We checked 7 multidisciplinary journals on Friday, August 29, 2025 using the Crossref API. For the period August 22 to August 28, we retrieved 17 new paper(s) in 6 journal(s).

Nature

GPT-4o mini: Non-social science research article
The evolution of hominin bipedalism in two steps
Gayani Senevirathne, Serena C. Fernandopulle, Daniel Richard, Stephanie L. Baumgart, Anika Liv Christensen, Matteo Fabbri, Jakob Höppner, Harald JĂŒppner, Peishu Li, Vivien Bothe, Nadia Fröbisch, Ian Simcock, Owen J. Arthurs, Alistair Calder, Naomi Freilich, Niamh C. Nowlan, Ian A. Glass, April Craft, Terence D. Capellini
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GPT-4o mini: Non-social science research article
Crystal structures of agonist-bound human cannabinoid receptor CB1
Tian Hua, Kiran Vemuri, Spyros P. Nikas, Yiran Wu, Lu Qu, Mengchen Pu, Anisha Korde, Shan Jiang, Jo-Hao Ho, Gye Won Han, Kang Ding, Xuanxuan Li, Haiguang Liu, Michael A. Hanson, Suwen Zhao, Laura M. Bohn, Alexandros Makriyannis, Raymond C. Stevens, Zhi-Jie Liu
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GPT-4o mini: Non-social science research article
Cocaine chemogenetics blunts drug-seeking by synthetic physiology
Juan L. Gomez, Christopher J. Magnus, Jordi Bonaventura, Oscar Solis, Fallon P. Curry, Marjorie R. Levinstein, Reece C. Budinich, Meghan L. Carlton, Emilya N. Ventriglia, Sherry Lam, Le Wang, Ingrid Schoenborn, William Dunne, Michael Michaelides, Scott M. Sternson
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Chemical feedback is ubiquitous in physiology but is challenging to study without perturbing basal functions. One example is addictive drugs, which elicit a positive-feedback cycle of drug-seeking and ingestion by acting on the brain to increase dopamine signalling 1–3 . However, interfering with this process by altering basal dopamine also adversely affects learning, movement, attention and wakefulness 4 . Here, inspired by physiological control systems, we developed a highly selective synthetic physiology approach to interfere with the positive-feedback cycle of addiction by installing a cocaine-dependent opposing signalling process into this body–brain signalling loop. We used protein engineering to create cocaine-gated ion channels that are selective for cocaine over other drugs and endogenous molecules. Expression of an excitatory cocaine-gated channel in the rat lateral habenula, a brain region that is normally inhibited by cocaine, suppressed cocaine self-administration without affecting food motivation. This artificial cocaine-activated chemogenetic process reduced the cocaine-induced extracellular dopamine rise in the nucleus accumbens. Our results show that cocaine chemogenetics is a selective approach for countering drug reinforcement by clamping dopamine release in the presence of cocaine. In the future, chemogenetic receptors could be developed for additional addictive drugs or hormones and metabolites, which would facilitate efforts to probe their neural circuit mechanisms using a synthetic physiology approach. As these chemogenetic ion channels are specific for cocaine over natural rewards, they may also offer a route towards gene therapies for cocaine addiction.
GPT-4o mini: Non-social science research article
Optical generative models
Shiqi Chen, Yuhang Li, Yuntian Wang, Hanlong Chen, Aydogan Ozcan
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Generative models cover various application areas, including image and video synthesis, natural language processing and molecular design, among many others 1–11 . As digital generative models become larger, scalable inference in a fast and energy-efficient manner becomes a challenge 12–14 . Here we present optical generative models inspired by diffusion models 4 , where a shallow and fast digital encoder first maps random noise into phase patterns that serve as optical generative seeds for a desired data distribution; a jointly trained free-space-based reconfigurable decoder all-optically processes these generative seeds to create images never seen before following the target data distribution. Except for the illumination power and the random seed generation through a shallow encoder, these optical generative models do not consume computing power during the synthesis of the images. We report the optical generation of monochrome and multicolour images of handwritten digits, fashion products, butterflies, human faces and artworks, following the data distributions of MNIST 15 , Fashion-MNIST 16 , Butterflies-100 17 , Celeb-A datasets 18 , and Van Gogh’s paintings and drawings 19 , respectively, achieving an overall performance comparable to digital neural-network-based generative models. To experimentally demonstrate optical generative models, we used visible light to generate images of handwritten digits and fashion products. In addition, we generated Van Gogh-style artworks using both monochrome and multiwavelength illumination. These optical generative models might pave the way for energy-efficient and scalable inference tasks, further exploiting the potentials of optics and photonics for artificial-intelligence-generated content.
GPT-4o mini: Non-social science research article
Topological prethermal strong zero modes on superconducting processors
Feitong Jin, Si Jiang, Xuhao Zhu, Zehang Bao, Fanhao Shen, Ke Wang, Zitian Zhu, Shibo Xu, Zixuan Song, Jiachen Chen, Ziqi Tan, Yaozu Wu, Chuanyu Zhang, Yu Gao, Ning Wang, Yiren Zou, Aosai Zhang, Tingting Li, Jiarun Zhong, Zhengyi Cui, Yihang Han, Yiyang He, Han Wang, Jia-Nan Yang, Yanzhe Wang, Jiayuan Shen, Gongyu Liu, Jinfeng Deng, Hang Dong, Pengfei Zhang, Weikang Li, Dong Yuan, Zhide Lu, Zheng-Zhi Sun, Hekang Li, Junxiang Zhang, Chao Song, Zhen Wang, Qiujiang Guo, Francisco Machado, Jack Kemp, Thomas Iadecola, Norman Y. Yao, H. Wang, Dong-Ling Deng
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Symmetry-protected topological phases 1–4 cannot be described by any local order parameter and are beyond the conventional symmetry-breaking model 5 . They are characterized by topological boundary modes that remain stable under symmetry respecting perturbations 1–4,6–8 . In clean, gapped systems without disorder, the stability of these edge modes is restricted to the zero-temperature manifold; at finite temperatures, interactions with mobile thermal excitations lead to their decay 9–11 . Here we report the observation of a distinct type of topological edge mode 12–14 , which is protected by emergent symmetries and persists across the entire spectrum, in an array of 100 programmable superconducting qubits. Through digital quantum simulation of a one-dimensional disorder-free stabilizer Hamiltonian, we observe robust long-lived topological edge modes over up to 30 cycles for a wide range of initial states. We show that the interaction between these edge modes and bulk excitations can be suppressed by dimerizing the stabilizer strength, leading to an emergent U(1) × U(1) symmetry in the prethermal regime of the system. Furthermore, we exploit these topological edge modes as logical qubits and prepare a logical Bell state, which exhibits persistent coherence, despite the system being disorder-free and at finite temperature. Our results establish a viable digital simulation approach 15–18 to experimentally study topological matter at finite temperature and demonstrate a potential route to construct long-lived, robust boundary qubits in disorder-free systems.
GPT-4o mini: Non-social science research article
Dual-scale chemical ordering for cryogenic properties in CoNiV-based alloys
Tiwen Lu, Binhan Sun, Yue Li, Sheng Dai, Ning Yao, Wenbo Li, Xizhen Dong, Xiyu Chen, Jiacheng Niu, Fan Ye, Alisson Kwiatkowski da Silva, Shuya Zhu, Yu Xie, Xiaofeng Yang, Sihao Deng, Jianping Tan, Zhiming Li, Dirk Ponge, Lunhua He, Xian-Cheng Zhang, Dierk Raabe, Shan-Tung Tu
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The mechanical properties of metallic materials often degrade under harsh cryogenic conditions, posing challenges for low-temperature infrastructures 1 . Here we introduce a dual-scale atomic-ordering nanostructure, characterized by an exceptionally high number density of co-existing subnanoscale short-range ordering (approximately 2.4 × 10 26 m −3 ) and nanoscale long-range ordering (approximately 4.5 × 10 25 m −3 ) domains, within a metallic solid-solution matrix in a CoNiV-based alloy to improve the synergy of strength and ductility at low temperatures. We observe an ordering-induced increase in dislocation shear stress as well as a more rapid dislocation multiplication owing to the dislocation blocking effect of nanoscale long-range ordering and the associated generation of new dislocations. The latter effect also releases stress concentrations at nanoscale long-range-ordered obstacles that otherwise would promote damage initiation and failure. Consequently, the alloy shows a strength–elongation product of 76 GPa % with a yield strength of approximately 1.2 GPa at 87 K, outperforming materials devoid of such ordering hierarchy, containing only short-range ordered or coherent precipitates of a few tens of nanometres. Our results highlight the impact of dual co-existing chemical ordering on the mechanical properties of complex alloys and offer guidelines to control these ordering states to enhance their mechanical performance for cryogenic applications.
GPT-4o mini: Non-social science research article
Thioester-mediated RNA aminoacylation and peptidyl-RNA synthesis in water
Jyoti Singh, Benjamin Thoma, Daniel Whitaker, Max Satterly Webley, Yuan Yao, Matthew W. Powner
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To orchestrate ribosomal peptide synthesis, transfer RNAs (tRNAs) must be aminoacylated, with activated amino acids, at their 2â€Č,3â€Č-diol moiety 1,2 , and so the selective aminoacylation of RNA in water is a key challenge that must be resolved to explain the origin of protein biosynthesis. So far, there have been no chemical methods to effectively and selectively aminoacylate RNA-2â€Č,3â€Č-diols with the breadth of proteinogenic amino acids in water 3–5 . Here we demonstrate that (biological) aminoacyl-thiols ( 1 ) react selectively with RNA diols over amine nucleophiles, promoting aminoacylation over adventitious (non-coded) peptide bond formation. Broad side-chain scope is demonstrated, including Ala, Arg, Asp, Glu, Gln, Gly, His, Leu, Lys, Met, Phe, Pro, Ser and Val, and Arg aminoacylation is enhanced by unprecedented side-chain nucleophilic catalysis. Duplex formation directs chemoselective 2â€Č,3â€Č-aminoacylation of RNA. We demonstrate that prebiotic nitriles, N -carboxyanhydrides and amino acid anhydrides, as well as biological aminoacyl-adenylates, all react with thiols (including coenzymes A and M) to selectively yield aminoacyl-thiols ( 1 ) in water. Finally, we demonstrate that the switch from thioester to thioacid activation inverts diol/amine selectivity, promoting peptide synthesis in excellent yield. Two-step, one-pot, chemically controlled formation of peptidyl-RNA is observed in water at neutral pH. Our results indicate an important role for thiol cofactors in RNA aminoacylation before the evolution of proteinaceous synthetase enzymes.
GPT-4o mini: Non-social science research article
Neural networks of the mouse visceromotor cortex
Houri Hintiryan, Muye Zhu, Pingping Zhao, Mingmin Zhang, Joshua Barry, Sumit Nanda, Mitchell Rudd, Angela Wong, Samara Miller, Lin Gou, Jinxing Wei, Brian Zingg, Jiandong Sun, Adriana Gutierrez, Hyun-Seung Mun, Yeji E. Han, Ian Bowman, Luis Garcia, Darrick Lo, Tyler Boesen, Chunru Cao, Qiuying Zhao, Nicholas N. Foster, Keivan Moradi, Seita Yamashita, Christian Estrada, Aishwarya Dev, Jennifer Gonzalez, Hanpeng Xu, Gavin Yang, Chang Sin Park, X. William Yang, Michael S. Levine, Li I. Zhang, Paul Micevych, Carlos Cepeda, Peyman Golshani, Weizhe Hong, Hong-Wei Dong
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GPT-4o mini: Non-social science research article
Extreme armour in the world’s oldest ankylosaur
Susannah C. R. Maidment, Driss Ouarhache, Kawtar Ech-charay, Ahmed Oussou, Khadija Boumir, Abdessalam El Khanchoufi, Alison Park, Luke E. Meade, D. Cary Woodruff, Simon Wills, Mike Smith, Paul M. Barrett, Richard J. Butler
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GPT-4o mini: Non-social science research article
Microbial iron oxide respiration coupled to sulfide oxidation
Song-Can Chen, Xiao-Min Li, Nicola Battisti, Guoqing Guan, Maria A. Montoya, Jay Osvatic, Petra Pjevac, Shaul Pollak, Andreas Richter, Arno Schintlmeister, Wolfgang Wanek, Marc Mussmann, Alexander Loy
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Microorganisms have driven Earth’s sulfur cycle since the emergence of life 1–6 , yet the sulfur-cycling capacities of microorganisms and their integration with other element cycles remain incompletely understood. One such uncharacterized metabolism is the coupling of sulfide oxidation with iron( iii ) oxide reduction, a ubiquitous environmental process hitherto considered to be strictly abiotic 7,8 . Here we present a comprehensive genomic analysis of sulfur metabolism across prokaryotes, and reveal bacteria that are capable of oxidizing sulfide using extracellular solid phase iron( iii ). Based on a phylogenetic framework of over hundred genes involved in dissimilatory transformation of sulfur compounds, we recorded sulfur-cycling capacity in most bacterial and archaeal phyla. Metabolic reconstructions predicted co-occurrence of sulfur compound oxidation and iron( iii ) oxide respiration in diverse members of 37 prokaryotic phyla. Physiological and transcriptomic evidence demonstrated that a cultivated representative, Desulfurivibrio alkaliphilus , grows autotrophically by oxidizing dissolved sulfide or iron monosulfide (FeS) to sulfate with ferrihydrite as an extracellular iron( iii ) electron acceptor. The biological process outpaced the abiotic process at environmentally relevant sulfide concentrations. These findings expand the known diversity of sulfur-cycling microorganisms and unveil a biological mechanism that links sulfur and iron cycling in anoxic environments, thus highlighting the fundamental role of microorganisms in global element cycles.
GPT-4o mini: Non-social science research article
Author Correction: Disease-associated astrocyte epigenetic memory promotes CNS pathology
Hong-Gyun Lee, Joseph M. Rone, Zhaorong Li, Camilo Faust Akl, Seung Won Shin, Joon-Hyuk Lee, Lucas E. Flausino, Florian Pernin, Chun-Cheih Chao, Kilian L. Kleemann, Lena Srun, Tomer Illouz, Federico Giovannoni, Marc Charabati, Liliana M. Sanmarco, Jessica E. Kenison, Gavin Piester, Stephanie E. J. Zandee, Jack P. Antel, Veit Rothhammer, Michael A. Wheeler, Alexandre Prat, Iain C. Clark, Francisco J. Quintana
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GPT-4o mini: Non-social science research article
Scalable total synthesis of saxitoxin and related natural products
Yinliang Guo, Yiheng Li, Sihan Chen, Yige Wu, Oscar Poll, Zhouyang Ren, Zhonglin Liu, Roman Vlkolinsky, Michal Bajo, Christopher K. Prier, Kai-Jiong Xiao, Benjamin F. Cravatt, Marisa Roberto, Phil S. Baran
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GPT-4o mini: Non-social science research article
Global phenology maps reveal the drivers and effects of seasonal asynchrony
Drew E. Terasaki Hart, TháșŁo-NguyĂȘn BĂči, Lauren Di Maggio, Ian J. Wang
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Terrestrial plant communities show great variation in their annual rhythms of growth, or seasonal phenology 1,2 . The geographical patterns resulting from this variation, known as land surface phenology (LSP) 3 , contain valuable information for the study of ecosystem function 4,5 , plant ecophysiology 6–8 , landscape ecology 9,10 and evolutionary biogeography 11–13 . Yet globally consistent LSP mapping has been hampered by methods that struggle to represent the full range of seasonal phenologies occurring across terrestrial biomes 14 , especially the subtle and complex phenologies of many arid and tropical ecosystems 1,15,16 . Here, using a data-driven analysis of satellite imagery to map LSP worldwide, we provide insights into Earth’s phenological diversity, documenting both intercontinental convergence between similar climates and regional heterogeneity associated with topoclimate, ecohydrology and vegetation structure. We then map spatial phenological asynchrony and the modes of asynchronous seasonality that control it, identifying hotspots of asynchrony in tropical mountains and Mediterranean climate regions and reporting evidence for the hypothesis that climatically similar sites exhibit greater phenological asynchrony within the tropics. Finally, we find that our global LSP map predicts complex geographical discontinuities in flowering phenology, genetic divergence and even harvest seasonality across a range of taxa, establishing remote sensing as a crucial tool for understanding the ecological and evolutionary consequences of allochrony by allopatry.
GPT-4o mini: Non-social science research article
Maternal stress triggers early-life eczema through fetal mast cell programming
Nadine Serhan, Nasser S. Abdullah, Nadine Gheziel, Alexia Loste, RĂŒĂ§han Ekren, Elodie Labit, Anne-Alicia Gonzalez, Giulia Oliva, Pauline Tarot, Camille Petitfils, GaĂ«lle Payros, Paolo D’Avino, Allison Voisin, Holly Freya Grace Tinsley, Rebecca Gentek, Carole Brosseau, Marie Bodinier, Laurent Reber, Pierre Val, Cezmi A. Akdis, Yasutaka Mitamura, Anand Kumar Andiappan, Jerry Kok Yen Chan, Florent Ginhoux, Amaury François, Nicolas CĂ©nac, Lilian Basso, Nicolas Gaudenzio
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GPT-4o mini: Non-social science research article
Attosecond control and measurement of chiral photoionization dynamics
Meng Han, Jia-Bao Ji, Alexander Blech, R. Esteban Goetz, Corbin Allison, Loren Greenman, Christiane P. Koch, Hans Jakob Wörner
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Many chirality-sensitive light–matter interactions are governed by chiral electron dynamics. Therefore, the development of advanced technologies making use of chiral phenomena would critically benefit from measuring and controlling chiral electron dynamics on their natural attosecond timescales. Such endeavours have so far been hampered by the lack of characterized circularly polarized attosecond pulses, an obstacle that has recently been overcome 1,2 . Here we introduce chiroptical spectroscopy with attosecond pulses and demonstrate attosecond coherent control over photoelectron circular dichroism (PECD) 3,4 , as well as the measurement of chiral asymmetries in the forward–backward and angle-resolved photoionization delays of chiral molecules. We show that co-rotating attosecond and near-infrared (IR) pulses can nearly double the PECD and even change its sign compared with single-photon ionization. We demonstrate that chiral photoionization delays depend on both polar and azimuthal angles of photoemission in the light-propagation frame, requiring 3D momentum resolution. We measure forward–backward chiral-sensitive delays of up to 60 as and polar-angle-resolved photoionization delays of up to 240 as, which include an asymmetry of about 60 as originating from chirality in the continuum–continuum transitions. Attosecond chiroptical spectroscopy opens the door to quantitatively understanding and controlling the dynamics of chiral molecules on the electronic timescale.
GPT-4o mini: Non-social science research article
A compressed hierarchy for visual form processing in the tree shrew
Frank F. Lanfranchi, Joseph Wekselblatt, Daniel A. Wagenaar, Doris Y. Tsao
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Our knowledge of the brain processes that govern vision is largely derived from studying primates, whose hierarchically organized visual system 1 inspired the architecture of deep neural networks 2 . This raises questions about the universality of such hierarchical structures. Here we examined the large-scale functional organization for vision in one of the closest living relatives to primates, the tree shrew. We performed Neuropixels recordings 3,4 across many cortical and thalamic areas spanning the tree shrew ventral visual system while presenting a large battery of visual stimuli in awake tree shrews. We found that receptive field size, response latency and selectivity for naturalistic textures, compared with spectrally matched noise 5 , all increased moving anteriorly along the tree shrew visual pathway, consistent with a primate-like hierarchical organization 6,7 . However, tree shrew area V2 already harboured a high-level representation of complex objects. First, V2 encoded a complete representation of a high-level object space 8 . Second, V2 activity supported the most accurate object decoding and reconstruction among all tree shrew visual areas. In fact, object decoding accuracy from tree shrew V2 was comparable to that in macaque posterior IT and substantially higher than that in macaque V2. Finally, starting in V2, we found strongly face-selective cells resembling those reported in macaque inferotemporal cortex 9 . Overall, these findings show how core computational principles of visual form processing found in primates are conserved, yet hierarchically compressed, in a small but highly visual mammal.
GPT-4o mini: Non-social science research article
Mechanical confinement governs phenotypic plasticity in melanoma
Miranda V. Hunter, Eshita Joshi, Sydney Bowker, Emily Montal, Yilun Ma, Young Hun Kim, Zhifan Yang, Laura Tuffery, Zhuoning Li, Eric Rosiek, Alexander Browning, Reuben Moncada, Itai Yanai, Helen Byrne, Mara Monetti, Elisa de Stanchina, Pierre-Jacques Hamard, Richard P. Koche, Richard M. White
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Phenotype switching is a form of cellular plasticity in which cancer cells reversibly move between two opposite extremes: proliferative versus invasive states 1,2 . Although it has long been hypothesized that such switching is triggered by external cues, the identity of these cues remains unclear. Here we demonstrate that mechanical confinement mediates phenotype switching through chromatin remodelling. Using a zebrafish model of melanoma coupled with human samples, we profiled tumour cells at the interface between the tumour and surrounding microenvironment. Morphological analysis of interface cells showed elliptical nuclei, suggestive of mechanical confinement by the adjacent tissue. Spatial and single-cell transcriptomics demonstrated that interface cells adopted a gene program of neuronal invasion, including the acquisition of an acetylated tubulin cage that protects the nucleus during migration. We identified the DNA-bending protein HMGB2 as a confinement-induced mediator of the neuronal state. HMGB2 is upregulated in confined cells, and quantitative modelling revealed that confinement prolongs the contact time between HMGB2 and chromatin, leading to changes in chromatin configuration that favour the neuronal phenotype. Genetic disruption of HMGB2 showed that it regulates the trade-off between proliferative and invasive states, in which confined HMGB2 high tumour cells are less proliferative but more drug-resistant. Our results implicate the mechanical microenvironment as a mechanism that drives phenotype switching in melanoma.
GPT-4o mini: Non-social science research article
Retraction Note: Crystal structures of agonist-bound human cannabinoid receptor CB1
Tian Hua, Kiran Vemuri, Spyros P. Nikas, Robert B. Laprairie, Yiran Wu, Lu Qu, Mengchen Pu, Anisha Korde, Shan Jiang, Jo-Hao Ho, Gye Won Han, Kang Ding, Xuanxuan Li, Haiguang Liu, Michael A. Hanson, Suwen Zhao, Laura M. Bohn, Alexandros Makriyannis, Raymond C. Stevens, Zhi-Jie Liu
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GPT-4o mini: Non-social science research article
Two-billion-year transitional oxygenation of the Earth’s surface
Haiyang Wang, Chao Li, Yongbo Peng, Junpeng Zhang, Meng Cheng, Xiaobin Cao, Wenkun Qie, Zihu Zhang, Matthew S. Dodd, Mingcai Hou, Malcolm Wallace, Ashleigh v. S. Hood, Timothy W. Lyons, Huiming Bao
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GPT-4o mini: Non-social science research article
Publisher Correction: Multiple oestradiol functions inhibit ferroptosis and acute kidney injury
Wulf Tonnus, Francesca Maremonti, Shubhangi Gavali, Marlena Nastassja Schlecht, Florian Gembardt, Alexia Belavgeni, Nadja Leinung, Karolin Flade, Natalie Bethe, Sofia Traikov, Anne Haag, Danny Schilling, Sider Penkov, Melodie Mallais, Christine Gaillet, Claudia Meyer, Melika Katebi, Anushka Ray, Louisa M. S. Gerhardt, Anne Brucker, Jorunn Naila Becker, Mirela Tmava, Lisa Schlicker, Almut Schulze, Nina Himmerkus, Andrej Shevchenko, Mirko Peitzsch, Uladzimir Barayeu, Sonia Nasi, Juliane Putz, Kenneth S. Korach, Joel Neugarten, Ladan Golestaneh, Christian Hugo, Jan Ulrich Becker, Joel M. Weinberg, Svenja Lorenz, Bettina Proneth, Marcus Conrad, Eckhard Wolf, Bernd Plietker, Raphaël Rodriguez, Derek A. Pratt, Tobias P. Dick, Maria Fedorova, Stefan R. Bornstein, Andreas Linkermann
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GPT-4o mini: Non-social science research article
Ultrabroadband on-chip photonics for full-spectrum wireless communications
Zihan Tao, Haoyu Wang, Hanke Feng, Yijun Guo, Bitao Shen, Dan Sun, Yuansheng Tao, Changhao Han, Yandong He, John E. Bowers, Haowen Shu, Cheng Wang, Xingjun Wang
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The forthcoming sixth-generation and beyond wireless networks are poised to operate across an expansive frequency range—from microwave, millimetre wave to terahertz bands—to support ubiquitous connectivity in diverse application scenarios 1–3 . This necessitates a one-size-fits-all hardware solution that can be adaptively reconfigured within this wide spectrum to support full-band coverage and dynamic spectrum management 4 . However, existing electrical or photonic-assisted solutions face a lot of challenges in meeting this demand because of the limited bandwidths of the devices and the intrinsically rigid nature of system architectures 5 . Here we demonstrate adaptive wireless communications over an unprecedented frequency range spanning over 100 GHz, driven by a thin-film lithium niobate (TFLN) photonic wireless system. Leveraging the Pockels effect and scalability of the TFLN platform, we achieve monolithic integration of essential functional elements, including baseband modulation, broadband wireless–photonic conversion and reconfigurable carrier and local signal generation. Powered by broadband tunable optoelectronic oscillators, our signal sources operate across a record-wide frequency range from 0.5 GHz to 115 GHz with high-frequency stability and consistent coherence. Based on the broadband and reconfigurable integrated photonic solution, we realize full-link wireless communication across nine consecutive bands, achieving record lane speeds of up to 100 Gbps. The real-time reconfigurability further enables adaptive frequency allocation, a crucial ability to ensure enhanced reliability in complex spectrum environments. Our proposed system represents a marked step towards future full-spectrum and omni-scenario wireless networks.
GPT-4o mini: Non-social science research article
Author Correction: Endophilin marks and controls a clathrin-independent endocytic pathway
Emmanuel Boucrot, Antonio P. A. Ferreira, Leonardo Almeida-Souza, Sylvain Debard, Yvonne Vallis, Gillian Howard, Laetitia Bertot, Nathalie Sauvonnet, Harvey T. McMahon
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GPT-4o mini: Non-social science research article
Electrically driven lasing from a dual-cavity perovskite device
Chen Zou, Zhixiang Ren, Kangshuo Hui, Zixiang Wang, Yangning Fan, Yichen Yang, Bo Yuan, Baodan Zhao, Dawei Di
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Solution-processed semiconductor lasers promise lightweight, wearable and scalable optoelectronic applications. Among the gain media for solution-processed lasers, metal halide perovskites stand out as an exceptional class because of their ability to achieve wavelength-adjustable, low-threshold lasing under optical pumping 1–8 . Despite the progress in this field, electrically driven lasing from perovskite semiconductors remains a critical challenge. Here we demonstrate an electrically driven perovskite laser, constructed by vertically integrating a low-threshold single-crystal perovskite microcavity sub-unit with a high-power microcavity perovskite LED (PeLED) sub-unit. Under pulsed electrical excitation, the dual-cavity perovskite device shows a minimum lasing threshold of 92 A cm −2 (average threshold: 129 A cm −2 , at about 22 °C, in air), which is an order of magnitude lower than that of state-of-the-art electrically driven organic lasers 9,10 . Key to this demonstration is the integrated dual-cavity device architecture, which allows the microcavity PeLED sub-unit to deliver directional emission into the single-crystal perovskite microcavity sub-unit (at a coupling efficiency of about 82.7%) to establish the lasing action. An operational half-life ( T 50 ) of 1.8 h (6.4 × 10 4 voltage pulses at 10 Hz) is achieved, outperforming the stability of electrically pumped organic lasers 9,10 . The dual-cavity perovskite laser can be rapidly modulated at a bandwidth of 36.2 MHz, indicating its potential for data transmission and computational applications.
GPT-4o mini: Non-social science research article
Haematopoietic stem cell number is not solely defined by niche availability
Shoichiro Takeishi, Tony Marchand, Wade R. Koba, Daniel K. Borger, Chunliang Xu, Chandan Guha, Aviv Bergman, Paul S. Frenette, Kira Gritsman, Ulrich Steidl
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GPT-4o mini: Non-social science research article
Author Correction: Complex genetic variation in nearly complete human genomes
Glennis A. Logsdon, Peter Ebert, Peter A. Audano, Mark Loftus, David Porubsky, Jana Ebler, Feyza Yilmaz, Pille Hallast, Timofey Prodanov, DongAhn Yoo, Carolyn A. Paisie, William T. Harvey, Xuefang Zhao, Gianni V. Martino, Mir Henglin, Katherine M. Munson, Keon Rabbani, Chen-Shan Chin, Bida Gu, Hufsah Ashraf, Stephan Scholz, Olanrewaju Austine-Orimoloye, Parithi Balachandran, Marc Jan Bonder, Haoyu Cheng, Zechen Chong, Jonathan Crabtree, Mark Gerstein, Lisbeth A. Guethlein, Patrick Hasenfeld, Glenn Hickey, Kendra Hoekzema, Sarah E. Hunt, Matthew Jensen, Yunzhe Jiang, Sergey Koren, Youngjun Kwon, Chong Li, Heng Li, Jiaqi Li, Paul J. Norman, Keisuke K. Oshima, Benedict Paten, Adam M. Phillippy, Nicholas R. Pollock, Tobias Rausch, Mikko Rautiainen, Yuwei Song, Arda Söylev, Arvis Sulovari, Likhitha Surapaneni, Vasiliki Tsapalou, Weichen Zhou, Ying Zhou, Qihui Zhu, Michael C. Zody, Ryan E. Mills, Scott E. Devine, Xinghua Shi, Michael E. Talkowski, Mark J. P. Chaisson, Alexander T. Dilthey, Miriam K. Konkel, Jan O. Korbel, Charles Lee, Christine R. Beck, Evan E. Eichler, Tobias Marschall
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GPT-4o mini: Non-social science research article
Rate and noise in human amygdala drive increased exploration in aversive learning
Tamar Reitich-Stolero, Kristoffer C. Aberg, Dean Halperin, Carmel Ariel, Genela Morris, Lilach Goldstein, Firas Fahoum, Ido Strauss, Rony Paz
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GPT-4o mini: Non-social science research article
Mapping urban gullies in the Democratic Republic of the Congo
Guy Ilombe Mawe, Eric Lutete Landu, Elise Dujardin, Fils Makanzu Imwangana, Charles Bielders, Aurélia Hubert, Caroline Michellier, Charles Nzolang, Jean Poesen, Olivier Dewitte, Matthias Vanmaercke
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Large urban gullies cause damage in many tropical cities across the Global South 1,2 . They can result from inappropriate urban planning and insufficient infrastructure to safely store and evacuate rainfall in environments that are already highly sensitive to soil erosion 1,3,4 . Although they can cause large destruction and societal impacts such as population displacement 1,2,5 , the magnitude of this geo-hydrological hazard remains poorly documented and understood 6,7 . Here we provide an assessment of the extent and impact of urban gullies at the scale of the Democratic Republic of the Congo (DRC). Through mapping, we identify 2,922 urban gullies across 26 cities. By combining their formation and growth rates with population density data 8 , we estimate that around 118,600 people (uncertainty range: ± 44,400 people) have been displaced by urban gullies over the period 2004–2023. We find that average displacement rates increased from about 4,650 persons yr −1 (pre-2020) to about 12,200 persons yr −1 (post-2020). Between 2010 and 2023, the number of people living in the potential expansion zone of urban gullies doubled from 1.6 (±0.6) to 3.2 (±1.3) million, with more likely to be exposed due to urban sprawl 9,10 and climate change 11 . We suggest that there is a need for tools and strategies to prevent and mitigate this hazard.
GPT-4o mini: Non-social science research article
One-shot design of functional protein binders with BindCraft
Martin Pacesa, Lennart Nickel, Christian Schellhaas, Joseph Schmidt, Ekaterina Pyatova, Lucas Kissling, Patrick Barendse, Jagrity Choudhury, Srajan Kapoor, Ana Alcaraz-Serna, Yehlin Cho, Kourosh H. Ghamary, Laura Vinué, Brahm J. Yachnin, Andrew M. Wollacott, Stephen Buckley, Adrie H. Westphal, Simon Lindhoud, Sandrine Georgeon, Casper A. Goverde, Georgios N. Hatzopoulos, Pierre Gönczy, Yannick D. Muller, Gerald Schwank, Daan C. Swarts, Alex J. Vecchio, Bernard L. Schneider, Sergey Ovchinnikov, Bruno E. Correia
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Nature DOI suffix ≠ "/s...": Not a research article
Einstein hated entanglement — and five other quantum myths
Maria Violaris, Estelle Inack, Sabine Hossenfelder, Norma G. Sanchez, Shweta Agrawal, Emily Adlam
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Nature DOI suffix ≠ "/s...": Not a research article
Label political AI and audit its hidden costs
Andres Hernandez-Serna
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Plastics pollution talks end in stalemate
Flora Graham
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Dermatology has a skin-colour dilemma
Valerie Harvey
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How did life get multicellular? Five simple organisms could have the answer
Alla Katsnelson
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RFK Jr demanded a vaccine study be retracted — the journal said no
Rachel Fieldhouse
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Rewire
Kathleen Schaefer
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Explaining the mental-health burden of atopic dermatitis
Amanda Keener
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Origins of life: the molecules that could have unlocked peptide synthesis
Arup Dalal, Sheref S. Mansy
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How the pelvis evolved to enable human bipedalism
Camille Berthelot
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Daily briefing: Fossil tracks might be earliest evidence of fish testing life on land
Flora Graham
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A psoriasis cure could be in touching distance
James Mitchell Crow
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AI versus skin cancer: the future of dermatology diagnosis
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Beer lovers fall into two flavour camps — which one are you in?
Jenna Ahart
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US Supreme Court allows NIH to cut $2 billion in research grants
Dan Garisto, Max Kozlov
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Five reasons why Nepal struggles to attract women into science
Dom Byrne
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Trial and error: research and the criminal justice system
Esme Hedley
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Net zero needs AI — five actions to realize its promise
Amy Luers
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How a fraudulent scientist faked his career and other cautionary tales: Books in brief
Andrew Robinson
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Deep brain stimulation data need public oversight
Alberto Priori, Sara Marceglia
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NASA’s Earth-observing satellites are crucial — commercial missions cannot replace them
Danielle Wood
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This deep-sea worm creates a toxic yellow pigment found in Rembrandt and CĂ©zanne paintings
Mohana Basu
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Daily briefing: Repeated heatwaves make your biological clock run fast
Flora Graham
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Daily briefing: What we know about autism and why it’s on the rise
Flora Graham
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Repeated heatwaves can age you as much as smoking or drinking
Freda Kreier
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Daily briefing: Why fertility rates are declining — and what to do about it
Flora Graham
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I trawl coastlines to study the impacts of microplastics on marine life
Josie Glausiusz
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My moonshot to preserve endangered species
Lesley Evans Ogden
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Gene therapy marks a turning point for rare skin diseases
Elie Dolgin
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Hazardous science that helps to save and improve lives needs more support
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An abiding mystery of the French Revolution is solved — by epidemiology
Mariana Lenharo
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Daily briefing: Mental password prevents brain implant from speaking people’s private thoughts out loud
Flora Graham
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Bright city lights make birds around the world sing longer
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A closer look at how cells sense dietary nutrients
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Does dark energy spawn from black holes? Could be a bright idea
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Arguments for blind peer review also need to be recognized
Daniele Roberto Giacobbe
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How tree shrews see the world
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Will the latest skin substitutes revolutionize the treatment of burns and other wounds?
Michael Eisenstein
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A contested skin condition triggered by medicines
Natalie Healey
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Viral spread: how rumours surged in revolutionary France
Benjamin Thompson, Nick Petrić Howe
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How a self-taught biologist transformed nature writing — and inspired Darwin
Gareth Thompson
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Autism is on the rise: what’s really behind the increase?
Helen Pearson
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Five single-celled species that dabble in multicellularity
Shamini Bundell
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Daily briefing: Tiny marsupial bounces back from near-extinction
Flora Graham
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Daily briefing: Primates might have evolved in the cold climate of North America
Flora Graham
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Why Texas is the hottest place for space right now
Jonathan O’Callaghan
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Gully formation in cities is displacing tens of thousands of people
Noah J. Finnegan
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Pig lung transplanted into a person in world first
Rachel Fieldhouse
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Five highlights from skin research
Liam Drew
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Here’s how to break into the Texas space industry
Sarah Wells
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Scientific meetings debate the effect of climate change on future food production
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Skin: preserving the health of a multi-talented organ
Herb Brody
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Acne vaccines could offer robust defence
Benjamin Plackett
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Childhood eczema linked to mother’s stress during pregnancy
Abhay P. S. Rathore, Soman N. Abraham
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How humans became upright: key changes to our pelvis found
Katie Kavanagh
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Climate models need more frequent releases of input data — here’s how to do it
Vaishali Naik, Paul J. Durack, Zebedee Nicholls, Carlo Buontempo, John P. Dunne, Helene T. Hewitt, Claire Macintosh, Eleanor O’Rourke
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A spiky armoured dinosaur from Africa causes a rethink of ankylosaur evolution
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Deep gashes in the earth are slicing up cities, swallowing houses and displacing vast numbers of people
Miryam Naddaf
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Glitch cop
Andrew Kozma
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Glow-in-the-dark houseplants shine in rainbow of colours
Katherine Bourzac
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Emotional AI is here — let’s shape it, not shun it
Hadar Fisher
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Machine-learning model generates images using light
Daniel Brunner
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Epidemiology models explain rumour spreading during France’s Great Fear of 1789
Stefano Zapperi, Constant Varlet-Bertrand, CĂ©cile Bastidon, Caterina A. M. La Porta, Antoine Parent
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Nature Human Behaviour

Complementary, alternative and integrative medicine for autism: an umbrella review and online platform
Corentin J. Gosling, Laure Boisseleau, Marco Solmi, Micheal Sandbank, Lucie Jurek, Mikail Nourredine, Gabriella Porcu, Elisa Murgia, Joaquim Radua, Paolo Fusar-Poli, Klara Kovarski, Serge Caparos, Ariane Cartigny, Samuele Cortese, Richard Delorme
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The use of complementary, alternative and integrative medicine (CAIM) is highly prevalent among autistic individuals, with up to 90% reporting having used CAIM at least once in their lifetime. However, the evidence base for the effects of CAIM for autism remains uncertain. Here, to fill this gap, we conducted an umbrella review of meta-analyses exploring the effects of CAIM in autism across the lifespan and developed a web platform to disseminate the generated results. Five databases were searched (up to 31 December 2023) for systematic reviews with meta-analyses exploring the effects of CAIM in autism. Independent pairs of investigators identified eligible papers and extracted relevant data. Included meta-analyses were reestimated using a consistent statistical approach, and their methodological quality was assessed with AMSTAR-2. The certainty of evidence generated by each meta-analysis was appraised using an algorithmic version of the GRADE framework. This process led to the identification of 53 meta-analytic reports, enabling us to conduct 248 meta-analyses exploring the effects of 19 CAIMs in autism. We found no high-quality evidence to support the efficacy of any CAIM for core or associated symptoms of autism. Although several CAIMs showed promising results, they were supported by very low-quality evidence. The safety of CAIMs has rarely been evaluated, making it a crucial area for future research. To support evidence-based consideration of CAIM interventions for autism, we developed an interactive platform that facilitates access to and interpretation of the present results ( https://ebiact-database.com ).
Spousal correlations for nine psychiatric disorders are consistent across cultures and persistent over generations
Chun Chieh Fan, Saeid Rasekhi Dehkordi, Richard Border, Lucy Shao, Bohan Xu, Robert Loughnan, Wesley K. Thompson, Le-Yin Hsu, Mei-Chen Lin, Chi-Fung Cheng, Rou-Yi Lai, Mei-Hsin Su, Wei-Yi Kao, Thomas Werge, Chi-Shin Wu, Andrew J. Schork, Noah Zaitlen, Alfonso Buil Demur, Shi-Heng Wang
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A latent measure of cultural racism and its association with US mortality and life expectancy
Tomi Akinyemiju, Oyomoare L. Osazuwa-Peters, Tyson H. Brown, Jude Ramos, Shaun Jones, Lauren E. Wilson, Nancy Krieger
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Systematic review and meta-analysis of educational approaches to reduce cognitive biases among students
Ghassani Swaryandini, Jessica Graham, Shantell Griffith, Vasco Grilo, Federica Ruzzante, Xingruo Zhang, Siu Kit Yeung, Marta Mangiarulo, Geetanjali Basarkod, Clarence Ng, Philip Parker, Jason Tangen, Alexander Saeri, Emily Grundy, Peter Slattery, Michael Noetel
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Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Structure of the Thomasclavelia ramosa immunoglobulin A protease reveals a modular and minimizable architecture distinct from other immunoglobulin A proteases
Norman Tran, Aaron Frenette, Todd Holyoak
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Immunoglobulin A proteases (IgAPs) are a diverse group of enzymes secreted from bacteria that inhabit human mucosal tissues. These enzymes have convergently evolved to cleave human immunoglobulin A as a means of modulating and evading host immunity. Only two of three known IgAP families have been biochemically characterized beyond their initial discovery. Here, we show using solution-scattering, steady-state kinetic, and crystallographic approaches that the protease from Thomasclavelia ramosa , representing the uncharacterized third family, has a truly modular and minimizable protein architecture. This analysis also revealed a unique metal-associated domain that likely functions as a molecular spacer and generated a working hypothesis detailing the structural mechanism behind the enzyme’s high substrate specificity. Our work provides an in-depth biochemical account of this IgAP family, paving the way for advancing clinically relevant IgAP-related research and our understanding of IgAPs as a whole.
GPT-4o mini: Non-social science research article
Profile of Johannes Lehmann
Jill Langlois
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Soil scientist Johannes Lehmann has spent his career examining how to improve soil quality to secure agricultural production, regulate climate, and keep water clean. His work with dark earths in the Brazilian Amazon led to the discovery of the importance of biochar in soil fertility and nutrient recycling from excreta. For more than 24 years, Lehmann has held a faculty position at Cornell University, where his research initially focused on carbon and nutrient cycles and went on to challenge the existence of soil humus and delve into the role of functional complexity in soil management.
GPT-4o mini: Non-social science research article
ARRDC4-mediated glycolysis enhances innate immunity to influenza A virus through fructose-1,6-bisphosphate
Yuhan Li, Zhen Wang, Jie Wang, Zhimin Jiang, Mingyue Chen, Hui Ai, Chao Ma, Qi Tong, Litao Liu, Tony Velkov, Honglei Sun, Juan Pu, Jinhua Liu, Chongshan Dai, Yipeng Sun
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Glucose metabolism impacts the innate immune response against viral infection. However, the key enzymes or the natural products and mechanisms involved are not well elucidated. Here, we found that arrestin domain containing 4 (ARRDC4), a critical regulator of glucose metabolism, senses influenza A virus (IAV) infection by interacting with viral PA protein. Upregulated ARRDC4 increases the enzymatic activity of phosphofructokinase, muscle type (PFKM) via binding its His298 site to promote the production of the metabolite fructose-1,6-bisphosphate (FBP). Consequently, FBP inhibits the K48-linked ubiquitination degradation of HSP90ÎČ, subsequently enhances its interaction with IKKÎČ and IKKΔ, and enhances NF-ÎșB- and IRF7-mediated antiviral innate immunity, respectively. Importantly, FBP supplementation enhanced IFN-ÎČ-mediated antiviral innate immunity in vitro and in vivo. Our findings highlight a unique immunometabolic regulatory mechanism in which ARRDC4 senses IAV infection and regulates antiviral innate immunity through the PFKM-FBP metabolic axis and provide a strategy for manipulating FBP-related metabolism to treat viral infection.
GPT-4o mini: Non-social science research article
Unveiling street art: A multimodal and multitechnique approach for analyzing and mapping painting materials on large murals
Francesca Sabatini, Fauzia Albertin, Brenda Doherty, Letizia Monico, Francesca Rosi, David Buti, Aldo Romani, Antonio Pecci, Nicodemo Abate, Maria Sileo, Antonio Minervino Amodio, Nicola Masini, Silvia Pizzimenti, Ilaria Degano, Francesca Modugno, Beatrice Campanella, Stefano Legnaioli, Laura Cartechini
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Street art murals are increasingly recognized as valuable contemporary artworks, often attaining significant artistic, historical, and social importance. As these murals become integral parts of cultural heritage, finding efficient strategies for their conservation is crucial. However, their typical large surface areas, heterogeneous materials, and high variability in exposure to environmental and pollution factors pose significant challenges in establishing appropriate analytical strategies to obtain the necessary information. This study proposes a multiscale and multitechnique noninvasive approach to investigate and monitor street art murals in situ. By combining portable point techniques—such as external reflection Fourier transform infrared spectroscopy, Raman spectroscopy, visible, near infrared, and short-wave infrared reflectance spectroscopy, and X-ray fluorescence spectroscopy—with visible and near infrared hyperspectral imaging, the mural’s composition across a square meter surface could be analyzed. Additionally, multispectral imaging mounted on a drone provided a global reconstruction and characterization of the overall mural. This method was complemented by microdestructive laboratory analyses of selected samples, using pyrolysis gas chromatography–mass spectrometry and liquid chromatography coupled with diode array detector and tandem mass spectrometry, to further investigate selected samples and support noninvasive results. The approach was applied to the iconic mural “Musica Popolare” (2017) by Orticanoodles in Milan, Italy, revealing detailed information about its pigments, binders, fillers, and degradation. The findings demonstrate the potential of this integrated methodology for the effective material identification, conservation assessment, and short-and long-term monitoring of urban heritage.
GPT-4o mini: Non-social science research article
Rising global temperatures reduce soil microbial diversity over the long term
Yuan Sun, Han Y. H Chen, Xin Chen, Masumi Hisano, Xinli Chen, Peter B. Reich
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Soil microbial diversity is crucial to sustaining ecosystem productivity and improving carbon sequestration. Global temperature continues to rise, but how climate warming affects microbial diversity and its capacity to sequester soil organic carbon (SOC) remains uncertain. Here, by conducting a global meta-analysis with 251 paired observations from 102 studies, we showed that, on average, warming reduced bacterial and fungal diversity (measured by richness and Shannon index) by 16.0 and 19.7%, respectively, and SOC by 18.1%. The negative responses of both soil bacterial and fungal diversity to warming became more pronounced with increasing warming magnitude, experimental duration, and decreasing soil nitrogen availability. Under the worst-case climate warming scenario (2010 to 2070, 3.4 increase in °C), soil bacterial diversity and fungal diversity are projected to reduce by 56% and 81%, respectively, over 60 y. Importantly, in addition to the direct impact of warming on SOC, warming-induced declines in microbial diversity also contributed to SOC losses. We highlight that prolonged warming could substantially reduce soil microbial diversity and decrease SOC sequestration, accelerating future warming and underscoring the urgent need for decisive actions to mitigate global climate change.
GPT-4o mini: Non-social science research article
Flavin-deficient erythrocytes offer protection against malaria parasites
Ayman Hemasa, Welmoed van Loon, Jonathan Fu, Christina Spry, Julia JĂ€ger, Donelly A. van Schalkwyk, Roberto Reverberi, Jules Ndoli, Frank P. Mockenhaupt, Carlo Contini, Kevin J. Saliba
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Studies from the 1980s and 1990s conducted in Italy, where malaria was once endemic, hypothesized that individuals with erythrocytes deficient in flavin mononucleotide and flavin adenine dinucleotide (FAD)—collectively known as flavins—are partially protected against malaria. The condition was reported to be familial, consistent with a genetic element. This hypothesis, however, has never been tested. Using an erythrocyte FAD-dependent glutathione reductase activity assay, we identified individuals with flavin-deficient erythrocytes (FDE) in Ferrara, Italy (23% of 150 individuals screened), and in Huye, Rwanda (13% of 169 individuals). None of the individuals with FDE had a dietary riboflavin deficiency. Importantly, FDE from individuals in Ferrara, as well as erythrocytes depleted of flavins in vitro by riboflavin starvation, inhibited the intraerythrocytic proliferation of Plasmodium falciparum . We provide evidence that these erythrocytes are susceptible to oxidative stress, potentially explaining their inhibitory effect on parasite proliferation. Genetic analysis identified mutations in the FAD synthase gene of three individuals with FDE from Huye, consistent with a potential genetic basis.
GPT-4o mini: Non-social science research article
Renormalization group for Anderson localization on high-dimensional lattices
Boris L. Altshuler, Vladimir E. Kravtsov, Antonello Scardicchio, Piotr Sierant, Carlo Vanoni
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We discuss the dependence of the critical properties of the Anderson model on the dimension d in the language of ÎČ -function and renormalization group recently introduced in Vanoni et al. [C. Vanoni et al. , Proc. Natl. Acad. Sci. U.S.A. 121 , e2401955121 (2024)] in the context of Anderson transition on random regular graphs. We show how in the delocalized region, including the transition point, the one-parameter scaling part of the ÎČ -function for the fractal dimension D 1 evolves smoothly from its d = 2 form, in which ÎČ 2 ≀ 0 , to its ÎČ âˆž ≄ 0 form, which is represented by the random regular graph (RRG) result. We show how the Ï” = d − 2 expansion and the 1 / d expansion around the RRG result can be reconciled and how the initial part of a renormalization group trajectory governed by the irrelevant exponent y depends on dimensionality. We also show how the irrelevant exponent emerges out of the high-gradient terms of expansion in the nonlinear sigma model and put forward a conjecture about a lower bound for the fractal dimension. The framework introduced here may serve as a basis for investigations of disordered many-body systems and of more general nonequilibrium quantum systems.
GPT-4o mini: Non-social science research article
De novo rates of a Trypanosoma -resistant mutation in two human populations
Daniel Melamed, Revital Shemer, Evgeni Bolotin, Michael B. Yakass, Dorit Fink-Barkai, Edem K. Hiadzi, Karl L. Skorecki, Adi Livnat
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Mutation rates have long been measured as averages across many genomic positions. Recently, a method to measure the rates of individual mutations was applied to a narrow region in the human hemoglobin subunit beta ( HBB ) gene containing the site of the hemoglobin S (HbS) mutation as well as to a paralogous hemoglobin subunit delta ( HBD ) region, in sperm samples from sub-Saharan African and northern European donors [Melamed et al ., Genome Res. 32 , 488–498 (2022)]. The HbS mutation, which protects against malaria while causing sickle-cell anemia in homozygotes, originated de novo significantly more frequently in the HBB gene in Africans compared to the other three test cases combined (the European HBB gene and the European and African HBD gene). Here, we apply this approach to the human apolipoprotein L1 ( APOL1 ) gene containing the site of the G1 1024A→G mutation, which protects against African sleeping sickness caused by Trypanosoma brucei gambiense while causing a substantially increased risk of chronic kidney disease in homozygotes. We find that the 1024A→G mutation is the mutation of highest de novo origination rate and deviates most from the genome-wide average rate for its type (A→G) compared to all other observable mutations in the region and that it originates de novo significantly more frequently in Africans than in Europeans—i.e., in the population where it is of adaptive significance. The results are unexpected given the notion that the probability of a specific mutational event is independent of its value to the organism and underscore the importance of studying mutation rates at the individual-mutation resolution.
GPT-4o mini: Non-social science research article
Evolutionarily conserved grammar rules viral factories of amoeba-infecting members of the hyperdiverse Nucleocytoviricota phylum
Sofia Rigou, Alain Schmitt, Anaísa B. Moreno, Audrey Lartigue, Lucile Danner, Lotte Mayer, Claire Giry, Feres Trabelsi, Lucid Belmudes, Natalia Olivero-Deibe, Hugo Le Guenno, Yohann Couté, Mabel Berois, Matthieu Legendre, Sandra Jeudy, Chantal Abergel, Hugo Bisio
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Despite sharing fewer than 10 core genes, the hyperdiverse Nucleocytoviricota phylum (ranging from poxviruses to giant viruses) universally assembles viral factories (VFs) resembling biomolecular condensates. Regardless, it is unclear how these viruses achieve such a level of functional conservation without clear conserved genetic information. We demonstrate that the VFs produced by amoeba-infecting viruses have liquid-like properties and identify a conserved molecular grammar governing viral factory scaffold protein: charge-patterned intrinsically disordered regions that drive phase separation independently of sequence homology. This grammar predicts functional scaffold proteins across the 15 viral families, revealing evolutionary constraints invisible to sequence or structural analysis. Strikingly, VFs exhibit subcompartmentalization analogous to nuclei, segregating transcription and mRNA processing (inner condensates) from replication (interphase zones) and translation (host cytoplasm). Our work establishes phase separation as a fundamental organizational principle bridging extreme genomic diversity, explaining how biological complexity emerges without gene conservation. This grammar is likely also conserved in non-amoeba-infecting members of the phylum and thus may represent a primordial solution for organelle-like organization, with broad implications for antiviral targeting.
GPT-4o mini: Non-social science research article
Local c-di-GMP signaling, triggered by cross-regulation of cAMP-CRP and c-di-GMP, controls biofilm formation under nutrient limitation
Di Sun, Xiaobo Liu, Ying Zhang, Rui Shi, Yunrui Ru, Xuge Zhou, Ying Chen, Jing Yang, Jiawen Liu, Jingrong Zhu, Cong Liu, Weijie Liu
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Bacteria have several nucleotide second messengers, most of which act as global regulators to control a wide range of bacterial physiological processes. Studies usually focus on a single second messenger, and the mechanisms and physiological significance of the cross-regulation between different nucleotide second messengers are often unclear. Here, we show that Shewanella putrefaciens can form biofilms in both nutrient-rich and nutrient-poor media. While both are controlled by c-di-GMP, the regulatory models differ. Under low nutrient conditions, cross-regulation of cAMP-CRP and c-di-GMP occurs at the transcriptional and posttranslational levels, thereby controlling biofilm development. During the early stages of biofilm development, cAMP-CRP directly promotes the transcription of a PDE gene, lrbR , by LrbA. Additionally, cAMP-CRP recruits LrbR to BpfD to suppress early biofilm formation via LrbR-dependent local degradation of c-di-GMP. Finally, as intracellular LrbR levels decrease, cAMP-CRP-BpfD enables a rapid shift to biofilm development and supports biofilm maintenance. Under high nutrient conditions, this cross-regulation does not occur, resulting in a positive correlation between global c-di-GMP levels and biofilm biomass. The identification of distinct modes of biofilm regulation in different nutrients will provide a theoretical basis for future targeted control of biofilm formation in different nutrient environments.
GPT-4o mini: Non-social science research article
Loss of ICOSL expression in the progression to cervical carcinoma
Gerard J. Nuovo, Esmerina Tili, Carlo M. Croce
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Human papillomavirus (HPV)–related lesions contain types with benign outcomes and those with a risk of progression to cancer. We addressed the role of immune surveillance in 76 cervical biopsies (normal = 23, HPV+ benign = 16, HPV+ precancer = 37) by studying the infiltration of cytotoxic T cells and the expression of the immune modulators PDL1, ICOSL, and miR-155 and compared the data to 101 cervical squamous cell carcinomas. In the normal cervix, ICOSL expression was restricted to the endocervical epithelia whereas neither miR-155 nor PDL1 were detected. MiR-155 was up-regulated in both the benign (88%) and precancerous (92%) HPV squamous intraepithelial lesions (SIL) and colocalized to cells in the upper part of the lesion that is the area with productive viral infection. Both PDL1 (95%) and ICOSL (89%) were only evident in the precancerous SIL and each localized to squamous cells in the basal aspect that lacked replicating virus. In both microinvasive and invasive cervical squamous cell cancer miR-155 expression remained high (83%) as did PDL1 expression (80%) but ICOSL detection was reduced to 17%. Infiltration by CD8+ T cells was intense in the invasive lesions and these cells were mostly inactive as determined by the lack of granzyme B colocalization. It is concluded that miR-155 expression is a marker of HPV infection in both benign and precancerous lesions, whereas the approximately 10% of the latter lesions that progress to cancer gain PDL1 and lose ICOSL expression, which are important factors in avoiding immune surveillance.
GPT-4o mini: Non-social science research article
CryoEM structure of ALK2:BMP6 reveals distinct mechanism that allow ALK2 to interact with both BMP and activin ligands
Erich J. Goebel, Senem Aykul, Warren W. Hom, Kei Saotome, Aris N. Economides, Matthew C. Franklin, Vincent J. Idone
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Ligands in the transforming growth factor ÎČ (TGF-ÎČ) family [activins, Bone Morphogenetic Proteins (BMPs), and TGF-ÎČs] signal by bringing together two type I and two type II receptors. Activin receptor-like kinase-2 (ALK2) is the only type I receptor among the seven TGF-ÎČ type I receptors that interacts with both activin and BMP ligands. With BMPs, ALK2 acts as a signaling receptor to activate small mothers against decapentaplegic 1 (SMAD1)/5/8 signaling. Alternatively, with activins, such as Activin A (ActA), ALK2 forms nonsignaling complexes that negatively regulate ALK2 and ActA signaling. To gain insight into how ALK2 interacts with two distinct classes of ligands, we resolved the cryoelectron microscopy structure of ALK2 in complex with the type II receptor, ActRIIB, and the ligand, BMP6, in parallel with the corresponding structure with ALK3 for direct comparison. These structures demonstrate that ALK2 and ALK3 utilize different mechanisms to interact with BMP6 at the wrist interface, with ALK2 relying on BMP6 glycosylation and ALK3 relying on a salt bridge. Modeling of ALK2:ActA reveals that binding relies on ActA’s fingertip region, mirroring the interaction of ActA with its other receptor, ALK4. Our results demonstrate that ALK2 is a “hybrid” receptor that incorporates features of BMP type I receptors such as ALK3 at the wrist interface and an activin type I receptor such as ALK4 at the fingertip.
GPT-4o mini: Non-social science research article
Candidate Denisovan fossils identified through gene regulatory phenotyping
Nadav Mishol, Gadi Herzlinger, Yoel Rak, Uzy Smilanksy, Liran Carmel, David Gokhman
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Denisovans are an extinct group of humans whose morphology is mostly unknown. The scarcity of verified Denisovan fossils makes it challenging to study their anatomy, and how well they were adapted to their environment. We previously developed a genetic phenotyping approach to gain insight into Denisovan anatomy by detecting gene regulatory changes that likely altered Denisovan skeletal morphology. Here, we scan the Middle Pleistocene fossil record for crania matching the predicted Denisovan morphology and might therefore be related to Denisovans. We developed quantitative measures to assess both the proportion and extent of matches. These analyses revealed that the East Asian specimens of Harbin and Dali show an exceptionally high concordance with the Denisovan profile, surpassing all other examined Middle Pleistocene hominin specimens, including Neanderthals. Specifically, 15 out of 18 of Dali ’s features and 16 out of 18 of Harbin ’s matched Denisovan predictions. These findings are robust to overall skull size and to correlations between phenotypes. We also found that Kabwe 1 shows a strong affinity to the Denisovan–Neanderthal clade and might be placed near its root. Our results show that gene regulatory phenotyping may assist in classifying poorly understood specimens.
GPT-4o mini: Non-social science research article
Cohort mortality forecasts indicate signs of deceleration in life expectancy gains
José Andrade, Carlo Giovanni Camarda, Héctor Pifarré i Arolas
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The fast-paced improvements in mortality in high-income countries since the early 1900s have led to a sustained increase in life expectancy. However, whether this linear trend will continue or life expectancy gains will decelerate in the near future remains unclear. To answer this question, we apply multiple established and recently developed mortality forecasting methods to estimate cohort life expectancy for individuals born between 1939 and 2000 in 23 high-income countries. Across all forecasting methods, our results robustly and consistently indicate a deceleration in cohort life expectancy. The previously observed pace of improvement, 0.46 y per cohort, declines by 37% to 52%, depending on the method used. Robustness checks suggest that these findings are unlikely to be solely due to downward bias in cohort life expectancy forecasts. Furthermore, an age-decomposition analysis indicates that this deceleration is primarily driven by a slower pace of mortality improvement at very young ages. Over half of the total deceleration is attributable to mortality trends under age 5, while more than two-thirds is explained by mortality trends under age 20. This pattern had already emerged in the observed data for the cohorts included in our analysis. Thus, even if these estimates turned out to be overly pessimistic, it is unlikely that the deceleration will reverse in the near future.
GPT-4o mini: Non-social science research article
Logging disrupts the ecology of molecules in headwater streams
Erika C. Freeman, Erik J. S. Emilson, Kara L. Webster, Thorsten Dittmar, Andrew J. Tanentzap
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Global demand for wood products is increasing forest harvest. One understudied consequence of logging is that it accelerates mobilization of dissolved organic matter (DOM) from soils to aquatic ecosystems where it is more easily rereleased to the atmosphere. Here, we tested how logging changed DOM in headwaters of hardwood-dominated catchments in northern Ontario, Canada. We applied a before-after-control-impact experiment across four catchments for 3 y and measured DOM monthly during ice-free seasons. DOM concentration in streams from logged catchments quadrupled, on average, only for the first 2 mo postharvest, but resulting changes to the molecular composition of DOM persisted for at least 2 y. Ultrahigh-resolution mass spectrometry revealed that DOM composition within logged streams became more available for microbial use and chemically diverse than in controls, with novel highly unsaturated polyphenols, carboxylic-rich alicyclic, and nitrogen-containing formulae. The molecular composition of stream DOM measured fortnightly postharvest was most similar to the DOM composition of surrounding soils, likely due to increased hydrological connectivity. Alongside carbon being more likely to be released into the atmosphere, we estimate that selective logging increased the total flux of dissolved organic carbon in streams by 6.4% of the carbon extracted as timber. Although these estimates are short-lived, they should affect the millions of hectares that are logged annually. Carbon accounting of forestry, including as a natural climate solution, must now consider the transport and fate of DOM from land into water.
GPT-4o mini: Non-social science research article
Scaling and mechanical optimality of bristled wings in microinsects
Dmitry Kolomenskiy, Sergey E. Farisenkov, Pyotr N. Petrov, Alexey A. Polilov
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It is crucial for both animal evolution and engineering to optimize the relative size of structures. Animal wings are no exception, every structural design having its limits in terms of achievable size and performance. For instance, many microinsects have bristled wings, which are more efficient at small scales than the membranous wings common in larger insects. However, the limitations and the optimal characteristics of bristled wings remain largely underinvestigated. We collected morphological and kinematic data on a variety of beetles ranging between 0.3 and 5 mm in wing length. This was followed by a theoretical analysis to explain from the mechanical standpoint the morphological traits and allometric scalings observed in the data. We derived functional dependencies for parameters such as the number of bristles, bristle length and diameter, size of the wing blade, etc., from considerations of wing inertia minimization under the aerodynamic and structural stiffness constraints. The solution of the optimization problem reveals scaling relationships aligning with empirical trends, which suggests that the reduction of wing membrane during miniaturization can be explained by mechanical optimality. Thus, scaling of the number of bristles and the average gap width between bristles follows directly from the aerodynamic condition of maintaining low permeability, while the bristle diameter and length are determined mainly by the structural stiffness requirement. Similar mechanical arguments are likely applicable to other miniature animals that propel through fluids.
GPT-4o mini: Non-social science research article
Multistep catalytic abiotic CO 2 conversion to sugars through C 1 intermediates
Nathan Soland, Jie Luo, Arifin Luthfi Maulana, Julian Feijoo, Hye-Jin Jo, Alexander M. Oddo, Yu Shan, Tianle Wang, Geonhui Lee, Jihoon Choi, Wei-Shan Huynh, Maria Fonseca Guzman, Lihini Jayasinghe, Cheng Zhu, Yao Yang, Peidong Yang
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Carbon dioxide (CO 2 ) to multicarbon (C n ) upgrading for commodity chemicals, fuel production, or artificial food synthesis using renewable energy input is a golden target for researchers in sustainable carbon emission reduction. Here, we explore and analyze a flexible modular roadmap for the task, utilizing sequential electro-, photo-, and organocatalysis to develop a strategy for CO 2 conversion using the key and elusive formaldehyde precursor of interest for sugar generation. We study the electrochemical carbon dioxide reduction reaction to methanol in a flow cell and its discontinuous photooxidation to formaldehyde (PMOR) with excellent selectivity. Utilizing a highly active N- heterocyclic carbene catalyst enables tunable generation of C 4 –C 6 aldoses without undesirable byproducts, with carbon conversion yield reaching 60 to 80% for desired pentose, tetrose, and triose product mixtures and over 20% for hexose. This approach presents a roadmap for CO 2 valorization, aiming to bridge carbon waste streams with sustainable sugar synthesis and opening broad avenues for green chemical production.
GPT-4o mini: Non-social science research article
Correction for Soni et al., BIK polymorphism and proteasome regulation unveil host risk factor for severe influenza
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GPT-4o mini: Non-social science research article
Community detection for directed networks revisited using bimodularity
Alexandre Cionca, Chun Hei Michael Chan, Dimitri Van De Ville
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Community structure is a key feature omnipresent in real-world network data. Plethora of methods have been proposed to reveal subsets of densely interconnected nodes using criteria such as the modularity index. These approaches have been successful for undirected graphs but directed edge information has not yet been dealt with in a satisfactory way. Here, we revisit the concept of directed communities as a mapping between sending and receiving communities. This translates into a definition that we term bimodularity. Using convex relaxation, bimodularity can be optimized with the singular value decomposition of the directed modularity matrix. Subsequently, we propose an edge-based clustering approach to reveal the directed communities including their mappings. The feasibility of the framework is illustrated on a synthetic model and further applied to the neuronal wiring diagram of the Caenorhabditis elegans , for which it yields meaningful feedforward loops of the head and body motion systems. This framework sets the ground for the understanding and detection of community structures in directed networks.
GPT-4o mini: Non-social science research article
Tunable effective diffusion of CO 2 in aqueous foam
CĂ©cile Aprili, Gwennou Coupier, Élise Lorenceau, Benjamin Dollet
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Aqueous foams are solid materials composed of gases and liquids, exhibiting a large gas/liquid surface area and enabling dynamic exchanges between their fluid components. The structure of binary-gas foams, whose bubbles consist of a mixture of two gases having different affinities with the liquid, thus offers real potential for the dynamic separation of these gases at low cost. In single-gas foams, the structure evolves under the effect of gas flow induced by Laplace pressure differences, arising from heterogeneities in bubble size. This leads to the well-documented Ostwald ripening. In addition to these capillary effects, the structure of binary-gas foams can evolve under the effect of gas flow induced by partial pressure differences, arising from heterogeneities in bubble composition. We experimentally investigate the shrinking of CO 2 -laden 2D foams exposed to air, observing a crust of tiny bubbles at the front. We derive a nonlinear diffusion model for the gas in the foam and propose a description of the whole foam as an effective, homogeneous medium, the key parameter being the gas permeability ratio across the foam’s soap films (≠1 for CO 2 /air). The effective diffusivity of the gas in the foam emerges from the coupling between foam structure and gas transport across soap films. We extrapolate it for various permeability ratios and show that it can vary continuously between the diffusivity of the gas in the liquid and that of the gas in the atmosphere, enabling tunable gas retention and release by controlling the composition of the atmosphere.
GPT-4o mini: Non-social science research article
Color-neutral and reversible tissue transparency enables longitudinal deep-tissue imaging in live mice
Carl H. C. Keck, Elizabeth L. Schmidt, Richard H. Roth, Brendan M. Floyd, Andy P. Tsai, Hassler B. Garcia, Miao Cui, Xiaoyu Chen, Chonghe Wang, Andrew Park, Su Zhao, Pinyu A. Liao, Kerriann M. Casey, Wencke Reineking, Sa Cai, Ling-Yi Zhang, Qianru Yang, Lei Yuan, Ani Baghdasaryan, Eduardo R. Lopez, Lauren Cooper, Han Cui, Daniel Esquivel, Kenneth Brinson, Xiaoke Chen, Tony Wyss-Coray, Todd P. Coleman, Mark L. Brongersma, Carolyn R. Bertozzi, Gordon X. Wang, Jun B. Ding, Guosong Hong
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Light scattering in biological tissue presents a significant challenge for deep in vivo imaging. Our previous work demonstrated the ability to achieve optical transparency in live mice using intensely absorbing dye molecules, which created transparency in the red spectrum while blocking shorter-wavelength photons. In this paper, we extend this capability to achieve optical transparency across the entire visible spectrum by employing molecules with strong absorption in the ultraviolet spectrum and sharp absorption edges that rapidly decline upon entering the visible spectrum. This color-neutral and reversible tissue transparency method enables optical transparency for imaging commonly used fluorophores in the green and yellow spectra. Notably, this approach facilitates tissue transparency for structural and functional imaging of the live mouse brain labeled with yellow fluorescent protein and GCaMP through the scalp and skull. We show that this method enables longitudinal imaging of the same brain regions in awake mice over multiple days during development. Histological analyses of the skin and systemic toxicology studies indicate minimal acute or chronic damage to the skin or body using this approach. This color-neutral and reversible tissue transparency technique opens opportunities for noninvasive deep-tissue optical imaging, enabling long-term visualization of cellular structures and dynamic activity with high spatiotemporal resolution and chronic tracking capabilities.
GPT-4o mini: Non-social science research article
STAGE: A compact and versatile TnpB-based genome editing toolkit for Streptomyces
Jing Luo, Natalie Chia, Yuxi Qin, Pan Tan, Lingwen Zhang, Sihan Yang, Zihan Yuan, Liang Hong, Sang Yup Lee, Yaojun Tong
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Streptomyces are naturally endowed with the capacity to produce a wide array of natural products with biomedical and biotechnological value. They have garnered great interest in synthetic biology applications given the abundance of uncharacterized biosynthetic gene clusters (BGCs). However, progress has been hindered by the limited availability of genetic tools for manipulating these bacteria. Several representative CRISPR-Cas systems have been established in Streptomyces to streamline experimental workflows and improve editing efficiency. Nevertheless, their broader applicability has been constrained by issues such as nuclease activity-related cytotoxicity and the large size of effector proteins. To address these challenges, we present Streptomyces -compatible TnpB-assisted genome editing (STAGE), a genetic toolkit based on ISDra2 TnpB, which is approximately one-third the size of Cas9 and enables precise, site-specific gene editing. We demonstrated that STAGE introduces genetic mutations with high efficiency and minimal off-target effects in two industrially important Streptomyces strains. Building on this platform, we developed STAGE-cBEST and STAGE-McBEST, enabling single and multiplexed C·G-to-T·A base editing, respectively, with editing efficiencies exceeding 75%. To further enhance performance, we engineered the ISDra2 TnpB system using an AI-assisted protein engineering framework, resulting in two variants that achieve nearly 100% genome editing efficiency. Additionally, through sequence homology analysis, we identified a TnpB ortholog from the same biological origin of ISDra2 TnpB, which also functions effectively as a gene editing tool. Our study establishes STAGE as a highly precise, programmable, and versatile genome editing platform for Streptomyces , paving the way for advanced genetic manipulation and synthetic biology applications in these industrially important bacteria.
GPT-4o mini: Non-social science research article
The US–Israel Blavatnik Scientific Forum on alleviating global water scarcity by desalination and water reuse
Sharon L. Walker, Gedeon Dagan, Avner Adin, Pedro J. J. Alvarez, Menachem Elimelech, Adi Radian
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GPT-4o mini: Non-social science research article
Precise antibody delivery to the brain via nanobubble-actuated focused ultrasound alleviates depression
Wenjing Li, Yifan Feng, Zhouyang Xu, Xing Xu, Kexin Yang, Xinya Yao, Jia-Ji Pan, Hengxiang Cui, Ji Hu, Bingbing Cheng
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Precise, noninvasive drug delivery to small but important brain regions is challenging and highly desired given the brain’s inherent complexity and heterogeneous nature. Here, we report an approach utilizing focused ultrasound (FUS) combined with nanobubbles to successfully navigate this challenge. Compared to traditional microbubbles, nanobubbles exhibit superior acoustic properties. The nanobubbles, when exposed to FUS, induce a highly localized and reversible opening of the blood–brain barrier (BBB) with significantly enhanced precision (up to fourfolds compared to microbubbles, as measured by the precision loss metric). Repeated multitarget FUS-NB precisely delivers macromolecular human-derived anti-N-methyl-D-aspartate receptors monoclonal antibodies (HuMAbs) into the small brain region within a 2-h half-life window per opening. Fluorescence images confirm HuMAb retention in the brain parenchyma for at least 10 d postadministration. With this approach, we targeted the lateral habenula, a small but effective brain target for antidepressant treatments, and significantly alleviated depression-like symptoms at least 2 wk in a mouse model (tail suspension test/forced swim test: P < 0.01/0.05). Moreover, minimal red blood cell extravasation (0.9‱ affected area) was observed in the treated region after multiple FUS treatments, indicating the safety and tolerability of FUS-nanobubble-mediated BBB opening. The enhanced delivery precision, coupled with a favorable safety profile, positions our approach as a promising strategy for antibody therapy with significant clinical translation potential.
GPT-4o mini: Non-social science research article
G-quadruplexes as a source of vulnerability in BRCA2 - deficient granule cell progenitors and medulloblastoma
Danielle L. Keahi, Mathijs A. Sanders, Matthew R. Paul, Andrew L. H. Webster, Yin Fang, Tom F. Wiley, Samer Shalaby, Thomas S. Carroll, Settara C. Chandrasekharappa, Carolina Sandoval-Garcia, Margaret L. MacMillan, John E. Wagner, Mary E. Hatten, Agata Smogorzewska
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Biallelic pathogenic variants in the essential DNA repair gene BRCA2 cause Fanconi anemia complementation group D1. Patients in this group are highly prone to develop embryonal tumors, most commonly medulloblastoma arising from the cerebellar granule cell progenitors (GCPs). GCPs undergo high proliferation in the postnatal cerebellum under Sonic Hedgehog (SHH) activation, but the type of DNA lesions that require the function of the BRCA2 to prevent tumorigenesis remains unknown. To identify such lesions, we assessed both GCP neurodevelopment and tumor formation using a mouse model with deletion of exons three and four of Brca2 in the central nervous system, coupled with global Trp53 loss. Brca2 Δex3-4 ;Trp53 −/− animals developed SHH subgroup medulloblastomas with complete penetrance. Whole-genome sequencing of the tumors identified structural variants with breakpoints enriched in areas overlapping putative G-quadruplexes (G4s). Brca2 -deficient GCPs exhibited decreased replication speed in the presence of the G4-stabilizer pyridostatin. Pif1 helicase, which resolves G4s during replication, was highly upregulated in tumors, and Pif1 knockout in primary medulloblastoma tumor cells resulted in increased genome instability upon pyridostatin treatment. These data suggest that G4s may represent sites prone to replication stalling in highly proliferative GCPs and without BRCA2, G4s become a source of genome instability. Tumor cells upregulate G4-resolving helicases to facilitate rapid proliferation through G4s highlighting PIF1 helicase as a potential therapeutic target for treatment of BRCA2-deficient medulloblastomas.
GPT-4o mini: Non-social science research article
Quantum relaxometry for detecting biomolecular interactions with single NV centers
Min Li, Qi Zhang, Xi Kong, Sheng Zhao, Bin-Bin Pan, Ziting Sun, Pei Yu, Zhecheng Wang, Mengqi Wang, Wentao Ji, Fei Kong, Guanglei Cheng, Si Wu, Ya Wang, Sanyou Chen, Xun-Cheng Su, Fazhan Shi
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The investigation of biomolecular interactions at the single-molecule level has emerged as a pivotal research area in life science, particularly through optical, mechanical, and electrochemical approaches. Spins existing widely in biological systems offer a unique degree of freedom for detecting such interactions. However, most previous studies have been largely confined to ensemble-level detection in the spin degree. Here, we developed a molecular interaction analysis method approaching single-molecule level based on relaxometry using the quantum sensor, nitrogen-vacancy (NV) center in diamond. Experiments utilized an optimized diamond surface functionalized with a polyethylenimine nanogel layer, achieving ∌ 10 nm average protein distance and mitigating interfacial steric hindrance. Then we measured the strong interaction between streptavidin and spin-labeled biotin complexes, as well as the weak interaction between bovine serum albumin and biotin complexes, at both the micrometer scale and nanoscale. For the micrometer-scale measurements using ensemble NV centers, we reexamined the often-neglected fast relaxation component and proposed a relaxation rate evaluation method, substantially enhancing the measurement sensitivity. Furthermore, we achieved nanoscale detection approaching single-molecule level using single NV centers. This methodology holds promise for applications in molecular screening, identification, and kinetic studies at the single-molecule level, offering critical insights into molecular function and activity mechanisms.
GPT-4o mini: Non-social science research article
Substantial reductions in black carbon from both fossil fuels and biomass burning during China’s Clean Air Action
Junwen Liu, Fan Jiang, Qiongqiong Wang, Gan Zhang, Jun Li, Weihua Chen, Ping Ding, Sanyuan Zhu, Zhineng Cheng, Xiangyun Zhang, Qinge Sha, Zhijiong Huang, Xin Yuan, Junyu Zheng, Yanlin Zhang, Caiqing Yan, Chongguo Tian, Yingjun Chen, Jian Zhen Yu, Örjan Gustafsson
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Black carbon (BC) aerosols exacerbate air pollution and climate warming, but their climatic impacts and sources are poorly constrained by bottom–up emission inventories (EIs). China’s Clean Air Action (CAA), which was launched in 2013, provides an excellent opportunity for investigating interannual variations in source contributions and validate the accuracy of EIs. Here, we present an 11-y (2008–2018) record of the BC concentration and its source-diagnostic radiocarbon ( 14 C) and stable carbon isotope ( 13 C) signatures at a receptor site in the Pearl River Delta (PRD) region, South China. The results revealed that the implementation of the CAA (2014–2018) led to a 41% reduction in the BC concentration compared with that in the preaction period (2008–2013). There is a large and systemic discrepancy over the whole period in the contribution of biomass burning to BC in South China between predictions from technology-based EIs (4 to 9%) and these source-diagnostic dual-isotopic fingerprints of actual ambient aerosols (21 to 32%). Observational constraints by source-diagnostic ή 13 C/Δ 14 C isotope measurements revealed that the reduction in biomass burning contributed 22% to the decrease in BC associated with the CAA, whereas predictions from EIs assigned a much smaller fraction. These results emphasize the need for observation-based source diagnostics of changing BC emission sources. Detailed source apportionment using independent ή 13 C/Δ 14 C isotope methodology is crucial for refining air pollution control strategies and improving the accuracy of models used for assessing the air quality and climate effects of BC in China and elsewhere.
GPT-4o mini: Non-social science research article
Correction for An et al., Impact of women’s political empowerment through gender quotas on improved drinking water access in Africa
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GPT-4o mini: Non-social science research article
Microvilli’s grip on T cell development
Allison T. Ryan, Minsoo Kim
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GPT-4o mini: Non-social science research article
Specificities of chemosensory receptors in the human gut microbiota
Wenhao Xu, Ekaterina Jalomo-Khayrova, Vadim M. Gumerov, Patricia A. Ross, Tania S. Köbel, Daniel Schindler, Gert Bange, Igor B. Zhulin, Victor Sourjik
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The human gut is rich in metabolites and harbors a complex microbial community, yet surprisingly little is known about the spectrum of chemical signals detected by the large variety of sensory receptors present in the gut microbiome. Here, we systematically mapped the ligand specificities of selected extracytoplasmic sensory domains from twenty members of the human gut microbiota, with a primary focus on the abundant and physiologically important class of Clostridia. Twenty-five metabolites from different chemical classes—including amino acids, nucleobase derivatives, amines, indole, and carboxylates—were identified as specific ligands for fifteen sensory domains from nine bacterial species, which represent all three major functional classes of transmembrane receptors: chemotaxis receptors, histidine kinases, and enzymatic sensors. We have further characterized the specificity and evolution of ligand binding to Cache superfamily sensors specific for lactate, dicarboxylic acids, and for uracil and short-chain fatty acids (SCFAs). Structural and biochemical analysis of the dCache sensor of uracil and SCFAs revealed that its two different ligand types bind at distinct sensory modules. Overall, combining experimental identification with computational analyses, we were able to assign ligands to approximately half of the Cache-type chemotaxis receptors found in the eleven gut commensal genomes from our set, with carboxylic acids representing the largest ligand class. Among these, the most commonly found ligand specificities were for lactate and formate, indicating a particular importance of these metabolites in the human gut microbiota and consistent with their observed growth-promoting effects on selected bacterial commensals.
GPT-4o mini: Non-social science research article
Organoid-based neutralization assays reveal a distinctive profile of SARS-CoV-2 antibodies and recapitulate the real-world efficacy
Zhixin Wan, Cun Li, Ying Zhou, Yifei Yu, Man Chun Chiu, Jingjing Huang, Shuxin Zhang, Xiaoxin Zhu, Qiaoshuai Lan, Yanlin Deng, Wei Xue, Chengfan Jiang, Jiali Wu, Zijun Zhao, Jian-Piao Cai, Lin Huang, Yong Zhang, Xiaojuan Liu, Zheng Zhang, Hin Chu, Linqi Zhang, Zhiwei Chen, Kelvin Kai-Wang To, Kwok-Yung Yuen, Hans Clevers, Jie Zhou
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The efficacy of VIR-7831, a class 3 anti-SARS-CoV-2 monoclonal antibody (mAb), was demonstrated repeatedly in clinical trials; yet, reduced neutralization against Omicron variants in cell-line-based neutralization assays led to its withdrawal from clinical use. We developed organoid-based neutralization assays to measure mAb potency. We found that most class 3 mAbs, especially those not blocking receptor-binding domain-ACE2 binding, including VIR-7831, were substantially underestimated in cell-line-based assays. Nasal organoids adequately recapitulated the real-world effectiveness of VIR-7831 because of biologically relevant low ACE2 expression, and exclusively reproduced the in vivo protection of S2 mAbs due to the high TMPRSS2 expression, reminiscent of native human respiratory epithelial cells. Collectively, the robust organoid culture system and biologically relevant expression profiles of ACE2 and TMPRSS2 make nasal organoids present a correlate of in vivo protection of neutralizing mAbs exclusively. The organoid-based neutralization assays, superior to conventional cell-line-based assays, can recapitulate and predict the real-world efficacy of mAbs.
GPT-4o mini: Non-social science research article
Amyloid ÎČ–dependent neuronal silencing through synaptic decoupling
Yonghai Zhang, Hsing-Jung Chen-Engerer, Kuan Zhang, Benedikt Zott, Zsuzsanna Varga, Yang Chen, Xiaowei Chen, Hongbo Jia, Bert Sakmann, Israel Nelken, Arthur Konnerth
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Amyloid ÎČ (AÎČ)-dependent circuit dysfunction in Alzheimer’s disease (AD) is determined by a puzzling mix of hyperactive and inactive (“silent”) brain neurons. Recent studies identified excessive glutamate accumulation as a key AÎČ-dependent determinant of hyperactivity. The cellular mechanisms underlying neuronal silence depend on both AÎČ and tau protein pathologies, with an unknown role of AÎČ. Here, by using single-cell-initiated rabies virus (RV) tracing in mouse models of ÎČ-amyloidosis, we demonstrate that the presynaptic connectivity of silent, but not that of hyperactive, neurons is severely disrupted. Furthermore, silent neurons display a major spine loss and strongly suppressed synaptic activity. Thus, we suggest that synaptic decoupling is an AÎČ-dependent cellular mechanism underlying progressive neuronal silencing and a critical factor for the cognitive impairments encountered in AD.
GPT-4o mini: Non-social science research article
In This Issue
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GPT-4o mini: Non-social science research article
Correction for Kalakonda et al., Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice
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GPT-4o mini: Non-social science research article
Seeding of visceral adipose tissue with perinatally generated regulatory T cells shapes the metabolic tenor in mice
Miguel Marin-Rodero, Teshika Jayewickreme, Christophe Benoist, Diane Mathis
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The Foxp3 + CD4 + regulatory T cells (Tregs) generated around birth are phenotypically and functionally distinct from those engendered during adulthood. That perinatally produced Tregs persist for a protracted period in peripheral lymphoid organs has been well documented, as has their superior ability to protect the organism from many autoimmune diseases. However, their contribution to pools of nonlymphoid-tissue Tregs and their homeostatic functions therein have been little studied. We show that perinatal Tregs preferentially derive from a CD25 + Foxp3 − thymocyte progenitor; that they seed and persist to varying degrees in every nonlymphoid tissue examined; and that transient depletion of perinatally generated Tregs in adults, but not in neonates, is followed by poor reconstitution of Treg numbers and phenotypes in epididymal visceral-adipose tissue (eVAT) and the skin but not in several lymphoid and other nonlymphoid tissues. Potential clinical implications of such a deficiency are highlighted by findings on mice subjected to weight cycling: Imposing a low-fat–high-fat–low-fat diet regimen in adult, but not juvenile, mice results in an impoverished eVAT, but not spleen, Treg compartment, accompanied by normal weight gain and glucose tolerance but profound insulin resistance. These findings point to a layered immune system, the different layers exerting specialized, nonredundant functions.
GPT-4o mini: Non-social science research article
Radiocarbon dating of Jerusalem’s Siloam Dam links climate data and major waterworks
Johanna Regev, Nahshon Szanton, Filip Vukosavović, Itamar Berko, Yiftah Shalev, Joe Uziel, Eugenia Mintz, Lior Regev, Elisabetta Boaretto
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Using well-established microarchaeological sampling methods, we reached a precise radiocarbon date of 800 BC for the Siloam Pool’s monumental water dam in Jerusalem. This date is a critical link connecting several imposing waterworks constructed at that time. Climate data pointing to droughts and flash floods during the last decades of the 9th century BC provide a logical framework for the reasons behind such endeavors. These included the fortification of the city’s primary water source, the Gihon Spring, and the redirection of the water into the city through a channel to an artificial reservoir created by building the Siloam Dam at the end of the Tyropoeon Valley, which blocked the drainage of rain and redirected spring waters.
GPT-4o mini: Non-social science research article
Magnetic decoupling as a proofreading strategy for high-yield, time-efficient microscale self-assembly
Zexi Liang, Melody Xuan Lim, Qian-Ze Zhu, Francesco Mottes, Jason Z. Kim, Livia Guttieres, Conrad Smart, Tanner Pearson, Chrisy Xiyu Du, Michael Brenner, Paul McEuen, Itai Cohen
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Life thrives due to its remarkable ability to create complex structures through the self-assembly of proteins, nucleic acids, and other biomolecules. Achieving such complex assemblies with the same level of fidelity, reproducibility, and advanced functionality in synthetic systems, however, has remained a grand challenge. One outstanding problem is the presence of parasitic products and long-lived intermediate states that slow the reaction process and limit the yield of the final product. Biology overcomes this challenge by proofreading to recognize and disassemble parasitic products. Such local checks, however, are currently difficult to implement in available self-assembly platforms. Here, we overcome this challenge by implementing a proofreading mechanism in a self-assembly platform. Specifically, we design intermediate states that strongly couple to an external force but a final product that is decoupled and thus highly stable to external driving, such that application of external forces selectively dissociates parasitic products. To implement this idea, we introduce lithographically patterned magnetic dipoles and an applied magnetic field to drive an assembly process similar to thermal self-assembly, but with additional controls. By applying patterns of magnetic driving that selectively destabilize parasitic states, we effectively implement a proofreading strategy to enable high-yield, time-efficient self-assembly. This realization of a general proofreading mechanism bridges the gap between artificial and biological self-assembly, paving the way for advanced self-assembled materials, with applications in next generation responsive materials, biomimetic devices, and microscale machines.
GPT-4o mini: Non-social science research article
STIM1 transmembrane helix dimerization captured by AI-guided transition path sampling
Ferdinand Horvath, Hendrik Jung, Herwig Grabmayr, Marc Fahrner, Christoph Romanin, Gerhard Hummer
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Stromal interaction molecule 1 (STIM1) is a Ca 2+ -sensing protein in the endoplasmic reticulum (ER) membrane. The depletion of ER Ca 2+ stores induces a large conformational transition of the cytosolic STIM1 C-terminus, initiated by the dimerization of the transmembrane (TM) domain. We use the AI-guided transition path sampling algorithm aimmd to extensively sample the dimerization of STIM1-TM helices in an ER-mimicking lipid bilayer. In nearly 0.5 ms of all-atom molecular dynamics simulations without bias potentials, we harvest over 170 transition paths, each about 1.2 ÎŒs long on average. We find that STIM1 dimerizes into three distinct and coexisting configurations, which reconciles conflicting results from earlier crosslinking studies. The dominant X-shaped bound state centers around contacts supported by the SxxxG TM interfacial motif. Mutating residues in this contact interface allows us to tune the STIM1-dimerization propensity in fluorescence experiments. From the trained model of the committor probability of dimerization, we identify the transition state ensemble for TM-helix dimerization. At the transition state, interhelical contacts in the luminal halves of the two monomers dominate, which likely enables the luminal Ca 2+ -sensing domain in STIM1 to condition the dimerization of the TM helices. Our work demonstrates the unique power of AI-guided simulations to sample rare and slow molecular transitions and to produce detailed atomistic insight into the mechanism of STIM1 TM-helix dimerization as a key step in ER Ca 2+ -sensing.
GPT-4o mini: Non-social science research article
Ovarian germline stem cell dedifferentiation is cytoneme dependent
Catherine Sutcliffe, Nabarun Nandy, Raluca Revici, Heather Johnson, Shukry J. Habib, Hilary L. Ashe, Scott G. Wilcockson
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Progenitor cell dedifferentiation is important for stem cell maintenance during tissue repair and age-related stem cell decline. Here, we use the Drosophila ovary as a model to study the role of cytonemes in bone morphogenic protein (BMP) signaling–directed germline stem cell (GSC) maintenance and dedifferentiation of germ cells to GSCs. We provide evidence that differentiating germ cell cysts extend longer cytonemes that are more polarized toward the niche during dedifferentiation to reactivate BMP signaling. The presence of additional somatic cells in the niche is associated with a failure of germ cell dedifferentiation, consistent with the formation of a physical barrier to cytoneme–niche contact and outcompetition of germ cells for BMP. Using BMP beads in vitro, we show that these are sufficient to induce cytoneme-dependent contacts in Drosophila tissue culture cells. We demonstrate that the Enabled (Ena) actin polymerase is localized to the tips of germ cell cytonemes and is necessary for robust cytoneme formation, as its mislocalization reduces the frequency, length, and directionality of cytonemes. During homeostasis, specifically perturbing cytoneme function through Ena mislocalization impairs GSC fitness by reducing GSC BMP signaling and niche occupancy. Disrupting cytonemes by targeting Ena during dedifferentiation reduces germ cell BMP responsiveness and the ability of differentiating cysts to dedifferentiate. Overall, our results provide evidence that cytonemes play a fundamental role in establishing polarized signaling and niche occupancy during stem cell maintenance and dedifferentiation.
GPT-4o mini: Non-social science research article
The Medicago truncatula lncRNA ENOD40 is a mediator of microRNA169 -controlled NF-YA activity in nodule initiation
Tristan Wijsman, Nadia A. Mohd-Radzman, Jieyu Liu, Giles E. D. Oldroyd, Wouter Kohlen, Olga Kulikova, Renze Heidstra, Ben Scheres, Henk J. Franssen
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The hallmark of the legume lncRNA EARLY NODULIN40 ( ENOD40 ), involved in rhizobium-induced nodulation, is the presence of a highly conserved stretch of 24 nucleotides, designated box2, preceded by a small open-reading-frame (sORF) coding for a peptide of 12 to 13 amino acids. Although there is a well-established link between ENOD40 and nodulation, it is not fully clear by which mechanism ENOD40 functions in this process. Here, we show that a region harboring box2 can complement nodule formation in an ENOD40 knock-out mutant ( enod40-1-2/1 ). The sequence of box2 bears the characteristics of a miR169 target mimic. We show that the artificial target mimic MIM169defg can indeed complement the reduced capability of nodule formation in enod40-1-2/1 , and that box2 exhibits target mimic activity in a transient luciferase assay. In addition, the introduction of a miR169 -resistant form of MtNF-YA1 also elevates the capacity to form nodules in enod40-1-2/1. We conclude that ENOD40 effectuates nodule initiation by posttranscriptional upregulation of the miR169 target NF-YA1 , which encodes an essential transcription factor in this step of the nodulation process.
GPT-4o mini: Non-social science research article
Laser-emitting aqueous bioreactors for ultrasensitive bioactivity analysis
Guocheng Fang, Po-Hao Tseng, Jie Liao, Song Zhu, Tian Zhou, Hangrui Liu, Hui Zhu, Dayong Jin, Lan Yang, Yu-Cheng Chen
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Water droplets, acting as natural bioreactors and optical whispering-gallery-mode (WGM) resonators, hold the potential for laser-assisted analysis. However, water/aqueous droplet lasers can only survive in air with a limited lifespan (<100 s) due to rapid evaporation, restricting their applications in bioreactions. To address this challenge, we introduce laser-emitting aqueous bioreactors (LEABs) in fluorocarbon oils. These LEABs enable stable laser emission and extend a droplet lifespan over 1,000-fold. LEABs enable the encapsulation of bioactive materials for long-term analysis with unique lasing characteristic fingerprints. The reactions within LEAB can interact with the most resonating light, enhancing detection sensitivity by over 100-fold compared to conventional WGM sensors. By integrating LEABs with microfluidic droplet technology, we demonstrated their application in monitoring enzyme activity and cellular metabolism at single-cell and multicellular levels. Furthermore, we showed the laser threshold-gated screening of single yeast. This platform can bridge the gap between laser technology and biochemical applications, broadening the scope of laser-based analysis.
GPT-4o mini: Non-social science research article
CRISPR with Transcriptional Readout reveals influenza transcription is modulated by NELF and can precipitate an interferon response
Alison C. Vicary, Sydney N. Z. Jordan, Marisa Mendes, Sharmada Swaminath, Lennice K. Castro, Justin S. Porter, Kevin D. Vo, Alistair B. Russell
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Transcription of interferons upon viral infection is critical for cell-intrinsic innate immunity. This process is influenced by many host and viral factors. To identify host factors that modulate interferon induction within cells infected by influenza A virus, we developed CRISPR with Transcriptional Readout using sequencing (CRITR-seq). CRITR-seq is a method linking CRISPR guide sequence to activity at a promoter of interest. Employing this method, we find that depletion of the Negative Elongation Factor (NELF) complex increases both flu transcription and interferon expression. We find that the process of flu transcription, both in the presence and absence of viral replication, is a key contributor to interferon induction. Taken together, our findings highlight innate immune ligand concentration as a limiting factor in triggering an interferon response, identify NELF as an important interface with the flu life cycle, and validate CRITR-seq as a tool for genome-wide screens for phenotypes of gene expression.
GPT-4o mini: Non-social science research article
Hottest year in recorded history compounds global biodiversity risks
Cory Merow, Brian S. Maitner, Andreas Schwarz Meyer, Alex L. Pigot, Josep M. Serra-Diaz, Mark C. Urban
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As climate change accelerates, effectively monitoring and managing the growing impacts on biodiversity is an urgent priority. Here, we identify the exposure of species to unprecedented heat to evaluate the potential impact of 2024—the hottest year on record—across >33,000 vertebrate species worldwide. One in six (5,368) species were exposed to unprecedented temperatures across >25% of their range—68% more species than in 2023. Most (81%) species exposed in 2023 were also exposed in 2024, potentially compounding risks. For the first time, widespread species were exposed to extreme temperatures across >10% of their ranges. We propose using these exposure estimates to inform monitoring and mitigation efforts to avoid the worst impacts of climate change.
GPT-4o mini: Non-social science research article
Correction for Sun et al., DNA2 protein destruction dictates DNA hyperexcision, cGAS–STING activation, and innate immune response in CDK12-deregulated cancers
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GPT-4o mini: Non-social science research article
CHP1 promotes lipid droplet growth and regulates the localization of key enzymes for triacylglycerol synthesis
Guang Yang, Ximing Du, Dougall Norris, Armella Zadoorian, Yuyuan Zheng, Mingming Gao, Andrew J. Brown, Shane T. Grey, Chun Zhou, Hongyuan Yang
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The glycerol-3-phosphate (G-3-P) pathway is central to the synthesis of triacylglycerols (TAGs) and glycerophospholipids, essential for membrane biogenesis and lipid storage. The first and rate-limiting step in this pathway is catalyzed by glycerol-3-phosphate acyltransferases (GPATs), with microsomal GPAT3 and GPAT4 being evolutionarily conserved and predominant in most tissues. While previous studies have implicated Calcineurin B homologous protein 1 (CHP1) as a cofactor for GPAT4, the broader role of CHP1 in regulating microsomal GPATs and TAG biosynthesis remains unclear. Here, we demonstrate that CHP1 is a critical regulator of both GPAT3 and GPAT4, essential for their stability, enzymatic activity, and lipid droplet (LD) localization. Structural modeling and mutational analyses identified key hydrophobic interfaces mediating the CHP1–GPAT interaction, which are required for optimal GPAT activity and LD growth. Loss of CHP1 impairs LD expansion and disrupts the localization of GPAT3/4 and downstream enzymes in the TAG synthesis pathway, including 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) and diacylglycerol O-acyltransferase 2 (DGAT2). Mechanistically, CHP1 helps circumvent seipin-mediated restriction of late LD-targeting enzymes, facilitating their access to mature LDs. Together, our findings reveal CHP1 as a dual-function regulator that stabilizes and activates microsomal GPATs while enabling the coordinated recruitment of TAG biosynthetic enzymes to LDs. This work uncovers a previously unrecognized mechanism for regulating LD growth and glycerolipid metabolism, with broad implications for lipid homeostasis and metabolic diseases.
GPT-4o mini: Non-social science research article
Coordinated actions of NLR-assembled and glutamate receptor–like calcium channels in plant effector-triggered immunity
Junli Wang, Xinhua Sun, Fei Xiong, Dmitry Lapin, Tak Lee, Sergio Martin-Ramirez, Anna Prakken, Qiaochu Shen, Jaqueline Bautor, Takaki Maekawa, Jane E. Parker
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The plant immune system utilizes nucleotide-binding/leucine-rich repeat (NLR) proteins to detect pathogen virulence factors (effectors) inside host cells and transduce recognition to rapid defense. In dicotyledenous plants, pathogen activated Toll-like/interleukin-1 receptor-containing NLRs (TNLs) establish a signaling network of enhanced susceptibility 1 (EDS1)-family dimers with RPW8-type coiled-coil (CC R ) domain NLRs (RNLs) to stimulate transcriptional reprogramming leading to host cell death and pathogen restriction. Evidence suggests that TNL- and EDS1-activated RNLs function as oligomeric Ca 2+ permeable ion channels at the plasma membrane. However, the downstream processes for immunity execution are poorly understood. Here, we studied pathogen effector-triggered immunity conferred by Nicotiana benthamiana TNL (Roq1) which signals almost exclusively through the EDS1-senescence associated gene101 (SAG101)-N required gene 1 (NRG1) RNL module. We identify a pair of glutamate receptor–like Ca 2+ ion channels (GLR2.9a and GLR2.9b) which, unlike most other pathogen-induced GLRs, are highly up-regulated by the EDS1-SAG101-NRG1 module in the TNL immune response. We show that oligomeric NRG1 Ca 2+ channel activity is necessary for GLR2.9a and GLR2.9b induced expression. Consequently, GLR2.9a and GLR2.9b proteins contribute to NRG1 -dependent Ca 2+ accumulation in host cells, and to pathogen resistance and host cell death. We establish that GLR2.9a localizes mainly to the plasma membrane/cytoplasm whereas GLR2.9b accumulates preferentially at the nuclear envelope. The data show that transcriptionally up-regulated canonical Ca 2+ ion channels GLR2.9a and GLR2.9b are a functional output of the EDS1-SAG101-NRG1 module for TNL-triggered immunity.
GPT-4o mini: Non-social science research article
Reply to Cummins et al.: GPT reveals cognitive dissonance that is both irrational and alarmingly humanlike
Steven A. Lehr, Ketan S. Saichandran, Eddie Harmon-Jones, Nykko Vitali, Mahzarin R. Banaji
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GPT-4o mini: Non-social science research article
Ice as a kinetic and mechanistic driver of oxalate-promoted iron oxyhydroxide dissolution
Angelo P. Sebaaly, Frank van Rijn, Khalil Hanna, Jean-François Boily
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Ice often mediates unexpected reactions in the Cryosphere, acting as a fascinating geochemical reactor. Mineral–organic interactions in frozen environments, such as soils and permafrost, are crucial for explaining the flux of soluble iron during melting events, yet the mechanisms remain misunderstood. This study elucidates the unique roles of freezing in the dissolution of iron oxyhydroxide nanoparticles (α–FeOOH) by oxalate, a low molecular weight dicarboxylate, under acidic conditions. From time-resolved experiments conducted over 4 d, we demonstrate that soluble iron was released through reactions in minute volumes of liquid water trapped between ice micrograins. Freeze concentration of nanoparticles, oxalate, and protons into this liquid water drove oxalate- and proton-promoted dissolution reactions at temperatures as low as −30 °C. Remarkably, ice at −10 °C dissolved more iron than liquid water at 4 °C under high oxalate loadings, and even more than at 25 °C under low oxalate loadings. In contrast, high salinity subdued dissolution. Also, sequential freeze-thaw cycles enhanced dissolution by releasing unreacted oxalate that was previously locked in ice. By resolving the chemical controls on mineral dissolution in ice, this work can help explain how freeze-thaw events are supplying new fluxes of soluble iron to nature.
GPT-4o mini: Non-social science research article
Echoes in AI: Quantifying lack of plot diversity in LLM outputs
Weijia Xu, Nebojsa Jojic, Sudha Rao, Chris Brockett, Bill Dolan
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With rapid advances in large language models (LLMs), there has been an increasing application of LLMs in creative content ideation and generation. A critical question emerges: can current LLMs provide ideas that are diverse enough to truly bolster collective creativity? We examine two state-of-the-art LLMs, GPT-4 and LLaMA-3, on story generation and discover that LLM-generated stories often consist of plot elements that are echoed across a number of generations. To quantify this phenomenon, we introduce the Sui Generis score, an automatic metric that measures the uniqueness of a plot element among alternative storylines generated using the same prompt under an LLM. Evaluating on 100 short stories, we find that LLM-generated stories often contain combinations of idiosyncratic plot elements echoed frequently across generations and across different LLMs, while plots from the original human-written stories are rarely recreated or even echoed in pieces. Moreover, our human evaluation shows that the ranking of Sui Generis scores among story segments correlates moderately with human judgment of surprise level, even though score computation is completely automatic without relying on human judgment.
GPT-4o mini: Non-social science research article
Hippocampal mismatch signals are based on episodic memories and not schematic knowledge
Dominika K. Varga, Petar P. Raykov, Elizabeth Jefferies, Aya Ben-Yakov, Chris M. Bird
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Prediction errors drive learning by signaling mismatches between expectations and reality, but the neural systems supporting these computations remain debated. The hippocampus is implicated in mismatch detection, yet it is not known whether it signals mismatches with episodic memories or generalized knowledge. Across three functional Magnetic Resonance Imaging (fMRI) experiments, we show that the hippocampus selectively responds to mismatches with episodic memories of specific events. In contrast, schematic mismatches engage Semantic Control and Multiple Demand Networks, as well as subcortical regions linked to prediction error signaling. Episodic mismatches also recruit the Default Mode Network. These findings challenge accounts that propose the hippocampus is a domain-general mismatch detector. Instead, the findings support a more specialized role for the hippocampus in learning that is underpinned by its well-established importance in processing episodic memories.
GPT-4o mini: Non-social science research article
Mid-Devonian ocean oxygenation enabled the expansion of animals into deeper-water habitats
Kunmanee Bubphamanee, Michael A. Kipp, Jana MeixnerovĂĄ, Eva E. StĂŒeken, Linda C. Ivany, Alexander J. Bartholomew, Thomas J. Algeo, Jochen J. Brocks, Tais W. Dahl, Jordan Kinsley, François L. H. Tissot, Roger Buick
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The oxygenation history of Earth’s surface environments has had a profound influence on the ecology and evolution of metazoan life. It was traditionally thought that the Neoproterozoic Oxygenation Event enabled the origin of animals in marine environments, followed by their persistence in aerobic marine habitats ever since. However, recent studies of redox proxies (e.g., Fe, Mo, Ce, I) have suggested that low dissolved oxygen levels persisted in the deep ocean until the Late Devonian, when the first heavily wooded ligniophyte forests raised atmospheric O 2 to modern levels. Here, we present a Paleozoic redox proxy record based on selenium enrichments and isotope ratios in fine-grained siliciclastic sediments. Our data reveal transient oxygenation of bottom waters around the Ediacaran–Cambrian boundary, followed by predominantly anoxic deep-water conditions through the Early Devonian (419 to 393 Ma). In the Middle Devonian (393 to 382 Ma), our data document the onset of permanent deep-ocean oxygenation, coincident with the spread of woody biomass across terrestrial landscapes. This episode is concurrent with the ecological occupation and evolutionary radiation of large active invertebrate and vertebrate organisms in deeper oceanic infaunal and epifaunal habitats, suggesting that the burial of recalcitrant wood from the first forests sequestered organic carbon, increased deep marine oxygen levels, and was ultimately responsible for the “mid-Paleozoic marine revolution.”
GPT-4o mini: Non-social science research article
Replay in the human visual cortex during brief task pauses is linked to implicit learning of successor representations
Lennart Wittkuhn, Lena M. Krippner, Christoph Koch, Nicolas W. Schuck
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Humans can implicitly learn about multistep sequential relationships between events in the environment from their statistical co-occurrence. Theoretical work has suggested that neural replay is a candidate mechanism that aids such learning. Here, we used functional MRI (fMRI) to test whether replay is related to implicit learning of higher-order sequential relationships. Human participants viewed sequences of images that followed probabilistic transitions determined by ring-like graph structures. Behavioral modeling of response times revealed that participants acquired multistep transition knowledge in a manner consistent with gradual updating of an internal successor representation (SR) model. Yet, half of participants did not report being aware of any sequential task structure, and most participants failed to provide meaningful transition probability ratings in a posttask test. Analyses of temporal dynamics of multivariate fMRI patterns during brief 10 s pauses from the ongoing statistical learning task indicated backward sequential replay of multistep sequences in visual cortical areas. Variations in model parameters between participants that captured response time patterns related to strength of neural replay. No corresponding relations between replay and measures of explicit awareness were found. These findings indicate that implicit learning of higher-order relationships establishes an internal SR-based map of the task and is accompanied by cortical on-task replay.
GPT-4o mini: Non-social science research article
Parallel trade-offs in human cognition and neural networks: The dynamic interplay between in-context and in-weight learning
Jacob Russin, Ellie Pavlick, Michael J. Frank
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Human learning embodies a striking duality: Sometimes, we can rapidly infer and compose logical rules, benefiting from structured curricula (e.g., in formal education), while other times, we rely on an incremental approach or trial-and-error, learning better from curricula that are randomly interleaved. Influential psychological theories explain this seemingly conflicting behavioral evidence by positing two qualitatively different learning systems—one for rapid, rule-based inferences (e.g., in working memory) and another for slow, incremental adaptation (e.g., in long-term and procedural memory). It remains unclear how to reconcile such theories with neural networks, which learn via incremental weight updates and are thus a natural model for the latter, but are not obviously compatible with the former. However, recent evidence suggests that metalearning neural networks and large language models are capable of in-context learning (ICL)—the ability to flexibly infer the structure of a new task from a few examples. In contrast to standard in-weight learning (IWL), which is analogous to synaptic change, ICL is more naturally linked to activation-based dynamics thought to underlie working memory in humans. Here, we show that the interplay between ICL and IWL naturally ties together a broad range of learning phenomena observed in humans, including curriculum effects on category-learning tasks, compositionality, and a trade-off between flexibility and retention in brain and behavior. Our work shows how emergent ICL can equip neural networks with fundamentally different learning properties that can coexist with their native IWL, thus offering an integrative perspective on dual-process theories of human cognition.
GPT-4o mini: Non-social science research article
Migration shapes senescence in a long-lived bird
Hugo Cayuela, SĂ©bastien Roques, Antoine Arnaud, Christophe Germain, Arnaud BĂ©chet, Jocelyn Champagnon
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Each year, billions of animals migrate across the globe on diverse spatial and temporal scales. Migration behavior thus plays a fundamental role in the life cycle and Darwinian fitness of many organisms. While the influence of migration on early-life survival and reproduction is well documented, its effects on senescence (aging) in advanced age remain largely unexplored. Using a unique 44-y ring-resighting dataset from a long-lived, partially migratory bird species, the Greater Flamingo ( Phoenicopterus roseus ), we demonstrate that migration plays a key role in shaping age-specific trajectories of mortality and reproduction. Resident flamingos exhibit higher early-life demographic performances, with lower baseline mortality than migrants, resulting in longer adult lifespan. Residents also have a higher probability of breeding than migrants, though their breeding success is similar. However, residents seem to pay for their early-life advantages in old age, experiencing accelerated actuarial and reproductive senescence compared to migrants. Overall, our study highlights the critical impact of migration on survival and reproduction throughout life, thereby illustrating the role played by behavioral decisions in the biology of aging in long-lived vertebrates.
GPT-4o mini: Non-social science research article
Single-strand DNA is the link between neutrophil extracellular traps and thrombin
Craig Jenne, Paul Kubes
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GPT-4o mini: Non-social science research article
Cognitive dissonance in large language models is neither cognitive nor dissonant
Jamie Cummins, Malte Elson, Ian Hussey
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GPT-4o mini: Non-social science research article
Shared metabolism between a bacterial and fungal species that reside in the human gut
Haley Gause, Alexander D. Johnson
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The fungal species Candida albicans and the bacterium Enterococcus faecalis are members of the human gut microbiome. To explore the range of interactions between these two species, we utilized dual RNA-sequencing to transcriptionally profile both C. albicans and E. faecalis during coculture (compared with monoculture controls) under two conditions: 1) an in vitro setting that mimics certain features of the gut environment and 2) a gnotobiotic mouse gut model. RNA-seq analysis revealed a large number of gene expression changes induced by one species in the presence of the other. More specifically, both species highly upregulate citrate-metabolizing genes during coculture: C. albicans upregulates CIT1 (citrate synthase) which produces citrate, while E. faecalis upregulates its cit operon, which breaks down citrate. In vitro analysis showed directly that citrate cross-feeding (production of citrate by C. albicans and breakdown by E. faecalis) enhances growth of E. faecalis . A main byproduct of citrate metabolism in E. faecalis is formate, a short chain fatty acid toxic to fungi. Our RNA profiling revealed that C. albicans upregulates three formate dehydrogenases (FDHs) during coculture; we show that the FDH genes confer a growth advantage to C. albicans when E. faecalis (or simply formate) is present. These findings reveal a metabolically driven cycle between C. albicans and E. faecalis in the mouse gut and in vitro, where cross-feeding of citrate and detoxification of formate facilitates the growth of both species when they are cultured together.
GPT-4o mini: Non-social science research article
Correction for Jankovic et al., Wireless arm-worn bioimpedance sensor for continuous assessment of whole-body hydration
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GPT-4o mini: Non-social science research article
SHP2 genetic variants in NSML-associated RASopathies disrupt the PZR–IRX transcription factor signaling axis
Sravan Perla, Amy L. Stiegler, Jae-Sung Yi, Liz Enyenihi, Lei Zhang, Muhammad Riaz, Elvira An, Yibing Qyang, Titus J. Boggon, Anton M. Bennett
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Noonan syndrome with multiple lentigines (NSML) is a rare autosomal dominant disorder caused by mutations in PTPN11 (protein tyrosine phosphatase nonreceptor type 11) which encodes for the protein tyrosine phosphatase, SHP2. Approximately 85% of NSML patients develop hypertrophic cardiomyopathy (HCM). Here, we show that SHP2 is recruited to tyrosyl phosphorylated protein-zero related (PZR) in NSML mice. This recruitment is required for the Iroquois homeobox (IRX) transcription factors 3 and 5 to suppress BMP10 which negatively regulates postnatal cardiac growth. The protein expression of IRX3 and IRX5 was elevated in hypertrophied NSML hearts. IRX3 and IRX5 upregulation was rescued in NSML mice harboring a knock-in mutation of PZR that fails to become tyrosyl phosphorylated and recruit SHP2. NSML mice treated with low-dose dasatinib also exhibited normalized IRX3 and IRX5 expression levels. Consistent with this, BMP10 expression levels were reduced in NSML mice and rescued in PZR tyrosyl phosphorylation-deficient and low-dose dasatinib-treated NSML mice. A crystal structure of the tandem SH2 domains of SHP2 bound to tyrosyl phosphorylated PZR reveals that recruitment constrains the open SHP2 conformation to facilitate cellular-Src (c-Src) binding. Disruption of c-Src binding to SHP2 abolished IRX activation and failure to suppress BMP10. Hence, NSML-associated SHP2 genetic variants disrupt IRX transcription factor signaling to BMP10, implicating this axis as a target for RASopathy-associated HCM.
GPT-4o mini: Non-social science research article
Broad neutralizing antibody response of a monomeric spike–based SARS-CoV-2 bivalent vaccine against diverse variants
Siling Wang, Hui Sun, Yizhen Wang, Zikang Wang, Lunzhi Yuan, Huilin Guo, Jiahua Gao, Miaolin Lan, Yangtao Wu, Huixian Shang, Xiuting Chen, Zheng Chen, Jiayi Hu, Zimin Tang, Guiping Wen, Dong Ying, Chang Liu, Yanan Jiang, Jinfu Su, Min Lin, Ting Wu, Shaowei Li, Tianying Zhang, Jun Zhang, Yi Guan, Ningshao Xia, Quan Yuan, Qingbing Zheng, Yali Zhang, Zizheng Zheng
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severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) bivalent vaccines show potential against variants but lack a full understanding of the immunological mechanisms that drive broadly neutralizing antibodies (bnAbs). This study explored the immunogenicity of a bivalent vaccine in rhesus macaques, containing spike (S) proteins from the prototype (S prototype ) and chimeric S protein (S 1628x ). The vaccine induced bnAbs against multiple variants, including challenging subvariants like EG.1, BA.2.86, and JN.1. The monomeric S protein exposed less accessible regions within the receptor-binding domain (RBD) “inner face” and “NTD face” and subdomains 1, eliciting a diverse array of bnAbs against various Omicron subvariants. Notably, antibodies targeting the conserved RBD inner face, such as 4A5, showed potent neutralization across all tested variants. Structural analyses provide insights into the broad protectiveness of these vaccine-elicited nAbs. This study underscores the potential of bivalent vaccines with monomeric spike proteins to confer broad-spectrum immunity, offering a promising direction for future SARS-CoV-2 universal vaccine design.
GPT-4o mini: Non-social science research article
9,000-year-old barley consumption in the foothills of central Asia
Xinying Zhou, Robert N. Spengler, Bahediyoh Sayfullaev, Khasanov Mutalibjon, Jian Ma, Junchi Liu, Hui Shen, Keliang Zhao, Guanhan Chen, Jian Wang, Thomas A. Stidham, Hai Xu, Guilin Zhang, Qingjiang Yang, Yemao Hou, Jiacheng Ma, Nasibillo Kambarov, Hongen Jiang, Farhod Maksudov, Steven Goldstein, Jianxin Wang, Dorian Q. Fuller, Xiaoqiang Li
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Scholars are increasingly favoring models for the origins of agriculture that involve a protracted process of increasing interdependence within a series of mutualistic relationships between humans and plants, as opposed to a rapid single event or innovation. Nonetheless, these scholars continue to debate over when people first started foraging for grass seeds, when they began to readily utilize sickles, how prominent the early selection pressures were, and when the first traits of domestication fully introgressed into the cultivated grass population. Here, we present complementary archaeobotanical and archaeological (stone tool) evidence for cereal foragers from Toda-1 Cave in the Surkhan Darya, dating to 9200 cal BP. We conclude that early Holocene foragers were processing grains along with nuts and fruits as far north as the rich river valleys of southern Uzbekistan. These data expand the known range that preagricultural cereal foragers covered in the early Holocene, adding to our understanding of the cultural processes that led to farming. Additionally, we present the earliest evidence for people interacting with the progenitors for pistachios and apples (or a close apple relative). The complex foraging behaviors that led to cultivation were being undertaken by people during the early Holocene across a wider area of Eurasia than previously thought.
GPT-4o mini: Non-social science research article
Abiotic synthesis during the interaction of ferrous chloride–rich silicic fluids with marble under high-grade metamorphic conditions
Chenhui Fei, Shun Guo, Yibing Li, Jingbo Liu
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Ferrous chloride–rich silicic fluid and melt infiltration led to the decarbonation of dolomitic marble in the Chinese Sulu ultrahigh-pressure metamorphic terrain under temperatures ranging from 670 to 800 °C, pressures from the aragonite + albite to calcite stability fields and the oxygen fugacities between the hematite–magnetite and pyrite–pyrrhotite–magnetite buffers, resulting in the formation of olivine marble and diopsidite. The inclusions in zircons trapped during the decarbonation process suggest that the H 2 -producing reaction 3FeCl 2 (aq) + 3CaCO 3 + H 2 O = Fe 3 O 4 (magnetite) + 3CaCl 2 (aq) + 3CO 2 + H 2 occurred and that it induced magnetite-catalyzed Fischer–Tropsch-type synthesis, as indicated by the presence of whewellite, disordered carbonaceous material, CH 4 , and CO in the inclusions. The results of this study highlight the role of aqueous Fe in generating H 2 and magnetite and have far-reaching implications for carbon speciation and solubility in deep fluids and for endogenic abiotic synthesis, which may be pivotal in the prebiotic occurrence of organic compounds on Earth.
GPT-4o mini: Non-social science research article
Quantum metric–induced giant and reversible nonreciprocal transport phenomena in chiral loop-current phases of kagome metals
Rina Tazai, Youichi Yamakawa, Takahiro Morimoto, Hiroshi Kontani
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Emergence of quantum orders with nontrivial quantum geometric properties in metals represent central issues in condensed matter physics. In this context, recently discovered chiral loop-current order in kagome metals has garnered significant attention. Particularly noteworthy is the giant electrical magnetochiral anisotropy (eMChA) observed in CsV 3 Sb 5 , which provides compelling evidence for the simultaneous breaking of time-reversal and inversion symmetries. However, the origin of the eMChA and its fundamental connection to the loop-current remain highly elusive, as the loop-current itself preserves inversion symmetry. Here, we demonstrate that the loop-current phase breaks inversion symmetry in the presence of the experimentally observed stripe charge-density wave, leading to finite eMChA coefficient Îł eM . In this mechanism, Îł eM is proportional to the product of the loop-current-induced orbital magnetization, M orb 0 , and the lifetime of conduction electrons, τ . Therefore, Îł eM is reversible by the magnetic fields, and it takes large value in kagome metals with τ v Fermi ≫ a 0 (=lattice constant). Surprisingly, the quantum metric, which defines a fundamental geometric aspect of Bloch wavefunctions, acquires significant momentum dependence in the loop-current phase, resulting in a dramatic enhancement of eMChA by ∌100 times. This research not only clarifies the fundamental symmetry-breaking states in kagome metals but also opens a path for exploring quantum metric–induced phenomena arising from exotic quantum phase transitions in various metals.
GPT-4o mini: Non-social science research article
Symbiosis with and mimicry of corals were facilitated by immune gene loss and body remodeling in the pygmy seahorse
Meng Qu, Yingyi Zhang, Joost Woltering, Yali Liu, Zixuan Liu, Shiming Wan, Han Jiang, Haiyan Yu, Zelin Chen, Xin Wang, Zhixin Zhang, Geng Qin, Ralf Schneider, Axel Meyer, Qiang Lin
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A remarkable example of symbiosis involves the pygmy seahorse ( Hippocampus bargibanti ). It lives obligatorily on gorgonian corals, mimicking their polyps with pink coloration and skin protuberances. Unique for seahorses, pygmy seahorses retain juvenile paedomorphic stunted snouts, resembling the coral’s polyps. We analyzed the tiny seahorse’s genome revealing the genomic bases of several adaptations to their mutualistic life including substantial reductions in conserved noncoding elements that are associated with genes in the vicinity of those CNEs that are known to play a role in growth and metamorphosis-related pathways. Comparative RNA- and ATAC-Seq analyses during their ontogeny suggest that their stunted snout might result from craniofacial remodeling associated with hoxa2b defunctionalization. This is consistent also with findings from in situ hybridization and CRISPR experiments. Their immune system shows extremely low numbers of MHC genes and additional considerable losses of other immune-related genes. This is likely facilitated by the host coral’s antimicrobial metabolites and by the earlier evolution of male pregnancy that requires immunotolerance.
GPT-4o mini: Non-social science research article
Cellular cartography reveals mouse prostate organization and determinants of castration resistance
Hanbyul Cho, Yuping Zhang, Jean C. Tien, Rahul Mannan, Jie Luo, Sathiya Pandi Narayanan, Somnath Mahapatra, Jing Hu, Greg Shelley, Gabriel Cruz, Miriam Shahine, Lisha Wang, Fengyun Su, Rui Wang, Xuhong Cao, Saravana Mohan Dhanasekaran, Evan T. Keller, Sethuramasundaram Pitchiaya, Arul M. Chinnaiyan
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Inadequate response to androgen deprivation therapy (ADT) frequently arises in prostate cancer, driven by cellular mechanisms that remain poorly understood. Here, we integrated single-cell RNA sequencing, single-cell multiomics, and spatial transcriptomics to define the transcriptional, epigenetic, and spatial basis of cell identity and castration response in the mouse prostate. Leveraging these data along with a meta-analysis of human prostates and prostate cancer (PCa), we identified cellular orthologs and key determinants of ADT response and resistance. Our findings reveal that mouse prostates harbor lobe-specific luminal epithelial cell types distinguished by unique gene regulatory modules and anatomically defined androgen-responsive transcriptional programs, indicative of divergent developmental origins. Androgen-insensitive, stem-like epithelial populations—resembling human club and hillock cells—are notably enriched in the urethra and ventral prostate but are rare in other lobes. Within the ventral prostate, we also uncovered two additional androgen-responsive luminal epithelial cell types, marked by Pbsn or Spink1 expression, which align with human luminal subsets and may define the origin of distinct PCa subtypes. Castration profoundly reshaped luminal epithelial transcriptomes, with castration-resistant luminal epithelial cells activating stress-responsive and stemness programs. These transcriptional signatures are enriched in tumor cells from ADT-treated and castration-resistant PCa patients, underscoring their likely role in driving treatment resistance. Temporal tracking of cells will precisely map disease-associated cellular transitions, and our technical framework facilitates such interrogations. Collectively, our comprehensive cellular atlas of the mouse prostate illuminates the importance of lobe-specific contexts for PCa modeling and reveals potential therapeutic targets to counter castration resistance.
GPT-4o mini: Non-social science research article
Interfacial electroneutrality controls transport of asymmetric salts through charge-patterned mosaic membranes
Feng Gao, John R. Hoffman, Jialing Xu, Anton V. Ievlev, Jonathan K. Whitmer, William A. Phillip
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Membranes that selectively enhance target solute permeation while rejecting competing species are essential for precision separations. This study introduces charge-patterned mosaic membranes (CMMs) that selectively transport divalent asymmetric salts by leveraging a net-neutral membrane–solution interface. This mechanism, dictated by the charge ratio of positive and negative domains on the membrane surface and the balance of cations and anions in the salt, is supported by analytical, numerical, and experimental results. Analytical solutions identified cationic domain coverages ( f + ) of 33%, 50%, and 66% as optimal for the selective transport of +2:−1 salts, +1:−1 salts, and +1:−2 salts, respectively, under conditions where the pattern size ( L ) is significantly larger than the Debye length. Numerical simulations and experiments using CMMs with alternating charged-stripes inkjet-printed onto nanostructure copolymer substrates confirmed these findings. By varying stripe widths to control f + , pressure-driven filtration experiments demonstrated selective enrichment of MgCl 2 and K 2 SO 4 at the predicted f + values, with deviations from these values leading to salt rejection. These results highlight the pivotal role of a net-neutral interface in enabling asymmetric salt enrichment. This study positions CMMs as a versatile platform for tuning ion selectivity, addressing challenges in resource recovery, water treatment, and precision separations.
GPT-4o mini: Non-social science research article
Thermodynamics of calcium binding to heparin: Implications of solvation and water structuring for polysaccharide biofunctions
Brenna M. Knight, Connor M. B. Gallagher, Michael D. Schulz, Kevin J. Edgar, Caylyn D. McNaul, Christina A. McCutchin, Patricia M. Dove
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Heparan sulfates are found in all animal tissues and have essential roles in living systems. This family of biomacromolecules modulates binding to calcium ions (Ca 2+ ) in low free energy reactions that influence biochemical processes from cell signaling and anticoagulant efficacy to biomineralization. Despite their ubiquity, the thermodynamic basis for how heparans and similarly functionalized biomolecules regulate Ca 2+ interactions is not yet established. Using heparosan (Control) and heparins with different positions of sulfate groups, we quantify how SO 3 − and COO − content and SO 3 − position modulate Ca 2+ binding by isothermal titration calorimetry. The free energy of all heparin-Ca 2+ interactions (Δ G rxn ) is dominated by entropic contributions due to favorable water release from polar, hydrophilic groups. Heparin with both sulfate esters ( O -SO 3 − ) and sulfamides ( N -SO 3 − ) has the strongest binding to Ca 2+ compared to heparosan and to heparin with only O -SO 3 − groups (~3X). By linking Ca 2+ binding thermodynamics to measurements of the interfacial energy for calcite (CaCO 3 ) crystallization onto polysaccharides, we show molecule-specific differences in nucleation rate can be explained by differences in water structuring during Ca 2+ interactions. A large entropic term (- T Δ S rxn ) upon Ca 2+ –polysaccharide binding correlates with high interfacial energy to CaCO 3 nucleation. Combining our measurements with literature values indicates many Ca 2+ –polysaccharide interactions have a shared thermodynamic signature. The resulting enthalpy–entropy compensation relationship suggests these interactions are generally dominated by water restructuring involving few conformational changes, distinct from Ca 2+ –protein binding. Our findings quantify the thermodynamic origins of heparin-specific interactions with Ca 2+ and demonstrate the contributions of solvation and functional group position during biomacromolecule-mediated ion regulation.
Early-life infectious disease exposure, the “hygiene hypothesis,” and lifespan: Evidence from hookworm disease
Ralph Lawton
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Exposure to infectious disease in early life may have long-term ramifications for health and lifespan. However, reducing pathogen exposure may not be uniformly beneficial. The rise of modern sanitation and reduction of infectious diseases has been implicated in increasing levels of allergy and immune dysregulation: termed, the “hygiene hypothesis.” This study leverages quasi-experimental variation from combining precampaign hookworm exposure with the Rockefeller Sanitary Commission’s deworming campaign in the early 20th century to rigorously examine the impacts of childhood hookworm exposure on adult lifespan and morbidity. Findings show deworming before age five leads to 2.5 additional months of life in a large sample of adult death records. Further, decreasing hookworm exposure is related to improvements in biomarkers for inflammation and skin-tested allergies, in contrast to predictions of the “hygiene hypothesis.” Placebo tests using health outcomes that should not be affected by deworming do not show similar patterns. Overall, childhood deworming leads to improvements in morbidity and lifespan decades later.
Ingroup solidarity drives social media engagement after political crises
Malia Marks, Yara Kyrychenko, Johan GĂ€rdebo, Jon Roozenbeek
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Social media are often said to exacerbate polarization by platforming hostility between groups. However, positive social emotions like ingroup solidarity may also drive social media engagement, particularly after major threats such as military invasions or terror attacks. In this preregistered study, we examine the socioemotional drivers of engagement following group threats in the context of the US 2024 presidential campaign trail, where both major political parties faced crises in July of 2024. We test how ingroup solidarity and outgroup hostility predicted social media users’ engagement with 62,118 posts by 484 US partisan accounts before and after the first Trump assassination attempt (July 13) and Biden’s re-election campaign suspension (July 21). We find that, while outgroup hostility is typically the dominant predictor of engagement, interactions with ingroup solidarity surged among Republicans after the Trump shooting and among Democrats after Biden’s withdrawal. We show that negativity toward other groups is not always key to going viral. Rather, positive ingroup emotions appear to play a leading role in times of crisis.
Communication increases cooperation among students in a coordination game
Elizabeth T. Hallers-Haalboom, Kris J. M. De Jaegher, Elisabeth H. M. Sterck, Sarah F. Brosnan, Marjolijn M. Vermande
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Cooperation often requires individuals to balance personal risk with mutual gain. The Stag Hunt game provides a well-established paradigm for studying such decision-making. Prior research suggested that verbal communication about the game correlated with participants finding the optimal coordinated solution, but these studies either did not manipulate communication directly or informed participants of the payoff structure in advance. This study examined whether communication improves cooperative decision-making among college students under conditions in which the payoff structure had to be inferred through repeated play. A total of 127 same-sex dyads ( M age = 22.8 y, 51.2% female) played 40 rounds of an online Stag Hunt game, with dyads randomly assigned to either a no communication or communication condition. Participants were not informed about the game’s payoff structure in advance and had to infer it during play. Results showed that coordination on the payoff-dominant outcome (Stag–Stag) increased across trials, but only when communication was possible. No significant sex differences were observed. These findings highlight the central role of communication in fostering cooperation, particularly in environments in which information must be jointly discovered. This is an important consideration for developing and interpreting future research. Moreover, subsequent research should explore how the content, timing, and relevance of communication shape cooperative outcomes over time.
Chants across seven traditions share acoustic traits that enhance subjective relaxation
Valentina Canessa-Pollard, Andrey Anikin, David Reby
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For over 5,000 y, chanting has been practiced across many Western and Eastern traditions. However, there is hardly any empirical research on 1) whether chants from across the globe share common acoustic properties, 2) whether these acoustic features make them distinct from other human vocalizations, and 3) the extent to which they may positively impact listeners’ well-being. Here, we collected 242 chants belonging to seven distinct traditions and associated with a wide range of language families, and compared them acoustically to a large corpus of song (n = 126) and speech (n = 616) samples from across 14 linguistic and 12 geographical regions. We show that, irrespective of language and geographical origin, chants share distinctive acoustic traits, namely relatively flat and slow-changing intonation and steady, unbroken voicing in a comfortable, rather low pitch range with a prevalence of mid-central vowels. Thus, chants are produced in a relaxed vocal tract configuration with minimal articulation. Additionally, playback experiments involving original chants (with a participant pool of 61 listeners), resynthesized chants (with 114 listeners), and fully synthetic chants (with 80 listeners) demonstrate that these acoustic characteristics enhance listeners’ perceived sensations of relaxation. Specifically, relatively flat and slow-changing intonation, combined with vowel production in a relatively relaxed vocal tract configuration, resulted in higher overall relaxation ratings. Together these results hint at a specific function of chants’ acoustic commonalities: the enhancement of well-being through relaxation.
An exploration of basic human values in 38 million obituaries over 30 years
David M. Markowitz, Thomas Mazzuchi, Stylianos Syropoulos, Kyle Fiore Law, Liane Young
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How societies remember the dead can reveal what people value in life. We analyzed 38 million obituaries from the United States to examine how personal values are encoded in individual and collective legacies. Using Schwartz’s theory of basic human values, we found that tradition and benevolence dominated legacy reflections, while values like power and stimulation appeared less frequently. Major cultural events—the terrorist attacks of September 11th, the 2008 financial crisis, and the COVID-19 pandemic—were systematically linked to changes in legacy reflections about personal values, with security declining after 9/11, achievement declining after the financial crisis, and benevolence declining for years after COVID-19 began and, to date, not yet returning to baseline. Gender and age of the deceased were also linked to differences in legacy: Men were remembered more for achievement , power , and conformity , while women were remembered more for benevolence and hedonism . Older people were remembered more for tradition and conformity than younger people. These patterns shifted dynamically across the lifespan, with obituaries for men showing more age-related variation than legacies for women. Our findings reveal how obituaries serve as psychological and cultural time capsules, preserving not just individual legacies, but also indicating what US society values collectively regarding a life well lived.
Mass support for conserving 30% of the Earth by 2030: Experimental evidence from five continents
Patrik Michaelsen, Aksel Sundström, Sverker C. Jagers
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Rapid global expansion of protected areas is critical for safeguarding biodiversity but depends on political action for successful implementation. Following widespread ratification of the Kunming-Montreal Global Biodiversity Framework, an unprecedented increase in area-based conservation is required to reach its target of conserving 30% of land, waters, and seas by 2030. These expansions prompt difficult trade-offs between conservation, social, and economic interests. A key factor in securing legitimacy and practical feasibility for expansion regimes is understanding what factors determine public support for them. Using survey and experimental data, we show that in eight countries across five continents, public opinion is 1) strongly in favor of the “30-by-30”-target and 2) highly consistent regarding policy priorities for the design of international- and domestic-level expansion regimes. We find that for international-level policy regimes, support increases with protection responsibilities equally split between countries, rich countries bearing higher costs, more countries actively cooperating, and placement trade not allowed. For domestic-level policy regimes, support generally increases when nature values are prioritized over social or economic values and, in many countries, decreases when costs are borne by a general tax increase, parks are managed by private companies, and when access to parks is restricted. Together, these results demonstrate how protected area expansion policies can be shaped to facilitate reaching 30% protected areas by 2030.
To implement the Belém Declaration, we need a structured and collaborative approach
SofĂ­a LĂłpez-Cubillos, Natalie Mason, Brendan Wintle, Pablo Pacheco, Jose Manuel Ochoa-Quintero, NathĂĄlia Nascimento, Bolier Torres, Rebecca K. Runting
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Using large language models to categorize strategic situations and decipher motivations behind human behaviors
Yutong Xie, Qiaozhu Mei, Walter Yuan, Matthew O. Jackson
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By varying prompts to a large language model, we can elicit the full range of human behaviors in a variety of different scenarios in classic economic games. By analyzing which prompts elicit which behaviors, we can categorize and compare different strategic situations, which can also help provide insight into what different economic scenarios might induce people to think about. We discuss how this provides a step toward a nonstandard method of inferring (deciphering) the motivations behind the human behaviors. We also show how this deciphering process can be used to categorize differences in the behavioral tendencies of different populations.
The nonadaptive advantage: Why our brains can’t quit gaming
Leanne Chukoskie, Casper Harteveld
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Science

GPT-4o mini: Non-social science research article
Deciphering icosahedra structural evolution with atomically precise silver nanoclusters
Feng Hu, Gaoyuan Yang, Lu-Ming Zheng, Gui-Jie Liang, Quan-Ming Wang
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Determining the atomic structure of nanoparticles (NPs) is critical for understanding their structural evolution and properties. However, controlling the growth of multiply-twinned metal NPs remains challenging because of numerous competing pathways. In this work, we report the synthesis of two giant silver icosahedral nanoclusters, [Ag 213 (C≡CR1) 96 ] 5− and [Ag 429 Cl 24 (C≡CR2) 150 ] 5− (Ag 213 and Ag 429 , R1 =3,4,5-F 3 C 6 H 2 and R2 = 4-CF 3 C 6 H 4 ), achieved through ligand engineering and kinetic control. Single-crystal x-ray diffraction reveals that Ag 213 and Ag 429 have multilayered icosahedral Ag 141 |(Ag 13 @Ag 42 @Ag 86 ) and Ag 297 (Ag 13 @Ag 42 @Ag 92 @Ag 150 ) cores, respectively. Notably, Ag 429 with 260 valence electrons is the largest Ag 0 -containing nanocluster reported to date. These two giant silver nanoclusters are metallic in nature, as confirmed by their plasmonic absorption and pump-power–dependent excited-state dynamics. Their atomically precise structures support the layer-by-layer evolution from nuclei to seeds of silver icosahedra.
GPT-4o mini: Non-social science research article
Launching by cavitation
Dalei Wang, Zixiao Liu, Hongping Zhao, Huanqi Qin, Gongxun Bai, Chi Chen, Pengju Shi, Yingjie Du, Yusen Zhao, Wei Liu, Dan Wang, Guoquan Zhou, Ximin He, Chaoqing Dai
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Cavitation, characterized by formation of vapor bubbles in a low-pressure or high-temperature region of a liquid, is often destructive, but it can be harnessed for actuators and robots. We exploit cavitation to accumulate substantial energy in superheated liquids by suppressing its immediate release until reaching a stability limit. The energetic, unstable bubbles collapse violently, producing a burst of high power and force that initiates motion. Notably, a millimeter-scale device launched by cavitation can jump to a height of 1.5 meters—reaching a 12 meters per second (m/s) peak velocity, a 7.14 × 10 4 m/s 2 acceleration, and a 0.64% energy efficiency—and can also swim on water at 12 centimeters per second. Cavitation-based launching works with a broad range of device materials, liquid media, stimuli, and operational environments.
GPT-4o mini: Non-social science research article
Somatotopic organization of brainstem analgesic circuitry
Lewis S. Crawford, Fernando A. Tinoco Mendoza, Rebecca V. Robertson, Noemi Meylakh, Paul M. Macey, Kirsty Bannister, Tor D. Wager, Vaughan G. Macefield, Kevin A. Keay, Luke A. Henderson
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The lateral periaqueductal gray (lPAG) evokes somatotopically appropriate defensive behaviors, including an analgesia that allows the animal to escape or fight unimpeded. Whether the lPAG and its descending targets are also able to drive somatotopically specific analgesic responses is not known. In this work, we performed ultrahigh-field functional magnetic resonance imaging of the lPAG in 93 participants during a placebo analgesia paradigm performed at different body locations. We found that analgesic responses are somatotopically organized in the lPAG and its descending outputs to the rostral ventromedial medulla. These data show that the PAG can regulate analgesic responses in a highly spatially localized manner and thus has the ability to mediate body site–selective control over pain.
GPT-4o mini: Non-social science research article
Taking nuclear energy to the Moon
Kathryn Huff
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Earlier this month, Sean Duffy, the acting head of the US National Aeronautics and Space Administration (NASA), announced an acceleration of the agency’s Fission Surface Power program, with the ambitious goal of placing a nuclear reactor on the Moon by 2030 that can produce 100 kilowatts of electric power. A surface reactor will be essential to enable sustained human exploration on both the Moon and Mars. However, an overly aggressive schedule could compromise both technical readiness and NASA’s other scientific priorities.
GPT-4o mini: Non-social science research article
Secondary organic aerosol in urban China: A distinct chemical regime for air pollution studies
Ru-Jin Huang, Yong Jie Li, Qi Chen, Yanli Zhang, Chunshui Lin, Chak K. Chan, Jian Zhen Yu, Joost de Gouw, Shengrui Tong, Jingkun Jiang, Weigang Wang, Xiang Ding, Xinming Wang, Maofa Ge, Weijian Zhou, Doug Worsnop, Michael Boy, Merete Bilde, Ulrike Dusek, Annmarie G. Carlton, Thorsten Hoffmann, V. Faye McNeill, Marianne Glasius
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In the past decades, China has witnessed high air pollution associated with rapid economic development, although regulatory efforts have alleviated the situation since 2013. Haze events characterized by high particulate matter (PM) levels in China are not only of enormous magnitude but also represent a distinct chemical regime. Once driven by direct emissions, these high-PM episodes are now more affected by secondary aerosol, especially secondary organic aerosol (SOA). This Review synthesizes the state of the science of SOA formation in urban China, specifically (i) how the dominance of anthropogenic precursors affects SOA formation, (ii) what are the prevailing SOA formation mechanisms, and (iii) how important are the multipollutant and multiphase processes in SOA formation and evolution. We also highlight essential directions for future studies.
GPT-4o mini: Non-social science research article
Seismic evidence for a highly heterogeneous martian mantle
Constantinos Charalambous, W. Thomas Pike, Doyeon Kim, Henri Samuel, Benjamin Fernando, Carys Bill, Philippe Lognonné, W. Bruce Banerdt
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A planet’s interior is a time capsule, preserving clues to its early history. We report the discovery of kilometer-scale heterogeneities throughout Mars’ mantle, detected seismically through pronounced wavefront distortion of energy arriving from deeply probing marsquakes. These heterogeneities, likely remnants of the planet’s formation, imply a mantle that has undergone limited mixing driven by sluggish convection. Their size and survival constrain Mars’ poorly known mantle rheology, indicating a high viscosity of 10 21.3 to 10 21.9 pascal-seconds and low temperature dependence, with an effective activation energy of 70 to 90 kilojoules per mole, suggesting a mantle deforming by dislocation creep. The limited mixing, coupled with ubiquitous, scale-invariant heterogeneities, reflects a highly disordered mantle, characteristic of the more primitive interior evolution of a single-plate planet, contrasting sharply with the tectonically active Earth.
GPT-4o mini: Non-social science research article
Classical-decisive quantum internet by integrated photonics
Yichi Zhang, Robert Broberg, Alan Zhu, Gushu Li, Li Ge, Jonathan M. Smith, Liang Feng
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Classical and quantum technologies have traditionally been viewed as orthogonal, with classical systems being deterministic and quantum systems inherently probabilistic. This distinction hinders the development of a scalable quantum internet even as the global internet continues expanding. We report a classical-decisive quantum internet architecture in which the integration of quantum information into advanced photonic technologies enables efficient entanglement distribution over a commercially deployed fiber network. On-chip precise synchronization between classical headers and quantum payloads enables dynamic routing and networking of high-fidelity entanglement guided by classical light. The quantum states are preserved through real-time error mitigation, relying solely on classical signal readout without disturbing quantum information. These classical-decisive features demonstrate a practical path to a scalable quantum internet using existing network infrastructure and operating systems.
GPT-4o mini: Non-social science research article
Deep generative models design mRNA sequences with enhanced translational capacity and stability
He Zhang, Hailong Liu, Yushan Xu, Haoran Huang, Yiming Liu, Jia Wang, Yan Qin, Haiyan Wang, Lili Ma, Zhiyuan Xun, Xuzhuang Hou, Timothy K. Lu, Jicong Cao
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Despite the success of mRNA COVID-19 vaccines, extending this modality to more diseases necessitates substantial enhancements. We present GEMORNA, a generative RNA model that utilizes Transformer architectures tailored for mRNA coding sequences (CDSs) and untranslated regions (UTRs), to design novel mRNAs with enhanced expression and stability. GEMORNA-designed full-length mRNAs exhibited up to a 41-fold increase in firefly luciferase expression compared to an optimized benchmark in vitro. GEMORNA-generated therapeutic mRNAs achieved up to a 15-fold enhancement in human erythropoietin (EPO) expression and substantially elicited antibody titers of COVID vaccine in mice. Additionally, GEMORNA’s versatility extends to circular RNA, substantially enhancing circular EPO expression and boosting anti-tumor cytotoxicity in CAR-T cells. These advancements highlight deep generative AI’s vast potential for mRNA therapeutics.
GPT-4o mini: Non-social science research article
Columbian mammoth mitogenomes from Mexico uncover the species’ complex evolutionary history
Eduardo Arrieta-Donato, Ángeles Tavares-Guzmån, Miriam Bravo-Lopez, Viridiana Villa-Islas, Alejandra Castillo-Carbajal, Wenxi Li, Ernesto Garfias-Morales, Rigoberto Padilla-Bustos, Marcela Sandoval-Velasco, Luis Córdoba-Barradas, Ruben Manzanilla-López, J. Camilo Chacón-Duque, Alejandro López-Jímenez, Mashaal Sohail, Joaquín Arroyo-Cabrales, María C. Ávila-Arcos, Federico Sånchez-Quinto
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Paleogenomic studies suggest that Mammuthus columbi derives from an ancient hybridization between Mammuthus primigenius and Mammuthus trogontherii . While its habitat spanned from North to Central America, available genetic data are limited to temperate regions, leaving gaps in knowledge of the species’ demographic history on the continent. In this study, we generated 61 capture-enriched M. columbi mitogenomes from the Basin of Mexico, in Central Mexico. Our analysis reveals that these mitogenomes belong to a mitochondrial lineage distinct from other North American mammoths. These divergent mitogenomes suggest a deep population structure in their ancestors, and challenge prior assumptions based on geographically restricted samples. Our findings underscore the importance of wider spatial sampling to reconstruct mammoths’ evolutionary history and demonstrate the feasibility of studying megafauna from tropical latitudes.
GPT-4o mini: Non-social science research article
Septal LYVE1 + macrophages control adipocyte stem cell adipogenic potential
Xiaotong Yu, Yanan Hu, Hwee Ying Lim, Ziyi Li, Diego Adhemar Jaitin, Katharine Yang, Wan Ting Kong, Jiaqian Xu, David Alejandro Bejarano, Mathilde Bied, Lucie Orliaguet, Gowshika Rengasamy, Zachary Chow, Christopher Zhe Wei Lee, Josephine Lum, Jing Tian, Xiao-Meng Zhang, Honghao Liu, Shu Wen Tan, Jinmiao Chen, Peter See, Yuin-Han Loh, Benoit Malleret, Sonia Baig, M. Shabeer M. Yassin, Sue-Anne Ee Shiow Toh, Bernard Malissen, Xiujun Fu, Kenji Kabashima, Lai Guan Ng, Camille Blériot, Zhaoyuan Liu, Lingling Sheng, Dan-Ning Zheng, Junwen Qu, Nicolas Venteclef, Bing Su, Ido Amit, Andreas Schlitzer, Veronique Angeli, Florent Ginhoux, Svetoslav Chakarov
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Tissue macrophages reside in anatomically distinct subtissular niches that shape their identity and function. In white adipose tissue (WAT), we identified three macrophage populations with distinct localization, turnover, and phenotypes. Septal adipose tissue macrophages (sATMs), marked by CD209b and lymphatic vessel endothelial hyaluronan receptor 1, were long-lived and positioned in close proximity to adipocyte stem cells (ASCs) within the WAT septum. Within this shared niche, sATMs instructed the differentiation of ASCs into white adipocytes through transforming growth factor–ÎČ1 (TGFÎČ1). Depletion of sATMs, or the selective loss of TGFÎČ1 within tissue-resident macrophages, redirected ASC fate toward thermogenic adipocytes, enhancing WAT beiging and protecting against diet-induced obesity. These findings highlight the role of a discrete, anatomically defined macrophage population that governs ASC fate and orchestrates adipose tissue expansion.
GPT-4o mini: Non-social science research article
Machine learning–based penetrance of genetic variants
Iain S. Forrest, Ha My T. Vy, Ghislain Rocheleau, Daniel M. Jordan, Ben O. Petrazzini, Girish N. Nadkarni, Judy H. Cho, Mythily Ganapathi, Kuan-Lin Huang, Wendy K. Chung, Ron Do
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Accurate variant penetrance estimation is crucial for precision medicine. We constructed machine learning (ML) models for 10 diseases using 1,347,298 participants with electronic health records, then applied them to an independent cohort with linked exome data. Resulting probabilities were used to evaluate ML penetrance of 1648 rare variants in 31 autosomal dominant disease-predisposition genes. ML penetrance was variable across variant classes, but highest for pathogenic and loss-of-function variants, and was associated with clinical outcomes and functional data. Compared with conventional case-versus-control approaches, ML penetrance provided refined quantitative estimates and aided the interpretation of variants of uncertain significance and loss-of-function variants by delineating clinical trajectories over time. By leveraging ML and deep phenotyping, we present a scalable approach to accurately quantify disease risk of variants.
GPT-4o mini: Non-social science research article
Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control
Daniel B. Grabarczyk, Julian F. Ehrmann, Paul Murphy, Woo Seok Yang, Robert Kurzbauer, Lillie E. Bell, Luiza Deszcz, Jana Neuhold, Alexander Schleiffer, Alexandra Shulkina, Juyeon Lee, Jin Seok Shin, Anton Meinhart, Gijs A. Versteeg, Eszter Zavodszky, Hyun Kyu Song, Ramanujan S. Hegde, Tim Clausen
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Eukaryotic cells have evolved sophisticated quality control mechanisms to eliminate aggregation-prone proteins that compromise cellular health. Central to this defense is the ubiquitin-proteasome system, where UBR4 acts as an essential E4 ubiquitin ligase, amplifying degradation marks on defective proteins. Cryo–electron microscopy analysis of UBR4 in complex with its cofactors KCMF1 and CALM1 reveals a massive 1.3-megadalton ring structure, featuring a central substrate-binding arena and flexibly attached catalytic units. Our structure shows how UBR4 binds substrate and extends lysine-48–specific ubiquitin chains. Efficient substrate targeting depends on both preubiquitination and specific N-degrons, with KCMF1 acting as a key substrate filter. The architecture of the E4 megacomplex is conserved across eukaryotes, but species-specific adaptations allow UBR4 to perform its precisely tuned quality control function in diverse cellular environments.
GPT-4o mini: Non-social science research article
Yellowstone’s free-moving large bison herds provide a glimpse of their past ecosystem function
Chris Geremia, E. William Hamilton, Jerod A. Merkle
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Although momentum is building to restore bison across North America, most efforts focus on small, managed herds, leaving unclear how large, migrating herds shape landscapes and whether their effects enhance or degrade ecosystems. We assessed carbon and nitrogen dynamics across the northern Yellowstone ecosystem, where one of the last remaining large migratory populations resides. Bison stabilized net aboveground production while accelerating nitrogen turnover, increasing aboveground nitrogen pools while carbon pools remained stable, which improved landscape nutritional quality. Effects were strongest in wet, nutrient-rich habitats that received higher bison densities and grazing than is recommended in rangeland management, while soil and plant conditions suggested landscape resilience. Restoration should embrace heterogeneity in densities and effects across habitats and spatial scales beyond those guiding most current recovery efforts.
GPT-4o mini: Non-social science research article
Heavily polluted Tijuana River drives regional air quality crisis
Benjamin Rico, Kelley C. Barsanti, William C. Porter, Karolina Cysneiros de Carvalho, Paula Stigler-Granados, Kimberly A. Prather
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Industrial chemicals and untreated sewage have polluted the Tijuana River for decades, recently causing >1300 consecutive days of California beach closures. In summer 2024, wastewater flows surged to millions of gallons per day despite no rain, enhancing water-to-air transfer of hydrogen sulfide (H 2 S) and other toxic gases at a turbulent hotspot. High wastewater flows and low winds led to nighttime H 2 S peaks, reaching 4500 parts per billion (ppb)—exceeding typical urban levels of <1 ppb. H 2 S levels and community malodor reports were strongly correlated (correlation coefficient r = 0.92), validating long-dismissed community voices and highlighting an environmental injustice. This study demonstrates that poor water quality can substantially affect air quality—although rarely included in air quality models and health assessments—with far-reaching implications as polluted waterways increase globally.
GPT-4o mini: Non-social science research article
Selection at the GSDMC locus in horses and its implications for human mobility
Xuexue Liu, Yaozhen Jia, Jianfei Pan, Yanli Zhang, Ying Gong, Xintong Wang, Yuehui Ma, Nadir Alvarez, Lin Jiang, Ludovic Orlando
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Horsepower revolutionized human history through enhanced mobility, transport, and warfare. However, the suite of biological traits that reshaped horses during domestication remains unclear. We scanned an extensive horse genome time series for selection signatures at 266 markers associated with key traits. We detected a signature of positive selection at ZFPM1 —known to be a modulator of behavior in mice—occurring ~5000 years ago (ya), suggesting that taming was one of the earliest steps toward domestication of horses. Intensive selection at GSDMC began ~4750 ya with the domestication bottleneck, leading regulatory variants to high frequency by ~4150 ya. GSDMC genotypes are linked to body conformation in horses and to spinal anatomy, motor coordination, and muscular strength in mice. Our results suggest that selection on standing variation at GSDMC was crucial for the emergence of horses that could facilitate fast mobility in human societies ~4200 ya.
GPT-4o mini: Non-social science research article
Transcription factors SP5 and SP8 drive primary cilia formation in mammalian embryos
Yinwen Liang, Richard Koche, Ravindra B. Chalamalasetty, Daniel N. Stephen, Mark W. Kennedy, Zhimin Lao, Yunong Pang, Ying-Yi Kuo, Moonsup Lee, Francisco Pereira Lobo, Xiaofeng Huang, Anna-Katerina Hadjantonakis, Terry P. Yamaguchi, Kathryn V. Anderson, Alexandra L. Joyner
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Although specific transcription factors (TFs) are known to regulate cell fate decisions, the degree to which they can stimulate formation of specific cell organelles is less clear. We used a multiomics comparison of the transcriptomes of ciliated and unciliated embryonic cells to identify TFs up-regulated in ciliated cells. We also used conditional genetics in mouse embryos and stem cells and found that the TFs SP5 and SP8 regulate cilia formation and gene expression. In embryos lacking Sp5 and Sp8 , primary and motile cilia were shorter than normal and reduced in number across cell types, contributing to situs inversus and hydrocephalus. Moreover, expression of SP8 was sufficient to induce primary cilia in unciliated cells. This work will facilitate the study of cilia assembly using stem cell models and promote further understanding of human ciliopathies.
GPT-4o mini: Non-social science research article
Land availability and policy commitments limit global climate mitigation from forestation
Yijie Wang, Yakun Zhu, Susan C. Cook-Patton, Wenjuan Sun, Wen Zhang, Philippe Ciais, Tingting Li, Pete Smith, Wenping Yuan, Xudong Zhu, Josep G. Canadell, Xiaopeng Deng, Yifan Xu, Hao Xu, Chao Yue, Zhangcai Qin
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Forestation (afforestation and reforestation) could mitigate climate change by sequestering carbon within biomass and soils. However, global mitigation from forestation remains uncertain owing to varying estimates of carbon sequestration rates (notably in soil) and land availability. In this study, we developed global maps of soil carbon change that reveal carbon gains and losses with forestation, primarily in the topsoil. Constraining land availability to avoid unintended albedo-induced warming and safeguard water and biodiversity (389 million hectares available for forestation globally) would sequester 39.9 petagrams of carbon by 2050, substantially below previous estimates. This estimate drops to 12.5 petagrams of carbon with land further limited to existing policy commitments (120 million hectares). Achieving greater mitigation requires expanding dedicated forestation areas and strengthening commitments from nations with considerable but untapped potential.
GPT-4o mini: Non-social science research article
A hypoxia-responsive tRNA-derived small RNA confers renal protection through RNA autophagy
Guoping Li, Lingfei Sun, Cuiyan Xin, Tian Hao, Prakash Kharel, Aidan C. Manning, Christopher L. O’Connor, Henry Moore, Shuwen Lei, Priyanka Gokulnath, Xinyu Yang, Ritin Sharma, Krystine Garcia-Mansfield, Priyadarshini Pantham, Chunyang Xiao, Hanna Y. Wang, Emeli Chatterjee, Seungbin Yim, Leo B. Ren, Michail Spanos, Hua Zhu, Haobo Li, Ji Lei, James F. Markmann, Louise C. Laurent, John J. Rossi, Oluwaseun Akeju, Quanhu Sheng, Ravi V. Shah, William A. Goddard, Todd M. Lowe, Patrick Pirrotte, Markus Bitzer, Pavel Ivanov, Joseph V. Bonventre, Saumya Das
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Transfer RNA–derived small RNAs (tsRNAs or tDRs) perform a range of cellular functions. Here, we showed that tRNA-Asp-GTC-3â€ČtDR, a hypoxia-induced tDR derived from the 3â€Č end of tRNA-Asp-GTC, activated autophagic flux in kidney cells and its silencing blocked autophagic flux. Functional gain-/loss-of-function studies in murine kidney disease models demonstrated a substantial renoprotective function of tRNA-Asp-GTC-3â€ČtDR. Mechanistically, tRNA-Asp-GTC-3â€ČtDR assembled stable G-quadruplex structures and sequestered pseudouridine synthase 7 (PUS7), preventing catalytic pseudouridylation of histone mRNAs. The resulting pseudouridylation deficiency directed histone mRNAs to the autophagosome-lysosome pathway, triggering RNA autophagy. This tDR-induced RNA autophagy pathway was activated during murine and human kidney diseases, suggesting clinical relevance. Thus, tRNA-Asp-GTC-3â€ČtDR plays a role in regulating RNA autophagy, which helps to maintain homeostasis in kidney cells and protects against kidney injury.
Science abstract < 200 char.: Not a research article
Gaps remain in college sports’ 15-year-old sickle cell policy
Rodrigo PĂ©rez Ortega
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Report recommends education, genetic counseling with NCAA screening
Science abstract < 200 char.: Not a research article
Academic leadership in uncertain times Peril And Promise Beverly Daniel Tatum Basic Books, 2025. 368 pp.
Susan Elrod
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A former college president offers advice for administrators navigating unprecedented challenges
Science abstract < 200 char.: Not a research article
Mapping the anatomy of placebo analgesia
Massieh Moayedi, Lauren Y. Atlas
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The identification of somatotopy in brainstem pain modulatory pathways could help treat chronic pain
Science abstract < 200 char.: Not a research article
Europe’s biggest quake may foretell Atlantic ‘ring of fire’
Evan Howell
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Earth’s mantle is peeling from the crust in the eastern Atlantic, a possible sign of the ocean’s eventual closure
Science abstract < 200 char.: Not a research article
Playing Possum: How Animals Understand Death Playing Possum: How Animals Understand Death Susana MonsĂł Princeton University Press, 2024, 264 pp.
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Science abstract < 200 char.: Not a research article
Sustainable personal cooling in a warming world
Dahua Shou, Ziqi Li
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Advanced textiles and intelligent wearable devices can provide cooling under extreme heat
Science abstract < 200 char.: Not a research article
New clues found about the assembly of life’s first proteins
Robert F. Service
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Lab study shows how RNA could have helped amino acids join up—without preexisting protein machinery
Science abstract < 200 char.: Not a research article
Growing into mentorship
Jasmine Gabriel Hughes
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Science abstract < 200 char.: Not a research article
Supply-chain vulnerabilities in critical medicines: A persistent risk to pharmaceutical security
Giona Casiraghi, Georges Andres, Frank Schweitzer, Luca Verginer
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Asymmetries in the global supply chain expose countries to systemic vulnerabilities that require investment in visibility, coordination, and resilience
Science abstract < 200 char.: Not a research article
In Science Journals
Angela Hessler, Bianca Lopez, Michael A. Funk, Marc S. Lavine, Ian S. Osborne, Vadim Cherezov, Jack Huang, Annalisa VanHook, Jesse Smith, Mattia Maroso, Yevgeniya Nusinovich, Stella M. Hurtley, Sarah H. Ross, Sacha Vignieri, Christiana N. Fogg, John Delaney, Catherine Charneski
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
The rise of rideable horses
Laurent Frantz
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Early horse riders selected a rare mutation in a single gene to enhance rideability
Science abstract < 200 char.: Not a research article
In Other Journals
Caroline Ash, Sarah LempriĂšre, Bianca Lopez, Yevgeniya Nusinovich, Yury Suleymanov, Keith T. Smith, Phil Szuromi
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
Unraveling the arc of vaccine progress
Seth Berkley
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Science abstract < 200 char.: Not a research article
Curtail North Korea’s illegal wildlife trade
Joshua Elves-Powell, Jan C. Axmacher, John D.C. Linnell, Sarah M. Durant
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Science abstract < 200 char.: Not a research article
Creating connection with wings and strings
Christine Harrison Elliott, Emily Jean Justus
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Science abstract < 200 char.: Not a research article
Copper threatens marine ecosystems
Luhua Yang, Shun Li, Ruiyong Zhang
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Science abstract < 200 char.: Not a research article
Supreme Court quashes restoration of NIH grants
Meredith Wadman, John Travis
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Emergency ruling may prompt Trump administration to again cancel research it dislikes
Science abstract < 200 char.: Not a research article
Penetrance and variant consequences—Two sides of the same coin?
Harper Raiken, Amelie Stein
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To get more out of genome sequences, the effects of variants need to be quantified
Science abstract < 200 char.: Not a research article
Bones beneath the runway
Rodrigo PĂ©rez Ortega
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How a military megaproject led to Mexico’s biggest paleontological discovery—and is reshaping what we know about mammoths
Science abstract < 200 char.: Not a research article
AI hypotheses lag human ones when put to the test
Jeffrey Brainard
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Machines still face hurdles in identifying fresh research paths, study suggests
Science abstract < 200 char.: Not a research article
Mars mania and the making of scientific authority The Martians: The True Story of an Alien Craze That Captured Turn-of-the-Century America David Baron Liveright, 2025. 336 pp.
Dov Greenbaum
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Twentieth-century speculation about martian life shed light on the interplay of science and culture

Science Advances

Generic title: Not a research article
Erratum for the Research Article “Deciphering co-ion and counterion transport in polyamide desalination membranes reveals ion selectivity mechanisms” by Y. Guo et al .
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GPT-4o mini: Non-social science research article
Size-dependent temporal decoupling of morphogenesis and transcriptional programs in pseudoembryos
Isma Bennabi, Pauline Hansen, Melody Merle, Judith Pineau, Lucille Lopez-Delisle, Dominique Kolly, Denis Duboule, Alexandre Mayran, Thomas Gregor
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Understanding the interplay between cell fate specification and morphogenetic changes remains a challenge in developmental biology. Gastruloids, stem cell models of postimplantation mammalian development, provide a platform to address this question. Here, using quantitative live imaging and transcriptomic profiling, we show that physical parameters, particularly system size, affect morphogenetic timing and outcomes. Larger gastruloids exhibit delayed symmetry breaking, increased multipolarity, and prolonged axial elongation, with morphogenesis driven by size. Despite these variations, transcriptional programs and cell fate composition remain stable across a broad size range, illustrating the scaling of gene expression domains. In particular, extreme sizes show distinct transcriptional modules and shifts in gene expression patterns. Size perturbation experiments rescued the morphogenetic and pattern phenotypes observed in extreme sizes, demonstrating the adaptability of gastruloids to their effective system size. These findings position gastruloids as versatile models for dissecting spatiotemporal coordination in mammalian development and reveal how physical constraints can decouple gene expression programs from morphogenetic progression.
GPT-4o mini: Non-social science research article
Notch signaling blockade links transcriptome heterogeneity in quiescent neural stem cells with reactivation routes and potential
David Morizet, Isabelle Foucher, Ilona Mignerey, Alessandro Alunni, Laure Bally-Cuif
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In the vertebrate brain, neural stem cell (NSC) quiescence is necessary for stemness maintenance. Using single-cell RNA sequencing (scRNAseq) in the zebrafish adult telencephalon, we identified different molecular clusters of quiescent NSCs, interpreted to sign different quiescence depths. Here, we show that these clusters, when challenged in vivo with an inhibitor of Notch signaling, a major quiescence promoting pathway, unfold different behaviors. Notably, deeply quiescent NSCs with astrocytic features display a unique activation phenotype that combines the maintenance of astrocytic markers with the rapid up-regulation of activation and neuronal commitment genes, reminiscent to murine periventricular astrocytes activating upon lesion. In contrast, an NSC cluster predicted to be in the deepest quiescence state resists Notch blockade, and we demonstrate that the transcription factor Nr2f1b mediates this resistance to activation in vivo. These results together link the molecular heterogeneity of quiescent NSCs with bona fide biological properties and their molecular regulators.
GPT-4o mini: Non-social science research article
X-ray phase measurements by time-energy correlated photon pairs
Yishai Klein, Edward Strizhevsky, Haim Aknin, Moshe Deutsch, Eliahu Cohen, Avi Pe’er, Kenji Tamasaku, Tobias Schulli, Ebrahim Karimi, Sharon Shwartz
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The resolution of a measurement system is fundamentally constrained by the wavelength of the used wave packet and the numerical aperture of the optical system. Overcoming these limits requires advanced interferometric techniques exploiting quantum correlations. While quantum interferometry can surpass the Heisenberg limit, it has been confined to the optical domain. Extending it to x-rays enables sub-angstrom spatial and zeptosecond temporal resolution, unlocking atomic-scale processes inaccessible to existing methods. Here, we demonstrate x-ray quantum interferometry using 17.5–kilo–electron volt ( λ = 70 picometers) photon pairs. Our approach introduces a phase measurement technique with exceptional noise resilience, mitigating the impact of mechanical instabilities, vibrations, and photonic noise—key challenges in x-ray interferometry. By generating and using entangled x-ray photons, we lay the foundation for next-generation techniques with unprecedented phase precision. This breakthrough carries far-reaching consequences for fundamental physics, high-resolution imaging, and spectroscopy, bringing to light quantum optical effects never before accessed in the x-ray regime.
GPT-4o mini: Non-social science research article
The source and thermal driver of young (<3.0 Ga) lunar volcanism
Chengyuan Wang, Yuqi Qian, Jintuan Wang, Liang Liu, Le Zhang, Zhiming Chen, Jingyou Chen, Guanhong Zhu, Xianglin Tu, Zexian Cui, Qing Yang, Yan-Qiang Zhang, Pengli He, Yonghua Cao, Haiyang Xian, James W. Head, Yi-Gang Xu
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The thermal mechanism that drives the prolonged volcanism on the Moon, especially after the major pulse of Imbrian-aged eruptions, remains unknown. Here, we present a petrological and geochemical study of two types of young farside mare basalts, the ~2.8–billion year (Ga) low-Ti and ~2.9-Ga very-low-Ti basalts, collected during the Chang’e-6 mission. The results of our study show that these basalts have pyroxenitic sources and originate from a depth of ~60 to 80 kilometers and ~120 kilometers, respectively. The depth of their source that became progressively shallower over time, combined with thermal modeling results, suggests that magmatic underplating beneath the ilmenite-bearing cumulate (IBC) that escaped the mantle overturn phase could be a thermal driver for the young lunar magmatism. Global remote-sensing investigations further reveal different TiO 2 contents between young basalts from each side of the Moon, attributable to asymmetric composition and thickness of the IBC in the uppermost mantle.
GPT-4o mini: Non-social science research article
Distinctive molecular features of radiation-induced thyroid cancers
Danielle M. Karyadi, Tetiana I. Bogdanova, Cato M. Milder, Stephen W. Hartley, Olivia W. Lee, Michael Dean, Vladimir Drozdovitch, Elizabeth K. Cahoon, Sergii Masiuk, Mykola Chepurny, Liudmyla Yu Zurnadzhy, Vibha Vij, Cari M. Kitahara, Gerry A. Thomas, Gayle E. Woloschak, Dale A. Ramsden, Mykola D. Tronko, Stephen J. Chanock, Lindsay M. Morton
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Papillary thyroid carcinoma (PTC) incidence increased after childhood exposure to radioactive fallout from the Chornobyl accident. We investigated PTC genomic profiles to distinguish radiation-induced versus sporadic oncogenic drivers by modeling dose and molecular characteristics by driver category: BRAF V600E ( n = 132), RAS mutation ( n = 31), fusions generated from two breakpoints and <20 base pairs (bp) breakpoint gain/loss (Fusion 2B<20bp ; n = 63), or ≄3 breakpoints and ≄1000 bp breakpoint loss ( n = 20). The frequency of Fusion 2B<20bp -PTC increased with increasing thyroid radiation dose, whereas all others declined. Clonal small deletion counts increased with increasing radiation dose for Fusion 2B<20bp -PTC ( P = 5.1 × 10 −4 ) but not other drivers ( P > 0.08). Clonal clock mutational signatures, marking the age of tumor initiation, were associated with age at the accident for Fusion 2B<20bp -PTC ( P = 8.2 × 10 −4 ) but not other drivers ( P > 0.21). Together, these results support a causal role for ionizing radiation in Fusion 2B<20bp -PTC as a group but not other drivers.
GPT-4o mini: Non-social science research article
In situ atomic-resolution imaging of water vapor–driven multistep oxidation dynamics in strontium cobaltite
Zhenzhong Yang, Ke Qu, Yifeng Zhao, Le Wang, Libor Kovarik, Peter V. Sushko, Yingjie Lyu, Jianbing Zhang, Pu Yu, Chungang Duan, Yingge Du
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Understanding how water vapor interacts with transition metal oxides (TMOs) is critical for tailoring material properties to improve performance and enable new technologies. Despite extensive research efforts, atomic-scale mechanisms underpinning dynamic reactions and reaction-induced phase transitions remain elusive. Here, we use in situ environmental transmission electron microscopy to investigate how water vapor oxidizes vacancy-ordered SrCoO 2.5 at moderately elevated temperatures, demonstrating that water molecules can initiate oxidation more effectively than oxygen under comparable conditions. We discover a distinct “staging” behavior during the oxidation process: A fully ordered intermediate phase, SrCoO 2.75 , forms before transitioning into a near-perovskite SrCoO 3−ή . In addition, antiphase boundaries, originating at step terraces of SrTiO 3 , alleviate strain by creating reversible nanoscale “gaps” during lattice contraction under oxidation, providing a pathway for preserving structural integrity throughout redox cycling. This work provides atomic-level guidance for engineering TMOs by leveraging water vapor to control their redox behavior and tailor functional properties.
GPT-4o mini: Non-social science research article
Large-scale complementary carbon nanotube integrated circuits for harsh radiation environments
Ke Zhang, Daming Zhou, Ningfei Gao, Jiahao Zhang, Zhongzhen Tong, Jibo Zhao, Peng Liu, Xinhe Wang, Xiaoyang Lin, Haitao Xu, Lian-Mao Peng, Weisheng Zhao
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Silicon-based integrated circuits operating in radiation environments require additional and complex hardening configurations, leading to performance lags compared to the International Roadmap for Devices and Systems. Carbon nanotubes (CNTs), with their ultrastrong chemical bonds and nanoscale dimensions, offer substantial potential for high-performance, radiation-tolerant electronics. However, the challenges associated with radiation-tolerant fabrication processes have hindered the development of macroelectronics using complementary CNT transistors (CNTFETs). In this study, we successfully fabricated radiation-tolerant, highly symmetric, and uniform CMOS building blocks, implementing various logic gates (inverters, NAND, and XOR gates) and ring oscillators (ROs) with 5, 11, and 501 stages. After irradiation up to 6 Mrad(Si), all devices maintained rail-to-rail outputs, and notably, the 501-stage RO, comprising 1004 CNTFETs, showed minimal delay variation (10.3 ± 0.8 ns). This work demonstrates the radiation-tolerant of large-scale CNTFETs, paving the way for their potential replacement of silicon-based FETs in radiation-heavy environments.
GPT-4o mini: Non-social science research article
Bayesian reconstruction of rapidly scanned mid-infrared optoacoustic signals enables fast, label-free chemical microscopy
Constantin Berger, Myeongseop Kim, Lukas Scheel-Platz, Andreas Eigenberger, Lukas Prantl, Panhang Liu, Vipul Gujrati, Vasilis Ntziachristos, Dominik JĂŒstel, Miguel A. Pleitez
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Hyperspectral optoacoustic microscopy (OAM) enables obtaining images with label-free biomolecular contrast, offering excellent perspectives as a diagnostic tool to assess freshly excised and unprocessed biological samples. However, time-consuming raster scanning image formation currently limits the translation potential of OAM into the clinical setting, for instance, in intraoperative histopathological assessments, where micrographs of excised tissue need to be taken within a few minutes for fast clinical decision-making. Here, we present a non–data-driven computational framework tailored to enable fast OAM by rapid data acquisition and model-based image reconstruction, termed Bayesian raster-computed optoacoustic microscopy (BayROM). Unlike data-driven approaches, BayROM does not require training datasets, but instead, it uses probabilistic model-based reconstruction to facilitate fast high-resolution imaging. We show that BayROM enables acquiring micrographs 10 times faster on average than conventional raster scanning microscopy and provides sufficient image quality to facilitate the intraoperative histological assessment of processed fat grafts for autologous fat transfer.
GPT-4o mini: Non-social science research article
Microbiota metabolite taurodeoxycholic acid maintains intestinal tissue residency of innate lymphoid cells via engagement with P2Y10 receptor
Yuwei Xu, Zhen Xiong, Peikang Zhang, Runyuan Wu, Cunzhen Li, Hui Guo, Ying Du, Xiaoxiao Zhu, Dongdong Fan, Hongzhe Fan, Yong Tian, Yun Chen, Zusen Fan
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Innate lymphoid cells (ILCs) play critical roles in innate immunity, epithelial barrier protection, and tissue homeostasis. However, the maintenance machinery of intestinal tissue residency of ILCs remains elusive. Here, we show that gut microbiota is necessary for the maintenance of intestinal tissue residency of ILCs. Microbiota metabolite taurodeoxycholic acid (TDCA) binds to P2Y10 receptor on ILCs to initiate downstream Ca 2+ and RhoA signaling pathways. TDCA-P2Y10 engagement induces Zfp414 transcription to prime expression of CD69 and integrin αE on ILCs, leading to intestinal residency of ILCs. Moreover, decreased levels of TDCA or P2Y10 deficiency abrogates the intestinal residency of ILCs, resulting in severer intestinal inflammation. Of note, TDCA administration can enhance intestinal tissue residency of ILCs and promote protection against intestinal inflammation. Thus, TDCA might be used as a potential drug to treat patients with inflammatory bowel disease.
GPT-4o mini: Non-social science research article
Multidecadal decoupling between coral calcifying fluid and seawater saturation states
Jessica C. Hankins, Thomas M. DeCarlo
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Ocean acidification poses a threat to coral skeleton formation via reductions in the saturation state of aragonite (Ω Ar ) in seawater. Given that corals precipitate their skeletons from a calcifying fluid supplied by seawater, reductions in seawater Ω Ar should, in theory, confound calcification. Here, we reconstruct up to 200 years of coral calcifying fluid Ω Ar , using Raman spectroscopy techniques, at approximately monthly resolution in two Porites sp. skeletal cores from the Coral Sea region to investigate (i) the regulation of coral calcifying fluid Ω Ar and (ii) the skeletal calcification response to industrial-era ocean acidification. Our results reveal a significant increase in calcifying fluid Ω Ar , suggesting that some corals may adjust to the pace of acidification in the wild more effectively than suggested by short-term laboratory studies.
GPT-4o mini: Non-social science research article
Gut-brain nexus: Mapping multimodal links to neurodegeneration at biobank scale
Mohammad Shafieinouri, Samantha Hong, Paul Suhwan Lee, Spencer M. Grant, Marzieh Khani, Anant Dadu, Artur F. Schumacher Schuh, Mary B. Makarious, Rodrigo Sandon, Emily Simmonds, Hirotaka Iwaki, Gracelyn Hill, Cornelis Blauwendraat, Valentina Escott-Price, Yue A. Qi, Alastair J. Noyce, Armando Reyes-Palomares, Hampton L. Leonard, Malu Tansey, Faraz Faghri, Andrew B. Singleton, Mike A. Nalls, Kristin S. Levine, Sara Bandres-Ciga
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Alzheimer’s disease (AD) and Parkinson’s disease (PD) are influenced by genetic and environmental factors. We conducted a biobank-scale study to (i) identify endocrine, nutritional, metabolic, and digestive disorders with potential causal or temporal associations with AD/PD risk before diagnosis; (ii) assess plasma biomarkers’ specificity for AD/PD in the context of co-occurring gut related traits and disorders; and (iii) integrate multimodal datasets to enhance AD/PD prediction. Our findings show that several disorders were associated with increased AD/PD risk before diagnosis, with variation in the strength and timing of associations across conditions. Polygenic risk scores reveal lower genetic predisposition for AD/PD in individuals with co-occurring disorders. Moreover, the proteomic profile of AD/PD cases was influenced by comorbid gut-brain axis disorders. Last, our multimodal prediction models outperform single-modality paradigms in disease classification. This endeavor illuminates the interplay between factors involved in the gut-brain axis and the development of AD/PD, opening avenues for therapeutic targeting and early diagnosis.
GPT-4o mini: Non-social science research article
Laboratory-based in situ and operando tricolor x-ray photoelectron spectroscopy
Iris C. G. van den Bosch, Jahid Uz Zaman, Genrikh Shterk, Mai Hussein Hamed, Michael Schneider, Vadim Ratovskii, Yibin Bu, Paul M. Dietrich, Gertjan Koster, Christoph Baeumer
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Innovative approaches to study buried interfaces and heterogeneous interactions under reaction conditions are crucial for advancing energy and catalytic materials. Our near-ambient pressure x-ray photoelectron spectroscopy (NAP-XPS) setup is equipped with a tricolor x-ray source, with Al Kα, Ag Lα, and Cr Kα excitation energies, enabling information depth–selective operando and in situ analysis of solid-liquid, solid-gas, and solid-solid interfaces. We present three case studies to demonstrate the systems’ capabilities. First, we compare experimental depth profiling of a LaMnO 3 /LaFeO 3 /Nb:SrTiO 3 multilayer with SESSA (simulation of electron spectra for surface analysis) simulations. Second, we examine the oxidation and reduction of Fe x O y as a function of environment and temperature. Last, the Pt/liquid electrolyte interface is examined, revealing surface oxidation in the absence of bulk oxidation. As our results confirm, the unique combination of a NAP-XPS with the tricolor x-ray source empowers laboratory-based in situ and operando XPS characterization of advanced materials under reaction conditions in a wide range of applications.
GPT-4o mini: Non-social science research article
Structure of the complete 14-subunit botulinum neurotoxin B complex reveals a unique anchoring through the narrow central pore of HA70
Ajda Krč, Sara Persson KoĆĄenina, Maria B. Nowakowska, Geoffrey Masuyer, PĂ„l Stenmark
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Botulinum neurotoxin serotype B1 (BoNT/B) is a highly potent neurotoxin and therapeutic agent. Here, we present the structure of the complete 14-subunit (780 kDa) progenitor toxin complex (L-PTC) and of five subcomplexes. The structures show how the toxin interacts with its associated components in their role to protect and deliver BoNT/B across epithelial barriers. Each subcomplex, including the M-PTC, M-PTC–HA70, NTNH-HA70, and HA70 trimer, provides detailed understanding of the assembly mechanism, in which the NTNH-nLoop adopts a unique fold that locks the M-PTC into a central pore formed by HA70. The HA subcomplex presents a tripod architecture with flexible legs that may adapt to the rugged cell surface. Mass photometry reveals the pH dependence of BoNT/B release from the complex which is unexpectedly influenced by the presence of HA70. This study provides the complete L-PTC structure, offering insights into its assemblage and supporting the development of countermeasures and therapeutic applications.
GPT-4o mini: Non-social science research article
Broad-spectrum synthetic carbohydrate receptors (SCRs) inhibit viral entry across multiple virus families
Shahrzad Ezzatpour, Khushabu Thakur, Kenneth Erzoah Ndede, David W. Buchholz, Annette Choi, Brian Imbiakha, Jordan Carter, David Onofrei, Brett Eaton, Elena Postnikova, Michael Murphy, Beicer C. Tapia, Diana Bello, Siddharth Pasari, Anthony Russo, Matthew Babayev, Gregory P. Holland, Michael R. Holbrook, Sara L. Caddy, Steven J. Moran, Seyed Mohammad Davachi, Isaac Abrrey Monreal, Julie Sahler, Victoria Ortega, Jose M. Miranda, Gary R. Whittaker, Mason C. Jager, Seema K. Bhagwat, Pradeep Chopra, Geert Jan-Boons, Mateusz Marianski, Adam B. Braunschweig, Hector C. Aguilar
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Viral pandemics continue to threaten global health and economic stability. Despite medical advances, the absence of broad-spectrum antivirals (BSAs) prevents rapid responses to emerging viral threats. This is largely due to the lack of universal drug targets across diverse viral families and high variability among viral proteins. In this study, we evaluated 57 synthetic carbohydrate receptors (SCRs) for antiviral activity in cellulo using pseudotyped virus particles (PVPs) from six high-risk viruses across three families: Paramyxoviridae, Filoviridae, and Coronaviridae. Four SCRs inhibited all tested PVPs, and their efficacy was confirmed against live viruses including SARS-CoV-2, MERS-CoV, EBOV, MARV, NiV, and HeV. Notably, SCR005 and SCR007 , which exhibited minimal toxicity, significantly reduced SARS-CoV-2 infection in a severe animal model with a single dose. Mechanistic studies suggested that SCRs bind viral envelope N-glycans, blocking viral attachment and/or fusion. These results identify conserved viral N-glycans as promising BSA targets and establish SCRs as candidate prophylactic agents against enveloped viruses with pandemic potential.
GPT-4o mini: Non-social science research article
Metabolism-dependent succinylation governs resource allocation for antibiotic resistance
Jia-han Wu, Xuan-wei Chen, Ying-li Liu, Jia-yao Wu, Zhuang-gui Chen, Bo Peng
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The mechanisms that organisms allocate resources to sustain biological phenotypes remain largely unknown. Here, we use mobilized colistin resistance ( mcr-1 ), which modifies lipopolysaccharide (LPS) to confer colistin resistance, as a model to explore how bacteria reallocate resources to support mcr-1 –mediated resistance. We show that bacteria redirect resources from glycolysis, the pyruvate cycle, and LPS biosynthesis toward glycerophospholipid metabolism to produce phosphatidylethanolamine, the substrate for mcr-1 to modify LPS, while reducing LPS content to limit colistin binding. This reallocation down-regulates succinyl–coenzyme A (CoA) to diminish succinylation of proteins including triosephosphate isomerase (TPI), CpxR, and PdhR, thereby sustaining resistance. Exogenous succinate or α-ketoglutarate restores succinylation in a succinyl-CoA–dependent manner. Succinylation of TPI redirects metabolic flux to glycolysis and the pyruvate cycle, while succinylation of CpxR and PdhR up-regulates LPS biosynthesis, ultimately attenuating colistin resistance. Thus, we reveal a previously unrecognized mechanism by which bacteria regulate resource allocation through metabolism-driven posttranslational protein modification, offering strategies to combat antibiotic resistance.
GPT-4o mini: Non-social science research article
Capturing carbon monoxide—Accessing bis(boryl)ketones through direct B–B bond carbonylation
Eva Beck, Ivo Krummenacher, Thomas Kupfer, Maximilian Dietz, Holger Braunschweig
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Carbon monoxide (CO) readily attacks the B–B bonds of the cyclic tetra(amino)tetraborane B 4 (NCy 2 ) 4 [cyclohexyl (Cy)], which led to insertion and ring expansion, creating tetraboron analogs of cyclopentanone and cyclohexane-1,3-dione. These intriguing molecules are rare instances of stable CO diborylation products that were made accessible by direct CO capture. While the monocarbonyl product shows remarkable thermal stability, the dicarbonyl product rearranges into a bicyclic tetraborylethylene structure under thermal stress. Combined analytical and theoretical efforts clearly highlight the unique electronic, spectroscopic, and structural characteristics of these carbonyl compounds. The cyclopentanone analog engages in stepwise one- and two-electron reduction processes to yield radical monoanion and dianion species while preserving the five-membered ring structure and the boron-boron bonds. Together, these boron heterocycles expand the limited class of stable boryl ketones containing direct boron-carbonyl carbon bonds, thus offering valuable opportunities for exploring the fundamental chemistry and synthetic applications of this functionality.
GPT-4o mini: Non-social science research article
A nut-and-bolt assembly of the bimodular large progenitor botulinum neurotoxin complex
Kwok-ho Lam, Linfeng Gao, Adina Przykopanski, Baohua Chen, Ting Huang, Maren KrĂŒger, Anna-Magdalena Bartels, Martin Bernhard Dorner, Kay Perry, Brigitte Gertrud Dorner, Andreas Rummel, Rongsheng Jin
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Botulinum neurotoxin serotype A (BoNT/A) is naturally produced by bacteria along with four nontoxic neurotoxin-associated proteins (NTNH, HA70, HA33, and HA17), forming a bimodular large progenitor toxin complex (L-PTC). The BoNT/A–NTNH complex protects the toxin from adverse environment, while the complex consisting of HA proteins facilitates toxin absorption during oral intoxication. How these two independent modules assemble into the L-PTC remains unclear. Here, we report the crystal structure of the BoNT/A–NTNH–HA70 complex at ~2.9-Å resolution. The structure reveals that the BoNT/A–NTNH complex is anchored into a concentric double ÎČ-barrel channel of trimeric HA70 through a short ÎČ-hairpin of NTNH (termed nLoop), resembling a nut-and-bolt attachment. We find that the nLoop of NTNH is strictly conserved across HA-containing BoNT complexes and that NTNH–HA70 binding is interchangeable among them. Furthermore, we demonstrate that the nLoop functions as a minimal motif enabling attachment of a protein-of-interest to the HA complex, with potential applications in oral biologics delivery.
GPT-4o mini: Non-social science research article
Bioinspired adaptive response speed for high-quality human-robot interactions
Zijuan He, Haigen Xiong, Qijie Lin, Song Wang, Fengjiao Zhang, Yinghui Han, Hao Chen, Hui Huang
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In human-robot interaction (HRI), the quality of user experience is paramount. Thus, developing strategies to tailor robotic responsiveness to user comfort zone is essential. However, current methods remain constrained by complex software and limited to unidirectional speed enhancement. Inspired by the adaptive pathways of biological brain, this study introduces a photochromic diarylethene–doped organic floating-gate field-effect transistor (OFGFET) capable of bidirectional response speed control. Mechanism investigations revealed that a light-controllable back charge transfer process facilitates dynamic speed adjustments. Notably, the OFGFET device potentially enables effective regulation of response speeds to enhance user comfort while maintaining efficient and detailed movie playback. This work establishes a distinctive paradigm in HRI, offering unprecedented adaptability that could transform user experience design across diverse interactive technologies.
GPT-4o mini: Non-social science research article
Mechanism and cellular actions of the potent AMPK inhibitor BAY-3827
Conchita Fraguas Bringas, Mohd Syed Ahangar, Joyceline Cuenco, Hongling Liu, Alex B. Addinsall, Maria Lindahl, Ashley J. Ovens, Mark A. Febbraio, Marc Foretz, Olga Göransson, John W. Scott, Elton Zeqiraj, Kei Sakamoto
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Inhibition of adenosine 5â€Č-monophosphate (AMP)–activated protein kinase (AMPK) is under increasing investigation for its therapeutic potential in many diseases. Existing AMPK inhibitors are however limited, with poor selectivity and substantial off-target effects. Here, we provide mechanistic insights and describe the cellular selectivity of the recently identified AMPK inhibitor BAY-3827. A 2.5-Å cocrystal structure of the AMPK kinase domain with BAY-3827 revealed distinct features including a disulfide bridge between the αD helix Cys 106 and the activation loop residue Cys 174 . This bridge appears to stabilize the activation loop such that Asn 162 repositions the Asp-Phe-Gly (DFG) motif Phe 158 toward the C-terminal lobe, displacing His 137 and disrupting the regulatory spine, promoting an inactive kinase state. In hepatocytes, BAY-3827 blocked AMPK activator (MK-8722)–mediated phosphorylation of ACC1 and corresponding inhibition of lipogenesis. Transcriptome analysis revealed that BAY-3827 down-regulated ~30% of MK-8722–stimulated AMPK-dependent genes. We establish the molecular and cellular basis of BAY-3827’s selectivity and utility for delineating AMPK functions while highlighting its limitations.
GPT-4o mini: Non-social science research article
Putative PINK1/Parkin activators lower the threshold for mitophagy by sensitizing cells to mitochondrial stress
William M. Rosencrans, Ryan W. Lee, Logan McGraw, Ian Horsburgh, Ting-Yu Wang, Baiyi Quan, Diana Huynh, Jennifer A. Johnston, David C. Chan, Tsui-Fen Chou
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The PINK1/Parkin pathway targets damaged mitochondria for degradation via mitophagy. Genetic evidence implicates impaired mitophagy in Parkinson’s disease, making its pharmacological enhancement a promising therapeutic strategy. Here, we characterize two mitophagy activators: a novel Parkin activator, FB231, and the reported PINK1 activator MTK458. Both compounds lower the threshold for mitochondrial toxins to induce PINK1/Parkin-mediated mitophagy. However, global proteomics revealed that FB231 and MTK458 independently induce mild mitochondrial stress, resulting in impaired mitochondrial function and activation of the integrated stress response, effects that result from PINK1/Parkin-independent off-target activities. We find that these compounds impair mitochondria by distinct mechanisms and synergistically decrease mitochondrial function and cell viability in combination with classical mitochondrial toxins. Our findings support a model whereby weak or “silent” mitochondrial toxins potentiate other mitochondrial stressors, enhancing PINK1/Parkin-mediated mitophagy. These insights highlight important considerations for therapeutic strategies targeting mitophagy activation in Parkinson’s disease.
GPT-4o mini: Non-social science research article
AKR1B10 dictates c-Myc stability to suppress colorectal cancer metastasis via PP2A nitration
Xiaoxue Wu, Shaoqing Huang, Jialing Gao, Shuting Huang, Lulu Chen, Ziyi Zhao, Ruihan Pu, Xiaojing Ma, Xianzhi Liu, Weiling He, Mei Song
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Metabolic enzymes, critical for cellular homeostasis, are frequently co-opted in a disease-specific manner to drive cancer progression. Here, we identify aldo-keto reductase family 1 member B10 (AKR1B10), down-regulated in gastrointestinal cancers, as a pivotal metastasis suppressor correlating with improved colorectal cancer (CRC) prognosis. Mechanistically, AKR1B10 activates protein phosphatase 2A (PP2A) by preventing redox-regulated nitration of its B56α subunit, preserving holoenzyme assembly and enabling c-Myc dephosphorylation at serine-62. Loss of AKR1B10 disrupts this pathway, stabilizing c-Myc, which drives integrin signaling and metastatic dissemination in CRC. We further demonstrate that lysine-125 of AKR1B10 is essential for its interaction with PP2A-Cα and B56α nitration, thereby attenuating CRC metastatic aggressiveness. Pharmacological restoration of PP2A activity effectively mitigates metastasis associated with AKR1B10 loss. In addition, c-Myc transcriptionally represses AKR1B10, establishing a feedback loop that sustains its down-regulation and enhances metastatic progression. This study uncovers an antimetastatic mechanism involving AKR1B10-mediated PP2A activation and highlights its potential as a biomarker and therapeutic target.
GPT-4o mini: Non-social science research article
A Dapl1 + subpopulation of naĂŻve CD8 T cells is enriched for memory-lineage precursors
Adam C. Lynch, Kaito A. Hioki, Xueting Liang, Iris Thesmar, Julia Cernjul, Xinjian Doris He, Jesse Mager, Wei Cui, Dominique Alfandari, Elena L. Pobezinskaya, Leonid A. Pobezinsky
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Memory CD8 T cells provide long-lasting immunity, but their developmental origins remain incompletely defined. Growing evidence suggests that functional heterogeneity exists within the naïve T cell pool, shaping lineage potential before antigen stimulation. Here, we identify a subpopulation of naïve CD8 T cells expressing death-associated protein-like 1 (Dapl1) that contains preprogrammed precursors biased toward memory differentiation. The differentiation of these precursors is independent of Dapl1 but relies on the transcription factor B-cell lymphoma/leukaemia 11b (Bcl11b), resulting in the generation of Dapl1 + central memory–like CD8 T cells after infection and stem-like memory cells in cancer. Dapl1 + naïve T cells originate among mature thymocytes and gradually appear in the periphery postnatally. Peripheral Dapl1 + and Dapl1 − populations show limited plasticity, supporting a thymic-imprinting model. These findings reveal a developmentally imprinted subset of naïve CD8 T cells committed to memory fate, uncovering an alternative pathway for memory T cell generation offering new avenues for therapeutic application.
GPT-4o mini: Non-social science research article
PhoCoil: A photodegradable and injectable single-component recombinant protein hydrogel for minimally invasive delivery and degradation
Nicole E. Gregorio, Fan Zhang, Yusuke Suita, Lisa S. Ang, Olivia Prado, Arafat Fasuyi, James M. Olson, Kelly R. Stevens, Cole A. DeForest
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Hydrogel biomaterials offer great promise for three-dimensional cell culture and therapeutic delivery. Despite many successes, challenges persist in that gels formed from natural proteins are only marginally tunable whereas those derived from synthetic polymers lack intrinsic bioinstructivity. Toward the creation of biomaterials with both excellent biocompatibility and customizability, recombinant protein–based hydrogels have emerged as molecularly defined and user-programmable platforms that mimic the proteinaceous nature of the extracellular matrix. Here, we introduce PhoCoil, a dynamically tunable recombinant hydrogel formed from a single protein component with unique multistimuli responsiveness. Physical cross-linking through coiled-coil interactions promotes rapid shear-thinning and self-healing behavior, rendering the gel injectable, whereas an included photodegradable motif affords on-demand network dissolution via visible light. PhoCoil gel photodegradation can be spatiotemporally and lithographically controlled in a dose-dependent manner, through complex tissue, and without harm to encapsulated cells. We anticipate that PhoCoil will further enable applications in tissue engineering and regenerative medicine.
GPT-4o mini: Non-social science research article
Integrated behavioral and metabolically flexible responses of wild orangutans to ecologically driven dietary variation
Erin R. Vogel, Shauhin E. Alavi, Malcolm Watford, Rebecca S.A. Brittain, Brooke E. Crowley, Daniel J. Naumenko, William D. Aguado, Timothy D. Bransford, Astri Zulfa, Alysse Moldawer, Wartika Rosa Farida, Maria A. van Noordwijk, Tatang Mitra Setia, Sri Suci Utami Atmoko, Jessica M. Rothman, David Raubenheimer
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Diet and nutrition are critical factors influencing energetics and health. Laboratory studies show that organisms adjust to changes in nutrient intake through flexible metabolic responses such as fuel switching. While the physiological effects of nutrient balance in humans have been studied, data from closely related species living in nature are lacking. We integrate macronutrient regulation and metabolic flexibility to elucidate how wild orangutans ( Pongo pygmaeus wurmbii ) are buffered against natural fluctuations in nutritional resources. We found that these orangutans regulate protein and regularly switch between exogenous and endogenous nutritional substrates as preferred food resource availability declines. When total caloric, lipid, and carbohydrate intake declined during episodes of fruit scarcity, orangutans drew on fat and endogenous amino acids for energy. This strategy is beneficial only in the context of alternating periods of fruit scarcity and abundance. We discuss our findings in relation to the current global obesity pandemic, which has arisen with transitions in human diets toward low-cost, energy-dense, protein-dilute foods.
GPT-4o mini: Non-social science research article
Smarter biopsy decisions in thyroid nodules via dual-modal photoacoustic and ultrasound imaging
Junho Ahn, Jaekyung Lee, Kwangsoon Kim, Ja Seong Bae, Chan Kwon Jung, Minseong Kim, Wonseok Choi, Byullee Park, Dong-Jun Lim, Chulhong Kim
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Thyroid nodules are primarily diagnosed using ultrasound imaging (USI), but its low specificity leads to unnecessary fine-needle aspiration biopsies (FNABs). In particular, USI’s limited ability to differentiate follicular neoplasms from benign nodules contributes to suboptimal biopsy decision-making. We propose a dual-modal imaging approach that combines multiparametric photoacoustic imaging (PAI) and USI to support smarter biopsy decisions. In 106 patients with 29 benign nodules, 45 papillary thyroid carcinomas, and 32 follicular neoplasms, three PAI-derived parameters—the photoacoustic spectral gradient, oxygen saturation, and skewness of the oxygen saturation distribution—were combined using a support vector machine. Following USI-based American Thyroid Association (ATA) guidelines, they were used to develop the ATA-Photoacoustic (ATAP) scoring system. The ATAP score achieved 97% sensitivity and 38% specificity in distinguishing nodules requiring FNAB. Our approach enabled better identification of benign nodules, reducing unnecessary FNAB in 11 of the 29 benign cases. This dual-modal strategy can assess thyroid nodules, effectively reducing unnecessary biopsies while maintaining high diagnostic accuracy.
GPT-4o mini: Non-social science research article
Annotation-free discovery of disease-relevant cells in single-cell datasets
Erin Craig, Timothy J. Keyes, Jolanda Sarno, Jeremy P. D’Silva, Pablo Domizi, Maxim Zaslavsky, Albert Tsai, David Glass, Garry P. Nolan, Trevor Hastie, Robert Tibshirani, Kara L. Davis
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In single-cell datasets, patient labels indicating disease status (e.g., “sick” or “not sick”) are typically available, but individual cell labels indicating which of a patient’s cells are associated with their disease state are generally unknown. To address this, we introduce mixture modeling for multiple-instance learning (MMIL), an expectation-maximization approach that trains cell-level binary classifiers using only patient-level labels. Applied to primary samples from patients with acute leukemia, MMIL accurately separates leukemia from nonleukemia baseline cells, including rare minimal residual disease (MRD) cells; generalizes across tissues and treatment time points; and identifies biologically relevant features with accuracy approaching that of a hematopathologist. MMIL can also incorporate cell labels when they are available, creating a robust framework for leveraging both labeled and unlabeled cells. MMIL provides a flexible modeling framework for cell classification, especially in scenarios with unknown gold-standard cell labels.
GPT-4o mini: Non-social science research article
High-resolution MRI reveals uteroplacental flow dynamics in a 3D-printed human placental cotyledon model
Nirav Barapatre, David Frank, Franz Edler von Koch, Sven Grundmann, Hans-Georg Frank, Martin Bruschewski
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Doppler measurements of the uterine arteries are indirect measures of the uteroplacental blood flow. Given that the intervillous flow cannot be resolved by clinical imaging, theoretical models are used to study the flow dynamics in the intervillous space (IVS). We propose an experimental method to visualize the flow within the IVS of a single placental cotyledon postpartum. At first, a cotyledon is measured by micro-computed tomography imaging. The reconstructed volume is then used to create a near-realistic placenta model. Four variations of arterial inlets are designed to simulate both normal and abnormal flow patterns. A scaled version of the model is printed in three dimensions. Magnetic resonance imaging–based velocity measurements inside the printed model, which is perfused with a Newtonian fluid at two Reynolds numbers, revealed that the flow patterns are primarily influenced by the Reynolds number and the dilation of the arterial inlet. The spiralization of the arterial pathway had only a minimal impact.
GPT-4o mini: Non-social science research article
Magnetically actuated multimaterial fiberbot for precise minimally invasive knee laser surgery
Yuqi Zou, Yu Liu, Yang Li, Lvyun Yang, Yang Liu, Kaidong He, Yuanzhuo Xiang, Jingyu Ouyang, Pan Li, Jun Liang, Ning Zhou, Huaping Zang, Nan Ruan, Peng Li, Mi Xiao, Xiang Lu, Ruilin Zheng, Lili Hu, Guangming Tao
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Conventional methods, such as open and arthroscopy-assisted surgery, still encounter challenges in terms of tool flexibility when addressing knee diseases in patients. Robotics has enhanced the precision and efficiency of numerous surgical procedures. However, there is still a lack of minimally invasive surgical tools capable of flexibly resecting knee lesions. Here, we present a flexible fiberbot that integrates steerable midinfrared laser ablation and active navigation functions. The fiberbot features an internal multicore structure for midinfrared laser delivery and an external magnetic elastomer, allowing precise control under an applied magnetic field. The fiberbot was demonstrated to perform precise navigation and steering in a constrained spherical model and an isolated pig knee joint. Moreover, the fiberbot was further demonstrated in steerable laser ablation for leg bones of rats in vivo. Given its compact design, safer actuation, and quicker manipulation, our fiberbot is expected to pave a promising avenue for future knee surgery.
GPT-4o mini: Non-social science research article
Phase separation in lead-saponified drying oils: Implications for historical painting techniques and paint stability
Lucie Laporte, David Touboul, Thierry Pouget, Nicolas Benoot, Guylaine Ducouret, Sophie Rochut, Maguy Jaber, Frédéric Gobeaux, Laurence de Viguerie
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Renaissance Masters often prepared siccative oils by heating linseed oil with siccatives, particularly lead oxide, inducing partial saponification and altering its properties. Our reconstructions show that lead-saponified oils naturally separate into two phases. In this study, we investigate the differences between these two phases through a comprehensive set of analytical methods, from macrolevel assessments (rheology) to microlevel characterizations (small and wide-angle x-ray scattering, optical microscopy, and scanning electron microscopy) and chemical analyses. The lower phase is enriched in free fatty acids and lead carboxylates, especially saturated species—both as free acids and metal soaps—prone to self-organization. As a result, the lower phase displays a pronounced lamellar organization with partial crystallization and exhibits viscoelastic and shear-thinning properties. In contrast, the unstructured upper phase behaves as a Newtonian fluid. The observed phenomena share similarities with the formation of soap-related defects such as protrusions, linked to saturated lead soaps.
GPT-4o mini: Non-social science research article
Light-triggered molecular mechanotherapy of tumor using membrane-mimicking conjugated oligoelectrolytes
Peirong Zhou, Di Zhang, Yingying Meng, Xiaoran Huang, Yongchuan Wu, Yuanqing Bai, Jingjing Guo, Hongwei Song, Kai Zhang, Liang Yao, Guillermo C. Bazan, Guangxue Feng, Cheng Zhou
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A class of light-mediated mechanotherapeutic agents was developed on the basis of conjugated oligoelectrolytes (COEs), which mimic the topology of lipid membranes and intrinsically exhibit excellent biocompatibility. Low-dose white light irradiation (20 milliwatts per square centimeter for 10 minutes) substantially decreased the half-maximal inhibitory concentration of the optimized COE against A549 cancer cells from more than 256 to 0.6 micromolar. Typical photodynamic and photothermal effects were not responsible for the potent anticancer efficacy. Biophysical and photophysical experiments using vesicle models revealed that COEs can induce mechanical force likely by molecular conformation change within lipid membranes under light exposure, supporting the mechanotherapeutic mechanism by which COEs after excitation can physically disrupt cell membrane. Investigation of two other COEs with similar spectral properties but different backbone architectures revealed that their mechanotherapeutic efficacy is dependent on molecular topology. These results highlight the potential to develop light-responsive mechanotherapeutic agents based on membrane-mimicking COE platform for cancer treatment.
GPT-4o mini: Non-social science research article
Identification of renal stem cells in zebrafish
Ting Yu, Xiaoliang Liu, Xiaoqin Tan, Yunfeng Zhang, Zhongwei He, Wenmin Yang, Tingting Tian, Yan Li, Jinghong Zhao, Chi Liu
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Renal stem cells (RSC) hold great promise as kidney disease regenerative therapies. However, RSCs capable of regenerating de novo nephrons remain unidentified in vertebrates. Therefore, this study aimed to identify RSCs in zebrafish. Single-cell RNA sequencing revealed eya2 , pax2a , and six2a as primary markers of zebrafish RSCs. Real-time imaging demonstrated that RSCs originated from eya2 -positive mesenchymal cells. Notably, photoconversion-based lineage tracing and serial transplantation assays revealed a unique RSC renewal process, characterized by a differentiation-proliferation-dedifferentiation mode. This process generates nephrons and nascent RSCs concurrently. In addition, precise Wnt signaling is key for RSC renewal and differentiation balance and directly activates eya2 expression to initiate renewal. This discovery establishes a foundation for the advancement of stem cell therapies for kidney diseases.
GPT-4o mini: Non-social science research article
Liver regeneration–associated hepatocellular YAP1 activation prevents colorectal cancer liver metastasis through glutamine competition
Qiang Yu, Mincheng Yu, Peiyi Xie, Lei Guo, Yufei Zhao, Wenxin Xu, Xian Li, Mengyuan Wu, Zihao Zhang, Zheng Chen, Yongsheng Xiao, Jian Zhou, Jia Fan, Mien-Chie Hung, Yongfeng Xu, Bo Zhang, Qinghai Ye, Hui Li
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The literature suggests that hepatocellular Yes-associated protein 1 (YAP1) signaling is activated following hepatectomy and that such activation can suppress the growth of metastatic liver tumors. The prognosis of a real-world cohort of 240 patients with colorectal cancer liver metastasis (CRLM) undergoing major and minor hepatectomy was compared after adjusting for confounding factors. To model CRLM, we induced liver metastasis in mice by transsplenically injecting MC38 cells. We found that patients with CRLM and mice undergoing major hepatectomy had better survival compared to those undergoing minor hepatectomy. Mechanistically, extensive hepatectomy activates hepatocellular YAP1 by regulating the epidermal growth factor receptor, altering glutamine metabolism–related gene expression and increasing liver glutamine consumption. This metabolic shift leads to glutamine scarcity in tumor cells, causing increased reactive oxygen species production, which promotes loss of YAP1 activity in tumor cells. Consequently, the production of the chemokine CXCL5 is suppressed, which inhibits myeloid-derived suppressor cell infiltration and enhancing the immunological function of CD8 + T cells.
GPT-4o mini: Non-social science research article
Naturally high fatigue performance of a 3D printing titanium alloy across all stress ratios
Zhan Qu, Zhenjun Zhang, Rui Liu, Zhefeng Zhang
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Three-dimensional printing of structural materials, namely, additive manufacturing (AM), has notable advantages in fabricating structurally complex engineering components. These complex components usually endure comprehensive fatigue examination due to their complex stress distribution with varying stress ratios during service. Therefore, it is important to ensure the fatigue reliability of additive manufactured materials across all stress ratios. We found that the AM microstructure itself in a Ti-6Al-4V alloy successfully synthesizes the tripartite advantages of fine prior ÎČ grain boundaries, void-free, and fine α grains, which are respectively sensitive to the low, medium, and high stress ratio regions. Under this synergistic effect, the fatigue performance of the natural AM microstructure across all stress ratios not only outperforms all additive manufactured and forged Ti-6Al-4V alloys, but also surpasses other metallic materials. Our finding highlights the potential advantage of additive manufacturing technology in producing complex components with high fatigue resistance, substantially expanding its application scope.
GPT-4o mini: Non-social science research article
High-confidence reconstruction for Laplace inversion in NMR based on uncertainty-informed deep learning
Bo Chen, Yuebin Zhang, Lina Wang, Zhe Zhan, Xun Guan, Zhuoran Rong, Yinping Cui, Enping Lin, Shuohui Cao, Yuqing Huang, Yu Yang, Zhong Chen
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Laplace-related techniques in nuclear magnetic resonance (NMR), including both standalone Laplace NMR and combined Laplace-Fourier NMR, provide detailed insights into molecular dynamics and spin interactions through the measurement of relaxation and diffusion parameters, offering complementary chemical resolution to Fourier NMR. Spectrum reconstruction with accurate diffusion coefficients or relaxation time is essential for the Laplace-related NMR experiments, but existing processing methods generally yield varying results because of the ill-posed nature of inverse Laplace transform, making it challenging to assess the accuracy and reliability of estimations without ideal references. To address this, we developed a deep learning–based method that not only recovers parameter distributions from exponential signals with improved accuracy but also provides an uncertainty estimation for each reconstruction result. This additional insight allows the user to assess the confidence across spectral regions, providing a clearer and more reliable framework for Laplace-related data interpretation, thus facilitating broader applications in fields such as chemistry and materials science.
GPT-4o mini: Non-social science research article
Reverse control of biological networks to restore phenotype landscapes
Insoo Jung, Corbin Hopper, Seong-Hoon Jang, Hyunsoo Yeo, Kwang-Hyun Cho
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Biological systems consist of genetic elements and their regulatory interactions, forming networks that maintain life. However, accumulated alterations such as DNA damage can distort biological behavior, leading to undesirable responses to stimulus. This raises the question of whether we can restore their nominal stimulus-response relationships. Current control approaches tend to enforce a single desired response rather than restore the proper capacity for variable responses to different stimulus. Here, we present an algebraic reverse control (ARC) framework for reversion of altered biological networks. ARC leverages matrix operations to quantify the phenotype landscape of the altered network and identifies reverse control targets for recovering the phenotype landscape of a nominal network. ARC is scalable to large Boolean networks and identifies effective control targets to restore biological behavior.
GPT-4o mini: Non-social science research article
Characterization of the glycoproteins of fish and amphibian influenza B–like viruses
Gagandeep Singh, Jiachen Huang, Disha Bhavsar, Kirill Vasilev, James A. Ferguson, Geert-Jan Boons, Viviana Simon, Robert P. de Vries, Julianna Han, Andrew Ward, Florian Krammer
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Influenza-like virus sequences previously identified in fish and amphibians cluster as a sister clade of influenza B viruses but remain largely uncharacterized. We demonstrate that salamander influenza-like virus (SILV) hemagglutinin (HA) is functionally divergent from influenza B virus HA and does not bind to α2,3- and α2,6-linked sialic acids. However, the HAs of Siamese algae-eater influenza-like virus (SAEILV) and chum salmon influenza-like virus (CSILV) bind to α2,3-linked sialic acid. Furthermore, SAEILV HA binds to sialyated Lewis X, is activated by human airway enzymes, and is fusogenic over a broad pH range. SAEILV neuraminidase (NA) has a highly conserved active site and a similar structure to other known NAs. We also determined the cryo–electron microscopy structure of the HA of a previously described virus from the same sister clade, the Wuhan spiny eel influenza virus (WSEIV). No cross-reactive antibodies against these HAs or NAs were found in human serum, suggesting that humans are immunologically naĂŻve to these viruses.
GPT-4o mini: Non-social science research article
Shoreline wave breaking strongly enhances the coastal sea spray aerosol population: Climate and air quality implications
Shengqian Zhou, Matthew Salter, Timothy Bertram, Eduardo Brito Azevedo, Francisco Reis, Jian Wang
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Sea spray aerosol (SSA) emission is a major source of atmospheric aerosols, influencing global climate and coastal air quality. Much of our knowledge about SSA derives from coastal observations near shorelines, but whether and when these observations accurately represent open oceans remain unclear. Here, we show that strong nearshore SSA production during high-wave periods greatly enhances downwind cloud condensation nuclei (CCN) and aerosol mass concentrations. Strong shoreline wave breaking is widespread globally, and swell waves, which are decoupled from local winds, play a dominant role in many coastal regions. Therefore, extrapolating results based on coastal measurements to open oceans may significantly overestimate SSA concentration and its contribution to CCN and, by extension, the impact of SSA on clouds and climate. Additionally, the strong enhancement of coastal aerosol population by shoreline wave breaking and its environmental impact on coastal communities cannot be captured by current regional models, which do not parameterize nearshore SSA generation using wave energy or completely neglect it.
GPT-4o mini: Non-social science research article
An alternative cytoplasmic SFPQ isoform with reduced phase separation potential is up-regulated in ALS
Jacob Neeves, Marija Petrić Howe, Oliver J. Ziff, Beth Callaghan, Daniel Jutzi, Koustav Pal, Theodoros I. Roumeliotis, Jyoti Choudhary, Adrian M. Isaacs, Frank Rigo, C. Frank Bennett, Marc-David Ruepp, Rickie Patani
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Splicing factor proline- and glutamine-rich (SFPQ) is an RNA binding protein that broadly regulates RNA metabolism. Although its nuclear roles are well studied, evidence of SFPQ’s cytoplasmic functionality is emerging. Altered expression and nuclear-to-cytoplasmic redistribution of SFPQ have been recognized in amyotrophic lateral sclerosis (ALS) pathology, yet the mechanistic bases for these phenomena remain undetermined. We identified altered SFPQ splicing in ALS, increasing the expression of an alternative mRNA isoform lacking a nuclear localization sequence, which we termed “ altSFPQ .” We find that altSFPQ mRNA contributes to SFPQ autoregulation and is highly unstable yet exhibits context-specific translation with cytoplasm-predominant localization. Notably, reduced canonical SFPQ coincides with increased altSFPQ transcript expression in familial and sporadic ALS models, providing a mechanistic basis for SFPQ nuclear-to-cytoplasmic redistribution in patients with ALS. Last, we observe that the altSFPQ protein has reduced phase separation potential and differential protein binding compared to its canonical counterpart, providing insight into its mechanistic relevance to physiology and ALS pathogenesis.
GPT-4o mini: Non-social science research article
Estimating the predictability of questionable open-access journals
Han Zhuang, Lizhen Liang, Daniel E. Acuna
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Questionable journals threaten global research integrity, yet manual vetting can be slow and inflexible. Here, we explore the potential of artificial intelligence (AI) to systematically identify such venues by analyzing website design, content, and publication metadata. Evaluated against extensive human-annotated datasets, our method achieves practical accuracy and uncovers previously overlooked indicators of journal legitimacy. By adjusting the decision threshold, our method can prioritize either comprehensive screening or precise, low-noise identification. At a balanced threshold, we flag over 1000 suspect journals, which collectively publish hundreds of thousands of articles, receive millions of citations, acknowledge funding from major agencies, and attract authors from developing countries. Error analysis reveals challenges involving discontinued titles, book series misclassified as journals, and small society outlets with limited online presence, which are issues addressable with improved data quality. Our findings demonstrate AI’s potential for scalable integrity checks, while also highlighting the need to pair automated triage with expert review.
GPT-4o mini: Non-social science research article
ACTN3 genotype influences androgen response in developing murine skeletal muscle
Kelly N. Roeszler, Michael See, Lyra R. Meehan, Giscard Lima, Alexander Kolliari-Turner, Sarah E. Alexander, Shanie Landen, Harrison D. Wood, Chrystal F. Tiong, Weiyi Chen, Tomris Mustafa, Peter J. Houweling, Nir Eynon, Severine Lamon, Yannis Pitsiladis, David J. Handelsman, Fernando J. Rossello, Mirana Ramialison, Kathryn N. North, Jane T. Seto
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Androgens act through androgen receptor (AR) to maintain muscle mass. Evidence suggests that this pathway is influenced by “the gene for speed,” ACTN3 (α-actinin-3). Given that one in five people lack α-actinin-3, it is possible that they may respond to androgens differently. Here, we show that α-actinin-3 deficiency decreases AR in muscles of mice and humans (in males and females) and that AR positively correlates with α-actinin-3 expression in a dosage-dependent manner. α-Actinin-3 deficiency exacerbates gastrocnemius mass loss with androgen deprivation in male mice and stunts the muscle growth response to dihydrotestosterone in female mice at the onset of puberty. This is mediated by differential activation of pathways regulating amino acid metabolism, intracellular transport, autophagy, mitochondrial activity, MAPK, and calcineurin signaling, likely driven by seven key genes that are both androgen sensitive and α-actinin-3–dependent in expression. Our results highlight a role for ACTN3 as a regulator of muscle mass and a genetic modifier of androgen action in skeletal muscle.
GPT-4o mini: Non-social science research article
Correlation between unconventional superconductivity and strange metallicity revealed by operando superfluid density measurements
Ruozhou Zhang, Mingyang Qin, Chenyuan Li, Zhanyi Zhao, Zhongxu Wei, Juan Xu, Xingyu Jiang, Wenxin Cheng, Qiuyan Shi, Xuewei Wang, Jie Yuan, Yangmu Li, Qihong Chen, Tao Xiang, Subir Sachdev, Zi-Xiang Li, Kui Jin, Zhongxian Zhao
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Strange-metal behavior has been observed in superconductors ranging from cuprates to pressurized nickelates, but its relationship to unconventional superconductivity remains elusive. Here, we perform operando superfluid density measurements on ion-gated FeSe films. We observe a synchronized evolution of the superconducting condensate and the strange-metal phase with electron doping, from which a linear scaling between zero-temperature superfluid density and strange-metal resistivity coefficient is further established. The scaling also applies to different iron-based and cuprate superconductors despite their distinct electronic structures and pairing symmetries. Such a correlation can be reproduced in a theoretical calculation on the two-dimensional Yukawa-Sachdev-Ye-Kitaev model by considering a cooperative effect of quantum critical fluctuation and disorder. These findings suggest that a common mechanism may govern both the Cooper pair condensation and the normal-state strange metallicity in unconventional superconductors.
GPT-4o mini: Non-social science research article
Source mechanism of impulsive seafloor events that track submarine lava flows
Peifeng Wang, Yen Joe Tan, DelWayne R. Bohnenstiehl, William S.D. Wilcock, Maya Tolstoy, Felix Waldhauser, Yan Zhan, Wei-Ran Li
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Most of Earth’s volcanic eruptions are hidden beneath the ocean in complete darkness. Recent studies suggested that a type of impulsive event can track submarine lava flows, but their source mechanism remains uncertain. We analyze >20,000 impulsive events from the 2015 Axial Seamount eruption and find that their seismo-acoustic waveform characteristics suggest an implosive source mechanism. Integrating constraints from their spatiotemporal evolution with heat transfer estimates and geological observations, we propose that while the largest events might be related to volatiles degassed from magma, most events are generated by the implosion of bubbles formed from the vaporization of entrapped seawater by hot erupted lava. Similar events have been detected at other seamounts and slow to fast-spreading mid-ocean ridges, although eruptions at >3000-meter depth have proportionately fewer events because seawater vaporization is inhibited. Therefore, these impulsive seafloor events can be leveraged to remotely characterize eruption dynamics in most submarine volcanic settings.
GPT-4o mini: Non-social science research article
Human endogenous retrovirus K (HERV-K) envelope structures in pre- and postfusion by cryo-EM
Jeremy Shek, Chen Sun, Elise M. Wilson, Fatemeh Moadab, Kathryn M. Hastie, Roshan R. Rajamanickam, Patrick J. Penalosa, Stephanie S. Harkins, Diptiben Parekh, Chitra Hariharan, Dawid S. Zyla, Cassandra Yu, Kelly C. L. Shaffer, Victoria I. Lewis, Ruben Diaz Avalos, Tomas Mustelin, Erica Ollmann Saphire
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Human endogenous retroviruses (HERVs) are remnants of ancient infections that comprise ~8% of the human genome. The HERV-K envelope glycoprotein (Env) is aberrantly expressed in cancers, autoimmune disorders, and neurodegenerative diseases, and is targeted by patients’ own antibodies. However, a lack of structural information has limited molecular and immunological studies of the roles of HERVs in disease. Here, we present cryo–electron microscopy structures of stabilized HERV-K Env in the prefusion conformation, revealing a distinct fold and architecture compared to HIV and simian immunodeficiency virus. We also generated and characterized a panel of monoclonal antibodies with subunit and conformational specificity, serving as valuable research tools. These antibodies enabled structure determination of the postfusion conformation of HERV-K Env, including its unique “tether” helix, and antibody-bound prefusion Env. Together, these results provide a structural framework that opens the door to mechanistic studies of HERV-K Env and tools for its evaluation as a potential therapeutic target.
GPT-4o mini: Non-social science research article
Cholinergic regulation of osteocyte mechanobiology: A paradigm for bone adaptation
Macy Mora-Antoinette, Andrea Garcia-Ortiz, Mariam Obaji, Alexander Saffari, Melia D. Matthews, Murtaza Wasi, Karl J. Lewis
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Recent evidence suggests that acetylcholine has a positive influence on bone mechanotransduction. Osteocytes express components for nicotinic acetylcholine receptors (nAChRs), which are known for mediating calcium signaling and may affect mechanosensitivity. Here, we use fluorescent imaging approaches to provide evidence of close spatial association between osteocytes and cholinergic nerve fibers in cortical bone in vivo. Moreover, we show that osteocytes are responsive to cholinergic signaling, influencing bone mechanoadaptation. We report sexually dimorphic patterns in bone structure and mechanobiology based on nAChR function. In females, osteocyte mechanosensitivity was decreased at small force magnitudes and tissue level deficits were recovered with anabolic loading. In males, osteocyte mechanosensitivity was increased in some groups and anabolic loading had very little effect on overall tissue architecture. This work establishes a previously unidentified paradigm wherein osteocytes interface with cholinergic nerves and bone mechanotransduction is regulated by osteocyte cholinergic signaling in a sexually dimorphic way.
GPT-4o mini: Non-social science research article
Bacteria induce an amoeboid phase in coccolithophores that persists after bloom collapse
Sophie T. Zweifel, Richard J. Henshaw, Oliver MĂŒller, Johannes M. Keegstra, Samuel G. V. Charlton, Roberto Pioli, Clara MartĂ­nez-PĂ©rez, Uria Alcolombri, Estelle Clerc, Roman Stocker
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Coccolithophores, including bloom-forming species, Gephyrocapsa huxleyi (formerly Emiliania huxleyi ), contribute ~1 to 10% of phytoplankton biomass and are critical for oceanic biogeochemical cycles. G. huxleyi is a model system for investigating algal-bacterial-viral interactions and responses to environmental changes and follows a biphasic lifecycle with motile haploid and nonmotile diploid phases. Here, we report a third, “amoeboid” phase: Light and electron microscopy revealed haploid cells rapidly transitioning to an elongated amoeboid cell with reduced motility. Metamorphosis was triggered by exposure to bacteria isolated from G. huxleyi mesocosm blooms, but not by classical phytoplankton stressors including viral infection. The amoeboid phase persisted beyond the collapse of the haploid population and was only observed in the bloom-forming coccolithophore species G. huxleyi and Gephyrocapsa oceanica under conditions reminiscent of late-stage algal blooms. These findings highlight a previously uncharacterized life phase in this ubiquitous phytoplankton and suggest a bacteria-resilient morphotype following algal bloom collapse.
GPT-4o mini: Non-social science research article
Declines of ebony and ivory are inextricably linked in an African rainforest
Vincent Deblauwe, Matthew Scott Luskin, Serge Désiré Assola, Olivier J. Hardy, Simon Jansen, Céline LoubiÚres, Gaston Guy Mempong, Jean Mathurin Ntsihe, Gilbert Oum Ndjock, Eric Rostand Onguene Kwecheu, Luke L. Powell, Bonaventure Sonké, Thomas B. Smith
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Critically endangered African forest elephants preferentially eat fruits and disperse seeds of carbon-dense trees, including the highly valued and threatened African ebony. The illegal ivory trade has led to severe declines in elephant populations, but the long-term impacts on tree species are poorly understood. Using a comprehensive dataset including age-class, spatial, genetic, and experimental data, across a hunting pressure gradient, we show how paired declines in elephant and ebony populations are linked by a previously unrecognized mutualism in which elephant dung protects ebony seeds against seed predators. Disruption of this mutualism by poaching exacerbates seed predation by herbivores and was associated with a 68% reduction in small sapling recruitment. This threat to the survival of a valuable and iconic tree species raises concerns about the far-reaching consequences of forest elephant extermination.
GPT-4o mini: Non-social science research article
BioFuse: A programmable timer switch of gene expression
Cheng Huang, Jie Zhao, Zichun Tan, Shang Dai, Binqiang Wang, Zhenming Xie, Furong Zhang, Yulong Zhou, Ning Yu, Chunhui Cai, Yonghua Yao, Baojun Wang, Bing Tian
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Current gene circuits designed to time gene expression depend on the intricate interactions among various regulators and their targets, which confines them to a limited range of temporal tunability. Here, we report a programmable timer switch of gene expression termed BioFuse, which allows the reaction time ranging from hours to days. BioFuse comprises a series of fuse-like tandem DNA cassettes that can be sequentially edited by the adenine base editors (ABEs), resulting in either the activation or deactivation of a downstream gene once the editing is complete. Adjusting the number of DNA cassettes incorporated allows precise programming of BioFuse’s reaction time. Applying BioFuse to control carotenoid biosynthesis genes decouples lycopene production from growth in E. coli and increases lycopene yield without external inducers. Using BioFuse in a bacterial autolysis system enables timely and efficient protein release. BioFuse offers a versatile tool for precise, wide-range timing of gene expression and metabolic activities in bacteria, with potential applications in industry and biomedicine.
GPT-4o mini: Non-social science research article
Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned
Stephan Wilmes, Jesse Tönjes, Maik Drechsler, Anita Ruf, Jan-Hannes SchĂ€fer, Anna LĂŒrick, Dovile Januliene, Steven Apelt, Daniele Di Iorio, Seraphine V. Wegner, Martin Loose, Arne Moeller, Achim Paululat, Daniel KĂŒmmel
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Rab GTPases organize intracellular trafficking and provide identity to organelles. Their spatiotemporal activation by guanine nucleotide exchange factors (GEFs) is tightly controlled to ensure fidelity. Our structural and functional comparison of the tri-longin domain RabGEFs Mon1-Ccz1 and Fuzzy-Inturned reveals the molecular basis for their target specificity. Both complexes rely on a conserved sequence motif of their substrate GTPases for the catalytic mechanism, while secondary interactions allow discrimination between targets. We also find that dimeric Mon1-Ccz1 from fungi and the metazoan homologs with the additional third subunit RMC1/Bulli bind membranes through electrostatic interactions via distinct interfaces. Protein-lipid interaction studies and functional characterization in flies reveal an essential function of RMC1/Bulli as mediator of GEF complex membrane recruitment. In the case of Fuzzy-Inturned, reconstitution experiments demonstrate that the BAR (Bin-Amphiphysin-Rvs) domain protein CiBAR1 can support membrane recruitment of the GEF. Collectively, our study demonstrates the molecular basis for the adaptation of TLD-RabGEFs to different cellular functions.
GPT-4o mini: Non-social science research article
Sequential effects in reaching reveal efficient coding in motor planning
Tianhe Wang, Yifan Fang, David Whitney
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The nervous system uses prior information to enhance movement accuracy, yet the underlying computational mechanisms remain relatively unclear. Prevailing motor control models emphasize Bayesian inference, where prior information is integrated to optimally estimate the current state. An alternative framework, efficient coding, proposes that the system dynamically reallocates encoding resources on the basis of environmental statistics—a mechanism highlighted in perception while underappreciated in motor control. We compared these frameworks in reaching movements, focusing on how the system leverages short-term priors in unpredictable environments. Unexpectedly, sequential effects aligned with the efficient coding model and contradicted Bayesian models. Specifically, current movements were biased in the opposite direction of previous movements, and movement variability decreased when successive reaches were similar. We further explored the temporal dynamics of these effects and showed that sequential bias is enhanced by intrinsic motor variability. These findings, accompanied by model comparisons, further support efficient coding in motor planning.
GPT-4o mini: Non-social science research article
Spatial and temporal heterogeneity foster high fish biodiversity in an Amazonian floodplain
Anne E. Magurran, Alexandre Pucci Hercos, Faye Moyes, Jonas Alves de Oliveira, Carolina Gomes Sarmento, Diego Matheus de Mello Mendes, FlĂĄvia Alessandra da Silva Nonato, Jomara Cavalcante de Oliveira, Danielle Pedrociane Cavalcante Rossato, TĂșlio Bernardo Caxias de Oliveira, Jade Beatriz Alves da Silva, Yana Karine da Silva Coelho, Tatiana Martins Vieira, Raphael Aquino Heleodoro, Peter A. Henderson, Helder Lima de Queiroz
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The high biodiversity of tropical ecosystems was one of the earliest ecological patterns to be reported, but the ecological processes that maintain this diversity remain unresolved. Here, we revisit Pianka’s 1966 hypothesis that spatial heterogeneity contributes to tropical biodiversity. Using a comprehensive survey of a fish community in a central Amazonian floodplain, conducted over the 2003, 2012, and 2022 hydrological cycles, we ask if the high levels of environmental heterogeneity (both temporal and spatial) that characterize this ecosystem constrain the capacity of species to dominate local assemblages. We find rapid replacement of dominant species, with local species richness inversely related to dominance. Marked turnover in fish community structure and composition is also present, with different functional groups favored under changing environmental conditions. By showing that turnover in dominant species fuels species coexistence, we identify an ecological mechanism that helps explain how environmental heterogeneity can foster tropical biodiversity.
GPT-4o mini: Non-social science research article
Elucidating tissue and subcellular specificity of the entire SUMO network reveals how stress responses are fine-tuned in a eukaryote
Jason Banda, Shraboni Ghosh, Dipan Roy, Kishor D. Ingole, Lisa Clark, Eshan Sharma, Sumesh Kakkunath, Kawinnat Sue-Ob, Rahul Bhosale, Leah Band, Srayan Ghosh, Darren Wells, Jonathan Atkinson, Nicholas J. Provart, Malcolm J. Bennett, Kathryn S. Lilley, Andrew Jones, Miguel De Lucas, Anthony Bishopp, Ari Sadanandom
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SUMOylation is essential in plant and animal cells, but it remains unknown how small ubiquitin-like modifier (SUMO) components act in concert to modify specific targets in response to environmental stresses. In this study, we characterize every SUMO component in the Arabidopsis root to create a complete SUMO Cell Atlas in eukaryotes. This unique resource reveals wide spatial variation, where SUMO proteins and proteases have subfunctionalized in both their expression and subcellular localization. During stress, SUMO conjugation is mainly driven by tissue-specific regulation of the SUMO E2-conjugating enzyme. Stress-specific modulation of the SUMO pathway reveals unique combinations of proteases being targeted for regulation in distinct root tissues by salt, osmotic, and biotic signals. Our SUMO Cell Atlas resources reveal how this posttranslational modification (PTM) influences cellular- and tissue-scale adaptations during root development and stress responses. To our knowledge, we provide the first comprehensive study elucidating how multiple stress inputs can regulate an entire PTM system.
GPT-4o mini: Non-social science research article
European supercell thunderstorms—A prevalent current threat and an increasing future hazard
Monika Feldmann, Michael Blanc, Killian P. Brennan, Iris Thurnherr, Patricio Velasquez, Olivia Martius, Christoph SchÀr
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Supercell thunderstorms are the most hazardous thunderstorm category and particularly impactful to society. Their monitoring is challenging and often confined to the radar networks of single countries. By exploiting kilometer-scale climate simulations, we have derived a previously unknown characterization of supercell occurrence in Europe for the current and a warmer climate. The current climate shows several hundred supercells per convective season. Occurrence peaks are colocated with complex topography, e.g., the Alps. The absolute frequency maximum lies along the southern Alps and minima over the oceans and flat areas. Comparing a current-climate simulation with a pseudo–global warming +3°C global warming scenario, the future climate simulation shows an average increase of supercell occurrence by 11%. However, there is a spatial dipole of change with strong increases in supercell frequencies in central and eastern Europe and a decrease in frequency over the Iberian Peninsula and southwestern France.
GPT-4o mini: Non-social science research article
Understanding monocyte-driven neuroinflammation in Alzheimer’s disease using human cortical organoid microphysiological systems
Chunhui Tian, Zheng Ao, Jonas Cerneckis, Hongwei Cai, Lei Chen, Hengyao Niu, Kazuo Takayama, Jungsu Kim, Yanhong Shi, Mingxia Gu, Takahisa Kanekiyo, Feng Guo
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Increasing evidence strongly links neuroinflammation to Alzheimer’s disease (AD) pathogenesis. Peripheral monocytes are crucial components of the human immune system, but their contribution to AD pathogenesis is still largely understudied partially due to limited human models. Here, we introduce human cortical organoid microphysiological systems (hCO-MPSs) to study AD monocyte-mediated neuroinflammation. By culturing doughnut-shape organoids on 3D-printed devices within standard 96-well plates, we generate hCO-MPSs with reduced necrosis, minimized hypoxia, and improved viability. Using these models, we found that monocytes from AD patients exhibit increased infiltration ability, decreased amyloid-ÎČ clearance capacity, and stronger inflammatory response than monocytes from age-matched control donors. Moreover, we observed that AD monocytes induce pro-inflammatory effects such as elevated astrocyte activation and neuronal apoptosis. Furthermore, the marked increase in IL1B and CCL3 expression underscores their pivotal role in AD monocyte-mediated neuroinflammation. Our findings provide insight into understanding monocytes’ role in AD pathogenesis, and our lab-compatible MPS models may offer a promising way for studying various neuroinflammatory diseases.
GPT-4o mini: Non-social science research article
Redox conduction facilitates direct interspecies electron transport in anaerobic methanotrophic consortia
Hang Yu, Shuai Xu, Yamini Jangir, Gunter Wegener, Victoria J. Orphan, Mohamed Y. El-Naggar
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Anaerobic methanotrophic archaea (ANME) and sulfate-reducing bacteria (SRB) form syntrophic partnerships in marine sediments to consume greenhouse gas methane. While direct interspecies electron transport is proposed to enable ANME/SRB symbiosis, its electrochemical properties remain uncharacterized. Here, using sediment-free enrichment cultures, we measured the electron transport capabilities of marine consortia under physiological conditions. Diverse ANME/SRB consortia exhibited high dry conductance close to electrogenic biofilms. This conductance diminished upon exposure to heat or oxygen but was preserved following paraformaldehyde fixation, indicating a biomolecular origin for this electric charge transfer. Cyclic voltammetry revealed redox activity centered at 28 ± 11, 94 ± 6, and 24 ± 7 millivolts for ANME-1/ Desulfofervidus , ANME-2a/Seep-SRB1, and ANME-2a+2c/Seep-SRB1+2 consortia, respectively. Generator-collector measurements further demonstrated that these redox components facilitate electron transport over micrometer-scale distances, sufficient to link archaeal and bacterial partners. Collectively, our results establish that marine ANME/SRB symbiosis uses redox conduction, consistent with multiheme cytochrome c , for direct interspecies electron transport.
GPT-4o mini: Non-social science research article
The Rayleigh-Taylor instability in a binary quantum fluid
Yanda Geng, Junheng Tao, Mingshu Zhao, Shouvik Mukherjee, Stephen P. Eckel, Gretchen K. Campbell, Ian B. Spielman
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Instabilities, where small fluctuations seed the formation of large-scale structures, govern dynamics in a variety of fluid systems. The Rayleigh-Taylor instability (RTI), present from tabletop to astronomical scales, is an iconic example characterized by mushroom-shaped incursions appearing when immiscible fluids are forced together. Despite its ubiquity, RTI experiments are challenging; here, we report the observation of the RTI in an immiscible binary superfluid consisting of a two-component Bose-Einstein condensate. We force these components together to initiate the instability, and observe the growth of mushroom-like structures. The interface can also be stabilized, allowing us to spectroscopically measure the “ripplon” interface modes. Last, we use matter-wave interferometry to transform the superfluid velocity field at the interface into a vortex chain. These results—in agreement with our theory—demonstrate the close connection between the RTI in classical and quantum fluids.
GPT-4o mini: Non-social science research article
Cells prioritize the regulation of cell mass density
Jinyu Fu, Qin Ni, Yufei Wu, Anoushka Gupta, Zhuoxu Ge, Hongru Yang, Yasin Afrida, Ishan Barman, Sean X. Sun
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A cell’s global physical state is characterized by its volume and dry mass. The ratio of cell mass to volume defines the cell mass density (CMD), which is also a measure of macromolecular crowding and concentrations of all proteins. Using the fluorescence eXclusion method (FXm) and quantitative phase microscopy (QPM), we investigate CMD dynamics following sudden changes in media osmolarity. We find that while cell volume and mass exhibit complex behavior after osmotic shock, CMD follows a straightforward monotonic recovery over 48 hours. This recovery is cell cycle independent and depends on coordinated adjustment of protein synthesis and volume growth rates. Unexpectedly, the protein synthesis rate decreases when CMD increases. We observe that nucleoplasm-cytoplasm transport is CMD dependent, which contributes to negative regulatory feedback on CMD. The Na + /H + exchanger helps regulate CMD by affecting both protein synthesis and volume change. Together, we reveal that cells have a robust control system that actively regulates CMD during environmental change.
GPT-4o mini: Non-social science research article
Coupling between ion transport and electronic properties in individual carbon nanotubes
Guandong Cui, Zhi Xu, Shuchen Zhang, Alessandro Siria, Ming Ma
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Carbon nanomaterials exhibit unique electrokinetic phenomena due to rapid ion transport within the Debye layer, which have been exploited for energy conversion, membrane technology, and liquid lubrication. The electronic properties of solids have been found to influence water permeation and proton transport; however, their effect on ion transport has not been observed. Here, we present an experimental investigation of ion transport in individual double-walled carbon nanotubes (CNTs) of both semiconducting and metallic nature. Systematic measurements show that conductance, streaming current, and osmotic current are larger in semiconducting tubes than in metallic ones. Together with a complete theoretical framework, we found that such behavior is caused by the smaller liquid-solid friction with the same surface charge density for the semiconducting system. As fast ion transport is the key element for efficient energy conversion, in CNTs, the thermoelectric conversion efficiency with ions is two orders of magnitude larger than with electrons, showing the supremacy of ions to recover the waste heat.
GPT-4o mini: Non-social science research article
Mitochondrial ROS drive foam cell formation via STAT5 signaling in atherosclerosis
Laura Boccuni, Frieda Marka, Manuel Salzmann, Alessia Schirripa, Elisabeth Ableitner, Magdalena Siller, Mira Brekalo, Patrick Haider, Stefan Stojkovic, Christoph Neumayer, Tiit Örd, Karoline Kollmann, Alice Assinger, Thomas Decker, Thomas Köcher, Michael B. Fischer, Marion Mußbacher, Andreas Bergthaler, Christian Hengstenberg, Bruno K. Podesser, Minna U. Kaikkonen, Johann Wojta, Philipp J. Hohensinner
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Macrophage-to-foam cell transition is an integral part of atherosclerotic plaque progression. Particularly, oxidized low-density lipoprotein (oxLDL) is a driving factor in foam cell formation, altering macrophage function and metabolism. The aim of our research was to understand the impact of oxLDL-induced mitochondrial reactive oxygen species on macrophage-to-foam cell differentiation. We demonstrate that macrophage oxLDL-derived superoxide modulates mitochondrial metabolic reprogramming, facilitating foam cell formation. Mechanistically, mitochondrial superoxide drives signal transducers and activators of transcription 5 (STAT5) activation, leading to reduced tricarboxylic acid cycle activity. In parallel, mitochondrial superoxide enhances chromatin accessibility at STAT5 target genes, establishing a distinct STAT5 signaling signature in foam cells ex vivo and in human and mouse plaques in vivo. Inhibition of STAT5 during atherosclerosis progression prevents the differentiation of macrophages to mature Trem2 hi Gpnmb hi foam cells. Collectively, our data describe an oxLDL-induced, mitochondrial superoxide–dependent STAT5 activation that leads to a self-amplifying feedback loop of reciprocal mitochondrial superoxide production and STAT5 activation, ultimately driving macrophage-to-foam cell transition.
GPT-4o mini: Non-social science research article
Amyloid-ÎČ oligomers, curvilinear and annular assemblies, imaged by cryo-ET, cryo-EM, and AFM
Ruina Liang, Anum Khursheed, Bogachan Tahirbegi, Andrea P. Torres-Flores, Shang Qi, Yao Tian, Hui Zhang, Piotr Szwedziak, Vladimir A. Volkov, Vidya C. Darbari, John H. Viles
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Prefibrillar structures of the amyloid-ÎČ (AÎČ) peptide are central to cytotoxicity in Alzheimer’s disease. Time-resolved imaging of oligomers has enabled quantification of their extension. A snapshot of these prefibrillar assemblies has been characterized using a combination of cryo–electron tomography (cryo-ET), cryo–electron microscopy (cryo-EM) single-particle analysis, and atomic force microscopy (AFM). A highly consistent diameter for all curvilinear protofibrils and oligomers of 2.8 nanometers suggests that these assemblies are structural extensions from the smaller oligomers. In situ AFM confirms that spherical oligomers template and extend over time into curvilinear protofibrils. Furthermore, their basic cross section suggests that amyloid fibrils might be initiated by the lateral binding of two curvilinear protofibrils. Cryo-ET/EM single particles also reveal ring-shaped annular assemblies. These have a central internal channel, ~1.4 nanometers in diameter, which is capable of traversing lipid membranes. Large conductance recorded using patch-clamp electrophysiology matches the internal diameter of the AÎČ annular architecture.
GPT-4o mini: Non-social science research article
Inhibition of craniosynostosis and premature suture fusion in Twist1 mutant mice with RNA nanoparticle gene therapy
Samuel Swearson, Steve Eliason, Dan Su, Kevin G. Rice, Brad A. Amendt
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Craniosynostosis is a common birth defect affecting 1 of the 2200 live births causing severe skull and cognitive defects, due to premature cranial suture fusion. The current surgical treatments require invasive calvaria vault remodeling and cranial bone resection in the baby. We demonstrate that inhibition of miR-200a in PMIS–miR-200a mice results in coronal suture fusion (craniosynostosis). Therefore, we use overexpression of miR-200a to prevent suture fusion in Twist1 mutant mice, a well-known model for craniosynostosis. We developed a PEGylated-peptide nanoparticle system to deliver plasmid DNA expressing miR-200a directly to the sutures of postnatal day 4 (P4) Twist1 mutant mice before suture fusion. Injection of the miR-200a nanoparticles under the scalp before suture fusion at P7 to P10 inhibited suture fusion. Treatments increased Gli1- and Six2-positive suture stem cells and the thickness of the periosteum layer. The treated Twist1 +/− mice increased body weight and were alert and active. We demonstrate an effective noninvasive gene therapy treatment for craniosynostosis.
GPT-4o mini: Non-social science research article
Field-free switching of perpendicular magnetization in a ferrimagnetic insulator with spin reorientation transition
Yixuan Song, Thanh Nguyen, Mingda Li, Caroline A. Ross, Geoffrey S. D. Beach
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Writing magnetic bits through spin-orbit torque (SOT) switching is promising for fast and efficient magnetic random-access memory devices. While SOT switching of out-of-plane (OOP) magnetized states requires lateral symmetry breaking, in-plane (IP) magnetized states suffer from low storage density. Here, we demonstrate a field-free switching scheme using a 5-nanometer europium iron garnet film grown with a (110) orientation that shows a spin reorientation transition from OOP to IP above room temperature. This scheme combines the benefits of high-density storage in the OOP states at room temperature and the efficient field-free SOT switching in the IP states at elevated temperatures. While conventional switching of OOP bits faces the dilemma that high OOP anisotropy is required to improve bit stability and low OOP anisotropy is required to lower switching current density, this scheme disentangles this interdependence, allowing for low switching currents to be possible without sacrificing the bit stability, offering opportunities for future memory devices.
GPT-4o mini: Non-social science research article
Engineering noncovalent π-stacked organic framework for intrinsic near-infrared photoactivated drug delivery
Ruxing Fu, Dong Meng, Xiao Han, Lu Liu, Chichia Chen, Ran Zheng, Yepin Zhao, Xuexiang Zhang, Xiao Lin, Mahdi Hasani, Yang Song, Tingxizi Liang, Di Wen, Hongjun Li, Ilhan Yavuz, Huiheng Feng, Zhen Gu, Zhenxing Li, Song Li, Feng Liu, Yang Yang
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Photoactivated drug delivery is a promising therapeutic strategy that enables spatial and temporal control of payload release. A critical component of this approach is the photoresponsive material that has sufficient drug-loading capacity and can be actuated by near-infrared (NIR) light with considerable penetration depths. Here, we establish a photoactivated drug delivery platform based on the π-stacked organic framework (πOF), which demonstrates an intrinsic NIR absorption and superior photothermal effect. πOF not only has considerable loading capacity for a variety of drugs but also prompts the inducible burst release of loaded cargoes under NIR irradiation with notable increase of the release rate. Based on these features, πOF is used to effectively modulate the delivery of resiquimod (R848) and simultaneously induce photothermal effect by NIR irradiation. In 4T1-bearing mouse models, the photoactivated release of R848 can significantly potentiate treatment efficacy.
The health burden and racial-ethnic disparities of air pollution from the major oil and gas lifecycle stages in the United States
Karn Vohra, Eloise A. Marais, Ploy Achakulwisut, Susan Anenberg, Colin Harkins
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The United States has one of the world’s largest oil and gas (O&G) industries, yet the health impacts and inequities from pollutants produced along the O&G lifecycle remain poorly characterized. Here, we model the contribution of major lifecycle stages (upstream, midstream, downstream, and end-use) to air pollution and estimate the associated chronic health outcomes and racial-ethnic disparities across the contiguous US in 2017. We estimate lifecycle annual burdens of 91,000 premature deaths attributable to fine particles (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone, 10,350 PM 2.5 -attributable preterm births, 216,000 incidences of NO 2 -attributable childhood-onset asthma, and 1610 lifetime cancers attributable to hazardous air pollutants (HAPs). Racial-ethnic minorities experience the greatest disparities in exposure and health burdens across almost all lifecycle stages. The greatest absolute disparities occur for Black and Asian populations from PM 2.5 and ozone, and the Asian population from NO 2 and HAPs. Relative inequities are most extreme from downstream activities, especially in Louisiana and Texas.

Socio-Economic Review

Agents and opponents of neoliberal globalization: military elites and the reorganization of global supply chains in a post-neoliberal era
Matthew J Baltz
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The reorganization of global supply chains and productive capabilities is arguably one the most significant indicators that the economic integration of previous decades and the neoliberal institutional arrangements that once supported them are weakening. A key driver of these trends has been the elevation of “national security” concerns, spurred by COVID-related lockdowns, war in Ukraine, and geopolitical rivalry between the USA and China. Yet the perspectives of military elites and planners who make war and preparation for war their vocation remain an understudied subject among scholars of neoliberalism and global governance. This article addresses this gap by focusing on how American militarists understood the threats and opportunities posed by greater economic integration during the previous era of neoliberalism’s ascendency. It identifies a noteworthy divergence in thinking and discusses how this divergence offers new insights on the significance of recent initiatives to achieve “supply chain security” in a post-neoliberal era.
Prosperity and inequality in mature knowledge economies
Nick O’Donovan
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In the 1990s, policymakers in affluent democracies viewed the ‘knowledge economy’ as a solution to economic stagnation and social exclusion. Yet, in many of these countries, the period from the mid-1990s to the mid-2020s has instead been associated with lacklustre levels of growth and widening inequalities. This article explores four potential explanations for growth trends during this period: skill-biased technological change, intellectual property monopoly, divergent national growth models, and automation. Using data from fourteen advanced democracies, it examines national-level transitions to and through the knowledge economy between 1995 and 2019, assessing how differences in inequality and prosperity trajectories link to differences in the knowledge-intensive industries in which different countries have specialized. It highlights how the inequality impacts of particular sectoral specialisms have changed as knowledge economies mature, with important implications for understanding the trajectories of different national growth models, and the possible effects of new technologies such as artificial intelligence on labour and capital in the near future.