I checked 6 multidisciplinary journals on Sunday, November 30, 2025 using the Crossref API. For the period November 23 to November 29, I found 23 new paper(s) in 5 journal(s).

Nature

GPT-4o mini: Non-social science research article
Multi-qubit nanoscale sensing with entanglement as a resource
Jared Rovny, Shimon Kolkowitz, Nathalie P. de Leon
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Nitrogen vacancy (NV) centres in diamond are widely deployed as local magnetic sensors, using single-qubit control to measure both time-averaged fields and noise with nanoscale spatial resolution1. Moving beyond single qubits to multi-qubit control enables new sensing modalities such as measuring nonlocal spatiotemporal correlators2 or using entangled states to enhance measurement sensitivity3. Here we describe protocols for using optically unresolved NV centre pairs and nuclear spins as multi-qubit sensors for measuring correlated noise at nanometre length scales. For noninteracting NV centres, we implement a phase-cycling protocol that disambiguates magnetic correlations from variance fluctuations, leveraging the presence of a third qubit, a 13C nucleus, to effect coherent single-NV spin flips and enable phase cycling even for co-aligned NV centres that are spectrally unresolved. For length scales around 10 nm, we create maximally entangled Bell states through dipole–dipole coupling between two NV centres and use these entangled states to directly read out the magnetic field correlation, rather than reconstructing it from independent measurements of unentangled NV centres. Importantly, this changes the scaling of sensitivity with readout noise from quadratic to linear. For conventional off-resonant readout of the NV centre spin state (for which the readout noise is roughly 30 times the quantum projection limit), this results in more than an order of magnitude improvement in sensitivity. Finally, we demonstrate methods for detecting high spatial- and temporal-resolution correlators with pairs of strongly interacting NV centres.
GPT-4o mini: Non-social science research article
Detection of triboelectric discharges during dust events on Mars
Baptiste Chide, Ralph D. Lorenz, Franck Montmessin, Sylvestre Maurice, Yann Parot, Ricardo Hueso, German Martinez, Alvaro Vicente-Retortillo, Xavier Jacob, Mark Lemmon, Bruno Dubois, Pierre-Yves Meslin, Claire Newman, Tanguy Bertrand, Grégoire Deprez, Daniel Toledo, Agustin Sånchez-Lavega, AgnÚs Cousin, Roger C. Wiens
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Lightning is among the most energetic manifestation of electrical activity in planetary atmospheres, with documented observations not only on Earth but also on Saturn and Jupiter1. On Mars, the existence of electrical activity has long been suspected2,3 but never directly demonstrated. The dusty atmosphere of Mars undergoes aeolian processes, ranging from wind-blown dust and sand, metre-to-hundred-metre-sized dust devils to thousand-kilometre-scale dust storms4, which, in Earth’s deserts, can become electrified through triboelectric charging5,6,7. For this reason, electric fields have been predicted to build up on Mars8,9,10, but with no measurement of Martian atmospheric electrical activity so far. Here we report in situ detections of triboelectric discharges, identified by their electrical and acoustic signatures captured by the SuperCam microphone aboard the Perseverance rover11,12. Fifty-five events have been detected over two Martian years, usually associated with dust devils and dust storm convective fronts. These serendipitous observations demonstrate that Martian electric fields can reach the breakdown threshold of the near-surface atmosphere of Mars, predicted to be on the order of several tens of kV m−1. Such electrical activity could affect dust dynamics13,14 and potentially fuel a reactive electrochemical environment enhancing the oxidizing capacity of the atmosphere, with consequences for the preservation of organic molecules15,16. This in situ evidence may have implications for surface chemistry, habitability and human exploration.
GPT-4o mini: Non-social science research article
Thalamocortical transcriptional gates coordinate memory stabilization
Andrea Terceros, Celine Chen, Yujin Harada, Tim Eilers, Millennium Gebremedhin, Pierre-Jacques Hamard, Richard Koche, Roshan Sharma, Priya Rajasethupathy
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The molecular mechanisms that enable memories to persist over long timescales from days to weeks and months are still poorly understood1. Here, to develop insights into this process, we created a behavioural task in which mice formed multiple memories but only consolidated some, while forgetting others, over the span of weeks. We then monitored circuit-specific molecular programs that diverged between consolidated and forgotten memories. We identified multiple distinct waves of transcription, that is, cellular macrostates, in the thalamocortical circuit that defined memory persistence. Of note, a small set of transcriptional regulators orchestrated broad molecular programs that enabled entry into these macrostates. Targeted CRISPR-knockout studies revealed that although these transcriptional regulators had no effects on memory formation, they had prominent, causal and strikingly time-dependent roles in memory stabilization. In particular, the calmodulin-dependent transcription factor CAMTA1 was required for initial memory maintenance over days, whereas the transcription factor TCF4 and the histone methyltransferase ASH1L were required later to maintain memory over weeks. These results identify a critical CAMTA1–TCF4–ASH1L thalamocortical transcriptional cascade that is required for memory stabilization and put forth a model in which the sequential recruitment of circuit-specific transcriptional programs enables memory maintenance over progressively longer timescales.
GPT-4o mini: Non-social science research article
Inhibitors supercharge kinase turnover through native proteolytic circuits
Natalie S. Scholes, Martino Bertoni, Arnau Comajuncosa-Creus, Katharina Kladnik, Xuefei Guo, Fabian Frommelt, Matthias Hinterndorfer, Hlib Razumkov, Polina Prokofeva, Martin P. Schwalm, Florian Born, Sandra Roehm, Hana Imrichova, Brianda L. Santini, Eleonora Barone, Caroline SchÀtz, Miquel Muñoz i Ordoño, Severin Lechner, Andrea Rukavina, Iciar Serrano, Miriam Abele, Anna Koren, Stefan Kubicek, Stefan Knapp, Nathanael S. Gray, Giulio Superti-Furga, Bernhard Kuster, Yigong Shi, Patrick Aloy, Georg E. Winter
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Targeted protein degradation is a pharmacological strategy that relies on small molecules such as proteolysis-targeting chimeras (PROTACs) or molecular glues, which induce proximity between a target protein and an E3 ubiquitin ligase to prompt target ubiquitination and proteasomal degradation 1 . Sporadic reports indicated that ligands designed to inhibit a target can also induce its destabilization 2–4 . Among others, this has repeatedly been observed for kinase inhibitors 5–7 . However, we lack an understanding of the frequency, generalizability and mechanistic underpinnings of these phenomena. Here, to address this knowledge gap, we generated dynamic abundance profiles of 98 kinases after cellular perturbations with 1,570 kinase inhibitors, revealing 160 selective instances of inhibitor-induced kinase destabilization. Kinases prone to degradation are frequently annotated as HSP90 clients, therefore affirming chaperone deprivation as an important route of destabilization. However, detailed investigation of inhibitor-induced degradation of LYN, BLK and RIPK2 revealed a differentiated, common mechanistic logic whereby inhibitors function by inducing a kinase state that is more efficiently cleared by endogenous degradation mechanisms. Mechanistically, effects can manifest by ligand-induced changes in cellular activity, localization or higher-order assemblies, which may be triggered by direct target engagement or network effects. Collectively, our data suggest that inhibitor-induced kinase degradation is a common event and positions supercharging of endogenous degradation circuits as an alternative to classical proximity-inducing degraders.
GPT-4o mini: Non-social science research article
Author Correction: Diversity-oriented synthesis yields novel multistage antimalarial inhibitors
Nobutaka Kato, Eamon Comer, Tomoyo Sakata-Kato, Arvind Sharma, Manmohan Sharma, Micah Maetani, Jessica Bastien, Nicolas M. Brancucci, Joshua A. Bittker, Victoria Corey, David Clarke, Emily R. Derbyshire, Gillian L. Dornan, Sandra Duffy, Sean Eckley, Maurice A. Itoe, Karin M. J. Koolen, Timothy A. Lewis, Ping S. Lui, Amanda K. Lukens, Emily Lund, Sandra March, Elamaran Meibalan, Bennett C. Meier, Jacob A. McPhail, Branko Mitasev, Eli L. Moss, Morgane Sayes, Yvonne Van Gessel, Mathias J. Wawer, Takashi Yoshinaga, Anne-Marie Zeeman, Vicky M. Avery, Sangeeta N. Bhatia, John E. Burke, Flaminia Catteruccia, Jon C. Clardy, Paul A. Clemons, Koen J. Dechering, Jeremy R. Duvall, Michael A. Foley, Fabian Gusovsky, Clemens H. M. Kocken, Matthias Marti, Marshall L. Morningstar, Benito Munoz, Daniel E. Neafsey, Amit Sharma, Elizabeth A. Winzeler, Dyann F. Wirth, Christina A. Scherer, Stuart L. Schreiber
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GPT-4o mini: Non-social science research article
Ethylene modulates cell wall mechanics for root responses to compaction
Jiao Zhang, Zengyu Liu, Edward J. Farrar, Minhao Li, Hui Lu, Zhuo Qu, Osvaldo Chara, Nobutaka Mitsuda, Shingo Sakamoto, Feiyang Xue, Qiji Shan, Ya Yu, Jingbin Li, Xiaobo Zhu, Mingyuan Zhu, Jin Shi, Lucas Peralta Ogorek, Augusto Borges, Malcolm J. Bennett, Wanqi Liang, Bipin K. Pandey, Dabing Zhang, Staffan Persson
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Soil stresses affect crop yields and present global agricultural challenges 1 . Soil compaction triggers reduction in root length and radial expansion driven by the plant hormone ethylene 2 . Here we report how ethylene controls cell wall biosynthesis to promote root radial expansion. We demonstrate how soil compaction stress, via ethylene, upregulates Auxin Response Factor1 in the root cortex, which represses cellulose synthase (CESA) genes. CESA repression drives radial expansion of root cortical cells by modifying the thickness of their cell walls, which results in a thicker epidermis and thinner cortex. Our research links ethylene signalling with root cell wall remodelling, and reveals how dynamic regulation of cellulose synthesis controls root growth in compacted soil.
GPT-4o mini: Non-social science research article
Polyclonal origins of human premalignant colorectal lesions
Debra Van Egeren, Ryan O. Schenck, Aziz Khan, Aaron M. Horning, Shanlan Mo, Clemens L. Weiß, Edward D. Esplin, Winston R. Becker, Si Wu, Casey Hanson, Nasim Barapour, Lihua Jiang, KĂ©vin Contrepois, Hayan Lee, Stephanie A. Nevins, Tuhin K. Guha, Hao Zhang, Zhen He, Zhicheng Ma, Emma Monte, Thomas V. Karathanos, Rozelle Laquindanum, Meredith A. Mills, Hassan Chaib, Roxanne Chiu, Ruiqi Jian, Joanne Chan, Mathew Ellenberger, Bahareh Bahmani, Basil Michael, Annika K. Weimer, D. Glen Esplin, Samuel Lancaster, Jeanne Shen, Uri Ladabaum, Teri A. Longacre, Anshul Kundaje, William J. Greenleaf, Zheng Hu, James M. Ford, Michael P. Snyder, Christina Curtis
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Cancer is generally thought to be caused by expansion of a single mutant cell1. However, analyses of early colorectal cancer lesions suggest that tumors may instead originate from multiple, genetically distinct cell populations2,3. Detecting polyclonal tumor initiation is challenging in patients, as it requires profiling early-stage lesions before clonal sweeps obscure diversity. To investigate this, we analyzed normal colorectal mucosa, benign and dysplastic premalignant polyps, and malignant adenocarcinomas (123 samples) from six individuals with familial adenomatous polyposis (FAP). Individuals with FAP have a germline heterozygous APC mutation, predisposing them to colorectal cancer and numerous premalignant polyps by early adulthood4. Whole-genome and/or whole-exome sequencing revealed that many premalignant polyps—40% with benign histology and 28% with dysplasia—were composed of multiple genetic lineages that diverged early, consistent with polyclonal origins. This conclusion was reinforced by whole-genome sequencing of single crypts from multiple polyps in additional patients which showed limited sharing of mutations among crypts within the same lesion. In some cases, multiple distinct APC mutations co-existed in different lineages of a single polyp, consistent with polyclonality. These findings reshape our understanding of early neoplastic events, demonstrating that tumor initiation can arise from the convergence of diverse mutant clones. They also suggest that cell-intrinsic growth advantages alone may not fully explain tumor initiation, highlighting the importance of microenvironmental and tissue-level factors in early cancer evolution.
GPT-4o mini: Non-social science research article
MAPK-driven epithelial cell plasticity drives colorectal cancer therapeutic resistance
Mark White, Megan L. Mills, Laura M. Millett, Kathryn Gilroy, Yourae Hong, Lucas B. Zeiger, Rosalin J. Simpson, Shania M. Corry, Amelia Ligeza, Tamsin R. M. Lannagan, Susanti Susanti, Rachel A. Ridgway, Ayse S. Yazgili, Lucile Grzesiak, Raheleh Amirkhah, Catriona A. Ford, Nikola Vlahov, Hannah Tovell, Leah Officer-Jones, Catherine Ficken, Rachel Pennie, Arafath K. Najumudeen, Alexander Raven, Nadia Nasreddin, Ekansh Chauhan, Andrew S. Papanastasiou, Colin Nixon, Vivienne Morrison, Rene Jackstadt, Janet S. Graham, Crispin J. Miller, Sarah J. Ross, Simon T. Barry, Valeria Pavet, Richard H. Wilson, John Le Quesne, Philip D. Dunne, Sabine Tejpar, Simon Leedham, Andrew D. Campbell, Owen J. Sansom
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The colorectal epithelium is rapidly renewing, with remarkable capacity to regenerate following injury. In colorectal cancer (CRC), this regenerative capacity can be co-opted to drive epithelial plasticity. While oncogenic MAPK signalling in CRC is common, with frequent mutations of both KRAS (40-50%) and BRAF (10%)1, inhibition of this pathway typically drives resistance clinically. Given the development of KRAS inhibitors, and licensing of BRAF inhibitor combinations2-4, we have interrogated key mechanisms of resistance to these agents in advanced preclinical CRC models. We show that oncogenic MAPK signalling induces epithelial state changes in vivo, driving adoption of a regenerative/revival stem like population, while inhibition leads to rapid transcriptional remodeling of both Kras- and Braf-mutant tumours, favoring a Wnt-associated, canonical stem phenotype. This drives acute therapeutic resistance in Kras- and delayed resistance in Braf-driven models. Importantly, where plasticity is restrained, such as in early metastatic disease, or through targeting ligand-dependent Wnt-pathway Rnf43 mutations, marked therapeutic responses are observed. This explains the super response to BRAF+EGFR targeted therapies previously observed in a BRAF/RNF43 co-mutant patient population, highlighting the criticality of cellular plasticity in therapeutic response. Together, our data provides clear insight into the mechanisms underpinning resistance to MAPK targeted therapies in CRC. Moreover, strategies that aim to corral stem cell fate, restrict epithelial plasticity or intervene when tumours lack heterogeneity may improve therapeutic efficacy of these agents.
GPT-4o mini: Non-social science research article
Building compositional tasks with shared neural subspaces
Sina Tafazoli, Flora M. Bouchacourt, Adel Ardalan, Nikola T. Markov, Motoaki Uchimura, Marcelo G. Mattar, Nathaniel D. Daw, Timothy J. Buschman
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Cognition is highly flexible—we perform many different tasks 1 and continually adapt our behaviour to changing demands 2,3 . Artificial neural networks trained to perform multiple tasks will reuse representations 4 and computational components 5 across tasks. By composing tasks from these subcomponents, an agent can flexibly switch between tasks and rapidly learn new tasks 6,7 . Yet, whether such compositionality is found in the brain is unclear. Here we show the same subspaces of neural activity represent task-relevant information across multiple tasks, with each task flexibly engaging these subspaces in a task-specific manner. We trained monkeys to switch between three compositionally related tasks. In neural recordings, we found that task-relevant information about stimulus features and motor actions were represented in subspaces of neural activity that were shared across tasks. When monkeys performed a task, neural representations in the relevant shared sensory subspace were transformed to the relevant shared motor subspace. Monkeys adapted to changes in the task by iteratively updating their internal belief about the current task and then, based on this belief, flexibly engaging the shared sensory and motor subspaces relevant to the task. In summary, our findings suggest that the brain can flexibly perform multiple tasks by compositionally combining task-relevant neural representations.
GPT-4o mini: Non-social science research article
Author Correction: Spatial fibroblast niches define Crohn’s fistulae
Colleen McGregor, Xiao Qin, Marta Jagielowicz, Tarun Gupta, Zinan Yin, Verena Lentsch, David Fawkner-Corbett, Vy Wien Lai, Paula Gomez Castro, Esther Bridges, Chloe Hyun-Jung Lee, Huei-Wen Chuang, Lei Deng, Anna Aulicino, Renuka Teague, Sorayya Moradi, Jun Sung Park, Jeongmin Woo, Kexin Xu, Ruchi Tandon, Nicole Cianci, Jan Bornschein, Ling-Pei Ho, Paulina Siejka-Zielinska, Zoe Christoforidou, Sarah Hill, Johannes Lehmann, Rhea Kujawa, Paola Vargas Gutierrez, Carol Cheng, Maria Greco, Katherine Baker, Mark Bignell, Bruce George, Eve Fryer, Michael Vieth, Agne Antanaviciute, Alison Simmons
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GPT-4o mini: Non-social science research article
Progressive coevolution of the yeast centromere and kinetochore
Jana Helsen, Kausthubh Ramachandran, Gavin Sherlock, Gautam Dey
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During mitosis, stable but dynamic interactions between centromere DNA and the kinetochore complex enable accurate and efficient chromosome segregation. Even though many proteins of the kinetochore are highly conserved 1,2 , centromeres are among the fastest evolving regions in a genome 3,4 , showing extensive variation even on short evolutionary timescales. Here we sought to understand how organisms evolve completely new sets of centromeres that still effectively engage with the kinetochore machinery by identifying and tracking thousands of centromeres across two major fungal clades, including more than 2,500 natural strain isolates and representing over 1,000 million years of evolution. We show that new centromeres spread progressively via drift and subsequent selection and that the kinetochore, which is evolving slowly in relative terms, appears to act as a filter to determine which new centromere variants are tolerated. Together, our findings provide insight into the evolutionary constraints and trajectories shaping centromere evolution.
GPT-4o mini: Non-social science research article
Author Correction: Matrix viscoelasticity promotes liver cancer progression in the pre-cirrhotic liver
Weiguo Fan, Kolade Adebowale, Lórånd Våncza, Yuan Li, Md Foysal Rabbi, Koshi Kunimoto, Dongning Chen, Gergely Mozes, David Kung-Chun Chiu, Yisi Li, Junyan Tao, Yi Wei, Nia Adeniji, Ryan L. Brunsing, Renumathy Dhanasekaran, Aatur Singhi, David Geller, Su Hao Lo, Louis Hodgson, Edgar G. Engleman, Gregory W. Charville, Vivek Charu, Satdarshan P. Monga, Taeyoon Kim, Rebecca G. Wells, Ovijit Chaudhuri, Natalie J. Török
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GPT-4o mini: Non-social science research article
NSD2 targeting reverses plasticity and drug resistance in prostate cancer
Jia J. Li, Alessandro Vasciaveo, Dimitris Karagiannis, Zhen Sun, Kristjan H. Gretarsson, Xiao Chen, Ouathek Ouerfelli, Fabio Socciarelli, Ziv Frankenstein, Hanyang Dong, Min Zou, Wei Yuan, Guangli Yang, Gabriel M. Aizenman, Tania Pannellini, Xinjing Xu, Himisha Beltran, Yu Chen, Kevin Gardner, Brian D. Robinson, Johann de Bono, Or Gozani, Cory Abate-Shen, Mark A. Rubin, Massimo Loda, Charles L. Sawyers, Andrea Califano, Chao Lu, Michael M. Shen
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Lineage plasticity is a cancer hallmark that drives disease progression and treatment resistance1,2. Plasticity is often mediated by epigenetic mechanisms that may be reversible; however, there are few examples of such reversibility. In castration-resistant prostate cancer (CRPC), plasticity mediates resistance to androgen receptor (AR) inhibitors and progression from adenocarcinoma to aggressive subtypes, including neuroendocrine prostate cancer (CRPC-NE)3,4,5. Here we show that plasticity-associated treatment resistance in CRPC can be reversed through the inhibition of NSD2, a histone methyltransferase6. NSD2 upregulation in CRPC-NE correlates with poor survival outcomes, and NSD2-mediated H3K36 dimethylation regulates enhancers of genes associated with neuroendocrine differentiation. In prostate tumour organoids established from genetically engineered mice7 that recapitulate the transdifferentiation to neuroendocrine states, and in human CRPC-NE organoids, CRISPR-mediated targeting of NSD2 reverts CRPC-NE to adenocarcinoma phenotypes. Moreover, a canonical AR program is upregulated and responses to the AR inhibitor enzalutamide are restored. Pharmacological inhibition of NSD2 with a first-in-class small molecule reverses plasticity and synergizes with enzalutamide to suppress growth and promote cell death in human patient-derived organoids of multiple CRPC subtypes in culture and in xenografts. Co-targeting of NSD2 and AR may represent a new therapeutic strategy for lethal forms of CRPC that are currently recalcitrant to treatment.
GPT-4o mini: Non-social science research article
iHALT unlocks liver functionality as a surrogate secondary lymphoid organ
John Gridley, David Pak, Anuradha Kumari, Jacob Shupak, Brantley Holland, Yifeng Shi, Sheetal Trivedi, Yongtao Wang, Sudhir Pai Kasturi, Amit Kapoor, Raymond T. Chung, Arash Grakoui
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Upon viral infection, the current paradigm of humoral immunity posits that germinal centre reactions occurring within secondary lymphoid organs (SLOs) yield effector plasma cells that subsequently traffic to infected organs or the bone marrow1,2,3. However, it is not well understood how viral tissue tropism may govern the spatiotemporal dynamics of such responses. Here we demonstrate that infection with a prototypical systemic virus indeed induces liver-trafficking plasma cells generated in SLOs, whereas strictly hepatotropic hepaciviral infection elicits locally primed, virus-specific plasma cells in the liver independently of SLO contribution. Such locally derived progenies emerged from inducible hepatic-associated lymphoid tissue (iHALT) structures containing generative foci of T follicular helper cells, myeloid cells and germinal centre-like B cells, often arising from single founder clones unique to individual periportal structures and locally supporting somatic hypermutation. Critically, the cellular composition, cell–cell contact partners and microarchitecture of such iHALT structures in mice were closely mirrored upon hepaciviral infection in humans. Functionally dependent upon CD40L signalling and cognate B cell receptor specificity, emerging CXCR4+VLA-4+LFA-1+CD44+CD138+ plasma cells were immediately retained along CXCL12+fibronectin+ICAM2+osteopontin+type I collagen+ periportal fibroblast tracts, acting as cognate anchoring pairs that were critical to their maintenance therein. In summary, we characterize humoral immunity exclusively generated and maintained within its extralymphoid site of viral infection in the liver amidst SLO dormancy, in which functional iHALT successfully compensates for strictly hepatotropic virus-induced SLO-evasion strategies to prevent persistent infection.
GPT-4o mini: Non-social science research article
Author Correction: Photocatalytic low-temperature defluorination of PFASs
Hao Zhang, Jin-Xiang Chen, Jian-Ping Qu, Yan-Biao Kang
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GPT-4o mini: Non-social science research article
Operating two exchange-only qubits in parallel
Mateusz T. Mądzik, Florian Luthi, Gian Giacomo Guerreschi, Fahd A. Mohiyaddin, Felix Borjans, Jason D. Chadwick, Matthew J. Curry, Joshua Ziegler, Sarah Atanasov, Peter L. Bavdaz, Elliot J. Connors, J. Corrigan, H. Ekmel Ercan, Robert Flory, Hubert C. George, Benjamin Harpt, Eric Henry, Mohammad M. Islam, Nader Khammassi, Daniel Keith, Lester F. Lampert, Todor M. Mladenov, Randy W. Morris, Aditi Nethwewala, Samuel Neyens, RenĂ© Otten, Linda P. Osuna Ibarra, Bishnu Patra, Ravi Pillarisetty, Shavindra Premaratne, Mick Ramsey, Andrew Risinger, John D. Rooney, Rostyslav Savytskyy, Thomas F. Watson, Otto K. Zietz, Anne Y. Matsuura, Stefano Pellerano, Nathaniel C. Bishop, Jeanette Roberts, James S. Clarke
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Semiconductors are among the most promising platforms to implement large-scale quantum computers, as advanced manufacturing techniques allow fabrication of large quantum dot arrays1. Various qubit encodings can be used to store and manipulate quantum information on these quantum dot arrays. Regardless of qubit encoding, precise control over the exchange interaction between electrons confined in quantum dots in the array is critical. Furthermore, it is necessary to execute high-fidelity quantum operations concurrently to make full use of the limited coherence of individual qubits. Here we demonstrate the parallel operation of two exchange-only qubits, consisting of six quantum dots in a linear arrangement. Using randomized benchmarking (RB) techniques, we show that issuing pulses on the five barrier gates to modulate exchange interactions in a maximally parallel way maintains the quality of qubit control relative to sequential operation. The techniques developed to perform parallel exchange pulses can be readily adapted to other quantum-dot-based encodings. Moreover, we show the first, to our knowledge, experimental demonstrations of an iSWAP gate for exchange-only qubits and of a charge-locking Pauli spin blockade (PSB) readout method. The results are validated using cross-entropy benchmarking (XEB)2, a technique useful for performance characterization of larger quantum computing systems; here it is used for the first time on a quantum system based on semiconductor technology.
GPT-4o mini: Non-social science research article
Author Correction: An asymmetric fission island driven by shell effects in light fragments
P. Morfouace, J. Taieb, A. Chatillon, L. Audouin, G. Blanchon, R. N. Bernard, N. Dubray, N. Pillet, D. Regnier, H. Alvarez-Pol, F. Amjad, P. AndrĂ©, G. Authelet, L. Atar, T. Aumann, J. Benlliure, K. Boretzky, L. Bott, T. Brecelj, C. Caesar, P. Carpentier, E. Casarejos, J. CederkĂ€ll, A. Corsi, D. Cortina-Gil, A. Cvetinović, E. De Filippo, T. Dickel, M. Feijoo, L. M. Fonseca, D. Galaviz, G. GarcĂ­a-JimĂ©nez, I. Gasparic, E. I. Geraci, R. GernhĂ€user, B. Gnoffo, K. Göbel, A. Graña-GonzĂĄlez, E. Haettner, A.-L. Hartig, M. Heil, A. Heinz, T. Hensel, M. Holl, C. Hornung, A. Horvat, A. Jedele, D. Jelavic Malenica, T. Jenegger, L. Ji, H. T. Johansson, B. Jonson, B. Jurado, N. Kalantar-Nayestanaki, E. Kazantseva, A. Kelic-Heil, O. A. Kiselev, P. Klenze, R. Knöbel, D. Körper, D. Kostyleva, T. Kröll, N. Kuzminchuk, B. Laurent, I. Lihtar, Yu. A. Litvinov, B. Löher, N. S. Martorana, B. Mauss, S. Murillo Morales, D. MĂŒcher, I. Mukha, E. Nacher, A. Obertelli, E. V. Pagano, V. Panin, J. Park, S. Paschalis, M. Petri, S. Pietri, S. Pirrone, G. Politi, L. Ponnath, A. Revel, H.-B. Rhee, J. L. RodrĂ­guez-SĂĄnchez, L. Rose, D. Rossi, P. Roy, P. Russotto, C. Scheidenberger, H. Scheit, H. Simon, S. Storck-Dutine, A. Stott, Y. L. Sun, C. SĂŒrder, Y. K. Tanaka, R. Taniuchi, O. Tengblad, I. Tisma, H. T. Törnqvist, M. Trimarchi, S. Velardita, J. Vesic, B. Voss, F. Wamers, H. Weick, F. Wienholtz, J. Zhao, M. Zhukov
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GPT-4o mini: Non-social science research article
Author Correction: Evidence for improved DNA repair in the long-lived bowhead whale
Denis Firsanov, Max Zacher, Xiao Tian, Todd L. Sformo, Yang Zhao, Gregory Tombline, J. Yuyang Lu, Zhizhong Zheng, Luigi Perelli, Enrico Gurreri, Li Zhang, Jing Guo, Anatoly Korotkov, Valentin Volobaev, Seyed Ali Biashad, Zhihui Zhang, Johanna Heid, Alexander Y. Maslov, Shixiang Sun, Zhuoer Wu, Jonathan Gigas, Eric C. Hillpot, John C. Martinez, Minseon Lee, Alyssa Williams, Abbey Gilman, Nicholas Hamilton, Ekaterina Strelkova, Ena Haseljic, Avnee Patel, Maggie E. Straight, Nalani Miller, Julia Ablaeva, Lok Ming Tam, Chloé Couderc, Michael R. Hoopmann, Robert L. Moritz, Shingo Fujii, Amandine Pelletier, Dan J. Hayman, Hongrui Liu, Yuxuan Cai, Anthony K. L. Leung, Zhengdong Zhang, C. Bradley Nelson, Lisa M. Abegglen, Joshua D. Schiffman, Vadim N. Gladyshev, Carlo C. Maley, Mauro Modesti, Giannicola Genovese, Mirre J. P. Simons, Jan Vijg, Andrei Seluanov, Vera Gorbunova
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GPT-4o mini: Non-social science research article
Author Correction: Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants
Zhiqiang Ku, Xuping Xie, Paul R. Hinton, Xinli Liu, Xiaohua Ye, Antonio E. Muruato, Dean C. Ng, Sujit Biswas, Jing Zou, Yang Liu, Deepal Pandya, Vineet D. Menachery, Sachi Rahman, Yu-An Cao, Hui Deng, Wei Xiong, Kevin B. Carlin, Junquan Liu, Hang Su, Elizabeth J. Haanes, Bruce A. Keyt, Ningyan Zhang, Stephen F. Carroll, Pei-Yong Shi, Zhiqiang An
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GPT-4o mini: Non-social science research article
Vicarious body maps bridge vision and touch in the human brain
Nicholas Hedger, Thomas Naselaris, Kendrick Kay, Tomas Knapen
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Our sensory systems work together to generate a cohesive experience of the world around us. Watching others being touched activates brain areas representing our own sense of touch: the visual system recruits touch-related computations to simulate bodily consequences of visual inputs 1 . One long-standing question is how the brain implements this interface between visual and somatosensory representations 2 . Here, to address this question, we developed a model to simultaneously map somatosensory body part tuning and visual field tuning throughout the brain. Applying our model to ongoing co-activations during rest resulted in detailed maps of body-part tuning in the brain’s endogenous somatotopic network. During video watching, somatotopic tuning explains responses throughout the entire dorsolateral visual system, revealing an array of somatotopic body maps that tile the cortical surface. The body-position tuning of these maps aligns with visual tuning, predicting both preferences for visual field locations and visual-category preferences for body parts. These results reveal a mode of brain organization in which aligned visual–somatosensory topographic maps connect visual and bodily reference frames. This cross-modal interface is ideally situated to translate raw sensory impressions into more abstract formats that are useful for action, social cognition and semantic processing 3 .
GPT-4o mini: Non-social science research article
Author Correction: Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury
Nobuhiko Kayagaki, Irma B. Stowe, Kamela Alegre, Ishan Deshpande, Shuang Wu, Zhonghua Lin, Opher S. Kornfeld, Bettina L. Lee, Juan Zhang, John Liu, Eric Suto, Wyne P. Lee, Kellen Schneider, WeiYu Lin, Dhaya Seshasayee, Tushar Bhangale, Cecile Chalouni, Matthew C. Johnson, Prajakta Joshi, Jan Mossemann, Sarah Zhao, Danish Ali, Neil M. Goldenberg, Blayne A. Sayed, Benjamin E. Steinberg, Kim Newton, Joshua D. Webster, Ryan L. Kelly, Vishva M. Dixit
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GPT-4o mini: Non-social science research article
Long-read metagenomics reveals phage dynamics in the human gut microbiome
Jakob Wirbel, Angela S. Hickey, Daniel Chang, Nora J. Enright, Mai Dvorak, Rachael B. Chanin, Danica T. Schmidtke, Ami S. Bhatt
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Gut bacteriophages profoundly impact microbial ecology and health1,2,3; yet, they are understudied. Using deep long-read bulk metagenomic sequencing, we tracked prophage integration dynamics in stool samples from six healthy individuals, spanning a 2-year timescale. Although most prophages remained stably integrated into their hosts, approximately 5% of phages were dynamically gained or lost from persistent bacterial hosts. Within a sample, we found that bacterial hosts with and without a given prophage coexisted simultaneously. Furthermore, phage induction, when detected, occurred predominantly at low levels (1–3× coverage compared to the host region), in line with theoretical expectations4. We identified multiple instances of integration of the same phage into bacteria of different taxonomic families, challenging the dogma that phages are specific to a host of a given species or strain5. Finally, we describe a new class of ‘IScream phages’, which co-opt bacterial IS30 transposases to mediate their mobilization, representing a previously unrecognized form of phage domestication of selfish bacterial elements. Taken together, these findings illuminate fundamental aspects of phage–bacterial dynamics in the human gut microbiome and expand our understanding of the evolutionary mechanisms that drive horizontal gene transfer and microbial genome plasticity.
GPT-4o mini: Non-social science research article
Glasses-free 3D display with ultrawide viewing range using deep learning
Weijie Ma, Zhangrui Zhao, Canyu Zhao, Wanli Ouyang, Han-Sen Zhong
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Glasses-free three-dimensional (3D) displays provide users with an immersive visual experience without the need of any wearable devices1,2. To achieve high-quality 3D imaging, a display should have both large linear dimensions and a wide viewing angle. However, the trade-off between spatial extent and bandwidth of optical systems, the space–bandwidth product, conventionally constrains the simultaneous maximization of the two. The two most common approaches to 3D displays are holographic3,4 and automultiscopic1,5,6, which, respectively, sacrifice either scale or viewing angle. Recently, some implementations enhanced by artificial intelligence have shown directions to mitigate these constraints, but they still operate within a set space–bandwidth product7,8. As a result, it remains challenging to fabricate large-scale wide-angle 3D displays9. Here we report the realization of a large-scale full-parallax 3D display with seamless viewing beyond 100°, maintained at over 50 Hz and 1,920 × 1,080 resolution on a low-cost light-field delivery setup. This device, called EyeReal, is realized by accurately modelling binocular view and combining it with a deep-learning real-time optimization, enabling the generation of optimal light-field outputs for each of the eyes. Our device could potentially enable applications in educational tools, 3D design and virtual reality10,11.
GPT-4o mini: Non-social science research article
Inhibitory PD-1 axis maintains high-avidity stem-like CD8+ T cells
Jyh Liang Hor, Edward C. Schrom, Abigail Wong-Rolle, Luke Vistain, Wanjing Shang, Qiang Dong, Chen Zhao, Chengcheng Jin, Ronald N. Germain
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Stem-like progenitors are self-renewing cytotoxic T cells that expand as effector cells during successful checkpoint immunotherapy 1,2 . Emerging evidence suggests that tumour-draining lymph nodes support the continuous generation of these stem-like cells that replenish tumour sites and are a key source of expanded effector populations 3–6 , underlining the importance of understanding what factors promote and maintain activated T cells in the stem-like state. Here, using advanced three-dimensional multiplex immunofluorescence imaging, we identify antigen-presentation niches in tumour-draining lymph nodes that support the expansion, maintenance and affinity evolution of TCF-1 + PD-1 + SLAMF6 high stem-like CD8 + T cells. Contrary to the prevailing view that persistent T cell receptor (TCR) signalling drives terminal effector differentiation, prolonged antigen engagement days beyond initial priming sustains the proliferation and self-renewal of these stem-like T cells in vivo. The inhibitory PD-1 pathway has a central role in this process through fine-tuning the TCR signal input that enables the selective expansion of high-affinity TCR stem-like clones as a renewable source of effector cells. PD-1 blockade disrupts this tuning, leading to terminal differentiation or death of the most avid anti-tumour stem-like cells. Our results therefore reveal a relationship between TCR ligand affinity recognition, a key negative-feedback regulatory loop and T cell stemness programming. Furthermore, these findings raise questions about whether anti-PD-1 blockade during cancer immunotherapy provides a short-term anti-tumour effect at the cost of diminishing efficacy due to progressive loss of these critical high-affinity precursors.
GPT-4o mini: Non-social science research article
Ferroelectric transistors for low-power NAND flash memory
Sijung Yoo, Taek Jung Kim, Seung-Geol Nam, Donghoon Kim, Kihong Kim, Yunseong Lee, Moonil Jung, Kwang-Hee Lee, Seokhoon Choi, Seung Dam Hyun, Min-Hyun Lee, Seogwoo Hong, Haesung Kim, Ki Deok Bae, Hyangsook Lee, Jung Yeon Won, Dong-Jin Yun, Byeong Gyu Chae, Wook Ghee Hahn, Chang Hyun Joo, Sanghyun Jo, Yoonsang Park, Kyung Mee Song, Kyooho Jung, Suhwan Lim, Kwangyou Seo, Kwangsoo Kim, Wanki Kim, Daewon Ha, Jee-Eun Yang, Seung-Yeul Yang, Sangwook Kim, Jinseong Heo, Duk-Hyun Choe
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NAND flash memory is essential in modern storage technology, amid growing demands for low-power operation fuelled by data-centric computing and artificial intelligence1,2. Its unique ‘string’ architecture3, where multiple cells are connected in series, requires high-voltage pass operation that causes a large amount of undesired power consumption4. Lowering the pass voltage, however, poses a challenge: it leads to an associated reduction in the memory window, restricting the multi-level operation capability. Here, with a gate stack composed of zirconium-doped hafnia and an oxide semiconductor channel, we report ultralow-power ferroelectric field-effect transistors (FeFETs) that resolve this dilemma. Our FeFETs secure up to 5-bit per cell multi-level capability, which is on par with or even exceeds current NAND technology, while showing nearly zero pass voltage, saving up to 96% power in string-level operations over conventional counterparts. Three-dimensional integration of FeFET stacks into vertical structures with a 25-nm short channel preserves robust electrical properties and highlights low-pass-voltage string operation in scaled dimensions. Our work paves the way for next-generation storage memory with enhanced capacity, power efficiency and reliability.
GPT-4o mini: Non-social science research article
Slipknot-gauged mechanical transmission and robotic operation
Yaoting Xue, Jiasheng Cao, Tao Feng, Kaihang Zhang, Siyang Li, Jiahao Hu, Haotian Guo, Jinming Zhang, Yaoxian Song, Zhuofan Wang, Lei Wang, Qishan Huang, Haofei Zhou, Fanghao Zhou, Jiliang Shen, Yaowei Fan, Zhe Wang, Xinge Li, Jie-Wei Wong, Zhiwei Chen, Dongrui Ruan, Zhikun Miao, Bin Zhang, Enjie Zhou, Letian Gan, Xuanqi Wang, Ertai Cao, Tong Chen, Weifeng Zou, Junhui Zhang, Haojian Lu, Qinghai Zhang, Song Liu, Huixu Dong, Shiying Xiong, Shuyou Peng, Tuck-Whye Wong, Yuanjie Chen, Tiefeng Li, Mingyu Chen, Xuxu Yang, Wei Yang, Xiujun Cai
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Mechanical transmission is essential in force-related activities ranging from the daily tying of shoe laces1 to sophisticated surgical2 and robotic operations3,4. Modern machines and robots typically use complex electronic devices designed to sense and limit force5, some of which still face challenges when operating space is limited (for example, in minimally invasive surgeries)6 or when resources are scarce (for example, operations in remote areas without electricity). Here we describe an alternative slipknot-based mechanical transmission mechanism to control the intelligent operation of both human and robotic systems. Through topological design, slipknot tying and release can encode and deliver force with a consistency of 95.4% in repeating operations, which circumvents the need for additional sensors and controllers. When applied to surgical repair, this mechanism helped inexperienced surgeons to improve their knotting-force precision by 121%, enabling them to perform surgical knots as good as those of experienced surgeons. Moreover, blood supply and tissue healing after surgery were improved. The mechano-intelligence exhibited in slipknots may inspire investigations of knotted structures across multiple length scales. This slipknot-gauged mechanical transmission strategy can be widely deployed, opening up opportunities for resource-limited healthcare, science education and field exploration.
GPT-4o mini: Non-social science research article
Land-use change undermines the stability of avian functional diversity
Thomas L. Weeks, Patrick A. Walkden, David P. Edwards, Alexander C. Lees, Alexander L. Pigot, Andy Purvis, Joseph A. Tobias
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Land-use change causes widespread shifts in the composition and functional diversity of species assemblages. However, its impact on ecosystem resilience remains uncertain. The stability of ecosystem functioning may increase after land-use change because the most sensitive species are removed, which leaves more resilient survivors 1–3 . Alternatively, ecosystems may be destabilized if land-use change reduces functional redundancy, which accentuates the ecological impacts of further species loss 4,5 . Current evidence is inconclusive, partly because trait data have not been available to quantify functional stability at sufficient scale. Here we use morphological measurements of 3,696 bird species to estimate shifts in functional redundancy after recent anthropogenic land-use change at 1,281 sites worldwide. We then use extinction simulations to assess the sensitivity of these altered assemblages to future species loss. Although the proportion of disturbance-tolerant species increases after land-use change, we show that this does not increase stability because functional redundancy is reduced. This decline in redundancy destabilizes ecosystem function because relatively few additional extinctions lead to accelerated losses of functional diversity, particularly in trophic groups that deliver important ecological services such as seed dispersal and insect predation. Our analyses indicate that land-use change may have major undetected impacts on the resilience of key ecological functions, hindering the capacity of natural ecosystems to absorb further reductions in functionality caused by ongoing perturbations.
GPT-4o mini: Non-social science research article
New finds shed light on diet and locomotion in Australopithecus deyiremeda
Yohannes Haile-Selassie, Gary T. Schwartz, Thomas C. Prang, Beverly Z. Saylor, Alan Deino, Luis Gibert, Anna Ragni, Naomi E. Levin
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The naming of Australopithecus deyiremeda1 from Woranso-Mille (less than 3.59 to more than 3.33 million years) indicated the presence of a species contemporaneous with Australopithecus afarensis in the Ethiopian Afar Rift. A partial foot (BRT-VP-2/73)2 and several isolated teeth from two Burtele (BRT) localities, however, were not identified to the species level. Recently recovered dentognathic specimens clarify not only the taxonomic affinity of the BRT hominin specimens but also shed light on the diet and locomotion of A. deyiremeda. Here we present a comparative description of these specimens and show that they are attributable to A. deyiremeda. We also find it parsimonious to attribute the BRT foot to this species based on the absence of other hominin species at BRT. The new material demonstrates that overall, A. deyiremeda was dentally and postcranially more primitive than A. afarensis, particularly in aspects of canine and premolar morphology, and in its retention of pedal grasping traits. Furthermore, the low and less variable distributions of its dental enamel ÎŽ13C values are similar to those from Ardipithecus ramidus and Australopithecus anamensis, indicating a reliance on C3 foods. This suggests that A. deyiremeda had a dietary strategy similar to the earlier A. ramidus and A. anamensis. The BRT foot and its assignment to A. deyiremeda provides conclusive evidence that arboreality was a significant component of the positional behaviour of this australopith, further corroborating that some degree of arboreality persisted among Pliocene hominins1,3,4,5,6,7.
GPT-4o mini: Non-social science research article
Entanglement-enhanced nanoscale single-spin sensing
Xu Zhou, Mengqi Wang, Xiangyu Ye, Haoyu Sun, Yuhang Guo, Shuo Han, Zihua Chai, Wentao Ji, Kangwei Xia, Fazhan Shi, Ya Wang, Jiangfeng Du
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Detecting individual spins—including stable and metastable states—represents a fundamental challenge in quantum sensing, with broad applications across condensed matter physics1,2, quantum chemistry3 and single-molecule magnetic resonance imaging4,5. Although nitrogen–vacancy (NV) centres in diamond have emerged as powerful nanoscale sensors, their performance for single-spin detection remains constrained by substantial environmental noise and restricted sensing volume6,7. Here we propose and demonstrate an entanglement-enhanced sensing protocol that overcomes these limitations through the strategic use of entangled NV pairs. Our approach achieves a 3.4-fold enhancement in sensitivity and a 1.6-fold improvement in spatial resolution relative to single NV centres under ambient conditions. The protocol uses carefully engineered entangled states that amplify target spin signals through quantum interference while suppressing environmental noise. Crucially, we extend these capabilities to resolve metastable single-spin dynamics, directly observing stochastic transitions between different spin states by identifying state-dependent coupling strengths. This dual functionality enables simultaneous detection of static and dynamic spin species for studying complex quantum systems. The achieved performance establishes entanglement-enhanced sensing as a viable pathway towards atomic-scale characterization of quantum materials and interfaces.
GPT-4o mini: Non-social science research article
Evolution of taste processing shifts dietary preference
Enrico Bertolini, Daniel MĂŒnch, Justine Pascual, Noemi Sgammeglia, Matteo Bruzzone, Carlos Ribeiro, Thomas O. Auer
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Food choice is an important driver of speciation and invasion of novel ecological niches. However, we know little about the mechanisms leading to changes in dietary preference. Here we use three closely related species, Drosophila sechellia (Dsec), Drosophila simulans and Drosophila melanogaster, to study taste circuit1 and food choice evolution. Dsec, a host specialist, feeds exclusively on a single fruit (Morinda citrifolia; noni), whereas the other two are generalists living on diverse diets2. Using quantitative feeding assays, we recapitulate the preference for noni in Dsec and detect conserved sweet but altered bitter sensitivity by means of calcium imaging in peripheral taste neurons. Noni activates bitter-sensing neurons more strongly in Dsec than in the other two species owing to a small deletion in a single gustatory receptor. Using volumetric calcium imaging in the ventral brain3, we show that instead of peripheral physiology, species-specific processing of noni and sucrose signals in sensorimotor circuits recapitulates differences in dietary preference. Our data indicate that altered food choice may not be explained by peripheral receptor changes alone but rather by modifications in how sensory information is transformed into feeding motor commands.
Nature DOI suffix ≠ "/s...": Not a research article
Shape-shifting electrodes tune optical-frequency converter
Kartik Srinivasan
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Tools that can perform several tasks are crucial for research, particularly in emerging fields, because they provide the flexibility to explore a problem without the need to build many types of prototype device. Writing in Nature, Yanagimoto et al.1 report an optical device that generates a spectrum of light with properties that can be adjusted in situ as needed. Their approach uses an optical process called second-harmonic generation, which doubles the frequency of light. The authors show that this process can be reprogrammed by projecting different patterns of light onto an electrode on the device’s surface.
Nature DOI suffix ≠ "/s...": Not a research article
Secrets of DeepSeek AI model revealed in landmark paper
Elizabeth Gibney
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The success of DeepSeek’s powerful artificial intelligence (AI) model R1 — which made the US stock market plummet when it was released in January — did not hinge on being trained on the output of its rivals, researchers at the Chinese firm have said. The statement came in documents released alongside a peer-reviewed version of the R1 model, published today in Nature1.
Nature DOI suffix ≠ "/s...": Not a research article
Putting nature on the balance sheet: how to account for the ecological costs of our actions
Jacob Hochard
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On Natural Capital: The Value of the World Around Us Partha Dasgupta Witness (2025) An economist might celebrate a nation achieving record economic growth on one day, yet overlook a coral reef lying bleached and lifeless on another. This contradiction must be challenged, writes economist Partha Dasgupta in his elegant account of why the global economic system is exploiting, rather than sustaining, life on our planet. On Natural Capital recaps the roaring economic advances of the past 75 years, including improved life expectancies and education and fewer people living in poverty. But it also shares how economic progress has benefited from the exploitation of our planet: an ecological debt that conventional accounting leaves off the balance sheet. How to build nature back better — read this manual Dasgupta starts by vividly portraying the essential workings of Earth’s life-support systems and how living processes regulate the climate, replenish soils and sustain food webs. He notes that one-third of the planet’s remaining wetlands, which are crucial for filtering nutrients, providing flood protection and storing carbon, have been lost between 1970 and 2015 owing to infrastructure construction, urban expansion and other human activities. He also describes how deforestation can create savannah-like conditions in parts of the tropics, because the disruption of moisture-recycling processes decreases rainfall and ecological productivity. Next, Dasgupta examines why economic principles have long treated nature’s functions as background scenery. He explains that this omission is rooted in the mid-twentieth-century origins of growth and development economics, in which economists constructed models that explained output using only human labour and skills, and physical goods. This was a reasonable assumption back when natural resources seemed abundant, the world wasn’t pressing against planetary limits and forests, soils and fisheries seemed too plentiful to constrain growth. What began as a practical simplification evolved into a blind spot. Uneasy trade-offs By stitching these two narratives together, Dasgupta succeeds in portraying woodlands, watersheds and wild species as bona fide assets, the depletion of which undermines the prosperity statistics that governments use to track and celebrate progress. He solidifies this narrative by estimating that humanity’s collective demand on nature now exceeds the planet’s regenerative capacity by around 70%. Effectively, this means that, since the early 1970s, we have been living off the planet’s ‘capital’ rather than the accrued ‘interest’, jeopardizing our biosphere’s solvency. Beyond growth — why we need to agree on an alternative to GDP now As Dasgupta’s writing flows between nature’s processes and economic principles, he stresses the uneasy trade-offs that societies navigate daily. Each tonne of fish landed or cubic metre of water taken for irrigation is a draw on assets that must remain intact to avoid compromising future yields of food, income and ecological stability. Dasgupta reminds us that these choices are not simply about extraction but also about stewardship. Overfishing might boost a nation’s gross domestic product for one fiscal quarter, yet deplete the reproductive stock that sustains the following year’s catch. Likewise, draining wetlands to generate farmland might bring an immediate harvest, yet erode the flood protection and nutrient-cycling processes that make such agriculture possible. Sustainable forestry management preserves biodiversity and allows forests to regenerate.Credit: Alexander Manzyuk/Anadolu Agency/Getty The constant tension between nature’s bounty and the ecological conditions that make that bounty possible is revealed brilliantly by Dasgupta but left out of the accounting practices that currently define progress. As a result, society perceives the conversion of natural resources as costless profit and celebrates growth figures, but the natural systems that made that growth possible decline quietly. Dasgupta’s call to put nature on the balance sheet is timely precisely because it indicates a rapidly expanding movement in policy that is beginning to give the natural world the accounting treatment it has often lacked. Challenges ahead Countries such as the Netherlands, Canada and Colombia are developing or trialling natural-capital accounting and statistical frameworks that treat ecosystems as assets: measuring their stock (for example, wetlands, forests and soil microorganisms), tracking their depreciation (or appreciation) and defining the ‘interest’ they generate, such as flood protection and carbon storage. Environmental politics is doomed to fail — unless we tell better stories In the corporate domain, the Taskforce on Nature-related Financial Disclosures is a market-led, government-supported and science-based global initiative that encourages companies to include nature in their financial reports. It provides firms with a framework for disclosing nature-related risks, including biodiversity loss, as well as dependencies, such as supply-chain access to clean water. Dasgupta highlights both the promise of natural-capital accounting as well as the areas that need improvement. Markets are finally aligning with the reality that woodlands, watersheds, wildlife and other aspects of the natural world are not ‘free’ inputs but assets, and their degradation erodes prosperity. The gaps, he emphasizes, lie in the valuation of natural systems (how to reliably price ecosystem services), governance (who owns and manages those assets) and integration (how to incorporate natural-capital metrics into macroeconomic indicators).
Nature DOI suffix ≠ "/s...": Not a research article
Major AI conference flooded with peer reviews written fully by AI
Miryam Naddaf
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An AI-detection tool developed by Pangram labs found that peer reviewers are increasingly using chatbots to draft responses to authors.Credit: breakermaximus/iStock via Getty What can researchers do if they suspect that their manuscripts have been peer reviewed using artificial intelligence (AI)? Dozens of academics have raised concerns on social media about manuscripts and peer reviews submitted to the organizers of next year’s International Conference on Learning Representations (ICLR), an annual gathering of specialists in machine learning. Among other things, they flagged hallucinated citations and suspiciously long and vague feedback on their work. Graham Neubig, an AI researcher at Carnegie Mellon University in Pittsburgh, Pennsylvania, was one of those who received peer reviews that seemed to have been produced using large language models (LLMs). The reports, he says, were “very verbose with lots of bullet points” and requested analyses that were not “the standard statistical analyses that reviewers ask for in typical AI or machine-learning papers.” But Neubig needed help proving that the reports were AI-generated. So, he posted on X (formerly Twitter) and offered a reward for anyone who could scan all the conference submissions and their peer reviews for AI-generated text. The next day, he got a response from Max Spero, chief executive of Pangram Labs in New York City, which develops tools to detect AI-generated text. Pangram screened all 19,490 studies and 75,800 peer reviews submitted for ICLR 2026, which will take place in Rio de Janeiro, Brazil, in April. Neubig and more than 11,000 other AI researchers will be attending. Pangram’s analysis revealed that around 21% of the ICLR peer reviews were fully AI-generated, and more than half contained signs of AI use. The findings were posted online by Pangram Labs. “People were suspicious, but they didn’t have any concrete proof,” says Spero. “Over the course of 12 hours, we wrote some code to parse out all of the text content from these paper submissions,” he adds. The conference organizers say they will now use automated tools to assess whether submissions and peer reviews breached policies on using AI in submissions and peer reviews. This is the first time that the conference has faced this issue at scale, says Bharath Hariharan, a computer scientist at Cornell University in Ithaca, New York, and senior programme chair for ICLR 2026. “After we go through all this process 
 that will give us a better notion of trust.” AI-written peer review The Pangram team used one of its own tools, which predicts whether text is generated or edited by LLMs. Pangram’s analysis flagged 15,899 peer reviews that were fully AI-generated. But it also identified many manuscripts that had been submitted to the conference with suspected cases of AI-generated text: 199 manuscripts (1%) were found to be fully AI-generated; 61% of submissions were mostly human-written; but 9% contained more than 50% AI-generated text. Pangram described the model in a preprint1, which it submitted to ICLR 2026. Of the four peer reviews received for the manuscript, one was flagged as fully AI-generated and another as lightly AI-edited, the team’s analysis found. AI is transforming peer review — and many scientists are worried For many researchers who received peer reviews for their submissions to ICLR, the Pangram analysis confirmed what they had suspected. Desmond Elliott, a computer scientist at the University of Copenhagen, says that one of three reviews he received seemed to have missed “the point of the paper”. His PhD student who led the work suspected that the review was generated by LLMs, because it mentioned numerical results from the manuscript that were incorrect and contained odd expressions. When Pangram released its findings, Elliott adds, “the first thing I did was I typed in the title of our paper because I wanted to know whether my student’s gut instinct was correct”. The suspect peer review, which Pangram’s analysis flagged as fully AI-generated, gave the manuscript the lowest rating, leaving it “on the borderline between accept and reject”, says Elliott. “It's deeply frustrating”. Repercussions
Nature DOI suffix ≠ "/s...": Not a research article
Why the world must wake up to China’s science leadership
Kerry Brown
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Two conversations have stayed with me over the past 25 years. Around 2001, a European Union official in Beijing — where I was then a UK diplomat — told a group of us that the reason countries such as Germany, France and the United Kingdom were allowing technology transfer to China was to see a day when the nation could return the favour. And, in 2017 in Austria, a retired UK security official stated wearily that if there was one constant in policymaking towards China, it was to perpetually be five to ten years behind the times. How China can become a biotechnology superpower Those points resonate in 2025. China has become an important player in research and development (R&D). Yet, most of the outside world has still not woken up to this fact. On 23 October, China’s Communist Party announced that, for the next five years, it will focus on “high-quality development” with “innovation as the fundamental driving force”. This will require, it says, “substantial improvements in scientific and technological self-reliance and strength” (see go.nature.com/4ahcvj8). Policymakers should take this statement seriously for three reasons. First, China has an incentive. At a meeting a few days later, Chinese President Xi Jinping and US President Donald Trump agreed to halt their tariff wars and trade skirmishes. But China knows that its technological dependence on the United States and others is a vulnerability, and that it needs to become autonomous. Second, it is not just words but hard cash that the Chinese government is committing to achieving its goals. The nation’s R&D investments increased nearly sixfold between 2007 and 2023, overtaking the EU’s and coming close to US figures (see go.nature.com/4a2xres). The latest plans indicate that this trend is set to continue. Chinese scientists increasingly lead joint projects with the UK, US and Europe And third, China has the human capital, too. In 2020, the nation produced 3.6 million graduates in science, technology, engineering and mathematics (STEM), compared with 2.6 million in India and 820,000 in the United States (see go.nature.com/4ppekyx). And, in 2022, some 50,000 people in China graduated with STEM PhDs, compared with 34,000 in the United States (see go.nature.com/4iedi4z). China’s leading universities, including Fudan in Shanghai and Tsinghua in Beijing, rank highly on global lists. Over the past half-century, China’s development was achieved mainly by 250 million labourers moving from rural areas to urban ones, making the country the ‘factory of the world’. By contrast, going forwards, it will be young Chinese scientists who will drive progress. A powerful example is the unexpected January release of DeepSeek, an app based on artificial intelligence developed by a 200-strong technology company in Hangzhou. Despite criticism that DeepSeek has a lower capacity than other AI models, the firm’s proof that China could produce its own AI systems provided a powerful symbolic moment. How provinces and cities can sustain US–China climate cooperation Chinese leaders admit that their country has a long way to go. But it would take a brave person to dismiss China’s chance of achieving its goal of becoming a technological superpower by 2035. That is why it is important for other governments to engage with China effectively.
Nature DOI suffix ≠ "/s...": Not a research article
Mystery owner of African hominin foot identified
Fred Spoor
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In 2009, a 3.4-million-year-old partial foot skeleton was discovered at Burtele in Ethiopia’s Afar region1. It could be identified clearly as from a hominin — those species that make up our branch of the evolutionary tree, after the human and chimpanzee lineages split. But the specific species was unknown. Writing in Nature, Haile-Selassie et al.2 now reveal the answer.
Nature DOI suffix ≠ "/s...": Not a research article
The ocular microbiome: more than meets the eye
Roxanne Khamsi
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Nature DOI suffix ≠ "/s...": Not a research article
The Venus project
Monti Sturzaker
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Afrodi sat on the very edge of her seat. They were here, they were finally here. Like the rest of her team, her eyes were glued to the full-wall screen. Venus: the final frontier. Not that the public thought that, of course: completely uninhabitable was completely uninteresting. Afrodi couldn’t disagree more. She’d been enamoured with Venus ever since childhood, staring up at it through her mum’s telescope. A perfect, rose-tinted disk. She’d loved the constellations, loved the other planets, but none had captured her like Venus. She felt drawn to it. As a teen, Afrodi had observed the public’s obsession with Mars. She read Kim Stanley Robinson’s Red Mars, listened to talks about a Mars landing, of potential colonization plans. She couldn’t understand the appeal. The next summer was the hottest on record, with each year after predicted to be ever hotter. Who wanted to live in a dusty red desert? People think Mars is Earth’s closest relative — but they’re wrong. Mars is small, more akin to the Moon. Venus is Earth’s dangerous sister. At university she’d studied astrophysics, absorbing everything she could about Venus’s history. She learnt that once, perhaps a billion years ago, Venus could have been habitable. Afrodi found this enchanting. What would it have been like on the surface? When they first found hints that there might have been life on Mars, her classmates buzzed with excitement. But why should she care about crusty old Mars when Venus rained diamonds? Read more science fiction from Nature Futures Top of her class was a boy named Res, from Greece. He wanted to be the next Michael Collins, overseeing his very own Neil and Buzz to their safe landing on Mars. He told everyone about Collins’s joke with the Moon landers, that they should say ‘Oh God, what is that thing?’ and cut their mic. He told everyone he had something even funnier he’d make his crew say. Afrodi wasn’t sure Res had the right impression of Collins’s job, but she didn’t care to correct him. Instead, she kept her nose down and learnt everything about Venus. The biggest problem astronomers had in viewing the surface was the temperature, which regularly rose to more than 800 K: robot-meltingly and electronic-fryingly hot. The picture they did have was mainly from spectroscopic data and wavelength information, rather than anything seen. Afrodi did a master’s in materials, and a joint PhD in robotics and astrophysics. She wanted to see Venus under her protective shell. She learnt about tungsten, which would withstand temperatures about ten times Venus’s heat. She risked her life hanging around active volcanoes, testing her tungsten-crafted cooling mechanisms and a heat-resistant nanopolymer designed by one of her classmates. When she got an active picture from the inside of a volcano, Afrodi leapt for joy. It would be possible. Her dream would be possible. She left the robot down there for four weeks, just to be completely sure, and once she pulled it out she sent it to Antarctica, to see if it could handle the cold of space. Res was in her postdoc programme. He didn’t remember her. She didn’t care. They worked together under a disinterested supervisor. Res told her he’d hoped to work on a Mars project, but slots were highly sought after and he’d missed out on a place, which is why he’d been stuck with this second-rate Venus shit. He asked her what she’d wanted to do. She told him they were going to be the first to see the surface of Venus and he should grow up — but in more colourful language. He was a nuisance for the next two or so months, rabbiting on about Mars. She learnt to tune it out, like the trains passing her window at night. Gradually — as they worked together on the templates she had for a robot, figured out landing gear, how to get it into space, the trajectory and timing — his Mars worship stopped. She was quiet and introspective, and he did not pick up enthusiasm, exactly, from her, but he grew to appreciate Venus nonetheless. In his own way. Their first date was to the observatory in Tartu, Estonia. He’d planned the trip without telling her where they were going, held her hand as they gazed up at Venus’s pink-gold surface. London was on fire while they were away. She’d had to pay for the taxi to get home, as surge pricing ballooned it to twice his budget. But he didn’t complain, eating packed cheese sandwiches every day for the next month to pay her back. She accepted only half.
Nature DOI suffix ≠ "/s...": Not a research article
The Internet is broken and the inventor of the World Wide Web wants to fix it
Chris Stokel-Walker
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This Is for Everyone: The Unfinished Story of the World Wide Web Tim Berners-Lee Farrar, Straus and Giroux (2025) The World Wide Web is one of those rare innovations that truly reshaped the world. It is now so deeply embedded in our daily lives that it is difficult to imagine a time before it existed or even remember how it all began. So, who better to re-examine the state of the modern Internet ecosystem, and champion reform, than the web’s creator himself: computer scientist Tim Berners-Lee? However, he is not the kind of charismatic leader who can inspire a revolution, at least not through his writing. How AI is reshaping science and society This Is for Everyone reads like a family newsletter: it tells you what happened, recounting the Internet’s origin and evolution in great detail, but rarely explaining why the ideal of a decentralized Internet was not realized. Berners-Lee’s central argument is that the web has strayed from its founding principles and been corrupted by profit-driven companies that seek to monetize our attention. But it’s still possible to “fix the internet”, he argues, outlining a utopian vision for how that might be done. In it, social media would be designed to “maximize the joy” the user experiences instead of fuelling division, and technical standards would be introduced to prevent the mistakes of the social-media era from being repeated in the age of artificial intelligence. Both ideas are optimistic — some might say naive — but coming from someone so integral to the web’s creation, they carry particular weight. In this personal history of the Internet, penned with co-writer Stephen Witt, Berners-Lee recounts decades of his career at various institutions, most notably CERN — the European centre for particle physics in Geneva, Switzerland. Here, his seminal invention, the World Wide Web, began as a side project that his managers tolerated grudgingly. Much of this is a well-known tale, both because the web is so prevalent in our lives and because Berners-Lee has given plenty of interviews about how it came to be. Computer scientist Tim Berners-Lee.Credit: Sam Ogden/SPL As an author, Berners-Lee is most powerful and persuasive when he looks beyond his own life to examine the web’s exploitative corners. For instance, he notes that some US Democrats — such as senator Ed Markey and former vice-president Al Gore, who both advocated for well-thought-out technology regulations — were more willing than Republicans to engage with the web’s inner workings. He argues that this imbalance partly shaped the web’s early development in the 2000s, establishing harmful norms that still persist today. Berners-Lee criticizes cookies — small pieces of data that websites store on users’ computers, often to track browsing behaviour — for needlessly spying on users. And he laments that the web is controlled by “a handful of providers” that “grew into dominant, unregulated monopolies”. He suggests that they ought to be brought into check. Are the Internet and AI affecting our memory? What the science says In the later sections of the book, Berners-Lee is refreshingly candid. He criticizes Google for attempting to dominate the World Wide Web Consortium — the non-profit organization in Cambridge, Massachusetts, that sets web standards — by embedding its preferred coding language into its Chrome browser, effectively making this language the default choice. This fight over standards is comparable to his earlier run-ins with the creators of the Mosaic browser, including entrepreneur Marc Andreessen, whose profit-driven vision for the web clashed with Berners-Lee’s original ideal of a distributed, decentralized and open system. Berners-Lee seems to have a grudging admiration for Andreessen’s success in commercializing early web browsing by ignoring the niceties of the online community that had been the norm until this point. He made changes to how browsers render images, “as was his right, I suppose”, Berners-Lee writes. Mosaic quickly became “a dominant monopoly” in the 1990s, making its rendering method the standard. Another firm Berners-Lee condemns is Apple — for steering users towards its tightly controlled app store and making it virtually impossible to download apps that are outside Apple’s ecosystem. Social-media algorithms also draw his ire; he warns that they act like “an undercover megaphone”, distorting and polluting public discourse. His solution is as radical today as the web was in 1989. Alongside his colleagues at the Massachusetts Institute of Technology in Cambridge, he has created a data protocol called Solid. This data-management framework gives users control over their personal information through secure ‘pods’ — individual data stores that let them decide which apps or services can access their data. This approach flips the power dynamic: sharing data with tech companies is possible, but only on the user’s terms.
Nature DOI suffix ≠ "/s...": Not a research article
These ‘programmable’ knots harness physics to make surgical stitches safer
Elizabeth Gibney
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Surgeons could use pre-tied slipknots to precisely control the tension of stitches. Credit: Addictive Stock Creatives/Alamy Inserting easy-to-release slipknots into surgical thread could help surgeons to tie perfect sutures — tight enough to help heal a wound but not so tight that they damage tissue. Researchers worked out how to precisely control a knot’s geometry and friction so that they could ‘program’ it to open when tugged on with a specific force. This allows a surgeon — or a robot — stitching up a wound to pull a suture closed with just the right amount of force, tugging the free end of the knotted thread and stopping when the knot unfurls. Getting the force right is important: stitches that are too tight or too loose can lead to complications. In simulated operations described in Nature on 26 November1, the slipknot technique allowed inexperienced surgeons to perform sutures as well as their experienced peers. When used in rats, slipknot-aided colon surgery led to blood flow being restored faster, fewer leaks and less scar tissue than is usually the case for conventional stitches. Stitches made simple Surgeons usually gauge how much tension is in stitches by look and feel — a skill that takes years to learn and remains variable even in experts. Adding a slipknot to the thread creates “a kind of built-in mechanical fuse” that limits how much force can be transmitted to the tissue, says Tiefeng Li, a researcher in mechanics and robotics at Zhejiang University in Hangzhou, China, who co-led the team of mathematicians, mechanics researchers and clinicians behind the research. “The surgeon only needs to follow a very simple rule: pull until it unfurls, then you know you are at the intended force.” A simple slipknot comes undone if the thread is pulled hard enough. Credit: Chaoyang Zhao, Kaihang Zhang, Tiefeng Li The type of knot used consists of a loop that unravels when one end of the thread is pulled. Although such knots seem simple, the mechanics inside them are complex, says Li. “When a slipknot opens, the thread bends, twists, slides and rubs against itself, and the geometry of the knot changes very quickly,” he says.
Nature DOI suffix ≠ "/s...": Not a research article
AlphaFold is five years old — these charts show how it revolutionized science
Ewen Callaway
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An AlphaFold model of Tmem81, a membrane protein involved in the fusion of egg and sperm.Credit: Google DeepMind/EMBL-EBI (CC-BY-4.0) For nearly a decade, Andrea Pauli, a biochemist at the Research Institute of Molecular Pathology in Vienna, has been trying to work out how sperm and egg get together. In 2018, her laboratory found a protein on the surface of zebrafish (Danio rerio) eggs, called Bouncer, that was essential for fertilization. But Pauli’s team and others struggled to show how Bouncer recognized sperm cells. Then a revolution happened. AlphaFold reveals how sperm and egg hook up in intimate detail Five years ago, in late November 2020, researchers at London-based Google DeepMind unveiled AlphaFold2. The artificial-intelligence tool for predicting protein structures generated stunningly accurate 3D models that, in some cases, were indistinguishable from experimental maps, dominating a long-running structure-prediction challenge. The first version of AlphaFold was announced in 2018, but its predictions weren’t nearly as good as its successor, which limited its impact. The 2021 release of AlphaFold2’s code and a database that has swelled to hundreds of millions of predicted structures mean that scientists can now get a reliable prediction for almost any protein. “Having models for anything has had a huge impact,” says Janet Thornton, a bioinformatician at the European Bioinformatics Institute in Hinxton, UK, part of the European Molecular Biology Laboratory (EMBL–EBI). “It’s like the second coming of structural biology.” Rapid discovery For Pauli’s team, the software shone a light on a path they might otherwise never have found. The model predicted that a protein, called Tmem81, stabilizes a complex of two other sperm proteins, creating a pocket for Bouncer to bind to1. Experiments backed up the tool’s predictions. AlphaFold “speeds up discovery”, says Pauli. “We use it for every project.” Her team’s paper about this, published in 2024, is one of nearly 40,000 journal articles to cite the 2021 Nature paper describing AlphaFold22. Unlike many other highly cited life-sciences and biomedical papers from the same period, including seminal reports about the COVID-19 pandemic, interest in AlphaFold doesn’t seem to be slowing down (see ‘Peak citations’). DeepMind’s John Jumper — who shared half of the 2024 Nobel Prize in Chemistry with chief executive Demis Hassabis for developing AlphaFold — says he is “deeply proud” of how useful the tool has been for scientists such as Pauli. “When will someone win one of these major awards because they used AlphaFold?” he wonders. Part of AlphaFold2’s rapid impact is down to its accessibility, say researchers. Google DeepMind made the underlying code and other parameters freely available to scientists, and it quickly became possible for them to run the software themselves at scale: this is what Pauli’s team did. Source: AlphaFold Protein Structure Database Some 3.3 million users in more than 190 countries have accessed the AlphaFold database (AFDB), which is hosted by EMBL–EBI and contains more than 240 million structural predictions, encompassing most known proteins. More than one million AFDB users come from low- and middle-income countries, including China and India (see ‘Global appeal’). Protein-structure revolution The field in which AlphaFold seems to have made its biggest impact is structural biology. Researchers who used AlphaFold submitted around 50% more protein structures to a repository of experimental models, called the Protein Data Bank (PDB), than did a non-AlphaFold-using ‘baseline’ of structural-biology researchers, finds a Google DeepMind-funded study of AlphaFold’s impacts released this week. AlphaFold2 use was also associated with higher rates of PDB submissions than those of researchers using other ‘frontier’ methods in AI, structural biology and protein structure prediction (see ‘Protein pile-up’). Source: AI in science: Emerging evidence of impact from AlphaFold2 Jumper says he is especially gratified that AlphaFold2 — which was trained using PDB data — has proved so useful for deducing protein structures. The predicted structures can help researchers to make sense of raw data generated by X-ray crystallography and cryo-electron microscopy. “I love that it helps the people that gave us the data,” Jumper adds.
Nature DOI suffix ≠ "/s...": Not a research article
This AI combo could unlock human-level intelligence
Nicola Jones
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Will computers ever match or surpass human-level intelligence — and, if so, how? When the Association for the Advancement of Artificial Intelligence (AAAI), based in Washington DC, asked its members earlier this year whether neural networks — the current star of artificial-intelligence systems — alone will be enough to hit this goal, the vast majority said no. Instead, most said, a heavy dose of an older kind of AI will be needed to get these systems up to par: symbolic AI. Will AI ever win its own Nobel? Some predict a prize-worthy science discovery soon Sometimes called ‘good old-fashioned AI’, symbolic AI is based on formal rules and an encoding of the logical relationships between concepts1. Mathematics is symbolic, for example, as are ‘if–then’ statements and computer coding languages such as Python, along with flow charts or Venn diagrams that map how, say, cats, mammals and animals are conceptually related. Decades ago, symbolic systems were an early front-runner in the AI effort. However, in the early 2010s, they were vastly outpaced by more-flexible neural networks. These machine-learning models excel at learning from vast amounts of data, and underlie large language models (LLMs), as well as chatbots such as ChatGPT. Now, however, the computer-science community is pushing hard for a better and bolder melding of the old and the new. ‘Neurosymbolic AI’ has become the hottest buzzword in town. Brandon Colelough, a computer scientist at the University of Maryland in College Park, has charted the meteoric rise of the concept in academic papers (see ‘Going up and up’). These reveal a spike of interest in neurosymbolic AI that started in around 2021 and shows no sign of slowing down2. Plenty of researchers are heralding the trend as an escape from what they see as an unhealthy monopoly of neural networks in AI research, and expect the shift to deliver smarter and more reliable AI. A better melding of these two strategies could lead to artificial general intelligence (AGI): AI that can reason and generalize its knowledge from one situation to another as well as humans do. It might also be useful for high-risk applications, such as military or medical decision-making, says Colelough. Because symbolic AI is transparent and understandable to humans, he says, it doesn’t suffer from the ‘black box’ syndrome that can make neural networks hard to trust. Source: updated from ref. 2 There are already good examples of neurosymbolic AI, including Google DeepMind’s AlphaGeometry, a system reported last year3 that can reliably solve maths Olympiad problems — questions aimed at talented secondary-school students. But working out how best to combine neural networks and symbolic AI into an all-purpose system is a formidable challenge. “You’re really architecting this kind of two-headed beast,” says computer scientist William Regli, also at the University of Maryland. War of words In 2019, computer scientist Richard Sutton posted a short essay entitled ‘The bitter lesson’ on his blog (see go.nature.com/4paxykf). In it, he argued that, since the 1950s, people have repeatedly assumed that the best way to make intelligent computers is to feed them with all the insights that humans have arrived at about the rules of the world, in fields from physics to social behaviour. The bitter pill to swallow, wrote Sutton, is that time and time again, symbolic methods have been outdone by systems that use a ton of raw data and scaled-up computational power to leverage ‘search and learning’. Early chess-playing computers, for example, that were trained on human-devised strategies were outperformed by those that were simply fed lots of game data. This lesson has been widely quoted by proponents of neural networks to support the idea that making these systems ever-bigger is the best path to AGI. But many researchers argue that the essay overstates its case and downplays the crucial part that symbolic systems can and do play in AI. For example, the best chess program today, Stockfish, pairs a neural network with a symbolic tree of allowable moves. AI models that lie, cheat and plot murder: how dangerous are LLMs really? Neural nets and symbolic algorithms both have pros and cons. Neural networks are made up of layers of nodes with weighted connections that are adjusted during training to recognize patterns and learn from data. They are fast and creative, but they are also bound to make things up and can’t reliably answer questions beyond the scope of their training data. Symbolic systems, meanwhile, struggle to encompass ‘messy’ concepts, such as human language, that involve vast rule databases that are difficult to build and slow to search. But their workings are clear, and they are good at reasoning, using logic to apply their general knowledge to fresh situations. When put to use in the real world, neural networks that lack symbolic knowledge make classic mistakes: image generators might draw people with six fingers on each hand because they haven’t learnt the general concept that hands typically have five; video generators struggle to make a ball bounce around a scene because they haven’t learnt that gravity pulls things downwards. Some researchers blame such mistakes on a lack of data or computing power, but others say that the mistakes illustrate neural networks’ fundamental inability to generalize knowledge and reason logically. Many argue that adding symbolism to neural nets might be the best — even the only — way to inject logical reasoning into AI. The global technology firm IBM, for example, is backing neurosymbolic techniques as a path to AGI. But others remain sceptical: Yann LeCun, one of the fathers of modern AI and chief AI scientist at tech giant Meta, has said that neurosymbolic approaches are “incompatible” with neural-network learning. Can AI be truly creative? Sutton, who is at the University of Alberta in Edmonton, Canada, and won the 2024 Turing prize, the equivalent of the Nobel prize for computer science, holds firm to his original argument: “The bitter lesson still applies to today’s AI,” he told Nature. This suggests, he says, that “adding a symbolic, more manually crafted element is probably a mistake”. Gary Marcus, an AI entrepreneur, writer and cognitive scientist based in Vancouver, Canada, and one of the most vocal advocates of neurosymbolic AI, tends to frame this difference of opinions as a philosophical battle that is now being settled in his favour. Others, such as roboticist Leslie Kaelbling at the Massachusetts Institute of Technology (MIT) in Cambridge, say that arguments over which view is right are a distraction, and that people should just get on with whatever works. “I’m a magpie. I’ll do anything that makes my robots better.” Mix and match Beyond the fact that neurosymbolic AI aims to meld the benefits of neural nets with the benefits of symbolism, its definition is blurry. Neurosymbolic AI encompasses “a very large universe”, says Marcus, “of which we’ve explored only a tiny bit”. There are many broad approaches, which people have attempted to categorize in various ways. One option highlighted by many is the use of symbolic techniques to improve neural nets4. AlphaGeometry is arguably one of the most sophisticated examples of this strategy: it trains a neural net on a synthetic data set of maths problems produced using a symbolic computer language, making the solutions easier to check and ensuring fewer mistakes. It combines the two elegantly, says Colelough. In another example, ‘logic tensor networks’ provide a way to encode symbolic logic for neural networks. Statements can be assigned a fuzzy-truth value5: a number somewhere between 1 (true) and 0 (false). This provides a framework of rules to help the system reason. Another broad approach does what some would say is the reverse, using neural nets to finesse symbolic algorithms. One problem with symbolic knowledge databases is that they are often so large that they take a very long time to search: the ‘tree’ of all possible moves in a game of Go, for example, contains about 10170 positions, which is unfeasibly large to crunch through. Neural networks can be trained to predict the most promising subset of moves, allowing the system to cut down how much of the ‘tree’ it has to search, and thus speeding up the time it takes to settle on the best move. That’s what Google’s AlphaGo did when it famously outperformed a Go grandmaster.
Nature DOI suffix ≠ "/s...": Not a research article
Chasing crayfish and the leeches that live on them
Stav Dimitropoulos
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“I study leeches called branchiobdellidans that live on crayfish. These leeches are just millimetres long and are symbionts — meaning they live in a close, long-term association with their host. They feed on microorganisms and debris that collect on the host’s surface. In small numbers, they help to keep the crayfish clean, but in large colonies, they can become mildly parasitic. Here, I’ve just caught a crayfish under torchlight, and I’m holding it carefully so that the symbionts aren’t washed away. After catching each crayfish, I measure its length and use a paintbrush to push a symbiont sample into a small vial. Tweezers would damage their delicate bodies. This photo was taken in June, in a small river in Slovenia where I recently discovered a new species of symbiont. Later, in the laboratory, I analysed the sample’s DNA to trace how Astacus astacus — the noble crayfish — and its symbionts have evolved together over millions of years. The leeches aren’t just passengers; they’re bioindicators. When they disappear, it can be a signal that crayfish populations — and the rivers themselves — are in trouble. Invasive crayfish from North America (Pacifastacus leniusculus), which were introduced for farming, are already disturbing the ecological balance in waterways in Slovenia.
Nature DOI suffix ≠ "/s...": Not a research article
Ancient DNA offers clues about mysterious prehistoric settlement in China
Yu Dong, Ripan S. Malhi
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In 2012, archaeologists started excavating a site called Shimao, located in the Yellow River valley in the northern part of China’s Shaanxi province. This massive and socially stratified settlement dates to the late Neolithic period — around 3,800–4,300 years ago. Writing in Nature, Chen et al.1 investigate the genomes of the people who inhabited this mysterious ancient city.
Nature DOI suffix ≠ "/s...": Not a research article
Audio long read: Faulty mitochondria cause deadly diseases — fixing them is about to get a lot easier
Gemma Conroy, Benjamin Thompson
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Nature DOI suffix ≠ "/s...": Not a research article
What is the future of intelligence? The answer could lie in the story of its evolution
Blaise AgĂŒera y Arcas
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Ten years ago, I would have turned my nose up at the idea that we already understood how to get machines to think. In the 2010s, my team at Google Research was working on a wide variety of artificial-intelligence models, including the next-word predictor that powers the keyboard on Android smartphones. Artificial neural networks of the sort we were training were finally solving long-standing challenges in visual perception, speech recognition, game playing and many other domains. But it seemed absurd to me that a mere next-word predictor could ever truly understand new concepts, write jokes, debug code or do any of the myriad other things that are hallmarks of human intelligence. ‘Solving’ this kind of intelligence would surely require some fundamentally new scientific insight. And that would probably be inspired by neuroscience — the study of the only known embodiment of general intelligence, the brain. Science and the new age of AI: a Nature special My views back then were comfortably within the scientific mainstream, but in retrospect were also tinged with snobbery. My training was in physics and computational neuroscience, and I found the Silicon Valley hype distasteful at times. The cultish view that Moore’s law — the observation that computing power increases exponentially over time — would solve not only every technological problem, but also all social and scientific ones, seemed naive to me. It was the epitome of the mindset “when you have a hammer, everything looks like a nail”. I was wrong. In 2019, colleagues at Google trained a massive (for the time) next-word predictor — technically, a next-token predictor, with each token corresponding to a word fragment — codenamed Meena1. It seemed able, albeit haltingly, to understand new concepts, write jokes, make logical arguments and much else. Meena’s scaled-up successor, LaMDA, did better2. This trend has continued since. In 2025, we find ourselves in the rather comical situation of expecting such large language models to respond fluently, intelligently, responsibly and accurately to all sorts of esoteric questions and demands that humans would fail to answer. People get irritated when these systems fail to answer appropriately — while simultaneously debating when artificial general intelligence will arrive. How to detect consciousness in people, animals and maybe even AI Large language models can be unreliable and say dumb things, but then, so can humans. Their strengths and weaknesses are certainly different from ours. But we are running out of intelligence tests that humans can pass reliably and AI models cannot. By those benchmarks, and if we accept that intelligence is essentially computational — the view held by most computational neuroscientists — we must accept that a working ‘simulation’ of intelligence actually is intelligence. There was no profound discovery that suddenly made obviously non-intelligent machines intelligent: it did turn out to be a matter of scaling computation. Other researchers disagree with my assessment of where we are with AI. But in what follows, I want to accept the premise that intelligent machines are already here, and turn the mirror back on ourselves. If scaling up computation yields AI, could the kind of intelligence shown by living organisms, humans included, also be the result of computational scaling? If so, what drove that — and how did living organisms become computational in the first place? Over the past several years, a growing group of collaborators and I have begun to find some tentative, but exciting answers. AI, biological intelligence and, indeed, life itself might all have emerged from the same process. This insight could shed fresh light not just on AI, neuroscience and neurophilosophy, but also on theoretical biology, evolution and complexity science. Moreover, it would give us a glimpse of how human and machine intelligence are destined to co-evolve in the future. Predictive brains The idea that brains are essentially prediction machines isn’t new. German physicist and physician Hermann von Helmholtz advanced it in the nineteenth century in his Treatise on Physiological Optics (1867). The idea was developed further by the founders of cybernetics, especially US mathematician Norbert Wiener, in the early 1940s — a starting point of modern, neural-net-based AI research. Wiener realized3 that all living systems have ‘purposive’ behaviours to stay alive, and that such actions require computational modelling. Our internal and external senses enable us to compute predictive models, both of ourselves and of our environment. But these are useful only if we can act to affect the future — specifically, to increase the odds that we will still be a thriving part of it. Evolution selects for entities that use predictions to make the best survival decisions. The actions we take, and the observations that ensue, become part of our past experience, creating a feedback loop that enables us to make further predictions. Hunting is a prime example of this predictive modelling. A predator must predict actions that will get the prey into its stomach; the prey must predict the predator’s behaviour to stop that from happening. Starting in the 1970s, neuropsychologists and anthropologists began to realize that other intelligent entities are often the most important parts of the environment to model — because they are the ones modelling you back, whether with friendly or hostile intent4. Increasingly intelligent predators put evolutionary pressure on their prey to become smarter, and vice versa. The hunting behaviour of whales is the product of a shared, social intelligence.Credit: Nick Garbutt/NaturePL The pressures towards intelligence become even more intense for members of social species. Winning mates, sharing resources, gaining followers, teaching, learning and dividing labour: all of these involve modelling and predicting the minds of others. But the more intelligent you become — the better to predict the minds of others (at least in theory) — the more intelligent, and thus hard to predict, those others have also become, because they are of the same species and doing the same thing. These runaway dynamics produce ‘intelligence explosions’: the rapid evolutionary increases in brain size that have been observed in highly social animals, including bats, whales and dolphins, birds and our own ancestors. During a social intelligence explosion, individuals get smarter, but so do groups. Bigger brains can model more relationships, allowing groups to become larger while retaining social cohesion. Sharing and division of labour enable these larger social units to do much more than individuals can on their own. Take humans. Individually, we aren’t much smarter than our primate ancestors. Humans raised in the wild, like the fictional Mowgli in Rudyard Kipling’s The Jungle Book (1894), would seem unexceptional relative to the forest’s other large-ish animals — if, indeed, they survive at all. But in large numbers, humans can achieve many improbably complex feats beyond any individual’s cognitive or physical capacity: transplanting organs, travelling to the Moon, manufacturing silicon chips. These feats require cooperation, thinking in parallel and division of labour. They are group-level phenomena, and can justifiably be called superhuman. Symbiogenic transitions What applies to human sociality arguably also applies to every previous major evolutionary transition throughout life’s history on Earth. These include the transition from simple prokaryotic cells to more-complex eukaryotic ones, from single-celled life to multicellular organisms, and from solitary insects to colony-dwellers. In each case, entities that previously led independent lives entered into a close symbiosis, dividing labour and working in parallel to create a super-entity5. AI language models killed the Turing test: do we even need a replacement? A growing body of evidence suggests that this ‘symbiogenesis’ is much more common than has generally been supposed. Horizontal gene transfer between cells, the incorporation of a useful retroviral element into a host’s genome and symbiotic bacteria establishing themselves in an animal’s gut are commonplace examples that would not count as ‘major’ transitions. Yet they have certainly produced organisms with innovative capabilities. The ability of termites to digest wood, for instance, depends entirely on enzymes produced by symbiotic microorganisms. The formation of the placental barrier in humans depends on syncytin, a protein derived from the envelope of a retrovirus that fused into the mammalian germ line tens of millions of years ago. Standard Darwinian evolution, involving the familiar mechanisms of mutation and selection, has no intrinsic bias towards increasing complexity. It is this less familiar mechanism of symbiogenesis that gives evolution its arrow of time: life progresses from simple to more-complex forms when existing parts merge to form new super-entities. This process speeds up over time, as the catalogue of parts available to be combined afresh increases in size and sophistication. Over the past billion years, symbiogenesis has produced increasingly complex nervous systems, colonies of social animals — and eventually our own technological society. Is this nature’s version of Moore’s law? Yes and no. As originally formulated in 1965 by US engineer Gordon Moore, the co-founder of chip company Intel, the ‘law’ states that transistor size shrinks exponentially6. This translates into exponential declines in computer size, cost and power consumption, and exponential increases in operating speed. Biological cells have not become exponentially smaller or faster throughout evolution. The advent of electrically excitable neurons sometime around 650 million years ago introduced a fast new computational timescale, but that was a one-off: since then, neurons have not become faster or smaller, nor have their energetic requirements decreased. This does not obviously resemble Moore’s law as it played out in the twentieth century. Will AI ever win its own Nobel? Some predict a prize-worthy science discovery soon But look at the law in the twenty-first century, and a connection becomes more apparent. Since around 2006, transistors have continued to shrink, but the rise in semiconductor operating speed has stalled. To keep increasing computer performance, chip-makers are instead adding more processing cores. They began, in other words, to parallelize silicon-based computation. It’s no coincidence that this is when modern, neural-net-based AI models finally began to take off. Practically speaking, neural nets require massively parallel processing; for a single modern processor to sequentially perform the trillion or so operations needed for a state-of-the-art large language model to predict the next token in a sequence would take minutes. This starts to look a lot more like the story of biological intelligence. AI emerged not through speed alone, but from a division of labour arising from the cooperation of many simple computational elements running in parallel: what we might term technological symbiogenesis. In this context, computer science is a natural science as well as an engineering discipline. Humans did not invent computation any more than they did electric current or optical lenses. We merely re-discovered a phenomenon nature had already exploited, developed mathematical theories to understand it better and worked out how to engineer it on a different substrate. Our phones, laptops and data centres could aptly be called ‘artificial computers’. Computogenesis If symbiogenesis explains the evolution of natural computational complexity and the emergence of intelligence, how and why did nature first become computational? Work that I and colleagues have been doing on artificial life over the past couple of years helps to clarify this. To set the scene, imagine an enormous variety of randomly configured feedback mechanisms that are simple enough to arise spontaneously in a thermally variable environment such as that of Earth. Now, assume that each of these mechanisms can work only within some narrow temperature range. After a while, the mechanisms that persist will be the ones that work as thermostats, maintaining their temperature within the right range, so that they can continue to operate. This thought experiment illustrates how purposive behaviour, oriented towards self-preservation — a kind of proto-life — can emerge from random initial conditions. Even a thermostat is, by definition, performing a computation: it implements a behaviour (turn the heat on or off) that is conditional on an information input (the temperature). Thus, a minimal kind of computation — perhaps nothing more than an ‘if 
 then’ operation — will arise and persist whenever the output can affect the likelihood of whatever is doing the computation continuing to exist. This kind of simple operation is still a long way from a general-purpose computer, which was defined by English computing pioneer Alan Turing using a theoretical construct we refer to today as a universal Turing machine. It consists of a ‘head’ that can move left or right along a tape, reading, writing and erasing symbols on that tape according to a table of rules. Turing realized that a rule table can also be encoded as a sequence of symbols on the tape — what we’d now call a program. Certain rule tables exist that will cause the machine to read that program from the tape, performing any computation it specifies. Humans and machines exist in a mutually dependent technological symbiosis.Credit: CFOTO/Future Publishing via Getty
Nature DOI suffix ≠ "/s...": Not a research article
This is what lightning on Mars sounds like
Benjamin Thompson, Nick Petrić Howe
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Nature DOI suffix ≠ "/s...": Not a research article
International environmental treaties cannot be reformed through rational design
Vito De Lucia, Jan Solski
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Your Comment article asserts rightly that the collapse of negotiations for the United Nations plastics treaty reflects broader systemic problems affecting international environmental law and governance (R. E. Kim and P. Bridgewater Nature 646, 1054–1056; 2025). But in our view, the authors’ suggested solution — a global scientific body that would assess and issue binding recommendations for environmental bodies and treaties — is wrong-headed.
Nature DOI suffix ≠ "/s...": Not a research article
‘Anti-woke’ policies blamed for falling attendance at some US conferences
Alexandra Witze
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Conferences offer researchers from under-represented backgrounds a chance to network.Credit: Dave Kotinsky/Getty Several US conferences that bring together scientists from under-represented groups have seen their attendance levels drop this year, in the wake of funding cuts and directives from the administration of US President Donald Trump targeting diversity, equity and inclusion (DEI) initiatives. Such conferences typically provide crucial networking opportunities for scientists from marginalized backgrounds, including Black, Latino and Indigenous researchers. Fewer people attending this year means fewer chances for students and scientists to advance their careers, says Allen Pierre-Louis, a physicist and PhD student at Duke University in Durham, North Carolina. “This is another leak in the pipeline that was already not in a great place.” Scientific conferences are leaving the US amid border fears The crowds have been noticeably thinner than usual at some major conferences held in the past few months. Fewer than 700 scientists — compared with last year’s 1,100 — gathered last week at a joint meeting of the National Society of Black Physicists (NSBP) and the National Society of Hispanic Physicists (NSHP) in San Jose, California. And last month, there were only a few thousand attendees, rather than the usual 5,000–6,000, at a multidisciplinary science conference in Columbus, Ohio, organized by the Society for the Advancement of Chicanos/Hispanics and Native Americans in Science (SACNAS). Federal agencies that would normally have exhibit booths at such meetings to promote their research, as well as staff members on site to speak to prospective employees, were also not present. Federal funding that is normally available to pay for students’ travel to these conferences has also dried up. “Investing in these students isn’t ‘charity’ — it’s essential for the nation’s scientific future,” says Mario Borunda, a physicist at Oklahoma State University in Stillwater and the NSHP president. “If we exclude brilliant minds because they can’t afford a plane ticket or because they don’t see themselves represented in the field, the US loses that talent forever.” Projects cancelled On his first day in office, Trump issued an executive order that directed the government to terminate programmes related to DEI, which it called “illegal and immoral discrimination”. Agencies soon began cancelling projects, affecting a wide swathe of researchers. One of those agencies was NASA, which terminated a US$530,000 grant that was meant to support the NSBP/NSHP meeting over three years. That and other cuts left the conference with none of the federal funding it usually relies on, says Stephen Roberson, the NSBP president. “The reason given for this behaviour is because our organization is considered a DEI organization instead of a scientific non-profit organization,” he says. NASA did not respond to a request for comment from Nature. Trump called for ‘gold-standard science’: how the NIH, NSF and others are answering Because of the cuts, the conference had to cut back on travel, lodging and other support it usually provides to students and other attendees. Without that support, “the costs become prohibitive for many people”, says Pierre-Louis, who is the student council representative on the NSBP board. “I think it sends a message to the country about who is doing science and is seen as being worthy of doing science.” There is no ‘woke’ agenda to the meeting, Borunda notes: conference registration is open to anyone, and the talks are on scientific topics, including quantum and plasma physics. “There is a sense of solidarity here that remains strong,” he says. The SACNAS conference, a meeting officially known as NDiSTEM, was held in Columbus last month, but many federal agencies and industry partners withdrew from participating because of Trump’s DEI directive and budget cuts, says the organization’s executive director, Juan Amador. One immediate consequence was that the conference lost much of the content meant to connect students with the latest in artificial intelligence (AI) research happening at government agencies and in the private sector. “With them being gone we didn’t have a whole lot of AI — that puts the students behind,” Amador says.
Nature DOI suffix ≠ "/s...": Not a research article
‘They don’t have symptoms’: CAR-T therapies send autoimmune diseases into remission
Rachel Fieldhouse
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CAR T cells (pictured) are being used to treat autoimmune diseases.Credit: Eye Of Science/SPL Engineered immune cells are being used to successfully treat people with a range of debilitating autoimmune conditions, such as ulcerative colitis, rheumatoid arthritis and lupus. Researchers say positive results from around a dozen studies over the past three years suggest CAR-T-cell therapy could eventually be used to treat any disease in which the immune system attacks the body. CAR-T-cell therapy exploits the immune system’s T cells that fight off infection: these cells are collected from a person and tweaked to produce proteins called chimeric antigen receptors. They are then reintroduced into the body to target antigens expressed by B cells, another type of immune cell. In autoimmune disorders, these B cells make antibodies that attack the body’s own healthy tissues. The use of the therapy for immune conditions has exploded since 2021, when a 20-year-old woman in Germany with severe lupus became the first person with an autoimmune disorder to be treated with CAR T cells1. Clinician–researcher David Simon, who was involved in that treatment2, says the CAR-T therapies have since entered phase I and II clinical trials for autoimmune conditions including systemic sclerosis, myositis and rheumatoid arthritis. Phase III trials are also under way for lupus and myasthenia gravis, a condition that causes weakness in the muscles that are used to breathe, swallow and see. Simon, who focuses on rheumatoid arthritis at the CharitĂ© University Hospital in Berlin, says people in CAR-T-cell therapy trials for rheumatoid arthritis and lupus seem to be ‘cured’. “They lose their autoantibodies which trigger the disease, and they don’t have any symptoms any more,” he adds. “This is something totally new which we didn’t observe before.” CAR-T-cell therapy has become a routine treatment for several types of cancer since it was first approved to treat blood cancers in 2017. A new frontier Ulcerative colitis, a condition that affects the colon and causes stomach pain, ulcers and bloody diarrhoea, is one of the latest diseases in which CAR-T-cell therapy has shown promise. In September, gastroenterologist Markus Neurath and his colleagues at the University Hospital Erlangen in Germany, reported using CAR T cells to treat a 21-year-old woman with ulcerative colitis3. After the treatment, she showed signs of remission that persisted for 14 weeks, no longer needed medication and could return to work. “The result was quite amazing,” adds Neurath. His team plans to test the treatment in a few more people before proceeding to a controlled clinical trial involving many individuals. Earlier this year, Bing Du, an immunologist at East China Normal University in Shanghai, and his team published the results of a CAR-T pilot study using immune cells from a donor to treat drug-resistant lupus4. Donor-derived cells could act like a generic version of CAR-T treatment that could be mass-produced, cutting manufacturing time and lowering costs5. Last year, Du was also involved in a world-first study of bioengineered and modified immune cells from a donor for the treatment of two rare and severe autoimmune diseases6. As part of the latest study, four women with a form of lupus that affects multiple organs received chemotherapy to reduce levels of their white blood cells, followed by an infusion of donor-derived CAR T cells. After three months, the women no longer experienced symptoms such as arthritis, swelling of blood vessels and alopecia, and one was in remission and no longer needed any medication. The other three women received low-dose steroids as a maintenance therapy. The results of the trial were “much better than we could imagine”, says Du, and might be due to CAR T cells triggering the total depletion of dysfunctional B cells that attack the body’s tissues. “The immune system had to reset not only B cells, but also the rest of the immune system,” he adds, potentially allowing new, healthy B cells to replace the dysfunctional cells.
Nature DOI suffix ≠ "/s...": Not a research article
Large language models are biased — local initiatives are fighting for change
Laura Vargas-Parada
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Nature DOI suffix ≠ "/s...": Not a research article
How to stop the revolving door of German academia
Diana Kwon
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Some German universities, such as the University of Hamburg, are trying to add more permanent research positions.Westend61 / Getty Images After 13 years of jumping between temporary contracts at German institutions, DorothĂ©e Goetze, who was a history postdoc, was fed up. So in 2021, when she was offered a full-time, permanent lecturing position at Mid Sweden University in Sundsvall she leapt at the opportunity. Part of the reason for leaving was simple: the permanence of the new post, a rarity both in and outside Germany. But Goetze says that there were other troubling aspects of German academia that led her to expand her job search. “When I started to look at other countries, I realized that there are other ways to structure an academic system.” Although Germany has become a hub for international students and researchers, attracting a growing number of foreign scholars each year, those who remain in academia after graduation often face an intensely hierarchical system with few permanent positions. This has led many, including Goetze, to search for jobs at universities and research institutions outside the country — or, in some cases, to leave academia completely. Nature Career Guide: Germany Last year, the Postdoc Network of the Max Planck Society published a survey of close to 900 postdocs from 74 of the 85 Max Planck Institutes, in which only one-quarter of international respondents said that they were sure they wanted to stay in Germany after their postdoc (see go.nature.com/486jceo). A similar survey by the postdoc network of the Leibniz Association revealed that some 42% of respondents had considered moving abroad (see go.nature.com/3xesmtz). “There are a lot of good reasons to embark on a PhD or research career in Germany,” says Shyam Krishnan, a stem-cell biologist at the Leibniz Institute for Natural Product Research and Infection Biology in Jena, Germany, and a spokesperson for the Leibniz PostDoc Network. These include the country’s globally respected research profile and ample opportunities for funding and collaborations, according to Krishnan. However, it is not always possible for early-career researchers to take advantage of these benefits — for example, most are on short-term contracts that don’t align with the long grant-application processes, Krishnan says. “When it comes to career paths, it becomes really difficult, especially for people coming from abroad.” A popular destination In 2025, Germany had the fourth highest number of international students globally, according to the Organisation for Economic Co-operation and Development (OECD), a figure totalling around 423,000 people. The number of international students in Germany has steadily increased in the past decade, thanks to factors such as the affordability of education, a high quality of life and employment opportunities after graduation. Between 2013 and 2023, the Wissenschaft weltoffen report — using data from the German Academic Exchange Service (DAAD) and the German Centre for Higher Education Research and Science Studies (DZHW) — highlighted a 74% rise in the number of foreign students enrolled at German universities. The majority of these individuals were in bachelor’s or master’s programmes. A structured system: the secrets of Germany’s scientific reputation International scholars are also common at the postdoctoral level and above. In 2022, foreign nationals made up around 15% of academic staff members across German universities — encompassing all roles from graduate-student research assistants to professors. At the Max Planck institutes, which employ the highest proportion of foreign scholars, more than half of the researchers come from abroad. These numbers will probably continue to rise. In the past few months alone, there have been several announcements of initiatives aimed at recruiting international students and scholars. In October, for example, the DAAD launched Academic Horizons, a funding programme that helps universities to attract international scholars to master’s and doctoral programmes in disciplines such as artificial intelligence and quantum technology. There are also several efforts aimed at attracting talent from the United States, where cuts to science funding and decreased workforce numbers have led many researchers to consider leaving the country. The Volkswagen Foundation, for example, recently announced the Transatlantic Bridge Professorships, which will provide financial support for US-based professors who are working on topics such as democracy and academic freedom to conduct their work in Germany. To stay or to leave? Although Germany is an attractive destination for scholars, those who remain in the academic system after their doctoral studies face notable challenges. Two of the frequently cited issues are a lack of job security, owing to the lack of permanent positions, and a strictly hierarchical system that places a disproportionate amount of power in the hands of a few. In German academia, short-term contracts are the norm: according to the 2025 National Report on Early Career Researchers (known as the BuWik), a mere 4% of early-career researchers are not on a temporary contract (see go.nature.com/4i78g4o). Older and more-experienced researchers tend to be in more permanent positions — this includes 38% of doctorate holders aged between 40 and 45 and 28% of junior research group leaders. Are these the happiest PhD students in the world? In a bid to alleviate this problem, the German government passed the Academic Fixed-Term Contract Act in 2007 (also known as the Wissenschaftszeitvertragsgesetz, or WissZeitVG; see go.nature.com/48kzoyl). This law limits the time that early-career researchers can be placed on fixed-term contracts to, in most cases, six years pre-PhD and six years post-PhD (nine years after medicine PhDs), with the intention of encouraging universities to hire these researchers permanently, rather than keeping them temporarily employed indefinitely. However, critics of the WissZeitVG argue that it backfired because it failed to lead to a growth in permanent positions. They say that it instead forces researchers out of academia — leading to knock-on effects such as lower-quality research and a loss of qualified personnel. “What universities do in most cases is say, ‘We cannot employ you temporarily any more, so we won’t employ you,’” says Mathias Kuhnt, a sociology postdoc at the Dresden University of Technology. In some fields, such as social science and the humanities, contracts are not only short-term; they’re also often part-time. Amrei Bahr, a philosopher at the University of Stuttgart, has had fixed-term, mostly part-time contracts during and after her doctoral studies. Now, with her non-tenure-track junior professorship, Bahr is on a four-year contract with a possible two-year extension. “If I get the two years, I will be 42 once this is over,” Bahr says. “Then I will probably drop out.” Bahr is currently applying for other, longer-term professorships, but given the dearth of these positions, dropping out of academia is a likely outcome. Planning an exit Bahr is not alone. In 2024, the DZHW published a Barometer for Science report — a nationwide survey that included more than 11,000 academics in Germany — which revealed that 57% of researchers had contemplated leaving academia in the past two years (see go.nature.com/3jdogk0). Among postdocs on fixed-term contracts (which make up the majority), this rose to 71%. Work–life balance, workload and the WissZeitVG were cited as contributing factors. Historian Astrid Wendel-Hanson left Germany for a position with a longer-term contract.Marten Puidak “Germany is incredibly valuable in terms of the resources it has for academics,” says Astrid Wendel-Hanson, a historian who moved to Germany after her PhD, but left earlier this year after accepting a position as an associate professor at Tallin University in Estonia. “But it can be very difficult to stay optimistic and to remain in a system that seems to actively be trying to push you away.” Although one of the reasons for the move was to be closer to family, Wendel-Hanson’s new contract is four years long — longer than what would be permitted under the WissZeitVG. Germany is not the only country with precarious employment in academia, however. According to a 2024 OECD report, in Australia, casual hires — those on hourly or seasonal contracts — make up the majority of academic staff members, and in the United States, part-time and non-tenure-track positions are increasingly becoming the norm (OECD. The State of Academic Careers in OECD Countries; 2024).
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A brain implant that could rival Neuralink’s enters clinical trials
Liam Drew
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A brain–computer interface developed by neurotechnology firm Paradromics contains electrodes that record from neurons in the cerebral cortex and then convert the information into intended speech patterns.Credit: Paradromics Paradromics, a neurotechnology developer, announced today that the US Food and Drug Administration (FDA) has approved a first long-term clinical trial of its brain–computer interface (BCI). Early next year, the company — one of the closet rivals to Elon Musk’s neurotechnology firm Neuralink — will implant its device into two volunteers who were left unable to speak owing to neurological diseases and injuries. It has two goals: to ensure the device is safe; and to restore a person’s ability to communicate with real-time speech. “We’re very excited about bringing this new hardware into a trial,” says Matt Angle, chief executive of Paradromics, which is based in Austin, Texas. Paradromics’ BCI has an active area of roughly 7.5 millimetres in diameter of thin, stiff, platinum–iridium electrodes that penetrate the surface of the cerebral cortex to record from individual neurons around 1.5 mm deep. This is then connected by wire to a power source and wireless transceiver implanted in an individual’s chest. Initially, the two volunteers will each have one electrode array implanted in the area of the motor cortex that controls the lips, tongue and larynx, Angle says. Neural activity will then be recorded from this region as the study participants imagine speaking sentences that are presented to them. Following previous work by researchers who are now collaborating with Paradromics1, the system learns what patterns of neural activity correspond to each intended speech sound. When participants imagine speaking, these neural patterns will be converted into text on a screen for participants to approve, or into a real-time voice output based on old recordings of participants’ own voices. This is the first BCI clinical trial to formally target synthetic-voice generation. “Arguably, the greatest quality of life change you can deliver right now with BCI is communication,” Angle says. Elon Musk’s Neuralink brain chip: what scientists think of first human trial The trial will also explore whether the system can reliably detect activity from imagined hand movements that would enable an individual to control a computer cursor. Depending on initial results, the trial could extend to ten volunteers, with these participants receiving two cortical implants to increase signal richness and to access other brain areas, says Angle. “I’m very curious. It’s an exciting step,” says Mariska Vansteensel, a BCI researcher at the University Medical Center Utrecht in the Netherlands. “For the field to move forward towards clinical applications, a fully implantable system is the only way to go.” Neuralink rivals Paradromics is now one of several companies testing an implanted BCI system that is similar to what it intends to market in a long-term trial. Several more companies hope to follow suit soon. Furthest along is Synchron, a BCI company in New York City, and its device Stentrode. By incorporating 12–16 electrodes into a device that is based on an endovascular stent, the Stentrode records the average activity of a neuronal population from inside a blood vessel. Initial trials utilized a vessel in the motor cortex to allow users to select onscreen options by imagining that they are moving their foot. Neuralink has prioritized obtaining high-bandwidth signals by recording outputs from many single neurons. Its BCI consists of 64 flexible polymer threads, each with 16 recording sites. In the company’s initial trial, it targeted the region of the motor cortex that controls the hand. Users controlled computers and robotic hands with their thoughts, and the company has regularly reported that it is able to transfer information from people’s brains to computers at record-breaking speeds. A clinical trial will assess the safety and durability of Paradromics’ brain–computer interface after it has been surgically implanted into the brains of two volunteers.Credit: University of Michigan Other systems in development include several BCIs that place high-density electrodes on the brain’s surface to record the average activity of underlying neuronal populations. As long-term trials now progress, clinicians and neuroscientists will be watching and comparing devices. Vansteensel says she hopes companies will be fully transparent and that, in time, they will make their devices available to academics to conduct independent studies.
Nature DOI suffix ≠ "/s...": Not a research article
Universities must help students faced with the death of a supervisor
Laura ZĂĄrraga-Vargas
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The sudden loss of a PhD supervisor is a profound crisis, which can be magnified by a lack of institutional contingency plans. My experience, similar to that described by Cailyn McKay in your Career Column (C. McKay Nature https://doi.org/qdn4; 2025), highlights this. When my supervisor died of COVID-19, the ensuing chaos threatened my studies.
Nature DOI suffix ≠ "/s...": Not a research article
Thirty years of Bose–Einstein condensation
Zoran Hadzibabic, Ulrich Schneider
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This year marks 30 years since the fulfilment of a decades-old dream that redefined atomic physics. In 1995, two papers, published in Science by Anderson et al.1 and in Physical Review Letters by Davis et al.2, reported the first conclusive experimental observation of Bose–Einstein condensates (BECs), a state of matter in which the constituent atoms in a many-body system behave as a single, quantum-mechanical object.
Nature DOI suffix ≠ "/s...": Not a research article
ADHD diagnoses are growing. What’s going on?
Helen Pearson
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In some parts of the world, record numbers of people are being diagnosed with attention deficit hyperactivity disorder (ADHD). In the United States, for example, government researchers last year reported that more than 11% of children had received an ADHD diagnosis at some point in their lives1 — a sharp increase from 2003, when around 8% of children had (see ‘ADHD among US boys and girls’). Why is autism really on the rise? What the science says But now, top US health officials argue that diagnoses have spiralled out of control. In May, the Make America Healthy Again Commission — led by US health secretary Robert F. Kennedy Jr — said ADHD was part of a “crisis of overdiagnosis and overtreatment” and suggested that ADHD medications did not help children in the long term. So what, exactly, is going on? One thing that’s clear is that several factors — including improved detection and greater awareness of ADHD — are causing people with symptoms to receive a diagnosis and treatment, whereas they wouldn’t have years earlier. Clinicians say this is especially true for women and girls, whose pattern of symptoms was often missed in the past. Although some specialists are concerned about the risks of overdiagnosis, many are more worried that too many people go undiagnosed and untreated. At the same time, the rise in awareness and diagnoses of ADHD has fuelled a public debate about how it should be viewed and how best to provide support, including when medication is required. The emergence of the neurodiversity movement is challenging the view of ADHD as a disorder that should be ‘treated’, and instead proposes that it’s a difference that should be better understood and supported — with more focus on adapting schools and workplaces, for instance. Source: Ref. 1 “I do have a big problem with ‘disorder’,” says Jeff Karp, a biomedical engineer at Brigham and Women’s Hospital in Boston, Massachusetts, who has ADHD. “It’s the school system that’s disordered. It’s not the kids.” But many clinicians and people with ADHD argue that it is associated with difficulties — ranging from academic struggles to an increased chance of injuries and substance misuse — that justify its label as a medical condition, and say that medication is an important and effective part of therapy for many people. “I hear a lot of people talking about ADHD being a gift and a superpower, and I do applaud that,” says Jeremy Didier, a clinician specializing in ADHD who is president of Children and Adults with Attention Deficit–Hyperactivity Disorder (CHADD), a non-profit US group based in Lanham, Maryland, and who has ADHD herself. “But I do not want to downplay the impact that ADHD can have on someone’s life when it’s either undiagnosed or poorly managed.” She and others say both models — neurodiversity and medical — have merit. “Bringing those two together in a meaningful and productive way, I think that’s maybe the biggest challenge” for the field, says Sven Bölte, a specialist in child and adolescent psychiatric science at the Karolinska Institute in Stockholm. A real rise A slew of studies suggests that diagnoses of ADHD have gone up in many high-income countries in the past two to three decades — similar to a rise in autism diagnoses (see ‘ADHD on the rise’). The rate of new ADHD diagnoses in the United Kingdom, for example, doubled in boys and quadrupled in girls between 2000 and 2018, according to one study2. In adults, the rate shot up even more. “We have numbers suggesting that we’re seeing a rise,” says Max Wiznitzer, a paediatric neurologist at Rainbow Babies and Children’s Hospital in Cleveland, Ohio. Source: US CDC NHIS Annu. Rep. (https://go.nature.com/3XEGYXJ). So what explains the surge? It doesn’t seem to be a big rise in the prevalence of the symptoms and traits that characterize ADHD — namely hyperactivity, impulsivity and inattention, researchers say. When scientists use standard procedures to rigorously assess symptoms in representative samples of a population, they find that the ‘true’ prevalence of ADHD is fairly consistent in different parts of the world — estimated at around 5.4% in children3 and 2.6% in adults4, according to two comprehensive global studies. Experts say there are several reasons these figures are much lower than the 11% diagnosis level in US children that the country’s health authorities reported last year1. That number comes from the US National Survey of Children’s Health conducted in 2022, in which parents were asked whether a doctor or other health-care provider had ever said their child has ADHD. But this method of assessing prevalence would lead to inflated counts, says Luis Rohde, a psychiatrist and ADHD specialist at the Federal University of Rio Grande do Sul in Porto Alegre, Brazil. Some children were probably misdiagnosed — perhaps by a physician without specialist training — and would not be classified as having ADHD in a thorough clinical evaluation. Some parents might have misremembered, perhaps if they were told that their child had symptoms without a formal diagnosis, he says. And some children who once had a diagnosis would no longer have received one at the time of the survey if their symptoms had waned and they were reassessed. How to make America healthy: the real problems — and best fixes Researchers and specialists highlight other factors that are likely to be driving up the number of diagnoses. One is a change in diagnostic criteria in The Diagnostic and Statistical Manual of Mental Disorders (DSM). In the fourth edition of this widely used manual, introduced in 1994, a child or adult ADHD diagnosis required the presence of at least six of a list of nine inattention symptoms and/or six or more of nine hyperactivity symptoms, and stipulated that these had to be present before the age of seven. (This reflects the idea that ADHD is a neurodevelopmental condition that arises during childhood brain development.) When the fifth edition, DSM-V, arrived in 2013, the criteria were slightly relaxed. Symptoms had to be present before age 12, and adult diagnosis required a minimum of five symptoms. (Children still had to have at least six.) “So when we expand the criteria, obviously you increase a little bit the prevalence,” says Rohde, who was involved in those revisions. It has also become more common for clinicians to diagnose ADHD along with other conditions, when in the past they tended to focus on one, says Bölte: “That fuels the figures.” ADHD commonly occurs with autism, as well as with anxiety, depression and other disorders. The impairment requirement Today, a thorough ADHD assessment involves collecting a detailed history and completing behaviour questionnaires, including input from family members and, for children, from schools. In the United States, the condition can be diagnosed by a range of health professionals, including psychiatrists, other mental-health specialists and primary-care physicians such as paediatricians, who might not have dedicated training in ADHD. But countries differ: in Brazil and many other low- and middle-income nations, people with ADHD symptoms tend to be sent to neurologists and psychiatrists for ADHD assessment and diagnoses, and there is a shortage of such specialists, Rohde says. The DSM-V defines three ‘presentations’ of ADHD. People with ‘predominantly inattentive’ ADHD show symptoms such as making careless mistakes, struggling to sustain attention, losing things and being easily distracted. Those with predominantly hyperactive-impulsive ADHD have traits such as fidgeting, restlessness, talking excessively and interrupting others. In a third, combined presentation, people show both sets of symptoms. A diagnosis requires that symptoms are present for at least six months and in two or more settings (such as school, home, work); are not explained by another condition such as anxiety; and cause an impairment, such as struggling with schoolwork, losing a job or having relationship problems. Illustration by Ada ZieliƄska The impairment requirement is key, clinicians say. These traits vary across the population: some individuals are very hyperactive or inattentive, and some not at all. But people tend to be diagnosed with ADHD when their symptoms significantly interfere with their lives. “The medical part of ADHD comes in when your life is becoming derailed,” says Margaret Sibley, a specialist in psychiatry and behavioural sciences at the University of Washington School of Medicine in Seattle. Bölte says that clinicians are interpreting the diagnostic criteria “far more liberally and openly” than in the past. This is another factor — aside from changes in the diagnostic criteria — that is driving the apparent surge in ADHD. But working out when someone crosses the impairment line involves a subjective and sometimes tricky judgement, say specialists. And there is an ongoing debate about whether a person’s level of impairment should be defined relative to their own potential or to a population average. What’s clear is that more parents as well as children are deemed as crossing that threshold. Wiznitzer says that when he diagnoses a child, “almost invariably [one of] the parents has it”, too. (That’s because genes are a major contributor to ADHD: the disorder has a heritability5 of roughly 70–80%.) Even though the parents were probably symptomatic as children, many were not identified as having the condition, he says. But now, they are. ADHD on TikTok Another reason why diagnoses have surged is an increase in public awareness of ADHD — fuelled by an explosion of discussion on TikTok and other social media. Information online “connects with some people who have had these symptoms and impairments for a long time, but never understood what they were,” says Sibley. That leads them to seek information and professional help, pushing diagnoses up. And people might be eager to receive a diagnosis if it allows them to access help and services for themselves or a child, such as adaptations to support learning at school. The surge in ADHD has led to concerns, particularly in the United States, about questionable diagnoses being given without a thorough clinical evaluation — through online services, for example, or by medical professionals without ADHD training. “They’ve got a visit for 15 or 20 minutes, and the diagnosis is made,” says Stephen Hinshaw, a specialist in child and adolescent mental health and ADHD at the University of California, Berkeley. But Didier says that a bigger problem is the number of people with ADHD who are undiagnosed or untreated. She emphasizes how important it is for people to have access to a thorough, accurate assessment from a trained professional who specializes in ADHD. The lack of recognition of ADHD is a particular problem in low- and middle-income countries, says Rohde. “The problem here is clearly underdiagnosis, stigma and undertreatment,” he says, which particularly affects “vulnerable people and communities”. Autism is on the rise: what’s really behind the increase? Many specialists say they’re observing a rapid rise of diagnoses in girls and women6. In part, that’s thought to be because women and girls are more likely to have symptoms of inattention — rather than more-noticeable hyperactivity — and to find organizational and other strategies that ‘mask’ those symptoms. Didier says that, despite being an ADHD specialist and diagnosing the condition in three of her sons, she and other ADHD practitioners missed the signs and symptoms in her daughter until she was a teenager. “It’s egregious that we don’t have more research on ADHD trajectories in women,” Sibley says. Changes in the world itself are yet another possible contributor to increased diagnoses. Some researchers speculate that schools, work, technology and other aspects of modern lives have become so complex and taxing that they are pushing more people beyond the threshold of impairment. In Sweden, says Bölte, schools are sometimes chaotic, with complex schedules and grading systems. “Many students are very confused and fed up with school and do not understand it any more,” he says. A study published last year7 revealed that parents think their children are struggling more. The research team examined how parents viewed the ADHD symptoms of more than 27,000 nine-year-old children born in Sweden. Parents consulted in 2016–18 tended to say that their children were more impaired than did parents consulted in 2004–06, even though their kids had the same number of symptoms. “Environment around the child is crucial,” says Samuele Cortese, who studies ADHD at the University of Southampton, UK, and was involved in the work. Context is key Karp describes ADHD as “context-dependent”. In a school where children are expected to sit still and be quiet, “it makes these traits seem like a problem”, he says. But when someone with ADHD is in an environment that nurtures and empowers them, they “can then channel their neurotype to do incredible things”. Karp is not against medication — and sometimes takes it himself — but would like more emphasis on institutions and society evolving so that people with ADHD can thrive. Researchers, meanwhile, are finding evidence that the severity of symptoms can vary over time. In a 2021 study, Sibley and her colleagues analysed detailed records of more than 550 children who were diagnosed with ADHD and followed for up to 16 years8. The researchers found that 64% of young people had fluctuations in ADHD — times when their symptoms faded but then recurred. Sibley and her team hypothesized that people’s symptoms might flare up when they were facing increased demands in their lives, such as when starting a new school or having a child. But in fact, the opposite seemed to be true, according to a later analysis by Sibley and her colleagues9. This could be because people are able to take on more responsibility when their symptoms abate. But the alternative explanation — one that has “really resonated”, Sibley says — is that people with ADHD need a degree of activity and accountability in their lives to perform and stay engaged. Sibley thinks there might be a U-shaped curve: too many or too few demands and obligations mean that people with ADHD don’t function at their best — but at a “sweet spot”, they do.
Nature DOI suffix ≠ "/s...": Not a research article
Land-use changes threaten the safety net for birds
Carlos P. Carmona
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Human-related changes in land use influence the prevalence of bird species, and animals with certain traits — such as particular body sizes, beak shapes or diets — are more likely to die out than others are. This process removes ecological roles and erodes the ‘insurance’ that enables such roles to continue after certain species disappear. Writing in Nature, Weeks et al.1 report their analysis of groups of bird species living together in one place (known as assemblages), including those in intact forests, croplands and cities around the world.
Nature DOI suffix ≠ "/s...": Not a research article
We are all mosaics: vast genetic diversity found between cells in a single person
Heidi Ledford
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Human chromosomes (artificially coloured) vary widely from cell to cell, according to an investigation of the DNA in more than 100 cells from a single person. Credit: Cavallini James/BSIP/Science Photo Library In a technological tour de force, researchers have sequenced the whole genomes of more than 100 individual cells from one 74-year-old man. The results exposed chaos within: an extra chromosome arm here, a missing chunk of chromosome there, and smaller snippets of DNA altered, deleted or duplicated. In several of the cells, the Y chromosome had been lost entirely. “There were some cells in there that were very messed up,” says Joe Luquette, who studies bioinformatics at Harvard Medical School in Boston, Massachusetts, and is an author of the study. Cancer drugs are closing in on some of the deadliest mutations The findings, which were posted earlier this month on the preprint server bioRxiv1 and have not yet been peer reviewed, paint a comprehensive portrait of the genetic variation present within a person. That portrait is just the beginning: the study is a pilot project for a US$140-million consortium that aims to catalogue mutations in cells from 19 sites in the body, using cells from 150 donors2. The resulting catalogue will provide a valuable tool for researchers studying the influence of genetic variation between the cells of a single individual — a phenomenon known as mosaicism — on health and on diseases such as cancer, says Soichi Sano, who studies mosaicism in the cardiovascular system at Japan’s National Cerebral and Cardiovascular Center in Suita. “I’m sure that this field will be accelerated very rapidly,” he says. A lifetime of mutations People accumulate changes to their DNA over the course of their life, whether from errors that occur during DNA replication and repair, or from exposure to DNA-damaging environmental factors, such as ultraviolet light or tobacco smoke. As DNA-sequencing technologies have improved, researchers have gained a clearer picture of how common mosaicism is, and how it can affect health. The accumulation of DNA mutations in some cells over time can cause cancer, for example, and loss of the Y chromosome in blood cells is linked to an increased risk of cardiovascular disease3 and fatal heart attack4. ‘Phenomenal’ tool sequences DNA and tracks proteins — without cracking cells open But it is difficult to catalogue those differences or to determine when in life they arise. Most genome sequencing is performed by isolating DNA from many cells at once and sequencing it in bulk, making it difficult to detect DNA variants that are present in only one or a few cells. And although methods for analysing the genomes of a single cell are becoming more advanced, these techniques often focus on sequencing RNA molecules, which can be present in many copies per cell, says Diane Shao, a neurologist at Boston Children’s Hospital who has studied mosaicism in the developing brain5. It is a much greater challenge to sequence DNA from individual cells, because there are only two copies of the genome to work with, she says.
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Where pigeons get their sense of direction
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
What happened at COP30? 4 science take-homes from the climate summit
Meghie Rodrigues, Jeff Tollefson
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COP30 left many countries disappointed because no new road maps were created to help nations transition away from fossil fuels.Credit: Wagner Meier/Getty Ten years after the Paris agreement was adopted, world leaders left the United Nations COP30 climate summit in BelĂ©m, Brazil, with an outcome that kept the process alive but does little to stave off the perils of global warming. Many scientists walked away dismayed and disappointed. Despite years of commitments and research that have laid the groundwork for action, the climate summit achieved “essentially nothing”, says Johan Rockström, director of the Potsdam Institute for Climate Impact Research in Germany. But, there were some signs of hope that multilateralism can tackle climate change. Over the course of two weeks, representatives from nearly 200 governments worked through hot days, long nights, a fire in the venue and numerous protests — including by Indigenous groups and others fighting for the protection of the Amazon and other tropical forests. Heatwaves linked to emissions of individual fossil-fuel and cement producers In the end, governments agreed to a package of measures that pushes forward discussions on financial aid and a new ‘just transition’ mechanism designed to ensure a fair and equitable shift from fossil fuels to clean energy. A glaring omission was language calling for the creation of road maps to phase out fossil fuels and halt deforestation, but Brazil has announced it will push those ideas forward independently of the COP process. Here, Nature takes a look at the results from COP30 and what comes next. Sidestepping fossil fuels The summit failed to deliver major new pledges to curb greenhouse-gas emissions. Of the 194 entities and countries that sent representatives to COP30, roughly 80 didn’t submit new commitments for 2035, as required under the accord, and the rest submitted weak pledges that are unlikely to alter the global trajectory. As a result, scientists with the Climate Action Tracker consortium still project that the world is on track for upwards of 2.6 ° C of warming by 2100. “The new commitments don’t even move the needle,” says Niklas Höhne, a climate-policy researcher at the NewClimate Institute, an environmental think tank based in Berlin. “It’s really a sign that countries have limited appetite to support something more ambitious on climate.” Fossil fuels took centre stage briefly. More than 80 countries joined Brazil’s President Luiz InĂĄcio Lula da Silva in the call for the creation of a road map to phase out fossil fuels, but the proposal ultimately foundered after reported opposition from oil-producing nations including Saudi Arabia. But the idea isn’t dead yet. Brazil promised to push forwards with it independently of the COP process, while the governments of Colombia and the Netherlands announced that they would host the first global conference on the just transition away from fossil fuels in April next year. Protesters carrying signs that read “our forests are not for sale” broke through security lines of the COP30 climate talks on 12 November.Credit: Pablo Porciuncula/AFP via Getty Financing climate action One of the largest disputes at the summit was who should pay for climate action and help developing nations to prepare for and adapt to the unavoidable impacts of global warming. Progress was made: wealthier nations committed to tripling the amount of money they provide to help low-income countries tackle global warming — to US$300 billion annually by 2035. The agreement also carries forward a broader goal of boosting the total to $1.3 trillion annually from all sources, including private investments. But questions remain about how this will be financed. Previous deals on climate action have been plagued by delays in achieving financial goals as well as by disagreements about how much money should come from publicly funded grants, as opposed to loans and private investments. China pledges to cut emissions by 2035: what does that mean for the climate? The final deal at COP30 lays out a process to clarify these issues over the next two years. It’s a step towards ensuring that wealthy countries meet their responsibilities to provide climate finance to those in need, says Jodi-Ann Wang, who researches equity and climate finance at the London School of Economics and Political Science.
Nature DOI suffix ≠ "/s...": Not a research article
Weighing up the wild-meat harvest in Amazonia
Carla Morsello, Patricia Carignano Torres
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An estimated 150 million people in the global south rely on wild meat as a key source of nutrition, especially the lowest-income households that have limited access to affordable alternatives1. The value of wildlife therefore extends beyond conservation concerns: it is fundamental for food security, health and well-being. In the Amazon rainforest, dependence on wild meat is widespread and the resource has economic value, including in the case of subsistence use. Until now, most of the data gathered about wild meat in Amazonia (a region comprising portions of Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Peru, Suriname and Venezuela) have come from case studies and a handful of large surveys2,3. Writing in Nature, Antunes et al.4 now offer the most comprehensive picture of this hidden economy so far.
Nature DOI suffix ≠ "/s...": Not a research article
A ten-year drive to credit authors for their work — and why there’s still more to do
Liz Allen, Veronique Kiermer, Simon Porter, Ruth Whittam
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A decade ago, we and others launched a tool for clarifying the roles of each author of a research paper. The Contributor Role Taxonomy (CRediT) includes 14 types of contribution, from conceptualization to software and data curation. It was designed to prevent questionable authorship practices and make it easier for researchers to demonstrate the diversity of their contributions to science, among other benefits. Credit where credit is due This year, taking stock, we’ve shown that adoption has risen steadily (see ‘More CRediT is being given’)1. By 2024, CRediT information was included in nearly 850,000 publications (encompassing articles, preprints and conference papers) — around 22% of the 3.7 million publications for which the full text was available that were recorded last year in Digital Science’s Dimensions, a database of scholarly publications. This level of uptake is remarkable, given that there have been no coordinated efforts or mandates from publishers and funders. But the issues that the taxonomy was conceived to tackle remain rampant in the research literature. Here we call for CRediT to become the norm, to support researchers and research integrity across the whole academic landscape. CRediT is still needed Despite widening use of CRediT, authorship conventions in scholarly publishing remain opaque and confusing, and differ by discipline. They typically provide little to no information about who contributed what in a study (see ‘The parts we played’). A name’s position in a list of authors is an unreliable indicator of the significance of that person’s work or the time they spent, particularly when the author list is long or alphabetical, as is common in economics2 and for large collaborations, and as also occurs in biomedical research3. Stop treating code like an afterthought: record, share and value it Questionable practices, such as including honorary authors, who are named but have not contributed, and excluding ‘ghost authors’, who have contributed but are not named, also remain prevalent — perhaps occurring in as much as one-fifth of biomedical papers4. Meanwhile, the volume of misconduct allegations and retractions in research is skyrocketing. When results are questioned after publication, transparency as to who did what helps investigators, supports accountability and can help to foster a responsible authorship culture more generally5. CRediT data can also be used to inform policy interventions that help to drive innovation, equity and impact in science. Data on author contributions have been used to study gender and the division of labour in research6,7, as well as variations in the distribution of roles across disciplines8, for example. Source: Analysis by L. Allen et al. The tool can help institutions and funders to identify skills being used in cutting-edge fields. Institutions could use the taxonomy to analyse the contributions of their researchers and identify talent that should be retained and developed. Funders can identify specialists — such as data scientists or research software engineers — for targeted funding opportunities or to serve as expert peer reviewers. Initiatives such as the San Francisco Declaration on Research Assessment (DORA), launched in 2012, and the Coalition for Advancing Research Assessment (CoARA) now champion the need to consider diverse contributions to research when assessing individuals’ performance9. And the value of CRediT is increasingly acknowledged by science organizations such as the UK Academy of Medical Sciences. In 2022, the taxonomy became a recognized standard of the US National Information Standards Organization (NISO) and the American National Standards Institute (ANSI) — meaning that publishers and other stakeholders internationally are encouraged to adopt it. Roadblocks to progress Despite the need for CRediT, further progress is held back by the changing research landscape, a lack of resources and inconsistent implementation. The use of CRediT has spread across disciplines and geographies1 — indicating that it strikes a chord. But some roles might fall outside the original 14 or be better represented by improving definitions of the existing roles, especially in fields such as social sciences and engineering, which were under-represented in the corpus of publications used to develop the taxonomy. For example, community engagement is becoming an increasingly important role as researchers strive to improve relationships with study participants, and because of citizen science. The CRediT term ‘software’ might need to be expanded to better reflect infrastructure development and data science. And the spread of new technologies, such as AI, could also alter the roles of scientists across the research landscape, from hypothesis generation to the writing-up of results.
Nature DOI suffix ≠ "/s...": Not a research article
Is there lightning on Mars?
Daniel Mitchard
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David Bowie famously asked if there is life on Mars, but an equally vexing question is whether lightning exists on the red planet and, if so, whether it is similar to the lightning on Earth. Lightning is known to occur on other planets: it was detected on Jupiter1,2 in 1979 by the Voyager I spacecraft, and has since been detected on Saturn, and possibly also on Uranus and Neptune3. But surprisingly, the lightning question has remained unanswered for Earth’s nearest planetary neighbours, Mars and Venus. Writing in Nature, Chide et al.4 now report bursts of sound and associated electromagnetic interference recorded by a microphone on top of Perseverance — one of NASA’s Mars rovers — as dust storms passed overhead. The authors attribute these signals to Martian lightning.
Nature DOI suffix ≠ "/s...": Not a research article
A structured system: the secrets of Germany’s scientific reputation
Katarina Zimmer
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The Max Planck Institutes in Germany house cutting-edge equipment, such as this ultra-high vacuum facility at The Max Planck Institute of Microstructure Physics in Halle. Credit: Hendrik Schmidt/dpa/ALAMY In 2019, shortly after finishing her master’s at Nanjing University in China, Xinyi Zhao opened an e-mail to learn that she had been offered a PhD position at the Max Planck Institute for Demographic Research in Rostock, Germany. “When I told my parents, they asked me to double-check whether the offer was real, as they weren’t familiar with the institute.” But Zhao knew of its glowing scientific reputation. “I felt very excited but also quite surprised,” says Zhao. “I heard they do amazing research.” Six years on, she’s still happily employed in Germany, now as a postdoc at the Berlin-based Max Planck Institute for Human Development. Nature Career Guide: Germany Between 2012 and 2022, the number of international scientists at the country’s four largest non-university research organizations doubled, from 8,115 to 16,6251. These institutes — the Max Planck Society, the Leibniz Association, the Helmholtz Association of German Research Centres and the Fraunhofer Society — all ranked among the world's top 20 non-profit organizations for research output in 2025, according to the Nature Index Research Leaders. The country’s universities also maintain a strong international profile, with 8 included in the world’s top 100, as reported in the Times Higher Education’s 2026 World University Rankings. Xinyi Zhao, a postdoc at the Max Planck Institute for Human Development in Berlin, likes the research environment in Germany. Credit: Sarah Otterstetter / Max Planck Institute for Human Development Germany’s success in academic-excellence rankings lies partly in the structure of its scientific ecosystem — in which each research organization specializes in a particular kind of science — alongside the remarkably stable flow of public research funding. “Germany is a country without natural resources,” says Otmar Wiestler, former president of the Helmholtz Association. “We don’t have cheap labour. All we have is the brains of our people.” As a result, he adds, “the German government is really committed to promoting research and innovation”. Streamlined systems In 2023, around 3.1% of Germany’s gross domestic product (GDP) — roughly €132 billion (US$152 billion) — was spent on research and development, a lower percentage than those of Israel (6%) and the United States (3.4%), but higher than the relative research spending of the United Kingdom (2.6%) and China (2.7%). Around one-third of this spending was from the public sector and the rest came from private industry. German governmental support for science has remained stable throughout various political leaderships. In the past 20 years, “we have never had a year where federal spending has decreased”, says Max Voegler, the vice-president of Global Strategic Networks for Germany, Austria and Switzerland at the Amsterdam-based academic publisher Elsevier, who co-wrote a report on Germany’s research system earlier this year2. Although the bulk of the funding for research and teaching in countries such as France and the United Kingdom comes from the central governments, in Germany, the task of supporting academic activities falls to both federal and state governments. These jointly provide the majority of the institutional funding for most of the country’s non-university research organizations. And in contrast to the United States and the United Kingdom, where universities draw much of their income from tuition fees, German states are responsible for providing the base funding for universities. Otmar Wiestler, former president of the Helmholtz Association, says that the German government is committed to promoting research and innovation.Phil Dera/Helmholtz Funding flows into a highly structured research ecosystem consisting of more than 420 universities, most of which are public, and four main non-university research organizations. Each of the four fulfils a defined, specialized task, says Rainer Frietsch, a specialist in science-and-innovation research at the Fraunhofer Institute for Systems and Innovation Research. The Max Planck Society, for instance, focuses on fundamental research, with each of its 84 institutes around the country specializing in a range of fields, such as animal behaviour and neurogenetics. The Leibniz Society’s institutes strive to integrate scientific knowledge into society by giving economic reports and providing museums that conduct research and communicate findings. The Helmholtz Association’s centres house some of the country’s largest pieces of research equipment, including the world’s largest artificial sun, used in the study of solar processes. The 75 institutes of the Fraunhofer Society, meanwhile, fulfil the distinct task of conducting applied research; for instance, researchers at the Fraunhofer Institute for Solar Energy Systems in Freiburg are developing more-efficient solar cells, and scientists at the Fraunhofer Institute for Manufacturing Technology and Advanced Materials, which has several centres across Germany, are identifying innovative non-stick coatings for food-processing tools. Some of the society’s projects are for and funded by industry partners. Many countries, including France, the United Kingdom and China, have tried to emulate the Fraunhofer model in some form, but it works best in Germany’s research landscape, according to Frietsch. “Fraunhofer is as successful as it is because the whole system has exactly the layout that it has,” he says: the defined task division of the research organizations efficiently avoids overlap. Although distinct in their operations, Germany’s universities and non-university research organizations aren’t siloed from one another, says Voegler; universities often work with the non-university institutions nearby. In 2005, partly as a way of encouraging collaboration, the federal and the state governments launched the Excellence Initiative, which includes funding for interdisciplinary research projects at clusters of institutions. From 2026 to 2032, the initiative — now called the Excellence Strategy — has pledged €539 million per year for 70 ‘clusters of excellence’ projects across the country. One of these is the Cardio–Pulmonary System Cluster of Excellence in the state of Hessen, which brings together researchers from Goethe University Frankfurt, Justus Liebig University Giessen and the Max Planck Institute for Heart and Lung Research in Bad Nauheim to study heart and lung disease. By promoting the exchange of expertise across research entities, “suddenly the whole becomes much more than the sum of its parts”, Voegler says. Championing discovery During discussions on European Union science-funding programmes, some member states have expressed a desire to invest mainly in applied research, Wiestler says. But German representatives have defended the need to focus on fundamental, ‘blue sky’ research — work for which practical applications aren’t immediately obvious. Enrico Schleiff, the president of Goethe University Frankfurt, attributes the emphasis on basic research to the fact that freedom of science is a constitutional right in Germany, enabling scientists to determine the direction of their research without government or political influence — something he says has led to many fruitful discoveries. Some of those impactful discoveries include the development of blinatumomab, the first T-cell engager drug, which coaxes patients’ immune cells into attacking leukaemia cells. More recently, scientists at Friedrich-Alexander University of Erlangen–Nuremberg were part of a team that discovered that these and other kinds of cancer immunotherapies could also be used to target the dysfunctional, body-attacking immune cells responsible for causing autoimmune diseases such as lupus. “Now the whole world is developing T-cell engagers” for this purpose, says Patrick Baeuerle, a biotechnology entrepreneur and the co-founder and chief scientific advisor of Cullinan Therapeutics, a company in Cambridge, Massachusetts, that licensed a T-cell engager drug from a China-based biotech firm in June. Patrick Baeuerle is a biotechnology entrepreneur and the co-founder and chief scientific adviser of Cullinan Therapeutics in Cambridge, Massachusetts.Credit: Cullinan Therapeutics One of Germany’s long-standing weaknesses, Wiestler says, is that its research products are seldom commercialized in the country, because it lacks the kind of start-up culture and abundant sources of venture-capital funding that supports the biotech scene in countries such as the United States and Israel. That’s partly why the Helmholtz Association, for instance, has been increasingly establishing partnerships with companies to translate findings into marketable products. One example is the creation in 2023 of the Solar TAP Innovation platform — a joint venture between several Helmholtz Centres and industry partners to develop innovative solar technologies — and the Joint Innovation Lab, a collaboration between the German Cancer Research Center and the Hamburg-based skincare company Beiersdorf to develop strategies to prevent skin cancer.
Nature DOI suffix ≠ "/s...": Not a research article
Lack of funding is pushing research in Romania to extinction
Lucian Pintilie
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Over the past decade, Romania has spent less on research and development (R&D) relative to gross domestic product (GDP) than any other nation in the European Union, and has the fewest researchers per one million inhabitants. If no concrete measures are taken to increase funding in the next few years, the Romanian research system will collapse.
Nature DOI suffix ≠ "/s...": Not a research article
Don’t scrap climate COPs, reform them
Kilaparti Ramakrishna
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A tropical forest meets the Atlantic Ocean at the Amazon Delta.Credit: NASA/Alamy As the world gathered in BelĂ©m, Brazil, for the COP30 United Nations climate conference, Brazilian President Luiz InĂĄcio Lula da Silva reignited an old but urgent debate: whether the multilateral process that has sustained climate diplomacy for three decades is still fit for purpose. His proposal for a global climate council — a smaller, more agile entity to lead negotiations and ensure that climate commitments are implemented — reflects mounting frustration with the slow pace of outcomes from the annual Conference of the Parties (COP). How to fight climate change without the US: a guide to global action Lula’s proposal deserves serious consideration. The COP process has become sprawling, performative and, at times, politically paralysed. Yet, as someone who helped to draft the UN Framework Convention on Climate Change (UNFCCC) in 1991–92, I think that the answer is not to abandon this architecture, but to reform it. When we negotiated the UNFCCC, our goal was to create a durable legal scaffold that was flexible enough to evolve with scientific understanding and national capacities for climate action. In 1992, there was no precedent for a framework that addressed an issue that spanned every economy, ecosystem and generation of people. We had the science, but not yet the institutions or political will to act at scale. The framework-convention model allowed successive protocols, decisions and mechanisms to develop. That design has proven remarkably resilient. If someone had told me in 1992 that the world would still be negotiating climate action at COP30, I might have sighed. Yet, if they had told me that every nation would still be adhering to the same framework, guided by science and law, I would have been profoundly hopeful — as I am today. Climate diplomacy is slow because it is systemic. It forces nations to reconcile competing imperatives — development versus decarbonization, growth versus justice, and responsibility versus capability. The principle of common but differentiated responsibilities was born from these tensions: recognition that all countries share the problem but not the same level of blame or means to act. ‘Almost utopian’: how protecting the environment is boosting the economy in Brazil Progress has been incremental but cumulative. The UNFCCC, Kyoto Protocol and Paris agreement have created a coherent legal architecture for climate governance. The International Court of Justice delivered an advisory opinion in July, reaffirming that states have binding obligations to protect the climate, an indication of how far we’ve come. Criticism of the COP process is understandable. Yearly gatherings of tens of thousands of people can seem detached from the crisis outside the conference halls. But dismissing COPs ignores their ability to provide universality, legitimacy and accountability. President Lula’s call for a leaner climate council acknowledges this frustration while maintaining the inclusivity of the COP process.
Nature DOI suffix ≠ "/s...": Not a research article
Chile must preserve international science in Antarctica
CristĂłbal GalbĂĄn MalagĂłn, Marcelo Leppe, Gustavo Chiang, Paulina Bahamonde
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For decades, Chile has helped scientists from across the world to study Antarctica, providing logistical support and rescue services from its southernmost region. But this role is under threat. These services are supported by annual short-term government funding. The two candidates who reached the second round of the ongoing presidential election have put little emphasis on Antarctica, suggesting a worrying lack of interest.
No meta-analytical effect of economic inequality on well-being or mental health
Nicolas Sommet, Adrien A. Fillon, Ocyna Rudmann, Alfredo Rossi Saldanha Cunha, Annahita Ehsan
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Exposure to economic inequality is widely thought to erode subjective well-being and mental health1,2,3,4,5, which carries important societal implications6,7,8,9,10. However, existing studies face reproducibility issues11,12,13, and theory suggests that inequality only affects individuals in disadvantaged contexts14,15,16. Here we present a meta-analysis of 168 studies using multilevel data (11,389,871 participants from 38,335 geographical units) identified across 10 bibliographical databases (2000–2022). Contrary to popular narratives, random-effects models showed that individuals in more unequal areas do not report lower subjective well-being (standardized odds ratio (OR+0.05) = 0.979, 95% confidence interval = 0.951–1.008). Moreover, although inequality initially seemed to undermine mental health, the publication-bias-corrected association was null (OR+0.05 = 1.019; 0.990–1.049)17. Meta-analytical effects were smaller than the smallest effect of interest, and specification curve analyses confirmed these results across ≈95% of 768 alternative models18. When assessing study quality and certainty of evidence using ROBINS-E and GRADE criteria, ROBINS-E rated 80% of studies at high risk of bias, and GRADE assigned greater certainty to the null effects than to the negative effects. Meta-regressions revealed that the adverse association between inequality and mental health was confined to low-income samples. Moreover, machine-learning analyses19 indicated that the association with well-being was negative in high-inflation contexts but positive in low-inflation contexts. These moderation effects were replicated using Gallup World Poll data (up to 2 million participants). These findings challenge the view that economic inequality universally harms psychological health and can inform public health policy.
Healthy forests safeguard traditional wild meat food systems in Amazonia
AndrĂ© Pinassi Antunes, Pedro de Araujo Lima Constantino, Julia E. Fa, Daniel P. Munari, Thais Q. Morcatty, Michelle C. M. Jacob, Bruce W. Nelson, Mariana Franco Cassino, Elildo A. R. Carvalho, Amy Ickowitz, Lauren Coad, Richard E. Bodmer, Pedro Mayor, Cecile Richard-Hansen, JoĂŁo Valsecchi, JoĂŁo V. Campos-Silva, Juarez C. B. Pezzuti, Miguel AparĂ­cio, Eduardo M. von Muhlen, Marcela Alvares Oliveira, Milton J. de Paula, Natalia C. Pimenta, Marina A. R. de Mattos Vieira, Marcelo A. Santos Junior, AndrĂ© V. Nunes, Jean P. Boubli, Luan M. G. SuruĂ­, Eneias C. S. Paumari, Abimael V. C. Paumari, JosĂ© Lino V. S. Paumari, Germano C. Paumari, Ana Paula L. R. Katukina, Dzoodzo Baniwa, Valencio S. M. Baniwa, Walter S. L. Baniwa, Abel O. F. Baniwa, Armindo B. Baniwa, IsaĂ­as J. S. Baniwa, Yaukuma Waura, Jairo Silvestre ApurinĂŁ, Valdir S. S. ApurinĂŁ, Josiane O. G. Tikuna, Elias P. A. L. Tikuna, JosĂ© L. KaxinauĂĄ, Kussugi B. Kuikuro, Jorge T. Penaforth Kaixana, George H. Rebelo, Dione Torquato, Vanessa S. F. ApurinĂŁ, Miguel AntĂșnez, Pedro E. Perez-Peña, Tula G. Fang, Pablo E. Puertas, Rolando M. Aquino, Louise MaranhĂŁo, Guillaume Longin, CĂ­ntia K. M. Lopes, Hani R. El Bizri
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Amazonia is the largest 1 and the most species-rich tropical forest region on Earth 2 , where hundreds of Indigenous cultures and thousands of animal species have interacted over millennia 3,4 . Although Amazonia offers a unique context to appraise the value of wildlife as a source of food to millions of rural inhabitants, the diversity, geographic extent, volumes and nutritional value of harvested wild meat are unknown. Here, leveraging a dataset comprising 447,438 animals hunted across 625 rural localities, we estimate an annual extraction of 0.57 Mt of undressed animal biomass across Amazonia, equivalent to 0.34 Mt of edible wild meat. Just 20 out of 174 taxa account for 72% of all animals hunted and 84% of the overall biomass extracted. We show that this amount of wild meat can meet nearly half of protein and iron dietary requirements for rural peoples, along with a substantial portion of their needs for B vitamins (18–126%) and zinc (23%). However, wild meat productivity is likely to have decreased by 67% in nearly 500,000 kmÂČ of highly deforested areas of Amazonia. Furthermore, the availability of wild meat per capita decreases significantly in areas with higher human population, greater proximity to cities, and more extensive deforestation. These findings highlight the urgent need to preserve the forest to safeguard biodiversity and traditional wild meat food systems, which will be essential for ensuring Amazonian peoples’ well-being and achieving several of the United Nations Sustainable Development Goals 5 .
Ancient DNA from Shimao city records kinship practices in Neolithic China
Zehui Chen, Jacob D. Gardner, Zhouyong Sun, E. Andrew Bennett, Qian Han, Xuesong Pei, Jing Shao, Han Shi, Wenjun Wang, Jiayang Xue, Fan Bai, Xiangming Dai, Nu He, Xiaoning Guo, Nan Di, Xiaowei Mao, Tianxiang Liu, Peng Cao, Feng Liu, Qingyan Dai, Xiaotian Feng, Wanjing Ping, Xiaohong Wu, Lizhao Zhang, Liang Chen, Qiaomei Fu
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The discovery of Shimao city (around 2300–1800 bce1), a premier state-level Neolithic fortified settlement in Shaanxi, China2, played an important role in helping us understand the emergence of socially stratified urban societies. However, key questions remain regarding how ancestry and kinship shaped the hierarchy of this class-based society characterized by human sacrifice. The origin of the founding populations of Shimao and other Loess Plateau settlements, and their interactions within the broader ancestral landscape, have yet to be determined. Here we present, by sequencing 144 ancient genomes from Shimao city and its satellites, pedigrees among tomb owners spanning up to four generations. These findings reveal a predominantly patrilineal descent structure across Shimao communities, and possibly sex-specific sacrificial rituals. We also characterize the population history, revealing that Shimao culture-related populations originated mostly from a Yangshao culture-related population present at least 1,000 years earlier, and the lasting inflow of Yumin-related populations from Inner Mongolia did not interrupt regional genetic continuity. Broader genetic influence from southern mainland ancestry over Shimao culture-related populations supports evidence of rice farming expanding further north than previously expected. Together, these results uncover fine details of the regional peopling and social structure of early state establishment.

Nature Human Behaviour

GPT-4o mini: Non-social science research article
Linguistic structure from a bottleneck on sequential information processing
Richard Futrell, Michael Hahn
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Human language has a distinct systematic structure, where utterances break into individually meaningful words that are combined to form phrases. Here we show that natural-language-like systematicity arises in codes that are constrained by a statistical measure of complexity called predictive information, also known as excess entropy. Predictive information is the mutual information between the past and future of a stochastic process. In simulations, we find that codes that minimize predictive information break messages into groups of approximately independent features that are expressed systematically and locally, corresponding to words and phrases. Next, drawing on cross-linguistic text corpora, we find that actual human languages are structured in a way that yields low predictive information compared with baselines at the levels of phonology, morphology, syntax and lexical semantics. Our results establish a link between the statistical and algebraic structure of language and reinforce the idea that these structures are shaped by communication under general cognitive constraints.
GPT-4o mini: Non-social science research article
Culture is critical in driving orangutan diet development past individual potentials
Elliot Howard-Spink, Claudio Tennie, Tatang Mitra Setia, Deana Perawati, Carel van Schaik, Brendan Barrett, Andrew Whiten, Caroline Schuppli
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Humans accumulate extensive repertoires of culturally transmitted information, reaching breadths exceeding any individual’s innovation capacity (culturally dependent repertoires). It is unclear whether other animals require social learning to acquire adult-like breadths of information in the wild, including by key developmental milestones, or whether animals are capable of constructing their knowledge repertoires primarily through independent exploration. We investigated whether social learning mediates orangutans’ diet-repertoire development, by translating an extensive dataset describing wild orangutans’ behaviour into an empirically validated agent-based model. In this model, diets reliably developed to adult-like breadths only when simulated immatures benefited from multiple forms of social learning. Moreover, social learning was required for diets to reach adult-like breadths by the age immatures become independent from their mothers. This implies that orangutan diets constitute culturally dependent repertoires, with social learning enhancing the rate and outcomes of diet development past individual potentials. We discuss prospective avenues for researching the building of cultural repertoires in hominids and other species.
State formation across cultures and the role of grain, intensive agriculture, taxation and writing
Christopher Opie, Quentin D. Atkinson
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The invention of agriculture is widely thought to have spurred the emergence of large-scale human societies. It has since been argued that only intensive agriculture can provide enough surplus for emerging states. Others have proposed it was the taxation potential of cereal grains that enabled the formation of states, making writing a critical development for recording those taxes. Here we test these hypotheses by mapping trait data from 868 cultures worldwide onto a language tree representing the relationships between cultures globally. Bayesian phylogenetic analyses indicate that intensive agriculture was as likely the result of state formation as its cause. By contrast, grain cultivation most likely preceded state formation. Grain cultivation also predicted the subsequent emergence of taxation. Writing, although not lost once states were formed, more likely emerged in tax-raising societies, consistent with the proposal that it was adopted to record those taxes. Although consistent with theory, a causal interpretation of the associations we identify is limited by the assumptions of our phylogenetic model, and several of the results are less reliable owing to the small sample size of some of the cross-cultural data we use.

Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
A balance of metabolism and diffusion articulates a gibberellin hormone gradient in the Arabidopsis root
Kristian B. Kiradjiev, Jayne Griffiths, Alexander M. Jones, Leah R. Band
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The plant hormone gibberellin (GA 4 ) regulates numerous developmental processes. Within the root, GA 4 controls growth, in part, by controlling the extent of cell elongation. The nlsGPS1 FRET biosensor revealed a GA 4 gradient within the Arabidopsis root growth zones, with GA 4 levels correlating with cell length. We developed a multiscale mathematical model to understand how biosynthesis, catabolism, and transport create the GA 4 distribution within the root growth zones. The model predicted that phloem delivery of the biosynthetic intermediate GA 12 contributes to higher levels of bioactive GA 4 in the elongation zone, with the GA 4 synthesis pattern being further modified by local GA 12 synthesis in the quiescent center region and the spatial distribution of biosynthesis enzymes (GA20ox and GA3ox). Model predictions suggested that while GA20ox and GA3ox transcript is present throughout the growth zones, these enzymes are inactive in the dividing cells, which explains steep GA 4 gradients observed in the GA3ox overexpression line and improves agreement between model predictions and data in wildtype. The model suggested that the GA 4 gradient also depends on a balance of diffusion through plasmodesmata and catabolism. Both model predictions and biosensor data demonstrated that plasmodesmatal diffusion enables a more gradual GA 4 gradient, with higher diffusion antagonizing the GA 4 gradient. Model predictions suggested that catabolism limits GA 4 levels, which we validated via biosensor imaging in the ga2oxhept mutant. In conclusion, our results suggest that local GA 4 synthesis combines with diffusion and catabolism to create a spatial GA 4 gradient that provides positional information and patterns cell elongation.
GPT-4o mini: Non-social science research article
The lysosomal carrier SLC29A3 supports antibacterial signaling, and promotes autophagy by activating TRPML1 in murine dendritic cells
Daniel J. Netting, Cynthia López-Haber, Zachary Hutchins, José A. Martina, Rosa Puertollano, Adriana R. Mantegazza
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The solute carrier (SLC)29A3 exports nucleosides from lysosomes into the cytosol, maintaining solute homeostasis and providing metabolic intermediates for cellular processes. Loss-of-function mutations in SLC29A3 cause H syndrome, characterized by histiocytosis, hyperinflammation, and immunodeficiency. While dysfunctions in various cell types contribute to H syndrome and to SLC29A3 deficiency in mice, the mechanisms driving hyperinflammation and immunodeficiency are incompletely understood. Remarkably, the possible role played by dendritic cells (DCs), the most efficient antigen (Ag)-presenting cells and the main cellular link between innate and adaptive immunity, remains unknown. We show that, in murine DCs, SLC29A3 is recruited to phagosomes after bacterial capture, maintains phagosomal pH homeostasis, and ensures optimal antimicrobial phagosomal signaling to the production of IL-6, IL-12, pro-IL-1ÎČ, and CCL22. In addition, SLC29A3 promotes Ag presentation on MHC-II molecules to initiate adaptive immune responses. Notably, SLC29A3 supports the activity of the lysosomal calcium channel TRPML1, promoting the nuclear translocation of transcription factor TFEB and inducing autophagy, a major anti-inflammatory mechanism. Overexpression of human SLC29A3, but not the transport mutant G437R, in SLC29A3-deficient murine DCs restores cytokine production in response to bacterial phagocytosis, suggesting that SLC29A3 transport activity is required to drive phagosomal signaling. Our data suggest that SLC29A3 supports and controls immune function in DCs by promoting effective antimicrobial signaling and Ag presentation, and inducing autophagy. Our findings also uncover a TRPML1-dependent mechanism by which SLC29A3 activates TFEB and suggest that defects in phagosomal antibacterial signaling, TFEB activation, and autophagy may contribute to immunodeficiency and hyperinflammation in SLC29A3 disorders.
GPT-4o mini: Non-social science research article
Measurement of cellular traction forces during confined migration
Max A. Hockenberry, Andrew J. Ulmer, Johann L. Rapp, Harrison H. Truscott, Frank A. Leibfarth, James E. Bear, Wesley R. Legant
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To migrate efficiently through tissues, cells must transit through small constrictions within the extracellular matrix. However, in vivo environments are geometrically, mechanically, and chemically complex, and it has been difficult to understand how each of these parameters contribute to the propulsive strategy utilized by cells in different confining environments. To address this, we employed a sacrificial micromolding approach to generate polymer substrates with tunable stiffness, controlled adhesivity, and user-defined microscale geometries. We combined this together with live-cell imaging and three-dimensional traction force microscopy to quantify the forces that cells use to transit through constricting channels. Surprisingly, rather than enlarging the constriction via pushing forces, we observe that mesenchymal cells migrating through compliant constrictions generate inwardly directed contractile forces that decrease the size of the opening and pull the channel walls closed around the nucleus. This had the effect of increasing nuclear deformation compared to cells migrating through comparably sized rigid confinements. Additionally, the nucleus took longer to transit through compliant constrictions compared to similarly sized rigid constrictions. These findings show that nuclear deformation during confined migration can be accomplished by internal cytoskeletal machinery rather than by reactive forces from the substrate, and our approach provides a mechanism to test between different models for how cells translocate their nucleus through narrow constrictions. The methods, analysis, and results presented here will be useful to understand how cells choose between propulsive strategies in different physical environments.
GPT-4o mini: Non-social science research article
Nitrogen-fixing microbes gain genes in diverse types of living environments
Hong-Wei Pi, Chun-Ping Yu, Ya-Fei Chen, Bing-Syuan Wu, Li-Yin Peng, Wen-Hsiung Li
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Biological nitrogen fixation (BNF), which is catalyzed by a large nitrogenase enzyme complex, has evolved in both bacteria and archaea. Indeed, nitrogen-fixing species are found in diverse living environments, and BNF has evolved even in aerobic bacteria, although the function of nitrogenase is inhibited by oxygen. BNF is, however, highly energy-costing, requiring 16 ATPs in a single nitrogen fixation reaction. To explain this paradox, we hypothesized that nitrogen-fixing species gain not only nitrogen-fixing ( nif ) genes but also non- nif genes to facilitate nitrogen fixation. We examined over 3500 nitrogen-fixing genomes and found that they have gained genes directly or indirectly related to BNF in diverse types of living environments, so that nitrogen-fixing species tend to have larger genomes than their non-nitrogen-fixing relatives. Interestingly, the non- nif genes gained tend to be located near nif -gene clusters, probably to achieve proximity effects such as coordinated gene regulation. For example, the most frequent among the genes gained are ABC transporter genes, which facilitate the absorption and physiological metabolism of carbon (e.g., sugars), nitrogen (e.g., amino acids), and trace elements (e.g., molybdenum), and many ABC transporter genes lie close to nif -gene clusters. From our findings, we propose the following scenario: BNF evolved in many archaea and bacteria because BNF is advantageous to its hosts, although it incurs a high energy cost. Then, gaining genes to facilitate BNF compensates the cost of BNF, facilitating the spread of nitrogen fixers to all living habitats. This expansion benefits the biosphere, as nitrogen is essential for all organisms.
GPT-4o mini: Non-social science research article
Stochastically evolving graphs via edit semigroups
Fan Chung, Sawyer Jack Robertson
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We investigate a randomly evolving process of subgraphs in an underlying host graph using the spectral theory of semigroups related to the Tsetlin library and hyperplane arrangements. Starting with some initial subgraph, at each iteration, we apply a randomly selected edit to the current subgraph. Such edits vary in nature from simple edits consisting of adding or deleting an edge, or compound edits which can affect several edges at once. This evolving process generates a random walk on the set of all possible subgraphs of the host graph. We show that the eigenvalues of this random walk can be naturally indexed by subsets of edges of the host graph. We also provide, in the case of simple edits, a closed-form formula for the eigenvectors of the transition probability matrix and a sharp bound for the rate of convergence of this random walk. We consider extensions to the case of compound edits; examples of this model include the previously studied Moran forest model and a dynamic random intersection graph model. Evolving graphs arise in a variety of fields ranging from deep learning and graph neural networks to epidemic modeling and social networks. Our random evolving process serves as a general stochastic model for sampling random subgraphs from a given graph.
GPT-4o mini: Non-social science research article
Lipidomic profiling of endometrial cancer using desorption electrospray ionization mass spectrometry imaging
Maria Paraskevaidi, Olivia Raglan, James McKenzie, Yuchen Xiang, Stefania Maneta-Stavrakaki, Maria Luisa Doria, Apostolia Galani, Nada Assi, Eftychios Manoli, Laura Burney Ellis, Baljeet Kaur, Francesca Rosini, Marc J. Gunter, Zoltan Takats, Maria Kyrgiou
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Novel technologies are required to improve endometrial cancer diagnosis and enhance the early detection of preinvasive precursors. Herein, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was used to differentiate malignant from benign endometrial tissues and assess lipidomic differences among patients with obesity and diabetes. Reverse phase protein array (RPPA) analysis was performed in the same patients to gain insights into the altered signaling pathways and investigate the protein expression levels in endometrial cancer cases and controls. Tissues from 64 women (50 cancer, 14 benign) were analyzed with DESI-MSI achieving 90% sensitivity and 93% specificity. Discriminatory spectral features were primarily phospholipids [phosphatidic acid (PA), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI)], all elevated in cancer. Proteomics revealed upregulated proteins linked to commonly dysregulated pathways in endometrial cancer, namely PI3K/AKT/mTOR, MAPK/RAS, and Wnt signaling pathways. Lipidomic differences were found between high- (obesity/diabetes) and low-risk phenotypes (no obesity/diabetes), with PE and PS elevated in high-risk benign and PE reduced in high-risk cancer cases. A single phospholipid (PE(O-38:4)) was found as discriminatory in both normal and cancer cohorts, which may serve as biomarker in women with benign histology at high-risk of developing endometrial cancer. This study reports the application of DESI-MSI for lipidomic characterisation of endometrial cancer.
GPT-4o mini: Non-social science research article
Probing direct interactions between nuclear proteins in cells with nxReLo
Sherif Ismail, Jana KubĂ­kovĂĄ, Maria Maichel, Peter Andersen, Mandy Jeske
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Nearly all biological processes depend on protein–protein interactions (PPIs). While various methods exist to study these interactions, investigating those that involve nuclear proteins, including structurally complex proteins containing long disordered regions, remains a significant challenge. Here, we developed nxReLo, a simple and fast cell culture-based colocalization assay, designed to identify and characterize interactions between nuclear proteins. PIWI-interacting RNAs (piRNAs) safeguard germline genome integrity, and the PPIs that facilitate piRNA production are therefore essential for animal reproduction, yet remain incompletely understood. We used nxReLo to investigate interactions between members of the Drosophila melanogaster Rhino–Deadlock–Cutoff (RDC) complex and two associated components, Bootlegger and Moonshiner, a nuclear protein network required for piRNA expression. We demonstrate the utility of the nxReLo assay by systematically screening pairwise interactions within the RDC network and by assembling a multiprotein complex from four components. By combining nxReLo assays with AlphaFold structural prediction, we characterized the Cutoff–Deadlock and the Bootlegger–Deadlock complexes in detail, providing molecular and structural insights. Specifically, we refined the domains involved in the interaction and identified interface point mutations that interfered with complex formation, validating the predicted structures. In conclusion, nxReLo facilitates rapid and simple testing of direct interactions between nuclear proteins in a cellular context, which is particularly important when working with structurally challenging proteins or when established interaction assays prove unsuccessful.
GPT-4o mini: Non-social science research article
Mechanisms of transport and analgesic compounds recognition by glycine transporter 2
Yuhang Wang, Jiawei Su, Jun Zhao, Renjie Li, Qinru Bai, Hongyi Song, Yufei Meng, Qiao Ma, Yan Zhao
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Glycine transporter 2 (GlyT2) regulates inhibitory glycinergic neurotransmission, and its inhibition potentiates glycinergic signaling, which is a promising strategy for managing neuropathic pain. This study presents high-resolution structures of GlyT2 in its apo state and in complexes with the substrate glycine, analgesic inhibitors, captured in three functional states: outward-facing, occluded, and inward-facing. The glycine-bound structure reveals the binding mode of the substrate, Na + and Cl − . Specifically, we identified the Na3 binding site, offering fundamental insights into Na + /Cl − coupled substrate binding and conformational changes. Moreover, we clearly elucidate a previously unseen allosteric binding pocket for the lipid-based oleoyl-D-lysine, which acts as a wedge to stabilize GlyT2 in the outward-facing conformation and prevents its transition. Furthermore, the complex structures with small compounds ALX1393, opiranserin, and ORG25543 reveal their competitive and allosteric inhibition mechanisms. Overall, our study provides a solid foundation for understanding glycine reuptake mechanisms and developing effective and safer analgesic agents.
GPT-4o mini: Non-social science research article
Solvation-induced local structure in liquids probed by high-harmonic spectroscopy
Eric Moore, Sucharita Giri, Andreas Koutsogiannis, Tahereh Alavi, Greg McCracken, Kenneth Lopata, John M. Herbert, Mette B. Gaarde, Louis F. DiMauro
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High-harmonic generation (HHG) has been established as a powerful tool for studying structure and dynamics of quantum systems in gas and solid phases. To date, only a few studies have extended HHG spectroscopy to liquids, and much remains unresolved concerning the information that can be extracted from HHG spectra about the local liquid environment and the potential of HHG as a nonlinear probe of solvation dynamics. In this work, we investigate HHG in liquid binary solutions consisting of mixtures of aromatic benzene derivatives solvated in methanol. We observe evidence of a localized solvation structure that is imprinted on the harmonic spectra in the form of a strongly suppressed harmonic order, and an overall reduction of the total harmonic yield. We characterize this behavior as a function of laser parameters, concentration, and other halogenated benzene derivatives in methanol solution. Guided by theory, we interpret the results in terms of a localized solvation shell that is formed in specific solutions and acts like a local scattering barrier in the HHG process. This work demonstrates the potential of high-harmonic spectroscopy in liquids to extract detailed information about the structure and dynamics of solvation while expanding our understanding of the fundamental mechanism of HHG in systems with short-range order.
GPT-4o mini: Non-social science research article
Crystalline guanine: Rediscovery of a long-overlooked structure of unicellular eukaryotes
Peter MojzeĆĄ
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GPT-4o mini: Non-social science research article
Reaching the full potential of cryo-EM reconstructions with molecular dynamics simulations at 310 K: Actin filaments as an example
Sahithya Sridharan Iyer, Kristina M. Herman, Tamsuk Paul, Yihang Wang, Thomas D. Pollard, Gregory A. Voth
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Cryoelectron microscopy (cryo-EM) structures of multiprotein complexes such as actin filaments help explain the mechanisms of assembly and interactions with partner proteins. Yet, rapid cooling during freezing may not preserve the conformations at physiological temperature. All-atom molecular dynamics simulations starting with cryo-EM reconstructions can provide additional insights. For example, at 310 K, adenosinediphosphate (ADP)-actin filaments fluctuate on a nanosecond time scale around higher entropy states with partly twisted subunits and smaller rotations along short-pitch helix than the cryo-EM reconstructions, while cryogenic temperatures favor flattened conformations. In the active site, the positions of Q137 and the catalytic water 1 and activating water 2 optimal for in-line attack on the Îł-phosphate of ATP are very rare at 310 K, explaining in part the slow rate of ATP hydrolysis in filaments. This favorable arrangement of the waters is not observed in simulations of actin monomers. At 310 K, subunits in ADP-P i -actin filaments have their backdoor gates open 60% of the time for phosphate release, a conformation not observed by cryo-EM. Rare fluctuations open binding sites for cofilin and phalloidin. The twisted conformations of pointed end subunits and interactions of the D-loop of the penultimate subunit explain the slow association of new subunits. The terminal subunit at the barbed end is tethered to its neighbor along the long-pitch helix but dissociates transiently from its lateral neighbor. These effects of subfreezing temperatures on actin filaments are surely not an isolated example, so molecular dynamics simulations of structures of other frozen proteins will be informative.
GPT-4o mini: Non-social science research article
Native metabolomics identifies pteridines as CutA ligands and modulators of copper binding
Berenike C. Wagner, Karoline Steuer-Lodd, Christian Geibel, Amelie Stadelmann, Johanna Rapp, Hannes Link, Tilman Schramm, Nouneh Boodaghian, Ansel Hsiao, Eva Nussbaum, Heinz-Paul Grenzendorfer, Reinhard Albrecht, Marcus D. Hartmann, Karl Forchhammer, Khaled A. Selim, Chambers C. Hughes, Daniel Petras
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CutA, a conserved protein across all domains of life, has been suggested to be involved in copper tolerance in bacteria, though recent studies have questioned this association, leaving its biological role unknown. To clarify its function, we studied cutA knockout mutants from two phylogenetically distant species, Synechococcus elongatus PCC 7942 and Escherichia coli , using phenotyping combined with metabolomics. To investigate the interaction of CutA with potential substrates and cofactors, we performed a series of native metabolomics experiments with CutA and cell extracts from which we identified the lumazine 2’-deoxyxanthopterin B2, a previously uncharacterized pteridine, to bind CutA in both species. Based on these results, we identified a set of other pteridines, including the essential cofactor tetrahydrobiopterin, as ligands of CutA. In the presence of pterins, we observed an increased affinity of CutA for copper ions. In addition, E. coli CutA mutants exhibited decreased copper resistance. These findings, alongside the known role of pteridines as redox shuttles, suggest a previously unrecognized role for CutA in coordinating cellular copper homeostasis and redox balance via pteridine metabolism.
GPT-4o mini: Non-social science research article
ROPGAP3 interacts with PIN2 and modulates its clustering and trafficking in Arabidopsis
Kwang-Ho Maeng, Hyodong Lee, Hyung-Taeg Cho
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Guanosine triphosphate (GTP)-hydrolyzing enzyme (GTPase) activating proteins (GAPs) negatively regulate small GTPase-mediated signaling by enhancing GTP to guanosine diphosphate (GDP) hydrolysis. The Rho small GTPase Of Plants (ROP) signaling pathway mediates the auxin-induced inhibition of endocytosis of PIN-FORMED (PIN) auxin efflux transporters. In our quest to find modulators of PIN behavior, we identified ROPGAP3 as a direct interactor of PINs in Arabidopsis . ROPGAP3 promoted PIN2 clustering, inhibited lateral diffusion and endocytosis, and reinforced its polarity even on loss- or gain-of-function conditions for ROP6 activity. In contrast, its close paralog ROPGAP1, adhering to ROP signaling, did not exhibit these characteristics. The specific molecular and cellular functions of ROPGAP3 also extended to developmental processes such as root gravitropism and lateral root formation. This study unveils a previously unrecognized role for GAPs beyond their traditional functions, providing insights into the mechanisms of protein clustering and plasma-membrane polarity reinforcement in plants.
GPT-4o mini: Non-social science research article
Mating system of free-ranging domestic dogs and its consequences for dog evolution
ClĂ©ment Car, Roya Adavoudi, Andreas BerghĂ€nel, Melissa Vanderheyden, Andre E. Moura, Friederike Range, Giulia Cimarelli, Martina Lazzaroni, Rachel Dale, Ikhlass El Berbri, Gabriella J. Spatola, Timothy A. Mousseau, Sarah Marshall-Pescini, MaƂgorzata Pilot
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The polygamous mating system of free-ranging domestic dogs (FRDs) contrasts with the social monogamy typical of gray wolves and all other wild canids. The transition to polygamy in dogs could have been initiated by a shift from apex predator to human commensal during the early domestication stages. Here, we test this hypothesis by investigating the characteristics of the FRD mating system that could have been important for domestication. This inference is based on genome-wide Single Nucleotide Polymorphism (SNP) data from three geographically distinct populations, including behavioral data for one of them. The reconstructed genealogies form a wide network of kinship relationships resulting from the frequent occurrence of maternal and paternal half-siblings, reflecting male and female polygamy. Reproductive success is positively correlated with the strength of social interactions and the number of connections with opposite-sex individuals, implying a preference toward familiar mates and the importance of social relationships in determining mating patterns. This is supported by a nonrandom distribution of reproductive partners and a reproductive skew in males and females. Multiple paternity within litters points to female polygamy within a single estrus, and sexual size dimorphism implies sexual selection favoring larger males. Physiological changes resulting from polygamy, including increased male fertility and reduced breeding seasonality, could have facilitated the natural spread of novel adaptive traits and limited the introgression from wolves. The change in reproductive patterns, typically considered a consequence of selective breeding, could instead have occurred naturally in response to the dietary niche change, triggering further changes that facilitated the domestication process.
GPT-4o mini: Non-social science research article
The impacts of European arrival on Australian dingoes
Lachie Scarsbrook, Kylie M. Cairns, Kieren J. Mitchell, Katia Bougiouri, Allowen Evin, Alexander C. Harris, Anna E. Wood, Zehui Zhang, Daniel J. Lawson, Joel M. Alves, Peter W. Ditchfield, Sofia Granja-Martins, Amy K. Styring, Kristina Tabbada, Olaf Thalmann, Mathew S. Crowther, Michael Curry, Tatiana R. Feuerborn, Loukas G. Koungoulos, Mike Letnic, Elizabeth H. Reed, Richard Sabin, Heidi G. Parker, Elaine A. Ostrander, Laurent A. F. Frantz, Greger Larson, Melanie A. Fillios
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The European colonial expansion had dramatic consequences on both Indigenous Peoples and local fauna. In Australia, the degree to which the arrival of Europeans and their dogs impacted the ecology and ancestry of dingoes is contentious. To test for gene flow with European dogs, we sequenced genomes of 18 ancient Australian dingoes from the Nullarbor Plain, two early 20th-century New Guinean dingoes, a mid-19th-century kangaroo hound, and 33 contemporary dingoes from across Australia. To quantify dietary shifts after the arrival of the First Fleet (AD1788), we generated stable isotopic ( ÎŽ 13 C, ÎŽ 15 N) data for 55 directly dated ancient Australian dingoes spanning the last ~2,300 y. We show that the diet of Nullarbor Plain dingoes shifted soon after European arrival, possibly due to shifts in prey abundance. Our genomic analyses demonstrated that pre-European dingoes were more inbred than most contemporary dog breeds, possibly as a result of population bottlenecks. We also showed that many dingoes, particularly those from Southeast Australia, experienced admixture with European dogs. Although we detected European ancestry dating to the early 18th-century, the majority of gene flow events coincided with the initiation of landscape-scale population control in the 1960s. Furthermore, some European dog alleles may have provided adaptive benefits to dingoes and alleviated inbreeding depression. Despite the existence of gene flow with European dogs, dingoes have maintained their distinctiveness. This suggests that management strategies should prioritize maintenance of substantial population sizes across Australia to both facilitate effective purifying and positive selection on introgressed alleles, and mitigate inbreeding.
GPT-4o mini: Non-social science research article
Climate warming reduces soil gaseous nitrogen losses in a temperate forest
Kai Huang, Di Wu, Dongwei Liu, Yihang Duan, Peter Dörsch, Klaus Butterbach-Bahl, Xiaoming Fang, Yuqi Liu, Chao Wang, Haoming Yu, Lingrui Qu, Jingwen Xu, Geshere Abdisa Gurmesa, Ronghua Kang, Shushi Peng, Erik A. Hobbie, Xiaotang Ju, Shuijin Hu, Oliver L. Phillips, Per Gundersen, Weixing Zhu, Peter M. Homyak, Yunting Fang
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Global warming is projected to accelerate ecosystem nitrogen (N) loss via gaseous pathways, thereby decreasing N availability, a critical nutrient for primary productivity and carbon sequestration. However, the models forecasting this ecosystem N loss are based on laboratory experiments that are inherently uncertain and have had few in situ validations. Over 6 y, we measured ~200,000 soil nitric oxide (NO; an air pollutant) and nitrous oxide (N 2 O; a powerful greenhouse gas) fluxes and used an upscaling approach to estimate N 2 fluxes after warming a temperate forest by 2 °C. Against thermodynamic theoretical predictions, warming unequivocally lowered emissions of NO by 19% and of N 2 O by 16%. These lower gaseous N losses were not explained by complete reduction of NO and N 2 O to N 2 , leaching, nor plant uptake, but rather by the warming-induced drying of soils that constrained microbial activity, consistent with other warming experiments where precipitation was less than 1,000 mm y −1 . Our findings challenge ecosystem model assumptions where warming, alone, accelerates N emissions and underscores how warming-induced losses in soil moisture and shortened freeze-thaw periods can offset temperature effects. Our data underscore the need for explicit consideration of in situ soil moisture when predicting changes on the terrestrial N cycle as the planet warms.
GPT-4o mini: Non-social science research article
USP1–TRAF2 axis–regulated mortalin stability mediates chemoresistance by disrupting calcium transport in peripheral T-cell lymphoma
Ailing Gui, Yichen Yan, Shiyu Jiang, Feng Chen, Xiaolong Zhou, Qi Sun, Shi Qiu, Jichuan Wu, Xiya Li, Junyi Zhang, Jie Liu, Shun Zhu, Lan Wang, Wen Liu, Ji Zuo, Qunling Zhang, Ling Yang
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Ubiquitin-specific peptidase 1 (USP1) plays a critical role in the progression and chemoresistance of various cancers, making USP1 inhibitors a promising therapeutic option in cancer treatment. However, the role of USP1 in peripheral T-cell lymphoma (PTCL) has remained unexplored. Our study uncovers a USP1-dependent survival axis driving chemoresistance in PTCL. USP1 is significantly upregulated in PTCL patients and correlates with poor prognosis through promoting mortalin degradation via TRAF2 deubiquitination. USP1 overexpression enhances TRAF2 stability by reducing its ubiquitination, thereby elevating TRAF2 levels. This, in turn, facilitates mortalin degradation, leading to diminished mortalin expression, reduced mitochondrial localization of mortalin, and impaired apoptosis. Notably, silencing mortalin in PTCL cells further decreases sensitivity to doxorubicin and suppresses apoptotic pathways. Mechanistically, reduced mitochondrial localization of mortalin disrupts calcium transport between the endoplasmic reticulum and mitochondria through the IP 3 R–mortalin–VDAC1 complex. The impaired calcium shuttling triggers the activation of NF-ÎșB and JAK-STAT signaling pathways, ultimately attenuating apoptosis. Importantly, pharmacological inhibition of USP1 with ML323 effectively enhances PTCL cell sensitivity to doxorubicin, suggesting a promising therapeutic strategy to improve treatment outcomes in PTCL patients. Collectively, we have found that USP1 represents a compelling therapeutic target for addressing chemoresistance and improving outcomes in PTCL therapy.
GPT-4o mini: Non-social science research article
Diversification of diterpene biosynthesis occurred early in octocoral evolution
Immo Burkhardt, Hannah K. Bone, Natalie E. Grayson, Helena A. Leucke, Johanna Gutleben, Paul R. Jensen, Andrea M. Quattrini, Alexander B. Chase, Bradley S. Moore
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Octocorals are the major source of marine-derived bioactive terpenoids. However, the vast majority of explored chemistry is known from shallow-water species, leaving deep-sea octocorals largely unexplored. Recent genomic work uncovered terpene biosynthetic pathways encoded in octocoral genomes, enabling deeper investigation into the evolution and ecological distribution of these compounds. Here, we collected nine deep-sea octocoral specimens representing both taxonomic orders and profiled their terpenoid chemistry. These samples revealed extensive diversity in sesquiterpene scaffolds, along with repeated detection of five widespread structural families of diterpenes (xeniaphyllene-, cembrene B-, elisabethatriene-, cembrene A-, and klysimplexin R; collectively, “XBECK-type” diterpenoids). Phylogenetic analysis of terpene cyclase (TC) sequences from these samples, combined with publicly available sequences and functional characterization of selected genes, indicated that most TC genes encode functionally diverse sesquiterpene cyclases that corresponded to deeply rooted taxonomic origins, rather than biochemical function. We further identified five monophyletic clades, each comprising isofunctional enzymes that produce precursors for distinct XBECK-type diterpenoids and showing broad representation across octocoral taxa. These findings suggest that diterpenoid biosynthesis evolved early in coral evolution, with the last common ancestor already possessing multiple functionally distinct TC enzymes. Our results establish terpenoid production as an ancient, central trait of octocorals, irrespective of habitat, thereby highlighting the tremendous potential of deep-sea corals as sources for bioactive terpenoids. Finally, these findings raise intriguing questions about the evolutionary origins of these pathways within early cnidarians and across animal phyla more broadly.
GPT-4o mini: Non-social science research article
Counterfeit judgments in large language models
MatjaĆŸ Perc
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GPT-4o mini: Non-social science research article
Actin isoform–specific interactions revealed by Vibrio VopV actin-binding repeats
Elena Kudryashova, Mark A. B. Kreutzberger, Ewa Niedzialkowska, Songyu Dong, Dmitri S. Kudryashov, Edward H. Egelman
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Despite an evolutionary separation of over 300 Mya, there are no amino acid substitutions in certain actin isoforms from reptiles to mammals. What divergence that does exist between different actin isoforms is primarily tissue–specific, rather than species-specific. Sorting of actin isoforms into distinct cellular compartments is believed to be controlled by actin-binding proteins (ABPs), but little is known about how ABPs can differentiate between actin isoforms. We show that the actin-binding repeat (ABR) of the Vibrio parahaemolyticus effector VopV binds to cytoplasmic actin in a unique mode with a low nanomolar affinity, over a thousand times stronger than to muscle actin. Actin mutagenesis and cryo-EM reconstructions reveal that isoform-specific residues of previously unassigned function deep in the cleft between the two actin protofilament strands determine this selectivity. These results suggest a mechanism of highly selective, isoform-specific interactions between actin and its partners, and have broad implications for understanding the evolution of actin. Furthermore, our findings have implications in the pathogenesis of V. parahaemolyticus , whose invasion of intestinal epithelial cells relies on the interaction of VopV with cytoplasmic F-actin.
GPT-4o mini: Non-social science research article
Light-field deep learning enables high-throughput, scattering-mitigated calcium imaging
Carmel L. Howe, Kate L. Y. Zhao, Herman Verinaz-Jadan, Pingfan Song, Samuel J. Barnes, Pier Luigi Dragotti, Amanda J. Foust
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Light-field microscopy (LFM) enables high-throughput functional imaging by scanlessly encoding entire volumes in single snapshots. However, LFM’s computational burden and vulnerability to scattering limit its application to biological imaging. We present a light-field strategy for volumetric, scattering-mitigated neural circuit activity monitoring. A physics-based deep neural network, 2PiLnet, is trained with two-photon volumes and one-photon light fields. Light-field videos of jGCaMP8f-expressing neurons are acquired in neocortical brain slices. 2PiLnet reconstructs volumes with two-photon-like contrast and source confinement from scattered, blurry one-photon light fields from fields-of-view for which no two-photon images are provided. This enables automated segmentation and extraction of calcium signals with high signal-to-noise ratios and reduces optical crosstalk compared to conventional volume reconstruction methods. Imaging 100 volumes per second, we observe putative spikes fired at up to 10 Hz and the spatial intermingling of putative ensembles throughout 530 × 530 × 100 -micron volumes. Compared to iterative algorithms, 2PiLnet workflows reduce light-field video processing times by several-fold, advancing the goal of real-time, scattering-robust volumetric neural circuit imaging for closed-loop and adaptive experimental paradigms.
GPT-4o mini: Non-social science research article
SUPPRESSOR OF LAZY QUADRUPLE 1 acts at ER–plasma membrane contact sites to control a gravitropism pathway in the Arabidopsis stem
Takeshi Yoshihara, Edgar P. Spalding
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LAZY proteins function early in the process of orienting growth of land plants with respect to the gravity vector (gravitropism). In Arabidopsis , an oppositely oriented and LAZY-independent form of gravitropism causes the inflorescence stems of a lazy quadruple mutant ( atlazy1 ; 2 ; 3 ; 4 ) to grow down and along the surface of the soil. Here, we report on a suppressor mutation that restores an upright inflorescence to a plant lacking LAZY functions. The suppressor of lazy quadruple 1 ( slq1 ) mutation alters one amino acid in a protein belonging to the NPH3/RPT2-like (NRL) family. The wild-type SLQ1 protein restores prostrate growth to the atlazy1 ; 2 ; 3 ; 4 mutant when expressed specifically in the gravity-sensing endodermal cells of the stem. The SLQ1 protein interacts head-to-tail with itself and, regardless of direction, with a homologous protein called SETH6. Distinct subcellular bodies apparently containing concentrated head-to-tail SLQ1 oligomers coated with SETH6 occurred primarily at sites of contact between the ER and the plasma membrane (PM), including plasmodesmata. The suppressing slq1 mutation (S149F) prevented these bodies from forming and reinverted the auxin gradient in the atlazy1 ; 2 ; 3 ; 4 inflorescence, switching its gravitropism from downward to upward. Thus, SLQ1 and at least one homolog (SETH6) function at ER–PM contact sites to counter the LAZY-dependent mechanism, not by inhibiting it but by regulating an apparently LAZY-independent gravity-directed process for creating an auxin gradient. Variation in the relative strengths of a LAZY-dependent and a SLQ1-mediated, LAZY-independent process of opposite effect may produce the great variety of stem organ postures observed in nature.
GPT-4o mini: Non-social science research article
Modulation of the PGRMC1/NLRP7/HLA-C axis by autophagy is linked to both spontaneous preterm birth and gestational choriocarcinoma
Qin Li, Huaxiao Yu, Dongyi Ling, Jie Zhou, Shanshan Zhen, Yangyang Li, Lijuan Wang, Zetong Zheng, Wenjian Cen, Hongyi Gao, Hui Chen, Jack L. Strominger, Ziming Du
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Spontaneous preterm birth (SPTB) and gestational choriocarcinoma are both associated with complex physiological processes that significantly impact maternal health. While the molecular mechanisms underlying SPTB and gestational choriocarcinoma remain poorly understood, emerging evidence suggests that immune regulation plays a crucial role in both conditions. In this study, we revealed that progesterone regulates autophagy via the noncanonical progesterone receptor membrane component 1 (PGRMC1), which then modulates NLRP7 levels, thereby impacting HLA-C expression in the JEG3 cell line, an extravillous trophoblast (EVT) model. Furthermore, a significant positive correlation between NLRP7 and HLA-C expression was observed in EVTs from placental tissues and choriocarcinoma samples. In cases of SPTB, we found both reduced expression of NLRP7 and HLA-C in EVTs. Similarly, in gestational choriocarcinoma samples, we observed significantly lower expression levels of NLRP7 and HLA-C, further suggesting a shared immune evasion mechanism. These findings not only provide insights into the molecular mechanisms underlying both SPTB and choriocarcinoma but also identify the progesterone-driven NLRP7/HLA-C axis as a promising target for therapeutic intervention, offering strategies for improving outcomes in both conditions.
GPT-4o mini: Non-social science research article
Chromosomal deletions in banana somaclonal variants reveal negative regulators of immunity underlying Fusarium wilt resistance
Puyam Tondonba Singh, Bo-Han Hou, Yi-Heng Tsai, Yuh Tzean, Chih-Ping Chao, Po-Xing Zheng, Yao-Cheng Lin, Wei-Chiang Shen, Hsin-Hung Yeh, Ho-Ming Chen
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Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense tropical race 4 (TR4), poses a severe threat to global banana production. Developing TR4-resistant banana cultivars has been challenging due to triploidy and sterility. Nevertheless, several Cavendish somaclonal variants with stable TR4 resistance have been developed and widely cultivated in Taiwan. Despite this success, the underlying genetic and molecular bases remain largely unknown, limiting the broader application of this resistance to other varieties. Here, we apply genomic and functional analyses to uncover somatic mutations and key genes associated with TR4 resistance. We observe recurrent selection for large deletions on chromosome 5 and a tendency for elevated expression of salicylic acid-responsive genes in resistant variants. Within deletion regions, we pinpoint two members of the autoinhibited Ca 2+ -ATPase ( ACA ) gene family, known negative regulators of plant immunity, as candidate susceptibility genes. Both ACA genes are downregulated in resistant variants. Silencing the ACAs in susceptible bananas enhances salicylic acid response and attenuates TR4 disease symptoms. Our study highlights the role of structural variation and copy number change of susceptibility genes like ACAs in shaping disease resistance in clonally propagated crops. Also, these findings provide a genomic framework for the development of TR4-resistant banana cultivars through targeted gene editing or selection of somatic variants.
GPT-4o mini: Non-social science research article
Acoustic printing of conductive polymers
Ethan Trepka, Lauren Cooper, Kenneth Brinson, Samuel Thompson, Marigold Gil Malinao, Nicholas J. Rommelfanger, Polly Fordyce, Guosong Hong
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Fabricating materials within optically opaque structures, such as biological tissue, is a considerable challenge. Recently, ultrasound-based printing (“sonoprinting”) approaches have emerged as a promising strategy to address this challenge. However, an approach to sonoprint conductive materials has yet to be realized, limiting potential bioelectronic applications. Here, we extend sonoprinting to conductive materials by designing temperature-based and pressure-based methods to polymerize conductive polymers with focused ultrasound (FUS). Our temperature-based approach relies on the acoustic attenuation of the surrounding medium to generate heat under FUS, whereas our pressure-based approach leverages the acoustic vaporization of perfluorohexane double emulsions to trigger polymerization. We demonstrate that both approaches can be used to print the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) through optically opaque hydrogels and biological tissue with high spatial resolution. Taken together, our results establish complementary temperature- and pressure-based methods for sonoprinting conductive polymers, paving the way for future efforts to fabricate bioelectronic interfaces in tissue.
GPT-4o mini: Non-social science research article
Modeling feasible locomotion of nanobots for cancer detection and treatment
Noble Harasha, Cristina Gava, Nancy Lynch, Claudia Contini, Frederik Mallmann-Trenn
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Deploying motile nanosized particles, also known as “nanobots,” in the human body promises to improve selectivity in drug delivery and reduce side effects. We consider a swarm of nanobots locating a single cancerous region and treating it by releasing an onboard payload of drugs at the site. At nanoscale, the computation, communication, sensing, and locomotion capabilities of individual agents are extremely limited, noisy, and/or nonexistent. We present a general model to formally describe the individual and collective behavior of agents in a colloidal environment, such as the bloodstream, for cancer detection and treatment by nanobots. This includes a feasible and precise model of agent locomotion, inspired by actual nanoparticles that, in the presence of an external chemical gradient, move toward areas of higher concentration by means of self-propulsion. We present two variants of our model: the first assumes an endogenous chemical gradient fixed over time and centered at the cancer site; the second is a more speculative, dynamic variant in which agents themselves create and amplify a gradient centered at the cancer site. In both settings, agents sense the gradient and ascend it noisily, locating the cancer site more quickly than by simple Brownian motion. For the first variant, we present simulation and analytical results to bound the time it takes for agents to reach the cancer site. For the second, simulations highlight collective benefit from agent-generated signaling, showing significant runtime improvement via chemical signal amplification.
GPT-4o mini: Non-social science research article
Human coronavirus 3CL protease manipulates host protein STIM1 to facilitate immune evasion
Yoon Young Lee, Ah Reum Lee, Seongkyung Seo, Uni Park, Taehun Kim, Sang Kwon Lee, Hyeongsun Jeong, Su Ji Jeong, Yeong Cheon Kweon, Go Eun Park, Min Ji Kim, Byung-Gyu Kim, Taejoon Kwon, Nam-Hyuk Cho, Hyug Moo Kwon, Kyungjae Myung, Sang Min Lee, Chan Young Park
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Coronaviruses rely on intricate interactions with host proteins to create an environment conducive to their replication and survival. The 3CL protease of coronavirus acts as a key mediator, serving a dual role in cleaving viral polyproteins to produce essential components for replication and targeting host proteins to disrupt regulatory pathways and suppress immune defenses. However, the mechanisms by which 3CL protease manipulates host proteins remain poorly understood. Here, we identify STIM1, a substrate of the 3CL protease, as a dual immune suppressor. Cleavage at the Q496 residue generates two stable products, N-terminal (NT) and C-terminal (CT) fragments, which acquire de novo immunomodulatory functions. NT suppresses MAVS aggregation and MAVS-TRAF2-TBK1 signalosome formation, while CT attenuates IKKα-induced p65 phosphorylation and nuclear translocation by interacting with HSP70. Collectively, these dual modules simultaneously lead to the suppression of IFN-ÎČ production and the weakening of antiviral defenses. These findings reveal a distinct function of STIM1 and delineate a strategy employed by coronaviruses to modulate host immunity, offering insights into viral pathogenesis and potential avenues for therapeutic intervention.
GPT-4o mini: Non-social science research article
Unmeasured prior viability selection resolves the paradox of stasis for body size in wild Soay sheep
Elizabeth A. Mittell, Josephine M. Pemberton, Loeske E. B. Kruuk, Michael B. Morrissey
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The estimation of natural selection is used to understand ecological and evolutionary processes in wild populations and is often used to predict change. However, the direct application of quantitative genetic methods, originally developed in animal breeding, has been less successful in the wild; in particular, predictions of evolutionary change are often made that are not observed. This misprediction, known as the “paradox of stasis,” can arise due to bias in estimates of selection via nonrandom missing data in phenotypes if viability selection has previously occurred on correlated traits. Here, we check for this bias in a wild population of Soay sheep where estimates of selection suggest that “bigger is better” for adult size, but evolutionary change of the predicted magnitude does not occur. We establish that standard procedures for estimating total lifetime selection are biased by prior viability selection. In particular, while phenotypically large lambs have high first year survival, we also show that lambs that are genetically predisposed to large adult size traits also suffer elevated juvenile mortality. While the phenotypic traits driving early-life selection against large adult body size are unknown, our genetic analysis reveals correlated selection against larger adult sizes that essentially resolves the paradox of stasis for adult body size traits in this wild population. The pattern we reveal is potentially widespread in nature; previous results showing predominantly positive selection of large body size could in general be explained by this kind of antagonistic prior viability selection.
GPT-4o mini: Non-social science research article
Precipitation increase promotes soil organic carbon formation and stability via the mycorrhizal fungal pathway
Tangqing He, Yunfeng Zhao, Xiaodong Wang, Yunpeng Qiu, Jun Deng, Kangcheng Zhang, Xinyu Xu, Yexin Zhao, Kaiyun Qian, Hao Wang, Tongshuo Bai, Yi Zhang, Cheng Feng, Lijin Guo, Huaihai Chen, Liang Guo, Yi Wang, Shuijin Hu
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Arbuscular mycorrhizal fungi (AMF) form symbiotic relationships with roots of most terrestrial plants, playing a crucial role in regulating soil organic carbon (SOC) dynamics. While precipitation increase (Pi) is a major facet of climate change, its impacts on root- and AMF-mediated SOC formation and stability remain largely unexplored. Here, we combined a meta-analysis across global grasslands with a multiyear precipitation manipulation experiment in a semiarid grassland on the Loess Plateau to disentangle the relative effects of roots and their associated AMF on microbial communities and SOC as influenced by Pi. We show that Pi induced tradeoffs between roots and AMF, and promoted SOC formation and stability via the mycelium- rather than the root-pathway, leading to an increase of 136% (±40) and 297% (±90) in mycelium-derived C and mineral-associated organic C (MAOC), respectively. Pi altered plant community composition, favoring subshrubs and forbs over grasses. Also, Pi reduced specific root length, but increased root diameter, tissue density, and root colonization and extraradical biomass of AMF. Furthermore, Pi-induced change in AMF shifted the soil bacterial community by favoring K-strategists, increasing bacterial necromass C and promoting MAOC accumulation. Our findings provide direct evidence that Pi enhances AMF-driven SOC sequestration by expanding the mycorrhizosphere and promoting microbiota with high C use efficiency, highlighting a key mechanism by which mycorrhizal fungi mediate SOC formation and stability under shifting precipitation regimes.
GPT-4o mini: Non-social science research article
Pathogens spread by high-flying wind-borne mosquitoes
Roland Bamou, Adama Dao, Alpha S. Yaro, Cedric Kouam, Koray Ergunay, Brian P. Bourke, Moussa Diallo, Zana L. Sanogo, Samake Djibril, Yaw A. Afrane, Abdul Rahim Mohammed, Christopher M. Owusu-Asenso, Gabriel Akosah-Brempong, Cosmos M. Pambit-Zong, Benjamin J. Krajacich, Roy Faiman, M. Andreina Pacheco, Ananias A. Escalante, Scott C. Weaver, Rita Nartey, Jason W. Chapman, Don R. Reynolds, Yvonne-Marie Linton, Tovi Lehmann
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Mosquito-borne diseases such as malaria and dengue threaten billions of people and cause the death of hundreds of thousands annually. Recent studies have revealed that many mosquito species regularly engage in high-altitude wind-borne migration, but its epidemiological significance remains unclear. The hypothesis that high-flying mosquitoes spread pathogens over long distances has not been directly tested. Here, we report that high-flying mosquitoes are commonly infected with arboviruses, protozoans, and helminths and provide a insights into this pathogen–vector aerial network. A total of 1,017 female mosquitoes intercepted on nets suspended from helium balloons at 120 to 290 m above ground over Mali and Ghana were screened for infection with arboviruses, Haemosporida, and filariae. The mosquitoes collected at altitude comprised 61 species, across 10 genera, dominated by Culex , Aedes, and Anopheles . Infection and infectiousness (capacity to transmit a pathogen to another host inferred based on disseminated infection) rates of migrant mosquitoes were 7.2% and 4.4% with Plasmodium spp., 1.6% and 0.6% with filariae, and 3.5% and 1.1% with flaviviruses, respectively. Twenty-one mosquito-borne pathogens were identified, including Dengue, West Nile, and M’Poko viruses, 15 avian Plasmodium species including Plasmodium matutinum , and three filariids, including Pelecitus sp. Confirmed head–thorax (disseminated) infections of multiple pathogens in Culex perexiguus , Mansonia uniformis , and Anopheles squamosus reveal that pathogens carried by high-altitude wind-borne mosquitoes are capable of infecting hosts far from their departure location. This high-altitude traffic of sylvatic pathogens (circulating in wild animals) may be key to their maintenance among enzootic foci as well as initiating outbreaks at distant locations.
GPT-4o mini: Non-social science research article
Emergence of a contrast-invariant representation of naturalistic texture in macaque visual cortex
Gerick M. Lee, Najib J. Majaj, C. L. RodrĂ­guez Deliz, Lynne Kiorpes, J. Anthony Movshon
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Sensory stimuli vary across a variety of dimensions, like contrast, orientation, or texture. The brain must rely on population representations to distinguish changes in one dimension from changes in another. To understand how the visual system might extract separable stimulus representations, we recorded multiunit neuronal responses to texture images varying along two dimensions: contrast, a property represented as early as the retina, and naturalistic statistical structure, a property that modulates neuronal responses in V2 and V4, but not in V1. We measured how sites in these 3 cortical areas responded to variation in both dimensions. Contrast modulated responses in all areas. In V2 and V4, the presence of naturalistic structure both modulated responses and increased contrast sensitivity. Tuning for naturalistic structure was both strongest and most dispersed in V4. We measured how well populations in each area could support the linear readout of both dimensions. Populations in V2 and V4 could support the linear readout of naturalistic structure, but in V4, this readout was more robust to variations in contrast.
GPT-4o mini: Non-social science research article
Using gnotobiotic mice to decipher effects of gut microbiome repair in undernourished children on tuft and goblet cell function
Yi Wang, Hao-Wei Chang, Jiye Cheng, Daniel M. Webber, Hannah M. Lynn, Matthew C. Hibberd, Clara Kao, Ishita Mostafa, Tahmeed Ahmed, Michael J. Barratt, Jeffrey I. Gordon
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Studies have implicated perturbations in the postnatal development of the gut microbiome as a contributing factor to childhood undernutrition. Compared to a standard ready-to-use supplementary food, a microbiome-directed complementary food (MDCF-2) designed to repair these perturbations produced superior improvements in ponderal and linear growth in clinical trials of Bangladeshi children with moderate acute malnutrition. Here, “reverse translation” experiments are performed where intact fecal microbiomes collected from trial participants before and at the end of treatment are introduced into female gnotobiotic mice just after delivery of their pups. Pups received diets designed to resemble those consumed by children in the trials to recreate “unrepaired” and “repaired” gut ecosystems. Analyses of the abundances of bacterial strains (metagenome-assembled genomes), their expressed genes, and metabolic products, combined with assessments of ponderal growth and intestinal epithelial lineage transcriptomes (single-nucleus RNA-Seq with follow-up immunocytochemistry) disclosed effects of MDCF-2 associated microbiome repair that cannot be determined, in part because “no treatment” control arms cannot be ethically incorporated into these trials. Specifically, microbiome repair in these mice produced significant increases in ponderal growth, changes in microbial gene expression consistent with a less virulent gut ecosystem and alterations in expression of i) components of cell junctions in the enterocytic and goblet cell lineages, ii) pathways for synthesis and secretion of eicosanoid immune effectors in chemosensory tuft cells, and iii) goblet cell pathways involved in glycosylation and secretion of mucin. Experiments of the type described can help formulate and test hypotheses about how microbiome repair affects host biology.
GPT-4o mini: Non-social science research article
Regulated coexpression of PrP from different species in mice impacts the replication and host range properties of prion strains
Joseph P. DeFranco, Jifeng Bian, Sehun Kim, Zoe N. Atkinson, Jenna Crowell, Hae-Eun Kang, Hannah O. Bodrogi, Jeffrey R. Christiansen, Carlos M. DĂ­az-DomĂ­nguez, Glenn C. Telling
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Our previous demonstration that replacement of murine cellular prion protein (PrP C ) expression with elk or deer PrP C eliminated the resistance of mice to chronic wasting disease (CWD) prions from deer, elk, and other cervids highlighted the importance of sequence homology between PrP C and its conformationally altered counterpart (PrP Sc ) for optimal prion replication. To further investigate the effects of species-specific PrP primary structural variation on the evolution of prion host range and strain properties during interspecies transmissions, we generated mice with precisely controlled expression of both murine and either deer or elk PrP C and challenged them with cervid or murine prions. While CWD prion transmission was inhibited to varying degrees under these conditions, the strain properties and species specificities of the resulting cervid prions were not impacted. By contrast, although murine prions induced conformational conversion of mouse but not coexpressed cervid PrP C , the resulting prions produced disease in mice expressing either cervid or mouse PrP C . Our findings show that while mouse PrP C inhibited conformational conversion of deer or elk PrP C without affecting the host range of CWD prions, coexpression of cervid PrP C influenced the selection of strains with expanded host range properties during conformational conversion of mouse PrP C by murine prions. Our studies reveal diverse influences of bystander PrP C expression on the replication, host range, and strain properties of prions generated during conformational conversion of their coexpressed cognate PrP C . These cooperative or inhibitory effects occur in trans and derive from species-specific primary structural variations between coexpressed PrP C substrates and infectious prions.
GPT-4o mini: Non-social science research article
The intermediate filament protein GFAP regulates mitochondrial fission in astrocytes
Ding Xiong, Ye Sing Tan, Fang Yuan, Yinglu Li, Kay En Low, Isabelle Bonne, Sakthikumar Mathivanan, Phil Jun Kang, Zijun Sun, Xueyan Li, Emily Abella, Albee Messing, Linghai Kong, Su-Chun Zhang
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Mitochondrial plasticity, coordinated by fission and fusion, is crucial to ensure cellular functions. Mitochondrial fission is mediated by the GTPase Drp1 at the constriction site, which is proposed to be driven by the actin–myosin contractile force. However, the mechanism that propels constriction remains unclear, and the potential involvement of additional mechanisms in this process remains an open question. Here, using structured illumination microscopy, electron microscopy, and correlative light electron microscopy (CLEM), we show that the type III intermediate filament glial fibrillary acidic protein (GFAP) participates in mitochondria constriction and fission by interacting with Drp1. Remarkably, loss of GFAP results in hyperfused mitochondria under physiological and even Ca 2+ -induced mitochondrial fission conditions. Additionally, mutations in GFAP, the cause of Alexander disease, result in more Drp1 localized to GFAP and lead to significantly increased mitochondrial fissions. Taken together, these findings propose a role of type III intermediate filaments in mitochondrial division.
GPT-4o mini: Non-social science research article
Cellular energy sensor SnRK1 suppresses salicylic acid–dependent and –independent defenses and bacterial resistance in Arabidopsis
Linnan Jie, Miho Sanagi, Shigetaka Yasuda, Kohji Yamada, Saki Ejima, Ayumi Sugisaki, Junpei Takagi, Mika Nomoto, Xiu-Fang Xin, Yasuomi Tada, Yusuke Saijo, Takeo Sato
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In nature, plants cope with various pathogens that compete for cellular resources during infection. It has long been suggested that plant defense activity must be linked to cellular energy and metabolic states to optimize the balance between growth and defense. However, the molecular mechanisms that regulate immune activity in relation to cellular energy status remain unclear. Here, we demonstrate that the plant energy sensor SNF1-RELATED KINASE 1 (SnRK1) plays a critical role in modulating defense responses and bacterial resistance in Arabidopsis thaliana . Bacterial elicitor-induced expression of defense marker genes, such as PATHOGENESIS-RELATED 1 ( PR1 ), is significantly repressed under sugar-limited conditions in wild-type seedlings, whereas this expression is markedly enhanced in the snrk1α1i/α2 knockdown mutants. SnRK1 restricts defense-related gene expression and resistance to the biotrophic bacterial pathogen Pseudomonas syringae pv. tomato DC3000, which are partly dependent on salicylic acid (SA). In addition, we found that the SnRK1 kinase activity is increased by high humidity. Consistently, SnRK1 is critical for the suppression of SA-mediated defense responses under high humidity conditions. SnRK1 physically associates with the SA-related transcription factors TGACG SEQUENCE-SPECIFIC BINDING PROTEIN 4 (TGA4) and TGA2 to attenuate PR1 expression. These findings provide valuable insight into the molecular mechanisms linking cellular energy status with immune regulation in plants.
GPT-4o mini: Non-social science research article
Electrostatics overcome acoustic collapse to assemble, adapt, and activate levitated matter
Sue Shi, Maximilian C. HĂŒbl, Galien Grosjean, Carl P. Goodrich, Scott Waitukaitis
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Acoustic levitation provides a unique method for manipulating small particles as it completely evades effects from gravity, container walls, or physical handling. These advantages make it a tantalizing platform for studying complex phenomena in many-particle systems. In most standing-wave traps, however, particles interact via acoustic scattering forces that cause them to merge into a single dense object. Here, we introduce a complementary approach that combines acoustic levitation with electrostatic charging to assemble, adapt, and activate complex, separated many-particle systems. The key idea is to superimpose electrostatic repulsion on the intrinsic acoustic attraction, rendering a so-called “mermaid” potential where interactions are attractive at short range and repulsive at long range. By controlling the attraction–repulsion balance, we can levitate expanded structures where all particles are separated, collapsed structures where they are in contact, and hybrid ones consisting of both expanded and collapsed components. We find that collapsed and expanded structures are inherently stable, whereas hybrid ones exhibit transient stability governed by acoustically unstable dimers. Furthermore, we show how electrostatics allow us to adapt between configurations on the fly, either by quasistatic discharge or discrete up/down charge steps. Finally, we demonstrate how large structures experience selective energy pumping from the acoustic field—thrusting some particles into motion while others remain stationary—leading to complex dynamics including coupled rotations and oscillations. Our approach establishes a design space beyond acoustic collapse, offering possibilities to study many-particle systems with complex interactions, while suggesting pathways toward scalable integration into materials processing and other applications.
GPT-4o mini: Non-social science research article
Nonionic signaling rapidly remodels postsynaptic DLG to induce retrograde homeostatic plasticity
Chengjie Qiu, Sarah Perry, Christine Chen, Jiawen Chen, Jin Zhuang, Yifu Han, Pragya Goel, Dion Dickman
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Synapses must be resilient to the challenges they confront during development, experience, disease, and aging. A conserved form of adaptive plasticity, observed at the glutamatergic Drosophila neuromuscular junction (NMJ), is expressed following acute pharmacological blockade of postsynaptic glutamate receptors (GluRs). This challenge is counteracted by enhanced presynaptic neurotransmitter release to maintain stable synaptic strength. This retrograde form of homeostatic plasticity is termed presynaptic homeostatic potentiation (PHP). How retrograde PHP signaling is acutely induced in the postsynaptic compartment is unknown. Here, we demonstrate that acute PHP induction does not require reductions in ionic flow through GluRs. Rather, pharmacological blockade provokes nanoscale changes in GluR organization that propagates remodeling of the postsynaptic apparatus. These postsynaptic structural changes are necessary for the presynaptic remodeling that characterizes PHP, including enhanced active zone intensity. Next, using a CRISPR-based genetic screen, we identify Discs large (DLG), the fly homolog of mammalian PSD-95, as a key postsynaptic substrate selectively required for acute PHP signaling. Finally, we find that homeostatic remodeling of both pre- and postsynaptic compartments persists in the absence of synaptic activity. Together, we propose that acute pharmacological perturbation of GluRs triggers activity-independent conformational signaling that is propagated throughout the postsynaptic apparatus, transmitting retrograde information that rapidly induces PHP.
GPT-4o mini: Non-social science research article
Inhibition of ice recrystallization with designed twistless helical repeat proteins
Robbert J. de Haas, Harley Pyles, Evelyn B. Huddy, Jannick van Ossenbruggen, Chuanbao Zheng, Daniëlle van den Broek, Sanne N. Giezen, Ann Carr, Asim K. Bera, Alex Kang, Evans Brackenbrough, Emily Joyce, Banumathi Sankaran, David Baker, Ilja K. Voets, Renko de Vries
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Given the repetitive structure of crystalline ice, it is unsurprising that highly active ice-binding proteins (IBPs), often with beta-roll structures, also have repeating motifs. Here, we introduce a de novo designed family of ice-binding twistless alpha-helical repeat (iTHR) proteins. Each iTHR protein comprises two planar layers of parallel alpha-helices connected by loops—a structural topology not seen in native IBPs. The ice-binding helices contain an ordered array of TXXXAXXXAXX motifs, precisely spaced to complement the pyramidal {201} and secondary prism {110} planes of the ice lattice, with a designed 98.2° residue turn angle that orients all threonines uniformly toward the ice surface. iTHR proteins show high solubility, thermostability, and produce varied ice crystal morphologies depending on their intended target facet. Crucially, iTHRs exhibit ice recrystallization inhibition (IRI) at critical concentrations comparable to those of many native globular IBPs. Extensive site-specific mutagenesis shows that ice-binding activity in iTHR proteins is robust, remaining largely unaffected by changes in chemical composition. Variation in the repeat number reveals a nonmonotonic relationship to IRI activity. X-ray crystal structures of two designs confirm the intended orientation of threonines, uniformly pointing toward the ice surface. The iTHR family provides a versatile platform to systematically investigate the complex structure–activity relationships underlying protein–ice interactions.
GPT-4o mini: Non-social science research article
Tattoo ink induces inflammation in the draining lymph node and alters the immune response to vaccination
Arianna Capucetti, Juliana Falivene, Chiara Pizzichetti, Irene Latino, Luca Mazzucchelli, Vivien Schacht, Urs Hauri, Andrea Raimondi, Tommaso Virgilio, Alain Pulfer, Simone Mosole, Llorenç Grau-Roma, Wolfgang BÀumler, Martin Palus, Louis Renner, Daniel Ruzek, Gabrielle Goldman Levy, Milena Foerster, Kamil Chahine, Santiago F. Gonzalez
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Despite safety concerns regarding the toxicity of tattoo ink, no studies have reported the consequences of tattooing on the immune response. In this work, we have characterized the transport and accumulation of different tattoo inks in the lymphatic system using a murine model. Upon quick lymphatic drainage, we observed that macrophages mainly capture the ink in the lymph node (LN). An initial inflammatory reaction at local and systemic levels follows ink capture. Notably, the inflammatory process is maintained over time, as we observed clear signs of inflammation in the draining LN 2 mo following tattooing. In addition, the capture of ink by macrophages was associated with the induction of apoptosis in both human and murine models. Furthermore, the ink accumulated in the LN altered the immune response against two different types of vaccines. On the one hand, we observed a reduced antibody response following vaccination with an messenger ribonucleic acid (mRNA)-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, which was associated with a decreased expression of the spike protein in macrophages in the draining LN. In contrast, we observed an enhanced response when vaccinated with influenza vaccine inactivated by ultraviolet (UV) radiation. Considering the unstoppable trend of tattooing in the population, our results are crucial in informing the toxicology programs, policymakers, and the general public regarding the potential risk of the tattooing practice associated with an altered immune response.
GPT-4o mini: Non-social science research article
The near-infrared bacteriophytochrome-derived fluorescent protein PENELOPE enables RESOLFT superresolution microscopy
Daniel Stumpf, Nickels Jensen, Cédric Mittelheisser, Jan Keller-Findeisen, Alexey I. Chizhik, Maria Kamper, Timo Diekmann, Florian Habenstein, Isabelle Jansen, Jörg Enderlein, Michel Sliwa, Kaushik Inamdar, Stefan W. Hell, Stefan Jakobs
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REversible Saturable Optical Linear Fluorescence Transitions (RESOLFT) superresolution microscopy fundamentally overcomes the diffraction barrier in far-field fluorescence microscopy. It relies on reversibly switchable fluorescent proteins (RSFPs) that allow repeated light-induced transitions between fluorescent on- and nonfluorescent off-states. Because these transitions are induced by low-light intensities, RESOLFT superresolution microscopy is particularly suitable for live-cell imaging. So far, RESOLFT imaging has only been performed in the visible range of the electromagnetic spectrum. To expand the RESOLFT concept into the near-infrared (NIR) region, which is characterized by reduced autofluorescence, lower scattering and decreased phototoxicity, we developed the p hotostabl e N IR r e versibly switchab l e flu o rescent p rot e in (PENELOPE), which is the first RSFP applicable in the NIR window. PENELOPE was generated by mutagenesis of the chromophore-binding domain of the Deinococcus radiodurans bacteriophytochrome. This NIR-RSFP exhibits high photostability and high ensemble switching contrast at low-light intensities. It also undergoes an unusually fast thermal fluorescence recovery from the dark state into an on-state. This was exploited for low-light intensity RESOLFT imaging with only a single wavelength, as the same light wavelength (660 nm) is used for off-switching and fluorescence readout, while the on-switching occurs in the absence of illumination. We demonstrate RESOLFT recordings both in chemically fixed and in living human cells using PENELOPE as a fusion protein.
GPT-4o mini: Non-social science research article
Impaired AIS plasticity in ankyrin-G mutant mice alters cortical excitability and behavior
Min Li, Bingqing Zhao, Zhimin Lu, Liu Zhe, Yue Han, Yating Chen, Huichao Wang, Yu Wang, Chunsheng Wu, Mingjie Zhang, Keyu Chen, Rui Yang
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The developing brain undergoes neuroplasticity driven by learning, experience, and memory formation. The axon initial segment (AIS) is a specialized membrane domain within the proximal axon that initiates action potential. Studies have demonstrated that the AIS exhibits plasticity by altering its length and/or localization to adjust the excitability in response to neural stimuli. However, how AIS plasticity may affect brain function is unclear. The 480-kDa giant ankyrin-G protein (gAnkG) is the master organizer of AISs and nodes of Ranvier. Previously, we reported that a neurodevelopmental disorder-linked variant (Thr1861Met) in the neuron-specific domain of gAnkG causes the formation of diffused AISs in cultured ankyrin-G null neurons. Here, we generated a knock-in mouse harboring this mutation. The knock-in mice displayed impairments in motor coordination and social interaction. Neurons from these knock-in mice formed elongated AISs with no significant reduction in the accumulation of key AIS components-including ankyrin-G, ÎČ4-spectrin, voltage-gated sodium channels, and neurofascin. Crucially, unlike wild-type AISs, which shorten in response to stimulation by high K + or chemogenetics (designer receptors exclusively activated by designer drugs), the elongated AISs in mutant neurons failed to undergo such shortening, indicating a deficit in AIS plasticity. Neurons in the primary motor cortex and anterior cingulate cortex of knock-in mice exhibited AISs of normal length at early stage but failed to undergo the developmental shortening observed in wild-type neurons; by postnatal day 60, this resulted in elongated AISs and increased neuronal excitability in these regions. Thus, the gAnkG protein mutation impairs activity-dependent AIS plasticity, leading to abnormal neuronal excitability and behavioral deficits.
GPT-4o mini: Non-social science research article
Gray wolves in an anthropogenic context on a small island in prehistoric Scandinavia
Linus Girdland-Flink, Anders Bergström, Jan StorĂ„, Erik Ersmark, Jan Apel, Maja KrzewiƄska, Love DalĂ©n, Anders Götherström, Pontus Skoglund
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Dogs were domesticated at least once from a yet-unidentified wolf population at least ~15,000 y ago. However, how domestication took place is a topic of ongoing debate, and the ability of human groups to manage wolves in their communities during early stages of domestication is poorly understood. Here, we report multiproxy data from two canids excavated from Late Neolithic and Bronze Age contexts in the Stora Förvar cave on the island of Stora Karlsö in the Baltic Sea. The island is small (2.5 sq km) and, like the neighboring island of Gotland, carries no endemic populations of terrestrial mammals. Instead, the current consensus is that human introductions account for some mammal fauna on Gotland, and for the majority of that on Stora Karlsö. Genome-wide data show that the two canids have ancestry indistinguishable from Eurasian wolves, with no shared ancestry with domestic dogs of the Canis familiaris lineage. Their genome-wide heterozygosity is lower than that observed in 72 previously published ancient wolf genomes, and instead comparable to dogs. Stable isotope data (Ύ 13 C and Ύ 15 N) reveals a diet rich in marine protein, which is consistent with habitation alongside the human groups who used Stora Karlsö as a seal-hunting, fowling, and sea fishing station, and in the Bronze Age probably also for grazing. Skeletal size is at the lower end of wolf variability, and one individual shows advanced pathology consistent with reduced mobility. While other scenarios are possible, a parsimonious explanation is that these wolves were brought to the island by humans and were possibly under human control.
GPT-4o mini: Non-social science research article
The sleep–wake history contributes to rhythmic BMAL1 chromatin binding in the cerebral cortex but not in the liver
Carlos Neves, Charlotte N. Hor, Sonia Jimenez, Paul Franken
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The timing and quality of sleep is regulated by circadian- and sleep–wake-driven processes. The core clock gene Bmal1 not only affects the circadian timing of sleep, but also the response to sleep deprivation (SD), which, in turn, causes long-term changes in cortical Bmal1 expression. We aimed at separating the circadian- and sleep–wake-driven contributions to BMAL1 binding to its target genes in the cerebral cortex by scheduling 6 SDs at 4 h intervals across the daily 12 h light/12 h dark cycle. We show that BMAL1 rhythmically bound its tissue-specific targets with tissue-specific dynamics, reaching peak binding 2 to 4 h later in the cortex than in the liver, while trough times did not differ. The SDs affected BMAL1 binding most significantly in the cortex, causing 80% of rhythmically bound regions to lose rhythmicity, suggesting BMAL1 binding has a prominent sleep–wake-driven component in this tissue. Analyses of the promoters of other core clock-genes indicate that BMAL1 binding to Bhlhe41 and Nr2d1 have a strong sleep–wake-driven component, while for Per2 two binding regions were identified one with circadian- and the other with sleep–wake-driven binding dynamics. Our results attest to a nonadditive interaction of time-of-day and time-spent-awake affecting the core molecular circadian circuitry. It further highlights that rhythms in gene expression in peripheral tissues are an emergent property of molecular interactions beyond that of the core molecular clock circuitry.
GPT-4o mini: Non-social science research article
Rroid2 regulates effector-to-memory CD8 + T cell differentiation during infection in vivo
Julia Erber, Carmen Stecher, Valerie Plajer, Nina Braun, William Mallard, Loyal A. Goff, Iros Barozzi, Thomas Mohr, John L. Rinn, Richard A. Flavell, Dietmar Herndler-Brandstetter
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CD8 + T cell differentiation has been associated with changes in the expression of long noncoding RNAs (lncRNAs). Yet, which and how lncRNAs regulate CD8 + T cell responses following infection in vivo remains incompletely understood. We performed deep RNA-seq to map the lncRNA expression landscape of CD8 + T cell subsets during infection and generated lncRNA knockout mouse models to evaluate the in vivo relevance of six lncRNAs. We identified Rroid2 to regulate effector CD8 + T cell function and effector-to-memory differentiation. Rroid2 -deficient mice displayed increased CD44 dim Foxp3 + regulatory T cells while the development of other immune cells, such as natural killer cells, was not affected. In CD8 + T cells, Rroid2 deficiency resulted in a fine-tuned downregulation of transcription factors Id2 and T-bet and impaired KLRG1 + and KLRG1 − effector CD8 + T cell proliferation and cytotoxicity as well as effector-to-memory CD8 + T cell differentiation. The human orthologue of Rroid2 , LINC01814 , is also upstream of the transcriptional regulator ID2 and is highly expressed in human memory CD8 + T cells. Taken together, Rroid2 represents a key regulatory layer that controls CD8 + T cell differentiation.
GPT-4o mini: Non-social science research article
China’s post-zero-COVID Omicron wave: A Bayesian analysis
Jun Cai, Yanpeng Wu, Hengcong Liu, Zhu Deng, Lan Yi, Liuhe Lai, Anna Funk, Marco Ajelli, Hongjie Yu
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Following the late 2022 transition from its “dynamic zero-COVID” policy, China experienced a major nationwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron wave. To characterize the wave’s transmission dynamics, we used a Bayesian framework to fit a deterministic transmission model to two key data streams: reported COVID-19 daily case counts preceding the policy shift (up to November 11, 2022) and weekly virological and influenza-like illness (ILI) surveillance data afterward (through February 12, 2023). We estimated a nationwide cumulative infection attack rate reaching 87.8% (95% CrI: 75.9 to 93.3%) by mid-February 2023. Notably, 84.1% of the population became infected within just 1 mo following the full policy relaxation on December 7. The estimated time-varying effective reproduction number peaked at 5.69 (95% CrI: 4.56 to 6.85) on December 8, 2022. Although transmission intensity increased during the Spring Festival travel rush (Chunyun), widespread population immunity prevented a subsequent wave. Prior to the Chunyun period, distinct relationships emerged: Estimated transmission rates showed a significant positive correlation with long-term population behavioral response coefficient (reflecting cumulative infections; Pearson correlation: ρ = 0.92, P < 0.001), while mobility patterns correlated positively with short-term behavioral response coefficient (reflecting current infection prevalence; Pearson correlation: ρ = 0.87, P < 0.001). These dynamic behavioral associations, which we further validated against empirical data on keyword search and media coverage, then weakened during the Chunyun period. In summary, this analysis quantifies Omicron’s transmission potential and highlights the importance of incorporating time-varying behavioral factors into epidemic models to accurately describe transmission dynamics, especially during periods of abrupt policy change.
GPT-4o mini: Non-social science research article
Tropics-wide intraseasonal oscillations
Jiawei Bao, Sandrine Bony, Daisuke Takasuka, Caroline Muller
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The tropical climate variability is characterized by various oscillations across a range of timescales. Oscillations that imprint the tropical mean state are generally attributed to slow processes, such as the seasonal cycle or interannual variability. Here, we identify a pronounced tropics-wide intraseasonal oscillation (TWISO) in satellite observations and reanalyses. This oscillation, with a period of 30 to 60 d, is evident across multiple variables and involves interactions between convection, radiation, surface fluxes, and large-scale circulation. It is primarily manifested as convective perturbations in the tropical Indo-Pacific warm pool accompanied by oscillations in the large-scale tropical overturning circulation. Here, we examine the relationship between TWISO, the Madden–Julian Oscillation (MJO), and the instability of radiative-convective equilibrium. Certain phases of TWISO coincide with specific phases of the MJO, suggesting a potential connection between the two. However, although the MJO can amplify the oscillation amplitude of TWISO, it is not essential for TWISO to occur. Finally, due to its broad manifestation across the tropics, TWISO potentially exerts widespread influence on tropical weather and climate at regional scales.
GPT-4o mini: Non-social science research article
Myeloid GPSM1 regulates atherosclerosis progression by governing monocyte and macrophage activation and chemotaxis
Yuemei Zhang, Yuxin Cao, Yongxin Sun, Chenxia Zhou, Xiaorui Lyu, Daixi Wang, Jiangfei Zheng, Yuxin Shu, Lijun Yao, Rong Zhang, Jingyong Li, Feng Jiang, Xiang Cheng, Jing Yan, Cheng Hu
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The activation of blood monocytes and the infiltration of monocyte-derived macrophages into the vessel walls are the central part of atherosclerosis. However, the mechanisms underlying the processes remain unclear. Here, we report that G-protein signaling modulator 1 (GPSM1) plays a critical role in atherogenesis. We found that GPSM1 expression in lesional macrophages was increased during atherosclerosis development both in mice and humans. Myeloid-specific GPSM1 ablation protects mice against atherosclerosis and reduces aortic inflammation in both Apoe −/− mice and an AAV-PCSK9 injection model. Conversely, myeloid-restricted overexpression of GPSM1 accelerates aortic inflammation and promotes atherosclerosis development in mice. Mechanistically, GPSM1 deficiency suppressed monocyte activation including chemotaxis and adhesion through inhibition of the p38/ERK MAPK pathway regulated by the cAMP/PKA/KLF4/PMP22 axis, thereby alleviating proinflammatory responses within atherosclerotic plaques. Blockade of PMP22 using siRNA-loaded liposomes protected GPSM1 overexpression mice from atherosclerosis. Furthermore, a small-molecule compound inhibiting GPSM1 function could suppress atherosclerosis in vivo. In conclusion, our findings establish that GPSM1 is a regulator of atherosclerosis development and targeting GPSM1 might be a promising therapy against atherosclerosis.
GPT-4o mini: Non-social science research article
Genetic control of seasonal meristem arrest in trees
Jun Wang, Xiaoli Liao, Zhihao Wu, Shashank Sane, Shaopeng Han, Qihui Chen, Xueping Shi, Xiaokang Dai, Maria KlintenÀs, Ove Nilsson, Jihua Ding
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Perennial plants, such as trees native to temperate and boreal regions, exhibit meristems that undergo annual cycles of activity and rest to synchronize their growth cycles with seasonal changes, ensuring survival under harsh winter conditions. The arrest of shoot meristem growth, known as growth cessation, is a critical initial step for trees to enter dormancy. This process is triggered by a combination of endogenous and exogenous signals, yet the molecular mechanisms and signaling pathways underlying growth cessation remain poorly understood. In this study, we demonstrate that Populus orthologs of APETALA2-like transcription factors (AP2Ls), the primary regulators of global proliferative arrest (GPA) in Arabidopsis , play a crucial role in the regulation of seasonal growth cessation in hybrid aspen trees. In particular, AP2Ls act as important activators of the expression of FLOWERING LOCUS T2 ( FT2 ), a key gene for short-day-induced growth cessation. This contrasts with the established role of AP2Ls as repressors of FT in annual plants. Yet, the pathway itself is conserved with the pathway regulating GPA in annual plants, a completely different process during the plant life cycle. Our research highlights both the conserved roles and functional diversities of AP2Ls in a more general balancing of meristem proliferation and arrest in perennial plants, providing insights into the evolutionary adaptation of growth regulation mechanisms across plant species.
GPT-4o mini: Non-social science research article
Preassembly and independent trafficking of the exocyst complex in Arabidopsis
Su Jiang, Zhendong Liu, Shuju Zhao, Tonghui Li, Juan Li, Can Bu, Long Ma, Xiaonan Liu, Shan Gao, Guangyou Duan, Dayong Cui, Chun-Ming Liu, Juan Dong, Jian Xu, Shanli Guo, Samantha Vernhettes, Shipeng Li
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Membrane fusion, the culmination of eukaryotic membrane trafficking, is orchestrated by the exocyst complex (a conserved octamer comprising SC1 and SC2 heterotetramers) and sensitive factor attachment protein receptor (SNARE) complexes. Although trans -SNARE complex formation is essential for function, a similar trans -interaction mechanism for the exocyst remains uncertain. We employed advanced live-cell imaging combined with genetic and pharmacological techniques to dissect the spatiotemporal dynamics of exocyst subunit interactions and cargo vesicle association in Arabidopsis thaliana hypocotyl cells. Our results demonstrate that subunits from SC1 and SC2 colocalize and undergo actin-dependent transport to the plasma membrane (PM). Disruption of either SEC6 (SC1) or EXO70A1 (SC2) prevented PM association of both subcomplexes, indicating cytoplasmic preassembly of the cis -exocyst complex before PM recruitment. Critically, we found that the exocyst does not directly bind vesicles carrying cellulose synthase complexes (CSCs). Instead, exocyst subunits first migrate on CSC-negative vesicles, which then coalesce with CSC-carrying vesicles at the cell cortex via heterotypic fusion. Together, our findings reveal a parallel mechanism for exocyst assembly and cargo loading. This coordinated process may represent a broadly conserved strategy to ensure efficient membrane trafficking in eukaryotic cells.
GPT-4o mini: Non-social science research article
Cell envelope maintenance by PhoP is essential for Mycobacterium tuberculosis methylglyoxal resistance
Phuong M. Tran, Andrea Anaya-Sanchez, Daisy X. Ji, Madeline C. R. Schwarz, Shiva K. Angala, Mary C. Jackson, Sarah A. Stanley, K. Heran Darwin
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During Mycobacterium tuberculosis infections bacteria are engulfed by macrophages, a main line of defense against invading pathogens. Upon activation, macrophages increase glycolysis, producing the antibacterial aldehyde methylglyoxal. To test whether bacterial methylglyoxal resistance is required for robust infections, we sought to identify M. tuberculosis defense mechanisms against methylglyoxal. We identified phoP mutants were among the most highly sensitive strains to methylglyoxal in vitro. phoP mutants are highly attenuated in mice but a phoP mutant was even more attenuated in mice that accumulate methylglyoxal. We further found phoP bacilli were more permeable to methylglyoxal and accumulated glycated proteins. Suppressor mutations in the fatty acid ÎČ-oxidation genes fadE25 or fixB restored impermeability and resistance to methylglyoxal to a phoP mutant. Together, our data show that an important role for PhoP is to provide M. tuberculosis resistance to methylglyoxal toxicity in vivo by regulating cell envelope integrity.
GPT-4o mini: Non-social science research article
Drug repurposing screen identifies an HRI activating compound that promotes adaptive mitochondrial remodeling in MFN2-deficient cells
Prerona Bora, Mashiat Zaman, Samantha Oviedo, Sergei Kutseikin, Nicole Madrazo, Prakhyat Mathur, Meera Pannikkat, Sophia Krasny, Rama Aldakhlallah, Alan Chu, Kristen A. Johnson, Danielle A. Grotjahn, Timothy E. Shutt, R. Luke Wiseman
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Pathogenic variants in the mitochondrial outer membrane GTPase MFN2 cause the peripheral neuropathy Charcot–Marie–Tooth type 2A (CMT2A). These mutations can disrupt MFN2-dependent regulation of diverse aspects of mitochondrial biology including organelle morphology, motility, mitochondrial-endoplasmic reticulum (ER) contacts (MERCs), and respiratory chain activity. However, no therapies currently exist to mitigate the mitochondrial dysfunction linked to genetic deficiencies in MFN2. Herein, we performed a drug repurposing screen to identify compounds that selectively activate the integrated stress response (ISR)—the predominant stress-responsive signaling pathway responsible for regulating mitochondrial morphology and function. This screen identified the compounds parogrelil and MBX-2982 as potent and selective activators of the ISR through the OMA1-DELE1-HRI signaling axis. We show that treatment with these compounds promotes adaptive, ISR-dependent remodeling of mitochondrial morphology and protects mitochondria against genetic and chemical insults. Moreover, we show that pharmacologic ISR activation afforded by parogrelil restores mitochondrial tubular morphology, promotes mitochondrial motility, rescues MERCs, and enhances mitochondrial respiration in MFN2 -deficient cells. These results demonstrate the potential for pharmacologic ISR activation through the OMA1-DELE1-HRI signaling pathway as a potential strategy to mitigate mitochondrial dysfunction in CMT2A and other pathologies associated with MFN2 deficiency.
GPT-4o mini: Non-social science research article
Delay-facilitated self-assembly in compartmentalized systems
Severin Angerpointner, Richard Swiderski, Erwin Frey
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Self-assembly processes in biological and synthetic biomolecular systems are often governed by the spatial separation of biochemical processes. While previous work has focused on optimizing self-assembly through fine-tuned reaction parameters or using phase-separated liquid compartments with fast particle exchange, the role of slow intercompartmental exchange remains poorly understood. Here, we demonstrate that slow particle exchange between reaction domains can enhance self-assembly efficiency through a cooperative mechanism: delay-facilitated assembly. Using a minimal model of irreversible self-assembly in two compartments with distinct reaction and exchange dynamics, we identify scenarios where slow particle exchange maximizes yield and minimizes assembly time for given suboptimal reaction dynamics, even under conditions where isolated compartments would fail to facilitate any self-assembly. The mechanism relies on a separation of timescales between intracompartmental reactions and intercompartmental exchange and is robust across a wide range of geometries, including spatially extended domains with diffusive transport. We demonstrate that this effect enables geometric control of self-assembly processes through compartment volumes and exchange rates, eliminating the need for fine-tuning local reaction rates. These results offer a conceptual framework for leveraging spatial separation in synthetic self-assembly design and suggest that biological systems may use slow particle exchange to improve assembly efficiency.
GPT-4o mini: Non-social science research article
From nematode to Nobel: How community-shared resources fueled the rise of Caenorhabditis elegans as a research organism
Victor R. Ambros, Martin Chalfie, Aric L. Daul, Andrew Z. Fire, David H. Hall, H. Robert Horvitz, Craig C. Mello, Gary Ruvkun, Nathan E. Schroeder, Paul W. Sternberg, Ann E. Rougvie
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Experimental organisms such as the nematode Caenorhabditis elegans are fundamental to biological discovery. The success of C. elegans research has been greatly enabled by infrastructure that allows thousands of scientists to share and access research materials and unpublished information efficiently. Here, we celebrate the worm by interweaving vignettes describing four Nobel Prize–winning discoveries with descriptions of how the major NIH-supported research resources—the Caenorhabditis Genetics Center, WormBase, and WormAtlas—provide invaluable support for all C. elegans research. The synergy between investigation and the availability of shared resources for the C. elegans community is a paradigm for all model organism research, and the continued support of such community research resources will be essential for maximizing impactful discoveries in the future.
GPT-4o mini: Non-social science research article
The far extracellular CUB domain of the adhesion GPCR ADGRG6/GPR126 is a key regulator of receptor signaling
Sumit J. Bandekar, Ethan E. Dintzner, Katherine Leon, Szymon P. Kordon, Tomasz Slezak, Kristina Cechova, Reza Vafabakhsh, Demet Araç
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Adhesion G protein–coupled receptors (aGPCRs) transduce extracellular adhesion events into cytoplasmic signaling pathways. ADGRG6/GPR126 is an aGPCR critical for axon myelination, heart development, and ear development; ADGRG6 is also associated with developmental diseases and cancers. ADGRG6 has a large, alternatively spliced, five-domain extracellular region (ECR) that samples different conformations and is essential for receptor function in vivo. However, the mechanistic details of how the ECR regulates signaling are unclear. Herein, we studied the conformational dynamics of the conserved CUB domain which is located at the distal N terminus of the ADGRG6 ECR and is deleted in an alternatively spliced isoform (ΔCUB). We show that the ΔCUB isoform has decreased signaling and is insensitive to inclusion of an activating splice insertion (+ss). Molecular dynamics simulations suggest that the CUB domain is involved in interdomain contacts to maintain a compact ECR conformation. A cancer-associated CUB domain mutant, C94Y, drastically perturbs the ECR conformation and results in elevated signaling, whereas another CUB mutant located near a conserved Ca 2+ -binding site, Y96A, decreases signaling. Our results suggest an ECR-mediated mechanism for ADGRG6 regulation in which the CUB domain instructs conformational changes within the ECR to regulate receptor signaling.
GPT-4o mini: Non-social science research article
Genomic ancestry, behavior, and the domestication of the dog
Kathryn A. Lord, Greger Larson, William J. Murphy, Elaine A. Ostrander
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GPT-4o mini: Non-social science research article
Engineered calcium-regulated affinity protein for efficient internalization and lysosomal toxin delivery
Malin Jönsson, Marit Möller, Leon Schierholz, Nicolai Dorka, Hanna Tegel, Emma Lundberg, Mathias Uhlén, Magnus Wolf-Watz, Hjalmar Brismar, Sophia Hober
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The emerging strategy of protein–drug conjugates (PDCs) for targeted cancer therapy holds great potential to improve treatment efficacy by specifically targeting cancer biomarkers and delivering toxic payloads directly to tumor cells, minimizing off-target toxicity. The success of this approach depends on the internalization and retention of the payload in target cells. This study introduces a method using a small protein domain engineered for conditional target affinity, enabling lysosomal trafficking independent of the biological fate of the receptor. Specifically, we describe the development of an EGF receptor binder, CaRA EGFR , with calcium-regulated affinity (CaRA), meaning the target binding strength is tailored by the available calcium concentration. This allows for endosomal dissociation, as calcium levels are lower in endosomes than in the bloodstream. Affinity measurements and structural modeling reveal the molecular basis of the calcium modulated affinity. Live cell imaging demonstrates efficient internalization and lysosomal trafficking of the calcium-dependent domain, while the EGF receptor is recycled to the membrane. When used as a drug carrier, CaRA EGFR effectively delivers the toxin to the lysosomes, resulting in potent cytotoxicity with an IC50 of 0.8 nM in EGFR-expressing cancer cells
GPT-4o mini: Non-social science research article
Lamprey FOXN1 rescues the block of thymic epithelial cell development in the mouse Foxn1 -deficient thymic rudiment
Ryo Morimoto, Gaoqun Zhang, Oliver S. Thomas, Margaret F. Docker, Jonah L. Yick, Floriaan Devloo-Delva, Jeremy Swann, Dagmar Diekhoff, Thomas Boehm
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All vertebrate adaptive immune systems exhibit distinct lymphocyte lineages. In jawless vertebrates, such as lampreys, T-like cells are thought to develop in lympho-epithelial structures at the tips of gill filaments, termed thymoids. However, it is unclear whether thymoids are functionally equivalent to the thymus of jawed vertebrates. Indeed, because the structural modules that are somatically assembled to form the antigen receptors of jawless and jawed vertebrates differ, development and selection of T cells may be governed by clade-specific genetic networks. To address this question, we have replaced the mouse Foxn1 gene, a key regulator of the thymic microenvironment in jawed vertebrates, with the orthologous FOXN1 lamprey gene, which is expressed in the thymoids alongside genes orthologous to known targets of the mouse Foxn1 transcription factor. The reconstituted thymi support normal T cell development, and, to a lesser extent, also support B cell development, indicating that the lamprey FOXN1 gene can rescue the block of thymic epithelial cell differentiation in mice deficient for the endogenous Foxn1 gene. The absence of overt autoimmunity in transgenic mice suggests that the reconstituted thymic microenvironment directs the development of a self-tolerant T cell repertoire. These findings highlight the remarkable similarity of thymic epithelial functions in jawed and jawless vertebrates, despite more than 500 My of independent evolution. Our results thus suggest that the emergence of the Foxn1 transcription factor in the common ancestor of vertebrates was associated with the advent of a specialized tissue environment supporting the development and selection of T cells.
GPT-4o mini: Non-social science research article
Isoform-specific regulation of PKM by acetylation
Dariia Pavlenko, Joaquin Tamargo-Azpilicueta, Hila Nudelman, Yuval Ankri, Anat Shahar, Irene DĂ­az-Moreno, Eyal Arbely
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Pyruvate kinase (PK) is a crucial glycolytic protein involved in vital cellular processes ranging from cell proliferation to immune responses. The activity and functions of PK are tightly regulated by diverse mechanisms, including posttranslational NÏ”-lysine acetylation. Although previous studies have explored the impact of acetylation on selected lysine residues within the M2 isoform of PK (PKM2), a more comprehensive selection of acetylation sites and their respective effects on both PKM2 and the highly homologous PKM1 isoform is lacking. Here, we describe the structural, functional, and regulatory effects of site-specific acetylation on an expanded set of conserved lysines in PKM2 and selected lysines in PKM1. To study homogeneously acetylated proteins, we genetically encoded the incorporation of acetylated lysine into PKM variants expressed in bacteria and cultured mammalian cells. Our integrated biochemical, structural, and computational approach revealed K115 acetylation as an inhibitory modification in both PKM1 and PKM2 that stabilizes a closed active site conformation of the proteins. We also show that, in contrast to K115 acetylation, previously reported acetylation of K305 inhibits PKM2 but has no effect on the activity and oligomerization of PKM1. These findings propose the existence of both uniform and isoform-specific regulatory mechanisms of PKM, mediated by acetylation.
GPT-4o mini: Non-social science research article
Lrig1 -expressing quiescent stem cells maintain vocal fold mucosal homeostasis via Notch signaling
Vlasta Lungova, Jessica M. Fernandez, Yujia Cai, Christina Kendziorski, Susan L. Thibeault
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Identifying progenitor cells in laryngeal and vocal fold (VF) mucosa is essential for advancing stem cell–based therapies for VF diseases. In this study, we used Lrig1 (leucine-rich repeats and immunoglobulin-like domains 1) gene to label tissue-resident stem cells within laryngeal and VF mucosa, aiming to investigate cellular networks underlying VF homeostasis and regeneration. Lrig1 + cells exhibited hallmark features of quiescent stem cells—including slow cycling, long-term persistence, and differentiation potential—and contributed to sustained VF regeneration and repair after naphthalene injury. By one week post injury Lrig1 + progeny restored the damaged VF epithelium. Transcriptionally, these cells suppressed cell type specific genes and proliferation while activating programs related to RNA metabolism, epigenetic regulation, and protein ubiquitination, consistent with quiescence and readiness for activation. Lrig1 + cells were enriched in basal, parabasal, and immature secretory populations within surface epithelium and submucosal glands, residing in niches characterized by transcriptional flexibility and spatial shielding from direct stress—features that likely prevent premature or chronic mobilization. Notably, analogous LRIG1 expressing cells were identified in human laryngeal and VF tissues, highlighting the translational relevance of our findings. To explore regulation of Lrig1 + cell quiescence, we conditionally deleted Notch1, which led to epithelial hyperplasia, expansion of secretory populations, and mucus hyperproduction. In summary, Lrig1 marks a conserved, quiescent stem cell population in the larynx and VFs that supports long-term tissue homeostasis and repair, with quiescence maintained via Notch1 signaling.
GPT-4o mini: Non-social science research article
Microbial necromass carbon enhances arsenic methylation in paddy soils
Jie Li, Zi-Yu Gao, Chuan Chen, Yurong Liu, Si-Yu Zhang, Jianming Xu, Yong-Guan Zhu, Xianjin Tang
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Microbial necromass carbon (MNC) constitutes a critical component of soil organic carbon. Yet, how MNC regulates microbial arsenic (As) methylation processes in soil remains unclear. Across major Chinese rice-growing regions, bacterial and fungal necromass carbon showed significant positive correlations ( P < 0.05) with the transcribed arsM gene. Soil incubation experiments with seven soils explored how straw and three types of MNC—gram-positive bacterial necromass carbon (G + -NC), gram-negative bacterial necromass carbon (G − -NC), and fungal necromass carbon (F-NC)—affect As methylation. Our results demonstrated that all types of MNC enhanced As methylation, and G − -NC exhibiting the most pronounced effect on methylated As accumulation. The addition of 10 to 60 mg G − -NC maximally increased As(III) by 43.0 to 75.9% and enhanced methylated As by 4.4- to 18.0-fold in soil porewater vs. the control. Further, metagenomic and metatranscriptomic analyses demonstrated that G − -NC addition upregulated the relative abundance of transcribed arsM and arsC2 genes, which were mostly assigned to Acidobacteriota , Pseudomonadota , Planctomycetota, and Bacteroidota . Notably, the transcriptional activity of arsM -harboring Methanosarcinales and Moorellales was markedly enhanced at the order level. By promoting As reduction process, G − -NC provides more substrates for As methylation process in soil. Furthermore, G − -NC could be used as a carbon source for As-methylating microorganisms, stimulating the transcriptional activity of arsM , which has been confirmed by the incubation experiment with pure culture of Paraclostridium benzoelyticum TC8. This study highlights the critical role of MNC in regulating As biogeochemistry, establishing a basis for predicting the extent of As methylation and risk of rice straighthead disease in paddy ecosystems.
GPT-4o mini: Non-social science research article
Neural representation of the decisional reference point in monkeys
Duc Nguyen, Erin L. Rich, Joni D. Wallis, Kenway Louie, Paul W. Glimcher
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The decisional reference point serves as a hidden benchmark for evaluating options in decision-making. Despite extensive behavioral evidence for the existence of the reference point, its neural instantiation remains unclear. To identify reference point encoding at both the single-neuron and population levels, we analyzed neural activity from macaques performing a wealth accumulation task that dissociated objective reward values from the reference point. Across six frontal regions, we found that reference-related signals were broadly distributed at the single-neuron level. However, at the population level, only the ventral bank of the anterior cingulate cortex (vbACC) encoded the reference point significantly. In contrast, the dorsal bank of ACC and dorsolateral prefrontal cortex showed population-level encoding of reference-dependent subjective value signals. The temporal sequence of these signals and their known anatomical connectivity hints at a dedicated neural circuit for reference dependence, with the vbACC potentially serving as a global source of reference point signal modulating activity in downstream value-encoding regions.
GPT-4o mini: Non-social science research article
SurFlex microscopy: Measuring flexibility of surface-tethered biomolecules
Aymeric Chorlay, Siddhansh Agarwal, Lena Blackmon, Andres Dextre, Daniel A. Fletcher
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The flexibility of tethered molecules, such as those bound to biological membranes, is an important property that can influence molecular height, mobility, and accessibility. However, quantifying the flexibility of surface-tethered biomolecules in aqueous environments has been difficult due to a lack of experimental tools. Here, we introduce SurFlex microscopy, a method based on fluorescence anisotropy that exploits the relationship between the conformational dynamics of a tethered molecule and the rotational diffusion of an attached fluorophore to extract information about molecular flexibility. By analyzing the polarization state of photons emitted after polarized excitation, we quantify apparent molecular flexibilities that include effects of tethering, self-interactions, and buffer conditions. We first demonstrate the capabilities of SurFlex microscopy by measuring the flexibility of bilayer-tethered single-stranded DNA (ssDNA) of different lengths and nucleotide sequences. We find that sequence significantly impacts ssDNA flexibility, consistent with theoretical estimates, with weak intramolecular interactions in random sequences leading to higher apparent stiffness. Interestingly, we show that a pathological DNA sequence linked to Huntington’s disease exhibits unusual flexibility despite intramolecular interactions. We next extend SurFlex microscopy to live cells by measuring surface glycoprotein flexibility on red blood cells using fluorescent lectins. We show that trypsinization decreases glycan fluctuations, demonstrating that modifications to the cell surface can alter the flexibility of remaining surface molecules. SurFlex microscopy provides a tool for quantifying molecular flexibility that can be used to study the role of tethered surface molecules in fundamental biological processes.
GPT-4o mini: Non-social science research article
VGLL1 contributes to both the transcriptome and epigenome of the developing trophoblast compartment
Ruben I. Calderon, Nirvay Sah, Molly Huang, Sampada Kallol, Ryan H. Kittle, Walee B. Shaik, Ahmed Abdelbaki, Jennifer N. Chousal, Robert Morey, Tony Bui, Alejandra Mitre, Norah M. E. Fogarty, Claudia Gerri, Zoe Manalo, Claire Zheng, Peter De Hoff, Pratik Home, Kathy K. Niakan, Heidi Cook-Andersen, Kathleen M. Fisch, Soumen Paul, Francesca Soncin
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The trophectoderm (TE), the first lineage specified during mammalian development, initiates implantation and gives rise to placental trophoblasts. While animal models have elucidated key conserved signaling pathways involved in early TE specification, including bone morphogenetic protein (BMP), WNT, and HIPPO, species-specific differences during early development emphasize the need for human-specific models. We previously identified VGLL1, a coactivator of TEAD transcription factors, as a human-specific placental marker. In this study, we employed a pluripotent stem cell (PSC)-based model of TE induction by BMP4 to investigate chromatin remodeling and transcriptional dynamics during TE formation. BMP4-induced chromatin accessibility changes promoted a trophoblast gene expression program, while mesoderm lineage markers were only transiently expressed upon canonical WNT activation. We found that VGLL1 was expressed downstream of key TE transcription factors (GATA2/3, TFAP2A/C) but was essential for establishment of full trophoblast identity by up-regulating the epidermal growth factor receptor (EGFR) and reinforcing GATA3 expression through positive feedback. Notably, VGLL1 enhanced canonical WNT signaling via direct regulation of WNT receptors and effectors. We also identified KDM6B, a histone demethylase that removes H3K27me3 repressive marks, as a direct VGLL1 target. KDM6B facilitated activation of bivalent promoters associated with TE markers, linking epigenetic regulation to lineage identity. Our findings establish a mechanistic framework positioning VGLL1 as a central regulator that integrates HIPPO, BMP, and WNT signaling pathways to drive establishment of human TE.
GPT-4o mini: Non-social science research article
Variability of annual polar motion and its relationship to the Chandler wobble
Songyun Wang, Clark R. Wilson, Jianli Chen, Ki-Weon Seo, Yuning Fu, Weijia Kuang
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Given the large amplitude of prograde annual polar motion, we are able to quantify year-to-year variability of prograde annual excitation amplitude since pre-1900 observations. We obtain a Prograde Annual Amplitude Modulation (PAAM) time series and use it to investigate several key topics, including variability in annual excitation amplitude, its climatic sources, and its potential role in Chandler wobble (CW) excitation. An important finding is that the PAAM series undergoes multiyear episodes of a near six-year oscillation (SYO). This provides observational evidence for a SYO in Earth’s climate and rotational dynamics seen in recent data and confirms SYO behavior in the climate system over the past century. Using climate model and other data, we find that several fluid components of Earth’s climate system contribute to the SYO, with atmospheric sources playing the dominant role. A SYO [~0.16 cycles per year (cpy)] modulation of the annual component introduces variations at the sum and difference frequencies (1 + 0.16 cpy and 1 − 0.16 cpy). Because the difference frequency 0.84 cpy is near the Chandler frequency, the SYO may be important in understanding CW excitation. Our results show the SYO contributes significantly to the excitation of CW. Year-to-year variability of the annual excitation was originally proposed as an excitation mechanism by Harold Jeffreys in 1940, and we confirm that more than half the CW excitation power can be attributed to this cause. We also found annual excitation modulation at a period near 17 mo (~0.7 cpy) that is a source of excitation power near 1 ± 0.7 cpy.
GPT-4o mini: Non-social science research article
A legacy of genetic entanglement with wolves shapes modern dogs
Audrey T. Lin, Regina A. Fairbanks, Jose Barba-Montoya, Hsiao-Lei Liu, Logan Kistler
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Dogs evolved through interactions between people and gray wolves during the Late Pleistocene and have been ubiquitous in human societies ever since. Instances of wolf-to-dog introgression are rare, but adaptive introgression has been shown in association with high-altitude survival. Any widespread gene flow, however, has fallen below thresholds of detection in genome-wide statistical assessments. To reexamine evidence of dog–wolf gene flow, we analyzed 2,693 published dog and wolf genomes and combined highly sensitive local ancestry inference and phylogenomic analyses of nuclear genes, mitochondrial genomes, and Y-chromosome sequences. Although dogs and wolves segregate decisively at the nuclear level, no individual nuclear gene tree supports dog monophyly. Uniparental markers show mixed and interleaved dog and wolf clades with strong support and incongruent phylogenetic topologies. Using local ancestry inference, we find that 64.1% of modern breed dogs carry wolf ancestry from admixture that occurred nearly a thousand generations ago on average and now covers ~0.14% of their individual nuclear genomes. Among modern free-living village dogs (n = 280), 100% of analyzed genomes carry wolf ancestry. We find that wolf ancestry in dog breeds correlates with functional traits including size, breed category, and personality characteristics. In village dogs, wolf ancestry is enriched at olfactory receptor genes, suggesting adaptive introgression for sensory acuity that may have helped these free-living dogs survive in more challenging environments. In total, dog–wolf admixture has likely been an important factor in shaping the evolution of modern dogs.
GPT-4o mini: Non-social science research article
Anomalous fracture behavior in borosilicate glass facilitated by stress-induced molecular rearrangements
Jet Lem, Eric R. Sung, Alexei A. Maznev, Yun Kai, Alan F. Schwartzman, Steven E. Kooi, Keith A. Nelson
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Silica-based glasses have found numerous applications in every field of human endeavor. Understanding their mechanical behavior under high strain rates is essential for the use of these materials in extreme environments. We report on a highly unusual fracture behavior observed in borosilicate glass facilitated by stress-induced molecular rearrangements, allowing the glass to withstand tensile stresses up to 11 GPa. Converging surface acoustic waves (SAW) with controlled amplitude are generated optically and used to investigate the high-strain-rate (10 8 s −1 ) fracture behavior of borosilicate glass. Above a tensile stress threshold of 6 GPa, fracture of the glass surface is observed, characterized by ejection of material and radial cracking. Unexpectedly, upon further increase of the SAW stress, a second threshold of 8 GPa tensile stress is observed above which the fracture probability dramatically decreases. Raman spectra and nanoindentation measurements of shocked samples indicate significant changes in the topology and coordination numbers of silicon and boron atoms in the amorphous network. These results suggest the ability of thresholded atomic rearrangements to serve as an intrinsic high-strain-rate toughening mechanism for enhanced fracture toughness in amorphous borosilicate glass under dynamic strain conditions.
GPT-4o mini: Non-social science research article
Small siphophage binding to an open state of the LptDE outer membrane lipopolysaccharide translocon
Emily Dunbar, Robert Clark, Arnaud Baslé, Shenaz Allyjaun, Hector Newman, Julia Hubbard, Syma Khalid, Bert van den Berg
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Bacteriophages are bacterial viruses that provide alternatives to small-molecule drugs to combat infections by antibiotic-resistant bacteria. To infect a bacterial host, a phage needs to bind to the bacterial surface via receptor binding proteins (RBPs), which are critical for determining host specificity. For functionally important receptors, the RBP–receptor interaction could be exploited via phage steering, where emerging bacterial resistance due to receptor modification could make bacteria less fit or virulent. Despite this, relatively little is known about RBP–receptor interactions. Here, we build on the recent discovery of coliphages that have the outer membrane (OM) lipopolysaccharide translocon LptDE as their terminal receptor and show via cryogenic electron microscopy that, surprisingly, the RBP of the small siphophage Oekolampad binds to a hitherto unobserved, open state of LptDE. The open lateral gate of LptD is occupied by a ÎČ-strand peptide originating from the degraded N-terminal jellyroll domain of LptD, suggesting the possibility of LptD inhibition via peptidomimetics. A structure of LptDE in complex with the superinfection exclusion (SE) protein Rtp45 of the Oekolampad-related phage Rtp shows a mechanism of SE where Rtp45-induced conformational changes in LptD resulting from steric clashes preclude RBP binding. Finally, analysis of spontaneous Oekolampad-resistant Escherichia coli mutants identifies mutations in LptD that abolish the LptDE–RBP interaction in vitro. SDS-EDTA sensitivity assays of the mutants show no major OM defects, consistent with largely preserved LptDE function, and suggesting that phage steering via LptDE might be challenging.
GPT-4o mini: Non-social science research article
Exercise suppresses DEAF1 to normalize mTORC1 activity and reverse muscle aging
Sze Mun Choy, Kah Yong Goh, Wen Xing Lee, Weiyi Jiang, Qian Gou, Priya D. Gopal Krishnan, Shi Chee Ong, Kenon Chua, Nathan Harmston, Hong-Wen Tang
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Skeletal muscle is essential for movement, respiration, and metabolism, with mTORC1 acting as a key regulator of protein synthesis and degradation. In aging muscle, mTORC1 becomes overactivated, contributing to sarcopenia, though the mechanisms remain unclear. Here, we identify DEAF1, a FOXO-regulated transcription factor, as a key upstream driver of mTORC1 in aged muscle. Elevated Deaf1 expression increases mTOR transcription, leading to heightened mTORC1 activity, impaired proteostasis, and muscle senescence. Remarkably, exercise suppresses Deaf1 expression via FOXO activation, restoring mTORC1 balance and alleviating muscle aging. Conversely, FOXO inhibition or Deaf1 overexpression blocks exercise benefits on muscle health. These findings highlight DEAF1 as a critical link between FOXO and mTORC1 and suggest that targeting the FOXO–DEAF1–mTORC1 axis may offer therapeutic potential to preserve muscle function during aging.
GPT-4o mini: Non-social science research article
Genetic testing predicts appearance but not behavior in dogs
Kathryn A. Lord, Vista Sohrab, Kasia Bryc, Michelle E. White, Brittney Kenney, Kathleen Morrill Pirovich, Frances L. Chen, Elinor K. Karlsson
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Genetic tests for behavioral and personality traits in dogs are now being marketed to pet owners, but their predictive accuracy has not been validated. To evaluate the reliability of such tests, we analyzed data from Darwin’s Ark, a community science initiative that includes over 3,000 dogs with both genetic data and individual-level behavioral phenotypes. None of the candidate variants had significant associations or predictive power for behavioral traits as previously reported. However, we found strong associations with aesthetic traits that differentiate breeds, such as height, leg length, and ear shape. Our results suggest that earlier studies using breed-average phenotypes, rather than individually measured phenotypes, were confounded by population structure. Behavior in dogs is polygenic and complex, and thus cannot be accurately predicted using tests that consider only a few genetic variants. Furthermore, behavior in dogs is only moderately heritable, and environmental influences inherently limit the potential accuracy of genomic predictions. Developing meaningful, accurate genetic predictions for complex traits that can improve dog health and welfare will require very large cohorts of individually phenotyped dogs.
GPT-4o mini: Non-social science research article
Brain-wide mapping of developmental trajectories of cerebellar efferent projections
Raquel Murcia-Ramón, Martina Riva, Sergio Muñoz-Cobos, Ángeles Arzalluz-Luque, Juan Antonio Moreno-Bravo
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Long-range cerebellar outputs are critical for shaping brain-wide functional architecture, influencing motor, cognitive, and affective domains. Proper cerebellar development and its efferent circuits are essential for brain maturation, and disruptions in these pathways have been implicated in neurodevelopmental disorders, such as autism spectrum disorder and schizophrenia. However, despite the early developmental onset, the spatiotemporal dynamics of cerebellar connectivity remain largely unknown, limiting mechanistic understanding of cerebellar contributions to brain development and disease. Here, we combine viral genetic tracing with high-resolution whole-brain 3D imaging to generate a comprehensive spatiotemporal map of cerebellar output development in mice. This systematic characterization uniquely distinguishes how excitatory and inhibitory cerebellar projections establish, expand, and refine their connectivity across the brain. Both axon types reach their principal brain targets within a narrow perinatal window, coinciding with the earliest formation of presynaptic terminals, and subsequently undergo postnatal expansion followed by region- and cell type–specific refinement. These findings define critical windows in the assembly of cerebellar output circuits, providing a framework to decipher the principles of cerebellar circuit formation and their impact on brain-wide function. Importantly, they also pinpoint periods of heightened vulnerability, when genetic or environmental perturbations are most likely to derail cerebellar-driven circuit maturation. By establishing this developmental blueprint, our study not only advances fundamental knowledge of brain wiring but also lays the groundwork for translational efforts to connect early cerebellar dysfunction with the origins of neurodevelopmental disorders.
GPT-4o mini: Non-social science research article
Uncovering heterogeneous intercommunity disease transmission from neutral allele frequency time series
Takashi Okada, Giulio Isacchini, QinQin Yu, Oskar Hallatschek
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The COVID-19 pandemic has underscored the need for accurate epidemic forecasting to predict pathogen spread, evolution, and evaluate intervention strategies. Forecast reliability hinges on detailed knowledge of disease transmission across population segments, which may be inferred from contact surveys or mobility data. However, these indirect approaches make it difficult to estimate rare transmissions between socially or geographically distant communities. We show that the steep ramp-up of genome sequencing surveillance during the pandemic can be leveraged to directly identify transmission patterns between geographically defined communities. Our approach uses a hidden Markov model to infer the fraction of infections a community imports from others based on how rapidly allele frequencies in the focal community converge to those in the donor communities. Applying this method to SARS-CoV-2 sequencing data from England and the United States, we uncover networks of intercommunity transmission that reflect geographical relationships while exposing significant long-range interactions. The scaling of importation rate with distance is consistent across both countries, yet weaker than expected based on mobility data, highlighting limitations of indirect inference. We show that transmission patterns can change between waves of variants of concern and analyze how the inferred heterogeneity in intercommunity transmission impacts evolutionary forecasts. While applied here to geographically defined communities, our approach could be applied to those defined by other traits (e.g., age, socioeconomic status), provided time-series data can be stratified accordingly. Overall, our study highlights population genomic time series data as a crucial record of epidemiological interactions, which can be deciphered using tree-free inference methods.
GPT-4o mini: Non-social science research article
Sugar caps protect mRNAs from decay
Rebecca Forbes, Boris Görke
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GPT-4o mini: Non-social science research article
Inhibition of fusidic acid resistance through restricting conformational flexibility in domain III of EF-G
Alexandra Schindl, Megan E. Jones, Leela Ghimire, Arnout P. Kalverda, Gemma Wildsmith, Antonio N. Calabrese, Jennifer H. Tomlinson
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Fusidic acid (FA) is one of few remaining antibiotics active against Methicillin-resistant Staphylococcus aureus . FusB confers resistance to FA by rescuing the translocation factor Elongation Factor-G (EF-G) from FA-stalled ribosome complexes. FusB induces allosteric effects on dynamics in EF-G, causing significant changes in the conformational flexibility of domain III that result in an increase in a minor, more disordered state, overcoming the steric block induced by FA. We show that restraining flexibility in the two central ÎČ-strands of EF-G domain III prevents the FusB-induced increase in this minor state population, preventing FusB-mediated release of EF-G from the ribosome and thereby reinstating FA-induced stalling of protein synthesis. We further identify a region controlling access to the minor state population, potentially pinpointing the allosteric mechanism within domain III by which FusB acts. Our findings suggest a possible region that could be targeted for rational design of an inhibitor of FusB-mediated conformational flexibility, reinstating FA sensitivity even in the presence of FusB, which could rejuvenate the efficacy of this clinically important antibiotic.
GPT-4o mini: Non-social science research article
Overestimated natural biological nitrogen fixation translates to an exaggerated CO 2 fertilization effect in Earth system models
Sian Kou-Giesbrecht, Carla R. Reis Ely, Steven S. Perakis, Cory C. Cleveland, Duncan N. L. Menge, Sasha C. Reed, Benton N. Taylor, Sarah A. Batterman, Timothy E. Crews, Katherine A. Dynarski, Maga Gei, Michael J. Gundale, David F. Herridge, Sarah E. Jovan, Mark B. Peoples, Johannes Piipponen, Emilio RodrĂ­guez-Caballero, Verity G. Salmon, Fiona M. Soper, Anika P. Staccone, Bettina Weber, Christopher A. Williams, Nina Wurzburger
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CO 2 fertilization of the terrestrial biosphere is limited by nitrogen. Biological nitrogen fixation (BNF) is the dominant natural nitrogen source to the terrestrial biosphere and can alleviate nitrogen limitation but is poorly constrained in Earth system models (ESMs). Here, we compare terrestrial BNF from an ensemble of ESMs of the 6th Coupled Model Intercomparison Project to a new global synthesis of observations across natural and agricultural biomes. We find that compared to observations, ESMs underestimate agricultural BNF but overestimate natural BNF in the present day by over 50%. Natural BNF is overestimated in the most productive ecosystems that contribute most to the terrestrial carbon sink (forests and grasslands). ESMs with different BNF representations yield a range of BNF responses to CO 2 enrichment. Some ESMs with phenomenological representations of BNF predict a natural BNF increase in response to a doubling of CO 2 that aligns with a meta-analysis of CO 2 enrichment experiments (31% increase) but fail to account for the substantial carbon cost of BNF. In contrast, ESMs with mechanistic representations of BNF account for its carbon cost as well as its regulation by nitrogen limitation but overestimate the BNF response to a doubling of CO 2 (135% increase). Overall, all current BNF representations in ESMs fall short of fully capturing its response to rising atmospheric CO 2 . Finally, we find a positive correlation between modeled present-day natural BNF and the CO 2 fertilization effect across ESMs, suggesting that overestimated natural BNF translates to an exaggerated CO 2 fertilization effect of approximately 11% in ESMs.
GPT-4o mini: Non-social science research article
ATG2 is a triglyceride transfer protein
Justin L. Korfhage, Helin Elhan, Neng Wan, Yingying Lu, Lisa Kauffmann, Govindaiah Pilli, Devin M. Fuller, Anna M. Rios, Karin M. Reinisch, Krishna Rao Maddipati, Abdou Rachid Thiam, Thomas J. Melia
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Bridge-like lipid transfer proteins (BLTPs) are established to function in phospholipid transport between bilayers at organelle–organelle contact sites. However, the BLTP ATG2A also associates with lipid droplets in cells, which present a unique phospholipid monolayer topology and which are composed of many additional types of lipids. Whether BLTPs are active in this environment and which lipid species are substrates for transport has been unknown. Here, we use synthetic organelles with bilayers (liposomes), monolayers (artificial lipid droplets), or a mixture of the two membrane structures to demonstrate the tight binding of ATG2 specifically to monolayers via its collection of COOH-terminal amphipathic helices. This stable binding enables ATG2 to transfer phospholipids much more effectively. Unexpectedly, the neutral lipid triacylglycerol is also rapidly transported, with kinetics similar to those of phospholipid transport. Lipidomics of purified ATG2A suggests that a similar transfer of both phospholipids and triacylglycerol occurs in cells. Our work implies that BLTPs likely collect on LDs as part of a broad lipid homeostasis program, which will include the movement of both phospholipids and neutral lipids.
GPT-4o mini: Non-social science research article
Large drainage systems produced half of Mars’ ancient river sediment
Abdallah S. Zaki, Timothy A. Goudge, David Mohrig
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Large, continental-scale drainage systems occupy nearly half of Earth’s land, shaping diverse ecosystems, with their activity primarily driven by climate and tectonism. Here, we investigate whether Mars, which lacks Earth’s tectonism, has similarly large drainage systems that could have impacted the extent of habitable environments, sediment transport, and the formation of large sedimentary basins. We reconstruct large drainage systems using globally mapped ancient martian water-formed topography—valley networks, outlet canyons, and fluvial depositional systems—revealing large drainage systems (>10 5 km 2 ) similar in scale to those on Earth. However, collectively these systems cover only ~5% of ancient martian terrain (>3.7 Ga), approximately nine times less than their counterparts on Earth. This estimate is conservative due to erosion, burial, and impact cratering, which have likely modified their preservation. Nevertheless, when quantifying the eroded sediment volumes from these large drainage systems, we show that they contributed nearly half (42%) of Mars’ ancient river-sediment budget. We further calculated the sediment eroded from large drainage systems surrounding the largest known fluvial depositional landforms on Mars and found that they potentially contributed ~21% of the planet’s river sediment budget, which we hypothesize facilitated the buildup of these sedimentary features. Our results indicate that although a substantial portion of Mars’ fluvial sediment was routed through large-scale drainage systems, sediment transport was predominantly accomplished within smaller-scale local basins. This drainage structure likely created a mosaic of habitable environments across the surface and facilitated significant sediment accumulation in a limited number of large sedimentary basins.
GPT-4o mini: Non-social science research article
Woodlands of Antiquity: A millennium of dendrochronological data on forest exploitation and timber economy between the Alps and the Atlantic
Bernhard Muigg, Kristof Haneca, Willy Tegel, Martin GrĂŒnewald, Vincent Bernard, Niels Bleicher, François Blondel, Matthias Bolliger, Manuel Broich, Yann Couturier, Sjoerd van Daalen, Marta DomĂ­nguez-DelmĂĄs, Olivier Girardclos, Franz Herzig, Fabien Langenegger, Yannick Le Digol, Oliver Nelle, Kurt Nicolussi, Monika OberhĂ€nsli, Christophe Perrault, Andreas Rzepecki, Yardeni Vorst, Julia WeidemĂŒller, Thorsten Westphal, Andrea Seim
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The Roman Empire dominated large parts of western and central Europe for over half a millennium, leaving a lasting cultural imprint on the continent. In the densely forested regions north of the Alps, material culture was characterized by the use of wood as a primary raw material. Yet, the drivers behind the Roman timber economy and its impact on woodland exploitation and forest dynamics remain poorly understood. To address this, we investigated a unique collection of 20.397 dendrochronologically dated archaeological woods spanning a millennium of European Antiquity (300 BCE–700 CE). Our results reveal significant increases in exploitation during Roman occupation, with regional differences in onset, intensity, and duration. Due to rising civilian and military demand for wood, Roman logging increasingly extended into primary forests far from settlements, which indicates a significantly improved infrastructure, professionalism, and organization of lumbering. The 3rd century CE marks a tipping point, with sharp declines in wood use and long-distance transport, alongside evidence of overexploitation of old-grown forests (trees aged over 200 y). Late Antiquity is characterized by an overall decline in felling activities during the 4th and 5th centuries and a reestablishment of old-grown forests, manifested by increased tree ages thereafter. These findings demonstrate how Roman imperial expansion fundamentally reshaped woodlands north of the Alps and contribute to the environmental and economic history of European Antiquity.
GPT-4o mini: Non-social science research article
Neuroplastin-55 is a receptor of Manf and protects against diet-induced obesity by promoting adipose browning
Qingyi Jia, Jinhang Zhang, Haiying Song, Jiahao Chen, Zhenyu Zhang, Huihui Yu, Yi Chen, Qinhui Liu, Xiandan Jing, Haixia Xu, Jingwei Li, Yimin Xiong, Meilin Ma, Na Yang, Junyan Li, Yining Xu, Yanping Li, Jinhan He
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The browning of white adipose tissue (WAT) enhances thermogenesis and holds great potential in obesity treatment. Membrane receptors have been proven as essential factors during WAT browning. In this study, we found that transmembrane receptor neuroplastin-55 (Np55) was markedly upregulated in the adipose tissue of both obese individuals and mice. Fat-specific Np55 knockout (Np55 FKO ) sensitized mice to high-fat diet-induced obesity and metabolic disorders, which was attributed to impaired energy expenditure and WAT browning. We identified that mesencephalic astrocyte-derived neurotrophic factor (Manf) acts as a ligand for Np55 with high binding affinity. Mechanistically, Np55 forms a complex with tumor necrosis factor receptor associated factor-2 (TRAF2) and apoptosis signal-regulating kinase 1 (ASK1) to activate p38 mitogen-activated protein kinase (MAPK) signaling pathway and conduct WAT browning after Manf stimulation. Additionally, we identified a single-nucleotide polymorphism (rs2470738600) in Manf compromised the binding affinity to Np55 and thermogenic capacity. Finally, we showed that Np55 is indispensable for Manf-induced thermogenesis and weight loss in obese mice. Our results underscore the pivotal role of Np55 as a receptor of Manf in maintaining metabolic homeostasis, highlighting its potential as a therapeutic target for obesity and related disorders.
GPT-4o mini: Non-social science research article
Cytomegalovirus disrupts Lamin A/C to control microtubule-mediated nuclear movement and cell migration
Jamil Mahmud, Ipsita Nandi, Dean J. Procter, Derek Walsh
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Human cytomegalovirus (HCMV) disrupts the inner nuclear Lamin A/C meshwork to facilitate virion egress. Here, we show that targeting Lamin A/C also plays a previously unrecognized role in HCMV-induced rewiring of cytoskeletal connections that control nuclear movement and cell migration at later stages of infection. Specifically, HCMV was found to employ distinct strategies to downregulate Lamin A/C and SUN2, which together regulate linker of nucleoskeleton and cytoskeleton (LINC) complexes that most often connect the nuclear membrane with cytoplasmic actin filaments. Unexpectedly, inhibition of the viral kinase, pUL97, or expression of nonphosphorylatable mutants of Lamin A/C failed to restore SUN2 expression or significant actin filament assembly. Moreover, exogenous reexpression of SUN2 also failed to restore actin filaments. Instead, restoration of SUN2 or Lamin A/C expression impaired the formation of acetylated microtubules in infected cells. Furthermore, inhibition of pUL97, expression of Lamin A/C mutants or depletion of the tubulin acetyl transferase, ATAT1, all impaired HCMV-induced nuclear movement and cell migration. Our findings reveal that HCMV uses multiple strategies to selectively downregulate Lamin A/C and SUN2 in order to prevent these proteins from interfering with the formation of acetylated microtubules that mediate nuclear movement and cell migration, revealing additional roles for Lamin A/C remodeling during infection and insights into how cells control cytoskeletal interactions with the nucleus.
GPT-4o mini: Non-social science research article
Lagrangian tracking reveals competing influences of clustering and turbulence on the rise velocity of bubble swarms
Hendrik Hessenkemper, Andrew D. Bragg, Dirk Lucas, Tian Ma
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The rise velocity of bubble swarms is a fundamental property in many natural and industrial flows. A central question is whether clustering of bubbles enhances or suppresses their rise velocity compared to isolated single bubbles in quiescent fluid. We address this issue using a recently developed three-dimensional Lagrangian bubble tracking technique, with accurate rise velocity measurements obtained by simultaneously tracking tracer particles around each bubble. For bubbles within swarms, we find that clustered bubbles rise faster than unclustered ones. A conditional analysis based on cluster orientation suggests that this enhancement results from a wake suction effect acting on trailing bubbles. However, even clustered bubbles rise considerably slower than isolated single bubbles due to their exposure to turbulence generated by other bubbles, which randomizes their trajectories and reduces rising efficiency.
GPT-4o mini: Non-social science research article
Immunogenic cell death unlocks the potential for combined radiation and immunotherapy
Somiya Rauf, Alexandra Smirnova, Andres Chang, Yuan Liu, Yi Jiang
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Immunogenic cell death (ICD) enhances antitumor immunity by releasing tumor-associated antigens and activating the antitumor immune system response. Here, we develop a mathematical model to quantify the role of ICD in optimizing the efficacy of combined radiotherapy (RT) and macrophage-based immunotherapy. Using preclinical murine data targeting the SIRP α -CD47 checkpoint, we show that RT alone induces minimal ICD, whereas disrupting the SIRP α -CD47 axis significantly enhances both phagocytosis and systemic immune activation. Our model predicts an optimal RT dose (6 to 8 Gy) for maximizing ICD, a dose-dependent abscopal effect, and a hierarchy of treatment efficacy, with SIRP α -knockout macrophages exhibiting the strongest tumoricidal activity. These findings provide a quantitative framework for designing more effective combination therapies, leveraging ICD to enhance immune checkpoint inhibition and radiotherapy synergy.
GPT-4o mini: Non-social science research article
Growth hormone regulates the stem cell population in the growth plate
Nelson Tsz Long Chu, Baoyi Zhou, Jussi O. Heinonen, Ostap Dregval, Xin Liu, Dana Trompet, Xin Tian, Phillip T. Newton, Lars SĂ€vendahl, Ameya Bendre, Ola Nilsson, Claes Ohlsson, Andrei S. Chagin
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Growth hormone (GH) is a key systemic regulator of longitudinal bone growth and is widely used in pediatric endocrinology, including in patients without GH deficiency. Its primary target is the growth plate—a cartilaginous structure driving bone elongation—yet the cellular mechanisms underlying GH action remain incompletely understood. Here, we identify a direct role for GH in regulating a recently defined population of cartilaginous stem cells within the growth plate. Using multiple transgenic mouse models, we show that GH reduces the pool of slow-cycling, label-retaining stem cells by promoting their differentiation into transient progenitors. Clonal and lineage-tracing analyses reveal that these stem cells renew via population asymmetry and that GH promotes their committed cell division, leading to stem cell depletion. Conversely, genetic deletion of the GH receptor in stem cells impairs their ability to generate chondrocytes, confirming a direct GH effect. These findings support a general principle by which endocrine cues regulate tissue regeneration, establish a mechanistic link between GH signaling and cartilaginous stem cells, and provide a potential explanation for certain related clinical observations, such as the declining long-term efficacy of GH therapy.
GPT-4o mini: Non-social science research article
Photoemission electron microscopy for connectomics
Gregg Wildenberg, Kevin M. Boergens, Lola Lambert, Ruiyu Li, Allison Craig, Michael K. L. Man, Amin Moradi, Janek Rieger, Hengli Duan, Sarnjeet S. Dhesi, Gabriel Karras, Francesco Maccherozzi, Keshav Dani, Rudolf Tromp, Sense Jan van der Molen, Sarah B. King, Narayanan Kasthuri
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Photoemission electron microscopy (PEEM) offers a potential third modality for large-volume connectomics alongside transmission electron microscopy (TEM) and scanning electron microscopy (SEM). We image osmium stained, ultrathin brain sections on gold coated silicon at synaptic resolution using commercial PEEMs. At coarser resolution, we demonstrate that ultraviolet laser illumination enables gigavoxel-per-second acquisition rates without thermal damage. PEEM combines TEM-like parallel detection with SEM-compatible solid supports into a potentially scalable and cost-effective approach for large-volume connectomes.
GPT-4o mini: Non-social science research article
Local negative frequency dependence can decrease global coexistence in fragmented populations
Anush Devadhasan, Oana Carja
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Most biological populations are rich in diversity, and negative frequency-dependent (NFD) selection is a well-known mechanism thought to underlie this stable coexistence of multiple variants. Recent studies confirm its widespread presence at local spatial scales, however it remains unclear whether these local-scale dynamics are sufficient to maintain diversity across larger, landscape-level scales. While prior theoretical work has found that local NFD selection can indeed promote global coexistence, these studies only analyzed contiguous landscapes. In contrast, many ecosystems are not contiguous, but rather spatially fragmented or exhibit spatial variation in the local carrying capacity. Using a population-genetic model based on the classic island framework, we show that, in fragmented populations, NFD selection can paradoxically reduce coexistence and shorten fixation times, relative to neutrality. Fragmentation also generates a nonmonotonic relationship between fixation time and population size, with diversity minimized at intermediate scales, contrasting with the classical species–area relationship. Extending the model to a multispecies context reveals that these effects also shape species-level diversity. This allows us to develop a test for the influence of NFD selection in fragmented systems, based on the predicted nonmonotonic species–area relationship. Applying this test to an avian diversity dataset from the Ryukyu Islands, we find a signature suggesting that NFD selection and habitat fragmentation may interact to suppress biodiversity in this system. Together, our findings suggest that fragmentation can undermine the stabilizing effects of NFD selection, calling into question its generality as a mechanism for maintaining biodiversity in heterogeneous landscapes.
GPT-4o mini: Non-social science research article
A machine learning protocol for predicting structural distributions of amyloid-forming proteins from 2D IR spectra
Sheng Ye, BinBin Wang, Zhipeng Li, Lvshuai Zhu, Chang Yin Sun, Shaul Mukamel, Jun Jiang
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Protein misfolding plays a central role in diseases such as Alzheimer’s disease, Parkinson’s disease, type 2 diabetes, and transthyretin amyloidosis (ATTR), often driven by specific aggregation-prone segments such as A ÎČ 17–23 and A ÎČ 37–42 of amyloid- ÎČ 42 (A ÎČ 42), α -Syn 66–74 and α -Syn 71–82 of α -synuclein ( α -syn), hIAPP 22–27 of human islet amyloid polypeptide (hIAPP), and TTR 105–115 of transthyretin (TTR). Capturing the atomic-level structural features of these transient and dynamically fluctuating regions remains challenging. Two-dimensional infrared (2DIR) spectroscopy provides rich vibrational fingerprints that are highly sensitive to protein conformational dynamics, but extracting atomic-resolution structural information from these complex signals is nontrivial. In this study, we present a machine learning framework that integrates 2DIR spectra with deep structural modeling to reconstruct the three-dimensional atomic structures of monomeric intrinsically disordered aggregation-prone segments of amyloidogenic proteins. Using this model, we were able to predict the conformational ensembles of aggregation-prone segments from amyloid- ÎČ 42, α -synuclein, human islet amyloid polypeptide, and transthyretin, as well as the structural evolution of A ÎČ 42 bound to a small-molecule inhibitor, directly from computationally derived 2DIR spectra. An attention module highlights the most informative spectral features associated with local structural variations, providing interpretable links between spectra and structure. This generalizable strategy paves the way for interpreting time-resolved spectroscopic studies and offers a promising computational framework for probing misfolding-related structural dynamics and therapeutic mechanisms.
GPT-4o mini: Non-social science research article
Multipotent progenitors with distinct origins, clonal lineage fates, transcriptomes, and surface markers yield two hematopoietic trees
Fuwei Shang, Tamar Nizharadze, Robin Thiele, Branko Cirovic, Larissa Frank, Katrin Busch, Weike Pei, Thorsten B. Feyerabend, Thomas Höfer, Xi Wang, Hans-Reimer Rodewald
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Multipotent progenitors (MPP) are the quantitative source of native hematopoiesis that have been thought to be replenished slowly by hematopoietic stem cells (HSC). However, recent fate mapping studies have revealed two developmentally distinct populations of MPP, HSC-derived MPP (hMPP), and HSC-independent, embryonic MPP (eMPP). These data raise fundamental questions on the distinctions and functions of these progenitors. Here, we mapped the clonal dynamics of the two independent MPP systems, using in situ barcoding, and barcode linkage (hMPP), or disconnect (eMPP), with HSC. The cumulative output of eMPP to hematopoiesis was 35%, and their output was enriched for lymphoid fates. Conversely, hMPP output was enriched for myeloid-restricted fates. Distinguishing HSC from eMPP outputs revealed that only ~15% of adult HSC clones underwent multilineage differentiation (lymphoid, myeloid, and erythroid). To prospectively identify eMPP, we developed PolySMART for joint profiling of PolyloxExpress RNA barcodes, surface markers, and transcriptomes, and we found that the plasma cell marker CD138 enriches for eMPP. CD138 + MPP are primed for self-renewal and toward lymphoid fate, and become largely but not completely replaced by CD138 − MPP over time, which may contribute to the loss of lymphoid output with age. Taken together, adult hematopoiesis consists of two distinct lineage trees. The source of the “eMPP tree” substantially contributes to hematopoiesis before it declines, while the HSC-hMPP tree supplies hematopoiesis life-long. Our molecular determinants distinguishing the two MPP systems may open avenues to further explore these unexpected layers of hematopoiesis.
GPT-4o mini: Non-social science research article
QnAs with Kathleen Hall Jamieson
Matthew Hardcastle
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GPT-4o mini: Non-social science research article
Skyrmions with multiple topological charges as orbital angular momentum encoders
Shuhua Guan, Xiaolong Zou, Wenhui Duan
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Magnons carrying intrinsic orbital angular momentum (OAM) hold great potential for orbitronics, optics, and communications, but the generation of such magnons poses great challenges. In this work, we propose that magnons with intrinsic OAM can be induced by antiferromagnetic (AFM) skyrmions with multiple topological charges ( Q ). The proposal is demonstrated in a tetragonal lattice frustrated AFM film, where magnetic anisotropy governs the formation of multiple- Q skyrmions. Out-of-plane polarized current induces ultrafast skyrmion helicity oscillation, which enables excitation of multipolar spin waves, with OAM quantum number identical to Q . The Q , and thus OAM, can be modulated by tuning magnetic anisotropy and temperature. In addition, we reveal an unexpected AFM skyrmion Hall effect driven by in-plane polarized current, and a nonlinear correction term in skyrmion dynamics induced by spin–orbit torque fluctuation. Our results reveal unique behaviors of AFM multiple- Q skyrmions and could extend their applications in information encoding and transmission.
GPT-4o mini: Non-social science research article
A 120-y time series of genomes reveals the consequences of closed breeding in German Shepherd Dogs
Lachie Scarsbrook, Gabriella J. Spatola, Dayna L. Dreger, Tatiana R. Feuerborn, Reuben M. Buckley, Alberto Carmagnini, Anne-Claire Fabre, Alexander C. Harris, Stefan T. Hertwig, Tosso Leeb, Timothy A. Mousseau, Kristina Tabbada, Olaf Thalmann, Greger Larson, Laurent A. F. Frantz, Elaine A. Ostrander
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Many contemporary breed dogs display reduced genomic health compared to mixed-breed dogs, including reduced heterozygosity and increased genetic load, likely due to strong directed breeding. Lack of historical genomes, however, has made it difficult to disentangle the timing and drivers of these declines given complex and breed-specific demographic histories, artificial selection, and crossbreeding. Here, we sequenced genomes of nine 20th-century museum specimens (1906–1993) of pedigree German Shepherd Dogs (GSDs) to directly assess the consequences of contemporary breeding practices on genomic diversity and health over time. The GSD breed offers an excellent case study, given the breed’s fluctuations in global popularity, differing selective regimes, and the GSD’s use in the establishment of other breeds, including wolfdogs. Genome-wide heterozygosity showed significant reductions after the Second World War (WWII), coincident with an increase in both the frequency of runs of homozygosity and load. We also detected repeated population bottlenecks linked to the use of popular sires throughout the 20th century. Finally, although hybridization with wolves has led to genome-wide increases in heterozygosity in wolfdog breeds derived from the GSD, nonadmixed ancestry blocks (dog or wolf) were severely depleted in diversity due to the limited number of founders involved in their establishment. Combined, our results indicate that declines in the genomic health of GSDs and related breeds occurred not at the onset of breed formation but throughout the last century, as a result of population bottlenecks associated with WWII and the repeated use of popular sires.
GPT-4o mini: Non-social science research article
Integrating extensive functional annotations and multiomics of cattle enhances climate resilience prediction and mapping
Ruidong Xiang, Edmond Breen, Sunduimijid Bolormaa, Zhiqian Liu, Christy J. Vander Jagt, Michael Dong, Kerstin Lindblad-Toh, Simone Rochfort, Jennie E. Pryce, Amanda J. Chamberlain, Michael E. Goddard
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To understand the biological function of genomic regions, vast molecular data have been generated to annotate mammalian genomes. However, how to effectively use such extensive information to improve the mapping and prediction of complex traits, including those that respond to climate change, remains unresolved. Here, we apply a Bayesian framework to estimate a Functional-And-Evolutionary Multi-trait Importance (FAEMI) score that combines extensive functional annotations to predict the probability that a variable genomic site causes variation in 16 complex traits of 103 K cattle. The functional annotations include information from the transcriptome, epigenome, and metabolome of cattle as well as genome constraints across species from multiple genome annotation consortia, covering 2.13 million molecular phenotypes from 24 tissues/cell types of 8,446 cattle worldwide. FAEMI analyses quantify the phenotypic importance of functional assays to guide future annotation efforts and reveal significant correlations between molecular functionality and genotype-to-phenotype associations. In new data of 45 K cattle with heat tolerance phenotypes, the FAEMI score demonstrates significant advantages in improving genomic prediction and mapping. The FAEMI score improved genomic prediction accuracy of multiple heat tolerance phenotypes by ~11%. A cellular stress-related locus, stress-associated endoplasmic reticulum protein family member 2 ( SERP2 ), was identified as underlying heat tolerance, with the lead variant (rs383130643) associated with enhancer activity. Additionally, high FAEMI-ranking variants are significantly enriched in variants affecting beef cattle traits. Together, our work provides methods and resources to map informative variants genome-wide, enhancing our understanding of the biology behind thermal tolerance and helping breed resilient cattle in a hotter world.
GPT-4o mini: Non-social science research article
Dimeric gold nanoparticles enable multiplexed labeling in cryoelectron tomography
Hoyoung Kim, Cathy J. Spangler, Aya Matsui, Johannes Elferich, Junhoe Kim, Alex Roseborough, May Nyman, Tanja M. Lahtinen, Eric Gouaux
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Cryoelectron tomography (cryo-ET) enables three-dimensional visualization of molecular structures within tissue and intact cells, providing a powerful tool for studying the spatial organization of biological components at nanometer resolution. Realizing this potential, particularly for submegadalton complexes, is facilitated by fiducial-based labeling. Gold nanoparticles (AuNPs) have emerged as powerful electron-dense labels for cryo-ET, but multiplexing using only conventional monomeric AuNPs is challenging, limiting their application in multitarget studies. Here, we describe functionalized dimeric AuNPs with a precisely defined size range applied to bioimaging, enabling multiplexed labeling by allowing reliable discrimination between monomeric and dimeric AuNPs, thereby supporting identification of distinct molecular targets within the same cryotomogram. Each dimer consists of two covalently linked gold particles of approximately 2.6 nm diameter separated by a defined spacing of about 1.4 nm, with high structural homogeneity validated by small-angle X-ray scattering (SAXS) and electron microscopy. The anti-GluN1 Fab, which targets the N -methyl-D-aspartate receptor (NMDAR), was site specifically conjugated to a dimeric AuNP. A deep learning classifier enabled reliable discrimination between monomeric and dimeric AuNPs in tomograms. We confirmed that the dimeric AuNP–Fab conjugates bind robustly to recombinant GluN1/GluN2A receptors, validating their use for structural labeling. In situ cryo-ET of brain tissue further confirms that the dimeric labels reach NMDARs within the glutamatergic synaptic cleft. Combined with monomeric AuNPs, this dimeric AuNP platform establishes a generalizable approach for distinguishable labels optimized for cryo-ET. The compact size and structural uniformity of monomeric and dimeric AuNPs make them ideally suited for nanoscale molecular mapping in crowded cellular environments.
GPT-4o mini: Non-social science research article
A general framework for branch length estimation in Ancestral Recombination Graphs
Yun Deng, William S. DeWitt, Yun S. Song, Rasmus Nielsen
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Inference of Ancestral Recombination Graphs (ARGs) is of central interest in the analysis of genomic variation. ARGs can be specified in terms of topologies and coalescence times. The coalescence times are usually estimated using an informative prior derived from coalescent theory, but this may generate biased estimates and can also complicate downstream inferences based on ARGs. Here, we introduce, Prior-Oblivious Length Estimation in Genealogies with Oriented Networks (POLEGON), an approach for estimating branch lengths for ARGs which uses an uninformative prior. Using extensive simulations, we show that this method provides improved estimates of coalescence times and leads to more accurate inferences of effective population sizes under a wide range of demographic assumptions (population expansion, bottleneck, split, etc.). It also improves other downstream inferences including estimates of mutation rates. We apply the method to data from the 1000 Genomes Project to investigate population size histories and differential mutation signatures across populations. We also estimate coalescence times in the Human Leukocyte Antigen (HLA) region and show that they exceed 30 My in multiple segments.
GPT-4o mini: Non-social science research article
Antibiotics accumulate in Klebsiella pneumoniae liver abscesses but fail to eliminate antibiotic-tolerant populations
Michelle Angeles-Solano, Zajeba Tabashsum, Jamie D. Liu, Zachary J. Lifschin, Nikki J. Wagner, Kaleb J. Tyson, Liang Chen, Rani S. Sellers, Kimberly A. Walker, Yury Desyaterik, Elias P. Rosen, Sarah E. Rowe
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Liver abscesses caused by hypervirulent Klebsiella pneumoniae (hvKp) can lead to severe metastatic complications, with mortality rates ranging from 5 to 40%. Even in the absence of antibiotic resistance, hvKp liver abscesses often respond poorly to treatment, sometimes requiring surgical resection. The reason for these poor outcomes remains unknown. Here, we established an hvKp wound model in outbred immunocompetent mice, which progresses to systemic infection and hepatic abscesses that were intractable to antibiotic therapy. Using a combination of quantitative and infrared matrix-assisted laser desorption electrospray ionization imaging mass spectrometry, we found that antibiotics fail to kill K. pneumoniae in liver abscesses, independently of resistance or spatial distribution of antibiotics. Our results show that antibiotic concentrations detected in the liver are sufficient to eradicate hvKp under standard in vitro conditions, but the continued presence of viable bacteria in vivo indicates that hvKp adopts an antibiotic-tolerant state within the liver. Notably, the inadequate antibiotic efficacy observed in our mouse studies mirrors clinical outcomes. These findings underscore the urgent need to elucidate the mechanism underlying hvKp tolerance, which could inform the development of novel therapeutic approaches.
GPT-4o mini: Non-social science research article
Evidence for nodal superconductivity in infinite-layer nickelates
Shannon P. Harvey, Bai Yang Wang, Jennifer Fowlie, Motoki Osada, Kyuho Lee, Yonghun Lee, Danfeng Li, Harold Y. Hwang
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Infinite-layer nickelates present a new family of potential unconventional superconductors. A key open question is the superconducting pairing symmetry. We present low-temperature measurements of the magnetic penetration depth in optimally doped La 0.8 Sr 0.2 NiO 2 , Pr 0.8 Sr 0.2 NiO 2 , Nd 0.8 Sr 0.2 NiO 2 , and Nd 0.7875 Sr 0.2125 NiO 2 . For La- and Pr-nickelates, the superfluid density shows a quadratic temperature dependence, indicating nodal superconductivity in the presence of disorder. Nd-nickelate exhibits complex low-temperature behavior associated with Nd 4 f magnetism, which precludes a direct measure of the nodal structure.
GPT-4o mini: Non-social science research article
Combinatorial asymmetric acoustic metamaterials with real-time programmability
Melanie R. Keogh, Osama R. Bilal
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Metamaterials can stretch the envelope of attainable material properties giving rise to negative effective dynamical parameters. Metamaterials usually achieve such superior functionality through hard-coded geometry, symmetry, and periodicity that cannot be altered postfabrication. While a great deal of research is dedicated to tunable metamaterials, the ability to tune metamaterials on-the-fly in a scalable manner remains an open challenge. Here, we introduce a real-time programmable, combinatorial metamaterial framework composed of asymmetric pillars that can manipulate acoustic waves based on the pillars’ angular orientation. First, we demonstrate the utility of our metamaterials with all pillars oriented in the same direction, exhibiting wave attenuation, localization, and topological insulation. Subsequently, we expand the unit-cells into multiple domains and supercells where the number of possible designs enlarges to exceed 10 100 . Our metamaterials offer real-time programmability at both the unit-cell level using individual motors for high versatility, and at a functional domain level using gears for simplicity. We also present a hybrid approach combining motors and gears in clusters providing a balance between versatility and simplicity. We expect our scalable, combinatorial approach with on-demand reprogrammability of acoustic properties to facilitate the development of advanced forms of acoustic devices.
GPT-4o mini: Non-social science research article
Lattice-decoupled rotatable stripe-like charge order within the strange metal phase of 2M-WS 2
Kebin Xiao, Yunkai Guo, Daran Fu, Yuqiang Fang, Yating Hu, Jingming Yan, Yucong Peng, Yuyang Wang, Yongkang Ju, Peizhe Tang, Xiangang Wan, Fuqiang Huang, Qi-Kun Xue, Wei Li
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In quantum materials, charge orders typically stabilize in specific crystallographic orientations, though their formation mechanisms may vary. Here, using low-temperature scanning tunneling microscopy, we find a lattice-decoupled rotatable stripe-like charge order coexisting with superconductivity in 2M-WS 2 . The charge order manifests five distinct orientations across different sample regions, yet maintains an identical wavelength. This directional decoupling from host lattice challenges existing paradigms. First-principles calculations of phonon spectra and nesting function fail to explain the ordering mechanism. Intriguingly, the transition temperature of the charge orders exhibits spatial variations (21 to 46 K), coinciding with the temperature range of the recently reported strange metal phase in this material. This correlation suggests that the interplay between strong electronic correlations and electron–phonon coupling must be critically evaluated to elucidate the emergence of this unconventional charge order.
GPT-4o mini: Non-social science research article
Redox regulation of memory formation by Rrp1 in Drosophila
Cheng-Tzu Hsu, Chun-Chao Chen, Yu-Ling Hung, Ya-Ting Yang, Yen-Hua Chiu, Sing-Shien Fong, Jung-Hsuan Yang, Zheng-Wen Wu, Jian-Wei Liou, Hsuan-Wen Lin, Kuan-Lin Feng, Jia-Ling Yang, Ann-Shyn Chiang
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Long-term memory (LTM) formation requires precise gene regulation, yet the role of redox activity in this process remains poorly understood. Here, we identify Drosophila recombination repair protein 1 (Rrp1), a homolog of human apurinic/apyrimidinic endonuclease 1 (APE1), as a key redox regulator of LTM. In paired dorsal-anterior-lateral neurons—critical for aversive olfactory memory—Rrp1 knockdown impairs memory formation, whereas its overexpression enhances retention. Pharmacological inhibition of Rrp1 redox activity with E3330 suppresses Period and CaMKII expression, disrupting LTM formation. Notably, human APE1 redox activity rescues memory deficits in Rrp1-deficient flies, promotes de novo Period synthesis, and facilitates LTM formation. Moreover, Rrp1 is required for CREBA-mediated LTM acceleration, revealing a redox-dependent link between transcriptional regulation and memory persistence. These findings establish Rrp1 as a critical modulator of LTM in Drosophila and highlight redox regulation as a conserved mechanism underlying memory formation.
GPT-4o mini: Non-social science research article
Prebiotic organic compounds in samples of asteroid Bennu indicate heterogeneous aqueous alteration
Angel Mojarro, José C. Aponte, Jason P. Dworkin, Jamie E. Elsila, Daniel P. Glavin, Harold C. Connolly, Dante S. Lauretta
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NASA’s OSIRIS-REx mission characterized the asteroid Bennu and delivered pristine samples of its regolith to Earth. Coordinated analyses of this primitive, carbonaceous material are elucidating the abiotic formation and inventory of prebiotic organic compounds in the early Solar System. Using pyrolysis and wet-chemistry techniques, we analyzed aggregate (unsorted particulate) material and three distinct stones that appear to correspond to different boulder types observed by the spacecraft. Results from the aggregate were consistent with previous work that detected the five canonical nucleobases and 14 of the 20 α-amino acids utilized by life to synthesize proteins. However, our analytical approach tentatively uncovered trace signals of a fifteenth α-amino acid, tryptophan, which has not been detected previously in extraterrestrial materials. Further, we found that the distributions of insoluble and soluble-derived organics differ between distinct stones, suggesting heterogeneous geologic processing within Bennu’s parent body. The distributions of alkylated polycyclic aromatic hydrocarbons resemble those in aqueously altered carbonaceous chondrites and are consistent with an abiotic origin through aqueous reactions. Our findings expand the evidence that prebiotic organic molecules can form within primitive accreting planetary bodies and could have been delivered via impacts to the early Earth and other Solar System bodies, potentially contributing to the origins of life.
GPT-4o mini: Non-social science research article
Nanorate sequencing reveals the Arabidopsis somatic mutation landscape
Cullan A. Meyer, Brad Nelms, Robert J. Schmitz
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The rate and spectrum of somatic mutations can diverge from that of germline mutations. This is because somatic tissues experience different mutagenic processes than germline tissues. Here, we use nanorate sequencing (NanoSeq) to identify somatic mutations in Arabidopsis shoots with high sensitivity. We report a somatic mutation rate of 3.6 × 10 −8 mutations/bp, ~2 to 7× measured germline mutation rates. Somatic mutations displayed elevated signatures consistent with oxidative damage, UV damage, and transcription-coupled nucleotide excision repair. Both somatic and germline mutations were enriched in transposable elements and depleted in genes, but this depletion was greater in germline mutations. Somatic mutation rate correlated with proximity to the centromere, DNA methylation, chromatin accessibility, and gene/TE content, properties which were also largely true of germline mutations. We note that DNA methylation and chromatin accessibility have different predicted effects on mutation rate for genic and nongenic regions; DNA methylation associates with a greater increase in mutation rate when in nongenic regions, and accessible chromatin associates with a lower mutation rate in nongenic regions but a higher mutation rate in genic regions. Together, these results characterize key differences and similarities in the genomic distribution of somatic and germline mutations.
GPT-4o mini: Non-social science research article
Deconstructing dynamics of symmetry breaking
Fumika Suzuki, Wojciech H. Zurek
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The Kibble–Zurek mechanism (KZM) successfully predicts the density of topological defects deposited by the phase transitions, but it is not clear why. Its key conjecture is that, near the critical point of the second-order phase transition, critical slowing down will result in a period when the system is too sluggish to follow the potential that is changing faster than its reaction time. The correlation length at the freeze-out instant t ̂ when the order parameter catches up with the posttransition broken symmetry configuration is then decisive, determining when the mosaic of broken symmetry domains locks in topological defects. To understand why the KZM works so well, we analyze the Landau–Ginzburg model and show why temporal evolution of the order parameter plays such a key role. The analytical solutions we obtain suggest experimentally accessible observables that can shed light on symmetry-breaking dynamics while testing the conjecture on which the KZM is based.
GPT-4o mini: Non-social science research article
The molecular-level diagenetic clock of sinking marine organic matter
Heather J. Forrer, Michael R. Stukel, Amy M. McKenna, Huan Chen, Amy D. Holt, Sven A. Kranz, Robert G. M. Spencer
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The marine biological carbon pump is driven by sinking particulate organic matter (POM). Sinking speed and remineralization rate determine flux attenuation in the mesopelagic. Since the fate of all marine organic matter is either complete remineralization or transformation to more stable products, diagenetic modifications impact carbon dioxide sequestration time from the atmosphere. To investigate particle transformation at the molecular level, we characterize the water-extractable organic matter (WEOM) fraction of sinking particles from dominant biogeochemical environments using ultrahigh-resolution mass spectrometry. We find distinct, inverse associations in molecular-level nitrogen content and degree of transformation (i.e., “stability”) of organic matter across a productivity gradient from coastal upwelling to oligotrophic conditions. Nitrogen enrichment and low stability were observed at the coastal upwelling site and persisted to depths >400 m. Further, carbon flux is strongly correlated with the relative abundance of stable WEOM (“Island of Stability” molecular formulae) across productivity regimes and depth. This suggests emergent patterns in epi- and mesopelagic diagenesis, highlighting that the molecular composition of sinking organic matter exiting the euphotic zone varies more across regions than as a function of depth. This is attributed to highly variable sinking rates and the microbial diagenetic histories within the euphotic zone. The stability–flux relationship is considered a “diagenetic clock” relative to organic matter formation where the relative abundance of Island of Stability molecular formulae describes the degree of departure from the organic matter molecular-level composition at formation. This ubiquitous trajectory of the diagenetic clock further underpins a global ocean molecular signature of sinking POM.
GPT-4o mini: Non-social science research article
Imputation of ancient canid genomes reveals inbreeding history over the past 10,000 years
Katia Bougiouri, Sabhrina Gita Aninta, Sophy Charlton, Alexander C. Harris, Martin Petr, Alberto Carmagnini, Giedrė Piličiauskienė, Tatiana R. Feuerborn, Lachie Scarsbrook, Kristina Tabbada, Povilas BlaĆŸevičius, Heidi G. Parker, Shyam Gopalakrishnan, Greger Larson, Elaine A. Ostrander, Evan K. Irving-Pease, Laurent A. F. Frantz, Fernando Racimo
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The multi-millennia-long history between dogs and humans has placed them at the forefront of archaeological and genomic research. Despite ongoing efforts including the analysis of ancient dog and wolf genomes, many questions remain regarding the evolutionary processes that led to the diversity of breeds today. Although ancient genome sequences provide valuable information about these processes, their utility is hindered by low depths of coverage and postmortem damage, which inhibits confident genotype calling. In the present study, we assess how genotype imputation of ancient dog and wolf genomes, using a large reference panel, can increase the amount of information provided by ancient datasets. We evaluated imputation accuracy by down-sampling high-coverage dog and wolf genomes to 0.05 to 2× coverage and compared concordance between imputed and high-coverage genotypes. We measured the impact of imputation on principal component analyses and runs of homozygosity (ROH). Our findings show high (R 2 > 0.9) imputation accuracy for dogs with coverage as low as 0.5× and for wolves as low as 1.0×. We then imputed a dataset of 90 ancient dog and wolf genomes to assess changes in inbreeding during the last 10,000 y of dog evolution. Ancient dog and wolf populations generally exhibit lower inbreeding levels than present-day individuals. Regions with low ROH density maintained across ancient and present-day dogs were significantly associated with genes related to immunity and chemosensory receptors. Our study indicates that imputing ancient canine genomes is a viable strategy that allows for the use of analytical methods previously limited to high-quality genetic data.
GPT-4o mini: Non-social science research article
Protein kinase A fuels positive feedback loops during Th1 cell differentiation
Jinfang Zhu
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GPT-4o mini: Non-social science research article
Single-molecule views of chromatin accessibility and structure during photomorphogenesis
Lei Li, Guanyu Chen, Guangquan Zhu, Jili Wu, Xinglong Kui, Zihui Zhang, Lingyang Feng, Minghan Huang, Wenbo Hua, Zhipeng Qu, Lina Zou, Changmei Lu, Bojian Zhong, Hang He, Xing Wang Deng, Linhua Sun
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The dynamic organization of chromatin governs gene expression by regulating DNA accessibility. In plants, light not only initiates photomorphogenesis but also reshapes higher-order chromatin architecture. However, the limited resolution of current techniques impedes investigation of chromatin dynamics at the single-molecule level. Here, we applied Fiber-seq, a long-read, single-molecule chromatin profiling method, to construct near-nucleotide resolution maps of chromatin accessibility, nucleosome positioning, and cytosine methylation in Arabidopsis thaliana and maize. We observed that light exposure during photomorphogenesis led to significant, locus-specific changes in chromatin accessibility—both increases and decreases—especially in genes related to photosynthesis, hormone signaling, and development. Analysis of chromatin accessibility changes in cop1-6 , pifq , and hy5 hyh mutants revealed that classical light signaling pathways regulate chromatin accessibility. Additionally, using high-fidelity long-read sequencing, we profiled DNA methylation in previously inaccessible repetitive regions such as 5S rRNA gene clusters and CEN180 satellite repeats. These heterochromatic loci exhibited distinct light-dependent changes in chromatin accessibility that were undetectable using prior methods. In maize, we demonstrated that Fiber-seq identifies a broader range of biologically relevant open chromatin regions, enabling both high-accuracy de novo genome assembly and the detection of fine-scale structural variants. Collectively, Fiber-seq offers an integrated view of chromatin states across regulatory and repetitive elements, providing critical insights into how environmental signals reshape plant epigenomes.
GWAS for behavioral traits in golden retrievers identifies genes implicated in human temperament, mental health, and cognition
Enoch Alex, Paul Gennotte, Anna Morros Nuevo, Yunzhu Yu, Benjamin Keep, Megan Sullivan, Daniel Mills, Varun Warrier, Eleanor Raffan
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Dogs display temperamental and behavioral variation between individuals, just as psychiatric, temperamental, and cognitive traits vary in humans. In both species, these traits are highly heritable, yet causal genes remain incompletely understood. We performed 14 genome-wide association studies (GWAS) for behavioral traits quantified using the Canine Behavioral Assessment and Research Questionnaire (C-BARQ) in ~1,000 golden retrievers, identifying 12 genome-wide significant loci ( P < 2.97 × 10 −6 ) for 8 traits and 9 additional loci exceeding a suggestive threshold ( P < 1 × 10 −5 ). A human phenome-wide association study (PheWAS) showed that most of the 18 canine positional candidate genes identified were associated with one or more of 190 psychiatric, temperamental, or cognitive traits in humans (7/12 genes at genome-wide loci and 5/9 at suggestive loci). For example, a genome-wide significant locus near PTPN1 (dog-directed aggression) overlapped with human measures of Intelligence, Educational attainment, and major depressive disorder. The gene ROMO1 was within a genome-wide significant locus for trainability in dogs and associated with intelligence, depression, irritability, and sensitivity/hurt feelings in humans. Other genes located at genome-wide significant loci associated with behavioral, psychiatric, temperamental, or cognitive traits in both species included PRDX1(dog-directed fear), VWA8 (touch sensitivity) , ITPR2, and ADGRL2/LPHN2 (trainability), and ADD2 (stranger-directed fear). From suggestive loci we also found cross-species associations for HUNK, and ZC3H12C, (dog-directed fear), SLC35F6 and IGSF11 (separation-related problems). These results suggest that shared genetic and molecular mechanisms underlie complex behavioral and temperamental states across species and may inform our understanding of emotional states driving undesirable behaviors in dogs.
Using a mental model approach to undercut the effects of exposure to mRNA vaccination misconceptions: Two randomized trials
Kathleen Hall Jamieson, Laura A. Gibson, Patrick E. Jamieson, Shawn Patterson
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Although messenger RNA (mRNA) technology revolutionized vaccine creation, its use is threatened by unwarranted fear that DNA left over from the vaccine manufacturing process could integrate into recipients’ DNA, increasing cancer and heritable risks. Drawing on the mental model theory of reasoning, our two preregistered interventions undercut these problematic conclusions. They do so by testing the effectiveness of two mental model-based interventions juxtaposing problematic claims with visualized or verbally explained models of basic biological and vaccination systems. Study 1: a) graphically modeled how mRNA COVID-19 vaccination works (Model 1); b) verbally modeled ways in which cells protect themselves from foreign DNA (Model 2); and c) provided ancillary material designed to bolster perceptions of mRNA vaccination safety. Study 2 deployed an animation of the cell-protection model (Model 2), alone, and in combination with Study 1’s messaging. Neither the mRNA vaccine nor the DNA protection model explicitly acknowledged the problematic DNA-integration claim. Both preemptive (before) and rebuttal (after) positioning of the models were effective. Within-person analyses suggested that preemptive positioning may be somewhat more effective than rebuttal positioning. Some positive effects of exposure to the modeled knowledge messaging condition in Study 1 persisted 2 mo after exposure.
Rice farming for climate change adaptation in the Northeastern United States
Chuan Liao, Jenny Kao-Kniffin, Matthew Reid, Wendong Zhang, Precious Tshabalala, Erik Andrus, Zachary Butler-Jones, Jordan LaPoint, Shuai Zhou, Radine Rafols, Seongmin Shin, Mai Ichihara, Autumn Pereira, Natalia Butler, Ying Tu, Susan R. McCouch
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In response to challenges posed by climate change, rice farming emerges as a strategic adaptation in the agriculture sector in the northeastern United States. Cultivating rice can diversify farming practices, create new sources of income, improve water management, and provide habitats for wildlife, enhancing the sustainability of agricultural systems and rural economies. However, challenges such as methane emissions from rice paddies and the risk of metal(loid) contamination highlight the need for adopting best practices in rice cultivation, particularly in land and water management and the selection of suitable rice varieties. By learning from the experience of other temperate rice farming regions and implementing supportive policies, technology, and cooperative frameworks, farming communities in the northeastern United States can learn to navigate these obstacles, ensuring the successful integration of rice farming into its agricultural landscape.
How social learning enhances—or undermines—efficiency and flexibility in collective decision-making under uncertainty
Hidezo Suganuma, Kentaro Katahira, Hisashi Ohtsuki, Tatsuya Kameda
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Balancing efficiency and flexibility in collective decision-making is increasingly critical in modern societies characterized by rapid sociocultural and technological change. Recent research in cognitive neuroscience has proposed two contrasting computational algorithms for social learning: value shaping (VS) and decision biasing (DB). VS posits that others’ choices serve as “pseudo-rewards” that directly shape an observer’s valuations, leading them to prefer popular options even in the absence of outcome feedback. In contrast, DB confines the influence of social information to behavior—observers may imitate popular actions, but they update their valuations solely through personal experience. Although both algorithms facilitate individual adaptation under uncertainty, their interactive dynamics and group-level consequences remain largely unexplored. To address this gap, we developed computational models of VS and DB within a reinforcement learning framework and conducted agent-based simulations to examine collective performance in uncertain and dynamically changing environments. The results reveal a trade-off: VS enables rapid convergence and high efficiency in stable contexts, whereas DB promotes greater adaptability under environmental volatility. These differences are amplified in larger groups, particularly under strong majority influence. Importantly, evolutionary analyses indicate that both learning types can coexist stably, allowing their complementary strengths to enhance group performance. Together, our findings provide a computational and evolutionary account of how social learning can both enhance and impair collective intelligence—and suggest design principles for fostering resilient collective decision systems in human and AI societies facing rapid change.
Migration and the persistence of violence
Martin VinĂŠs Larsen, Gabriel S. Lenz, Anna Mikkelborg
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Using data on millions of internal US migrants, we document that historical homicide rates follow migrants around the United States. Individuals born in historically safe states remain safer wherever they go, while individuals born in historically dangerous states face a greater risk, including from police violence. This pattern holds across demographic characteristics such as age, gender, and marital status, across migrant groups with different average levels of education, income, and even when comparing migrants from different states who reside in the same county. To help understand why, we conducted a large national survey that oversampled internal White US migrants. The results suggest this persistence may reflect a sociocultural adaptation to dangerous settings. Residents and migrants from historically unsafe states—mainly former frontier states and the deep South—see the world as more dangerous, react more forcefully in aggressive scenarios, value toughness, distrust law enforcement, and say they rely on self and family in violent situations. These adaptations may have kept them safe in historically dangerous states, but may increase their vulnerability to harm in safer states.
Stochastic responses and marginal valuation
Lars Peter Hansen, Panagiotis Souganidis
Full text
The analysis of policy impacts in a dynamic and uncertain reality is vital to supporting informed economic policy design and implementation. Dynamic, stochastic economic models used in policy evaluation necessarily simplify the world as we know it. This motivates us to explore, refine, and extend tools aimed at producing marginal valuations that shed light on why some policies are optimal and how others, though suboptimal, can be improved. We present representations of these marginal valuations that embrace uncertainty and support robust implementation-even in environments characterized by “deep uncertainties.” These representations offer a more complete understanding of how interactions among multiple state variables, concerns about model misspecification, and uncertainties surrounding potentially long-term implications contribute to the cogent assessment of policies. We argue that these methods are particularly salient for evaluating the global cost of climate change and the global value of research and development with long-term prospects for success.
Simulating human well-being with large language models: Systematic validation and misestimation across 64,000 individuals from 64 countries
Pat Pataranutaporn, Nattavudh Powdthavee, Chayapatr Archiwaranguprok, Pattie Maes
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Subjective well-being is central to economic, medical, and policy decision-making. We evaluate whether large language models (LLMs) can provide valid predictions of well-being across global populations. Using natural-language profiles from 64,000 individuals in 64 countries, we benchmark four leading LLMs against self-reports and statistical models. Unlike regressions, which estimate relationships from survey data, LLMs draw only on individual characteristics (e.g., sociodemographic, attitudinal, and psychological factors) together with associations encoded during pretraining, rather than from the survey’s subjective well-being responses. They produced plausible patterns consistent with known correlates such as income and health, but systematically underperformed relative to regressions and showed the largest errors in underrepresented countries, reflecting biases rooted in global digital and economic inequality. A preregistered experiment revealed that LLMs rely on surface-level linguistic associations rather than conceptual understanding, leading to predictable distortions in unfamiliar contexts. Injecting contextual information partly reduced—but did not remove—these biases. These findings demonstrate that while LLMs can simulate broad correlates of life satisfaction, they fail to capture its experiential and cultural depth. Accordingly, they should not be used as substitutes for human self-reports of well-being; doing so would risk reinforcing inequality and undermining human agency.
Scaling up actionable climate knowledge
Maria Carmen Lemos, Lisa Maillard, Natalie Herbert, Simone J. Domingue, Kripa Jagannathan, Gabrielle Wong-Parodi, Erica Akemi Goto, Devin Gill, Derek Van Berkel, Scott Kalafatis, Jenna L. Jorns, Alex Basaraba, Teal Harrison
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To address climate-driven crises, we need actionable climate knowledge to inform decision-making and support problem solving. Although the science of actionable knowledge is rapidly evolving, less is known about how and why actionable climate knowledge scales up and with what outcomes. We advance three outcome-driven pathways to scale up actionable climate knowledge: 1) broadening participation by increasing the diversity and number of actors involved in actionable climate knowledge coproduction; 2) diffusing actionable climate knowledge uptake among actors not originally involved in its coproduction, and 3) aggregating impact by coproducing actionable climate knowledge with influential actors, such as practitioners and policy-makers, whose decisions affect many others. These pathways can intersect, complement, interact, and tradeoff with each other. Understanding how these pathways work, evolve, and change is critical if we want to better inform the production and scaling of climate actionable knowledge to solve climate problems.
Understanding the strengths and limitations of community-based responses to misinformation
Emily K. Vraga
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The importance of local racial demographic changes in democratic erosion in the mass American public
Andrew Ifedapo Thompson, Stefan D. McCabe
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Violent sentiment is deeply tied to racial threat from the changing racial demography of the United States. Extending the historical idea of White flight, we find shifting local racial demographic conditions in tandem with a simple prime of national conditions causally drive more violent, antidemocratic attitudes across White Americans. We term this as “White fight sentiment.” Across four experiments conducted over the span of 3 y, using probability, state targeted, and convenience samples, we find that when we randomly prime national diversification among White Americans in locations that experienced local Black population increase or White decline, they become expressively, consistently more extreme when primed. Surprisingly, we consistently find null effects in communities that recently experienced Hispanic and Asian population change, short of one case across our four studies. Through a series of robustness checks we confirm national considerations specifically activate White fight.
Elevated risk of infectious diseases in adulthood after prenatal or early postnatal exposure to the Great Chinese Famine
Qi Li, Philip A. Collender, Hailan Yu, Kristin N. Nelson, Jon Zelner, Xinqiang Wang, Xiaolu Wang, Jiayi Tang, Leonardo Martinez, Justin V. Remais, Changhong Yang, Qu Cheng
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Although prenatal exposure to famine is known to increase the risk of various noncommunicable conditions, its effects on infectious diseases remain poorly understood. We examined the effect of prenatal exposure to the Great Chinese Famine on risks for 11 notifiable infectious diseases in two consecutive generations through the analysis of >4.4 million surveillance records in Sichuan Province, China. Using an approach combining cohort models with counterfactual effect imputation, we estimated the ratio of observed to expected incidence rates (incidence rate ratio, IRR) in the absence of famine among both the directly affected birth cohort (F1) and their possible offspring (F2). We further examined whether there was a dose–response relationship between famine severity and infectious disease outcomes using meta-regression at the prefecture level. We found that the risk of acquiring any of the 11 infectious diseases studied increased significantly among both the F1 (IRR: 1.13, 95% CI: 1.04 to 1.21) and the F2 cohort (IRR: 1.08, 95% CI: 1.00 to 1.15). IRRs for the F1 generation were higher in prefectures that experienced more severe famine, with one interquartile range increase in famine severity associated with a 3.95% (95% CI: 1.87 to 6.05%) increase in F1 IRR. Positive associations of varying magnitudes were estimated between increased risks in the F1 cohort and famine intensity for most individual diseases. Prenatal exposure to famine may have long-term and potential intergenerational impacts on the risk of a broad range of infectious diseases. Ensuring adequate prenatal nutrition may be crucial in reducing the burden of infectious diseases across generations.

Science

GPT-4o mini: Non-social science research article
Realization of three- and four-body interactions between momentum states in a cavity
Chengyi Luo, Haoqing Zhang, Chitose Maruko, Eliot A. Bohr, Anjun Chu, Ana Maria Rey, James K. Thompson
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Spin Hamiltonians in condensed matter and quantum sensing typically utilize pairwise or two-body interactions between constituents in the material or ensemble. However, there is growing interest in exploring more general n -body interactions for n > 2. In this study, we realized an effective n = 3-body Hamiltonian interaction using an ensemble of laser-cooled atoms in a high-finesse optical cavity with the pseudospin 1 / 2 encoded by two atomic momentum states. We applied two dressing tones that induce the atoms to exchange photons via the cavity to realize a virtual six-photon process; lower-order interactions destructively interfered. We also observed signatures of a n = 4-body interaction mediated by a virtual eight-photon process. Our approach may be extensible to three-body interactions in multilevel systems or to even higher-order interactions.
GPT-4o mini: Non-social science research article
Monkeys have rhythm
Vani G. Rajendran, Luis Prado, Juan Pablo Marquez, Hugo Merchant
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Synchronizing movements to music is a hallmark of human culture, but its evolutionary and neurobiological origins remain unknown. This ability requires (i) extracting a steady rhythmic pulse, or beat, out of continuous sounds; (ii) projecting this pattern forward in time; and (iii) timing motor commands to anticipate future beats. Here, we demonstrate that macaques can synchronize to a subjective beat in real music and even spontaneously do so over alternative strategies. This contradicts the influential “vocal-learning hypothesis” that musical beat synchronization is privileged to species with complex learned vocalizations. We propose an alternative view of musical beat perception and synchronization as a continuum onto which different species can be mapped based on their capacity to coordinate the general abilities listed above through association with reward.
GPT-4o mini: Non-social science research article
Targeted protein degradation in the transmembrane and extracellular space
Rongfeng Zhu, Heng Zhang, Peng R. Chen
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Transmembrane and extracellular proteins play crucial roles in diverse cellular functions and communication, affecting the progression and treatment of various diseases by mediating vital cellular processes. Whereas targeted protein degradation (TPD) represents an advancing therapeutic modality that leverages cellular degradation machinery to eliminate proteins of interest, present strategies have been largely confined to intracellular targets. Now, emerging strategies toward transmembrane and extracellular proteins are rapidly expanding the horizon of this powerful technology. Here, we review TPD in the transmembrane and extracellular space (meTPD) and discuss platform technologies, features, applications, and limitations. We focus on the conceptual innovations used in developing the present meTPD technology as well as its potential value for biological research and therapeutic interventions.
GPT-4o mini: Non-social science research article
Characterizing transport in a quantum gas by measuring Drude weights
Philipp SchĂŒttelkopf, Mohammadamin Tajik, Nataliia Bazhan, Federica Cataldini, Si-Cong Ji, Jörg Schmiedmayer, Frederik MĂžller
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Transport properties define materials as insulators, metals, or superconductors. A fundamental parameter is the Drude weight, which quantifies the ballistic transport of charge carriers. Here, we measure the Drude weights of an ultracold gas of interacting bosonic atoms confined to one dimension, characterizing atomic and energy currents induced by applying a constant force and by joining two subsystems prepared in different equilibrium states. We demonstrate dissipationless transport, even in the presence of interactions and finite temperature, signifying ballistic propagation of conserved quantities corresponding to lowest order hydrodynamics. Our approach provides a robust and transparent framework for characterizing transport in strongly correlated quantum matter, applicable in regimes where theory remains incomplete.
GPT-4o mini: Non-social science research article
Avian-origin influenza A viruses tolerate elevated pyrexic temperatures in mammals
Matthew L. Turnbull, Yingxue Wang, Simon Clare, Gauthier Lieber, Stephanie L. Williams, Marko Noerenberg, Akira J. T. Alexander, Sara Clohisey Hendry, Douglas G. Stewart, Joseph Hughes, Simon Swingler, Spyros Lytras, Emma L. Davies, Katherine Harcourt, Katherine Smollett, Rute M. Pinto, Hui-Min Lee, Eleanor R. Gaunt, Colin Loney, Johanna S. Jung, Paul A. Lyons, Darrell R. Kapczynski, Edward Hutchinson, Ana da Silva Filipe, Jeffery K. Taubenberger, Suzannah J. Rihn, J. Kenneth Baillie, Ervin Fodor, Alfredo Castello, Kenneth G. C. Smith, Paul Digard, Sam J. Wilson
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Host body temperature can define a virus’s replicative profile—influenza A viruses (IAVs) adapted to 40° to 42°C in birds are less temperature sensitive in vitro compared with human isolates adapted to 33° to 37°C. In this work, we show that avian-origin PB1 polymerase subunits enable IAV replication at elevated temperatures, including avian-origin PB1s from the 1918, 1957, and 1968 pandemic viruses. Using a model system to ensure biosafety, we show that a small increase in body temperature protects against severe disease in mice and that this protection is overcome by a febrile temperature–resistant PB1. These findings indicate that although elevated temperature itself can be a potent antiviral defense, it may not be effective against all influenza strains. These data inform both the clinical use of antipyretics and IAV surveillance efforts.
GPT-4o mini: Non-social science research article
Spectral kernel machines with electrically tunable photodetectors
Dehui Zhang, Yuhang Li, Jamie Geng, Hyong Min Kim, Marco Ma, Shifan Wang, Inha Kim, Theodorus Jonathan Wijaya, Naoki Higashitarumizu, I. K. M. Reaz Rahman, Dorottya Urmossy, James Bullock, Aydogan Ozcan, Ali Javey
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Spectral machine vision collects spectral and spatial information as three-dimensional hypercubes and digitally processes them, which causes a data bottleneck, limiting power efficiency, frame rate, and spectral-spatial resolution. This work introduces spectral kernel machines (SKMs) to overcome these bottlenecks. SKM directly compresses spectral analysis through the output photocurrent and learns from example objects to identify and classify new samples in a “sniff-and-seek” mode. We experimentally demonstrated SKMs with electrically tunable bipolar black phosphorus–molybdenum disulfide (bP-MoS 2 ) photodiodes in the near- and mid-infrared band and silicon photoconductors in the visible band, performing versatile intelligent tasks from chemometrics to semiconductor metrology. This architecture consumed substantially less power and was more than an order of magnitude faster than existing solutions for hyperspectral image analysis, defining an intelligent imaging and sensing paradigm with intriguing possibilities.
GPT-4o mini: Non-social science research article
Rapid compensatory evolution within a multiprotein complex preserves telomere integrity
Sung-Ya Lin, Hannah R. Futeran, Briana N. Cruga, Andrew Santiago-Frangos, Mia T. Levine
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Intragenomic conflict with selfish genetic elements spurs adaptive changes in subunits of essential multiprotein complexes. Whether and how these adaptive changes disrupt interactions within such complexes and threaten their essential functions remains unexplored. To investigate this, we exploited a Drosophila melanogaster multiprotein complex that protects telomeres from lethal fusions despite one subunit, HOAP (HP1/ORC–associated protein), evolving adaptively to restrict selfish telomeric retrotransposons. Swapping HOAP’s adaptively evolving interaction partner, HipHop (HP1-HOAP–interacting protein), between closely related Drosophila species disrupted HOAP recruitment to the telomere, leading to lethal telomere fusions. Reverting six adaptively evolving sites on HipHop’s interaction surface with HOAP, or introducing its conspecific HOAP, restored protein recruitment, telomere protection, and viability. Our in vivo, evolution-guided manipulations illuminate how intermolecular compensatory evolution preserves essential functions in the face of antagonism by selfish elements.
GPT-4o mini: Non-social science research article
The dispersal of domestic cats from North Africa to Europe around 2000 years ago
M. De Martino, B. De Cupere, V. Rovelli, P. Serventi, B. Mouraud, M. Baldoni, T. Di Corcia, S. Geiger, F. Alhaique, P. C. Alves, H. Buitenhuis, E. Ceccaroni, E. Cerilli, J. De Grossi Mazzorin, C. Detry, M. Dowd, I. Fiore, L. Gourichon, I. Grau-Sologestoa, H. C. KĂŒchelmann, G. K. Kunst, M. McCarthy, R. MiccichĂš, C. Minniti, M. Moreno, N. Mrđić, V. Onar, T. Oueslati, M. Parrag, B. Pino Uria, G. Romagnoli, M. Rugge, L. Salari, K. Saliari, A. B. Santos, U. Schmölcke, A. Sforzi, G. Soranna, N. Spassov, A. Tagliacozzo, V. TinĂš, S. Trixl, S. Vuković, U. Wierer, B. Wilkens, S. Doherty, N. Sykes, L. Frantz, F. Mattucci, R. Caniglia, G. Larson, J. Peters, W. Van Neer, C. Ottoni
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The domestic cat ( Felis catus ) descends from the African wildcat Felis lybica lybica . Its global distribution alongside humans testifies to its successful adaptation to anthropogenic environments. Uncertainty remains regarding whether domestic cats originated in the Levant, Egypt, or elsewhere in the natural range of African wildcats. The timing and circumstances of their dispersal into Europe are also unknown. In this study, the analysis of 87 ancient and modern cat genomes suggests that domestic cats did not spread to Europe with Neolithic farmers. Conversely, they were introduced to Europe around 2000 years ago, probably from North Africa. In addition, a separate earlier introduction (first millennium before the common era) of wildcats from Northwest Africa may have been responsible for the present-day wild population in Sardinia.
GPT-4o mini: Non-social science research article
Structural basis for the recruitment and selective phosphorylation of Akt by mTORC2
Martin S. Taylor, Maggie Chen, Matthew Hancock, Maximilian Wranik, Bryant D. Miller, Timothy R. O’Meara, Brad A. Palanski, Scott B. Ficarro, Brian J. Groendyke, Yufei Xiang, Kazuma T. Kondo, Karen Y. Linde-Garelli, Michelle J. Lee, Dibyendu Mondal, Daniel Freund, Samantha Congreve, Kaay Matas, Maximiliaan Hennink, Kera Xibinaku, Max L. Valenstein, Trevor van Eeuwen, Jarrod A. Marto, Andrej Sali, Yi Shi, Nathanael S. Gray, David M. Sabatini, Nam Chu, Kacper B. Rogala, Philip A. Cole
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The mTOR protein kinase forms two multiprotein complexes, mTORC1 and mTORC2, that function in distinct signaling pathways. mTORC1 is regulated by nutrients, and mTORC2 is a central node in phosphoinositide-3 kinase (PI3K) and small guanosine triphosphate Ras signaling networks commonly deregulated in cancer and diabetes. Although mTOR phosphorylates many substrates in vitro, in cells, mTORC1 and mTORC2 have high specificity: mTORC2 phosphorylates the protein kinases Akt and PKC, but not closely related kinases that are mTORC1 substrates. To understand how mTORC2 recognizes substrates, we created semisynthetic probes to trap the mTORC2-Akt complex and determine its structure. Whereas most protein kinases recognize amino acids adjacent to the phosphorylation site, local sequence contributes little to substrate recognition by mTORC2. Instead, the specificity determinants were secondary and tertiary structural elements of Akt that bound the mTORC2 component mSin1 distal to the mTOR active site and were conserved amongst at least 18 related substrates. These results reveal how mTORC2 recognizes its canonical substrates and may enable the design of mTORC2-specific inhibitors.
GPT-4o mini: Non-social science research article
Elasticity of davemaoite as a primary contributor to lower-mantle heterogeneities
Wen-Yi Zhou, Ming Hao, Wenhao Su, Taehyun Kim, Sibo Chen, Sang-Heon Shim, Dongzhou Zhang, Phuong Q. H. Nguyen, Katherine Armstrong, Jin S. Zhang
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Geophysical detection of subducted mid–ocean ridge basalt (MORB) in the lower mantle is hindered by uncertainties in the elasticity of Fe,Al,Mg,Ti–bearing davemaoite, a key MORB component. Using Brillouin spectroscopy and x-ray diffraction, we determined the elasticity of a Ca 0.906(1) Fe 2+ 0.027(1) Fe 3+ 0.042(1) Mg 0.033(1) Al 0.072(1) Ti 0.020(1) Si 0.912(1) O 3 davemaoite up to 113 gigapascals and 2294 K. We found that it exhibited a shear wave velocity 10 to 20% slower than end-member davemaoite, making it the slowest phase among major lower-mantle minerals. Our models show that MORB, containing 20 to 25 volume percent davemaoite, potentially contributes to large low-shear-velocity provinces (LLSVPs), whereas a cumulate layer enriched in davemaoite crystallized from basal magma ocean may comprise ultralow-velocity zones (ULVZs). Davemaoite’s ability to host incompatible and heat-producing elements possibly links LLSVPs and ULVZs to mantle plume initiation and geochemical signatures of ocean island basalts.
GPT-4o mini: Non-social science research article
Laser annealing enables rapid, degradation-free ambient processing of perovskite solar modules
Zhaoyang Chu, Baojin Fan, Yue Zhao, Yihuan Xie, Yaling Luo, Junliang Li, Chenxiang Gong, Yong Zhang, Xiangchuan Meng, Yu Chen, Hongxiang Li, Xiaotian Hu, Yiwang Chen
Full text
Unlike small-area perovskite films produced by spin coating, which undergo prolonged thermal annealing in inert atmosphere for full crystallization, printable perovskite photovoltaics face a critical trade-off between crystal growth quality and ambient degradation from water and oxygen exposure. Through in situ grazing-incidence wide-angle x-ray scattering analysis, we reveal a four-stage degradation mechanism during thermal processing and identify a 123 ± 18–second ambient degradation-free window where water and oxygen effects are mitigated. The laser annealing (455-nanometer wavelength, 20 watts per square centimeter) provides irradiance that is two orders of magnitude higher than that of conventional thermal methods (0.06 watts per square centimeter), which prevents 6H perovskite phase accumulation. The strategy yields power conversion efficiencies of 24.0% (in a 100–square centimeter rigid module) and 20.7% (in a flexible counterpart), representing high reported values for scalable perovskite photovoltaics.
GPT-4o mini: Non-social science research article
Synergy between regulatory elements can render cohesin dispensable for distal enhancer function
Karissa L. Hansen, Annie S. Adachi, Luca Braccioli, Smit Kadvani, Ryan M. Boileau, Moreno Martinovic, Bozhena Pokorny, Rini Shah, Erika C. Anderson, Kaite Zhang, Irié Carel, Kenya Bonitto, Robert Blelloch, Geoffrey Fudenberg, Elzo de Wit, ElphÚge P. Nora
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Enhancers are critical genetic elements controlling transcription from promoters, yet how they convey regulatory information across large genomic distances remains unclear. Here, we engineer pluripotent stem cells in which cohesin loop extrusion can be inducibly disrupted without confounding cell cycle defects. Transcriptional dysregulation is cell type-specific, and not all loci with distal enhancers depend equally on cohesin extrusion. Using comparative genome editing, we demonstrate that enhancer-promoter communication over just 20 kilobases can require cohesin. However, promoter-proximal elements can support long-range, cohesin-independent enhancer action – even across strong CTCF insulators. Finally, transcriptional dynamics and the emergence of embryonic cell types remain largely robust despite disrupted extrusion. Beyond establishing strategies to study cohesin in enhancer biology, our work provides mechanistic insight into cell type- and genomic context-specificity.
GPT-4o mini: Non-social science research article
Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration
Mamta Singla, Yu Xin Wang, Elena Monti, Yudhishtar Bedi, Pranay Agarwal, Shiqi Su, Sara Ancel, Maiko Hermsmeier, Nitya Devisetti, Akshay Pandey, Mohsen Afshar Bakooshli, Adelaida R. Palla, Stuart Goodman, Helen M Blau, Nidhi Bhutani
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Aging or injury to the joints can lead to cartilage degeneration and osteoarthritis (OA), for which there are limited effective treatments. We found that expression of 15-hydroxy prostaglandin dehydrogenase (15-PGDH) is increased in the articular cartilage of aged or injured mice. Both systemic and local inhibition of 15-PGDH with a small molecule inhibitor (PGDHi) led to regeneration of articular cartilage and reduction in OA-associated pain. Using single cell RNA-sequencing and multiplexed immunofluorescence imaging of cartilage, we identified the major chondrocyte subpopulations. Inhibition of 15-PGDH decreased hypertrophic-like chondrocytes expressing 15-PGDH and increased extracellular matrix-synthesizing articular chondrocytes. Cartilage regeneration appears to occur through gene expression changes in pre-existing chondrocytes, rather than stem or progenitor cell proliferation. 15-PGDH inhibition could be a potential disease-modifying and regenerative approach for osteoarthritis.
GPT-4o mini: Non-social science research article
Programmable higher-order nonequilibrium topological phases on a superconducting quantum processor
Haoran Qian, Ming Gong, Jiahui Zhang, Shaojun Guo, Chen Zha, Fusheng Chen, Yangsen Ye, Yulin Wu, Sirui Cao, Chong Ying, Qingling Zhu, He-Liang Huang, Youwei Zhao, ShaoWei Li, Jiale Yu, Daojin Fan, Dachao Wu, Hong Su, Hui Deng, Hao Rong, Yuan Li, Kaili Zhang, Tung-Hsun Chung, Futian Liang, Jin Lin, Yu Xu, Cheng Guo, Na Li, Kai Yan, Fei-Fan Su, Gang Wu, Yong-Heng Huo, Cheng-Zhi Peng, Chao-Yang Lu, Feng Mei, Suotang Jia, Xiaobo Zhu, Jian-Wei Pan
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Topological phases of matter are of both fundamental and practical interest. In this study, we implemented both equilibrium and nonequilibrium higher-order topological phases using a two-dimensional programmable superconducting quantum processor. Quantum programming of nonequilibrium higher-order topological phases was achieved by constructing quantum circuits comprising >50 cycles of Floquet operators on a six-by-six qubit array. Additionally, we introduce a universal approach based on measuring the dynamics of chiral density to identify distinct nonequilibrium higher-order topological features, including Floquet corner topological invariants and π-energy topological corner modes. Our work may enable the use of programmable quantum processors to explore exotic higher-order nonequilibrium topological phases of matter.
GPT-4o mini: Non-social science research article
Seasonal dynamics of Earth’s glaciers and ice sheets
Chad A. Greene, Alex S. Gardner
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The sensitivity of Earth’s glaciers to environmental change is on display each year as they change speed with the seasons, and a glacier’s response to warming from winter to summer may help predict its response to warming on multiyear timescales. We present a global analysis of seasonal glacier and ice sheet dynamics, finding that seasonal velocity amplitudes are greatest where annual maximum surface temperature exceeds 0°C. We see evidence of basal hydrological systems affecting glacier flow on seasonal timescales and find a weak but significant global correlation between seasonal and interannual flow variability. Glaciers appear to accelerate and decelerate yearly in response to surface melt, and the data suggest that future atmospheric warming could amplify and alter the timing of seasonal glacier dynamics worldwide.
GPT-4o mini: Non-social science research article
Full utilization of noble metals by atom abstraction for propane dehydrogenation
Guodong Sun, Ran Luo, Donglong Fu, Kexin Wu, Xianhui Wang, Xiaoqing Bian, Zhenpu Lu, Xin Chang, Zhi Wang, Siwei Huang, Yihan Zhu, Jihan Zhou, Sai Chen, Chunlei Pei, Zhi-Jian Zhao, Jinlong Gong
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Maximizing atomic utilization of noble metals is crucial for efficient industrial catalysis. We demonstrate that minimal platinum (Pt) loading for propane dehydrogenation (PDH) can be achieved through atom abstraction. At low loadings of Pt with copper (Cu), reduction over silica or other oxide supports formed nanoparticles (NPs) with Pt mainly dispersed in the bulk. Addition of tin (Sn) to the alloy led to formation of surface Pt 1 Sn 1 dimers. The larger atomic radius of Sn compared with Cu drove it to the surface, and its stronger interactions with Pt abstracted Pt from the bulk. Single metallic Pt atoms were stabilized on fully open surfaces, resulting in nearly 100% surface exposure. This configuration reduced Pt usage by one order of magnitude for propane dehydrogenation and improved catalytic stability.
GPT-4o mini: Non-social science research article
Liquid-state dipolarcaloric refrigeration cycle with nitrate-based salts
Seonggon Kim, Jae Hyeon Shin, Gil Jeong, Dae Young Jung, Jiachen Li, Zhenyuan Xu, Ruzhu Wang, Yong Tae Kang
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The environmental burden of vapor compression refrigeration has driven interest in alternatives. Caloric refrigeration cycles offer a path forward, but most rely on solid-state materials with limited temperature lift, low performance, and poor fluidity, which hinder scalability. We introduce a liquid-phase dipolarcaloric refrigeration cycle utilizing endothermic dissolution of nitrate-based salts regenerated through electrodialysis. This cycle achieves large adiabatic temperature changes and high coefficients of performance. We identified effective saltwater pairs and validated the cycle experimentally, supported by thermodynamic modeling. Among these pairs, ammonium nitrate is suited for refrigeration, and potassium nitrate is appropriate for air conditioning. The system uses abundant, low-cost materials, and its fluidic nature ensures efficient heat transfer and scalability. This work establishes dipolarcaloric cooling as a viable alternative for environmentally responsible refrigeration.
GPT-4o mini: Non-social science research article
Structural basis of T-loop–independent recognition and activation of CDKs by the CDK-activating kinase
Victoria I. Cushing, Amy J. S. McGeoch, Sophie L. Williams, Theodoros I. Roumeliotis, Junjie Feng, Lucy M. Dan, Jyoti S. Choudhary, Norman E. Davey, Basil J. Greber
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Cyclin-dependent kinases (CDKs) are prototypical regulators of the cell cycle. The CDK-activating kinase (CAK) acts as a master regulator of CDK activity by catalyzing the activating phosphorylation of CDKs on a conserved threonine residue within the regulatory T-loop. However, structural data illuminating the mechanism by which the CAK recognizes and activates CDKs have remained elusive. In this study, we determined high-resolution structures of the CAK in complex with CDK2 and CDK2–cyclin A2 by cryogenic electron microscopy. Our structures reveal a T-loop–independent kinase-kinase interface with contributions from both kinase lobes. Computational analysis and structures of the CAK in complex with CDK1–cyclin B1 and CDK11 indicate that these structures represent the general architecture of CAK-CDK complexes. These results advance our mechanistic understanding of cell cycle regulation and kinase signaling cascades.
GPT-4o mini: Non-social science research article
Active learning framework leveraging transcriptomics identifies modulators of disease phenotypes
Benjamin DeMeo, Charlotte Nesbitt, Samuel A. Miller, Daniel B. Burkhardt, Inna Lipchina, Doris Fu, Peter Holderrieth, David Kim, Sergey Kolchenko, Artur Szalata, Ishan Gupta, Christine Kerr, Thomas Pfefer, Raziel Rojas-Rodriguez, Sunil Kuppassani, Laurens Kruidenier, Parul B. Doshi, Mahdi Zamanighomi, James J. Collins, Alex K. Shalek, Fabian J. Theis, Mauricio Cortes
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Phenotypic drug screening remains constrained by the vastness of chemical space and the technical challenges of scaling experimental workflows. To overcome these barriers, computational methods have been developed to prioritize compounds, but they rely on either single-task models lacking generalizability or heuristic-based genomic proxies that resist optimization. We designed an active deep learning framework that leverages omics to enable scalable, optimizable identification of compounds that induce complex phenotypes. Our generalizable algorithm outperformed state-of-the-art models on classical recall, translating to a 13- to 17-fold increase in phenotypic hit rate across two hematological discovery campaigns. Combining this algorithm with a lab-in-the-loop signature refinement step, we achieved an additional twofold increase in hit rate along with molecular insights. In sum, our framework enables efficient phenotypic hit identification campaigns, with broad potential to accelerate drug discovery.
Science abstract < 200 char.: Not a research article
Whither the world’s winds The Breath of the Gods: The History and Future of the Wind Simon Winchester Harper, 2025. 416 pp.
Sarah Boon
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An author probes the history and future of the planet’s gentle breezes and brisk gales
Science abstract < 200 char.: Not a research article
A fish story
Hervé Rogissart
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Science abstract < 200 char.: Not a research article
Pasteur’s quadrant researchers bring novelty, impact to publishing, and patenting
E. Scharfmann, M. Marx, L. Fleming
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A new dataset highlights distinctive contributions of scientists who both publish and patent their research
Science abstract < 200 char.: Not a research article
Accelerating science with AI
DarĂ­o Gil, Kathryn A. Moler
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Science abstract < 200 char.: Not a research article
In Science Journals
Julie S. Haas, Phil Szuromi, Jelena Stajic, Corinne Simonti, Angela Hessler, Leoma Bere, Michael A. Funk, Yevgeniya Nusinovich, Caroline Ash, Yury Suleymanov, Ekeoma Uzogara, Sacha Vignieri, Jesse Smith, Leslie Ferrarelli, Melissa Norton
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
Despite Trump chaos, NSF avoided feared dip in research financing
Jeffrey Brainard, Monica Hersher
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But it awarded fewer, larger grants as it braced for possible budget cut
Science abstract < 200 char.: Not a research article
A New Chapter for Science in the Caribbean
Jade Prévost-Manuel
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Science abstract < 200 char.: Not a research article
The cat diaspora out of Africa
Jonathan B. Losos
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Ancient DNA illuminates the origin and spread of the domestic cat
Science abstract < 200 char.: Not a research article
How does glacier flow vary by season?
Lizz Ultee
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Satellite data reveal regional differences in glaciers’ seasonal flow
Science abstract < 200 char.: Not a research article
Curious gravitational wave may hint at primordial black holes—or just be noise
Adrian Cho
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Astronomers approach unusual observation with caution and excitement
Science abstract < 200 char.: Not a research article
Turning point
Paul Voosen
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Global greenhouse emissions will soon flatten or decline—a historic moment driven by China’s surge in renewable energy
Science abstract < 200 char.: Not a research article
Political appointee tells CDC to end monkey research
David Grimm
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Agency scientists and outside researchers decry the sudden decision
Science abstract < 200 char.: Not a research article
New tool could make mosquito control simpler and easier
Kai Kupferschmidt
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“Spatial repellents” protect against disease by slowly releasing insecticide in homes
Science abstract < 200 char.: Not a research article
Decolonizing climate action or denying responsibility?
Shairik Sengupta
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Science abstract < 200 char.: Not a research article
A science club for senior citizens
Ellison Powers Rhea
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Science abstract < 200 char.: Not a research article
Mathematics is hard for mathematicians to understand too
Emily Riehl
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Science abstract < 200 char.: Not a research article
A human history of machines The Body Digital Vanessa Chang Melville House, 2025. 256 pp.
Amit Chandra
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Our lived experiences inform technology and are, in turn, transformed by it
Science abstract < 200 char.: Not a research article
Platform-independent experiments on social media
Jennifer Allen, Joshua A. Tucker
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Changing algorithms with artificial intelligence tools can influence partisan animosity
Science abstract < 200 char.: Not a research article
Groove to the music
Asif A. Ghazanfar, Gavin Steingo
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What can tapping macaques reveal about the evolution of musicality?
Science abstract < 200 char.: Not a research article
Himalayan rivers face a hydropower surge
Ling Tang, Baker Matovu, Weilong Kong, Shaokun Li, Mingrong Liang, Hong Yang
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Science abstract < 200 char.: Not a research article
In Other Journals
L. Bryan Ray, Yevgeniya Nusinovich, Peter Stern, Jake S. Yeston, Angela Hessler, Marc S. Lavine, Corinne Simonti
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
Contrails may not be the climate villain once feared
Paul Voosen
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Studies raise questions about how to adjust flight paths to minimize heat-trapping clouds
Reranking partisan animosity in algorithmic social media feeds alters affective polarization
Tiziano Piccardi, Martin Saveski, Chenyan Jia, Jeffrey Hancock, Jeanne L. Tsai, Michael S. Bernstein
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Today, social media platforms hold the sole power to study the effects of feed-ranking algorithms. We developed a platform-independent method that reranks participants’ feeds in real time and used this method to conduct a preregistered 10-day field experiment with 1256 participants on X during the 2024 US presidential campaign. Our experiment used a large language model to rerank posts that expressed antidemocratic attitudes and partisan animosity (AAPA). Decreasing or increasing AAPA exposure shifted out-party partisan animosity by more than 2 points on a 100-point feeling thermometer, with no detectable differences across party lines, providing causal evidence that exposure to AAPA content alters affective polarization. This work establishes a method to study feed algorithms without requiring platform cooperation, enabling independent evaluation of ranking interventions in naturalistic settings.
My not-so-favorite year
H. Holden Thorp
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As 2025 comes to a close, it’s a good time to step back and assess one of the most tumultuous years in the history of American science. The second Trump administration has brought cuts to so many important efforts. Grants aimed at important aspects of science have been abruptly terminated, and the ability of science to welcome talent from all over the world was curtailed. Government attacks on the scientific enterprise have sent a discouraging message to future scientists, raising the specter of a lost generation of scientific talent in the United States. All of this has been compounded by the slashing of programs that allow people who have been traditionally excluded from science to participate more fully.

Science Advances

GPT-4o mini: Non-social science research article
Metabolic reprogramming in Fanconi anemia: Evidence of compromised glucose oxidation, enhanced ketogenesis, and metabolic inflexibility
Sara Vicente-Muñoz, Suzanne S. Summer, Thomas J. Galletta, Khyati Y. Mehta, Andrew N. Lane, Stella M. Davies, Lindsey E. Romick
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Fanconi anemia (FA) is a rare genetic disorder characterized by congenital abnormalities, bone marrow failure, and cancer predisposition. Approximately 80% of individuals with FA exhibit metabolic abnormalities, including failure to thrive and increased diabetes risk. Current management relies on physical examinations and glucose tolerance tests, which lack dynamic metabolic assessment. We used stable isotope labeling with 13 C 6 -glucose to track nutrient metabolism in individuals with FA. Unlike controls, persons with FA showed no postprandial increase in energy expenditure, sustained hyperglycemia accompanied by elevated glycolysis, and a markedly higher ketogenic response supporting a shift toward lipid utilization. Hormonal analysis revealed secretion of pancreatic hormones and ghrelin in individuals with FA, while incretins were unaffected. These results reflect a profound alteration in substrate utilization involving glucose intolerance, insulin resistance, and ÎČ-cell dysfunction. This innovative approach provides unprecedented insights into FA pathophysiology, which will inform more targeted nutritional and therapeutic interventions for this complex disorder.
GPT-4o mini: Non-social science research article
Arp2/3-dependent regulation of ciliogenesis governs adaptive distal tubular epithelial cell states in kidney disease
Manuel Rogg, Lisa Weißer, Jasmin I. Maier, August Sigle, Martin HelmstĂ€dter, Marlene Stigler, Alena Sammarco, Katja GrĂ€we, Grigor Andreev, Charlotte Kark, Suresh K. Ramakrishnan, Cem Özel, Linus Butt, Frederic Arnold, Wibke Bechtel-Walz, Oliver Schilling, Yakup Tanriver, Paul Brinkkötter, Markus Grabbert, Matias Simons, Martin Werner, Oliver Kretz, Thomas Benzing, Tobias B. Huber, Christoph Schell
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Proteinuric kidney disease substantially affects renal tubules through incompletely understood mechanisms. We identify elongation of primary cilia in distal renal tubules in the context of glomerular nephropathy. In renal biopsies and mouse models, tubular injury correlates with ciliary elongation, tubule dilation, and disruption of the cortical actin cytoskeleton. In vitro studies implicate biophysical cues of the glomerular filtrate and subsequent dysregulation of the actin cytoskeleton as contributing factors, confirmed by conditional deletion of N-WASP and Arp2/3 in vivo and in vitro. Electron and fluorescence microscopy revealed enlarged ciliary pockets, basal body mislocalization, and intracellular cilia formation in Arp3 knockout conditions. Transcriptome analysis identifies the essential role of cilia in maintaining adaptive tubular cell states, while persistent activation leads to disease progression through extracellular matrix remodeling, exemplified by Tenascin-C. Our findings establish cilia as central mediators of tubular adaptation to injury and identify the Arp2/3-dependent actin cytoskeleton as a critical regulator, providing essential insights into the pathogenesis of chronic kidney disease.
GPT-4o mini: Non-social science research article
Spatiotemporally programmed dielectric liquid crystal elastomer: Electro-reversible 3D morphing via inverse 4D printing
Huiyao Zhao, Zike Chen, Jiahao Li, Yingwu Luo, Zhike Peng, Guoyong Mao, Rui Xiao, Jie Mao
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Programmable shape-morphing materials offer transformative potential in soft robotics and biomedical engineering, yet achieving reversible and precise control over complex 3D deformations remains a notable challenge due to the difficulty in spatially programming nonlinear mechanics. Here, we introduce a shear-assisted digital light-processing 4D printing strategy for spatiotemporal programming the mechanical anisotropy of dielectric liquid crystal elastomers (DLCEs). The printed DLCE actuators exhibit reversible multidimensional shape morphing (e.g., bending, twisting, and complex curved surfaces) under electric fields, governed by regional stiffness gradients. An inverse design algorithm is also developed to convert target 3D surfaces into executable printing tasks. Submillimeter-scale fidelity in reconstructing complex geometries, such as a panda face, a biomimetic plant and the Yellow River’s landform, demonstrates capabilities applicable to soft robotics and adaptive systems.
GPT-4o mini: Non-social science research article
Ultrasonic cavitation shock wave exfoliation dynamics of 2D materials revealed in situ by MHz XFEL imaging and multiphysics modeling
Kang Xiang, Ling Qin, Shi Huang, Hongyuan Song, Vasilii Bazhenov, Valerio Bellucci, Sarlota Birnơteinová, Raphael de Wijn, Jayanath C. P. Koliyadu, Faisal H. M. Koua, Adam Round, Ekaterina Round, Abhisakh Sarma, Tokushi Sato, Marcin Sikorski, Yuhe Zhang, Eleni Myrto Asimakopoulou, Pablo Villanueva-Perez, Kyriakos Porfyrakis, Iakovos Tzanakis, Dmitry G. Eskin, Nicole Grobert, Adrian P. Mancuso, Richard Bean, Patrik Vagovič, Jiawei Mi
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Using megahertz x-ray free electron laser imaging with x-ray pulses of ~25 femtoseconds and a machine-learning strategy, we have conducted comprehensive in situ imaging studies on the dynamics of cavitation bubble clouds in ultrasound fields at the SPB/SFX beamline of the European XFEL. The research unambiguously revealed the quasi-simultaneous implosion of multiple bubbles and simultaneous collapse of bubble cloud in nanosecond scale and their dynamic impacts onto two-dimensional (2D) materials for layer exfoliation. We have also performed multiphysics modeling to simulate the shock wave emission, propagation, impact, and stresses produced. We elucidated the critical conditions for producing instant or fatigue exfoliation and the effects of bonding strengths and structural defects on the exfoliation rate. The discoveries have filled the long-standing missing knowledge gaps in the underlying physics of exfoliating 2D materials in ultrasound fields, providing a solid theoretical foundation for optimizing and scaling-up operation to produce 2D materials in a much more cost-effective and sustainable way.
GPT-4o mini: Non-social science research article
Large-amplitude variability driven by giant dust storms on a planetary-mass companion
Xianyu Tan, Xi Zhang, Mark S. Marley, Yifan Zhou, Ben W. P. Lew, Brittany E. Miles, Natasha E. Batalha, Beth A. Biller, Gaël Chauvin, Sasha Hinkley, Kielan K. W. Hoch, Elena Manjavacas, Stanimir Metchev, Simon Petrus, Emily Rickman, Andrew Skemer, Genaro Suårez, Ben J. Sutlieff, Johanna M. Vos, Niall Whiteford
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Large-amplitude variations are commonly observed in the atmospheres of directly imaged exoplanets and brown dwarfs. VHS 1256B, the most variable known planet-mass object, exhibits a near-infrared flux change of nearly 40%, with red color and silicate features revealed in recent JWST spectra, challenging current theories. Using a general circulation model, we demonstrate that VHS 1256B’s atmosphere is dominated by planetary-scale dust storms persisting for tens of days, with large patchy clouds propagating with equatorial waves. This weather pattern, distinct from the banded structures seen on solar system giants, simultaneously explains the observed spectra and critical features in the rotational light curves, including the large amplitude, irregular evolution, and wavelength dependence, as well as the variability trends observed in near-infrared color-magnitude diagrams of dusty substellar atmospheres.
GPT-4o mini: Non-social science research article
FeaSion decodes the regulatory landscape and functional diversity of RNA polymerase II CTD phosphorylation
Junyi Zhu, Lijun Bao, Shengchun Xu, Xiong Ji
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RNA polymerase II’s (RNAPII) C-terminal domain (CTD) contains five phosphorylation sites (pY1, pS2, pT4, pS5, and pS7). However, their regulatome and immediate functions remain elusive. Using the FeaSion (Feature-Screening-Function) strategy, we mapped RNAPII phosphorylation site-specific interactors and genomic occupancy, revealing links to preferential gene length, exon number, and transcription factor binding. CRISPR-FACS screens identified different candidate regulators modulating individual phosphorylation sites. Rapid replacement showed site-specific mutations influence different transcriptional processes, histone modifications (H3K36me3 and H2A.Zac), and preferentially affect developmental and signaling genes. Moreover, we demonstrate kinases CLK1/4 and YES1 directly regulate RNAPII transcription—via site-specific CTD phosphorylation—to control developmental, metabolic, and signal transduction programs. Our findings reveal an expanded regulatory network involving >100 kinase and phosphatases that potentially orchestrate CTD phosphorylation beyond their canonical functions, establishing a multilayered phospho-regulatory network with broad implications for gene expression control in development and disease.
GPT-4o mini: Non-social science research article
Adsorption-enhanced carbon membranes derived from copolyimide for ultrafast subangstrom discriminating CO 2 separation
Kaifang Wang, Zhongtai Zhu, Yuqi Liu, Weiran Zheng, Ziyi Yuan, Zhihong Lin, Raphael Semiat, Lu Shao, Xuezhong He
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Carbon membranes are emerging as a versatile platform for the selective separation of gas mixtures with similar molecular sizes. Here, a high-performance carbon membrane is developed from an asymmetric, rigid copolyimide precursor via a precisely controlled carbonization process. Membranes carbonized at 800°C exhibit exceptional CO 2 separation performance, with CO 2 permeabilities up to 15,700 barrer and CO 2 /N 2 and CO 2 /CH 4 selectivities of 63 and 52, respectively—surpassing the 2019 upper bounds. Molecular dynamic simulations, in conjunction with in situ thermogravimetric analysis-mass spectroscopy and thermogravimetric analysis-Fourier transform infrared spectroscopy, reveal the evolution of a bimodal carbon matrix with micropores (7 to 20 angstroms) and ultramicropores (4 to 7 angstroms). Gas transport is dominated by synergistic adsorption-selective and molecular sieving mechanisms, enabling subangstrom discrimination between CO 2 and larger gases. This work demonstrates a facile, tunable strategy to engineer carbon membranes with outstanding CO 2 separation capabilities, offering previously unexplored opportunities for energy-efficient gas separation processes in industrial applications.
GPT-4o mini: Non-social science research article
Dynamic visual effects enhance flower conspicuousness but compromise color perception
Alexander Dietz, Johannes Spaethe, Casper J. van der Kooi
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Dynamic visual effects such as glossiness are taxonomically widespread and have evolved repeatedly across the tree of life. Their changeable nature poses a challenge for reliable signaling, because for signals to be reliable, they should be consistent. Glossy visual effects defy that principle, because the bright, directional pulse of light that dominates their appearance is highly variable across space and time. Here, we investigate how dynamic light reflections influence signal efficacy using bumblebees as a model of insect vision and plant-pollinator interactions. We show that glossy floral signals occur across Angiosperm lineages. Through behavioral experiments with artificial stimuli that mimic the spectral and spatial reflectance properties of glossy and matte floral surfaces, we demonstrate that glossiness enhances long-range detectability but compromises fine-scale color discrimination at close range. Glossiness thus poses an optical property by which organisms can attune their visual appearance independent of pigmentary properties, representing a functional trade-off between conspicuousness and signal reliability.
GPT-4o mini: Non-social science research article
How ATP and dATP reposition class III ribonucleotide reductase cone domains to regulate enzyme activity
Gisele A. Andree, Kelsey R. Miller-Brown, Zhuangyu Zhao, Ally K. Smith, Christopher D. Dawson, Daniel J. Deredge, Catherine L. Drennan
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Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotides to deoxyribonucleotides. In the majority of cases, RNR activity is allosterically regulated by the cellular 2â€Č-deoxyadenosine 5â€Č-triphosphate (dATP)/adenosine 5â€Č-triphosphate (ATP) ratio. To investigate allosteric activity regulation in anaerobic or class III (glycyl radical containing) RNRs, we determine cryo–electron microscopy structures of the class III RNR from Streptococcus thermophilus (StNrdD). We find that StNrdD’s regulatory “cone” domains adopt markedly different conformations depending on whether the activator ATP or the inhibitor dATP is bound and that these different conformations alternatively position an “active site flap” toward the active site (ATP-bound) or away (dATP-bound). In contrast, the position of the glycyl radical domain is unaffected by the cone domain conformations, suggesting that StNrdD activity is regulated through control of substrate binding rather than control of radical transfer. Hydrogen-deuterium exchange mass spectrometry and mutagenesis support the structural findings. In addition, our structural data provide insight into the molecular basis by which ATP and dATP binding lead to the observed differential cone domain conformations.
GPT-4o mini: Non-social science research article
Brain-derived extracellular vesicles circUsp32 polarized macrophages causing acute kidney injury after traumatic brain injury
Jiayuanyuan Fu, Jingheng Wu, Mengran Du, Xu Wang, Qi Shi, Yehong Fang, Yu Lan, Qiaoli Wu, Guobin Zhang, Lixia Xu, Hua Yan
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Brain-kidney cross-talk following traumatic brain injury (TBI) can induce acute kidney injury (AKI), but mechanisms remain unclear. Extracellular vesicles derived from injured brain tissue (TBI-EVs) may mediate brain-kidney interactions. In vivo experiments demonstrated that TBI-EVs causes AKI by promoting pro-inflammatory macrophage polarization. TBI-EVs markedly increased AKI markers and proportion of pro-inflammatory-polarized macrophages. Mechanistically, transcriptomics of TBI-EVs revealed high circUsp32 expression. Subsequent in vitro assays showed that circUsp32 competitively binds to the SH2 domain of suppressor of cytokine signaling 1 (Socs1), affecting interferon regulator factor 7 (IRF7) ubiquitination and promoting pro-inflammatory polarization. CircUsp32 knockdown reduced pro-inflammatory polarization and alleviated AKI in TBI mice. In addition, circUsp32 is homologous to hsa_circ_0044940, which may serve as a predicted biomarker of AKI after TBI. Notably, AKI following TBI may contribute to neuroinflammation via uremic toxins. Collectively, these findings suggest that circUsp32 mediates macrophage polarization through the Socs1/IRF7 axis and could be a potential biomarker for AKI following TBI.
GPT-4o mini: Non-social science research article
Chain ends excite polymer cooperative motion
Quanyin Xu, Zhenghao Wu, Katelyn Randazzo, Wen-Sheng Xu, Bokai Zhang, Rodney D. Priestley, Biao Zuo
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Among glasses, polymers stand out as the chain connectivity endows them with distinct properties in glass formation, among them the transition temperature ( T g ) and dynamic fragility ( m ) varying with chain length. Here, we resolve the nature of the chain length–dependent behaviors, revealing the strong correlation between the number of chain ends within the cooperatively rearranging region and glassy properties including T g and m . The correlations suggest a simple yet common mechanism of glass formation for the chain molecules, i.e., fast-relaxing chain ends alleviate the requirements of cooperativity for structural rearrangement, thus facilitating the cooperative motion that reduces T g and m as chain length is shortened. We categorize the role of end groups between soft and rigid by proposing a physical quantifier—index of rigidity. Our results provide a unifying picture of polymer glass formation, regarding the role of chain end, length, and topology, a foundational phenomenon with implications across fields of chemistry, soft-condensed matters, and material science.
GPT-4o mini: Non-social science research article
Lysosomal control of proteostasis and reproductive capacity by conserved LMD-3 protein in C. elegans
Yile Zhai, Tiantian Wang, Jiangxue Han, Mengxiao Wu, Meixi Gong, Wenfei Li, Zhe Zhang
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Human female fertility declines markedly with age, a pattern mirrored in C. elegans fecundity. This shared vulnerability stems from evolutionarily conserved molecular pathways. A growing body of evidence links impaired proteostasis—the cell’s ability to manage its proteins—to this age-related fertility drop in both species, although the underlying mechanisms are not fully understood. Here, we identify that LMD-3, a LysM domain protein, is a critical regulator of proteostasis and reproductive capacity in C. elegans . Deficiency of lmd-3 leads to notable defects in oxidation resistance and constitutively high cellular stress responses. We demonstrate that LMD-3, localized to the lysosome, interacts with vitellogenin and a proton-pumping V-type ATPase via its TLDc domain to regulate lysosomal function and maintain yolk protein homeostasis. We also found that supplementing with vitamin B12 can restore fertility in lmd-3 mutants by reducing oxidative stress and improving lysosomal function. These findings establish a model for studying reproductive health and finding potential therapeutic strategies.
GPT-4o mini: Non-social science research article
A three-dimensional photoacoustic and ultrasound automated breast volume scanner (PAUS-ABVS) for breast cancer patients
Sinyoung Park, Minsik Sung, Hyunhee Kim, Ki Jong Lee, Eun-Yeong Park, Joongho Ahn, Sung Sik Park, Ji-Hye Kim, Yongseok Cho, Jungyung Lee, Namsun Paik, Chulhong Kim
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Breast cancer screening with mammography is less effective in women with dense breast tissue, prompting the use of ultrasound (US) imaging. While two- (2D) and three-dimensional (3D) US improve cancer detection, their low specificity leads to frequent unnecessary biopsies. Operator dependence on 2D US has led to the development of 3D automated breast volume scanners (ABVS), but challenges remain in distinguishing benign from malignant lesions. We developed a 3D photoacoustic and ultrasound (PAUS)–ABVS system that integrates a large field-of-view, 768-element transducer to improve diagnostic accuracy. In a clinical study of 61 patients with 36 benign and 30 malignant lesions, multispectral photoacoustic imaging was used to measure blood volume and oxygen saturation within lesions. When combined with standard US BI-RADS (breast imaging reporting and data system) scores, the system achieved a sensitivity of 96.7% and specificity of 66.7%. This performance matched the best outcomes of 2D PAUS and outperformed conventional US. Our results suggest that the PAUS-ABVS can support more accurate breast cancer diagnosis while reducing unnecessary biopsies.
GPT-4o mini: Non-social science research article
Potential-modulated orbital interactions determine domino CO/methanol selectivity for CO 2 electroreduction on cobalt phthalocyanine
Juan Zhang, Yu Wang, Yafei Li
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Heterogenized cobalt phthalocyanine (hetero-CoPc) molecular catalysts exhibit domino CO/methanol selectivity during CO 2 electroreduction. However, the origin of this selectivity is not well understood, impeding the strategic optimization for methanol generation. Here, we show potential-modulated orbital interaction mechanisms governing the selectivity in hetero-CoPc based on first-principles calculations with consideration of carbon support and electrochemical interfaces. Specifically, constant-potential orbital-resolved analyses reveal that electrons introduced by applied potentials initially occupy the semi-occupied Co-3d z 2 orbital, thus suppressing CO-5σ → Co-3d z 2 electron donation. This induces gradual weakening of *CO adsorption while establishing high *CO hydrogenation barriers (restricting the product to CO) over the medium potential range. With further decreasing potentials, a progressive electron population occurs in the Co-3d yz /d xz orbitals, promoting the Co-3d xz /d yz → CO-2π* back-donation. This facilitates the activation of the C─O bond of *CO, thereby reducing its hydrogenation barriers and enabling methanol production at more negative potentials. Similar analyses also rationalize experimental observations for other heterogenized metal phthalocyanines, showing the importance of potential-modulated orbital interactions for selectivity engineering.
GPT-4o mini: Non-social science research article
Dynamic imaging reveals subnanometer gap distance controls electron transfer processes at plasmonic nanointerfaces
Gang Wu, Yi Sun, Jun-Hao Wan, Wen-Li Lv, Chen Qian, Xian-Wei Liu
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Understanding electron transfer dynamics at subnanometer gaps between nanomaterial interfaces and electrodes is crucial for applications in catalysis, electrochemistry, and nanophotonics. However, experimentally visualizing and correlating electron transfer processes with dynamic nanoscale gap evolution remains challenging. Here, we use plasmonic scattering interferometric microscopy (PSIM) combined with nanoelectrochemical modulation to dynamically probe electron transfer processes at interfaces between Au nanoparticles and an Au electrode in real time, achieving subnanometer resolution. By tuning interfacial chemical forces and validating our observations through simulations, we correlate the electron transfer–related optical signatures with entry into the nanogap coupling regime. These findings highlight gap distance as the primary determinant of heterogeneous electron transfer at nanomaterial interfaces. This work provides a direct experimental framework for probing nanoscale electron transfer dynamics at optical frequencies, with implications for the rational design of advanced electrocatalytic interfaces, nano-sensing platforms, and optoelectronic devices.
GPT-4o mini: Non-social science research article
North Atlantic Subtropical High forcing of Atlantic Warm Pool hydroclimate variability on millennial to orbital timescales
Hanying Li, Ashish Sinha, Amos Winter, Pengzhen Duan, Sophie Warken, Jun Hu, Shihao Lei, Xiyu Dong, Lijuan Sha, Haiwei Zhang, Gayatri Kathayat, Liang Yi, Youfeng Ning, Hai Cheng
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Orbital-scale variations in insolation are widely considered to drive tropical and monsoonal rainfall, with higher summer insolation linked to stronger precipitation. Here, we present a precisely dated speleothem record from Cuba that reconstructs Atlantic Warm Pool (AWP) hydroclimate over the past 129,000 years and challenges this paradigm. Instead, we identify a previously unrecognized link between AWP hydroclimate and the North Atlantic Subtropical High (NASH) operating on millennial to orbital timescales. During intervals of high summer insolation coupled with cooler tropical North Atlantic sea surface temperatures (SSTs), NASH strengthens and expands westward, reducing rainfall across the AWP. This SST-NASH coupling amplified precessional-scale hydroclimate variability between 130 and 60 ka, when insolation amplitude was nearly twice that of the 60- to 12-ka interval. Our data further show that particularly strong insolation peaks at 105 and 126 ka caused pronounced westward NASH expansion, triggering two extreme dry events, similar to the process observed during modern midsummer dry spells.
GPT-4o mini: Non-social science research article
View-invariant representations in ancestral cortex
Milan Becker, Nimrod Leberstein, Mark Shein-Idelson
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A multilayered, thalamorecipient visual cortex emerged ~320 million years ago in stem amniotes. Despite its importance for understanding the evolution of cortical computation, its function remains unknown. We recorded visually evoked responses in the dorsal cortex of behaving turtles, considered a mammalian neocortex homolog. Using a spatial oddball paradigm, we found tuning to stimuli in deviant positions alongside adaptation to standard positions within the visual field. Eye tracking demonstrated that responses remained spatially selective despite gaze shifts altering retinal stimulus position. Thus, the turtle cortex encodes unexpected visual stimuli using computations invariant to retinal position, a property previously observed only in higher mammalian cortices. These results indicate that invariance computations preceded the evolution of local filtering computations in mammalian primary cortices, pointing to a previously unidentified function for ancestral cortices. They also challenge hierarchical models of invariance computations, which assume that invariance is built from low-level features across multiple processing steps.
GPT-4o mini: Non-social science research article
Optogenetic silencing by combining a rhodopsin cyclase with an engineered cGMP-gated potassium channel
Anika Spreen, Nidish Ponath Sadanandan, Martin Winfried Schneider, Enrico Kuehn, Andries Napo Leemisa, Roberta De Zio, Niklas Meyer, Wayne Busse, Bela Erlinghagen, Lea Adenauer, Thoralf Opitz, Wolfgang Bönigk, Enrico Schiewer, Jonas Heer, Dietmar Schmitz, Johannes Vierock, Heinz Beck, Peter Hegemann, Herwig Baier, Franziska Schneider-Warme, Yinth Andrea Bernal Sierra, Reinhard Seifert
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Since the advent of optogenetics, great progress has been made in developing tools to modulate and detect cellular activity using light. We present a two-component optogenetic silencing tool, RoCK (rhodopsin cyclase/K + channel), which pairs the rhodopsin-guanylyl cyclase CaRhGC with customized SthK K + channels that are engineered to open selectively upon guanosine 3â€Č,5â€Č-monophosphate (cGMP) binding. By enhancing the cGMP sensitivity and open probability of SthK mutants, we obtained four channel variants suited for different levels of cGMP concentration. CaRhGC’s membrane-bound nature enables localized cGMP production, and the lack of dark activity reduces the risk for off-target effects. Optimized RoCK effectively modulated cellular activity in mouse hippocampal neurons, in acute hippocampal slices, and in rabbit cardiomyocytes. In zebrafish, RoCK silenced motor neurons in vivo, suppressing the characteristic coiling behavior of embryos, thus highlighting its potential for behavioral studies. In summary, RoCK expands our optogenetic toolkit threefold for fast cGMP production, fast cGMP sensing, and K + -based cell silencing.
GPT-4o mini: Non-social science research article
Neurophysiological signatures of default mode network dysfunction and cognitive decline in Alzheimer’s disease
Recep A. Ozdemir, Brice Passera, Peter J. Fried, Daniel Press, Lynn W. Shaughnessy, Stephanie Buss, Mouhsin M. Shafi
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Neural hyperexcitability and network dysfunction are neurophysiological hallmarks of Alzheimer’s disease (AD) in animal studies, but their presence and clinical relevance in humans remain poorly understood. We introduce a perturbation-based approach combining transcranial magnetic stimulation and electroencephalography (TMS-EEG), alongside resting-state EEG (rsEEG), to investigate neurophysiological basis of default mode network (DMN) dysfunction in early AD. While rsEEG revealed global neural slowing and disrupted synchrony, these measures reflected widespread changes in brain neurophysiology without network-specific insights. In contrast, TMS-EEG identified network-specific local hyperexcitability in the parietal DMN and disrupted connectivity with frontal DMN regions, which uniquely predicted distinct cognitive impairments and mediated the link between structural brain integrity and cognition. Our findings provide critical insights into how network-specific neurophysiological disruptions contribute to AD-related cognitive dysfunction. Perturbation-based assessments hold promise as potential markers of early detection, disease progression, and target engagement for disease-modifying therapies aiming to restore abnormal neurophysiology in AD.
GPT-4o mini: Non-social science research article
Role of CEBPa in trophectoderm competence installment
Xiao Wei, Irepan Salvador-Martinez, Maciej Meglicki, Marcos Plana-Carmona, Antonios Klonizakis, Barbara Pernaute, Manuel Irimia, Gregoire Stik, Mina Popovic, Guillem Torcal Garcia, Holger Heyn, Magdalena Zernicka-Goetz, Thomas Graf
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During mouse embryogenesis, totipotency is gradually lost, and, at the 16-cell stage, blastomeres begin to bifurcate into trophectoderm (future placenta) and inner cell mass (future fetus). Although this process is well studied, when and how blastomeres acquire the competence for lineage specification remains unclear. Here, we describe that CEBPa becomes up-regulated at the transition from the two- to the four-cell stage by NR5A2 and is also selectively expressed in the trophectoderm at the blastocyst stage. Its knockout decreases the proportion of trophectoderm cells and delays the morula to blastocyst transition. Conversely, CEBPa overexpression in mouse embryonic stem cells, used as a proxy, drives their differentiation into trophectoderm-like cells, enabling the identification of CEBPa-regulated trophectoderm-specific enhancers. A subset of these enhancers, associated with key trophectoderm-related transcription factor genes, is primed or activated in four- and eight-cell embryos. Together, our data suggest that CEBPa plays a role in the installment of trophectoderm competence before the first lineage bifurcation and in trophectoderm specification.
GPT-4o mini: Non-social science research article
Understanding generative AI output with embedding models
Max Vargas, Reilly Cannon, Andrew Engel, Anand D. Sarwate, Tony Chiang
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Constructing high-quality features is critical to any quantitative data analysis. While feature engineering was historically addressed by carefully handcrafting data representations on the basis of domain expertise, deep neural networks (DNNs) now offer a radically different approach. DNNs implicitly engineer features by transforming their input data into hidden feature vectors called embeddings. For embedding vectors produced by foundation models—which are trained to be useful across many contexts—we demonstrate that simple and well-studied dimensionality-reduction techniques such as principal components analysis uncover inherent heterogeneity in input data concordant with human-understandable explanations. Of the many applications for this framework, we find empirical evidence that there is intrinsic separability between real samples and those generated by artificial intelligence.
GPT-4o mini: Non-social science research article
Toward AI ecosystems for electrolyte and interface engineering in solid-state batteries
Zhilong Wang, Wolfgang G. Zeier, Fengqi You
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Solid-state batteries (SSBs) are pivotal for sustainable energy storage, delivering extended life span, low-temperature resilience, and enhanced safety. However, designing stable solid electrolytes and interfaces in SSBs remains a formidable challenge. As a disruptive catalyst for paradigm shifts spanning materials discovery and energy system redesign, artificial intelligence (AI) is unleashing unprecedented possibilities—could it be the key breakthrough for SSB innovation? Here, we critically review the progress of AI applications in electrolyte and interface engineering, covering key aspects such as stability, conductivity, mechanical properties, and interface resistance. This work emphasizes the integration of cutting-edge modeling strategies, including the materials’ screening pipelines, machine learning force fields, and generative models. Furthermore, we conduct an in-depth analysis of persistent challenges and propose a roadmap featuring multiscale modeling and multimodal models with physical constraints to build an intelligent ecosystem for SSB development. This review is expected to inspire interdisciplinary collaborations and drive forward energy materials design, ultimately accelerating the development of sustainable and cutting-edge battery technologies.
GPT-4o mini: Non-social science research article
Specialized signaling centers direct cell fate and spatial organization in a mesodermal organoid model
Evangelia Skoufa, Jixing Zhong, Kelly Hu, Oliver Kahre, Georgios Tsissios, Louise Carrau, Antonio Herrera, Albert Dominguez Mantes, Marion Leleu, Alejandro Castilla-Ibeas, Hwanseok Jang, Martin Weigert, Gioele La Manno, Matthias Lutolf, Marian Ros, Can Aztekin
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Specialized signaling centers orchestrate robust development and regeneration. Limb morphogenesis, for instance, requires interactions between the mesoderm and the signaling center apical-ectodermal ridge (AER), whose properties and role in cell fate decisions have remained challenging to dissect. To tackle this, we developed mouse embryonic stem cell (mESC)–based heterogeneous cultures and a three-dimensional (3D) organoid model, termed budoids, comprising cells with AER, surface ectoderm, and mesoderm properties. mESCs were first induced into heterogeneous cultures that self-organized into domes in 2D. Aggregating these cultures formed mesodermal organoids with certain limb bud–like features in 3D, exhibiting chondrogenesis-based symmetry breaking and elongation. Using our organoids and quantitative in situ expression profiling, we uncovered that AER-like cells support nearby limb mesoderm and fibroblast identities while enhancing tissue polarization that permits distant cartilage formation. Together, our findings provide a powerful model to study epithelial signaling center-mesoderm interactions during morphogenesis and reveal the ability of signaling center AER cells to concurrently modulate cell fate and spatial organization.
GPT-4o mini: Non-social science research article
Negligible contribution from aerosols to recent trends in Earth’s energy imbalance
Chanyoung Park, Brian J. Soden
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During the 21st century, Earth’s energy imbalance (EEI) at the top of atmosphere has markedly increased because of greater absorbed shortwave (SW) rather than reduced outgoing longwave radiation. Previous studies using single-forcing (aerosol-only) experiments attributed approximately half of the positive SW trend to reductions in anthropogenic aerosols, particularly in the Northern Hemisphere (NH). In contrast, our analysis using observations and reanalysis indicates that both aerosol-radiation and aerosol-cloud interactions have made a negligible contribution to recent EEI trends. While NH anthropogenic aerosols have decreased, enhanced emissions from wildfires and volcanic activity in the Southern Hemisphere (SH) have produced comparable increases, yielding little net global impact. This hemispheric compensation also suggests that model-based estimates may overestimate aerosol influence by overlooking SH aerosol contributions. Despite uncertainties in aerosol proxies, the consistent results from two complementary proxies—satellite-derived aerosol index and reanalysis-based sulfate mass concentration—highlight the importance of accounting for natural source aerosols when assessing EEI trends.
GPT-4o mini: Non-social science research article
Quantum tunneling of homogeneous catalyst altering CO 2 reduction reaction pathway for stable Mg-CO 2 batteries
Wenbo Liu, Lu Li, Menggang Li, Zongqiang Sun, Youxing Liu, Shaojun Guo
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Mg-CO 2 battery has emerged as a promising battery technology by harnessing greenhouse gas as an active material. However, its development is greatly hindered by sluggish CO 2 conversion kinetics, resulting in high overpotentials and poor reversibility. Herein, we report a class of 2,2,6,6-tetramethylpiperidoxyl (TEMPO) homogeneous catalyst to regulate CO 2 adsorption and optimize reaction pathways through a quantum tunneling effect induced by electron transfer from the TEMPO free radical to CO 2 that classical electron transfer mechanisms cannot overcome. This quantum tunneling effect not only enables CO 2 reduction at lower voltage but also regulates the CO 2 adsorption environment, leading to the alternated reaction pathway for the formation of flower-like MgC 2 O 4 as the discharge product, rather than the dense MgCO 3 typically formed in traditional models. The TEMPO-based Mg-CO 2 batteries achieve an exceptional discharge voltage of 1.1 volts and a charge voltage of 1.3 volts, with stable cycling performance for over 450 hours, representing the best-reported performance among Mg-CO 2 battery systems to date.
GPT-4o mini: Non-social science research article
An intelligent, compact wearable pressure-strain combo sensor system for continuous fetal movement monitoring
Lim Wei Yap, Arie Levin, Yiwen Jiang, Duong Nhu, Shu Gong, Ritesh Warty, David Vera Anaya, Qinhao Li, Yan Lu, Rui Gao, Xin Zhang, Talha Ilyas, Vinayak Smith, Allison Thomas, Aswandi Wibrianto, Yuxin Zhang, Jane Limas, Sharon A. McCracken, Jonathan M. Morris, Ben W. Mol, Euan M. Wallace, Arnold Lining Ju, Zongyuan Ge, Faezeh Marzbanrad, Wenlong Cheng
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Continuous fetal movement monitoring in late pregnancy may improve fetal wellbeing and pregnancy outcomes. While fetal movements can be visualized with ultrasound, it is intermittent and limited to clinical settings. Inertial measurement units may enable at-home fetal monitoring but usually require a large-footprint, multisensor design. Here, we report smart, compact wearable pressure-strain combo sensors continuously monitoring fetal movements through maternal abdominal skin motions. In the 2D and 3D artificial abdomen systems, our octagonal-shaped gold nanowire–based strain sensor served as an isotropic sensor, enabling omnidirectional simulated “kicking load” detection within an area of ~77 (2D) and ~217 cm 2 (3D), while an interdigitated electrode–based pressure sensor showed highly sensitive localized load detection. Building upon these findings, we designed compact pressure- and strain-sensing integrated Band-Aids and tested on 59 pregnant women. We developed machine learning models to distinguish fetal from nonfetal movements with >90% accuracy in ultrasound-based validation studies. This AI-powered, Band-Aid–like sensing system offers potential as a compact, comfortable, and accurate continuous out-of-hospital fetal movement monitoring technology.
GPT-4o mini: Non-social science research article
Animal tracking with particle algorithms informs protected area design
Edward Lavender, Andreas Scheidegger, Carlo Albert, StanisƂaw W. Biber, Jakob Brodersen, Dmitry Aleynik, Georgina Cole, Jane Dodd, Peter J. Wright, Janine Illian, Mark James, Sophie Smout, James Thorburn, Helen Moor
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Animal movements affect their exposure to threats and the efficacy of conservation measures, such as marine protected areas (MPAs). However, many species’ movements are difficult to reconstruct from available datasets, hampering conservation efforts. This is especially the case for aquatic species that rarely surface, for which data are often limited to observations from acoustic telemetry (detections) and ancillary sensors. Here, we pioneer the use of state-of-the-art particle algorithms to model movements, integrate datasets, and assess MPA design, leveraging a case study of a Critically Endangered elasmobranch. Our algorithms led to 5-fold improvements in space-use maps and 30-fold improvements in residency estimates compared to prevailing methods. By integrating tracking datasets, we were uniquely able to examine movements beyond acoustic receivers, MPA-scale residency, and specific habitats beyond protected areas that warrant protection. This work reveals a modeling framework that enhances the conservation value of acoustic telemetry, supporting analyses of MPA efficacy worldwide.
GPT-4o mini: Non-social science research article
Widespread association of Polycomb complex–deposited histone H2A monoubiquitylation with enhancers and neuronal gene regulation
Kailynn MacGillivray, Daniel Fusca, Luomeng Tan, Reta Aram, Arneet L. Saltzman
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Disruption of histone H2A monoubiquitylation (H2AK119ub) causes neurodevelopmental disorders through poorly understood mechanisms. Polycomb complex–deposited H2AK119ub and trimethylation of histone H3 at lysine 27 (H3K27me3) can cooperatively maintain gene repression. However, the extent to which H2AK119ub functions independently of H3K27me3 to repress or potentiate gene expression, and the evolutionary conservation of these roles, remains unclear. Here, we address the interplay among Polycomb-deposited marks and chromatin states in Caenorhabditis elegans embryos. We find that H2AK119ub distribution is distinct from and largely dispensable for H3K27me3 patterns. Unexpectedly, H2AK119ub is enriched at predicted enhancers with developmentally dynamic changes in accessibility, including in neurons. More than two-thirds of well-documented axon guidance genes and neuronal identity transcription factors are associated with H2AK119ub. Many of the genes differentially expressed in H2AK119ub-deficient animals are involved in neuronal differentiation and signaling and feature H2AK119ub-enriched promoters and enhancers, including a subset that is H3K27me3 repressed. We uncover a likely conserved yet underappreciated dual role for H2AK119ub at enhancers and H3K27me3-repressed chromatin, with implications for nervous system development.
GPT-4o mini: Non-social science research article
Bias-controlled multistate spintronics with giant TMR and polarity switch via localized spin states in 2D half-metals
Jialin Yang, Chuyao Chen, Shengli Zhang, Chen Pan, Bin Cheng, Feng Xu, Xi Chen, Erjun Kan, Haibo Zeng
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The relentless downscaling of integrated circuit systems imposes critical demands on spintronic technologies, particularly requiring superior storage density and efficient tunability beyond conventional magnetic-field approaches. A notable challenge persists in realizing multistate spintronic devices with electrical control at nanoscale. Here, we propose a breakthrough strategy for achieving bias-controlled giant tunneling magnetoresistance (TMR) for multistate memory applications. Our design uses two-dimensional (2D) half-metals hosting strongly localized spin states (LSSs) at the Fermi level as two ferromagnet layers in magnetic tunnel junctions (MTJs). Multiple memory states emerge from bias-driven alignment/misalignment of LSSs on two sides, generating sudden tunneling pathway changes and distinguishable TMR. First-principles quantum transport simulations on MTJs based on 2D VCl 3 and FeCl 2 reveal unprecedented bias-controlled and widely modulable TMR ratios spanning −194 to 2677% and −130 to 37,424%, respectively, accompanied by rare polarity switch capabilities. Our work opens a promising route for realizing electrical control of multistate spintronics.
GPT-4o mini: Non-social science research article
Visualizing dynamics of membrane rafts on live cells
Hsiang-Ling Chuang, Yu-Chen Fa, Kum-Yi Cheng, Er-Chien Horng, Yi-Te Chou, Richard P. Cheng, Li-Chen Wu, Ja-an Annie Ho, Chun-hsien Chen
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Membrane rafts are cellular portals to external stimuli that trigger signaling cascades for sophisticated yet remarkable biochemical activities. Visualization of the topographic evolution of membrane rafts remains unreported on live cells due to the nanosized and dynamic nature. Here, an imaging strategy involving atomic force microscopy and Hadamard product is developed to unveil membrane-raft features. Michigan Cancer Foundation-7 (MCF-7) cells were subjected to fibrinogen or manganese(II) (Mn 2+ )/resveratrol, both of which are ligands of integrin α V ÎČ 3 embedded within membrane rafts; the former promotes metastasis, and the latter enables apoptosis. MCF-7 cellular membranes responded to the two stimulants markedly different. The size, height, spatiotemporal trajectory, and persistent time of ligand-activated nanodomains are revealed. This approach opens up a visualized platform toward the understanding of activation-associated signaling cascades.
GPT-4o mini: Non-social science research article
Substitution of human olfaction by the trigeminal system
Halina B. Stanley, Clémentine Lipp, Coralie Mignot, Susanne Weise, Konstantinos Garefis, Maxime Fieux, Evangelia Tsakiropoulou, Sotiria Genetzaki, Romain Dubreuil, Camille Ferdenzi, Marina Carulli, Michele Bertolini, Marco Rossoni, Arnaud Bertsch, Juergen Brugger, Thomas Hummel, Iordanis Konstantinidis, Moustafa Bensafi
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Smell loss is a sensory impairment that has major consequences in many areas of daily life and for which current therapies are insufficient. A prosthesis-type technology enabling patients to sample their olfactory environment has not yet been developed. The aim of our study was, therefore, to test whether stimulation of the intranasal trigeminal system by a device combining an artificial nose with an intranasal electrical stimulator will enable patients to detect and discriminate odorant molecules. Four experiments involving normosmic individuals ( n  = 13) and patients with olfactory loss ( n  = 52) showed that individuals were able to detect their olfactory environment using the device. For discrimination, the results are less clear-cut but show that most patients can distinguish between two external stimuli. Although this substitution approach does not allow patients to smell real odors, it is a genuine first substitution solution that we could imagine offering to patients in the future.
GPT-4o mini: Non-social science research article
Inclusion of JNK-independent drugs within multiagent chemotherapy improves response in relapsed high-risk neuroblastoma
Jeremy Z. R. Han, Monica Phimmachanh, Jordan F. Hastings, King Ho Leong, Boaz H. Ng, Jenny Ni, Angela Fontaine-Titley, Antonia L. Cadell, Yolande EI O’Donnell, Misaki Clearwater, Alvin Kamili, Michelle Haber, Murray Norris, Paul Timpson, Toby N. Trahair, Jamie I. Fletcher, Dirk Fey, Walter Kolch, Sharissa L. Latham, David R. Croucher
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The acquisition of a chemoresistant state underlies poor prognosis in many cancers, including neuroblastoma. We previously demonstrated that heterogeneity in apoptosis induction through c-Jun amino-terminal kinase (JNK) promotes a form of nongenetic chemoresistance in neuroblastoma observable at both patient and single-cell levels. As the maintenance of this JNK-impaired state in the relapse setting is a substantial barrier to the efficacy of many standard-of-care chemotherapy drugs, we combined a mechanistic, mathematical model of JNK activation with a pediatric-focused drug screen and identified approved oncology drugs capable of inducing apoptosis in a JNK-independent manner. Functional genomics further revealed that synergy between these JNK-independent drugs and standard-of-care chemotherapies emerged from differential utilization of apoptotic network components, rather than from their direct mechanistic targets. Efficacy studies with patient-derived xenograft models also confirmed that including a JNK-independent drug within existing chemotherapy backbones significantly improved response in the relapse setting, where new approaches are urgently needed.
GPT-4o mini: Non-social science research article
Noncovalent interaction–driven regio- and enantioselective hydroalkynylation of unactivated alkenes to access remote chiral nitriles
Fanling Meng, Xian He, Rui He, Guodong Ju, Genping Huang, Chao Wang
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Unactivated alkenes represent a challenging substrate for selective functionalization, particularly in achieving both regioselectivity and enantioselectivity. In this study, we present a strategy for the regio- and enantioselective hydroalkynylation of unactivated alkenes through the integration of noncovalent Ï€â‹ŻÏ€ interactions between the cyano group of the substrate and a chiral bis(oxazoline) ligand. The weak Ï€â‹ŻÏ€ interaction was supported by control experiments and computational studies. The method provides a reliable approach for synthesizing chiral nitriles with remote (ÎČ-, Îł-, and ÎŽ-) stereocenters, which exhibit orthogonal reactivities and serve as valuable intermediates for further derivatization into otherwise difficult-to-access compounds. Our work provides a strategy for olefin functionalization and opens up avenues for the selective synthesis of chiral nitriles with remote stereocenters.
GPT-4o mini: Non-social science research article
Gut microbial-derived indole-3-propionate improves cognitive function in Alzheimer’s disease
Ling Li, Mengzhen Jia, Cong Yang, Yihang Zhao, Jun Hu, Yu Zhao, Xinyu Hu, Fangjie Ning, Chen Ding, Qingyuan Li, Jun Gong, Xiaoran Jia, Kun Xu, Yuhao Wang, Shuang Zhou, Lu Deng, Lin Shi, Xuhui Chen, Xuebo Liu, Zhigang Liu
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Intermittent fasting (IF) offers a potential strategy to counteract Alzheimer’s disease (AD) progression. In our 16-week study on AD transgenic mice, IF positively affected cognitive function and reduced amyloid-ÎČ (AÎČ) accumulation, verifying the IF’s role in modulating neuroinflammation. Multiomics integration revealed strong links between IF-induced hippocampal gene expression, gut microbiota, and serum metabolites beneficial for cognition. Indole-3-propionic acid (IPA) emerged as a pivotal microbial metabolite. Blocking its neuronal receptor, pregnane X receptor (PXR), abolished IF’s effects. Human data paralleled these findings, showing lower IPA levels in patients with mild cognitive impairment and AD than in controls. IPA supplementation and IPA-producing Clostridium sporogenes reproduced IF’s cognitive benefits, whereas PXR blockade in neurons or disruption of IPA synthesis abrogated them. IPA crossed the blood-brain barrier, exhibited potent anti-inflammatory activity, and suppressed AÎČ accumulation, essential for neuroprotection. These results underscore microbial metabolites regulated by IF, particularly IPA, as therapeutic candidates for AD, highlighting the critical role of the gut-brain axis in neurodegeneration.
GPT-4o mini: Non-social science research article
The pulvinar regulates plasticity in human visual cortex
Miriam Acquafredda, Jan W. Kurzawski, Laura Biagi, Michela Tosetti, Maria Concetta Morrone, Paola Binda
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In normally sighted human adults, 2 hours of monocular deprivation is sufficient to transiently alter ocular dominance. Here, we show that this is associated with a reduction of functional connectivity between the pulvinar and primary visual cortex (V1), selective for the pulvinar-to-V1 directionality. Across participants, the strength of the pulvinar-to-V1 connectivity was negatively correlated with the ocular dominance shift, implying less plasticity in participants with stronger influence of the pulvinar over V1. Our results support a revised model of adult V1 plasticity, where short-term reorganization is gated by modulatory signals relayed by the pulvinar.
GPT-4o mini: Non-social science research article
Articular neural bioelectronics by decoupling mechanical strain from electron transport
Tong Li, Fei Jin, Lisha Hua, Juan Ma, Fuyi Wang, Zhidong Wei, Ting Wang, Steven Wang, Zhang-Qi Feng
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Implantable bioelectronics for dynamic articular nerves require interfaces that harmonize extreme mechanical compliance at extreme strains exceeding 120%, stable conductivity, and metabolic permeability—a triad unattained by current stretchable devices. Here, we introduce liquid metal–based ultraelastic fibrous bioelectronics for articular nerves that overcome interfacial and mechanical limitations through molecular engineering and structural design. Thiol-functionalized self-assembled monolayers on liquid metal nanoparticles enhance interfacial adhesion with neural tissues, eliminating fibrous encapsulation, while anisotropic silver nanowire networks decouple mechanical strain from electron transport, achieving negligible resistance variation under 150% repetitive strain. The porous mesh structure enables fluid permeability five orders of magnitude higher than conventional materials, ensuring physiological nutrient exchange in synovial joints. In vivo integration with rat ulnar nerves demonstrated chronic neuromodulation over 6 weeks without disruption of functional behavior. This work redefines biomechanically adaptive neuroelectronics, offering a universal framework for interfacing dynamic biological systems, from prosthetic sensory feedback to treating neurodegenerative pathologies.
GPT-4o mini: Non-social science research article
Genomic evidence supports the “long chronology” for the peopling of Sahul
Francesca Gandini, Mafalda Almeida, M. George B. Foody, Nano Nagle, Anders Bergström, Anna Olivieri, SimĂŁo Rodrigues, Alessandro Fichera, Gonzalo Oteo-Garcia, Antonio Torroni, Alessandro Achilli, William Pomat, Zafarina Zainuddin, Ken Khong Eng, Tarek Shoeib, Teresa Rito, David Bulbeck, Sue O’Connor, JarosƂaw Bryk, Maria Pala, Michael J. Grant, Ceiridwen J. Edwards, Stephen J. Oppenheimer, Robert J. Mitchell, Pedro A. Soares, Helen Farr, Martin B. Richards
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The timing of the settlement of Sahul—the Pleistocene landmass formed by present-day New Guinea, Australia, and Tasmania that existed until ~9000 years ago (~9 ka)—remains highly contentious. The so-called “long chronology” posits the first main arrivals at ~60 to 65 ka, whereas a “short chronology” proposes 47 to 51 ka. Here, we exhaustively analyze an unprecedentedly large mitogenome dataset ( n  = 2456) encompassing the full range of diversity from the indigenous populations of Australia, New Guinea, and Oceania, including a lineage related to those of New Guinea in an archaeological sample from Wallacea. We assess these lineages in the context of variation from Southeast Asia and a reevaluation of the mitogenome mutation rate, alongside genome-wide and Y-chromosome variation, and archaeological and climatological evidence. In contrast to recent recombinational dating approaches, we find support for the long chronology, suggesting settlement by ~60 ka via at least two distinct routes into Sahul.
GPT-4o mini: Non-social science research article
Distributional bias compromises leave-one-out cross-validation
George I. Austin, Itsik Pe’er, Tal Korem
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Cross-validation is a common method for evaluating machine learning models. “Leave-one-out cross-validation,” in which each data instance is used to test a model trained on all other instances, is often used in data-scarce regimes. As common metrics such as the R 2 score cannot be calculated for a single prediction, predictions are commonly aggregated across folds for performance evaluation. Here, we prove that this creates “distributional bias”: a negative correlation between the average label of each training fold and the label of its corresponding test instance. As machine learning models tend to regress to the mean of their training data, this bias tends to negatively affect performance evaluation and hyperparameter optimization. We demonstrate that distributional bias exists across diverse tasks, models, and evaluation approaches, and can bias against stronger regularization. To address it, we developed a generalizable rebalanced cross-validation that is robust to distributional bias in both classification and regression, and demonstrates improved performance in simulations, machine learning benchmarks, and several published analyses.
GPT-4o mini: Non-social science research article
Entropy transfer from solar radio bursts to energetic particles
George Livadiotis, Manuel E. Cuesta, Leng Y. Khoo, Mitchell M. Shen, David J. McComas, Marc Pulupa, Stuart D. Bale, Roberto Livi
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Space plasma thermodynamics is thought to be affected by wave activity. Here, we show that solar radio bursts (SRBs) can transfer entropy to solar energetic protons (SEPs), affecting their thermodynamics. In particular, our analysis (i) detects the statistically significant SEP density fluctuations, associated with SRB activity that triggers a systematic increase in the thermodynamic kappa; (ii) estimates the polytropic index of SEPs, which is anticorrelated with kappa, serving as an independent measure to validate the increase in kappa; (iii) derives the entropy transfer by using its theoretical relationship with kappa; and (iv) compares SRB wave intensity with the entropy transferring to SEPs to demonstrate their wave-particle coupling. We lastly expose the thermodynamic association between type III SRB wave intensity and SEP entropy transfer as well as their respective coupling, thus developing a paradigm for further systematic investigations among other types of wave activity and particle populations.
GPT-4o mini: Non-social science research article
TOP2B modulates DNA supercoiling and chromatin contacts during transcriptional induction
José Terrón-Bautista, Marina Bejarano-Franco, María del Mar Martínez-Sånchez, Laura López-Hernåndez, Héctor Díaz-Maldonado, Angélica Santiago-Gómez, Sara Kidane, Ananda Ayyappan Jaguva Vasudevan, Mario García-Domínguez, R. Scott Williams, Andrés Aguilera, Gonzalo Millån-Zambrano, Felipe Cortés-Ledesma
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Human type-II topoisomerases, TOP2A and TOP2B, resolve transcription-associated DNA supercoiling, thereby influencing gene expression programs, and have been recently linked to three-dimensional genome architecture through yet poorly understood mechanisms. Here, we investigate the regulatory roles of TOP2 paralogs using estrogen signaling, which triggers an acute transcriptional induction that involves extensive rewiring of genome organization, as a model system. Unexpectedly, we find that estrogen treatment strongly inhibits TOP2B catalytic activity—although not its binding—specifically at estrogen-responsive enhancers and promoters. This inhibition results in an accumulation of negative DNA supercoiling and promotes the formation of regulatory chromatin contacts. Estrogen-mediated inhibition of TOP2B activity depends on estrogen receptor α, a noncatalytic function of TOP2A, and, most importantly, the action of zinc finger protein associated with tyrosyl-DNA phosphodiesterase 2 and TOP2, an atypical small ubiquitin-like modifier ligase that directly inhibits TOP2 activity. This mechanism of transcriptional control, involving the fine-tuning of DNA supercoiling levels, highlights the role of DNA topoisomerases as central regulators of genome dynamics.
GPT-4o mini: Non-social science research article
Mechanoadaptive polysaccharide conjugates architect pro-healing microenvironments via dynamic stress redistribution in skin defects
Rui Zhang, Guo Zhang, Xiaoyang Liang, Zhixuan Xu, Bingran Yu, Yang Li, Fu-Jian Xu
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The tip stress concentration in linear wounds, a clinically prevalent issue yet overshadowed by circular defect studies, and chronic biotemporal discordance (static biomaterials versus dynamic tissue remodeling) remain largely underexplored, severely impeding wound healing. Here, an adhesive bioconjugate platform, HADEX, composed of two types of micrometer-sized polysaccharide-derived granules, was constructed for precise shaping and manipulation. Combining finite element modeling with a dynamically cross-linking adhesive driven by fluid convection, HADEX achieved both conformal tissue adhesion and modulation of the stress distribution within wet, linear wounds, thereby restoring tissue pretension. Furthermore, HADEX facilitated a seamless load transfer to regenerating tissue through synchronized HADEX degradation and endogenous extracellular matrix deposition. To validate the efficacy of HADEX, we demonstrated successful sutureless in vivo closure and healing of linear wounds in both the normal/diabetic rat and porcine skin incision models. The integration of computational design with biomaterials established a foundation for personalized, mechanics-informed regenerative therapies.
GPT-4o mini: Non-social science research article
Mechanistic insights into 50 S precursor recognition and targeting by erythromycin resistance methyltransferase
Sombuddha Sengupta, Rajat Mukherjee, Michael Pilsl, Siddharam Bagale, Arijit Das Adhikary, Aditi N. Borkar, Pushpangadan Indira Pradeepkumar, Christoph Engel, Arindam Chowdhury, Prem S. Kaushal, Ruchi Anand
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Erythromycin resistance methyltransferases (Erms) confer resistance to macrolide, lincosamide, and streptogramin B antibiotics by methylating an internal base (A2058, E. coli numbering) in an elusive precursor ribosomal state. Here, we capture the 50 S ribosomal precursor–Erm complex by cryo-EM and show that a transient pocket formed in the early steps of ribosome biogenesis, situated 35 angstrom from the methylation site, serves as an anchor for the auxiliary C-terminal domain of Erm, thereby playing a crucial role in achieving specificity in this short-lived substrate with evolving structural features. Cryo-EM reveals that the catalytic Rossman fold of Erm undergoes a swaying motion to facilitate substrate scouting. Corroboratory smFRET studies show that for effective catalysis, Erm transitions between multiple conformations, an effective strategy adopted to orient the dynamic helix where methylation occurs. Unraveling this unique mechanism of targeting adopted by Erm paves the way for selective design of allosteric inhibitors directed toward reversing MLS B resistance.
GPT-4o mini: Non-social science research article
CTCF-RNA interactions orchestrate cell-specific chromatin loop organization
Kimberly Lucero, Sungwook Han, Pin-Yao Huang, Xiang Qiu, Esteban O. Mazzoni, Danny Reinberg
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CCCTC-binding factor (CTCF) is essential for chromatin organization. CTCF interacts with endogenous RNAs, and deletion of its ZF1 RNA binding region (∆ZF1) disrupts chromatin loops in mouse embryonic stem cells (ESCs). However, the functional significance of CTCF-ZF1 RNA interactions during cell differentiation is unknown. Using an ESC–to–neural progenitor cell (NPC) differentiation model, we show that CTCF-ZF1 is crucial for maintaining cell type–specific chromatin loops. Expression of CTCF-∆ZF1 leads to disrupted loops and dysregulation of genes within these loops, particularly those involved in neuronal development and function. We identified NPC-specific, CTCF-ZF1 interacting RNAs. Truncation of two such coding RNAs, Podxl and Grb10 , disrupted chromatin loops in cis, similar to the disruption seen in CTCF-∆ZF1–expressing NPCs. These findings underscore the inherent importance of CTCF-ZF1 RNA interactions in preserving cell-specific genome structure and cellular identity.
GPT-4o mini: Non-social science research article
MeCP2 interacts with the super elongation complex to regulate transcription
Jun Young Sonn, Wonho Kim, Marta Iwanaszko, Yuki Aoi, Yan Li, Guantong Qi, Luke Parkitny, Janice L. Brissette, Lorin Weiner, Juan Botas, Ismael Al-Ramahi, Ali Shilatifard, Huda Y. Zoghbi
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Loss-of-function mutations in methyl-CpG binding protein 2 ( MECP2 ) cause Rett syndrome. While we know that MeCP2 binds to methylated cytosines on DNA, the full breadth of the molecular mechanisms by which MeCP2 regulates gene expression remains incompletely understood. Here, using a genetic modifier screen, we identify the super elongation complex, a P-TEFb–containing elongation factor that releases promoter-proximally paused RNA polymerase II, as a genetic interactor of MECP2 . MeCP2 physically interacts with SEC subunits and directly binds AFF4, the scaffold of the SEC, via the transcriptional repression domain. Furthermore, MeCP2 facilitates the binding of AFF4 on a subset of genes in the mouse brain regulating synaptic plasticity and concordantly promotes the binding of RNA polymerase II on these genes. Last, while haploinsufficiency of Aff4 does not exhibit any behavioral deficits in mice, it exacerbates the impaired contextual learning behavior of Mecp2 hypomorphic mice. We propose a previously unknown mechanism by which MePC2 regulates gene expression underlying synaptic plasticity.
GPT-4o mini: Non-social science research article
Unlocking the secrets of ancient Texas cave paintings
David S. Whitley
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Recent research decodes the most visible, least accessible remnants of prehistoric hunter-gatherer lives using iconographic analysis, data collection, and an innovative dating technique.
GPT-4o mini: Non-social science research article
Soft 3D electromagnetic structures with rapid, complex shape morphing
Jeonhyeong Park, Qifeng Lu, Ben Jeffery, Heling Wang, Xinchen Ni
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Soft 3D systems capable of dynamic, real-time shape morphing have broad applications in flexible electronics, biomedical devices, and soft robotics. Existing methods typically rely on stress relaxation in prestretched elastomeric substrates to transform 2D precursors into 3D structures. However, these structures lack the ability for further localized programmability after transformation. This work introduces a class of soft, 3D morphable electromagnetic structures that enable fast, reversible shape transformations, with precise local programmability even after the initial 3D transformation. These systems provide access to sophisticated geometries and motions that were previously unattainable. This approach combines controlled compressive buckling of liquid metal microfluidics and Lorentz force actuation to drive the transformation, guided by multiphysics computational modeling. A 4D electronic system serves as an application example, demonstrating the potential of these spatially and temporally programmable soft systems.
GPT-4o mini: Non-social science research article
Complementary roles of dorsal and ventral hippocampus in the flexible adaptation of goal-directed behavior
Maryam Hasantash, Yifei Li, Arturo Torres-Herraez, Christoph Kellendonk, Christoph Anacker
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The ability to adapt previously learned behaviors is crucial for survival in dynamically changing environments. The hippocampus has been implicated in associative learning, but how hippocampus activity along its septotemporal axis contributes to flexible adaptation is unknown. Using in vivo Ca 2+ recordings and functional inhibition of dorsal CA1 (dCA1) and ventral CA1 (vCA1) neurons in mice during complementary cognitive flexibility tasks, we find that dCA1 is engaged and functionally required during consolidation of a learned contingency both before and after a rule change, whereas vCA1 is uniquely recruited during, and necessary for, early adaptation to a new contingency. This vCA1-dependent adaptation relies on a perseverative error signal, which is encoded in vCA1 and required for behavior updating. These results highlight a previously unknown division of labor within the hippocampus, in which vCA1 enables flexible adaptation when mismatches in expected and actual outcomes are detected, whereas dCA1 stabilizes newly learned information.
GPT-4o mini: Non-social science research article
Predicting the preservation of buried ore deposits using deep-time landscape evolution modeling
Addison Tu, Sabin Zahirovic, Sara Polanco, Samuel C. Boone, Matt Boyd, Claire Mallard, Pedro Restrepo, Youseph Ibrahim, Luke Mahoney, Tristan Salles, Brent McInnes, Ehsan Farahbakhsh, Fabian Kohlmann, Maria Seton, Dietmar R. MĂŒller
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Porphyry copper discoveries are declining despite rising demand to meet net-zero targets, highlighting the need for innovative exploration strategies. While many advances have focused on ore formation at depth, a major challenge remains in understanding how erosion and uplift over millions of years affect deposit preservation. These postmineralization processes determine whether porphyry systems are exposed, buried, or eroded entirely. We present a physically based landscape evolution model that incorporates spatially variable erodibility, dynamic uplift histories, climate and sea level change, and evolving topography over geological timescales. This richer input data, combined with tighter calibration, enables quantification of preservation potential and marks a step beyond prior conceptual and time-static models. We apply the model to New Guinea’s geologically complex mountains and integrate it with machine learning–derived ore formation probabilities. The combined model predicts known porphyry endowment, identifies new targets, and constrains preservation likelihood, validating this open-source method as a flexible and affordable exploration tool in dynamic tectonic settings.
GPT-4o mini: Non-social science research article
Maintaining local alkalinity of CO-electroreduction full cell by silica-confined electrocatalysts in membrane electrode assembly
Shuangxi Jing, Gongwei Wang, Zhe Li, Wei Xiao, Lin Zhuang
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Carbon monoxide electroreduction in alkaline membrane electrode assembly represents an effective approach to achieve carbon neutrality. However, its performance is currently limited by the insufficient modulation of local alkalinity at a full cell level. In this work, we reveal that confining the in situ generated hydroxide at cathode and enriching the bulk hydroxide to anode are the key factors for an efficient carbon monoxide–electroreduction full cell. We thereby propose a silica-confined strategy for electrocatalyst design to maintain high local alkalinity at both cathode and anode by the strong Lewis acid–base interaction between highly electrophilic silicon atom and hydroxide. The developed copper/silica cathode and cobalt/silica anode successfully promote cathodic multicarbon formation and anodic oxygen evolution, thereby improving the full cell energy efficiency. Even under high-rate electrolysis at 900 milliamperes per square centimeter, the selectivity and energy efficiency of multicarbon products remain above 80 and 30%. This achievement highlights the significance of modulating the dynamic hydroxide transport at full cell in enhancing carbon monoxide electroreduction performance.
GPT-4o mini: Non-social science research article
High variability in flood discharge and stage accelerates river mobility
Chenliang Wu, Wonsuck Kim, Shuo Yang, Frank T.-C. Tsai, Jeffrey A. Nittrouer, Tian Y. Dong, Duhwan Keum, Kyle M. Straub
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Lateral channel migration is a fundamental process in natural alluvial rivers; however, the factors that control the rate of migration remain unclear. Despite its importance in shaping river morphology, the impact of water discharge on river mobility is still largely unexplored. Here, we leverage a dataset of 64 rivers across the globe to show that higher variability in river discharge and stage promotes higher rates of river migration. To reveal the physical processes behind this relationship, we focused analyses on the lowermost 500 kilometers of the Mississippi River, where a pronounced gradient in water stage variability and migration rate exists. We demonstrate that stage variability affects channel mobility by influencing the sediment size of riverbanks and thereby controlling riverbank erodibility. These results can be used to predict river responses to climate change and decipher past hydroclimates using stratigraphy from Earth and Mars.
GPT-4o mini: Non-social science research article
Cortical dopaminergic signaling mediates planning of directional movements
John Chen, Alfredo Fontanini
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The anterior-lateral motor cortex (ALM) has been extensively studied as a model for understanding the cortical mechanisms involved in planning directional movements. ALM neurons show preparatory activity that predict whether the mouse will produce a left- or right-directed lick. While the neural mechanisms underlying ALM dynamics and their links to behavior are beginning to be elucidated, the sources of this directional activity remain unclear. Here, we examined the role of ALM dopaminergic circuits in mice performing a directional licking task. We report that dopamine (DA) signals and the activity of neurons expressing D1 receptors (D1R + ) tracked the preparation and execution of licking and demonstrated a bias for planning of licks aimed at the direction contralateral to the recording site. Unilateral optogenetic manipulations of D1R + neurons or DA afferents affected lateral licking in a way consistent with their role in planning contralateral movements. Together, these results show that cortical DA modulation plays an important role in the motor preparation of directional movements.
Mapping the chronology of an ancient cosmovision: 4000 years of continuity in Pecos River style mural painting and symbolism
Karen L. Steelman, Carolyn E. Boyd, J. Phil Dering
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Forager societies in southwest Texas and northern Mexico painted polychromatic Pecos River style murals in limestone rock shelters containing well-preserved archaeological assemblages. To establish the temporal context of the murals, we obtained 57 direct radiocarbon dates and 25 indirect oxalate dates for pictographs across 12 sites using plasma oxidation and accelerator mass spectrometry. Bayesian modeling estimates that Pecos River style began between 5760 and 5385 calibrated years before the present (cal B.P.) and probably ended in 1370 to 1035 cal B.P. Painting spanned a duration of 4095 to 4780 years (68.3%). Stratigraphic and iconographic analyses revealed that eight of the murals were created as compositions adhering to a set of rules and an established iconographic vocabulary. Results suggest consistent messaging throughout a period marked by changes in material culture, land use, and climate. We propose that Pecos River style paintings, embedded in a cultural keystone landscape, faithfully transmitted a sophisticated metaphysics that later informed the beliefs and symbolic expression of Mesoamerican agriculturalists.
Predicting and controlling infectious disease epidemics in cities
Benjamin D. Dalziel
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Modeling across urban-rural gradients shows city size and structure shape RSV epidemics and can guide more effective immunization strategies.
Urban contact patterns shape respiratory syncytial virus epidemics with implications for vaccination
Presley Kimball, Jean-Sebastien Casalegno, Pamela P. Martinez, Ayesha S. Mahmud, Bjorn Sandstede, Rachel E. Baker
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Urban environments may alter the landscape of disease transmission with implications for control. Yet, it is unclear whether urban-rural differences exist in the dynamics of childhood respiratory diseases, given specific mixing patterns in younger age groups. Here, we leverage county-level data on respiratory syncytial virus (RSV) from the United States to reveal an urban-rural gradient in both the intensity and age structure of the RSV epidemic, where urban locations experience more prolonged epidemics with higher burden in infants (under 1 year of age). We develop a mechanistic epidemiological model to show that these differences can be explained by daycare utilization rates in children under 5. Using our model to consider control measures, we find that expanding seasonal immunization access in urban and rural areas may limit the risk of off season RSV epidemics.
Escalated heatwave mortality risk in sub-Saharan Africa under recent warming trend
Cheng He, Yixiang Zhu, Yichen Guo, Jovine Bachwenkizi, Renjie Chen, Haidong Kan, Wafaie W. Fawzi
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Evidence from high-income countries indicates populations are adapting to frequent heatwaves, but similar trends in resource-constrained regions remain unknown. We analyzed mortality data from 11 Health and Demographic Surveillance Systems across sub-Saharan Africa (2005 to 2015) to examine temporal changes in heat-related mortality risk. Contrary to global trends, our findings suggest that heat vulnerability is increasing across African populations. Nighttime heatwave mortality risk increased significantly between 2005 to 2010 and 2011 to 2015 [OR from 1.02 (95% CI: 0.87 to 1.13) to 1.18 (95% CI: 1.13 to 1.23)], while daytime heatwaves showed no significant impact. Compound heatwaves transformed from nonsignificant to significant risk factors [OR = 1.11 (95% CI: 1.03 to 1.22)]. Males showed increased risks across all heatwave types, females only for nighttime and compound heat. Children under 5 showed universal risk increases, while the elderly showed the highest increases for nighttime and compound heat. These findings suggest that physiological adaptation alone is insufficient to cope with increasingly frequent heatwaves without adequate socioeconomic resources. Heightened nighttime vulnerability underscores the need for context-specific adaptations reflecting Africa’s distinct conditions.
Societal restraint of behavior during the pre-vaccine pandemic saved working-age men but not women
Ralph Catalano
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Risky behavior disproportionately contributes to death in the working-age (i.e., 15 to 64 years old) population. Men exhibit riskier behavior than do women. As a result, working-age men die more frequently than do working-age women. Despite these circumstances, surprisingly little research has attempted to estimate the gender-specific efficacy of societal restraint of risky behavior. This study provides such estimations by exploiting differences among the Nordic countries in the dose of forced restraint adopted to reduce mortality in the pre-vaccine COVID-19 pandemic. Results show that relatively great restraint reduced the likelihood of death among working-age men but not among working-age women. The findings suggest that debate over the wisdom of forced restraint of behavior as a strategy to reduce deaths should reflect the likely divergent effects of such interventions on working-age men and women.
Climate stability and low population pressure predict peaceful interactions over 10,000 years of Central Andean history
Weston C. McCool, Kurt M. Wilson, Elizabeth N. Arkush, Daniel A. Contreras, Brian F. Codding
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As anthropogenic climate change threatens to destabilize global societies and ecosystems, anticipating likely human responses becomes ever more urgent. A key global initiative is the promotion of peaceful relations. Nonetheless, studies that systematically evaluate factors that promote peace are limited, and research focuses on recent centuries when climate conditions were stable. Here, we couple evolutionary ecology theory with machine learning models to investigate the relative effects of climatological, demographic, and socio-political conditions on the persistence of peace over the 10,000-year Central Andean Holocene sequence. We find that stable climate conditions and low population density have a strong influence on peace, even when average climate conditions are not ideal for farming. Given that climate projection models predict increasing climate volatility in coming decades, our results suggest that future climate instability may weaken peaceful interactions, particularly among subsistence populations in marginal environments.