I checked 6 multidisciplinary journals on Tuesday, May 12, 2026 using the Crossref API. For the period May 05 to May 11, I found 20 new paper(s) in 5 journal(s).

Nature

GPT-4o mini: Non-social science research article
Prefrontal to ventral tegmental area dynamics drive contingency degradation
Madelyn M. Hjort, Zoe Q. Garrett, Adam G. Gordon, Ethan Ancell, Marta Trzeciak, Pei-Yun Lu, Michael R. Bruchas, Daniela M. Witten, Nicholas A. Steinmetz, Garret D. Stuber
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Cognitive flexibility refers to the adaptive neural processes that adjust learned behaviours as circumstances shift, supporting optimal decision-making and behavioural control. This includes the capacity to modify specific behaviours as the contingency between cues and rewards degrades. Across species1,2,3,4, the medial prefrontal cortex (mPFC) has a well-established role in controlling contingency degradation5; however, the precise neural circuit mechanisms underlying this cognitive process remain unclear. To address this gap, we developed a quantitative model of cognitive flexibility that incorporates a meta-learning parameter into an established reward prediction error learning model6,7. Our meta-reward prediction error model significantly improves accurate representation of mouse cue-evoked licking behaviour in response to degraded or enhanced cue–reward associations. Using longitudinal two-photon calcium imaging and single-cell holographic optogenetics, we found that a subset of neurons in the mPFC specifically encode the contingency degradation in a significant and causal manner. Recognizing that behavioural flexibility probably requires interactions between the mPFC and canonical reward learning circuitry, we then examined how mPFC neural signalling during contingency degradation interacts with the ventral tegmental area (VTA)—a critical hub for reward processing8. Our imaging and optogenetics data show that mPFC sends this signal to VTA, with most mPFC→VTA neurons reflecting this transmission, and that selective optogenetic stimulation of these ensembles accelerates contingency degradation. These findings reveal how prefrontal circuits facilitate flexibility, selectively halting learned behaviours through connections with subcortical reward networks.
GPT-4o mini: Non-social science research article
Author Correction: Proteasome-guided haem signalling axis contributes to T cell exhaustion
Yingxi Xu, Yangtao Shangguan, Yu-Ming Chuang, Tzu-Hsuan Chang, Wenbing Liu, Jhan-Jie Peng, Josep Garnica, Leling Xie, Pei-Chun Hsueh, Mei-Chun Lin, Yi-Hao Wang, Karina Lobo Hajdu, Yibo Wu, Maryam Akrami, Chen Wang, Anna Kohl, Alfred Zippelius, Wei Qi, Min Wang, Bugi Ratno Budiarto, Shih-Yu Chen, Zhengtao Xiao, Panagiota Vardaka, Rahul Roychoudhuri, Zhiliang Bai, Rong Fan, Santiago Carmona, Yi-Ru Yu, Christoph Scheiermann, Jianxiang Wang, Ping-Chih Ho
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GPT-4o mini: Non-social science research article
Androgen loss accelerates brain tumour growth via HPA axis activation
Juyeun Lee, Yoon-Mi Chung, Daniel J. Silver, Yue Hao, Dylan Scott Lykke Harwood, Alyssa Ealy, Amanda M. Serapiglia, Lee Curtin, Julia R. Benedetti, Christine Ann Pittman Ballard, Kamya Lapsley, Andrea Alvarez-Vazquez, Jessica Goldberg, Cathy Li, Sehaj Kaur, Rian Neal, Sabrina Z. Wang, Kristen E. Kay, Josephine Volovetz, Ellen S. Hong, R’ay Fodor, Jakub Jarmula, Michael Nicosia, Joshua B. Rubin, Kristin R. Swanson, Quinn T. Ostrom, Nikhil Panicker, Bjarne Winther Kristensen, Michael Berens, Nima Sharifi, Justin D. Lathia
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Many cancers, including glioblastoma (GBM), show a male-biased incidence and associated worse outcomes1. The mechanisms that underlie this sex difference remain unclear but may involve an immune response2 that is partly driven by sex hormones such as androgens. Such hormones are thought to suppress antitumour T cell immunity and to promote tumour progression3,4. However, here we report a previously unreported tumour-suppressive role for androgens in brain tumours. Using mouse models, we demonstrate that androgen loss via castration accelerates intracranial tumour growth, whereas the opposite effect (delayed tumour growth) is observed in extracranial tumours. Similar effects were observed in male patients with GBM, in whom testosterone treatment significantly reduced the risk of death. In male mice with GBM tumours, castration-induced systemic T cell dysfunction driven by increased levels of serum glucocorticoids, which act on myeloid cells to promote an immunosuppressive tumour microenvironment. Mechanistically, hyperactivation of the hypothalamus–pituitary–adrenal axis in castrated mice with GBM is driven by increased neuroinflammatory signalling through IL-1ÎČ and TNF. Spatial transcriptomic analysis further revealed that androgen loss enhances inflammasome activation in microglia, which promotes this neuroinflammatory state. Together, our findings demonstrate that brain tumours drive distinct neuroinflammatory and neuroendocrine pathways in the androgen-deprived setting and highlight organ-specific regulation of antitumour immunity.
GPT-4o mini: Non-social science research article
Two decades of PARP inhibitor synthetic lethality in cancer
Christopher J. Lord, Andrew N. J. Tutt, Alan Ashworth
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Two decades ago, two papers in Nature described how PARP inhibitors selectively killed cells deficient in the BRCA1 or BRCA2 tumour suppressor genes, observations that led to the first clinically approved treatment of a cancer with a targeted therapy selected based on a germline biomarker. This work was recognized by Nature as one of the top 20 discoveries in cancer in the twenty-first century and provides a compelling example of leveraging fundamental biology discovery for patient benefit. For people with specific forms of breast, ovarian, prostate or pancreatic cancer, these discoveries changed their care, enabling the use of more effective and better tolerated targeted therapies that both improve survival and quality of life. This in turn extended the role of germline BRCA1 and BRCA2 mutation testing from determining risk in the unaffected, to being a companion diagnostic biomarker used to determine therapy for a patient with cancer. The significance of these discoveries spread beyond BRCA1-mutant and BRCA2-mutant cancers: the synthetic lethal concept of the BRCA–PARP inhibitor effect highlighted the myriad levels of functional redundancy that exist in tumour cells and stimulated the search for other tumour-specific synthetic lethal effects that could be exploited therapeutically. Here we distill the learnings from the past two decades in this field.
GPT-4o mini: Non-social science research article
RNA-triggered cell killing with CRISPR–Cas12a2
Paul Scholz, Jared Thompson, Kadin T. Crosby, Torsten Fauth, Nathan M. Krah, Grant Schlauderaff, Robin Back, Zachary A. Berkheimer, Alivia Jolley, Dirk Sombroek, Rebekka Medert, Christian Zurek, Oleg Dmytrenko, Emily Wilson, Friso T. Schut, Jared Rutter, Xiaoyang Zhang, Michael Krohn, Ryan N. Jackson, Chase L. Beisel, Yang Liu
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Selectively eradicating target cells on the basis of their genetic or transcriptional identity remains important in basic research, medicine, biotechnology and agriculture1,2,3. For applications involving bacteria, CRISPR nucleases offer promising options due to their ability to enact RNA-guided counterselection4,5,6,7; however, using these same nucleases for counterselection in eukaryotes has proven much more restrictive8,9,10,11,12,13,14. Here we show that Cas12a2, a recently discovered type V CRISPR nuclease, exhibits RNA-triggered DNA shredding15,16, and enables programmable and sequence-specific elimination of yeast and human cells expressing a target transcript. Triggering Cas12a2 elicits rampant double-stranded DNA breaks in trans, leading to cell death. Cell killing can be activated by a wide range of target transcripts, with no observed off-target activation. Leveraging this approach, we selectively eliminate cells that harbour human papillomavirus, cells that failed to undergo gene editing, or cells that encode a prevalent oncogenic point mutation in KRAS. These findings expand the CRISPR toolbox to allow the selective elimination of eukaryotic cells on the basis of their transcriptional profile.
GPT-4o mini: Non-social science research article
Editorial Expression of Concern: Nociceptive neurons promote gastric tumour progression via a CGRP–RAMP1 axis
Xiaofei Zhi, Feijing Wu, Jin Qian, Yosuke Ochiai, Guodong Lian, Ermanno Malagola, Biyun Zheng, Ruhong Tu, Yi Zeng, Hiroki Kobayashi, Zhangchuan Xia, Ruizhi Wang, Yueqing Peng, Qiongyu Shi, Duan Chen, Sandra W. Ryeom, Timothy C. Wang
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GPT-4o mini: Non-social science research article
Steric hindrance of antibody binding in an Omicron spike fusion intermediate
Zhiheng Bao, Zhimin Liu, Zhaoyong Zhang, Xuanjia Wang, Xiaohui Jin, Jiaxiu Bai, Hanwen Ma, Yaxin Li, Chunyan Yi, Zhiyang Ling, Zhong Huang, Lu Zhang, Zhenguo Chen, Youhua Xie, Yanqun Wang, Lei Sun, Xiaoyu Sun
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Understanding conformational changes of the coronavirus spike protein is critical for developing broad-spectrum therapies. The pan-coronavirus epitope spike residues 815–825 (centred on the S2â€Č site) are buried in the prefusion spike but are transiently exposed upon ACE2 binding1,2. Here, using integrated functional and structural analyses, we demonstrate that 76E1, an antibody targeting spike residues 815–825, specifically recognizes an open early fusion intermediate conformation in which this epitope adopts a helical conformation, designated the S2â€Č-helix. SARS-CoV-2 Omicron variants evade such antibodies via steric hindrance resulting from S2â€Č-helix shifts and restricted S1–ACE2 distancing in the early fusion intermediate conformation, together with increased reliance on cathepsin-mediated entry that impairs 76E1 inhibition of S2â€Č cleavage. The H655Y mutation is central to this evasion. Antibody size directly affects its access to the S2â€Č-helix. Crucially, antibody size minimization reversed the evasion mechanisms and significantly enhanced neutralizing activity against authentic Omicron variants and other human coronaviruses, including SARS-CoV-1 and HCoV-229E. These findings establish small-molecule targeting of the S2â€Č-helix as a strategy for pan-coronavirus therapies.
GPT-4o mini: Non-social science research article
Specific expansion of motor cortical projections in a singing mouse
Emily C. Isko, Clifford E. Harpole, Xiaoyue Mike Zheng, Huiqing Zhan, Martin B. Davis, Anthony M. Zador, Arkarup Banerjee
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Elucidating how modifications in neural circuit architecture drive behavioural innovation remains a key challenge in neuroscience and evolutionary biology. In mammals, the neocortex is posited to play a crucial part in facilitating rapid behavioural innovations1,2,3. Although changes in long-range connectivity have been proposed to underlie such innovations4,5, these hypotheses remain largely untested quantitatively, which is partly due to the lack of high-throughput neuronal projection data at single-neuron resolution across species. Here we studied the Alston’s singing mouse (Scotinomys teguina), which exhibits a striking vocal behaviour absent in the laboratory mouse (Mus musculus), to quantitatively determine species-specific changes in motor cortical projections throughout the brain. We used bulk tracing, serial two-photon tomography and high-throughput DNA sequencing of more than 76,000 barcoded neurons to discover a specific and substantial expansion of orofacial motor cortical projections to an auditory cortical region and the midbrain periaqueductal grey, regions that are implicated in vocal behaviours6,7,8,9. Moreover, analyses of projection motifs of individual orofacial motor cortical neurons revealed preferential expansion of exclusive projections to the auditory cortical region in the singing mouse. Our results suggest that selective expansion of ancestral motor cortical projections may lead to behavioural divergence over short timescales. Furthermore, the results facilitate mechanistic investigations of enhanced cortical control over vocalizations—a crucial preadaptation for human language10,11. This approach of comparing recently diverged species with substantial behavioural divergences can be readily generalized across other model clades to discover quantitative rules of neural circuit evolution.
GPT-4o mini: Non-social science research article
Predicting temporal stability and resilience from resistance and recovery
Forest Isbell, Akira S. Mori, Michel Loreau, Peter B. Reich, David Tilman, Maggie I. Anderson, Caroline Brophy, Karen Castillioni, Qingqing Chen, Amber C. Churchill, Adam T. Clark, Dylan Craven, Nico Eisenhauer, Hanan C. Farah, Lau A. Gherardi, Yann Hautier, Miao He, Jin-Sheng He, Andy Hector, Sydney Hedberg, Sarah E. Hobbie, Pubin Hong, Guopeng Liang, Maowei Liang, Shan Luo, Neha Mohanbabu, Shahid Naeem, Pascal A. Niklaus, Xiaobin Pan, Cristy Portales-Reyes, Bernhard Schmid, Harry E. R. Shepherd, Steph Varghese, Michiel P. Veldhuis, Shaopeng Wang, Carmen R. E. Watkins, Qianna Xu, Liting Zheng, Chad R. Zirbel
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Stability can be desirable for many natural and social systems. Temporal stability, the invariability of a system over time, can be enhanced by resisting displacement during perturbations, accelerating recovery after them, or both1,2,3,4. Likewise, resilience (sensu proximity to unperturbed levels after a perturbation5,6,7,8,9,10) also has components of withstanding (resistance) and recovering after perturbations11,12. Here we develop and test new predictions for how temporal stability and resilience depend on their resistance and recovery components. We find that temporal stability could often be predicted from resistance, even without information about how quickly the system recovers. By contrast, resilience is predicted to depend at least as much on recovery as on resistance, as in earlier theory11,12. Using plant productivity data from the world’s longest-running biodiversity experiment, we find that long-term temporal stability, quantified over a quarter century at the ecosystem or species level, is predicted with moderate accuracy from single-year estimates of resistance alone, with only slight improvement by also considering recovery. Resilience was predicted with moderate accuracy by a combination of resistance and recovery at the ecosystem level. We also find that ecosystem drought resistance can be forecasted by monitoring temporal stability before the drought. Our results reveal that long-term temporal stability and short-term resistance may often be predicted from one another and clarify how resistance and recovery can be leveraged to enhance the stability of both natural and managed systems.
GPT-4o mini: Non-social science research article
Deforestation-induced drying lowers Amazon climate threshold
Nico Wunderling, Boris Sakschewski, Johan Rockström, Bernardo M. Flores, Marina Hirota, Arie Staal
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Humanity is putting unprecedented pressures on the Amazon forest system through global warming and land use changes 1,2 . As the Amazon forest may undergo self-reinforcing transitions, these pressures could lead to system-wide changes across major parts of Amazonian ecosystems 1–4 . Here we apply a dynamical systems model to assess the local and far-reaching cascading transition risks towards degraded ecosystems in the Amazon biome under different Shared Socioeconomic Pathways. For these emission scenarios, we constructed how moisture is transported through the atmosphere within the Amazon basin using an established atmospheric moisture-tracking model 5 . Without accounting for deforestation, we find a critical global warming threshold of 3.7–4.0 °C, beyond which up to a third of the Amazon forest risks losing stability. However, when considering deforestation, we find a near system-wide transition of the Amazon forest (62−77% of the area) under the combination of a lower threshold range of global warming of 1.5–1.9 °C and deforestation of 22–28%. The large majority of the simulated transitions is caused by spatial knock-on effects from increasing drought intensities, leading to long-ranging and self-propelling cascades on scales of hundreds to thousands of kilometres. Overall, our results reinforce the need to keep global warming levels below 1.5 °C and halt deforestation, as well as ecologically restore degraded forests to avoid high transition risks across the Amazon forest system.
GPT-4o mini: Non-social science research article
Author Correction: Multidimensional profiling of heterogeneity in supratentorial ependymomas
Daeun Jeong, Sara G. Danielli, Kendra K. Maaß, David R. Ghasemi, Svenja K. Tetzlaff, Ekin Reyhan, Li Jiang, Shashank Katiyar, Julia K. Sundheimer, Costanza Lo Cascio, Sina Neyazi, Carlos Alberto Oliveira de Biagi-Junior, Elsa Couvillon, Sophia Castellani, Maria Pazyra-Murphy, Matthew Mullally, Marc Philipp Dehler, Bernhard Englinger, Andrezza Nascimento, Gustavo Alencastro Veiga Cruzeiro, Joana G. Marques, Rebecca D. Haase, Cuong M. Nguyen, Alicia-Christina Baumgartner, Jacob S. Rozowsky, Olivia A. Hack, McKenzie L. Shaw, Daniela Lotsch-Gojo, Katharina Bruckner, Andrey Korshunov, Stefan M. Pfister, Marcel Kool, Tomasz J. Nowakowski, Johannes Gojo, Lissa Baird, Sanda Alexandrescu, Kristian W. Pajtler, Varun Venkataramani, Mariella G. Filbin
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GPT-4o mini: Non-social science research article
A brain reward circuit inhibited by next-generation weight-loss drugs in mice
Elizabeth N. Godschall, Taha Bugra Gungul, Isabelle R. Sajonia, Aleyna K. Buyukaksakal, Orien Li, Sophia Ogilvie, Austin B. Keeler, Guilian Tian, Yu Shi, Omar Koita, Chloe Xinzhu Guo, Tyler C. J. Deutsch, Eric J. Steacy, Maisie Crook, YuChen Zhang, Nicholas J. Conley, Gulsun Memi, Addison N. Webster, O. Yipkin Calhan, Weile Liu, Amani Akkoub, Karan Malik, Kaleigh I. West, Sara Michel-Le, Arun Karthikeyan, Grace van Gerven, Olivia A. Dell’Aglio, Kevin T. Beier, Larry S. Zweifel, Manoj K. Patel, John N. Campbell, Christopher D. Deppmann, Ali D. GĂŒler
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Glucagon-like peptide 1 receptor agonists (GLP1RAs) effectively reduce body weight and improve metabolic outcomes; however, established peptide-based therapies require injections and are complex to manufacture1,2,3. Small-molecule GLP1RAs promise oral bioavailability and scalable manufacturing, but their selective binding to human versus rodent receptors has limited mechanistic studies4,5,6,7,8,9. Here we developed humanized GLP1R mouse models to investigate how small-molecule GLP1RAs influence feeding behaviour. We found that these compounds regulate both homeostatic and hedonic feeding through parallel neural circuits. Beyond engaging canonical hypothalamic and hindbrain networks that control metabolic homeostasis, GLP1RAs recruit a discrete population of Glp1r-expressing neurons in the central amygdala, which selectively suppress the consumption of palatable foods by reducing dopamine release in the nucleus accumbens. Stimulating these central amygdalar neurons curtails hedonic feeding, whereas targeted deletion of the receptor in this cell population specifically diminishes the anorectic efficacy of GLP1RAs for reward-driven intake. These findings identify a neural circuit through which small-molecule GLP1RAs modulate reward processing, with implications for the treatment of substance-use disorder and binge eating.
GPT-4o mini: Non-social science research article
Foreshock-induced slip transients set mainshock nucleation timing
Barnaby Fryer, Dmitry Garagash, Mathias Lebihain, François PasselÚgue
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Foreshocks are sometimes observed before earthquakes 1–13 , yet their role in controlling rupture nucleation remains unclear 1,11,14 . Classical models often assume that nucleation arises from slow, quasi-static slip governed primarily by fault weakening 15–21 , typically neglecting impulsive precursory events. Here we show, using laboratory experiments and a rate-and-state-based Griffith-like rupture framework 22 , that foreshocks, when they occur at the onset of or during nucleation, can fundamentally regulate earthquake initiation. We find that the slip burst induced by foreshocks imparts a transient sliding velocity, V min , whose magnitude is set by foreshock size and which robustly predicts both nucleation duration and spatial length. Larger foreshocks generate higher V min and trigger a more rapid transition to dynamic rupture, whereas smaller foreshocks produce long-duration quasi-static growth and very small impulses lead to ruptures entirely arresting. Extending our theoretical framework to tectonic faults, we show that foreshock and associated slow-slip sequences preceding natural earthquakes seem to follow the same scaling. These observations allow us to constrain realistic characteristic nucleation slip distances of 0.3–3.0 mm, orders of magnitude smaller than those inferred for dynamic rupture 23 . Our results demonstrate that foreshock-induced transients set the timing and potential detectability of earthquake nucleation 24 .
GPT-4o mini: Non-social science research article
Molecular skeleton programming of premediators in sulfur electrochemistry
Runhua Gao, Yifei Zhu, Shengyu Tao, Mengtian Zhang, Zhoujie Lao, Zhiyuan Han, Yanze Song, Hongtai Li, Linxuan Song, Xuan Zhang, Yanfei Zhu, Guangmin Zhou
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Molecular mediators have demonstrated broad applicability in electrolyte chemistry of lithium–sulfur batteries, transforming sulfur conversion from traditional multiphase reactions to highly reactive pathways1,2,3,4,5,6. Despite tremendous efforts to elucidate the mechanistic roles of molecular mediators7,8,9, the influence of molecular skeleton regulation on their mediating effects remains barely understood. Here we propose 2-chloropyrimidine as a potential ‘premediator’ and a model material for molecular skeleton design, which can be in situ activated into a molecular mediator during sulfur reaction progression by means of aromatic nucleophilic substitution, homogeneously inducing a rapid redox loop over the electrode. Integrating quantum chemistry and machine learning, we develop a molecular skeleton programming strategy that illuminates the structure–property relationship between electronic, geometric and site features of side-chain groups and mediating performance, offering control over the activation rate and mediating activity of premediators. The strategy identifies 2-chloro-4-(trifluoromethyl)pyrimidine as a favourable premediator from 196 candidates, enabling lithium–sulfur batteries to achieve an average capacity retention of 81.7% over 800 cycles together with an energy density of 549 Wh kg−1 in a 14.2-Ah-level pouch cell. We expect that our work on molecular skeleton programming may find application in designing functional molecules in broader organic chemical spaces.
GPT-4o mini: Non-social science research article
Purcell-enhanced spin–phonon coupling with a single colour centre
Graham Joe, Michael Haas, Kazuhiro Kuruma, Chang Jin, Dongyeon Daniel Kang, Sophie W. Ding, Cleaven Chia, Hana Warner, Benjamin Pingault, Bartholomeus Machielse, Srujan Meesala, Marko Lončar
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The radiative properties of emitters are inherently linked to their surrounding environment1. Placing an electromagnetic resonator around emitters can enhance spontaneous emission, as shown by Purcell in the 1940s2. This approach is now routinely used in quantum computing and communication to channel photons emitted by atoms into well-defined modes and control atom–photon interactions3,4,5,6,7,8,9. For solid-state emitters, such as colour centres, the host lattice introduces an acoustic environment, allowing excited atoms to relax by emitting phonons10,11. Here we observe the acoustic Purcell effect by constructing a specially engineered, microwave-frequency nanomechanical resonator around a colour-centre spin qubit in diamond. Using a co-localized optical mode of the structure that strongly couples to the excited state of the colour centre, we perform single-photon-level laser spectroscopy at millikelvin temperatures and observe a 10-fold faster spin relaxation when the spin qubit is tuned into resonance with a 12 GHz acoustic mode. Moreover, we use the colour centre as an atomic-scale probe to measure the broadband phonon spectrum of the nanostructure up to 28 GHz. Our work establishes a new regime of control for quantum defects in solids and paves the way for interconnects between atomic-scale quantum memories12 and qubits encoded in acoustic and superconducting devices13.
GPT-4o mini: Non-social science research article
Genome-wide sweeps create ecological units in the human gut microbiome
Xiaoqian Annie Yu, Cameron R. Strachan, Craig W. Herbold, Michaela Lang, Christoph Gasche, Athanasios Makristathis, Nicola Segata, Shaul Pollak, Adrian Tett, Martin F. Polz
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The human gut microbiome is shaped by diverse selective forces that originate from host and environmental factors and it substantially influences health and disease. Whereas the association of microbial lineages with various health conditions has been shown at different taxonomic levels 1–5 , the extent to which unifying adaptive mechanisms sort microbial lineages into ecologically differentiated populations remains poorly understood. Here we show that genome-wide selective sweeps are a pervasive mechanism that differentiates bacteria in the microbiome. This mechanism leads to population structures akin to global epidemics across geographically and ethnically diverse human populations. Such sweeps arise when an adaptation allows a clone to outcompete others in its niche followed by rediversification, and they manifest as clusters of closely related genomes on long branches in phylogenetic trees. This structure is revealed by excluding recombination events that mask the clonal descent of the genomes. Indeed, we show that genome-wide sweeps originate under a wide range of recombination rates in at least 66 taxa from 25 bacterial families. Estimated ages of divergence suggest that sweep clusters can spread globally within decades and that this process has occurred throughout human history. Sweep clusters are associated with different host conditions—such as age, colorectal cancer, inflammatory bowel diseases and type 2 diabetes—as an indication of their ecological differentiation. Our results reveal an evolutionary mechanism for the observation of stably inherited strains with differential associations and provide a theoretical foundation for analysing adaptation among microbial populations.
GPT-4o mini: Non-social science research article
Plasticity and language in the anaesthetized human hippocampus
Kalman A. Katlowitz, Eric R. Cole, Elizabeth A. Mickiewicz, Shraddha Shah, Melissa Franch, Joshua A. Adkinson, James L. Belanger, Raissa K. Mathura, Domokos Meszéna, Matthew McGinley, William Muñoz, Garrett P. Banks, Sydney S. Cash, Chih-Wei Hsu, Angelique C. Paulk, Nicole R. Provenza, Andrew J. Watrous, Ziv Williams, Alica M. Goldman, Vaishnav Krishnan, Atul Maheshwari, Sarah R. Heilbronner, Robert Kim, Nuttida Rungratsameetaweemana, Benjamin Y. Hayden, Sameer A. Sheth
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Consciousness is a fundamental component of cognition1, but the degree to which higher-order pattern recognition relies on it remains disputed2,3. Here we demonstrate the persistence of oddball discrimination, semantic processing and online prediction in individuals under general-anaesthesia-induced loss of consciousness4,5. Using high-density Neuropixels microelectrodes6 to record both single-unit and local-field-potential neural activity in the human hippocampus while playing a series of tones to anaesthetized patients, we found that hippocampal neurons and local oscillations retained some detection of oddball tones. This effect size grew over the course of the experiment (around 10 min), demonstrating representational plasticity. A biologically plausible recurrent neural network model showed that learning and oddball representation are an emergent property of flexible tone discrimination. Moreover, when we played language stimuli, single units and local field potentials carried information about the semantic and grammatical features of natural speech, even predicting semantic information about upcoming words. Together these results indicate that in the hippocampus, which is anatomically and functionally distant from primary sensory cortices7, complex processing of sensory stimuli occurs even in the unconscious state.
GPT-4o mini: Non-social science research article
Two-qubit logic and teleportation with mobile spin qubits in silicon
Y. Matsumoto, M. De Smet, L. Tryputen, S. L. de Snoo, S. V. Amitonov, A. Sammak, M. Rimbach-Russ, G. Scappucci, L. M. K. Vandersypen
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The scalability and power of quantum computing architectures depend critically on high-fidelity operations and robust and flexible qubit connectivity 1–3 . In this respect, mobile qubits are particularly attractive as they enable dynamic and reconfigurable qubit arrays. This approach allows quantum processors to adapt their connectivity patterns during operation, implement different quantum error correction codes on the same hardware and optimize resource use through dedicated functional zones for specific operations such as measurement or entanglement generation 4–7 . Such flexibility also relieves architectural constraints, as recently demonstrated in atomic systems based on trapped ions 4,5 and neutral atoms manipulated with optical tweezers 6,7 . In solid-state platforms, highly coherent shuttling of electron spins was recently reported 8,9 . A key outstanding question is whether it may be possible to perform quantum gates directly on the mobile spins. Here we demonstrate two-qubit operations between two electron spins carried towards each other in separate travelling potential minima in a semiconductor device. We find that the interaction strength is highly tunable by their spatial separation. When we shuttle the two spins towards the centre by 120 nm each for a total displacement of 240 nm, we achieve an average two-qubit gate fidelity of about 99%. Furthermore, we implement conditional post-selected quantum state teleportation between qubits separated by 320 nm with an average gate fidelity of 87%, showcasing the potential of mobile spin qubits for non-local quantum information processing. We expect that operations on mobile qubits will become a universal feature of future large-scale semiconductor quantum processors.
GPT-4o mini: Non-social science research article
Quantum coherent manipulation and readout of superconducting vortex states
Ameya Nambisan, Simon GĂŒnzler, Dennis Rieger, Nicolas Gosling, Simon Geisert, Victor Carpentier, Nicolas Zapata, Mitchell Field, Milorad V. MiloĆĄević, Carlos A. Diaz Lopez, Ciprian Padurariu, Björn Kubala, Joachim Ankerhold, Wolfgang Wernsdorfer, Martin Spiecker, Ioan M. Pop
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A defining characteristic of superconductors is their tendency to expel magnetic fields, yet above a critical threshold, magnetic flux penetrates in discrete quanta carried by Abrikosov vortices 1 . The superconducting gap is completely suppressed at the vortex core, rendering them dissipative, semi-classical entities that impact applications from high-current-density wires to quantum devices. Material disorder can drive a crossover to vortices that preserve an energy gap at the core 2–4 , owing to intrinsic 5 or emergent granularity on the scale of the coherence length 2,6 . Although quantum vortex behaviour could emerge in this effective tunnel-junction regime 7 , and signatures have been observed in diverse systems 8–10 , coherent manipulation of vortex states has remained elusive. Here we present evidence that vortices trapped in granular superconducting films can behave as two-level systems, exhibiting microsecond-range quantum coherence and energy relaxation times that reach fractions of a millisecond. Using the tools of circuit quantum electrodynamics 11 , we perform coherent manipulation and quantum non-demolition readout of vortex states in granular aluminium microwave resonators, heralding future directions for quantum information processing, materials characterization and sensing.
GPT-4o mini: Non-social science research article
Multiplexed magnetic resonance imaging
Yudu Li, Rong Guo, Yibo Zhao, Wen Jin, Ziwen Ke, Liang Chen, Xiangjun Chen, Weijun Tang, Yao Li, Zhi-Pei Liang
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Magnetic resonance imaging (MRI) has revolutionized diagnostic radiology and medicine over the past five decades1,2. However, clinical applications of MRI are still mainly limited to visual examination of macroscopic tissue pathology3,4. Because diseases, such as tumours, multiple sclerosis (MS) and neurodegenerative disorders, are highly heterogeneous, there is a critical need for a non-invasive imaging technology that can provide quantitative biomarkers for tissue characterization for personalized and precision medicine5. Here we introduce a new approach to MRI data acquisition and processing, called ‘multiplexed MRI’ (MRx), to achieve high-resolution simultaneous multiparametric mapping of several molecules. We demonstrate that MRx can obtain a large set of quantitative structural, physiological and molecular biomarkers of the whole brain in standard clinical settings. We further demonstrate that these biomarkers could define an effective tissue state index for disease subtyping and lesion characterization in tumours and MS. We anticipate that the new quantitative multiplexed imaging capabilities of MRx would substantially enhance the capability of MRI for diagnosis, monitoring and assessment of therapeutic efficacy of many neurological diseases and potentially transform brain imaging for both research and clinical applications.
GPT-4o mini: Non-social science research article
Author Correction: Enteric neurons increase maternal food intake during reproduction
Dafni Hadjieconomou, George King, Pedro Gaspar, Alessandro Mineo, Laura Blackie, Tomotsune Ameku, Chris Studd, Alex de Mendoza, Fengqiu Diao, Benjamin H. White, André E. X. Brown, Pierre-Yves Plaçais, Thomas Préat, Irene Miguel-Aliaga
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GPT-4o mini: Non-social science research article
Non-invasive profiling of the tumour microenvironment with spatial ecotypes
Wubing Zhang, Erin L. Brown, Abul Usmani, Noah Earland, Minji Kang, Chibuzor Olelewe, Anushka Viswanathan, Pradeep S. Chauhan, Chloé B. Steen, Hyun Soo Jeon, Susanna Avagyan, Irfan Alahi, Nicholas P. Semenkovich, Janella C. Schwab, Chloe M. Sachs, Faridi Qaium, Peter K. Harris, Qingyuan Cai, Andrew J. Gentles, James Knight, Rondell P. Graham, Antonietta Bacchiocchi, Peter C. Lucas, Ryan C. Fields, Mario Sznol, Ruth Halaban, David Y. Chen, Aadel A. Chaudhuri, Aaron M. Newman
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Multicellular programs in the tumour microenvironment (TME) drive cancer pathogenesis and response to therapy but remain challenging to identify and profile clinically1,2,3. Here, we present a machine-learning framework for multi-analyte profiling of spatially dependent cell states and multicellular ecosystems, termed spatial ecotypes (SEs). By integrating over 10 million single-cell and spot-level spatial transcriptomes from diverse human carcinomas and melanomas, we identified nine SEs with broad conservation, each of which has unique biology, geospatial features and clinical outcome associations, including several linked to immunotherapy response. Notably, SEs were distinguishable by DNA methylation profiling and were recoverable from plasma cell-free DNA (cfDNA) using deep learning. In cfDNA from nearly 100 patients with melanoma, SE levels exhibited striking associations with immunotherapy response. Our data reveal fundamental units of TME organization and demonstrate a multimodal platform for profiling solid and liquid TMEs, with implications for improved risk stratification and therapy personalization.
GPT-4o mini: Non-social science research article
Publisher Correction: Presymptomatic training mitigates functional deficits in a mouse model of Rett syndrome
Nathan P. Achilly, Wei Wang, Huda Y. Zoghbi
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GPT-4o mini: Non-social science research article
Expanding the human proteome with microproteins and peptideins
Eric W. Deutsch, Leron W. Kok, Jonathan M. Mudge, Cristian F. Valls, Irwin Jungreis, Jorge Ruiz-Orera, Zhi Sun, Ulrike Kusebauch, Ivo Fierro-Monti, Jennifer G. Abelin, M. Mar Alba, Julie L. Aspden, Sreejan Bandyopadhyay, Kaushik Banerjee, Pavel V. Baranov, Ariel A. Bazzini, Francis Bourassa, Elspeth A. Bruford, Lorenzo Calviello, Steven A. Carr, Anne-Ruxandra Carvunis, Sonia Chothani, Jim Clauwaert, Kellie Dean, Pouya Faridi, Adam Frankish, Amy Goodale, Thomas Green, Norbert Hubner, Nicholas T. Ingolia, Manolis Kellis, Michele Magrane, Maria Jesus Martin, Thomas F. Martinez, Gerben Menschaert, Uwe Ohler, Sandra Orchard, Alisa Potter, Owen J. L. Rackham, Matthew G. Rees, David E. Root, Jennifer A. Roth, Xavier Roucou, Fernando J. Sialana, Sarah A. Slavoff, MichaƂ I. Úwirski, Jack A. S. Tierney, FĂ©lix-Antoine Trifiro, Eivind Valen, Valeriia Vasylieva, Aaron Wacholder, Shengbo Wang, Li Wang, Jonathan S. Weissman, Wei Wu, Zhi Xie, Jyoti S. Choudhary, Michal Bassani-Sternberg, Juan Antonio VizcaĂ­no, Nicola Ternette, Marie A. Brunet, Robert L. Moritz, John R. Prensner, Sebastiaan van Heesch
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A major scientific drive is to characterize the protein-coding genome, which is a primary basis for studying human health. But the fundamental question remains of what has been missed in previous analyses. Over the past decade, the translation of non-canonical open reading frames (ncORFs) has been observed across human cell types and disease states1,2,3, with major implications for biomedical science. However, a key gap in knowledge has been which ncORFs produce small microproteins or alternative protein molecules that contribute to the human proteome. Here we report the collaborative efforts of the TransCODE Consortium4 to produce a consensus landscape of protein-level evidence for ncORFs. We show that about 25% of a set of 7,264 ncORFs gives rise to detectable peptides in a large-scale analysis of 95,520 proteomics experiments. We develop an annotation framework for ncORF-encoded microproteins as human proteins and codify the new conceptual model of ‘peptideins’ as microproteins that have indeterminate potential as functional proteins. To probe the biological implications of peptideins, we create an evolutionary analysis approach, termed ORF relative branch length (ORBL), and determine that evolutionary constraint is common and associates with observation of ncORF-derived peptides. We then characterize a pan-essential cellular phenotype for one peptidein from the OLMALINC long non-coding RNA. Overall, we generate public research tools supported by GENCODE and PeptideAtlas and advance biomedical discovery for understudied components of the human proteome.
GPT-4o mini: Non-social science research article
Imaging the flat bands of magic-angle graphene reshaped by interactions
J. Xiao, A. Inbar, J. Birkbeck, N. Gershon, Y. Zamir, Y. Vituri, T. Taniguchi, K. Watanabe, E. Berg, S. Ilani
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Electron interactions in quantum materials fundamentally shape their energy bands and, with them, the material’s most intriguing quantum phases. Magic-angle twisted bilayer graphene (MATBG) 1–3 has emerged as a model system in which flat bands lead to a variety of such phases, yet the precise nature of these bands has remained elusive owing to the lack of high-resolution momentum-space probes. Here we use the quantum twisting microscope (QTM) to directly image the interacting energy bands of MATBG with unprecedented momentum and energy resolution. Away from the magic angle, the observed bands closely follow the single-particle theory. At the magic angle, however, we observe bands that are completely transformed by interactions, exhibiting light and heavy electronic character at different parts of momentum space. On doping, the interplay between these light and heavy components leads to a variety of notable phenomena, including interaction-induced bandwidth renormalization, Mott-like cascades of the heavy particles and Dirac revivals of the light particles. We also uncover a persistent low-energy excitation tied to the heavy sector, suggesting a new unaccounted degree of freedom. These results resolve the long-standing puzzle in MATBG—the dual nature of its electrons—by showing that it originates from electrons at different momenta within the same topological heavy-fermion-like flat bands. More broadly, our results establish the QTM as a powerful tool for high-resolution spectroscopic studies of quantum materials previously inaccessible to conventional techniques.
GPT-4o mini: Non-social science research article
Extreme galaxy-scale outflows are frequent among luminous early quasars
Weizhe Liu, Xiaohui Fan, Huan Li, Richard Green, Jinyi Yang, Xiangyu Jin, Jianwei Lyu, Maria Pudoka, Yongda Zhu, Eduardo Bañados, Silvia Belladitta, Thomas Connor, Tiago Costa, Roberto Decarli, Anna-Christina Eilers, Hyunsung D. Jun, Madeline A. Marshall, Chiara Mazzucchelli, Jan-Torge Schindler, Yue Shen, Sylvain Veilleux, Julien Wolf, Huanian Zhang, Mingyang Zhuang, Siwei Zou, Mingyu Li
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The existence of abundant post-starburst and quiescent galaxies just about 1–2 Gyr after the Big Bang challenges our current model of galaxy evolution1,2,3. Cosmological simulations suggest that quasar feedback is likely the most promising mechanism responsible for this rapid quenching4,5,6. Here we report a high detection rate (6/27) of exceptionally fast and powerful galaxy-scale outflows traced by [O iii] emission in z ≈ 5–6 luminous quasars as shown by the James Webb Space Telescope, with velocity up to about 8,400 km s−1 and order-of-magnitude kinetic energy outflow rates up to around 260% of the observed quasar bolometric luminosities. This fraction is >3.9 and 8.8 times that in comparison samples at z ≈ 1.5–3.5 and z < 1, respectively. These extreme outflows are comparable to or even faster than the most rapid [O iii] outflows reported at z â‰Č 3, and could reach the circumgalactic medium or even the intergalactic medium. The average kinetic energy outflow rate of our sample is more than 2 dex higher than that of the lower-redshift comparison samples. The substantially higher frequency of outflows with energetics well above the threshold for negative feedback in our sample strongly suggests that quasar feedback plays an important part in efficiently quenching and regulating early massive galaxies.
GPT-4o mini: Non-social science research article
Electrocaloric effects across room temperature in multilayer capacitors
M. Guo, V. Farenkov, X. Chen, A. Mohanathan, A. Z. K. Goh, Y. Tang, J. Zhang, M. Vickers, S. M. Fairclough, C. Ducati, X. Moya, S. Hirose, N. D. Mathur
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A growing number of cooling devices 1–4 exploit large electrocaloric effects associated with a supercritically driven first-order ferroelectric phase transition in multilayer capacitors of PbSc 0.5 Ta 0.5 O 3 (PST) 5 . However, these multilayer capacitors only operate above the room-temperature Curie temperature and require an energetically expensive 42-day anneal for high B-site order to maximize latent heat. Here we show that exaggerating valence mismatch through dilution with PbMg 0.5 W 0.5 O 3 (PMW) maintains high B-site order and latent heat with no anneal, while disrupting dipolar order to reduce the Curie temperature as low as 230 K. Our multilayer capacitors of PST–PMW show supercritical electrocaloric effects of about 3 K across and well below room temperature owing to 17.1 V ÎŒm −1 fields we apply >10 7 times without breakdown. Using our multilayer capacitors in an ideal fluid regenerator and assuming work recovery yields cycle efficiencies of 70–90%. Taken together, our findings imply that multilayer capacitors of PST–PMW should now replace multilayer capacitors of PST in electrocaloric prototypes to permit electrocaloric refrigeration.
GPT-4o mini: Non-social science research article
Tree community resource economics control soil food web multifunctionality
Ludovic Henneron, David A. Wardle, Matty P. Berg, Stephan HĂ€ttenschwiler, JĂŒrgen Bauhus, François Buscot, Sylvain Coq, Thibaud DecaĂ«ns, Nathalie Fromin, Pierre Ganault, Lauren M. Gillespie, Kezia Goldmann, Radim Matula, Alexandru Milcu, Bart Muys, Johanne Nahmani, Luis Daniel Prada-Salcedo, Michael Scherer-Lorenzen, Kris Verheyen, Janna Wambsganss, Paul Kardol
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Plants affect terrestrial ecosystem functioning by shaping microenvironments 1 and by providing the primary production that fuels energy flow into food webs 2 . However, how plant community properties affect ecosystem functioning via energy fluxes in food webs has been little studied 3,4 , especially for the soil food webs that channel most plant-derived energy 2,5 . Applying a food web energetics approach 6,7 , we show that the resource economics of dominant tree species control soil food web multifunctionality across European forests. Tree communities dominated by resource-acquisitive species promoted faster rates of multiple soil trophic functions than did communities dominated by resource-conservative species. These effects were primarily driven by higher-quality litter and warmer forest microclimates, leading to increased metabolic activity of soil organisms 8 . Accordingly, tree species composition explained a large portion of variation in soil food web multifunctionality, comparable to that explained by biogeographic differences among locations. By contrast, mixtures of three tree species had weakly negative effects relative to single-species stands, mostly due to shifts in energy channelling from living fine roots to litter and a cooling effect on forest microclimate. This occurred despite an overyielding effect in aboveground tree biomass production, suggesting contrasting diversity effects above- and belowground. Our findings emphasize the importance of plant functional traits related to resource economics as drivers of soil food web functioning 5,9 and demonstrate how climate-driven shifts in tree community composition may alter forest soil functioning.
GPT-4o mini: Non-social science research article
HIV-1 signalling remodels nuclear pores to licence infection
Dejan Mesner, Matthew V. X. Whelan, Maitreyi Shivkumar, Ann-Kathrin Reuschl, Riccardo Zenezini Chiozzi, Konstantinos Thalassinos, Robertus A. M. de Bruin, Clare Jolly
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HIV-1 is readily detected in resting CD4 + T cells in vivo 1–4 . However, resting T cells are highly refractory to cell-free virus infection in vitro 5–7 and require mitogenic activation to become permissive. This paradox raises the fundamental question of what makes a T cell permissive for HIV-1. Here we address this and show that HIV-1 capsid nuclear import at the nuclear pore complex (NPC) is a bottleneck to resting T cell infection, but that HIV-1 overcomes this by triggering receptor-mediated signalling during cell–cell spread to drive nuclear import and licence infection. Coupling viral and cellular assays with super-resolution imaging, we show that contact between HIV-1 infected and uninfected T cells triggers CD4–LCK signalling that activates CDK1, independent of cell-cycle entry, phosphorylating nucleoporins and priming the NPC to promote HIV-1 nuclear import. Critically, cell–cell contact also accelerates nuclear import in activated T cells, providing a paradigm for why cell–cell spread dominates infection. By contrast, HIV-1 virions do not trigger this response, explaining why resting T cells cannot be efficiently infected by cell-free virus. We propose that HIV-1 has evolved to selectively activate CD4 signalling during cell–cell spread to regulate infection at the step of the NPC, offering an explanation for how resting T cells can be infected in vivo.
Nature DOI suffix ≠ "/s...": Not a research article
NIH grant cuts disproportionately hit minority and female scientists
Max Kozlov
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Nature DOI suffix ≠ "/s...": Not a research article
How a passion for baking fermented a fresh career move
Dom Byrne
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Nature DOI suffix ≠ "/s...": Not a research article
A life in pictures: celebrating David Attenborough at 100
Alexia Austin, Amelia Hennighausen
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Nature DOI suffix ≠ "/s...": Not a research article
Elsevier vs Meta: first science publisher sues over scraped research papers
Elizabeth Gibney
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: A stunningly detailed map of the Universe and the month’s best science images
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Briefing Chat: Can’t focus? It’s not your attention span, it’s your notifications
Nick Petrić Howe, Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Giant map reveals thousands of cities worldwide with successful green policies
Chris Simms
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Nature DOI suffix ≠ "/s...": Not a research article
In twisted graphene, some electrons are heavier than others
Hongyun Zhang, Shuyun Zhou
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Nature DOI suffix ≠ "/s...": Not a research article
Male sex hormone loss aids brain tumour growth
Frederick S. Varn
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Nature DOI suffix ≠ "/s...": Not a research article
J. Craig Venter obituary: maverick biotechnologist who sequenced the human genome
Kevin Davies
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Nature DOI suffix ≠ "/s...": Not a research article
Even the unconscious brain can learn — and predict what you’ll say next
Max Kozlov
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Nature DOI suffix ≠ "/s...": Not a research article
Three mental-health claims from RFK’s wellness movement: what scientists say
Heidi Ledford
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Nature DOI suffix ≠ "/s...": Not a research article
How fertilizer shortages caused by the energy crisis threaten food security
Meihua Yang, Xing Wang, Solmaz Fathololoumi, Hiteshkumar B. Vasava, Yuhong Zhou, Henry W. Chau, Huijie Li, Bingcheng Si, Hongyi Li, Asim Biswas
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Nature DOI suffix ≠ "/s...": Not a research article
Meet the academics refusing to use generative AI
Hannah Docter-Loeb
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Nature DOI suffix ≠ "/s...": Not a research article
Are attention spans really shrinking? What the science says
David Adam
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Nature DOI suffix ≠ "/s...": Not a research article
Surge in fake citations uncovered by audit of 2.5 million biomedical science papers
Miryam Naddaf
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Nature DOI suffix ≠ "/s...": Not a research article
World’s largest forest research agency faces severe cutback by Trump administration
Edward Chen
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Nature DOI suffix ≠ "/s...": Not a research article
The sleep paradox: why do humans sleep so little when we need it so much?
Nathaniel J. Dominy
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Nature DOI suffix ≠ "/s...": Not a research article
Quantum ‘thermometer’ takes temperatures inside living cancer cells
Matthew Hutson
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Nature DOI suffix ≠ "/s...": Not a research article
There is no vaccine for deadly hantavirus: what that means for future outbreaks
Mohana Basu
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Nature DOI suffix ≠ "/s...": Not a research article
25 years of chemistry that simply clicks
Willow A. Davis, Ellen M. Sletten
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Nature DOI suffix ≠ "/s...": Not a research article
Matter of taste
Mari Harrison
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Nature DOI suffix ≠ "/s...": Not a research article
Audio long read: The air is full of DNA — here’s what scientists are using it for
Aisling Irwin, Benjamin Thompson
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Nature DOI suffix ≠ "/s...": Not a research article
First AI tool to detect suspicious peer reviews rolled out by academic publisher
Miryam Naddaf
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Nature DOI suffix ≠ "/s...": Not a research article
Engineering resilient food systems in a warming world
Laura Woodrow
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Nature DOI suffix ≠ "/s...": Not a research article
Thymic health under the microscope
Henry J. Kaminski, Linda L. Kusner, Gary Cutter, Rozen Le Panse
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Nature DOI suffix ≠ "/s...": Not a research article
I’m burnt out and leaving academia. How do I finish my PhD?
Nikki Forrester
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Nature DOI suffix ≠ "/s...": Not a research article
How much of the scientific literature is generated by AI?
Miryam Naddaf
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Five inspiring science stories to lift your mood
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: ‘A true pioneer and maverick’, Craig Venter dead at 79
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
My English skills are hurting my chances in academic publishing — how can I improve?
Katarina Zimmer
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Nature DOI suffix ≠ "/s...": Not a research article
Hantavirus outbreak exposes uncertainty about how disease spreads
Mohana Basu, Rachel Fieldhouse
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Nature DOI suffix ≠ "/s...": Not a research article
To move beyond GDP, don’t ignore ecological economics
Pushpam Kumar
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Nature DOI suffix ≠ "/s...": Not a research article
Testosterone therapy is trending. Who really needs it, and why?
Mariana Lenharo
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Nature DOI suffix ≠ "/s...": Not a research article
Revealed: the mysterious ‘dark’ proteins that might play a big role in biology
Ewen Callaway
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Nature DOI suffix ≠ "/s...": Not a research article
Early-career researchers do more ‘disruptive’ science than veterans
Mariana Lenharo
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Nature DOI suffix ≠ "/s...": Not a research article
Radioactive rain and proving relativity: Books in brief
Andrew Robinson
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Nature DOI suffix ≠ "/s...": Not a research article
Goodbye GDP? 31 ways to replace the world’s favourite measure of economic health
Mariana Lenharo
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Who needs testosterone therapy?
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Anaesthetized brains can still process podcasts
Benjamin Thompson
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Nature DOI suffix ≠ "/s...": Not a research article
AI agents in research: when productivity comes at the cost of apprenticeship
Jing Hu, Tony Huiquan Zhang
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Nature DOI suffix ≠ "/s...": Not a research article
Origin story
Alex Shvartsman
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Nature DOI suffix ≠ "/s...": Not a research article
Explore a stunningly detailed map of the Universe in April's best science images
Miryam Naddaf, Davide Castelvecchi
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Nature DOI suffix ≠ "/s...": Not a research article
Best. Day. Ever. What does a good day in science look like?
Virginia Gewin
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Nature DOI suffix ≠ "/s...": Not a research article
Nanoscale ‘conveyor belt’ teleports quantum state of electron
Lars R. Schreiber
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Nature DOI suffix ≠ "/s...": Not a research article
World-leading climate centre takes Trump administration to court
Alexandra Witze
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Nature DOI suffix ≠ "/s...": Not a research article
Are microbes the future of pollution clean-up?
Rachel Nuwer
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Nature DOI suffix ≠ "/s...": Not a research article
Why AI chatbots that follow human laws are hard to build
Mohana Basu
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Digital distractions are real — but you can rescue your attention span
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Precision medicine without equity is just stratified inequality
Afsaneh Shirani
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Nature DOI suffix ≠ "/s...": Not a research article
Legal rights for insects: a global imperative for stingless-bee conservation
Shi-Jie Wang, A. J. Wubie
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Systematic partisan content skews in TikTok during the 2024 US elections
Hazem Ibrahim, HyunSeok Daniel Jang, Nouar Aldahoul, Aaron R. Kaufman, Talal Rahwan, Yasir Zaki
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Social media platforms increasingly mediate political information exposure, yet the role of algorithmic curation in shaping political exposure remains contested 1,2 . This question is difficult to resolve on platforms in which users retain substantial control over their feeds 3,4 . The ‘For You’ feed of TikTok, which delivers content almost entirely through algorithmic recommendation, offers a setting in which user agency is sharply constrained. Here we show, through 323 audit experiments with controlled ‘sock puppet’ accounts seeded with Democratic or Republican content across three US states, that accounts seeded with partisan content exhibited systematic, asymmetric differences in partisan exposure. Across more than 280,000 recommendations collected over 27 weeks during the 2024 US presidential election campaign, Republican-seeded accounts received about 11.5% more co-partisan content than Democratic-seeded accounts, whereas Democratic-seeded accounts were exposed to about 7.5% more cross-partisan content—largely anti-Democratic material—even after adjusting for engagement metrics. These asymmetries are concentrated among high-reach Republican channels and in specific policy domains, including immigration, crime and foreign policy for Democrats, and abortion for Republicans. Our findings show partisan imbalances in political information exposure on a platform dominated by algorithmic recommendations, with implications for platform governance and democratic discourse.
Pollinators support the nutrition and income of vulnerable communities
T. P. Timberlake, S. Sapkota, N. M. Saville, A. R. Cirtwill, S. C. Baral, D. R. Bhusal, K. Devkota, S. Giri, H. A. Harris-Fry, D. Joshi, S. Kortsch, S. S. Myers, T. Roslin, M. R. Smith, J. Memmott
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Biodiversity loss threatens human health and welfare through the degradation of ecosystem services like pollination 1–3 . However, without clear mechanistic links between ecosystems and people, these services can remain abstract and intangible. Consequently, it is challenging to predict the effects of environmental degradation on human welfare or to identify effective ecological interventions that improve human lives. Here we record individual-level diets, crop yields, farming income and crop–pollinator interactions in replicate smallholder communities in Nepal to quantify the links among insect pollinators, crop plants and nutrient intake and income of individual families. Insect pollinators were directly responsible for 44% of people’s farming income and more than 20% of their vitamin A, folate and vitamin E intake. We show how declines in local pollinator species are anticipated to exacerbate rates of poverty and micronutrient deficiency in vulnerable communities such as the ones studied here. However, our results demonstrate that management of local pollination services can improve human nutrition and household income. Indeed, abundant pollinators like native honeybees, bumblebees and hoverflies are the most important for sustaining and enhancing nutrient flows. Applied more widely, this approach of linking biodiversity to human health and livelihoods could reveal sustainable new pathways for improving the lives of millions of smallholders worldwide.

Nature Human Behaviour

GPT-4o mini: Non-social science research article
Human curriculum learning of a cue combination task
Qingtian Mi, Christopher Summerfield
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Humans often learn better when problems are broken down into parts, but this phenomenon has eluded explanation at the computational level. Here we study how differing training curricula help or hinder learning in a classic probabilistic cue combination task. Training curricula that ‘divide and conquer’ by presenting one cue at a time facilitate later performance on test trials involving multiple cues. This effect is captured by a hybrid learning framework that arbitrates between two different learning strategies: a marginal updating process, which assigns credit to each cue independent of every other, and a joint updating process, which distributes credit across cues on the basis of their joint presence. We use this theory to generate new ‘skewed distribution’ multi-cue curricula that should and should not successfully promote human learning. It makes accurate predictions, demonstrating that we can use computational insights of learning to accelerate human probabilistic learning.
Government policy documents across 185 countries largely cite Global North sources
Sebastian Ramirez-Ruiz, Roman Senninger
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Evidence is widely acknowledged as essential for crafting effective public policies. Despite its critical role, we know surprisingly little about the specific sources that inform decisions around the world. This paper explores the sources of evidence in the policymaking arena by analysing evidence cited in over 1.2 million policy documents from 185 countries. Our analyses capture references to 3.5 million scholarly works and 740,000 policy sources, including contributions from government agencies, academic researchers, international organizations and think tanks. We map global patterns in citation practices, highlighting regional and policy domain variation, focusing on the documented, accessible and digitally visible evidence available to policymakers. Our findings reveal a pronounced concentration of attention: the vast majority of foreign evidence cited—both academic and policy—is produced in the Global North, even in documents authored by governments in the Global South. These patterns persist across policy areas, though with notable variation in the types of source commonly used. Overall, the findings reveal a highly concentrated evidence landscape, where a small number of countries disproportionately serve as global reference points, underscoring persistent asymmetries in visibility, access and influence within the international policy knowledge ecosystem.
Population-based RCT of a digital cognitive-behavioural guided self-help intervention for anxiety, depression and eating disorders in college students
Michelle G. Newman, Ellen E. Fitzsimmons-Craft, Seung Yeon Baik, Nur Hani Zainal, Adam Calderon, Gavin N. Rackoff, Marie-Laure Firebaugh, Elsa Rojas-Ashe, Yan Leykin, Daphne Lew, Daniel Eisenberg, C. Barr Taylor, Denise E. Wilfley
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Scalable approaches such as digital cognitive-behavioural therapy guided self-help (D-CBTgsh) may help close the treatment gap for college students with mental disorders. In a randomized clinical trial (ClinicalTrials.gov: NCT04162847) across 26 US colleges, populations were offered a mental health screen (39,194 assessed). Students with clinical levels or high risk for anxiety, depression and/or eating disorders (N = 6,205) were randomized to screening+D-CBTgsh or screening+referral-to-college-provided-care groups. Screening+D-CBTgsh reduced prevalence of any mental disorder (primary outcome) at 6 weeks (odds ratio (OR) = 0.80, 95% CI = 0.70–0.91), 6 months (OR = 0.77, 95% CI = 0.68–0.88) and 2 years (OR = 0.82, 95% CI = 0.72–0.93). Services uptake was greater in screening+D-CBTgsh (74.4%) versus screening+referral (30.2%) at 6 months (OR = 6.72, 95% CI = 6.01–7.52) and 2 years (OR = 1.83, 95% CI = 1.64–2.04), including for minoritized groups. Screening+D-CBTgsh (versus screening+referral to college-provided care) also improved dimensional outcomes of generalized anxiety, social anxiety, depression, eating disorder symptoms and mental health functioning. Findings supported transdiagnostic prevention and intervention benefits of screening+D-CBTgsh and its viability as a scalable, population-based approach.
An individual participant data meta-analysis of how physical activity relates to affective well-being in daily life
Johanna Rehder, Irina Timm, Gesa Berretz, Iris Reinhard, Andreas B. Neubauer, Onur GĂŒntĂŒrkĂŒn, Keisuke Takano, Walter Bierbauer, Miriam Cabrita, Matthew Bourke, Joshua Smyth, Jinhyuk Kim, Johannes Michalak, Joshua Curtiss, Björn Pannicke, Jacob B. Gallagher, Ana M. Abrantes, Toru Nakamura, Yoshiharu Yamamoto, Paul Cook, Lena M. Wieland, Birte von Haaren-Mack, Bryan McCormick, Justin Hachenberger, Tomas Vetrovsky, Benajmin Henwood, Louise Poppe, Gorden Sudeck, Laura Hollands, Andrea B. Goldschmidt, Lynn Martire, Martina Kanning, Jaclyn P. Maher, Yu-Mei Li, Ulrich Reininghaus, Corina Berli, Caroline Seiferth, Derek J. Hevel, Kate Leger, Amanda E. Staiano, Almut Zeeck, Stefano Calza, Yue Liao, Geralyn R. Ruissen, character(0), Andreas Reif, Oliver Grimm, Christine Freitag, Jutta Mayer, Toni Ramos-Quiroga, Christian Fadeuilhe, Jonna Kuntsi, Philip Asherson, Adam Pawley, Jan Buitelaar, Elena Suess, Ulrich Ebner-Priemer, Andreas R. Schwerdtfeger, Matthias Haucke, Loree T. Pham, Siwei Liu, Mark C. Thomas, Andreas Meyer-Lindenberg, Genevieve F. Dunton, Steriani Elavsky, Ulrich W. Ebner-Priemer, Marco Giurgiu, Julian Packheiser, Markus Reichert
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Physical inactivity constitutes a pressing societal problem. To realize physical activity’s (PA) potential as a key health resource, mechanisms of PA engagement need to be understood. Laboratory and interventional studies documented that exercise relates to affective well-being (AWB) and suggested that AWB may shape PA behaviour. Digitalization enabled the investigation of how PA relates to AWB in everyday life, but findings from individual studies are ambiguous. Here we compiled 67 datasets (55.2% of eligible records) including 321,345 smartphone-based AWB ratings and nearly 1,000,000 h of accelerometer-measured PA ( N = 8,223 participants) until December 2023 to clarify the nature and extent of PA–AWB associations. One- and two-stage individual participant data meta-analyses reveal that momentary AWB is associated with both prior (within, r = 0.05, 99.2% confidence intervals (CI) 0.03 to 0.06; between, r = 0.08, 99.2% CI 0.04 to 0.12) and subsequent (within, r = 0.04, 99.2% CI 0.03 to 0.05; between, r = 0.08, 99.2% CI 0.04 to 0.13) short-term PA in everyday life. Within persons, PA displays a positive association with energetic arousal, positive affective states and valence, yet a negative relation to calmness. The practical effect sizes are comparable to other daily life activities, with energetic arousal evincing the strongest relation to PA. Considerable heterogeneity in associations across individuals can be partially explained by sociodemographic moderators. Between participants, PA relates to positive affective states. The results document the critical relevance of PA–AWB relations in everyday life. They can contribute to the revision and development of health behaviour models and establish a starting point to approach behavioural, physiological and neuronal mechanisms underlying PA–AWB associations.
Domain generality is an emergent, not inherent, property of metacognition
Carolyn Baer, Simona Ghetti, Darko Odic
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We experience some level of confidence in all decisions we make, yet our understanding of how confidence is generated remains elusive. Here we examine three potential aspects of metacognitive confidence judgements that could be similar across the distinct domains of memory and perception in adults (n = 236) and children (aged four to seven years, n = 263; 122 girls and 141 boys) from Vancouver, Canada. Using episodic memory and perceptual tasks, we reveal that while confidence bias correlates across domains at all ages, confidence sensitivity and efficiency are both distinct. Crucially, children aged six and older can flexibly contrast confidence states across memory and perceptual decisions, indicating a shared internal metric of confidence. In contrast, four-to-five-year-old children struggle with cross-domain comparisons, highlighting a developmental transition in metacognitive processing. Overall, our findings highlight the distinct yet commensurable nature of memory and perceptual confidence, with domain-general processes emerging by age six.

Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Coordinated stomatal, mesophyll, and biochemical functions in photosynthetic responses to heat and dryness
Xingyu Hu, Suan Chin Wong, Graham D. Farquhar
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The intrinsic link between temperature and leaf-to-air vapor pressure difference (Δ e ) complicates isolation of their individual effects on photosynthesis. Consequently, how CO 2 diffusion changes under heat and high evaporative demand, particularly through mesophyll conductance ( g m ) responses, remains poorly understood. The conditions under which biochemical colimitation occurs, meaning Rubisco carboxylation and RuBP regeneration capacities match, are also unclear. To advance understanding of plant responses to climate change, we separated temperature and Δ e effects by holding Δ e at 1 and 2 kPa while varying leaf temperature ( T leaf ) from 20 to 40 °C across five CO 2 levels (150 to 800 ÎŒmol mol −1 ) in cotton, sunflower, and dwarf bean. Gas exchange and chlorophyll fluorescence measurements showed that g m responses partly counteract increases in stomatal conductance to CO 2 ( g sc ) at high temperatures and declines in g sc at elevated Δ e . Coordination between g sc and g m buffers effects of heat and dryness on CO 2 diffusion and stabilizes chloroplast-to-ambient CO 2 ratio ( C c / C a ) across measured T leaf and Δ e ranges. C c / C a is more conservative with increasing T leaf at C a ≀ 400 ÎŒmol mol −1 than at elevated C a . Across tested T leaf and Δ e conditions, the transition from Rubisco carboxylation to RuBP regeneration limitation remains near C a of 400 ÎŒmol mol −1 , indicating that biochemical colimitation occurs near current atmospheric CO 2 levels. Our findings reveal that plants alleviate diffusional limitations under heat and dryness through coordinated responses of g sc and g m , and maintain biochemical colimitation over broad T leaf and Δ e conditions to efficiently utilize Rubisco carboxylation and RuBP regeneration capacities at near-atmospheric CO 2 levels.
GPT-4o mini: Non-social science research article
Compositionality and systematicity emerge from iterated learning in deep linear networks
Devon Jarvis, Richard Klein, Benjamin Rosman, Andrew M. Saxe
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Humans have a remarkable ability to systematically generalize—reasoning about new situations by combining aspects of previous experiences. Language provides one of the primary examples of this ability and modern machine learning has drawn much inspiration from linguistics. A recent example is iterated learning, a procedure where generations of networks learn from the output of earlier learners. The result is a refinement of the network’s “language” or output labels for given inputs toward compositional structure. Here we theoretically study the emergence of compositional language, and the ability of simple neural networks to leverage this compositionality to systematically generalize. We build on prior theoretical work on linear networks, which mathematically define systematic generalization, by a) applying the analysis of shallow and deep linear network to the iterated learning procedure by deriving exact dynamics of learning over generations; b) refining the definition of systematicity to understand the benefits and limitations of iterated learning. We find that iterated learning does facilitate systematic generalization over standard training paradigms by uncovering compositional substructure in the output labels. Our results confirm a long standing conjecture: that multiple generations of iterated learning are required for compositional structure to emerge, which can outperform a single generation network trained with optimal early-stopping. However, for the network to treat the input systematically and ignore features which do not generalize, the network must be trained on an extremely large dataset. Hence, we define “weak systematic generalization” to explain this emergent systematicity from scale.
GPT-4o mini: Non-social science research article
Beyond antibodies in GAD65 autoimmunity: Reframing pathogenesis through intrathecal B–T cell cross-talk
Simon Faissner, Ralf Gold
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GPT-4o mini: Non-social science research article
The heterogeneous selection landscape of genome evolution in prokaryotes
Roman Kogay, Svetlana Karamycheva, Nash D. Rochman, Yuri I. Wolf, Eugene V. Koonin
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Evolution of prokaryote genomes appears to be defined by the interplay of selection for genome streamlining, deletion bias, and selection for functional diversification. The previously observed overall positive correlation between the strength of selection, measured as the ratio of nonsynonymous to synonymous nucleotide substitutions ( dN/dS ), points to diversification as the primary factor of prokaryote genome evolution. Here, we investigated the interplay between genome size and selection pressure by analyzing an expanded collection of closely related prokaryotic genomes, evaluating genome-wide selection by measuring dN/dS by using an accurate, phylogeny-based method and decomposing the resulting values into lineage-specific and gene-specific components. These analyses reveal a pronounced heterogeneity in the relationship between genome size and the strength of selection across the diversity of prokaryotes. Most bacteria display a positive correlation consistent with selection for diversification, whereas all analyzed archaeal lineages show strong negative correlation which is the signature of streamlining. These findings indicate that the selection regimes broadly vary across the diversity of prokaryotes rather than following a single, universal pattern. Genome streamlining, selection for functional diversity and drift in small populations are all important factors of evolution, with their relative contributions depending on the population genetics and ecology of a given lineage.
GPT-4o mini: Non-social science research article
Functional dissection of SPOP at the amino acid level reveals a comprehensive functional landscape of variants during tumorigenesis
Seong Kyun Park, Jeongha Lee, Seon Ju Park, Ye Na Kim, Gi Hyun Shin, Kisoon Dan, Hee-Jung Choi, Dohyun Han, Byung Joon Hwang, Murim Choi
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Numerous proteins display pleiotropic functions in different clinical contexts. However, the molecular mechanism underlying such effects is rarely understood. Speckle-type POZ protein ( SPOP ) is a typical example, exhibiting tumor-suppressing or tumor-promoting effects in different tumor types in accordance with different amino acid changes; specifically, two distinct sets of variants in SPOP are commonly found in subsets of prostate cancer and endometrial cancer patients. To comprehensively characterize the functional landscape of SPOP alteration, we performed a deep mutational screening (DMS), elucidating the functionality of 7,933 out of 8,228 possible single amino acid changes (96.4% coverage). Leveraging the observation that overexpression of human SPOP leads to yeast growth arrest, we assessed the functionality of each variant using a yeast proliferation assay. In addition, our approach combined long-read and short-read sequencing. Finally, our DMS model enables a clear distinction of likely-loss-of-function variants that are enriched in prostate cancers and reveals their differential characteristics in both protein structure and genetic assessments. These results demonstrate the utility of our approach in high-resolution mapping and amino acid–level interpretation of protein function.
GPT-4o mini: Non-social science research article
A PKA-selective inhibitor captures an open but more ordered conformation of the PKA catalytic subunit
Jessica G. H. Bruystens, Jian Wu, Gerald Tan, Daniela Bertinetti, Hans-Michael Zenn, Bastian Zimmermann, Lisa Chen, Johannes Köckenberger, Federica Massaro, Banumathi Sankaran, Matthew S. Walters, Gianluigi Veglia, Fleur M. Ferguson, Friedrich W. Herberg, Susan S. Taylor
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The structure of the catalytic subunit of cAMP-dependent protein kinase (PKA-C), a prototype for the protein kinase superfamily, laid the foundation for the development of targeted kinase inhibitors. Here we describe the structure and biophysical characterization of a PKA-C complex with BLU0588, a small PKA-selective inhibitor. The high-resolution crystal structure not only captures the inhibitor’s unusual T-shaped geometry, but also shows how the four rings of BLU0588 serve as surrogates for ATP’s adenosine and phosphate-organizing sites. Each site contains two subsites. BLU0588’s planar azaindole and pyridine rings, which are buried beneath the glycine-rich loop in a hydrophobic shell at the base of the active site cleft, fill the adenine and ribose subsites. In contrast, BLU0588’s indane and pyrrolidine rings fill the phosphate-organizing site. The indane ring occupies the α/ÎČ-phosphate organizing site while the pyrrolidine ring fills the Mg/Îł-phosphate organizing site. The structure also shows how BLU0588 nucleates an open but stable conformation of the entire hydrophobic architecture of the N- and C-lobes. In addition to potently blocking phosphoryl transfer activity, BLU0588 also abolishes the synergistic high-affinity binding of the physiological pseudosubstrate inhibitor, protein kinase inhibitor. The residence time of BLU0588, measured by surface plasmon residence, contributes to its picomolar affinity and is distinct from H89, a commonly used but more promiscuous PKA inhibitor. These molecular insights provide a valuable framework for dissecting the organization of the active site cleft as well as different strategies for the rational design of more potent and selective kinase inhibitors in general.
GPT-4o mini: Non-social science research article
Stag2-mediated chromatin dynamics regulates antibody class switch recombination
Zhichen Wan, Leyi Yu, Zifan Yang, Sha Luo, Yutao Zhou, Ruolin Qiao, Hailiang Zha, Xiaoling Shan, Yifan Wang, Shuchan Li, Xuefei Zhang
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Class switch recombination (CSR) in B lymphocytes switches immunoglobulin heavy chain ( Igh ) constant regions (C H s) to generate different functional antibody isotypes and chromatin loop extrusion has been proposed to regulate CSR. Stag1 and Stag2 are key components for stabilizing cohesin during chromatin loop extrusion, but the regulatory mechanism of Stag1 and Stag2 in CSR is unknown. Here, we reported that Stag2 is a specific cohesin component playing critical roles in promoting CSR. In contrast to the dispensable roles of Stag1 in CSR, Stag2 deficiency significantly decreases CSR without affecting DNA damage repair pathways. Mechanistically, loss of Stag2, not Stag1, significantly decreases the chromatin interaction of acceptor C H with CSR center, leading to decreased synapsis of donor and acceptor C H units, decreased transcription of acceptor C H , and impaired CSR. Notably, Stag2 deficiency significantly decreases Stag1 binding within Igh , while Stag2 could compensate for Stag1 binding within Igh upon Stag1 deficiency. Interestingly, Stag2 expression is higher than Stag1 during both mouse and human germinal center (GC) B cell development and Stag2 expression has a high correlation with CSR level in vaccinated and SARS-CoV-2-infected patients. Furthermore, Stag2 is also highly expressed in the GC B cells within different cancers, corresponding to the high level of CSR. Our findings uncover the unrecognized specific roles of Stag2 in regulating CSR.
GPT-4o mini: Non-social science research article
A change in the cell wall status initiates the elimination of the nucellus in Arabidopsis
Miryam Iannaccone, Wenjia Xu, Dennys-Marcela Gomez-Paez, Sandrine Choinard, Elisa Maricchiolo, Alexis Peaucelle, Aline Voxeur, Kalina Tamara Haas, Catherine Lapierre, Jose M. Jiménez-Gómez, Andrea Pompa, Enrico Magnani
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The evolution of the seed habit can be traced back to a change in the cell fate of the nucellus, the sporophytic tissue responsible for female meiosis. Seeds arose when the nucellus retained the female spores instead of releasing them into the environment. As a consequence, the nucellus was partially eliminated to accommodate the growth of the female gametophyte inside the sporophyte. With the evolution of angiosperm seeds, the process of nucellus elimination was requisitioned to allow the growth of the endosperm, the fertilization product devoted to storing nutrients that are at the foundation of the human diet. Cell elimination differs from most known cell death programs as it leads to the apparent dismantling of the cell wall. Here, we show that nucellus elimination in Arabidopsis is initiated by demethylesterification and subsequent lysis of the pectic polysaccharides in the cell wall. This process exposes other cell wall components to possible further degradation and precedes a cell death program that leads to nuclear DNA fragmentation. Both pathways are regulated by TRANSPARENT TESTA 16, a MADS-domain transcription factor that evolved with seed plants. Our results highlight a convergence in the structure and function of extracellular polysaccharides in animals and plants and emphasize their crucial contribution to the development of multicellular organisms.
GPT-4o mini: Non-social science research article
A molecular timer couples organism-wide temporal identity to developmental checkpoints
Peipei Wu, Jing Wang, Brett Pryor, Isabella Valentino, David F. Ritter, Kaiser Loel, Olya Yarychkivska, Shai Shaham, Justin Kinney, Sevinc Ercan, Leemor Joshua-Tor, Christopher M. Hammell
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Coordinated development requires that growth and cell-fate transitions occur in a defined temporal order across tissues, yet how multicellular organisms generate and synchronize developmental timing information remains unclear. In Caenorhabditis elegans , stage-specific cell-fate transitions are driven by pulsatile transcription of microRNAs, including lin-4 and let-7 family members, but the mechanism that produces these rhythms has been unknown. Here, we identify a developmental timer composed of the transcription factor MYRF-1 and the PERIOD-like repressor LIN-42 that operates synchronously across all somatic tissues. MYRF-1 binds conserved regulatory elements upstream of heterochronic microRNA genes and drives once-per-stage transcriptional pulses that are phase-locked across tissues, while simultaneously activating lin-42 expression. Newly synthesized LIN-42 directly associates with MYRF-1, limiting its nuclear residence and transcriptional activity and thereby constraining the amplitude and duration of each pulse. Beyond regulating stage-specific gene expression, we show that MYRF-1 activity is also required to license a developmental checkpoint essential for growth and successful ecdysis. Together, these findings define a reciprocal transcriptional–translational feedback loop that generates organism-wide developmental timing information, coupling tissue-specific differentiation programs to coordinated organismal growth through a shared molecular timer.
GPT-4o mini: Non-social science research article
Climate mediates phenological and phylogenetic differentiation in plant invasions
Tadeo H. Ramirez-Parada, Isaac W. Park, Shijia Peng, Misako Nishino, John T. Kartesz, Sydne Record, Charles C. Davis, Susan J. Mazer
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Darwin’s Naturalization Conundrum holds that both functional similarity and distinctiveness can facilitate biological invasions: invaders similar to natives may succeed through preadaptation to local abiotic conditions, whereas functionally distinct invaders may succeed by reducing competition. Yet the contexts in which either mechanism dominates are unclear. Prior research has primarily attributed variability in native–invasive differentiation to shifts in the balance between biotic and climatic barriers to invasion from local to regional scales. However, similarity and distinctiveness are frequent at both local and regional levels, indicating key drivers of native–invasive differentiation remain overlooked. Crucially, theory and evidence show that as climatic stress increases, competition weakens. This implies that harsh climates should favor invaders functionally similar to natives, whereas mesic climates should favor distinctiveness. However, this hypothesis has not been tested across climate regimes and functional traits. We addressed this gap by combining models of species distributions and flowering phenology for 2,810 species across the United States, estimating phylogenetic distance and phenological differentiation between natives and invasives relative to differentiation among co-occurring natives. In warm, humid regions, invasives flowered earlier, less synchronously, and were more distantly related to natives. In cold or dry regions, they flowered at similar or later times, more synchronously, and were more closely related than natives themselves. Across all climates, invasives consistently exhibited longer flowering durations, with little evidence of greater phenological plasticity. These findings reveal that Darwin’s Conundrum reflects a predictable continuum shaped by environmental context, highlighting climate as a key axis of invasion success.
GPT-4o mini: Non-social science research article
Decoding the structure of GPR151 via NELiS
Yumeng Wang, Luyu Fan, Qianqian Song, Yaning Li, Jiayu Jin, Qiaoyu Zhao, Weijie Gu, Xiangyi Shi, Dianfan Li, Yao Cong, Sheng Wang
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Structure determination of orphan G protein–coupled receptors (GPCRs) is hindered by lack of known ligands and their inherent instability during purification. Conventional thermostability screening requires ligands or purified protein, limiting its utility for orphan GPCRs. Here, we present the Nb6-Enabled Ligand-Free Stabilization Platform (NELiS)—a ligand- and purification-independent method for identifying stabilizing mutations. Applied to GPR151, an orphan GPCR enriched in habenula and implicated in neuropsychiatric disorders, NELiS identified four mutations that significantly improved thermostability and expression, allowing receptor purification. Using the stabilized and purified receptor, we further found a high-affinity, GPR151-specific nanobody that facilitated structural determination. Structural analysis revealed unconventional activation-resistant features across canonical motifs and an autoinhibitory N-terminal region occupying the orthosteric pocket. Functional studies confirmed a unique activation mechanism and the critical role of the N terminus in receptor maturation and trafficking. These results establish NELiS as a generalizable tool for structural and functional investigation of orphan GPCRs.
GPT-4o mini: Non-social science research article
ATP2B1 expression identifies human hematopoietic stem cells with superior repopulation and self-renewal
Angelica Varesi, Murtaza S. Nagree, Isabella Di Biasio, Andy G. X. Zeng, Sayyam Shah, Michael Zhang, Hyerin Kim, Alex Murison, Rohail Badami, Olga Gan, Liqing Jin, Jessica McLeod, Sheela A. Abraham, Mark D. Minden, Andrea Arruda, Igor Novitzky-Basso, Jonas Mattsson, John E. Dick, Stephanie Z. Xie
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Long-term hematopoietic stem cells (LT-HSC) maintain lifelong hematopoiesis while preserving the stem cell compartment through self-renewal. The human LT-HSC compartment is molecularly and functionally heterogeneous and also varies across ontogeny. Dissecting the molecular basis for this variation is impeded by the paucity of immunophenotypic markers to resolve LT-HSC heterogeneity. Here, we identified ATPase plasma membrane calcium transporting 1 (ATP2B1/PMCA1) as a cell surface marker that is heterogeneously expressed by CD49f + LT-HSC from fetal to adult hematopoiesis. ATP2B1 immunophenotypic expression stratified human CD49f + LT-HSC from fetal liver, neonatal cord blood, and adult mobilized peripheral blood sources into functionally distinct subpopulations in single-cell (sc) clonogenic assays. CD49f + ATP2B1 + LT-HSC exhibited superior long-term repopulation and self-renewal capacities in vivo compared to CD49f + ATP2B1 – LT-HSC. Molecular profiling by scMultiome and immunofluorescence microscopy point to enrichment of an HSC self-renewal program that includes the TFEB–endolysosomal axis in CD49f + ATP2B1 + LT-HSC. Our study provides a framework to dissect the heterogeneous molecular programs in LT-HSC.
GPT-4o mini: Non-social science research article
Swartkrans Paranthropus and Sterkfontein Australopithecus from southern Africa had different locomotor repertoires
Marine Cazenave, Annalisa Pietrobelli, Andrea LukovĂĄ, Sebastian Bachmann, Matthew V. Caruana, Ronald J. Clarke, Christopher J. Dunmore, Ashley S. Hammond, Jason L. Heaton, A. J. Heile, Jakobus Hoffman, Kathleen Kuman, Dieter H. Pahr, Christopher M. Smith, Dominic Stratford, Alexander Synek, Zewdi J. Tsegai, Tracy L. Kivell, Travis Rayne Pickering, Matthew M. Skinner
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Southern African hominin fossils traditionally attributed to Paranthropus robustus and Australopithecus africanus are differentiated from each other by their dentition and cranial architecture, but their postcranial anatomy has typically been regarded functionally as broadly similar (i.e., terrestrial bipedalism with some degree of arboreal locomotion). Testing the hypothesis of a similar locomotor repertoire between these two taxa has been complicated by a lack of postcranial fossils attributable to P. robustus . Here, we detail our comparative examination of the internal bone anatomy of a recently described c. 1.8 Ma P. robustus articulating femur and tibia, which suggests distinct patterns of joint loading and locomotor behavior. Our analysis of cortical bone in the hip and trabecular bone in the ankle, knee, and hip joints suggests that P . robustus habitually adopted a high frequency of ankle, knee, and hip flexion, as required for climbing, while Australopithecus from a c. 3.4 Ma level at the site of Sterkfontein displays a more modern human-like structural pattern across the lower limb joints consistent with comparatively more frequent terrestrial bipedalism. These results reveal that geologically younger P . robustus likely used arboreality more frequently than older Sterkfontein Australopithecus . Together with differences in masticatory behavior, this line of evidence indicates that these two hominin taxa occupied distinct ecological niches.
GPT-4o mini: Non-social science research article
Linkage of nucleotide and functional diversity varies across gut bacteria
Veronika Dubinkina, Byron J. Smith, Chunyu Zhao, Cindy Pino, Katherine S. Pollard
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Understanding the forces shaping genomic diversity within bacterial species is essential for interpreting microbiome evolution, ecology, and host associations. Here, we analyze over one hundred prevalent gut bacterial species using the Unified Human Gut Genome collection to characterize patterns of intraspecific genomic variability. Gene content divergence scales predictably with divergence in core genome single nucleotide polymorphisms (SNPs), though there is substantial variability in evolutionary dynamics across species. Overall, accessory genes exhibit consistently faster linkage decay compared to core SNPs, highlighting the fluidity of functional repertoires within species boundaries. This signal is strongest for mobile genetic elements, which show minimal linkage to core genome SNPs. Together, our findings reveal species-specific recombination regimes in the gut microbiome, underscoring the importance of accounting for horizontal gene transfer and genome plasticity in microbiome-wide association studies and evolutionary models.
GPT-4o mini: Non-social science research article
Oak masting breaks down in a highly fragmented, pollen-limited landscape
Ian S. Pearse, Jill H. Baty, Mario B. Pesendorfer, Robert Olson, Walter D. Koenig
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Masting, the production of variable and synchronous seed crops, is common among wind pollinated trees, and periodic pollen limitation is thought to be an important component of the process of masting. However, little is known either about the dynamics of mast seed production or pollen limitation in isolated trees. We tracked seed production of valley oak ( Quercus lobata ) over 11 years in a highly fragmented landscape in California’s Central Valley in which many trees lacked conspecific neighbors within 500 m. We found that oaks with closer neighbors produced more acorns on average than oaks with fewer neighbors. Consistent with theories linking mast seeding and pollination, the isolation effect was most apparent in the highest seed production years. While individual trees showed substantial interannual variation in seed production, we observed little synchrony in seed production among individuals compared to intact oak populations throughout California. Our results indicate that highly fragmented populations suffer signs of pollen limitation and do not produce synchronous seed crops. Fragmentation, alongside climate change, is a dimension of global change that interrupts the typical seed production dynamics of trees.
GPT-4o mini: Non-social science research article
VEGF-D-induced intraosseous lymphangiogenesis drives site-specific heterotopic bone resorption
Neda Vishlaghi, Danielle Griswold-Wheeler, Sneha Korlakunta, Angelica Vallejo, Monisha Mittal, Yuxiao Sun, Peng Zhao, Yunzhi Peter Yang, Joseph M. Rutkowski, Benjamin Levi, Michael Dellinger
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Heterotopic ossification (HO) is a debilitating condition that commonly occurs after musculoskeletal injury and is characterized by the formation of bone in soft tissues. Despite advances in understanding its pathogenesis, effective therapies to reverse established heterotopic bone remain lacking. While lymphatic vessels are associated with the destruction of bone in rare diseases such as Gorham-Stout disease, their effect on HO has not been widely explored. Here, we use transgenic mice to determine whether targeted expression of the lymphatic growth factor VEGF-D can promote the therapeutic resorption of bone in a mouse model of HO. We show that control mice lack lymphatic vessels in heterotopic bone. In contrast, Vegfd -overexpressing ( Vegfd-OE ) mice develop lymphatic vessels in heterotopic bone and form significantly less heterotopic bone than control mice. Additionally, we demonstrate that VEGF-D overexpression or local delivery promotes the therapeutic resorption of established heterotopic bone. Mechanistically, we show that the transition of myeloid cells to osteoclasts and osteoclast-mediated bone resorption are enhanced in Vegfd-OE mice. These findings reveal a previously unrecognized role for lymphatic vessels in regulating heterotopic bone resorption and identify VEGF-D-mediated lymphangiogenesis as a promising therapeutic strategy for HO.
GPT-4o mini: Non-social science research article
Traveling-wave transcranial alternating current stimulation (twtACS) causally links neural timing to cognitive function
Sangjun Lee, Jimin Park, Ivan Alekseichuk, Taylor A. Berger, Ana M. G. Manea, Harry Tran, Gabriela Delgado Salazar, Seth D. König, Alexander B. Herman, David P. Darrow, Jan Zimmermann, Alexander Opitz
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Cortical traveling waves (TWs) are brain oscillation patterns that support the transfer of neural information across distinct brain regions, with their direction shaping cognitive function. However, direct evidence for their causal influence on brain dynamics and behavior remains lacking. Here, we establish such a causal link by externally applying TW-like electric field patterns. To achieve this, we develop a noninvasive brain stimulation protocol, traveling-wave transcranial alternating current stimulation (twtACS). twtACS can generate a precise directional electric field that propagates across the cortical surface, which we validate using human intracranial recordings. In monkey recordings, we show that neural spiking was directionally modulated, shifting systematically across space in line with the direction of twtACS. In humans, twtACS led to direction-dependent improvements in cognitive performance. Together, these findings demonstrate that externally imposed TWs can causally shape neural activity and cognition, highlighting the potential of twtACS as a neuromodulation technique for cognitive enhancement.
GPT-4o mini: Non-social science research article
Incentive valence differentially engages open- and closed-loop basal ganglia circuits during movement initiation
Neil M. Dundon, Elizabeth J. Rizor, Joanne E. Stasiak, Jingyi Wang, Taylor Li, Kiana Sabugo, Christina Villanueva, Parker Barandon, Viktoriya Babenko, Renee Beverly-Aylwin, Alexandra Stump, Tyler Santander, Andreea C. Bostan, Regina C. Lapate, Scott T. Grafton
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Incentives modulate voluntary movement, yet the circuitry channeling these signals into motor output remains unclear. Classical models emphasize a closed-loop circuit (CLC) linking dorsal putamen (PUTd) with the motor cortex, but this pathway is anatomically segregated from affective processing regions. Anatomical and clinical evidence point to an alternative: an open-loop circuit (OLC) from ventral putamen (PUTv) that may route affective signals to the motor cortex. Here, we conducted two experiments to test whether a functional OLC exists in humans and whether it is differentially engaged by incentive conditions. First, in 7 T resting-state fMRI (multi-echo), PUTv showed robust functional connectivity with both affective and motor regions, including the cingulate motor area, even after accounting for PUTd variance. This connectivity pattern supports the plausibility of an independent pathway linking affective basal ganglia regions to the motor cortex. Second, in 3 T task fMRI (incentivized reaching), jackpot (high-reward) and robber (high-loss avoidance) incentive conditions produced distinct behavioral and neural signatures. Jackpot produced a speed–accuracy trade-off, with faster movement initiation but more false starts. Neurally, this coincided with reduced engagement (BOLD responses relevant for initiation speed) in CLC nodes but not in OLC. Robber, in contrast, eliminated engagement in both OLC and CLC nodes, instead recruiting stopping-related regions (e.g., subthalamic nucleus), consistent with an avoidance phenomenology. Together, these findings support a versatile architecture for movement initiation that flexibly engages distinct cortico-subcortical circuits depending on incentive phenomenology, and offer a candidate mechanism through which affective salience and valence modulate voluntary movement.
GPT-4o mini: Non-social science research article
Peripheral complement C4 protein in schizophrenia: Association with gene copy number and immune cell subtypes
Agnieszka Kalinowski, Claudia Macaubas, Hanmin Guo, Lauren A. Anker, Diane E. Wakeham, Marcus Ho, Reenal Pattni, Batuhan Bayram, Surbhi Sharma, Joanna Liliental, Jong H. Yoon, Elizabeth D. Mellins, Lawrence Steinman, Alexander E. Urban
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The lack of highly effective disease-modifying treatments for schizophrenia necessitates exploration of novel aspects of its pathophysiology, including attention to innate immune mechanisms outside the brain. C4 protein activation, associated with the complement cascade of innate immunity, associates with symptoms and predicts outcomes in schizophrenia. However, C4 protein activation does not coincide with expected changes to other proteins in the complement cascade, suggesting another source of C4 protein activation. Studying a combination of fresh whole blood from 10 anonymous donors and a large set of publicly available microarray data, we show that C4 protein is found and expressed primarily in neutrophils and monocytes. Then, we compared the correlation between C4 protein in neutrophils, classical monocytes, plasma, and the number of C4A gene copies. We determined the number of C4A genes using digital droplet PCR, C4 protein in neutrophils (15 patients/21 controls) and plasma (30 patients/38 controls) using Western blotting, and classical monocytes (30 patients/38 controls) using flow cytometry. We found a large positive correlation between the number of C4A gene copies and the amount of C4 protein only in neutrophils and only in the schizophrenia group (Spearman’s rho = 0.63, 95% BCa CI: 0.12 to 0.89, P = 0.012). Our results indicate a convergence of innate immunity mechanisms associated with schizophrenia. The involvement of innate immunity deserves further attention to determine whether it could be a target for therapy in schizophrenia.
GPT-4o mini: Non-social science research article
Intramolecular bonding as a design strategy for robust intermolecular binding of oligomers
Mohammed Suliman Alshammasi, R. Kenton Weigel, Christopher A. Alabi, Fernando A. Escobedo
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In this study, a combined multiscale-modeling and experimental framework is presented to elucidate design rules to optimize the binding thermodynamics and kinetics of sequence-defined oligomers. It is shown that, contrary to conventional notions, entropy can be designed to favor not only binding affinity but also the rapid hybridization of stable complementary complexes. This entropic gain of binding arises from a strategic interplay between intermolecular contacts and intramolecular interactions that maintain restricted oligomer conformations when unbound. Furthermore, our analysis underscores the important role that solvent quality plays in modulating this interplay through structural changes upon binding in both the oligomers and their solvation shells. While these insights are in principle chemistry-agnostic and can be deployed for a wide range of materials platforms and applications, oligocarbamates are used as testbeds for experimental validation. Oligocarbamates are economical DNA-mimics that, unlike DNA-based constructs, form stable Watson–Crick bonds in common nonaqueous solvents, are not susceptible to enzymatic degradation and can be economically produced at scale.
GPT-4o mini: Non-social science research article
Deep-learning endomicroscope with large field-of-view and depth-of-field for real-time in vivo imaging of epithelial cancer hallmarks
Huayu Hou, Jimin Wu, Jinyun Liu, Vivek Boominathan, Argaja Shende, Karthik Goli, Jennifer Carns, Richard A. Schwarz, Ann M. Gillenwater, Preetha Ramalingam, Mila P. Salcedo, Kathleen M. Schmeler, Tomasz S. Tkaczyk, Jacob T. Robinson, Ashok Veeraraghavan, Rebecca R. Richards-Kortum
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In vivo microscopy (IVM) has shown great promise to improve early detection of epithelial precancer, but it suffers from fundamental trade-offs that limit the resolution, field-of-view (FOV) and depth-of-field (DOF). Here, we present PrecisionView, a compact, deep learning-enabled endomicroscope that breaks these constraints and achieves 20 mm 2 FOV and 500 ”m DOF with 4 ”m resolution, representing approximately 5× increase in FOV and 8× larger DOF compared to conventional IVM with similar resolution. PrecisionView integrates a deep learning-optimized phase mask and real-time reconstruction, enabling rapid in vivo assessment of two key hallmarks of cancer: epithelial cell nuclear morphology and subsurface microvasculature through fluorescence and reflectance imaging. By imaging the oral cavity of healthy volunteers and cervical specimens with precancerous lesions, PrecisionView generates large-scale (1 to 3 cm 2 ) coregistered maps of cellular and vascular structures, revealing distinct microscopic patterns associated with anatomic structures and precancerous lesions. Our results suggest the potential of this computational endomicroscope to address the unmet need for early cancer detection at the point of care.
GPT-4o mini: Non-social science research article
Structural and dynamic basis of indirect apoptosis inhibition by Bcl-xL: A case study with Bid
Christina Elsner, Anton Hanke, Oscar Vadas, Francesco Luigi Gervasio, Enrica Bordignon
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Intrinsic apoptosis is a form of cell death which is activated, executed, and inhibited by the Bcl-2 protein family. The structural basis of the inhibition mechanisms remains elusive. Here, we characterize the ensemble structural model of the inhibitory Bcl-xL/tBid complex at the mitochondrial membrane by probing interresidue distances and dynamic solvent accessibilities complemented by integrative modeling and molecular dynamics simulations. We show that Bcl-xL and tBid form a heterodimer anchored to the membrane by the C-terminal helix of Bcl-xL. The BH3 domain of tBid is wedged between the exposed hydrophobic groove of Bcl-xL and the membrane headgroups, while tBid’s C-terminal helices remain dynamically engaged with the bilayer. This dynamic architecture sheds light on the mechanism of indirect inhibition of apoptosis.
GPT-4o mini: Non-social science research article
Acupuncture does not work and has no place in science-based medicine
Piet Borst, Anton Berns, Roel Nusse
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GPT-4o mini: Non-social science research article
Alternative vegetation states on the Loess Plateau and implications for large-scale afforestation success
Li Ma, Xuan Li, Xingchao Xu, Liping Yang, Qinqin Chang, Siqing Wang, Chao Guan, Miaojun Ma, Chi Xu, Yanchuang Zhao, Emilio Guirado, Ning Chen, Changming Zhao
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Large-scale afforestation on the Loess Plateau, costing hundreds of billions of Chinese yuan, has increased vegetation cover but also depleted soil water, raising concerns about the long-term ecosystem sustainability. While debates continue over suitable afforestation areas and precipitation thresholds, the potential role of alternative stable states, a captivating nonlinear dynamical phenomenon, in afforestation success has been largely overlooked. Here, we combined a systematic field survey (4,875 sites, survey mileage of 80,000 km) with a minimal model to explore potential alternative vegetation states, using tree cover as a state variable along a mean annual precipitation gradient. The results showed a clear signature of alternative states of tree cover across the Loess Plateau: Within the 350 to 500 mm mean annual precipitation range, three vegetation states coexist, which are identified as treeless (cover < 5%), open woodland (5 to 50%), and forest (cover > 50%). For areas with mean annual precipitation between 500 and 700 mm, the ecosystem displays bistability consisting of an open woodland and a forest state. Our minimal model revealed that vegetation-precipitation positive feedbacks expanded the range over which alternative vegetation states are permitted and shifted the associated thresholds. Regime shifts between the alternative vegetation states have a strong impact on carbon storage potential, suggesting that afforestation strategies should prioritize bistable and tristable zones where restoration is feasible. These findings provide a framework for afforestation planning and advance the theory of alternative stable states in dryland forests.
GPT-4o mini: Non-social science research article
MCM8-9 helicase activity protects primordial germ cell development to prevent premature ovarian insufficiency
Xiaofei Jiao, Zhifang Li, Zhenghui Tang, Jun Xu, Lin-Yu Lu, Yidan Liu
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MCM8 and MCM9 form a hexameric helicase critical for homologous recombination (HR). While their variants are strongly associated with premature ovarian insufficiency (POI), with many clustering within their AAA+ ATPase domains, the requirement for their helicase activity remains unknown. Here, we show that MCM8-9’s helicase activity is essential for ovarian reserve preservation and POI prevention. Using a series of helicase-deficient mouse models, we demonstrate that this activity is dispensable for meiotic recombination but critically required for mitotic HR and primordial germ cell (PGC) development. The two distinct ATPase active sites of MCM8-9 exhibit marked functional asymmetry, a property regulated by residues within their Walker B motifs. Despite this asymmetry, both ATPase active sites are equally essential for MCM8-9’s function in HR, PGC development, ovarian reserve preservation, and POI prevention. Our findings establish a direct mechanistic link between compromised MCM8-9 helicase activity and POI pathogenesis through its essential role in PGC development.
GPT-4o mini: Non-social science research article
Single-cell multiomic and spatial landscape of the primate pineal gland reveals circadian and melatonin regulatory architecture
Jihong Zheng, Yuchen Xiao, Jianjun Lyu, Hongtao Xu, Yaqun Zhang, Yanchuan Li, Yihao Li, Tianjun Wang, Liu Liu, Lingjing Jin, Xuhui Zhou, Chao Zhang
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The mammalian pineal gland maintains normal circadian rhythms and homeostasis by secreting melatonin. However, the lack of a single-cell-resolved regulatory map limits our understanding of how these neuroendocrine functions are orchestrated. Here, we constructed a multiomics atlas of the pineal gland from Macaca fascicularis by integrating snRNA-seq, snATAC-seq, and spatial transcriptomics. We identified pinealocytes as the predominant cell type, alongside six glial and vascular lineages. Chromatin accessibility analysis delineated cell-type-specific regions enriched for melatonin synthesis and phototransduction genes. Notably, we resolved a dual-layer regulatory architecture: While melatonin synthesis programs are robustly organized, circadian clock regulators exhibit a distinct, sparse spatial pattern. Coexpression networks further identified core modules and regulatory hubs—including CRX/OTX2, LHX4, and RORA—that integrate these circadian and light-responsive signals. Cell-cell communication analysis identified signaling axes, such as PTN - ALK / SDC2 , RA - RORB , and NRG1 - ERBB4 , that potentially coordinate this spatial functional organization. Integrating genetic traits showed that sleep and neuropsychiatric risk variants preferentially map to these pineal regulatory modules. Specifically, sleep-associated loci converged on MEIS1 -linked elements, while bipolar disorder-associated loci highlighted candidate genes of RDH12 and SDK2 . Overall, this study reveals the cellular diversity and spatial regulatory logic of the primate pineal gland, providing a physiological foundation for investigating circadian and neuroendocrine regulation in healthy and disease models.
GPT-4o mini: Non-social science research article
Low-barrier hydrogen bond powers long-range radical transfer in the metal-free ribonucleotide reductase
Abhishek Sirohiwal, Juliane John, Yury Kutin, Rohit Kumar, Federico Baserga, Vivek Srinivas, Hugo Lebrette, Maximilian C. Pöverlein, Ana P. Gamiz-Hernandez, Joachim Heberle, MĂŒge Kasanmascheff, Martin Högbom, Ville R. I. Kaila
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Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotide (RNA) to deoxyribonucleotide (DNA) building blocks initiated by a long-range (>30 Å) proton-coupled electron transfer (PCET) by mechanistic principles that remain much debated. By combining multiscale quantum and classical simulations with directed mutagenesis, X-ray crystallography, and vibrational and electron paramagnetic resonance spectroscopy, we elucidate here the molecular principles underlying how metal-free RNRs initiate the long-range PCET process by creating a highly stable 3,4-dihydroxyphenylalanine (DOPA) initiator radical. We show that DOPA‱ is redox-tuned by a low-barrier hydrogen bond (LBHB), with a delocalized proton that provides the catalytic power for the ribonucleotide reduction. We find that the LBHB couples to an extended hydrogen-bonded network, with distant mutations resulting in the loss of radical formation, and providing key molecular insight into the long-range radical transport mechanism in RNRs. On a general level, our findings support the direct involvement of LBHB in protein chemistry and the importance of quantum effects in enzyme catalysis.
GPT-4o mini: Non-social science research article
Exploring entropy landscapes using hard particle Monte Carlo metadynamics
Charlotte Shiqi Zhao, Sun-Ting Tsai, Sharon C. Glotzer
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For more than two decades, metadynamics has been a powerful tool for improving the sampling of rare events and metastable states in molecular systems. It has been sparingly used, however, to study the crystallization of colloidal systems, especially those comprised of hard particles with anisotropic shapes. In this work, we propose a method, hard particle Monte Carlo metadynamics (HPMC-MetaD), that combines the HPMC-scheme with metadynamics, thereby extending the application of metadynamics to hard particle systems whose phase transitions are driven solely by entropy. As illustrative examples, we use HPMC-MetaD to study five shapes previously reported to be candidate glass formers because of their stubbornness to crystallization. With HPMC-MetaD, we observe crystallization for all five shapes and construct entropy landscapes. These results demonstrate the effectiveness of HPMC-MetaD as a tool for exploring self-assembly in hard particle systems, which will enable a more comprehensive understanding of the underlying mechanisms, ultimately allowing predictive control over the assembly pathways.
GPT-4o mini: Non-social science research article
Extreme nonequilibrium synthesis of a Ca–Cu–Si clathrate during the Trinity nuclear test
Luca Bindi, Marek Mihalkovič, Michael Widom, Paul J. Steinhardt
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The Trinity nuclear test of July 16, 1945, generated extreme transient conditions that produced trinitite, a silicate glass containing rare metallic phases. Here we report the discovery and structural and chemical characterization of a previously unknown Ca–Cu–Si type-I clathrate, (Ca 3.3 Cu 0.4 Fe 0.3 ) Σ=4 Si 23 , identified within a Cu-rich metallic droplet embedded in red trinitite. Single-crystal X-ray diffraction shows that this phase adopts the cubic clathrate-I topology, representing the first crystallographically confirmed clathrate structure documented among the solid-state products of a nuclear explosion. Beyond its intrinsic significance, this phase is notable for its close contextual association with the previously reported Si-rich icosahedral quasicrystal formed in the same detonation. Both phases formed under identical extreme conditions, occur within similar Cu-rich droplets, and share an unusually Si-rich Ca–Cu–Si–(Fe) chemistry, motivating an evaluation of whether the quasicrystal could be structurally derived from a clathrate framework. To evaluate this possibility, we performed density functional theory calculations on clathrate-based icosahedral models across a range of Cu contents. The results indicate that clathrate-derived icosahedral structures are mechanically plausible and metastable at low Cu concentrations (~10 to 11%) but become unstable as Cu content approaches that of the Trinity quasicrystal. These findings constrain viable structural models for the quasicrystal and argue against a simple clathrate-derived interpretation.
GPT-4o mini: Non-social science research article
Lactylated NAT10 contributes to elesclomol-triggered cuproptosis via the NAT10/ac4C-DLAT-mRNA/DLAT positive feedback loop in CRC
Wen-Dong Yang, Meng-Ru Lu, Qi Shen, Pei-Heng Zhou, Yang Diao, Shan Xia, Ya-Chun Lu, Yong-Qiang Cui, Bing-Qiang Li, Wen-Xia Xu, Lin Chen, Chao Zhang, Ning Ma, Yao Guo, Zhi-Ying Shao, Wen-Jie Ge, Jin Bai
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Cuproptosis represents a promising therapeutic strategy for cancer; however, its clinical application remains limited. We observed elevated copper levels and increased expression of DLAT, a key procuproptosis gene, in colorectal cancer (CRC) tissues, suggesting inherent susceptibility to cuproptosis. Furthermore, NAT10 enhances DLAT mRNA stability by mediating its N 4 -acetylcytidine (ac4C) modification, thereby promoting cuproptosis. We also discovered that lactylation of NAT10 at lysine 426 (K426) enhances NAT10 catalytic activity. Conversely, SIRT1 mediates the delactylation of NAT10-K426, leading to the inhibition of cuproptosis. The combination of elesclomol (a cuproptosis inducer) and selisistat (a SIRT1 inhibitor) effectively induced cuproptosis in CRC. Notably, the reduction of soluble DLAT induced by elesclomol treatment was found to enhance NAT10-K426 lactylation. Moreover, DLAT supplementation establishes a positive feedback loop that amplifies cuproptosis. These results underscore the critical role of nonhistone NAT10 lactylation in tumor cuproptosis and highlight the therapeutic potential of targeting this pathway for CRC treatment.
GPT-4o mini: Non-social science research article
Chaperone-mediated autophagy protects against retinal photoreceptor degeneration by modulating proteostasis of glucose metabolism enzymes
Raquel GĂłmez-Sintes, Inmaculada Tasset, Ignacio RamĂ­rez-Pardo, AdriĂĄn MartĂ­n-Segura, Sandra Alonso-Gil, Antonio DĂ­az, Kristen Lindenau, ConcepciĂłn Lillo, Pedro de la Villa, Simone Sidoli, Evripidis Gavathiotis, Ana MarĂ­a Cuervo, Patricia Boya
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Defective proteostasis is a hallmark of aging cells and tissues. Among the different components of the proteostasis network, in this study, we focus on a selective form of autophagy known as chaperone-mediated autophagy (CMA), and we set out to understand its physiological role in the retina. Using mice deficient for CMA [knockout for lysosome-associated membrane protein type 2A ( Lamp2A )], we have found that CMA blockade leads to impaired visual function, altered retinal proteostasis, and photoreceptor cell death. Conversely, mice that overexpress human LAMP2A show higher resistance to chemically induced photoreceptor degeneration and slower visual function decline. We found a similar protective effect against retinal degeneration upon pharmacological activation of CMA. To start elucidating the mechanisms behind CMA’s protective role in the retina, we used comparative proteomics and found elevated levels of enzymes related with glucose metabolism in CMA-deficient retinas that phenocopy those observed in old mice retinas. Overall, our results highlight a cytoprotective role for CMA in retina, in part through proteostatic regulation of enzymes involved in glucose metabolism, and support the feasibility of pharmacologically upregulating CMA against retinal degeneration.
GPT-4o mini: Non-social science research article
Energetic interactions of water around ions determine transport properties of electrolyte solutions
Athanassios Z. Panagiotopoulos
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GPT-4o mini: Non-social science research article
Observing the mechanism of delayed collapse in colloidal gels: Yielding while becoming stronger
Rui Cheng, Malcolm A. Faers, Francesco Turci, Abraham Mauleon-Amieva, Tanniemola B. Liverpool, Robert L. Jack, C. Patrick Royall
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The delayed collapse of colloidal gels is a vexing problem. Although the equilibrium behavior of colloid-polymer mixtures is well understood, that of far-from-equilibrium gels is surprisingly complex. As the gels age, they become stronger due to coarsening but exhibit no other macroscopic change. Quite counterintuitively for a material whose strength increases with time, gels may undergo sudden, catastrophic collapse under gravity, sometimes weeks or even years after preparation. An understanding of such delayed collapse has long remained elusive. Here, we probe delayed collapse using a variety of techniques across a range of length scales, from time-lapse imaging, particle-image velocimetry, and in situ vane rheology at the macroscopic scale to multiscale confocal microscopy, with which we image a complete sample with a microscopic level of detail. The insight obtained enables us to identify a mechanism for delayed collapse: increased heterogeneity at the top of the gel leads to droplets of solvent-rich material which are denser than the gel. Upon reaching a sufficient size, these droplets overcome the yield stress of the gel, creating channels in the gel as they fall. When they reach the bottom of the gel, these channels then enable rapid solvent flow and sudden, catastrophic collapse.
GPT-4o mini: Non-social science research article
SAGA1 and SAGA2 localize the starch sheath to the pyrenoid in Chlamydomonas reinhardtii
Victoria L. Crans, Micah I. Burton, Aastha Garde, Lianyong Wang, Martin C. Jonikas
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Most algae enhance their CO 2 assimilation by concentrating CO 2 within the pyrenoid, a biomolecular condensate of the CO 2 -fixing enzyme Rubisco. Many pyrenoids are surrounded by a starch sheath thought to slow the escape of CO 2 from the pyrenoid, but how the starch sheath is localized to the pyrenoid remains poorly understood. Here, in the model alga Chlamydomonas reinhardtii , we find that the protein SAGA2 is necessary for early pyrenoid starch sheath biogenesis and works redundantly with its homolog, SAGA1, to localize the starch sheath to the pyrenoid. SAGA2 and SAGA1 were enriched in different regions of the pyrenoid–starch sheath interface: SAGA1 at pyrenoid tubule-associated puncta and SAGA2 along the rest of the interface, suggesting that SAGA2 and SAGA1 play complementary roles. Both saga2 and saga1 mutants showed decreased starch sheath coverage early during pyrenoid formation that was remedied at a later timepoint. Strikingly, a saga1;saga2 double mutant did not have a starch sheath around the pyrenoid at any timepoint. SAGA1 and SAGA2 starch-binding domains bound to starch, the starch mimic ÎČ-cyclodextrin, and the starch precursor maltoheptaose, suggesting a role for SAGA1 and SAGA2 in starch granule initiation. We propose a model where SAGA1 and SAGA2 each locally prime starch sheath initiation in a distinct region of the pyrenoid surface by enriching starch precursor molecules around the pyrenoid. These findings advance the understanding of algal starch sheath biogenesis and provide insights into the associations between biomolecular condensates and other cellular structures.
GPT-4o mini: Non-social science research article
Randomized iterative trajectory reweighting for steady-state distributions without discretization error
Sagar Kania, Robert J. Webber, Gideon Simpson, David Aristoff, Daniel M. Zuckerman
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A significant challenge in molecular dynamics (MD) simulations is ensuring that sampled configurations converge to the equilibrium or nonequilibrium stationary distribution of interest. Lack of convergence constrains the estimation of free energies and of rates and mechanisms for molecular transitions. Here, we introduce the “Randomized ITErative trajectory reWeighting” (RiteWeight) algorithm to estimate a stationary distribution from unconverged simulation data. This method iteratively reweights trajectory segments in a self-consistent way by solving for the stationary distribution of a Markov state model (MSM), updating segment weights, and employing a new random clustering in each iteration. The repeated clustering mitigates the configuration-space discretization error inherent in existing trajectory reweighting techniques and yields quasi-continuous configuration-space distributions. RiteWeight accurately recovers the stationary distribution even without requiring the Markov property at the cluster level. We present mathematical analysis of the RiteWeight fixed point. We empirically validate the method using both synthetic MD Trp-cage trajectories, for which the stationary solution is exactly calculable, and standard atomistic MD Trp-cage trajectories, which are extracted from a long reference simulation. In both test systems, RiteWeight corrects flawed distributions and generates accurate observables for equilibrium and nonequilibrium steady states. The results highlight the value of correcting the underlying trajectory distribution rather than using a standard MSM.
GPT-4o mini: Non-social science research article
Real-time tracking of carbon corrosion by atomic force microscopy reveals the impact of defect topography on degradation dynamics
Austin J. Reese, Jingzhi Hu, Jin Suntivich
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Carbon materials are widely deployed in electrochemical energy technologies; however, the nanoscale mechanisms underlying their durability remain incompletely understood. We report the visualization of the corrosion dynamics of highly oriented pyrolytic graphite in aqueous acidic environments using in situ atomic force microscopy. By tracking topography in real time, we correlate local corrosion kinetics with specific defect classes. Three salient findings emerge: i) corrosion preferentially occurs through point and line defects, ii) the corrosion rate at individual defects scales with applied potential, and iii) deeper defects propagate more slowly. We further show that corrosion rates are faster when originating from defects than from bulk carbon. These results demonstrate that defects govern corrosion susceptibility in highly crystalline carbon and that the corrosion propagation rate depends on defect geometry. Our findings provide evidence of defect-mediated corrosion in carbon materials and reveal how defect geometry dictates corrosion dynamics, linking nanoscale heterogeneity to electrochemical durability.
GPT-4o mini: Non-social science research article
Refining the mechanism of heme acquisition from free hemoglobin by Staphylococcus aureus IsdH
Valeria Buoli Comani, Omar De Bei, Giulia Paris, Marialaura Marchetti, Francesca Pancrazi, Barbara Campanini, Luca Ronda, Ben F. Luisi, Serena Faggiano, Anna Rita Bizzarri, Stefano Bettati
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Staphylococcus aureus is a human pathogen whose virulence depends on iron acquisition. The bacterium expresses the hemophores IsdB and IsdH that enable heme capture from host hemoglobin (Hb). Unlike IsdB, IsdH can bind both free Hb and Hb:haptoglobin (Hb:Hp) complexes. Here, we present a comprehensive structural analysis of full-length IsdH in complex with free Hb, overcoming the limitations of previous studies based on truncated IsdH constructs. Cryo-EM revealed a previously unobserved oligomeric state and a unique binding pose of the N-terminal Hb-binding domain, likely representing the initial step of Hb engagement. Time-resolved and single-molecule force spectroscopy experiments delineated the sequential steps and mechanical aspects of Hb binding and heme extraction. Together, these findings provide an integrated structural and functional view of the IsdH–Hb interaction in the absence of Hp, as may occur during hemolysis, and offer insights into S. aureus heme scavenging and potential avenues for therapeutic inhibition.
GPT-4o mini: Non-social science research article
Early-life adversity shapes the relationship between growth and reproduction in free-ranging female rhesus macaques
Rachel M. Petersen, Sam K. Patterson, Anja Widdig, Cassandra M. Turcotte, Susan C. AntĂłn, Scott A. Williams, Ashly N. Romero, Samuel E. Bauman Surratt, Angelina Ruiz-Lambides, character(0), Michael J. Montague, Noah Snyder-Mackler, Lauren J. N. Brent, James P. Higham, Amanda J. Lea
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Life history theory predicts that organisms allocate resources across physiological processes to maximize fitness. Under this framework, early-life adversity (ELA) which limits energetic capital could shape investment in growth and reproduction, ultimately contributing to evolutionary fitness. Integrating 64 y of long-term demographic information with cross-sectional behavioral and physiological data from female rhesus macaques ( Macaca mulatta ; n = 163 to 2,105 females depending on the analysis), we tested whether naturally occurring ELA influences investment in the competing physiological demands of growth and reproduction. By analyzing ELA, growth, and reproduction in the same individuals, we also assessed whether adversity intensifies constraints and induces trade-offs between life history domains. Similar to cohort effects described in other species, we found that ELA was associated with modified growth, delayed reproductive maturity, and small adult body size. These effects largely reflected generalized constraints: females that experienced growth limitations also exhibited reproductive concessions, with ELA linked to reduced investment in both. Interestingly, however, two types of adversity were associated with shifts in growth–reproduction trade-offs, such that ELA-exposed females invested relatively more in reproduction at the expense of growth. Finally, we examined how traits modified by ELA related to lifetime reproductive success, addressing understudied links between ELA, life history, and fitness. Across the population, starting reproduction earlier and maintaining a moderate reproductive rate conferred the greatest number of surviving offspring. These findings suggest that ELA impacts key life history traits as well as the relationships between them, and can constrain individuals from adopting the most optimal reproductive strategy.
GPT-4o mini: Non-social science research article
Subsurface soil inorganic carbon gains offset half of surface losses in China’s upland croplands over the last four decades
Andong Cai, Tianfu Han, Zhenghu Zhou, Kailou Liu, Xinpeng Xu, Pete Smith, Qingzhu Gao, Yue Li, Minggang Xu
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Soil inorganic carbon (SIC) constitutes half of the terrestrial carbon pool and exerts a profound influence on global carbon cycling and ecosystem multifunctionality. Contrary to the view of millennial-scale stability, SIC in cropland are undergoing rapid changes due to intense anthropogenic disturbances. However, the direction, magnitude, and drivers of SIC changes over recent decades remain poorly quantified, especially in entire soil profile. Here, we quantified changes in SIC across a 1-m soil profile across China’s upland croplands at 204 matched sites (4,305 soil profiles) in 1980s and 2023, relocated using legacy site descriptions and field verification. Over the past four decades, the mean of surface SIC density (0 to 40 cm) depleted by 0.68 kg m −2 , primarily associated with increased precipitation and soil acidification, whereas subsurface SIC density (40 to 100 cm) increased by 0.49 kg m −2 , attributed to carbon inputs and an increase in soil pH. Subsurface SIC accumulation amounted to 0.48 0.39 0.58 Pg, offsetting 44% surface losses within the upper 1 m soil profile. Importantly, this offset reflects vertical redistribution of SIC rather than net carbon sequestration at the ecosystem scale. These findings highlight the need to incorporate depth-resolved SIC dynamics into terrestrial carbon accounting and climate projections.
GPT-4o mini: Non-social science research article
Trade-offs between light absorption and energy transfer in a marine light-harvesting complex 2
Graham P. Schmidt, Dihao Wang, Amala Phadkule, Chern Chuang, Mike Reppert, Gabriela S. Schlau-Cohen
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Purple bacteria are a diverse group of photosynthetic organisms that can capture and convert light energy with high quantum efficiency across a variety of ecological niches. They absorb light via an array of antenna proteins, primarily light-harvesting complex 2 (LH2), and rapidly transport the energy to the reaction center, where charge separation occurs. LH2 typically consists of eight or nine subunits that each contain three bacteriochlorophyll and one carotenoid. In the marine species Marichromatium (Mch.) purpuratum , the LH2 subunits bind an additional carotenoid, boosting absorbance in the blue where the underwater solar spectrum peaks. In order to accommodate the additional carotenoid, LH2 from Mch. purpuratum consists of only seven subunits, unique among known LH2. Using ultrafast transient absorption (TA) spectroscopy, time-resolved fluorescence, and steady-state techniques, we investigated the effects of these structural differences on the energy transfer dynamics of LH2 from Mch. purpuratum . Our results show, relative to other species, significantly slower rates of energy transfer within LH2 and an excited-state manifold likely to also slow energy transfer between LH2. LH2 from Mch. purpuratum is therefore tuned to match the solar spectrum of its ecological niche, suggesting that the variations in the molecular organization of these antenna proteins may be primarily for optimal light absorption.
GPT-4o mini: Non-social science research article
Visualization of the interaction between sphingomyelin and cholesterol in lipid bilayer membranes
Jared C. Smothers, Chieu H. B. Nguyen, Yan Han, Yang Li, Zhe Chen, Arun Radhakrishnan
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Biomembranes are complex two-dimensional liquids composed of hundreds of lipid species that interact in a myriad of ways. One such interaction, that between sphingomyelin (SM) and cholesterol in plasma membranes of animal cells, provides many functional benefits, including protection from microbial infection, prevention of unrestrained cell growth, and proper maintenance of cellular lipid composition. Owing to the liquid nature of membranes, the structure of the SM/cholesterol interaction, or any other functionally critical lipid–lipid interaction, has remained elusive. Here, we overcome this challenge using a fungal toxin called Ostreolysin A (OlyA), that has been shown to specifically bind to SM/cholesterol complexes in membranes. We used OlyA to stabilize the SM/cholesterol interaction much in the same way as antibodies are used to stabilize preexisting protein complexes. Cryoelectron microscopy analysis of OlyA bound to SM/cholesterol membranes reveals the details of the tight interaction between these two lipids—the steroid nucleus of cholesterol packs against the acyl chains of SM, and a hydrogen bond forms between the nitrogen on SM’s ceramide base and the oxygen on cholesterol’s hydroxyl group, thus sequestering this key functional group of cholesterol. The importance of hydrogen bonding in stabilizing the SM/cholesterol interaction is supported by structural analysis of a mutant form of OlyA that binds free SM in a cholesterol-independent manner. These results provide structural insights into the organization of cholesterol in membranes.
GPT-4o mini: Non-social science research article
Pde4 mediates MHCII expression in oligodendroglia
Miguel M. Madeira, Zachary Hage, Dimitris Koliatsis, Alexandros G. Kokkosis, Kimberly Nnah, Alexander J. Rhee, Gilbert J. Rahme, Katherine Kamvisios, Antonis E. Koromilas, Barbara Rosati, David McKinnon, Stella E. Tsirka
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Chronic psychosocial stress is a major precipitant of Major Depressive Disorder (MDD), yet the glial mechanisms that translate sustained stress into maladaptive myelin and immune changes remain unclear. Using chronic social defeat stress and single-nucleus RNA sequencing of anterior medial PFC (mPFC) oligodendroglia, we identified a mature-oligodendrocyte cluster almost exclusively from stress-susceptible animals, marked by immune genes (MHCII) and upregulated Pde4b. Integration with a human MDD single-nucleus RNA sequencing dataset confirmed a conserved immune-like oligodendrocyte (ImOL) subset coexpressing Plp1 and Cd74 and enriched for Pde4b. Mechanistically, PDE4 inhibition with crisaborole elevated cAMP–PKA–CREB signaling, blocked IFNÎł-induced MHCII expression, and engaged the eIF2α–ATF4/CHOP arm of the integrated stress response (ISR). In vivo modulation of the ISR with ISRIB or guanabenz bidirectionally controlled ImOL prevalence and stress-related behaviors. These findings position Pde4b–cAMP–ISR signaling as a regulator of oligodendroglial immune phenotypes and a promising target to modulate myelination and neuroinflammation in stress-related disorders.
GPT-4o mini: Non-social science research article
Anoxic photo-oxidation of Mn(II)-bearing carbonates on Mars and early Earth
Jiye Guo, Yuke Zhu, Nicholas J. Tosca, Lu Pan, David C. Catling, Yi Liu, Wenhua Zhang, Amrit S. Chaddha, Pengcheng Ju, Jie Li, Zongbin Zhang, Anya Huo, Yunguo Li, Fang Huang, Paul G. Falkowski, Jihua Hao
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Manganese oxides, thought to form almost exclusively through reactions between Mn 2+ and O 2 , catalyze oxidative transformations among redox-sensitive metals. Thus, the occurrence of Mn oxides, either observed or inferred from sedimentary geochemical data, has formed the basis for multiple hypotheses concerning the evolution of the atmospheric redox state on the early Earth and Mars. Here, using theory and experiments, we report that the band gap of common Ca/Mg carbonate minerals (including calcite, magnesite, and aragonite) is significantly lowered by trace incorporation (0.8 wt% or lower) of Mn(II) into their bulk structure or surface, conferring photochemical reactivity under ultraviolet conditions relevant to early Earth and Mars (200 to 400 nm). Moreover, we show that surface incorporation of Mn(II) reduces the fundamental band gap much more effectively (by >1 eV) than bulk incorporation. Our results suggest that photo-oxidation of Mn(II)-bearing carbonates could have occurred widely on planetary surfaces, resulting in the abiotic formation of manganese oxides without free molecular oxygen. Photochemically driven redox cycling of manganese could help sustain redox disequilibria for microbial metabolisms, but compromises the use of manganese oxides as oxygen barometers.
GPT-4o mini: Non-social science research article
Synovial fibroblasts modulate endothelial activation in an acute injury-on-a-chip model
Hannah M. Zlotnick, Declan N. Goddard, Christopher J. Calo, Abhishek P. Dhand, Matthew D. Davidson, Aina Solsona-Pujol, Jonathan T. Makhoul, Hannah K. Weppner, Melissa Wong, Carla R. Scanzello, Laurel E. Hind, Jason A. Burdick
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Most patients who sustain an acute joint injury develop degenerative joint disease or osteoarthritis (OA). Animal models have informed the design of OA therapeutics; however, no disease-modifying therapy has successfully translated to human patients. Thus, there is a strong motivation to develop humanized in vitro platforms to fill a critical gap in knowledge of disease progression postinjury. Here, we develop an acute injury-on-a-chip model of the synovium, a vascularized, joint-lining tissue that has been implicated in OA progression and as a key driver of joint disease. We apply this chip-based system to investigate the crosstalk between endothelial cells, lining an engineered vessel, and synovial fibroblasts, embedded within an extracellular matrix hydrogel. Our data indicate that synovial fibroblasts, rather than initiating disease, attempt to support and maintain vascular function in the presence of acute inflammation (i.e., interleukin-1ÎČ). Such knowledge may provide new targets for OA therapeutics, preventing the progression from joint injury to disease in patients.
GPT-4o mini: Non-social science research article
Chiral inversion mutagenesis identifies geometrically constrained residues within self-associating low-complexity domains
Ryan L. Beckner, Lily Kim, Christien Carter, Abby Walterscheid, Glen Liszczak
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Many protein low-complexity domains (LCDs) self-associate to enable cellular function, yet fundamental questions remain regarding how polypeptide chemical and structural features beyond side chain identity contribute to LCD–LCD interactions. For instance, the folds adopted by globular proteins emerge from constraints enforced by homochirality of genetically encoded polypeptides. However, it remains unclear to what extent similar geometric constraints apply to LCD self-association. Herein, we use protein total and semi-synthesis to probe the contribution of C α stereochemistry to LCD self-association with synthetic Chiral Inversion Mutagenesis (ChIM). By introducing targeted L-to-D amino acid inversions, ChIM identifies C α stereocenters under geometric constraint without modification of side-chain functionalities. We apply ChIM to the LCDs of inner nuclear lamina protein Emerin and neurofilament light chain and find that chiral inversion produces strongly position-dependent effects upon LCD self-association. Our study describes essential structural features that enable LCD self-association and chemical strategies to interrogate LCD biochemistry.
GPT-4o mini: Non-social science research article
Temperature-dependent feedbacks drive the pattern of Antarctic temperature change
Bradley R. Markle, Eric J. Steig
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Antarctica is an important component of the Earth’s climate system. Here we investigate temperature change in Antarctica across a range of timescales, from millennial to orbital, over the last 4 × 10 5 y, using a compilation of ice-core water-isotope records. We identify a persistent pattern of change in which the temperature variability of an Antarctic site increases with its mean surface temperature. When the entire continent warms, the warmest parts of Antarctica warm more; when the entire continent cools, the warmest parts cool more. This pattern is inconsistent with the Planck response, the simplest possible null hypothesis for Antarctic temperature change. However, a temperature-dependent feedback explains the fundamental pattern of temperature change. The feedback arises from a nonlinearity of the greenhouse effect, evident only at the cold surface temperatures of the Antarctic. This feedback may be initiated by any mean energetic forcing and thus manifests across all timescales. Local deviations from the expected pattern of temperature change indicate regional forcing such as changes in ice-sheet elevation. We reconstruct the surface elevation of the main ice divide in West Antarctica over the last deglaciation, finding a history that is supported by geological and glaciological evidence and consistent with ice-sheet modeling.
GPT-4o mini: Non-social science research article
A molecular lattice reinforces the sperm head–tail junction
Anna J. Wood, Pulan Liu, Shaogeng Tang
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GPT-4o mini: Non-social science research article
Vertical conveyor driving the integration of moisture transported by the westerlies to the Asian water towers’ atmospheric water cycle
Jing Gao, Tandong Yao, Valérie Masson-Delmotte, Martin Werner, Jean Jouzel, Lonnie Thompson, Mathieu Casado, Hans Christian Steen-Larsen, Alexandre Cauquoin, Ellen Mosley-Thompson, Zeqing He, Rong Cai, Taihua Zhang, Yigang Liu, Gebanruo Chen, Baiqing Xu, Guangjian Wu, Hongxi Pang, Maosheng He
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The westerlies moisture transport underpins water security for over two billion people dependent on the Asian water towers (AWTs). However, the mechanisms by which large-scale westerlies-advected moisture is integrated into the AWTs’ atmospheric water budget remain poorly understood due to observational gaps. Here, we combine three-dimensional observations of atmospheric water vapor stable isotopes with isotope-enabled modeling. We identify the conveyor mechanism that regulates the vertical moisture transport under calm conditions during the winter-spring period when the westerlies are dominant. Sharp vertical isotopic gradients show that large-scale westerlies-advected moisture is predominantly confined aloft, while local residual moisture persists near the surface. Our results show the interplay of the westerlies’ subsidence at night with thermodynamically distinct local residual air, yielding thermal inversions and condensation that suppresses vertical mixing and decouples moisture between the free troposphere and the atmospheric boundary layer. This process constitutes a primary pathway for integrating westerlies-advected moisture into the local moisture budget without precipitation, sustaining near-surface moisture accumulation. Our results provide critical benchmarks for improving atmospheric models, refining climate projections of the intensifying water cycle over the AWTs, and advancing interpretations of isotopic records in regional climatic archives.
GPT-4o mini: Non-social science research article
Spectral mapping reveals a resemblance of the anesthetic brain state to both sleep and coma
Janna D. Helfrich, Jerzy Szaflarski, Marianne C. J. NÊvra, Luis Romunstad, Matthew P. Walker, Bryce A. Mander, Robert T. Knight, PÄl G. Larsson, Randolph F. Helfrich
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General anesthesia is often compared to sleep but may more closely resemble a medically induced coma. While all three states involve a loss of awareness, the extent of their neural similarity remains unclear. Electrophysiological markers, such as delta activity (< 4 Hz), are present in slow wave sleep, disorders of consciousness (DoC, including coma), and propofol anesthesia but are absent during rapid eye movement (REM) sleep. Frontal alpha oscillations are a key feature of propofol anesthesia and detectable via intraoperative EEG. However, it remains unclear whether alpha and delta activity fully define the brain state. Using whole-head EEG, we analyzed brain activity in individuals under propofol anesthesia, during sleep, or in DoC in the intensive care unit. Our spectral parameterization and similarity analyses revealed that propofol anesthesia exhibits spatiotemporal patterns resembling both coma and sleep. We introduced a spectral orthogonalization approach, identifying unique signatures of propofol anesthesia, including posterior slow waves, frontocentral delta, and reduced aperiodic activity. Critically, the reduction in aperiodic activity partially overlaps with REM sleep and may reflect decreased cortical excitability, contributing to reduced arousal, muscle atonia, and immobility common to both states. These results imply that propofol anesthesia creates a brain state where some features resemble sleep while others are more similar to coma. Embracing its full spatiotemporal complexity could improve titration of sedation, thus minimizing excessive suppression and the risk of postoperative cognitive deficits.
GPT-4o mini: Non-social science research article
MHC-I diversity enables rapid adaptation during a viral pandemic in wild rabbit populations
Yexin Zhang, Jonathan P. Day, Marina Lirintzi, Jiayi Ji, Clive A. Tregaskes, Miguel Carneiro, Joel M. Alves, Tanja Strive, Jim Kaufman, Francis M. Jiggins
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Emerging diseases can have devastating consequences for wild species, with long-term effects depending on the ability of the host to evolve resistance. Here, we show that major histocompatibility complex (MHC) genes provided standing genetic variation that enabled rabbits to mount a rapid evolutionary response to the myxoma virus pandemic that began in the 1950s. Using historical and modern specimens starting in 1865 and spanning the pandemic, we found strong parallel shifts in MHC-I allele frequencies across Australia, Britain, and France, alongside population-specific signals. These evolutionary shifts are predicted to alter the peptides presented to T cells. Our results provide evidence that MHC-I is under strong selection in natural populations during a pandemic and that the high polymorphism of MHC may have contributed to the recovery of these populations.
GPT-4o mini: Non-social science research article
Contributions of the basolateral amygdala and nucleus accumbens to sustaining not just initiating cognitive effort
Matthew L. Dixon, Elizabeth Blevins, Carol S. Dweck, Kai Görgen, Brian Knutson
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People must often sustain cognitive effort to achieve important goals. Although current models recognize that subcortical valuation regions are important for initiating such effort, they have not seen them as playing meaningful roles in sustaining effort throughout task performance. Here, we demonstrate that core subcortical valuation regions—the basolateral amygdala (BLA) and nucleus accumbens (NAcc)—contribute to sustaining cognitive effort on a challenging working memory task. First, convergent univariate and multivariate analyses revealed that the BLA and NAcc represented incentive value, cognitive effort demands, or both, during every task period (encoding, maintenance, and probe/response). Second, trial-to-trial fluctuations in BLA/NAcc multivariate value coding predicted both the strength of frontoparietal cortical engagement and behavioral performance. Third, the BLA and NAcc functionally interacted with frontoparietal regions throughout the task, suggesting that they work in a coordinated manner. These findings reveal a continuous and dynamic role for subcortical valuation regions in sustaining cognitive effort.
GPT-4o mini: Non-social science research article
A brain circuit of bidirectional modulation of social and nonsocial cognition by androgens and estrogens in male mice
Dario Aspesi, Anjana Varatharajah, Lucia Cioffi, Silvia Diviccaro, Donatella Caruso, Natalina Becke, Jasmin Lalonde, Melissa L. Perreault, Roberto C. Melcangi, Neil J. MacLusky, Elena Choleris
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Androgens and estrogens rapidly influence brain function and behaviors critical to social species, including social recognition, which is essential for group living and modulating social interactions. The specific brain regions involved and their hormonal regulation remain poorly understood. This regulation is complex, as the main circulating androgen, testosterone (T), is metabolized into estrogenic (17ÎČ-estradiol, E2) and androgenic (dihydrotestosterone, DHT) compounds, meaning its actions can be mediated through both androgen (AR) and estrogen receptors (ERs). This study identifies an estrogen-regulated, social recognition-specific brain circuit, demonstrating that T and E2, but not DHT, interact with the arginine–vasopressin (AVP) system in the bed nucleus of the stria terminalis (BNST)–lateral septum (LS) pathway to promote social recognition in male mice. T, E2, and DHT all facilitated social recognition and impaired object recognition within forty minutes of infusion into the BNST, but only the effects of T and E2 were blocked by an AVP receptor 1a (V1aR) antagonist, suggesting distinct mechanisms underlie the facilitation of social recognition by estrogens and androgens. Using CRISPR/Cas9 to selectively knock down AR, ERα, ERÎČ, or G protein–coupled estrogen receptor (GPER) in the BNST of male mice four weeks before steroid infusion, we found that ERα and ERÎČ (but not GPER) are necessary for T and E2 to rapidly facilitate social recognition, whereas DHT acts through AR. Our findings highlight the distinct roles of AR and ERs in the modulation of social recognition by steroid hormones, revealing redundant and nonoverlapping mechanisms of androgens and estrogens in the functioning of the male social brain.
GPT-4o mini: Non-social science research article
Microhomology-mediated tandem duplication is a conserved mechanism of genomic variation with implications for human disease
Xianfang Wei, Wanxin Gong, Yifan Zheng, Jing Zhang, Xianyuan Wei, Chen Peng, Xiangwei He, Chao Jiang
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Tandem repeats are highly mutable genomic elements with significant functional consequences, yet the mechanisms underlying their evolutionary origin remain unclear. One proposed mechanism is microhomology-mediated tandem duplication (MTD), in which single-copy DNA segments flanked by microhomology undergo duplication and may subsequently expand. Although MTD was first described in Schizosaccharomyces pombe , its prevalence and evolutionary significance across life have not been systematically established. Using whole-genome deep sequencing and a unified analytical framework, we show that MTDs arise de novo across bacteria, archaea, fungi, and viruses. Analyses of 2,245 reference genomes, millions of genomes from 103 microbial species, and human datasets reveal that microhomology-mediated duplications constitute a major source of tandem duplication across domains of life. Genome-wide analyses show that most MTDs evolve under neutral or nearly neutral dynamics, while purifying selection preferentially depletes MTDs from coding regions. Mechanistically, deletion of the conserved flap endonuclease Rad27 specifically increases de novo MTD formation in budding yeast, implicating Okazaki fragment maturation in the generation of MTDs. In humans, microhomology signatures are pervasive among reference, polymorphic, and disease-associated tandem duplications and are enriched among pathogenic variants linked to genome stability and cancer. Together, these findings establish MTD as a conserved mechanism that shapes genomic variation, with implications for human disease.
GPT-4o mini: Non-social science research article
Emergent anisotropic three-phase order in critically doped superconducting diamond films
Jyotirmay Dwivedi, Saurav Islam, Jake Morris, Kalana D. Halanayake, Gabriel A. VĂĄzquez-Lizardi, David Snyder, Anthony Richardella, Luke Lyle, Danielle Reifsnyder Hickey, Nazar Delegan, F. Joseph Heremans, David D. Awschalom, Nitin Samarth
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Two decades since its discovery, superconducting heavily boron-doped diamond (HBDD) still poses fundamental questions that need to be answered to unlock its full potential for quantum applications. We use electrical magnetotransport measurements of critically doped homoepitaxial single crystal HBDD films to reveal signatures of intrinsically granular superconductivity. By studying the dependence of electrical resistivity on temperature and magnetic field vector, we infer that this granularity arises from doping induced disorder. We observe an unexpected three-phase anisotropy in the magnetoresistance, accompanied by a spontaneous transverse voltage (Hall anomaly). Our findings indicate the emergence of an anisotropic order in an otherwise isotropic single crystal HBDD film, offering insights into the mechanism of superconductivity in this quantum material.
GPT-4o mini: Non-social science research article
Genomic ancestry predicts rapid responses to drought across spatiotemporal scales
Rozenn M. Pineau, Natalia Bercovich, Loren H. Rieseberg, Julia M. Kreiner
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How genetic diversity responds to environmental change across spatiotemporal scales remains poorly understood despite its importance for species persistence in changing landscapes. Agricultural weeds offer ideal models for studying these adaptive dynamics as they rapidly evolve under both the intensive management practices designed to eliminate them and increasingly severe climate challenges such as drought. Here, we combine experimental and herbarium genomic approaches spanning within-generation to century-long timescales to understand how genome-wide variation responds to drought in Amaranthus tuberculatus . In this native species, a history of divergent selection between two ancestral lineages followed by secondary contact is thought to have facilitated its invasion into agriculture. A drought survival experiment on accessions from paired agricultural and natural populations across its range revealed substantial phenotypic variation differentiated by habitat, geography, and ancestry. Admixture mapping revealed 43 independent loci across nearly all chromosomes that confer protective effects under drought, demonstrate particularly rapid allele frequency changes, and exhibit duration-specific selection over the course of the imposed drought. Observation of allele frequencies across the past century reveals evidence for climate-dependent fluctuating selection governing the evolution of drought-associated loci. Selection favors drought alleles during hot/dry years and selects against them in cool/wet years—a pattern more evident in long-term trends than in shorter temporal intervals, suggestive of adaptive lag in rapidly changing environments. By combining short and long-term spatiotemporal data, we demonstrate that fluctuating selection has preserved the polygenic variation underlying population responses to drought, enabling ongoing adaptive responses to contemporary land use and climate change.
GPT-4o mini: Non-social science research article
Structural promiscuity in the human circulatory IgA1 clonal repertoire
Amber D. Rolland, Sofia Kalaidopoulou Nteak, Gestur Vidarsson, Albert Bondt, Albert J. R. Heck
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Immunoglobulin A (IgA) is the most abundant antibody in humans, with high concentrations in both mucosae/secretions and circulation. While mucosal IgA has been studied extensively, characterization of human IgA in serum and its distinctive functions lags behind. Circulatory IgA is regularly assumed to be monomeric, despite some reports describing a minor population of J-chain-coupled dimers. Here, we first charted the compositional landscape of human serum IgA in individual healthy donors. In addition to the expected predominating monomers, we consistently observed J-coupled dimers, even representing ~30% of one donor’s total serum IgA. To determine whether these structurally distinct populations were also clonally distinct, we employed mass spectrometry–based IgA1 clonal profiling in sera of two donors. Our data revealed the majority of IgA1 clones are present solely as monomers, with a smaller number exclusively dimeric. Strikingly, a third population of IgA1 clones is present in circulation as both monomers and J-coupled dimers. In fact, these shared, structurally promiscuous IgA1 clones dominated both individuals’ serum IgA1 clonal repertoires. Our findings suggest every unique IgA1 clone could potentially be produced as a variable mixture of monomers and J-coupled dimers, but what exactly determines this ratio requires further investigation. This finding is important, as monomers and J-coupled dimers have distinct characteristics in antigen binding, receptor activation, and clearance from circulation, with several reports highlighting, for instance, the enhanced neutralization capacity of dimeric IgA. As we show here, the human immune system is not merely capable of producing both forms but apparently prefers doing so in parallel.
GPT-4o mini: Non-social science research article
Force patterning drives quasistratification and graded tissue-scale spatial order in auditory epithelia
Julian Weninger, Anubhav Prakash, Sukanya Raman, Raj K. Ladher, Madan Rao, Karsten Kruse
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During development, coordinated cell behaviors drive epithelial morphogenesis toward precise three-dimensional architectures essential for physiological function. How such coordination arises in epithelia composed of multiple cell types remains unclear. Here, we study development of the avian auditory epithelium comprising sensory hair cells (HCs) and nonsensory supporting cells (SCs). Initially, HCs and SCs are arranged into mosaics by Notch–Delta signaling. As development proceeds, HCs partially extrude from the epithelium, establish a tenfold gradient in apical surface area across the tissue, and rearrange with SCs to form near-hexagonal order. Using experiments combined with a three-dimensional vertex model, we show that increased contractility at apical junctions between SCs relative to HC–SC junctions drives spatial organization both within the epithelial plane and along the apical–basal axis. Consistent with experimental findings, our simulation shows systematic differences in HC apical area expansion generate opposing coordinated movements of HCs and SCs, establishing gradients in HC apical surface area and density while maintaining uniform hexagonal order. Together, these results demonstrate that spatial patterning of junctional contractility coordinates cell behavior across both the plane and depth of a mixed epithelium, producing quasi-stratified architecture and tissue-scale three-dimensional order.
GPT-4o mini: Non-social science research article
Developmental landmarks and cellular transitions during extravillous trophoblast cell differentiation
Ayelen Moreno-Irusta, Malay Kumar Basu, Esteban M. Dominguez, Thomas S. Chen, Sawyer H. Smith, Kaela M. Varberg, Hiroaki Okae, Takahiro Arima, Michael J. Soares
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Human trophoblast stem (TS) can be captured, maintained in vitro under specific conditions, and differentiated into extravillous trophoblast (EVT) cells. The regulatory mechanisms that govern the self-renewal and differentiation of human TS cells into EVT cells are largely unknown. In this study, bulk RNA-sequencing (RNA-seq) and single cell RNA-seq (scRNA-seq) were performed on human TS cells maintained in the stem state and on cells progressing from the stem state into EVT cells (differentiation days 3, 6, and 8). Distinct bulk and single cell transcript profiles were identified for each day of analysis. Day 3 of EVT cell differentiation represented a striking transition point and was readily distinguished from stem state and days 6 and 8 of EVT cell differentiation. Analysis of scRNA-seq led to the identification of several unique cell populations, trophoblast cell developmental state-specific regulons, and trajectories. We elucidated functional roles of key regulators of EVT cell development: cyclin B1, CCAAT/enhancer-binding protein beta, and A Disintegrin And Metalloproteinase (ADAM) metallopeptidase with thrombospondin type 1 motif 20. Collectively, we have defined developmental landmarks and transitional cell populations during EVT cell differentiation. These findings provide a valuable resource and foundation for future investigations into regulatory mechanisms controlling TS cell differentiation into the EVT cell lineage.
GPT-4o mini: Non-social science research article
3D epithelial cell topology tunes signaling range to promote precise patterning
Giulia Paci, Francisco Berkemeier, Buzz Baum, Karen M. Page, Yanlan Mao
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Cell behaviors in multicellular organisms are coordinated via both diffusible molecules and by signals based on direct cell–cell contacts. The mode of cell communication used influences the signaling range. In many developing epithelia, contact-based Notch-Delta lateral inhibition signaling is used to pattern cell fates. While previous work revealed that cells can use protrusions to extend the range of Notch-Delta signaling to alter these patterns, this is not a general feature of epithelia. In addition, it is not known how the complex three-dimensional (3D) shapes of epithelial cells influence cell communication. In exploring this question, we show that epithelial cells at the Drosophila wing margin, which lack basal protrusions, contact different neighbors at different heights along their apico-basal axis, effectively increasing the number of neighbors each cell touches. To quantitatively assess this behavior, we develop a mathematical modeling framework (Multilayer Signaling Model) to simulate Notch-Delta signaling over data-derived 3D cell topologies. The model predicts that lateral cell surface signaling is essential to tune the spacing between sensory organ precursors (SOPs). In agreement, we show that perturbing cortical stiffness and cell tortuosity in vivo modifies SOP spacing. These results emphasize the importance of 3D cell geometry and topology in fine-tuning signaling range.
GPT-4o mini: Non-social science research article
2024 global temperature record is consistent with model-predicted warming
Michael E. Mann, Byron A. Steinman, Alejandro Fernandez, Shannon A. Christiansen, Xueke Li
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We employ a semiempirical approach combining climate model simulations and observational temperatures to assess the likelihood of recent global temperature records. Monte Carlo simulations are used to generate global temperature series consistent with combined estimates of forced (anthropogenic + natural) and internal variability derived from observations and CMIP6 multimodel simulations. We find that the El Niño-boosted 2024 global temperature record had a ~12% likelihood of occurrence (a one-in-eight-year event), similar to the prior (also El Niño-boosted) record year 2016 (~14% likelihood). Of the records set during the past three decades, only 1998 is found to have been truly anomalous, with a ~2.5% likelihood of occurrence. Each of these records is found to have been nearly impossible in the absence of human-caused warming.
GPT-4o mini: Non-social science research article
Synthetic control over proximity of metal and acid dual sites switches the selectivity of acetophenone hydrodeoxygenation
Luyan Li, Xinhui Guo, Jiajia Huang, Zhenhe Jia, Xiaoshuo Liu, Qiaoqiao Guan, Yu Gu, Weijie Yang, Junling Lu, Shaojun Guo, Hai-Long Jiang
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Though spatial arrangement between metal and acid has proven efficiency for enhancing catalytic performance, their precise regulation on controlling the product selectivity and revealing related catalytic mechanism remains scarce. Herein, we report a class of Pd nanoparticles integrated into isoreticular UiO-66-type metal-organic frameworks with or without sulfonic acid groups (denoted UiO-S and UiO), which allows for precise distance tuning between Pd and acid site by controlling UiO-66 interlayer thickness. Unlike traditional studies focusing on substrate/intermediate diffusion by dual-site regulation, we herein demonstrate that significant modulation of electron transfer and proton concentration around Pd over UiO-S@UiO 25 @Pd@UiO switches reaction pathways and profoundly tunes selectivity in acetophenone hydrodeoxygenation. Specifically, we show that UiO-S@UiO 25 @Pd@UiO with a 25 nm separation between Pd and acid sites achieves the highest selectivity (~94%) to phenylethanol via homolytic H 2 cleavage, mitigating prevalent overhydrogenation pathway; whereas UiO-S@Pd@UiO and UiO@Pd@UiO-S, with closely positioned dual sites, dramatically enhance hydrodeoxygenation activity, and display >99% selectivity to high-energy-density ethylbenzene. Notably, a proton-assisted mechanism involving H 2 heterolysis is elucidated over UiO@Pd@UiO-S, particularly significant for implementing the catalytic process under mild conditions.
GPT-4o mini: Non-social science research article
Simultaneous multielectrode recordings along the human scala tympani: Evidence for level-dependent place coding
Amit Walia, Matthew A. Shew, Shannon M. Lefler, Amanda J. Ortmann, Patrick Ioerger, Jordan Varghese, Jacques A. Herzog, Craig A. Buchman
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The cochlea systematically encodes sound frequency and intensity via a precisely organized tonotopic map, in which traveling waves peak at specific cochlear locations. A fundamental but incompletely understood aspect of auditory coding involves how stimulus intensity shapes this tonotopic organization. In animal models, increasing intensity shifts the cochlear traveling wave peak basally; however, physiological evidence for such intensity-dependent shifts in human cochlear processing is limited. Here, we performed simultaneous multielectrode electrocochleography recordings along the human scala tympani to characterize how cochlear place coding varies as a function of stimulus intensity. In subjects with preserved cochlear mechanics, including individuals with auditory neuropathy spectrum disorder and a subject with normal hearing, we observed pronounced basalward shifts in best-frequency responses of up to ~158° (~one octave) at higher stimulus intensities, along with broader spatial activation. Leveraging the fixed, known distances between electrodes, we quantified cochlear traveling-wave velocity and demonstrated that, although intensity significantly altered spatial activation patterns, the traveling wave’s phase response remained stable across intensities. These results establish physiological evidence that human cochlear frequency representation changes systematically with sound intensity, providing insights into fundamental auditory processing.
GPT-4o mini: Non-social science research article
IL-33-induced ILC2 effector cytokine responses promote the expansion of red pulp macrophages
Irina R. Iten, Nikolaos D. Sidiropoulos, Lucas Onder, Aneta JoƄczy, Christoph S. N. Klose, Philippe Krebs, Katarzyna Mleczko-Sanecka, Burkhard Ludewig, Christoph Schneider, Manfred Kopf
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Red pulp macrophages (RPMs) remove senescent erythrocytes from the circulation and recycle their iron for erythropoiesis. The development of RPMs is guided by signals from the microenvironment, which promote expansion and tissue adaptation through the induction of transcription factors, including Spi-C and PPARÎł. Here, we show that infection with the nematode Nippostrongylus brasiliensis or treatment with IL-33 results in the accumulation of activated group 2 innate lymphocytes (ILC2s) in the spleen. ILC2s activated by IL-33 drive the expansion of RPMs by secretion of the effector cytokines IL-4/IL-13 and GM-CSF. By contrast, we show that IL-33 is dispensable for RPM development and function under homeostatic conditions. Overall, our work uncovers a previously unrecognized crosstalk between ILC2s and RPMs during type 2 immune responses.
GPT-4o mini: Non-social science research article
A multiplant transcriptomic atlas reveals conserved and lineage-specific defense architectures in response to Botrytis cinerea
Ritu Singh, Anna Jo Muhich, Cloe Tom, Celine Caseys, Daniel J. Kliebenstein
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Generalist pathogens pose a challenge to plant immunity by infecting diverse hosts while harboring extensive intraspecific genetic variation. Whether evolutionary distant plant lineages rely on a shared immune strategy or deploy distinct, lineage-specific defenses when confronted by these genetically variable members of the same pathogen species remains unresolved. Here, we employed a large-scale cotranscriptomic approach to map the immune landscape of 10 diverse eudicot species infected with 72 genetically distinct Botrytis cinerea isolates. We identified a limited core of evolutionarily conserved defense orthologs, along with a vast landscape of lineage-dependent regulatory genes. Host shared the broad physiological outcome such as metabolic reprogramming, cell wall modification, and suppression of growth-associated processes, yet the regulatory pathways associated with these responses were largely lineage-dependent. Crucially, this immune landscape is dynamically shaped by pathogen diversity. Nearly three-quarters of host transcriptional responses were isolate dependent, with the magnitude of transcriptional reprogramming defined by specific host–isolate combinations rather than a universal species-level response. Even host transcriptional responses correlated with shared virulence factors, including broadly expressed pathogens phytotoxins, were lineage specific. These findings suggest that plant immunity to generalist pathogens is built on conserved physiological outcomes that appear to occur by evolving lineage-dependent regulatory mechanisms. The causal relationship between these lineage-dependent components and the conserved outcomes require further mechanistic investigation. This distinct regulatory architecture creates an immune landscape heavily modulated by specific host–isolate combinations, highlighting the necessity of integrating pathogen diversity into models of plant defense evolution and resistance breeding.
GPT-4o mini: Non-social science research article
Conserved regulatory core and lineage-specific diversification of light–temperature integration in plants
Bruno Catarino, Fernando RodrĂ­guez-MarĂ­n, Cristina Úrbez, Christina Arvanitidou, Eva Álvarez, Federico Valverde, JosĂ© Manuel Franco-Zorrilla, Francisco Romero-Campero, Miguel A. BlĂĄzquez
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Plants rely on environmental information such as light and temperature to control growth and development. Integrating these cues improves developmental precision, yet it remains unclear how this capacity is distributed across major plant lineages and how it diversified during evolution. We investigated light–temperature integration across major green plant lineages with particular attention to the origin and early diversification of land plants. Using comparative phenotypic and transcriptomic analyses, we examined responses to combined light and temperature signals in a chlorophyte alga, a streptophyte alga, a bryophyte, and a flowering plant. Streptophytes showed synergistic developmental and transcriptional responses, whereas the chlorophyte representative displayed predominantly additive behavior, indicating that the streptophyte lineage underwent a significant elaboration in environmental signal integration. Functional genetic analyses revealed that phytochromes and the transcription factors PHYTOCHROME INTERACTING FACTOR and ELONGATED HYPOCOTYL 5 are conserved regulators of this integration in land plants. Cistromic analyses further showed that diversification of downstream transcriptional responses is associated with lineage-specific redistribution of conserved cis -regulatory elements. Together, these results support the view that the capacity for light–temperature integration was established early during streptophyte evolution and diversified through lineage-specific changes in gene regulatory landscapes.
GPT-4o mini: Non-social science research article
Comparing variable selection and model averaging methods for logistic regression
Nikola Sekulovski, FrantiĆĄek BartoĆĄ, Don van den Bergh, Giuseppe Arena, Henrik R. Godmann, Vipasha Goyal, Julius M. Pfadt, Maarten Marsman, Adrian E. Raftery
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Model uncertainty is a central challenge in statistical models for binary outcomes such as logistic regression, arising when it is unclear which predictors should be included in the model. Many methods have been proposed to address this issue for logistic regression, but their relative performance under realistic conditions remains poorly understood. We therefore conducted a preregistered, simulation-based comparison of 28 established methods for variable selection and inference under model uncertainty, using 11 empirical datasets spanning a range of sample sizes and numbers of predictors, in cases both with and without separation. We found that Bayesian model averaging (BMA) methods based on g –priors, particularly g = max ( n , p 2 ) , show the strongest overall performance when separation is absent. When separation occurs, penalized likelihood approaches, especially the LASSO, provide the most stable results, while BMA with the local empirical Bayes (EB-local) prior is competitive in both situations. These findings offer practical guidance for applied researchers on how to effectively address model uncertainty in logistic regression in modern empirical and machine learning research.
GPT-4o mini: Non-social science research article
Surrounding landscapes shape species persistence in fragmented forests
Juan Pablo RamĂ­rez-Delgado
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GPT-4o mini: Non-social science research article
Choice of cardioplegia influences metabolomics of human cardiac tissue
Sho Tanosaki, Yuan Zhang, Kenneth Bedi, Kenneth Margulies, James E. Cox, Zoltan Arany, E. Dale Abel
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Cardioplegia is often used prior to acquisition of human cardiac tissue to minimize warm ischemia time, which can severely confound studies of cardiac metabolism. However, there are several choices of cardioplegia solutions, and whether these solutions differentially impact tissue metabolism or metabolomic studies is not known. Here, we perform untargeted metabolomics, using both liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry, on a large cohort of hearts transplanted for cardiomyopathy or from gift-of-life donors, and who have received different cardioplegia solutions. We show that different cardioplegia solutions distinctly impact cardiac metabolism and tissue metabolomic studies. Notably, these differences are mild relative to those seen comparing failing to nonfailing hearts, and identification of cardioplegia components in mass spectra should enable rigorous interpretation of changes between conditions. These data demonstrate how cardioplegia solutions may influence cardiac metabolism in human heart samples and underscore the need to report specific details of cardioplegia solution use in studies of human cardiac metabolism.
GPT-4o mini: Non-social science research article
Sperm, egg, and embryo proteins critical for genetic adaptation of herring to low salinity in the Baltic Sea
Cheng Ma, Fahime Mohamadnejad Sangdehi, Mari Kawaguchi, Kaori Sano, Svenja V. Dannenberg, Mats E. Pettersson, Andreas Wallberg, Joshua L. Wort, Yumeng Yan, Sergei Moshkovskii, Florian Berg, Arild Folkvord, Christof Lenz, Henning Urlaub, U. Benjamin Kaupp, Shigeki Yasumasu, Leif Andersson
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How species genetically adapt to new environments is a central question in evolutionary biology. Here whole-genome sequencing combined with functional analysis is used to dissect how Atlantic herring, a marine fish, has adapted to the brackish Baltic Sea. Genes involved in reproduction and early development emerge as primary targets of natural selection, with key changes in a sperm-specific anion channel ( LRRC8C2 ), a zona pellucida protein ( ZPBA1 ), a cluster of three genes for fish transglutaminase ( FTG1-3 ), and a copy number expansion of a fish hatching enzyme gene ( HE1C ). The large diameter of LRRC8C2 homomers facilitates transport of ions and osmolytes, likely preventing swelling of sperm when spawning in low salinity. Altered ZPBA1 sequence together with modified FTG1-3 enzyme activity produces a harder egg envelope that prevents egg swelling in brackish waters, while the enhanced activity of the adapted HE1C enzyme enables larvae to digest this reinforced egg envelope during hatching. Baltic Sea herring populations reproducing in brackish water are fixed or nearly fixed for variant alleles at these four unlinked loci, each carrying multiple amino acid substitutions compared to the alleles prevalent in the Atlantic Ocean populations. The alleles at two of these loci ( FTG1-3, and HE1C ) have been introgressed from the sister species Pacific herring. These findings reveal concrete molecular mechanisms by which a marine species has adapted to a novel, low-salinity environment.
GPT-4o mini: Non-social science research article
Distinct activity in prefrontal projections promotes temporal control of action
Xin Ding, Matthew A. Weber, Trevor C. Butler, Alexandra S. Bova, Stephanie G. Guerrero, Christopher M. Hunter, Rachel C. Cole, Hannah R. Stutt, Madison S. McMurrin, Mackenzie M. Spicer, Mackenzie M. Conlon, Shane A. Heiney, Youngcho Kim, Jon M. Resch, Nandakumar S. Narayanan
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Prefrontal neurons exhibit diverse activity during cognitive functions such as working memory, attention, and timing; however, the importance of this heterogeneity is unclear. Our goal was to better understand the diversity of prefrontal activity through anatomical connectivity. We harnessed circuit-specific tools in mice to capture activity within prefrontal projections during interval timing, a highly translational cognitive process that requires working memory for temporal rules and attention to the passage of time to estimate a temporal interval of several seconds. We used neuronal recordings to capture prefrontal activity during interval timing, with major patterns characterized by monotonic time-dependent ramping over a temporal interval. We then leveraged retrograde viruses to interrogate prefrontal cortex (PFC) projections to the mediodorsal thalamus (PFC-MD) and the dorsomedial striatum (PFC-DMS). We report three main findings. First, circuit-specific fiber photometry revealed that PFC-MD and PFC-DMS activity encoded distinct temporal signals, with PFC-MD projections ramping down and PFC-DMS ramping up to interval timing response times. Second, circuit-specific inactivation revealed that suppressing PFC-DMS projections disrupted animals’ internal estimates of time. Third, circuit-specific single-nucleus RNA sequencing of projection-defined prefrontal neurons revealed distinct transcriptomic profiles of PFC-MD and PFC-DMS projections, with enrichment of cortical layer-associated genes as well as genes such as Cux2, Camk2n1, Htr4, and Foxp2 . These data suggest that differences in gene expression and connectivity distinguish prefrontal activity during interval timing. These findings advance our fundamental understanding of prefrontal function and dysfunction in human disease.
The electoral choice context and support for democratic norms
Kang Huang, Mitchell Lovett, Gretchen Helmke
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In this paper, we explore whether different choice environments affect voters’ willingness to put democracy over party and policy. Using a series of candidate choice experiments in which we manipulate not only candidate attributes, but also the number of races on the ballot, we find that when voters are able to vote in multiple races on a ballot they are substantially more likely to punish antidemocratic candidates than when they are only given the opportunity to cast one vote. We refer to this effect as “democratic balancing.” Substantively, our experiments show that the magnitude of the total punishment effect increases from 11% in single-race ballot settings to 17.9% in multirace ballot settings. Such effects remain largely consistent across different candidate platforms, separate waves of the survey, different types of norm violations, and are robust to different electoral race combinations and different information environments. Observational data from the 2022 U.S. midterm elections further corroborates our experimental findings. For researchers, our results underscore the importance of taking into account the institutional context in which voters make decisions. For citizens concerned with democratic backsliding, our results offer some reassurance: Moving to a more realistic electoral context in which multiple races appear on the ballot tempers the willingness of respondents to trade off democracy for their preferred policies and party.
Politics embodied: How politics shapes and is shaped by the bodily experience of emotions
Andrea Vik, Alejandro Galvez-Pol, Sohee Park, Manos Tsakiris
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Political emotions are widely acknowledged as key drivers of political participation and polarization. Yet while it is well established that political emotions matter, far less is known about how they are felt and represented in the body. Across a preregistered, nationally representative study ( N = 992), we introduce an embodied approach to political emotion using the validated emBODY-tool, which allows participants to map where in the body they experience sensations when feeling canonical emotions (e.g., anger) and their political counterparts (e.g., “political anger”). Specifically, we address three questions: 1) how political emotions are embodied and differ from their nonpolitical counterparts, 2) whether political dispositions influence how these political emotions are embodied, and 3) how their embodied experience interacts with political dispositions in explaining political attitudes and behavior. Pixelwise bodily sensation maps and aggregated “embodied impact” metrics show that political anger, anxiety, depression, disgust, and hope do not merely mirror their canonical forms, but take on distinct bodily patterns. Political ideology, but not political sophistication, modulates these bodily experiences, with Democrat-leaning participants reporting more intense sensations for negative political emotions, suggesting the presence of “ideological bodies.” Crucially, political participation is not explained by how intensely people report feeling emotions, but is instead closely linked to how strongly these emotions are embodied in the body. Together, our findings underscore the body’s central role in democratic engagement by showing how political contexts shape embodied emotional experience and how these embodied experiences shape politics and democracy.
Global and regional climate modes modulate armed conflict risk
Tyler E. Bagwell, Sylvia G. Dee, Xinyue Luo, Anna Stravato, Divya Saikumar, Frederi Viens, Bomi K. Lee, Diana Z. O’Brien, Justin S. Mankin
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Because of their impacts on droughts, famines, and floods, modes of climate variability can shape patterns of social instability. Yet the mechanisms linking climate variability to armed conflict remain contested, especially relative to the myriad sociopolitical and economic determinants of conflict. A key challenge is that most studies rely on coarse, state-level data and treat climatic teleconnections as invariant. As such, it is unknown whether there are distinct climate hazards that select for conflict risk; whether conflict scales with climate hazard exposure; and whether such associations exist for more regional forms of climate variability. Here we leverage empirical modeling using a high-resolution gridded dataset of armed conflicts and the natural experiment afforded by two major climate modes—the El Niño–Southern Oscillation (ENSO) and the Indian Ocean Dipole (IOD)—to clarify how systematic hydroclimatic anomalies influence conflict emergence. Our results reveal the following: First, conflict risk heightens during El Niño, but ENSO-associated risk does not scale linearly with teleconnection strength; and, evidence for threshold behavior varies with spatial aggregation. Second, El Niño-related increases in conflict risk arise through its dry teleconnections, with limited evidence for wet teleconnections. Finally, the more regionally confined IOD also influences conflict, with both positive and negative phases elevating risk in strongly teleconnected regions, namely the Horn of Africa and Southeast Asia. These results reveal that modes of climate variability can differentially shape conflict risk, offering insight into societies’ vulnerabilities to natural climate fluctuations and, by extension, anthropogenic climate change.
Robust associations of emotional intelligence with human flourishing: A second-order meta-analysis
Tyler J. Robinson, Ethan Zell
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Emotional intelligence (EI) is an umbrella term that has been used to describe i) the ability to reason accurately about emotions and use emotions to augment thought processes, ii) a constellation of traits reflecting social and emotional functioning, or iii) a mix of relevant abilities and traits. Research on EI has expanded considerably since the 1990s, resulting in dozens of meta-analyses on its relationship with various indices of flourishing (e.g., psychological well-being, adaptive traits, and adaptive functioning in the classroom and workplace). In this second-order meta-analysis, we synthesized data from 62 meta-analyses including over 3,000 studies and 1 million participants. Our findings suggest a robust association between human flourishing and an overall index of EI, r = 0.28, 95% CI [0.25, 0.31], as well as separate indices of ability, trait, and mixed EI. Favorable EI associations were found across several outcome categories (e.g., cognitive abilities, psychological adjustment, mental health, workplace outcomes) as well as age and cultural groups. Nevertheless, effect sizes were most pronounced for self-report EI measures, especially when flourishing was likewise measured subjectively. Further, there was substantial heterogeneity of EI-flourishing effect sizes. We recommend that future research identify additional moderators of EI-flourishing associations. We also discuss ongoing debates about the conceptualization of EI and suggest that future work consider alternative EI schemes.
Hard and soft power in immigration enforcement
Emily Ryo
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Social cognition and interpersonal violence
Megan Kang, Kathryn Edin, Jens Ludwig, Timothy Nelson, Sendhil Mullainathan
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Why do some people resort to violence while others in similar circumstances do not? Drawing on 99 in-depth interviews with men from high-violence Chicago neighborhoods who participated in a community violence intervention, we examine how past exposure to violence shapes the social cognitions that influence future involvement in violence—through the schemas and scripts people use to interpret social situations and guide behavior. We identify three specific social cognitions that respondents associated with violence: misconstruing ambiguous cues as threats, defaulting to a narrow set of behavioral responses, and attributing violent behavior to fixed personal traits rather than situational factors. Respondents reported that participation in the program’s cognitive behavioral component shifted these social cognitions in ways they associated with reduced violence involvement. The consistency of these self-reports combined with the program’s experimental impacts suggest the hypothesis that these specific social cognitions could play an important role in violence and may be modifiable through intervention.
A transparent universal credit system to incentivize peer review
Angela Moles, Russell Bonduriansky, Stephen Bonser, Daniel Falster, Shinichi Nakagawa, Nigel Andrew, Malgorzata Lagisz
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Reply to Zhang: Causal identification, social networks, and biological aging
Byungkyu Lee, Gabriele Ciciurkaite, Siyun Peng, Colter Mitchell, Brea L. Perry
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A multinational megastudy of the effects of gratitude practices on subjective well-being
Nicholas A. Coles, Annabel V. Dang, Shigehiro Oishi, Abigail Adade, Aderonke A. Akintola, Beatriz B. de Souza, Biljana Gjoneska, Christine R. Harris, Dev Kesarwani, Dinara Pisareva, Eugene Y. J. Tee, Goo Lyann, Gul Gunaydin, Gyuri Lee, Hongbo Yu, Hyewon Choi, JohnBosco Chika Chukwuorji, Karoline Klitgaard, Maciej Behnke, Magnus Bergquist, Marit Gunda Gundersen Engeset, Nattasuda Taephant, Nikita Durnev, Ognen Spasovski, Paulo Sergio Boggio, Ram Manohar Singh, Robin Irmel, Sergio Barbosa, Shangcheng Zhao, Sinem Acar-Burkay, Stefan Pfattheicher, Tatsunori Ishii, Victor Goh Weng Yew, Vivian Dzokoto, Zeynep Soyalan, Michael E. McCullough
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Scholars have observed people from a variety of cultures using a variety of gratitude-related practices to change their emotions, outlooks, and social relationships. Across 34 countries purposively sampled to cover a broad set of cross-cultural differences (total N = 10,696), we experimentally tested the effects of 6 brief gratitude interventions on subjective moods, life outlooks, and social evaluations. Compared to 3 control tasks, gratitude practices immediately produced theorized improvements in positive affect ( d = 0.37), negative affect ( d = −0.22), optimism ( d = 0.24), life satisfaction ( d = 0.12), indebtedness ( d = 0.15), and envy ( d = −0.16). Notably, these effects varied across different gratitude practices (0.00 < τ practice < 0.08) and countries (0.10 < τ country < 0.19). For instance, based on existing evidence, stakeholders can expect gratitude interventions deployed in a randomly selected country to improve positive affect—but not our other measured outcomes. To guide future inquiry into why this might be the case, we provide exploratory Bayesian estimates of the importance of 12 cross-cultural differences.
Discovering regularity and mechanisms of word sense acquisition in childhood
Jiangtian Li, Blair C. Armstrong, Yang Xu
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How does language use inform the emergence of word meanings in early life? Prior work in developmental psychology and the cognitive sciences typically focuses on studying word acquisition in children without specifying how different senses within a word emerge through time. To shed light on word sense acquisition, we propose a framework grounded in state-of-the-art computational methodologies of contextual word embedding to characterize how different senses of a word unfold as children acquire their lexicon. Our framework identifies word senses automatically by forming semantic clusters through natural language use, and analyzes 1,270 words from approximately 4 million utterances produced by children (19 to 144 mo) and their caretakers. The psychological validity of these senses was assessed based on a combination of dictionaries, human judgment of semantic similarity, and evaluation from a large language model. We then tested three hypotheses motivated by existing work on word sense emergence in language evolution. First, concrete senses of a word tend to emerge earlier than more abstract senses in child language. Second, word senses grow incrementally in semantic space across development. Third, algorithms of semantic chaining—how words spawn new senses by extending from existing senses—recapitulate the order of word senses in development. We find support for all three hypotheses. Our work suggests that the development of word meaning in language acquisition resembles that in language evolution and offers a converging view on the cognitive principles and mechanisms across timescales in the ontogeny and phylogeny of word sense emergence.
Observational epidemiological studies can mitigate genetic confounding with a genetic relatedness matrix
Roshni A. Patel, Joshua G. Schraiber, Matt Pennell, Michael D. Edge
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Observational studies are commonly used in psychology and epidemiology to identify risk factors correlated with health outcomes. However, these studies are vulnerable to confounding when shared genetic variation influences both the putative risk factor and outcome. Researchers have often controlled for this type of genetic confounding using polygenic scores, but these scores are noisy and biased estimators of a trait’s genetic component. While some newer methods offer significant improvements over polygenic scores, they still rely on genome-wide association studies (GWAS) summary statistics, which may be untenable for certain datasets. Here, we develop an analogous method that leverages a genetic relatedness matrix to control genetic confounding when testing for nongenetic risk factors. In simulations, we find that our method outperforms existing approaches, particularly at sample sizes that are large by the standards of much human research but smaller than datasets often used in human genetics. We also demonstrate that existing methods are susceptible to poor GWAS portability, whereas our method is inherently robust to such concerns, conditional on the availability of individual genotype data. Finally, we apply our method to the UK Biobank to reanalyze social risk factors for health outcomes in previously understudied cohorts.
Can privacy technologies replace cookies? Ad revenue in a field experiment
Zhengrong Gu, Garrett A. Johnson, Shunto J. Kobayashi
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Digital advertising finances much of the open web, yet relies on tracking technologies that regulators increasingly seek to restrict. In response, industry has developed privacy-enhancing technologies intended to preserve advertising performance while limiting data collection, but their economic effects remain largely untested. We study this question using an open, industry-wide field experiment jointly overseen by Google and the UK Competition and Markets Authority, in which Chrome users were randomly assigned to browse with third-party cookies enabled, with cookies disabled, or with Google’s Privacy Sandbox replacing cookies. Combining this experimental variation with proprietary data from a major ad management firm, we analyze more than 200 million ad impressions across over 5,000 publishers worldwide. Removing third-party cookies reduces publisher advertising revenue by 29.1%. Privacy Sandbox recovers only 4.2% of this lost revenue; this estimate reflects observed adoption and performance during the study period and may reflect modest industry adoption. Privacy-preserving auctions also increase ad latency, reducing impression delivery and further limiting revenue performance. Together, these findings provide a large-scale experimental benchmark for evaluating privacy-preserving reforms and demonstrate the difficulty of reconciling privacy protection with the economics of online content provision.
Do negative social ties accelerate aging in adults, or does aging erode social ties?
Quan Zhang
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Science

GPT-4o mini: Non-social science research article
Climate-induced range shifts support local plant diversity but don’t reduce extinction risk
Junna Wang, Brunno F. Oliveira, Frances C. Moore, Daniel J. Kozar, Yongshuo Fu, Xiaoli Dong
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INTRODUCTION Anthropogenic climate change is reshaping where plants can live. As temperature and precipitation patterns shift, many species are moving to stay within suitable environmental conditions. Predicting how these range shifts will affect future biodiversity requires knowing both where suitable habitats will occur and whether species can reach them. The latter is challenging because dispersal abilities differ widely among species and depend on landscape structure, anthropogenic barriers, and climatic conditions. Large-scale biodiversity forecasts therefore often rely on overly simple assumptions—such as no dispersal, unlimited dispersal, or identical movement rates for all species—thus adding major uncertainty to projections and conservation planning. RATIONALE We used the largest global database of observed plant range shifts (BioShifts; 14,488 records across 6579 plant species) to build models that predict species-specific range shift velocities. Combining 6.8 million plant occurrence records, an ensemble of two top-performing habitat models, and climate projections from 10 global circulation models, we mapped current and future suitable habitats—areas with favorable climate, soil, and land use—at 8 × 8 km resolution for each species. Our analysis covers 18% of known vascular plant species under four greenhouse-gas emissions scenarios for 2081 to 2100. We then overlaid the projected future suitable habitats with species-specific range shift velocities to determine where each species is likely to persist or expand by the end of this century. From these results, we estimated global extinction risks, changes in local species richness, and temporal species turnover in community composition. RESULTS Overall, 7 to 16% of modeled plant species are projected to lose >90% of their range across emissions scenarios, placing them at high risk of extinction. Most of these losses (70 to 80%) stem from suitable habitats disappearing as a result of climate change, rather than from dispersal limitations, indicating that climate-induced habitat loss, rather than an inability to keep pace with changing climate, is the primary threat. Although range shifts are unlikely to prevent many global extinctions, they will strongly reshape local species composition. Plant movements into newly suitable habitats are expected to increase local species richness across 28% of Earth’s land surface, maintain latitudinally averaged species richness in the tropics and subtropics (35°S to 35°N), and generate substantial species turnover in mid-latitudes (30° to 50° in both hemispheres). By contrast, in regions north of 50°N, warming is so rapid that most plants cannot keep pace, leading to widespread local extirpations and sharp declines in species richness. CONCLUSION Range shifts can help sustain local species richness but are unlikely to provide much relief from global extinctions. To reduce extinction risks, identifying and protecting climate change refugia to safeguard biodiversity, and expanding ex situ conservation efforts, such as global seed bank and botanic garden networks, may be more effective than facilitating migrations. At the same time, conservation strategies should anticipate changing community compositions and ecosystem functioning as new species arrive and ecosystems reorganize. In high-latitude regions where dispersal lags considerably behind the rapid warming, improving habitat connectivity, reducing human-made barriers, and where appropriate, assisting species movement could help maintain local species richness, ecosystem productivity, carbon sequestration, and ecosystem stability. Future climate-driven plant range shifts and consequences for global species diversity redistribution. [Credits: icons in this figure are from https://www.flaticon.com/ ]
GPT-4o mini: Non-social science research article
Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design
Ashwin N. Skelly, Harry B. Gristick, Hui Li, Edem Gavor, Andrew J. Connell, Edward F. Kreider, Lorie Marchitto, Michael P. Hogarty, Maddy L. Newby, Joel D. Allen, Weimin Liu, Anthony P. West, Kasirajan Ayyanathan, Mary S. Campion, Kaitlyn Winters, Colette G. Gordon, Rebecca A. Osbaldeston, Macy J. Akeley, Emily Lewis, Yingying Li, Ajay Singh, Kendra Cruickshank, Younghoon Park, Chengyan Zhao, Xuduo Li, Khaled Amereh, Elizabeth Van Itallie, John W. Carey, Amie Albertus, Andrew T. DeLaitsch, Jennifer R. Keeffe, Melinda G. Lituchy, Agnes A. Walsh, Daniel J. Morris, Rumi Habib, Frederic Bibollet-Ruche, Nitesh Mishra, Gabriel Avillion, Nicholas S. Koranda, Samantha J. Plante, Christian L. Martella, Jinery Lora, Eric J. D. Wang, Mark G. Lewis, Malcolm A. Martin, Michel C. Nussenzweig, Michael S. Seaman, Darrell J. Irvine, Kevin J. Wiehe, Barton F. Haynes, Kshitij Wagh, Bette Korber, Raiees Andrabi, Max Crispin, Drew Weissman, Pamela J. Bjorkman, Beatrice H. Hahn, George M. Shaw
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A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.
GPT-4o mini: Non-social science research article
Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration
Katie E. Copley, Jocelyn C. Mauna, Helen L. Danielson, Qizan Chen, Busra Ozguney, Marilyn Ngo, Longxin Xie, Ashleigh Smirnov, Matt Davis, Leland Mayne, Miriam Linsenmeier, Jack D. Rubien, Cristian A. Bergmann, Bede Portz, Bo Lim Lee, Hana M. Odeh, Longsheng Lai, Yi-Wei Chang, Martina Hallegger, Jernej Ule, Piera Pasinelli, Yan Poon, Jeetain Mittal, Nicolas L. Fawzi, Ben E. Black, Christopher J. Donnelly, Brigid K. Jensen, James Shorter
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Aberrant aggregation of the prion-like RNA binding protein TDP-43 drives several fatal neurodegenerative proteinopathies, including amyotrophic lateral sclerosis (ALS). In this work, we define how short, specific RNAs solubilize TDP-43. These short RNAs engage and stabilize the TDP-43 RNA recognition motifs, which allosterically destabilizes a conserved helical region in the prion-like domain, thereby promoting aggregation-resistant conformers. Sequence-space mining identified short RNA chaperones with enhanced activity against TDP-43 and disease-linked variants. Enhanced short RNA chaperones mitigated aberrant TDP-43 phenotypes in optogenetic models and in ALS patient–derived and control motor neurons. In mice with cytoplasmic TDP-43 aggregation and motor neuron loss, an enhanced short RNA chaperone reduced pathological aggregation, restored TDP-43 function, and conferred neuroprotection. These results define a mechanistic and therapeutic framework for RNA-based strategies to counter TDP-43 proteinopathies.
GPT-4o mini: Non-social science research article
High risk of extinction across the flowering plant tree of life
Félix Forest, Ruth Brown, Sven Buerki, Jonathan F. Colville, Justin Moat, Eimear Nic Lughadha, Nisha R. Owen, Domitilla C. Raimondo, Malin Rivers, James Rosindell, Barnaby E. Walker, Steven P. Bachman, Sebastian Pipins, Rikki Gumbs, Matilda J. M. Brown
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Global biodiversity policies recognize the necessity to preserve evolutionary lineages, as their diversity underpins current and future benefits to people and the future of life on Earth. Plants are largely absent from global biodiversity assessments, resulting in a taxonomic imbalance that has undermined their conservation for decades. We present a tree of life and extinction risk estimates for all species of flowering plants (angiosperms), representing a global assessment of their threatened evolutionary history. We estimate that 21.2% of angiosperm evolutionary history is at risk of extinction and identify 9945 priority species that disproportionately account for total threatened evolutionary history. These prioritizations serve to redress imbalances between plants and animals, monitor conservation effectiveness, and optimize resource allocation in the face of increasing human pressures on biodiversity.
GPT-4o mini: Non-social science research article
Realization of a spin glass in a two-dimensional van der Waals material
Banabir Pal, Ajesh Kollakuzhiyil Gopi, Yicheng Guan, Ruifeng Wang, Anirban Chakraborty, Kajal Tiwari, Anagha Mathew, Abhay K. Srivastava, Wenjie Zhang, Ilya Kostanovski, Binoy K. Hazra, Holger Meyerheim, Stuart S. P. Parkin
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Recent advances in van der Waals materials have sparked renewed interest in the impact of dimensionality on magnetic phase transitions. Although ordered magnetic phases have been demonstrated to survive in the two-dimensional (2D) limit, the quest for a spin glass with quenched magnetic disorder in lower dimensions has proven elusive. Here, we provide evidence of a spin glass emerging from randomly distributed Fe atoms in Fe 3 GeTe 2 (FGT). ac magnetic susceptibility displays a strong frequency dependence indicative of slow spin dynamics. Additional distinctive phenomena, including aging, chaos, and memory effects, further substantiate the existence of a glassy state. Notably, we found that this state persists even in single-cell–thick FGT, thereby confirming the existence of a 2D spin glass.
GPT-4o mini: Non-social science research article
Dynamic segmentation of the Sagaing fault
Mingqi Liu, Binhao Wang, Sezim E. Guvercin, Zhen Li, Teng Wang, Chuanjin Liu, Lingyun Ji, Sylvain Barbot
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The structurally simple Sagaing fault, which ruptured during the 2025 moment magnitude 7.7 Mandalay earthquake, exhibits clear dynamic segmentation despite lacking major geometric complexities. Using physics-based seismic cycle simulations, we tested the hypothesis that dynamic segmentation on the Sagaing fault is influenced by a northward increase in long-term slip rates from 18 to 28 millimeter/year. Models incorporating geodetically constrained long-term slip rates reproduced the rupture extent of historical earthquakes and the geodetically inferred slip distribution of the 2025 mainshock. Slip rate contrasts of 10 to 20% between adjacent segments generate sufficient heterogeneous stress accumulation to initiate dynamic segmentation, regulating earthquake recurrence patterns and maximum magnitudes across the fault system. These results highlight the value of integrating geodetic, geological, and seismological observations to improve seismic hazard assessment.
GPT-4o mini: Non-social science research article
Wildfire damages and the cost-effective role of forest fuel treatments
Frederik Strabo, Calvin Bryan, Matthew N. Reimer
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Wildfires are among the most pressing environmental challenges of the 21st century, intensified by the accumulation of forest fuels after a century of fire suppression policies. Although fuel-reduction treatments (“fuel treatments”) are a primary tool for reducing wildfire risk, they remain underutilized, partly owing to limited evidence of their economic value. In this study, we integrated high-resolution data on wildfires, fuel treatments, suppression effort, and damages across the Western United States to assess their cost-effectiveness. Using a quasi-experimental design, we found that fuel treatments reduced wildfire spread and severity, avoiding an estimated $2.8 billion in damages by limiting structure loss, cutting carbon dioxide emissions, and lowering fine particulate matter (PM 2.5 ) exposure. Each dollar invested yielded $3.73 in expected benefits. Our findings demonstrate the value of fuel treatment investments and offer guidance for maximizing their effectiveness.
GPT-4o mini: Non-social science research article
A 481-meter-high landslide-tsunami in a cruise ship–frequented Alaska fjord
Dan H. Shugar, Katherine R. Barnhart, Mira Berdahl, Jacqueline Caplan-Auerbach, Göran Ekström, Aram Fathian, Marten Geertsema, Stephen P. Hicks, Bretwood Higman, Erin K. Jensen, Ezgi Karasözen, Patrick Lynett, John Lyons, Thomas Monahan, Gerard Roe, Kristian Svennevig, Liam Toney, Maximillian Van Wyk de Vries, Michael E. West
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Early in the morning of 10 August 2025, a >64 × 10 6 m 3 landslide struck Tracy Arm fjord in Alaska. The landslide was preconditioned by glacial retreat caused by climate change. The resulting 481 m runup megatsunami followed an initial 100-m-high breaking wave traveling >70 m s −1 . The landslide was preceded by several days of microseismicity, which increased in rate and magnitude until ~1 hour before failure. The landslide produced globally observed long-period seismic waves equivalent in size to a M5.4 earthquake. A long-period (~66 s) global seismic signal, produced by a landslide-induced seiche trapped within the fjord, persisted for up to 36 hours, the second time a days-long seiche has been thus observed. With fjord regions increasingly visited by cruise ships, and climate change making similar events more likely, this unanticipated, near-miss event highlights the growing risk from landslides and tsunamis in coastal environments.
GPT-4o mini: Non-social science research article
Lessons in resistance from Tim Snyder
H. Holden Thorp
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Federal grant cancellations, restrictions on immigration for foreign scientists, and attempts to cut the budgets of science funding agencies by 60%—the past 18 months have been tumultuous for American science. Even after Congress restored the budgets, following the successful lobbying by leaders of the scientific community, universities are still hampered by the slow dispersal of the appropriated funds. Meanwhile, the continual attacks on science and the uncertainty brought on by the Trump administration have put many scientists in a state of fear and anxiety about the future of the American scientific enterprise, or at the very least, whiplash over the dizzying pace of defeats and victories. Equally nerve-wracking are the differing perspectives across the scientific community on the best course of action.
GPT-4o mini: Non-social science research article
TranscriptFormer: A generative cell atlas across 1.5 billion years of evolution
James D. Pearce, Sara E. Simmonds, Gita Mahmoudabadi, Lakshmi Krishnan, Giovanni Palla, Ana-Maria Istrate, Alexander Tarashansky, Benjamin Nelson, Omar Valenzuela, Donghui Li, Stephen R. Quake, Theofanis Karaletsos
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Single-cell transcriptomics is revolutionizing our understanding of cellular diversity, yet comparing transcriptional programs across the tree of life remains challenging. We developed TranscriptFormer, a family of generative foundation models trained on up to 112 million cells spanning 1.53 billion years of evolution across 12 species. We demonstrate state-of-the-art performance on cell type classification, even for species separated over 685 million years of evolution, and zero-shot disease state identification in human cells. Developmental trajectories, phylogenetic relationships and cellular hierarchies emerge naturally in TranscriptFormer’s representations without any explicit training on these annotations. This work establishes a powerful framework for quantitative single-cell analysis and comparative cellular biology, thus demonstrating that universal principles of cellular organization can be learned and predicted across the tree of life.
GPT-4o mini: Non-social science research article
Knowledge gaps for neuromorphic ionic computing
Narayana R. Aluru, Seth B. Darling, Jeffrey W. Elam, Oleg Gang, Alberto Salleo, Zuzanna Siwy, A. Alec Talin, Aleksandr Noy
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Neuromorphic ionic computing is inspired by the brain’s use of ions for ultralow-energy computation—its massive parallelism, adaptability, and learning capabilities. This emerging paradigm can overcome limitations of conventional silicon-based computing by enabling colocated memory and processing, multicarrier information streams, and massive three-dimensional connectivity. However, substantial knowledge gaps remain in understanding and engineering ionic transport, energy dissipation, materials design, and scalable device architectures. This Review explores these critical challenges across seven key domains, highlighting the need for new theoretical approaches, materials, device concepts, and fabrication strategies. We argue that advancing ionic neuromorphic systems requires an interdisciplinary approach, integrating insights from biology and neuroscience, nanofluidics, materials science, and systems engineering to enable a new class of energy-efficient, robust, and reconfigurable computing technologies.
GPT-4o mini: Non-social science research article
Competitive reactivity drives size- and composition-focusing in multimetallic nanocrystals
Jeesoo Yoon, Jinwon Oh, Dongjun Kim, Pin-Hung Chung, NaHyeon Hong, Jake Heinlein, Carlos Lizandara-Pueyo, Roel S. SĂĄnchez-Carrera, Jungwon Park, Hee-Tae Jung, Matteo Cargnello
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Multimetallic nanocrystals (NCs) offer distinctive properties driven by synergistic interactions among their constituent metals. Although colloidal chemistry enables control over size and composition, competing reactivities among metal precursors often complicate the synthesis of complex NCs. In this study, we systematically elucidate how the competitive reactivity of different metals in solution can be exploited to synthesize uniform pentametallic NCs despite numerous competing pathways. Mechanistic studies reveal heterodimers as key intermediates that mediate further metal incorporation through selective nucleation. Notably, the addition of more metals suppresses homogeneous nucleation, resulting in size- and composition-focusing to produce complex NCs with distinct multimetallic domains. When supported, these NCs show excellent thermal stability and catalytic activity for ammonia decomposition, offering a promising strategy for designing complex nanomaterials for energy-related applications.
GPT-4o mini: Non-social science research article
Biocatalytic cascades enable manufacture of the macrocyclic peptide enlicitide
Artis Klapars, Anna Fryszkowska, Stephanie Galanie, Omer Ad, Ellen Y. Aguilera, Nnamdi Akporji, Chihui An, Stephanus Axnanda, Tewoderos M. Ayele, Richard S. Ayikpoe, Rodell C. Barrientos, Matthew R. Bauerle, Marc R. Becker, Kevin M. Belyk, Lisa Bereznitski, Jackson K. B. Cahn, Karla Camacho Soto, Louis-Charles Campeau, Kevin R. Campos, Anagha Chandra, Hsieh Yao Darryl Chang, Mengbin Chen, Zhiwei Chen, Wai Ling Cheung-Lee, Cheol K. Chung, Stephanie W. Chun, Sarah S. Co, Ryan D. Cohen, Stephen M. Dalby, Guilherme Dal Poggetto, Truc Do, Spencer D. Dreher, Riki J. Drout, Noah P. Dunham, Yi Fan, Ryan M. Flessner, Jacob H. Forstater, Scott P. France, Janaka C. Gamekkanda, Donald R. Gauthier, Agnieszka A. Gil, Jacob W. Greenwood, Noel Ha, Holst M. Halsey, Xinxin Han, Michael Hartmann, Clara Hartmanshenn, Yu He, Edgar Hernandez, Kaori Hiraga, Hsing-I Ho, Cynthia M. Hong, Alan Hruza, Hang Hu, Kari Hullen, Alan M. Hyde, Tetsuji Itoh, Chey M. Jones, Woo-Ok Jung, Kanan Kanuga, James Levi Knippel, Joshua N. Kolev, Jongrock Kong, Birgit Kosjek, Sara Koynov, Michael H. Kress, Bharath Krishnamurthi, Jeffrey T. Kuethe, Thomas T. Kwok, Alfred Y. Lee, Joshua Lee, Qiuhan Li, Shasha Li, Jing Liao, Wenjun Liu, Gurpreet Longia, Emma Madrigal, Peter E. Maligres, Kevin M. Maloney, Erin L. McCarthy, John A. McIntosh, Samaneh Mesbahi-Vasey, Margaret Miller, Mansi Modi, Jeffrey C. Moore, Debopreeti Mukherjee, Grant S. Murphy, Jennifer Victoriano Obligacion, Weilan Pan, Julia Parzecki, Anisha Patel, Teng Peng, Byron K. Peters, Tiffany Piou, Carlos A. Pons Siepermann, Christopher K. Prier, Akasha K. Purohit, Yangzhong Qin, Erik L. Regalado, Mikhail Reibarkh, Nelo R. Rivera, Sandra A. Robaire, Lee Robison, Syamantak Roy, Rebecca T. Ruck, Katie A. Rykaczewski, Christopher H. Schuster, Erica L. Schwalm, Andrew N. Singh, Eric Sirota, Alexandra C. Sun, Weijuan Tang, David A. Thaisrivongs, Nimisha Thakur, Weidong Tong, Van Truong, Ryan Tsoi, Qiang Tu, Ben W. H. Turnbull, Ophelia Ukaegbu, David A. Vargas, Juan E. Velasquez, Deeptak Verma, Heather Wang, Tao Wang, Xiao Wang, Ying Wang, Zhixun Wang, Matthew S. Winston, Chunyu Wu, Brian M. Wyvratt, Kai-Jiong Xiao, Yingju Xu, Jia-Xuan Yan, Hao Yang, Victoria Zhang, Yongqian Zhang, Michelle Zheng, Wendy Zhong
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Historically, many compelling therapeutic targets have been accessible only by injectable biologic drugs. Macrocyclic peptides, such as the proprotein convertase subtilisin/kexin type 9 inhibitor enlicitide for the treatment of atherosclerotic cardiovascular disease, are beginning to unlock these targets to orally administered therapies to enable broader patient access. We report the convergent biocatalytic assembly of enlicitide from simple building blocks enabled by a suite of engineered enzymes to catalyze selective peptide fragment formation, coupling, and macrocyclization in a protecting group–free manner. Together with efficient crystallizations that obviate the need for chromatography, this approach reduces the number of steps by greater than half compared with prior state-of-the-art methods, addressing long-standing synthetic challenges and offering a sustainable blueprint for the scalable development of complex peptide therapeutics.
GPT-4o mini: Non-social science research article
Ferrimagnetism of ultracold fermions in a multiband Hubbard system
Martin Lebrat, Anant Kale, Lev Haldar Kendrick, Muqing Xu, Youqi Gang, Alexander Nikolaenko, Pietro M. Bonetti, Subir Sachdev, Markus Greiner
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Strongly correlated materials feature multiple electronic orbitals, which are crucial to accurately understanding their many-body properties. In such multiband models, quantum interference can lead to flat energy bands with large degeneracy that gives rise to itinerant magnetic phases. We report on signatures of a ferrimagnetic state realized in a Lieb lattice with ultracold fermions, characterized by antialigned magnetic moments with antiferromagnetic correlations, and concomitant with a finite spin polarization. The signatures remain robust when increasing repulsive interactions from the weakly interacting to the Heisenberg regime and emerge when continuously tuning the lattice unit cell from a square to a Lieb geometry. Our flexible approach paves the way toward exploring exotic phases, such as quantum spin liquids in kagome lattices and heavy fermion behavior in Kondo models.
GPT-4o mini: Non-social science research article
Tuft dendrites in frontal motor cortex enable flexible learning
Eduardo Maristany de las Casas, Kris Killmann, Moritz DrĂŒke, Lukas MĂŒnster, Christian Ebner, Robert Sachdev, Dieter Jaeger, Matthew E. Larkum
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Flexible learning relies on integrating sensory and contextual information to adjust behavioral output in different environments. The anterolateral motor cortex (ALM) is a frontal area critical for action selection in rodents. We found that inputs critical to decision-making converge on the apical tuft dendrites of layer 5b pyramidal neurons in ALM. We therefore investigated the role of these dendrites in a rule-switching paradigm. Activation of dendrite-inhibiting layer 1 interneurons impaired relearning, without affecting previously learned behavior. This inhibition profoundly suppressed global calcium activity in dendritic shafts but not local transients in spines, while additionally reducing burst firing. Moreover, excitatory synaptic inputs to tuft dendrites exhibited rule-dependent clustering. We conclude that dendritic calcium signaling is a key computational component of flexible learning.
GPT-4o mini: Non-social science research article
Alkylidene functionalization produces highly recyclable and scalable polyhydroxyalkanoates
Li Zhou, James H. May, Ravikumar R. Gowda, Levi J. Hamernik, Jacob K. Kenny, Lili Wang, Christopher D. Stubbs, Ethan C. Quinn, Jason S. DesVeaux, Katrina M. Knauer, Gregg T. Beckham, Eugene Y.-X. Chen
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Recyclable polymers that can be produced at scale and readily tuned within the same polymer framework for specific properties are critical to achieving a circular materials economy. To this end, synthetic poly(3-hydroxyalkanoate)s (PHAs) have emerged as high-performance, chemically recyclable variants of biological PHAs, but their difficult monomer syntheses and suboptimal recycling efficiencies pose challenges for large-scale deployment. In this study, we investigated a ÎČ-isopropylidene PHA, i -PHA, for which the lactone monomer can be synthesized by existing industrial methods from biomass-derived isobutyric acid. The alkylidene substituent prevents decarboxylative degradation typically observed during PHA depolymerization, enabling near-quantitative chemical recycling to monomer. Controlled hydrogenation of the ÎČ-isopropylidene side group produces PHAs with diverse performance metrics that are competitive with a range of commodity polymers, spanning strong fibers to ductile thermoplastics to superglue epoxy resins.
GPT-4o mini: Non-social science research article
Intermetallic nanoassemblies potentiate systemic STING activation
Xingwu Zhou, Xiang Ling, Xiaoqi Sun, Ziye Wan, Tobias Dwyer, Timothy C. Moore, Quguang Li, Hannah E. Dobson, Qi Wu, Xiangbo Kong, Fang Xie, Xinran An, Jingyao Gan, Kaikai Wang, Young Seok Cho, Wang Gong, Katherine Dong, Jie Zhang, Mariko Takahashi, Cheng Xu, Swetha Kodamasimham, Jie Xu, Vilma Yuzbasiyan-Gurkan, Steven B. Chinn, Anna Schwendeman, Sharon C. Glotzer, Yu Leo Lei, James J. Moon
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Natural systems use metal ions to form ordered structures that regulate biological processes, inspiring the rational design of nanotherapeutics. The cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes (cGAS-STING) pathway drives antitumor immunity but has been difficult to activate systemically owing to poor pharmacology and toxicity. Here, we report CRYSTAL, a structurally ordered intermetallic nanoparticle for potent systemic STING activation. CRYSTAL self-assembles from manganese ions intercalated with cyclic dinucleotides, enabling precise structural control. At an ultralow intravenous dose (0.003 milligrams per kilogram), CRYSTAL activated STING in mice, dogs, and nonhuman primates without cytokine release syndrome. CRYSTAL induced robust tumor regression in advanced murine and rabbit models, remodeled immunosuppressive environments, and promoted host STING–dependent CD8 + T cell priming. CRYSTAL activated interferon responses in human head and neck squamous cell carcinoma biopsies, underscoring its translational potential for cancer immunotherapy.
GPT-4o mini: Non-social science research article
A molecule with half-Möbius topology
Igor Rončević, Fabian Paschke, Yueze Gao, Leonard-Alexander Lieske, Lene A. Gödde, Stefano Barison, Samuele Piccinelli, Alberto Baiardi, Ivano Tavernelli, Jascha Repp, Florian Albrecht, Harry L. Anderson, Leo Gross
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Stereoisomers of C 13 Cl 2 exhibiting helical orbitals around a ring of carbon atoms were synthesized by atom manipulation on NaCl surfaces. We resolved the enantiomeric geometries of the singlet states by atomic force microscopy and mapped their helical orbital densities by scanning tunneling microscopy. A π-orbital basis of the helical, nonplanar singlets that twists by 90° in one circulation is consistent with a half-Möbius topology. In such a topology, the π-orbital basis changes sign with respect to two circumnavigations and is periodic with respect to four circumnavigations. A quasiparticle on a ring with this boundary condition could be interpreted as carrying a Berry phase of π/2. We demonstrate reversible switching of the topology between the two singlets of oppositely threaded half-Möbius topology and the planar, topologically trivial triplet state. Multireference calculations, including large-scale, sample-based ab initio calculations executed on quantum hardware, revealed that the switching is associated with a helical pseudo–Jahn-Teller effect.
GPT-4o mini: Non-social science research article
Human DHX29 detects nonoptimal codon usage to regulate mRNA stability
Fabian Hia, Yitong Wu, Masanori Yoshinaga, Sakurako Goto-Ito, Wakana Iwasaki, Koshi Imami, Hirotaka Toh, Peixun Han, Ting Cai, Takayuki Ohira, Akira Fukao, Daron M. Standley, Yuichi Shichino, Masaki Takegawa, Toshinobu Fujiwara, Tsutomu Suzuki, Shintaro Iwasaki, Michael C. Bassik, Takuhiro Ito, Osamu Takeuchi
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Synonymous codon usage controls global gene expression in both prokaryotic and eukaryotic species. Nonoptimal codons are known to induce messenger RNA (mRNA) decay; however, the underlying molecular mechanism remains poorly understood in human cells. Through genome-wide CRISPR screening, we identified the RNA binding protein DHX29 as a critical regulator of codon-dependent gene expression. Cryo–electron microscopy and selective ribosome profiling demonstrated that DHX29 directly interacts with the A-site entrance of the translating 80 S ribosome, the binding site for the eEF1A‱GTP‱aminoacyl-tRNA ternary complex, suggesting a role in monitoring aminoacyl-tRNA sampling. Proteomic analysis further revealed that DHX29 recruits the GIGYF2‱4EHP complex to mediate global suppression of nonoptimal mRNAs. These findings establish a mechanistic link between synonymous codon usage and the regulation of gene expression.
GPT-4o mini: Non-social science research article
Rapid directed evolution guided by protein language models and epistatic interactions
Vincent Q. Tran, Matthew Nemeth, Liam J. Bartie, Sita S. Chandrasekaran, Alison Fanton, Hyungseok C. Moon, Brian L. Hie, Silvana Konermann, Patrick D. Hsu
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Protein engineering is limited by the inefficient search through a high-dimensional sequence space to find combinations of synergistic mutations. Traditional approaches use stepwise mutation stacking, whereas machine learning methods require extensive datasets or multiple experimental rounds and are bottlenecked by costly, length-limited gene synthesis. We present MULTI-evolve (where MULTI stands for model-guided, universal, targeted installation of multimutants), a rapid evolution framework that systematically engineers multimutants. Our approach combines protein language models or existing functional data with epistatic modeling to predict synergistic combinations. Proposed multimutants are built through MULTI-assembly, a mutagenesis method enabling high-efficiency assembly across multikilobase sequences. Applying MULTI-evolve to three proteins achieved up to 10-fold improvements with a single round of machine learning–guided directed evolution. MULTI-evolve provides a streamlined approach for end-to-end, multimutant engineering for a broad range of protein types and functions.
Science abstract < 200 char.: Not a research article
The future of plant extinction
Rosa A. Scherson, Federico Luebert
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Analyses of large-scale datasets call for urgent action to conserve plant diversity
Science abstract < 200 char.: Not a research article
Conflict imperils Middle East marine life
Hui Wang, Peng Liu, Lijuan Feng, Ning Wang
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Science abstract < 200 char.: Not a research article
How ‘spikes’ in the epileptic brain are harmful—and might be tamed
Jennie Erin Smith
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Abnormal electrical bursts hijack neurons involved in cognition and can be predicted up to 1 second in advance, new study finds
Science abstract < 200 char.: Not a research article
Building an oral peptide drug
Rebecca Buller, Joelle N. Pelletier
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Engineered enzymes enable kilogram-scale synthesis of drug for high-cholesterol conditions
Science abstract < 200 char.: Not a research article
Arrest of Fauci aide for records violations decried as political
Jon Cohen
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David Morens’s indictment centers on help he gave nonprofit that funded China research blamed for pandemic
Science abstract < 200 char.: Not a research article
Chaotic whale rescue shocks marine biologists
Martin Enserink
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Timmy, a humpback stranded in Germany 6 weeks ago, was freed after a media outcry. But the whale was in poor health and may already be dead
Science abstract < 200 char.: Not a research article
AI scientist agents violate research integrity rules
Nicola Jones
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Advanced AI systems are shown to make up data and “p-hack” their results
Science abstract < 200 char.: Not a research article
Data-driven decisions in a fast-and-loose world Beyond Belief Helen Pearson Princeton University Press, 2026. 368 pp.
Jonathan Wai
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A journalist probes the history and future of evidence-based action
Science abstract < 200 char.: Not a research article
Leap of faith
FrantiĆĄek Ć ebek
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Science abstract < 200 char.: Not a research article
Bury them in bureaucracy The Radical Spanish Empire Jorge Cañizares-Esguerra and Adrian Masters Harvard University Press, 2026. 472 pp.
Roger Atwood
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Indigenous challenges to Spanish colonizers shaped Latin America in profound ways, argue two historians
Science abstract < 200 char.: Not a research article
In Science Journals
Jesse Smith, Phil Szuromi, Michael A. Funk, Jack Huang, Peter Stern, Angela Hessler, Jelena Stajic, Jake S. Yeston, Christiana N. Fogg, Yury Suleymanov, Mattia Maroso, Di Jiang, Sarah H. Ross, Bianca Lopez, Courtney Malo, Annalisa M. VanHook
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
Safeguard water infrastructure amid conflict
Xue Xiao, Yichen Tao
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Science abstract < 200 char.: Not a research article
After pulling vaccine study, CDC leader calls for new journal
Jon Cohen
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Jay Bhattacharya clashes with epidemiologists over widely used design
Science abstract < 200 char.: Not a research article
Magic mushroom compound shows promise against cocaine addiction
Rachel Nuwer
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Small study that prioritized Black and low-income participants yields “remarkable” results
Science abstract < 200 char.: Not a research article
In Other Journals
Sacha Vignieri, Ekeoma Uzogara, Michael A. Funk, Stella M. Hurtley, Sarah H. Ross, Brad Wible, Jelena Stajic
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
Forecasting volcanic eruptions across scales
MagnĂșs T. Gudmundsson, Christopher J. Bean
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Predicting future volcanic eruptions requires better understanding of crustal magma storage
Science abstract < 200 char.: Not a research article
Delivering a STING to tumors
Rick Liao, Darrell J. Irvine
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STING agonist nanoparticles trigger potent antitumor immunity in mice and rabbits
Science abstract < 200 char.: Not a research article
Deep-Earth map points to a lost U.S. continent
Paul Voosen
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Sensor array traces how rocks conduct electricity, revealing mineral riches, crust that can amplify solar storms, and fragments of ancient landmasses
Science abstract < 200 char.: Not a research article
The vulnerability of Middle East desalination
Menachem Elimelech
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Science abstract < 200 char.: Not a research article
Aging and the narrowing of scientific innovation
Haochuan Cui, Yiling Lin, Lingfei Wu, James A. Evans
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Aging researchers and the removal of retirement policies yield decreased disruptive innovation in science
Science abstract < 200 char.: Not a research article
The power of a fish
Warren Cornwall
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In the remote reaches of the Amazon, scientists are working with villages to protect an ecosystem while boosting the economy

Science Advances

GPT-4o mini: Non-social science research article
Formation of calcium silicate perovskite above the core-mantle boundary during solidification of Earth’s magma ocean
Tianhua Wang, James Badro, Razvan Caracas, Héloïse Gendre, Cécile Hébert
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Calcium silicate perovskite (CaPv) is the host for many trace elements in the lower mantle. Whether, when, and where it forms during the solidification of the magma ocean is fundamental to understanding the geochemical and geodynamical evolution of the early Earth. We performed first-principles molecular dynamics simulations to investigate the partitioning of Ca (alongside Sr and Ba) between bridgmanite and molten pyrolite and laser-heated diamond anvil cell experiments to replicate the crystallization of pyrolitic melt. Results show that Ca is incompatible in bridgmanite at all relevant crystallization conditions in the lower mantle, indicating a progressive enrichment of Ca in the magma ocean as it solidifies. This leads to the crystallization of CaPv during the final stages of solidification in the deep mantle. Coupled with the low bridgmanite-melt partition coefficients for Sr and Ba, our findings infer that both large ion lithophile elements and their host, CaPv, will be concentrated in the deep mantle at the end of magma ocean solidification.
GPT-4o mini: Non-social science research article
CKS1B is a tumor-intrinsic factor driving CD8 + T cell exhaustion via maintaining persistent tumor-antigen stimulation
Siqi Yu, Pujie Wu, Xiaoting Xie, Liang Zhu, Liping Chen, Yibo Yu, Wen Tan, Shaosen Zhang, Chen Wu, Dongxin Lin
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T cell exhaustion is a major barrier to effective antitumor immunity, yet the tumor-intrinsic mechanisms remain poorly defined. Through single-cell and spatial proteomics analyses of esophageal squamous cell carcinoma (ESCC), we uncover two infection-like CD8 + T cell trajectories, acute-like and chronic-like responses, whose fates are dictated by the tumor cell subtypes they encounter. This concept links tumor heterogeneity to the shaping of local immune niches. Mechanistically, we identify CDC28 protein kinase regulatory subunit 1B (CKS1B) as a tumor-intrinsic inducer of chronic-like exhaustion. CKS1B forms a complex with S-phase kinase-associated protein to promote interferon regulatory factor 3 (IRF3) ubiquitination and degradation, thereby suppressing type I interferon signaling and antigen presentation. This impairs tumor cell elimination and drives progressive CD8 + T cell stimulation and exhaustion. Pharmacological blockade of the CKS1B-IRF3 interaction with 14i restores CD8 + T cell function and synergizes with immune checkpoint blockade. The tumor-intrinsic oncogenic-immune axis, which connects cancer cell signaling to immune dysfunction, is conserved across multiple malignancies, establishing a conceptual and therapeutic framework for overcoming tumor-driven T cell exhaustion.
GPT-4o mini: Non-social science research article
Hooked hairs: A cellular key adaptation aiding seedling survival in nutrient-limited and drought conditions
Sergio Alan Cervantes-Pérez, Ankita Roy, Addison Bralick, Peter Pietrzyk, Sandra Thibivilliers, Marc Libault, Alexander Bucksch
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Understanding plant survival mechanisms in degraded, drought-affected, and nutrient-limited soils can help mitigate the effects of climate change on crop production. Roots extend deep into soil through straight, tubular root hairs that facilitate resource uptake. In this study, we found a unicellular structure, termed the “hooked hair,” characterized by a pointed hook morphology that supports seedling establishment before root hair emergence. We observed a phenotypic response of hooked hairs to phosphorus and nitrogen limitations. Coexpression analysis identified gene signatures associated with nutrient transport and suberin biosynthesis in hooked hairs. These biological functions are likely critical for seedling establishment, nutrient acquisition, and protection against biotic stress. Therefore, the hooked hair offers potential for the development climate-resilient seedlings, reducing reliance on unsustainable fertilizers and securing agricultural productivity.
GPT-4o mini: Non-social science research article
A southward differentiated impactor forms the tapered shape of the South Pole–Aitken impact basin on the Moon
Shigeru Wakita, Brandon C. Johnson, Jeffrey C. Andrews-Hanna, Gabriel Gowman, Thomas M. Davison, Gareth S. Collins, Carys A. Bill, Simone Marchi, Amanda M. Alexander, William F. Bottke, Alexander J. Evans
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The South Pole–Aitken (SPA) basin-forming impact was a critical event in the Moon’s history. Despite being the oldest and largest acknowledged basin, critical details including the impactor’s size, nature, direction, and fate of the ejecta remain uncertain. Here, we simulate SPA’s formation and resultant crustal structure. We find that SPA’s observed shape of an ellipse tapered toward the south is best reproduced by a 260-km-diameter differentiated impactor striking with a north-to-south trajectory. In this scenario, the impact disperses lunar mantle materials in the cross-range and the downrange directions away from the lunar farside. Much of the mantle ejecta collapses into the basin interior, consistent with the distribution inferred from gravity. These results suggest that the Artemis landing sites near the lunar south pole should contain abundant SPA ejecta including mantle materials. Samples returned from these regions should therefore reveal the age of SPA and the composition of the lunar mantle.
GPT-4o mini: Non-social science research article
SnRK2.6 phosphorylates sucrose transporter ZmSUT1 to enhance yield by modulating leaf senescence in maize
Tao Yang, Yunqin Huang, Zan Wu, Zhenglan Long, Hongwei Zhu, Shanshan Wang, Lei Tang, Ruirui Li, Zhengchen Liang, Haoyu Zhang, Yongcai Huang, Xiaoling Li, Xiaoduo Lu, Yongrui Wu
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The extended stay-green trait is beneficial to increase photosynthetic efficiency, thereby enhancing crop yield. However, factors and mechanisms affecting this process remain largely unknown. Here, we cloned a leaf precocious senescence gene ( lps1-1 ) and created additional null alleles. All lps1 mutants exhibited accelerated leaf senescence with reduced chlorophyll contents and photosynthetic efficiency. The 100-kernel weight and storage reserve content were decreased in lps1 kernels, while the opposite was observed in overexpression lines. Lps1 encoded a protein kinase SnRK2.6 that phosphorylated the sucrose transporter ZmSUT1 in the BETL region, thereby enhancing protein stability, homodimer formation ability, and sucrose transport activity. Overexpression of ZmSUT1 delayed leaf senescence and enhanced photosynthetic capacity and kernel weight, while mutation of ZmSUT1 did the opposite. This mechanism appears to be conserved in grasses. Our findings provide insights for yield and quality improvement in crops through delaying leaf senescence.
GPT-4o mini: Non-social science research article
Powering Ganymede’s dynamo with protracted core formation
Kevin T. Trinh, Flavio Petricca, Douglas J. Hemingway, Steven D. Vance
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Ganymede is the only known moon with an active dynamo today. Previous studies interpret Ganymede’s dynamo as arising from convection in a metal core that formed billions of years ago. However, Ganymede likely accreted too cold to form with a metal core, which confounds interpretations of Ganymede’s magnetic field as a constraint on the moon’s broader history. Here, we reevaluate the thermal evolution of Ganymede’s rock-metal interior from a cold start. Our models show that Ganymede’s observed dynamo is consistent with ongoing core formation, a process not yet observed elsewhere. If Ganymede has an Fe-FeS core with a sub-eutectic composition, then gradual mantle warming may expel dense Fe melt onto the growing protocore and stir liquid metal, sustaining a dynamo for billions of years.
GPT-4o mini: Non-social science research article
Integrated analysis of insulin resistance reveals metabolic remodeling following diet switch–triggered calorie reduction
Xiaowen Duan, Lucy M. Davis, Satish Patel, Guillaume Bidault, Lu Long, Benjamin Jenkins, Yao Yi, Pushpa Pushpa, Julia R. Wesseling, Albert Koulman, Antonio Vidal-Puig, Daniel J. Fazakerley, David B. Savage
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Insulin resistance (IR) links obesity to metabolic disorders. While weight loss reverses IR, we show that calorie reduction (CR) can do so in obese mice within a day before significant weight loss. In contrast to whole-body IR, individual tissues do not revert to their original chow diet–fed states after CR. In the liver, improved insulin sensitivity correlates with reduced triacylglycerol and diacylglycerol and protein kinase C epsilon activity, alongside substantially decreased de novo lipogenesis and increased ketones. In muscle, insulin-sensitive glucose disposal was restored, whereas obesity-associated adipose tissue changes largely persisted following CR, specifically the reduction in fasting lipolytic activity mediated at least, in part, by lower ÎČ-adrenergic receptor 3 expression. This, combined with enhanced oxidative pathways in muscle and liver, resulted in lowered plasma free fatty acid levels and muscle and liver lipids, facilitating insulin-stimulated glucose disposal and thus restored insulin sensitivity.
GPT-4o mini: Non-social science research article
Ecosystem technology (ecotech): Harnessing natural processes to address global challenges
Brian R. Silliman, Marc J. S. Hensel, Ralph J. M. Temmink, Avery B. Paxton, Daniel J. Wieczynski, Jean Phillipe Gibert, David W. Johnston, Devon Noonan, William N. Ferris, Mark E. Hay, Tiffany Paalman, Christy Cutshaw, Mark Borsuk, Christine Angelini, Laura E. Dalton, Johan van de Koppel, Jim van Belzen, Benjamin Strong, Mark D. Bertness, Thomas E. Angelini, Andrea W. Gutierrez, Mads S. Thomsen, Tigerlily Kaynor, Lydia Olander, Nicolas Cassar, Marte M. Stoorvogel, Tjeerd J. Bouma, Stephanie Wear, Tjisse van der Heide, Pedro Daleo, Shannon Parker, Akash Aithal, Rachel K. Gittman, Parker Silliman, Eric Wade, Dhruv Rungta, Tong Qiu, Liyin He, David S. Cerino, Qiang He, Jesko von Windheim, Shila K. Nordone
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Over the past 80 years, biotechnology has advanced agriculture, health care, and economic development by harnessing biological processes from the organism inward, i.e., from the organ system to the molecular scale. Today’s global challenges, including biodiversity loss, climate change, and pollution, demand a complementary technological expansion inspired by processes operating from the organism outward, i.e., at the levels of populations, communities, ecosystems, and the biosphere. Here, we present the components of this technological expansion through ecosystem technology, or ecotech. We propose a framework for ecotech to integrate elements of ecology, engineering, and earth science and to function as a practical and conceptual convergence accelerator. Ecotech will advance critical environmental solutions by uniting independently evolving technologies, generating diverse fields of inquiry (e.g., ecomimicry, ecosystem materials science, ecosystem sensing and signaling), and inspiring innovation. To harness this innovation to improve nature restoration, carbon storage, water quality, ecosystem energy, and infrastructure resistance to disasters, ecotech is guided by cross-cutting actions to ensure scalability, equity, and accountability. When integrated into strategies across nongovernmental organizations, business, and governments, ecotech offers a pathway to advance climate adaptation, biodiversity recovery, and economic diversification and growth. By uniting ecology, engineering, and earth sciences at scale, ecotech transforms technology into a tool to confront humanity’s most urgent existential needs and secure a livable future.
GPT-4o mini: Non-social science research article
Integrated climate effects on nitrogen cycles in global grasslands
Miao Zheng, Jinglan Cui, Luxi Cheng, Sitong Wang, Xiaoxi Wang, Xin Xu, Xiuming Zhang, Chen Wang, Chenchen Ren, Baojing Gu
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Grasslands play a crucial role in providing essential ecosystem services through biogeochemical processes. Improving grassland productivity and nitrogen use efficiency, reducing reactive nitrogen losses, and ensuring environmental sustainability represent major challenges, especially under the influence of global climate change. While previous studies have shown substantial effects of individual climate change factors on grassland nitrogen cycling, a comprehensive understanding of how grassland nitrogen cycling responds to multiple climate change remains limited. In this study, using data from 150 countries, we identified climate warming as the primary driver of increased nitrogen harvest, biological nitrogen fixation, and nitrogen surplus in global managed and undisturbed grasslands. These increases, with respective increments of 19.8, 8.8, and 28.2%, were determined by comparing scenarios with and without climate change from 1980 to 2020. Precipitation variability further amplifies these nitrogen increases, displaying notable spatial heterogeneity. Conversely, elevated atmospheric CO 2 levels mitigate nitrogen surplus by enhancing plant nitrogen uptake. Under the SSP2-RCP4.5 scenario for the year 2050, nitrogen input, harvest, and surplus in global grasslands are projected to increase annually by 22.3, 7.2, and 15.1 million tonnes, respectively, compared to baseline scenarios. These climate-induced alterations in nitrogen budgets could incur additional costs up to USD $69 billion because of associated impacts on human health and ecosystem integrity. Our findings emphasize the urgent need for robust management strategies aimed at mitigating the negative effects of climate change on grassland nitrogen cycling, thereby supporting global sustainable development objectives.
GPT-4o mini: Non-social science research article
Elastic rod origami (RodOri) for programming static and dynamic mechanical properties
Sophie Leanza, Jeseung Lee, Lu Lu, Ruike Renee Zhao
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Reconfigurable mechanical systems enable precise programmable control over structural properties, expanding opportunities in architected materials, adaptive devices, and multifunctional structures. Here, we introduce elastic rod origami (RodOri), a platform that exploits remarkably simple elements—prestressed, naturally curved rods—into a system with an extraordinary degree of multistability and configurational richness. For example, a single six-rod RodOri unit can easily access 11 distinct configurations, far exceeding the reconfigurability of conventional origami or general mechanical reconfigurable systems. Individual rods, constrained under clamped boundary conditions, undergo transitions between discrete morphologies whose strain energy and stiffness are precisely prescribed by their natural curvature. Assembling these rods into modular multirod architectures yields metamaterials with numerous stable configurations that can be selectively and reversibly programmed. This configurational diversity enables tunable static stiffness and nonlinear force response, thus enabling tunable dynamic behaviors such as vibration filtering, wave propagation switching, and mode conversion within a single, easily manufactured platform. By leveraging curvature-induced mechanical instability, RodOri unlocks highly programmable static and dynamic mechanical behavior, offering tailorable design strategies for reconfigurable structures, soft robotics, medical devices, and adaptive materials.
GPT-4o mini: Non-social science research article
Tunable TriPcides suppress virulence factor secretion during Staphylococcus aureus infection and kill dormant cells
Hasan TĂŒkenmez, Taylor M. Nye, Pardeep Singh, Aaron Mychack, Mari Bonde, Suzanne Hickerson, Chloe L. P. Obernuefemann, Jerome S. Pinkner, Shaochun Zhu, Souvik Sarkar, Jaideep B. Bharate, Ingeborg van der Lingen, Anh Quoc Ntuyenm, V. U. Bhaskara Rao, Anders E. G. Lindgren, Hanna Klein, Zongsen Zou, Karen W. Dodson, Suzanne Walker, Andre Mateus, Jörgen Johansson, Michael G. Caparon, Fredrik Almqvist, Scott J. Hultgren
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Antimicrobial resistance (AMR) in common bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), is an increasingly dire public health threat, with MRSA accounting for up to 90% of S. aureus infections. To expand the treatment arsenal against MRSA infections, we developed a class of tunable three-dimensional tricyclic 2-pyridones, termed TriPcides, that can kill MRSA resistant to last-resort antibiotics and eliminate MRSA persister cells. No preexisting resistance was detected across hundreds of clinical isolates, and continuous exposure of MRSA to TriPcides did not elicit detectable resistance. Treatment with TriPcides causes a rapid decrease in membrane integrity and increased levels of reactive oxygen species. Last, TriPcides effectively reduce secretion of important virulence factors and result in reduced ulcer size and healing time in S. aureus murine skin and soft tissue infections but do not reduce bacterial burden.
GPT-4o mini: Non-social science research article
ATRA improves megakaryopoiesis in immune thrombocytopenia through up-regulating the HIF-1α/SPHK2/S1P pathway
Qiu-Sha Huang, Jing Xue, Feng-qi Liu, Qi Chen, Gaochao Zhang, Xue-yan Sun, Chencong Wang, Liping Yang, Yu Hou, Yueying Li, Qianfei Wang, Jun Peng, Ming Hou, Xiaosu Zhao, Yuan Kong, Yingjun Chang, Xiangyu Zhao, Xiao-Jun Huang, Xiao-hui Zhang
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Our previous clinical studies show that all-trans retinoic acid (ATRA) induces a sustained response in patients with immune thrombocytopenia (ITP). However, its mechanisms of action remain unclear. In this study, we observed disorganized cytoskeleton and impaired proplatelet formation (PPF) in megakaryocytes from patients with ITP. Metabolite profiling revealed reduced sphingosine 1-phosphate (S1P) levels in ITP. Decreased sphingosine kinase 2 (SPHK2) expression was responsible for the low S1P levels in ITP. In addition, S1P was essential for activating S1P receptor 1 and Rac1, which regulate cytoskeletal reorganization and PPF. Furthermore, hypoxia-inducible factor-1α (HIF-1α) was shown to mediate SPHK2 and S1P production. Decreased HIF-1α expression in megakaryocytes from patients with ITP contributed to impaired PPF. We subsequently found that ATRA up-regulated HIF-1α and corrected impaired PPF in vitro and in vivo. These findings reveal that ATRA targets the HIF-1α/SPHK2/S1P pathway to improve PPF dysfunction, offering mechanistic insights into its clinical efficacy in ITP.
GPT-4o mini: Non-social science research article
A chromatin-associated pool of Aurora A controls kinetochore-microtubule attachments to ensure chromosome biorientation
Johnathan L. Meaders, Alyssa A. Rodriguez, Smriti Variyar, SungWoo Park, Alessandro E. Cirulli, Karen Oegema, Kevin D. Corbett, Arshad Desai
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Accurate chromosome segregation requires dynamic kinetochore-microtubule attachments that, under the regulation of Aurora family kinases, biorient and align replicated chromosomes. In Caenorhabditis elegans , Aurora A acts with the TPX2-related activator TPXL-1 to regulate these attachments and control spindle length. We show that, in addition to prominent spindle pole localization, TPXL-1–AurA has a chromatin-associated pool positioned between the sister kinetochores. Structural modeling and biochemical analysis support TPXL-1 directly recognizing the nucleosome acidic patch via an arginine anchor. Disrupting this interaction selectively removed chromatin-bound TPXL-1–AurA and caused chromosome missegregation, whereas elevation of the chromatin pool disrupted chromosome alignment. These opposing perturbations inversely affected kinetochore recruitment of the microtubule-binding Ska complex. These results support spatially distinct TPXL-1–AurA populations acting sequentially, with the spindle pole pool controlling spindle length by switching kinetochores out of a depolymerization-coupled state, and the chromatin pool controlling attachment stabilization to ensure biorientation prior to anaphase.
GPT-4o mini: Non-social science research article
Electroactive microneedle augmented stem cell therapy in myocardial infarction
Wentao Zhang, Yiqi Shen, Shuangxu Jia, Yingxin Chen, Ruisi Cai, Yunlong Jiao, Quanquan Han, Jiahuan You, Shiqi Wang, Xingyi Wan, Jicheng Yu, Zhen Gu, Zhuxiao Gu, Yuqi Zhang
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Ischemic heart disease and related sequelae pose tremendous burdens on worldwide medical care. The excessive activation of cardiomyocytes and cardiac fibroblasts further exacerbates the prognosis after necrosis. Decades of stem cell therapy in preclinical studies suggested promising results in cardiomyocyte regeneration and tissue remodeling. However, few formulations achieved clinical translation due to the limited stem cell engraftment and insufficient arousal of resident cardiomyocytes. Here, we reported an implantable electroactive device to leverage stem cell therapy and cardiomyocyte restoration for effective heart recovery. Assisted by the piezoelectric microneedle patch with 80–cubic millimeter cavity, 1.5 × 10 5 mesenchymal stem cells could be delivered efficiently to the infarcted site and sustained longer for continuous paracrine effects. Meanwhile, the piezoelectric stimulation generated from the poly( l -lactic) acid microneedle matrix further potentiated the stem cells and elicited more vigorous self-repair responses in cardiomyocytes. This approach was validated to effectively suppress inflammatory monocytes, reduce cardiomyocyte necrosis, and improve heart remodeling in a rat heart infarction model.
GPT-4o mini: Non-social science research article
3D mapping of defects and moiré corrugations via electron ptychography atomic coordinate retrieval
Jeffrey Huang, Yichao Zhang, Sang hyun Bae, Ballal Ahammed, Elif Ertekin, Pinshane Y. Huang
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Defects and reconstructions in two-dimensional (2D) moiré materials cause out-of-plane deformations that strongly modify their electronic properties but are difficult to experimentally access. Here, we solve the 3D atomic coordinates of twisted bilayer WSe 2 with picometer-scale accuracy using multislice electron ptychography (MEP) acquired from a single orientation. The resulting atomic models individually visualize each of the six atomic planes, revealing the curvature of each WSe 2 layer, variations in the interlayer spacing, and the 3D locations of individual vacancies, which lie exclusively in the outer Se planes. We also observe an unexpected type of structural disorder consisting of mixed bending- and breathing-type moiré-induced corrugations that should strongly affect the emergent electronic properties. Broadly, our methods generate 3D atom-by-atom models of a 2D heterointerface from data acquired in about 30 seconds, methods that should unlock routine access to 3D atomic information in 2D systems and catalyze design methods to control out-of-plane deformations.
GPT-4o mini: Non-social science research article
Whole-body in vivo MPI cytometry reveals injection route-, dose-, cell size–, and disease-dependent differences in organ distribution
Ali Shakeri-Zadeh, Shreyas Kuddannaya, Chengyan Chu, Kritika Sood, Asif Itoo, Cristina Zivko, Aline M. Thomas, Vasiliki Mahairaki, Piotr Walczak, Jeff W. M. Bulte
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Robust quantification of the whole-body biodistribution of injected therapeutic cells remains a major challenge. We performed in vivo cytometry using magnetic particle imaging (MPI) to track magnetically labeled cells on a timescale of minutes with high sensitivity, zero background signal, and simple linear quantification. Human mesenchymal stem cells (hMSCs; ~25 micrometers) and human neural precursor cells (~10 micrometers) were labeled with superparamagnetic iron oxide nanoparticles and mapped with MPI after intravenous or intra-arterial injection in normal mice. The tissue site and numbers of cell accumulation and retention were dependent on cell size, dose, injection frequency, and injection route, with the lung and liver serving as the major entrapment organs. In mice with experimental autoimmune encephalomyelitis, but not in normal mice, hMSCs also homed to the spleen. Integrating MPI cytometry with cell therapy may aid in further optimization of the route, dose, and frequency of cell administration.
GPT-4o mini: Non-social science research article
Machine learning–driven discovery of optimal designs for water electrolysis devices
Zirui Zhang, Zhihao Wang, Yiwen Liao, Yu Chang, Li Ding, Guangsheng Luo, Xiaonan Wang, Haihui Wang
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Green hydrogen production via water electrolysis is key to decarbonizing energy systems, but current electrolyzer designs are energy-intensive due to gas bubble entrapment and manual optimization. This study introduces a machine learning (ML) strategy that autonomously designs high-efficiency electrolyzer flow channels. We identify an array-type channel geometry that enhances bubble removal using a mixture-of-experts framework, with a parametric analysis establishing structure-performance relationships. A prototype electrolyzer incorporating the artificial intelligence–optimized channel demonstrated ~23% improvement in current density at 2 V compared to a conventional serpentine design. This enhancement was consistently in scaled-up devices, underscoring the effectiveness of the design across scales. In contrast to computational fluid dynamics–based approaches simulating every geometry, our ML surrogate performs data-driven screening to efficiently identify and validate high-performance channel structures. By decoding the relationships between topological features and multiphase transport, this work outlines a scalable pathway toward autonomous design of next-generation electrochemical systems.
GPT-4o mini: Non-social science research article
Glutathione induces trap closure for carnivory in Cape sundew
Rui Li, Yongfang Yang, Weicheng Wang, Hao Lou, Ran Du, Haidong Chen, Feng Li, Xiaokang Liu, Xiaoyi Shan, Jianbin Yan, Daoxin Xie
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Charles Darwin was profoundly fascinated by Drosera (sundew plants), which have evolved as flesh-eaters with modified leaves, called traps, to catch small animals yet do not respond to transient mechanical stimuli. Despite Darwin’s early insights, and recent advances in characterizing these mechanisms, our knowledge of the signaling molecules underlying prey capture responses remains limited. Here, we identify glutathione (GSH) as an important mediator within the signaling cascade of sundew carnivory, implicated in trap closure in a calcium-dependent manner. We show that prey capture promotes GSH accumulation in sundew leaves, while GSH depletion inhibits the movement. Furthermore, application of GSH is sufficient to induce trap closure across the Droseraceae family, including both the snap traps of Venus flytrap and the adhesive traps of sundew species. These findings advance our understanding of the enigmatic mechanisms of plant carnivory, a phenomenon that has intrigued scientists since Darwin’s era.
GPT-4o mini: Non-social science research article
HSPCs and T reg cells cooperate to preserve extramedullary hematopoiesis under chronic inflammation
Maria Kuzmina, Srdjan Grusanovic, Jiri Brezina, Flavian Thelen, Karolina Vanickova, Mirko Milosevic, Irina Ribeiro Bas, Nataliia Pavliuchenko, Sarka Ruzickova, Jakub Rohlena, Dominik Filipp, Katerina Rohlenova, Cesar Nombela-Arrieta, Tomas Brdicka, Meritxell Alberich-Jorda
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Hematopoietic stem and progenitor cells (HSPCs) are localized within specialized niches of the bone marrow (BM). However, during hematological disorders or infections, the functionality of these cells in the BM is compromised, leading to extramedullary hematopoiesis (EMH). Chronic inflammation drives EMH, yet its impact on HSPCs outside the BM is poorly understood. Using a mouse model of chronic autoinflammatory disease, we demonstrated the presence of extramedullary HSPCs in blood, spleen, and inflamed tails and paws. Single-cell transcriptomics revealed a unique expression profile in extramedullary HSCs, with significant up-regulation of Cd53 , MHCII-associated, and immunosuppressive genes. We further demonstrated that extramedullary CD53 + HSPCs act as antigen-presenting cells, promoting the development of regulatory T cells (T reg cells) to control chronic inflammation at extramedullary sites. Conversely, T reg cells exert a protective role on extramedullary HSPCs. Together, our findings revealed a mutually supportive relationship between a unique subset of HSPCs and T cells in inflamed tissues during chronic inflammation.
GPT-4o mini: Non-social science research article
Chemical stimulation sustains bioluminescence of living light materials
Giulia Brachi, Jessica McKean, Cheng Pau Lee, Joy Edwin-Ezeh, Wil V. Srubar
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Bioluminescence offers a powerful tool for real-time, label-free sensing for living materials. However, conventional approaches often rely on mechanical stimulation, which is difficult to standardize, localize, and sustain. Here, we introduce a chemical strategy to stimulate and sustain bioluminescence in the marine dinoflagellate Pyrocystis lunula , enabling durable, adaptive, light-emitting living materials. By embedding P. lunula into 3D-printed, alginate scaffolds, we engineered architecturally stable constructs with long-term cellular retention, viability, and light-emitting capacity. Exposure to acidic and basic environments produced chemically encoded bioluminescent signatures: Acid triggered localized, persistent emission, while base induced diffuse, biphasic emission indicative of cellular stress. Notably, combining chemical and mechanical stimulation led to enhanced total bioluminescence emission, achieving greater amplitude and duration of light emission without compromising cell mechanoresponsiveness. Longitudinal studies over 4 weeks demonstrated that our materials retain responsiveness and structural integrity across repeated stimulation cycles, overcoming single-use limitations. Together, these findings establish a chemistry-controlled platform for light-emitting living materials for biosensing, soft robotics, and environmental monitoring.
GPT-4o mini: Non-social science research article
HONO emission from marine algae
Hengqing Shen, Xuelian Zhong, Yujiao Zhu, Yanqiu Nie, Min Zhao, Qinyi Li, Yuqiang Zhang, Liubin Huang, Zheng Zong, Qi Yuan, Tao Wang, Alfonso Saiz-Lopez, Wenxing Wang, Likun Xue
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Nitrous acid (HONO) is a key precursor to hydroxyl radicals (OH) and a reservoir of reactive nitrogen. Here, we identify abiotic photodecomposition of marine algae as a previously unrecognized HONO source. During Ulva prolifera green tides, daytime HONO levels closely followed tidal cycles, peaking at low tide, contrasting with typical inland nocturnal peaks. Chamber experiments confirm that common algae (e.g., U. prolifera and Sargassum ) emit HONO under irradiation, with fluxes increasing with light intensity and algal surface area. This light-driven, abiotic process is mechanistically distinct from microbial soil HONO production. Measured fluxes (1.08 × 10 −7 to 2.31 × 10 −6 mole per square meter per hour) are comparable to soil HONO emissions and exceed marine NO fluxes by two to three orders of magnitude. Incorporating this source into atmospheric models substantially elevated HONO concentrations, enhancing OH and ozone production and oxidation of climate-relevant gases. With intensifying global algal blooms driven by eutrophication and climate warming, this process is expected to become increasingly important.
GPT-4o mini: Non-social science research article
TCF3::HLF orchestrates an enhancer-promoter network with activation of MEF2C to promote immature HSC gene expression in leukemia
Valdemar Priebe, BartimĂ©e Galvan, Aneta Drakul, Nicola Margelisch, JĂșlia AguadĂ©-GorgoriĂł, Kaivalya Walavalkar, Yun Huang, Hanna K. A. Mikkola, Beat Bornhauser, Raffaella Santoro, Jean-Pierre Bourquin
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Oncogenic fusion transcription factors (TFs) frequently drive hematopoietic malignancies by altering gene expression in key developmental programs. TCF3::HLF is a fusion TF that characterizes a rare, treatment-resistant subtype of B cell acute lymphoblastic leukemia [t(17;19) TCF3::HLF-positive B-ALL]. Despite its clinical significance, the mechanisms by which TCF3::HLF induces leukemia are unclear. We used HiChIP mapping and genetic interference to analyze TCF3::HLF at the 3D genome level, revealing enhancer-promoter interactions that control gene activation or repression. Notably, TCF3::HLF directly regulates MEF2C expression through its enhancer, as interference disrupted MEF2C transcription and inhibited leukemia propagation. This disruption also diminished embryonal hematopoietic stem cell (HSC) gene signatures and restored mature HSC and B-lymphoid markers. These findings highlight MEF2C as a critical component of the transcriptional network reprogrammed by TCF3::HLF. Our study provides insight into how TCF3::HLF rewires the 3D genome to drive leukemia and serves as a resource for further exploration of the TCF3::HLF regulome.
GPT-4o mini: Non-social science research article
Dynamic drives allow independent control of material bits for targeted memory
Eduardo Gutierrez-Prieto, Colin M. Meulblok, Martin van Hecke, Pedro M. Reis
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Mechanical metamaterials with bistable elements can store vast amounts of information, but writing these memories requires impractical local control or lengthy multicycle protocols. We overcome this limitation with a dynamic control strategy that accesses any configuration in a single global drive cycle by leveraging the system’s sensitivity to the drive and its time derivatives. We realize this strategy with bistable beams on a rotating platform, where drive cycles become orbits in a control space of angular velocity and acceleration. State changes occur when these orbits cross switching thresholds, which we rationally design so that each state can be accessed by a single drive orbit. We construct a five-bit system and demonstrate its full addressability by selecting drive orbits that write all 26 uppercase letters of the alphabet in ASCII representation. This dynamic control paradigm offers a general route toward smart, remotely operated devices across various physical domains.
GPT-4o mini: Non-social science research article
Cis-regulatory evolution shapes facial diversity in birds and mammals
Stella Kyomen, Louk W. G. Seton, Laura E. Cook, Elio Escamilla-Vega, Andrea P. Murillo-Rincón, Alexander Jacobsen, Amor Damatac, Carsten Fortmann-Grote, Janina Fuss, Axel Visel, Markéta Kauckå
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Birds and mammals exhibit extraordinary facial diversity, reflecting adaptations to distinct ecological niches and feeding strategies. While core face-building developmental programs are conserved and orchestrated by interactions between ectodermal organizers and the underlying mesenchyme, mechanisms driving facial shape variation remain poorly understood. Here, we integrate single-cell transcriptomic and chromatin accessibility profiling of mouse and chicken developing face to construct a comparative regulatory map. Although both ectodermal and mesenchymal populations display distinct regulatory features in each species, the mesenchyme exhibits markedly greater divergence, pointing to its central role in shaping facial morphology. We further reveal unexpected molecular complexity in the main face-shaping organizer, including a mouse-specific Shh/Wnt5a expression domain. At key morphogen loci ( Bmp4 , Fgf8 , and Wnt5a ), conserved and lineage-specific enhancers exhibit spatially restricted activity patterns that mirror divergent signaling domains. These findings demonstrate how cis-regulatory evolution modulates conserved developmental programs to generate morphological novelty, providing a valuable resource for studying vertebrate facial evolution.
GPT-4o mini: Non-social science research article
A redox-sensitive phosphatase regulates glycolysis as a metabolic switch in the bacterial inner membrane
Lei Zheng, Wei Niu, Xianfa Xie, Trung Vu, Guangwei Du
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Microorganisms rapidly adjust their metabolism to survive fluctuating environmental conditions, but how they coordinate glycolytic control with redox signals remains unclear. We found that the membrane phosphatase PgpA acts as a redox-sensitive switch to regulate glycolytic flux in Escherichia coli . PgpA dephosphorylates key glycolytic intermediates, glyceraldehyde-3-phosphate and glycerol-3-phosphate, to modulate central metabolism. This activity is controlled by a reversible disulfide bond that forms an inactive dimer under oxidative stress and restores activity when reduced. This redox-dependent regulation enables E. coli to fine-tune metabolism in response to changes in nutrients and oxygen availability. PgpA inactivation increases glucose uptake and promotes metabolism, while constitutive activation impairs growth under anaerobic conditions. We also found that PgpA influences redox homeostasis by regulating glutathione biosynthesis. These findings reveal a negative feedback mechanism in which PgpA integrates glycolysis with redox balance, serving as a central regulator of bacterial metabolic homeostasis in response to environmental changes.
GPT-4o mini: Non-social science research article
Optical corner detection with azimuthal Hilbert transform metasurfaces
Chen Chen, Junyi Wang, Rong Lin, Jiacheng Sun, Wange Song, Shining Zhu, Tao Li, Din Ping Tsai
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Many animals efficiently interpret their environment by detecting geometric features like corners, highlighting the power of feature extraction for reducing visual complexity; similarly, with the surge in visual data, nature-inspired optical corner detection offers a promising yet still elusive solution for energy-efficient information processing and compression. Here, we propose a universal strategy for optical corner imaging with azimuthal Hilbert transformation metasurfaces. Multiple objects, regardless of their amplitude, phase, or angular characteristics, can be detected simultaneously with a single metasurface, featuring broadband and full–field-of-view properties. Trade-offs between spatial and angular resolution are assessed, offering practical guidance for implementation. We further demonstrate motion tracking as a proof-of-concept application leveraging the data-compressed corner imaging framework. This work paves the way for next-generation optical information processing technologies.
GPT-4o mini: Non-social science research article
SHANK3 mutations disrupt olfactory valence coding across species, with cortical amygdala mechanisms identified in mice
Yu Hu, Yuli Wu, Mingyu Wei, Jingchao Ma, Jianbang Lin, Gaowei Chen, Qi Li, Jianqing Zhang, Ruiqi Wang, Yingjie Zhu, Qian Chen, Bo Peng, Yingying Zou, Bo Zhang, Wen Zhou, Zhonghua Lu
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Mutations in SHANK3 are a leading monogenic cause of autism spectrum disorder (ASD), often associated with profound sensory abnormalities. However, the impact of SHANK3 deficiency on olfactory processing and the underlying neural mechanisms remains unclear. Here, we identify a cross-species disruption of olfactory valence perception in individuals with SHANK3 mutations and in Shank3 mutant mice. Patients carrying SHANK3 mutations exhibited impaired valence-oriented sniffing and electroencephalography (EEG) responses, whereas Shank3B −/− mice displayed blunted behavioral responses to both attractive and aversive odors. In mice, these behavioral deficits were associated with attenuated odor-evoked calcium signals and reduced excitatory synaptic transmission in the cortical amygdala (CoA), a key node for olfactory valence processing. Acute CoA-specific Shank3 deletion recapitulated these deficits, whereas targeted restoration of CoA Shank3 expression rescued odor-induced appetitive and aversive behaviors. Our findings reveal a conserved function for SHANK3 in encoding olfactory valence and identify CoA dysfunction as a circuit mechanism in mice.
GPT-4o mini: Non-social science research article
Contrasting temporal dynamics of fluorescence and photoacoustic signals from Cetuximab-IRDye800 conjugate in EGFR-overexpressing tumors
Mohammad A. Saad, Derek Allen, Allison Sweeney, Marvin Xavierselvan, Srivalleesha Mallidi, Tayyaba Hasan
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Molecular fluorescence imaging is effective for tumor diagnosis but limited by low-depth profiling, which can be addressed by photoacoustic (PA) imaging. However, PA imaging has low sensitivity due to microenvironment-induced effects on exogenous contrast agents. Accordingly, the temporal and biophysical determinants of PA contrast in Cetuximab-IRDye800 conjugates should be performed to complement fluorescence-based diagnostics. In this study, we compare the temporal dynamics of PA and fluorescence signals from a Cetuximab-IRDye800 conjugate in a tumor xenograft model. We demonstrate that while fluorescence signal increases steadily over time after administration of Cetuximab-IRDye800, PA signal peaks early (~75% higher at 3 hours), followed by a decrease (~24% higher at 24 hours). Mechanistic analysis revealed formation of H-aggregates with Cetuximab-IRDye800 conjugation, which results in enhanced PA contrast, while receptor-mediated endocytosis disrupts these aggregates, reducing PA signal intensity over time. These findings underscore the complementary nature of PA and fluorescence imaging and emphasize timing as a critical factor for capturing peak PA contrast for tumor diagnostics.
GPT-4o mini: Non-social science research article
Ambient one-step synthesis and direct coating of highly crystalline covalent organic frameworks on arbitrary surfaces
Javad Khosravi Farsani, Juan Pablo Cavalieri, Omid Mazaheri, Fred Junghans, Jorge Albalad, Billy J. Murdoch, Caiden J. Parker, Ravichandar Babarao, Daniel Maspoch, Amgad R. Rezk, Joseph J. Richardson, Leslie Y. Yeo
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Covalent organic frameworks (COFs) are promising materials for wide-ranging applications. Challenges with coating them onto surfaces have however limited their wider implementation in practice. We report an acoustomicrofluidic nebulization platform that enables rapid, one-step synthesis of highly crystalline COFs and their direct deposition as a coating under ambient conditions. Demonstrated with both two- and three-dimensional imine-based COFs, the method yields uniform COF films with nanometer to micrometer thicknesses, tuned simply by adjusting the nebulization time. Unlike conventional COF coating approaches, this strategy eliminates the need for any postsynthetic substrate heating or processing, thereby offering a general and scalable route for fabricating functional COF coatings on a variety of sensitive and complex substrates, including living tissue. As proof of concept, we demonstrate that COFs can constitute protective coatings on plant leaves for solar ultraviolet shielding, thus highlighting the potential of the platform to extend the deployment of COFs in real-world devices, biological systems, and environmental interfaces.
GPT-4o mini: Non-social science research article
Activating the Mn 2+ /Mn 7+ redox for a neutral Zn||Mn-compound battery with 2.2-V discharge plateau
Chuan Li, Xiu Hu, Rong Zhang, Shaoce Zhang, Huilin Cui, Qinshun Nian, Yuwei Zhao, Chunyi Zhi
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In 1952, the first commercially alkaline Zn||MnO 2 primary battery was developed, which is based on Mn 4+ /Mn 3+ redox reactions (MnO 2 ↔Mn 2 O 3 ). Subsequently, the single-electron (Mn 3+ /Mn 2+ and Mn 7+ /Mn 6+ ) and two-electron (Mn 4+ /Mn 2+ ) redox reactions of Mn compound (Mn-Comp) were achieved in aqueous Zn-based batteries. After that, however, the new Mn multivalent change redox reaction was no longer observed. In this study, we report a neutral superhydrophilic hydrogel electrolyte that activates a Mn 2+ /Mn 7+ conversion reaction (Mn 2+ ↔MnO 4 − ). This advance is attributed to an expanding electrochemical stability window and high Mn 2+ reaction activity. This enables a discharge plateau of ≄2.2 V in aqueous Zn metal batteries. The high reversibility of Mn 2+ /Mn 7+ conversion reactions during cycling was achieved by incorporating chelation groups in the designed hydrogel electrolyte, which effectively stabilizes the MnO 4 − . The aqueous Zn||Mn-Comp battery with a 2.2-V discharge plateau operates stably for ≄360 hours.
GPT-4o mini: Non-social science research article
Internally promoted reactivity of carbonized butadiene and amines enables a recyclable polymer composite
Keaton M. Turney, Abdol Hadi Mokarizadeh, Mesfin Tsige, James M. Eagan
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The catalytic conversion of carbon dioxide into polymers via high-energy comonomers offers a sustainable, low-cost, and low-emission approach to developing conveniently manufactured high-performance materials without competing for land use or food resources. We present the synthesis of poly(amidoamine) polymers stoichiometrically derived from carbon dioxide, butadiene, and amines displaying useful mechanical properties (tensile strength, 43 MPa; Young’s modulus, 840 MPa; and flexural modulus, 2.6 GPa). The low viscosity precursors (20 centipoise at 25°C) are applicable to producing carbon fiber reinforced polymers with fiber wetting and rapid network formation (16 min at 150°C). This work reveals that the reactivity of the internal hydrogen bonding catalyzes the ring-opening polymerization, and the intramolecular alcohol moiety promotes chemical recyclability to the monomers under acidic conditions, allowing the carbon fibers to be recovered with <1.0 wt % difference and reused in the manufacturing of recycled composites.
GPT-4o mini: Non-social science research article
Generation of carbonated peridotite melts via biogenic sediment recycling in modern subduction zones
Carlos ErrĂĄzuriz-Henao, Arturo GĂłmez-Tuena, Marion Weber, Mattia Parolari, Berengere Mougel, Marine Paquet, Eric Hellebrand, Oliver PlĂŒmper, Paul Mason, FrĂ©dĂ©ric Moynier
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The subduction of carbonate-rich biogenic sediments influences Earth’s carbon cycle and regulates long-term climate. Yet, the processes controlling their behavior at the subduction interface remain debated. Here, we investigate the role of carbonate subduction through the petrogenesis of Quaternary rear-arc monogenetic volcanoes in Colombia. These volcanoes display unusual compositions resembling intraplate carbonated peridotite melts and experimental melts from peridotite + CO 2 systems. Their geochemistry reflects an anomalous mantle source modified by subducted sediments from the Panama Basin, a large-scale region of high primary productivity and carbonate accumulation. However, pristine subducted sediments alone cannot explain the full compositional range of rear-arc Colombian lavas. Instead, we propose that sediment partial melting beneath the arc front produces carbonate- and apatite-rich restites that act as a recycled carbonated component, contributing to mantle chemical heterogeneity. This model helps explain the geochemical diversity of mantle-derived intraplate lavas and establishes a direct link between biogeochemical cycles, subduction, and the evolution of the solid Earth.
GPT-4o mini: Non-social science research article
Loss of the autoimmune risk gene TREX1 reveals a convergence of mechanisms promoting immune tolerance loss and antitumor immunity
Junghyun Lim, Katherine Williams, Stephanie Mittman, Patricia Pacheco Sanchez, Ryan Rodriguez, Annie Ogasawara, Grace Barnett, Mayra Cruz Tleugabulova, Barzin Y. Nabet, Jeffrey Hung, Kevin A. Marroquin, Shari Lau, Serena Y. Lee, Paul Tyler, Elizabeth T. Carbone, Bridget Hough, Janice Corpuz, Haruka Murota, Edward Dere, Smadar Shiffman, Leah K. Schutt, Herman Gill, Julia Lau, Marco De Simone, Lucinda Tam, Merone Roose-Girma, SĂžren Warming, Soyoung A. Oh, Sascha Rutz, Meng Xiao He, Sören MĂŒller, Nathaniel R. West, Thomas F. Brewer, Prashant Desai, Simon Williams, James Ziai, Yan Qu, Klaus Heger
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Checkpoint inhibitors targeting PD-1 and CTLA-4 have transformed cancer therapy. Both are genetically associated with autoimmune disorders. Moreover, certain immune-related adverse events and autoimmune risk variants are linked to the clinical efficacy of checkpoint inhibition. These associations suggest common principles governing successful cancer immunotherapy and autoimmune susceptibility. Here, we show that ablation of the cytosolic DNA exonuclease TREX1 predisposes mice to autoimmunity while promoting robust antitumor immunity. Constitutive TREX1 loss leads to early onset autoimmunity, characterized by multiorgan CD8+ T cell infiltration, myocarditis, and Sjögren’s syndrome–like disease. In contrast, induced systemic TREX1 ablation is well tolerated and promotes effective CD8+ T cell–driven antitumor immunity. Detailed phenotypic studies revealed a notable overlap between productive antitumor and pathogenic autoimmune CD8+ T cell responses. Collectively, we provide mechanistic evidence for interrelated mechanisms underlying autoimmunity and successful cancer immunotherapy, uncover key parallels between adaptive T cell and innate immune checkpoints, and suggest that targeting autoimmune risk genes represents a promising future avenue for cancer immunotherapy.
GPT-4o mini: Non-social science research article
Ousiometrics: The essence of meaning aligns with a power-danger-structure framework instead of valence-arousal-dominance
Peter Sheridan Dodds, Thayer Alshaabi, Mikaela Irene Fudolig, Julia Witte Zimmerman, Juniper Lovato, Shawn Beaulieu, Joshua R. Minot, Michael V. Arnold, Andrew J. Reagan, Christopher M. Danforth
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From work emerging through the middle of the 20th century, the essence of meaning has become widely accepted as being described by the three orthogonal dimensions of valence, arousal, and dominance. These essential dimensions have become the cornerstone of sentiment analysis across many fields. By reexamining first types and then tokens for the English language, and through the use of automatically annotated histograms—“ousiograms”—we find here that the essence of meaning conveyed by words is instead best described by a goodness-power-aggression-danger-structure (GPADS) circumplex framework; that large-scale English language corpora reveal a systematic bias toward safe, low-danger words; and that the power-danger-structure framework is the minimal framework that represents essential meaning. We find remarkable congruences between the GPADS framework and other spaces including mental states and fictional archetypes, and we construct and demonstrate a prototype ousiometer.
GPT-4o mini: Non-social science research article
Super-stable two-dimensional radical conjugated metal-organic frameworks for efficient NIR-II photothermal conversion
Shanzhi Lyu, Yang Lu, Shiyi Feng, Nan Zhang, Yanji Chu, Yuge Yao, Chao Sun, Yonglin He, Xinliang Feng, Yapei Wang
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Radical-functionalized chromophores hold promise as noninvasive NIR-II agents due to their narrow HOMO-SOMO gaps, but inherent instability from radical quenching has limited their practical applications. Here, we report a molecularly engineered class of two-dimensional conjugated metal-organic frameworks (2D c-MOFs) that simultaneously integrate stable radicals (>24 months), extended π-delocalization, and metal-ligand coordination. This synergistic architecture achieves an ultrabroad NIR-II absorption peak extending beyond 1400 nm with extinction coefficients approaching ~10 6 M −1  cm −1 , which outperform traditional photothermal agents by orders of magnitude. Through strategic graft of side chains, we promote vibrational relaxation pathways, markedly enhancing nonradiative decay and enabling a photothermal conversion efficiency of 92.9%. In cell experiments, 2D c-MOFs achieve complete tumor cell ablation under ultralow NIR-II irradiation intensity (0.1 W cm −2 ) that highlights their potential for deep-tissue photothermal therapy. Our work establishes a robust and generalizable molecular design strategy for developing stable radical-based NIR-II agents with exceptional photothermal performance, paving the way for their application in deep-tissue therapy.
Decadal East Asian monsoon anomalies and implications for societal conflicts
Kan Zhao, Yijia Liang, Changchun Huang, Yongjin Wang, Weiyi Sun, Hai Cheng, Jianjun Yin, Di Hu, Mi Yan, Liang Ning, Zhaoyuan Yu, R. Lawrence Edwards
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The East Asian summer monsoon anomalies, responsible for floods and droughts across China, pose great challenges to the climate resilience of human society. However, mechanisms and impacts of decadal-scale monsoon variability remain poorly understood due to limited instrumental data. Our annual-resolution speleothem record (1787–2007 CE) from China, along with simulation results, reveals a persistent monsoon weakening since the end of the Little Ice Age, superimposed by decadal oscillations. Five monsoon extremes, triggered by diminished solar output and further amplified by ocean-atmosphere processes in the Atlantic and Pacific oceans, caused widespread megadroughts in China. One marked flood-drought abrupt alternation in the 1850s substantially contributed to the Taiping Rebellion (1851–1864 CE). Our findings demonstrate that monsoon anomalies can cause crop failure and exacerbate overpopulation, ultimately leading to social unrest, particularly in regions experiencing rapid demographic expansion.