I checked 6 multidisciplinary journals on Sunday, July 12, 2026 using the Crossref API. For the period July 05 to July 11, I found 23 new paper(s) in 5 journal(s).

Nature

GPT-4o mini: Non-social science research article
LARES-2 satellite measures frame-dragging effect around the Earth
Ignazio Ciufolini, Antonio Paolozzi, Erricos C. Pavlis, John C. Ries, Claudio Paris, Emiliano Ortore, Richard Matzner, Magdalena Kuzmicz-Cieslak, Darpanjeet Deka, Despina E. Pavlis, Patrick Schreiner, Wei-Tou Ni, Roger Penrose, Vahe Gurzadyan
Full text
Laser-ranging provides some of the most precise tests of gravity in the weak-field regime, enabling experimental probes of Einstein’s general theory of relativity using the Earth as a laboratory1. A central test of general relativity is the amplitude of frame-dragging, that is, the dragging of spacetime by a rotating mass2,3,4,5. Owing to its optimized orbit, a very low surface-to-mass ratio and a highly uniform retroreflector distribution, we show that the recently launched Laser Relativity Satellite 2 (LARES-2)6—together with its predecessor LAGEOS and the GRACE satellites—enables a measurement of terrestrial frame-dragging with a relative uncertainty at the one-part-in-a-thousand level, representing an order-of-magnitude improvement over previous Solar System determinations. This result provides a stringent confirmation of general relativity in the near-Earth environment and places strong constraints on alternative gravitational models that predict deviations specifically in frame-dragging, including scalar–tensor extensions such as Chern–Simons gravity7,8. Beyond tests of fundamental physics, the combined analysis of LARES-2 and LAGEOS also improves the determination of Earth’s lunisolar tides, illustrating the broader geophysical impact of high-precision relativistic satellite experiments.
GPT-4o mini: Non-social science research article
Non-genotoxic transplantation and in vivo selection through epitope editing
Gabriele Casirati, Andrea Cosentino, Marta Freschi, Jing Zeng, Adele Mucci, Sébastien Levesque, Nola Neri, Enrico Drago, Viola Carzaniga, Francesco Romano, Varun Katta, Azusa Matsubara, Yichao Li, Mohammed S. Mahmoud, Moisés Chåvez-Navarro, Christian Brendel, John P. Manis, Shengdar Tsai, Danilo Pellin, Daniel Bauer, Pietro Genovese
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The short-term and long-term effects of genotoxic pre-transplant conditioning remain barriers to the broader application of haematopoietic stem/progenitor cell (HSPC) transplantation and gene therapies1,2,3,4. Although monoclonal antibodies targeting KIT have been proposed as alternatives to chemotherapy or radiotherapy5,6,7, their pharmacokinetics hinder clinical applications owing to the risk of depleting transplanted HSPCs. Here, to address this issue, we identified amino acid changes in the extracellular domain of KIT that disrupt the binding of two therapeutic monoclonal antibodies8,9, which impair stem cell factor (SCF)-mediated signalling without affecting KIT expression or functionality. We exploited adenine base editing10 or prime editing11 to efficiently introduce these mutations in HSPCs and combined them with the disruption of the BCL11A erythroid enhancer to promote expression of fetal haemoglobin (HbF)12,13, a therapeutic approach for several haemoglobinopathies. This strategy enables in vivo co-selection of gene-engineered cells to reach the threshold required to provide therapeutic benefit in patients affected by sickle cell disease and ÎČ-thalassaemia. We show progressive enrichment of KIT plus BCL11A multiplex-edited haematopoiesis under selective pressure with KIT monoclonal antibody, in vitro and in vivo. We report that extended treatment with anti-KIT regimens leads to superior in vivo enrichment while avoiding clonal selection, as assessed by a lentiviral barcoded library. Finally, by overcoming the limitations of monoclonal antibody pharmacokinetics, epitope editing enables novel haematopoietic replacement regimens that are not limited by on-target graft elimination, allowing prolonged immune-based conditioning that maximizes haematopoietic niche clearance without chemo-radiotherapy or monoclonal antibody wash-out.
GPT-4o mini: Non-social science research article
In vivo feasibility study of humanoid robots in surgery
Zekai Liang, Nikita Thareja, Peihan Zhang, Calvin Joyce, Soofiyan Atar, Florian Richter, Garth Jacobsen, Shanglei Liu, Ryan Broderick, Michael Yip
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Recent advances in actuation, control and learning have rapidly pushed humanoid robots from a distant vision towards near-term real-world deployment1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18. Healthcare is a particularly pressing domain, in which staffing shortages and increasing care demand are widening the gap between clinical workload and available skilled labour19,20,21. Although current automation has largely focused on digital and logistical tasks22, much hospital work remains embodied, requiring mobility, manipulation and safe interaction in human-designed environments. Humanoid form factors offer unique potential, particularly for assisting with surgical tasks. Traditionally, robotic systems for surgery are purpose-built platforms such as Intuitive Surgical’s da Vinci Surgical System23,24, and it remains unclear how close current humanoid systems are to meeting the precision, control and safety requirements of minimally invasive surgery. Here we present a systematic evaluation of contemporary humanoid technology for laparoscopic surgical tasks. We develop a humanoid-based laparoscopic teleoperation framework using general-purpose instruments and assess its abilities through benchtop characterization, dry-laboratory user studies spanning diverse surgical experience levels and in vivo porcine studies. Across these evaluations, we quantify technical feasibility, task performance and clinical readiness relative to established surgical platforms. Together, our study provides an evidence-based assessment of current humanoid abilities and limitations for surgical applications, highlighting both their promise and key technical challenges that must be addressed before clinical deployment.
GPT-4o mini: Non-social science research article
Publisher Correction: A 98-qubit trapped-ion quantum computer with all-to-all connectivity
Anthony Ransford, M. S. Allman, Jake Arkinstall, J. P. Campora, Samuel F. Cooper, Robert D. Delaney, Joan M. Dreiling, Brian Estey, Caroline Figgatt, Alex Hall, Ali A. Husain, Akhil Isanaka, Colin J. Kennedy, Nikhil Kotibhaskar, Ivaylo S. Madjarov, Karl Mayer, Alistair R. Milne, Annie J. Park, Adam P. Reed, Riley Ancona, Molly P. Andersen, Pablo Andres-Martinez, Will Angenent, Liz Argueta, Benjamin Arkin, Leonardo Ascarrunz, William Baker, Corey Barnes, John Bartolotta, Jordan Berg, Ryan Besand, Bryce Bjork, Matt Blain, Paul Blanchard, Robin Blume-Kohout, Matt Bohn, AgustĂ­n Borgna, Daniel Y. Botamanenko, Robert Boutelle, Natalie Brown, Grant T. Buckingham, Nathaniel Q. Burdick, William Cody Burton, Varis Carey, Christopher J. Carron, Joe Chambers, Jia Wen Chan, John Children, Victor E. Colussi, Steven Crepinsek, Andrew Cureton, Joe Davies, Daniel Davis, Matthew DeCross, David Deen, Conor Delaney, Davide DelVento, B. J. DeSalvo, Jason Dominy, Sydney Drotar, Ross Duncan, Vanya Eccles, Alec Edgington, Neal Erickson, Stephen Erickson, Christopher T. Ertsgaard, Jay Esposito, Bruce Evans, Tyler Evans, Maya I. Fabrikant, Andrew Fischer, Cameron Foltz, Michael Foss-Feig, David Francois, Brad Freyberg, Charles Gao, Robert Garay, Jane Garvin, David M. Gaudiosi, Christopher N. Gilbreth, Josh Giles, Erin Glynn, Jeff Graves, Azure Hansen, David Hayes, Lukas Heidemann, Bob Higashi, Tyler Hilbun, Jordan Hines, Ariana Hlavaty, Kyle Hoffman, Ian M. Hoffman, Craig Holliman, Isobel Hooper, Bob Horning, James Hostetter, Daniel Hothem, Jack Houlton, Jared Hout, Ross Hutson, Ryan T. Jacobs, Trent Jacobs, Melf Johannsen, Jacob Johansen, Loren Jones, Sydney Julian, Ryan Jung, Aidan Keay, Todd Klein, Mark Koch, Ryo Kondo, Chang Kong, Asa Kosto, Alan Lawrence, David Liefer, Michelle Lollie, Dominic Lucchetti, Nathan K. Lysne, Christian Lytle, Callum MacPherson, Andrew Malm, Spencer Mather, Brian Mathewson, Daniel Maxwell, Lauren McCaffrey, Hannah McDougall, Robin Mendoza, David B. Miller, Michael Mills, Richard Morrison, Louis Narmour, Nhung Nguyen, Lora Nugent, Scott Olson, Daniel Ouellette, Jeremy Parks, Zach Peters, Timothy A. Peterson, Jessie Petricka, Juan M. Pino, Frank Polito, Andrew C. Potter, Matthias Preidl, Gabriel Price, Timothy Proctor, McKinley Pugh, Noah Ratcliff, Daisy Raymondson, Peter Rhodes, Conrad Roman, Craig Roy, Ciaran Ryan-Anderson, Fernando Betanzo Sanchez, George Sangiolo, Tatiana Sawadski, Andrew Schaffer, Peter Schow, Jon Sedlacek, Henry Semenenko, Peter Shevchuk, Susan Shore, Peter Siegfried, Kartik Singhal, Seyon Sivarajah, Thomas Skripka, Lucas Sletten, Ben Spaun, R. Tucker Sprenkle, Paul Stoufer, Mariel Tader, Stephen F. Taylor, Travis H. Thompson, Raanan Tobey, Anh Tran, Tam Tran, Grahame Vittorini, Curtis Volin, Jim Walker, Sam White, Garrett R. Williams, Douglas Wilson, Quinn Wolf, Chester Wringe, Kevin Young, Jian Zheng, Kristen Zuraski, Charles H. Baldwin, Alex Chernoguzov, John P. Gaebler, Steven J. Sanders, Brian Neyenhuis, Russell Stutz, Justin G. Bohnet
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GPT-4o mini: Non-social science research article
Single-phase gradient-solvation-electrolyte-stabilized Li metal batteries
Wujie Yang, Jianfeng Cai, Aoyuan Chen, Xiang Li, Ping He, Haoshen Zhou
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Ether-based electrolytes have shown great success for lithium metal electrodes1,2,3,4,5. However, during the charging process of high-voltage full cells, the desolvation of solvents and anions to accommodate Li ions released from the positive electrode exacerbates oxidative decomposition of the electrolyte6. In addition, the continuous consumption of components over extended cycling substantially alters the solvation structure, resulting in deteriorating redox stability. Here we incorporate a targeted ligand anti-solvent (TLAS) into an anion-rich ether-based electrolyte. The TLAS barely participates in the solvation of Li+ owing to its relatively weaker association ability in a static state. Under the strong electric field of high-voltage full cells, the orientation and distribution of the TLAS undergo substantial transformation, with coordination ability activated on the positive electrode surface. The TLAS-mediated dynamic solvation behaviour bypasses the inherent decoordination and recoordination of solvents and anions on the positive electrode in conventional electrolyte systems, thus minimizing electrolyte reconstruction and interphase deterioration. Leveraging this gradient solvation electrolyte, we develop a 450 Wh kg−1 lithium metal pouch cell that achieves a long cycle life exceeding 750 cycles (80% capacity retention). Furthermore, we validated a lithium metal pouch cell with a high energy density of 605 Wh kg−1, which achieves 150 cycles with 96% capacity retention. This gradient solvation strategy provides a feasible pathway of electrolyte engineering for metal-ion batteries.
GPT-4o mini: Non-social science research article
Reconfigurable mmWave microchips co-integrating hBN switches on GaN
Sebastian Pazos, Andrés Fontana, Yaqing Shen, Yue Yuan, Yiyang Yu, Atif Shamim, Dimitra Psychogiou, Mario Lanza
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Monolithic microwave integrated circuits (MMICs) are an emerging technology that is expected to substantially improve telecommunications in the next few years1,2. MMICs use application-specific semiconductors to meet the performance needs of 5G standards and beyond; however, integrating high-frequency switches into these platforms is very demanding in terms of area and cost and doing so is also a bottleneck for performance3. Memristive radio-frequency switches are an appealing alternative due to their easy fabrication and high device-level electrical performance, but their use in circuit implementations of MMICs has never been realized4. Here we demonstrate programmable millimetre-wave (mmWave) gallium nitride (GaN) MMICs fabricated with memristive radio-frequency switches made from two-dimensional layered hexagonal boron nitride (hBN) integrated directly on the back-end-of-line. We fabricated back-end-of-line wideband switches operating up to 100 GHz with insertion losses as low as 0.3 dB and isolation better than 15 dB. The switches delivered long-term state retention (2 weeks), stable on-state resistance at 175 °C, linear power handling within 0.28 dB measured up to 18 dBm, and an extrapolated 1-dB compression point mean of 30.52 dBm. We use one-transistor, one-memristor cell integration for the switch drivers, achieving 3,250 cycles of endurance, an improvement for two-dimensional-material-based memristive radio-frequency switches. Finally, we demonstrate the implementation of memristive-configurable attenuators, power dividers and programmable resonators on the GaN MMIC platform.
GPT-4o mini: Non-social science research article
Anatomy of a seafloor spreading event captured by in situ seismogeodesy
Jean-Yves Royer, Jean-Arthur Olive, Sara Bazin, Valérie Ballu, Anne Briais, Lise Retailleau, Pierre-Yves Raumer, Edgar Lenhof, character(0), J. Beesau, R. Daniel, D. Dausse, S. Furst, A. Gros-Martial, C. Guerin, E. Klein, D. Pacaud, C. Poitou, J. Tanrin, L. Testut
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Over geological time, the growth of the ocean floor involves magmatic and tectonic extension 1 at mid-ocean ridges (MORs). Because seismogeodetic monitoring of these submarine plate boundaries remains challenging 2–7 , little is known about how these systems operate on yearly timescales. Here we report the first, to our knowledge, in situ observation of a rifting event at a MOR segment that combines hydroacoustic, direct-path ranging and bottom-pressure measurements, with repeated seafloor mapping. This event started on 26 April 2024 at the axis of the Southeast Indian Ridge (SEIR) near 37° S, two months after instruments had been deployed across the ridge axis and nearby Amsterdam transform fault (TF). The event began as a rapidly migrating swarm of extensional seismicity along the axial valley. It caused 4 m of subsidence of the valley floor and more than a metre of horizontal extension across the valley. We interpret this as the deflation of a sill-like reservoir feeding propagating dykes along the ridge axis. The dykes eventually led to the outpouring of about 160 million m 3 of lava at the seafloor in about 16 days, while inducing both seismic and aseismic slip on valley-bounding normal faults and finally triggering seismic activity on the abutting TFs. Large-scale aseismic slip induced by magmatic processes could therefore be the primary mechanism by which MOR normal faults accrue their displacement, which would account for their well-documented seismic deficit 8,9 .
GPT-4o mini: Non-social science research article
Air-permeable hydrogels through viscoelastic phase separation of aerogels
Xiao-Yun Yan, Shucong Li, Won Jun Song, Runze Li, Aarosh Dahal, Bastien F. G. Aymon, Haodong Hu, Deep K. Malu, Gabriella E. Carreira, Jingjing Wu, Gengxi Lu, Bolei Deng, Jiayi Liu, Siqin Yu, Shu Wang, Eric Lu, Hyunhee Lee, Hui Xu, Anqi Chen, Yuxing Yao, James H. Zhang, Chen Gong, Yiyuan Sun, Jeong-Yun Sun, David A. Weitz, Casey O’Brien, Yuhang Hu, Zachary P. Smith, Aditya Kumar, Xuanhe Zhao
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Hydrogels are widely used in biomedical interfaces, in which effective gas exchange (for example, O2, CO2) within a water-rich environment is essential. However, hydrogels show intrinsically limited air exchange efficiency, owing to the low solubility (C) and diffusivity (D) of non-polar gases in the polar water medium1. This limitation poses a substantial bottleneck in long-term applications, such as wearable health monitors2,3,4,5,6,7 and tissue engineering8,9,10,11,12. Existing methods13,14,15,16 to enhance air permeability suffer from poor robustness and/or an inherent trade-off between permeability and water content (for example, <50 vol%). Here we introduce a viscoelastic phase separation17 (VPS)-enabled strategy to create a non-collapsible, air-rich network in high-water-content hydrogels, achieving a record-high oxygen permeability of 185 barrer with 70 vol% water—a tenfold increase compared with pristine hydrogels. VPS, a ubiquitous phenomenon in soft matter, is used to drive hydrophobic, dry gas particles within a hydrophilic, wet medium into a thin, stable three-dimensional network. This approach allows the facile and scalable fabrication of air-permeable hydrogels across diverse chemistries and form factors. Physiological tests over a 10-day continuous wear condition confirmed their effectiveness in preventing fluid accumulation and maintaining skin health. This strategy paves the way for hydrogels in long-term biomedical applications in which efficient and sustained air exchange becomes critical.
GPT-4o mini: Non-social science research article
Chromatin landscape and epigenetic heterogeneity of acute myeloid leukaemia
Yotaro Ochi, Markus Liew-Littorin, Yasuhito Nannya, Sofia Bengtzen, Benedicte Piauger, Stefan Deneberg, Martin JĂ€dersten, Vladimir Lazarevic, Jörg Cammenga, Anna Robelius, Lovisa Wennström, Emma Ölander, Senji Kasahara, Nobuhiro Hiramoto, Nobuhiro Kanemura, Nobuo Sezaki, Maki Sakurada, Makoto Iwasaki, Junya Kanda, Yasunori Ueda, Satoshi Yoshihara, Tom Erkers, Nona Struyf, Yu Watanabe, Masanori Motomura, Masahiro M. Nakagawa, Ryunosuke Saiki, Hidehito Fukushima, Koji Okazaki, Suguru Morimoto, Akinori Yoda, Rurika Okuda, Shintaro Komatsu, Guoxiang Xie, Albin Österroos, Ayana Kon, Lanying Zhao, Yuichi Shiraishi, Takayuki Ishikawa, Satoru Miyano, Kotoe Katayama, Seiya Imoto, Shuichi Matsuda, Akifumi Takaori-Kondo, Hiroyuki Aburatani, Hiroshi I. Suzuki, Olli Kallioniemi, Gunnar Juliusson, Martin Höglund, Sören Lehmann, Seishi Ogawa
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Acute myeloid leukaemia (AML) is an aggressive blood cancer characterized by the unregulated proliferation of immature myeloblasts. Gene mutations have been shown to have a large effect on pathogenesis, inter-tumour heterogeneity and clinical outcomes in AML1,2,3,4,5,6,7,8; however, the role of epigenetic alterations in these respects has been investigated less extensively. Here we use ATAC-seq (assay for transposase-accessible chromatin with sequencing) in a cohort of 1,563 individuals with a recent diagnosis of AML (the ‘eCHROMA’ cohort) to show that AML can be classified into 16 subgroups on the basis of chromatin accessibility profiles. Multiomics analyses of gene mutations, the transcriptome, DNA methylation and histone marks show that these ATAC subgroups exhibit distinct driver mutations, differentiation states, gene expression, DNA methylation and super-enhancer profiles, and are also associated with clinical outcomes. These findings were validated in independent cohorts. Single-cell ATAC sequencing reveals that all leukaemic cells in each subgroup share a common chromatin accessibility profile, which suggests that subgroup-specific epigenomic fingerprints underlie the ATAC-based classification. Mechanistically, the subgroups have distinct gene-regulatory networks that are driven by the activities of key transcription factors in haematopoiesis, and in which subgroup-specific super-enhancers have a pivotal role. Multiomics single-cell analysis further reveals deregulated trajectories of differentiation coupled with chromatin accessibility and gene expression. Notably, ATAC subgroups have an independent prognostic effect, compared with genomic classification, and are associated with particular drug sensitivities. In summary, ATAC-based chromatin profiling, combined with multiomics data, provides insights into AML pathogenesis beyond genomics and constitutes a valuable resource for AML research.
GPT-4o mini: Non-social science research article
Diet–microbiome synergy underlies obesity-associated immunotherapy efficacy
Lysanne Desharnais, Anikka Swaby, Meriem Messaoudene, Samuel Doré, Miranda W. Yu, Benoit Fiset, Valérie Breton, Mayra Ponce, Yongjia Hu, Liam Wilson, Mark Sorin, Ye Wang, Ken Dewar, Michael Pollak, Arielle Elkrief, Bertrand Routy, Logan A. Walsh, Daniela F. Quail
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Physiological host factors, such as the gut microbiome and obesity, independently influence anti-tumour immunity and responses to immune checkpoint inhibitors (ICIs)1, with high body mass index (BMI) having an unexpected link with greater ICI efficacy2,3,4,5,6. However, how these factors interact across diverse dietary contexts remains unclear. Here, using 12 mouse diet models that reflect a spectrum of obesity biology, we characterize diet-driven metabolic, immune and gut microbiota features associated with ICI sensitivity. We find that obesity-associated ICI responses are poorly correlated with metabolic dysfunction and are instead dependent on the diet–gut axis. Obesogenic diets promote a robust and persistent gut microbial ecosystem that is capable of restoring ICI sensitivity following a short-term diet switch or fecal microbiota transplants (FMTs) from non-responder models. Monocolonization of germ-free mice with favourable bacteria such as Lactobacillus johnsonii, together with an obesogenic diet, synergistically promotes tumour regression through an enrichment of microbiota-derived aromatic amino acid metabolites. Moreover, human-to-mouse FMT from donors with a high BMI enhanced ICI efficacy compared with donors with a normal BMI, and an obesogenic diet restored sensitivity following FMT from a non-responder patient. Our study provides insight on epidemiological associations between BMI and ICI efficacy, and suggests that immunomodulatory synergy between diet and the gut microbiota could be leveraged to improve ICI outcomes and FMT interventions.
GPT-4o mini: Non-social science research article
Architecture of the 8 MDa Hdr–Vhu–Fwd super-assembly in class I methanogens
Sophia Paul, Tomas C. Pascoa, Max A. Klamke, Stefan Bohn, Frank Abendroth, Darja Deobald, Olalla VĂĄzquez, Sven T. Stripp, Jan M. Schuller
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Methanogens are central to global carbon cycling and among the largest biological sources of methane, a potent greenhouse gas 1 . At the heart of their energy metabolism lies the Hdr–Vhu–Fwd super-assembly, which couples H 2 oxidation with CO 2 reduction through flavin-based electron bifurcation. Here we present the cryogenic electron microscopy structure of the Hdr–Vhu–Fwd super-assembly from Methanococcus maripaludis , revealing an 8 MDa complex comprising 252 polypeptide chains and over 600 redox cofactors. Cryo-electron tomography further support that this super-assembly forms an intact structure within the cytoplasm of intact cells. This architecture comprises two hexameric HdrABC–Vhu rings linked by a tetrameric FwdF core, forming a continuous, circular electron chain. In this unique arrangement, 12 polyferredoxin subunits (VhuB) connect the Vhu–Hdr and Fwd complexes, thereby coupling electron bifurcation with CO 2 reduction and directly linking the last and the first step of methanogenesis. Moreover, we identify a modular variant of the complex in which the [NiFe]-hydrogenase Vhu is substituted by tungsten-containing formate dehydrogenase (FdhAB), indicating flexible integration of electron-input modules facilitating metabolic adaptation under diverse environmental conditions 2 . Analysis of the taxonomic distribution reveals that this architecture is specific to class I methanogens and is distinct from the smaller Hdr–Fmd complex of class II 3 . Together, our study reveals that the the Hdr–Vhu–Fwd super-assembly has a modular and adaptable bioenergetic assembly, suggesting a lineage-specific architecture to adapt to diverse anaerobic niches.
GPT-4o mini: Non-social science research article
Aneuploidy selects for the acquisition of driver genes in breast cancer
Khalid N. Al-Zahrani, Ellen R. Langille, Jocelyn Nurtanto, Andreea Obersterescu, Katie Teng, Christopher Lowden, Julien Dessapt, Cynthia H. Chiu, Lauren V. Caldwell, David P. Cook, Miguel A. PĂ©rez-Castro, Jacob M. Berman, Ricky Tsai, Alexander T. Bahcheli, Geraldine Mbamalu, Shifei Wu, Masahiro Narimatsu, Adele G. Lopes, Iosifina Fotiadou, Kin Chan, Linkang Zhang, K. W. Annie Bang, Michael J. Parsons, Larissa Mourao, E. Idil Temel, Liddy McCulla, Palavalasa Sravya, Li Zhang, Peter Sajjakulnukit, Costas A. Lyssiotis, Alexander D. Borowsky, Colinda L. G. J. Scheele, Daniel R. Wahl, Hartland W. Jackson, Katherine S. Stewart, Elaine Fuchs, Sean E. Egan, Miguel Angel Pujana, JĂŒri Reimand, Jeffrey L. Wrana, Daniel Schramek
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Chromosome instability is highly prevalent in cancer and drives large-scale chromosomal imbalances, known as aneuploidies1,2,3,4. How aneuploidy contributes to tumorigenesis remains difficult to study due to the vast numbers of genes affected. Here we established a CRISPR knockout- and activation-linked assay (CRISPR-KOALA), enabling high-throughput bidirectional genetic screens in immunocompetent mouse models of cancer. We developed a compendium of the ten most frequent human chromosome-arm-level alterations in basal-like breast cancer (BLBC), a disease type that is driven by large copy-number alterations (CNAs)5,6,7,8. Using CRISPR-KOALA, we screened the mouse orthologues of 3,752 genes on these arms and identified 90 cancer driver genes, the function of the vast majority of which is unknown. These genes drive distinct signalling pathways including MAPK, HIPPO and WNT, reflecting the high degree of BLBC heterogeneity. Manipulating the identified cancer driver genes overcomes the need for CNAs in Trp53-mutant BLBC mouse models. Mechanistically, we identify that PLGRKT is a potent oncogene that lies on chromosome 9p and show that its tumour-promoting activity is associated with highly stress-resistant mitochondria and an increased ability to detoxify reactive oxygen species. Together, our findings reveal that arm-level CNAs can function to select specific driver genes to promote heterogeneous biological processes.
GPT-4o mini: Non-social science research article
Observation of Floquet rotational super-radiance
Hadiseh Nasari, Hady Moussa, Yoshiaki Kasahara, Arno Thielens, Andrea AlĂč
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Time-driven systems provide a framework for controlling waves through spatio-temporal modulation, which enables the synthesis of effective motion without mechanical displacement1,2,3,4,5,6,7. Within this framework, travelling-wave modulations can emulate moving media and give rise to phenomena such as Doppler-induced non-reciprocity8,9,10. A related effect is the extraction of energy from rotating media, which has been theoretically predicted to occur when waves experience sufficiently large rotational Doppler shifts11,12,13,14,15,16,17. Experimental access to this regime has remained limited due to the extreme rotation speeds required in mechanically rotating systems18,19,20,21. Here we show that Floquet-induced rotation enables access to such ultrafast rotational regimes using purely spatio-temporal modulation. When spinning at effective superluminal speeds, angular-momentum bandgaps emerge in the band structure of the underlying space–time crystal. These gaps host parametric processes that efficiently extract energy from the Floquet-rotating medium, resulting in angular-momentum-selective amplification of orbital waves within a dissipation-shaped spectral bandwidth. We realize this effect experimentally in a ring network of time-modulated resonators, where we observe a Floquet regime of rotational super-radiance mediated by non-Hermitian and parametric dynamics in space–time structured media. These results demonstrate a controllable platform for studying rotational energy transfer and angular-momentum-dependent wave amplification in space–time-modulated media.
GPT-4o mini: Non-social science research article
Reinforcement learning control of quantum error correction
Volodymyr Sivak, Alexis Morvan, Michael Broughton, Rodrigo G. Cortiñas, Johannes Bausch, Andrew W. Senior, Matthew Neeley, Alec Eickbusch, Noah Shutty, Laleh Aghababaie Beni, James S. Spencer, Francisco J. Heras, Thomas Edlich, Dmitry Abanin, Amira Abbas, Rajeev Acharya, Georg Aigeldinger, Ross Alcaraz, Sayra Alcaraz, Trond I. Andersen, Markus Ansmann, Frank Arute, Kunal Arya, Walt Askew, Nikita Astrakhantsev, Juan Atalaya, Brian Ballard, Joseph C. Bardin, Hector Bates, Andreas Bengtsson, Majid Bigdeli Karimi, Alexander Bilmes, Simon Bilodeau, Felix Borjans, Alexandre Bourassa, Jenna Bovaird, Dylan Bowers, Leon Brill, Peter Brooks, David A. Browne, Brett Buchea, Bob B. Buckley, Tim Burger, Brian Burkett, Nicholas Bushnell, Jamal Busnaina, Anthony Cabrera, Juan Campero, Hung-Shen Chang, Silas Chen, Ben Chiaro, Liang-Ying Chih, Agnetta Y. Cleland, Bryan Cochrane, Matt Cockrell, Josh Cogan, Roberto Collins, Paul Conner, Harold Cook, William Courtney, Alexander L. Crook, Ben Curtin, Martin Damyanov, Sayan Das, Dripto M. Debroy, Sean Demura, Paul Donohoe, Ilya Drozdov, Andrew Dunsworth, Valerie Ehimhen, Aviv Moshe Elbag, Lior Ella, Mahmoud Elzouka, David Enriquez, Catherine Erickson, Vinicius S. Ferreira, Marcos Flores, Leslie Flores Burgos, Ebrahim Forati, Jeremiah Ford, Austin G. Fowler, Brooks Foxen, Masaya Fukami, Alan Wing Lun Fung, Lenny Fuste, Suhas Ganjam, Gonzalo Garcia, Christopher Garrick, Robert Gasca, Helge Gehring, Robert Geiger, Élie Genois, William Giang, Dar Gilboa, James E. Goeders, Edward C. Gonzales, Raja Gosula, Stijn J. de Graaf, Alejandro Grajales Dau, Dietrich Graumann, Joel Grebel, Alex Greene, Jonathan A. Gross, Jose Guerrero, LoĂŻck Le Guevel, Tan Ha, Steve Habegger, Tanner Hadick, Ali Hadjikhani, Michael C. Hamilton, Matthew P. Harrigan, Sean D. Harrington, Jeanne Hartshorn, Stephen Heslin, Paula Heu, Oscar Higgott, Reno Hiltermann, Hsin-Yuan Huang, Mike Hucka, Christopher Hudspeth, Ashley Huff, William J. Huggins, Evan Jeffrey, Shaun Jevons, Zhang Jiang, Xiaoxuan Jin, Chaitali Joshi, Pavol Juhas, Andreas Kabel, Dvir Kafri, Hui Kang, Kiseo Kang, Amir H. Karamlou, Ryan Kaufman, Kostyantyn Kechedzhi, Tanuj Khattar, Mostafa Khezri, Seon Kim, Can M. Knaut, Bryce Kobrin, Fedor Kostritsa, John Mark Kreikebaum, Ryuho Kudo, Ben Kueffler, Arun Kumar, Vladislav D. Kurilovich, Vitali Kutsko, Nathan Lacroix, David Landhuis, Tiano Lange-Dei, Brandon W. Langley, Pavel Laptev, Kim-Ming Lau, Justin Ledford, Joy Lee, Kenny Lee, Brian J. Lester, Wendy Leung, Lily Li, Wing Yan Li, Ming Li, Alexander T. Lill, William P. Livingston, Matthew T. Lloyd, Aditya Locharla, Laura De Lorenzo, Daniel Lundahl, Aaron Lunt, Sid Madhuk, Aniket Maiti, Ashley Maloney, Salvatore MandrĂĄ, Leigh S. Martin, Orion Martin, Eric Mascot, Paul Masih Das, Dmitri Maslov, Melvin Mathews, Cameron Maxfield, Jarrod R. McClean, Matt McEwen, Seneca Meeks, Kevin C. Miao, Zlatko K. Minev, Reza Molavi, Sebastian Molina, Shirin Montazeri, Charles Neill, Michael Newman, Anthony Nguyen, Murray Nguyen, Chia-Hung Ni, Murphy Yuezhen Niu, Logan Oas, Raymond Orosco, Kristoffer Ottosson, Alice Pagano, Agustin Di Paolo, Sherman Peek, David Peterson, Alex Pizzuto, Elias Portoles, Rebecca Potter, Orion Pritchard, Michael Qian, Chris Quintana, Arpit Ranadive, Matthew J. Reagor, Rachel Resnick, David M. Rhodes, Daniel Riley, Gabrielle Roberts, Roberto Rodriguez, Emma Ropes, Lucia B. De Rose, Eliott Rosenberg, Emma Rosenfeld, Dario Rosenstock, Elizabeth Rossi, Pedram Roushan, David A. Rower, Robert Salazar, Kannan Sankaragomathi, Murat Can Sarihan, Kevin J. Satzinger, Max Schaefer, Sebastian Schroeder, Henry F. Schurkus, Aria Shahingohar, Michael J. Shearn, Aaron Shorter, Vladimir Shvarts, Spencer Small, W. Clarke Smith, David A. Sobel, Barrett Spells, Sofia Springer, George Sterling, Jordan Suchard, Aaron Szasz, Alexander Sztein, Madeline Taylor, Jothi Priyanka Thiruraman, Douglas Thor, Dogan Timucin, Eifu Tomita, Alfredo Torres, M. Mert Torunbalci, Hao Tran, Abeer Vaishnav, Justin Vargas, Sergey Vdovichev, Guifre Vidal, Catherine Vollgraff Heidweiller, Meghan Voorhees, Steven Waltman, Jonathan Waltz, Shannon X. Wang, Brayden Ware, James D. Watson, Yonghua Wei, Travis Weidel, Theodore White, Kristi Wong, Bryan W. K. Woo, Christopher J. Wood, Maddy Woodson, Cheng Xing, Z. Jamie Yao, Ping Yeh, Bicheng Ying, Juhwan Yoo, Noureldin Yosri, Elliot Young, Grayson Young, Adam Zalcman, Ran Zhang, Yaxing Zhang, Ningfeng Zhu, Nicholas Zobrist, Zhenjie Zou, Ryan Babbush, Dave Bacon, Sergio Boixo, Yu Chen, Zijun Chen, Michel Devoret, Monica Hansen, Jeremy Hilton, Cody Jones, Julian Kelly, Alexander N. Korotkov, Erik Lucero, Anthony Megrant, Hartmut Neven, William D. Oliver, Ganesh Ramachandran, Vadim Smelyanskiy, Paul V. Klimov
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Quantum error correction (QEC) is the primary strategy for protecting a quantum computer from the environment1,2. The prerequisite of QEC is that errors must remain sufficiently rare, which requires perpetually adapting the control parameters of the computer to the drifting environmental conditions. The current solution to this problem is to terminate the entire quantum computation for recalibration, but it is incompatible with the long runtimes of future quantum algorithms3,4. Here we address this challenge by unifying calibration with computation. We grant the QEC process5,6,7,8,9,10,11 a dual role: its error-detection events are not only used to correct the logical quantum state but are also repurposed as a learning signal, teaching a reinforcement learning agent12,13,14,15,16 to continuously steer the control parameters and stabilize the quantum system during computation. We experimentally demonstrate this framework on a Willow superconducting processor, improving the logical stability of the surface code 3.5-fold against injected drift. By synthesizing our full suite of technological advances, we achieve record performance of the surface and colour codes, with average logical error per cycle of 7.72(9) × 10−4 and 8.19(14) × 10−3, respectively. Numerical simulations of large codes with tens of thousands of control parameters confirm the scalability of our RL framework, revealing an optimization speed that is independent of system size. This work thus enables a new paradigm: a quantum computer that learns from its errors and never stops computing.
GPT-4o mini: Non-social science research article
Author Correction: Authigenic mineral phases as a driver of the upper-ocean iron cycle
Alessandro Tagliabue, Kristen N. Buck, Laura E. Sofen, Benjamin S. Twining, Olivier Aumont, Philip W. Boyd, Salvatore Caprara, William B. Homoky, Rod Johnson, Daniela König, Daniel C. Ohnemus, Bettina Sohst, Peter Sedwick
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GPT-4o mini: Non-social science research article
Universal cell embedding provides a foundation model for cell biology
Yanay Rosen, Yusuf Roohani, Ayush Agrawal, Leon Samotorčan, character(0), Stephen R. Quake, Jure Leskovec
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Developing a universal representation space for cells that encompasses the tremendous molecular diversity of cell types across species would be transformative for cell biology. Recent work using single-cell transcriptomic approaches to create molecular definitions of cell types in the form of cell atlases has provided the necessary data for such an endeavour1,2,3. Here we present the universal cell embedding (UCE) foundation model. UCE was trained on a large corpus of cell data using self-supervision, creating a unified biological latent space that can represent cells across diverse tissues and species. This latent space captures important biological variation despite the presence of experimental noise. UCE’s universality means that new cells can be embedded with no data labelling, model training or fine-tuning. We used UCE to create the Integrated Mega-scale Atlas, embedding 36 million cells, with more than 1,000 uniquely named cell types, from hundreds of experiments, dozens of tissues and eight species. We gain insights into the organization of cell types and tissues within the space. UCE’s embedding space exhibits emergent behaviour, identifying biology that it was never trained for, such as identifying developmental lineages and embedding data from species that were not included in the training set. Overall, by enabling a universal representation for every cell state and type, UCE is a valuable tool for analysis, annotation and hypothesis generation over single-cell data.
GPT-4o mini: Non-social science research article
Verification of the Outer Space Treaty with cosmic protons
Areg Danagoulian
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The Outer Space Treaty (OST) was opened to signatures in 1967 and, since then, 117 countries, including China, the USA and Russia, have become part of it1. Among other stipulations, the treaty bans the placement of nuclear weapons in outer space. Recently, the US government has raised worries that Russia is testing nuclear-armed anti-satellite weapon (ASAT) components, with the possibility that it will place a nuclear weapon in space. Such a device, if detonated, would destroy most of the satellites in the low Earth orbit. This danger is compounded by the lack of a verification mechanism for the OST. No methodologies of verification have been proposed in the open peer-reviewed literature. Here a concept and feasibility study is presented for verifying a satellite’s compliance to the OST by observing the neutrons induced by spallation from the approximately GeV protons in the inner Van Allen radiation belts2. The calculations show that a 9U-CubeSat-sized detection platform can identify a thermonuclear weapon from a distance of 4 km in approximately one week of observation. This conceptual study will stimulate and inform future research and development of verification platforms for the OST.
GPT-4o mini: Non-social science research article
Ancient feeding-related neuropeptides regulate alloparenting in ants
Alexander Paul, Tomas Kay, Ivan Lacroix, Vikram Chandra, Asaf Gal, Patrick K. Piekarski, Stephany Valdés-Rodríguez, Amelia L. Ritger, Katelyn S. Lee, Kip D. Lacy, Daniel J. C. Kronauer
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Alloparental care and division of labour are hallmarks of insect societies 1 . Social insect workers typically care for brood within the nest when they are young and transition to foraging outside the nest as they age 2–5 . This provides a powerful paradigm to study the neural basis of parenting and age-related behavioural change. Although previous work has interrogated aspects of these dynamics 6–14 , the underlying neural and molecular mechanisms remain poorly understood. Here, using an unbiased pharmacological screen of neuropeptides, we show that two ancestral regulators of feeding, neuropeptide F (NPF) and allatostatin A (AstA), modulate brood-care behaviour in the clonal raider ant. Through functional manipulations, we show that NPF increases brood-care behaviour, whereas AstA has the opposite effect. Furthermore, we find that the levels of NPF and AstA in the brain change naturally as ants age, suggesting that these changes underlie the age-related changes in brood-care behaviour. Finally, we show that, as in solitary species 15,16 , NPF and AstA remain sensitive to nutritional state, and nutritional state affects brood-care behaviour accordingly. Our results reveal that evolution has co-opted molecular mechanisms that regulated feeding ancestrally to enable cooperative brood care and age-associated division of labour.
GPT-4o mini: Non-social science research article
An intrinsic cytoskeletal oscillator establishes neuronal polarity
Tien-chen Lin, Charlotte H. Coles, Eissa Alfadil, Florian FĂ€ĂŸler, Andreas Husch, Sebastian Dupraz, Thorben Pietralla, Akihiro Narita, Max Schelski, Kevin C. Flynn, Sina Stern, Christoph Möhl, Brett J. Hilton, Franz Vauti, Hans-Henning Arnold, Florian K. M. Schur, Frank Bradke
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Neurons acquire polarity by specifying one neurite as the axon, whereas the others become dendrites. But how this fundamental asymmetry is established remains unclear 1 . Neuronal polarization has been thought to rely primarily on growth cones that sense external cues 2 . Here we show that growth cones alone do not direct this process and that the soma acts as a central organizer of neuronal polarization. Using live imaging and genetic loss-of-function approaches in vivo, combined with optogenetic control and local cytoskeletal perturbations in cultured neurons, we uncover a soma-initiated oscillatory program that primes axon selection. Periodic actin branching that depends on the actin-related protein 2/3 (ARP2/3) complex at the soma remodels a global actomyosin network, thereby generating an actin wave that retracts neurites before propagating into a single neurite tip. Exposure to this wave relaxes local actomyosin contractility, which drives a transient microtubule-based protrusion and biases this neurite towards axon fate. As the cell exits this oscillatory stage, this neurite can overcome global inhibition and extend independently of ARP2/3, whereas actomyosin activity suppresses axon formation in the remaining neurites so that they subsequently become dendrites. This soma-driven mechanism ensures the emergence of a single axon independent of environmental cues and underpins the unidirectional information flow in neuronal circuits.
Nature DOI suffix ≠ "/s...": Not a research article
Time to give hydration breaks the red card? What science says about keeping cool
Harry Brown
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Nature DOI suffix ≠ "/s...": Not a research article
Nuclear weapons lurking in space could be tracked down by satellites
Angela Di Fulvio
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Nature DOI suffix ≠ "/s...": Not a research article
Briefing Chat: The 30 year-legacy of a science icon — Dolly the sheep
Benjamin Thompson, Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Graduating without a thesis: meet the people getting ‘practical’ PhDs in China
Xiaoying You
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: World Cup ‘hydration breaks’ miss the mark
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Save Hubble: the race to preserve the space telescope kicks off
Rogier Windhorst
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Nature DOI suffix ≠ "/s...": Not a research article
Regenerating people–nature relationships to counter biocultural erosion in the Amazon
Victoria Reyes-GarcĂ­a
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Nature DOI suffix ≠ "/s...": Not a research article
The rise of computer chips — and the race to control them
Chris Stokel-Walker
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Nature DOI suffix ≠ "/s...": Not a research article
Think preprints are unreliable? Analysis of 70,000 studies might change your mind
Mohana Basu
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Nature DOI suffix ≠ "/s...": Not a research article
Nobel-winning chemist leaves US to direct AI materials lab in China
Jenna Ahart, Mohana Basu
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Mutation lets octopuses make proteins with precision
Jacob Smith
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Nature DOI suffix ≠ "/s...": Not a research article
Nukes in space? Orbital detector could sniff out warheads
Benjamin Thompson, Nick Petrić Howe
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Nature DOI suffix ≠ "/s...": Not a research article
Listen to Gen Z when it comes to AI in education
Ian Robertson, Vincent C. MĂŒller, Eleonora Catena
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Nature DOI suffix ≠ "/s...": Not a research article
I want to see a prison-to-PhD pipeline
Virginia Gewin
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Three decades of Dolly
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Those who forget
Michael Adam Robson
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Nature DOI suffix ≠ "/s...": Not a research article
How to advance revolutionary science: high turnover, high risk and a licence to fail
Elizabeth Gibney
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Nature DOI suffix ≠ "/s...": Not a research article
Whoops! Most arXiv papers contain information never meant to be shared
David Brzostowicki
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Mountain bongos still roam the forest
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
How to avoid dementia — what the science really says
Helen Pearson
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Nature DOI suffix ≠ "/s...": Not a research article
How long can humans live? All evidence points to a maximum of 125 years
Brandon Milholland, Xiao Dong, Jan Vijg
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Nature DOI suffix ≠ "/s...": Not a research article
AI can cause harm: safeguards must catch up
Ziv Ben-Zion
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Nature DOI suffix ≠ "/s...": Not a research article
How to widen access to the critical minerals that the world needs
Rabah Arezki, Grégoire Rota-Graziosi
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: How cooperation built the world
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Sea-floor spreading captured by undersea observatory
Ingo Grevemeyer, Lars H. Ruepke
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Nature DOI suffix ≠ "/s...": Not a research article
Universities are relying on AI-detection software to catch cheating. How well do the programs work?
Anna McKie
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Nature DOI suffix ≠ "/s...": Not a research article
‘Humanizer’ tool can erase signs of AI-written text — alarming scientists
Edward Chen
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Nature DOI suffix ≠ "/s...": Not a research article
NSF plans cuts to core science programmes to fund White House initiative
Dan Garisto
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Nature DOI suffix ≠ "/s...": Not a research article
Judicious use of LLMs could speed up progress in the social sciences
James N. Druckman
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Nature DOI suffix ≠ "/s...": Not a research article
Deep-sea oddities and boatloads of other new species — June’s best science images
Miryam Naddaf, Dhruv Shenai
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Nature DOI suffix ≠ "/s...": Not a research article
Ocean floor witnessed splitting apart for the first time — releasing lava
Davide Castelvecchi
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Nature DOI suffix ≠ "/s...": Not a research article
‘This time, it’s the other way around’: how Indonesia is reclaiming the science of human history
Dyna Rochmyaningsih
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Nature DOI suffix ≠ "/s...": Not a research article
Lab-grown sperm: scientists inch closer to fertility breakthrough
Heidi Ledford
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Nature DOI suffix ≠ "/s...": Not a research article
Body-plan organizer in comb jellies hints at animal ancestry
Ruth Styfhals, Pawel Burkhardt
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Nature DOI suffix ≠ "/s...": Not a research article
Which ‘AI scientist’ suits your lab? A guide for the perplexed
Ewen Callaway
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The forest of knowledge under global change
Rodrigo CĂĄmara-Leret, Patrick R. Roehrdanz, Jordi Bascompte
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Amazonia harbours more than 10% of the terrestrial biodiversity of the Earth 1 and more than 400 Indigenous groups 2 . So far, however, no study has assessed how climate change and the loss of Indigenous languages may simultaneously impact its biological and cultural heritage. Here, to bridge this gap, we first assembled a database of 90,536 reports from 700 references to understand the societal benefits that native plants provide across all countries of the Amazon basin. We found that humans utilize 5,796 native plant species, which amounts to one-third of the known Amazon vascular seed plant flora. Next, analysing 8,429 species distribution models across three future climate scenarios (SSP1–2.6, SSP3–7.0 and SSP5–8.5), we show that climate change will produce a greater reduction in the ranges of utilized than of non-utilized species by 2060–2080. Locally, Indigenous cultures may lose an average of 28–34% of their utilized plant species and 18–23% of their associated services from climate change. Regionally, the loss of threatened Indigenous languages may result in a 26% reduction in the Amazonian knowledge pool. Overall, our results point to the strong climate and language vulnerability of Amazonian biocultural heritage. At the same time, these results—together with our publicly available dataset—may serve to guide biocultural restoration and reverse the growing global change effects on ecosystems and cultural traditions.
Large language models can predict the results of social science experiments
Ashwini Ashokkumar, Luke Hewitt, Isaias Ghezae, Robb Willer
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There is growing interest in how large language models (LLMs) can advance social and behavioural science1,2,3,4,5. Previous work has assessed LLMs’ ability to predict survey responses6,7,8,9, but less is known about whether they can predict the outcomes of social science experiments10, particularly those absent from training data. Here we built an archive of 70 preregistered, nationally representative survey experiments in the USA involving 469 experimental effects and 119,330 participants. We prompted an LLM to simulate how representative samples from American individuals would respond to experimental stimuli, and then we inferred treatment effects by comparing simulated responses across conditions. Predictions derived from GPT-4, whose training-data cutoff predated the publication of many studies in our archive, were strongly correlated with actual treatment effects, achieving accuracy similar to pooled human forecasts. Correlations remained high for studies not published or publicly posted by the model’s training-data cutoff date and for predictions from prominent open-weight models. Despite high correlations, predictions systematically overestimated effect sizes. In a secondary archive of 15 megastudies featuring 606 effects, correlations were lower but comparable to those of pooled expert forecasters. To assess implications for scientific practice, we surveyed 460 social scientists about probable uses and perceived risks and used our archives to assess several applications (pilot testing, intervention selection, identifying effects needing replication) and risks (bias, misuse). Together, these results indicate that LLMs can augment experimental methods in science and practice while raising important considerations for responsible use.
Computational approaches and the future of urban crime research
Gian Maria Campedelli, Zubin Jelveh, Aaron Chalfin, Daniel Semenza, Eric Piza, Ariadna Albors Zumel, Bruno Lepri, Patrick Sharkey
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Urban environments have long been a central focus for crime researchers across diverse disciplines. Over the past few decades, this heterogeneous area of inquiry has experienced substantial methodological and empirical change, driven by the emergence of novel datasets and the increasing use of flexible computational methods. In this Review, we take stock of this evolution and examine the potential that these developments hold for advancing urban crime research, while also addressing the persistent challenges that continue to shape the field. Building on this overview, we emphasize the promise that computational methods offer for more rigorous causal inference beyond traditional prediction tasks. Finally, we outline three key directions for future research to ensure that new data and computational tools are used effectively: greater integration across disciplines, improved open science standards and a broader scope of inquiry beyond Western contexts. In doing so, we aim to support more rigorous research and inform the development of more effective policies for safer and more sustainable cities worldwide.
Intergenerational mobility fosters innovation in Europe
Sarah McNamara, Guido Neidhöfer, Patrick Lehnert
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The circumstances into which individuals are born can place fundamental constraints on their future economic opportunities1,2,3,4,5, leading to a mismatch between talent, education and occupation. One major determinant of this inequality of opportunity is the absence of intergenerational educational mobility2. Here we extend existing knowledge on intergenerational mobility by presenting The European Atlas of Spatially Disaggregated Intergenerational Mobility (EUROPE-IGM-ATLAS), a panel database comprising indicators of intergenerational mobility for European subnational regions. In doing so, we make two contributions. First, we extend existing knowledge on the development of intergenerational mobility in European regions. The EUROPE-IGM-ATLAS reveals several spatiotemporal trends that characterize the changing geography of opportunity in Europe. For example, we show that observed increases in intergenerational mobility primarily stem from improvements in educational achievements among individuals from families at the lower end of the educational distribution, with fewer changes in rank across the educational spectrum. However, these increases are not uniformly distributed. Regions with a high degree of educational inequality also exhibit lower levels of intergenerational mobility, implying the co-existence of inequality both within and between generations. Second, we use this database to provide evidence on the relationship between intergenerational mobility and innovation. We provide large-scale time-series evidence that European regions with higher intergenerational mobility achieve higher innovation outcomes, one important driver of economic growth. Subsets of results further indicate that this relationship is nonlinear and that distinct mechanisms operate in major innovation hubs.

Nature Human Behaviour

GPT-4o mini: Non-social science research article
Smallpox in colonial Australia
Kalinda Elizabeth Griffiths
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GPT-4o mini: Non-social science research article
Active vision is linked to category selectivity in the individual brain
Diana Kollenda, Elaheh Akbari, Maximilian D. Broda, Benjamin de Haas
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Individuals reliably differ in how they look at complex visual scenes, with the most prominent variation in their propensity to fixate faces and text. Here we tested the hypothesis that these differences in gaze are linked to representational properties of the individual visual system in 61 adults. Eye-tracking captured each observer’s characteristic gaze tendencies during naturalistic scene viewing, and independent functional magnetic resonance imaging recorded category-selective responses to faces, words and other stimuli when participants were instructed to fixate centrally. We find that the propensity to fixate faces or text goes along with enhanced distinctiveness and enlarged functional regions of corresponding categorical representations in the ventral stream. These in turn predicted performance on reading and face recognition tasks. Thus, active vision appears linked to the precision of category-selective encoding and corresponding neural resources in the individual brain.
GPT-4o mini: Non-social science research article
Common and rare genetic variant associations with cognitive performance across development in British birth cohorts
Daniel S. Malawsky, Mahmoud Koko, Petr Danacek, Wei Huang, Olivia Wootton, Qin Qin Huang, Emma E. Wade, Sarah J. Lindsay, Rosalind Arden, Matthew E. Hurles, Hilary C. Martin
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Genetic variants that correlate with adult cognitive performance are also associated with rare neurodevelopmental conditions involving cognitive deficits in children. However, their association with cognition across early life remains poorly understood. Using 6,495 children from the Avon Longitudinal Study of Parents and Children, we show that, as children age, the association between cognitive ability and polygenic indices for educational attainment and its cognitive component increases (PGI EA × age interaction per 10 years: 0.033 [0.020, 0.047], PGI Cog × age: 0.0232 [0.0096, 0.0367]). Conversely, negative associations with deleterious rare variant burden attenuate with age (RVB pLoF × age: 0.0239 [0.0110, 0.0368]). Using trio analyses, we show that these age-related trends are consistent with contributions from direct genetic effects. We find that the increasing associations with polygenic indices are stronger in individuals at the upper end of the phenotype distribution, whereas the attenuating associations with rare variant burden are stronger in those at the lower end. Our findings may help explain the apparent incomplete penetrance of rare damaging variants associated with neurodevelopmental conditions.
Stochastic models indicate rapid smallpox spread and mass mortality of Indigenous Australians after colonial exposure
Matthew C. Nitschke, Alan N. Williams, Shane D. Ingrey, Billy Griffiths, Nicholas Pitt, Lynette Russell, Sean Ulm, Kirsty Beller, Michael I. Bird, Syeda H. Fatima, Ian J. McNiven, Frédérik Saltré, Alison Bashford, Christopher Wilson, Corey J. A. Bradshaw
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The impact of smallpox (variola) on Aboriginal communities in Australia beginning in 1789 was catastrophic and continues to cause intergenerational trauma. Historically biased perspectives and contemporary misinformation of the disease’s introduction and spread impede modern-day truth-telling and efforts towards reconciliation and national healing. Understanding whether the disease entered and spread from pre-colonial Makassan (Indonesian) trade along the northern coast, or from the British First Fleet’s arrival in southeastern Australia in 1788, is necessary to estimate the demographic impact. Here we developed stochastic, multipatch epidemiological models supported by systematic evaluation of historical observations to test hypotheses regarding possible disease entry points, spread rate and demographic impacts. Our models support the hypothesis that entry of the disease was in southeastern Australia. Even under ideal conditions and with higher-than-probable infection rates, simulations show that smallpox was unlikely to reach Sydney from a northern entry. We found no evidence that the 1789 epidemic was Australia-wide. Assuming 60% lethality based on global data, the loss of approximately 220,000 people would have occurred in these regions. While catastrophic to traditional Indigenous lifeways in the southeast, the disease also provided the catalyst for population decline and marginalization of Indigenous people in the face of expanding European populations. Our models indicate that it is unlikely that other parts of Australia were affected by the initial epidemic. We warn readers that the content of this study might be distressing.
Bridging the divide in motor learning research
Eric Grießbach, Alfredo Hernandez-Inostroza, Rouwen Cañal-Bruland, Adrian M. Haith
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Motor learning underlies our ability to acquire and perfect movements across all domains of human behaviour. Its study encompasses two distinct but related endeavours: basic research on how we learn movement skills and applied research on how to enhance skill acquisition in real-world contexts. Despite their natural complementarity, these approaches developed historically in two largely independent communities with different disciplinary roots. One is closely associated with computational neuroscience and focuses predominantly on basic research. The other comes from experimental psychology and movement sciences with a stronger focus on applied research. The division between these communities is reflected in the experimental tasks they use, the theoretical frameworks they develop and the cultural norms that shape their training and communication. In this Perspective, we scrutinize this divide, review emerging efforts towards better integration and identify future opportunities. We contend that bridging these gaps can build a more comprehensive science of motor learning.
Two roads to prosociality
Tobias Grossmann
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Stable intuition and the rise of deliberative prosociality in childhood
Francesco Margoni, Francesco Nava, Chiara Sotis, Matthew R. Levy, Valerio Capraro, Elena Nava
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We examine how social behaviours emerge and stabilize across childhood. A sample of 537 Italian-speaking children (3–10 years) were randomly assigned to respond under time pressure (intuitive) or time delay (deliberative) in social decision tasks (Public Goods, Dictator, Ultimatum, Deception and Moral Dilemmas). Factor analysis identified three latent dimensions: Prosociality (cooperative, altruistic and honest actions), Social Optimism (beliefs about others’ cooperation) and Acquiescence (tendency to accept offers). Intuitive responses were more prosocial than deliberative ones in early childhood ( ÎČ = 0.66; 95% CI = (0.35, 0.97)), but this difference diminished with age ( ÎČ = −0.11; 95% CI = (−0.18, −0.05)). We found no evidence that Social Optimism varied across age or decision mode, whereas Acquiescence declined with age ( ÎČ = −0.14; 95% CI = (−0.19, −0.10)). These findings suggest a developmental shift whereby prosocial behaviour is initially driven by intuitive responses and gradually becomes embedded within reflective, deliberative decision-making systems, as cooperative dispositions stabilize across childhood.

Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Divergent population trajectories despite similar response to temperature in a widespread aerial insectivore
Conor C. Taff, J. Ryan Shipley, Daniel R. Ardia, David Aborn, Lauren Albert, Marc Bélisle, Amos Belmaker, Lisha L. Berzins, Tricia Blake, Frances Bonier, Hannah C. Brewer, Michael W. Butler, Kyle Cameron, Samuel B. Case, David Chang van Oordt, Robert G. Clark, Ethan D. Clotfelter, Amelia R. Cox, Russell D. Dawson, Elizabeth P. Derryberry, Ana M. Diaz Bohorquez, Peter O. Dunn, Valentina Ferretti, Anna M. Forsman, Matthew Fuirst, Dany Garant, Daniel R. Garrett, Jessica Gutiérrez, Julie C. Hagelin, Braelei M. Hardt, Mercy E. Harris, Kyle Horton, Carolyne Houle, Jennifer L. Houtz, Patricia L. Jones, Kimberley C. Jordan, Amanda S. Kindel, Robert Klaver, Sarah A. Knutie, Katherine S. Lauck, Michael P. Lombardo, Stephen C. Lougheed, Ashley C. Love, Stuart A. Mackenzie, John P. McCarty, Ann E. McKellar, Nicole Mejia, Christy A. Morrissey, Mia L. Nahom, D. Ryan Norris, Lillian M. Para, Fanie Pelletier, Cody K. Porter, Wallace B. Rendell, Eric A. Riddell, James W. Rivers, Raleigh J. Robertson, Alexandra Rose, Kimberly A. Rosvall, Thomas A. Ryan, Ryan P. Shannon, Dave Shutler, Victoria F. Simons, Mark Stanback, Corey E. Tarwater, Patrick A. Thorpe, Morgan W. Tingley, Christine L. Tischer, Benjamin A. Tonelli, Melanie L. Truan, Cornelia W. Twining, Jennifer J. Uehling, Carol Vleck, David Vlec, Michael L. Watson, Nathaniel T. Wheelwright, Linda A. Whittingham, David W. Winkler, Casey Youngflesh, Cedric Zimmer, Maren N. Vitousek
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Climate change is shifting when animals breed [C. Parmesan, G. Yohe, Nature 421 , 37–42 (2003) and S. J. Thackeray et al. , Nature 535 , 241–245 (2016)], but it is not clear why some populations keep pace with warming while others fall behind [L. D. Bailey et al. , Nat. Commun. 13 , 2112 (2022) and J. M. Samplonius et al. , Glob. Change Biol. 24 , 3780–3790 (2018)]. Differences could arise from variation in sensitivity to temperature [L. D. Bailey et al. , Nat. Commun. 13 , 2112 (2022)] or constraints on the ability to respond to temperature. Without knowing whether populations differ in sensitivity—or in their ability to act on that sensitivity—we cannot identify which are most at risk. Using 1,555 population-years from 123 populations of tree swallows ( Tachycineta bicolor ), we show that populations have similar sensitivity to local temperature, advancing breeding by about one day per degree of warming. However, northern populations face tighter time constraints and greater exposure to recent warming. Northern populations have advanced laying dates the most, but still experience stronger selection for earlier breeding, especially in warm years; they have also declined most in breeding abundance. These findings suggest that vulnerability to climate change can arise not just from different sensitivity to warming, but from when and where populations can respond effectively. By disentangling sensitivity from timing constraints, our results are consistent with a general mechanism by which even uniformly responsive species can show uneven impacts of climate change across their ranges.
GPT-4o mini: Non-social science research article
The LV map leads to misleading interpretations of coexistence
Isabell C. Ernst, Jurg W. Spaak
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GPT-4o mini: Non-social science research article
Tropical forests are facing increasing risks of exposure to critical temperature thresholds
Nina van Tiel, Gaston Lenczner, Mukund P. Rao, Charlotte Grossiord, Devis Tuia
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Understanding how close tropical tree species are to critical temperature thresholds that might impede photosynthetic activity is vital in a world where heat waves have become more severe and frequent. Using remotely sensed surface temperature and species distribution maps, we studied the spatiotemporal variation in the thermal safety margins (TSM, i.e., the difference between T crit , the critical photosynthetic temperature, and the maximum canopy temperature) of 208 tropical tree species in South America, Southeast Asia, and Central Africa during the period 2001–2020. Despite overall high-temperature tolerance with an average T crit of 46.1 ° C, we observed a consistent decline in the TSM of tropical forests across the globe. The average pantropical TSM decline was 0.4 ° C per decade, with the strongest decline in South America ( 0.5 ° C per decade). Over the 20 -y period, areas that experienced canopy temperatures surpassing the average T crit across reported species increased from 43 Mha to 57 Mha in the tropics, representing 4 % of the studied area. This number increases to 10 % when computing areas where temperatures have surpassed the T crit of the most vulnerable reported species. When considering future trends, as predicted by Earth System Models under medium-to-high emission scenarios, average T crit may be exceeded in an area of 83 Mha by 2050 and 160 Mha by 2100 (over 10 % of the studied area), suggesting major feedback to the global carbon cycle and the world’s biodiversity.
GPT-4o mini: Non-social science research article
Cell competition overcomes host tissue resistance to unleash tumor growth in a Drosophila brain cancer model
Marco Gualtieri, Saline Jabre, Damien Mornico, Maëlwenn Hamon, Gaëlle Letort, Cédric Maurange, Pauline Spéder
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Primary tumors of the central nervous system are extremely aggressive and often incurable. While tumor cells are known to interact with their microenvironment, the complexity and temporal dynamics of this interplay and its impacts on tumor progression remains to be fully understood. We addressed this question in a Drosophila model of cancer stem cell–driven tumor which originates during development and grows extensively within a network of cortex glia cells through adulthood. We revealed a biphasic interplay between tumor and cortex glia cells, characterized by morphological, molecular, and functional changes. In early stages, glial cells infiltrate the tumor, display a distinct transcriptional signature, and resist its growth, supported by the intrinsic neuroprotective activity of the c-Jun N-terminal kinase (JNK) signaling pathway. However, cancer stem cell–driven competition takes place, eliminating cortex glia by apoptosis and ultimately unleashing tumor growth. This second phase sees the breakdown of the glial meshwork and adhesions to neurons, along with the downregulation of the JNK pathway and a decline in essential cellular functions. Ultimately, the host tissue collapses, in turn curbing tumor growth. This study uncovers a dynamic and complex interplay between host tissue resistance and tumor-driven competition, which shapes tumor progression.
GPT-4o mini: Non-social science research article
Spatially structured heterogeneity shapes large-scale cortical dynamics in a model of the human cortex
Leonardo Dalla Porta, Jan Fousek, Alain Destexhe, Maria V. Sanchez-Vives
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The human brain displays substantial spatial variability in molecular, anatomical, and physiological organization. Yet, how this heterogeneity shapes large-scale neuronal dynamics remains poorly understood. To address this question, we employed a biologically informed large-scale cortical model capable of generating distinct brain states, from awake-like to sleep-like dynamics. Our model was constrained by empirical human structural connectivity (SC) and regional cholinergic muscarinic receptor (CHRM) maps derived from transcriptomic data, together with complementary positron emission tomography (PET)-based receptor maps. These regional maps were implemented as modulators of adaptation-related excitability. We found that modulating excitability according to the spatial organization of CHRM maps significantly impacted large-scale cortical dynamics: It not only facilitated network synchronization but also enhanced information flow between cortical regions. Importantly, these effects were conserved across transcriptomic and PET-derived maps and could not be fully reproduced by multiple null models preserving generic forms of heterogeneity. Moreover, we addressed a particularly intricate dynamic regime characterized by the coexistence of localized sleep-like activity within otherwise awake-like states. We showed that the emergence of these sleep-like slow waves was a byproduct of both regional levels of neuronal adaptation and SC. In summary, our findings highlight the critical role of molecular and anatomical heterogeneity in shaping widespread cortical dynamics, suggesting broad avenues for linking microscale diversity to macroscale function.
GPT-4o mini: Non-social science research article
Evolvable AI needs operational risk thresholds
Shweta Rana, Harpreet Singh
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GPT-4o mini: Non-social science research article
Structural insights into the nairovirus nucleoprotein endonuclease activity
Zan Li, Shan Du, Feng Gao, Yanshuang Xiao, Qilu Weng, Wenni Zhang, Pufei Chen, Wenbo Xu, Yuanzhi Wang, Quan Liu, Yan Wu, Litao Sun
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Nairoviruses are emerging tick-borne pathogens for which effective antiviral therapies are currently unavailable. Although nucleoproteins (NPs) are essential for viral genome encapsulation and have been extensively characterized at the structural level, whether they perform additional functions during viral replication remains unclear. Here, we investigated the NP of the representative nairovirus Tacheng tick virus 1 (TcTV1). We found that the TcTV1 NP binds to nucleic acids in a sequence-independent manner and assembles into tetramer-based ribonucleoprotein complexes upon nucleic acid binding. This assembly process is accompanied by a pronounced conformational rearrangement that facilitates NP polymerization. In addition to its role in RNA encapsulation, TcTV1 NP exhibits intrinsic endonuclease activity that does not require metal ions and preferentially cleaves unstructured single-stranded RNA, while structured RNA substrates are largely resistant to cleavage. Functional analysis indicates that the stalk domain of NP plays a central role in coordinating RNA binding, oligomerization, and access to the nuclease-active site, thereby influencing whether an RNA molecule is protected or degraded. Finally, we identified a small-molecule compound that interferes with both RNA binding and nuclease activity by targeting a conserved functional region of nairovirus NP. Together, these results reveal an expanded functional repertoire of nairovirus NPs and suggest that NP-mediated RNA discrimination may contribute to viral replication. Our findings also support the feasibility of targeting NP for the development of antiviral drugs against emerging nairoviruses.
GPT-4o mini: Non-social science research article
Human and animal morbillivirus strains causing chronic neurological infections share key genotypic and phenotypic traits
Melvin Daniel Roji, Franziska Geiselhardt, Georg Beythien, Kristin Laudeley, Monica Mirolo, Wendy K. Jo, Laura Martino, Andreas Beineke, Wolfgang BaumgÀrtner, Martin Peters, Judith M. A. van den Brand, Trine H. Jensen, Thijs Kuiken, Johannes P. M. Langedijk, Mariano Domingo, Albert D. M. E. Osterhaus, Martin Ludlow
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Long-term persistent measles virus (MeV) infection of the central nervous system (CNS) can result in subacute sclerosing panencephalitis (SSPE), an invariably fatal late neurological complication of measles. Analogous SSPE-like chronic diseases have also been reported in adult dogs, cetaceans, and more recently harbor seals following infection by canine distemper virus (CDV), dolphin morbillivirus (DMV), and phocine distemper virus (PDV), respectively. Here, we characterize different animal morbilliviruses (CDV lynx , PDV 2001 , PDV 2014 , and DMV 232-18 ) that persisted in the CNS of their respective host species for several years after the initial infections. The CDV lynx and DMV 232-18 strains encode nonfunctional matrix proteins and hyperfusogenic fusion proteins which are hallmark features of SSPE MeV strains. The complex mutational profile apparent in the PDV 2001 strain also has parallels with MeV strains from SSPE cases. In contrast, the PDV 2014 strain encodes for a nonfunctional matrix protein but an unmodified F protein supporting the evolutionary precedence of M protein changes in facilitating long-term morbillivirus infections of the CNS. Consequently, our findings show that similar evolutionary pathways across different animal species drive morbilliviruses to evolve analogous mechanisms favoring virus persistence in the CNS and the development of chronic neurological disease. Such naturally occurring chronic animal morbillivirus infections of the CNS provide natural analogues for studying the evolutionary trajectory and molecular basis of the pathogenesis of SSPE in humans. This may pave the way for developing early diagnostics and intervention strategies.
GPT-4o mini: Non-social science research article
A phase oscillator model of cell cycles reveals nuclear density control in a branched fungal network
Grace A. McLaughlin, Benjamin M. Stormo, Ameya P. Jalihal, Taylor L. Pompan, Madhav Mani, Timothy C. Elston, Amy S. Gladfelter
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Maintaining an appropriate nuclear-to-cytoplasmic ratio is essential across cell types for physiological function, and mechanisms of size control have been extensively studied in mononucleate cells. Much less is known about how comparable control is achieved in cells where many nuclei share a common cytoplasm, which are seen in many contexts including muscle, placenta, and filamentous fungi. The filamentous fungus Ashbya gossypii forms a branching mycelial network in which individual nuclei divide asynchronously, while the number of nuclei per cell volume (the nuclear density) is tightly controlled. How global regulation of nuclear density coexists with local cell cycle asynchrony remains unclear. To address this we model nuclei as a dividing population of phase oscillators within a branching cell network and parameterize the model with measurements from Ashbya cells. The model demonstrates that asynchrony is required to prevent large density fluctuations that would result from synchronous division, and that introducing a nuclear density checkpoint to the cell cycles leads to synchrony if it is the only mechanism of density control. We find that coupling branch formation to nuclear density both stabilizes nuclear density and prevents the emergence of synchronous cycles. Supporting these predictions, we demonstrate that mutants with branching defects and increased cell cycle synchrony display greater variability in nuclear density. Our results indicate that asynchronous nuclear cycles together with density-responsive branching maintain a constant nuclear density, revealing a strategy for regulating the nuclear-to-cytoplasmic ratio in large multinucleate cells.
GPT-4o mini: Non-social science research article
Regional variability but global flux balance in the deep sulfur cycle
Ji-Lei Li, Jay J. Ague, Timm John, Botao Li, Peter D. Clift, Esther M. Schwarzenbach, Jun Gao
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Sulfur is a key volatile that influences Earth’s redox state, climate, and deep geochemical cycles. Subduction zones are the primary pathways carrying sulfur from the surface into the mantle, yet the global sulfur budget and recycling efficiency remain uncertain. Here, we compile a trench-by-trench inventory of subducting sulfur using sediment compositions from ocean drilling programs collected near major trenches, integrated with spatially resolved estimates of oceanic crustal and serpentinite thicknesses derived from seismic data. Our results reveal pronounced spatial heterogeneity in sulfur fluxes, driven by large variations in sedimentary sulfur contents and fundamental tectonic differences between erosive and accretionary margins. Slab-to-arc sulfur recycling efficiency averages 37% globally but varies markedly among individual subduction systems. Despite this heterogeneity, the global sulfur cycle appears balanced on the modern Earth: Sulfur input into the mantle via slab subduction (57 ± 3 Mt y –1 ) is matched within uncertainty by mantle output (~60 ± 14 Mt y –1 ) through mid-ocean ridges, volcanic arcs, and intraplate magmatism. This balance suggests that Earth’s deep sulfur cycle operates in a steady state today. Sulfur isotopes reveal a systematic decoupling, with subducted sulfur carrying negative ÎŽ 34 S values, whereas arc sulfur output is consistently positive. The strong spatial variability in sulfur inputs and recycling efficiency underscores the individuality of Earth’s subduction zones, but the balanced input–output fluxes highlight its capacity for self-regulation. These findings have important implications for atmospheric chemistry, surface environments, and the long-term evolution of the deep Earth’s sulfur cycle.
GPT-4o mini: Non-social science research article
Glycolipids slow interfacial proton migration while preserving surface proton retention
Anna Maznichenko, Peter Pohl
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Proton gradients power diverse biological processes, yet how interfacial proton migration is regulated remains unclear. Here we quantify how membrane composition controls interfacial proton migration using an approach that releases protons directly at the surface of a membrane patch via an embedded ionophore. Fluorometrically monitoring proton arrival at a distant patch across neutral, negatively charged, and positively charged membranes, we confirm that both the lateral surface diffusion coefficient and the activation barrier for proton release into the bulk vary rather modestly. In contrast to membrane electrostatics, membrane incorporation of glycolipids typical of thylakoid membranes—digalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol—leads to a more pronounced reduction of the lateral proton diffusion coefficient, with comparatively small effects on the surface-to-bulk release barrier. Thus, interfacial proton migration is governed primarily by hydration-layer properties rather than membrane charge. These results establish membrane-anchored sugars as potent modulators of long-range proton conduction and provide a mechanistic framework for localized proton coupling in glycolipid-rich biological membranes.
GPT-4o mini: Non-social science research article
Small but mighty: The outsized role of small water bodies in the global carbon cycle
Marcia N. Macedo
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GPT-4o mini: Non-social science research article
4D force patterning enables spatial control of angiogenesis
Sina Kheiri, Jessica Shah, Peiyuan Chai, Shashaank A. Venkatesh, Ryan A. Flynn, Roger D. Kamm, Ritu Raman
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Engineering organized microvascular networks remains a critical challenge in tissue engineering and regenerative medicine. While biochemical approaches for patterning angiogenesis via growth factor delivery have shown promise, their inability to pattern sustained growth factors with spatiotemporal control limits effectiveness. Here, we demonstrate that dynamically patterned mechanical forces enable precise spatiotemporal control over angiogenic sprouting. We developed a magnetically actuated human vessel-on-a-chip platform that integrates a perfusable endothelialized microchannel within a collagen matrix and allows noninvasive and tunable mechanical stimulation across three spatial dimensions and time (4D). Using an automated 3-axis actuator, we systematically investigated how strain magnitude, frequency, and direction modulate endothelial cell behavior and vessel morphogenesis. Dynamic mechanical stimulation at physiological strain magnitudes (5 to 15%) enhanced endothelial alignment and barrier function while promoting angiogenesis in a strain magnitude–dependent manner: lower dynamic strain (5%) maximized sprout initiation, whereas higher dynamic strain (15%) promoted elongation of sprouts. Sequential reorientation of strain direction reprogrammed sprouting trajectories along X, Y, and Z directions, generating complex sprout geometries such as L-shaped branches. RNA sequencing revealed mechanically induced transcriptional profiles distinct from unstimulated controls, characterized by upregulation of genes associated with angiogenesis, mechanotransduction, and extracellular matrix remodeling. Functional perturbation of PIEZO1 reduced strain-induced sprouting without altering barrier function, indicating that dynamic mechanical stimulation engages multiple mechanotransduction pathways to regulate angiogenesis. Collectively, these findings establish a strategy for spatiotemporally controlled angiogenesis through 4D force patterning to program vascular morphogenesis while preserving function. This approach provides a foundation for engineering hierarchically organized vascular networks for tissue regeneration.
GPT-4o mini: Non-social science research article
Circulating PEG-indoleamine 2,3-dioxygenase ameliorates diverse inflammatory diseases without toxicity or compromising immunocompetence
Jennifer A. Simonovich, Ryan A. Clark, Alexander J. Kwiatkowski, Madeline J. Fuchs, Mariana E. Viso, Chen Lu, Sabrina L. Macias, Isabella Pinto, Abhishek P. Shrestha, Tran B. Ngo, Sergio Duarte, Yong He, Qiongyao Hu, Guanyi Lu, Joseph B. Hartman, Gang Su, Salvatore T. Scali, Scott A. Berceli, Ashish K. Sharma, Gilbert R. Upchurch, Shamima Islam, Arun Wanchoo, Gregory A. Hudalla, Scott T. Robinson, Ali Zarrinpar, Dorina Avram, Benjamin G. Keselowsky
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Indoleamine 2,3-dioxygenase (IDO), the enzyme responsible for tryptophan catabolism, is protective in many autoimmune and inflammatory diseases. We previously developed a localized immunomodulation approach through the fusion of IDO to a carbohydrate binding protein [E. Bracho-Sanchez et al. , Nat. Biomed. Eng. 7 , 1156–1169 (2023)]. Here we further develop IDO as a protein therapeutic for inflammation, investigating systemic delivery via conjugation of poly(ethylene glycol) (PEG) to IDO. PEGylation extended circulation time and treatment PEG-IDO demonstrated therapeutic efficacy in five autoimmune and inflammatory models. Treatment with a single dose of PEG-IDO resulted in reversal of hind limb paralysis in experimental autoimmune encephalomyelitis as model of multiple sclerosis; protected against hepatic damage in liver ischemia-reperfusion injury; prevention of abdominal aortic aneurysm; and decreased severity of imiquimod-induced psoriasis. Treatment with two doses of PEG-IDO provided maintenance of body weight and colon length in acute ulcerative colitis. PEG-IDO treatment increased regulatory T cell populations and reduced pathogenic Th17 cell populations and inflammatory cytokine production. Systemic delivery of PEG-IDO had little-to-no off-target effects. Mice maintained immunocompetency, clearing the Listeria monocytogenes infection, and had no observed toxicity. Additionally, PEG-IDO increased serum kynurenine, consistent with a kynurenine-mediated mechanism of action. These findings demonstrate systemic immunomodulation via circulating PEG-IDO ameliorates a breadth of disparate autoinflammatory diseases, protecting against inflammation-driven tissue destruction in spinal cord, liver, abdominal aorta, skin, and colon, while presenting a positive safety profile, and expanding the scope of potential applications for this therapeutic approach.
GPT-4o mini: Non-social science research article
Localized sample-based quantum diagonalization for strongly correlated chemistry
Qiaohong Wang, Kevin J. Sung, Ruhee D’Cunha, Matthew R. Hermes, Tanvi Gujarati, Yukio Kawashima, Yu-ya Ohnishi, Gavin O. Jones, Mario Motta, Laura Gagliardi
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We develop a hybrid quantum-classical workflow combining sample-based quantum diagonalization (SQD) and the localized active space self-consistent field method (LASSCF) to solve for the ground states of transition-metal complexes, a longstanding challenge for both classical and quantum algorithms. The resulting approach, named LASSQD, integrates quantum sampling with fragment-based multireference theory to reduce the computational cost of solving strongly correlated active spaces. We test LASSQD on multiple iron-based complexes and demonstrate that it agrees with LASSCF within 1 kcal/mol, albeit at a much reduced computational cost. The cost reduction originates from the use of a sparse approximation of the exact and combinatorially large ground-state wavefunction, which also enables LASSQD to treat fragment sizes that are computationally inaccessible to LASSCF, as demonstrated by our computation of the spin gap of iron-porphyrin. These results establish that LASSQD is a scalable strategy for generating reliable multireference wave functions, providing a robust starting point for post-SCF correlation methods that recover dynamic correlation beyond the active space, and a promising pathway toward quantum-enhanced electronic structure calculations.
GPT-4o mini: Non-social science research article
Magnetically actuated microrobotic system for sequential treatment of biofilm
Shunyao Li, Yu Mei, Kai Xu, Huaixuan Sheng, Yu-an Chen, Mingda Teng, Bohan Xu, Bingqian Jiang, Chengxuan Yu, Huizhu Li, Shiyun Zhao, Yi Wang, Xiao Zhang, Yiyang Zhao, Yueming Wang, Yan Wo, Zhaochen Li, Siwen Shen, Yunxia Li, Min Tang, Yongfeng Mei, Jun Chen, Gaoshan Huang, Sijia Feng
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Biofilm-associated infections present a critical therapeutic challenge due to antibiotic resistance and impaired tissue healing. Here, we present a microrobotic system (MZ-8) that integrates real-time human-steered navigation with autonomous, microenvironment-responsive therapy to actively eradicate biofilms and promote tissue regeneration. This microrobotic system features a spine-inspired structure for mechanical biofilm disruption, a pH-responsive ZIF-8 coating for immunomodulatory Zn 2+ release, and closed-loop actuation under second near-infrared fluorescence guidance. In a rat model of periprosthetic joint infection, MZ-8 achieved effective biofilm removal, induced a pro-regenerative immune response by polarizing macrophages toward the M2 phenotype, and significantly enhanced tissue regeneration. Transcriptomic analysis further revealed the activation of immunomodulatory pathways and upregulation of M2-associated genes, confirming the system’s sequential shift from eradication to repair. Moreover, validation in a rabbit model and human knee joint confirmed its operational feasibility under clinical imaging guidance and excellent biosafety. This work establishes that integrating physical eradication, biochemical immunomodulation, and interactive control within a single system is essential for advancing from infection clearance to functional tissue restoration. Thus, it provides a therapeutic paradigm for biofilm-associated diseases and lays a foundation for future intelligent, clinically adaptive anti-infective systems.
GPT-4o mini: Non-social science research article
Per os infectivity factors are essential for bracovirus infection and wasp parasitism
Xi Wang, Zhe Lin, Fei Wang, Hengrui Hu, Heya Na, Tao Zhang, Just M. Vlak, Zhen Zou, Manli Wang, Zhihong Hu
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Many parasitoid wasps in the family Braconidae rely on bracoviruses to parasitize lepidopteran hosts. Bracoviruses evolved from a virus in the family Nudiviridae , while nudiviruses are closely related to baculoviruses. A per os infectivity factor (PIF) complex is essential for oral infection of hosts by baculoviruses. Bracoviruses encode 8 PIF homologs but have no per os infection route because wasps inject virions into hosts. Thus, the mechanism underlying how bracoviruses enter lepidopteran host cells is unknown. Here we used the parasitoid Microplitis mediator , its lepidopteran hosts Mythimna separata and Helicoverpa armigera , and M. mediator bracovirus (MmBV) to elucidate the function of bracoviral PIFs. We identified a ~720-kDa PIF complex on the envelope of MmBV virions. In addition to PIF0-4, PIF6, and PIF8, we identified two other proteins in the MmBV PIF complex: PIF5-3 and a wasp encoded ÎČ-propeller domain-containing protein named P52. The other two PIF5 paralogs (PIF5-1 and PIF5-2) were not associated with the PIF complex. Knocking down any component in the PIF complex resulted in degradation, which suggested all components are essential for stability. Using expression of an MmBV ankyrin gene as a marker, we determined that MmBV PIFs are essential for systemic infection of host larvae. Knocking down any PIF complex component or double silencing of PIF5-1 and PIF5-2 also resulted in failed parasitism as measured by no survival of M. mediator offspring. Altogether, our results demonstrate an essential role for the MmBV PIFs in systemic infection of a lepidopteran host.
GPT-4o mini: Non-social science research article
Reply to Ernst and Spaak: The LV-map accurately estimates species interactions even when functional responses are nonlinear
Phuong Linh Nguyen, Francesco Pomati, Rudolf P. Rohr
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GPT-4o mini: Non-social science research article
Inhibition of elastin degradation alleviates joint degeneration in aging mice, dogs, and human models
Junzhi Yi, Xiao Xiao, Hui Zhang, Xinjie Xu, Keyu Chen, Xinqi Cai, Yutao Zhu, Xianan Mo, Shihan Xiong, Zhichu Chen, Hairu Sui, JiaChun Wu, Jiaqi Xu, Xuri Chen, Yan Wu, Zi Yin, Youzhi Cai, Xianzhu Zhang, Jing Zhou, Hua Liu, Hongwei Ouyang
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Extracellular matrix degradation is a fundamental pathological feature of osteoarthritis, while the roles of degraded matrix remain largely unknown. We previously showed that serum elastin fragments were a systemic aging driver. Here, we found that elastin fragments were upregulated in synovial fluid in dual-center osteoarthritis patients. Elastin fragments actively impaired joint tissue in mice and human explants. Mechanistically, a specific elastin motif containing Valine-Glycine-Valine-Alanine-Proline-Glycine (VGVAPG) oligopeptide (E-motif) promoted macrophage secretion of inflammatory factors via the neuraminidase-1, a component of the elastin receptor complex. These inflammatory factors, together with the E-motif, upregulated serum amyloid A3 protein in chondrocytes, accelerating cartilage degeneration. Therapeutically, both the myeloid-specific knockout of neutrophil elastase and the pharmacological inhibition using a clinically applied drug (sivelestat) alleviated joint degeneration in naturally aging mice partly by reducing elastin fragments levels. The pharmacological inhibitor exhibited 1-y systemic safety in dogs and alleviated osteoarthritis-like phenotypes in naturally aging dogs and human explants. Finally, several matrix fragments, including the fragments of type II collagen, fibronectin, hyaluronic acid, and aggrecan, were demonstrated to universally induce cartilage degeneration. Conclusively, this study identifies degraded matrix, especially elastin fragments, as one of the drivers of joint degeneration via pathological macrophage–chondrocyte crosstalk, suggesting elastase inhibitors as a potential therapeutic strategy for aging-related osteoarthritis.
GPT-4o mini: Non-social science research article
Endothelial Arf6 sustains electrical signaling and cerebral blood flow in mice through PIP 2 -dependent activation of Kir2.1 channels
Maria F. Noterman-Soulinthavong, MarĂ­a Sancho, SaĂșl Huerta de la Cruz, Michael Yarboro, Maurizio MandalĂ , Masayo Koide, Nathalie Beaufort, Katalin Todorov-Völgyi, Emma Moreland, David Hill-Eubanks, Martin Dichgans, Mark T. Nelson
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Brain capillaries sense neural activity and direct blood flow to active regions—a process termed neurovascular coupling that underlies activity-dependent increases in local perfusion (functional hyperemia). A key contributor to functional hyperemic responses is the capillary endothelial cell (cEC) inward rectifier K + (Kir2.1) channel, which, when activated by neuronal activity–derived extracellular K + , initiates vasodilatory electrical signals that propagate through the vascular network. Kir2.1 channel function requires continual production of its lipid cofactor, phosphatidylinositol-4,5-bisphosphate (PIP 2 ), and is compromised in mouse models of cerebral small vessel (cSVD). Although decreased PIP 2 availability is a common feature of cSVDs, mechanisms underlying PIP 2 synthesis remain poorly understood. We hypothesized that Arf6, a small GTPase expressed in cECs that stimulates PIP 2 production, is critical for this process. Using patch-clamp electrophysiology, we demonstrate that inhibiting Arf6 activity progressively decreased cEC Kir2.1 channel activity. This deficit manifested as loss of capillary-to-arteriole electrical signaling in isolated vessels and diminished functional hyperemia in vivo. Exogenously provided PIP 2 restored Kir2.1 currents and functional hyperemia after Arf6 inhibition or genetic knockdown. Collectively, our data suggest that cEC Arf6 sustains Kir2.1 activity by maintaining PIP 2 levels and demonstrate that diminished PIP 2 synthesis is sufficient to impair functional hyperemia. Furthermore, we identify Arf6 as a mechanistic link between PIP 2 production and endothelial electrical signaling, highlighting Arf6 as a potential therapeutic target for restoring functional hyperemia.
GPT-4o mini: Non-social science research article
Mitonuclear discordance modulates mitochondrial ageing dynamics in natural Drosophila populations
Stefano Bettinazzi, Avishikta Chakraborty, Finley Grover-Thomas, Damian K. Dowling, M. Florencia Camus
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Mitochondrial decline is a hallmark of ageing, yet the role of intergenomic compatibility in shaping ageing trajectories remains poorly understood, particularly in an ecologically relevant framework. Hormetic interventions have been proposed as strategies to modulate metabolism and lifespan, but it is unknown how this operates in the context of mitonuclear discordance. Here, we demonstrate that mitonuclear mismatch accelerates age-related mitochondrial decline, elevates reactive oxygen species production, and shortens lifespan. Strikingly, early-life mitochondrial stress induced by dietary modulation counteracts these effects, promoting mitochondrial homeostasis and longevity. Our findings reveal mitonuclear interactions shaping ageing trajectories in natural populations and provide unique evidence that targeted interventions can act as a buffer against the detrimental impact of genetic discordance.
GPT-4o mini: Non-social science research article
Dendritic morphology and synaptic nonlinearities enhance functional complexity in human cortical neurons
Ido Aizenbud, Daniela Yoeli, David Beniaguev, Christiaan P. J. de Kock, Michael London, Idan Segev
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Humans exhibit unique cognitive abilities within the animal kingdom, but the neural mechanisms driving these advanced capabilities remain poorly understood. Human cortical neurons differ from those of other species, such as rodents, in both their morphological and physiological characteristics. Could the distinct properties of human cortical neurons help explain the superior cognitive capabilities of humans? Understanding this relationship requires a measure to quantify how neuronal properties contribute to the functional complexity of single neurons; yet, such a standardized measure is currently missing. Here, we propose the Functional Complexity Index (FCI), a general, deep-learning-based framework for assessing the input–output complexity of neurons. By comparing the FCI of cortical pyramidal neurons across layers in rats and humans, we identified key morpho-electrical factors that underlie neuronal functional complexity. Human cortical pyramidal neurons are significantly more functionally complex than their rat counterparts, primarily due to differences in dendritic membrane area and branching patterns, as well as in the density and nonlinearity of NMDA-mediated synaptic receptors. These findings reveal the structural and biophysical basis for the enhanced functional properties of human cortical neurons, providing a key step toward understanding the underpinnings of our enhanced cognitive capabilities.
GPT-4o mini: Non-social science research article
Distinguishing direct androgenic signaling from local aromatization in the lateral septum
Dong’e Huang, Junqing Dong
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GPT-4o mini: Non-social science research article
Functional traits produce conditional outcomes in different community contexts
Ye Su, Ragan M. Callaway
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GPT-4o mini: Non-social science research article
Opportunity and risk in achieving food production and conservation goals at high altitude: Evidence from the Tibetan Plateau
Lijing Wang, Stephen Polasky, Fei Lu, Colleen R. Miller, Lingxiao Ying, Yi Xiao, Zhiyun Ouyang
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The Tibetan Plateau, the Earth’s highest and largest plateau, has a harsh environment for agriculture, and is a global biodiversity hotspot, raising the challenge of simultaneously satisfying food production and conservation goals. Currently, agriculture involves crop production on steep slopes and overgrazing, which threatens future productivity. The Tibetan Plateau is also undergoing climate change. We evaluate food production from 1990 to 2020 and use these results to model future trends and risks to food production on the Tibetan Plateau. We assess the feasibility of achieving both food production and conservation goals simultaneously under climate change scenarios. Food production increased 32.33% over three decades, providing 2,892.98 kcal d −1 cap −1 , more than enough to satisfy food self-sufficiency. Under climate change, the Tibetan Plateau will become warmer and wetter under Shared Socioeconomic Pathways (SSPs) SSP126, SSP245, and SSP585, which combined with agricultural advances (e.g., improved mechanization and irrigation), will likely result in increased yields even with a 10% reduction in cropland area—greater than the total area of all steeply sloping cropland, thereby allowing retirement of steeply sloping cropland and livestock reductions while still meeting food production goals. Meanwhile, key ecosystem services, including carbon sequestration, water retention, and habitat quality, are also projected to improve substantially. Nonetheless, the increasing frequency and severity of extreme weather events are expected to reduce food production, undermine current dietary requirements and may threaten the minimum nutritional intake required for humans.
GPT-4o mini: Non-social science research article
Mesoscale developmental rivalry in the human extrastriate visual cortex
Shahin Nasr, Jan Skerswetat, Bryan Kennedy, Marianna E. Schmidt, Eric D. Gaier, Antony B. Morland, Peter Bex, David G. Hunter
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The human extrastriate visual cortex contains fine-scale columns selectively responsive to motion, disparity, and color. However, the developmental interplay between these functional modules remains poorly understood. Using high-resolution functional MRI, we compared the mesoscale organization of the extrastriate cortex in 16 individuals with normal vision and 15 participants with amblyopia (PwA) caused by strabismus (n = 8) or anisometropia (n = 7). In controls, the cortical territory occupied by disparity-selective columns exhibited a competitive relationship with that of motion- and color-selective columns. In PwA, we witnessed a reduction in the size of disparity-selective columns accompanied by expansion of the cortical territory allocated to motion- and color-selective columns, while the interdigitated organization of these sites remained unchanged. At the macroscale, this phenomenon simply manifested as weaker disparity- plus stronger motion- and color-selective responses in PwA than controls. Our results show that the mesoscale modules are rivals in development allowing intact functions to usurp those that are compromised.
GPT-4o mini: Non-social science research article
Identification and distribution of a downregulatory signaling alkyloxazole in Streptomyces
Michael Madden, Dan Xue, Mingming Xu, Katherine Holandez-Lopez, Joseph Budiselich, Sarah Tran, Cole Espinosa, Jie Li
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Streptomyces use small molecules to dictate morphological development and secondary metabolism. Most of these signaling compounds are inducers derived from γ-butyrolactone (GBL)-synthesizing enzymes. As such, biosynthetically distinct and downregulatory signaling molecules remain understudied in Streptomyces . Here, we report the identification of alkyloxaozle (AOX, 1 ), a downregulator of sporulation and antibiotic production in Streptomyces . 1 ’s structure features an oxazole head flanked by an alkyl tail synthesized by a nonribosomal peptide synthetase (NRPS) that has not been reported in Streptomyces signaling molecules. Functional studies found that 1 downregulated sporulation and secondary metabolism in several Streptomyces strains. Genome mining identified 45 homologous biosynthetic gene clusters (BGCs) only distributed in Streptomyces , underscoring the importance of AOXs to this productive genus. Altogether, this report presents a downregulatory class of signaling molecules that broadly affect Streptomyces and highlights their importance to the genus.
GPT-4o mini: Non-social science research article
Chaos-generating periodic orbits of topological defects in confined active nematics
Brandon Klein, Alejandro J. Soto Franco, Md Mainul Hasan Sabbir, Matthew J. Deutsch, Ross Kliegman, Robin L. B. Selinger, Kevin A. Mitchell, Daniel A. Beller
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Active nematics in two dimensions stir themselves efficiently through internally generated chaotic flows, largely driven by motile + 1 / 2 disclinations.We investigate how this tendency toward chaotic fluid stirring can, counterintuitively, produce certain ordered, periodic flows in confinement, characterized by stable periodic orbits of + 1 / 2 disclinations. We computationally study two-dimensional active nematics in systems with boundary conditions requiring a prescribed number n of excess + 1 / 2 disclinations, using Beris-Edwards nematohydrodynamics simulations alongside an agent-based simulation approach. We find that when confinement is sufficiently strong to prevent defect pair-nucleation, but not strong enough to arrest all flow, then n = 3 defects generically follow a “golden braid” orbit as observed recently in experiments, and we predict a “silver braid” orbit of n = 4 defects. For these results and for greater numbers of defects, we show that the periodic or chaotic nature of the dynamics is determined by a balance between the number of defects and the number of vortices in the flow field, suggesting a design criterion for ordered flows in active nematics.
GPT-4o mini: Non-social science research article
The combinatorial innexin code of heterochannel electrical synapses governs synaptic function and is maintained by distinct cellular mechanisms
Atal Vats, Muraleedharan Sudhanand, Ananya Bandyopadhyay, Marlyn Xavier Mascarenhas, Nayantara Varma, Sandhya Padmanabhan Koushika, Abhishek Bhattacharya
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Diversity in the molecular composition of intercellular gap junction channels, the functional units of electrical synapses, determines their physiological properties. Yet the mechanisms by which neurons coordinate the use of multiple coexpressed gap junction proteins—connexins or innexins—to establish selective connections with distinct synaptic partners remain largely unknown. Using the posterior mechanosensory circuit in Caenorhabditis elegans, we found that individual electrical synapses can form by clustering molecularly distinct gap junction channel types composed of three different innexin proteins: INX-1, UNC-7, and UNC-9. This previously uncharacterized combinatorial configuration, which we term heterochannel synapses, enables molecularly distinct gap junction channel types to collaborate functionally to regulate posterior touch sensory behavior and enhance functional robustness. We show that the synaptic trafficking of these molecularly distinct channel types within a heterochannel synapse is independently regulated by specific and conserved kinesin motor proteins, while distinct molecular pathways involving channel type-specific retrograde kinesins control their turnover. These independent, channel-specific regulatory mechanisms allow for individual synapse-level alterations in the combinatorial innexin code of heterochannel synapses in response to altered environmental conditions, providing a mechanism for electrical synapse plasticity. Finally, we present evidence and functional significance of heterochannel electrical synapses in C. elegans locomotory circuits. Altogether, our findings demonstrate a combinatorial heterochannel organization of electrical synapses, their functional significance, and the regulatory mechanisms that govern them.
GPT-4o mini: Non-social science research article
Vimentin promotes actin assembly by stabilizing ATP-actin subunits at the barbed end
Lilian Paty, Lukas Kalvoda, Maritzaida Varela-Salgado, Quang D. Tran, Martin Lenz, Antoine JĂ©gou, Guillaume Romet-Lemonne, CĂ©cile Leduc
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Vimentin intermediate filaments play essential roles in maintaining cell integrity and regulating numerous cellular functions. In particular, vimentin cooperates with the actin cytoskeleton in key cellular processes that rely on actin dynamics, such as migration, division, and mechanosensing. While there is evidence that these two cytoskeletal components interact in cells, the underlying molecular mechanisms are only partially understood. Actin and vimentin can interact through biochemical signaling pathways or via cross-linkers, but whether they engage in a direct protein–protein interaction has remained controversial, in part because such interactions are difficult to isolate and characterize in cells. Using in vitro reconstitution coupled to theoretical modeling, and total internal reflection fluorescence microscopy to monitor the elongation of single actin filaments, we show that vimentin promotes actin elongation by stabilizing actin subunits at the barbed end in a dose-dependent manner. Strikingly, this effect depends on the nucleotide state of actin, as the acceleration is only observed for the elongation from adenosine triphosphate (ATP)-actin, and not adenosine diphosphate (ADP)-actin monomers. We further establish that neither the vimentin tail nor head domains are required for this effect, and both filamentous and nonfilamentous vimentin enhance actin elongation. Finally, we find that vimentin promotes the nucleation of actin filaments. Consistently, magnetic pull-down assays demonstrate a direct interaction between vimentin and ATP-actin monomers. Altogether, these findings identify vimentin as an unexpected new actor in the regulation of actin dynamics at the barbed end and bring new insights into the functional role of vimentin through cytoskeletal crosstalk.
GPT-4o mini: Non-social science research article
Structural characterization of human neutralizing antibodies against JC and BK polyomaviruses
Christina Harprecht, Luisa J. Ströh, Bethany A. O’Hara, Jasmin Freytag, Felix Nagel, Sheila A. Haley, York-Dieter Stierhof, Walter J. Atwood, Thilo Stehle
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The human JC polyomavirus (JCPyV) causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals. JCPyV frequently undergoes mutations in PML patients, and these variants are thought to establish “antibody recognition holes” that enable the virus to circumvent the antibody response of infected individuals. Many of these PML-associated mutations cluster in the glycan receptor-binding site of the virus. Using X-ray crystallography, we investigated the binding modes of JCPyV VP1-specific human monoclonal antibodies (mAbs) that were isolated from healthy donors and individuals who recovered from PML, and that can recognize a panel of PML-associated JCPyV variants. Our structural analyses show that three out of four of these mAbs bind epitopes that overlap with the glycan–receptor binding site at the surface of the virus particle. The observed interactions explain how PML-associated mutations strategically interfere with antibody recognition, resulting in immune evasion. In contrast, mAb 29B1 engages a region of the capsid that is distant from the glycan site and does not feature mutations associated with PML. The binding site is conserved in the closely related BK polyomavirus (BKPyV), and we show that mAb 29B1 binds both viruses with high affinity and blocks infection. Our findings form an excellent platform for the development of therapeutic Ab approaches and potential vaccination strategies that could protect at-risk patients from infections with both JCPyV and BKPyV. Moreover, small molecules that target the mAb 29B1 binding site could be potentially effective against both viruses.
GPT-4o mini: Non-social science research article
Costunolide ameliorates autoimmune uveitis by targeting USP15 to suppress TNF-α-induced retinal endothelial inflammation
Yu Gao, Xingran Li, Lingyu Dai, Xiang Luo, Guannan Su, Kai Shi, Ling Chen, Peizeng Yang
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Autoimmune uveitis is a sight-threatening inflammatory disease, with the majority of entities driven by leukocyte infiltration into the retina. A critical early step in this process is the activation of retinal vascular endothelial cells (ECs), which up-regulate adhesion molecules that mediate T cell adhesion and subsequent extravasation. Here, we identify the small terpenoid compound costunolide (COS) as a potent suppressor of retinal endothelial inflammation and disease progression in experimental autoimmune uveitis (EAU). Quantitative proteomics of primary human retinal endothelial cells stimulated with TNF-α defined a proinflammatory endothelial signature and revealed induction of adhesion molecules. Screening of a focused library of 337 terpenoids uncovered COS as a top hit that markedly attenuated TNF-α-induced endothelial activation. In vivo, COS treatment significantly reduced clinical and histopathologic EAU scores, accompanied with reduced endothelial adhesion molecule expression and decreased T cell infiltration. Mechanistically, COS directly targeted deubiquitinase USP15, inhibiting USP15-dependent deubiquitination of TRAF1 and TNF signaling in retinal ECs. These findings establish COS as a candidate therapeutic agent for autoimmune uveitis and reveal a TNF-α–USP15–TRAF1 axis in retinal endothelium that can be pharmacologically exploited to limit pathogenic leukocyte trafficking.
GPT-4o mini: Non-social science research article
Liquid–liquid phase separation enables chromatography-free purification and high-performance spidroin-amyloid hybrid silk fibers
Karin Tufvesson, Viktoria Langwallner, Tomas Bohn Pessatti, Gabriele Greco, Elin Karlsson, Sarah Stadlmayr, Axel Leppert, Michael Landreh, Anna Rising, Benjamin Schmuck
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Large-scale production of artificial spider silk fibers requires heterologous expression of spider silk proteins (spidroins), yet current methods remain limited by low yields and costly purification processes. To overcome these challenges, we engineered mini-spidroins in which the poly-alanine motifs of the repetitive region were replaced with the non-natural amyloidogenic ÎČ16 peptide, significantly enhancing expression yields and solubility. Furthermore, we developed a simple, chromatography-free purification method for these constructs based on NaCl-induced liquid–liquid phase separation (LLPS). This one-step purification strategy reduced processing costs by up to 99% compared to conventional affinity chromatography while achieving yields of ~300 mg of purified protein per liter of shake flask culture and ~25 g L −1 from bioreactor cultivations. The purified engineered mini-spidroins could be spun into continuous fibers using an all-aqueous, biomimetic spinning process triggered by a pH drop. The resulting fibers exhibited mechanical properties comparable to those produced from the mini-spidroin NT2RepCT, which requires conventional chromatographic purification. Together, our protein-engineering approach and LLPS-based purification method provide a potentially scalable, sustainable, and cost-effective platform for artificial spider silk, representing a major step toward the commercial viability of recombinant silk-based materials.
GPT-4o mini: Non-social science research article
Louis E. Brus (1943–2026): A consummate physical chemist and a pioneer in the exploration of spectroscopy of materials at the nanoscale
William L. Wilson, A. L. Harris, T. D. Harris, M. L. Steigerwald, J. C. Tully, S. Wong
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Last year we lost a true pioneer in the field of nanoscience. Louis E. Brus didn’t chase fame, he chased “the problem.” His career is a monument to the power of curiosity driven science, the kind of impactful science nurtured by Bell Laboratories in the 1980s and 1990s. Collaborative to his core, Louis is as good an example of a “Bell Labs type” as you can find. His intellect, mentorship, and kindness will be greatly missed by his friends, students, and colleagues.
GPT-4o mini: Non-social science research article
SpyCEP dismantles neutrophil immunity via disorder-driven chemokine remodeling and GAG targeting
Rikin J. Lau, Sean P. Giblin, Andra Sugar, Antonio Di Maio, Giulio Tassini, Kristin Huse, Dror Chorev, Yuan Chen, Grace Ho-Yan Wu, Camilla Berg Huemer, Seung Yon Kim, Jayden Matthews, Bel Muloud, Lu Chen, Sophie McKenna, Yingqi Xu, Luisa Massai, Chiara Muzzi, Xhenti Ferhati, Francesca Necchi, Danilo Gomes Moriel, Ten Feizi, Yan Liu, James E. Pease, Shiranee Sriskandan, Steve Matthews
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Streptococcus pyogenes (Group A Streptococcus ) employs sophisticated virulence strategies to evade human immunity, including secretion of the cell envelope protease SpyCEP, which cleaves and inactivates key neutrophil-attracting chemokines such as CXCL8. Here, we integrate cryo-electron microscopy, NMR spectroscopy, and native mass spectrometry to investigate how SpyCEP disrupts CXCL8 function. We demonstrate that a disordered aromatic and acidic region within the cleaved autocatalytic maturation loop (CAML) of SpyCEP mimics receptor N-domains and binds an allosteric site on CXCL8. The resulting interaction forms a dynamic fuzzy complex and is coupled to dimer dissociation, consistent with enhanced access to the cleavage site. This disorder-mediated substrate engagement differs from classical protease mechanisms that rely on rigid recognition interfaces. Additionally, glycan microarray and NMR analyses show that the CAML region mediates glycosaminoglycan (GAG) binding, suggesting a means for SpyCEP to maximize encounters with GAG-enriched CXCL8 reservoirs. Together, these findings provide a structural and biophysical framework for understanding how SpyCEP combines substrate engagement with GAG targeting to dismantle chemokine gradients and inhibit neutrophil recruitment. More broadly, this work highlights the role of intrinsic disorder in protease recognition and suggests avenues for anti-virulence therapies and vaccine strategies targeting SpyCEP.
GPT-4o mini: Non-social science research article
mRNA lipid nanoparticle cancer vaccine platform delivering multiple STING activators for enhanced antitumor activity
Ye Zeng, Junchao Xu, Jinjin Wang, Lulu Xue, Jiageng Liu, Hannah C. Geisler, Xu Ma, Jilian R. Melamed, Qiangqiang Shi, Marshall S. Padilla, Zhangyi Luo, Jingcheng Zhu, Ajay S. Thatte, Christian G. Figueroa-Espada, Melgious Jin Yan Ang, Amanda M. Murray, Hannah M. Yamagata, Dongyoon Kim, Ann E. Metzloff, Drew Weissman, Michael J. Mitchell
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mRNA-based cancer vaccines offer a modular and safe platform to elicit antitumor immunity, yet their efficacy is often limited by inefficient mRNA delivery and inadequate dendritic cell (DC) activation, both of which are essential for initiating robust cytotoxic T cell responses. Inadequate innate immune activation coupled with poor antigen presentation further diminishes their effectiveness, particularly in immunologically “cold” tumors. While stimulator of interferon genes (STING) agonists can enhance DC maturation and cross-presentation, their therapeutic utility is constrained by poor intracellular delivery and limited colocalization with tumor antigens. In this study, we developed a lipid nanoparticle (LNP) platform via high-throughput screening of ionizable lipids for potent mRNA delivery to DCs both in vitro and in vivo. To amplify immune activation, we coencapsulated the STING agonists c-di-AMP (AMP) and manganese (Mn 2+ ) together with tumor antigen-encoding mRNA into the lead LNP formulation. This codelivery strategy synergistically activated type I interferon signaling, upregulated costimulatory molecules, enhanced antigen presentation, and elicited potent tumor-specific T cell responses and superior antitumor efficacy. Our results demonstrate that integrating innate immune stimulation with mRNA-LNP delivery provides a promising strategy to overcome current limitations in mRNA vaccine efficacy and to improve cancer immunotherapy outcomes.
GPT-4o mini: Non-social science research article
QnAs with Daniel Herschlag
Sandeep Ravindran
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GPT-4o mini: Non-social science research article
A ligandable PNT domain establishes ERG as a directly targetable oncogenic driver in prostate cancer
Xiaoju Wang, Wenyan Liu, Jiehao Yang, Jean Ching-Yi Tien, Yu Chang, Rahul Mannan, Somnath Mahapatra, Yang Zhou, Lihao Gan, Xuhong Cao, Jiayi Zhou, Yuping Zhang, Sharpkate Shaker, Yichao Huang, Hang Qiao, Rudana Hamadeh, Grafton Ervine, Cynthia Wang, Fengyun Su, Rui Wang, Lanbo Xiao, Raghunath Ranga Sudharshan, Arvind Rao, Zaneta Nikolovska-Coleska, Cole Stephens, Lifeng Pan, James J. Chou, Debashish Sahu, Jeanne Stuckey, Zhen Wang, Ke Ding, Arul M. Chinnaiyan
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The TMPRSS2:ERG gene fusion, present in approximately 50% of prostate cancers in patients of European ancestry, drives oncogenesis through aberrant overexpression of the ERG transcription factor. Despite its role as a truncal oncogenic driver, ERG has been considered undruggable due to the absence of enzymatic activity and apparent lack of ligandable pockets. Here, we demonstrate continued dependency on ERG in metastatic prostate cancer and identify a druggable pocket within its N-terminal Pointed (PNT) domain. Using an inducible shRNA system in TMPRSS2:ERG -positive VCaP cells, we show that ERG depletion causes profound growth inhibition. To therapeutically exploit this vulnerability, we conducted a domain-focused differential scanning fluorimetry screen targeting the ERG PNT domain, followed by structure–activity relationship optimization. This approach yielded PBITE-1 (PNT-Binding Inhibitor of the Transcription factor ERG), a small molecule that selectively binds the ERG PNT domain. NMR chemical-shift perturbation mapping and molecular docking revealed that PBITE-1 engages a discrete, solvent-exposed surface comprising two α-helices and an adjacent flexible loop, defining a ligand-binding pocket within the PNT domain. In cellular models, PBITE-1 directly engaged ERG, selectively inhibited proliferation and invasion, and induced apoptosis in ERG-driven prostate and hematologic malignancies. PBITE-1 potently suppressed growth of ERG-positive mouse and human-derived prostate cancer organoids. Furthermore, PBITE-1 treatment significantly induced tumor cell apoptosis in VCaP xenograft models. These findings establish the ERG PNT domain as ligandable and provide preclinical evidence that ERG is directly targetable by small molecules, enabling future development of ERG-directed inhibitors and targeted protein degraders.
GPT-4o mini: Non-social science research article
Divergent trait controls on soluble sugars and starch underlie global strategies of tree carbohydrate storage
Weibin Li, Henry D. Adams, Antoine Cabon, Kailiang Yu, Drew M. P. Peltier, Nate McDowell
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Nonstructural carbohydrate (NSC) stores buffer tree metabolism, osmotic regulation, and defense, thereby mediating tolerance and survival under climate extremes. Yet, the functional and evolutionary determinants of interspecific variation in NSC remain elusive, limiting understanding and prediction of forest carbon allocation and mortality under global change. Here, we present a cross-species synthesis of NSC concentrations across multiple organs for 281 woody species from 102 mixed forest communities worldwide, where we quantified species-specific deviations from community means to disentangle intrinsic trait effects from environmental and methodological variation. We found phylogenetic signals in NSC deviations, with coniferous gymnosperms and evergreen species consistently maintaining lower stem soluble sugars and starch concentrations than co-occurring angiosperms and deciduous species, respectively. A global pattern emerged where greater stomatal sensitivity to leaf water potential was associated with declines in the relative concentrations of both sugars and starch. In contrast, xylem hydraulic safety traits showed weak and organ-dependent relationships with NSC concentrations. Sugars increased with photosynthetic capacity and declined with wood density, whereas starch showed the reverse pattern, which aligned with the distinct functional-metabolic roles of sugars and starch. By integrating trait-based ecology with a community-centered framework, our study provides global evidence that stomatal regulation, photosynthetic capacity, specific leaf area, and wood density jointly govern interspecific NSC variation, through contrasting effects on sugars and starch. These are among the most broadly measured traits globally, thus the emergent carbohydrate–trait relationships can have broad applications toward understanding and predicting forest growth and survival under climate change.
GPT-4o mini: Non-social science research article
Reply to Rana and Singh: Critical thresholds and critical actions for evolvable AI
Viktor MĂŒller, Luc Steels, Eörs SzathmĂĄry
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GPT-4o mini: Non-social science research article
Stress granules as RNA triage hubs suppress extracellular vesicle secretion under oxidative stress in cancer
Yue Dong, Takeshi Yoshida, Mitsuyo Maeda, Haruki Adachi, Asami Eguchi, Emi Mishiro-Sato, Daisuke Okuzaki, Yosky Kataoka, Takuya Yoshida, Chitose Oneyama
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Cancer cells confronting oxidative stress must coordinate their extracellular vesicle (EV) secretion to balance intercellular signaling with the intracellular programs required for survival, yet how these decisions are integrated remains poorly understood. Here, we identify a stress-adaptive mechanism in which stress granules (SGs) selectively suppress CD63 + EV release. Using a bioluminescent EV–reporter screen, we found that the clinical compound YM155 selectively inhibits CD63 + EV secretion across diverse tumor cells. Mechanistically, YM155 rapidly inactivates the antioxidant transcription factor FOXO3a, diminishing expression of key detoxifying enzymes and leading to delayed but sustained accumulation of reactive oxygen species (ROS). Elevated ROS drives SG formation, and these SGs function not as passive storage sites but as RNA triage hubs that exclude and destabilize a subset of transcripts. Among them, Rab27A mRNA—encoding a GTPase essential for multivesicular-body docking to the plasma membrane—is selectively excluded and degraded, resulting in loss of Rab27A protein and suppression of CD63 + EV secretion. Forced Rab27A expression restores EV release but paradoxically reduces proliferation under oxidative stress, indicating that EV suppression is prosurvival. The same FOXO3a–ROS–SG–Rab27A axis operates during physiological glucose deprivation and is evident in vivo, where SGs form in xenograft tumors and circulating CD63 + EVs decline. Pancancer transcriptomic analyses further show that Rab27A expression correlates with FOXO3a-dependent antioxidant programs, underscoring clinical relevance. These findings reveal that SGs actively reprogram RNA fate to tune vesicle output, establishing a redox-responsive mechanism by which cancer cells transiently suppress EV secretion to enhance survival.
GPT-4o mini: Non-social science research article
Asymmetric and Intermittent Supershear Rupture Mediated by Local Fault Complexity during the 2025 M W 7.7 Myanmar Earthquake
Tao Xia, Lingling Ye, Jinlai Hao, Haijun Gao, Thorne Lay, Xiaotian Ding, Zhenxing Yao
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We determine the detailed rupture process of the 2025 M W 7.7 Myanmar earthquake by joint inversion of near-fault strong-motion, geodetic, and teleseismic data. The rupture initiated with significant slip of up to ~5 m near the epicenter. Localized fault geometric complexity and stress heterogeneity might have led to small-scale slip segmentation and intermittent episodes of supershear rupture. Northward rupture propagation was subshear overall and terminated rapidly after extending ~80 km within the partial stress shadow of a 2012 earthquake. In contrast, southward rupture propagated ~380 km, fully traversing a predefined seismic gap that had been unruptured since 1839, and undergoing cycles of acceleration and deceleration that included at least two episodes of intermittent supershear rupture before gradually stopping after traversing a segment that ruptured in 1930. Slip exceeding 3 m is confined to the shallow fault above a 15 km locking depth and the average static stress drop is 4.7 MPa. The long-term stress accumulation on multiple asperities along the central Sagaing fault promotes localized ruptures in discrete events but sometimes leads to rupture cascades with intermittent supershear behavior as in 2025. Local slip duration also displays a north–south asymmetry, being longer near the epicenter and progressively shorter toward the south before the end. This pattern may be associated with lower rigidity near the epicenter and rupture dynamics being modulated by fault edges for long, narrow strike-slip faults. Our findings highlight the roles of localized fault structure and stress heterogeneity in controlling slip distribution and rupture speed.
GPT-4o mini: Non-social science research article
Sex- and experience-dependent regulation of synaptic protein turnover
Seok Heo, Shiyu Zhang, Dong-Gi Mun, Akhilesh Pandey, Alexei M. Bygrave, Richard L. Huganir
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Synaptic transmission can be tuned through plasticity mechanisms that regulate synaptic strength, structure, and number. In vivo measurements demonstrate remarkable spine dynamics, with subsets of synapses persisting for months. This correlates with the longevity of certain memories, which can persist for an organism’s lifetime. The molecular basis supporting the long-term stability of specific synapses and the long-term durability of memories remains unknown. At the protein level, most proteins persist for a relatively short amount of time before they are degraded and replaced with new molecules. However, recent work has identified a population of proteins, including those present at the synapse, that are exceptionally long-lived. It has been speculated that long-lived proteins (LLPs) could contribute to long-term synapse stability, function, and memory. Here, we used stable isotope labeling in mammals to first identify LLPs in the post synaptic density (PSD) of the hippocampus and subsequently determine if protein turnover rates varied by sex or following learning. We identified synaptic LLPs and found that both sex and experience can regulate synaptic protein turnover rates. We identified sex-dependent changes in protein turnover rates in autism spectrum disorder risk genes, including increased stability of Gabrg2, a GABA-A receptor subunit, in male mice. Furthermore, we observed stabilization of a subset of PSD proteins, such as Shank3, following contextual fear conditioning. We propose that sex- and experience-dependent changes in protein turnover rates could help explain sex-differences in psychiatric risk and aid our understanding of the molecular mechanisms that support learning and memory.
GPT-4o mini: Non-social science research article
Time-resolved morphological and transcriptomic characterization of early enteric neuron subtype emergence in chick
Maëlys André, Raphael Gury, Maxime Lepetit, Franck Boismoreau, Muriel Bozon, Jérémy Ganofsky, Cassandre Heritier-Tellier, Ingrid Plotton, Rémi Duclaux-Loras, Noël Peretti, Guillaume Marcy, Valérie Castellani, Julien Falk
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The genetic programs directing nascent enteric nervous circuits and their unique architecture remain poorly characterized. To gain insight, we combined manipulations in the chick embryo model, whole gut three-dimensional (3D) imaging, and single-nucleus transcriptomics at very short intervals for time-resolved analyses of neuronal subtype trajectories. In imaging, we found highly dynamic axon network growth, with rapid increase in axon density and spatial orientation diversification. At transcriptomic levels, we correlated these changes to cell-state transitions with specific axon guidance gene sets. Cross-analyses with human and mouse embryo scRNAseq and expression profiles revealed globally conserved enteric lineage trajectories and subtypes specific axon guidance programs in all species. Finally, manipulation of DSCAM and ISLR2 evolutionary conserved networks in chick whole gut cultures altered enteric axon patterns, validating our paradigm and its applicability to advance current knowledge on human enteric circuit wiring.
GPT-4o mini: Non-social science research article
Identification of cellular intermediates unveils unique enzymes for flagellar glycan biosynthesis in Clostridioides difficile
Paul J. Hensbergen, Bob van Puffelen, Nina Musch, Augustinus N. A. Ammerlaan, Paul L. C. Zuidgeest, Loes van Huijkelom, Rembrandt J. V. Kanbier, Maaike M. Vet, Xuan S. Zheng, Pranav V. N. Bhamidipati, Martin F. Larralde, Niek Blomberg, Sarantos Kostidis, Peter A. van Veelen, Robert A. Cordfunke, Jordy van Angeren, Arnoud H. de Ru, Zachary W. B. Armstrong, Wiep Klaas Smits, Dmitri V. Filippov, Martin Giera, Jeroen D. C. Codée, Jeroen Corver
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Glycosylation of bacterial surface proteins, such as flagellin (FliC), is important for their function and is often involved in virulence of pathogens. Glycans can be further modified by so-called postglycosylation modifications (PGMs), often resulting in exclusive molecular structures. In Clostridioides difficile, a unique glycan structure (Type A) decorates FliC (which forms the flagellar filament) that consists of an O -linked N -acetyl-ÎČ- d -glucosamine (GlcNAc) modified with an N -methyl-L-threonine via a phosphodiester linkage. This PGM is synthesized by a set of four enzymes encoded in one operon ( ftaABCD ), but the exact biosynthesis pathway and biosynthetic intermediates remain unknown. In this study, we chemically synthesized two hitherto undescribed biosynthetic intermediates that we predicted based on bioinformatic analyses, CDP-threonine and CDP- N -methylthreonine. We showed that they are involved in the Type A PGM biosynthesis, as evidenced by mass spectrometric analyses of extracts of a set of C. difficile mutant strains. Furthermore, we characterized FtaC to be a SAM-dependent CDP-threonine N -methyltransferase that installs the methyl group on CDP-threonine prior to transfer of the PGM to GlcNAc-FliC, and we revealed FtaD as the CDP- N -methylthreonine:GlcNAc N -methylthreoninephosphotransferase. Finally, using recombinantly expressed FtaC and FtaD in combination with synthetic CDP-threonine, we reconstituted the biosynthesis pathway of the Type A PGM in vitro. Overall, our results open avenues to explore these unique biosynthesis enzymes in molecular detail to provide new points of entry for the development of biosynthesis inhibitors and tools to study the role of this PGM in virulence and flagellar function.
GPT-4o mini: Non-social science research article
Bumblebees’ orofacial reactions to tastes provide evidence for affective evaluation
Yonghe Zhou, Thomas Ingraham, Andrew B. Barron, Fei Peng, Cwyn Solvi
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Facial expressions provide a critical window into the internal states of animals, allowing the identification of affective processes and their underlying neural mechanisms. In mammals, postconsumption orofacial reactions—such as tongue protrusions to sweet tastes—are among the most robust and widely accepted behavioral markers of positive hedonic impact (liking), distinct from motivation (wanting). However, no equivalent markers have been established in insects, leaving their capacity for affective evaluation unresolved. Here, we show that bumblebees exhibit discrete orofacial reactions that are functionally analogous to those described in mammals. Bees displayed postconsumption glossa protrusions to rewarding solutions and head-shaking and mouth-wiping to aversive tastes. These reactions were not tied to any specific taste identity. Behavioral and pharmacological experiments demonstrated that glossa protrusions did not automatically occur due to consumption, were independent of ongoing feeding mechanisms and dopamine-mediated motivation, and were enhanced by the endocannabinoid anandamide. Our findings support postconsumption glossa protrusions as a fast, reliable, and evolutionarily comparable candidate behavioral marker of affective evaluation in an invertebrate. By providing evidence that a behavior which tracks liking can be dissociated from motivational (wanting) responsiveness in bumblebees, this work establishes an experimental framework for investigating the neural basis and evolutionary origins of affective processing. More broadly, these results open the door to rigorous cross-phyletic approaches to emotion.
GPT-4o mini: Non-social science research article
A DNA break-5mC cycle activates transposable elements in Arabidopsis
Wenjie Liang, Haokai Cao, Chen Zou, Xindong Tong, Yongbo Ma, Yitong Shen, Xue Han, Yilin Zhang, Binglian Zheng, Jinchao Li
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Plant genomic and epigenomic integrity are perpetually threatened by exogenous and endogenous DNA damage. However, the interplay between DNA damage, DNA methylation (5mC), and transposable element (TE) activity remains poorly understood. Here, we demonstrate that defective single-strand break (SSB) repair acts as a potent trigger for genome-wide TE derepression and extensive de novo DNA methylation in Arabidopsis . Mutations in ZDP/APE2, which encode conserved DNA 3’-end repair enzymes, impair the repair of 3’-blocked SSBs arising from base excision repair, ultimately leading to widespread TE activation. Concurrently, inefficient SSB repair activates the ATR–SOG1-mediated DNA damage response, which enhances the RNA-directed DNA methylation (RdDM) pathway to counteract TE activation by depositing 5mC. Paradoxically, the resulting methylation is excised by the DNA demethylase ROS1—a process that itself generates 3’-blocked SSBs requiring resolution by ZDP/APE2. In zdp ape2 mutants, ROS1-mediated 5mC excision produces additional SSBs, which in turn reactivate RdDM. This establishes a self-sustaining SSB–5mC cycle that perpetuates DNA damage and drives massive TE activation in the mutant. Our findings reveal a critical mechanistic link between SSB repair, DNA methylation dynamics, and TE derepression, positioning defective SSB repair as a major inducer of epigenomic instability.
GPT-4o mini: Non-social science research article
Probing anharmonic and heterogeneous carrier dynamics across sublattice melting in a minimal model superionic conductor
Sucharita Niyogi, Takenobu Nakamura, Genki Kobayashi, Yasunobu Ando, Takeshi Kawasaki
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Despite decades of research, the microscopic origin of sublattice melting and fast ion transport in superionic conductors remains elusive. Here, we introduce a chemically neutral minimal binary model consisting of a rigid host lattice stabilized by short-range steric repulsion and a soft carrier sublattice interacting via long-range Wigner-type forces. This contrast naturally produces distinct melting temperatures and an intermediate sublattice-melting phase in which carriers become fluidlike while the host remains crystalline. Molecular dynamics simulations identify multiple dynamical regimes–crystalline, sublattice-melt, and fully molten–marked by sharp changes in diffusivity, structural correlations, and dynamical heterogeneity. Near sublattice melting, carrier motion is strongly anharmonic and spatially heterogeneous, beyond mean-field hopping descriptions. By tuning the density, we demonstrate that sublattice melting can be continuously controlled, establishing a direct link between lattice softness, anharmonicity, and collective ion transport. Comparison with conventional long-range Coulombic models confirms that our minimal model reproduces the key dynamical signatures of superionicity, providing a unified microscopic foundation for designing mechanically robust superionic conductors.
GPT-4o mini: Non-social science research article
Covalent phytobilin adducts of GUN4 implicate a photoprotective mechanism in chlorophyll biosynthesis
Yan Wang, Chunhui Hou, Nathan C. Rockwell, Pawel Brzezowski, Weiqing Zhang, Xiahe Huang, Qiuling Fan, Yingchun Wang, Bernhard Grimm, J. Clark Lagarias, Deqiang Duanmu
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In the green alga Chlamydomonas reinhardtii, loss of chlorophyll synthesis under light stress is associated with degradation of the porphyrin-binding H-subunit (CHLH1) of magnesium chelatase (MgCh). This degradation is exacerbated by the absence of GENOMES UNCOUPLED 4 protein (GUN4) or its phycocyanobilin (PCB) ligand. PCB is synthesized from heme via the action of heme oxygenase HMOX1 followed by a ferredoxin-dependent bilin reductase (FDBR), a ubiquitous enzyme family in oxyphototrophs. We show that C. reinhardtii cells lacking GUN4 and/or HMOX1 accumulate the MgCh substrate protoporphyrin IX (PPIX), a potent generator of singlet oxygen ( 1 O 2 ). CHLH1 is unstable in gun4 or hmox1 mutants, phenotypes that can be rescued by deletion of known cytosolic 1 O 2 response proteins SAK1 or SOR1. GUN4 Trp residues are oxidized in the presence of PPIX and near-ultraviolet light (nUV), and spectroscopic changes in GUN4 seen in the presence of PCB are ablated by PPIX and nUV. The combination of PPIX, PCB, and nUV result in formation of covalent GUN4–bilin adducts. Such adducts are formed both in vivo and in vitro and are also formed in GUN4 proteins from cyanobacteria and plants. In GUN4 variants, loss of adduct formation correlates with Chlamydomonas growth defects under light stress. We propose that phytobilin adduct formation provides a mechanism for detoxifying 1 O 2 and sustaining chlorophyll synthesis in the presence of light and oxygen, thereby explaining the ubiquity of FDBRs in eukaryotic algae.
GPT-4o mini: Non-social science research article
Arabidopsis BSL phosphatases regulate zygote polarity through a brassinosteroid-independent essential function in MAP kinase signaling
Sangho Jeong, Gabriel Eschedor, Magdy Alabady, Wolfgang Lukowitz
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The main axis of the plant body is established in early embryogenesis. Polar growth and asymmetric division of the Arabidopsis zygote require the Mitogen-Activated Protein (MAP) kinase kinase kinase YODA and the MAP kinases MPK3/MPK6, but regulation of this signaling cascade is not well understood. Here, we show that three BSU1-LIKE phosphatases (BSL1-3) are essential positive regulators: A combined loss causes closely similar defects to loss of the YODA MAP kinase cascade, resulting in nonpolar embryos; transcriptional profiling and cell-fate markers confirm that BSL phosphatases and the MAP kinase cascade regulate the same process. Unexpectedly, the founding member of the family, BSU1, appears dispensable. These results cast doubt on the view of BSU1-family phosphatases as core components of brassinosteroid hormone signaling. MPK3 activity shows striking sensitivity to BSL dosage, and genetic interactions with activated MPK3 suggest that BSL phosphatases function downstream of YODA and either in conjunction with or downstream of MPK3/MPK6, implying a novel mechanism of MPK regulation.
GPT-4o mini: Non-social science research article
Spontaneous phase separation and pattern formation in a lyotropic nematic mixture
Ana Bensabat, Órlaith Skelton, Jochen Arlt, Marko Bjelogrlić, Davide Marenduzzo, Giuseppe Negro, Tyler N. Shendruk, Tiffany A. Wood
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Lyotropic liquid crystals can display rich phase behavior and self-organization, yet the physical principles underlying their self-assembly into large scale patterns remains understudied. Here, we combine theory, simulations, and experiments on Sunset Yellow-water chromonic mixtures to show that such materials spontaneously phase separate, even without assuming any underlying microscopic attraction between the molecular species. In our minimal model, demixing depends solely on the Onsager-like coupling between local nematogen density and orientational order. If such a coupling is sufficiently strong, nematic defects trigger the nucleation of isotropic droplets, which then coalesce due to elastic or interfacial tensions. We further show that strong anchoring of the director field at the interface arrests this coarsening process, resulting in a stable microphase-separated lamellar pattern. This self-assembled lamellar phase has striking and unusual features, including spontaneous undulations, heterogeneous layer spacing, long-lived glassy defect patterns and lamellar onions. Our results identify orientational-density coupling and elastocapillarity as fundamental mechanisms to guide self-assembly in lyotropic and chromonic liquid crystals.
GPT-4o mini: Non-social science research article
Strengthening of negative fire–fuel feedbacks by large fires in eastern Canadian boreal forests
Zackary Shakeri, Dominique Arseneault, Martin Simard, Marc-André Parisien
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Fire-induced reductions in biomass limit the likelihood of reburning during early vegetation recovery in several crown-fire ecosystems; however, it is unclear how this negative fire–fuel feedback will buffer the rising fire activity expected with climate change. Although the feedback weakens with increasing time since the last fire and with increasing fire-weather severity, how the spatial configuration of fuel influences fire-return intervals remains unknown. Using a detailed 204-y fire history reconstruction along a 300-km longitudinal transect in eastern Canadian boreal forests, we show that interior areas of large fires (>8 km from the fire edge) are much less likely to reburn at short intervals than edges (<2 km from the edge), indicating a strengthening of the feedback within large burns. This process results in fewer fires in immature stands that are vulnerable to poor tree regeneration, thus conferring substantial resistance against compositional changes. However, the reduction in short-interval fires also fosters the development of large patches of mature forest that become extremely fire-prone after 4 to 5 decades and thereby predisposes landscapes to recurrent large fires. This study highlights an overlooked mechanism by which increases in fire size due to climate change may expose boreal forests of eastern Canada to large fires burning at longer intervals rather than to more frequent short-interval fires, which should sustain their capacity to recover.
GPT-4o mini: Non-social science research article
Mapping the dialogue: Decoding alveolar stem–niche interactions
Ahmad N. Nabhan, Anne Biton, Christine Everett, Conrad Foo, Diana Wu, Joshua D. Webster, Alina A. Alam, Elisa Penna, Sandra Rost, Neha Rohatgi, Rohit Reja, Ranel J. Tulpano, Shiqi Xie, Celine Eidenschenk, Kim Newton, Joseph R. Arron, Vishva M. Dixit
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While cellular atlases have revealed remarkable phenotypic diversity, how cells navigate this landscape to influence tissue behavior remains poorly understood. We present an alveolosphere screening platform for investigating interactions between lung stem cells and their fibroblast niche. We assessed the role of 201 candidate genes in stem cells via imaging, then used chimeric RNAseq analysis for a transcriptome-wide understanding of cell-autonomous effects on stem cells and non-cell-autonomous effects on the niche. This phenome-transcriptome map uncovered cellular states and pathways regulating proliferation, metabolism, and immune signaling. Notably, stem cells influenced scar-forming and immune programs in fibroblasts. This injury response was dependent on stem cell identity; loss of Nkx2.1 , encoding the transcription factor conferring lung epithelial identity, rewired stem cell–niche interactions and had a greater non-cell-autonomous effect than eliminating the cancer genes Trp53, Egfr, or Cdkn2b . Our study highlights how functional atlases complement the cellular diversity revealed by descriptive methods.
GPT-4o mini: Non-social science research article
Provable cluster-preserving visualizations with curvature-based stochastic neighbor embeddings
Tristan Luca Saidi, Abigail Hickok, Bastian Rieck, Andrew J. Blumberg
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Stochastic Neighbor Embedding (SNE) algorithms like UMAP and tSNE often produce visualizations that do not preserve the geometry of noisy and high dimensional data. In particular, they can spuriously separate connected components of the underlying data submanifold and can fail to find clusters in well-clusterable data. To address these limitations, we propose EmbedOR, a SNE algorithm that incorporates discrete graph curvature. Our algorithm stochastically embeds the data using a curvature-enhanced distance metric that emphasizes underlying cluster structure. Critically, we prove that the EmbedOR distance metric extends consistency results for tSNE to a much broader class of datasets. We also describe extensive experiments on synthetic and real data that demonstrate the visualization and geometry-preservation capabilities of EmbedOR. We find that, unlike other SNE algorithms and UMAP, EmbedOR is much less likely to fragment continuous, high-density regions of the data. Finally, we demonstrate that the EmbedOR distance metric can be used as a tool to annotate existing visualizations to identify fragmentation and provide deeper insight into the underlying geometry of the data.
GPT-4o mini: Non-social science research article
Transregional astrocyte-dependent metaplasticity in the hippocampus
Shruthi Sateesh, Barbara J. Logan, Miki Suzuki, David Stellwagen, Wickliffe C. Abraham
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Learning-related synaptic plasticity is regulated by metaplasticity, which adjusts plasticity thresholds in an activity-dependent manner. We have previously described a heterodendritic form of metaplasticity whereby priming stimulation in stratum oriens (SO) inhibits subsequent long-term potentiation (LTP) in the neighboring stratum radiatum of the hippocampal CA1 region. Here, we report that this metaplasticity is transregional, in that the SO priming stimulation also inhibits later LTP induction at dentate gyrus (DG) middle molecular layer (MML) synapses, both in vitro and in vivo. This effect operates across the hippocampal fissure and occurs in the absence of CA3, highlighting a previously unappreciated reverse-direction and long-distance hippocampal crosstalk. Our findings demonstrate an essential role of astrocytes as SO priming elicited an increase in the frequency of calcium (Ca 2+ ) events in astrocytes in the DG MML, while the metaplasticity effect was blocked by calcium-buffering in MML astrocytes. It could be triggered by either activation of M1 muscarinic acetylcholine receptors or group II metabotropic glutamate receptors, and was critically dependent on inositol 1,4,5-trisphosphate receptor type 2 signaling. The transregional inhibition of LTP was mediated by astrocytic release of tumor necrosis factor (TNF), which likely acts in an autocrine fashion on astrocytic TNF type 1 receptors (TNFR1s). Downstream of TNF-TNFR1 signaling, the inhibition of MML LTP was mediated by the activation of GluN2B-containing N-methyl-D-aspartate receptors. Thus, a complex, bidirectional neuron–glia signaling cascade orchestrates long-distance metaplasticity across hippocampal subregions, providing a framework for understanding how hippocampal neuronal networks dynamically regulate plasticity thresholds across space and time.
GPT-4o mini: Non-social science research article
Physically intelligent capsule robots with embodied memory and logic in the gastrointestinal tract
Huyue Chen, Xurui Liu, Jiahai Ma, Yishen Zhao, Chaoyu Yang, Kai-Fung Chan, Philip Wai Yan Chiu, Lei Shao, Wenming Zhang, Li Zhang, Qiguang He, Metin Sitti
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Miniaturized medical robots offer a promising solution for minimally invasive measurements and interventions in the gastrointestinal (GI) tract. Clinical assessment of GI disorders is commonly guided by threshold-based physiological indicators, including pressure, temperature, and pH, which motivate event-triggered strategies for personalized medicine. However, identifying homeostatic dysregulation and enabling in-situ therapy remains challenging, because ingestible robotic systems must tightly integrate sensing, decision-making, and actuation under severe constraints of size, power, and biosafety. Inspired by the autonomy of microorganisms that operate without neural processing, this work introduces physically intelligent capsule robots (PI Capbots) that enable homeostatic monitoring and targeted delivery within the GI tract, without relying on centralized electronic control. Through embodied stimuli-responsive memory and logic, PI Capbots effectively distill rich, detailed, and redundant physiological information into a small set of decoupled and event-triggered outputs suitable for operations in in vivo environments. In each PI Capbot, multistable metamaterials encode intraluminal pressure as mechanical memory, programmable hydrogels implement orthogonal sensing and logic operations, and helical fibers enable multimodal locomotion. Ex vivo and in vivo studies in large animal models demonstrate the efficacy, robustness, and reproducibility of PI Capbots, highlighting its potential for their translational medical applications.
GPT-4o mini: Non-social science research article
The structure of correlated variability reflects task-relevant information in sensory neurons
Ramanujan Srinath, Yunlong Xu, Douglas A. Ruff, Amy M. Ni, Brent Doiron, Marlene R. Cohen
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Shared trial-to-trial variability across sensory neurons is reliably reduced when perceptual performance improves, yet this variability is low dimensional, so it could be ignored by an optimal readout mechanism. Why then is it so consistently related to behavior? We propose that shared variability both reflects circuit structure and reveals the information communicated to downstream areas. In this framework, the same connectivity that shapes signal propagation also shapes shared variability. Using a circuit model, we show that when sensory signals align with shared variability, behaviorally relevant information is amplified without compromising coding fidelity. Analyses of neural population recordings from multiple brain areas and tasks reveal that the dominant axis of shared variability consistently aligns with task-relevant stimulus features and action plans. Finally, the behavioral impact of microstimulation can be explained by the extent to which it changes projections onto the shared variability axis. These findings suggest that shared variability may illuminate, rather than obscure, the neural dimensions that guide behavior.
GPT-4o mini: Non-social science research article
Intracellular structural modifications of natural peptidoglycan fragments preceding NOD2 signaling in mammalian cells
Shiliu Feng, Christopher Adamson, Chenyu Li, Evan Wei Long Ng, Yuan Qiao
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Bacterial peptidoglycan fragments (PGNs) are pathogen-associated molecular patterns that activate the mammalian innate immune system, particularly through NOD2 signaling pathways. Since NOD2 is a cytosolic sensor in mammalian cells, cellular assays are commonly used to identify bioactive PGNs that elicit NOD2 response, with muramyl dipeptide (MDP) long recognized as the minimal NOD2 agonist. However, recent studies have highlighted the intracellular phosphorylation of MDP by mammalian N -acetylglucosamine kinase (NAGK) as a critical prerequisite for NOD2 activation, emphasizing the need for further investigation into other host-mediated processing of PGNs. In this study, we examined how various bacterial PGNs, differing in saccharide and stem peptide length, undergo intracellular structural modifications within mammalian cells. Our findings show that disaccharide PGNs are processed through intracellular glycosidic cleavage to generate monosaccharide MurNAc-containing PGNs intracellularly, followed by NAGK-dependent phosphorylation, uncovering an additional essential step that precedes NOD2 activation. To identify the glycosidase responsible for disaccharide PGN cleavage, we provide biochemical and cellular observations that human O -GlcNAcase functions as a promiscuous glycosidase capable of processing certain disaccharide PGNs and potentially modulate their NOD2 activation. Furthermore, we demonstrate that PGNs with a lysine-type tripeptide stem are specifically cleaved into dipeptides and that phosphorylated PGNs are subjected to dephosphorylation in mammalian cells. Together, these findings offer insights into the metabolism and intracellular processing of PGNs in mammalian cells, which are crucial in shaping the host innate immune responses.
GPT-4o mini: Non-social science research article
Fracture-driven weakening amplifies projected ice loss from West Antarctica
Javier Blasco, Violaine Coulon, Maaike Izeboud, Thomas Gregov, Yanjun Li, Frank Pattyn
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Ice shelves buttress the flow of the Antarctic ice sheet, but this stabilizing effect weakens as fractures form, reducing ice viscosity and accelerating ice discharge toward the ocean. Here, we incorporate physically consistent damage mechanics into an ice-sheet model and apply it across the Amundsen Sea Embayment, the largest current contributor to Antarctic mass loss. Simulations reproduce key satellite-derived damage patterns under present-day conditions. Projections to 2300 show that allowing damage to evolve strongly amplifies future ice loss, increasing sea-level contributions by up to a factor of ∌ 4.5. Even when damage is held fixed at its present-day extent, projected contributions increase by 50 to 130 % , indicating that existing fractures already commit the system to enhanced ice loss. Basal crevasses dominate this response, accounting for ∌ 90% of damage-induced amplification. Healing mechanisms substantially moderate damage, as neglecting gravitational crevasse closure and compressive healing overestimates ice loss by almost 50%. Together, these results suggest that fracture-driven weakening substantially alters Antarctic ice-sheet dynamics and should be represented in projections of future sea-level rise.
GPT-4o mini: Non-social science research article
Differences in physiological tolerance to global warming caused the Permian–Triassic transition between the Paleozoic and Modern faunas
J. Andres Marquez, Justin L. Penn, Richard G. Stockey, Thomas H. Boag, Murray I. Duncan, Kyra N. McClure, Kendall Matsumoto, Kemi F. Ashing-Giwa, Christopher P. Noll, Curtis Deutsch, Jonathan L. Payne, Erik A. Sperling
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The rapid global climate change at the end of the Permian Period (~251.9 Mya) coincided with the greatest macroevolutionary faunal turnover event in Earth’s history. As the oceans warmed, lost dissolved oxygen, and became more acidic, the dominant animal groups in the Paleozoic fauna (including brachiopods and crinoids) suffered differentially high rates of extinction, allowing the Modern fauna (including bivalves and gastropods) to rise to ecological dominance. The end-Permian kill mechanism(s) are not fully understood, but differences in extinction intensity among Linnaean classes suggest an important physiological component. Here, we use a trait-based model of species’ metabolic O 2 balance to demonstrate that temperature-dependent hypoxia can explain the taxonomic selectivity of the end-Permian mass extinction. Direct respirometry experiments and physiological trait estimates derived from biogeographic data reveal that species belonging to the Paleozoic fauna have a higher temperature dependence of hypoxia than those belonging to the Modern fauna. In simulations of the climate transition, this trait difference leads to a greater loss of aerobic habitat for Paleozoic fauna, consistent with their observed greater extinction intensity. These results demonstrate that differences in average physiological tolerances to environmental change across biogeography, taxonomy, and functional ecology drove end-Permian extinction patterns and could eventually characterize the modern biodiversity crisis. Temperature-dependent hypoxia is the only kill mechanism that has been shown to explain the magnitude, biogeography, and now taxonomic selectivity of the end-Permian mass extinction, ultimately underlying the permanent shift in marine ecosystems across this transition.
GPT-4o mini: Non-social science research article
Histone chaperone HIRA regulates adiponectin expression and obesity-associated adipose expansion by facilitating Pol II pause release
Danyang Wan, Ji-Eun Lee, Young-Kwon Park, Guojia Xie, Susanna Maisto, Christabelle Agyapong, Keiko Ozato, Oksana Gavrilova, Kai Ge
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Adipose tissue is essential for maintaining glucose and lipid homeostasis in mammals. However, epigenomic mechanisms underlying adipose tissue function remain largely unclear. Here, we identify the histone chaperone HIRA as an epigenomic regulator of adipose tissue function. Adipose tissue-specific knockout of Hira in mice impairs insulin sensitivity and restrains adipose tissue expansion during high-fat diet-induced obesity. Mechanistically, HIRA is required for the expression of Adipoq , encoding the adipokine adiponectin, and lipid metabolism genes in adipose tissue. Genomic mapping reveals that HIRA binds to promoters and enhancers of Adipoq and lipid metabolism genes in adipocytes. Acute HIRA depletion using the dTAG system, followed by nascent RNA-Seq and ChIP-Seq, demonstrates that while HIRA is largely dispensable for enhancer activation and coactivator binding, it promotes transcription of target genes by facilitating RNA polymerase II pause release and subsequent elongation likely independently of H3.3 deposition. Our findings uncover a mechanism by which HIRA regulates transcription and establish HIRA’s critical role in insulin sensitivity and lipid metabolism, providing a potential therapeutic target for obesity and insulin resistance.
GPT-4o mini: Non-social science research article
Helfrich walls in nematic toroidal droplets in the presence of magnetic fields
Javier Rojo-Gonzalez, Charlotte G. Slaughter, Peter J. Collings, Jay Kikkawa, Arjun G. Yodh, Alberto Fernandez-Nieves
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We observe the formation of stable, magnetic field induced, alignment inversion walls, also called Helfrich walls, in nematic liquid crystals (NLCs) confined to a toroidal droplet with tangential anchoring at the boundaries. Walls are rare in NLCs due to their high energy compared to lower-dimensional defect structures. However, we find that Helfrich walls naturally form, transform, and migrate in this unconventional toroidal setting, generating intricate director-field configurations due to the interplay of confining geometry and external fields. Interestingly, the presence and number of point defects in the zero field nematic configuration of the toroid influences the types of walls that arise. In the absence of point defects, splay-bend walls emerge. By contrast, when a point defect pair exists on the toroidal surface, a wall not previously classified by Helfrich, and that involves both twist and splay-bend distortions, forms, and transforms. Our experiments and numerical simulations enable the quantification and elucidation of the physics behind the formation and transformation of these wall structures, extending the class of walls that were believed to occur in NLCs.
GPT-4o mini: Non-social science research article
Long-term stability and performance of Cas9/guide RNA-based gene drives in anopheline mosquitoes
Rebeca Carballar-LejarazĂș, Yuemei Dong, Thai Binh Pham, Taylor Tushar, Drusilla Stillinger, Devin Ngoc Nguyen, Lorena Winokur, Mihra Tavadia, Mabel Tao, George Dimopoulos, Anthony A. James
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Gene-drive population modification strategies are being developed to control the transmission by anopheline mosquitoes of the parasites that cause human malaria. These approaches are designed to reduce disease prevalence and incidence by spreading dominant antiparasite effector genes throughout vector populations. The strains must sustain drive and parasite suppression properties over extended periods of time to have an epidemiological impact. Three gene-drive strains, AcTP13 and AcTP43 in Anopheles coluzzii and AgTP13 in Anopheles gambiae , carrying autonomous Cas9/guide RNA-based drive systems linked to multiple antiparasite effector genes were remarkably stable in all A. coluzzii replicates over a 2-y (35 generation) period in laboratory cage trials. Two of three A. gambiae replicates performed equally well. Stability was assessed as a function of population dynamics (size), molecular integrity of the gene-drive cassettes, maintenance of drive efficiency (gene conversion), generation and accumulation of mutant drive-resistant target alleles, drive system-generated off-target effects, and effector gene parasite suppression activity. All lines met stability requirements with the exception of one AgTP13 cage replicate that was affected by drive-resistant target-site mutations. Notably, all strains retained parasite suppression activity and high drive efficiencies throughout the duration of the trials. These results support the further development and deployment of these strains for malaria control.
GPT-4o mini: Non-social science research article
Spatial transcriptomic mapping of postnatal mouse uterine development
M. Fairuz B. Jamaluddin, Shafiq M. Syed, Riazuddin Mohammed, Jyoti Goad, Mehedi Hasan, Manish Kumar, Isabella Moore, Prathima B. Nagendra, Naga Veera Srikanth Vallabani, Florence Bartlett, Vimala Anthonydhason, Pradeep S. Tanwar
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Postnatal uterine development requires precise coordination of epithelial differentiation, gland formation, and stromal organization, yet how transcriptional programs are spatially integrated during this process remains poorly understood. Here, we generated a spatially resolved transcriptomic map of the mouse uterus across key postnatal stages from day 3 to day 21 by combining high resolution in situ transcriptomics with histology, proteomics, genetic models, and functional assays. This approach defines the temporal emergence and spatial arrangement of all major uterine cell types and demonstrates that endometrial glands arise from luminal epithelium through progressive transcriptional reprogramming rather than from a prespecified progenitor population. Spatial analysis reveals marked compartmentalization of signaling pathways during adenogenesis. Luminal epithelium is enriched for Wnt ligands and hormone receptors, whereas glandular epithelium engages inhibitory and negative feedback programs that constrain Wnt activity while supporting proliferation and differentiation. Functional genetic studies establish that epithelial canonical Wnt signaling is essential for prepubertal gland establishment and long-term epithelial maintenance but is dispensable for postpartum gland regeneration. Retinoic acid synthesis becomes increasingly concentrated within glands, while hedgehog signaling polarizes into an epithelial to stromal axis during gland morphogenesis. Additional pathways including RTK, Notch, TGFÎČ, BMP, hypoxia, Hippo, and PI3K-mTOR exhibit distinct spatial biases that collectively shape epithelial identity and tissue maturation. Together, these findings provide a comprehensive spatial framework for uterine gland development and reveal how compartment specific signaling networks coordinate postnatal uterine morphogenesis.
GPT-4o mini: Non-social science research article
Morphological and functional diversity of spatially resolved vestibular ganglion neuron cell types
Ruiqi Liu, Jingyue Liu, Zhiyu Chen, Jingying Li, Zhiyong Liu, Shuohao Sun
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Vestibular ganglion neurons (VGNs) are the primary sensory neurons of the vestibular system, a relatively understudied sensory modality that is essential for maintaining visual stability and postural balance. Compared with other sensory systems, our understanding of the molecular heterogeneity of VGNs and its contribution to the diverse functions of the vestibular system remains limited. Using single-cell and spatial transcriptomics, we defined five transcriptionally distinct VGN cell types with discrete spatial distributions across the ganglion. These VGN cell types demonstrate organ-specific innervation patterns, target defined zones within each organ, and form characteristic synaptic endings. To probe their functional roles, we generated genetic tools that selectively label each VGN cell type. Leveraging these tools, we identified a cell type contributing to gravity sensing and otolith-dependent vestibulo-ocular reflexes, revealing a cell type–specific basis for modality-selective vestibular computations.
GPT-4o mini: Non-social science research article
Controlled generation of 3D vortices in driven atomic Josephson junctions
Vijay Pal Singh, Ludwig Mathey, Herwig Ott, Luigi Amico
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We propose an ac-driven atomic Josephson junction as a clean and tunable source of three-dimensional (3D) solitary waves in quantum fluids. Depending on the height of the junction barrier, the emitted excitations appear as vortex rings at low velocity or vorticity-free rarefaction pulses near the sound velocity, thus spanning the complete Jones-Roberts family of solitons. The Shapiro-step phenomenon renders the emission deterministic: on the first, second, third Shapiro steps, the junction ejects one, two, and three solitary excitations per drive cycle. This enables controlled generation of single- and multiexcitation configurations, allowing detailed studies of the full crossover between vortex rings and rarefaction pulses and their interaction dynamics. By Shapiro phase locking, multiexcitations are emitted in succession and interact, revealing leapfrogging motion of two and three coaxial rings and their decay via boundary-assisted, sound-mediated processes. This ac-driven protocol establishes a compact and reproducible platform for generating, classifying, and controlling 3D solitonic excitations, paving the way for precision studies of nonlinear vortex dynamics, dissipation, and quantum turbulence in trapped superfluids.
GPT-4o mini: Non-social science research article
Shared neurogenetic substrates of nonplanning impulsivity and procrastination
Yuanyuan Hu, Jie Xiang, Yuening Jin, Qingchen Fan, Changshuo Wang, Yihan Wu, Dang Zheng, Yancheng Tang, Wei Li, Bowen Hu, Tingyong Feng, Yuan Zhou, Zhiyi Chen
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Procrastination has a maladaptive impact on health and survival, yet it remains moderately heritable, presenting a biological paradox. Procrastination has been conceptualized as a byproduct of impulsivity, explaining its prevalence despite no discernible adaptive benefit. However, their shared neurobiological substrates have yet to be elucidated. Using a longitudinal twin cohort ( N = 154), we show that nonplanning impulsivity (NPI) during late adolescence and early adulthood is prospectively associated with procrastination in later life. This effect was independently replicated in two cross-sectional cohorts ( N = 327; N = 1,543). Twin modeling using an additive genetic and nonshared environmental (AE) framework, together with a meta-analysis of twin studies ( N = 3,656 twin pairs), revealed significant shared genetic contributions ( r g = 0.51). Beyond genetic overlap, neuroimaging meta-analysis ( NeuroSynth meta-analysis for impulsivity: k = 198 studies, 5855 loci; mini meta-analysis for procrastination: k = 5 studies, 7 independent samples, N cumulative = 893 participants), normative modeling ( N = 37,407), and seed-based d mapping (SDM) converged on the left dorsolateral prefrontal cortex (DLPFC) as the region of maximal overlap between NPI and procrastination. The transcriptional profiles of the left DLPFC and impulsivity-associated genes exhibited functional convergence on regulation of biological and cellular processes. These genes showed brain-specific expression and associations with cortical metabolism, neurodegenerative disease, and developmental expression peaks, indicating a shared molecular basis for the neurogenetic architecture of procrastination. Together, our findings delineate a cross-scale characterization of the shared neurogenetic substrates linking NPI and procrastination, offering empirical evidence that elucidates the biological origins of procrastination.
GPT-4o mini: Non-social science research article
High-resolution structure of monomorphic AÎČ 1-40 fibrils
Salima Bahri, Ravi Shankar Palani, Robert Silvers, Brian Michael, Veronica Lattanzi, Ingemar André, Sara Linse, Robert G. Griffin
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Amyloid-ÎČ (AÎČ) fibrils primarily composed of AÎČ 1-40 and AÎČ 1-42 form the core of senile plaques in Alzheimer’s disease. AÎČ 1-40 fibrils may exhibit significant polymorphism influenced by sample preparation conditions, complicating atomic resolution structural characterization. To establish a reliable structural baseline, we developed a protocol for expressing and purifying recombinant AÎČ 1-40 that forms monomorphic fibrils under physiological conditions (pH 7.4). We present a high-resolution structure of these unseeded, monomorphic AÎČ 1-40 fibrils obtained using magic-angle spinning NMR spectroscopy (PDB ID 12GB). We obtained unambiguous chemical shift assignments for approximately 90% of the residues and measured over 500 distance and torsion angle restraints. The resolved structure, with a backbone RMSD of 0.63 ± 0.06 Å, shows two monomers per filament plane, with two distinct ÎČ-sheets (residues E11-E22 and K28-V39, respectively) running along the fibril axis with H-bonding between each plane, and the two strands linked by a flexible loop region. This structure reveals three continuous hydrophobic cores inside each filament which bury 24 hydrophobic side chains per filament plane: those of L17, F19, A21, V24, A30, I32, M35, V40 between the two ÎČ-strands within each monomer and I31, L34, V36, V39 between the two monomers. Small angle X-ray scattering reveals the size and geometry of the fibril cross-section, which is compatible with a two-filament arrangement with a total of 4 monomers per fibril plane.
GPT-4o mini: Non-social science research article
Dopamine-driven mitochondrial reverse electron transport in immune cells mediates gut–brain ROS signaling during sleep deprivation
Yan Zhang, Jae-Hyuk Lee, Ziqi Yu, Yinrui Tao, Suman Rimal, Yanzi He, Lei Lv, Bingwei Lu, Yong Ping
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Sleep deprivation (SD), together with inevitable stress inherent to conventional SD protocols, can induce oxidative stress and inflammation, thereby increasing the risk of premature death. However, the source and signaling pathways underlying reactive oxygen species (ROS) generation remain unclear. Here, we demonstrate that both mechanical and thermogenetic SD, along with possible stress induced by both protocols, lead to initial ROS accumulation in Drosophila gut subregions, including the proventriculus (PV) and PV-resident hemocytes, via upregulation of dopamine (DA) biosynthesis. Intriguingly, DA acts unconventionally by activating mitochondrial reverse electron transfer (RET), presumably through modifying interactions between the respiratory complex I proteins NDUFV1 and NDUFS3. RET-ROS elicits hemolymphatic IMD/Relish-mediated antibacterial defense. However, during chronic SD, downregulation of the Drosophila APOE/D ortholog Neural Lazarillo promotes the recruitment of hemocytes to the central brain and, together with this process, leads to widespread neuronal ROS accumulation in an Alzheimer’s disease (AD) fly model. Inhibiting RET or hemocytic DA levels extends the survival of animals under chronic SD. Our work reveals DA-driven RET-ROS in innate immune cells during SD, highlights the pivotal role of a gut-innate immune-brain crosstalk in mediating the effect of SD manipulation on aging and AD pathogenesis, and suggests ways to lessen the consequence of SD, a profound health issue in modern society.
GPT-4o mini: Non-social science research article
Structural basis of complement anaphylatoxin receptor activation by an immunostimulant lead candidate
Annu Dalal, Manish K. Yadav, Manisankar Ganguly, Sudha Mishra, Ravi Yadav, Shachie Sinha, Nabarun Roy, Divyanshu Tiwari, Debdatta Mukherjee, Ashna Reyaz, Calvin A. Dsouza, Ameesha Nigam, Nilanjana Banerjee, Xaria X. Li, Richard J. Clark, Trent M. Woodruff, Ramanuj Banerjee, Cornelius Gati, Arun K. Shukla
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Activation of the complement cascade is a primary innate immune response mechanism to combat pathogenic infections. Complement anaphylatoxins (i.e., C3a and C5a) exert a robust inflammatory response via prototypical GPCRs (i.e., C3aR and C5aR1). Several peptides derived from anaphylatoxins have shown promise as immunostimulants from therapeutic standpoint by eliciting immune response without excessive inflammation. EP67, a C5a-derived decapeptide, is the most advanced candidate with preclinical indications in antiviral and antibacterial context. Still, the molecular mechanism and the precise receptor target of EP67 remain unclear. Here, we perform a comprehensive pharmacological profiling of EP67 on the human and mouse C3aR and C5aR1 and find that it preferentially activates human C3aR in transducer-coupling assays. Subsequently, we determined four cryo-EM structures of C3aR and C5aR1 in complex with EP67, which elucidate the molecular details of its interaction with, and activation of, these receptors. Interestingly, we observe that EP67 adopts a hook-like structure and binds in the orthosteric pocket of the receptors, analogous to that of the carboxyl terminus of C3a and C5a. We employ site-directed mutagenesis studies to validate the key interactions of EP67 with these receptors and corroborate the structural observations including the engagement of a critical activation switch. Finally, we observe that EP67 induces distinct conformations of the TM7–Helix8 interface for C3aR and C5aR1, which provides a plausible explanation for its ability to preferentially activate C3aR. In summary, our study elucidates molecular insights into the interaction of EP67 with the complement anaphylatoxin receptors, and it should facilitate further optimization for therapeutic applications.
GPT-4o mini: Non-social science research article
Energy costs of Hannibal’s alpine crossing
Emilio Berti, Fritz Vollrath
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Hannibal crossed the Alps with a large army containing 37 war elephants in 218 BC. Details of his route have scholars regularly debate historical reports in the light of logistical and topographical considerations. Among the possible alpine passes, the route crossing at the Col du Clapier was considered the most likely candidate. Recent philological and geomorphological analyses suggest instead a route via the Col de la Traversette. Here, we examined these options focusing on the energy costs of the crossing with an emphasis on the war elephants. Our analysis favors the route of the Traversette while also providing possible insights into Hannibal’s thinking concerning both the logistics and psychology of elephant warfare.
GPT-4o mini: Non-social science research article
Invariant nonequilibrium dynamics in gene regulation optimize information flow
Benjamin Zoller, Alexis BĂ©nichou, Thomas Gregor, GaĆĄper Tkačik
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Eukaryotic gene regulation relies on stochastic yet controlled promoter switching, in which genes transition between transcriptionally active and inactive states. Despite the molecular complexity of this process, recent studies have revealed a surprising invariance of the “switching correlation time” ( T C )—the characteristic decay time of the autocorrelation function of promoter activity fluctuations—across gene expression levels in multiple genes and organisms. A biophysically plausible explanation for this invariance has so far been lacking. Here, we show that this empirical constraint imposes stringent requirements on minimal yet realistic models of transcriptional regulation. Specifically, reproducing T C –invariance requires regulatory architectures with at least four internal states and nonequilibrium dynamics that break detailed balance. Using Bayesian inference on Drosophila gap gene expression data, we demonstrate that such models i) quantitatively reproduce the observed T C –invariance, ii) remain robust to parameter perturbations, and iii) maximize information transmission from transcription factor concentration to gene expression. Remarkably, the T C -invariant modulation strategy we identify as optimal closely parallels contemporary control-theoretic results on the modulation of stochastic switching systems. Taken together, our results suggest that eukaryotic transcriptional regulation operates in a nonequilibrium regime to balance precision, reaction-rate limitations, and energy dissipation, thereby achieving near-optimal information transmission under fundamental physical constraints.
GPT-4o mini: Non-social science research article
Diffusion-induced instabilities promote cooperation in eco-evolutionary networks
Sourav Roy, Md Sayeed Anwar, Timoteo Carletti, MatjaĆŸ Perc, Dibakar Ghosh
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Understanding how cooperation persists despite the advantage of selfish behavior remains a central challenge in evolutionary dynamics. Classical models of public goods dilemmas predict dominance of defectors, yet natural and social systems often sustain cooperation. We study an eco-evolutionary public goods game on complex networks where cooperators and defectors diffuse at different rates. When the isolated system is in a defector-dominated coexistence regime, faster dispersal of defectors than cooperators leads to a symmetry-breaking transition that produces localized clusters of cooperators. In heterogeneous networks, nodes with higher connectivity become significantly more likely to exhibit cooperative dominance. A degree-based mean-field reduction supports this result by showing that network connectivity controls an effective coupling strength proportional to node degree, thereby producing a bifurcation that separates defector-dominated and cooperative states. We also address why not all hubs become cooperative by means of a multistability analysis. These results reveal how asymmetric mobility and heterogeneous connectivity jointly promote cooperation in structured populations.
GPT-4o mini: Non-social science research article
Topological expansion of Boehm’s brushes via structured light
Dmitry A. Pushin, Iman Salehi, Amy Chow, Andrew E. Silva, Pinki Chahal, David G. Cory, Mukhit Kulmaganbetov, Gary P. Misson, Naume Shentevski, Taranjit Singh, Shelby E. Temple, Benjamin Thompson, Dusan Sarenac
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We report an entoptic phenomenon in which the classical two-lobed Boehm’s brushes are transformed into a multilobed structure by projecting spin–orbit-coupled light onto the human retina. These structured beams, composed of nonseparable superpositions of circular polarization and orbital angular momentum, produce azimuthally modulated entoptic patterns through polarization-dependent scattering in the retina. Unlike Haidinger’s brushes, which arise from dichroic absorption in the macula, the observed effect is driven by angular variations in scattering strength relative to the local polarization direction. In regions where scattering centers exhibit polarization orientations that converge toward a common point, their combined contributions reinforce one another, producing brighter and more sharply defined entoptic lobes whose number and orientation vary systematically with the topology of the spin–orbit stimulus. Psychophysical measurements across retinal eccentricities from 0.5 ° to 4 ° in eleven participants revealed that contrast detection thresholds decreased exponentially with eccentricity, consistent with polarization-sensitive scattering by isotropic structures in the nonfoveal retinal regions. From the psychophysical fits, the mean eccentricity at which the entoptic pattern reached a 50% threshold was r 50 = 1 . 03 ° with a 95% CI of [0.72, 1.34] ° , indicating that the spin–orbit-induced entoptic structure becomes perceptually robust at approximately 1 ° retinal eccentricity and that perception improves with increasing retinal eccentricity. Together, these findings demonstrate that spin–orbit light modulates scattering-based visual phenomena in previously unrecognized ways, enabling approaches for probing retinal structure and visual processing using topological features of light.
GPT-4o mini: Non-social science research article
Physical encounters impose a consistency–amount trade-off on bacterial group formation in marine environments
Thomas C. Day, Julia A. Schwartzman
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Physically associated bacterial groups can enhance resilience through emergent traits, including access to inaccessible substrates, increased stress tolerance, and reduced predation. These traits arise from physical and chemical interactions between cells and constitute multicellular behavior, yet we lack general principles predicting when this form of multicellularity provides ecological advantages. Here, we examine how the size of bacterial groups influence encounters with two particle types: resources and lytic bacteriophage. Using a size-dependent encounter theory, we identify regimes where encounter rates depend on group size. Experiments with the group-forming marine bacterium Vibrio splendidus 12B01 confirm that larger groups encounter particles more frequently. However, increasing group size reduces both the mean and variance of particle encounters per cell, revealing a trade-off between the consistency and amount of resource encountered. Stochastic simulations support this trade-off and predict conditions under which consistent encounters with resource particles benefit groups more than single cells, and where multicellular behaviors can alleviate resource limitation within groups. Simulations of encounters with phage-like particles predict that consistent encounters can stabilize the average time to infection for individual cells—the livable timescale—by disrupting viral replication and burst feedback. Overall, our results suggest that bacterial group formation can support resource acquisition despite predation. We predict that this advantage emerges in fluctuating fluid environments and is constrained by size- and concentration-dependent encounter physics. More broadly, these findings identify a simple physical mechanism through which multicellular groups may provide ecological advantages across diverse microbial systems.
GPT-4o mini: Non-social science research article
Circadian screening of neutrophils identifies therapeutic targets in multiple sclerosis
Francesco De Virgiliis, Coline Barnoud, Wenyan He, Qun Zeng, Robert Pick, Tianyue Sun, Stéphane Jemelin, Valeria Maria Oliva, Tiphaine Furlan, Carmen Picon-Muñoz, Doron Merkler, Christoph Scheiermann
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Circadian rhythms are intrinsic time-keeping mechanisms that play a critical role in tuning immunity. Here, we investigated the impact of circadian rhythms on the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis (MS). We demonstrate that circulating neutrophils in blood significantly increase early in EAE, prior to symptoms onset. Importantly, we found that these cells infiltrate the central nervous system (CNS) in a time-of-day (ToD)-dependent manner, with increased infiltration at the onset of the behavioral active phase of the mice (evening). Transcriptomic analysis of CNS-infiltrating neutrophils revealed distinct ToD-dependent gene expression profiles, which identified Formyl peptide receptor 2 (FPR2) as a potential therapeutic candidate, since pharmacological inhibition of FPR2 led to reduced EAE disease severity. Furthermore, combinatorial treatment with a drug that targets VLA-4 (used in clinical practice under the trade name Natalizumab to treat MS) led to additive effects, substantially reducing EAE symptoms. Together, these findings highlight the importance of circadian immune cell dynamics during EAE development and provide a characterization of the circadian immune landscape in an animal model of MS, identifying potential targets for MS therapies.
GPT-4o mini: Non-social science research article
Evidence from formal logical reasoning reveals that the language of thought is not natural language
Hope Kean, Alexander Fung, Paris Jaggers, Jason Chen, Joshua S. Rule, Yael Benn, Joshua B. Tenenbaum, Steven T. Piantadosi, Rosemary A. Varley, Evelina Fedorenko
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Humans are endowed with a powerful capacity for inductive and deductive logical thought: we easily form generalizations based on a few examples and draw conclusions from known premises. Humans also arguably have the most sophisticated communication system in the animal kingdom: natural language allows us to express complex and structured meanings. Some have therefore argued for a tight relationship between complex thought and language, postulating that reasoning, including logical reasoning, relies on linguistic representations. We systematically investigated the relationship between logical reasoning and language using two complementary approaches. First, we used noninvasive brain imaging (fMRI) to examine neural activity as healthy adults engaged in logical reasoning tasks. And second, we behaviorally evaluated logical abilities in individuals with extensive lesions to the language brain areas and consequent severe linguistic impairment. Our findings reveal that the language brain network is not engaged during logical reasoning, and patients with severe aphasia exhibit intact performance on logic tasks. Instead, inductive reasoning recruits the domain-general multiple demand network implicated broadly in goal-directed behaviors, whereas deductive reasoning draws on brain regions that are distinct from both the language and the multiple demand networks. Together, these results indicate that linguistic representations are neither utilized nor required for inductive or deductive logical reasoning.
GPT-4o mini: Non-social science research article
Interleukin-6 is critical in the development of pulmonary vascular disease in Gcn2- deficient mice
Max Schwiening, Qingyue Gao, Mark Southwood, Alexi Crosby, Stephen Moore, Jose A. Valer, Niki Veale, Benjamin J. Dunmore, Paul D. Upton, A. A. Roger Thompson, Nicholas W. Morrell, Stefan J. Marciniak, Elaine Soon
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Biallelic mutations in EIF2AK4, encoding Eukaryotic Translation Initiation Factor 2α kinase 4 or General Control Nonderepressible 2 (GCN2), cause pulmonary veno-occlusive disease (PVOD), a fatal form of pulmonary hypertension. The mechanisms linking GCN2 deficiency with pulmonary vascular pathology are poorly understood. To investigate this, we developed two mouse models: genetic ablation of Gcn2 , to mirror GCN2 -mutation positive PVOD, and a pharmacological model using mitomycin C, a drug which can cause PVOD as an idiosyncratic drug reaction. Both models were phenotyped, and lungs from wild-type and Gcn2 -deficient mice were analyzed using single-cell RNA sequencing. We show that homozygous loss of Gcn2 is sufficient to induce mild pulmonary hypertension in mice. Single-cell transcriptomic profiling identified adventitial fibroblasts as the cell population exhibiting the most Gcn2 -dependent transcriptional changes. Pathway analysis revealed upregulation of inflammatory signaling in Gcn2 −/− adventitial fibroblasts. Consistent with this, we demonstrate a proinflammatory phenotype in Gcn2 −/− mouse fibroblasts and in Gcn2 −/− mice. Using a mitomycin C–induced murine model, genetic deletion of interleukin-6 ( Il6 ) rescued the pulmonary vascular phenotype. Furthermore, chronic lipopolysaccharide exposure exaggerated pulmonary hypertension in Gcn2 −/− mice, and Il6 ablation rescued both baseline and lipopolysaccharide-exacerbated disease. Pharmacological inhibition or genetic ablation of the Integrated Stress Response, which can be driven by GCN2-activation, phenocopies Gcn2 deficiency. Therefore, we establish a regulatory effect of an intact GCN2-Integrated Stress Response on IL-6 signaling. Together, we show that interleukin-6 is a critical mediator of both Gcn2 deficiency–associated and mitomycin C–triggered pulmonary vascular disease in mice and highlight IL-6-dependent pathways as potential therapeutic targets.
GPT-4o mini: Non-social science research article
Selective and direct hydrogen generation from mixed plastic waste via alkaline thermal treatment with inherent carbon storage
Jieun Park, Hyunah Kim, Hyerin Seo, Jiwon Lee, Hyung-Kyu Lim, Wonho Jung, Ah-Hyung Alissa Park, Woo-Jae Kim
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The global accumulation of plastic waste has spurred extensive research into chemical recycling methods to mitigate environmental issues and convert waste into valuable resources. A major challenge in plastic recycling is the requirement for presorting, which complicates processing and increases costs. Here, we demonstrate alkaline thermal treatment (ATT) as a highly efficient strategy for directly converting mixed plastic waste, including polyethylene terephthalate (PET), polyethylene (PE), and polypropylene (PP), into clean hydrogen energy at low temperatures and atmospheric pressure. Unlike conventional gasification, NaOH-assisted ATT enables plastic decomposition at significantly lower temperatures while producing high-purity hydrogen and minimizing carbon emissions. A key advancement in this work is the oxidation pretreatment of PP and PE, which enhances their reactivity in ATT and allows efficient hydrogen generation even from typically resistant polyolefins. Through systematic optimization of the NaOH-to-plastic ratio and thermal oxidation conditions, hydrogen yields of 43.7, 51.9, and 30.2 mmol/g plastic were achieved for PET, PE, and PP, respectively. Furthermore, ATT efficiently converts both individual and mixed plastic waste without requiring extensive separation, demonstrating its commercial potential and scalability with real-world waste compositions. Overall, this study establishes ATT as a promising and sustainable solution for plastic waste management and clean energy production, providing an economically viable low-carbon pathway for hydrogen generation.
GPT-4o mini: Non-social science research article
Long-term cultural continuity across the Neanderthal–modern human sequence at Üçağızlı II Cave, northern Levant
Ä°smail Baykara, Didem Turan, Ece Eren Kural, Derya Silibolatlaz, Mustafa Kenan Agras, Eren ƞahiner, Salih Kavak, ClĂ©ment Zanolli, Yoshiro Ishihara, Wataru Morita, Naoki Morimoto
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We present evidence from Üçağızlı II Cave in the northern Levant, TĂŒrkiye, documenting the sequential occupation by Neanderthals ( Homo neanderthalensis ; 77–59 ka) and modern humans ( Homo sapiens ; 59–47 ka). The combined evidence of human fossils, faunal and floral remains, lithics, and manuports demonstrates significant behavioral and technological continuity across this taxonomic sequence, characterized by consistent subsistence strategies and the persistent selection and transport of specific nondietary mollusk shells. The lithic assemblages largely align with late Middle Paleolithic traditions, exhibiting characteristic Mousterian variants. The association of diagnostic human fossils with these archaeological remains demonstrates that the shift from Neanderthals to modern humans occurred within a cultural continuum. Our findings suggest shared behaviors between Neanderthals and modern humans that extended beyond subsistence to include nonutilitarian behaviors within the specific geographic and temporal context studied here.
GPT-4o mini: Non-social science research article
IL-13 signaling in cDC2 is required for systemic anaphylactic responses
Yasuyo Harada, Takanori Sasaki, Kazushige Obata-Ninomiya, Takahiro Matsuyama, Satoshi Ueha, Shigeyuki Shichino, Takashi Watanabe, Shuhei Ogawa, Sewon Ki, Yoshie Suzuki, Naoto Ito, Yasutaka Motomura, Hideki Ueno, Steven F. Ziegler, Hiromasa Inoue, Peter Burrows, Brian S. Kim, Kenneth M. Murphy, Masato Kubo
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Cutaneous allergen sensitization (CAS) is a primary driver of atopic dermatitis (AD) and a key initiator of the “atopic march”, which can lead to systemic conditions such as food allergy and anaphylaxis. The type 2 cytokine interleukin-13 (IL-13) is an important regulator of high-affinity IgE antibodies, yet the precise cellular targets and mechanisms by which it orchestrates systemic allergic responses remain incompletely understood. Here, we evaluated the role of IL-13 in a murine CAS model that links skin inflammation to systemic anaphylaxis. Using cell-specific deletions of the IL-13 receptor α1 subunit ( Il13ra1 ), we identify conventional dendritic cells (cDCs), and not T or B cells, as the essential targets of IL-13 for generating high-affinity IgE. Single-cell transcriptomics reveal that IL-13 signaling acts specifically in a cDC2 subset characterized by high expression of CX3CR1, Clec10a (CD301a), and CD301b (Mgl2). Licensing by IL-13 endows these cDC2 with superior antigen-presenting capacity, characterized by the upregulation of MHC class II and costimulatory molecules, including CD301a, CD301b, and ICOSL. These mature cDC2s are mobilized from the periphery to the spleen by a CX3CR1-dependent mechanism, where they are uniquely equipped to induce the differentiation of IL-13-producing T follicular helper (T FH 13) cells. This cascade results in robust germinal center reactions and production of pathogenic, high-affinity IgE. Our findings define an IL-13–cDC2 axis that functions as a critical regulator of the atopic march, providing a mechanistic rationale for the clinical efficacy of IL-13-targeted therapies in allergic diseases.
GPT-4o mini: Non-social science research article
HIV-1 capsid interactions with Nuclear Pore Complex components support nuclear entry via affinity gradient
Ivo Melčák, Ryan L. Slack, Zachary C. Lorson, Andres Emanuelli Castaner, Krisztina Ambrus, Jonathan S. Winkjer, Karen A. Kirby, Robert A. Dick, Stefan G. Sarafianos
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Before entering the nucleus, the HIV capsid core [composed of capsid (CA) proteins] must translocate through the Nuclear Pore Complex (NPC). This process relies on direct interactions between CA and the phenylalanine-glycine (FG) repeats in nucleoporins (NUPs) within the NPC. FG repeats are generally classified into three canonical motifs: FG, GLFG, and FxFG, which are differentially distributed along the NPC axis: FG and FxFG motifs are predominantly at the cytoplasmic periphery and in the nuclear basket, whereas GLFG motifs are primarily in the central channel of the NPC. We demonstrate that the capsid engages the diverse FG repeats with markedly different affinities. Notably, GLFGs of NUP98 located in the central channel display significantly increased affinity to CA than conventional FGs/FxFGs. NUP153, which is located at the nuclear basket, contains an atypical FxFG that is adjacent to a PSGV sequence, thus forming additional favorable interactions. We designate this nonconventional FxFG motif as an “FG super-motif.” In addition, the C-terminus of NUP153 also contains a cluster of basic residues that serve as an enhancer of the NUP153 FG super-motif, dramatically increasing CA affinity by ~1,000-fold. Other binding enhancers for FG motifs were also identified in NUP58 and POM121 that are in the central channel and its nuclear boundary, respectively. Affinities of NUP58, POM121, and NUP153 enhancers to CA increase with proximity to the nuclear basket. Thus, we propose that the diverse FG repeats and their binding enhancers create an affinity gradient that potentiates HIV capsid translocation through the NPC.
The role of nonfinancial factors in the Congressional Budget Office’s health insurance coverage projections
Nianyi Hong, Ben Hopkins
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Nonfinancial factors play an important role in people’s coverage decisions as premiums, cost sharing, and other factors that determine the financial value of health insurance cannot fully explain patterns in take-up rates. The Congressional Budget Office (CBO) is tasked with estimating the budgetary and coverage effects of policy and economic changes that affect health insurance markets, which includes considering the interactions between nonfinancial factors and policy design. The agency groups the nonfinancial factors it considers into three categories: ease of enrollment, awareness, and attitudes. Many recent policies have affected nonfinancial factors related to the take-up of Medicaid and marketplace insurance, such as the introduction of work requirements for Medicaid and access to zero-premium marketplace plans. This article explains how nonfinancial factors are handled and incorporated into CBO’s baseline health insurance projections and cost estimates, highlights the recent literature on the effect of these nonfinancial factors on insurance take-up decisions, and suggests future areas of research.
Feeding health inequality through platform-based food delivery in China
Hai Ding, Chenran Liu, Yu Xie, Jia Yu, Zhengrong Yuan
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This study examines how the expansion of online food delivery platforms affects health inequality in China. Exploiting the staggered rollout of platforms across counties and nationally representative panel data from 2010 to 2022, we find that platform entry increases overweight among low-income individuals while reducing it among high-income individuals. This divergence operates through two channels: low-income users increase consumption of fried foods and reallocate time from cooking to sedentary leisure, whereas high-income users reduce intake of calorie-dense foods and increase physical activity. These behavioral changes accumulate into downstream health consequences affecting weight-related chronic diseases and children's overweight in low-income households. Equal access to digital convenience thus does not translate into equal health benefits, suggesting that technological diffusion may amplify health disparities.
Reply to Huang and Dong: Clarifying the interpretation of rapid steroid effects in social recognition
Dario Aspesi, Anjana Varatharajah, Lucia Cioffi, Silvia Diviccaro, Donatella Caruso, Natalina Becke, Jasmin Lalonde, Melissa L. Perreault, Roberto C. Melcangi, Neil J. MacLusky, Elena Choleris
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User interaction with digital platforms: A consumer protection perspective
Nellie Lew, Devesh R. Raval
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The rapid growth of digital platforms has transformed how consumers interact with the marketplace and led to new challenges for consumer protection. This Perspective describes how the Federal Trade Commission’s Bureau of Economics uses behavioral insights and empirical methods to support efforts to prevent unfair or deceptive business practices in digital markets. We highlight two studies that address critical knowledge gaps in digital consumer protection, including how consumers perceive and respond to advertising disclosures and how digital design choices affect the accessibility and effectiveness of consumer reporting tools. The studies illustrate how behavioral research can be used both prospectively, to evaluate potential remedies, and retrospectively, to assess the effects of past Federal Trade Commission (FTC) actions. The first study is a laboratory experiment that examines how the salience of advertising disclosures influences consumer recognition of and engagement with advertising content, where engagement is defined as the time users spend viewing ads. The second is a retrospective analysis of a redesigned consumer complaint website, using a natural experiment to evaluate the effect of usability improvements on complaint submission rates and information quality. Together, these studies demonstrate how applied research on user behavior can inform marketplace oversight and the design of consumer-facing tools. We conclude by outlining ongoing efforts to expand the role of empirical research at the FTC to strengthen the foundation for evidence-based policymaking in an increasingly complex digital environment.
Applied behavioral and decision sciences in support of US FDA’s drug regulatory mission
Sara L. Eggers, Tamar Krishnamurti, Baruch Fischhoff
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The US Food and Drug Administration (FDA) makes and communicates decisions that directly affect the health choices and well-being of the US public. Behavioral and decision scientists have long supported FDA’s pharmaceutical (medical drug) regulatory and public health mission, working alongside clinical and pharmaceutical scientists. This Perspective describes four interrelated cases illustrating these collaborations: a) creating the Benefit–Risk Framework to guide regulatory decisions regarding new drug approvals; b) launching an internal decision support service to facilitate specific regulatory decisions; c) implementing the Patient-Focused Drug Development initiative to strengthen the use of patient input to inform regulatory decision making; and d) developing FDA SOURCE, a dynamic systems simulation model to assess potential strategies to address the US opioid overdose crisis. Key to the success of these efforts has been their behavioral and decision science foundations, strategically implemented by an expert team dedicated to fostering trusted collaborations with internal and external partners. These cases offer a model for other agencies facing complex decisions of public impact.
Multiplexing in networks and diffusion
Arun G. Chandrasekhar, Vasu Chaudhary, Benjamin Golub, Matthew O. Jackson
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We study multiplexing—the extent to which people have multiple, distinct types of relationships with the same others. We document empirical multiplexing patterns in Indian village data. We show that relationships such as socializing, advising, helping, and lending are correlated but distinct, while commonly used proxies for networks based on ethnicity and geography are nearly uncorrelated with actual relationships. We also show that these layers and their overlap affect information diffusion in a field experiment. On the theoretical side, we show that increased overlap in people’s different types of relationships impedes the spread of simple contagions—such as diseases or basic information that spread through a single interaction. In contrast, such higher levels of multiplexing enhance the spread of a complex contagion (e.g., a behavior or belief that requires multiple interactions for transmission) when infection rates are low, but impede complex contagion if infection rates are high. Finally, we identify empirical differences in multiplexing by gender and connectedness.
Turning policy implications into policy impact: Lessons from behavioral science in financial markets
Alycia Chin, Katherine G. Carman, Adam W. Craig, Jonathan A. Cook, David B. Zimmerman
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We describe how research can inform policymaking. We begin by summarizing the policy formation process, offering a framework illustrating how interactions between scientists and policymakers can provide mutual benefits. We then describe four research initiatives from the Securities and Exchange Commission’s Office of Investor Research (OIR) as examples of how behavioral sciences can help inform policymakers. The first initiative established a probability-based nationally representative survey panel focused on US investor behavior. The remaining three examined investor communications for mutual fund benchmarks, emerging annuities (known as registered index-linked annuities), and mutual fund fee visuals. We conclude by synthesizing our work and describing practices that can help scientists have policy impact, not just policy implications.
Science in service: Behavioral research applications across federal agencies
Alycia Chin, Baruch Fischhoff
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Educational expansion and the hidden reversal of the Flynn effect—Differential trends across socioeconomic strata
Bernt Bratsberg, Anders M. Fjell, Ole J. Rogeberg, Kristine B. Walhovd
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In recent decades, the United States and several European countries have seen a plateau and reversal of the population-level gains in cognitive test scores that accumulated over the 20th century—the Flynn effect. We examined whether the Flynn effect and its reversal—declining mean scores across cohorts—differ by socioeconomic status, and whether changes in education can account for this. Using compulsory military conscription cognitive tests linked to administrative records with near-complete population coverage, we studied 579,379 Norwegian men from 25 birth cohorts (1967–1991). Trend reversals appeared first among sons of high-income fathers, with low- and middle-income groups peaking later and showing smaller postpeak declines. These socioeconomic differences were consistent with convergence in educational attainment at conscription: across paternal-income ranks, cohort changes in test scores aligned with cohort gains in education at conscription age, with estimated schooling effect sizes in line with quasi-experimental evidence. Results were robust to adjustment for parental education, and birth weight and height at testing as proxies for prenatal conditions and childhood nutrition. Together, the findings suggest an underlying population-level decline in cognitive scores that began earlier than previously assumed but was temporarily offset in lower-income strata by expanding educational attainment. After educational expansion plateaued, scores declined across all groups, most steeply among higher-income strata. Upper-secondary education completion thus emerges as a potential lever for improving cognitive performance and reducing income-related disparities in cognitive ability scores, while highlighting that broader societal pressures on cognitive test performance may have started earlier than recognized.
Dolphins use names to remember whom to avoid
Laela Sayigh
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Payment integrity in government programs: Takeaways from incorporating the behavioral sciences in US federal evaluations
Maya Duru, Hanna Hoover, Heather Barry Kappes, David Schwegman, Brigitte Seim, Mattie Toma, Mary Clair Turner
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A primary way the US federal government delivers public goods and services is via monetary payments. Ensuring that these payments are calculated accurately, delivered on time, and made to the correct recipients is important for government fiscal health. Inaccurate or delayed payments can weaken public trust in the government and undermine government accountability. In this article, we examine findings from a set of impact evaluations assessing interventions designed to improve payment integrity in US federal programs. The low-cost, evidence-based interventions draw on insights from the social and behavioral sciences and include modification of forms, changes to how and when agencies request information, and altering existing communications. The evaluations were conducted by the US General Services Administration’s Office of Evaluation Sciences in collaboration with agency partners. We extract three takeaways across four representative evaluations. First, the real-world evaluations validate a key implication of the behavioral science literature: interventions that reduce burdens for individuals have small effects that meaningfully improve payment integrity at scale. Second, effects attenuate across interventions and over time, suggesting a need for iterative evaluation. Finally, bureaucratic hurdles and administrative complexity are the main barriers to translating academic insights into real-world government programs. Addressing these challenges will require close collaboration between behavioral scientists and practitioners throughout the intervention design and evaluation process.
Why human societies adopt rigid moral rules: The efficiency–robustness trade-off
Julien Lie-Panis, Léo Fitouchi, Nicolas Baumard, Jean-Baptiste André
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Humans are capable of remarkably flexible moral judgment. Yet societies rely on rigid rules—obligations and prohibitions that apply categorically, even when case-by-case reasoning could yield better outcomes. Why would a species capable of flexibility bind itself to rigid rules? We propose that rigid rules arise as social technologies for managing ambiguity about noncooperation. People often have legitimate reasons for failing to cooperate, yet those reasons are typically opaque to observers, allowing opportunists to disguise selfishness as justified hardship. We formalize this idea with a game-theoretic model. Two cooperative equilibria emerge: a flexible norm that accommodates legitimate excuses but is vulnerable to exploitation, and a rigid norm that closes this loophole by mandating cooperation even when inefficient. Comparing these equilibria reveals an efficiency–robustness trade-off: Flexibility maximizes welfare when trust is secure, whereas rigidity preserves cooperation when trust is fragile. This explains why rigid rules prevail in interactions with strangers, formal institutions, or in tight societies, while flexibility is more common when trust is secure.

Science

GPT-4o mini: Non-social science research article
Roots navigate around decay regions by sensing local pH gradients
Zhulatai Bao, Huihui Wang, Ai Zhang, Ruxi Gao, Wen Gu, Ni Fan, Jiƙí Friml, Yuzhou Zhang
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Plant tropisms enable roots to navigate complex soils by responding to directional environmental cues. Biological decay, although central to nutrient cycling, also creates microbially active and potentially hostile niches. In this work, we identified “saprotropism,” a previously unrecognized growth response that enables roots to actively bend away from decaying plant-derived matter. Fungal-driven microbial decomposition released organic acids and formed stable pH gradients in surrounding soil, allowing roots to pinpoint decay without direct contact. Root epidermal cells sensed this acidic gradient through the root meristem growth factor peptide-receptor module, converting external pH asymmetry into asymmetric abscisic acid (ABA) distribution. ABA asymmetry drove microtubule reorganization, which was decoded into decay-avoidant root bending. Together, these findings establish microbial decay–derived chemical gradients as an instructive signal for root navigation and expand the framework of microbe-soil-plant communication.
GPT-4o mini: Non-social science research article
Adaptation across an extreme elevational gradient in Andean leaf-eared mice, the world’s highest-dwelling mammal
Schuyler Liphardt, Naim M. Bautista, Marcial Quiroga-Carmona, Nathanael D. Herrera, L. Moritz Blumer, Juan C. Opazo, Federico G. Hoffmann, Ranim Saleem, Derek A. Somo, Francisco Del Basto Llancaqueo, Timothy J. Thurman, Timothy B. Wheeler, Daniel E. Shaw, Hunter K. Walt, Till S. Harter, Grant B. McClelland, Graham R. Scott, Pablo Sabat, Zachary A. Cheviron, Guillermo D’Elía, Jeffrey M. Good, Jay F. Storz
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Andean leaf-eared mice ( Phyllotis vaccarum ) live at the highest elevations of any mammal, and they also have the broadest elevational range, from sea level to mountain summits of >6700 meters. Highland populations have evolved an enhanced thermogenic capacity in hypoxia relative to lowland conspecifics, and this improved physiological performance is associated with an increased mitochondrial respiratory capacity in skeletal muscle. Population genomic analyses identified mechanisms of hypoxia adaptation and revealed an unanticipated dimension of environmental adaptation in P. vaccarum because selection on biotransformation pathways suggests an evolved capacity to metabolize plant-derived dietary toxins. The world’s highest-dwelling mammal has adapted to habitats at both the low- and high-elevation limits of its range, and much of the elevation-related selection relates to previously unappreciated aspects of feeding ecology.
GPT-4o mini: Non-social science research article
Leaping out of the water: Aerial-aquatic locomotion with flapping wings
Raphael Zufferey, Simon L. Jeger, Moritz HĂŒsser, Fernando Ruiz, Anthony Lapsansky, Auke Ijspeert, Dario Floreano
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Wing-propelled diving birds flap their wings to move through air and water, yet the wing morphology and kinematics that enable this behavior remain poorly understood because of the difficulty of collecting in situ data. The impact of flapping frequency, wing size, and stiffness on locomotion in—and transition between—the two media are still unknown. We compared data from diving birds against experiments using a flapping-wing robot capable of flying, swimming, plunge diving, and exiting the water. We show that frequency adaptation, flexible wings, and powerful actuation enable seamless transitions without folding wings or legs, that large wings enhance flight without substantially reducing underwater efficiency, and that tail-body distance and egress angle affect water exit. These results clarify how birds (and robots) balance multifluid locomotion constraints.
GPT-4o mini: Non-social science research article
Neural circuits for valence updating in social memory
Narutoshi Suto, Mu-Yun Wang, Shota Morikawa, Myung Chung, Kentaro Tao, Ziyan Huang, Yuji Ikegaya, Haruki Takeuchi, Shinichiro Kira, Teruhiro Okuyama
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Social animals recognize familiar conspecifics and selectively avoid harmful ones. As social relationships shift, continuous updating of social valence is essential, yet the underlying neural mechanisms remain unclear. Here, by artificially transforming a previously neutral conspecific into an aggressive one, we show that valence updating depends on enhanced synaptic connectivity and physiological changes within the hippocampal ventral CA1 (vCA1)–basolateral amygdala (BLA)–nucleus accumbens (NAc) circuit. Following defeat, social memory engram neurons in the vCA1 strengthened their connections with BLA neurons carrying negative valence. The vCA1–BLA–NAc neural circuit flexibly regulates adaptive social behaviors.
GPT-4o mini: Non-social science research article
A single freeze cycle redirects iron mineral transformation
Tao Luo, Tao Chen, Tra My Bui Thi, James Behan, Crispin Hetherington, Khalil Hanna, Jean-François Boily
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Polycrystalline ice formation concentrates mineral nanoparticles into liquid boundaries between growing ice crystals. Here we show that minutes of freezing dictate iron mineral fate over subsequent months of aqueous aging. A single freeze–thaw cycle irreversibly aggregates ferrihydrite through converging physical and chemical mechanisms. Freeze concentration collapses electrostatic barriers while cryosuction strips hydration layers and compresses nanoparticles into micrometer-scale planar aggregates. Chemical evidence points to interfacial (hydr)oxo bridging, alongside hydrogen bonding, that resists disaggregation. These mechanisms lock nanoparticles into mesocrystal-like assemblages that retain their nanoscale identity but inhibit dissolution–reprecipitation to goethite, instead favoring solid-state transformation to hematite. Ice formation thus acts as a geochemical reactor, driving aggregation and interfacial bonding that redirect iron speciation, with broad implications for nutrient cycling and carbon preservation across the cryosphere.
GPT-4o mini: Non-social science research article
Relativistic collapse of the classical triple bond in the CBi − molecular ion
Deniz Kahraman, Jie Hui, Xin-Yu Zhang, Neil A. Ellis, Hyun Wook Choi, Kirk A. Peterson, Lai-Sheng Wang
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The conventional framework for chemical bonding between main-group elements involves separate σ and π orbitals to describe multiple bonds. However, relativistic effects mix these orbitals in molecules containing heavy elements through spin–orbit coupling, leaving the total angular-momentum projection (ω) as the only good quantum number. Direct experimental evidence that relativistic effects change the σ-π bonding framework has remained elusive. Here, we probe the carbon-bismuth triple bond in the CBi − anion using high-resolution cryogenic photoelectron spectroscopy, coupled with relativistic four-component Dirac-Coulomb coupled-cluster calculations. Even though the CBi − anion is isovalent to the well-known CN − species, we demonstrate that the traditional σ + 2π triple-bond picture collapses into a pure π-like |ω| = 3/2 and two |ω| = 1/2 Kramers pairs containing substantial σ/π mixing.
GPT-4o mini: Non-social science research article
A phase microscope for quantum gases
J. C. BrĂŒggenjĂŒrgen, M. S. Fischer, C. Weitenberg
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Coherence properties are central to quantum systems and are at the heart of phenomena such as superconductivity. In this work, we studied coherence properties of an ultracold Bose gas in a two-dimensional optical lattice across the thermal phase transition. To infer the phase coherence and phase fluctuation profiles, we used direct matter-wave imaging of higher Talbot revivals and introduced a phase microscope based on a site-resolved mapping of phase fluctuations to density fluctuations during matter-wave imaging. We observed the algebraic decay of the phase correlations in the superfluid phase and a linear temperature increase of the exponent. These techniques may enable studying coherence properties in strongly correlated quantum systems with full spatial resolution.
GPT-4o mini: Non-social science research article
C1q and immunoglobulins mediate activity-dependent synapse loss in the adult brain
Gerard Crowley, Minjung Kim, Nathanael O’Neill, Emir Turkes, Fateme Ghasemi, Luca Giudice, Sebastiaan De Schepper, Benjy J. Y. Tan, Benito Maffei, Laís S. S. Ferreira, Julie Rebejac, Javier Rueda-Carrasco, Margarita Toneva, John Christian Fajardo, Judy Z. Ge, Zhengyue Grace Yang, Paula Korhonen, Phillip Muckett, Damaris Bennett, Camille Paoletti, Tammie T. M. Sow, David A. Posner, Annerieke Sierksma, Dimitra Sokolova, Viktoras Konstantellos, Leen Ali, Kiavash Movahedi, Andrew F. MacAskill, Victor L. J. Tybulewicz, Tarja Malm, Gabriele Lignani, Menna R. Clatworthy, Soyon Hong
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Complement component 1q (C1q), the initiator of the classical complement cascade, mediates synaptic elimination in development and disease, yet the triggers for its deposition on synapses remain unclear. Using in vivo chemogenetics, we demonstrate that neuronal hyperactivity induces region-specific, C1q-dependent synapse loss in the adult hippocampus. Suppressing perforant pathway hyperactivity in a mouse model of Alzheimer’s disease reduced local amyloid-ÎČ amounts and C1q deposition and partially rescued synapse loss. Combining spatial transcriptomics, live cell tracking, and super-resolution microscopy, we identified association of antibody-secreting B-lineage cells in the adult hippocampus with activity-dependent, C1q-mediated synapse loss under physiological conditions. Together, these findings link neuronal hyperactivity to C1q-mediated synapse loss in the adult brain and implicate immunoglobulins as players in this process.
GPT-4o mini: Non-social science research article
Autonomous biomedical research with an artificial intelligence agent
Kexin Huang, Serena Zhang, Hanchen Wang, Yuanhao Qu, Yingzhou Lu, Ryan Li, Yusuf Roohani, Lin Qiu, Shiyi Cao, Gavin Li, Junze Zhang, Di Yin, Rick Wierenga, Deniz Kavi, Sherry Liu, Tianwei She, Shruti Marwaha, Jennefer N. Carter, Xin Zhou, Matthew T. Wheeler, Jonathan A. Bernstein, Mengdi Wang, Peng He, Jingtian Zhou, Michael P. Snyder, Le Cong, Aviv Regev, Jure Leskovec
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Biomedical research is increasingly constrained by repetitive, fragmented workflows that slow discovery. We introduce Biomni, a general-purpose biomedical artificial intelligence agent that autonomously executes diverse research tasks. To map the biomedical action space, Biomni’s action-discovery agent mines tools, databases, and protocols from thousands of publications across 25 domains, building a unified agentic environment. Its general-purpose architecture integrates large language model reasoning with retrieval-augmented planning and code-based execution, dynamically composing workflows without predefined templates. Systematic benchmarking shows strong generalization across heterogeneous tasks—causal gene prioritization, drug repurposing, rare-disease diagnosis, microbiome analysis, and molecular cloning—without task-specific tuning. Real-world case studies demonstrate Biomni interpreting multi-modal datasets, optimizing protein stability, orchestrating wet-lab instruments, and generating experimentally testable protocols. Biomni envisions artificial intelligence augmenting human scientists and accelerating discovery.
GPT-4o mini: Non-social science research article
Transient assembly of precision-tuned platinum-skin intermetallic catalysts for fuel cells
Jia Ding, Tao Zhang, Wanqing Song, Zezhou Li, Xin Wang, Xinyi Yang, Jiahui Feng, Ming Wen, Yanan Chen, Zhong Wu, Jihan Zhou, Bin Liu, Wenbin Hu
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Highly efficient catalysts require precisely engineered intricate structures, yet conventional thermodynamically controlled syntheses often involve cumbersome procedures and limited structural precision. We report a nonequilibrium transient assembly strategy for the ultrafast synthesis of intricately structured nanocatalysts, including core-shell platinum (Pt)–skinned intermetallic nanocrystals exemplified by Pt@PtFe-i. By using a periodic thermal-pulse protocol to drive the continuous evolution of high-energy transient PtFe configurations, we achieved the synchronous assembly of a high-order PtFe intermetallic core and an atomic-layer-precise Pt skin. The Pt@PtFe-i catalyst exhibits coordination-dependent compressive strain within the Pt skin, creating a high density of highly active sites for the oxygen reduction reaction. The H 2 -air fuel cell with Pt@PtFe-i delivers a peak power of 1.25 watts per square centimeter at a cathode Pt loading of 0.1 milligrams per square centimeter, with a small peak power loss of 3.2% after 30,000 accelerated durability testing cycles.
GPT-4o mini: Non-social science research article
The CARM1 epigenetic enzyme inhibits cross-presenting dendritic cell function in cancer immunity
Xixi Zhang, Sherin Xirenayi, Ye Zhao, Wen Wang, Yuyang Han, Miguel Sobral, Shawn Kang, Chi Zhang, Graham L. Barlow, Jason Pyrdol, Jae-Won Cho, Kun Huang, Xiaohan Ning, Martin Hemberg, Guo-Cheng Yuan, Eliezer M. Van Allen, David J. Mooney, Kai W. Wucherpfennig
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The cancer-immunity cycle requires cross-presenting type I conventional dendritic cells (cDC1s) that induce T cell–mediated immunity, but therapeutic strategies for enhancing intratumoral cDC1 function are currently inadequate. We found the epigenetic enzyme CARM1 (coactivator-associated arginine methyltransferase 1) to be a selective negative regulator of cancer antigen presentation by cDC1s but not cDC2s. Inactivation of the Carm1 gene promoted cDC1 antigen cross-presentation, activation, and accumulation in tumors, and a CARM1 inhibitor enhanced cDC1-mediated priming of T cells by means of a cancer neoantigen vaccine. CARM1 inhibition increased chromatin accessibility at BATF3-Jun and RelA sites that are critical for cDC1 function and activation. Transforming growth factor–ÎČ regulated Carm1 expression, which suggests that CARM1 inactivation enhanced intratumoral cDC1 function without altering cDC1 homeostasis. These studies identify CARM1 as a potential therapeutic target for enhancing the antitumor function of mouse and human cDC1s.
GPT-4o mini: Non-social science research article
Vicinal disubstitution of alkyl C–X synthons via alkene radical cation generation
Yufei Zhang, Tamal Das, Zi Xuan, Mrinmoy Das, Hammed O. Bisiriyu, Alon Nudler, Ben D. Parasch, Matthew D. Resmini, Aubrey E. Graham, David F. Watson, Jennifer S. Hirschi, Patricia Z. Musacchio
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In organic chemistry, functionalization of two adjacent carbons often starts from alkenes or already disubstituted precursors. Herein, we report an exergonic activation mode that directly generates alkene radical cation intermediates from monofunctional C(sp 3 )–X handles through a photoredox-triggered hydrogen-atom abstraction (HAT) and spin-center shift (SCS) process. Computations show that electron delocalization and a network of hydrogen-bonding solvent molecules facilitate a concerted [HAT+SCS] mechanism. The catalytic platform was used to design a transfer of electrophilic reactivity (C–X) from one carbon to another, which we refer to as electrophilic shuttling. Thus, two nucleophiles can be used in the construction of 1,2-difunctionalization adducts from homobenzylic C–X synthons, delivering bisazole architectures and demonstrating compatibility with other nucleophile classes. A suite of transformations is developed that departs from conventional synthetic logic, for which alkyl C–X scaffolds are confined to single-site substitutions, now transforming them into nonintuitive precursors for building vicinal complexity.
GPT-4o mini: Non-social science research article
Virome-wide ubiquitin ligase discovery reveals diverse mechanisms of immune evasion
Caleb R. Glassman, Kheewoong Baek, Gaopeng Hou, Qiru Zeng, Christopher Nardone, Kate B. Juergens, Eric Fujimura, Colin N. O’Leary, Mamie Z. Li, Joao A. Paulo, Eric S. Fischer, Siyuan Ding, J. Wade Harper, Stephen J. Elledge
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Viruses are intracellular parasites that reprogram the host proteome to promote replication and evade immune recognition. We applied a virome-wide library of ~10,000 open reading frames to discover viral ubiquitin ligases, mapping their mechanisms of degradation and host substrates using targeted CRISPR screens and proteomics. These viral effectors could be classified as canonical ligases that mimic host E3s, hijackers that redirect host E3s, and non-canonical ligases that rewire Cullin-RING ligase machinery. These diverse strategies of virus-mediated degradation converged on immune-related substrates, including JAK1 and CUL1 ÎČ−TrCP , underscoring immune evasion as a major driver of viral ubiquitin ligase evolution. Our findings elucidate viral strategies for exploiting the ubiquitin–proteasome system with potential for therapeutic targeting.
GPT-4o mini: Non-social science research article
Bacteria sense virus-induced genome degradation via methylated mononucleotides
Ilya Osterman, Bohdana Hurieva, Sarit Moses, Alla H. Falkovich, Maxim Itkin, Sergey Malitsky, Eliane Hadas Yardeni, Erez Yirmiya, Rotem Sorek
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Phages often degrade the genome of their bacterial host to individual nucleotides. Here we describe Metis, a bacterial defense system that directly senses phage-mediated host genome degradation. Metis aborts phage infection once it detects the modified mono-nucleotide m 6 dAMP. As methylation of deoxyadenosines usually occurs on the DNA polymer, accumulation of m 6 dAMP signals that the host genome has been degraded. In type I Metis, sensing of m 6 dAMP activates an NAD + diphosphatase, leading to NAD + depletion and cessation of the infection process; while the effector in type II Metis is a membrane-spanning protein whose toxicity is triggered in response to the modified mono-nucleotide. We further show that Metis defense depends on endogenous DNA methylases, and that phages can escape Metis via mutations that inactivate host genome degradation.
GPT-4o mini: Non-social science research article
Degron-independent recruitment of KAT2A expands the target space of CRBN molecular glues
Samuel Ojeda, Meng Wang, Kheewoong Baek, Wallace Bourgeois, Alba Sommerschield, Hong Yue, Rebecca J. Metivier, Panos Karagiannis, Talya S. Levitz, Yuan Xiong, Katherine A. Donovan, Scott A. Armstrong, Eric S. Fischer
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Lysine acetyltransferases (KATs) cooperate with oncogenes such as c-Myc, estrogen receptor, and lysine methyltransferase 2A (KMT2A) fusions to sustain malignant programs. Targeting of KAT proteins has shown clinical efficacy; however, achieving homolog selectivity for most KATs remains a major challenge. By extending cereblon (CRBN)–based molecular glues beyond the canonical degron space, we developed an exquisitely selective degrader of KAT2A. Cryo–electron microscopy revealed that CRBN recruits KAT2A independently of a degron; instead, the molecular glue engages a surface-exposed tyrosine, mimicking antibody-like molecular recognition. Selective KAT2A degradation leads to potent ablation of histone H3 lysine 9 acetylation (H3K9Ac), antiproliferative effects in acute myeloid leukemia cell lines, and in vivo efficacy in a patient-derived xenograft model, establishing KAT2A as a targetable vulnerability to treat a wide range of malignancies. More generally, degron-independent recruitment extends the CRBN-targetable proteome.
GPT-4o mini: Non-social science research article
Indium-free perovskite/silicon tandem solar cells with tin oxide recombination layer and electrodes
Wei Shi, Shibo Wang, Shumao Wang, Yue Zhang, Xiaoqiong Ren, Cao Yu, Xinya Niu, Bo Gao, Liu Yang, Bowen Yang, Wenhao Li, Xinyao Sun, Jianwei Yu, Jun Zhu, Shengxing Zhou, Yihua Chen, Fengxian Cao, Kun Gao, Chang Wang, Xi Chen, Shaofei Yang, Jian Zhou, Chenxu He, Ruy Sebastian Bonilla, Yiliang Wu, Qi Chen, Zijia Li, Yuan Cheng, Xinbo Yang, Xiaohong Zhang
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Indium-based transparent conductive oxides are widely used as electrodes and recombination layers in perovskite/silicon tandem solar cells, yet their scalability is constrained by indium scarcity and sputtering-induced damage. We report high-efficiency and stable indium-free perovskite/silicon tandem solar cells enabled by reactive plasma deposited tin oxide (RPD-SnO x ). For RPD-SnO x as the recombination layer, we achieved a certified efficiency of 33.6%. Fully indium-free tandems that used RPD-SnO x as both recombination layer and electrodes delivered a champion power conversion efficiency of 33.2% (1 square centimeter) and a minimodule with a certified efficiency of 31.0% (207.9 square centimeters). Dense and uniform self-assembled monolayer anchoring enabled by RPD-SnO x suppressed nonradiative recombination and reduced halide migration. Indium-free minimodules exhibited high thermal, damp-heat, and outdoor operational stability and retained 65% of their maximum initial efficiency after 105 days of outdoor operation.
GPT-4o mini: Non-social science research article
The origin, history, and resistance architecture of an invasive urban malaria mosquito in Africa
Tristan P. W. Dennis, Jihad Eltaher Sulieman, Mujahid Nouredayem, Temesgen Ashine, Yehenew Ebstie, Adane Eyasu, Eba A. Simma, Endalew Zemene, Nigatu Negash, Abena Yigeremu, Muluken Assefa, Hamza Elzack, Alemayehu Dagne, Biniam Lukas, Mikiyas Gebremichael Bulto, Michael C. Fontaine, Loïc Talignani, Ahmadali Enayati, Fatemeh Nikpoor, Ashwaq M. Al-Nazawi, Mohammed H. Al-Zahrani, Bouh Abdi Khaireh, Samatar Guelleh, Abdoul-Ilah Ahmed Abdi, Richard Allan, Seline Omondi, Bernard Abong’o, Sylvia Milanoi, Eric Ochomo, Ayman Ahmed, Jeanne N. Samake, John E. Gimnig, Cristina Rafferty, Faisal Ashraf, Patricia Pignatelli, Marion Morris, Sanjay C. Nagi, Eric R. Lucas, Anastasia Hernandez-Koutoucheva, Chris S. Clarkson, Patricia Doumbe-Belisse, Adrienne Epstein, Rebecca Brown, Anne L. Wilson, Alison M. Reynolds, Ellie Sherrard-Smith, Delenasaw Yewhalaw, Endalamaw Gadisa, Elfatih Malik, Hmooda Toto Kafy, Martin J. Donnelly, David Weetman
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The invasive urban malaria vector Anopheles stephensi threatens 126 million city dwellers in Africa. Controlling An. stephensi requires greater understanding of its origin, invasion dynamics, and insecticide resistance mechanisms. Analysis of 645 whole genomes sampled across Africa, the Middle East, and Asia supports an invasion scenario in which an initial South Asian introduction established a bridgehead population in Djibouti, which seeded distinct invasion fronts in Sudan, Ethiopia/Kenya, and Yemen. These incursions show contrasting rates and routes of spread shaped by landscape topology. Insecticide resistance is predominantly mediated by metabolic detoxification genes, with resistance haplotypes and copy-number amplifications introduced from South Asia. These findings, alongside a companion genomic resource, enable genomic surveillance of An. stephensi spread and resistance to aid control strategies.
GPT-4o mini: Non-social science research article
Laser phase plate improves structure determination of small proteins by cryo-EM
Petar N. Petrov, Jessie T. Zhang, Jonathan Remis, Jeremy J. Axelrod, Hang Cheng, Eric S. Cooper, Ian K. Hicklin, Shahar Sandhaus, Cooper Schnurr, Robert M. Glaeser, Holger MĂŒller
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Phase plates can, in principle, overcome the poor image contrast in cryo–electron microscopy (cryo-EM) and the resulting limits on the structural reconstruction of small proteins. However, previous designs have been unstable and compromised the high-resolution signal and have thus been unable to surpass results achieved by standard cryo-EM. Here, we show that the laser phase plate (LPP), installed in a modern, custom Titan Krios microscope, enhances the resolution in single-particle reconstruction of small proteins by improving specimen-motion correction and recovery of information from the early frames, as well as particle visualization, three-dimensional classification, and alignment. These advances use standard defocus ranges and reconstruction procedures but open the door to LPP-tailored protocols, offering further improvements by leveraging the LPP demonstrated here.
GPT-4o mini: Non-social science research article
Long-range extended chains arising from polymerization-driven spontaneous assembly
Min Chen, Dongyang Wang, Ye Zou, Changsheng Chen, Xixian Yang, Lixin Niu, Guan Sheng, Jin Wang, Lucas Q. Flagg, Lee J. Richter, Bethany A. Phillips, Bufan Xiao, Guangchao Liu, Liyan You, Julia Laskin, Dean M. DeLongchamp, Kejie Zhao, Ye Zhu, Chong-an Di, Jianguo Mei
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A central challenge for conjugated polymers is to achieve long-range order while remaining solution processable, which is essential for matching the electrical performance of their counterparts of crystalline inorganic semiconductors. In this work, we show that n-doped poly(benzodifurandione) (n-PBDF) can undergo polymerization-driven spontaneous assembly (PSA), in which chain growth, chemical doping, and structural ordering are intrinsically coupled, yielding long-range chain extension over hundreds of nanometers. We reveal that the spontaneously formed n-PBDF nanoribbons arise from a self-initiated, convergent growth mechanism driven by cooperative monomer-polymer interactions and stabilized by proton-coupled duplex chains and the polymer’s intrinsic polyelectrolyte character. With long-range extended chains in the nanoribbons, the aligned n-PBDF thin films demonstrate metallic-level conductivity (>10 4 siemens per centimeter).
Science abstract < 200 char.: Not a research article
Prison release is an opportunity for addiction research
John Strang
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Science abstract < 200 char.: Not a research article
The hidden logic of emotion
Xiaowei Gu, Joshua P. Johansen
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Internal emotion models unify research across species and spark fresh ideas for treating anxiety and trauma
Science abstract < 200 char.: Not a research article
Neil Shubin wants NAS to stay relevant
Jeffrey Mervis
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New president of the beleaguered National Academy of Sciences discusses its future and the precarious state of U.S. science under Trump
Science abstract < 200 char.: Not a research article
Prioritizing a vital river’s restoration
Zhi-Tao Wang, Ping Zhuang
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Science abstract < 200 char.: Not a research article
Uranus and Neptune may not be ‘ice giants’ after all
Hannah Richter
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A growing number of theories propose Uranus and Neptune are rocky worlds
Science abstract < 200 char.: Not a research article
A note to my younger self
Becca Neumann
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Science abstract < 200 char.: Not a research article
What do we know about sex? Poking the Squid: What We Can Learn from Animal Sex Perrin Roosevelt Ireland Norton, 2026. 272 pp. On the Origin of Sex: The Weird and Wonderful Science of Reproduction Lixing Sun Basic Books, 2026. 368 pp.
Nathan H. Lents
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It depends on whom you ask
Science abstract < 200 char.: Not a research article
The owl wars
Warren Cornwall
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Northern spotted owls were spared from logging. Now, scientists are making a last stand to save them from a new threat
Science abstract < 200 char.: Not a research article
British ‘First Fleet’ brought smallpox to Australia
Andrew Curry
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Colonists likely introduced the disease to a more populous continent than many imagined
Science abstract < 200 char.: Not a research article
Antibodies sculpt adult brain circuits
Lauritz Miarka, Marco Prinz
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Immune cells target hyperactive neurons to eliminate synaptic connections
Science abstract < 200 char.: Not a research article
USDA accelerates plan to close its flagship scientific campus
Joanna Thompson
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Agency says closing the research center will improve efficiency, but skeptics argue it will undercut research critical to farmers
Science abstract < 200 char.: Not a research article
Ice as a geochemical reactor
Kevin M. Rosso
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Freezing redirects the fate of iron in Earth’s cryosphere
Science abstract < 200 char.: Not a research article
Does AI work for us, or do we work for AI? The Reverse Centaur’s Guide to Life After AI Cory Doctorow MCD, 2026. 240 pp.
Timothy Wu
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There is little enthusiasm for a technology that turns human users into “reverse centaurs,” argues a critic
Science abstract < 200 char.: Not a research article
In Science Journals
Ellen Wohl, Jelena Stajic, Jack Huang, Jake S. Yeston, Michael A. Funk, Di Jiang, Marc S. Lavine, Courtney Malo, Unnati Sonawala, Madeleine Seale, Corinne Simonti, Ekeoma Uzogara, Mattia Maroso, Priscilla N. Kelly, Sacha Vignieri, Angela Hessler, Phil Szuromi, John Foley, John C. H. Chiang
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
To eat or to breathe?
M. Denise Dearing
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In highland mice, the responses to low oxygen and toxins compete for a shared molecular regulator
Science abstract < 200 char.: Not a research article
US military expansion and deep-sea mining pose environmental risks to Guam
Maia Raymundo, Miranda Bernard, Leevin Camacho, Amber Datta, Ezra Kottler, Ann Marie Gawel
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Science abstract < 200 char.: Not a research article
As bird flu threatens, New Zealand vaccinates endangered birds
Christina Larson
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Arrival of H5N1 virus on Australian mainland triggers ambitious vaccination program
Science abstract < 200 char.: Not a research article
Bridging data gaps to support the Global Plastics Treaty
Quanyin Tan, Khaoula Houssini, Fan Wei, Roland Geyer, Douglas J. McCauley, Jinhui Li
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Reporting should consider data harmonization, supply chain metrics, and pollution hotspot identification
Science abstract < 200 char.: Not a research article
EU horse legislation compromises ecosystem restoration efforts
Carl-Gustaf Thulin
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Science abstract < 200 char.: Not a research article
In Other Journals
Jelena Stajic, Corinne Simonti, Jesse Smith, Bianca Lopez, Joana OsĂłrio, Priscilla N. Kelly, Brad Wible
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Editors’ selections from the current scientific literature
A statistical test for the benefits of personalizing interventions
Zhaoqi Li, Emma Brunskill
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From medicine to marketing to social sciences, the promise of tailoring interventions to individuals is undeniable. However, practical applications force weighing personalization’s potential benefits with its possible increased cost and fragility. We introduce a statistical hypothesis test that evaluates, given historical data, evidence that a personalized intervention policy’s performance will surpass deploying the best single intervention. The test maintains strict Type I error control while achieving asymptotic normality with the minimal possible variance under specified conditions. Results on diverse datasets from job training, depression treatment, education, and recommendation systems demonstrate the test’s versatility and its superior performance over alternatives. This test can support decision-makers throughout the intervention sciences by providing a simple and powerful quantification of the potential benefits of personalization.
Why cities cannot learn
Zaheer Allam
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For most of the world’s urban history, changes in policies and responses to hazards have proceeded on a timescale that made adaptation possible, however slow or politically contested. The Great Fire of London in 1666 produced building regulations within 2 years of the devastating blaze. Repeated flooding events along the Rhine and Danube Rivers through the late 20th century spurred zoning rules and hazard mapping that are now standard across Europe’s urban planning systems. What drove these improvements was a general pathway in which disruption produced evidence, evidence generated pressure, and pressure forced modifications by agencies responsible for governing a city’s well-being. However, that process has been degrading across every inhabited continent. What has emerged in its place is a volatile urbanism that is threatening resilience.

Science Advances

GPT-4o mini: Non-social science research article
Effect of cellular nutrient economy on the evolution of genome size in phytoplankton
Carlos Caceres, Marc Krasovec, Olivier Crispi, Sebastien Gourbiere, Gwenael Piganeau
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The origin of genome size variation remains a central question in evolutionary biology. While energetic costs have been proposed to influence genome size through selection on insertions and deletions (indels), nutrient availability may be a more relevant constraint in primary producers such as phytoplankton. We derived an expression for the selection coefficient of indels based on the phosphorus and nitrogen costs of nucleotides and the cellular nutrient requirements. Selection coefficient estimates indicate that natural selection dominates over genetic drift and favors the fixation of mutations that reduce genome size in phytoplankton with low nutrient requirements. Model predictions are supported by comparative genomics and metagenomic analyses. Together, this model provides a rigorous quantitative framework for understanding genome size evolution, particularly in small cells and oligotrophic environments, highlighting how nutrient limitation drives genome streamlining.
GPT-4o mini: Non-social science research article
Mechanical control of polar order
Pushpendra Gupta, Peter Meisenheimer, Xinyan Li, Sajid Husain, Vishantak Srikrishna, Ashley Cortesis, Yimo Han, Ramamoorthy Ramesh
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BiFeO 3 is a model multiferroic in which the ferroelectric polarization is coupled to ferroelastic lattice distortions, yet deterministic control of its domain structure remains limited by high switching fields and competing polarization variants. Here, we identify a mechanically assisted polarization switching pathway in epitaxial BiFeO 3 thin films that fundamentally alters the switching energetics. Using just out-of-plane electric fields, polarization reversal requires voltages of approximately 4 volts and stabilizes coexisting polarization states. In contrast, when mechanical pressure is applied concurrently, the positive coercive voltage can be substantially reduced, even to 0 volts, resulting in spontaneous switching. Piezoresponse force microscopy measurements reveal that applied mechanical pressure suppresses ferroelastic domain competition, indicating a decrease in the required electrical energy barrier associated with polarization rotation and domain wall motion. This frames the strain field from the AFM tip directly as an effective voltage that assists in ferroelectric switching. By directly coupling lattice distortions to polarization reversal, mechanically assisted switching provides a general framework for controlling coupled order parameters in multiferroic oxides, which can be directly applied in the device-level architecture, where a small mechanical pressure can help in achieving a lower switching energy of ferroelectric polarization. This work advances the fundamental understanding of electromechanical coupling in complex ferroics and establishes mechanical energy as a powerful tool for probing and manipulating ferroelastic-ferroelectric interactions.
GPT-4o mini: Non-social science research article
A soft wearable near-infrared spectroscopy system for detecting brain water dynamics linked to glymphatic activity during sleep
Seunghyeb Ban, Junwoo Kwon, Ikhwan Shin, Youngjin Kwon, Kang-Min Choi, Yunuo Huang, Chang-Ho Yun, Woon-Hong Yeo
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Sleep is a critical physiological process essential for overall brain health. Recent research shows that the glymphatic system is a key player in facilitating the metabolic waste clearance. However, the continuous real-time monitoring of brain water dynamics during sleep remains substantially challenging. Here, we introduce a soft, wearable near-infrared spectroscopy (NIRS) system to detect brain water dynamics potentially linked to glymphatic activity. The device features an integration of multi-wavelength LEDs and photodetectors. The in vivo study with multiple human subjects captures the device’s overnight sleep monitoring in a natural home environment, revealing continuous changes in brain water dynamics across different sleep stages. Our results support the link between sleep stage-dependent water dynamics and glymphatic activity. Spectral analysis identifies several physiological rhythms during sleep, including respiration, heart rate, and oscillations linked to slow-wave activity. These advancements significantly enhance the NIRS system’s potential for a deeper understanding of brain health.
GPT-4o mini: Non-social science research article
ER-mitochondria tether ML1 coordinates peripheral fission and wholesale mitophagy for plant adaptation to carbon starvation
Benhui Shi, Baolei Li, Songyang Wang, Xu Zhang, Yu Tang, Jun Jiang, Liting Zhai, Yang Shao, Jiaqi Sun
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Plants frequently encounter carbon starvation from extended darkness or canopy shading or in nonphotosynthetic tissues, requiring rapid mitochondrial remodeling to match reduced metabolic flux. Here, we reveal a coordinated program integrating peripheral fission–mediated damage segregation and wholesale mitophagy. Carbon starvation triggers a shift from symmetric midzone fission to asymmetric peripheral fission, generating small depolarized fragments alongside larger polarized mitochondria. Unexpectedly, damage-independent wholesale mitophagy targets medium-sized mitochondria for both burden reduction and resource mobilization while excluding small peripheral fission products. We identify mitochondria-ER (endoplasmic reticulum) linker 1 (ML1), a carbon starvation–inducible ER-mitochondria tether, as the central coordinator. At ER-mitochondria contact sites, ML1 promotes peripheral fission and recruits ATG18a (autophagy-related protein 18a) for wholesale mitophagy. Loss of ML1 impairs this coordinated remodeling, resulting in elongated mitochondria, compromised function, and hypersensitivity to carbon starvation. These findings reveal how plants achieve rapid metabolic adaptation through coordinated mitochondrial remodeling.
GPT-4o mini: Non-social science research article
Mineralized carbonates contribute to the millennial durability of Roman concrete
Xiaohong Zhu, Sejung Rosie Chae, Stuart McElhany, Chengyao Liang, Qi Zheng, Jiaqi Li, Veronica Fondi, Sergio Del Ferro, Ascanio Modena Altieri, Harrison P. Lisabeth, Arun Bhattacharjee, Bruce W. Fouke, Hans-Rudolf Wenk, Paulo J. M. Monteiro
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Roman concrete structures have remained serviceable for nearly two millennia and are widely regarded as outstanding examples of durable ancient engineering. Existing literature attributes Roman concrete longevity to the pozzolanic reaction that occurs between reactive volcanic ashes and lime. While the pozzolanic reaction is of fundamental importance, we argue that carbonation over a long period of time also substantially enhances the durability and potential self-healing properties of concrete. To validate this claim, a comprehensive analysis of the concrete used in a latrine included in the Canopus western substructures, in Hadrian’s Villa (Roman imperial residence, Tivoli, Italy, 2nd century AD), is performed using multiscale spectroscopic and tomographic approaches to uncover the mechanisms behind the resilience of these enduring structures. Microstructural evidence reveals that volcanic lava composed of leucite, analcime, and ferrian diopside was combined by the Romans with lime at a water-to-binder ratio of ~0.4 to 0.45 to mix the concrete. Calcite cementation in pore spaces and fractures served as the primary binding mineral phase, while the formation of a relatively minor amount of calcium-aluminum-silicate-hydrate precipitated around and between lava fragments to further enhance the integrity of concrete. Conversely, unhydrated calcium oxide reacted with atmospheric carbon dioxide and moisture to form volumetrically dominant calcite cements, creating the primary driver to reinforce structural strength and occlude porosity. This radiaxial fibrous calcite has the potential to mitigate environmental and mechanical stresses in modern concrete infrastructure and advance the development of sustainable and resilient construction materials in the future.
GPT-4o mini: Non-social science research article
Global expansion of the sensitive aerosol-limited marine cloud regime under emission reductions
Xiao Han, Wenxiang Shen, Minghuai Wang, Yannian Zhu, Yichuan Wang, Jihu Liu, Daniel Rosenfeld, Hao Wang
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Aerosol-cloud interactions (ACIs) are fundamentally nonlinear, with their strongest climatic effects emerging where cloud properties are highly sensitive to aerosol changes—the aerosol-limited regime. Quantifying this regime’s evolution is therefore critical for constraining uncertainties in climate forcing and future projections. By integrating satellite observations with climate model simulations, we map this regime globally and track its recent change. We find it expanded by 4.8% per decade over the past 20 years, primarily due to a sharp increase (∌14.7% per decade) in the Northern Hemisphere driven by anthropogenic emission reductions. Under a strong emission reduction pathway, its frequency is projected to double or triple in key ocean regions. This systematic shift pushes marine clouds into a state of heightened aerosol sensitivity, thereby amplifying the cloud-mediated radiative response to aerosol changes. Our findings underscore the need to account for this evolving sensitivity in climate projections.
GPT-4o mini: Non-social science research article
Periodic shifts in viral load increase risk of Hendra virus spillover from Pteropus bats
Tamika J. Lunn, Benny Borremans, Devin N. Jones-Slobodian, Maureen K. Kessler, Adrienne S. Dale, Claude K. Yinda, Manuel Ruiz-Aravena, Caylee A. Falvo, Daniel E. Crowley, James O. Lloyd-Smith, Vincent J. Munster, Peggy Eby, Hamish McCallum, Peter Hudson, Olivier Restif, Liam P. McGuire, Ina L. Smith, character(0), Raina K. Plowright, Alison J. Peel
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Prediction and management of zoonotic spillover requires an understanding of infection dynamics within reservoir host populations. Spillover risk is commonly inferred from infection prevalence based on detection of viral genomic material, yet detection alone does not indicate the presence of infectious virus or a sufficient dose for transmission. We undertook a comprehensive investigation of Hendra virus shedding in its primary reservoir, Pteropus bats, analyzing quantitative PCR with reverse transcription (RT–qPCR) data from 6151 pooled urine samples collected across five sites over 3 years. We assessed longitudinal associations between viral prevalence (proportion of positive pooled urine samples), viral load proxies, and equine spillover, using generalized additive models and a permutation analysis. Peak prevalence periods associated with spillover events ( N  = 5) had a higher proportion of samples with high viral loads than periods without spillover. Prolonged periods of low viral load and low prevalence likely reflect noninfectious RNA or doses insufficient for cross-species transmission. Incorporating viral load metrics alongside prevalence can improve prediction of spillover risk.
GPT-4o mini: Non-social science research article
Satellite observations reveal widespread alteration of river thermal regimes by US dams
Emily A. Ellis, George H. Allen, Christian E. Torgersen, Katie A. McQuillan
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Dams are well known to alter river thermal regimes, but assessments of downstream temperature changes have been constrained to single dams, single basins, or specific seasonal windows, thus limiting knowledge of their widespread impacts. We used satellite-based thermal infrared observations to quantify river surface temperature differences up- and downstream of 287 large dams in the United States from 2013 to 2024 across all seasons. We found downstream river temperature differences for the majority (71%) of longitudinal river profiles. These downstream changes were typically warmer (60%) and, on average, were sustained or continued to increase within 20 km downstream of the dam. We also found that the magnitude and frequency of downstream alterations varied by dam type, with 91% of extreme (≄±4°C) differences occurring at dams with reservoirs. This work documents the thermal effects of large dams on downstream ecosystems across all seasons on a national scale.
GPT-4o mini: Non-social science research article
Parallel anterior cingulate cortex pathways underlie dissociable social and attentional outputs
Feidi Wang, Mingyue Chen, Mi Lyu, Ying Zhang, Huan Sun, Yu Lu, Dongqi Cui, Wenting Xu, Yixuan Lyu, Yifang Zhai, Jiao Han, Jun Li, Han Xu, Wenting Wang, Li Chen, Xiancang Ma, Yan Li
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The neural mechanisms coordinating social behavior and attentional control are often disrupted together in individuals with neuropsychiatric disorders such as autism spectrum disorder (ASD); however, how distinct circuits within a shared brain region separately regulate these functions remains unclear. Here, we identified two functionally distinct subpopulations of glutamatergic neurons in the anterior cingulate cortex (ACC) that project to different downstream targets: the zona incerta (ZI) and the limbic sector of the thalamic reticular nucleus (lTRN). These two ACC subpopulations differentially mediate social interaction and attentional allocation. Deficits in both behaviors were observed in Shank3b mutant ASD model mice. Optogenetic activation of the ACC→ZI circuit rescued social impairments, whereas activation of the ACC→lTRN pathway restored attentional performance. Our findings reveal dissociable ACC subpopulations and their downstream circuits for social and attentional behaviors, providing circuit-level insights that may inform future research on modulating related symptoms in patients with psychiatric disorders.
GPT-4o mini: Non-social science research article
A caddisfly larva case–mimicked gel polymer electrolyte with high toughness and enhanced ion transport for safe lithium metal batteries
Quan Liu, Xin Liang, Bing Liu, Yuan Yuan, Kang Wang, Yuxin Xia, Bingbing Li, Huakun Liu, Shixue Dou, Xiang Li, Huaxia Deng, Xinglong Gong
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Lithium (Li) metal batteries (LMBs) promise higher energy density than Li-ion cells but face a trade-off between ionic conductivity and mechanical strength in gel polymer electrolytes (GPEs). Inspired by caddisfly larvae cases, which assemble silk with particles for toughness and permeability, we develop a caddisfly larva case–mimicked gel polymer electrolyte (CLC GPE) with high toughness and enhanced ion transport. It integrates an electrospun polyvinylidene fluoride-hexafluoropropylene scaffold with shear thickening fluid. CLC GPE achieves a high ionic conductivity (2.80 × 10 −3 siemens per centimeter), a Li + transference number of 0.89, superior toughness (7.29 megajoules per cubic meter), and a puncture energy of 49.69 millijoules, which can resist thermal abuse (150°C), flame, and bullet impact (225 kilometers per hour). Symmetric Li||Li cells exhibit stable cycling over 800 hours, while Li||LFP (LiFePO 4 ) full cells maintain 97.6% capacity after 700 cycles at 0.5C. This design couples mechanical robustness with fast ion transport, offering a scalable route to safer, high-performance LMBs.
GPT-4o mini: Non-social science research article
Two distinct regions in micellar aggregates identified with pyrene-labeled dendrimers
Donghan Liu, Sanjay Patel, Jean Duhamel
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This study challenges the basic representation that micellar aggregates (MAs) are simple assemblies of ionic surfactants held together by their hydrophobic tails and stabilized by their charged headgroups by demonstrating that they exhibit specific surfactant microdomains. These microdomains are the result of local phase separation between charged and partially neutralized with sodium chloride surfactants inside the same MA of SDS. They were characterized with pyrene-labeled polyamidoamine dendrimers. The charged and partially neutralized surfactants were found to constitute the polar edge and apolar middle regions of MA, respectively, among which the dendrimers would spatially partition themselves. The fluorescence response of the dendrimers was directly related to the volume fraction of the edge region calculated by assuming that the MAs were cylinders whose edges were capped with two identical hemispheres consisting of 35 charged SDS molecules. The fact that merging the two hemispheres generates a spherical SDS micelle led to a general mechanism rationalizing the formation of MA.
GPT-4o mini: Non-social science research article
Implantable bioelectronic outlet
Hyung Joon Shim, Liang Ma, Jose Ferrero Lopez, Duncan J. Wisniewski, Kimberly Gokoffski, Jennifer N. Gelinas, Dion Khodagholy
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Developing a reliable, long-term electrical interface for implanted bioelectronics is essential for chronic diagnostics, therapeutics, and device maintenance. Here, we introduce the implantable bioelectronic outlet (IBO), a soft, tissue-like electronic interface that enables on-demand, direct ohmic connection between implanted electronics and external devices. IBO is composed of a conducting polymer–coated low-density polymer matrix that is jacketed with a hydrophobic elastomer, allowing repetitive insertion of external electrical contacts without crack propagation. IBO was functional after 1 year of implantation with minimal tissue effects. We demonstrate that IBO enables high-fidelity, bidirectional transmission of signals and power, including low-voltage neurophysiological signals, high-speed digital signals, neurostimulation protocols, and efficient high-current power delivery, validated in small and large animal model studies. The IBO provides a robust and scalable platform for safe, direct, and durable electrical interfacing with implantable bioelectronics.
GPT-4o mini: Non-social science research article
Motor-free hip exosuit via high-output fibrous dielectric elastomer actuators
Ziqi Zhang, Wei Yu, Jixiao Liu, Qinghai Zhang, Jianghua Zhao, Guoxian Li, Wenjing Yuan, Xinmeng Ma, Chuizhou Meng, Jiuke Mu, Huichan Zhao, Shijie Guo
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Exosuits can assist gait and reduce fatigue for both healthy and pathological populations, yet their bulky, rigid actuators (usually motors or pneumatic actuators) hinder natural, comfortable movement. Dielectric elastomer actuators (DEAs) provide a lightweight, compliant alternative, but are constrained by insufficient force, energy output, and integration challenges. Herein, we propose a motor-free hip exosuit driven by high-output fibrous DEAs, offering a previously unexplored paradigm for lower-limb assistance. We develop high-aspect-ratio fibrous DEAs that deliver high blocked stress (381.6 mN·mm −2 ), energy density (260 J/kg), and power density (1,664 W/kg), enabled by a dual-polar molecular design of the elastomer to overcome the intrinsic trade-offs between dielectric and mechanical properties. A Lego-like integration strategy is established to efficiently bundle fibers for force amplification. The resulting exosuit reduces the walking metabolic cost by 13.9% compared to no assistance, surpassing most hip exoskeletons. These findings advance DEAs toward practical wearable robotics for real-world human assistance.
GPT-4o mini: Non-social science research article
Improper geometric ferroelectricity at the monolayer limit
Yilin Evan Li, Harikrishnan KP, Haidong Lu, Rachel A. Steinhardt, Megan E. Holtz, Matthew M. Dykes, Mario BrĂŒtzam, Elke Arenholz, Sankalpa Hazra, Adriana LaVopa, Xiaoxi Huang, Wenwen Zhao, Piush Behera, Maya Ramesh, Evan Krysko, Venkatraman Gopalan, Ramamoorthy Ramesh, Craig J. Fennie, Robert J. Cava, Christo Guguschev, Alexei Gruverman, David A. Muller, Darrell G. Schlom
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Improper ferroelectrics, in which electric polarization emerges as a secondary effect of primary order parameters such as nonpolar structural distortions, are theoretically predicted to exhibit no intrinsic thickness limit. Yet, this prediction is inconsistent with experiment where ferroelectricity is observed to disappear in improper ferroelectric films under six formula units thick. We transcend this limitation by moving beyond the conventional epitaxial design paradigm that focuses largely on in-plane lattice mismatch and chemical bonding. By considering structural compatibility in the out-of-plane direction, we realize undiminished improper ferroelectricity at the monolayer limit. Our findings confirm the theoretically predicted absence of a critical thickness for improper ferroelectrics and establish a broadly applicable strategy for designing additional ultrathin ferroelectric materials.
GPT-4o mini: Non-social science research article
Crystalline 3D covalent organic frameworks with nbo topology
Soshi Hirota, Haruki Sugiyama, Nao Hirata, Sachiko Nakano, Junichi Usuba, Yuh Hijikata, Ryotaro Matsuda, Takanori Nakane, Akihiro Kawamoto, Genji Kurisu, Yasutomo Segawa
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Three-dimensional covalent organic frameworks (3D COFs) are promising crystalline porous materials, but the elucidation of their structure remains challenging, particularly for those featuring spiroborate linkages. Herein, we report the synthesis of a 3D crystalline COF with nbo topology, constructed from a rigid square-planar monomer, tetracyclopentatetraphenylene (TCTP), and spiroborate linkages. Theoretical calculations revealed that the TCTP core has higher rigidity than phthalocyanine, effectively suppressing structural fluctuations during framework formation. The structure of the resulting TCTP-COF was successfully determined using microcrystal electron diffraction (MicroED), revealing a noninterpenetrated cubic framework. TCTP-COF exhibits high crystallinity, thermal stability up to 320°C, and permanent porosity with a Brunauer-Emmett-Teller surface area of 1360 square meters per gram. This work represents the structural determination of a spiroborate-linked 3D crystalline COF using MicroED methods, providing a design strategy for expanding the chemical space of highly ordered 3D COF architectures.
GPT-4o mini: Non-social science research article
Deep magma underpressure and connectivity drive large dike intrusions
Carolina Pagli, Alessandro La Rosa, Simone Cesca, Torsten Dahm, Hua Wang, Manuela Bonano, Pasquale Striano, Pinar BĂŒyĂŒkakpınar, Eleonora Rivalta, Derek Keir, Francesco Casu, Atalay Ayele, Elias Lewi
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Large dikes are the main mechanism of crustal extension in volcanic areas, but the processes in the underlying magma system that supply the required volumes remain unclear. We show that 1.4 cubic kilometers of magma propagated under the Ethiopian rift in December 2024 and continued for ~3 months. Geodesy and seismicity reveal that the dike was fed from a network of magma reservoirs between 6 to 12 kilometers in depth with pathways rapidly forming between them. We calculate pressure changes in the reservoirs and show that underpressure developed in the deeper portion, creating the conditions to drain large magma volumes. We find that tectonic stress and availability of magma alone are not enough to drive intrusion of massive dikes. These events will start only after magma connectivity and deep underpressure develop. Similar conditions may be important for the transfer of large magma volumes from the mantle and the formation of large igneous provinces.
GPT-4o mini: Non-social science research article
A chemistry-informed deep learning network for mitigating the stratospheric OH data gap
Wenjie Yin, Chen Zhou, Wuhu Feng, Sandip S. Dhomse, Richard J. Pope, Luis MillĂĄn, Martyn P. Chipperfield
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The hydroxyl (OH) radical is a key species in stratospheric chemistry, driving ozone loss and the coupling of other chemical families. However, global OH observations are very sparse, with a critical gap in satellite-based observations since 2009. Although alternative chemical methods attempt to mitigate such gaps, they have limitations. Here, we present DRCAT, a chemistry-informed deep learning network to predict stratospheric OH profiles using coincident satellite observations of chemically related species. Trained on only 2 years of data, DRCAT provides reconstruction of a continuous and reliable global stratospheric OH dataset from late 2004 to the present. Results show that DRCAT outperforms both a chemical transport model and an observation-constrained steady-state approximation. Moreover, DRCAT successfully predicts anomalous OH enhancements after the 2022 Hunga volcanic eruption, showing generalizability to extreme conditions outside of the training regime. DRCAT thus provides a robust pathway to fill OH observational voids. Beyond OH, this work offers a scalable framework for similar reconstruction of other key short-lived species.
GPT-4o mini: Non-social science research article
Photonic arbitrary Chern vectors
Xiang Xi, Linyun Yang, Ziyao Wang, Bei Yan, Jing-Ming Chen, Yan Meng, Zhen-Xiao Zhu, Tao Xiao, Min-Qi Cheng, Zebin Zhu, Gui-Geng Liu, Hongcheng Wang, Xiankai Sun, Zhen Gao
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The hallmark feature of three-dimensional (3D) Chern insulators is the topological Chern vector, C  = ( C 1 , C 2 , C 3 ), which extends the celebrated Chern-type bulk-edge correspondence from 2D to 3D systems. However, topological Chern vectors have thus far been limited to the simplest form with a single nonzero component, C  = (0, 0, C 3 ), which restricts chiral surface states to appear only on four side surfaces with nonchiral transport along the direction of the Chern vector. Here, we theoretically propose and experimentally realize a 3D photonic Chern insulator with a Chern vector C  = (1, 1, −1) in a tilted gyromagnetic photonic crystal. Its multiple nonzero components enable chiral surface states on all six crystal surfaces, exhibiting genuine chiral transport in arbitrary directions and nonreciprocal topological negative or positive refraction at the hinges. Furthermore, we demonstrate that arbitrary Chern vectors can be achieved via supercell modulation, enabling multimodal transport of chiral and torus knot or link surface states within a single crystal. This work establishes a comprehensive framework for topological Chern vectors and opens possibilities for nonreciprocal photonic devices.
GPT-4o mini: Non-social science research article
Modeling Parkinson’s pathology in human iPSC dopaminergic neurons uncovers key mechanisms of Lewy body formation and heterogeneity
Anne-Laure Mahul-Mellier, Lukas van den Heuvel, Maxime Teixeira, Manel L. N. Boussouf, Gaspard Oudinot, Amélie Thonet, Davide Speri, Yllza Jasiqi, Christina Ulrich, Razan Sheta, Walid Idi, Mary Croisier, Stéphanie Clerc-Rosset, JérÎme Blanc, Graham Knott, Abid Oueslati, Hilal A. Lashuel
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The aggregation of alpha-synuclein (aSyn) into intraneuronal inclusions of heterogeneous morphology, known as Lewy bodies (LBs), is a defining hallmark of Parkinson’s disease (PD); yet, our understanding of the mechanisms underpinning their formation and heterogeneity remains incomplete. Here, we present a human isogenic induced pluripotent stem cell–derived dopaminergic neuron (iDA) model that faithfully recapitulates the diverse biochemical, morphological, and ultrastructural features of LB neuropathology. The iDA model accurately reproduces the temporal relationships between neuritic and cell-body aSyn pathology and recapitulates the proteome, posttranslational modifications, and morphological diversity of aSyn aggregates found in human PD tissue. Moreover, our work provides critical insight into how different pathways to aSyn fibrillization and the complex interaction between aSyn fibrils and membranous organelles shape the morphological diversity of LB-like inclusions. This model represents a versatile platform to investigate the mechanisms of pathology formation, maturation, and neuronal dysfunction and to develop diagnostics and therapeutics that account for the diversity of aSyn pathology in PD and related synucleinopathies.
GPT-4o mini: Non-social science research article
A prolactin-receptive neural circuit drives maternal interactions with pups in mice
Jenny Clarkson, Michael R. Perkinson, Tapasya Pal, Isaiah Cheong, H. James McQuillan, Judith M. Swart, Joon S. Kim, Emmet M. Power, David R. Grattan, Rosemary S. E. Brown
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The medial preoptic area (MPOA) of the hypothalamus drives the expression of maternal behaviors. Although prolactin action in the MPOA is essential for the onset of postpartum maternal behavior, it is still unknown how prolactin acts on underlying neural circuitry to modulate different aspects of maternal behavior. Here, we have identified a prolactin-receptive projection from the MPOA to the ventral tegmental area (VTA) that is specifically activated during interactions with pups. Activation of this prolactin-receptive MPOA-VTA projection stimulated increased maternal interactions with pups in virgin female mice, and the removal of prolactin action within this projection prevented the postpartum increase in maternal-pup interactions. Prolactin-receptive MPOA-VTA neurons modulate dopamine release into the nucleus accumbens (NAc), with stimulation of this projecting inducing dopamine release and increased pup interactions and inhibition blocking pup-induced dopamine release into the NAc. These data define a prolactin-receptive neural circuit that engages with reward pathways to drive increased motivation in mothers to interact with newborn offspring.
GPT-4o mini: Non-social science research article
The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart
Kelsey H. Fisher-Wellman, Richard D. Lutze, Logan G. Kirkland, Ju Youn Beak, Mansi Goyal, Raghu Nagalingam, Samantha M. Morrissey, Peyton B. Sandroni, Wei Huang, Julian D. Bailon, Melissa A. Schroder, Lars A. Albrecht, Ethelyn Ofei, Andrew L. Chin, Thomas D. Green, Joseph M. McClung, McLane M. Montgomery, James T. Hagen, Brett R. Chrest, Edziu M. Franczak, Polina Krassovkaia, Raphael T. Aruleba, Jon S. Zawistowski, Timothy J. Stuhlmiller, Shawn M. Gomez, Nanthip Prathumsap, Qing Zhang, Jing Zhang, Weiyi Xu, Lilei Zhang, Jeremy A. Meier, Lisa A. Carey, Jonathan C. Schisler, Gary L. Johnson, Brian C. Jensen
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Trametinib (Trm) is a highly selective mitogen-activated protein kinase kinase (MEK) inhibitor that potently and persistently abrogates extracellular signal–regulated kinase 1/2 activation. Trm initially was used to treat BRAF Val 600 →Glu (V600E)-mutated melanoma, but its Food and Drug Administration–approved indications are expanding rapidly. Trm generally is well tolerated, but it can cause dose-limiting cardiomyopathy and heart failure. Here, we characterize a mouse model of Trm cardiotoxicity using complementary in vitro approaches to show that Trm induces mitochondrial dysfunction in cardiomyocytes and some cancer cell types. In vivo, Trm caused contractile dysfunction within 3 days and heart failure within 2 weeks. High-resolution respirometry using isolated cardiac mitochondria revealed that Trm compromises oxidative metabolism, in part, through blunted activity of electron transport system complexes. Trm-mediated mitochondrial injury led to the release of mitochondrial damage–associated molecular patterns including mitochondrial DNA in both mice and humans, triggering activation of canonical innate immune pathways including cGAS-STING. In multiple rodent and human cardiomyocyte platforms, Trm diminished mitochondrial respiratory capacity at nanomolar concentrations, but this lesion was reversed by expression of a phosphomimetic signal transducer and activator of transcription 3–S727 construct. We also found that Trm induced mitochondrial dysfunction in some but not all cancer cell lines, identifying a previously unrecognized effect that could contribute to Trm’s anticancer efficacy.
GPT-4o mini: Non-social science research article
Oxidant-free Au(I)/Au(III) catalysis: Rational development of hemilabile proximity-guided N-heterocyclic carbenes
Pengcheng Gao, Jihong Xu, Wenchao Chu, Yanhong Liu, Alejandro Cervantes-Reyes, Elwira Bisz, BƂaĆŒej Dziuk, Roger Lalancette, Roman Szostak, Dongju Zhang, Michal Szostak
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In the past two decades, oxidant-free, ligand-enabled gold(I)/gold(III) [Au(I)/Au(III)] catalysis has become a potential complement to palladium(0)/palladium(II) [Pd(0)/Pd(II)] catalysis in diverse transformation, yet broadly general ligands for Au(I)/Au(III) catalysis remain lacking. Herein, we report a platform for ligand-enabled Au(I)/Au(III) catalysis through the rational development of hemilabile ImQun N-heterocyclic carbene (NHC) nitrogen (N),carbon (C) ligands (ImQun = imidazo[1,5- a ]quinoline). Intriguingly, the best Au catalyst ImQunDippNMe 2 AuCl features the shortest distances between the chelating N atom and the Au center for oxidant-free reaction paradigms. The excellent activity has been demonstrated in alkene difunctionalization via the oxidant-free Au(I)/Au(III) cycle through C─O, C─N, and C─C bond formation, including highly challenging aromatic olefins (>60 examples) and late-stage modification of complex pharmaceuticals (>15 examples). Comprehensive density functional theory (DFT) studies have provided fundamental insight into the reaction mechanism and highlight the central effect of this NHC on the Au(I)/Au(III) redox cycle. The facile access to hemilabile, closely coordinating NHC will enable accelerated development of Au(I)/Au(III) oxidant-free reactivity paradigms using powerful Au catalysis.
GPT-4o mini: Non-social science research article
A multifunctional porous interface bridging 3D architected electronics with skin
Zhangming Shen, Xu Cheng, Xiaobin Luo, Zhenjia Tang, Xiaonan Hu, Hongyun Zhang, Yue Xiao, Qing Liu, Shiwei Xu, Zhi Liu, Renheng Bo, Shenglian Yao, Fan Zhang, Yihui Zhang
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Skin-integrated flexible electronics are rapidly advancing from short-term use to continuous, long-term wear to meet the demands of health monitoring, wound healing, and skin disease treatment. While three-dimensionally (3D) architected devices offer sensing capabilities and outstanding mechanical performances, the development of a conformal interface between these 3D electronic devices and skin for long-term comfortable wear remains challenging due to their geometric complexity and mechanical fragility. Here, we introduce a multifunctional porous interface that bridges 3D flexible electronics with skin through engineered microporous networks. Such a porous design enhances elastic stretchability and electrical reliability while providing moisture permeability, thermal buffering, impact mitigation, and drug delivery capability. Stiffness reduction and localized pore-wall-shell buckling synergistically underpin the outstanding mechanical resilience under large deformations. The proposed multifunctional porous interface allows development of a 3D closed-loop wound administration patch capable of multimodal sensing and on-demand therapy, markedly accelerating scald wound healing in vivo.
GPT-4o mini: Non-social science research article
Discovery of flat-band 2D materials via physics-informed scoring and structure-based learning
Xiangwen Wang, Yihao Wei, Anupam Bhattacharya, Qian Yang, Artem Mishchenko
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Flat electronic bands are a fertile ground for exotic quantum phenomena, from unconventional superconductivity to fractional topology. However, their rarity and the reliance on density functional theory (DFT) calculations for identification have limited systematic exploration across large material spaces. Here, we report the discovery of multiple previously unrecognized flat-band two-dimensional materials through a structure-informed, data-driven framework. We introduce a physically motivated flatness score that combines band dispersion and density-of-states features, enabling algorithmic labeling of known materials without requiring manual inspection. This score is then used to train a multimodal deep learning model that predicts flat-band propensity directly from atomic structure. Applied to more than 10,000 unlabeled materials, our framework identifies numerous flat-band candidates. Among the top-scoring structures (flatness score higher than 0.9), DFT calculations on materials with kagome-like lattices confirm a flat-band prediction accuracy of 98%, demonstrating the ability to discover topologically nontrivial systems. By bypassing the need for precomputed band structures, our approach enables large-scale, interpretable screening and expands the design space for correlated quantum phases in low-dimensional systems.
GPT-4o mini: Non-social science research article
Multicellular simulations with shape and volume constraints using optimal transport
Antoine Diez, Jean Feydy
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Many living and physical systems such as cell aggregates, tissues, or bacterial colonies behave as unconventional systems of particles that are strongly constrained by volume exclusion and shape interactions. Understanding how these constraints lead to macroscopic self-organized structures is a fundamental question in, e.g., developmental biology. Here, we introduce a framework to model particle systems with arbitrary volumes, dynamical shapes, and deformability properties. Our method is grounded in optimal transport theory and its recent applications in incompressible fluid flows, crowd dynamics, and material sciences. Our approach supports a wide range of interaction and deformation mechanisms, while automatically taking care of the volume exclusion constraint with state-of-the-art numerical performance. We showcase the versatility of this approach through a series of experiments, demonstrating how it extends and refines results from previous approaches, with a special focus on challenging 3D situations in biophysics.
GPT-4o mini: Non-social science research article
High- Q microresonators unveil quantum rare events
Sricharan Raghavan-Chitra, Arghadip Koner, Joel Yuen-Zhou
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Classical linear optics posits that at sufficiently low intensities, light propagation in dielectric media is governed solely by their linear susceptibilities. Here, we demonstrate a departure from this paradigm in high–quality (high- Q ) microresonators, where prolonged photon confinement enables rare quantum electrodynamical (QED) events, mediated by the quantum vacuum, to embed distinctive Raman signatures of the coupled analyte into the resonator’s linear transmission spectrum despite their absence from linear susceptibility. We further show that increasing the amount of adsorbed analyte sample amplifies these Raman fingerprints well above typical noise floors, rendering them experimentally accessible with state-of-the-art photonic architectures and detection schemes. This weak-coupling cavity QED effect offers unique routes to harness extended photon lifetimes and constrained geometries for leveraging vacuum fluctuations in next-generation photonic technologies for chemical and biological sensing and high-precision optical spectroscopy.
GPT-4o mini: Non-social science research article
Chondrite parent bodies as escaped satellites of proto-planetary embryos
Harold F. Levison, Rogerio Deienno, Kevin J. Walsh, Brandon C. Johnson, Harold C. Connolly, Shigeru Wakita, Robert E. Grimm
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Chondrites are composed of formerly partially molten material, known as chondrules, surrounded by fine-grained matrix. They date from the earliest times in Solar System history. However, their role in the formation of the planets is uncertain because, in part, it is not clear how they were produced. Here, we show a robust pathway for forming meteorite-producing asteroids that contain chondrules through embryo-embryo collisions during the late stages of terrestrial planet formation. Melted material from these impacts cool into chondrules and mix with unmelted material in embryo-centric disks that formed from the ejecta. This material accretes into numerous asteroid-sized satellites. These objects are later ejected onto heliocentric orbits because of gravitational encounters with other embryos, thereby becoming the parent bodies of chondrites. This mechanism provides a pathway to form chondrites in Solar System history at times commensurate with measured chondrule ages, while explaining many of their physical properties.
GPT-4o mini: Non-social science research article
Enhancing Sn-Pb perovskite homogeneity via thioether coordination for efficient and stable all-perovskite tandem solar cells
Lijuan He, Haoran Wang, Zhaojin Wang, Zhongliang Yan, Arui Huang, Jing Zhang, Xueying Yang, Miao Zeng, Zaiwei Wang, Guang Yang, Zhifang Shi, Wei Zhang, Liang Shen, Yang Bai, Hui-Ming Cheng
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All-perovskite tandem solar cells (TSCs) hold a substantial promise for achieving ultrahigh-efficiency photovoltaics beyond the Shockley-Queisser limit. However, their development has been hampered by challenges associated with a narrow-bandgap tin-lead (Sn-Pb) perovskite subcell. A key issue is inhomogeneous Sn/Pb distribution during crystallization, which generates trap states and accelerates degradation. Here, we introduce a molecular stabilization strategy by using S -allyl- l -cysteine (SALC) as a ligand that preferentially coordinates with tin(II) iodide (SnI 2 ), thereby modulating crystallization kinetics. The strong thioether coordination leads to spatially uniform Sn/Pb distribution, and 3.5-fold reduction in Sn(IV) content due to the reduction capability of functional groups in SALC. Consequently, the resulting Sn-Pb perovskite solar cells achieve a champion power conversion efficiency (PCE) of 22.99% with an exceptional open-circuit voltage of 0.892 V. When integrated into all-perovskite TSCs, a certified PCE of 28.84% (29.44% laboratory-measured) is achieved along with a great improvement in operational stability compared to control devices, retaining nearly 90% of initial PCE after 420 hours of the maximum power point tracking under 1 sun illumination in ambient air.
GPT-4o mini: Non-social science research article
Recent equatorward shift of the summer North Atlantic jet dominated by internal climate variability
Chen Sheng, John Methven, Buwen Dong, Bian He, Guoxiong Wu, Pengfei Zhang, Yimin Liu
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The North Atlantic jet (NAJ), a fast-flowing westerly wind in the upper troposphere, influences the movement of extreme weather systems and affects the safety of commercial flights. In recent decades, the summer NAJ exhibited a substantial equatorward shift over the eastern Atlantic, contrasting with the poleward shift of zonal-mean jet. However, whether this equatorward shift is driven by external forcing or internal variability remains unclear. Here, we show that the recent equatorward shift of the summer NAJ was dominated by internal climate variability. Using simulations from state-of-the-art numerical models and reanalyses, we identify the recent decadal component of the North Atlantic warming hole in summer as the key factor. Through turbulent heat release, this distinctive pattern altered the local atmospheric thermal structure, causing the shift of the summer NAJ via thermal wind response and eddy feedback. However, this internal variability–dominated situation is not expected to persist. Our results indicate that as early as the 2050s, the latitudinal shift of the summer NAJ is projected to emerge beyond the range of internal climate variability.
GPT-4o mini: Non-social science research article
VCAM-1–targeting peptide assemblies protect vascular endothelium and prolong cardiac xenograft survival
Yi-Jing Li, Hang Zhang, Zhe Sun, Kai Xing, Xiumeng Hua, Peiyuan Li, Xiao Chen, Han Mo, Jiangping Song
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Cardiac xenotransplantation represents a promising strategy to address the shortage of donor hearts, yet endothelial cell dysfunction remains a major obstacle to long-term graft survival. Using integrated single-cell RNA sequencing in a porcine-to-primate xenotransplantation model, we identified a VCAM-1 + endothelial subpopulation as the primary endothelial subtype susceptible to acute rejection, characterized by its selective depletion after transplantation. To protect this population, we develop VCAM-1–targeted nanoparticles (VTNs) integrating three functional modules: (i) a VCAM-1–binding peptide identified, (ii) a self-assembling peptide module by one-bead one-compound screening for precise targeting that forms protective nanofibrous coatings, and (iii) localized delivery of mycophenolate mofetil (MMF) for immune modulation. VTN reduces immune cell adhesion by 73% ( P  < 0.001) and extends xenograft survival nearly fourfold, from 6.7 to 27.0 days. These findings establish VCAM-1 + endothelial cells as a therapeutic target and highlight VCAM-1–targeted nanomedicine as a promising approach to improve xenograft outcomes.
GPT-4o mini: Non-social science research article
Transforming static interfaces into tactile channels with steerable transdermal foci
Qiutong Liu, Yi Tang, Jingyue Luo, Wenhao Xue, Ziyi Lin, Zhirui Liu, Miao Luo, Jing Wang, Xuezhi Ma, Jiezhou Pan, Yuan Ma
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Grasping objects such as handles, mice, and phones plays a central role in human-machine interaction, yet the contact surfaces of the hand, despite their exquisite tactile sensitivity, are rarely exploited as channels for information transfer. Here, we introduce transdermal all-directional targeting (TADT), a static-contact interface design strategy that converts passive grip surfaces into active tactile displays, allowing users to grasp stably while receiving spatially and temporally evolving information on the fingertips. TADT enhances sub-actuator-pitch energy delivery by integrating a microtextured skin-coupling interface with phase-controlled vibrotactile actuation, thereby generating steerable three-dimensional tactile foci beneath the skin, enabling >200-hertz vibration and sub-actuator-pitch spatial super-resolution. Psychophysical experiments show that TADT lowers detection thresholds by 30% and reduces power consumption by 80% compared with designs without TADT. Using static grip alone, users reliably identified six directional cues and completed nonvisual indoor navigation and virtual reality interaction tasks, demonstrating a compact, energy-efficient modality for expressive tactile communication.
GPT-4o mini: Non-social science research article
Moonlighting role of meiotic SYCP1 in breast cancer: A chromatin-bound regulator of DNA repair, transcription, and drug resistance
Louise C. Brennan, Oleg V. Grinchuk, Miguel Pachon-Penalba, Ieng F. Sou, Conor J. Fawcett, Claudia G. Nogueira, Megan Guthrie, Andrew D. Bates, Megan Hine, Amanda Thomaz, Andew B. Fielding, Owen R. Davies, Wee-Wei Tee, Urszula L. McClurg
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Maintenance of genome integrity is essential for cellular homeostasis, and its perturbation leads to tumorigenesis. Here, we uncover an unanticipated somatic role for the synaptonemal complex protein SYCP1, previously regarded as strictly meiosis specific, in a broad spectrum of human cancers including breast cancer. Through integrative genomic, proteomic, and functional analyses, we demonstrate that SYCP1 is aberrantly reexpressed in tumor cells, where it actively promotes DNA damage repair, cell cycle progression, and malignant growth. SYCP1 binds chromatin at regulatory elements and directly controls transcriptional programs governing genome maintenance, including key effectors such as CCNB1 , PCNA , RAD51C , and H2AX . Loss of SYCP1 impairs DNA repair kinetics, attenuates tumor cell proliferation and migration, and increases sensitivity to chemotherapeutics cisplatin and gemcitabine. Mechanistically, SYCP1 coimmunoprecipitates with chromatin remodeling complexes and transcription factors SP1 and SP2 and modulates their genomic occupancy and oncogenic transcriptional outputs. Clinically, high SYCP1 expression stratifies patients with poor prognosis and therapy resistance across multiple cancer types. Our findings illuminate a previously unrecognized moonlighting function of SYCP1 in somatic cancer cells and position it as a critical chromatin-associated regulator of genome stability, with implications for biomarker development and therapeutic targeting.
GPT-4o mini: Non-social science research article
Redirecting radical phosphonylation via energy-transfer–enabled diradical rearrangement
Kai-Dian Li, Yi-Hui Tang, Huan-Ming Huang
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Radical phosphonylation has traditionally relied on single-electron transfer mechanisms. In contrast, strategies using energy-transfer pathways to enable scaffold rearrangement are rare. Here, we report an energy transfer catalysis strategy that diverts reactivity toward a previously unexplored pathway: a direct photochemical diradical rearrangement between homoallylic alcohols and phosphorus(III) reagents. Mechanistic studies, supported by computational calculation, provide definitive support for an energy-transfer–mediated diradical mechanism. This operationally simple and mild process, driven by visible light, forges strained phosphorylated cyclopropanes with high efficiency via diradical intermediates that undergo radical addition to phosphorus, ÎČ-scission, and recombination. With broad substrate compatibility and excellent functional group tolerance, this method delivers diverse three-membered rings containing phosphine oxide in good to excellent yields. This work establishes a new reaction manifold for organophosphorus synthesis, demonstrating how energy transfer catalysis can redirect traditional reactivity to access valuable strained architectures through previously inaccessible rearrangement pathways.
GPT-4o mini: Non-social science research article
Trade-offs in mechanical performance influence the diversity of fangs, stingers, and spines
Philip S. L. Anderson, Bingyang Zhang, Kehan Pan, Bradley Scott, Abby Weber
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Puncturing structures such as fangs, stingers, and spines have evolved convergently across all biological realms. Although superficially similar in form, the diversity of these features calls into question whether simple geometric laws can fully describe their evolution. We examine biological puncture tools through the lens of engineering to evaluate how mechanical principles influence their diversity in nature. Plotting biological puncture tools from more than 140 organisms onto mechanically informed performance landscapes shows that tool diversity is heavily influenced by trade-offs between buckling resistance and puncture efficiency. Where an organism falls on this trade-off is partly related to biological function but shows little relation to the replaceability of the tool. Our results highlight multiple avenues for the evolutionary adaptation of biological puncture systems to constraints imposed by physical laws.
GPT-4o mini: Non-social science research article
In vivo engineering tumor cells to a universal “all-in-one” cancer vaccine with full antigen spectrum
Wanting Wang, Yue Huang, Junshi Zhang, Yuan Wang, Zekun Yu, Fanmeng Zhang, Huihui Zhang, Ruiqi Zhang, Runbo Zhong, Hua Zhong, Lu Zhang, Chen Liu, Chenchen Shen, Zhaoyu Li, Mei Wang, Xuanming Yang
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Cancer vaccines offer a promising strategy to initiate de novo T cell responses or enhance existing ones, either functioning independently or synergizing with T cell–modulating therapeutics to reduce tumor burden. The clinical development of cancer vaccines faces challenges such as limited antigen coverage, insufficient antigen presentation, immune suppressive microenvironment, and the availability of personalized vaccines. In this study, we developed a universal “all-in-one” cancer cell–derived vaccine (UniCVac) with comprehensive antigen spectrum coverage by programming tumor cells into antigen-presenting cells (APCs) through the codelivery of CIITA, NLRC5, CD80, and IL-2. This reprogramming mimics the professional APC phenotype, providing simultaneous HLA-I and HLA-II antigen presentation, costimulation, and T cell proliferation signals. These tumor-derived UniCVac can directly activate both CD4 + and CD8 + T cells in vitro, independent of APCs. In addition, their costimulation and T cell growth-stimulating capabilities result in superior CD4 + and CD8 + T cell activation and proliferation comparable to traditional APCs, with enhanced PI3K-AKT pathways activation. Single-cell transcriptome analysis confirmed the similarity in cellular subtypes between UniCVac-activated and traditional APC-activated T cells. In mouse models, the UniCVac vaccination reprogramed the tumor microenvironment from immunosuppressive to immune-permissive, induced robust CD4 + and CD8 + T cell expansion in both preventive and therapeutic tumor models, and achieved complete tumor regression in vivo. Our approach provides a platform for the development of universal cancer vaccines with full antigen spectrum coverage and the ability to directly activate both CD4 + and CD8 + T cells, offering potential combinatorial opportunities with existing T cell–based immunotherapies against cancer.
GPT-4o mini: Non-social science research article
Light hydrogen isotopes in terrestrial core
Yu Zhang, Wenzhong Wang, Zhengbin Deng, Zhongqing Wu, Bowen Chen
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The origin of Earth’s water remains unresolved. Hydrogen isotopes provide a key tracer of planetary water history, yet the isotope composition of Earth’s core—the planet’s largest internal reservoir—has remained unconstrained. Here, we use first-principles calculations combined with machine-learning–accelerated path-integral molecular dynamics to quantify hydrogen isotope fractionation between silicate and metallic melts under core-forming conditions. We find that core formation enriched the silicate Earth in deuterium while concentrating isotopically light hydrogen in the core, requiring the proto-Earth to have started with a lower deuterium-to-hydrogen (D/H) ratio than that preserves in the present-day mantle. Our models show that the bulk-Earth D/H ratio can be explained either by direct accretion of enstatite chondrite–dominated material or by isotopic resetting of deuterium-rich planetesimals through interactions with solar nebular gas. These results suggest that Earth’s water inventory was established during the earliest stages of accretion.
GPT-4o mini: Non-social science research article
Fatigue-resistant and tough double network granular elastomers
Eva Baur, John Kolinski, Esther Amstad
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Elastomers can be engineered as stretchable, compliant materials capable of bearing load, making them attractive for soft robotics, wearable electronics, and biomedical devices. Unfortunately, single-network elastomers are constrained by a stiffness-toughness compromise. While multinetwork elastomers can mitigate this limitation, tough multinetwork elastomers typically exhibit a limited fatigue resistance. Here, we demonstrate that double-network granular elastomers (DNGEs) composed of stiff elastomer microparticles connected through a softer second network combine toughness and fatigue resistance. Their locally varying composition and structure enable DNGEs to efficiently deconcentrate stress and repetitively dissipate energy if stretched to moderate strains, imparting them a good fatigue resistance. Leveraging the three-dimensional printability of DNGEs, we spatially vary the composition to combine stiffness, toughness, and fatigue resistance within one elastomer. We anticipate that DNGEs will unlock opportunities in soft robotics, wearables, and biomedicine, where current soft materials remain limited by the stiffness-toughness-fatigue resistance trade-off.
GPT-4o mini: Non-social science research article
Multiscale metabolic mapping of lung tissue via coregistered mass spectrometry and nonlinear optical imaging
Brittney L. Gorman, Zhi Li, Gail Deutsch, Heidie L. Huyck, Niana Beishembieva, Harsh Bhotika, Heather Olson, Jorge Villazon, Ping Yu, Gloria S. Pryhuber, Geremy Clair, Lingyan Shi, Christopher R. Anderton
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The lung is a highly heterogeneous organ that is composed of numerous microanatomical units, each essential for maintaining intricate functions that work in concert. Disruptions in the molecular and cellular mechanisms can cause tissue fibrosis, inflammation, and severe breathing difficulties, which are common characteristics of the disease of prematurity, bronchopulmonary dysplasia (BPD). BPD’s molecular changes are not well understood, and this has hindered effective diagnosis and treatment. Here, we present a multimodal imaging workflow for detailed molecular and metabolic characterization of lung tissue at multiple spatial scales. We also developed a hierarchical multimodal registration network for precise coregistration of the data from each modality. Our results show that this approach can reveal previously unknown metabolic changes in distinct functional tissue units affected by disease, including altered lipid distributions, reduced optical redox states, and collagen remodeling. This multimodal approach provided detailed maps of molecular shifts occurring in distinct microanatomical features that, when adopted to interrogate this and other tissue types, has the potential to enable the discovery of new therapeutics.
GPT-4o mini: Non-social science research article
Congenital blindness reduces myelination in human visual cortex
Anna-Lena Stroh, Luke J. Edwards, Daniel Haenelt, Fakhereh Movahedian Attar, Kerrin J. Pine, Robert Trampel, Marcin Szwed, Nikolaus Weiskopf
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Sensory experience is critical for cortical maturation, but the cellular consequences of its absence remain poorly understood in humans. Using in vivo sub-millimeter 3 T and 7 T MRI and ultra-high-gradient diffusion MRI, we investigated the effects of congenital blindness on the human early visual cortex. Blind individuals showed reduced R 2 * and MT sat —markers of iron and myelin—along with increased diffusivity, orientation dispersion, and reduced neurite density in the gray and superficial white matter. Cortical thickness was increased in blind individuals and associated with lower myelin and iron, questioning the long-standing assumption that increased thickness primarily reflects disrupted pruning. Our results provide no direct evidence for disrupted pruning. However, they suggest reduced myelination and oligodendrogenesis as key effects of congenital blindness and highlight the critical role of sensory input in shaping and stabilizing cortical circuits.
GPT-4o mini: Non-social science research article
Mechanical multiaxis force sensor for directly bridging sensing and fluidic actuation
Zhexin Xie, Kelu Yu, Peiyi Wang, Si Li, Shaohua Ling, Zhihang Qin, Yu Zhang, Jingyi Yang, Ceng Zhang, Wei Zhang, Wenci Xin, Yaonan Gu, Yu Jun Tan, Cecilia Laschi, Benjamin C. K. Tee
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Robots are the intelligent systems that connect sensors and actuators. Many sensorimotor architectures use close-loop control codes that arbitrate sensing signals, entailing processing modules. Reactive architectures minimize computational demands by establishing direct sensor-actuator connections and have proven to be effective and robust. Here, we introduce a mechanical analogy of such reactive systems: a fluidic-based multiaxis mechanical soft force sensor (ME-SOFS) that directly couples sensory signals with fluidic actuation, eliminating the need for external computation or energy input. The ME-SOFS can be easily reconfigured and integrated to endow robots with somatosensory multiaxis force sensing capabilities. Based on fluid transduction, ME-SOFS converts applied force into mechanical output for fluidic actuators. We demonstrate this sensing-actuation loop in three scenarios: directional droplet manipulation, unified bending of cilia-like array guided by detected force vectors, and haptic feedback system that accelerates robotic grasping learning. ME-SOFSs demonstrate how fluidic approach can realize multiaxis force sensing for soft robots, and enable simplified, closed sensing-actuation loops and haptic human-machine interfaces.
GPT-4o mini: Non-social science research article
Counterfactual modeling isolates sand mining impacts, revealing it as a key driver of Mekong Delta destabilization
Sonu Kumar, Edward Park, Dung Duc Tran, Thanh Quoc Vo, Karl KĂ€stner, Sameh Kantoush, Doan Van Binh, Jiachun Huang, Jingyu Wang, Adam D. Switzer
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Sand mining is a poorly quantified threat to river deltas because its impacts are often confounded with those of dams and climate change. Here, we isolate its effects in the Vietnamese Mekong Delta, a global sand mining hot spot, using a long-term numerical model and observed mining data. Results show that mining exceeds natural sediment supply by 6 to 15 times, causing riverbed erosion across ~65% of channels, with mean incision rates of ~0.10 meters per year (~25 to 30% of total incision driven by all drivers). This channel deepening alters flow, reduces sediment transport, and enhances saltwater intrusion. Sand mining alone contributes ~16 to 30% of the annual salinity increase, extending intrusion up to ~1.5 kilometers further inland during the dry season. These changes demonstrate that sand mining is a major, previously underquantified driver of delta instability, affecting river morphology, flow, sediment, and salinity. This study provides a framework to quantify these impacts and support better management of sand extraction in vulnerable deltas worldwide.
GPT-4o mini: Non-social science research article
Targeted marine cloud brightening weakens subsequent El Niño
Jessica S. Wan, John T. Fasullo, Nan Rosenbloom, Chih-Chieh Chen, Katharine Ricke
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Extreme events are often attributable to the compounding effects of anthropogenic warming and natural variability. Marine cloud brightening (MCB), a solar geoengineering proposal to reduce long-term warming, could theoretically mitigate extremes by instead targeting seasonal-to-multiyear phenomena, such as El Niño–Southern Oscillation (ENSO). Yet the effectiveness of regional MCB to deliberately modify ENSO has not been tested. By exploiting the 2019–2020 Australian wildfire opportunistic experiment, we demonstrate that the “natural” cloud brightening and ensuing La Niña–like response can be reproduced by simulating MCB in the southeast Pacific. We then explore how MCB modifies the 1997–1998 and 2015–2016 El Niño events. MCB initiated during the El Niño growth phase disrupts the Bjerknes feedbacks that normally amplify El Niño conditions, but those effects weaken after MCB is terminated. Only the earliest and longest interventions restore neutral ENSO conditions and weaken teleconnections. Weakening El Niño can result in unintended consequences including an earlier La Niña following the targeted El Niño, although early and short interventions may counter these effects. Our results support the consideration of climate variability and teleconnections as targets in solar geoengineering research.
GPT-4o mini: Non-social science research article
Metamorphic sulfur release as a driver of sustained cooling and mass extinction
Emily M. Stewart, Michael S. Diamond, Lindsi J. Allman
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The emplacement of large igneous provinces may drive catastrophic volatile release, both directly through volcanic degassing and indirectly through heating of carbon- and sulfur-bearing host sediments. It is broadly assumed that sulfur injection must reach the stratosphere to drive long-term cooling; thus, these indirect metamorphic sulfur emissions have been almost entirely ignored. Here, we demonstrate that plausible carbon and sulfur emissions from contact metamorphism may be sustained long enough to cause centennial-scale sulfate aerosol–driven cooling spikes of several kelvins superimposed on millennial-scale warming from the carbon dioxide greenhouse effect. We use modeling of sediment metamorphism along with simple carbon cycle and planetary energy balance models of the climate response to explore this relationship. Our results suggest that a metamorphic sulfur source should be considered as a driver of sustained global cooling during large igneous province emplacement, with potential implications for Phanerozoic biotic crises such as the End-Triassic Mass Extinction.
GPT-4o mini: Non-social science research article
Direct visualization of native GSDMD pores reveals lipid-driven stabilization during pyroptosis
Shirin Kappelhoff, Michael Holtmannspötter, Stefan L. Schaefer, Eleonora G. Margheritis, ÖzgĂŒn Doga Asik, Nadine Gehle, Hannah Veit, John S.H. Danial, Rico Franzkoch, Sebastian Strauss, Jonatan Alvelid, Agnes Koerfer, Christian Eggeling, Olympia E. Psathaki, Ralf Jungmann, Rainer Kurre, Gerhard Hummer, Jacob Piehler, Katia Cosentino
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Gasdermin D (GSDMD) executes pyroptosis by forming membrane pores, yet how these structures assemble and are regulated in cells has remained technically inaccessible. We introduce polymer-supported plasma membranes (PSPMs), which preserve native PM properties while providing cytosolic access for nanoscopic imaging. Combining PSPMs with DNA-PAINT super-resolution microscopy, we visualize human and mouse GSDMD nanostructures directly at the PM of pyroptotic cells and uncover species-specific differences in pore size. Quantitative analyses reveal that GSDMD assembles into heterogeneous macromolecular architectures, including ring-shaped structures, which correlate with PM permeabilization. The palmitoylation-deficient C191A mutant retains minor membrane association but fails to form complete rings, indicating that ring assembly, more than membrane binding, determines pore activity. Last, we identify PI(3,4,5)P 3 as a key regulator of pore stabilization. Its early increase during pyroptosis promotes growth of large rings, and mutations in PI(3,4,5)P 3 -interacting residues undermine assembly. These findings define the native architecture of GSDMD pores and reveal lipid-dependent stabilization as a central mechanism regulating pyroptotic membrane permeabilization.
GPT-4o mini: Non-social science research article
Reprogramming of valine metabolism mediated by abnormally low ALDH6A1 expression promotes invasive metastasis of gastric cancer
Jipeng Wang, Lei Han, Gang Li, Hantao Guo, Wenyue Xu, Lianghui Xia, Menghan Nie, Qing Yang, Yinghao Luo, Yaxu Wang, Qiuming He, Yan-Xiao Ji, Bin Xiong, Shuyi Wang
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Metastasis in gastric cancer requires metabolic reprogramming, but its key drivers remain unclear. Using a CRISPR-Cas9 metabolic knockout screen integrated with patient transcriptomes, we identified the mitochondrial enzyme ALDH6A1 as an anti-invasive factor. ALDH6A1 down-regulation blocked the terminal step of valine catabolism and caused intracellular accumulation of methylmalonic acid (MMA). MMA competitively occupied the α-ketoglutarate (α-KG) cofactor pocket of the histone demethylase KDM5C, suppressing its activity and increasing H3K4 dimethylation (H3K4me2) at promoters of invasion-related genes, including ANGPT2 (angiopoietin-2) and MMP7 (matrix metalloproteinase 7). This epigenetic reprogramming promoted gastric cancer liver metastasis in mice. Pharmacologic ALDH6A1 activation with Alda-1 or systemic MMA clearance with l -carnitine lowered H3K4me2, dampened the invasive program, and reduced metastatic burden. These findings identify the ALDH6A1-MMA axis as a targetable metabolic-epigenetic pathway in gastric cancer metastasis.
GPT-4o mini: Non-social science research article
Morphological and chemical changes in Cd-free colloidal QD-LEDs during operation
Ruiqi Zhang, Jamie Geng, Shaun Tan, Mike Dillender, Shreyas Srinivasan, Taehyung Kim, Mayuran Saravanapavanantham, Kwang-Hee Kim, Heejae Chung, Sujin Park, Thienan Nguyen, Karen Yang, Yongli Lu, Tae-Gon Kim, Moungi G. Bawendi, Vladimir Bulović
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Heavy-metal-free quantum-dot light-emitting devices (QD-LEDs) demonstrate high brightness, saturated color, and high efficiency, yet their operational lifetimes remain limited, with the underlying degradation mechanisms not fully understood. Here, we show that InP/ZnSe/ZnS (red-emitting) and ZnTeSe/ZnSe/ZnS (blue-emitting) colloidal QD-LEDs undergo nanoscale morphological changes during operation. Interparticle coarsening and layer thinning are observed in the core functional layers, accompanied by the generation and diffusion of compositional-oxygen and hydrogen across the device, with oxygen accumulating at the Al electrode/ZnMgO electron-transport layer (ETL) interface. In situ transmission electron microscopy reveals that electron beam exposure, in presence of atomic hydrogen species, accelerates ZnMgO nanoparticles coarsening. To mitigate these degradation pathways, we show that acrylate-based resin encapsulation can stabilize the ETL, HTL, and QD layers by suppressing atomic species formation and halting morphology changes. This approach achieves over 50-fold and 5000-fold lifetime improvement in InP/ZnSe/ZnS and ZnTeSe/ZnSe/ZnS QD-LEDs, respectively. Our findings establish the causal relationships between morphological degradation, interlayer dynamics, and QD-LED instability, providing insight into the acrylate encapsulation treatment that enables efficient and long-lived QD-LEDs.
GPT-4o mini: Non-social science research article
CO 2 -assisted dehydrogenation-hydroformylation cascade enables syngas self-sufficiency and carbon-efficient propane upgrading
Kaige Tian, Pengyu Xiang, Xianhui Wang, Jingyi Zhao, Donglong Fu, Zhi-Jian Zhao, Xinbin Ma, Sai Chen, Chunlei Pei, Jinlong Gong
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Propane upgrading is fundamentally constrained by the high energy demand of conventional dehydrogenation and the reliance of hydroformylation on fossil-derived syngas, limiting both efficiency and sustainability. We redesign this architecture by establishing a carbon dioxide (CO 2 )–assisted oxidative dehydrogenation–hydroformylation (CO 2 -ODH-HF) cascade that replaces propane dehydrogenation (PDH) with a CO 2 -ODH reactor and circulates CO 2 to generate carbon monoxide (CO) and dihydrogen (H 2 ) internally. Aspen Plus simulations show that this shift in reaction route creates a syngas self-sufficient system in which propylene formation, CO 2 utilization, and hydroformylation become directly coupled. The integrated cascade enhances carbon-utilization efficiency, eliminates external CO procurement, and substantially reduces total production costs compared with PDH-HF. Life-cycle assessment further indicates ~42% lower greenhouse-gas emissions per kilogram of aldehyde produced, without triggering economic-environmental trade-offs. Sensitivity analyses reveal strong robustness against fluctuations in the feed price of liquefied petroleum gas (LPG) containing propane compounds, CO cost, and hydroformylation catalyst loss. By restructuring underlying reaction pathways and carbon flows, the CO 2 -ODH-HF cascade establishes a scalable and carbon-efficient route for propane upgrading and aldehyde synthesis.
GPT-4o mini: Non-social science research article
Stiffness-tunable oral nanoparticles facilitate damaged islet ÎČ cell restoration for diabetes treatment
Wenyan She, Xiaojuan Jiang, Siying Deng, Luyuan Hu, Chenxi Huang, Lin Hou
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Diabetes mellitus remains a global health challenge, as current insulin-based therapies merely control blood glucose without restoring islet ÎČ cell function, leaving patients dependent on lifelong medication and vulnerable to hypoglycemia. Antioxidant drugs hold promise for islet ÎČ cell repair but are limited by poor gastrointestinal transportation and insufficient pancreatic targetability. Here, we initially identify ferroptosis-associated oxidative stress as a key cause of islet ÎČ cell death and develop six stiffness-gradient nanoparticles by embedding bent oleic acid into ordered 1,2-distearoyl- sn -glycero-3-phosphoethanolamine to enhance drug bioavailability. Nanoparticles with intermediate stiffness optimize membrane wrapping and minimize energetic cost, enhancing intestinal M cell transcytosis and macrophage-mediated hitchhiking, thereby increasing pancreatic curcumin accumulation by ~4.5-fold. In diabetic models, this formulation suppresses ferroptosis-associated oxidative stress, promotes in situ islet ÎČ cell repair, and restores insulin homeostasis and autonomous glycemic control, maintaining normoglycemia without hypoglycemia even after treatment cessation. This study represents a patient-friendly oral nanotherapy that outperforms insulin therapy in long-standing diabetes management.
GPT-4o mini: Non-social science research article
Trainable soft electronics with memory in liquid crystal polymers
Pengrong Lyu, SamuĂ«l A. M. Weima, Jaeryang Baek, Ouassim L’Karkouri, Dirk J. Broer, Mert O. Astam, Danqing Liu
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State-of-the-art soft materials can be engineered as sensors and actuators, yet, methods for learning from external information remain a subject of current research. Inspired by the use of large datasets to train artificial intelligence, tuning physical responsiveness to relayed data would introduce learning behavior in soft materials. In this work, we develop a trainable liquid crystal oligomer network (LCON) that stores digital information directly into its molecular configuration. By functionalizing the anisotropic LCON with photo-switchable azobenzene, we simultaneously integrate basic logic and memory in a material through a binary-state system; we coin this design the trainable self-propelled gate (T-SPG). We can tune the memory of our T-SPG with photonic stimuli, allowing the system to be trained by a conventional digital controller. We demonstrate the trainability of the T-SPG through two hierarchical tasks: a lower-level binary classification task where the decision boundary is stored as material memory, and a higher-level motion task that uses the stored memory to trigger actuation.
GPT-4o mini: Non-social science research article
G protein selectivity in group I metabotropic glutamate receptors
Yue Lu, Tianlei Wen, Xuhang Lu, Guimin Zhang, Tingting Meng, Tianjin Liu, Xinyan Wang, Yuequan Shen, Xue Yang
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Metabotropic glutamate (mGlu) receptors are class C G protein–coupled receptor involved in synaptic transmission and neurological disorders. Group I mGlu receptors (mGlu1 and mGlu5) predominantly couple to G q/11 , whereas group II and III receptors primarily engage G i/o . Although G i/o -coupling mechanisms have been defined for several group II/III receptors, how group I receptors preferentially engage G q/11 remains unclear. Here we report cryo–electron microscopy structures of active mGlu–G protein complexes (mGlu1-G q , mGlu1-G i , mGlu5-G q , and mGlu5-G i ) bound to l -glutamate and positive allosteric modulators (PAMs), together with two additional activated-state structures of mGlu1. Comparative structural and biochemical analyses identify a group I–specific ICL2 insertion that promotes preferential G q engagement. Each receptor dimer asymmetrically binds one G protein heterotrimer via an intracellular pocket engaging the Gα amino-terminal helix. PAM binding to one 7TM domain induces W 6.50 rotation and TM6 outward movement, bringing the two 7TMs into closer. These findings provide a structural basis for preferential G q/11 engagement and activation of group I mGlu receptors.
GPT-4o mini: Non-social science research article
Progressive intestinal tumor cell plasticity, Myc activation, and loss of Lgr5 + tumor stem cell lineage commitment upon Wnt depletion
Marika Lassila, Fatemeh Seyednasrollah, Cinzia Bessone, Maritta RÀisÀnen, Inkeri Vuori, Davide G. Berta, Johanna Aspholm, Tatiana V. Petrova, Lauri A. Aaltonen, Kari Alitalo, Pauliina Kallio
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Plasticity, the capability of tumor cells to go through phenotypic transitions, promotes colorectal cancer (CRC) progression and treatment resistance. Although plasticity is evident in advanced CRCs, little is known about plasticity in early-stage tumors and tumor stem cells. Here, we demonstrate that a plastic cell state (PCS) is present already in polyps from patients with familial adenomatous polyposis and in mouse intestinal adenomas, in which PCS is associated with PROX1 + tumor stem cells. We furthermore analyzed progressive plasticity upon loss of the canonical wingless-related integration site (Wnt) effector Tcf7 or Lef1 in Apc mutant mice. Deletion of either gene led to emergence of new plastic tumor cell populations, failure of leucine-rich repeat–containing G protein-coupled receptor 5 (Lgr5) tumor stem cell differentiation into enterocyte-like cells, enhanced Myc pathway activation, and increased tumor cell proliferation and tumorigenesis. Together, we demonstrate that PCS is associated with early CRC development and identify multiple potentially druggable mechanisms activated during progressive tumor cell plasticity.
GPT-4o mini: Non-social science research article
Low-intensity stimulation drives macrophage efferocytosis via ACSL4 lipid remodeling and CCL9-CCR1 signaling for tendon-bone healing
Juncheng Yao, Yuhao Wu, Xuan Wang, Jiexin Zhang, Yan Shao, Huabin Chen, Haiyan Zhang, Haobin Li, Jianying Pan, Yitao Zhao, Daozhang Cai, Denghui Xie, Chun Zeng
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The mechanisms underlying exercise rehabilitation–induced tendon-bone healing remain unclear. Using a mouse model of anterior cruciate ligament reconstruction, we found that low-intensity mechanical stimulation promoted macrophage M2 polarization, phagocytosis, and efferocytosis at the tendon-bone interface via acyl-CoA synthetase long-chain family member 4 (ACSL4)–mediated lipid metabolism reprogramming. Acsl4 silencing reduced fatty acid oxidation and efferocytosis, impairing exercise rehabilitation–induced tendon-bone healing. Notably, the CCL9-CCR1 axis contributed to bone marrow stromal cell homing following macrophage efferocytosis. In addition, engineered CCL9-expressing exosomes accelerated tendon-bone repair.
GPT-4o mini: Non-social science research article
A scalable deep-learning framework for cancer detection using cell-free DNA shallow whole-genome sequencing
Haichao Wang, Paulius D. Mennea, Grainne McAndrew, Ozge Sonmezler, Dmitry S. Shcherbo, Emma-Jane Ditter, Sarah Østrup Jensen, Alessandra I. G. Buma, Christopher G. Smith, Zhao Cheng, Clare Harris, Rosalind. J. Cutts, Sarah Hrebien, Philip A. J. Crosbie, Pippa G. Corrie, Michel M. van den Heuvel, Amit Roshan, Frank McCaughan, Robert C. Rintoul, Florian Markowetz, Tommy Kaplan, Wendy N. Cooper, Hui Zhao, Nitzan Rosenfeld
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Cell-free DNA (cfDNA) in body fluids enables noninvasive cancer detection. Multifeature artificial intelligence (AI) can improve sensitivity by integrating diverse biomarkers when cancer signals are sparse. Tumor-informed assays that rely on mutations have limited practicality for early cancer detection. Emerging fragmentomic and epigenetic features underpin tumor-naive approaches to screening for individuals with low tumor burden. Here, we designed UNITE—a universal cfDNA feature ensemble framework that provides scalable cancer detection methods based on “genomic bin–fragment length” matrices derived from shallow whole-genome sequencing (sWGS) data at 0.1× depth. Using sWGS data from 2063 plasma samples (631 controls and 1432 cases from 26 cancer types), we systematically evaluated both XGBoost (UNITE-XGB) and convolutional neural networks (UNITE-CNN) across multiple feature spaces and cancer stages. In stage I-II cancer, UNITE-XGB and UNITE-CNN achieved 31 and 21% sensitivity, respectively, at 95% specificity. These findings provide roadmaps for developing multifeature AI beyond plasma biopsies.
GPT-4o mini: Non-social science research article
Disordered vacancy-isolated Ce-Gd-O clusters achieve exceptional low-temperature oxygen-ion conductivity for fuel cells
Shengli Pang, Xudong He, Hao Lou, Kaijie Xu, Jintong Guan, Yi Zhuang, Xuyao Luo, Lianxu Xu, Qiangsheng Xiao, Yifei Gao, Peijie Zhang, Juan Yang, Yi Li, Chonglin Chen
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Oxygen-ion conductors are central to clean energy technologies. Conventional long-range–ordered oxide-ion conductors require high operating temperatures, which increase cost and limit durability; overcoming the low temperature conductivity gap is a long-standing challenge. We created cerium (Ce)–gadolinium (Gd)–oxygen (O) clusters by thermal-shock exfoliation of fluorite Gd 0.1 Ce 0.9 O 1.95 and examined their structure and ion transport. These disordered, vacancy-isolated clusters form percolative oxygen-ion pathways without long-range order, delivering exceptional conductivity of 2.14 ± 0.09 siemens per centimeter at 400°C—more than 320-fold higher than most previously reported oxide-ion conductors under comparable conditions. Used as a 0.5 weight % cathode additive in solid oxide fuel cells, they tripled the peak power density to 2.87 ± 0.04 watts per square centimeter at 750°C compared with the pristine Pr 0.5 Ba 0.25 Ca 0.25 CoO 3–ή /Gd 0.1 Ce 0.9 O 1.95 cathode and reversed degradation from −13.2 to +3.4% per 100 hours. These findings overturn the paradigm that high oxygen-ion conductivity requires long-range order and highlight Ce-Gd-O clusters as enablers for advanced energy technologies.
GPT-4o mini: Non-social science research article
Remote network for cognitive symptoms derived from tau accumulation in progressive supranuclear palsy
Yuki Hori, Hironobu Endo, Kenji Tagai, Yuko Kataoka, Ryoji Goto, Shin Kurose, Yuki Momota, Naomi Kokubo, Chie Seki, Sho Moriguchi, Hitoshi Shimada, Hitoshi Shinotoh, Takahiko Tokuda, Keisuke Takahata, Takafumi Minamimoto, Makoto Higuchi, Toshiyuki Hirabayashi
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Progressive supranuclear palsy (PSP) is a neurodegenerative disorder with motor and cognitive impairments. Whereas motor symptoms are associated with subcortical tau deposits, the mechanisms underlying the cognitive symptoms remain unclear due to heterogeneous and primarily subcortical distribution of pathological tau deposits. Here, we combined tau-PET (tau positron emission tomography) using a high-contrast probe we developed with a normative connectome in 37 patients with PSP and 48 healthy controls. We found that tau deposition sites functionally connected to a common cortical network that could not be derived from atrophy. This network predominantly overlapped with canonical action-mode and frontoparietal networks, which support adaptive, goal-directed behavior. Whereas the extent of primary tau deposition predicted motor symptoms, the normative connectivity strength from tau deposition sites to the identified cortical network explained the severity of cognitive deficits. These findings suggest a previously unknown mechanism that cognitive, but not motor, deficits in PSP arise from remote effects of tau deposition—independent of atrophy—via convergent connectivity to a common cortical network.
GPT-4o mini: Non-social science research article
All-two-dimensional, ion-gating synaptic transistors for high-temperature and ultralow-energy-consumption neuromorphic applications
Yonghuang Wu, Xiangpeng Liang, Ting Pan, Chenghui Wu, Wenxin Wang, Jiayuan Chen, Ruixuan Peng, Yuanmin Zhu, Cheng Zhen, Run Shi, Bochen Zhao, Zonglin Li, Yiqun Liu, Zhou Zhu, Jing Ma, Meng Danny Gu, Jianshi Tang, Kai Liu
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High-temperature intelligent devices operating above 125°C are crucial for applications where cooling is insufficient or impossible. Synaptic transistors, as an intelligent hardware in neuromorphic computing, allow multifunctionality and precise control of channel conductance, but they face challenges in achieving low energy consumption and optimal performance at high temperatures. This study introduces an all-two-dimensional (2D) high-temperature ion-gating synaptic transistor (A2D-HTIGST) using tungsten disulfide (WS 2 ) as the channel, copper indium thiophosphate (CuInP 2 S 6 ) as the ion-gating layer, hexagonal boron nitride (h-BN) as the electron barrier, and graphene as the gate. The A2D-HTIGST demonstrates efficient ion gating, low leakage current, high on/off ratio, pronounced hysteresis, and linear synaptic plasticity at elevated temperatures. Notably, it achieves an energy consumption of under 3 femtojoules per pulse at 200°C, surpassing other high-temperature and nearing room-temperature synaptic devices. The A2D-HTIGST further enables self-powered neuromorphic applications coupled with thermoelectric generators that use waste heat and advances high-temperature reservoir computing for temporal signal processing.
GPT-4o mini: Non-social science research article
Epigenetic landscape, key transcriptional regulators, and in vivo identification of human Tr1 cells
Alma-Martina Cepika, Laura Amaya, Colin Waichler, Mansi Narula, Michelle Mantilla, Benjamin C. Thomas, Pauline P. Chen, Robert A. Freeborn, Mara Pavel-Dinu, Jason Nideffer, Matthew Porteus, Rosa Bacchetta, Fabian MĂŒller, William J. Greenleaf, Howard Y. Chang, Maria Grazia Roncarolo
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Type 1 regulatory T (Tr1) cells are CD4 + T cells with suppressive function that are induced from conventional T cells exposed to persistent or strong antigens. Human Tr1 cells are understudied; the regulators of their antigen-driven differentiation are unknown, and identifying them in tissues, where antigen interactions occur, is challenging. Here, we conducted a multiomic profiling of human antigen-induced Tr1 cells. Using CRISPR-based functional genomics, we uncovered essential roles of transcription factors IRF4, BATF, and MAF in human Tr1 differentiation, phenotype, and function. We also derived a Tr1 transcriptional signature that detects cells with a Tr1 phenotype in single-cell datasets from patients treated with Tr1 therapy and those with solid tumors. Cross-species analysis confirmed this signature identifies bona fide Tr1 cells induced in vivo in a murine solid tumor model. These findings provide a framework for development of Tr1-based and Tr1-targeting therapies and studies of Tr1 cell biology.
GPT-4o mini: Non-social science research article
Inverse design of guanine-defects in carbon nanotubes for high-resolution emission tuning
Yinong Li, Xiao-Kun Zhao, Jiajie Wu, Li Zhu, Shishan Tian, Yannan Feng, Zhilong Zhang, Cong-Qiao Xu, Zhiwei Lin
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Defect engineering in single-wall carbon nanotubes (CNTs) offers a powerful means of tuning their properties. However, existing strategies predominantly rely on post hoc characterization of defects, and rational approaches for the pre-design of defects remain lacking. Here, we present an inverse defect-design strategy that leverages DNA-directed, guanine-specific chemistry to introduce guanine-defects into CNTs. We assign these modifications as sp 2 defects, which—unlike conventional sp 3 defects—largely preserve the π-conjugation of CNT lattice while enabling tunable property modulation via lattice restructuring. This approach was applied to five distinct single-chirality CNT species, yielding a chirality-dependent modification index, M( n , m ), capable of predicting defect-induced property changes, even for CNTs lacking prior experimental data. Guided by this index, we achieved deterministic control over emission wavelengths with an accuracy of ±1 nm and Raman profiles within 1% deviation from predictions. These precisely engineered CNTs were further utilized for pattern switching and multilayer information encryption, highlighting the potential of precision defect design in advancing next-generation CNT-based materials.
GPT-4o mini: Non-social science research article
Optical photothermal infrared imaging of fatty acid esterification in the ER of living cells
Hannah B. Castillo, Caitlin M. Davis
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Lipotoxicity is an accumulation of lipids that leads to cell death and metabolic disease. Saturated fatty acids are more likely to cause lipotoxicity; however, the mechanism remains unclear due to challenges visualizing reactions in live cells. Here, we use optical photothermal infrared microspectroscopy to investigate palmitic acid (PA) metabolism in hepatocytes with submicron spatial resolution. Upon PA feeding, we found a time-dependent ester carbonyl stretch localized to the endoplasmic reticulum (ER) near lipid droplets with abnormal morphology. This stretch is assigned to diacylglycerol intermediates in the glycerol-3-phosphate pathway. C─D stretches of deuterated PA provide complementary molecular details, supporting a model whereby PA acyl chain packing in the ER reduces enzyme diffusion slowing PA metabolism. Our results provide a deeper understanding of how phase changes induced by high melting temperature fatty acids and their metabolites change ER chemistry as well as provide a tool for detecting chemical and environmental changes associated with lipotoxicity in live cells.
GPT-4o mini: Non-social science research article
Modeling human embryo adhesion using a microfluidic platform
SofĂ­a Zaragozano, MarĂ­a Pardo-Figuerez, Ana Monteagudo-Sanchez, Anna Quirant, Javier Moncayo-Arlandi, Javier Gonzalez-Fernandez, Jaime Llera-Oyola, Petr Volkov, Sara Maggi, Luis Quintero, Francisco Raga, Pablo Grases, Xavier Santamaria, Inmaculada Moreno, Nicolas Plachta, Carlos Simon, Felipe Vilella
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Embryo adhesion represents a critical step of implantation, yet understanding this process has been hindered by the lack of human in vitro platforms that replicate endometrial physiology. Here, we present a dual-channel microfluidic platform containing organoid-derived endometrial epithelium and primary stromal cells. Our model recapitulates important endometrial hallmarks including epithelial polarization, stromal decidualization, extracellular vesicle release, and hormone-induced receptivity. We validated the model using mouse embryos and human blastocysts, where we showed that embryos displayed features of initial adhesion. These included establishment of embryo-epithelial contacts initiated via the polar trophectoderm, inner cell mass repositioning, and lineage reorganization. Moreover, human embryos secreted ÎČhCG indicating a functional trophoblast. Thus, this work provides a platform to study key features of embryo adhesion and endometrial receptivity and disorders affecting embryo-endometrium interactions.
GPT-4o mini: Non-social science research article
Atomically chemical heterogeneity endowing dielectric ceramics with ultrahigh energy storage
Bing Xie, Qingqing Wu, Zhiqing Li, Zhen Wang, Zhiyong Liu, Kun Guo, Haibo Zhang, Huajie Luo, Tianyu Li
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Harnessing local structural and chemical complexity in dielectric ceramics to reconcile large polarization, low hysteretic loss, and high breakdown strength is central to advancing dielectric capacitors for pulsed-power and high-voltage electronics. Here, we show that atomic-scale chemical heterogeneity, deliberately engineered in a relaxor ferroelectric perovskite matrix, provides an effective route to simultaneously elevate energy density and efficiency in bulk lead-free ceramics. Using canonical (Bi 0.5 Na 0.5 )TiO 3 -based relaxor ferroelectric as a host, we propose an atomically chemical heterogeneity design by manipulating coupled A/B-sublattice occupancy correlations while preserving the average pseudocubic perovskite framework. Systematic characterizations of local chemical structures reveal nonrandom cation configurations at the atomic scale, severe local lattice distortion, and ultrafine slush-like multipolar nanodomains (1 to 4 nanometers in size) in which tetragonal, rhombohedral, orthorhombic, and nonpolar cubic regions coexist. This nanoscale polar landscape sustains a large electric field–induced polarization while strongly suppressing remanence and hysteresis, enabling an ultrahigh breakdown strength of 74.2 kilovolts per millimeter. As a result, the optimized ceramic delivers a recoverable energy density of 17.4 joules per cubic centimeter with 88% efficiency, together with excellent stability across different operation conditions. In particular, the fatigue endurance remains up to 10 8 charge-discharge cycles under high electric fields. These results identify atomically chemical heterogeneity as a powerful and general design principle for high-reliability dielectric ceramics combining ultrahigh energy density with high efficiency.
GPT-4o mini: Non-social science research article
Propagation of fluid-driven aseismic slip fronts under upper crustal conditions
François PasselÚgue, Nicolas Brantut, Hervé Chauris, Pierre Dublanchet
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Fracture mechanics models suggest that aseismic slip may either lag behind or outpace the fluid pressure front, depending on injection conditions and the fault’s initial stress state. However, direct experimental validation of these predictions has been lacking. Here, we report laboratory experiments on granite samples under upper crustal stress conditions, where we simultaneously tracked the propagation of fluid pressure and aseismic slip during fluid injection. We show that aseismic slip lags the pressure front at low injection rates and low initial stress but rapidly outpaces it under high-rate injection or near-failure initial stress conditions. The transition is governed by a dimensionless loading parameter that integrates injection rate, fault strength, and initial shear stress. Our results provide direct support for fracture mechanics models of fluid-induced aseismic slip and suggest that in critically stressed crustal faults, rupture propagation may commonly outpace fluid diffusion.
GPT-4o mini: Non-social science research article
Submicromolar imaging of intrinsic chromophores by two-photon photothermal microscopy captures mitochondrial response to chemotherapy
Nathaniel Hai, Chinmayee Vallabh Prabhu Dessai, Dingcheng Sun, Jianpeng Ao, Pin-Tian Lyu, Yifan Zhu, Ji-Xin Cheng
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Intracellular chromophores {e.g., NADH [reduced form of nicotinamide adenine dinucleotide (oxidized form)] and FAD (flavin adenine dinucleotide)} play a central role in regulation of cellular metabolism. Although autofluorescence has been extensively used for label-free mapping of chromophores inside a cell, its sensitivity and molecular specificity are constrained by the low quantum yield and the fluorescence spectral overlap. Here, we address these challenges by using a photothermal approach to measure the optical absorption of chromophores rather than its autofluorescence. Our two-photon photothermal (2PPT) microscope exploits localized thermal transients generated through two-photon absorption, enabling detection of chromophore-specific signatures beyond the reach of autofluorescence. We demonstrate submicromolar limits of detection for the metabolic coenzymes NADH and FAD of 0.87 and 0.99 ÎŒM, respectively. Such high sensitivity enables differentiating the influence of mitochondrial shapes on metabolism. 2PPT can identify the biomolecular source of contrast from cellular mitochondria in a label-free manner on the basis of spectroscopy. 2PPT microscopy is used to study metabolic alterations of mitochondria in cancer under chemotherapy at the single-organelle level.
GPT-4o mini: Non-social science research article
Barium senses subtle pore changes in a voltage-gated K + channel associated with voltage sensor states and regulatory subunits
Lei Huang, Nitzan Daus, Yuyin Wang, Guohui Zhang, Manar Khier, Ariel Ben-Bassat, Jingyi Shi, Lu Zhao, Borui Zhang, Lu Han, Yoni Haitin, Bernard Attali, Jianmin Cui
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In classic models of voltage-dependent channel activation, the pore only opens after the voltage sensor domains (VSDs) activate in an “all-or-none” fashion. Whether the VSD alters open pore properties remains unclear. Here, we examine the properties of the KCNQ1 channel pore in relation with the VSD and regulatory subunits that are located outside of the pore using barium ion (Ba 2+ ) block as a probe. We find that the external Ba 2+ block of KCNQ1 channels is voltage-dependent, and the voltage-dependent channel opening in Ba 2+ mainly derives from voltage-dependent Ba 2+ unblock. Open pore conformational changes indicated by the voltage dependence of Ba 2+ unblock vary with the states of the VSD, the alterations of VSD-pore coupling, and the association with regulatory KCNE subunits. Contrary to the classic view, our results suggest that, instead of being independent of the voltage gating machinery, the pore of KCNQ1 is flexible and influenced by the subtle changes in the voltage sensor state and the environment outside of the pore.
GPT-4o mini: Non-social science research article
Equal in death: Ancient genomic analysis of children’s early Christian burials
Maja KrzewiƄska, Anna Kjellström, Reyhan Yaka, Ricardo RodrĂ­guez-Varela, ZoĂ© Pochon, Vendela Kempe Lagerholm, Charlotte Hedenstierna-Jonson, Torun Zachrisson, Natalija Kashuba, VerĂłnica Sobrado, Thijessen Naidoo, Kıvılcım BaƟak Vural, Mattias Jakobsson, GĂŒlƟah Merve Kılınç, Jan StorĂ„, Anders Götherström
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Sexing the skeletal remains of young individuals is crucial yet notoriously difficult in archaeology. Children, who cannot be reliably sexed morphologically, are often excluded from gender-related research, limiting our understanding of past childhood. This issue is compounded in contexts lacking grave goods, such as early Christian burials. We conducted genomic screening of 142 individuals from Sweden dating from the late Viking Age to the Medieval period, including 68 subadults and 74 adults from 27 single and 50 multiple burials. To investigate the treatment of children in death and the role of collective graves, we applied genomic sexing and kinship analyses to individuals from three sites. Contrary to the assumption that collective burials reflect close kinship, our results show that children interred with adults rarely shared close biological ties. Burial patterns indicate that gender roles were established early, with both boys and most girls mirroring adult spatial patterns. However, flexibility existed, and extended kinship likely played a central role in structuring these communities.
GPT-4o mini: Non-social science research article
Multifunctional electrochemical memory stabilized by phase coexistence
Sangheon Oh, Adam L. Gross, Adam S. Christensen, Jacklyn Zhu, Patrick S. Finnegan, Joshua D. Sugar, Sean R. Bishop, Simeon J. Gilbert, R. Stanley Williams, Perla B. Balbuena, Kyung Seok Woo, Timothy D. Brown, Elliot J. Fuller, Suhas Kumar, A. Alec Talin
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Our growing computing needs, especially in applications that heavily rely on artificial intelligence (AI), motivate a search for new components that could substantially augment the performance of general-purpose digital computers. Beyond ON/OFF switching, new components with linear multistate analog resistive tuning, nonlinear volatile switching, spiking, oscillatory, stochastic and other complex functionalities could enable highly efficient neuromorphic computing schemes for AI information processing. Compared to the extreme multifunctionality of biological neurons, realizing all the above characteristics in a single, scalable analog component remains a grand challenge. Here we investigate electrochemical gating combined with localized thermal activation to program and switch a single, vertically integrated and dimensionally scaled electrothermal chemical random access memory (ETCRAM) with a channel and reservoir composed of phase-separated vanadium oxide. Closely related to electrochemical RAM (ECRAM), ETCRAM uses an integrated gate-heater electrode to overcome kinetic barriers that help retain states at ambient temperatures. In addition to synapse-like stable and programmable analog resistance states arising from redox-tunable phase coexistence, a single component exhibits neuron-like nonlinear conductance switching with a tunable threshold and self-driven dynamics owing to the thermally driven metal-insulator phase transition in vanadium dioxide. More broadly, we demonstrate that electrochemically stabilized phase coexistence could unlock analog electronics with novel functionality, stability, reconfigurability, and scalability.
GPT-4o mini: Non-social science research article
Biogeography of community canopy leaf traits and their links to global forest photosynthesis
Feng Jiang, Bernhard Schmid, Xucai Pu, Chengjun Ji, Zehao Shen, Zhiyao Tang, Xiangping Wang, Chengyang Zheng, Biao Zhu, Peter B. Reich, Jingyun Fang, Zhiheng Wang
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Leaf traits influence biotic interactions and ecosystem functions in forests. However, biogeographic drivers of leaf traits remain highly uncertain, limiting their integration into global vegetation models. Using a global dataset of forest plots, we show that community canopy leaf traits align along three dimensions: leaf economy, leaf density, and nitrogen-to-phosphorus (N:P) ratio. Changes in these trait dimensions across forest communities were driven by different variables: leaf economy was primarily shaped by the proportion of deciduous trees, leaf density by soil available P and temperature, and leaf N:P ratio by temperature. These three leaf trait dimensions together explained 60.2% of the variation in ecosystem-scale forest maximum photosynthesis, with the leaf N:P ratio showing the strongest association, followed by the dimensions of leaf economy and leaf density. Forests with moderate leaf N:P ratios and more acquisitive traits had higher photosynthesis than other forests. Our findings highlight the potential of community canopy leaf traits in predicting biogeographic variation in ecosystem-scale forest functioning.
GPT-4o mini: Non-social science research article
p38 MAP kinase senses short-chain fatty acids to attenuate Toll-like receptor signaling and intestinal inflammation
Qingang Wu, Rongkai Shi, Liwei Xiao, Xuxiao He, Zhuoneng Chen, Hong Zhao, Junwei Liu, Shudi Luo, Xiaoming Jiang, Dong Guo, Ying Meng, Rongxuan Zhu, Shan Li, Min Li, Guijun Liu, Suyao Li, Qingqing Yang, Zhe Shen, Zhimin Lu
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Toll-like receptor (TLR) signaling is critical for innate immune system. However, whether it is directly modulated by microbiota-derived metabolites remains unclear. Here, we show that the short-chain fatty acids (SCFAs) propionate and butyrate suppress TLR signaling by directly binding p38α MAP kinase, promoting its interaction with TAB1, thereby activating p38α via autophosphorylation. Activated p38α then phosphorylates TRAF3 at serine 85, inhibiting K63-linked polyubiquitylation of TRAF3 and disrupting TBK1-IRF3 activation, leading to reduced macrophage activation and intestinal inflammation. In ulcerative colitis patients, fecal levels of propionate and butyrate positively correlate with p38α activity and TRAF3 S85 phosphorylation, but inversely correlate with TBK1 activation, and cytokine levels. Notably, oral administration of propionate in three patients with ulcerative colitis markedly improved intestinal inflammation and clinical symptoms. These findings reveal p38α as a direct sensor for microbiota-derived SCFAs that suppress TLR signaling through nonmetabolic functions of propionate and butyrate, providing the first clinical evidence that propionate supplementation represents a practical dietary strategy for ulcerative colitis management.
GPT-4o mini: Non-social science research article
H2BE113K mutation promotes breast cancer metastasis through modulating chromatin dynamics
Shiman Hu (èƒĄèŻ—æ›Œ), Jiaxian Liu, Jiaqi Zhou, Jiaohua Chen, Tiantian Qin, Yi Ching Esther Wan, Xiaoxuan Zhu, Danyi Wang, Chuting Shao, Yabin Chen, Xin Wang, Junhong Han, Hoi Leong Xavier Wong, Robert S. Weiss, Haojie Jin, Mo Chen, Qing Li, Yogen Saunthararajah, Haiyun Gan, Kui Ming Chan (é™ˆć±…æ˜Ž)
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Cancer progression is driven by the accumulation of DNA mutations and aberrant gene regulation. Recent studies have demonstrated that multiple H3 mutations serve as drivers of tumorigenesis. However, the role and significance of various cancer-associated histone H2B mutations in cancer development remain unknown. Here, we investigate H2BE113K, a missense mutation of histone H2B predominantly found in patients with breast cancer. We show that H2BE113K promotes colony formation in breast cancer. Notably, transcriptomic analysis reveals differential expression of genes in various cancer pathways in H2BE113K cells. The loci with elevated gene expression display increased chromatin accessibility, accompanied by H2BE113K enrichment. Depletion of G3BP2 , one of the H2BE113K target genes that has been implicated in breast cancer, reduces the colony formation phenotype in H2BE113K cells. In addition, H2BE113K knock-in mice crossbred with an MMTV-PyMT breast cancer model show elevated lung metastasis. Together, our findings provide critical insights in the mechanistic role of H2BE113K in gene regulation, chromatin function, and breast cancer progression.
GPT-4o mini: Non-social science research article
Origin of sulfur allotropes on the carbonaceous asteroid Ryugu and implications to the sulfur chemistry in the interstellar medium
Mason McAnally, Chaojiang Zhang, Jia Wang, Ashanie Herath, Andrew M. Turner, Ralf I. Kaiser
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The unexpected detection of the sulfur allotropes (S 8 , S 7 , and S 6 ) on the carbonaceous asteroid Ryugu following the Hayabusa2 mission has offered insights into the unconventional sulfur chemistry in space. These molecules can be traced to processes occurring in the early stages of the evolution of cold molecular clouds, where interstellar icy mantles facilitate the formation of complex sulfur-bearing species by energetic processing. Exploiting interstellar ice analogs, the present study affords compelling evidence on the production of sulfur allotropes (S 8 , S 7 , and S 6 ) in sulfur-doped interstellar analog ices composed of sulfur dioxide (SO 2 ), hydrogen sulfide (H 2 S), and water (H 2 O) using soft photoionization reflectron time-of-flight mass spectrometry. The synthesis of these allotropes offers fundamental insights into their possible origin on Ryugu while also presenting a plausible mechanism for the sulfur depletion in cold molecular clouds. Notably, the oxidation of sulfur (-II) in hydrogen sulfide (H 2 S) represents the driving force in sulfur allotrope formation.
GPT-4o mini: Non-social science research article
High thermal conductivity in noncrystalline enriched polyethylene fibers
Yongzheng Zhang, Die Wu, Yanlin Zhu, Jinghan Wu, Ke Wang, Kai Wu, Qiang Fu
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Polyethylene represents an exceptional thermal conductor in theory: The perfectly extended chain is predicted to conduct heat extremely well. However, its practical scalable forms fall far below this limit because noncrystalline structures disrupt heat transport across multiple length scales. Here, we identify that a partially ordered, noncrystalline transitional phase in highly aligned polyethylene is not a negative by-product of processing but a key contributor to heat conduction. Guided by this insight, we develop a gel-state intermittent slow stretching method that directs noncrystalline evolution during polyethylene fiber formation. This approach enables chain relaxation and structural reorganization in regions typically regarded as amorphous and interfacial, promoting their conversion into the transitional phase and their seamless integration with crystalline domains. The resulting structure extends the continuity of ordered shish segments within the period structure, increasing the distance over which heat can travel quasi-ballistically. As a result, polyethylene fibers with 26.79% noncrystalline content achieve thermal conductivities up to 70.61 watts per meter per kelvin, representing 1.45 to 2.60 times of leading commercial polyethylene fibers. These findings establish control of noncrystalline structure as an essential route to unlocking high thermal conductivity in polymers and open a pathway toward lightweight, fully organic thermal conductors.
GPT-4o mini: Non-social science research article
Nutritional adaptations to early maize cultivation: Earliest isotopic evidence of maize-based animal provisioning in the Neotropics
Nadia C. Neff, Geraldine Busquets-Vass, Erin E. Ray, Mark Robinson, Amy E. Thompson, Jose Mes, Douglas J. Kennett, Seth D. Newsome, Keith M. Prufer
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The adoption of maize as a dietary staple shaped human societies. While a reliable carbohydrate-rich source, its inherent nutritional limitations posed substantial challenges. Maize is deficient in lysine, an essential amino acid crucial for maintaining balanced health. Maize-dependent diets, therefore, necessitated complementary dietary strategies. We report amino acid stable carbon isotope data from 39 directly dated humans from southern Belize [6100 to 1100 before present (B.P.)] to investigate how early populations mitigated nutritional deficiencies. Concentration-dependent mixing model results indicate that protein supplementation from maize-eating animals contributed maize-derived lysine to human diets through trophic magnification (elevated proportions of isotopically distinct nutrients in tissues from trophic transfer). Our results indicate that such strategies were in place by 6100 B.P., consistent with evidence of early maize cultivation but predating reliance by ~2000 years. Our findings highlight early coevolutionary dynamics linking maize cultivation and human-animal provisioning relationships, deepening understandings of adaptive food systems during agricultural transitions and offering insights into nutritional strategies underpinning sustainable subsistence.
GPT-4o mini: Non-social science research article
Interfacial solvothermal synthesis of superhydrophilic ionic salt-derived chiral helical COFs with strong chiroptical activity
Xinlin Zha, Zhenzhen Jiang, Mengjuan Zuo, Mengying Luo, Yue Xin, Qian Zou, Niaz Ali Khan, Yingying Li, Haining You, Yi Xiong, Ying Liu, Liu Liu, Mufang Li, Dong Wang
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Traditional chiral induction strategies for nonionic covalent organic frameworks (COFs) often produce disordered aggregates with low dissymmetry factors and weak chiroptical activity due to uncontrolled crystallization kinetics. Here, we report an interfacial solvothermal strategy that spatially separates superhydrophilic ionic amines in an aqueous phase from aldehyde monomers in an organic phase, enabling precise kinetic regulation and efficient molecular-to-mesoscale chiral amplification. This method yields highly ordered helical ionic COFs, including anionic, cationic, and zwitterionic frameworks, with outstanding chiroptical properties, featuring ellipticities exceeding 3600 millidegrees (mdeg) and | g abs | values up to 0.07. By tuning the acid concentration and chiral inducer stoichiometry, the dimensions of superhelical anionic COFs can be controlled from the nanoscale to the micrometer scale. Furthermore, oppositely charged aggregation-induced emission luminogens are incorporated into the COF channels through electrostatic interactions, generating blue, yellow, and green circularly polarized luminescence. This work establishes a versatile platform for constructing chiral COFs with amplified chiroptical responses for chiral optoelectronics, sensing, and asymmetric catalysis.
GPT-4o mini: Non-social science research article
Unconventional vesicle transport driven by formin-actin-myosin working system during pollen germination
Tonghui Li, Chang Liu, Tongtong Shen, Bo Li, Qi Wang, Zhe Zhu, Xuna Wu, Ting Wang, Huimin Wang, Haiyun Ren
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Directional transport of massive secretory vesicles to the germination site is a key process for pollen germination, but the molecular mechanism remains unclear. Here, we find that Myo11C proteins, Myo11C1 and Myo11C2, act redundantly. This functional redundancy is evidenced by impaired vesicle tethering efficiency and aberrant F-actin organization in myo11c1 myo11c2 double mutant. Myo11C1 unexpectedly colocalized with AtFH5-located secretory vesicles (AtFH5-SVs), rather than with actin filaments. Simulated modeling and truncation mutation analyses show that Myo11C binds actin filaments nucleated from AtFH5-SVs and exhibits plus-end–directed motility, leading to its polarized localization at F-actin plus-ends. Upon dissociating from F-actin, Myo11C directly interacts with AtFH5-SVs to promote their aggregation. E447 is identified as a critical residue for Myo11C1 binding to F-actin, while R1377 and R1452 are conserved residues essential for Myo11C1’s interaction with secretory vesicle–located SEC5B. Together, our work uncovers the molecular basis by which formin-actin-myosin working system generates force driving massive secretory vesicles for directional transport during pollen germination.
Communicating coral: Art and science for global reef action
MĂłnica Medina, Or Ben-Zvi, Oren Levy, character(0)
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Coral reefs are experiencing unprecedented rapid decline. Art can act as a beacon to engage audiences, influence policy, and inspire global action.