suppressor gene. In an effort to understand the genetics underlying breast cancer in these families, we evaluated 136 such families for coinheritance of breast cancer with each of 79 common variants reported as high-confidence “risk alleles” for breast cancer by meta-analyses of genome-wide association studies. Simulations based on allele frequencies and family structures revealed one (and only one) of these 79 variants to cosegregate with breast cancer in the families significantly more frequently than expected by chance. This variant (rs2046210) is located 180 kb proximal to ESR1 , encoding the estrogen receptor alpha. Reporter assays in MCF7 cells revealed enhancement by the genomic segment at this site of activity of ESR1 promoters, but no difference in effect among alternative haplotypes. In contrast, the 600 kb genomic region including ESR1 and rs2046210 harbored 11 rare variants, each of which cosegregated with breast cancer in one or a few families. For 9 of these 11 variants, reporter assays indicated significant allele-specific effects on ESR1 promoters, with the breast-cancer-linked allele of each variant yielding higher promoter activity. At the site with the most striking effect, the breast-cancer-linked allele was associated with increased binding by transcription factor AP2-gamma TFAP2C in both MCF7 and T47D cells. These results demonstrate coinheritance with breast cancer of rare alleles that increase activity of ESR1 promoters, and suggest that rare ESR1 regulatory alleles may contribute to inherited predisposition to breast cancer.
GPT-4o mini: Non-social science research article
Lamin A/C loss promotes R-loop-mediated genomic instability and poor survival in small-cell lung cancer
Christopher W. Schultz, Sourav Saha, Anjali Dhall, Yang Zhang, Parth Desai, Lorinc S. Pongor, David A. Scheiblin, Valentin Magidson, Ravi P. Shuklah, Robin Sebastian, Umeshkumar M. Vekariya, Shahbaz Ahmed, Yilun Sun, Christophe Redon, Suresh Kumar, Manan Krishnamurthy, Henrique B. Dias, Vasilisa Aksenova, Elizabeth Giordano, Nobuyuki Takahashi, Michael Nirula, Mohit Arora, Chiori Tabe, Maria Sebastian Thomas, Rajesh Kumar, Yasuhiro Arakawa, Ukhyun Jo, Tomasz Skorski, Beverly A. Teicher, Roshan Shreshta, Mirit I. Aladjem, Stephen Lockett, Mary Dasso, Yves Pommier, Ajit K. Sharma, Anish Thomas
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Lamin A/C ( LMNA ), a key component of the nuclear envelope, is essential for maintaining nuclear integrity and genome organization [W. Xie et al. , Curr. Biol. 26 , 2651–2658 (2016)]. While LMNA dysregulation has been implicated in genomic instability across cancer and aging, the underlying mechanisms remain poorly understood [S. Graziano et al. , Nucleus 9 , 258–275 (2018)]. Here, we define a mechanistic role for LMNA in preserving genome stability in small-cell lung cancer (SCLC), a malignancy marked by extreme genomic instability [N. Takahashi et al. , Cancer Res. Commun. 2 , 503–517 (2022)]. LMNA depletion promotes R-loop accumulation, transcription-replication conflicts, replication stress, DNA breaks, and micronuclei formation. Mechanistically, LMNA deficiency disrupts nuclear pore complex organization, specifically reducing phenylalanine-glycine (FG)-nucleoporin incorporation, resulting in impaired RNA export and nuclear retention of RNA. LMNA expression is repressed by EZH2 and reexpressed during SCLC differentiation from neuroendocrine (NE) to non-NE states, and low LMNA levels correlate with poor clinical outcomes. These findings establish LMNA as a key regulator of nuclear transport and genome integrity, linking nuclear architecture to SCLC progression and therapeutic vulnerability.
GPT-4o mini: Non-social science research article
A PHF19-YTHDC1 condensate switches EZH2-mediated gene suppression to activation for prostate cancer progression
Shuai Yuan, Dao-Jing Ming, Jiapeng He, Meng-Yang Liu, Shao-Hua He, Hong Weng, Shu Xi, Jin-Hui Zhang, Ming-Hui Shi, Jin-Long Cui, Lu-Yao Li, Haozhe Zhang, Dan-Qi Wang, Fei Li, Meng-Meng Guo, Yi Cai, Shi-Di Tang, Shuang-Ying Wang, Xing-Huan Wang, Xian-Tao Zeng, Hailiang Hu
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EZH2, a core component of PRC2 complex, silences global gene expression by tri-methylating histone H3K27. It remains an elusive question that EZH2 hyperexpression discords with its H3K27me3 activity of gene suppression in advanced prostate cancer. Here, we report a nascent RNA-dependent PHF19-YTHDC1 condensate capable of switching EZH2-mediated gene suppression to activation during prostate cancer progression. We found that the long isoform of PRC2 accessory subunit PHF19, PHF19L, was highly expressed in advanced prostate cancer that promoted the tumor progression and hormonal therapy resistance. Mechanistically, PHF19L was recruited to the m 6 A modified nascent RNA through YTHDC1 and formed a liquid-like YTHDC1-PHF19L condensate that pulled the EZH2 away from chromatin, resulting in reduced H3K27me3 deposition and the activated expression of EZH2-repressed genes. Therefore, our study reveals a biomolecular condensate that modulates the switch from EZH2-mediated epigenetic gene silence to activation during the progression of prostate cancer.
GPT-4o mini: Non-social science research article
Engineered 3D immuno-glial-neurovascular human miBrain model
Alice E. Stanton, Adele Bubnys, Emre Agbas, Benjamin James, Dong Shin Park, Alan Jiang, Rebecca L. Pinals, Liwang Liu, Nhat Truong, Anjanet Loon, Colin Staab, Oyku Cerit, Hsin-Lan Wen, David Mankus, Margaret E. Bisher, Abigail K. R. Lytton-Jean, Manolis Kellis, Joel W. Blanchard, Robert Langer, Li-Huei Tsai
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Patient-specific, human-based cellular models integrating a biomimetic blood–brain barrier, immune, and myelinated neuron components are critically needed to enable accelerated, translationally relevant discovery of neurological disease mechanisms and interventions. To construct a human cell-based model that includes these features and all six major brain cell types needed to mimic disease and dissect pathological mechanisms, we have constructed, characterized, and utilized a multicellular integrated brain (miBrain) immuno-glial-neurovascular model by engineering a brain-inspired 3D hydrogel and identifying conditions to coculture these six brain cell types, all differentiated from patient induced pluripotent stem cells. miBrains recapitulate in vivo – like hallmarks inclusive of neuronal activity, functional connectivity, barrier function, myelin-producing oligodendrocyte engagement with neurons, multicellular interactions, and transcriptomic profiles. We implemented the model to study Alzheimer’s Disease pathologies associated with APOE4 genetic risk. APOE4 miBrains differentially exhibit amyloid aggregation, tau phosphorylation, and astrocytic glial fibrillary acidic protein. Unlike the coemergent fate specification of glia and neurons in other organoid approaches, miBrains integrate independently differentiated cell types, a feature we harnessed to identify that APOE4 in astrocytes promotes neuronal tau pathogenesis and dysregulation through crosstalk with microglia.
GPT-4o mini: Non-social science research article
Intracellular pH regulates ubiquitin-mediated degradation of the MAP kinase ERK3
Chloé TesniÚre, Fadia Boudghene-Stambouli, Marc Severin, Mallorie Poët, Laure Voisin, Muthulakshmi Ponniah, Mirela Pascariu, Eric Bonneil, Jean-François Trempe, Pierre Thibault, Laurent Counillon, Stine Falsig Pedersen, Sylvain Meloche
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Intracellular pH (pHi) influences diverse cellular processes, including cell proliferation, metabolism, and migration, and is linked to metabolic diseases and cancer. Protonation alters protein charge and conformation, modulating different aspects of protein function. How pHi fluctuations are sensed by signaling proteins and translated into cellular responses remains incompletely understood. Here, we reveal that pHi plays a key role in regulating the stability of the mitogen-activated protein kinase Extracellular signal-regulated kinase 3 (ERK3). Intracellular acidification markedly increases the half-life of ERK3, whereas alkalinization accelerates its degradation. The pH-dependent regulation of ERK3 is rapid, reversible, and consistent across cell types. Mechanistically, we identified a region in the C-terminus of ERK3 that contains pH-sensing motifs. We further show by quantitative proteomics that short-term acidification or alkalinization globally affects the cellular proteome. Our findings underscore the critical role of pHi in ERK3 turnover and suggest a broader role for pH in regulating protein stability and cell signaling.
GPT-4o mini: Non-social science research article
Amyloid precursor protein and C99 are subunits in human microglial Hv1 channels that enhance current and inflammatory mediator release
Ruiming Zhao, Punyanuch Sophanpanichkul, Jean Paul Chadarevian, Yiwen Ding, Hui Dai, Maha Nayak, Hayk Davtyan, Mathew Blurton-Jones, Steve A. N. Goldstein
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In Alzheimer’s disease (AD), hyperactivated microglia produce inflammatory mediators that contribute to neuroinflammation and neuronal damage. Amyloid precursor protein (APP), a transmembrane protein expressed in many cell types, including neurons and microglia, plays a critical role in AD pathogenesis via its secretase-mediated processing to release the C-terminal 99-residue transmembrane fragment (C99) that is further cleaved to yield amyloid-ÎČ peptides. Voltage-gated proton channels (Hv1) have been implicated in microglial activation and release of inflammatory mediators, but the potential role of these channels in human microglia and AD pathogenesis remains unclear. Here, we demonstrate that human induced pluripotent stem cell–derived microglia (iMG) express native Hv1 channels with biophysical and pharmacological attributes determined by their coassembly with APP and that APP knockdown decreases Hv1 currents, suppressing cytokine and reactive oxygen species release. In HEK293T cells, APP is shown to increase current by favoring channel opening at more negative membrane potentials. C99 is sufficient to assemble with Hv1 and alters channel function even more significantly than APP. Coimmunoprecipitation, total internal reflection fluorescence microscopy, and altered pharmacology further demonstrate that C99 forms stable complexes with Hv1 in the plasma membrane. In addition, we find that two early-onset AD mutations in APP (E682K and D694N) that reside within C99 significantly increase voltage-dependent channel activity beyond that induced by wild type C99, rationalizing their enhanced mediation of neuroinflammation.
GPT-4o mini: Non-social science research article
Mutant p53 regulates cancer cell invasion in complex three-dimensional environments through mevalonate pathway–dependent Rho/ROCK signaling
Asja Guzman, Tatsuya Kawase, Alexander J. Devanny, Gizem Efe, RaĂșl Navaridas, Karen Yu, Kausik Regunath, Iris G. Mercer, Rachel C. Avard, Rafaela Muniz de Queiroz, Anil K. Rustgi, Laura J. Kaufman, Carol Prives
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Certain TP53 mutations can confer neomorphic gain of function (GOF) activities to the p53 protein that affect cancer progression. Yet the concept of mutant p53 GOF has been challenged. Here, using various strategies to alter the status of mutant versions of p53 in different cell lines, we demonstrate that mutant p53 stimulates cancer cell invasion in three-dimensional environments. Mechanistically, mutant p53 enhances RhoA/ROCK-dependent cell contractility and cell-mediated extracellular matrix (ECM) reorganization via increasing mevalonate pathway–dependent RhoA localization to the membrane. In line with this, RhoA-dependent proinvasive activity is also mediated by IDI-1, a mevalonate pathway product. Further, the invasion-enhancing effect of mutant p53 is dictated by the biomechanical properties of the surrounding ECM, thereby adding a cell-independent layer of regulation to mutant p53 GOF activity that is mediated by dynamic reciprocal cell–ECM interactions. Together our findings link mutant p53 metabolic GOF activity with a context-dependent invasive cellular phenotype.
GPT-4o mini: Non-social science research article
Bridging microscopic dynamics and rheology in the yielding of charged colloidal suspensions
Hongrui He, Heyi Liang, Miaoqi Chu, Zhang Jiang, Juan J. de Pablo, Matthew V. Tirrell, Suresh Narayanan, Wei Chen
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The yielding of soft materials is critical to many natural and industrial processes, yet experimental insights into microscopic aspects of yielding are limited. This study combines angle X-ray scattering, X-ray photon correlation spectroscopy, and in situ rheology (Rheo-SAXS-XPCS) with fast lubrication dynamics simulations to examine how interparticle interactions influence yielding in charged colloidal suspensions. By tuning attraction through salt addition, we compare repulsive and attractive systems under deformation. Repulsive suspensions yield uniformly with Andrade-like creep and minimal structural change. In contrast, attractive suspensions show complex behaviors, including shear banding, delayed yielding, and resolidification, governed by transient dynamics at shear band interfaces. These results directly link microscopic particle dynamics to macroscopic flow and demonstrate how interaction potentials control rheological behavior. This work offers a framework for designing soft materials with tailored properties for applications in coatings, food processing, drug delivery, and other technologies requiring precise mechanical control.
GPT-4o mini: Non-social science research article
Capillary self-thinning of threads of polyelectrolyte solutions with axial electric fields
Patrick Martin, Gleb Vasilyev, Eyal Zussman, Alexander L. Yarin
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A theory of solutions of charged polyelectrolyte (PE) macromolecules, treating them as electric dipoles, is proposed. In a thin thread of PE solution sustained between two disks—whether wettable or nonwettable—these dipoles are reoriented by an axial electric field, aligning themselves with the field direction. This alignment causes significant axial elastic stresses and affects capillary self-thinning dynamics of the thread, slowing the process and potentially arresting it entirely, and even leading to oscillatory regimes. Accordingly, the evolution of the thread radius deviates significantly from the exponential decay characteristic of solutions of flexible polymer macromolecules and the linear decay characteristic of Newtonian fluids. At relatively high electric field strengths, in a thread where elastic stresses become dominant, an oscillatory regime emerges. Here, the cross-sectional radius not only decreases but also increases and oscillates in time—a behavior rooted in an ill-posedness of the problem reducing to the Laplace equation in case of strong electric fields. This indicates a manifestation of Hadamard instability. The theory is supported by experimental data acquired in this work.
GPT-4o mini: Non-social science research article
Evolutionary histories of functional mutations during the domestication and spread of japonica rice in Asia
Ornob Alam, Rafal Gutaker, Niketh Surya, Cristina Castillo, Dorian Fuller, Jade d’Alpoim Guedes, Michael Purugganan
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Rice ( Oryza sativa ) was first domesticated beginning ~9,000 y ago in China as the japonica variety group/subspecies. Using genomic data from 456 japonica landraces, including data for 47 herbarium specimens collected over the last 167 y, we reconstruct how japonica rice moved from its center of origin to other parts of Asia beginning ~4,000 to 5,500 y ago. We observe an enrichment of pathogen resistance loci in selective sweeps associated with distinct geographic populations, suggesting that biotic interactions may be a key driver of local adaptation. We also find that the majority of 76 known functional mutations present in our japonica landraces—many of them associated with japonica rice domestication and diversification and important for modern breeding—had their origins in the Pleistocene >11,700 y ago and increased in allele frequency during key events in the evolution of rice.
GPT-4o mini: Non-social science research article
Proteolytically activated antibacterial toxins inhibit the growth of diverse gram-positive bacteria
Jake Colautti, Stephen R. Garrett, John C. Whitney
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Many species of bacteria produce small-molecule antibiotics that enter and kill a wide range of competitor microbes. However, diffusible antibacterial proteins (ABPs) that share this broad-spectrum activity are not known to exist. Here, we report a family of proteins widespread in gram-positive bacteria that display potent antibacterial activity against a diverse range of target organisms. Upon entering susceptible cells, these ABPs enzymatically degrade essential cellular components including DNA, transfer ribonucleic acid (tRNA), and ribosomal ribonucleic acid (rRNA). Unlike previously characterized bactericidal proteins, which require a specific cell surface receptor and therefore display a narrow spectrum of activity, we find that ABPs act in a receptor-independent manner and consequently kill bacteria spanning multiple phyla. Target cell entry by ABPs requires proteolytic activation by a cognate, coexported serine protease, and the liberated toxin component of the cleaved ABP is driven across the target cell membrane by the proton motive force. By examining representative ABPs from diverse pathogenic, commensal, and environmental bacteria, we show that broad-spectrum antibacterial activity is a conserved property of this protein family. Collectively, our work demonstrates that secreted proteins can act as broad-spectrum antibiotics, suggesting that ABPs represent one of potentially many such families produced in nature.
GPT-4o mini: Non-social science research article
From retinotopic to ordinal coding: Dissecting the cortical stages of visual word recognition
Aakash Agrawal, Stanislas Dehaene
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Fluent reading requires the brain to precisely encode the positions of letters within words, distinguishing for instance FORM and FROM across variations in size, position, and font. Early visual areas, however, are known to encode retinotopic positions, and how these representations get transformed into a position-invariant neural code remains unclear. Building upon a computational model of reading, we used 7T functional MRI and magnetoencephalography (MEG) to reveal a cortical hierarchy in which early visual areas (V1–V4) predominantly encode retinotopic information, whereas higher-level regions, including the visual word form area, transition to an ordinal letter-position code. MEG analyses confirm that retinotopic encoding emerges early (60 to 200 ms), followed by a shift toward ordinal representations in later time windows (220 to 450 ms). Despite this transition, word position remained a dominant factor across all time points, suggesting a concurrent coding of both retinotopic and abstract positional information. These findings uncover the spatiotemporal dynamics by which the human brain transforms visual input into structured prelexical representations, shedding light on the cortical stages of reading and their developmental and clinical implications.
GPT-4o mini: Non-social science research article
Cytosolic proliferating cell nuclear antigen (PCNA) orchestrates neutrophil hyperactivation in COVID-19
Rodrigo de Oliveira Formiga, Lucie Pesenti, François Chable de la HéronniÚre, Maha Zohra Ladjemi, Darko Stojkov, Shida Yousefi, Philippe Frachet, Lisa Krafft, Laura Tiberio, Daniela Bosisio, Muriel Andrieu, Souganya Many, Vaarany Karunanithy, Karine Bailly, Théo DhÎte, Giovanni Saraceni-Tasso, Manon Castel, Christophe Rousseau, Marick Rodrigues Starick, Edroaldo Lummertz da Rocha, Emilia Puig Lombardi, Cicero José Luíz dos Ramos Almeida, Anderson dos Santos Ramos, Fernando Queiroz Cunha, José Carlos Alves-Filho, Natålia Ribeiro Cabacinha Nóbrega, Matheus Rodrigues Gonçalves, Celso Martins Queiroz-Junior, Viviane Lima Batista, Mauro Martins Teixeira, Vanessa Granger, Sylvie Chollet-Martin, Luc De Chaisemartin, Luc Mouthon, Anne Hosmalin, Margarita Hurtado-Nedelec, Clémence Martin, Fernando Spiller, Hans-Uwe Simon, Nicolas Tamassia, Marco Antonio Cassatella, Frédéric PÚne, Thomas Vogl, Pierre-Regis Burgel, Vivian Vasconcelos Costa, Véronique Witko-Sarsat
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Neutrophils are central mediators of the hyperinflammatory response in severe SARS-CoV-2 infection. We report elevated cytosolic levels of proliferating cell nuclear antigen (PCNA) in neutrophils from patients with severe and critical COVID-19, correlating with enhanced NADPH oxidase–dependent reactive oxygen species (ROS) generation and neutrophil extracellular trap (NET) formation. Using T2AA, a small-molecule inhibitor of the PCNA scaffold, we demonstrate potent suppression of NADPH oxidase activation and NET release, particularly in response to SARS-CoV-2 RNA. Mechanistically, we identify a previously unrecognized interaction between PCNA and the heterodimeric S100A8/S100A9 (calprotectin), predominantly enriched in CD16 high CD62L low neutrophils expanded during COVID-19. PCNA binds the dimeric S100A8/S100A9 complex mediated via S100A8 subunit with micromolar affinity, and this interaction is abrogated by tetramerization, suggesting regulation by intracellular calcium. Disruption of this complex by T2AA inhibited ROS production in an S100A8/S100A9-dependent manner, implicating calprotectin as a functional regulator of neutrophil activation. In a betacoronavirus mouse model, T2AA treatment attenuated lung inflammation, reduced NET and calprotectin levels, and shifted pulmonary neutrophils away from hyperactivated and immunosuppressive phenotypes, consistent with immune reprogramming toward resolution. These findings establish cytosolic PCNA as a central scaffold in neutrophil hyperactivation during COVID-19 and highlight its pharmacological disruption as a promising host-directed strategy to limit inflammation and prevent organ damage.
GPT-4o mini: Non-social science research article
Impactor relics of CI-like chondrites in Chang’e-6 lunar samples
Jintuan Wang, Zhiming Chen, Zexian Cui, Qing Yang, Le Zhang, Pengli He, Jingyou Chen, Chengyuan Wang, Yan-Qiang Zhang, Jiangze Wang, Yonghua Cao, James W. Head, Hugh O’Neill, Akira Tsuchiyama, Yuri Amelin, Maxwell M. Thiemens, Chang-ming Xing, Bo Wei, Wenhua Lu, Mang Lin, Yi-Gang Xu
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The impact history of the Moon provides the opportunity to better understand mass transfer in the Solar System. While Earth’s meteorite collection serves as a key reference for material flux in the Earth–Moon system, it suffers from profound biases arising from Earth’s orbital dynamics and atmospheric filtering. Systematic identification and classification of meteorites on the airless Moon thus provide additional critical constraints for reconstructing the primordial accretion history and impactor population of the inner Solar System. However, identifying impactors on the Moon remains challenging due to their vaporization upon colliding at high velocities with the lunar surface. In situ remote sensing has previously detected chondritic impactor materials in the South-Pole-Aitken (SPA) basin of the far side of the Moon. The first opportunity to measure materials from the SPA basin has come via the Chang’e-6 (CE-6) mission, which returned samples from the Apollo basin inside the SPA basin. In this study, we screened seven olivine-porphyritic clasts as potential impactor relics in regolith returned by the CE-6 mission. These clasts were identified, via textural characterization, olivine Fe–Mn–Zn systematics, and in-situ triple oxygen isotopes, as impact relics solidified from melted chondritic parent bodies. Intriguingly, the parent body of all the identified impactor relics in this study resemble CI-like chondrites, a volatile-rich meteorite group that is relatively rare in Earth’s meteorite collection. The detection and classification of these impactor relics impose significant constraints on the proportions of meteoritic materials in the Earth–Moon system and their potential contributions to water inventories on the lunar surface.
GPT-4o mini: Non-social science research article
Museum genomics suggests long-term population decline in a putatively extinct bumble bee
Rena M. Schweizer, Jared A. Grummer, Kerrigan B. Tobin, Renee Corpuz, Scott M. Geib, Diana Cox-Foster, Lynn S. Kimsey, Jonathan B. Uhuad Koch, Michael G. Branstetter
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Pollinator declines globally threaten ecosystem stability and agricultural productivity. Reconstructing pollinator historic demographies provides an evolutionary perspective to understand contemporary population declines. The Franklin bumble bee ( Bombus franklini ), once endemic to Oregon and California and last observed alive in 2006, is emblematic of this phenomenon. We collected whole-genome sequence data from museum specimens spanning four decades to elucidate the genetic and demographic history of this potentially extinct species. Heterozygosity estimates of 25 individuals were remarkably low, and runs of homozygosity (ROH) patterns identified short segments suggestive of historical inbreeding, with some individuals having almost entire chromosomes in ROH. Demographic reconstructions revealed a marked decline in effective population size beginning in the late Pleistocene, with further declines in the last 400 y, which may have been influenced by fire and drought stressors. We found little to no genomic evidence implicating pathogens in the species’ decline and used coalescent simulations to show that we would be able to detect recently reduced heterozygosity only when colony-level survival rates are 15 to 30%. We conclude that a combination of historically low effective population size and genetic diversity along with environmental stochasticity heightened this species’ extinction vulnerability prior to recent anthropogenic stressors. This study demonstrates the utility of museum collections for clarifying genetic and demographic dynamics of rare species and suggests that B. franklini may have already been on a trajectory of decline prior to human impacts.
GPT-4o mini: Non-social science research article
Viscoelastic structural damping enables broadband low-frequency sound absorption
Yanlin Zhang, Junyin Li, Qiongying Wu, Marco Amabili, Diego Misseroni, Hanqing Jiang
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Low-frequency sound absorption has traditionally relied on air-resonant structures, such as Helmholtz resonators, which are made of stiff materials that undergo negligible deformation. In these systems, energy dissipation arises primarily from air motion and thermal–viscous effects, resulting in inherently narrowband performance and bulky, complex designs for broadband absorption. Here, we presented a composite acoustic metamaterial that replaces the high-stiffness neck of a Helmholtz resonator with a soft, viscoelastic cylindrical shell. This structural modification enables material deformation and shifts the dominant energy dissipation mechanism from air resonance to intrinsic viscoelastic damping. A single unit achieves over 97% absorption across a broad low-frequency range (227 to 329 Hz) with deep-subwavelength thickness (λ/15 at 227 Hz). We developed a discretized impedance model that quantitatively links material properties and geometry to absorption behavior. Our results established a materials-centered design paradigm in which both material selection and geometry serve as coequal, tunable parameters for compact, broadband low-frequency sound control.
GPT-4o mini: Non-social science research article
Differential O -glucose elongation on a specific EGF repeat within the canonical ligand–binding domain regulates DLL1/4-NOTCH1 signaling
Yohei Tsukamoto, Kazuhiro Aoki, Yuichi Kama, Hiroyuki Hosokawa, Wataru Saiki, Natsumi Tsukamoto, Koki Kato, Yohei Hosokawa, Rie Sato, Naoki Uesugi, Yuki Fujita, Kana Fukazawa, Daichi Funada, Fuga Suzuki, Yuuki Kurebayashi, Yusuke Urata, Sae Uchiyama, Weiwei Wang, Akira Minami, Tadanobu Takahashi, Michael Tiemeyer, Yoshiki Narimatsu, Tetsuya Okajima, Hideyuki Takeuchi
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Three types of O -linked glycosylation— O -glucose, O -fucose, and O - N -acetylglucosamine— are crucial for the function of Notch receptors, which regulate critical cell fate determination processes in a wide variety of contexts. O -Glucose glycans are transferred to serine residues located between the first and second conserved cysteines within the epidermal growth factor-like (EGF) repeats in the Notch extracellular domain. Previously, O -glucose glycans were shown to be extended to a trisaccharide structure with two xyloses via α1-3 linkages. Our recent studies, however, indicated that the O -glucose glycan on NOTCH1 EGF10 can be extended by hexose and Neu5Ac. Here, we demonstrated that this hexose- and Neu5Ac-extended glycan has a 3’-sialyllactose-like structure synthesized by specific members of two isoenzyme families, B4GALT1 and ST3GAL4. Using mass spectrometry, we identified this modification exclusively on NOTCH1 EGF10 and the analogous NOTCH3 EGF9 domain, with no detection in any other EGF domains in NOTCH1, NOTCH2, and NOTCH3. Sequence comparison and mutagenesis experiments identified one amino acid at position -2 of the fourth cysteine (C 4 -2) in the EGF domain as crucial for the galactose elongation of O -glucose glycans. We further demonstrated that this site-specific elongation of O -glucose on NOTCH1 EGF10 significantly impacts ligand binding and signal transduction of NOTCH1. In the context of early T cell development, the C 4 -2 mutants NOTCH1 A396Y and A396F enhance T cell differentiation through DLL1- and DLL4-dependent NOTCH1 signaling. Our findings contribute to the understanding of the intricate regulatory mechanisms of Notch receptor function mediated by distinct positions and structures of O -glycans.
GPT-4o mini: Non-social science research article
Nir2 crystal structures reveal a phosphatidic acid–sensing mechanism at ER–PM contact sites
Dongyoung Kim, Seowhang Lee, Youngsoo Jun, Changwook Lee
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Agonist-induced activation of phosphoinositide-specific phospholipase C (PLC) converts phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] to diacylglycerol (DAG) at the inner leaflet of the plasma membrane (PM). DAG can be enzymatically transformed into phosphatidic acid (PA) and accumulated at the PM. PYK2 N-terminal domain-interacting receptor 2 (Nir2) mediates the formation of ER–PM membrane contact sites (MCSs) by specifically recognizing PA at the PM and directly interacting with ER membrane protein vesicle-associated membrane protein-associated proteins (VAPs). The N-terminal phosphatidylinositol transfer protein domain of Nir2 facilitates PI/PA exchange at ER–PM MCSs to maintain PI and PA levels. Here, we reveal the mechanisms by which Nir2 senses phosphatidic acid (PA) and associates with membranes, based on three crystal structures of its C-terminal Lipin/Ned1/Smp2 (LNS2) domain bound to PA, the diphenylalanine [FF]–containing acidic tract (FFAT) motif complexed with vesicle-associated membrane protein–associated protein B/C (VAPB), and the Asp-Asp-His-Asp (DDHD) domain. The C-terminal LNS2 domain of Nir2 directly interacts with the phosphate in the headgroup of PA via hydrogen bonds involving S1025, T1065, K1103, and K1126. Formation of a salt bridge between E355 in Nir2 and R55 in VAPB is essential for Nir2 FFAT–VAPB interaction. The central DDHD domain of Nir2 forms a twofold symmetric dimer, and this self-association contributes to stable and tight membrane association. These findings reveal how Nir2-mediated ER–PM MCS formation maintains continued PI(4,5)P 2 -dependent PLC signaling.
GPT-4o mini: Non-social science research article
Anomalous grain dynamics and grain locomotion of odd crystals
Zhi-Feng Huang, Michael te Vrugt, Raphael Wittkowski, Hartmut Löwen
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Crystalline or polycrystalline systems governed by odd elastic responses are known to exhibit complex dynamical behaviors involving self-propelled dynamics of topological defects with spontaneous self-rotation of chiral crystallites. Unveiling and controlling the underlying mechanisms require studies across multiple scales. We develop such a type of approach that bridges between microscopic and mesoscopic scales, in the form of a phase field crystal model incorporating transverse interactions. This continuum density field theory features two-dimensional parity symmetry breaking and odd elasticity, and generates a variety of interesting phenomena that agree well with recent experiments and particle-based simulations of active and living chiral crystals, including self-rotating crystallites, dislocation self-propulsion and proliferation, and fragmentation in polycrystals. We identify a distinct type of surface cusp instability induced by self-generated surface odd stress that results in self-fission of single-crystalline grains. This mechanism is pivotal for the occurrence of various anomalous grain dynamics for odd crystals, particularly the predictions of a transition from normal to reverse Ostwald ripening for self-rotating odd grains, and a transition from grain coarsening to grain self-fragmentation in the dynamical polycrystalline state with an increase of transverse interaction strength. We also demonstrate that the single-grain dynamics can be maneuvered through the variation of interparticle transverse interactions. This allows to steer the desired pathway of grain locomotion and to control the transition between grain self-rotation, self-rolling, and self-translation. Our results provide insights for the design and control of structural and dynamical properties of active odd elastic materials.
GPT-4o mini: Non-social science research article
Forest recovery after deforestation is fueled by mineral weathering at the expense of ecosystem buffering capacity
Emily S. Bernhardt, Emma J. Rosi, Christopher T. Solomon, John Campbell, Charles T. Driscoll, Mark B. Green, Gene E. Likens, William H. McDowell
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The pace and trajectory of ecosystem development are governed by the availability and cycling of limiting nutrients, and anthropogenic disturbances such as acid rain and deforestation alter these trajectories by removing substantial quantities of nutrients via titration or harvest. Here, we use six decades of continuous chemical and hydrologic data from three adjacent headwater catchments in the Hubbard Brook Experimental Forest, New Hampshire—one deforested (W5), one CaSiO 3 -enriched (W1), and one reference (W6)—to quantify long-term nutrient and mineral fluxes. Acid deposition since 1900 drove pronounced depletion and export of base cations, particularly calcium, across all watersheds. Experimental deforestation of W5 intensified loss of biomass and nutrient cations and triggered sustained increases in streamwater pH, Ca 2+ , and SiO 2 exports over nearly four decades, greatly exceeding the effects of direct CaSiO 3 enrichment in both duration and magnitude. We detect no long-term changes in water yield or water flow paths in the experimental watersheds, and we attribute this multidecadal increase in weathering rates following deforestation to biological responses to severe nutrient limitation. Our evidence suggests that in the regrowing forest, plants are investing photosynthate into belowground processes that amplify mineral weathering to access phosphorus and micronutrients, consequently elevating the export of less limiting elements present in silicate parent material. Throughout decades of forest regrowth, enhanced biotic weathering has continued to deplete the acid buffering capacity of the terrestrial ecosystem while the export of weathering products has elevated the pH of the receiving stream.
GPT-4o mini: Non-social science research article
A yellow warbler is for the climate as a canary is for the coal mine
Peter R. Grant
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GPT-4o mini: Non-social science research article
Asymmetric gating of a homopentameric ion channel GLIC revealed by cryo-EM
Zhuowen Li, Nikhil Bharambe, Kashmiri Manishrao Lande, Bjarne Feddersen, Asha Manikkoth Balakrishna, Philip C. Biggin, Giriraj Sahu, Sandip Basak
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Pentameric ligand-gated ion channels (pLGICs) are vital neurotransmitter receptors that are key therapeutic targets for neurological disorders. Although the high-resolution structures of these channels have been elucidated, capturing their dynamic conformational transitions remains challenging due to the transient nature of intermediate states. In this study, we investigated a prokaryotic proton-gated pLGIC, GLIC. In our cryo-EM data at pH 4.0, we identified and segregated asymmetric particles, which we precisely aligned to resolve high-resolution structures of several previously unresolved asymmetric intermediate states, in addition to symmetric closed and open states. Detailed structural analysis revealed systematic conformational changes at individual subunits driving the channel opening. Molecular dynamics simulations were used to assign the functional states. We further examined the roles of the F116 and Y251 residues, located at the domain interface, playing a central role in interdomain communication. In addition, patch-clamp experiments on GLIC I240A and L241A mutants, located in the M2 helix, demonstrated their importance in channel gating. Together, these results shed light on the sequential and asymmetric conformational transitions that occur during GLIC activation, offering a deeper mechanistic understanding of asymmetric gating in pLGICs.
GPT-4o mini: Non-social science research article
Physical activity is directly associated with total energy expenditure without evidence of constraint or compensation
Kristen R. Howard, Olalla Prado-NĂłvoa, Guillermo Zorrilla-Revilla, Eleni Laskaridou, Glen R. Reid, Elaina L. Marinik, Marina Stamatiou, Catherine Hambly, Brenda M. Davy, John R. Speakman, Kevin P. Davy
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The prevailing linear model of physical activity (PA) and total energy expenditure (TEE) has been challenged by models that predict an upper limit of TEE linked to a compensatory reduction elsewhere in the energy budget in response to increased PA. We determined the equation of best fit between PA and TEE and explored relationships between PA and behavioral and physiological compensation. Using linear and nonlinear modeling, we observed a positive linear relationship between PA and TEE either without or after adjustment for fat-free mass (R 2 = 0.3492, TEE = 0.00685*PA + 7.124: R 2 =0.3667, TEE_ADJ(FFM) = 0.00511*PA + 8.598). Higher PA was associated with lower sedentary time (R 2 = 0.7207, %SPA= −0.0211*X + 91.261). There was no association between PA, TEE, or resting metabolic rate and adjusted biomarkers of immune, reproductive, or thyroid function after Bonferroni correction. The findings of this observational study do not support the constrained/compensated model but affirm the conventional additive relationship between PA and TEE across a broad range of PA levels.
GPT-4o mini: Non-social science research article
Logarithmic coding leads to adaptive stabilization in the presence of sensorimotor delays
Leonardo Demarchi, Monica Coraggioso, Antoine Hubert, Thomas Panier, Ghislaine Morvan-Dubois, Volker Bormuth, Georges Debrégeas
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Animals respond to sensory stimuli with motor actions, which in turn generate new sensory inputs. This sensorimotor loop is constrained by time delays that impose a trade-off between responsiveness and stability. Additionally, as the relationship between a motor command and the corresponding sensory feedback is context-dependent, the response must be adapted in real time. It is generally believed that this adaptation process relies on an internal model that is continuously updated through prediction error minimization. Here, we experimentally reveal an alternative strategy based on a simpler feedback mechanism that does not require any internal model. We developed a virtual reality system for the miniature transparent fish Danionella cerebrum that enables in vivo brain-wide imaging during fictive navigation. By systematically manipulating the feedback parameters, we dissected the motor control process that allows the animal to stabilize its position using optic flow. The sensorimotor loop can be fully described by a single delay differential equation, whose solutions quantitatively capture the observed behavior across all experimental conditions. Both behavioral and neural data indicate that the observed adaptive response arises from logarithmic nonlinearities at the sensory (Weber–Fechner law) and motor (Henneman’s size principle) ends. These fundamental properties of the nervous system, conserved across species and sensory modalities, have traditionally been interpreted in terms of efficient coding. Our findings unveil a distinct functional role for such nonlinear transformations: ensuring stability in sensorimotor control despite inherent delays and sensory uncertainty.
GPT-4o mini: Non-social science research article
All the world’s a phage
Graham F. Hatfull
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A renewed interest in bacteriophages has emerged from the explosive discovery of the complex pan-immune bacterial defense system and a revival of the therapeutic potential of phages in the age of widespread antimicrobial resistance to antibiotics. However, the road ahead is daunting because of the huge genetic diversity of phages and the vast numbers of genes of unknown function. A fully integrated approach that includes curiosity-driven exploration of phage biology, the development of integrated and inclusive research-education programs based on phage discovery and genomics (SEA-PHAGES), and the advancement of phage therapeutics provides a holistic structure for advancing the field. The phages of mycobacteria illustrate this model and a large mycobacteriophage collection reveals the enormous diversity of phages infecting a single bacterial strain and illuminates the evolutionary mechanisms giving rise to genomes with mosaic architectures. A set of 2,600 fully sequenced and annotated mycobacteriophage genomes and the development of tools for engineering them with desirable properties enable phage therapies for treating Mycobacterium infections for which antibiotics frequently fail. Technological advances in synthetic genomics and structural biology promise to rapidly advance this field and powerfully stimulate developments in all aspects of bacteriophage investigation and application. Here I describe what we have learned from the study of mycobacteriophages and how a holistic approach—integrating curiosity-driven research, inclusive education, and medicine—can serve as a model for advancing microbiology broadly.
GPT-4o mini: Non-social science research article
In This Issue
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GPT-4o mini: Non-social science research article
Neuronal plasticity at puberty in mouse hypothalamic Kiss1 neurons that control fertility
Yuanxin Zhang, Leonie M. Pakulat, Szabolcs TakĂĄcs, Lauren Campbell, Elisa Galliano, Erik Hrabovszky, William H. Colledge, Susan Jones
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Puberty is a critical transition period to achieve reproductive capacity in all mammalian species. At puberty, hypothalamic Kiss1 neurons release kisspeptin, stimulating gonadotropin-releasing hormone (GnRH) release and activating the hypothalamic–pituitary–gonadal (HPG) axis. Here, we show that Kiss1 neurons in the arcuate nucleus of the hypothalamus ( Kiss1 ARC ) of female mice undergo profound intrinsic plasticity at puberty. Kiss1 ARC neurons in brain slices from 3-wk-old mice, when depolarized, typically fire a short high-frequency burst of action potentials before falling silent. This would make them unsuitable for the sustained activity that is required to activate pulsatile GnRH secretion and the HPG axis. At 4 wk of age and after puberty, Kiss1 ARC neurons can fire a sustained train of action potentials. There is a concomitant hyperpolarization in action potential threshold and postspike minimum voltage and larger medium after-hyperpolarizations (mAHP) and hyperpolarization-induced voltage sags. Transcriptomic profiling showed significant changes in ion channel expression after puberty. Using quantitative PCR, we confirmed changes in genes encoding voltage-gated sodium, calcium, potassium, and cation channels. Blocking hyperpolarization-induced cation channels caused Kiss1 ARC neurons from postpuberty mice to fire less sustained trains of action potentials. Recordings from Kiss1 ARC neurons in mice after ovariectomy and 17ÎČ-estradiol replacement revealed a critical window of estrogen-dependent plasticity between 3 and 6 wk, which is essential for the maturation of Kiss1 ARC neurons and the development of their adult electrophysiological activity. This represents an example of sex steroid–dependent plasticity in the mammalian brain at puberty.
GPT-4o mini: Non-social science research article
Correction for Yu et al., Tetraphenylethene-based highly emissive metallacage as a component of theranostic supramolecular nanoparticles
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GPT-4o mini: Non-social science research article
Adipose cullin 3 mediates the antiobesity effect of pan neddylation inhibitors
Lijie Gu, Yanhong Du, Mohammad Nazmul Hasan, Yung-Dai Clayton, Tiangang Li
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Cullin Ring E3 Ligases (CRLs) belong to the largest family of multisubunit ubiquitin E3 ligases. A cullin serves as the scaffold protein that recruits E3 ligases and substrate receptors in a CRL complex, whose activity requires cullin neddylation, a posttranslational modification that can be pharmacologically targeted by neddylation inhibitors. Elevated neddylation activity has been observed in the liver and adipose tissue of obese mice, implicating a pathogenic link between altered CRL activity and the development of metabolic disorders. Emerging evidence has also shown that neddylation inhibitors possess antiobesity and hypoglycemic property. However, the roles of cullin proteins in regulating adipocyte biology are still incompletely defined. Here, we report that pan neddylation inhibitor TAS4464 treatment reversed obesity and adipose inflammation, resulting in improved hepatic steatosis and insulin sensitivity in obese mice. Among all mammalian cullin proteins that were targeted by TAS4464, we identified that cullin 3 (Cul3) was required for adipogenesis and adipocyte hypertrophy. A complete absence of Cul3 in adipocytes caused severely inhibited adipose expansion associated with ectopic fat accumulation in the liver and brown adipose tissue and insulin resistance, while adipocyte-specific Cul3 haploinsufficiency attenuated obesity and improved overall metabolic homeostasis, which recapitulated the metabolic benefits of TAS4464. Mechanistically, we found that Cul3 inhibition caused adipose nuclear factor erythroid 2-related factor 2 (NRF2) stabilization, which contributed to impaired adipogenesis by inhibiting lipogenesis. Together, these findings demonstrate that Cul3 is required during adipogenesis and acts as a downstream mediator of the antiobesity effect of pan neddylation inhibitors.
GPT-4o mini: Non-social science research article
Squamous cell carcinoma antigen-1/SerpinB3 is an endogenous skin injury response element
Jordan R. Yaron, Shubham Pallod, Sepideh Nezhadi, Holly M. Gildar, Jayda Hylton-Pelaia, Jordan Roberts, Jacquelyn Kilbourne, Kaushal Rege
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The squamous cell carcinoma antigen SerpinB3 is a serum-circulating biomarker of epithelial cancers associated with high metastasis, treatment resistance, and poor prognosis. Despite its clinical significance, the endogenous role of SerpinB3 has remained undefined. Here, we identify SerpinB3 as a mediator of epithelial wound healing. Injury induces SerpinB3 expression in vitro and in vivo in the migrating epidermal tongue; overexpression of the protein promotes epithelial-to-mesenchymal transition–like changes. Recombinant Serpinb3a, the mouse ortholog, enhances re-epithelialization in vitro and accelerates wound closure and collagen remodeling in vivo. These findings reveal a physiological function for SerpinB3 in epithelial repair and suggest that its expression in cancer, chronic wounds, and inflammatory diseases may reflect reactivation of a conserved wound response program—positioning SerpinB3 as a compelling therapeutic target.
GPT-4o mini: Non-social science research article
Spatial gene expression analysis reveals pathological niches in Japanese encephalitis virus neuroinvasion
Yasuko Orba, Yukie Kashima, Koshiro Tabata, Yukari Itakura, Takuma Ariizumi, William W. Hall, Hirofumi Sawa, Yutaka Suzuki, Michihito Sasaki
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Japanese encephalitis virus (JEV) infection causes encephalitis in humans and animals. Following intradermal infection, JEV crosses the blood–brain barrier (BBB) and reaches target cells in the brain parenchyma. However, the cellular dynamics and pathological niches involved in JEV neuroinvasion remain poorly understood. In this study, we investigated the early stages of JEV infection in the mouse brain employing a highly multiplexed spatial transcriptomics platform to map viral RNA and host gene expressions in intact brain sections at a single-cell resolution. Although JEV RNA was undetectable in brain sections at 1-day postinfection (dpi), innate immune responses were transiently activated across the brain. At 4 dpi, we detected limited viral RNA and mapped its spatial distribution, identifying glial cells surrounding microvessels as early targets of brain infection. We further characterized transcriptional changes in infected and surrounding bystander cells, revealing cell-type–specific antiviral responses. Notably, JEV neuroinvasion led to the downregulation of endothelial tight junction genes, indicative of an early event that precedes BBB impairment during subsequent disease progression. Our spatial transcriptomic analysis provides insights into cell-type– and region-specific responses to JEV infection, and highlights the early role of glial cells in shaping the immune response landscape of the brain. These findings greatly improve our understanding of JEV pathogenesis before the onset of clinical encephalitis.
GPT-4o mini: Non-social science research article
Single-cell sequencing uncovers sensory neuron–mediated CGRP signaling as a driver of sarcoma progression
Sowmya Ramesh, Qizhi Qin, Zhao Li, Masnsen Cherief, Lingke Zhong, Mary Archer, Xin Xing, Neelima Thottappillil, Devadutta Balaji, Sam Bae, Mario Gomez-Salazar, Mingxin Xu, Manyu Zhu, Ankit Uniyal, Leslie Chang, Khadijah Mazhar, Monisha Mittal, Alexander Birbrair, Edward F. McCarthy, Carol D. Morris, Benjamin Levi, Yun Guan, Thomas L. Clemens, Theodore J. Price, Aaron W. James
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Bone pain is a presenting feature of bone cancers such as osteosarcoma (OS), relayed by skeletal-innervating peripheral afferent neurons. Potential functions of tumor-associated sensory neurons in bone cancers beyond pain sensation are unknown. To uncover neural regulatory functions, a chemical-genetic approach in mice with a knock-in allele for TrkA was used to functionally perturb sensory nerve innervation during OS growth and disease progression. TrkA inhibition in transgenic mice led to significant reductions in sarcoma-associated sensory innervation and vascularization, skewed tumor associated macrophage polarization, reduced tumor growth and metastasis, and prolonged overall survival. Single-cell transcriptomics revealed that sarcoma denervation was associated with phenotypic alterations in both OS tumor cells and cells within the tumor microenvironment, and with reduced calcitonin gene-related peptide (CGRP) and vascular endothelial growth factor (VEGF) signaling. Multimodal and multiomics analyses of human OS bone samples further implicated peripheral innervation and neurotrophin signaling in OS tumor biology. Next and in two parallel approaches to inhibit nerve ingrowth, we repurposed FDA-approved bupivacaine liposomes and separately blocked CGRP signaling using FDA-approved Rimegepant. Both strategies led to significant reductions in sarcoma growth, vascularity, and sarcoma-induced hyperalgesia. In sum, TrkA-expressing peripheral neurons positively regulate key aspects of OS progression and sensory neural inhibition disrupts CGRP signaling within the sarcoma microenvironment leading to significantly reduced tumor growth and improved survival. These data suggest that interventions to prevent pathological innervation of OS represent an adjunctive therapy to improve clinical outcomes and survival.
GPT-4o mini: Non-social science research article
Foot placement control underlies stable locomotion across species
Antoine De Comite, Nidhi Seethapathi
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Animals navigate their environment stably without inefficient course corrections despite unavoidable errors. In humans, this stability is achieved by modulating the placement of the foot on each step such that recent errors are corrected. However, it is unknown whether animals with diverse nervous systems and body mechanics use such foot placement control; foot trajectories of many-legged animals are considered to be stereotypical velocity-driven patterns, as opposed to error-driven. Here, we put forth a unified “feedforward-feedback” control structure for stable locomotion that combines velocity-driven and body state error-driven foot placement. We provide empirical support for this control structure across flies, mice, and humans by mining their natural locomotor variability, finding that a competing control structure with purely velocity-driven foot placement is not supported by the data. This work finds shared behavioral signatures of foot placement control in flies, mice, and humans. We find that key characteristics of these signatures, such as their urgency and centralization, vary with neuromechanical embodiment across species. For example, more inherently stable multilegged animals exhibit less urgent control with a lower control magnitude and a slower correction timescale compared to humans. Furthermore, many-legged animals display modular, direction-, and leg-specific control signatures, whereas humans exhibit common signatures across both legs. Overall, our findings provide insight into stable locomotion across species, revealing how species with diverse neuromechanics achieve a shared functional goal: foot placement control.
GPT-4o mini: Non-social science research article
Disrupted developmental signaling induces novel transcriptional states
Aleena L. Patel, Vanessa Gonzalez, Triveni Menon, Stanislav Y. Shvartsman, Rebecca D. Burdine, Maria Avdeeva
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Signaling pathways induce stereotyped transcriptional changes as stem cells progress into mature cell types during embryogenesis. Signaling perturbations are necessary to discover which genes are responsive or insensitive to pathway activity. However, gene regulation is additionally dependent on cell state-specific factors like chromatin modifications or transcription factor binding. Thus, transcriptional profiles need to be assayed in single cells to identify potentially multiple, distinct perturbation responses among heterogeneous cell states in an embryo. In perturbation studies, comparing heterogeneous transcriptional states among experimental conditions often requires samples to be collected over multiple independent experiments, which can introduce confounding batch effects. We present Design-Aware Integration of Single Cell ExpEriments (DAISEE), a new algorithm that models perturbation responses in single-cell datasets collected according to complex experimental designs. We demonstrate that DAISEE improves upon a previously available integrative nonnegative matrix factorization framework, more efficiently separating perturbation responses from confounding variation. We use DAISEE to integrate newly collected single-cell RNA sequencing datasets from 5-h-old zebrafish embryos expressing optimized photoswitchable MEK (psMEK), which globally activates the extracellular signal-regulated kinase (ERK), a signaling molecule involved in many cell specification events. psMEK drives some cells that are normally not exposed to ERK signals toward other wild type states and induces novel states expressing early-acting endothelial genes. Overactive signaling is therefore capable of producing unexpected gene expression states in developing embryos.
GPT-4o mini: Non-social science research article
Reply to Auspurg: On the limits of “justified” model spaces
Michael Ganslmeier, Tim Vlandas
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GPT-4o mini: Non-social science research article
Magnon-induced electric polarization and magnon Nernst effects
D. Quang To, Federico Garcia-Gaitan, Yafei Ren, Joshua M. O. Zide, M. Benjamin Jungfleisch, John Q. Xiao, Branislav K. Nikolić, Garnett W. Bryant, Matthew F. Doty
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Magnons offer a promising path toward energy-efficient information transmission and the development of next-generation classical and quantum computing technologies. However, efficiently exciting, manipulating, and detecting magnons remains a critical need. We show that magnons, despite their charge-neutrality, can induce electric polarization through their spin and orbital moments. This effect is governed by system symmetry, magnon band hybridization, and interactions with other quasiparticles. We calculate the electric polarization induced by magnons in two-dimensional collinear honeycomb and noncollinear antiferromagnets (AFMs), showing that the presence of the Dzyaloshinskii–Moriya interaction yields a finite net electric polarization. In NiPSe 3 , a collinear honeycomb AFM with Zigzag order, the induced net electric polarization is about three orders of magnitude greater than in MnPS 3 , a collinear honeycomb AFM with NĂ©el phase. In the noncollinear AFM KFe 3 (OH) 6 (SO 4 ) 2 , the net electric polarization can be tuned via magnon hybridization, which can be controlled by external magnetic fields. These findings reveal that electric fields could be used to both detect and manipulate magnons under certain conditions by leveraging their spin and orbital angular moment. They also suggest that the discovery or engineering of materials with substantial magnon orbital moments could enhance practical uses of magnons for future computing and information transmission applications.
GPT-4o mini: Non-social science research article
Important design rules discovered for supramolecular multivalent ligands interacting with dynamic receptors
Heather D. Maynard
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GPT-4o mini: Non-social science research article
Driving forces of RNA condensation revealed through coarse-grained modeling with explicit Mg 2+
Shanlong Li, Jianhan Chen
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RNAs are major drivers of phase separation in the formation of biomolecular condensates and can undergo protein-free phase separation in the presence of divalent ions or crowding agents. Much remains to be understood regarding how the complex interplay of base stacking, base pairing, electrostatics, ion interactions, and particularly structural propensities governs RNA phase behavior. Here, we develop an intermediate resolution model for condensates of RNAs (iConRNA) that can capture key local and long-range structural features of dynamic RNAs and simulate their spontaneous phase transitions with Mg 2+ . Representing each nucleotide using 6 to 7 beads, iConRNA accurately captures base stacking and pairing and includes explicit Mg 2+ . The model not only reproduces major conformational properties of poly(rA) and poly(rU) but also correctly folds small structured RNAs and predicts their melting temperatures. With an effective model of explicit Mg 2+ , iConRNA successfully recapitulates experimentally observed lower critical solution temperature phase separation of poly(rA) and triplet repeats, and critically, the nontrivial dependence of phase transitions on RNA sequence, length, concentration, and Mg 2+ level. Further mechanistic analysis reveals a key role of RNA folding in modulating phase separation as well as its temperature and ion dependence, besides other driving forces such as Mg 2+ –phosphate interactions, base stacking, and base pairing. These studies also support iConRNA as a powerful tool for direct simulation of RNA-driven phase transitions, enabling molecular studies of how RNA conformational dynamics and its response to complex condensate environments control the phase behavior and condensate material properties.
GPT-4o mini: Non-social science research article
Hierarchical dynamic coding coordinates speech comprehension in the human brain
Laura Gwilliams, Alec Marantz, David Poeppel, Jean-Rémi King
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Speech comprehension involves transforming an acoustic waveform into meaning. To do so, the human brain generates a hierarchy of features that converts the sensory input into increasingly abstract language properties. However, little is known about how rapid incoming sequences of hierarchical features are continuously coordinated. Here, we propose that each language feature is supported by a dynamic neural code, which represents the sequence history of hierarchical features in parallel. To test this “hierarchical dynamic coding” (HDC) hypothesis, we use time-resolved decoding of brain activity to track the construction, maintenance, and update of a comprehensive hierarchy of language features spanning phonetic, word form, lexical–syntactic, syntactic, and semantic representations. For this, we recorded 21 native English participants with magnetoencephalography (MEG), while they listened to two hours of short stories in English. Our analyses reveal three main findings. First, the brain represents and simultaneously maintains a sequence of hierarchical features. Second, the duration of these representations depends on their level in the language hierarchy. Third, each representation is maintained by a dynamic neural code, which evolves at a speed commensurate with its corresponding linguistic level. This HDC preserves the maintenance of information over time while limiting destructive interference between successive features. Overall, HDC reveals how the human brain maintains and updates the continuously unfolding language hierarchy during natural speech comprehension, thereby anchoring linguistic theories to their biological implementations.
GPT-4o mini: Non-social science research article
Do color similarity judgments vary with age, and do they reveal anything about qualia?
Jenny M. Bosten, Anna Franklin
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GPT-4o mini: Non-social science research article
On the scale of heterogeneity in composite electrodes of batteries
Aishwary Shrivastava, Nikhil Sharma, Xiaomei He, Yijin Liu, Kejie Zhao
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An electrode in cylindrical or pouch cell batteries contains millions of active particles embedded in a conductive network. Battery performance, such as voltage, capacity, and cyclic efficiency, is a collective response of the particle network. We use optical microscopy to measure the local, heterogeneous state of charge of individual particles upon charging and discharging. The optical reflectivity is proportional to Li composition in the ternary oxide LiNi x Mn y Co z O 2 (NMC) cathode. Through clustering analysis, we determine the scale of heterogeneity where a representative volume in the composite electrode contains 100 to 1,000 particles. The heterogeneous activity in the particle network can be described by Weibull defect population at the particle interface with the conductive matrix.
GPT-4o mini: Non-social science research article
Oxygen isotopic evidence that Gale crater, Mars, was home to an Early Hesperian water reservoir that underwent significant evaporation
Amy E. Hofmann, P. Douglas Archer, Amy C. McAdam, Brad Sutter, Thomas F. Bristow, John M. Eiler, Christopher R. Webster, Gregory J. Flesch, Abigail A. Fraeman, Heather B. Franz, Christopher H. House, Elizabeth B. Rampe, Jennifer C. Stern, Paul R. Mahaffy, Charles A. Malespin, John P. Grotzinger, Ashwin R. Vasavada
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Simultaneous measurements of HDO, H 2 18 O, and H 2 16 O in water evolved during pyrolysis of powdered rock samples acquired by the Curiosity rover within Gale crater’s clay-bearing units indicate extreme and variable heavy-isotope enrichments averaging ~4.5 times the D/H ratio and ~1.03 times the 18 O/ 16 O ratio of terrestrial seawater. These enrichments are recorded in water desorbed from mineral surfaces and evolved from poorly crystalline phases, hydrated salts, jarosite, and clays. All evolved waters are deuterium-enriched relative to common terrestrial waters, reflecting hydrogen loss to space. Because oxygen in structurally bound hydroxyl groups is least likely to exchange with other sources over geologic timescales, we focus on oxygen in water evolved during dehydroxylation of smectite clays. Several samples have 18 O/ 16 O ratios commensurate with precipitation from, or near-complete equilibration with, water moderately 18 O-enriched relative to terrestrial meteoric waters—consistent with other evidence that Mars’s hydrosphere is basically like Earth’s in terms of oxygen isotopes. Unlike hydrogen, oxygen atmospheric escape did not lead to extreme 18 O enrichments on Mars. Locally, however, most Gale smectites’ 18 O/ 16 O values require a pronounced 18 O-enrichment of their parental waters. On Earth, the most extreme 18 O enrichments in surface waters are found in closed basins having undergone significant evaporative loss into a low-humidity atmosphere, and the 18 O/ 16 O of authigenic clay minerals formed in these environs reflect those enrichments. A similar process acting on the hydrologic reservoir local to Gale at the time of clay formation and early diagenesis is a plausible explanation for the distinctive oxygen isotopic compositions of these clays.
GPT-4o mini: Non-social science research article
Theta-nested gamma oscillations balance prediction and vigilance in spatial navigation
Kwan Tung Li, Ziqun Wang, Pulin Gong, Dongping Yang
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Recent experimental findings challenge the traditional belief that vigilance is solely attributed to the sensorimotor system, suggesting instead that hippocampal activity, coupled with locomotor processes, enhances environmental sampling and planning. Here, we propose that hippocampal theta-nested gamma oscillations (TGOs), widely observed in experiments, play essential roles in both prediction and vigilance, in terms of recalling reward sites and avoiding unexpected dangers through synfire chains (SFCs). Despite the recognized importance of TGOs in navigation, their precise functional roles remain unclear. By building a biologically plausible spiking neuronal network model and reproducing experimental results, we leverage SFC properties-length and separation-to reveal that the positive correlation between theta frequency and motion velocity optimally balances planning for predictable events and staying alert to unexpected ones. Based on this adaptive mechanism, we further explain the distinct functional contributions of TGOs consistent with experimental findings: Theta oscillations facilitate self-location awareness, gamma oscillations enhance predictive capabilities, and their coupling ensures sufficient time windows for prediction. Our study provides insights into the functional roles of TGOs in the hippocampus, highlighting their importance in achieving both planning and vigilance during goal-directed navigation.
GPT-4o mini: Non-social science research article
Hierarchical self-assembly for high-yield addressable complexity at fixed conditions
Miranda Holmes-Cerfon, Matthieu Wyart
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There is evidence that the self-assembly of complex molecular systems often proceeds hierarchically, by first building subunits that later assemble in larger entities, in a process that can repeat multiple times. Yet, our understanding of this phenomenon and its performance is limited. Here, we introduce a simple model for hierarchical addressable self-assembly, where interactions between particles can be optimized to maximize the fraction of a well-formed target structure, or yield. We find that a hierarchical strategy leads to an impressive yield up to at least five generations of the hierarchy and does not require a cycle of temperatures as used in previous methods. High yield is obtained when the microscopic interaction decreases with the scale of units considered, such that the total interaction between intermediate structures remains identical at all scales. We provide thermodynamic and dynamical arguments constraining the interaction strengths where this strategy is effective. Overall, our work characterizes an alternative strategy for addressable self-assembly at a fixed temperature, and provides insight into the mechanisms sustaining hierarchical assembly in biological systems.
GPT-4o mini: Non-social science research article
Reply to Bosten and Franklin: Children’s color qualia structure is similar to adults’
Yusuke Moriguchi, Ryoichi Watanabe, Chifumi Sakata, Ariel Zeleznikow-Johnston, Jue Wang, Noburo Saji, Naotsugu Tsuchiya
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GPT-4o mini: Non-social science research article
Invariant HVC size in female canaries singing under testosterone: Unlocking function through neural differentiation, not growth
Shouwen Ma, Carolina Frankl-Vilches, Manfred Gahr
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Testosterone administration to nonsinging adult female canaries induces song, making this a model for behavioral plasticity and its underlying neural mechanisms in vertebrates. The song control nucleus HVC is traditionally believed to undergo a substantial size change when transitioning from a nonfunctional to a functional (song-producing) state. Using 2-photon in vivo imaging, we tracked the spatial distribution and anatomical properties of HVC neurons over several weeks of testosterone-induced song development. Surprisingly, despite ultrastructural changes of HVC neurons, testosterone did neither alter neuronal spacing nor HVC size. Instead, spatial transcriptomics revealed that testosterone modulates gene networks throughout HVC, aligning transcriptomic profiles between its peripheral and central HVC regions in singing birds, thereby mimicking the histological appearance of an enlarging HVC. Our results demonstrate that changes in HVC size in adults reflect phenotypic changes in neurons within a stable framework. Importantly, the nonfunctional state is not associated with a reduced brain area volume, preserving HVC’s capacity for functional differentiation throughout life.
GPT-4o mini: Non-social science research article
Rewarding touch limits lifespan through neural to intestinal signaling
Elizabeth S. Kitto, Safa Beydoun, Scott F. Leiser
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In multicellular organisms, sensory perception affects many aspects of behavior and physiology. Perception of environmental stressors like food scarcity often leads to physiological changes that promote survival and slow aging. However, recent work shows that perception of attractive food smells can block the health benefits of dietary restriction in multiple model organisms. While it is known that sensory perception and cell nonautonomous signaling can modulate health and longevity, our knowledge of the specific sensory cues and mechanistic pathways that define this signaling is still limited. Here we find that the sense of touch interacts with nutritional state to modulate lifespan in Caenorhabditis elegans . Worms subjected to dietary restriction are shorter-lived when they perceive tactile stimuli that mimic bacterial food and/or protective soil. Touch modulation of dietary restriction requires putative mechanoreceptor proteins, the neurotransmitters dopamine and tyramine/adrenaline, and the neuropeptides INS-11 and GnRH. Ultimately, the touch circuit regulates the longevity effectors DAF-2/IGF1R and FMO-2/FMO5. These results establish a physiological touch circuit and connect neural reward pathways to the growth and reproductive axes. Finding that texture mechanosensation can modulate longevity suggests a role for touch in lifespan.
GPT-4o mini: Non-social science research article
Morphological specializations of mosquito CO 2 -sensing olfactory receptor neurons
Shadi Charara, Jonathan Choy, Kalyani Cauwenberghs, Pawel Vijayakumar, Renny Ng, Keun-Young Kim, Shih-Che Weng, Omar S. Akbari, Mark H. Ellisman, Scott A. Rifkin, Chih-Ying Su
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Hematophagous mosquitoes use CO 2 as a key arousal signal that gates behavioral responses to host-derived cues. In Aedes aegypti , CO 2 is detected by olfactory receptor neurons (ORNs) housed in the sensory hairs (sensilla) on the maxillary palp. While the molecular mechanism and behavioral significance of CO 2 sensing have been well studied in mosquitoes, the nanoscale three-dimensional structures of their CO 2 -sensing ORNs and associated cells have remained unclear. Using serial block-face scanning electron microscopy, we characterize the CO 2 -sensing cpA neuron and its odor-sensitive neighbors, cpB and cpC, within the capitate sensilla of A. aegypti. Notably, cpA neurons are significantly larger, with an outer dendritic surface area 8 to 12 times greater than that of cpB and cpC neurons. This expanded CO 2 -sensing surface arises from its unique architecture, consisting of numerous flattened dendritic sheets folded into intricate lamellae. In contrast, cpB and cpC dendrites exhibit sparse, narrow cylindrical branches. Moreover, the cpA axon displays a prominent pearls-on-a-string morphology, with numerous mitochondria-rich, nonsynaptic varicosities connected by thin cables. Remarkably, a glial cell and an auxiliary cell together ensheathe the cpA soma but not cpB or cpC, suggesting a specialized role in supporting cpA function. Compared to Drosophila CO 2 -sensitive ORNs, a larger portion of the cpA outer dendrite is embedded within the sensillum cuticle, potentially improving access to environmental CO 2 . These findings reveal key morphological specializations of cpA neurons, thereby advancing our understanding of mosquito sensory biology and laying the groundwork for future studies on the molecular basis and functional ramifications of these anatomical adaptations.
GPT-4o mini: Non-social science research article
Optimal disk packing of chloroplasts in plant cells
Nico Schramma, Eric R. Weeks, Maziyar Jalaal
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Photosynthesis is essential for ecosystem survival, but while plants require light, excessive exposure can damage cells. Chloroplasts, photosynthetic organelles, respond via self-organized motion within cells to optimize light absorption. These disk-shaped organelles must balance two competing needs: dense packing to enhance absorption under dim light and rapid spatial rearrangement to avoid damage from excess light. Using microscopy, we show that plant cell shape and chloroplast size achieve both goals: dense monolayer packing for optimal absorption in low light and sidewall packing for light avoidance. We present a theoretical model using random close packing simulations of polydispersed hard disks in rectangular boxes and find optimal cell shapes that match plant cell measurements. Our findings highlight how particle packing principles under confinement enable light adaptation in plants, offering insights into organelle organization under confinement, a physical challenge relevant across biological systems.
GPT-4o mini: Non-social science research article
Correction to Supporting Information for Milkman et al., A megastudy of text-based nudges encouraging patients to get vaccinated at an upcoming doctor’s appointment
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GPT-4o mini: Non-social science research article
Robustness is better assessed with a few thoughtful models than with billions of regressions
Katrin Auspurg
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GPT-4o mini: Non-social science research article
HEIP1 orchestrates pro-crossover protein activity during mammalian meiosis
Arnaud De Muyt, Sunkyung Lee, Sushil Khanal, Laurine Dal Toe, Céline Adam, Raphael Mercier, Valérie Borde, Neil Hunter, Thomas Robert
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Meiotic crossovers (COs) are needed to produce genetically balanced gametes. In mammals, CO formation is mediated by a conserved set of pro-CO proteins via mechanisms that remain unclear. Here, we characterize a mammalian pro-CO factor HEIP1. In mouse HEIP1 is essential for crossover and fertility of both sexes. HEIP1 promotes crossover by orchestrating the recruitment of other pro-CO proteins, including the MutSÎł complex (MSH4-MSH5) and E3 ligases (HEI10, RNF212, and RNF212B), that are required to mature CO sites and recruit the CO-specific resolution complex MutLÎł. Moreover, HEIP1 directly interacts with HEI10, suggesting a direct role in controlling the recruitment of pro-CO E3 ligases. During early stages of meiotic prophase I, HEIP1 interacts with the chromosome axes, independently of recombination, before relocalizing to the central region of the synaptonemal complex. We propose that HEIP1 is a conserved master regulator of CO proteins that controls different CO maturation steps.
GPT-4o mini: Non-social science research article
Parallel shifts in differential gene expression reveal convergent miniaturization in fishes
Emily M. Troyer, William T. White, Ricardo Betancur-R, Dahiana Arcila
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Body size variation in vertebrates is a complex polygenic trait, tightly correlated with numerous aspects of a species’ biology, ecology, and physiology. Miniaturization, the extreme reduction of adult body size, is a common phenomenon across the Tree of Life, yet the mechanisms underlying this process are poorly understood. Here, we investigate the molecular basis of body size evolution in goby fishes, a clade encompassing some of the smallest vertebrates on Earth. We generate a genome-wide phylogeny for 162 Gobioidei species and perform comparative transcriptomics across three clades with repeated instances of miniaturization and large-bodied forms. We identified 54 differentially expressed one-to-one orthologs between miniature and large-bodied species. These genes reveal distinct functional profiles, suggesting that regulation of cell numbers is a key mechanism governing body size control. Miniature species consistently overexpress growth inhibitors like CDKN1B and ING2 , associated with tighter cell cycle regulation and decreased proliferation rates, while large-bodied species upregulate growth-promoting genes such as TGFB3 , linked to tissue development and growth signaling. These enriched functional pathways, conserved since the Eocene (50 Ma), suggest macroevolutionary convergence in size regulation over deep time. Our findings provide insights into how size determination is governed at a genetic level and highlights the importance of exploring these factors in nonmodel organisms to uncover the fundamental processes regulating vertebrate body size evolution.
Beyond adoption: The persistence of conservation and climate-smart agricultural practices in the United States
Paul J. Ferraro, Maria Bowman, Hannah E. Correia, Jing Gao, Kelsey R. Larson, Kent D. Messer, Laura A. Paul, Bryan Pratt, Linda S. Prokopy
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Achieving sustainability goals requires that humans change their behavior not just once but persistently. Yet despite decades of research on the adoption of conservation and climate-smart agricultural practices, little is known about the extent to which these practices persist over time. One key reason is the lack of longitudinal, field-level data. Using ground-verified, longitudinal data on cover cropping across thousands of farm parcels in Indiana (USA), we find that persistence is low and contrasts sharply with the predictions made by Indiana conservation experts. We also find low persistence in a new national dataset of self-reported cover cropping by farm operators. The potential for low behavioral persistence in sustainable agricultural practices raises essential questions about the design of conservation programs and the modeling and valuation of ecosystem services.
The persistence of cross-cutting discussion in a politicized public sphere
Diana C. Mutz
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Although studies of Americans’ general discussant networks have been repeated over time, research that assesses change in the nature of Americans’ political discussion networks has yet to be conducted in nationally representative probability surveys. In this study I answer two questions about the quality of the American public sphere that have generated widespread speculation, but little evidence to date. First, how have Americans’ political discussion networks changed over the past 25 y? Second, are the consequences of these changes what one would expect based on previous theory linking Americans’ interpersonal information environments to political tolerance and political participation? I resolve competing claims suggesting that people feel less free to discuss politics, with claims suggesting instead that political discussion now permeates everyday life to a greater extent than in the past. Findings suggest widespread increases in political discussion, changes driven almost entirely by increases in like-minded political discussion partners. Surprisingly, Americans are no more or less likely to engage in conversations across lines of political difference. The predicted consequences of these fluctuations confirm an intrinsic tension between characteristics valued in democratic citizens. Political tolerance has declined significantly, along with decreased awareness of rationales for others’ relative to one’s own views. Political participation is significantly higher on average than 25 y ago. Few people reported engaging with online political discussants, despite efforts to make sure they were included in network measures.
A national randomized controlled trial of the impact of public Montessori preschool at the end of kindergarten
Angeline S. Lillard, David Loeb, Juliette Berg, Maya Escueta, Karen Manship, Alison Hauser, Emily D. Daggett
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Although seminal studies from the early 1960s suggested quality preschool can have lasting positive effects, agreement is lacking on the efficacy of different preschool models. The Montessori model is longstanding but lacks rigorous impact studies; prior random lottery studies included just one or two schools, among other compromises. Here, we report on end-of-kindergarten (age 5 to 6) impacts from a national study of public Montessori preschool. We compared children offered a Montessori seat via competitive lottery admission processes at one of 24 public Montessori schools at age 3 ( n = 242 ) to children not offered a seat ( n = 346 ), estimating Montessori impacts with intention-to-treat and complier average causal effect models. Roughly half of the treatment sample still attended Montessori for kindergarten. Although there were no notable impacts at the end of PK3 or PK4, at the end of kindergarten, controlling for baseline scores and demographics, Montessori children had significantly higher reading, short-term memory, theory of mind, and executive function scores. Intention-to-treat effect sizes exceeded a fifth of a SD, considered large in field-based school research [M. A. Kraft, Educ. Res. 49 , 241–253 (2020)]. This contrasts sharply with the more typical finding, where impacts of preschool are observed immediately following the program but disappear by the end of kindergarten. Further, a cost analysis suggested three years of public Montessori preschool costs less per child than traditional programs, largely due to Montessori having higher child:teacher ratios in PK3 and PK4. Although sensitivity and robustness analyses yielded similar results, important limitations of the study should be noted.

Science

GPT-4o mini: Non-social science research article
Global mean sea level over the past 4.5 million years
Peter U. Clark, Jeremy D. Shakun, Yair Rosenthal, David Pollard, Steven W. Hostetler, Peter Köhler, Patrick J. Bartlein, Jonathan M. Gregory, Chenyu Zhu, Daniel P. Schrag, Zhengyu Liu, Nicklas G. Pisias
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Changes in global mean sea level (GMSL) during the late Cenozoic remain uncertain. We use a reconstruction of changes in ÎŽ 18 O of seawater to reconstruct GMSL since 4.5 million years ago (Ma) that accounts for temperature-driven changes in the ÎŽ 18 O of global ice sheets. Between 4.5 and 3 Ma, sea level highstands remained up to 20 m above present whereas the first lowstands below present suggest onset of Northern Hemisphere glaciation at 4 Ma. Intensification of global glaciation occurred from 3 Ma to 2.5 Ma, culminating in lowstands similar to the Last Glacial Maximum lowstand at 21,000 years ago and that reoccurred throughout much of the Pleistocene. We attribute the middle Pleistocene transition in ice sheet variability (1.2 Ma to 0.62 Ma) to modulation of 41-thousand-year (kyr) obliquity forcing by an increase in ~100-kyr CO 2 variability.
GPT-4o mini: Non-social science research article
Calcifying plankton: From biomineralization to global change
Patrizia Ziveri, Gerald Langer, Sonia Chaabane, Joost de Vries, William Robert Gray, Nina Keul, Ian A. Hatton, Clara Manno, Richard Norris, Sven Pallacks, Jeremy R. Young, Ralf Schiebel, Stergios Zarkogiannis, Griselda Anglada-Ortiz, Stefania Bianco, Thibault de Garidel-Thoron, Michaël Grelaud, Arturo Lucas, Ian Probert, P. Graham Mortyn
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The cycling of calcium carbonate (CaCO 3 ) in the ocean is closely linked to seawater alkalinity and the regulation of atmospheric CO 2 . In the modern pelagic ocean, almost all CaCO 3 is produced by three groups of calcifying planktonic organisms: coccolithophores, foraminifers, and shelled pteropods. In this Review, we examine the differences in functional traits that define each group’s distinctive role in the global carbon cycle and their sensitivity to climate change and ocean acidification. This synthesis reveals that a single representation of CaCO 3 in climate models is unlikely to accurately reflect system dynamics or their impacts on biogeochemical cycling under climate change. We argue that understanding past and future CaCO 3 cycle requires a better delineation of the traits that make up the diversity of calcifying plankton groups.
GPT-4o mini: Non-social science research article
Positive affective contagion in bumble bees
José E. Romero-Gonzålez, Zhenwei Zhuo, Lulu Chen, Chaoyang Peng, Cwyn Solvi, Fei Peng
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Affective contagion, a core component of empathy, has been widely characterized in social vertebrates but its existence in any invertebrate is unknown. Using a cognitive bias paradigm we demonstrate positive affective contagion in bumble bees. After being trained on colored flowers with different reinforcements, bees that interacted with a conspecific in a positive affective state were quicker and more likely than controls to land on ambiguous colored flowers, indicating the transfer of a positive judgment bias between bees. Additional observations and experiments showed that affect could be transmitted between bees without physical contact, i.e., through visual modality alone. Our findings suggest that affective contagion may be an evolutionarily widespread mechanism present in both social vertebrates and social insects.
GPT-4o mini: Non-social science research article
Synthesis of triple stranded porphyrin nanobelts
Arnau RodrĂ­guez-Rubio, He Zhu, Ka Man Cheung, Igor Rončević, Lene A. Gödde, Janko Hergenhahn, Joshua L. Field, Prakhar Gupta, Wojciech Stawski, Henrik Gotfredsen, Joseph Straw, Matthew Edmondson, James N. O’Shea, Alex Saywell, Harry L. Anderson
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Molecular nanobelts are fascinating analogs of carbon nanotubes. Their rigid geometries and strongly coupled π-electrons have the potential to generate a wave function resembling that of a quantum ring. Here, we report the synthesis of triple stranded nanobelts consisting of 8 to 12 edge-fused porphyrin units with diameters of 21 to 32 angstroms. We synthesized these nanobelts by nickel-mediated coupling of meso -bromoporphyrins to form singly linked nanorings, followed by oxidation with gold(III) chloride. Experimental 1 H nuclear magnetic resonance spectra, supported by computational simulations, revealed that belts containing odd numbers of porphyrins, with circuits of 90 or 110 π-electrons, display global aromatic ring currents, whereas even-numbered belts, with 80, 100, or 120 π-electrons, are globally antiaromatic.
GPT-4o mini: Non-social science research article
Drought-induced peatland carbon loss exacerbated by elevated CO 2 and warming
Quan Quan, Jian Zhou, Paul J. Hanson, Daniel Ricciuto, Stephen D. Sebestyen, David J. Weston, Jeffrey P. Chanton, Rachel M. Wilson, Joel E. Kostka, Yu Zhou, Ning Wei, Lifen Jiang, Melanie A. Mayes, Jonathan M. Stelling, Andrew D. Richardson, Mirindi Eric Dusenge, Danielle Way, Jeffrey M. Warren, Yiqi Luo
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Extreme drought events are predicted to increase with climate change, yet their impacts on ecosystem carbon dynamics under warming and elevated carbon dioxide (eCO 2 ) remain unclear. In a peatland experiment with five warming treatments each under ambient carbon dioxide (aCO 2 ) and eCO 2 (+500 parts per million), a 2-month extreme drought in 2021 reduced net ecosystem productivity by 444.0 ± 65.8 and 736.6 ± 57.8 grams of carbon per square meter at +9°C under aCO 2 and eCO 2 , respectively—228.6 ± 56.8% and 381.9 ± 83.4% of the reduction at +0°C under aCO 2 . This exacerbation was driven by warming-induced water table decline, prolonged low water tables, and CO 2 -enhanced substrate availability through increased plant carbon inputs. Findings indicate that future climate will greatly amplify carbon loss during extreme drought, reinforcing positive carbon-climate feedbacks.
GPT-4o mini: Non-social science research article
Quantum critical electro-optic and piezo-electric nonlinearities
Christopher P. Anderson, Giovanni Scuri, Aaron Chan, Sungjun Eun, Alexander D. White, Geun Ho Ahn, Christine Jilly, Amir Safavi-Naeini, Kasper Van Gasse, Lu Li, Jelena Vučković
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Although electro-optic (EO) nonlinearities are essential for many quantum and classical photonics applications, a major challenge is inefficient modulation in cryogenic environments. Guided by the connection between phase transitions and nonlinearity, we identify the quantum paraelectric perovskite SrTiO 3 as a strong cryogenic EO [>500 picometers per volt (pm/V)] and piezo-electric material (>90 picocoulombs per newton) at T = 5 K, at frequencies to at least 1 megahertz. Furthermore, by tuning SrTiO 3 toward quantum criticality, we more than double the EO and piezo-electric effects, demonstrating a linear Pockels coefficient above 1000 pm/V. Our results probe the link between quantum phase transitions, dielectric susceptibility, and nonlinearity, unlocking opportunities in cryogenic optical and mechanical systems and providing a framework for discovering new nonlinear materials.
GPT-4o mini: Non-social science research article
A mosaic of modular variation at a single gene underpins convergent plumage coloration
Dave Lutgen, Valentina Peona, Madeline A. Chase, Niloofar Alaei Kakhki, Fritjof Lammers, Stacey G. de Souza, Anne-Lyse Ducrest, Marta Burri, Pavlos Andriopoulos, Sifiso M. Lukhele, Michaella Moysi, Elizabeth Yohannes, Abdin Abbasov, Tamer Albayrak, Mansour Aliabadian, Nicolas Auchli, Vasileios Bontzorlos, Ioulios Christoforou, José Luis Copete, Egidio Fulco, Jesus T. Garcia, Zura Javakhishvili, Anna Kazazou, Fumin Lei, Yang Liu, Nika Paposhvili, Robert Patchett, Áron Péter, Raphael Ritter, Attila D. Såndor, Fabian Schneider, Petar Shurulinkov, Sergey Sklyarenko, Borut Stumberger, Abulfaz Tagiyev, Alessia Uboldi, Nikitas Vogiatzis, Fanny Taborsak-Lines, Joel Gruselius, Liqun Yao, Catherine L. Peichel, Alexander Suh, Pierre-Alexandre Gagnaire, Alexander N. G. Kirschel, Manuel Schweizer, Holger Schielzeth, Reto Burri
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The reshuffling of genomic variation from multiple origins is an important contributor to phenotypic diversification, yet insights into the evolutionary trajectories of this combinatorial process and their interplay with genetic architecture remain scarce. We show that convergent plumage color evolution in wheatears involves a monogenic architecture with modular variation introgressed at the agouti signaling protein (ASIP) locus. Introgression of a new transposable element insertion and linked protein-coding variation underpin a transspecific throat color polymorphism, which stable isotopes suggest is associated with alternative foraging niches. Cointrogression of linked regulatory ASIP variation resulted in mantle color convergence in one species, whereas convergent color evolution at the genus level required new variation. Our results demonstrate evolutionary trajectories from introgressed variation realized within the constraints of a monogenic architecture.
GPT-4o mini: Non-social science research article
Durable, pure water–fed, anion-exchange membrane electrolyzers through interphase engineering
Shujin Hou, Archana Sekar, Yang Zhao, Minkyoung Kwak, Juhyun Oh, Kelvin Kam-Yun Li, Peiyao Wu, Ryan T. Hannagan, Valeria Cartagena, Anthony C. Ekennia, Hui Duan, Michael J. Zachman, Joelle Frechette, Gregory M. Su, Balsu Lakshmanan, Yushan Yan, Thomas F. Jaramillo, Shannon W. Boettcher
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Anion-exchange membrane water electrolyzers (AEMWEs) promise scalable, low-cost hydrogen production but are limited by the electrochemical instability of their anode ionomers. We report interphase engineering using inorganic-containing molecular additives that coassemble with ionomer, enabling pure water–fed AEMWEs to operate with a degradation rate <0.5 millivolt per hour at 2.0 amperes per square centimeter and 70°C—a >20-fold durability improvement. Analysis of different additives and ionomers shows that the stabilization mechanism involves cross-links between metal oxo/hydroxo oligomers and ionomers. Under operation, the inorganic additive enriches, forming an interphase near the water-oxidation catalyst that passivates the anode ionomer against continuous degradation while maintaining mechanical integrity and hydroxide conductivity. This additive-based interphase-engineering strategy provides a path to durable AEMWEs that operate without supporting electrolytes and is adaptable across diverse catalysts and ionomers for electrochemical technologies.
GPT-4o mini: Non-social science research article
“Kiss-shrink-run” unifies mechanisms for synaptic vesicle exocytosis and hyperfast recycling
Chang-Lu Tao, Chong-Li Tian, Yun-Tao Liu, Zhen-Hang Lu, Lei Qi, Xiao-Wei Li, Chao Li, Xuefeng Shen, Min-Ling Gu, Wen-Lan Huang, Shuo Liu, Lei-Qing Yang, Zhenghan Liao, Xiaomin Ma, Jing Wu, Jianyuan Sun, Peiyi Wang, Pak-Ming Lau, Z. Hong Zhou, Guo-Qiang Bi
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Synaptic vesicle (SV) exocytosis underpins neuronal communication, yet its nanoscale dynamics remain poorly understood owing to limitations in visualizing rapid events in situ. Here, we used optogenetics-coupled, time-resolved cryo–electron tomography to capture SV exocytosis in rat hippocampal synapses. Within 4 milliseconds of synaptic activation, SVs transiently “kiss” the plasma membrane, forming a ~4-nanometer lipidic fusion pore flanked by putative soluble NSF-attachment protein receptor (SNARE) complexes and then rapidly “shrink” to approximately half of their original surface area. By 70 milliseconds, most shrunken SVs recycle via a “run-away” pathway, whereas others collapse into the presynaptic membrane. Ultrafast endocytosis retrieves the expanded presynaptic membrane after 100 milliseconds. These findings reveal a “kiss-shrink-run” mechanism of SV exocytosis and hyperfast recycling, reconciling conflicting models and elucidating the efficiency and fidelity of synaptic transmission.
GPT-4o mini: Non-social science research article
Duck-billed dinosaur fleshy midline and hooves reveal terrestrial clay-template “mummification”
Paul C. Sereno, Evan T. Saitta, Daniel Vidal, Nathan Myhrvold, MarĂ­a Ciudad Real, Stephanie L. Baumgart, Lauren L. Bop, Tyler M. Keillor, Marcus Eriksen, Kraig Derstler
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Two “mummies” of the end-Cretaceous, duck-billed dinosaur Edmontosaurus annectens preserve a fleshy crest over the neck and trunk, an interdigitating spike row over the hips and tail, and hooves capping the toes of the hind feet. A battery of tests shows that all the fossilized integument (skin, spike, hoof) are preserved as a thin (< 1mm) clay template that formed on the surface of a buried carcass during decay prior to loss of all soft tissues and organic compounds. Unlike the underlying permineralized skeletal bone, the integument renderings of these “dinosaur mummies” are preserved as a thin external clay mask, a templating process documented previously only in anoxic marine settings.
GPT-4o mini: Non-social science research article
Engineering high Pockels coefficients in thin-film strontium titanate for cryogenic quantum electro-optic applications
Anja Ulrich, Kamal Brahim, Andries Boelen, Michiel Debaets, Ahmed Khalil, Conglin Sun, Yishu Huang, Sandeep Seema Saseendran, Marina Baryshnikova, Paola Favia, Thomas Nuytten, Stefanie Sergeant, Kasper Van Gasse, Bart Kuyken, Kristiaan De Greve, Clement Merckling, Christian Haffner
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Pockels materials are notable for their strong electro-optic interaction and rapid response times and are therefore used extensively in optical communications. However, at cryogenic temperatures, Pockels coefficients are reduced in many materials optimized for room-temperature operation, which is a major hurdle for emerging quantum technologies. Here, we show that strontium titanate (SrTiO 3 ) can be engineered to exhibit a Pockels coefficient of 345 picometers per volt at 20 hertz at cryogenic temperatures, a value twice as high as any other thin-film electro-optic material. By adjusting the stoichiometry, we were able to increase the Curie temperature and realize a ferroelectric phase yielding a high Pockels coefficient, so far with limited optical losses of decibels per centimeter. Our findings position SrTiO 3 as a promising material for cryogenic quantum photonics applications.
GPT-4o mini: Non-social science research article
An equilibrium trion liquid in atomic double layers
Phuong X. Nguyen, Raghav Chaturvedi, Liguo Ma, Patrick Knuppel, Kenji Watanabe, Takashi Taniguchi, Kin Fai Mak, Jie Shan
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A trion is a bound state of two electrons and one hole or two holes and one electron. To date, trions have been observed only as optically excited states in doped semiconductors. We report the emergence of an equilibrium trion liquid in Coulomb-coupled molybdenum diselenide (MoSe 2 ) and tungsten diselenide (WSe 2 ) monolayers. By electrically tuning the hole density in WSe 2 to be two times the electron density in MoSe 2 , we generated equilibrium interlayer trions with binding energy in the milli–electron volt energy scale at temperatures two orders of magnitude below the Fermi temperature. We observed a density-tuned phase transition to an electron-hole plasma, spin-singlet correlations for the constituent holes, and Zeeman field–induced dissociation of the trions. Our results pave the way for exploration of the correlated phases of composite particles in solids.
GPT-4o mini: Non-social science research article
Defensive fungal symbiosis on insect hindlegs
Takanori Nishino, Minoru Moriyama, Hiromi Mukai, Masahiko Tanahashi, Takahiro Hosokawa, Hsin-Yi Chang, Shuji Tachikawa, Naruo Nikoh, Ryuichi Koga, Chih-Horng Kuo, Takema Fukatsu
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Dinidorid stinkbugs were reported to possess a conspicuous tympanal organ on female hindlegs. In this study, we show that this organ is specialized to retain microbial symbionts rather than to perceive sound. The organ’s surface is not membranous but consists of porous cuticle in which each pore connects to glandular secretory cells. In reproductive females, the hindleg organ is covered with fungal hyphae that grow from the pores. Upon oviposition, the females transfer the fungi from the organ to the eggs, where the hyphae physically protect the eggs against wasp parasitism. The fungi comprise a diversity of mostly low-pathogenicity Cordycipitaceae.
GPT-4o mini: Non-social science research article
Visible light–driven stereodivergent allylation of cyclic hemiacetals with butene for polypropionate synthesis
Hiroyasu Nakao, Mirja Md Mahamudul Hassan, Yusuke Nakamura, Moe Toyobe, Masahiro Higashi, Harunobu Mitsunuma, Motomu Kanai
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Catalytically transforming abundant hydrocarbon feedstocks into structurally complex, high-value molecules is a pivotal yet challenging goal in organic synthesis. The key difficulty lies in the simultaneous activation of chemically inert feedstocks and precise stereochemical control. Here, we report a catalytic stereodivergent allylation of unprotected cyclic hemiacetal aldols with butene, enabling the programmable synthesis of polypropionates—privileged structural motifs prevalent in biologically active compounds, including pharmaceuticals. This visible light–driven, selective transformation exhibits broad functional group compatibility, furnishing 1,3-polyols with multiple contiguous stereocenters in high yield and stereochemical fidelity. Moreover, this method provides a concise and practical route to key natural product intermediates with minimal protection–deprotection sequences. This strategy has the potential to streamline polypropionate synthesis while reducing the time, cost, and environmental impact.
GPT-4o mini: Non-social science research article
Observation of the distribution of nuclear magnetization in a molecule
S. G. Wilkins, S. M. Udrescu, M. Athanasakis-Kaklamanakis, R. F. Garcia Ruiz, M. Au, I. BeloĆĄević, R. Berger, M. L. Bissell, A. A. Breier, A. J. Brinson, K. Chrysalidis, T. E. Cocolios, R. P. de Groote, A. Dorne, K. T. Flanagan, S. Franchoo, K. Gaul, S. Geldhof, T. F. Giesen, D. Hanstorp, R. Heinke, T. Isaev, Á. KoszorĂșs, S. KujanpÀÀ, L. Lalanne, G. Neyens, M. Nichols, H. A. Perrett, J. R. Reilly, L. V. Skripnikov, S. Rothe, B. van den Borne, Q. Wang, J. Wessolek, X. F. Yang, C. ZĂŒlch
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Precise experimental control and interrogation of molecules and calculations of their structure are enriching the investigation of nuclear and particle physics phenomena. Molecules containing heavy, octupole-deformed nuclei, such as radium, are of particular interest. Here, we report precision laser spectroscopy measurements and theoretical calculations of the structure of the radioactive radium monofluoride molecule 225 Ra 19 F. Our results reveal fine details of the short-range electron-nucleus interaction, indicating the high sensitivity of this molecule to the distribution of magnetization, within the radium nucleus. These results provide a stringent test of the description of the electronic wave function inside the nuclear volume, highlighting the suitability of these molecules for investigating subatomic phenomena.
GPT-4o mini: Non-social science research article
Electrically controlled interlayer trion fluid in electron-hole bilayers
Ruishi Qi, Qize Li, Zuocheng Zhang, Sudi Chen, Jingxu Xie, Yunbo Ou, Zhiyuan Cui, David D. Dai, Andrew Y. Joe, Takashi Taniguchi, Kenji Watanabe, Sefaattin Tongay, Alex Zettl, Liang Fu, Feng Wang
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The combination of repulsive and attractive Coulomb interactions in a quantum electron-hole (e-h) fluid can produce correlated phases of multiparticle charge complexes, such as excitons, trions, and biexcitons. We report an experimental realization of an electrically controlled interlayer trion fluid in van der Waals heterostructures. In strongly coupled e-h bilayers, electrons and holes spontaneously form three-particle trion bound states. The interlayer trions can assume 1e-2h and 2e-1h configurations. We show that the two holes in 1e-2h trions form a spin-singlet with a spin gap of approximately one milli–electron volt. By electrostatic gating, the equilibrium state can be continuously tuned into an exciton fluid, a trion fluid, an exciton-trion mixture, or a trion-charge mixture. Our work demonstrates a platform to study correlated phases of tunable Bose-Fermi mixtures.
GPT-4o mini: Non-social science research article
Room-temperature charge localization in ion-coupled bilayer transistors
Mengyu Gao, Hanyu Hong, Sicheng Fan, Tomojit Chowdhury, Zehra Naqvi, Jingyuan Ge, Ce Liang, Yu Han, Nathan P. Guisinger, Yuqing Qiu, Dong Hyup Kim, Suriyanarayanan Vaikuntanathan, Chong Liu, Jiwoong Park
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Controlling the localization of mobile charges in solids enables the discovery of correlated physical phenomena, but applying it for the development of next-generation electronics requires achieving such control under practical conditions. In this study, we report room-temperature, switchable charge localization in high-quality bilayer transistors that comprise a monolayer of molecular crystal on top of a monolayer semiconductor. By using an ion gate, we selectively populated either localized molecular states or semiconductor band states, achieving complete localization from mobile charges at densities up to 3 × 10 13 per square centimeter. This transition was energetically stabilized by the formation of coupled electron-ion dipoles, which could be tuned through Coulomb engineering. These properties further enabled single-band ambipolar transistor operation without substitutional dopants, demonstrating the potential of electron-ion correlations for practical electronic applications.
GPT-4o mini: Non-social science research article
Invasion impacts in terrestrial ecosystems: Global patterns and predictors
Madhav P. Thakur, Zhizhuang Gu, Mark van Kleunen, Xuhui Zhou
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Biological invasions can alter ecosystems, yet their impacts vary across ecological contexts. Using a global meta-analysis of 775 studies (2223 effect sizes) in terrestrial systems, we show that the most consistent negative impacts are reductions in native plant diversity caused by invasive plants and increases in greenhouse gas emissions driven by both invasive plants and animals. However, evidence of publication bias suggests the latter should be interpreted with caution. Invader residence time emerged as a key predictor: Longer residence times intensified the negative effects of invasive plants on native diversity, whereas impacts on soil abiotic properties tended to weaken over time. Our synthesis reveals that some properties, such as native plant diversity, remain persistently sensitive to invasion, whereas others are more variable as invasions persist.
GPT-4o mini: Non-social science research article
Liquid-state dipolarcaloric refrigeration cycle with nitrate-based salts
Seonggon Kim, Jae Hyeon Shin, Gil Jeong, Dae Young Jung, Jiachen Li, Zhenyuan Xu, Ruzhu Wang, Yong Tae Kang
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Environmental burden of vapor compression refrigeration has driven interest in alternatives. Caloric refrigeration cycles offer a path forward but most rely on solid-state materials with limited temperature lift, low performance, and poor fluidity, which hinder scalability. We introduce a liquid-phase dipolarcaloric refrigeration cycle utilizing endothermic dissolution of nitrate-based salts regenerated via electrodialysis. This cycle achieves large adiabatic temperature changes and high coefficients of performance. We identify effective salt-water pairs and validate the cycle experimentally, supported by thermodynamic modeling. Among these, ammonium nitrate is suited for refrigeration, while potassium nitrate is appropriate for air conditioning. The system uses abundant, low-cost materials, and its fluidic nature ensures efficient heat transfer and scalability. This work establishes dipolarcaloric cooling as a viable alternative for environmentally responsible refrigeration.
GPT-4o mini: Non-social science research article
Nonlinear wave dynamics on a chip
Matthew T. Reeves, Walter W. Wasserman, Raymond A. Harrison, Igor Marinković, Nicole Luu, Andreas Sawadsky, Yasmine L. Sfendla, Glen I. Harris, Warwick P. Bowen, Christopher G. Baker
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Shallow-water waves are a notable example of nonlinear hydrodynamics, giving rise to phenomena such as tsunamis and undular waves. These dynamics are typically studied in hundreds-of-meters-long wave flumes. In this work, we demonstrate a chip-scale wave flume, which exploits nanometer-thick superfluid helium films and optomechanical interactions to achieve nonlinearities surpassing those of extreme terrestrial flows. Measurements reveal wave steepening, shock fronts, and solitary wave fission—nonlinear behaviors predicted in superfluid helium but never directly observed. Our approach enables lithography-defined wave flume geometries, optomechanical control of hydrodynamic properties, and orders-of-magnitude faster measurements than terrestrial flumes. This approach combining quantum fluids and nanophotonics provides a platform to explore complex wave dynamics at the microscale.
GPT-4o mini: Non-social science research article
Nematode telomerase RNA hitchhikes on introns of germline–up-regulated genes
Yutaka Takeda, Masahiro Onoguchi, Fumiya Ito, Io Yamamoto, Shunsuke Sumi, Tatsuyuki Yoshii, Morié Ishida, Eriko Kajikawa, Jingjing Zhang, Osamu Nishimura, Mitsutaka Kadota, Shunsuke Tagami, Takefumi Kondo, Hirohide Saito, Michiaki Hamada, Hiroki Shibuya
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Telomerase is a ribonucleoprotein complex that elongates telomeric DNA, ensuring germline immortality. In this study, we identified the Caenorhabditis elegans telomerase RNA component 1 ( terc-1 ), as the first known telomerase RNA expressed as an intronic long noncoding RNA (lncRNA), embedded in an intron of germline–up-regulated gene nmy-2 . terc-1 undergoes splicing, polyadenylation, and nuclear RNA exosome–dependent maturation, stabilized by H/ACA small nucleolar ribonucleoproteins, thus co-opting the H/ACA small nucleolar RNA (snoRNA) biogenesis machinery. Mutations in terc-1 led to progressive telomere shortening and sterility in successive generations. Artificially transplanting the nmy-2 intron into the introns of germline-expressed genes but not non–germline-expressed genes restored germline immortality, highlighting the importance of genomic context. Our findings suggest that nematode telomerase RNA is a snoRNA-like intronic lncRNA that exploits the introns of germline–up-regulated genes to ensure species survival.
GPT-4o mini: Non-social science research article
Drought intensity and duration interact to magnify losses in primary productivity
Timothy Ohlert, Melinda D. Smith, Scott L. Collins, Alan K. Knapp, Jeffrey S. Dukes, Osvaldo Sala, Kate D. Wilkins, Seth M. Munson, Maggie I. Anderson, Meghan L. Avolio, Anping Chen, Meghan T. Hayden, Martin C. Holdrege, Ingrid J. Slette, Peter Wilfahrt, Claus Beier, Lauchlan H. Fraser, Anke Jentsch, Michael E. Loik, Yiqi Luo, Fernando T. Maestre, Richard P. Phillips, Sally A. Power, Laura Yahdjian, Qiang Yu, Angel Chen, Andrew J. Felton, Laureano A. Gherardi, Nicholas J. Lyon, Hamed Abdoli, Mehdi Abedi, Juan Alberti, Antonio I. Arroyo, Heidi Asbjornsen, Harald Auge, Seton Bachle, Michael Bahn, David C. Bartholomew, Amgaa Batbaatar, Taryn L. Bauerle, Karen H. Beard, Kai Behn, Ilka Beil, Lucio Biancari, Irmgard Blindow, Viviana Florencia Bondaruk, Elizabeth T. Borer, Edward W. Bork, Carlos Martin Bruschetti, Kerry M. Byrne, James F. Cahill, Dianela A. Calvo, Michele Carbognani, Cameron N. Carlyle, Karen Castillioni, Miguel Castillo-Garcia, Manjunatha H. Chandregowda, Scott X. Chang, Jeff Chieppa, Amber C. Churchill, Marcus Vinicius Cianciaruso, Amanda L Cordeiro, Sara A. O. Cousins, Daniela F. Cusack, Sven Dahlke, Pedro Daleo, Lee H. Dietterich, Maren Dubbert, Nico Eisenhauer, T’ai G. W. Forte, Flavia A. Funk, Darcy Galiano, Aaron C. Greenville, Liebao Han, Siri VatsĂž Haugum, Yann Hautier, Andy Hector, Hugh A. L. Henry, Daniela Hoss, Forest Isbell, Samuel E. Jordan, Yuguang Ke, Eugene F. Kelly, Sally E. Koerner, Juergen Kreyling, György Kröel-Dulay, Alicia I. Kröpfl, Angelika KĂŒbert, Andrew Kulmatiski, Eric G. Lamb, Klaus Steenberg Larsen, Steven Lee, Smriti Pehim Limbu, Anja LinstĂ€dter, Shirong Liu, Grisel Longo, Alejandro Loydi, Junwei Luan, F. Curtis Lubbe, Andrey V. Malyshev, Cameron D. McIntire, Daniel B. Metcalfe, Malesela Vincent Mokoka, Akira S. Mori, Edwin Mudongo, Gregory S. Newman, Uffe N. Nielsen, RaĂșl Ochoa-Hueso, Rory C. O’Connor, RomĂ  Ogaya, GastĂłn R. Oñatibia, IldikĂł OrbĂĄn, Brooke B. Osborne, Rafael Otfinowski, Meelis PĂ€rtel, JesĂșs Pascual, Josep Peñuelas, Pablo L. Peri, David S. Pescador, Guadalupe Peter, Alessandro Petraglia, Catherine Picon-Cochard, ValĂ©rio D. Pillar, Juan M. Piñeiro-Guerra, Laura Weber Ploughe, Robert M. Plowes, Cristy Portales-Reyes, Suzanne M. Prober, Yolanda Pueyo, Golsa Rahmati, Sasha C. Reed, Dana AylĂ©n RodrĂ­guez, William E. Rogers, Christiane Roscher, David W. Rowley, Ana M. SĂĄnchez, BrĂĄulio A. Santos, Michael P. Schellenberg, Michael Scherer-Lorenzen, Eric W. Seabloom, Ruonan Shen, Baoku Shi, Lara Souza, Andreas Stampfli, Rachel J. Standish, Marcelo Sternberg, Wei Sun, Marie SĂŒnnemann, Michelle Tedder, Tyson J. Terry, PĂ„l Thorvaldsen, Katja Tielbörger, Maud Tissink, Matthew A. Vadeboncoeur, Alejandro Valdecantos, Liesbeth van den Brink, Vigdis Vandvik, Liv Guri Velle, Svenja Wanke, Glenda M. Wardle, Cunzheng Wei, Christiane Werner, Georg Wiehl, Jennifer L. Williams, Amelia A. Wolf, Honghui Wu, Chong Xu, Xuechen Yang, Yadong Yang, Jenifer L. Yost, Alyssa L. Young, Ping Yue, Juan M. Zeberio, Michaela Zeiter, Haiyang Zhang, Juntao Zhu, Xiaoan Zuo
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As droughts become longer and more intense, impacts on terrestrial primary productivity are expected to increase progressively. Yet, some ecosystems appear to acclimate to multiyear drought, with constant or diminishing reductions in productivity as drought duration increases. We quantified the combined effects of drought duration and intensity on aboveground productivity in 74 grasslands and shrublands distributed globally. Ecosystem acclimation with multiyear drought was observed overall, except when droughts were extreme (i.e., ≀1-in-100-year likelihood of occurrence). Productivity losses after four consecutive years of extreme drought increased by ~2.5-fold compared with those of the first year. These results portend a foundational shift in ecosystem behavior if drought duration and intensity increase, from maintenance of reduced functioning over time to progressive and profound losses of productivity when droughts are extreme.
GPT-4o mini: Non-social science research article
Architectural immunity: Ants alter their nest networks to prevent epidemics
Luke Leckie, Mischa Sinha Andon, Katherine Bruce, Nathalie Stroeymeyt
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In animal groups, spatial structure shapes social interaction patterns, thereby influencing the transmission of infectious diseases. Active modifications to the spatial environment could therefore be a potent tool to mitigate epidemic risk. We tested whether Lasius niger ants modify their nest architecture in response to pathogens by introducing control- or pathogen-treated individuals into nest-digging groups and monitoring three-dimensional nest morphogenesis. Pathogen exposure led to architectural changes, including faster nest growth, increased interentrance distance, transmission-inhibitory changes in nest network topology, and reduced chamber centrality. Simulations confirmed that these changes reduced transmission and highlighted a synergy between architectural and behavioral responses to disease. These results provide evidence for architectural immunity in a social animal and offer insights into how spatial organization can be leveraged to decrease epidemic susceptibility.
GPT-4o mini: Non-social science research article
Head-direction cells as a neural compass in bats navigating outdoors on a remote oceanic island
Shaked Palgi, Saikat Ray, Shir R. Maimon, Yuval Waserman, Liron Ben-Ari, Tamir Eliav, Avishag Tuval, Chen Cohen, Julius D. Keyyu, Abdalla I. Ali, Henrik Mouritsen, Liora Las, Nachum Ulanovsky
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Animals and humans rely on their navigation skills to survive. However, spatial neurons in the brain’s “navigation circuit” had not previously been studied under real-world conditions. We conducted an electrophysiological study of spatial neurons in the wild: We recorded head-direction cells from the presubiculum of bats flying unconstrained and navigating outdoors on a remote oceanic island. These neurons represented the bats’ orientation stably across the island’s entire geographical scale and irrespective of the dynamics of the Moon and the Milky Way. The directional tuning stabilized over several nights from the first exploration of the island. These results imply that head-direction cells can serve as a learned, reliable neural compass for real-world navigation—highlighting the power of taking neuroscience out into the wild.
GPT-4o mini: Non-social science research article
Glucosylation of endogenous haustorium-inducing factors underpins kin avoidance in parasitic plants
Lei Xiang, Songkui Cui, Simon B. Saucet, Moe Takahashi, Shoko Inaba, Bing Xie, Mario Schilder, Shota Shimada, Mengqi Cui, Yanmei Li, Mutsumi Watanabe, Yuki Tobimatsu, Harro J. Bouwmeester, Takayuki Tohge, Ken Shirasu, Satoko Yoshida
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Parasitic plants rarely attack themselves, suggesting the existence of a kin-avoidance mechanism. In the root parasitic plant Phtheirospermum japonicum , prehaustorium formation is triggered by host-secreted haustorium-inducing factors (HIFs), but it is unresponsive to its own exudates. Here we report the identification of the spontaneous prehaustorium 1 ( spoh1 ) mutant, which forms prehaustoria without external host signals. spoh1 harbors a point mutation in the gene encoding uridine diphosphate–glucosyltransferase UGT72B1, an enzyme that glucosylates and thereby inactivates phenolic HIFs. PjUGT72B1 has a different substrate specificity than its ortholog of the host Arabidopsis . Introduction of PjUGT72B1 into Arabidopsis reduced prehaustorium induction activity, indicating that UGT72B1 regulates haustorium induction by hosts. Our findings suggest that Orobanchaceae hemiparasitic plants have evolved kin-avoidance mechanisms through the glucosylation of endogenous HIFs.
GPT-4o mini: Non-social science research article
Ancient origin of an urban underground mosquito
Yuki Haba, character(0), Petra Korlević, Erica McAlister, Mara K. N. Lawniczak, Molly Schumer, Noah H. Rose, Carolyn S. McBride, Matthew L. Aardema, Maria O. Afonso, Natasha M. Agramonte, John Albright, Ana Margarida Alho, Antonio P. G. Almeida, Haoues Alout, Bulent Alten, Mine Altinli, Raouf Amara Korba, Stefanos S. Andreadis, Vincent Anghel, Soukaina Arich, Arielle Arsenault-Benoit, CĂ©lestine Atyame, Fabien Aubry, Frank W. Avila, Diego Ayala, Rasha S. Azrag, Lilit Babayan, Allon Bear, Norbert Becker, Anna G. Bega, Sophia Bejarano, Ira Ben-Avi, Joshua B. Benoit, SaĂŻd C. Boubidi, William E. Bradshaw, Daniel Bravo-Barriga, RubĂ©n Bueno-MarĂ­, NataĆĄa BuĆĄić, Viktoria ČabanovĂĄ, Brittany Cabeje, Beniamino Caputo, Maria V. Cardo, Simon Carpenter, Elena Carreton, Mouhamadou S. ChouaĂŻbou, Michelle Christian, Maureen Coetzee, William R. Conner, Anton Cornel, C. Lorna Culverwell, Aleksandra I. Cupina, Katrien De Wolf, Isra Deblauwe, Brittany Deegan, Sarah Delacour-Estrella, Alessandra della Torre, Debora Diaz, Serena E. Dool, Vitor L. dos Anjos, Sisay Dugassa, Babak Ebrahimi, Samar Y. M. Eisa, Nohal Elissa, Sahar A. B. Fallatah, Ary Faraji, Marina V. Fedorova, Emily Ferrill, Dina M. Fonseca, Kimberly A. Foss, Cipriano Foxi, Caio M. França, Stephen R. Fricker, Megan L. Fritz, Eva Frontera, Hans-Peter Fuehrer, Kyoko Futami, Enas H. S. Ghallab, Romain Girod, Mikhail I. Gordeev, David Greer, Martin Gschwind, Milehna M. Guarido, Teoh Guat Ney, Filiz Gunay, Eran Haklay, Alwia A. E. Hamad, Jun Hang, Christopher M. Hardy, Jacob W. Hartle, Jenny C. Hesson, Yukiko Higa, Christina M. Holzapfel, Ann-Christin Honnen, Angela M. Ionica, Laura Jones, PĂ«rparim Kadriaj, Hany A. Kamal, Colince Kamdem, Dmitry A. Karagodin, Shinji Kasai, Mihaela Kavran, Emad I. M. Khater, Frederik Kiene, Heung-Chul Kim, Ilias Kioulos, Annette Klein, Marko Klemenčić, Ana Klobučar, Erin Knutson, Constantianus J. M. Koenraadt, Linda Kothera, Pauline KreienbĂŒhl, Pierrick LabbĂ©, Itay Lachmi, Louis Lambrechts, Nediljko Landeka, Christopher H. Lee, Bryan D. Lessard, Ignacio Leycegui, Jan O. Lundström, Yoav Lustigman, Caitlin MacIntyre, Andrew J. Mackay, Krisztian Magori, Carla Maia, Colin A. Malcolm, Ralph-Joncyn O. Marquez, Dino Martins, Reem A. Masri, Gillian McDivitt, Rebekah J. McMinn, Johana Medina, Karen S. Mellor, Jason Mendoza, Enrih Merdić, Stacey Mesler, Camille Mestre, Homer Miranda, Martina MiterpĂĄkovĂĄ, Fabrizio Montarsi, Anton V. Moskaev, Tong Mu, Tim W. R. Möhlmann, Alice Namias, Ivy Ng’iru, Marc F. NganguĂ©, Maria T. Novo, Laor Orshan, JosĂ© A. Oteo, Yasushi Otsuka, Rossella Panarese, Claudia Paredes-Esquivel, Lusine Paronyan, Steven T. Peper, DuĆĄan V. Petrić, Kervin Pilapil, Cristina Pou-Barreto, Sebastien J. Puechmaille, Ute Radespiel, Nil Rahola, Vivek K. Raman, Hamadouche Redouane, Michael H. Reiskind, Nadja M. Reissen, Benjamin L. Rice, Vincent Robert, Ignacio Ruiz-Arrondo, Ryan Salamat, Amy Salamone, M’hammed Sarih, Giuseppe Satta, Kyoko Sawabe, Francis Schaffner, Karen E. Schultz, Elena V. Shaikevich, Igor V. Sharakhov, Maria V. Sharakhova, Nader Shatara, Anuarbek K. Sibataev, Mathieu Sicard, Evan Smith, Ryan C. Smith, Nathalie Smitz, Nicolas Soriano, Christos G. Spanoudis, Christopher M. Stone, Liora Studentsky, Tatiana Sulesco, Luciano M. Tantely, La K. Thao, Noor Tietze, Ryan E. Tokarz, Kun-Hsien Tsai, Yoshio Tsuda, NataĆĄa Turić, Melissa R. Uhran, Isik Unlu, Wim Van Bortel, Haykuhi Vardanyan, Laura Vavassori, Enkelejda Velo, Marietjie Venter, Goran Vignjević, Chantal B. F. Vogels, Tatsiana Volkava, John Vontas, Heather M. Ward, Nazni Wasi Ahmad, MylĂšne Weill, Jennifer D. West, Sarah S. Wheeler, Gregory S. White, Nadja C. Wipf, Tai-Ping Wu, Kai-Di Yu, Elke Zimmermann, Carina Zittra
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Understanding how life is adapting to urban environments represents an important challenge in evolutionary biology. In this work, we investigate a widely cited example of urban adaptation, Culex pipiens form molestus , also known as the London Underground mosquito. Population genomic analysis of ~350 contemporary and historical samples counters the popular hypothesis that molestus originated belowground in London <200 years ago. Instead, we show that molestus first adapted to human environments aboveground in the Mediterranean or Middle East over the course of more than 1000 years, possibly in association with ancient agricultural civilizations of the Middle East. Our results highlight the role of early human society in priming taxa for contemporary urban evolution. They also provide insight into whether and how molestus contributes to West Nile virus transmission in modern cities.
GPT-4o mini: Non-social science research article
Robust epitaxy of single-crystal transition-metal dichalcogenides on lanthanum-passivated sapphire
Xilu Zou, Yuanyuan Zhao, Dongxu Fan, Shengqiang Wu, Yushu Wang, Caiqi Zou, Yuliang Bian, Lei Liu, Lang Wu, Zhoushuo Han, Wenjie Sun, Yuefeng Nie, Junfeng Gao, Shitong Zhu, Yi Shi, Taotao Li, Feng Ding, Xinran Wang
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Two-dimensional (2D) transition-metal dichalcogenide (TMDC) semiconductors are promising materials for beyond-silicon electronics, but the growth of single-crystalline TMDCs has been limited to small wafer sizes in laboratory settings. We report the epitaxy of 150-millimeter single-crystalline TMDC wafers on lanthanum-passivated c -plane sapphire. The single atomic layer of lanthanum reduces the surface symmetry and increases the energy difference between antiparallel domains by as much as 200 times, leading to unidirectional domain alignment. We grew single-crystalline molybdenum disulfide (MoS 2 ), molybdenum diselenide (MoSe 2 ), tungsten disulfide (WS 2 ), and tungsten diselenide (WSe 2 ) by means of both chemical vapor deposition (CVD) and metal-organic CVD processes. Wafer-scale spectroscopies and device measurements demonstrate the exceptional quality and uniformity of 150-millimeter TMDCs, with average mobility of 110 and 131 square centimeters per volt per second for MoS 2 and WSe 2 , respectively, at room temperature.
GPT-4o mini: Non-social science research article
A view of Horizon Europe’s future
Lidia Borrell-DamiĂĄn
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The European Union (EU) has the world’s largest funding program exclusively for research and innovation (R&I)—Horizon Europe—which is now preparing its 10th edition for 2028–2034. The good news is that the EU aims to raise Horizon Europe’s budget by 83% and continue the trend of supporting all types of institutions and partnerships, including universities, research institutes, small- and medium-sized enterprises, nonprofit organizations, and a widening circle of international collaborations.
GPT-4o mini: Non-social science research article
Unsaturated fat alters clock phosphorylation to align rhythms to the season in mice
Daniel C. Levine, Rasmus H. Reeh, Thomas McMahon, Thomas Mandrup-Poulsen, Ying-Hui Fu, Louis J. Ptáček
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The circadian clock maintains synchrony between biological processes and light/dark cycles by integrating environmental cues. How the clock adapts to seasonal variations in the environment is incompletely understood. We found that a high-fat diet increased phosphorylation of the clock protein PERIOD2 (PER2) on serine 662 (S662), which was necessary and sufficient for regulating phase shifting of daily locomotor activity to entrain to seasonal light cycles. PER2-S662 phosphorylation correlated with genome-wide expression pathways that regulate polyunsaturated fatty acid (PUFA) conversion into oxylipins in the hypothalamus. Partial hydrogenation of dietary PUFAs increased hypothalamic PER2-S662 phosphorylation and entrainment to a summer photoperiod in control mice, but not in mice for which PER2-S662 could not be phosphorylated. PER2-S662 phosphorylation is influenced by, and alters the regulation of, unsaturated fat to control circadian phase shifting across the seasons.
GPT-4o mini: Non-social science research article
Active learning framework leveraging transcriptomics identifies modulators of disease phenotypes
Benjamin DeMeo, Charlotte Nesbitt, Samuel A. Miller, Daniel B. Burkhardt, Inna Lipchina, Doris Fu, Peter Holderreith, David Kim, Sergey Kolchenko, Artur Szalata, Ishan Gupta, Christine Kerr, Thomas Pfefer, Raziel Rojas-Rodriguez, Sunil Kuppassani, Laurens Kruidenier, Parul B. Doshi, Mahdi Zamanighomi, James J. Collins, Alex K. Shalek, Fabian J. Theis, Mauricio Cortes
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Phenotypic drug screening remains constrained by the vastness of chemical space and technical challenges scaling experimental workflows. To overcome these barriers, computational methods have been developed to prioritize compounds, but they rely on either single-task models lacking generalizability or heuristic-based genomic proxies that resist optimization. We designed an active deep-learning framework that leverages omics to enable scalable, optimizable identification of compounds that induce complex phenotypes. Our generalizable algorithm outperformed state-of-the-art models on classical recall, translating to a 13-17x increase in phenotypic hit-rate across two hematological discovery campaigns. Combining this algorithm with a lab-in-the-loop signature refinement step, we achieved an additional two-fold increase in hit-rate and molecular insights. In sum, our framework enables efficient phenotypic hit identification campaigns, with broad potential to accelerate drug discovery.
GPT-4o mini: Non-social science research article
Late-surviving New Mexican dinosaurs illuminate high end-Cretaceous diversity and provinciality
Andrew G. Flynn, Stephen L. Brusatte, Alfio Alessandro Chiarenza, Jorge GarcĂ­a-GirĂłn, Adam J. Davis, C. Will Fenley, Caitlin E. Leslie, Ross Secord, Sarah Shelley, Anne Weil, Matthew T. Heizler, Thomas E. Williamson, Daniel J. Peppe
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It has long been debated whether non-avian dinosaurs went extinct abruptly or gradually at the end-Cretaceous (66 million years ago), because their fossil record at this time is mostly limited to northern North America. We constrain a dinosaur-rich unit to the south, the Naashoibito Member in New Mexico, to the very latest Cretaceous (~66.4 to 66.0 million years), preserving some of the last-known non-avian dinosaurs. Ecological modeling shows that North American terrestrial vertebrates maintained high diversity and endemism in the latest Cretaceous and early Paleogene, with bioprovinces shaped by temperature and geography. This counters the notion of a low-diversity cross-continental fauna and suggests that dinosaurs were diverse and partitioned into regionally distinct assemblages during the final few hundred thousand years before the end-Cretaceous asteroid impact.
GPT-4o mini: Non-social science research article
Heat-driven functional extinction of Caribbean Acropora corals from Florida’s Coral Reef
Derek P. Manzello, Ross Cunning, Richard F. Karp, Andrew C. Baker, Erich Bartels, Ryan Bonhag, Alexandra Borreil, Amanda Bourque, Kristen T. Brown, Andrew W. Bruckner, Bryce Corbett, Martine D’Alessandro, Craig Dahlgren, Jenna Dilworth, Erick Geiger, David S. Gilliam, Maya Gomez, Grace Hanson, Cailin Harrell, Dalton Hesley, Lindsay K. Huebner, Carly D. Kenkel, Hanna R. Koch, Joe Kuehl, Ilsa B. Kuffner, Mark C. Ladd, Sophia Lee, Kathryn C. Lesneski, Amanda Lewan, Diego Lirman, Gang Liu, Shayle B. Matsuda, Phanor H. Montoya-Maya, Jennifer Moore, Erinn M. Muller, Ken Nedimyer, John Everett Parkinson, Rob Ruzicka, Jason Spadaro, Blake L. Spady, Jennifer Stein, Joseph D. Unsworth, Cory Walter, Alexandra D. E. Wen, Dana E. Williams, Sara D. Williams, Olivia M. Williamson
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In 2023, a record-setting marine heat wave triggered the ninth mass coral bleaching event on Florida’s Coral Reef (FCR). We examined spatial patterns of heat exposure along the ~560-kilometer length of FCR and the mortality of two ecologically important, critically endangered reef-building corals. Sea surface temperatures were ≄31°C for an average of 40.7 days, leading to heat exposures 2.2- to fourfold higher than all prior years on record. In the Florida Keys and Dry Tortugas, 97.8 to 100% of the Acropora palmata and Acropora cervicornis colonies died. Mortality was lower offshore southeast Florida (37.9%), reflecting cooler temperatures in this region. Since the late 1970s, multiple stressors had already reduced the ecological relevance of Acropora in Florida, but the 2023 heat wave marks their functional extinction from FCR.
GPT-4o mini: Non-social science research article
The total synthesis of (−)-spiroaspertrione A: A divinylcyclopropane rearrangement approach
Wenbo Huang, Lu Pan, Heng Zhao, Fabian Schneider, Tanja Gaich
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The rise of multidrug-resistant pathogens poses a major threat to global health, with methicillin-resistant Staphylococcus aureus (MRSA) among the most challenging. One promising approach to overcoming resistance is using small molecules that resensitize MRSA to existing drugs. Here, we report the enantioselective total synthesis of one such promising candidate, (−)-spiroaspertrione A, a complex meroterpenoid of the andiconin family. This natural product has long eluded synthesis because of its densely functionalized polycyclic backbone. Our route features a stereoselective Diels-Alder cycloaddition, followed by a key divinylcyclopropane rearrangement forming the spirobicyclo[3.2.2]nonane core, which proved to be reversible and was further investigated by density functional theory calculations. Strategic late-stage functionalization of the compact cage architecture enabled access to the natural product and provided evidence for a plausible biosynthetic relationship with (−)-aspermerodione.
GPT-4o mini: Non-social science research article
Mesoscale volumetric fluorescence imaging at nanoscale resolution by photochemical sectioning
Wei Wang, Xiongtao Ruan, Gaoxiang Liu, Daniel E. Milkie, Wenping Li, Eric Betzig, Srigokul Upadhyayula, Ruixuan Gao
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Optical nanoscopy of intact biological specimens has been transformed by recent advancements in hydrogel-based tissue clearing and expansion, enabling the imaging of cellular and subcellular structures with molecular contrast. However, existing high-resolution fluorescence microscopes are physically limited by objective-to-specimen distance, which prevents the study of whole-mount specimens without physical sectioning. To address this challenge, we developed a photochemical strategy for spatially precise sectioning of specimens. By combining serial photochemical sectioning with lattice light-sheet imaging and petabyte-scale computation, we imaged and reconstructed axons and myelin sheaths across entire mouse olfactory bulbs at nanoscale resolution. An olfactory bulb–wide analysis of myelinated and unmyelinated axons revealed distinctive patterns of axon degeneration and de-/dysmyelination in the neurodegenerative brain, highlighting the potential for peta- to exabyte-scale super-resolution studies using this approach.
Science abstract < 200 char.: Not a research article
Architects of molecular cages win Chemistry Nobel
Daniel Clery, Catherine Offord
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Spongelike materials called metal-organic frameworks can separate and store gases
Science abstract < 200 char.: Not a research article
Dinosaur diversity before the asteroid
Lindsay Zanno
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Evidence for low dinosaur diversity ahead of extinction event grows dimmer
Science abstract < 200 char.: Not a research article
Kiss, shrink, run
Katharina Lichter
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A unified mechanism directs synaptic vesicle release
Science abstract < 200 char.: Not a research article
Homogenizing two-dimensional crystals
Dongyoung Kim, Kibum Kang
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An atom-thick layer of lanthanum orients semiconductor crystals in one direction
Science abstract < 200 char.: Not a research article
Knowledge for two When Everyone Knows That Everyone Knows
 Steven Pinker Scribner, 2025. 384 pp.
Jeremy Goodman, Chaz Firestone
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A psychologist explores common knowledge and coordination
Science abstract < 200 char.: Not a research article
Making hydrogen production durable
Yu Seung Kim
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An interphase shields polymer electrolytes from electrochemical oxidation in an alkaline environment
Science abstract < 200 char.: Not a research article
Cybersecurity mandate alarms University of California faculty
Celina Zhao
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Professors say required security software undermines academic freedom
Science abstract < 200 char.: Not a research article
Neural compass in the sky
Yue-Qing Zhou, James J. Knierim
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Head-direction neurons maintain stable directional signals during large-scale navigation in the wild
Science abstract < 200 char.: Not a research article
Stemming green tides in the Yellow Sea
Luhua Yang, Ruiyong Zhang, Li Zhuo, Bin-Bin Xie, Jianqun Lin, Shun Li
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Science abstract < 200 char.: Not a research article
DNA from rum-soaked fishes chronicles century of change
Erik Stokstad
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Museum specimens reveal loss of genetic diversity in marine fishes of the Philippines
Science abstract < 200 char.: Not a research article
Vaccinations for all Fair Doses Seth Berkley University of California Press, 2025. 408 pp.
Arthur Caplan
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An epidemiologist advocates for vaccine equity
Science abstract < 200 char.: Not a research article
In Other Journals
Stella M. Hurtley, Priscilla N. Kelly, Caroline Ash, Brad Wible, Di Jiang, Jesse Smith, Michael A. Funk
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
Quantum trions in equilibrium
Tianyi Ouyang, Su-Fei Shi
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Quantum fluid of trions is demonstrated in two-dimensional material systems
Science abstract < 200 char.: Not a research article
US should expand EIA requirements
Sean P. Powers, John Lehrter
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Science abstract < 200 char.: Not a research article
Trojan gold: New US “standard” is another veiled attack on science
Stephan Lewandowsky
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Science abstract < 200 char.: Not a research article
Australian algal blooms require national action
Dominic McAfee, Brad Martin
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Science abstract < 200 char.: Not a research article
Working on Juneteenth
Jania Williams
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Science abstract < 200 char.: Not a research article
An immigrant’s dilemma
Mariana Gelambi
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Science abstract < 200 char.: Not a research article
Mobilizing capital and technology for a clean aviation industry
David G. Victor, Thomas Conlon, Philipp Goedeking, Andreas W. SchÀfer
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Research managers and investors need better approaches to weigh risks and potential benefits of scalable, transformational technologies
Science abstract < 200 char.: Not a research article
New frontiers in research on industrial decarbonization
Kenneth T. Gillingham, Lint Barrage, Sarah Armitage, Dallas Burtraw, Jonathan Colmer, Laure de Preux, Jonathan Hawkins-Pierot, Charles Holt, Valerie J. Karplus, Åsa Löfgren, Ralf Martin, Nathan Miller, Mirabelle MuĂ»ls, Matthew Osborne, Edson Severnini, William Shobe, Gretchen Sileo, Vladimir Smirnyagin, Thomas Stoerk, Aleh Tsyvinski, Katherine Wagner, Ulrich J. Wagner, Xi Wu
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Research is needed to quantify impacts and understand interactions with the broader economy
Science abstract < 200 char.: Not a research article
Chaos and confusion as U.S. shutdown drags on
character(0)
Full text
Mass layoffs, and subsequent reversals, have added to research spending woes
Science abstract < 200 char.: Not a research article
Halt China’s waste incinerator expansion
Xinhui Feng, Yan Li, Siyu Huang, Feng Li
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Science abstract < 200 char.: Not a research article
In Other Journals
Sarah LempriĂšre, Caroline Ash, Sumin Jin, Joana OsĂłrio, Bianca Lopez, Yury Suleymanov, Angela Hessler
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
Stranded coral boulders point to a medieval tsunami in the Caribbean
Katherine Kornei
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Study pinpoints likely date for a massive earthquake on the Puerto Rico Trench—and highlights an underappreciated regional hazard
Science abstract < 200 char.: Not a research article
Interstellar visitors: Smoking and nonsmoking
Andy Lawrence
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Science abstract < 200 char.: Not a research article
Correcting the record on race and medicine Why Black People Die Sooner: What Medicine Gets Wrong About Race and How to Fix It Joseph L. Graves Jr Columbia University Press, 2025. 272 pp.
Darrell J. Gaskin
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Social variables often underlie racial differences in health and disease, argues a biologist
Science abstract < 200 char.: Not a research article
Chile’s framework law erodes institutions
IvĂĄn Ojeda-Pereira
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Science abstract < 200 char.: Not a research article
Protect Uruguay’s seas from politics
Omar Defeo, Nelson Rangel-Buitrago
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Science abstract < 200 char.: Not a research article
Lab mice can now have periods like humans
Holly Barker
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Studies of rodents with a menstrual on/off switch could help people with endometriosis and other disorders
Science abstract < 200 char.: Not a research article
Papers based on open health data face bans
Cathleen O’Grady
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PLOS, Frontiers, and others announce policies intended to stem the tide of suspect papers
Science abstract < 200 char.: Not a research article
Cold storage
Kai Kupferschmidt
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On an Arctic archipelago, frozen soil may preserve a hidden history of viruses
Science abstract < 200 char.: Not a research article
In Science Journals
Caroline Ash, Ian S. Osborne, Bianca Lopez, Jelena Stajic, Mark Aldenderfer, Courtney Malo, Jesse Smith, L. Bryan Ray, Di Jiang, Michael A. Funk, Phil Szuromi, Corinne Simonti, Sacha Vignieri, Madeleine Seale, Leslie Ferrarelli, Yury Suleymanov, Claire Olingy
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
Urban pests traveled with ancient humans
Jason Munshi-South, Ann Evankow
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Population genomics reveals the pre-urban origins of a common mosquito
Science abstract < 200 char.: Not a research article
The paradox of kin avoidance in parasitic plants
Steven Runo
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Parasitic plants use glucosylation to avoid kin parasitism
Science abstract < 200 char.: Not a research article
In Science Journals
Caroline Ash, Jake S. Yeston, Sacha Vignieri, Bianca Lopez, Mark Aldenderfer, Leoma Bere, Yevgeniya Nusinovich, Di Jiang, Corinne Simonti, Stella M. Hurtley, Peter Stern, Jesse Smith, Jack Huang, Jelena Stajic, John Foley, Brandon Berry, Craig Cameron
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
A better recipe for generating immune peacemakers
Catherine Offord
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Nobel laureate develops new method of making regulatory T cells that could treat autoimmune conditions
Science abstract < 200 char.: Not a research article
Stormy seas
Warren Cornwall
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Warmer waters in the Bering Sea caused snow crabs to crash. Now, scientists are racing to predict the future of the lucrative fishery
Science abstract < 200 char.: Not a research article
New head of NIH institute has close ties to JD Vance
Jocelyn Kaiser
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Unusual hiring process raises concerns about political favoritism
Science abstract < 200 char.: Not a research article
Did lead poisoning help drive human evolution?
Michael Price
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“Bold” hypothesis suggests tolerance for lead allowed Homo sapiens to outlive Neanderthals
Science abstract < 200 char.: Not a research article
COVID-19 vaccines may boost cancer immunotherapy
Phie Jacobs
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Messenger RNA in the shots could act like a “siren” calling immune cells to destroy tumors
Science abstract < 200 char.: Not a research article
A radically organic worldview turns 100 Science and the Modern World Alfred North Whitehead The MacMillan Company, 1925. 212 pp.
Àlex Gómez-Marín
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A philosopher’s seminal book traced how science shaped the mentality of the modern world
Science abstract < 200 char.: Not a research article
New study fuels debate over lifesaving antibiotic strategy for children in Africa
Gretchen Vogel
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Mass distribution increases risk of antibiotic resistance, but benefits vanish when treatment is restricted to babies

Science Advances

GPT-4o mini: Non-social science research article
CysMP reveals metal ion–specific metalloproteomes and copper-regulated PGK1 activity in glycolysis
Yamei Yuan, Zhiyuan Wang, Chenfang Si, Jianlong Li, Fandong Ren, Yi Yuan, Ziqi Shi, Nana Sun, Xiaonuo Ma, Xingbang Dai, Yunxia Li, Yixiao Zhang, Jianping Liu, Hongbin Wang, Zhengjiang Zhu, Bing Shan, Yaoyang Zhang
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Metal ions are essential in regulating protein functions through interactions with residues such as cysteine, but comprehensive mapping of metal-specific metalloproteomes in mammals remains limited. Here, we introduce CysMP, a cysteine-centered metalloprotein profiling strategy to profile the metalloproteomes of 11 key metal ions. CysMP identified 8895 metal-binding sites across 4150 proteins, enabling quantitative comparisons between different metals and revealing both their binding promiscuity and preferences. Notably, zinc and copper ions exhibit the broadest protein interaction profiles. CysMP uncovers numerous potential metalloproteins. We demonstrate that copper and zinc bind to and inhibit 5â€Č-methylthioadenosine phosphorylase, resulting in the accumulation of 5â€Č-methylthioadenosine. Furthermore, copper binding suppresses phosphoglycerate kinase 1 activity, leading to a down-regulation of glycolysis. Our work not only establishes a valuable resource for a dual-specific metalloproteome database but also paves the way for understanding the molecular insights of metalloprotein functions.
GPT-4o mini: Non-social science research article
Bacterial communities co-develop with respiratory immunity early in life, linking dysbiosis to systemic monocyte signature and wheezing
CĂ©line Pattaroni, Matthew Macowan, Roxanne Chatzis, Giulia Iacono, Bailey Cardwell, Mindy Gore, Adnan Custovic, Michael D. Shields, Ultan F. Power, Jonathan Grigg, Graham Roberts, Peter Ghazal, JĂŒrgen Schwarze, Steve Turner, Andrew Bush, Sejal Saglani, Clare M. Lloyd, Benjamin J. Marsland
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Early microbial colonization influences respiratory disease risk, yet mechanisms remain unclear. In a prospective birth cohort of 256 infants, we profiled bacterial, fungal, and viral communities in the upper airway and assessed local immune gene expression longitudinally and systemic gene expression at 1 year. Bacterial populations, not fungal or viral, correlated most strongly with immune development during the first 3 months, coinciding with composition shifts and immune-related gene expression changes, including interferon and adaptive immunity pathways. In contrast, the mycobiome and resident viruses showed no significant coevolution with host immunity. By 1 year, infants who previously wheezed displayed an upper airway microbiota enriched in Haemophilus influenzae and Moraxella , accompanied by a distinct local and systemic immune gene signature featuring elevated classical monocyte-related genes. These findings reveal a specific link between early-life bacterial dysbiosis, monocyte-related immunity, and wheezing onset, suggesting potential targets for early intervention in respiratory disease.
GPT-4o mini: Non-social science research article
Earth’s core-mantle differentiation shaped by water
Haiyang Luo, Donghao Zheng, Jie Deng
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Earth’s core-mantle segregation set the initial conditions for its subsequent evolution. However, the effect of water on core-mantle element partitioning remains poorly constrained. Using machine learning molecular dynamics simulations trained on quantum mechanical data, we show that increasing water content promotes magnesium partitioning into the metallic core, whereas silicon, iron, and hydrogen increasingly prefer the silicate mantle. On the basis of Earth’s core mass fraction and oxygen fugacity during core formation, a self-consistent hydrous core-mantle differentiation model yields a bulk Earth water content of ~0.23 weight % (equivalently ~10 ocean masses), a bulk Earth magnesium/silicon ratio of 1.16 ± 0.01, and a mantle magnesium/silicon ratio of 1.25 to 1.28. The initial core would contain 3.5 to 4.1 weight % silicon, 2.9 to 3.1 weight % oxygen, 0.11 to 0.14 weight % magnesium, and 0.04 to 0.10 weight % hydrogen, along with sulfur and carbon. We predict that super-Earths can retain large metallic cores even with several weight % water.
GPT-4o mini: Non-social science research article
Structures of rotary ATP synthase from Thermus thermophilus during proton powered ATP synthesis
Atsuki Nakano, Jun-ichi Kishikawa, Nishida Yui, Kyosuke Sugawara, Yuto Kan, Christoph Gerle, Hideki Shigematsu, Kaoru Mitsuoka, Ken Yokoyama
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ATP synthases are rotary molecular machines that use the proton motive force to rotate the central rotor complex relative to the surrounding stator apparatus, thereby coupling the ATP synthesis. We reconstituted the V/A-ATPase into liposomes and performed structural analysis using cryo-EM under conditions where the proton motive force was applied in the presence of ADP and Pi. ATP molecules were bound at two of the three catalytic sites of V/A-ATPase, confirming that the structure represents a state adopted during ATP synthesis. In this structure, the catalytic site closes upon binding of ADP and Pi through an induced fit mechanism. Multiple structures were obtained where the membrane-embedded rotor ring was in a different position relative to the stator. By comparing these structures, we found that torsion occurs in both the central rotor and the peripheral stator during 31° rotation of rotor ring. These structural snapshots of V/A-ATPase provide crucial insights into the mechanism of rotary catalysis of ATP synthesis.
GPT-4o mini: Non-social science research article
Genomic parallelism defines repeated evolution of an inducible offense
Nicholas A. Levis, Erik J. Ragsdale
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A common developmental response to resource competition is an inducible offense, the facultative predation of competitors. At its extreme, this response involves the development of alternative phenotypic morphs, or polyphenism. However, how polyphenism evolves to meet ecological challenges, such as competitor species, is unknown. Using replicated experimental evolution, during which starved nematodes could consume heterospecific competitors, we investigated whether induction of a predatory morph could evolve and how generalizable this change’s genetic basis is. Fifty generations of evolution across multiple populations resulted in parallel changes in higher morph-induction and parallel genomic responses, including repeated selection for a specific transcription-factor binding-site variant. In tandem, we artificially selected directly for tooth morphology and drove the predatory morph near to fixation. That trait-specific selection promoted greater changes in predatory morph induction than experimental evolution indicates that polyphenism evolution is balanced by selection for whole-organism performance. Our results thus describe the predictability by which a resource polyphenism evolves amid scarce resources.
GPT-4o mini: Non-social science research article
Extrachromosomal circular DNA promotes inflammation and hepatocellular carcinoma development
Lap Kwan Chan, Juanjuan Shan, Elias Rodriguez-Fos, Marc Eamonn Healy, Peter Leary, Rossella Parrotta, Nina Desboeufs, Gabriel Semere, Nadine Wittstruck, Anton G. Henssen, Achim Weber
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Two decades after the initial report on increased micronuclei in human chronic liver disease (CLD) and hepatocellular carcinoma (HCC), their role in HCC development is still poorly understood. Here, we show that micronuclei in hepatocytes trigger a hepatic immune response and promote HCC development via an increased level of extrachromosomal circular DNA (eccDNA). Livers of a CLD model ( Mcl1 Δhep mice) show increased micronuclei and eccDNA levels. Circular sequencing confirms higher eccDNA levels in micronuclei compared to primary nuclei. The nuclei-segregated DNA fiber (NuSeF) assay we developed demonstrates that micronuclei are more susceptible to replication stress, exhibiting increased replication fork slowing. Comparing different murine liver disease models reveals that high eccDNA correlates with an increased tumor incidence. eccDNA is a strong immunostimulant and promotes a cross-talk between hepatocytes and immune cells through the cGAS-STING pathway. Deletion of Sting1 in Mcl1 Δhep mice reduces immune cell chemotaxis and tumor incidence. Our findings suggest that eccDNA from micronuclei mediates inflammation-driven liver carcinogenesis in CLD.
GPT-4o mini: Non-social science research article
Enhanced FOS expression improves tumor clearance and resists exhaustion in NR4A3-deficient CAR T cells under chronic antigen exposure
Peidi Yin, Jigui Yang, Yiyang Jiang, Linhong Han, Tianchen Xiong, Haofei Liu, Yiliang Fang, Wenchen Ruan, Jiayang Wu, Longjuan Chen, Leyong Tan, Yonglin Zuo, Xin Wu, Fangyuan Mao, Rui Huang, Xindong Liu, Xiu-Wu Bian
Full text
The dysfunction of chimeric antigen receptor (CAR) T cells in the tumor microenvironment is a major obstacle to their therapeutic efficacy against solid tumors. Through single-cell RNA sequencing analysis of tumor-infiltrating T cells from patients with glioma, NR4A family genes were identified as closely associated with T cell exhaustion and were coexpressed with dysfunctional genes HAVCR2 and TIGIT . Notably, CAR T cells with NR4A3 knockdown exhibited enhanced cytotoxic activity against tumors, leading to improved tumor clearance and prolonged survival in vivo. However, the promoted antiexhausted phenotype diminished with prolonged tumor burden. This decline in T cell function correlates with the compensatory down-regulation of FOS induced by chronic antigen exposure following NR4A3 knockdown. Overexpressing FOS alongside NR4A3 knockdown robustly boosted the antitumor responses of CAR T cells by skewing their phenotypes and transcriptional profiles away from exhaustion and toward increased effector function. These findings offer a promising strategy for the clinical modification of CAR T cell therapy.
GPT-4o mini: Non-social science research article
Palmitoyltransferase ZDHHC19 regulates histone-to-protamine exchange during spermiogenesis in mice
Jiaoyang Li, Zhizhou Xia, Bo Jiao, Zhitong Li, Donghe Li, Pengfei Xu, Yi Huang, Jiawei Nie, Yuqing Dan, Xu Huang, Lei Yan, Rui Zhang, Wei Huang, Xinru Wang, Shiyu Ji, Mofang Liu, Ping Liu, Ruibao Ren
Full text
Spermiogenesis, the final phrase of spermatogenesis, involves replacing histones by protamines, a process known as histone-to-protamine exchange, which is crucial for chromatin condensation. While this exchange is essential, the precise mechanisms remain incompletely understood. In this study, we discovered that the palmitoyltransferase ZDHHC19 functions as a key regulator of mouse spermiogenesis. Loss of Zdhhc19 leads to male infertility and abnormal sperm morphology. Zdhhc19 -deficient sperm exhibit impaired histone-to-protamine exchange, leading to retention of histones and misdistribution of protamines. Similarly, the palmitoyltransferase catalytic site mutant Zdhhc19 C142S knock-in mice show reduced fertility, sperm abnormalities, and histone retention. Mechanistically, ZDHHC19 mediates histone H3 palmitoylation at cysteine-110, weakening H3-H4 interactions and increasing chromatin accessibility. Palmitoylation of H3 facilitates histone-to-protamine exchange. This study highlights the essential role of ZDHHC19’s palmitoyl-transferase activity in histone-to-protamine exchange during spermiogenesis and underscores the broader role of histone palmitoylation in chromatin remodeling.
GPT-4o mini: Non-social science research article
A multistep platform identifies spleen-tropic lipid nanoparticles for in vivo T cell–targeted delivery of gene-editing proteins
Xiaoya Lu, Yining Zhu, Christine Wei, Leonardo Cheng, Kailei D. Goodier, Jiayuan Kong, Xiangyu Gao, Di Yu, Xiang Liu, Yuanmuhuang Long, Jinghan Lin, Jingyao Ma, Yunhe Su, Hai-Quan Mao
Full text
Lipid nanoparticles (LNPs) are a promising nonviral delivery system for gene-editing proteins, but optimal formulations remain underexplored. Unlike messenger RNA–based approaches, ribonucleoprotein delivery enables immediate genome editing without relying on endogenous translation. However, intracellular delivery remains a major challenge due to protein size, charge variability, and susceptibility to denaturation and degradation. Here, we present a multistep screening platform to optimize LNP formulations for gene-editing protein delivery, focusing on in vivo T cell targeting. Through in vitro screening of a composition library, we identified top-performing candidates. In vivo screening in Ai9 mice revealed a spleen-tropic LNP formulation that preferentially targets T cells, enabling efficient gene editing in vivo. Using this LNP formulation, we achieved targeted knockout of CCR5 and PD-1 in splenic T cells, supporting potential applications in HIV resistance and cancer immunotherapy. Furthermore, a machine learning–guided mechanistic study revealed key design principles for LNP-based protein delivery, highlighting unexplored opportunities for in vivo genome-editing therapies.
GPT-4o mini: Non-social science research article
A choline-sensing regulator coordinates metabolic adaptation and pathogenesis in Pseudomonas aeruginosa pulmonary infections
Yingjie Song, Xiyu Wu, Bo Song, Ziqi Zhu, Derong Dai, Qinqin Ma, Rui Bao
Full text
Pseudomonas aeruginosa exploits host-derived phosphatidylcholine (PC) to establish persistent lung infections, yet the mechanistic link between metabolic adaptation and pathogenesis remains unclear. Here, we demonstrate that choline (Cho)–induced regulator (CodR), a GcvA-type transcriptional regulator, serves as a master regulator integrating virulence, antibiotic resistance, and PC catabolism during pulmonary infection. CodR directly binds Cho, the key metabolite of PC degradation, to activate pchP and norA , facilitating exogenous PC/Cho utilization. Genome-wide profiling reveals that CodR targets conserved motifs in promoters of mexA , pslA , and amrZ , synchronizing virulence and tolerance pathways. codR deletion attenuated biofilm formation, type III secretion system activity, siderophore production, and PC catabolism, reducing bacterial pathogenicity in a murine pneumonia model. Notably, Cho/PC pretreatment potentiates CodR-dependent transcriptional activation of antibiotic resistance genes, elevating tolerance to ciprofloxacin and meropenem. Our findings elucidate a paradigm wherein P. aeruginosa co-opts host-derived Cho via CodR to simultaneously potentiate virulence and antibiotic resilience, exposing CodR as a druggable node to break infection-resistance synergies.
GPT-4o mini: Non-social science research article
Biomechanical simulations of hindlimb function in Alligator provide insights into postural shifts and body size evolution
Masaya Iijima, Richard W. Blob, John R. Hutchinson
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The shift from sprawling to erect limb postures in archosaurs during the Triassic represents a major evolutionary transformation in vertebrates. One unresolved question regarding the limb posture transition is its association with body size evolution. If adopting more erect limb postures reduces mass-specific muscle forces and bone stresses, it would enable the evolution of larger body sizes. We tested this prediction using computational modeling and simulation of hindlimb muscle activations and femoral stresses across limb postures and body sizes in juvenile to adult American alligators and a scaled model of the extinct giant alligatoroid Deinosuchus riograndensis . We showed that larger alligators and D. riograndensis encounter challenges in generating sufficient muscle forces to support their bodies and maintain bone stresses, whereas adopting more erect hindlimb postures helps mitigate bone stresses among individuals of similar sizes. These results show how the shift from sprawling to erect limb posture relaxed biomechanical constraints, potentially facilitating the evolution of larger body sizes in terrestrial tetrapods.
GPT-4o mini: Non-social science research article
Lightweight and ultrastrong 3D nanoarchitected high-entropy ceramic metamaterials
Modong Jiang, Rui Li, Binzhao Li, Jincheng Ni, Guorui Wang, Zhong Zhang, Yang Chen, Yanlei Hu, Dong Wu, Jiaru Chu, Heng-An Wu, Jiawen Li
Full text
Three-dimensional (3D) nanoarchitecture ceramics, such as ceramic nanolattices, have attracted intensive research interest due to good thermal stability, oxidation resistance, and damage tolerance. The high performance of lightweight ceramic nanolattices is still a goal to pursue. Herein, we report a high-entropy ceramic (HEC) 3D architecture with feature size down to 150 nanometers, exhibiting simultaneous high strength and energy absorption. A versatile strategy is proposed to synthesize fully transparent precursors with metal salt loading of up to 70%, which allows for high-resolution optical nanofabrication. Combining two-photon polymerization with a two-step sintering process, we fabricate fully dense and high-fidelity HEC 3D architectures. The high-entropy effect promotes the generation of high-density dislocations, thus enhancing both the strength and ductility of HEC nanolattices. This study demonstrates a promising strategy for developing exceptional-performance ceramics, with engineering application prospects in mechanical metamaterials, nanoelectromechanical systems, and damage-tolerant lightweight materials.
GPT-4o mini: Non-social science research article
Resistance to radiation enhances metastasis by altering RNA metabolism
Ayush Kumar, Kensei Kishimoto, Hira L. Goel, Christi A. Silva, Rui Li, Brendan Pacheco, Lihua J. Zhu, William A. Flavahan, Arthur M. Mercurio
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The cellular programs that mediate therapy resistance are often important drivers of metastasis, a phenomenon that needs to be understood better to improve screening and treatment options for patients with cancer. Although this issue has been studied extensively for chemotherapy, less is known about a causal link between resistance to radiation therapy and metastasis. We investigated this problem in triple-negative breast cancer and established that radiation-resistant tumor cells have enhanced metastatic capacity. Resistance to radiation increases the expression of integrin ÎČ3 ( ITGB3 ), which promotes enhanced migration and invasion. Bioinformatic analysis and subsequent experimentation revealed an enrichment of RNA metabolism pathways that stabilize ITGB3 transcripts. Specifically, the RNA binding protein heterogeneous nuclear ribonucleoprotein L ( HNRNPL ), whose expression is regulated by Nrf2, mediates the formation of circular RNAs that sponge the family of let-7 microRNAs that target ITGB3 . Collectively, our findings identify a mechanism of radiation-induced metastasis that is driven by alterations in RNA metabolism.
GPT-4o mini: Non-social science research article
The late formation of chondrites as a consequence of Jupiter-induced gaps and rings
Baibhav Srivastava, André Izidoro
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Accretion ages of the first planetesimals—parent bodies of magmatic iron meteorites—suggest that they formed within the first 0.5 to 1 million years of Solar System history. Yet, planetesimal formation appears to have occurred in at least two distinct phases. A temporal offset separates early-forming bodies from later-forming chondrite parent bodies, which accreted 2 to 3 million years after the Solar System onset—an unresolved aspect of Solar System formation. Here, we use numerical simulations to show that Jupiter’s early formation reshaped its natal protoplanetary disk. Jupiter’s rapid growth depleted the inner disk gas and generated pressure bumps and dust traps that manifested as rings. These structures caused dust to accumulate and led to a second-generation planetesimal population, with ages matching those of noncarbonaceous chondrites. Meanwhile, the evolving gas structure suppressed terrestrial embryos’ inward migration, preventing them from reaching the innermost regions. Jupiter likely played a key role in shaping the inner Solar System, consistent with structures observed in class II and transition disks.
GPT-4o mini: Non-social science research article
In situ characterization of mitochondrial Hsp60-Hsp10 chaperone complex under folding stress
Mingyu Jung, Minjung Kim, Su Jin Ham, Jongkyeong Chung, Soung-Hun Roh
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Mitochondrial proteostasis is critical for maintaining mitochondrial function, and its disruption induces mitochondrial unfolded protein response, which up-regulates chaperones to alleviate protein-folding stress. However, how these chaperones mitigate protein-folding stress remains unclear. Here, using correlated cryo–electron tomography, we show that folding stress triggers marked mitochondrial morphological changes, including the accumulation of amorphous protein aggregates and increased abundance and spatial clustering of the mitochondrial heat shock protein 60-heat shock protein 10 (mtHsp60-Hsp10) complex. Subtomogram analysis revealed the in situ architecture and conformational heterogeneity of mtHsp60-Hsp10 under stress, which retains its canonical double-ring structure while adopting distinct football, half-football, and bullet-like states. Notably, the mtHsp60-Hsp10 complex encapsulates unstructured substrates through conserved hydrophobic interactions. We further demonstrate that knockdown of the mtHsp60-Hsp10 complex exacerbates folding stress, as evidenced by elevated cellular stress responses and activation of mitophagy. Our study defines the in situ structural properties of the mtHsp60-Hsp10 complex and provides mechanistic insight into how it safeguards mitochondrial proteostasis under folding stress.
GPT-4o mini: Non-social science research article
Lysosomal damage is a therapeutic target in Duchenne muscular dystrophy
Abbass Jaber, Laura Palmieri, Rania Bakour, Nathalie Bourg, Ai Vu Hong, Elise Lachiver, Carinne Roudaut, JérÎme Poupiot, Sonia Albini, Daniel Stockholm, Laetitia Van Wittenberghe, Adeline Miranda, Guillaume Tanniou, Nathalie DaniÚle, InÚs Barthélémy, Stephane Blot, Mai Thao Bui, Bornale Das, Edoardo Malfatti, Teresinha Evangelista, Isabelle Richard, David Israeli
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Duchenne muscular dystrophy (DMD), a muscle degenerative disease affecting young boys, arises from the loss of dystrophin. Current gene therapy approaches aim to restore a shortened form of dystrophin (microdystrophin) via adeno-associated vector delivery. While recent clinical studies show promise, therapeutic efficacy remains incomplete, emphasizing the need for improved approaches. Here, we identified lysosomal perturbations in myofibers of patients with DMD and animal models, an overlooked mechanism of cellular damage in muscular dystrophies. These were notably marked by the up-regulation and recruitment of Galectin-3, a biomarker of lysosomal membrane permeabilization, to lysosomes, alongside alterations in lysosome number, morphology, and function. Microdystrophin therapy in Dmd mdx mice fails to fully correct these damages. However, combining it with trehalose, a lysosome-protective disaccharide, substantially improves the outcome, enhancing muscle function, myopathology, and transcriptome. These findings highlight lysosomal damage as an important pathomechanism in DMD and suggest that combining trehalose with gene therapy could enhance therapeutic efficacy.
GPT-4o mini: Non-social science research article
Task-related activity in auditory cortex enhances sound representation
Ana Polterovich, Maciej M. Jankowski, Johannes Niediek, Alex Kazakov, Israel Nelken
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We describe here a mode of activity of neurons in auditory cortex of freely moving rats consisting of large, slow firing rate modulations, which were not driven by sounds, were larger than the sound evoked responses, and were locked to specific time points during the task, similar to responses of hippocampal time-sensitive neurons. This activity mode had important functional consequences to sound processing during task performance. We show that the slow firing rate modulations caused the ongoing activity just before sound presentations to be higher during task performance than during passive listening. Concurrently, during task performance, the responses to target stimuli were weaker but more informative about the task-relevant sounds. In a model, higher ongoing activity caused more synaptic depression of the cortico-cortical synapses, reducing the tendency of the network to produce population spikes and resulting in weaker but more informative responses to sounds.
GPT-4o mini: Non-social science research article
Vasa vasorum plexus formation in intracranial aneurysm associates with microcalcification and wall thickening
Mukhayyirkhuja Abdurakhmonov, Yasutaka Tobe, Juan R. Cebral, Alireza Asadbeygi, Mehdi Ramezanpour, Masoud Zamani, Simon C. Watkins, Julie A. Phillippi, Alexander K. Yu, Sepideh Amin-Hanjani, Fady T. Charbel, Naoki Kaneko, Boyle C. Cheng, Amir R. Dehdashti, Timothy White, Anne M. Robertson
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Intracranial aneurysms (IAs) affect about 3% of the population, often leading to catastrophic outcomes upon rupture. Vasa vasorum, microvessels supplying arterial walls, are conjectured to induce inflammation and leakage in IAs that drive adverse remodeling. Using scanning immunofluorescent multiphoton imaging and micro–computed tomography to visualize intact IA specimens, we identified an extensive vasa vasorum plexus in the IA wall. Our quantitative analyses show significant colocalization of vasa vasorum with calcifications, a strong correlation with increased wall thickness ( R 2  = 0.96, P  < 0.001), and associations with well-defined multiaxially oriented collagen fibers. These findings highlight a more nuanced role for vasa vasorum, suggesting both adverse and protective remodeling influences, which may critically affect IA rupture risk. Contrary to the prevailing view of vasa vasorum as solely adverse, this study underscores the contribution to IA wall stability and the need to elucidate their functional impact on IA pathophysiology. Hence, these microvessels warrant further investigation for therapeutic targeting.
GPT-4o mini: Non-social science research article
Femtosecond spectroscopy with paired single photons: Emulating a double-slit experiment in the time-frequency domain
EunHo Hong, EunSeo Jang, JunWoo Kim
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Time-resolved spectroscopy has long served as a cornerstone technique for investigating the photophysics of materials. However, conventional methods based on intense optical pulses and ensemble measurements often fail to resolve quantum dynamics due to spectral overlap, coherent artifacts, and multiphoton effects. To overcome these limitations, single-photon transient stimulated emission (SP-TSE) has been proposed as a femtosecond spectroscopy technique using quantum light and detection principles. Here, we theoretically demonstrate frequency-resolved SP-TSE. Unlike semiclassical techniques, SP-TSE reveals a strong dependence of the time-resolved spectrum on the frequency-resolving method. With a tunable optical filter, the observed spectrum reflects a quantum double-slit interference in the time-frequency domain. In contrast, interferometric detection produces spectra resembling semiclassical results, but the signal emerges specifically from the second harmonic frequency window due to quantum interference. This framework provides insight into ultrafast quantum processes and suggests a foundation for future applications in quantum spectroscopy and technologies.
GPT-4o mini: Non-social science research article
Nuclear 2â€Č- O -methylation regulates RNA splicing through its binding protein FUBP1
Boyang Gao, Bochen Jiang, Zhongyu Zou, Bei Liu, Weijin Liu, Li Chen, Lisheng Zhang, Chuan He
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2â€Č- O -methylation (N m ) is an abundant RNA modification exists on different mammalian RNA species. However, potential N m recognition by proteins has not been extensively explored. Here, we used RNA affinity purification, followed by mass spectrometry to identify N m -binding proteins. The N m -binding protein candidates exhibit enriched binding at known N m sites. Some candidates display nuclear localization and functions. We focused on the splicing factor FUBP1. Electrophoretic mobility shift assay validated preference of FUBP1 to N m -modified RNA. As FUBP1 predominantly binds intronic regions, we profiled N m sites in chromatin-associated RNA (caRNA) and found N m enrichment within introns. Depletion of N m led to skipped exons, suggesting N m -dependent splicing regulation. The caRNA N m sites overlap with FUBP1-binding sites, and N m depletion reduced FUBP1 occupancy on modified regions. Furthermore, FUBP1 depletion induced exon skipping in N m -modified genes, supporting its role in mediating N m -dependent splicing regulation. Overall, our findings identify FUBP1 as an N m -binding protein and uncover previously unrecognized nuclear functions for RNA N m modification.
GPT-4o mini: Non-social science research article
Activatable fluorescent ratiometric probes for early diagnosis and prognostic assessment of acute kidney injury
Ni Li, Zeyang Liu, Chunda Chen, Hongjing Jiang, Yiting Liu, Dalong Ni
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Early and accurate diagnosis of acute kidney injury (AKI) is crucial for clinical treatment. However, most existing fluorescent probes are prone to background interference and limited renal targeting. We developed a ratiometric nanoprobe (RP-SC) that synergistically responded to H 2 O 2 and targeted kidney injury molecule-1 (KIM-1). In AKI kidneys, RP-SC was hydrolyzed and slowly released encapsulated Hcy-BOH and Cy-Dopa. The H 2 O 2 level was semi-quantitatively analyzed by fluorescence ratio ( F Hcy-BOH / F Cy-Dopa ). RP-SC exhibited prominent renal fluorescence in AKI mice, making it possible to accurately diagnose AKI and dynamically monitor renal function for up to 60 hours. RP-SC could monitor the process of AKI in vivo and provide an earlier warning of AKI than traditional strategies, subsequently evaluating the recovery of renal function after N -acetyl cysteine (NAC) treatment. Our study confirmed the ability of RP-SC for longitudinal monitoring of renal function in vivo by dual-targeting capacity, providing an effective tool for accurate diagnosis of early AKI while tracking the dynamic process of AKI treatment.
GPT-4o mini: Non-social science research article
Label-free robotic mitochondrial biopsy
Yanmei Ma, Weikang Hu, Muyang Ruan, Feixiang Bao, Xingguo Liu, Dong Sun, Hongri Gu, Chengzhi Hu
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Robotic micromanipulation has advanced cellular probing, yet achieving precise, minimally invasive intracellular operations without fluorescent labeling remains challenging. Fluorescent techniques often cause photodamage and cytotoxicity and interfere with downstream analyses. Here, we introduce an automated, multifunctional nanoprobing platform capable of label-free extraction of mitochondria from living cells with high spatiotemporal resolution. The nanoprobe integrates two individually addressable nanoelectrodes that perform electrochemical detection of reactive oxygen and nitrogen species, produced by mitochondrial metabolism, followed by dielectrophoretic trapping, manipulation, and extraction of mitochondria. We successfully demonstrated the extraction of mitochondria from living cells, which is validated through fluorescence labeling before and after extraction. Subsequent quantitative polymerase chain reaction further confirmed that the extracted sample contained mitochondria. The fusion of the transplanted mitochondria within the recipient cell’s mitochondrial network confirms their activity. This automated, label-free, in situ organelle extraction micromanipulation system offers a powerful tool for understanding disease mechanisms linked to dysfunctional organelles and enables single-cell surgeries for organelle transplantation.
GPT-4o mini: Non-social science research article
Dissociable cortical contributions to impulse control during waiting
Malcolm Ho Zheng Hao, Tsukasa Kamigaki
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Self-control requires regulating actions over time, particularly suppressing impulsive actions to obtain future rewards. Using a delayed-response task in mice, we identified distinct cortical contributions to impulse control during waiting. Optogenetic inhibition revealed that the dorsomedial frontal cortex (dmFC) promotes patience, the anterior insular cortex (AIC) drives impulsivity, and the posterior parietal cortex (PPC) regulates temporal precision in waiting. Calcium imaging uncovered region-specific computations: PPC neurons predominantly encoded absolute elapsed time through time cell-like activity, tiling the waiting period independently of patience levels. Their activity predicted the waiting precision. Meanwhile, dmFC and AIC neurons exhibited opposing lick-related activity—dmFC neurons preferentially decreasing and AIC neurons increasing activity during licking. Furthermore, their activity changes during waiting predicted patience. These findings reveal distinct yet complementary mechanisms underlying impulse control during waiting: The PPC encodes temporal information crucial for regulating waiting behavior, while the dmFC-AIC circuit orchestrates a push-pull dynamic to regulate patience.
GPT-4o mini: Non-social science research article
Integrated spatial morpho-transcriptomics predicts functional traits in pancreatic cancer
Dennis Gong, Rachel Liu, Yi Cui, Michael Rhodes, Jung Woo Bae, Joseph M. Beechem, William L. Hwang
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Analyses of patient-derived cell lines have greatly enhanced discovery of molecular biomarkers and therapeutic targets. However, characterization of cellular morphological properties is limited. We studied cell morphologies of human pancreatic adenocarcinoma (PDAC) cell lines and their associations with drug sensitivity, gene expression, and functional properties. By integrating live cell and spatial messenger RNA imaging, we identified KRAS inhibitor–induced morphological changes specific for drug-resistant cells that correlated with gene expression changes. We then categorized a large panel of patient-derived PDAC cell lines into morphological and organizational subtypes and found differences in gene expression, therapeutic targeting potential, and metastatic proclivity. Patterns of cancer cell organization in human PDAC tissues stratified distinct gene expression signatures with clinical significance. In summary, we highlight the potential of cell morphological information in rapid, cost-effective assays to aid precision oncology efforts leveraging patient-derived in vitro models and tissues.
GPT-4o mini: Non-social science research article
Chemical hydrodynamics of nuclear spin states
Anupama Acharya, Madhukar Said, Sylwia J. Barker, Marcel Utz, Bruno Linclau, Ilya Kuprov
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Quantum mechanical equations of motion are strictly linear in density operators, but equations describing chemical kinetics and hydrodynamics may be nonlinear in concentrations. This incompatibility is fundamental, but special cases can be handled—for example, in magnetic resonance where nuclear spin interactions may be too weak influence concentration dynamics. For isolated spins and first-order reactions, this is a well-researched topic, but time evolution of complex nuclear spin systems in the presence of second-order kinetics, diffusion, and flow has so far remained intractable. In this communication, we report a numerically stable formalism for time-domain description of nuclear spin dynamics and relaxation in the simultaneous presence of diffusion, flow, and second-order chemical reactions. As an illustration, we use Diels-Alder cycloaddition of acrylonitrile to cyclopentadiene in the presence of diffusion and flow in a microfluidic NMR probe (a finite element model with thousands of Voronoi cells) with a spatially localized stripline radio frequency coil.
GPT-4o mini: Non-social science research article
CEP76 impairment at the centrosome-cilium interface contributes to a spectrum of ciliopathies
Kamal Khan, Erika Tavares, Katherine Bishara, Aysegul Ozanturk, Leila Qebibo, Stephan Frangakis, Daniel G. Calame, Isabelle Meunier, Béatrice Bocquet, Rafal Ploski, Mohammad Ayman Al Khateeb, Dana Marafi, Luke Mansard, Lena Damaj, Richard A. Lewis, Farid Ullah, Thomas Arbogast, Jackson P. Ogden, Madeleine Harion, Marjolaine Willems, Maha S. Zaki, Tobias Bartolomaeus, Anne-Françoise Roux, James R. Lupski, Malgorzata Rydzanicz, Rami Abou Jamra, Francis Ramond, Elise Heon, Lydie Burglen, Erica E. Davis
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Dysfunction at the centrosome-cilium interface underlies a broad range of ciliopathies. Here, we identify biallelic variants in CEP76 , encoding a centrosomal protein, in eight unrelated individuals presenting with neurodevelopmental, ocular, and variable additional multisystem features. Proband-derived fibroblasts and CEP76-depleted RPE1 cells display ciliary deficits, including impaired cilium formation and length, disrupted transition zone architecture, and impaired IFT88-mediated anterograde intraflagellar transport. Zebrafish cep76 mutants recapitulate key clinical phenotypes, and in vitro complementation assays confirm pathogenicity for all tested human disease-associated variants. Proteomics analysis identifies CEP76 interactors, including known partners CCP110 and CEP97, and highlights clinically and functionally relevant candidates, including ALMS1 and LUZP1. Together, these findings expand the role of CEP76 beyond centriole duplication to include ciliary assembly and trafficking, establishing it as a ciliopathy gene. This work provides mechanistic insights into CEP76 -related disease and broadens our understanding of centrosome-cilium biology.
GPT-4o mini: Non-social science research article
Characterizing the American Upper Paleolithic
David B. Madsen, Loren G. Davis, Thomas J. Williams, Masami Izuho, Fumie Iizuka
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In North America, there are enough sites with relatively large tool assemblages predating ~13,500 calibrated years before the present (cal yr B.P.) to allow assessment of the underlying characteristics of their shared lithic tradition. Their shared technological features involve the use of dual core-and-blade and biface technologies similar to those in the Northeast Asian Late Upper Paleolithic. These dual approaches were often merged to produce small projectile points, including stemmed point forms using an elliptical cross-sectional ogive design. Similar dual lithic technologies are found in assemblages in northern Japan dating to ~20,000 cal yr B.P. We suggest a group with a similar lithic technology became isolated somewhere in the vicinity of the Paleo-Sakhalin-Hokkaido-Kuril region, developing genetically into ancestral American populations. Between ~22,000 and ~18,000 cal yr B.P., a subset of this population migrated along the southern Beringian and Northwest coasts into the Americas. By ~16,000 to ~15,000 cal yr B.P., they had become widely dispersed across North America.
GPT-4o mini: Non-social science research article
Metabolic dysfunction–associated steatotic liver disease alters brain function and behavior: Insights from liver-targeted siRNA therapy
Teresa Cardoso Delgado, Celia Martín-Cuevas, Ana C. Sånchez Hidalgo, Antonio Gil Gómez, Claudia M. Rejano Gordillo, Jon Landa, Rocío Gallego Durån, Naroa Goikoetxea-Usandizaga, Irene Gonzålez-Recio, Clàudia Gil-Pitarch, L. Estefanía Zapata-Pavas, Jon Ander Barrenechea-Barrenechea, Carolina Conter, Luis Alfonso Martínez-Cruz, Víctor D. Ramos Herrero, Rubén Nogueiras, Mikel Azkargorta, Felix Elortza, Verónica Moncho-Amor, Javier Crespo, Ander Matheu, Manuel Romero Gómez, Benedicto Crespo-Facorro, María Luz Martínez-Chantar
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Metabolic dysfunction–associated steatotic liver disease (MASLD), a liver-centric condition, is associated with cognitive impairment and sensorimotor alterations. However, it remains unclear whether MASLD is sufficient to drive central nervous system deficits. Here, using diet-induced mouse models, we showed that MASLD was associated with alterations in social memory, sensorimotor processing, and hippocampal function, including decreased parvalbumin-positive interneurons, reduced dendritic spine density, and diminished dentate gyrus neurogenesis and neuronal differentiation. Then, we selectively modulated liver metabolism through N -acetylgalactosamine small interfering RNA (siRNA) therapy against Cyclin M4 ( CNNM4 ), a magnesium transporter dysregulated in MASLD. Liver-specific intervention with siRNA- Cnnm4 reversed impaired social memory and sensorimotor processing in association with recovery of hippocampal synaptogenesis and mitochondrial function pathways, alongside activation of neurogenesis-associated transcriptional programs. Our findings demonstrate that liver pathology is sufficient to drive neurobehavioral and hippocampal dysfunction in MASLD. Hepatic-specific intervention restores brain function, strongly supporting the existence of a causal and therapeutically targetable liver-brain axis for MASLD-associated neurological complications.
GPT-4o mini: Non-social science research article
Cooperative role of distinctive TP53 and PTEN combined loss in the peripheral T cell lymphoma–GATA3 molecular subgroup
Waseem G. Lone, Jiayu Yu, Xuxiang Liu, Dylan T. Jochum, Alyssa Bouska, Kunal Shetty, Tyler Herek, Sunandini Sharma, Chengfeng Bi, Rauf Shah, Zaina W. Nasser, Catalina Amador, Aiza Arif, Abdul Rouf Mir, Yuping Li, Tayla B. Heavican-Foral, Jacob Robinson, R. Katherine Hyde, Mamiko Sakata-Yanagimoto, Satyanarayana Rachagani, Timothy W. McKeithan, David W. Scott, Louis M. Staudt, Giorgio Inghirami, Andrew Feldman, Timothy Greiner, Julie M. Vose, Lisa Rimsza, Joesph Khoury, Wing C. Chan, Javeed Iqbal, character(0)
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Peripheral T cell lymphoma (PTCL) is a heterogeneous group of postthymic T cell neoplasms, with ~40% classified as PTCL–not otherwise specified (PTCL-NOS). PTCL-GATA3, a molecularly defined subtype, associated with T helper 2 (T H 2)–like differentiation and poor prognosis, has frequent co-occurrence of TP53 loss/mutation and heterozygous PTEN loss. CD4+ T cell conditional mouse models with Trp53 mutation/deletion and Pten loss demonstrated mature T cell lymphomas (mTCLs) with T H 2-like transcriptomic and immunophenotypic profiles. Molecular studies revealed that codeletion of Trp53/Pten induced T cell receptor and Janus kinase–signal transducer and activator of transcription signaling, promoting T H 2 differentiation while inhibiting T H 1 differentiation. These findings were validated by CRISPR editing of TP53/PTEN loss in human CD4+ T cells and mechanistically evaluated the p53 binding region in intron-3 of GATA3, resulting in transcriptional repression. Transcriptomic profiles of m-TCLs recapitulated human-PTCL-GATA3 transcriptome and distinguished PTCL-NOS subtypes. Preclinical assessment of m-TCLs with PI3Kγ/ή inhibitors significantly improved survival, supporting a therapeutic approach for the p53-aberrant PTCL-GATA3.
GPT-4o mini: Non-social science research article
Activation of the coagulation cascade as a mechanism for selective nanoparticle-mediated RNA delivery to the endothelium in vivo
Edward B. Guzman, Piotr S. Kowalski, Robert S. Langer, Daniel G. Anderson
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Nanoparticles formulated with certain cationic lipids or polymers have been shown to facilitate RNA delivery to the endothelium. Here, we show that these nanoparticles become coated with coagulating proteins and induce coagulation for RNA delivery in vivo, without leading to histological evidence of clot formation. We further show that nanoparticles previously reported to transfect the liver can be redirected to other organs by preincubating them with procoagulant proteins. Our data demonstrate that activation of the coagulation cascade mediates endothelial RNA delivery and indicate that nanoparticles can be targeted to the endothelium of various organs by integrating procoagulant components in their formulation.
GPT-4o mini: Non-social science research article
Excitation of Tamm plasmon polariton in ultrathin metals
Jiangwei Zhang (ćŒ æ±ŸäŒŸ), Pengsen Wang (王éčæŁź), Maobin Xie (è°ąèŒ‚ćœŹ), Qingquan Liu (ćˆ˜æž…æƒ), Anping Ge (è‘›ćź‰è), Xueyu Guan (ć…łć­Šæ˜±), Hengyi Cui (ćŽ”æ’æŻ…), Qixiang Jia (èŽŸć„‡ç„„), Ruonan Ji (ć†€è‹„æ„ ), Zhipei Sun (歙濗ćŸč), Shaowei Wang (çŽ‹ć°‘äŒŸ)
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Tamm plasmon polariton (TPP) has unique localization and manipulability but cannot be excited with ultrathin metal films. We propose a strategy to realize generalized TPP (GTPP) in an ultrathin metal film as metainterface by introducing a low-loss dielectric Bragg reflector compensation layer, enabling effectively excitation of GTPP at its interface and achieving near-perfect absorption (~99.1%) at the resonant wavelength of 532 nanometers. This excitation has topological robustness, which fundamentally stems from its intrinsic tolerance to fabrication imperfections. A 14-channel narrowband absorbers chip based on GTPP has been fabricated. Compared to conventional structures without GTPP excitation, this device can lower the reverse saturable absorption threshold (~7.7 × 10 −5 nanojoules per square micrometer) and increase the fluorescence intensity above the residual laser intensity to enhance the extinction capability by two orders of magnitude. These findings provide both evidence for applications of micro-nano photonic devices in fields such as laser elimination and offer insights for other scenarios.
GPT-4o mini: Non-social science research article
Starspots as the origin of ultrafast drifting radio bursts from an active M dwarf
Jiale Zhang, Hui Tian, Stefano Bellotti, Tianqi Cang, Joseph R. Callingham, Harish K. Vedantham, Bin Chen, Sijie Yu, Philippe Zarka, Corentin K. Louis, Peng Jiang, Hongpeng Lu, Yang Gao, Jinghai Sun, Hengqian Gan, Hui Li, Chun Sun, Zheng Lei, Menglin Huang
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Detecting coherent radio bursts from nearby M dwarfs provides opportunities for exploring their magnetic activity and interaction with orbiting exoplanets. However, it remains uncertain whether the emission is related to flare-like activity similar to the Sun or magnetospheric process akin to magnetized planets. Using observations (1.0 to 1.5 gigahertz) taken by the Five-hundred-meter Aperture Spherical radio Telescope, we found a type of millisecond-scale radio bursts with exceptionally high-frequency drift rates (~8 gigahertz per second) from an active M dwarf, AD Leo. The ultrafast drift rates point to a source region with a notably low magnetic scale height (<0.15 r ⋆ , r ⋆ as the stellar radius), a feature not expected in a commonly assumed dipole-like global field but highly possible in localized strong-field structures, i.e., starspots. Our findings suggest that a concentrated magnetic field above starspots could be responsible for some of the most intense radio bursts from M dwarfs, supporting a solar-like electron acceleration mechanism.
GPT-4o mini: Non-social science research article
Remolding laccase for whole-cell and in vivo modulation of dopamine signal
Xiaoti Yang, Shilong Fan, Jing Liu, Shuli Chen, Wenjie Wu, Xiling Chen, Wenliang Ji, Shuxin Li, Yifei Xue, Xinjie Sun, Ming Wang, Ji Liu, Fei Wu, Ping Yu, Lanqun Mao
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Biocatalytic regulation of dopamine signals paves an effective and biocompatible way to modulate dopaminergic functions and disorders. Here, we report the remolding of bacterial laccase, catalyzing conversions of dopamine and O 2 to o -quinone and H 2 O, into a biocatalytic neuromodulator by reactive oxygen species–free dopamine catabolism. Given the poor activity of native laccase in the physiological context because of OH − inhibition of its geometrically constrained O 2 -reducing center, we designed a highly dynamic Ru-Cu binuclear center to counteract the inhibition effect. Structural and computational investigations unravel a self-adaptive catalytic mechanism by reversive Ru-Cu active site reconfiguration that lowers the kinetic barriers for O 2 -to-H 2 O conversion in neutral solution. The remolded laccase exhibits substantial enhancement of physiological activity (up to one order of magnitude) and improved catecholamine substrate specificity, enabling whole-cell down-regulation of vesicular dopamine and extracellular erasure of evoked dopamine signals in intact brains. Our work elucidates a picture of artificial metalloenzymes for neuromodulation through a rationalized neurotransmitter metabolism pathway.
GPT-4o mini: Non-social science research article
The nuclear import receptor importin-7 targets HPV from the Golgi to the nucleus to promote infection
Tai-Ting Woo, Yuka Takeo, Mara C. Harwood, Ethan T. Houck, Daniel DiMaio, Billy Tsai
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During human papillomavirus (HPV) entry, the virus exploits COPI-dependent retrograde transport to cross the Golgi apparatus before reaching the nucleus to cause infection. How HPV enters the nucleus after exiting the Golgi is unclear, although mitotic nuclear envelope breakdown (NEB) appears important. Here, we show that importin-7 (IPO7), a nuclear pore import receptor, is present at the Golgi and promotes HPV infection. IPO7 knockdown inhibits infection and causes HPV to accumulate in the Golgi without reaching mitotic chromosomes, demonstrating that IPO7 promotes Golgi-to-nucleus transport of HPV. Golgi-to-nucleus transport of a cellular cargo also requires IPO7, suggesting that HPV hijacks a preexisting pathway for nuclear entry. Furthermore, the C-terminal nuclear localization sequence of HPV L2 protein, which overlaps its cell-penetrating peptide sequence, binds IPO7 directly in a COPI-dependent virus trafficking step. Together, these data identify a role for an importin in HPV infection and suggest that the canonical nuclear pore import machinery plays an unanticipated role in NEB-dependent nuclear entry.
GPT-4o mini: Non-social science research article
The hazard of large debris flows
Erin L. Harvey, Tristram C. Hales, Alexander J. Horton, Oliver R. Francis, Fan Yang, Jie Liu, Xuanmei Fan
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Large (>10 6 cubic meters), highly mobile debris flows represent one of the deadliest yet least understood types of landslides on Earth. These flows often originate when smaller events entrain water and sediment along their channel. The conditions controlling when and where these flows bulk are not well understood, making their hazard unpredictable. Here, we examine this hazard by combining a unique inventory of debris flows from the Wenchuan earthquake with numerical modeling to constrain their magnitude and frequency. We show that large debris flows occur more frequently than expected, on the basis of magnitude-frequency relationships for all debris flows, when high volumes of sediment are deposited in channels. These findings are consistent with other large sediment-generating events globally, such as Mount St. Helens and Mount Pinatubo where multiple large debris flows were triggered following volcanic eruptions that produced several cubic kilometers of sediment.
GPT-4o mini: Non-social science research article
The evolution of nanomedicine: The rise of next-generation nanomaterials in cancer nanomedicine
Helen Forgham, Yixin Chang, Yao Wang, Jiayuan Zhu, Liwei Liu, Heather Biggs, Aleksandr Kakinen, Yuhao Jiang, Xinru You, Kristofer J. Thurecht, Shaohua Ma, Lining Arnold Ju, Wei Tao, Thomas P. Davis, Joyce Y. Wong, Ruirui Qiao
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The nanomedicine field continues to gain momentum, with several groundbreaking clinical trials underway. However, despite the promise of advanced antifouling nanoparticles incorporating poly(ethylene glycol)—a key component in the development of COVID-19 vaccines—the clinical translation of nanomedicine remains limited. This is primarily due to the relatively low delivery efficacy, with passive targeting relying on the enhanced permeability and retention effect, and active targeting leading to only modest improvements in target tissue accumulation. Improving the targeting, biocompatibility, and functionality of nanoparticles has the potential to create more effective, personalized, and minimally invasive therapies. This review aims to highlight the rise of a previously unidentified order of immune-minded nanomaterials and explores how mechanobiological principles and biomechanical nanotools are revolutionizing our understanding of nano-bio interactions in relation to disease. By considering mechanical properties such as stiffness, surface topology, and behavior under physiological flow conditions, researchers can better engineer nanoparticles for improved therapeutic outcomes.
GPT-4o mini: Non-social science research article
Cluster nanoarchitecture and structural diversity of PIEZO1 at rest and during activation in intact cells
Clement Verkest, Lucas Roettger, Nadja Zeitzschel, James Hall, Oscar SĂĄnchez-Carranza, Angela Tzu-Lun Huang, Gary R. Lewin, Stefan G. Lechner
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The force-gated ion channel PIEZO1 confers mechanosensitivity to many cell types. While the structure and physiological roles of PIEZO1 are well-described, the subcellular distribution and the impact of the cellular microenvironment on PIEZO1 conformation and function are poorly understood. Here, using MINFLUX nanoscopy, we demonstrate that PIEZO1 channels accumulate in pit-shaped invaginations that are distinct from classical membrane invaginations such as clathrin-coated pits and caveolae, thereby possibly creating hotspots for mechanotransduction. Moreover, by measuring intramolecular distances in individual PIEZO1 channels with nanometer precision, we reveal subcellular compartment-specific differences in PIEZO1 conformation at rest and during activation that correlate with differences in PIEZO1 function and are possibly caused by differences in cytoskeletal architecture. Together, our data provide previously unrecognized insights into the complex interplay of forces that determine how PIEZO1 alters membrane shape and, vice versa, how the membrane together with the cytoskeleton affect the conformation and function of individual PIEZO1 channels.
GPT-4o mini: Non-social science research article
Lyn restrains lupus via kinase-independent mechanisms that limit Toll-like receptor activation and type I interferon responsiveness
Elan L’Estrange-Stranieri, Timothy A. Gottschalk, Anne M. Kong, Mhairi J. Maxwell, Ee Shan Pang, Evelyn Tsantikos, David M. Tarlinton, Meredith O’Keeffe, Mark D. Wright, Margaret L. Hibbs
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Lyn phosphorylates inhibitory immunoreceptors to terminate signaling; consequently, Lyn deficiency in mice causes hyperactive immune cells and lupus-like autoimmune disease. Lyn may also suppress autoimmunity independent of its kinase activity through inhibitory protein-protein binding interactions, although the importance of this mechanism is unclear. To analyze the kinase-independent functions of Lyn, mice expressing a catalytically inactive mutant of Lyn were generated and their phenotype compared to Lyn-deficient mice. Disease progression was blunted in Lyn kinase-dead mice indicating a contribution for kinase-independent Lyn functions in restraining autoantibody production, glomerulonephritis, Toll-like receptor signaling, and splenomegaly. Further comparative analyses identified an exclusive role for the kinase-dependent functions of Lyn in regulating B cell receptor signaling, dendritic cell phenotype, and type I interferon production. By contrast, interferon-stimulated gene expression and the regulation of thymic epithelial cell development and T cell selection are previously unidentified, exclusively kinase-independent functions for Lyn. Collectively, these findings further our understanding of the nuanced roles of Lyn in health and disease.
GPT-4o mini: Non-social science research article
Immunopeptidome analysis reveals SERPINB3 as an autoantigen driving eczematized psoriasis
Manja Jargosch, Jomy Kuruvila, Emanuele Scala, Johannes Grosch, Jessica Eigemann, Sophia Wasserer, Shalva Lekiashvili, Nico Trautwein, Daniel Johannes Kowalewski, Alexander Böhner, Yigit Köseoglu, Christina Hillig, Jenny Thomas, Felix Lauffer, Carsten B. Schmidt-Weber, Michael P. Menden, Juliane S. Walz, Susanne Kaesler, Stefanie Eyerich, Simon Blank, Hans-Georg Rammensee, Tilo Biedermann, Kilian Eyerich, Zsuzsanna Kurgyis, Lena K. Freudenmann, Natalie Garzorz-Stark
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Psoriasis (Pso) is a chronic inflammatory skin disease driven by T helper 17 (T H 17) cells, with several clinical subtypes. While self-reactive immune responses have been observed, the role of autoantigens in Pso remains unclear. Using immunopeptidomics, we identified serpin family B member 3 (SERPINB3) and SERPINB4 as candidate autoantigens in Pso skin. In a mouse model, the SERPINB3 ortholog Serpinb3b enhanced inflammation, promoted tissue-resident memory T cells, and skewed immunity toward a T H 2 phenotype. In humans, SERPINB3 reactivity was specifically associated with “eczematized psoriasis” (EczPso), a subtype marked by T H 2/T H 17 immune signatures. SERPINB3 protein was enriched in EczPso lesions and highly secreted by keratinocytes under combined T H 2/T H 17 stimulation. Lesional T cells from EczPso—but not from eczema or classical plaque Pso—proliferated in response to SERPINB3 and induced EczPso-like features in a skin model. Our findings identify SERPINB3 as an autoantigen driving a distinct Pso subtype, supporting more precise diagnosis and therapy.
GPT-4o mini: Non-social science research article
Beyond the limit: The estimated air pollution damages of overshooting the temperature target
Clàudia Rodés-Bachs, Laurent Drouet, Peter Rafaj, Massimo Tavoni, Lara Aleluia Reis
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Exposure to outdoor air pollution results in millions of premature deaths and illnesses that are associated with substantial economic loss. According to the Global Burden of Disease, outdoor air pollution was responsible for 4.7 million deaths in 2021. Climate change mitigation policies could provide cobenefits by reducing air pollution. The Intergovernmental Panel on Climate Change AR6 report explores scenarios using an updated carbon budget approach—the net-zero pathways—designed to avoid temporary overshoot of the 1.5°C temperature limit. We assess whether net-zero pathways consistently improve air pollution outcomes using a global source-receptor air pollution model to estimate concentrations, health impacts, and economic damages. To analyze key uncertainties, we apply multiple relative risk functions and economic damage models. Our findings show that stringent climate policies, avoiding overshoot and keeping below 2°C, offer substantial health and economic cobenefits, particularly for China and India, and avoid 207,000 premature deaths and 2269 billion USD2020 in damages by 2030.
GPT-4o mini: Non-social science research article
Short tandem repeats in populations of the Qinghai-Tibet Plateau and adjacent regions provide insights into high-altitude adaptation
Yuguo Huang, Mengge Wang, Zhiyong Wang, Xiaojun Liu, Yuhang Feng, Jie Zhong, Hailin Huang, Jia Geng, Ting Tang, Chao Liu, Yu Lu, Jing Cheng, Fengxiao Bu, Guanglin He, Huijun Yuan
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Short tandem repeats (STRs) confer evolutionary advantages across various species, yet their roles in human high-altitude adaptation remain largely unexplored. In this study, we analyzed over 1.1 million STRs in 7876 whole-genome sequencing samples, including 3808 newly sequenced Tibeto-Burman (TB) speakers and Han Chinese individuals inhabiting the Qinghai-Tibet Plateau and neighboring regions. We characterized more than 570,000 polymorphic STRs across coding/noncoding genomic and functional contexts, revealing distinct STR variation patterns specific to TB speakers. Notably, divergent STRs in TB speakers were predominantly located in high-altitude adaptive genes and frequently associated with gene expression levels. Additionally, we identified over 17,000 STRs strongly associated with environmental conditions on the Qinghai-Tibet Plateau. These STRs exerted multilevel gene regulation through modulating protein coding, fine-tuning cis-regulatory elements, and modulating biological pathways. Furthermore, we observed substantial contributions of functional and adaptive STRs to human phenotypic diversity. Collectively, our findings provide genomic STR resources of TB speakers and genetic insights into their roles in human adaptive evolution.
GPT-4o mini: Non-social science research article
An overhead-reduced, efficient, fully analog neural-network computing hardware
Jiabao Ye, Wannian Wang, Caiping Shi, Xuecheng Cui, Wanyuan Qu, Peng Lin, Xiao Yu, Ran Cheng, Hanming Wu, Bing Chen
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Human brain–inspired neural-network computing hardware has the potential to overcome the energy efficiency and resource overhead challenges caused by the von Neumann bottleneck. However, existing neural-network computing hardware still exhibits a considerable gap compared to the human brain, likely due to the absence of complex data compression functions and the fully analog domain operating strategy adopted by the brain. To solve these problems, a fully analog neural - network computing hardware (FANCH) with input data compression is proposed and fabricated at both the chip and system levels in this work. FANCH implements the complete computational process of the neural networks using fully analog circuits. FANCH achieves an accuracy with only a 0.36% reduction from the software baseline in the handwritten digit recognition task. FANCH demonstrates advantages in energy efficiency compared to state-of-the-art artificial intelligence acceleration chips and systems. Our work provides an efficient fully analog hardware solution for edge computing applications with low hardware resource demands.
GPT-4o mini: Non-social science research article
The design and reconstructible history of the Mayan eclipse table of the Dresden Codex
John Justeson, Justin Lowry
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This paper explores how ancient Mayan calendar specialists designed a predictive eclipse table, revising a century of interpretation. The table’s length, 405 months, was originally implemented in a general lunar calendar table of 405 successive months; within a few passes through this lunar calendar, intervals among observed eclipses could have stimulated an approximation to the series of lunar intervals that were later compiled as stations of an eclipse table; and for all and only these lunar stations to correspond to dates of upcoming eclipses, dates in successive 405-month eclipse tables would have to have overlapped. It identifies optimal procedures for the amounts of overlap that would maintain its predictions’ correctness and shows that these procedures could yield a sequence of tables that would anticipate every solar eclipse observable in the Mayan territory from a century or two after the first evidence of the Mayan lunar calendar to at least the era of the extant eclipse table, 700 years later.
GPT-4o mini: Non-social science research article
Wireless nonresonant stimulation of neurons on a magnetoelectric film surface
Asli Aydin, Ali Jahanshahi, Pouria Esmaeili-Dokht, Mertcan Han, Gaurav Gardi, Yan Yu, Ren Hao Soon, Yasin Temel, Metin Sitti
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Wireless neural interfaces are emerging as a minimally invasive treatment option for neurological disorders. Among the wireless technologies, magnetically powered systems are effective for targeting deep brain sites. However, dependence on high-frequency electromagnetic fields in such systems limits their safe implementation. In this study, we demonstrate the use of millimeter-scale magnetoelectric (ME) films as a direct neural interface for wireless neurostimulation, powered by static and alternating magnetic fields in the nonresonant regime (10 hertz). To accomplish this objective, electrical potential trends of the ME films under varying low-frequency magnetic fields are investigated and used to demonstrate neural stimulation by calcium imaging on primary neurons in vitro via a capacitive-like charge injection mechanism. In addition, electrical polarization orientation is revealed as a critical design parameter in direct neuron-ME interfaces. These findings collectively demonstrate the potential of nonresonant powering of ME films as a promising minimally invasive wireless neural stimulation technique.
GPT-4o mini: Non-social science research article
Leptin as a key driver for organ fibrogenesis
Xue-Nan Sun, Shiuhwei Chen, Shangang Zhao, Jan-Bernd Funcke, Megan Virostek, Line Pedersen, Chao Li, Chanmin Joung, Qian Lin, Yan Li, Ayanna Cobb, May-Yun Wang, Kyounghee Min, Lisandro Maya-Ramos, Giovanna Degasperi, Junquan Liu, Ningyan Zhang, Zhiqiang An, Diana R. Tomchick, R. Max Wynn, Da Young Oh, Philipp E. Scherer
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Leptin, a hormone primarily secreted by adipocytes, regulates energy balance and systemic metabolism through its interaction with the leptin receptor (LEPR). Beyond these functions, leptin signaling has been implicated in the pathogenesis of tissue fibrosis. Here, we report the x-ray crystal structures of a leptin-neutralizing antibody (hLep3) in the unbound and leptin-bound states. The interaction of this antibody with leptin mimics the interaction of the LEPR with leptin, providing direct insights into the mechanism by which the antibody disrupts leptin signaling. We furthermore evaluate the therapeutic potential of neutralizing leptin with this antibody across distinct mouse models of fibrosis affecting the kidney, liver, lung, heart, and blood vessels. Leptin neutralization markedly inhibited fibrosis progression in all models. Mechanistically, suppression of leptin activity reduces pro-inflammatory and profibrotic processes, underscoring its therapeutic potential. These findings suggest that leptin signaling plays a vital role in tissue fibrosis and that treatment with a leptin-neutralizing antibody may be a promising therapeutic approach.
GPT-4o mini: Non-social science research article
Chemically tailored anionic antibiotic adjuvants targeting divalent cations to overcome carbapenem resistance in gram-negative bacteria
Hao Tang, Xiaomeng Zhao, Mengsi Sun, Jie Qi, Zhihao Huang, Yihang Zhu, Yingmin Zeng, Yong Xia, Zhi Luo, Xingyu Jiang
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No clinically available antibiotic adjuvants can overcome metallo-ÎČ-lactamase (MBL) resistance in carbapenem-resistant Gram-negative ESKAPE pathogens. Divalent cations in MBL and quasicrystalline lipopolysaccharides (LPS) are key determinants of acquired and intrinsic resistance in these bacteria. Chemically depriving these cations would block multiple resistance pathways simultaneously and restore carbapenem susceptibility. Here, we chemically engineer a class of anionic adjuvants to tailor their interactions with MBL, enhancing the enzymatic inhibition by up to ~5885-fold compared to parent compounds. An orthogonal screen identifies the tiopronin-engineered anionic adjuvant (TINA), which achieves complete rescue of all tested carbapenems against diverse New Delhi metallo-ÎČ-lactamase-1–producing Gram-negative ESKAPE bacteria. TINA targets both MBL and LPS, depriving divalent cations to inactivate MBL and damage membrane collaboratively while also preventing resistance evolution. Moreover, TINA’s anionic nature minimizes serum adsorption, enabling safe and effective in vivo treatment of bacterial pneumonia. This work provides an innovative chemical biology strategy leveraging anionic materials to combat superbugs globally.
GPT-4o mini: Non-social science research article
Mechanical contribution of germ cell specification in Arabidopsis anthers
Chan Liu, Hui Shi, Yuting Han, Pan Wang, Kexin Li, Zhishuai Zhang, Jiazheng Liu, Yafeng Zheng, Linlin Li, Limei Lin, Chen Liang, Binjun Qin, Hua Han, Shunong Bai, Xiao Liu, Wenqian Chen, Feng Zhao
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A central question in developmental biology is how germ lines are established. We studied the specification of male germ cells (GCs) within the anther. Here, we focused on the potential role of mechanics, an aspect of anther development that has been very poorly characterized. Using a combination of live imaging and mechanical measurements, we showed that GCs emerge within a special micromechanical niche, where the inner tissues exert pressure on the outer cell layers, placing themselves under compression. Mechanical perturbations impair tissue expansion patterns and severely compromise GC specification. Further investigations revealed that the master genetic regulator SPOROCYTELESS/NOZZLE (SPL/NZZ) was central in establishing this micromechanical environment via cell wall softening. In turn, the mechanical cues stabilized the transcription of SPL/NZZ . Here, we propose an intrinsic growth-derived mechanochemical feedback loop that safeguards the fate of GCs.
GPT-4o mini: Non-social science research article
Antibiotic stress–induced hormesis in phytoplankton and bacteria through their mutual cooperation
Xiuqi You, Qian Chen, Lingrui Kong, Yiming Feng, Jingrun Hu, Sitong Liu, Weiling Sun
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Phytoplankton–bacteria interactions are critical but often overlooked in assessing the impacts of pollutants on ecosystems. Herein, we used a coculture consisting of the green alga Chlamydomonas reinhardtii and river bacteria to investigate their responses to antibiotic stress. Both partners exhibited hormesis in cocultures but were inhibited in monocultures under exposure to 10 different antibiotics, especially azithromycin (AZM). Notably, mutualistic cooperation between the partners shifted the effect of AZM from inhibition in monocultures to promotion in cocultures. C. reinhardtii alleviates AZM stress on bacteria by providing organic carbon and efficiently removing antibiotics. In turn, the altered phycospheric bacteriome supplied ammonia, phosphate, vitamin B 12 , and indole-3-acetic acid to promote C. reinhardtii growth. The antibiotic-induced growth promotion was also observed in natural phytoplankton–bacteria communities. Our findings challenge the reliability of ecotoxicity assessment that is typically based on single-species tests, emphasizing the importance of cross-kingdom interactions in assessing pollutant effects.
GPT-4o mini: Non-social science research article
GENRISE-induced superior extracellular vesicles for scalable therapeutic cargo delivery
Hyejin Kim, Sunghyun Moon, Dajeong Kim, In-Ho Jeong, Eun-Koung An, Hae-Bin Park, Seon-Mi Jin, Yoonbin Ji, Ohsung Ko, Ju Hong Min, Hwankyu Lee, Eunji Lee, Young Jik Kwon, Jun-O Jin, Peter C. W. Lee, Jong Bum Lee
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Extracellular vesicles (EVs) demonstrate immense potential as naturally derived carriers of active therapeutics. To maximize their capacity, it is crucial to develop effective methods for manipulating cargo and ensuring scalability. To address this challenge, we propose that protein-free mRNA granule-like structures, named gene-encoded nanoparticle RNA for inducing superior EVs (GENRISE), can function as active translational sponge and as transient subcellular compartments. The overexpression of proteins in proximity to RNA assemblies stimulates parental cells to release excess exogenous proteins in induced superior EVs (iSEVs). The iSEV system enables the single-module–based enrichment of exogenous cargo in EVs with scalable manufacturing. By harnessing mass-produced iSEVs induced by GENRISEs, encoding an antigenic peptide, we have successfully demonstrated target-specific in vivo cancer immunotherapy. These findings suggest that the emerging iSEV platform shows considerable potential for biomedical applications by enabling the controlled production of cargo-specific EVs.
GPT-4o mini: Non-social science research article
Oxygen isotope composition of Mesoproterozoic (~1360 Ma) seawater constrained by clumped isotopes of North China limestones
Pingping Li, Fang Hao, Shijie He, Haobo Chai, Yongfei Jiao, Yaxuan Gao, Huayao Zou
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The oxygen isotope composition (ÎŽ 18 O) of Phanerozoic seawater has been widely investigated, but the ÎŽ 18 O values of Precambrian seawater remain poorly constrained, with ongoing debate over whether they were substantially lower than those of Phanerozoic seawater. To address this question, we analyzed the clumped isotopes of limestones from the North China Craton to reconstruct Mesoproterozoic seawater temperature and ÎŽ 18 O values. Our results indicate that the Mesoproterozoic seawater had a temperature of 26.9° ± 0.4°C and a ÎŽ 18 O value of −6.3 ± 0.2 per mil (relative to standard mean ocean water). This ÎŽ 18 O estimate aligns with previous inferences from geochemical modeling, marine iron oxides, and oxygen isotope ensembles, supporting the hypothesis that Mesoproterozoic seawater was isotopically lighter than its Phanerozoic counterpart. These findings provide insights into the Earth’s paleoclimate and the evolution of seawater composition during the Mesoproterozoic era.
GPT-4o mini: Non-social science research article
Mode-locked optomechanical frequency combs in a graphene-silica microresonator
Hao Zhang, Yu-Pei Liang, Teng Tan, Shi-Da Wen, Yan Yu, Ning An, Yan-Wu Liu, Yan-Hong Guo, Qi-Huang Gong, Yong-Jun Huang, Yun-Jiang Rao, Yun-Feng Xiao, Qi-Fan Yang, Bai-Cheng Yao
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Mode locking is an essential process through which resonant modes achieve stable synchronization via nonlinear interactions. This self-organization allows photonic and electronic sources to produce pulsed waveforms and is vital for applications in ultrafast and high-field optics as well as frequency comb generation. Here, we report a mechanism to include photon-electron-phonon interactions, demonstrating the excitation of mode-locked optomechanical microcombs in a graphene-deposited silica microresonator, determined by the synergy of optomechanical back action and graphene saturable absorption. The circulating optical field induces mechanical oscillations that modulate the light wave, while Pauli blocking in graphene locks a single optomechanical mode, forming a localized coherent optical wave packet within a single microcavity. In addition, using frequency division techniques, the mode-locked optomechanical microcomb achieves repetition stability with phase noise reduced to −110.5 decibels relative to the carrier per hertz at a 1-hertz offset and an Allan deviation as low as 3 × 10 −12 @ 20 seconds, comparable to a standard rubidium clock.
GPT-4o mini: Non-social science research article
Visualizing the chronicle of multiple cell fates using a near-IR dual-RNA/DNA–targeting probe
Linawati Sutrisno, Gary J. Richards, Jack D. Evans, Michio Matsumoto, Xianglan Li, Koichiro Uto, Jonathan P. Hill, Masayasu Taki, Shigehiro Yamaguchi, Katsuhiko Ariga
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Early detection and late-stage cell fate assessment are key factors to develop therapeutic strategies, although current methods cannot capture early responses or distinguish multiple injury states, especially in ultraviolet-visible (UV-vis)–sensitive cells. Here, we introduce a method to simultaneously detect variations in RNA and DNA under near-infrared photoexcitation. Using a pyrazinacene-based probe ( TEG 8 -N14 ), we unexpectedly achieved discrimination of multiple cell states, including apoptosis, necrosis, necroptosis, and senescence, based on RNA/DNA changes. Specifically, TEG 8 -N14 selectively stains necrotic cells in live samples, while after fixation, it allows detection of ultraearly senescence in UV-vis–sensitive cells, providing approximately twofold greater informational content than existing RNA or DNA fluorophores. These findings break current imaging barriers by enabling comprehensive visualization of single-cell fate histories without being affected by UV-vis or genetic manipulation.
GPT-4o mini: Non-social science research article
Modular magnetic microrobot system for robust endoluminal navigation and high–radial force stent delivery in complex ductal anatomy
Lin Su, Dongdong Jin, Neng Xia, Bo Hao, Yihang Jiang, Qinglong Wang, Haojin Yang, Xin Wang, Kai Fung Chan, Xing Ma, Jacqueline Pui Wah Chung, Philip Wai Yan Chiu, Li Zhang
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Endoluminal stent implantation is a common intervention strategy for treating obstructive lesions, but conventional delivery systems struggle to reach deep, tortuous ducts. To overcome this limitation, we present a magnetically controlled microrobot that integrates two functional modules: a magnetic actuation (MA) module for agile navigation and an ultrasound-responsive self-expanding stent module (ST module) for lesion-specific dilation. The system uses a dynamically tunable assembly mechanism governed by rotational direction enabling integrated locomotion (clockwise) and on-demand module separation (counterclockwise) at stenotic sites. The platform is compatible with intraoperative ultrasound, allowing real-time navigation and thermally triggered expansion in physiological environments. By synergizing programmable magnetic actuation, ultrasound-mediated expansion, and clinical workflow compatibility, the robot can navigate tortuous phantom ducts, achieving controlled stent deployment within 3 seconds and complete expansion within 30 seconds, permitting minimally invasive treatment of biliary strictures. This work advances microrobotic stent delivery by overcoming key barriers to clinical translation in endoluminal interventions.
GPT-4o mini: Non-social science research article
The chloride intracellular channel 1 (CLIC1) is essential for microglial morphodynamics and neuroinflammation
Ali Rifat, Tom Bickel, Patricia Kreis, Thorsten Trimbuch, Julia Onken, Andranik Ivanov, Giulia Albertini, Dieter Beule, Michele Mazzanti, Harpreet Singh, Britta J. Eickholt, Bart De Strooper, Jörg R. P. Geiger, Christian Madry
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Microglial functions rely on their morphodynamic versatility and inflammatory response, yet the molecular determinants, particularly ion channels and receptors, remain poorly understood. Here, we identify chloride intracellular channel 1 (CLIC1), a protein known to exist in both soluble and membrane-associated forms, as highly enriched in human and murine microglia, with minimal expression in other brain cells. Acute blockade or genetic deletion of CLIC1 markedly attenuates microglial surveillance by reducing ramification and motility, without affecting chemotaxis. This phenotype is recapitulated in xenografted human microglia and human brain tissue. Mechanistically, CLIC1 effects involve interactions with actin-binding ezrin, radixin, and moesin (ERM) proteins, suggesting a role in linking the plasma membrane to the cytoskeleton. Contrary to its name, CLIC1 functions are chloride-independent and thus unlikely to reflect ion channel activity. This is supported by patch-clamp electrophysiology revealing lack of chloride conductance in surveillant microglia. Following ATP–evoked activation, CLIC1 blockade strongly suppresses NLRP3–dependent interleukin-1ÎČ release, suggesting therapeutic potential against neuroinflammation.
GPT-4o mini: Non-social science research article
A dynamic gene regulatory code drives synaptic development of hippocampal granule cells
Blanca Lorente-EcheverrĂ­a, Danie Daaboul, Jeroen Vandensteen, Gabriele Marcassa, Willem Naert, Joris Vandenbempt, Elke Leysen, Malou Reverendo, Ine Vlaeminck, Lise Vervloessem, Jochen Lamote, Suresh Poovathingal, Kristofer Davie, Keimpe Wierda, Dan Dascenco, Stein Aerts, Joris de Wit
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Connecting neurons into functional circuits requires the formation, maturation, and plasticity of synapses. While advances have been made in identifying individual genes regulating synapse development, the molecular programs orchestrating their action during circuit integration of neurons remain poorly understood. Here, we take a multiomic approach to reconstruct gene regulatory networks (GRNs), comprising transcription factors (TFs), regulatory regions, and predicted target genes, in hippocampal granule cells (GCs). We find a dynamic gene regulatory code, with early and late postnatal GRNs regulating cell morphogenesis and synapse organization and plasticity, respectively. Our results predict sequential regulations, with early-active TFs delaying the activation of later GRNs and their putative synaptic targets. Using a loss-of-function approach, we identify Bcl6 as a regulator of pre- and postsynaptic structural maturation and synaptic transmission and Smad3 as a modulator of inhibitory synaptic transmission in GCs. Together, these findings highlight the networks of key TFs and target genes orchestrating GC synapse development.
GPT-4o mini: Non-social science research article
In vivo expression of VCAM1 precedes nephron loss following kidney tubular necrosis
Anders M. Kristensen, Luca Bordoni, Marie B. Nielsen, Anna Faivre, Hanne Kidmose, Donato Sardella, Katherine E. Shipman, Nicoline V. Krogstrup, Joachim StĂžrling, Henrik Birn, Rune Enger, Ina Maria Schiessl
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Nephron loss is a key event during onset and progression of chronic kidney disease, yet the mechanisms dictating tubule repair versus atrophy remain poorly understood. While fibrosis has been proposed to drive progressive organ damage, antifibrotic therapies have failed in clinical trials. Here, we reveal that tubular vascular cell adhesion molecule 1 (VCAM1) expression precedes nephron loss, fibrosis, and long-term kidney dysfunction. Using serial intravital microscopy in transgenic mice, we track tubulointerstitial remodeling between injured and intact tissue over 3 weeks. VCAM1 is rapidly induced in a distinct subset of injured tubules, preceding atrophy with sustained fibroblast recruitment. However, fibroblasts remain confined to injury sites and do not cause secondary damage in uninjured tubules. Last, in human kidney transplant biopsies, tubular VCAM1 expression, but not kidney injury molecule 1, correlates negatively with early and 12-month graft function, underscoring its potential as a biomarker of adverse outcomes. These findings position VCAM1 as an early indicator of tubular fate and nephron loss.
GPT-4o mini: Non-social science research article
Individually addressable nanoscale OLEDs
Cheng Zhang, Björn Ewald, Leo Siebigs, Luca Steinbrecher, Maximilian Rödel, Thomas Fleischmann, Monika Emmerling, Jens Pflaum, Bert Hecht
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When reducing pixel size below the wavelength of light, the conventional stacked geometry of organic light-emitting diodes (OLEDs) is dominated by sharp nanoelectrode contours. This causes spatially imbalanced charge carrier transport and recombination resulting in low external quantum efficiency (EQE) and filament formation accelerating device failure. Here, we circumvent these limitations by selectively passivating nanoelectrode edges with an insulating layer, while simultaneously defining a nanoaperture in flat areas. We thereby ensure controlled charge carrier recombination and suppress filament growth. After demonstrating efficient hole injection by gold nanoelectrodes, we realize individually addressable subwavelength OLED pixels (300 nanometers by 300 nanometers) based on plasmonic gold patch antennas for light extraction. We achieve an EQE of 1%, a maximum luminance of 3000 candela per square meter, and fast response times exceeding video rates. Our results highlight a scalable strategy to overcome key electronic and optical bottlenecks of nanoscale optoelectronic devices and demonstrate the potential of plasmonic patch antennas for high-density, high-performance OLED integration.
GPT-4o mini: Non-social science research article
Kinesin-1 coordinates cross-talk between microtubule and actin cytoskeletons during dendritic cell migration
Pierre Duquesne, Céline Aoun, Mathieu Kurowska, Brieuc P. Perot, Kerui Zhang, Mounia Debili, Mirjana Weimershaus, François-Xavier Mauvais, Nicolas Cagnard, Nicolas Goudin, Bernardita Medel, Juan Eduardo Montero-Hermåndez, Linda Diedhiou, Jian-Dong Huang, Alain Fischer, GeneviÚve de Saint Basile, Mickaël M. Ménager, Pablo Vargas, Fernando E. Sepulveda, Gaël Ménasché
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Dendritic cells (DCs) are professional antigen (Ag)–presenting cells that excel in initiating adaptive immune responses by continuously scanning peripheral tissues for Ags. To facilitate efficient DC migration, constant cross-talk between actin and microtubules is required to coordinate cytoskeletal networks and actomyosin contractility, but the related mechanisms have not been extensively characterized. We show that mouse DCs lacking Kif5b (the heavy chain of kinesin-1) exhibit a major impairment in cell migration in vivo and in vitro. Mechanistically, kinesin-1 coordinates cytoskeletal cross-talk between actin and microtubules during DC migration by modulating negatively RhoA activity through its interaction with GEF-H1, thereby limiting GEF-H1’s availability in the cytosol. The same mechanism operates in human primary monocyte–derived DCs and regulates efficient migration in a confined environment. Thus, our results highlight kinesin-1 as a key regulator of DC migration, through its coordinated control of cytoskeletal dynamics.
GPT-4o mini: Non-social science research article
Targeting RRM2 with dual-modal theranostic smart nanoresponder overcomes osimertinib resistance and triggers immune remodeling in NSCLC
Jinyu Zhu, Kaihui Cui, Wenyuan Zhou, Xin Zhou, Yuan Yao, Chuanke Zhao, Yuwen Yang, Yang Liu, Jinping Tao, Zhi Yang, Hua Zhu, Bufu Tang, Nan Li
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Osimertinib (Osi) resistance limits its efficacy in EGFR-mutant non–small cell lung cancer (NSCLC). Here, we developed a pH-responsive cationic nanovesicle ( 124 I/Cy5.5-sO@FCLs), equipped with dual-modal positron emission tomography (PET) and fluorescence imaging capabilities, to enable dynamic monitoring of the role of ribonucleotide reductase M2 subunit (RRM2) disruption in overcoming Osi resistance and enhance targeted anticancer efficacy in NSCLC. RRM2 was identified as a critical driver of poor prognosis and Osi resistance in NSCLC. The 124 I/Cy5.5-sO@FCLs enabled real-time tracking of tumor targeting and biodistribution, and CRISPR-Cas9–mediated RRM2 disruption efficiently reversed Osi resistance and potentiated synergistic anticancer effects, which was attributed to counteracting TGF-ÎČ/Smad2/3–mediated epithelial-mesenchymal transition (EMT) and amplifying cGAS/STING-induced ferroptosis. Furthermore, the nanovesicles triggered STING-dependent immunogenic cell death (ICD), stimulating tumor infiltration of dendritic cells (DCs) and T cells; combination with anti–PD-L1 therapy augmented NSCLC regression. Collectively, 124 I/Cy5.5-sO@FCLs integrate gene editing with targeted therapies while enabling dynamic, quantitative monitoring, providing an approach for precision-targeted treatment in Osi-resistant NSCLC.
GPT-4o mini: Non-social science research article
Slowing artemisinin resistance in Africa
Maciej F. Boni, Issiaka Soulama, Jimmy Opigo, Oliver J. Watson, Bernhards Ogutu
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Diversifying antimalarial drug use across Africa offers the most immediate strategy to slow antimalarial resistance and limit potential increases in treatment failure rates.
GPT-4o mini: Non-social science research article
Distributed direct air capture by carbon nanofiber air filters
Ronghui Wu, Hernan E. Delgado, Yi Xie, Yuanke Chen, Gangbin Yan, Edward Luo, Qizhang Li, Qingsong Fan, Yu Han, Genesis M. Higueros, Amar Ruthen, Chenxi Sui, Adarsh Suresh, David B. Mitzi, Chong Liu, Amgad Elgowainy, Po-Chun Hsu
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The rising atmospheric CO 2 concentration is one of the biggest challenges human civilization faces. Direct air capture (DAC) that removes CO 2 from the atmosphere provides great potential in carbon neutralization. However, the massive land use and capital investment of centralized DAC plants and the energy-intensive process of adsorbent regeneration limit its wide employment. We develop a distributed carbon nanofiber (CNF)–based DAC air filter capable of adsorbing CO 2 downstream in ventilation systems. The DAC air filter not only has the potential to remove 596 MtCO 2 year −1 globally but can also decrease energy consumption in existing building systems. The CNF-based adsorbent has a capacity of 4 mmol/g and can be regenerated via solar thermal or electrothermal methods with low carbon footprints. Through life cycle assessment, the CNF air filter shows a carbon removal efficiency of 92.1% from cradle to grave. Additionally, techno-economic analysis estimates a cost of $209 to 668 in capturing and storing 1 tonne of CO 2 from direct air.
GPT-4o mini: Non-social science research article
Ultrafast, remote-controlled protonation reaction enables structural changes in a phytochrome
Madan Kumar Shankar, Lukas Grunewald, Weixiao Yuan Wahlgren, Brigitte Stucki-Buchli, Amke Nimmrich, Moona Kurttila, Anna-Lena Fischer, Giacomo Salvadori, Andrea Cellini, Piotr Maj, Atsarina Larasati Anindya, Elin Claesson, Fangjia Luo, Tek Narsingh Malla, Suraj Pandey, Takehiko Tosha, Nuemket Nipawan, Shigeki Owada, Kensuke Tono, Rie Tanaka, Emina A. Stojković, Dmitry Mozorov, Pasi Myllyperkiö, Tatu Kumpulainen, Heikki Takala, Marius Schmidt, Janne A. Ihalainen, Sebastian Westenhoff
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In photoactive proteins, coupling between the chromophore and protein matrix is exquisitely tuned. Proton transfer reactions can mediate this coupling, as in proton-coupled electron transfer and excited-state proton transfer. Additional mechanisms involving proton dislocations may exist but remain undiscovered. Here, we present a femtosecond crystallographic movie of the phytochrome from Deinococcus radiodurans . The structures reveal a space-conserving mechanism for rotation of the D-ring in the excited state. We observe rearrangement of a conserved hydrogen bond network within 300 fs, which precedes the isomerization reaction of the chromophore. Aided by molecular modeling and independently confirmed by femtosecond infrared spectroscopy, we attribute these changes to a protonation shift of the strictly conserved histidine-260. Although this histidine lies close to the photoexcited π-orbitals of the chromophore, it is not directly part of them. We propose that this “remote-controlled” proton transfer relays photoexcitation near-instantaneously to the protein matrix. This mechanism may be widely used to transduce cofactor signals to their hosting enzymes.
GPT-4o mini: Non-social science research article
Declining ocean greenness and phytoplankton blooms in low to mid-latitudes under a warming climate
Zhongkun Hong, Di Long, Kaiyue Shan, Jian-Min Zhang, R. Iestyn Woolway, Maofeng Liu, Michael E. Mann, Hongwei Fang
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Marine phytoplankton are crucial to oceanic ecosystems, yet trends in their activity, monitored through chlorophyll a, remain uncertain due to observational limitations. We generated an ocean chlorophyll a dataset (2001 to 2023) across low to mid-latitudes (45°N to 45°S) using multisource data and a deep learning approach. Our analysis suggests widespread decline in ocean greenness, with chlorophyll a concentrations decreasing at a rate of (−0.35 ± 0.10) × 10 −3 milligrams per cubic meter per year (mg m −3  year −1 ). The decline is steeper in coastal regions [(−0.73 ± 0.22) × 10 −3 mg m −3  year −1 ]. The frequency of high chlorophyll a concentration events in coastal waters has decreased at a relative rate of −1.78% per year. These trends are predominantly driven by rising sea surface temperatures, which enhance ocean stratification, suppress nutrient upwelling, and limit phytoplankton growth. These findings suggest a long-term decline in marine primary production and a reduced occurrence of phytoplankton blooms, potentially disrupting trophic interactions and oceanic carbon cycling.