I checked 6 multidisciplinary journals on Friday, February 13, 2026 using the Crossref API. For the period February 06 to February 12, I found 16 new paper(s) in 5 journal(s).

Nature

GPT-4o mini: Non-social science research article
Conformational diversity and fully opening mechanism of native NMDA receptor
Ruisheng Xu, Qiqi Jiang, Hongwei Xu, Lu Zhang, Xiangzi Hu, Zizhuo Lu, Huaqin Deng, Haolin Xiong, Sensen Zhang, Zhongwen Chen, Yifan Ge, Zhengjiang Zhu, Yaoyang Zhang, Yelin Chen, Jingpeng Ge, Jie Yu
Full text
N-methyl-d-aspartate receptors (NMDARs) are glutamate-gated ion channels that mediate excitatory neurotransmission throughout the brain1. As obligate heterotetramers, their activation requires the binding of both glycine and glutamate2. Although recent structural studies have provided insights into endogenous receptors from select brain regions3, most previous work has relied on recombinant receptors and engineered constructs, which limits our understanding of native NMDARs across the whole brain. Here we identify and resolve ten distinct native NMDAR assemblies from the whole-brain tissue of female C57BL/6 mice using immunoaffinity purification, single-molecule total internal reflection fluorescence microscopy and cryo-electron microscopy. Analyses of the GluN1–GluN2A(S1), GluN1–GluN2A(S2), GluN1–GluN2A(S3), GluN1–GluN2B, GluN1–GluN2A–GluN2B(S1), GluN1–GluN2A–GluN2B(S2), GluN1–GluN2A–GluNX(S1), GluN1–GluN2A–GluNX(S2), GluN1–GluN2B–GluNX and GluN1–GluNX structures reveal that GluN2A is the most prevalent subunit across assemblies. Moreover, the substantial conformational flexibility observed in the GluN2A amino-terminal domain may explain its fast kinetics and dominant role in gating. Dynamic movements of S-ketamine were also captured at the channel vestibule, as was pore dilation in both the GluN1 and GluN2B subunits of a native GluN1–GluN2B receptor. The latter observation represents a previously unknown fully open state of NMDAR. Our large collection of heterogeneous NMDAR structures from whole brain reveals previously unrecognized properties of conformational diversity and channel dilation.
GPT-4o mini: Non-social science research article
Continuous-wave narrow-linewidth vacuum ultraviolet laser source
Qi Xiao, Gleb Penyazkov, Xiangliang Li, Beichen Huang, Wenhao Bu, Juanlang Shi, Haoyu Shi, Tangyin Liao, Gaowei Yan, Haochen Tian, Yixuan Li, Jiatong Li, Bingkun Lu, Li You, Yige Lin, Yuxiang Mo, Shiqian Ding
Full text
The exceptionally low-energy isomeric transition in 229Th at around 148.4 nm (refs. 1,2,3,4,5,6) offers a unique opportunity for coherent nuclear control and the realization of a nuclear clock7,8. Recent advances, most notably the incorporation of large ensembles of 229Th nuclei in transparent crystals6,9,10,11 and the development of pulsed vacuum ultraviolet (VUV) lasers12,13,14, have enabled initial laser spectroscopy of this transition15,16,17. However, the lack of an intense, narrow-linewidth VUV laser has precluded coherent nuclear manipulation8,18. Here we introduce and report a continuous-wave (CW) laser at 148.4 nm, generated by means of four-wave mixing (FWM)19 in cadmium vapour. The source delivers more than 100 nW of power with a projected linewidth well below 100 Hz and supports broad wavelength tunability. This represents a five-orders-of-magnitude improvement in linewidth over all previous single-frequency lasers below 190 nm (refs. 12,13,14,20). We develop a spatially resolved homodyne technique that places a stringent upper bound on FWM-induced phase noise, thereby supporting the feasibility of sub-hertz VUV linewidths. Our work addresses the central challenge towards a 229Th-based nuclear clock and establishes a widely tunable, ultranarrow-linewidth laser platform for potential applications across quantum information science21,22,23,24, condensed-matter physics25 and high-resolution VUV spectroscopy26.
GPT-4o mini: Non-social science research article
Large-scale quantum communication networks with integrated photonics
Yun Zheng, Hanyu Wang, Xinyu Jia, Jiahui Huang, Huihong Yuan, Chonghao Zhai, Junhao Dai, Jingbo Shi, Lei Zhang, Xuguang Zhang, Minxue Zhuang, Jinchang Liu, Jun Mao, Tianxiang Dai, Zhaorong Fu, Yuqing Jiao, Yaocheng Shi, Daoxin Dai, Xingjun Wang, Yan Li, Qihuang Gong, Zhiliang Yuan, Lin Chang, Jianwei Wang
Full text
Quantum key distribution (QKD) makes use of the principles of quantum mechanics to enable provably secure communication1,2. One substantial challenge persists in building large-scale QKD networks with many clients over long communication distances3. Although quantum relays continue to pose practical difficulties4, existing trusted-node networks5,6,7,8,9, point-to-multipoint networks10,11 and wavelength-multiplexed entanglement networks12,13 encounter issues such as reliance on trusted intermediaries or limited distances. Twin-field quantum key distribution (TF-QKD) provides a compelling architecture that can overcome those issues while enhancing communication distance14. Although long-distance point-to-point TF-QKD has been achieved15,16,17,18,19,20,21, realizing large-scale networks requires scalable quantum devices. Here we report a proof-of-principle demonstration of an integrated-photonics TF-QKD network with exceptional scalability and reliability. This network includes 20 independent client-side QKD transmitter chips with one server-side optical microcomb chip. The microcomb generates a broad range of ultralow-noise coherent frequency combs with Hz-level linewidths, which serve as seeds and references for all client chips. Each client chip regenerates ultralow-noise light phase-locked to microcombs and prepares quantum keys. We sequentially implement pairwise QKD across 20 client chips through ten wavelength-multiplexed channels, with each surpassing the repeaterless bound at 370 km in spooled fibre, achieving a networking capability (client pairs × communication distance) of 3,700 km. We further demonstrate the wafer-scale reproducibility of both server-side microcomb chips and client-side QKD transmitter chips, together establishing system-level scalability. Combining mass-manufacturability, cost-effectiveness and high scalability of integrated photonics with long-distance quantum communication represents a viable path to large-scale quantum networks.
GPT-4o mini: Non-social science research article
SLAMF6 as a drug-targetable suppressor of T cell immunity against cancer
Bin Li, Ming-Chao Zhong, Cristian Camilo Galindo, Jiayu Dou, Jin Qian, Zhenghai Tang, Dominique Davidson, André Veillette
Full text
Inhibitory receptors like PD-1 and CTLA-4 contribute to T cell dysfunction in cancer1,2,3. Monoclonal antibodies (mAbs) blocking the interactions in trans of these receptors with their ligands on cancer cells or in the tumour microenvironment lead to clinical responses in some but not all types of cancer. Signalling lymphocytic activation molecule 6 (SLAMF6, also known as Ly108) is a homotypic receptor preferentially expressed on progenitor or stem-like exhausted T (Tpex) cells, but not on terminally exhausted T (Tex) cells, as demonstrated in mouse models4,5,6,7,8,9. In contrast to Tex cells, Tpex cells retain the capacity for functional restoration after immune checkpoint blockade10,11,12. The role of SLAMF6 in T cells remains ambiguous, as it has both activating and inhibitory effects, complicating its evaluation as a therapeutic target. Here we find that SLAMF6 was triggered in cis by homotypic interactions at the T cell surface. These interactions elicited inhibitory effects that suppressed activation of T cells and limited anti-tumour immunity, independently of SLAMF6 expression on tumour cells. mAbs against human SLAMF6 with a robust ability to disrupt the cis interactions strongly augmented T cell activation, reduced the proportions of exhausted T cells and inhibited tumour growth in vivo. Collectively, these findings show that SLAMF6 functions exclusively as a T cell inhibitory receptor, which is triggered by cis homotypic interactions. They also position SLAMF6 as a promising target for therapies aimed at enhancing anti-tumour immunity, regardless of SLAMF6 expression on tumour cells.
GPT-4o mini: Non-social science research article
Transferable enantioselectivity models from sparse data
Simone Gallarati, Erin M. Bucci, Abigail G. Doyle, Matthew S. Sigman
Full text
Identifying a catalyst class to optimize the enantioselectivity of a new reaction, either involving a different combination of known substrate types or an entirely unfamiliar class of compounds, is a formidable challenge. Statistical models trained on a reported set of reactions can help predict out-of-sample transformations1–5 but often face two challenges: (1) only sparse data are available i.e., limited information on catalyst–substrate interactions, and (2) simple stereoelectronic parameters may fail to describe mechanistically complex transformations.6,7 Here we report a descriptor generation strategy that accounts for changes in the enantiodetermining step with catalyst or substrate identity, allowing us to model reactions involving distinct ligand and substrate types. As validating case studies, we collected data on enantioselective nickel-catalyzed C(sp3)-couplings8 and trained statistical models with features extracted from the transition states and intermediates proposed to be involved in asymmetric induction. These models allow for the optimization of poorly performing examples reported in a substrate scope and are applicable to unseen ligands and reaction partners. This approach offers the opportunity to streamline catalyst and reaction development, quantitatively transferring knowledge learned on sparse data to novel chemical spaces.
GPT-4o mini: Non-social science research article
Astrocytes enable amygdala neural representations supporting memory
Olena Bukalo, Ruairi O’Sullivan, Yuta Tanisumi, Adriana Mendez, Chase Weinholtz, Sydney Zimmerman, Victoria Offenberg, Olivia Carpenter, Hrishikesh Bhagwat, Sophie Mosley, John J. O’Malley, Kerri Lyons, Yulan Fang, Jess Goldschlager, Linnaea E. Ostroff, Mario A. Penzo, Hiroaki Wake, Lindsay R. Halladay, Andrew Holmes
Full text
Brain systems mediating responses to previously encountered threats provide critical survival functions. Fear memory and extinction are underpinned by neural representations in the basolateral amygdala (BLA) 1–7 , but the contribution of non-neuronal cells, including astrocytes, to these processes remains unresolved. Here, using in vivo calcium (Ca 2+ ) imaging and causal astrocyte manipulations, we find that BLA astrocytes dynamically track fear state and support fear memory retrieval and extinction. By combining astrocyte manipulations with in vivo BLA neuronal Ca 2+ imaging and electrophysiological recordings, we show that astrocyte Ca 2+ signalling enables neuronal encoding of fear memory retrieval and extinction, and readout through a BLA–prefrontal circuit. Our findings reveal a key role for astrocytes in the generation and adaptation of fear-state-related neural representations, revising neurocentric models of critical amygdala-mediated adaptive functions.
GPT-4o mini: Non-social science research article
Transmission of MPXV from fire-footed rope squirrels to sooty mangabeys
Carme Riutord-Fe, Jasmin Schlotterbeck, Lorenzo Lagostina, Leonce Kouadio, Harriet R. Herridge, Moritz J. S. Jochum, Nea Yves Noma, Ane LĂłpez-Morales, Donata Hoffmann, Sten Calvelage, Hjalmar KĂŒhl, Alexander Mielke, Catherine Crockford, Liran Samuni, Roman M. Wittig, Martin Beer, Sery GonedelĂ©-Bi, Jan F. Gogarten, SĂ©bastien Calvignac-Spencer, Ariane DĂŒx, Livia V. Patrono, Fabian H. Leendertz
Full text
Mpox, caused by the monkeypox virus (MPXV; Orthopoxvirus monkeypox ), is on the rise in West and Central Africa 1–3 . African rodents, especially squirrels, are suspected to be involved in MPXV emergence, but no evidence of a direct transmission to humans or non-human primates has been established 4–9 . Here we describe an outbreak of MPXV in a group of wild sooty mangabeys ( Cercocebus atys ) in Taï National Park (Cîte d’Ivoire). The outbreak affected one-third of the group, killing four infants. To track its origin, we analysed rodents and wildlife carcasses from the region. We identified a MPXV-infected fire-footed rope squirrel ( Funisciurus pyrropus ), found dead 3 km from the mangabey territory 12 weeks before the outbreak. MPXV genomes from the squirrel and the mangabey were nearly identical. A video record from 2014 showed a mangabey from this group eating the same squirrel species and diet metabarcoding of faecal samples collected from mangabeys before the outbreak identified two samples containing fire-footed rope squirrel DNA. One of these samples was also the first positive for MPXV. This represents a rare case of direct detection of interspecies transmission. Our findings indicate that rope squirrels were the source of the MPXV outbreak in mangabeys. Because squirrels and non-human primates are hunted, traded and consumed by humans in West and Central Africa 10,11 , exposure to these animals probably represents risk for zoonotic transmission of MPXV.
GPT-4o mini: Non-social science research article
Targeting excessive cholesterol deposition alleviates secondary lymphoedema
Hwee Ying Lim, Yuning Zhang, Syaza Hazwany Mohammad Azhar, Chung Hwee Thiam, Michaela Taylor, Xuan Han Koh, Mohamed Ameen Shah Bin Mohamed Yunos, Shu Wen Tan, Sheau Yng Lim, Wei Siong Ong, Jasmine Goh, Si Hui Ng, Blake J. Cochran, Wai Kin Tham, Owen Ang, Sheng Jie Lim, Tze Chin Lim, Yanjun Chen, Sebastian Frederik Mause, Federico Torta, Markus R. Wenk, Kerry-Anne Rye, Bien Keem Tan, Veronique Angeli
Full text
Lymphoedema is a chronic debilitating disease caused by impaired lymphatic drainage and is characterized by tissue swelling, fat expansion, inflammation and fibrosis1,2. However, the exact mechanisms that drive lymphoedema are poorly understood. Although lymphatic vessels are known to transport cholesterol from peripheral tissues back to the systemic circulation3, the importance of impaired lymphatic drainage for cholesterol clearance in humans and its relevance to lymphoedema remain unknown. Here we show that lymphatic drainage insufficiency in human lymphoedema leads to excessive cholesterol accumulation in the lymphoedematous dermal tissue and around lymphatic vessels. Cholesterol deposition resulted in dermal adipose tissue remodelling, characterized by adipocyte hypertrophy and dysfunction, progressing to death and dermal fibrosis. Surgical intervention improved lymphatic drainage and reduced cholesterol deposition. Using two mouse models that reproduce features of human lymphoedema, we demonstrated that tissue swelling and dermal adipose tissue remodelling were ameliorated by the cholesterol-depleting agent cyclodextrin. Mechanistically, we demonstrated that cyclodextrin restored lymphatic drainage by promoting the regeneration of lymphatic vessels. This study unravels the role of impaired cholesterol clearance in driving lymphoedema and identifies tissue cholesterol as a promising therapeutic target for this currently incurable disease.
GPT-4o mini: Non-social science research article
Single-shot parity readout of a minimal Kitaev chain
Nick van Loo, Francesco Zatelli, Gorm O. Steffensen, Bart Roovers, Guanzhong Wang, Thomas Van Caekenberghe, Alberto Bordin, David van Driel, Yining Zhang, Wietze D. Huisman, Ghada Badawy, Erik P. A. M. Bakkers, Grzegorz P. Mazur, RamĂłn Aguado, Leo P. Kouwenhoven
Full text
Protecting qubits from noise is essential for building reliable quantum computers. Topological qubits offer a route to this goal by encoding quantum information non-locally, using pairs of Majorana zero modes. These modes form a shared fermionic state whose occupation—either even or odd—defines the fermionic parity that encodes the qubit1. Notably, this parity can only be accessed by a measurement that couples two Majoranas to each other. A promising platform for realizing such qubits is the Kitaev chain1, implemented in quantum dots coupled using superconductors2. Even the minimal two-site chain hosts a pair of Majorana modes, often called ‘poor man’s Majoranas’, which are spatially separated but offer limited protection compared with longer chains3,4,5. Here we introduce a measurement technique that reads out their parity through quantum capacitance. Our method couples two Majoranas and resolves their parity in real time, visible as random telegraph switching with lifetimes exceeding a millisecond. Simultaneous charge sensing confirms that the two parity states are charge neutral and remain indistinguishable to a probe that does not couple the modes. These results establish the essential readout step for time-domain control of Majorana qubits, resolving a long-standing experimental challenge.
GPT-4o mini: Non-social science research article
CSN5i-3 is an orthosteric molecular glue inhibitor of COP9 signalosome
Huigang Shi, Xiaorong Wang, Clinton Yu, Haibin Mao, Fenglong Jiao, Merav Braitbard, Ben Shor, Zhongsheng Zhang, Thomas R. Hinds, Shiyun Cao, Erkang Fan, Dina Schneidman-Duhovny, Lan Huang, Ning Zheng
Full text
Orthosteric inhibitors block enzyme active sites and prevent substrates from binding 1 . Enhancing their specificity through substrate dependence seems inherently unlikely, as their mechanism hinges on direct competition rather than selective recognition. Here we show that a molecular glue mechanism unexpectedly imparts substrate-dependent potency to CSN5i-3, an orthosteric inhibitor of the COP9 signalosome (CSN). We first confirm that CSN5i-3 inhibits CSN, which catalyses NEDD8 (N8) deconjugation from the cullin-RING ubiquitin ligases, by occupying the active site of its catalytic subunit, CSN5, and directly competing with the iso-peptide bond substrate. Notably, the orthosteric inhibitor binds free CSN with only micromolar affinity, yet achieves nanomolar potency in blocking its deneddylase activity. Cryogenic electron microscopy structures of the enzyme–substrate–inhibitor complex reveal that active site-engaged CSN5i-3 occludes the substrate iso-peptide linkage while simultaneously extending an N8-binding exosite of CSN5, acting as a molecular glue to cement the N8–CSN5 interaction. The cooperativity of this trimolecular CSN5i-3–N8–CSN5 assembly, in turn, sequesters CSN5i-3 at its binding site, conferring high potency to the orthosteric inhibitor despite its low affinity for the free enzyme. Together, our findings highlight the modest affinity requirements of molecule glues for individual target proteins and establish orthosteric molecular glue inhibitors as a new class of substrate-dependent enzyme antagonists.
GPT-4o mini: Non-social science research article
Months-long stability of the head-direction system
Sofia Skromne Carrasco, Guillaume Viejo, Adrien Peyrache
Full text
Spatial orientation enables animals to navigate their environment by rapidly mapping the external world and remembering key locations1. In mammals, the head-direction (HD) system is an essential component of the navigation system of the brain2. Although the tuning of neurons in other areas of this system is unstable—evidenced, for example, by the change in the spatial tuning of hippocampal place cells3 across days4,5,6,7,8,9,10,11—the stability of the neuronal code that underlies the sense of direction remains unclear. Here, by longitudinally tracking the activity of the same HD cells in the post-subiculum of freely moving mice, we show stability and plasticity at two levels. Although the population structure remained highly conserved across environments and over time, subtle shifts in population coherence encoded environment identity. In addition, the HD system established a distinct, environment-specific alignment between its internal representation and external landmarks, which persisted for weeks, even after a single exposure. These findings suggest that the HD system forms long-lasting orientation memories that are anchored to specific environments.
GPT-4o mini: Non-social science research article
Striatum-wide dopamine encodes trajectory errors separated from value
Eleanor H. Brown, Yihan Zi, Mai-Anh Vu, Safa Bouabid, Jack Lindsey, Chinyere Godfrey-Nwachukwu, Aaquib Attarwala, Ashok Litwin-Kumar, Brian DePasquale, Mark W. Howe
Full text
Goal-directed navigation requires animals to continuously evaluate their current direction and speed of travel relative to landmarks to discern whether they are approaching or deviating from their goal. Striatal dopamine release signals the reward-predictive value of cues1,2, probably contributing to motivation3,4, but it is unclear how dopamine incorporates an animal’s ongoing trajectory for effective behavioural guidance. Here we demonstrate that cue-evoked striatal dopamine release in mice encodes bidirectional trajectory errors reflecting the relationship between the speed and direction of ongoing movement relative to optimal goal trajectories. Trajectory error signals could be computed from locomotion or visual flow, and were independent from simultaneous dopamine increases reflecting learned cue value. Joint trajectory error and cue-value encoding were reproduced by the reward prediction error term in a standard reinforcement learning algorithm with mixed sensorimotor inputs. However, these two signals had distinct state space requirements, suggesting that they could arise from a common reinforcement learning algorithm with distinct neural inputs. Striatum-wide multifibre array measurements resolved overlapping, yet temporally and anatomically separable, representations of trajectory error and cue value, indicating how functionally distinct dopamine signals for motivation and guidance are multiplexed across striatal regions to facilitate goal-directed behaviour.
GPT-4o mini: Non-social science research article
Aluminium redox catalysis enables cyclotrimerization of alkynes
Xin Zhang, Liu Leo Liu
Full text
Aluminium comprises over 8% of Earth’s crust and is the most abundant metallic constituent1. Historically, aluminium catalysis has predominantly exploited the inherent Lewis acidity associated with its stable +III oxidation state2. Owing to its uniquely low electronegativity (1.61)—the lowest among p-block elements—and the absence of an inert-pair effect, aluminium presents formidable intrinsic challenges for engaging in catalytic redox transformations. Here we report the redox catalytic capability of a low-valent aluminium species, carbazolylaluminylene3, which carries out a complete Al(I)/Al(III) catalytic cycle encompassing oxidative addition, double insertion, intramolecular isomerization and reductive elimination—fundamental mechanistic steps conventionally exclusive to transition-metal catalysis. Leveraging this Al(I)/Al(III) redox cycle, we achieve highly efficient and regioselective Reppe cyclotrimerization of alkynes4,5, producing diverse benzene derivatives with a turnover number of up to 2,290. Through X-ray crystallographic and quantum chemical analyses, we elucidate how the dynamic nitrogen geometry within the carbazolyl ligand framework precisely modulates the aluminium coordination environment, thereby facilitating the catalytic cycle. This work fundamentally advances the conceptual understanding of main-group redox catalysis. It further sets a compelling precedent for future catalyst design and sustainable synthetic methodologies centred on aluminium redox transformations.
GPT-4o mini: Non-social science research article
Sub-second volumetric 3D printing by synthesis of holographic light fields
Xukang Wang, Yuanzhu Ma, Yihan Niu, Bo Xiong, Anke Zhang, Guoxun Zhang, Yifan Chen, Wei Wei, Lu Fang, Jiamin Wu, Qionghai Dai
Full text
Volumetric additive manufacturing has emerged as a promising technique for the flexible production of complex structures, with diverse applications in engineering, photonics and biology1,2. However, present methods still face a trade-off between resolution and volumetric build rate, restricting efficient and flexible production of high-resolution 3D structures. Here we propose a method, called digital incoherent synthesis of holographic light fields (DISH), to generate high-resolution 3D light distributions through continuous multi-angle projections with a high-speed rotating periscope without the requirement of sample rotation. The iterative optimization of the holograms for different angles in DISH maintains 19-ÎŒm printing resolution across the 1-cm range that is far beyond the depth of field of the objective and enables high-resolution in situ 3D printing of millimetre-scale objects within only 0.6 s. Acrylate materials in a range of viscosities are used to demonstrate the general compatibility of DISH. Integrating DISH with a fluid channel, we achieved mass production of complex and diverse 3D structures within low-viscosity materials, demonstrating its potential for broad applications in diverse fields.
GPT-4o mini: Non-social science research article
Maximizing perovskite electroluminescence with ordered 3D/2D heterojunction
Jingyu Peng, Xulan Xue, Shihao Liu, Yingguo Yang, Tianqi Yang, Bingyan Zhu, Xin Wang, Hanzhuang Zhang, Wenfa Xie, Gengsheng Chen, Shanglei Feng, Lina Li, Renzhong Tai, Aiwei Tang, Haizhou Lu, Wenyu Ji
Full text
Metal halide perovskite light-emitting diodes (PeLEDs) have demonstrated excellent external quantum efficiency (EQE), easy colour tunability and low-cost processability, making them promising next-generation display techniques1,2,3. However, PeLEDs still underperform compared with organic light-emitting diodes (LEDs) with an EQE of about 40% because of insufficient charge confinement and defect-caused non-radiative recombination on the film surface. Here we report a spontaneously formed 3D/2D vertically oriented perovskite heterojunction by means of a simple one-step spin-coating method, which could effectively confine the charge carriers and shift the radiation zone away from the defect-rich surface region. Notably, the 2D perovskite on top exhibits a wrinkled surface morphology, which offers up to 45.4% light extraction efficiency. The resulting PeLEDs achieved an EQE of 42.9% for the green emission (certified 42.3%). Our work sheds light on the strategies for fabricating high-efficiency PeLEDs in the future.
GPT-4o mini: Non-social science research article
Fossil isotope evidence for trophic simplification on modern Caribbean reefs
Jessica A. Lueders-Dumont, Aaron O’Dea, Erin M. Dillon, Brigida de Gracia, Chien-Hsiang Lin, Sergey Oleynik, Seth Finnegan, Daniel M. Sigman, Xingchen Tony Wang
Full text
Caribbean reefs have experienced major human-driven changes to their coral and fish communities 1–4 , yet how these changes have affected trophic dynamics remains poorly understood owing to challenges in reconstructing the trophic structure of pre-human-impact reefs. Advances in fossil-bound protein nitrogen isotope ( 15 N/ 14 N) analysis now enable the reconstruction of ancient trophic dynamics 5,6 , as the 15 N to  14 N ratio reflects an animal’s trophic position 7 . Here we apply this method to modern and prehistoric (7,000-year-old) fish otoliths (ear stones) and corals from Caribbean Panama and the Dominican Republic, focusing on fishes occupying low to middle trophic levels. We find that although the trophic level typically declined in high-trophic-level fishes over time, it increased or remained unchanged in low-trophic-level fishes, indicating that modern food chains are 60–70% shorter than on the prehistoric reefs in both Panama and the Dominican Republic. Furthermore, across all trophic groups, we observed a marked reduction in dietary variation, with a 20–70% lower trophic range on the modern reefs compared to the prehistoric reefs. This pattern is best explained by less dietary specialization in modern reefs, consistent with less ecological complexity than in prehistoric reefs. These differences document and quantify the trophic simplification that has occurred on modern Caribbean reefs, a change that may increase their vulnerability to ecosystem collapse.
GPT-4o mini: Non-social science research article
Publisher Correction: Physiology and immunology of a pig-to-human decedent kidney xenotransplant
Robert A. Montgomery, Jeffrey M. Stern, Farshid Fathi, Nathan Suek, Jacqueline I. Kim, Karen Khalil, Benjamin Vermette, Vasishta S. Tatapudi, Aprajita Mattoo, Edward Y. Skolnik, Ian S. Jaffe, Imad Aljabban, Tal Eitan, Shivani Bisen, Elaina P. Weldon, Valentin Goutaudier, Erwan Morgand, Fariza Mezine, Alessia Giarraputo, Idris Boudhabhay, Patrick Bruneval, Aurelie Sannier, Kevin Breen, Yasmeen S. Saad, Constanza Bay Muntnich, Simon H. Williams, Weimin Zhang, Larisa Kagermazova, Eloi Schmauch, Chandra Goparaju, Rebecca Dieter, Nikki Lawson, Amy Dandro, Ana Laura Fazio-Kroll, Lars Burdorf, David Ayares, Marc Lorber, Dorry Segev, Nicole Ali, David S. Goldfarb, Victoria Costa, Timothy Hilbert, Sapna A. Mehta, Ramin S. Herati, Harvey I. Pass, Ming Wu, Jef D. Boeke, Brendan Keating, Massimo Mangiola, Philip M. Sommer, Alexandre Loupy, Adam Griesemer, Megan Sykes
Full text
GPT-4o mini: Non-social science research article
Sub-part-per-trillion test of the Standard Model with atomic hydrogen
Lothar Maisenbacher, Vitaly Wirthl, Arthur Matveev, Alexey Grinin, Randolf Pohl, Theodor W. HĂ€nsch, Thomas Udem
Full text
Quantum electrodynamics (QED), the first relativistic quantum field theory, describes light–matter interactions at a fundamental level and is one of the pillars of the Standard Model (SM). Through the extraordinary precision of QED, the SM predicts the energy levels of simple systems such as the hydrogen atom with up to 13 significant digits 1 , making hydrogen spectroscopy an ideal test bed. The consistency of physical constants extracted from different transitions in hydrogen using QED, such as the proton charge radius r p , constitutes a test of the theory. However, values of r p from recent measurements 2–7 of atomic hydrogen are partly discrepant with each other and with a more precise value from spectroscopy of muonic hydrogen 8,9 . This prevents a test of QED at the level of experimental uncertainties. Here we present a measurement of the 2S–6P transition in atomic hydrogen with sufficient precision to distinguish between the discrepant values of r p and enable rigorous testing of QED and the SM overall. Our result Îœ 2S–6P = 730,690,248,610.79(48) kHz gives a value of r p = 0.8406(15) fm at least 2.5-fold more precise than from other atomic hydrogen determinations and in excellent agreement with the muonic value. The SM prediction of the transition frequency (730,690,248,610.79(23) kHz) is in excellent agreement with our result, testing the SM to 0.7 parts per trillion (ppt) and, specifically, bound-state QED corrections to 0.5 parts per million (ppm), their most precise test so far.
GPT-4o mini: Non-social science research article
Author Correction: Inference and reconstruction of the heimdallarchaeial ancestry of eukaryotes
Laura Eme, Daniel Tamarit, Eva F. Caceres, Courtney W. Stairs, Valerie De Anda, Max E. Schön, Kiley W. Seitz, Nina Dombrowski, William H. Lewis, Felix Homa, Jimmy H. Saw, Jonathan Lombard, Takuro Nunoura, Wen-Jun Li, Zheng-Shuang Hua, Lin-Xing Chen, Jillian F. Banfield, Emily St John, Anna-Louise Reysenbach, Matthew B. Stott, Andreas Schramm, Kasper U. Kjeldsen, Andreas P. Teske, Brett J. Baker, Thijs J. G. Ettema
Full text
GPT-4o mini: Non-social science research article
Author Correction: Environmentally driven immune imprinting protects against allergy
S. Erickson, B. Lauring, J. Cullen, R. Medzhitov
Full text
GPT-4o mini: Non-social science research article
Giant magnetocaloric effect and spin supersolid in a metallic dipolar magnet
Mingfang Shu, Xitong Xu, Ning Xi, Miao He, Junsen Xiang, Gexing Qu, Dmitry Khalyavin, Pascal Manuel, Jumpei G. Nakamura, Jinlong Jiao, Yonglai Liu, Guoliang Wu, Kaizhen Guo, Haitian Zhao, Wei Xu, Qingchen Duan, Ruidan Zhong, Xinqing Wang, Yuyan Han, Langsheng Ling, Xuefeng Sun, Dongsheng Song, Yuan Gao, Zhentao Wang, Xi Chen, Tian Qian, Shuang Jia, Haifeng Du, Gang Su, Wei Li, Jie Ma, Zhe Qu
Full text
The spin supersolid—a magnetic analogue of the supersolid that simultaneously exhibits solid and superfluid orders—has emerged as a promising sub-Kelvin refrigerant with strong low-energy fluctuations and associated entropic effects1. However, the stringent prerequisites have so far confined its presence to certain magnetic insulators. Here we report the discovery of a metallic spin supersolid in a rare-earth compound EuCo2Al9 (ECA), which is a good metal with excellent electrical and thermal conductivity. The high-spin Eu2+ ions form a three-dimensional lattice with stacked triangular layers, in which the spin-supersolid state is stabilized through a mechanism involving both Ruderman–Kittel–Kasuya–Yosida (RKKY) and dipolar couplings. Neutron diffraction shows microscopic evidence of spin supersolidity, demonstrating the coexistence of out-of-plane and in-plane spin orders in this alloy. Our RKKY–dipolar model successfully captures the metallic spin-supersolid Y and V phases in ECA, along with the 1/3 magnetization plateau. The observed nonclassical magnetization behaviours within these phases point to significant quantum fluctuations, probably enhanced by the conduction electrons. The resistivity measurements provide a transport probe for the spin-supersolid transitions, because of scattering of conduction electrons from local moments. Through the adiabatic demagnetization process, ECA achieves ultralow cooling to 106 mK, exhibiting a giant magnetocaloric effect that manifests sharp anomalies in the magnetic GrĂŒneisen ratio. ECA emerges as one of the first metallic spin supersolids, combining low cooling temperature, large magnetic entropy and ultrahigh thermal conductivity for high-performance sub-Kelvin refrigeration.
GPT-4o mini: Non-social science research article
Lasting Lower Rhine–Meuse forager ancestry shaped Bell Beaker expansion
Iñigo Olalde, Eveline Altena, Quentin Bourgeois, Harry Fokkens, Luc Amkreutz, Steffen Baetsen, Marie-France Deguilloux, Alessandro Fichera, Damien Flas, Francesca Gandini, Jan F. Kegler, Lisette M. Kootker, Judith van der Leije, Kirsten Leijnse, Constance van der Linde, Leendert Louwe Kooijmans, Roel Lauwerier, Rebecca Miller, Helle Molthof, Pierre Noiret, Daan C. M. Raemaekers, Maïté Rivollat, Liesbeth Smits, John R. Stewart, Theo ten Anscher, Michel Toussaint, Kim Callan, Olivia Cheronet, Trudi Frost, Lora Iliev, Matthew Mah, Adam Micco, Jonas Oppenheimer, Iris Patterson, Lijun Qiu, Gregory Soos, J. Noah Workman, Ceiridwen J. Edwards, Iosif Lazaridis, Swapan Mallick, Nick Patterson, Nadin Rohland, Martin B. Richards, Ron Pinhasi, Wolfgang Haak, Maria Pala, David Reich
Full text
Ancient DNA studies revealed that, in Europe from 6500 to 4000 bce, descendants of western Anatolian farmers mixed with local hunter-gatherers resulting in 70–100% ancestry turnover1, then steppe ancestry spread with the Corded Ware complex 3000–2500 bce2. Here we document an exception in the wetland, riverine and coastal areas of the Netherlands, Belgium and western Germany, using genome-wide data from 112 people 8500–1700 bce. A distinctive population with high (approximately 50%) hunter-gatherer ancestry persisted 3,000 years later than in most European regions, reflecting incorporation of female individuals of Early European Farmer ancestry into local communities. In the western Netherlands, the arrival of the Corded Ware complex was also exceptional: lowland individuals from settlements adopting Corded Ware pottery had hardly any steppe ancestry, despite a Y-chromosome characteristic of people associated with the early Corded Ware complex. These distinctive patterns may reflect the specific ecology that they inhabited, which was not amenable to full adoption of the early Neolithic type of farming introduced with Linearbandkeramik3, and resulted in distinct communities where transfer of ideas was accompanied by little gene flow. This changed with the formation of Lower Rhine–Meuse Bell Beaker users by fusion of local people (13–18%) and Corded Ware associated migrants of both sexes. Their subsequent expansion then had a disruptive impact across a much wider part of northwestern Europe, especially in Great Britain where they were the main source of a 90–100% replacement of local Neolithic ancestry.
GPT-4o mini: Non-social science research article
Parity-doublet coherence times in optically trapped polyatomic molecules
Paige Robichaud, Christian Hallas, Junheng Tao, Giseok Lee, Nathaniel B. Vilas, John M. Doyle
Full text
Polyatomic molecules provide complex internal structures that are ideal for applications in quantum information science1, quantum simulation2,3,4 and precision searches for physics beyond the standard model5,6,7,8,9. A key feature of polyatomic molecules is the presence of parity-doublet states. These structures, which generically arise from the rotational and vibrational degrees of freedom afforded by polyatomic molecules, are a powerful feature to pursue diverse quantum science applications7. Linear triatomic molecules contain ℓ-type parity-doublet states in the vibrational bending mode, which are predicted to exhibit robust coherence properties. Here we report optically trapped CaOH molecules prepared in ℓ-type parity-doublet states and realize a bare qubit coherence time of \({T}_{2}^{* }=0.8(2)\,{\rm{s}}\), which is longer than the 0.36 s lifetime of the bending mode10,11. We suppress differential Stark shifts by cancelling ambient electric fields using molecular spectroscopy and characterize parity-dependent trap shifts, which are found to limit the coherence time. The parity-doublet coherence times achieved in this work are a defining milestone for the use of polyatomic molecules in quantum science.
GPT-4o mini: Non-social science research article
Sleep-dependent clearance of brain lipids by peripheral blood cells
Bumsik Cho, Diane E. Youngstrom, Samantha Killiany, Camilo Guevara, Caitlin E. Randolph, Connor H. Beveridge, Pooja Saklani, Gaurav Chopra, Amita Sehgal
Full text
Sleep is viewed typically through a brain-centric lens, with little known about the role of the periphery 1,2 . Here we identify a sleep function for peripheral macrophage-like cells (haemocytes) in the Drosophila circulation, showing that haemocytes track to the brain during sleep and take up lipids accumulated in cortex glia due to wake-associated oxidative damage. Through a screen of phagocytic receptors expressed in haemocytes, we discovered that knockdown of eater —a member of the Nimrod receptor family—reduces sleep. Loss of eater also disrupts haemocyte localization to the brain and lipid uptake, which results in increased brain levels of acetyl-CoA and acetylated proteins, including mitochondrial proteins PGC1α and DRP1. Dysregulation of mitochondria, reflected in high oxidation and reduced NAD + , is accompanied by impaired memory and lifespan. Thus, peripheral blood cells, which we suggest are precursors of mammalian microglia, perform a daily function of sleep to maintain brain function and fitness.
GPT-4o mini: Non-social science research article
Pre-incision structures reveal principles of DNA nucleotide excision repair
Eric C. L. Li, Jinseok Kim, Sem J. Brussee, Kaoru Sugasawa, Martijn S. Luijsterburg, Wei Yang
Full text
Nucleotide excision repair (NER) removes bulky adducts from genomic DNA and prevents the ultraviolet light-sensitivity disease xeroderma pigmentosum, cancer and premature ageing1. After initial lesion recognition by XPC in global genome repair or by stalled RNA polymerases in transcription-coupled repair, a lesion and surrounding DNA duplex are unwound by TFIIH, which includes the ATPases XPB and XPD, and additional NER factors XPA, XPF, XPG and RPA, to form a DNA bubble2 comprising around 27 nucleotides. The double strand–single strand (ds-ss) junction-specific endonucleases XPF and XPG cleave DNA on the 5â€Č and 3â€Č sides of the lesion, respectively. Here we report the functional steps and atomic structures of the ATPase-driven and lesion-dependent DNA bubble formation and arrangement of the complete NER factors for dual incision. The unwinding of nearly 30 base pairs of DNA depends mainly on the double strand DNA translocase XPB and the duplex dividers XPA and XPF. XPD binds the lesion strand with XPF at the 5â€Č ds-ss junction. XPF cuts the lesion strand only after XPG binds the 3â€Č ds-ss junction. The ERCC1 subunit of XPF facilitates DNA strand separation and recruitment of RPA to the non-lesion strand. These findings provide insights on the causes of human diseases and potential targets for enhancing chemotherapeutic efficacy.
Nature DOI suffix ≠ "/s...": Not a research article
Ten years since the first reported observation of gravitational waves
Gudrun Wanner
Full text
Nature DOI suffix ≠ "/s...": Not a research article
China to punish universities that fail to sanction research misconduct
Mohana Basu
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How some COVID vaccines triggered rare blood-clot disorder
Mohana Basu
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Internet blackout: Iran’s academic shutdown
Encieh Erfani
Full text
Nature DOI suffix ≠ "/s...": Not a research article
What drugs are safe during pregnancy? There’s a shocking lack of data
Giorgia Guglielmi
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Can the clean-energy revolution save us from climate catastrophe?
Jeff Tollefson
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Public-speaking tips from the experts: what scientists can learn from comics, musicians and actors
John Tregoning
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How to rescue the aid industry: focus on conflict prevention, not just relief
Rabah Arezki
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Universities in exile: displaced scholars count the costs of starting afresh
Rachel Brazil
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Untapped catalytic ability of aluminium has been unlocked
Stuart Burnett, Catherine Weetman
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Cheap AI chatbots transform medical diagnoses in places with limited care
Chris Simms
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Trump team’s new rule could make firing government scientists easier
Dan Garisto
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Bonobo’s tea party is first demonstration of pretend play in a non-human
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Marine protection in the Azores: a triumph for conservation and sustainability
Enric Sala
Full text
Nature DOI suffix ≠ "/s...": Not a research article
What can I do if my idea has been plagiarized?
Bianca Nogrady
Full text
Nature DOI suffix ≠ "/s...": Not a research article
These hungry immune cells tidy sleeping flies’ brains
Benjamin Thompson, Nick Petrić Howe
Full text
Nature DOI suffix ≠ "/s...": Not a research article
My ‘detective’ job as a competitive-intelligence consultant for pharma
Christina Szalinski
Full text
Nature DOI suffix ≠ "/s...": Not a research article
OpenClaw AI chatbots are running amok — these scientists are listening in
Mohana Basu
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Epstein files reveal deeper ties to scientists than previously known
Dan Garisto
Full text
Nature DOI suffix ≠ "/s...": Not a research article
The dark side of green technology: what do electric vehicles really cost?
Chris Stokel-Walker
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Dozens of researchers will move to France from US following high-profile bid to lure talent
Elizabeth Gibney, Max Kozlov
Full text
Nature DOI suffix ≠ "/s...": Not a research article
These mysterious ridges could be the secret to younger skin
Nick Petrić Howe
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How to deal with the survey-taking AI agents that threaten to upend social science
Folco Panizza, Yara Kyrychenko, Jon Roozenbeek
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Four ways I ensured my research brought about real-world change
Lan Nguyen Chaplin
Full text
Nature DOI suffix ≠ "/s...": Not a research article
AI help in grant proposals tied to higher funding odds at NIH
Max Kozlov
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Squirrels could be a reservoir for the virus that causes mpox
Edyth Parker, Christian Happi
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Briefing Chat: 'External lungs' keep man alive for 48 hours until transplant
Benjamin Thompson, Maren Hunsberger
Full text
Nature DOI suffix ≠ "/s...": Not a research article
My mission to make life more user friendly for the disability community
Laurie Udesky
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Clearing trapped cholesterol could relieve lymphoedema
Babak Mehrara
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Tumours use neurons as hotline to the brain
Jacob Smith
Full text
Nature DOI suffix ≠ "/s...": Not a research article
US repeals key ‘endangerment finding’ that climate change is a public threat
Alexandra Witze
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: The dark side of the battery boom
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
China’s biotech boom: why the nation must collaborate to stay ahead
Lizzi C. Lee, Jing Qian
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Preserving water under megacities is crucial — and urgent
Yaqiang Wei, Hui Li
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Hunter-gatherers took refuge in European 'water world' for millennia
Ewen Callaway
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Self-powered vibration sensor for wearable health care and voice detection
Seungjae Lee, Hyunhyub Ko
Full text
Nature DOI suffix ≠ "/s...": Not a research article
The ‘astounding’ rise of semaglutide — and what’s next for weight-loss drugs
Bianca Nogrady
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Publishing less won’t save the research system
Malgorzata Lagisz
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Science funding needs fixing — but not through chaotic reforms
John S. Tregoning
Full text
Nature DOI suffix ≠ "/s...": Not a research article
18,000,000 minutes
Spencer Nitkey
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Charge-neutral electrons are odd — except when they’re even
Andrew P. Higginbotham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Exercise rewires the brain — boosting the body’s endurance
Mariana Lenharo
Full text
Nature DOI suffix ≠ "/s...": Not a research article
US applications for prestigious European research grants surge
Elizabeth Gibney
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Lab morale got you down? Try a handbook
Amanda Heidt
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Caffeine might reduce dementia risk and slow cognitive decline
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Measles is raging worldwide: are you at risk?
Mariana Lenharo
Full text
Nature DOI suffix ≠ "/s...": Not a research article
From ancient temples to bomb craters: explore Laos’s layered history — in photos
Dave Tacon
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Coffee linked to slower brain ageing in study of 130,000 people
Amanda Heidt
Full text

Nature Human Behaviour

GPT-4o mini: Non-social science research article
Humans can use positive and negative spectrotemporal correlations to detect rising and falling pitch
Parisa A. Vaziri, Samuel D. McDougle, Damon A. Clark
Full text
To discern speech or appreciate music, the human auditory system detects how pitch changes over time (pitch motion). Here, using psychophysics, computational modelling, functional neuroimaging and analysis of recorded speech, we ask whether humans can detect pitch motion using computations analogous to those used by the visual system. We adapted stimuli from studies of vision to create novel auditory correlated noise stimuli that elicited robust pitch motion percepts. In psychophysical experiments, we discovered that humans can judge pitch direction from spectrotemporal intensity correlations. Robust sensitivity to negative spectrotemporal correlations is a direct analogue of illusory ‘reverse-phi’ motion in vision, constituting a new auditory illusion. Functional MRI measurements in auditory cortex supported the hypothesis that human auditory processing may employ pitch direction opponency. Linking lab findings to real-world perception, we analysed recordings of English and Mandarin speech and found that pitch direction was signalled by both positive and negative spectrotemporal correlations, suggesting that sensitivity to both types confers ecological benefits. This work reveals how motion detection algorithms sensitive to local correlations are deployed by the central nervous system across disparate modalities (vision and audition) and dimensions (space and frequency).
GPT-4o mini: Non-social science research article
Caprine dairy exploitation on the Iranian Plateau from the seventh millennium BC
Emmanuelle Casanova, Hossein Davoudi, Antoine Zazzo, Séverine Zirah, Jérémy Jacob, Christine Hatté, Audrey Boco-Simon, François Thil, Caroline Gauthier, Jebrael Nokandeh, Abbas Alizadeh, Fereidoun Biglari, Reinhard Bernbeck, Susan Pollock, Akira Tsuneki, Omolbanin Ghafoori, Homa Fathi, Frank Hole, Emmanuelle Demey-Thomas, Joëlle Vinh, Marjan Mashkour
Full text
Animal domestication and development of pastoralism in southwest Asia revolutionized human subsistence strategies. Various centres of ruminant domestication and diffusion routes of agropastoralism have been identified. The area between the northern and central Zagros Mountains on the Iranian Plateau is a cradle for goat domestication and eastward spread of agropastoralism. However, the early exploitation of ruminant milk by pastoral communities in the Zagros remains insufficiently studied. Here we show residues of caprine dairy products that were detected from the analysis of lipid residues in pottery vessels and protein residues in human dental calculus. These results, combined with the faunal spectra and radiocarbon analyses directly on the dairy residues, show that sheep and goat dairy products were widely exploited in the Zagros from the seventh millennium BC. This pattern parallels the contemporaneous exploitation of cattle milk in Anatolia. Neolithic communities in both regions reveal similarly complex dynamics of early ruminant milk use, marking the emergence of independent yet synchronous trajectories in the diffusion of agropastoral lifeways.
Language barriers and the speed of international knowledge diffusion
Kyle Higham, Sadao Nagaoka
Full text
Language barriers and translation costs are persistent obstacles to communication and have particularly pronounced economic impacts in technical domains. Here we provide causal evidence on the effects of language barriers on the speed and extent of knowledge diffusion by exploiting a change in US patent policy that resulted in earlier disclosure of English-language technical knowledge from Japan. Using a targeted sample of 2,770 citations from US-based inventors to Japanese inventions, we find that language barriers accounted for almost half the diffusion lag of Japan-originating knowledge to US-based inventors, relative to Japan-based inventors. This acceleration is significant only for firms with limited ability to translate (small research and development scale, or little involvement in the Japanese market) and is more pronounced for the diffusion of high-quality inventions, suggesting difficulties in quality-targeted translation. Thus, early publication of patent applications provides a substantial public good for cumulative innovation through accelerated access to translated foreign patents.
The role of context in continuity and segmentation
Shira Baror, Mor Cohen, Nofar Haik, Guy Avraham, Aya Ben-Yakov
Full text
Human experience intertwines continuity, the seamless flow of events, with segmentation, the spontaneous partitioning of experience into discrete units. Despite their cognitive significance, it is unclear whether these processes operate independently or share a common mechanism. Here we explored this question by examining the link between serial dependence (SD)—the tendency to align perceptions with prior decisions—and the impact of event boundaries, prompted by contextual shifts, on memory. Considering a Bayesian perspective that associates SD with predictions, and segmentation with prediction errors, a common mechanism may govern both processes. Across three experiments (N = 816), we tested how contextual changes affect SD and segmentation-related memory effects. The results indicate that both processes are context-sensitive. Contextual boundaries can reduce SD even in the absence of sensory change, and boundaries modulate memory in ways consistent with event segmentation. Yet, across experiments we observed dissociable patterns of boundary effects on SD and memory, which are slightly more consistent with distinct contextual influences on perception and memory than with a single unified predictive system. Boundary effects on SD and memory did not covary across participants, but given the low within-participant reliability of these measures, this absence of correlation cannot be taken as strong evidence for independence. Overall, our findings show that both SD and memory are shaped by context, but clarifying whether they reflect a shared or partly distinct mechanism will require further research.

Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Decoding antibody response to MERS-CoV in wild dromedary camels
Faten Idoudi, Ruoke Wang, Long Tian, Ziqing Yang, Kenn Ka-Heng Chik, Peng Chen, Rahma Benabderrazek, Lili Fu, Ruijie Tan, Sayda Dhaouadi, Zakaria Benlasfar, Mahmoud Somia, Qi Zhang, Xuanling Shi, Jasper Fuk-Woo Chan, Kwok-Yung Yuen, Xinquan Wang, Balkiss Bouhaouala-Zahar, Linqi Zhang
Full text
Wild dromedary camels in the Arabian Peninsula and Africa have harbored antibodies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) for decades, predating zoonotic spillover to humans. However, the potency, specificity, and structural characteristics of these antibodies remain poorly understood. Here, we characterize the antibody responses of naturally infected wild dromedary camels in Tunisia, a MERS-CoV-endemic region. Plasma antibodies from nine camels exhibited variable neutralizing activity, generally increasing with age, and were largely autologous, with minimal cross-reactivity to SARS-CoV-1 or SARS-CoV-2. From a VHH antibody library derived from the peripheral blood mononuclear cells (PBMCs) of a single camel (D17), we identified 34 unique sequences with previously unreported germline origins and unusually long complementarity-determining region 3 (CDR3) sequences. Eight representative VHHs, expressed as human Fc fusions, displayed high-affinity binding to the MERS-CoV receptor-binding domain (RBD) and broad neutralization to RBD mutants (IC 50 : 1.05 to 9.55 ng/mL). Crystal structural analysis revealed distinct neutralization mechanisms: VHH-227 fully blocked DPP4 binding, achieving complete neutralization, while VHH-T71, with partial neutralization (~80%), targeted the RBD core subdomain. This study provides comprehensive characterization of wild dromedary antibody responses, identifying novel nanobodies (Nbs) with broad and potent neutralization to naturally occurring RBD mutants. These findings offer insights into camel immunity and highlight promising candidates for MERS-CoV prophylactic and therapeutic development.
GPT-4o mini: Non-social science research article
Abdominal ultrasound activates afferent vagus nerve fibers and induces anti-inflammatory effects
Kotaro Shimoyama, Mamoru Tanida, Jun Aruga, Tomohiro Furusato, Chia-Hsien Wu, Yasuna Nakamura, Daisuke Takahashi, Go Kanzaki, Atsuhiro Maeda, Takao Shioya, Nobuo Tsuboi, Chikara Abe, Takashi Yokoo, Ryusuke Umene, Tsuyoshi Inoue
Full text
Abdominal ultrasound has emerged as a noninvasive modality with immunomodulatory potential. Although its anti-inflammatory effects have been demonstrated in various disease models, the underlying mechanisms remain unclear. Previous studies suggest that ultrasound promotes anti-inflammatory macrophage polarization via α7 nicotinic acetylcholine receptor (α7nAChR) signaling in the spleen. However, the upstream events initiating this response have not been elucidated. Here, we demonstrate that abdominal ultrasound activates afferent vagal fibers and suppress systemic inflammation. In a murine model of lipopolysaccharide (LPS)-induced endotoxemia, abdominal ultrasound significantly reduced plasma TNF-α levels. This anti-inflammatory effect was attenuated by subdiaphragmatic vagotomy (SDVx) or afferent vagal blockade. Electrophysiological recordings revealed increased cervical vagus nerve activity during ultrasound stimulation, which was eliminated by intraperitoneal lidocaine, confirming activation of abdominal sensory afferents. Furthermore, abdominal ultrasound induced c-Fos expression in the nucleus tractus solitarius (NTS), consistent with central activation via vagal afferent input. These findings provide direct mechanistic evidence that abdominal ultrasound stimulates afferent vagal pathways.
GPT-4o mini: Non-social science research article
Topological signatures of collective dynamics and turbulent-like energy cascades in apolar active granular matter
Zihan Zheng, Cunyuan Jiang, Yangrui Chen, Matteo Baggioli, Jie Zhang
Full text
Active matter refers to a broad class of nonequilibrium systems where energy is continuously injected at the level of individual “particles.” These systems exhibit emergent collective behaviors that have no direct thermal-equilibrium counterpart. Their scale ranges from micrometer-sized swarms of bacteria to meter-scale human crowds. In recent years, the role of topology and self-propelled topological defects in active systems has garnered significant attention, particularly in polar and nematic active matter. Building on these ideas, we investigate emergent collective dynamics in apolar active granular fluids. Using isotropic granular vibrators as a model experimental system of apolar active Ornstein–Uhlenbeck particles in a dry environment, we uncover a distinctive three-stage time evolution arising from the intricate interplay between activity and inelastic interactions. By analyzing the statistics, spatial correlations, and dynamics of vortex-like topological defects in the displacement vector field, we demonstrate their ability to describe this intrinsic collective motion. Furthermore, associated to these topological defects, we reveal the onset of a turbulent-like inverse energy cascade, where kinetic energy transfers across different length scales over time. As the system evolves, the power scaling of the energy transfer increases with the duration of observation. Our findings show that topological concepts can be extended to the nonequilibrium dynamics of apolar active matter, revealing a direct link between microscopic topological processes and emergent large-scale behaviors in active granular fluids that lack both a well-defined direction of motion and an intrinsic axis of orientation at the particle scale.
GPT-4o mini: Non-social science research article
Learning nature’s assembly language with polymers
Oliver Xie, Alexander E. Cohen, Martin Z. Bazant, Bradley D. Olsen
Full text
The self-assembly of matter into ordered structures is ubiquitous throughout nature and engineered systems. Programming a material’s macroscopic properties via molecular-level structural control is a grand scientific challenge, requiring methods for inverse design that can design a targeted molecule to achieve a given self-assembled structure. One model system that serves as a common proving ground for inverse design algorithms is block copolymers. In these systems, self-consistent field-theory (SCFT) provides a robust thermodynamic model for predicting self-assembly for a given molecular sequence. This work presents a computational algorithm which learns the reverse translation, allowing a target structure to be achieved by varying molecular sequence. The algorithm is based on development of an adjoint solution of the SCFT equations allowing incorporation of automatic differentiation. The power of this algorithm is demonstrated by inverse designing polymer sequences to yield equilibrium structures, resolving the long-standing dilemma of navigating the combinatorial explosion of sequence possibilities offered by complex copolymer designs. The inverse designed sequences show that the algorithm learns to modulate unfavorable block interactions to stabilize these complex morphologies. By learning how to program self-assembly at the molecular-level using only a thermodynamic model, this work opens the door to similar computational inverse design across other soft matter systems.
GPT-4o mini: Non-social science research article
Bacterial iron acquisition by Escherichia coli is facilitated by amino acid complexation in a rapid-renewal environment
Juanita Lara-Gutiérrez, Jen Nguyen, Matthew R. McIlvin, Ichiko Sugiyama, Zachary C. Landry, Uria Alcolombri, Sammy Pontrelli, Joaquín Jiménez-Martínez, Uwe Sauer, Terence Hwa, Johannes M. Keegstra, Mak A. Saito, Roman Stocker
Full text
In natural environments, bacteria often encounter low concentrations of nutrient mixtures that are continuously replenished by physical processes such as fluid flow. Studying bacterial physiology under such conditions is experimentally challenging because it is difficult to maintain steady, low nutrient concentrations with rapid renewal. Most studies on nutrient limitation have used approaches such as the chemostat, which rely on long renewal times to sustain low concentrations. We developed a Millifluidic Continuous Culture Device (MCCD), inspired by microfluidics, that enables bacterial cultivation in nutrient mixtures at low micromolar concentrations with rapid renewal driven by fluid flow. Unlike microfluidic systems, the MCCD retains sufficient culture volume to support batch-scale ‘omic analyses. Using the MCCD, we cultured Escherichia coli in a mixture of amino acids and nucleobases at three concentration ranges spanning a fivefold difference in growth rates. Surprisingly, at the lowest concentration range, cells exhibited proteomic signatures of iron limitation despite equal total ferrous iron across conditions. Uptake experiments with labeled iron–histidine and iron–cysteine complexes confirmed that amino acids facilitated ferrous iron acquisition. Under continuous flow, siderophores were washed out, rendering this pathway ineffective and revealing a previously unrecognized mechanism of iron acquisition via soluble ferrous iron–amino acid complexes. These findings highlight the importance of studying bacterial physiology at low nutrient concentrations and also suggest a broader role for other organic substrates capable of complexing iron as potential iron sources in environments with rapid renewal.
GPT-4o mini: Non-social science research article
Theoretical limits for sensing through phase separation
Henry Alston, Mason Rouches, Arvind Murugan, Aleksandra M. Walczak, Thierry Mora
Full text
Biomolecular condensates form on timescales of seconds in cells upon environmental or compositional changes. Condensate formation is thus argued to act as a mechanism for sensing such changes and quickly initiating downstream processes, such as forming stress granules in response to heat stress and amplifying cyclic GMP-AMP synthase enzymatic activity upon detection of cytosolic DNA. Here, we study a dynamical model of droplet nucleation and growth to demonstrate how phase separation allows cells to discriminate small concentration differences on finite, biologically relevant timescales. We propose optimal sensing protocols, which use the sharp onset of phase separation. We show how, given experimentally measured rates, cells can achieve rapid and robust sensing of concentration differences of 1 % on a timescale of minutes, offering an alternative to classical biochemical mechanisms.
GPT-4o mini: Non-social science research article
HSCs/MPPs as cells of origin with altered differentiation hierarchy impairing immunomicroenvironment in PML::RARA and CBFα/ÎČ fusion AML
Niu Qiao, Zi-Xuan Wang, Yu-Liang Zhang, Liu-Qing-Qing Zhang, Hong-Ming Zhu, Xiang-Qin Weng, Yong-Mei Zhu, Wen-Yan Cheng, Jian-Feng Li, Lu Jiang, Xiao-Yu Yan, Guang Yang, Yang Shen, Sheng-Yue Wang, Zhu Chen, Xiao-Jian Sun, Feng Liu, Sai-Juan Chen
Full text
The theoretical possibility for leukemia stem cells (LSCs) to produce both leukemia blasts and dysfunctional immune cells remains underexplored. Here, we investigate three major fusion transcription factor (fTF)-driven acute myeloid leukemia (AML) subtypes [ RUNX1(CBFα)::RUNX1T1 , PML::RARA , and CBFB::MYH11 ] using two optimized single-cell RNA-sequencing technologies to trace fTF expression in 24 de novo AML patients. We demonstrate that the fTFs are widely expressed not only in leukemia blasts but also in differentiated myeloid and lymphoid cells, indicating hematopoietic stem cells or multipotent progenitors (HSCs/MPPs) as LSCs that propagate altered cellular differentiation hierarchies, including immune cells. DNA-FISH confirms the presence of fTFs in T lymphoid and erythroid cells, and targeted sequencing of secondary mutations in sublineages of cells corroborates hierarchical and stepwise leukemogenesis. By tracking RUNX1::RUNX1T1 -expressing cells in patients with or without relapse post–frontline chemotherapy, we highlight the necessity of eradicating LSCs to achieve sustained long-term complete remission and restore a functional immune system capable of suppressing residual disease over time. Comparative single-cell transcriptome analyses further reveal that fTFs are associated with AML subtype-specific differentiation defects in both innate and adaptive immune compartments, suggesting an altered landscape of immune cell–cell communication networks that may facilitate the survival and proliferation of leukemic blasts. Through the examination of intercellular communications among various putative fTF + and normal cell populations, we developed a ligand–receptor (L–R)-based risk-scoring model with independent prognostic value. Collectively, these findings provide insights into the cells of origin of LSCs and the implications of fTF expression for the immune landscape of AML.
GPT-4o mini: Non-social science research article
Climate change drives a decline in global grazing systems
Chaohui Li, Maximilian Kotz, Prajal Pradhan, Xudong Wu, Yuanchao Hu, Zhi Li, Guoqian Chen
Full text
Grazing systems represent the most extensive production systems in the world and are highly sensitive to climate change. However, their global-scale sensitivity and vulnerability to climate impacts remain poorly understood. Here, we apply the safe climatic space framework to assess how changes in core climatic drivers of grazing suitability, including temperature, precipitation, humidity, and wind speed, will reshape global grassland-based grazing systems. Our analysis projects a net decline of 36 to 50% of areas in climate suitability for grazing by 2100, accompanied by inter- and intracontinental shift of grazing suitability. These changes are expected to negatively affect 110 to 140 million pastoralists and 1.4 to 1.6 billion livestock, with particularly severe impacts in Africa. We further show that 51 to 81% of these impacted populations reside in countries with low income, serious hunger, severe gender inequality, and high political fragility. Our study implies that future climate change will threaten grazing suitability across large portions of Earth, endangering the livelihoods of numerous communities and potentially triggering widespread socioeconomic consequences.
GPT-4o mini: Non-social science research article
In vitro sex-specific function–structure relationship in neonatal rat cardiac monolayers
Mary Tran, Toby Viet Nguyen, Suhani Khandelwal, Anna Grosberg
Full text
Even though in vivo rodent studies have been instrumental in investigating sex-specific differences in cardiac health, function, and pathology, they fall short in providing a fast and flexible platform for investigating sex differences of cardiac anisotropic monolayer in isolation. In vitro platforms offer an accessible and more controlled alternative to dissect and study the mechanisms by which male and female cardiac tissue sheets differ from one another. Here, we have shown on an in vitro heart-on-a-chip platform, primary neonatal rat ventricular myocytes can serve as a viable model showing sex chromosome-driven characteristics when presented with identical experimental conditions. With controlled experimental conditions, the self-assembly of isolated cardiomyocytes resulted in morphological differences in the structure of the contractile apparatus. More importantly, the assembly of cardiac cells into confluent monolayers had a sex chromosome-driven divergence in both structure and the corresponding function. This work reports the characterization of the difference between sex-specific neonatal rat ventricular myocytes in in vitro culture. Thus, this offers an avenue to investigate sex-based variations in cardiac function that are otherwise difficult to study.
GPT-4o mini: Non-social science research article
Carbon–phosphorus exchange rate constrains density–speed trade-off in arbuscular mycorrhizal fungal growth
Corentin Bisot, Loreto Oyarte Galvez, FĂ©lix Kahane, Marije van Son, Bianca Turcu, Rob Broekman, Kai-Kai Lin, Paco Bontenbal, Max Kerr Winter, Vasilis Kokkoris, Stuart A. West, Christophe Godin, E. Toby Kiers, Thomas S. Shimizu
Full text
Symbiotic nutrient exchange between arbuscular mycorrhizal (AM) fungi and their host plants varies widely depending on their physical, chemical, and biological environment. Yet dissecting this context dependency remains challenging because we lack methods for tracking nutrients such as carbon (C) and phosphorus (P). Here, we developed an approach to quantitatively estimate C and P fluxes in the AM symbiosis from comprehensive network morphology quantification, achieved by robotic imaging and machine learning based on roughly 100 million hyphal shape measurements. We found that rates of C transfer from the plant and P transfer from the fungus were, on average, related proportionally to one another. This ratio was nearly invariant across AM fungal strains despite contrasting growth phenotypes but was strongly affected by plant host genotype. Fungal phenotype distributions were bounded by a Pareto front with a shape favoring specialization in an exploration–exploitation trade-off. This means AM fungi can be fast range expanders or fast resource extractors, but not both. Manipulating the C/P exchange rate by swapping the plant host genotype shifted this Pareto front, indicating that the exchange rate constrains possible AM fungal growth strategies. We show by mathematical modeling how AM fungal growth at fixed exchange rate leads to qualitatively different symbiotic outcomes depending on fungal traits and nutrient availability.
GPT-4o mini: Non-social science research article
A systems approach identifies MERTK as a therapeutic vulnerability in ZFTA-RELA-driven ependymomas
Marina Chan, Songli Zhu, Zachary R. Russell, Sonali Arora, Aleena K. S. Arakaki, Joel M. Vaz, Deby Kumasaka, Frank Szulzewsky, Antony Michealraj, Eric C. Holland, Taranjit S. Gujral
Full text
Ependymomas (EPN) are rare central nervous system tumors that account for approximately 10% of intracranial tumors in children and 4% in adults. Despite their clinical and molecular heterogeneity, spanning supratentorial, posterior fossa, and spinal subtypes, treatment remains limited to surgery and radiotherapy, with chemotherapy offering minimal benefit. Here, we performed transcriptomic analysis of 370 human ependymoma samples and identified two distinct molecular subgroups: EPN-E1 and EPN-E2. The EPN-E1 cluster is enriched for supratentorial tumors harboring ZFTA-RELA fusions (ZFTA-RELA fus ), which occur in over 70% of cases and are associated with poor prognosis. To identify targeted therapies for this aggressive subtype, we validated a ZFTA-RELA fus mouse model that recapitulates the human EPN-E1 transcriptome and used it for target discovery. Through Kinome Regularization, a machine learning-driven polypharmacology approach, we identified MERTK as a critical regulator of tumor cell viability. Genetic depletion or pharmacologic inhibition of Mertk reduced cell growth ex vivo, and treatment with a clinical-grade MERTK inhibitor significantly suppressed tumor proliferation in vivo. Both human EPN-E1 tumors and ZFTA-RELA fus mouse tumors exhibited elevated expression of MERTK and its ligand GAS6, and MERTK inhibition led to suppression of pro-survival signaling pathways including MEK/ERK (Mitogen-Activated Protein Kinase Kinase/Extracellular Signal-Regulated Kinase) and PI3K/AKT (Phosphoinositide 3-Kinase/Protein Kinase B). Notably, over 80% of genes upregulated in ZFTA-RELA fus tumors were downregulated following MERTK inhibition, indicating a strong dependency on this pathway for tumor maintenance. These findings define a signaling vulnerability in ZFTA-RELA-driven ependymomas and support the clinical development of MERTK-targeted therapies for patients with the high-risk EPN-E1 subtype.
GPT-4o mini: Non-social science research article
Molecular assemblies and pharmacology of cerebellar GABA A receptors
Chang Sun, Jennifer N. Jahncke, Kevin M. Wright, Eric Gouaux
Full text
GABA A receptors (GABA A Rs) mediate fast inhibitory neurotransmission in the brain and are assembled from 19 subunit isoforms into multiple pentameric assemblies. Although α1-containing GABA A Rs are broadly expressed and are pharmacologically important, the molecular diversity of native α1-based assemblies in specific brain regions remains incompletely understood. Here, we use immunofluorescence, mass spectrometry, and cryogenic electron microscopy (cryo-EM) to characterize the spatial distribution, subunit composition, and structural architecture of native α1-containing GABA A Rs in the rat cerebellum. Confocal microscopy reveals robust colocalization of α1 and Îł2 subunits across cerebellar layers, including prominent labeling at glomerular synapses. Biochemical purification and proteomic analysis identify a range of α, ÎČ, and Îł subunits, along with abundant α6 and ÎŽ subunits. Using cryo-EM and automated subunit identification, we resolve eight α1-containing receptor assemblies, including the first structure of α6-containing receptors. We further determine the binding mode of the α6-selective pyrazoloquinolinone modulator PZ-II-029 at the α + /Îł – interface, showing ligand-induced expansion of the entire extracellular domain (ECD). Together, our study defines the structure and subunit composition of the α1-containing cerebellar GABA A Rs and elaborates the molecular interactions between native receptors and pyrazoloquinolinone, thereby laying the groundwork for brain region and subunit-specific pharmacology.
GPT-4o mini: Non-social science research article
Neurotensin in the extended amygdala maintains wakefulness in novel environments
Chi Jung Hung, Shuhei Ueda, Sheikh Mizanur Rahaman, Mikiyasu Yamamoto, Jiahui Li, Noriaki Fukatsu, Haruhiko Bito, Hiroshi Yamaguchi, Akihiro Yamanaka, Sayaka Takemoto-Kimura, Daisuke Ono
Full text
Animals remain awake in unfamiliar environments to assess potential safety threats, a process involving changes in neuronal activity within sleep–wake regulatory brain regions. However, the specific circuits and neurotransmitters involved remain poorly understood. Here, we show that neurotensin (NTS) peptides in corticotropin-releasing factor (CRF) neurons of the lateral part of the interstitial nucleus of the posterior limb of the anterior commissure (IPACL) play a key role in maintaining wakefulness in response to environmental changes. Activation of IPACL CRF neurons increased wakefulness, whereas their inhibition or deletion of NTS reduced wakefulness in novel environments. These neurons are activated in response to exposure to a novel environment and project primarily to the substantia nigra pars reticulata (SNr) and release NTS, which modulates wakefulness. These findings suggest that NTS signaling from IPACL CRF neurons to the SNr is essential for sustaining wakefulness in unfamiliar or changing environments.
GPT-4o mini: Non-social science research article
Ultrasonic vocal communication of negative affective states in laboratory mice
Hideaki Inagaki, Takahiro Ushida
Full text
Anxiety disorders are the most common mental disorders, resulting in substantial social and economic costs stemming from reduced productivity. Pharmacotherapy is the most widely used treatment for these disorders, and effective improvement requires a reliable animal model of human anxiety. Although communication in rats using ultrasonic vocalizations (USVs) has been reported as a biologically valid animal model of human anxiety, an equivalent model in mice has not yet been established. To identify such USVs, we conducted physiological, behavioral, and pharmacological experiments using ddY strain mice. Ultrasonic sine waves within a limited frequency range enhanced anxiety levels in male mice. When female mice were exposed to ethologically stressful situations, they emitted a specific type of USV that was not only quantitatively abundant and qualitatively distinct but also within a frequency range that induced increased anxiety in male mice. Playback of these female USVs induced anxiety-related affective changes in male mice. We believe that these findings represent a step toward demonstrating ultrasonic vocal communication of negative affective states in laboratory mice. This study offers a foundation for developing mouse models using USVs as a tool to understand the pathogenic mechanisms of human anxiety disorders and to develop neuropharmacological therapies.
GPT-4o mini: Non-social science research article
Short-range electrostatic screening in ionic liquids as inferred by direct force measurements
Benjamin Cross, LĂ©o Garcia, Elisabeth Charlaix, Patrick KĂ©kicheff
Full text
Previous experimental reports of long-range interactions in ionic liquids (ILs) stand in contradiction with theoretical predictions and numerical simulations. To provide insights into the literature discrepancies regarding the experimental ranges of electrostatic screening, claimed with orders of magnitude larger, the interactions between pairs of mica and borosilicate surfaces confining ILs are investigated by two complementary advanced Surface Force Apparatuses. Regardless of differences in confinement geometries (crossed-cylinders, sphere-flat), radii of curvature (cm-mm), and measurement techniques (stepwise versus continuous approach), two ever present force regimes are evidenced. At small surface separations, oscillatory forces reflect IL structuration and layering, while outside this gap, the interaction is monotonic repulsive. In both regimes the spatial extent and force magnitude depend critically on motion conditions, as demonstrated by achieving velocities as low as 9 pm/s with equilibration times up to 90 s. At large separations, fast surface displacements generate long-range interactions (over tens of ion size) creating the illusion of anomalous underscreening, whereas increasingly slow ones shrink both magnitude and range of the repulsion with decay-lengths converging ultimately to a screening length consistent with Poisson–Boltzmann theory with finite ion sizes. The transition from apparent long-range to short-range screening unfolds over nearly two orders of magnitude in time, revealing slow relaxation dynamics reminiscent of aging phenomena. These findings definitely resolve a decade-old controversy on force measurements and reveal rich out-of-equilibrium dynamics. The hydrodynamic contribution to the net force is admittedly crucial to be reduced especially when relaxations span decades in time, but approaching thermodynamic equilibrium during measurements proves essential.
GPT-4o mini: Non-social science research article
EPOP and MTF2 activate PRC2 activity through DNA-sequence specificity
Jeffrey Granat, Sanxiong Liu, Luis Popoca, Ozgur Oksuz, Danny Reinberg
Full text
Polycomb Repressive Complex 2 (PRC2) facilitates the formation of facultative heterochromatin, instrumental to tissue specific gene expression. PRC2 catalyzes trimethylation of lysine 27 of histone H3 (H3K27me3), which is targeted for chromatin compaction by PRC1. Importantly, PRC2-associated cofactors regulate its distinct activities, as in the case of MTF2 and JARID2 that direct PRC2 to specific chromatin nucleation sites based on preferred DNA-binding motifs. Here, we investigated EPOP whose role in regulating PRC2 was not well-defined. We find that both EPOP and MTF2 stimulate PRC2 histone methyltransferase (HMT) activity in vitro. Unlike MTF2, EPOP is ineffectual in PRC2 chromatin recruitment as evidenced by an EED-rescue system in vivo but promotes H3K27me3 deposition de novo in cooperation with MTF2 and JARID2. Binding assays using reconstituted dinucleosome substrates revealed that similar to MTF2, EPOP promotes PRC2 chromatin-binding activity in a distinct DNA-sequence-dependent manner (GCN-rich and GA-rich, respectively). Thus, EPOP and MTF2 in conjunction with JARID2 foster PRC2-mediated HMT activity at chromatin sites comprising cofactor-preferred DNA-binding sequences during the formation of H3K27me3-chromatin domains.
GPT-4o mini: Non-social science research article
ARP2/3 complex mediates the neuropathology of PTEN-deficient human neural cells downstream of mTORC1 and mTORC2 hyperactivation
Navroop K. Dhaliwal, Octavia Yifang Weng, Ai Tian, Aditi Aggarwal, Mai Ahmed, Guoria Sun, Afrin Bhattacharya, Wendy W. Y. Choi, Haruka Nishimura, Pragnya Chakraborty, Xiaoxue Dong, Yuncheng Wu, Michael D. Wilson, Lu-Yang Wang, Luis F. Parada, Julien Muffat, Yun Li
Full text
Mutations in the phosphatase and tensin homolog ( PTEN ) gene are linked to severe neurodevelopmental disorders. Loss of PTEN causes hyperactivation of both mechanistic target of rapamycin (mTOR) complexes, mTORC1 and mTORC2. Recent studies have shown that this dual hyperactivation is required for the neuropathology observed in PTEN -deficient human stem cell–derived neural cells. However, the molecular effectors that integrate these synergistic signals remain unknown. Here, we identify the actin-regulating ARP2/3 complex as a critical point of convergence downstream of mTORC1 and mTORC2. We show that concurrent hyperactivation of both complexes drives increased filamentous actin and elevated levels of the ARP2/3 complex subunits in PTEN -deficient human neural precursors (NPs) and neurons. Pharmacological or genetic inhibition of ARP2/3 is sufficient to rescue multiple disease-relevant phenotypes, including NP hyperproliferation, neuronal hypertrophy, and electrical hyperactivity, without affecting the upstream mTORC1 or mTORC2 hyperactivation. Together, these findings reveal the PTEN –mTOR–ARP2/3 signaling axis as a core mechanism of neuropathology and highlight ARP2/3 inhibition as a potential therapeutic strategy for PTEN -related neurodevelopmental disorders.
GPT-4o mini: Non-social science research article
Metabolic stress conditions dictate MAPKAPK2-dependent efficiency of MEK1/2 inhibition in colorectal carcinoma
Niti Kumari, Xu Chen, Amber M. Baldwin, Kristin I. Clemons, Mohammad El-Harakeh, Lilian E. Calisto, Balawant Kumar, Qiaoqiao Zhang, Jiang Min, Bin Xiao, Amar B. Singh, Bin Wang, Brian J. North
Full text
The kinase MAPKAPK2 regulates cell survival, proliferation, and death, and is upregulated in colorectal carcinoma (CRC) where it is associated with tumor growth and progression. However, how it regulates tumor progression in conjunction with other signaling pathways, such as MEK/ERK, remains elusive. Solid tumors are often subjected to metabolic stress, notably glucose deprivation. Here, we demonstrate that MAPKAPK2 protein levels in CRC regulate cell fate decision during stress conditions, such as glucose deprivation and therapeutic treatment. While MAPKAPK2 expression is a limiting factor for CRC growth in vitro, depleting MAPKAPK2 or inhibiting its activity pharmacologically provides a survival advantage to CRC cells under glucose limiting conditions. Subjecting CRC cells to low glucose resulted in an ERK1/2-mediated decline in MAPKAPK2 to promote survival. Additionally, cells with reduced MAPKAPK2 activity were less sensitive to trametinib under glucose limiting conditions. Utilizing transcriptomic profiling, we found that glucose deprivation and MAPKAPK2 depletion activate pathways associated with survival during metabolic stress. This relationship was also observed in CRC patients (TCGA), where tumors with low MAPKAPK2 expression had higher ERK1/2 activation and upregulated stress-induced pathways, leading to poor survival. Finally, MAPKAPK2 modulated growth of CRC organoids, subcutaneous tumors, and patient-derived xenografts (PDX), and reduced MAPKAPK2 levels decreased efficacy of trametinib, in vitro and in vivo. Overall, this study identifies an interrelationship between MEK/ERK and p38/MAPKAPK2 signaling pathways during glucose deprivation to support cell survival and features MAPKAPK2 loss as a possible mechanism leading to reduced efficacy of trametinib-based anticancer therapy and poor patient outcomes in CRC.
GPT-4o mini: Non-social science research article
Natalizumab exacerbates astrocytopathy in NMOSD via blockade of endothelial VCAM1–astrocytic integrin α4 interaction
Tingting Cui, Qing Wen, Zixuan An, Jingqi Kang, Pei Li, Yuechen Zeng, Lan Lin, Rui Gao, Guo Cheng, Luhang Dai, Zhe Feng, Ye Gong, Xin Zhang, Ke Li, Xiaoli Ding, Xiaochang Xue, Luting Yang, Lei Zhang, Yaling Zhang, Yaping Yan
Full text
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory disorder of the central nervous system (CNS) that shares clinical features with multiple sclerosis (MS) but typically manifests with more severe symptoms. The presence of pathogenic IgG autoantibodies targeting aquaporin-4 (AQP4) channels on astrocytes serves as a highly specific biomarker that distinguishes NMOSD from MS. Unlike MS, NMOSD is characterized by profound astrocytic destruction and exhibits a distinct response to therapies. Notably, disease-modifying therapies (DMTs) effective in MS, including natalizumab, interferon-ÎČ, and fingolimod, not only fail to benefit NMOSD patients but may also exacerbate disease progression. The precise molecular mechanisms underlying this immunomodulator-induced exacerbation, however, remain not yet fully elucidated. Here, we demonstrate that natalizumab alleviated experimental autoimmune encephalomyelitis (EAE) while exacerbating the autoimmune astrocytopathy in an “EAE-NMOSD” mouse model, a phenomenon associated with a reduction in actively proliferating astrocytes. Through molecular and signaling pathway analyses, we identify that endothelial-derived vascular cell adhesion molecule 1 (VCAM1) activates astrocytes via integrin α4 signaling, thereby mitigating astrocytopathy in NMOSD-like mice. Furthermore, astrocyte-specific integrin α4 deficiency exacerbates astrocytopathy, and notably, natalizumab-induced disease exacerbation does not occur in integrin α4-conditional knockout (CKO) mice. Finally, pharmacological activation of astrocytes rescues natalizumab-induced damage and ameliorates demyelination in NMOSD-like mice. Collectively, our findings provide mechanistic gaps regarding the clinical phenomenon underlying natalizumab-induced NMOSD exacerbation and suggest astrocyte-targeted therapeutic strategies as a potential intervention for NMOSD.
GPT-4o mini: Non-social science research article
Listening to the quiescence of single STIM1 dimers
Patrick G. Hogan
Full text
GPT-4o mini: Non-social science research article
Variable thresholds for phosphorylation targets of the ERK signaling pathway
Kristyn Hayashi, Suganya Sekaran, Pelle Simpson, Christopher C. Ebmeier, Cole R. Michel, Natalie G. Ahn
Full text
Cell fates regulated by ERK respond to different thresholds of signaling strength. In mammalian cells, conditions that activate ERK to submaximal levels are sufficient to sustain proliferation, survival, and transformation, while stimuli that activate ERK to very high levels often lead to cell death or cell cycle arrest. But while this “Goldilocks effect” is well known, the mechanisms have never been fully explained. In particular, threshold responses have been shown at the level of transcription and cell state changes, but whether phosphorylation responses upstream of these events also respond to thresholds is unknown. Here, we used mass spectrometry-based phosphoproteomics to ask if molecular events in the ERK pathway respond to different thresholds of signaling strength, by quantifying changes in phosphorylation of pathway targets against the occupancy of the two activating phosphosites in ERK. The results show that most phosphorylation events track ERK activation faithfully, responding linearly with increasing 2P-ERK occupancy. But some sites respond nonlinearly, reaching maximal phosphorylation when 2P-ERK exceeds lower thresholds (10 to 40%), or increasing substantially after 2P-ERK exceeds higher thresholds (>60%). Low threshold sites are found on transcriptional repressors that facilitate proliferation when inactivated by ERK/ribosomal s6 kinase (RSK) phosphorylation. By contrast, high threshold sites are found on proteins that are recruited to double-stranded DNA breaks and mediate DNA repair. Measurement of phosphorylation occupancies also revealed unexpected differences between cell states not apparent from inhibitor fold-changes. Our findings demonstrate that signaling thresholds exist at the level of the phosphoproteome, providing potential mechanisms for regulating cellular responses to pathway strength.
GPT-4o mini: Non-social science research article
Probabilistic mapping and automated segmentation of human brainstem white matter bundles
Mark D. Olchanyi, David R. Schreier, Jian Li, Chiara Maffei, Annabel Sorby-Adams, Hannah C. Kinney, Brian C. Healy, Holly J. Freeman, Jared Shless, Christophe Destrieux, Henry Tregidgo, Juan Eugenio Iglesias, Emery N. Brown, Brian L. Edlow
Full text
Brainstem white matter (WM) bundles are essential conduits for neural signals that modulate homeostasis and consciousness. Their architecture forms the anatomic basis for brainstem connectomics, subcortical circuit models, and deep brain navigation tools. However, their small size and complex morphology, compared to cerebral WM, makes mapping and segmentation challenging in neuroimaging. As a result, fundamental questions about brainstem modulation of human homeostasis and consciousness remain unanswered. We leverage diffusion MRI tractography to create BrainStem Bundle Tool (BSBT), which automatically segments eight WM bundles in the rostral brainstem. BSBT performs segmentation on a custom probabilistic fiber map using a convolutional neural network architecture tailored to detect small anatomic structures. We demonstrate BSBT’s robustness across diffusion MRI acquisition protocols with in vivo scans of healthy subjects and ex vivo scans of human brain specimens with corresponding histology. BSBT also detected distinct brainstem bundle alterations in patients with Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and traumatic brain injury through tract-based analysis and classification tasks. Finally, we provide proof-of-principle evidence for the prognostic utility of BSBT in a longitudinal analysis of traumatic coma recovery. BSBT creates opportunities for scalable mapping of brainstem WM bundles and investigation of their role in a broad spectrum of neurological disorders.
GPT-4o mini: Non-social science research article
Spatiotemporal histogenesis of the developing human cerebellum reveals dynamic layering of Bergmann glia
Guanyi He, Simon Du, Henry Tan, Sri Yellampally, Anders W. Erickson, Virginia Fernandez, Ferechte Encha-Razavi, Kimberley A. Phillips, Christine Haberler, Nicole Amberg, Victor Borrell, Paul A. Northcott, Michael D. Taylor, Kathleen J. Millen, Parthiv Haldipur
Full text
Bergmann glia (BG) are a specialized glial population essential for cerebellar development, yet their developmental timeline and molecular identity in the human cerebellum remain poorly understood. Here, we combined detailed histopathological analysis with spatial transcriptomics and single-nucleus RNA sequencing to generate a developmental atlas of human cerebellar BG. Histology revealed that BG emerge around 11 postconception weeks (PCW), initially serving as a scaffold for Purkinje cells (PCs) migrating into the PC layer of the cerebellar cortex. Following the establishment of a multilayered PC arrangement, BG form a distinct parallel layer separated from the PCs by the lamina dissecans (LD), with both layers merging in the third trimester. This developmental sequence challenges earlier studies that suggested BG appear late in the third trimester. Comparative histology in mice, ferrets, and marmosets indicates that this trilaminar organization, including the LD, is likely unique to humans. Integration of spatial and single-nucleus transcriptomic datasets identified an ASCL1 + PTF1A + ventricular zone progenitor cluster giving rise to BG, astrocytes, and oligodendrocytes. Pseudotime analyses delineated three gliogenic lineages and revealed two temporally and transcriptionally distinct BG populations, emerging at 11–12PCW and 17PCW, suggesting multiphasic BG ontogeny. Together, these multimodal data link cellular lineage, spatial organization, and molecular identity of human cerebellar glia, providing a framework for future studies on the role of BG in cerebellar function and their potential contributions to vulnerability in neurodevelopmental disorders.
GPT-4o mini: Non-social science research article
Beta arrestin 1 is a key regulator of pulmonary vascular tone
Leonard F. Lebender, Alexander Seidinger, Michaela Matthey, Birte Dyck, Christian Schlamm, Abdullah Kaddoura, Maximilian Hausherr, Britta Eggers, Katrin Marcus, Evi Kostenis, Volkmar Gieselmann, Michael Adamzik, Anna Klinke, Björn Koos, Bernd K. Fleischmann, Daniela Wenzel
Full text
Pulmonary arterial hypertension (PAH) is a serious disorder, in which increased vascular tone is one of the critical hallmarks. Since beta arrestins (bArrs) have been shown to regulate smooth muscle tone in the airways, we investigated the function of bArr1 in the pulmonary vasculature. Here, we report that bArr1 is essential for maintaining normal pulmonary arterial tone. Specifically, pulmonary arteries from bArr1−/− mice exhibited reduced NO-dependent vasorelaxation due to impaired soluble guanylyl cyclase (sGC) activity, which was restored by the heme-independent sGC activator BAY58-2667. We identified bArr1 as a binding partner of sGC and the sGC heme reductase cytochrome b5 reductase (Cyb5r3), indicating that bArr1 is vital for sensitizing sGC to NO. Finally, mice with either ubiquitous or smooth muscle-specific bArr1 deficiency developed pulmonary hypertension (PH). These findings highlight the important role of bArr1 in regulating pulmonary vascular tone and propose it as a potential therapeutic target for the treatment of PH.
GPT-4o mini: Non-social science research article
Diverse, distinct, and densely packed DNA nanostar droplets
Aria S. Chaderjian, Sam Wilken, Omar A. Saleh
Full text
The liquid–liquid phase separation of biomolecules is an important process for intracellular organization. Biomolecular sequence combinatorics leads to a large variety of proteins and nucleic acids which can interact to form a diversity of dense liquid (“condensate”) phases. The relationship between sequence design and the diversity of the resultant phases is therefore of interest. Here, we explore this question using the DNA nanostar system which permits the creation of multiphase condensate droplets through sequence engineering of the sticky end bonds that drive particle–particle attraction. We explore the theoretical limits of nanostar phase diversity, then experimentally demonstrate the ability to create nine distinct, nonadhering nanostar phases that do not share components. We further study how different thermal histories affect the morphology and dynamics of such a highly diverse condensate system. We particularly show that a rapid temperature quench leads to the formation of a densely packed 2-D layer of droplets that is transiently stabilized by caging effects enabled by the phase diversity, leading to glassy dynamics such as slow coarsening and dynamic heterogeneity. Generally, our work provides experimental insight into the thermodynamics of phase separation of complex mixtures and demonstrates the rational engineering of complex, long-range, multiphase droplet structures.
GPT-4o mini: Non-social science research article
Hydration gradients drive lipid self-segregation
Nikol Labecka, Jenny M. Andersson, Emma Sparr, Kevin Roger
Full text
Evaporation from a multicomponent aqueous mixture not only establishes a hydration gradient but may also lead to composition gradients in the other components. Here, we show that such a gradient induces a strong segregation between two phospholipids that differ only in the saturation of their acyl chains. Using high-resolution confocal Raman microscopy combined with small- and wide-angle X-ray scattering, we simultaneously resolve local composition and structure along the evaporation direction. We find that the saturated phospholipid, dipalmitoyl phosphatidylcholine (DPPC), accumulates near the air–liquid interface, while the unsaturated phospholipid, dioleoyl phosphocholine (DOPC), is displaced toward a more hydrated intermediate region, resulting in a complete inversion of their initial proportions. This nonmonotonic lipid gradient reflects the different water swelling capacities of the L ÎČâ€Č and L α lamellar phases favored by DPPC and DOPC, respectively. Despite the system being out of equilibrium, the segregation is quantitatively captured by a description based on local equilibrium chemical potentials and multicomponent diffusion with cross-coupling. Our findings identify hydration gradients as a robust driver of lipid segregation and establish a general framework for predicting transport and organization in evaporating soft-matter systems.
GPT-4o mini: Non-social science research article
Magnetic field–enhanced alkaline water electrolysis from laboratory to industry
Hao Li, Jiakun Fang, Danji Huang, Zhiyao Zhong, Qunlei Wen, Youwen Liu, Kewei Hu, Zhenhong Yang, Ang Lu, Xiaomeng Ai, Tianyou Zhai, Jinyu Wen, Yuan Pan
Full text
The fundamental limitation of water oxidation in alkaline water electrolysis (AWE) lies in the progressive depletion of dynamic active sites and rapid dissipation of local active ion concentration, a critical thermodynamic constraint that conventional electrochemical strategies struggle to overcome. Here, we propose a magnetic field–enhanced AWE (ME-AWE) strategy that enables in-situ directional enrichment of local active iron ions near the anode, thus breaking the concentration limit and boosting the coverage of dynamic iron active sites without elevating bulk impurity levels. Laboratory-scale three-electrode experiments confirm improved oxygen evolution reaction (OER) kinetics by the magnetically induced optimization of iron incorporation dynamics and the increase in the coverage of dynamic iron active sites. A multiphysics model coupling magnetic field, fluid flow, mass transport, and electrochemical reaction is developed to spatially interpret the mechanism, revealing that the magnetic modulation enables OER kinetics at 0.3 ppm iron equivalent to those at tenfold higher concentration without a magnetic field. Guided by mechanistic insights, an industry-scale ME-AWE device is designed and implemented, achieving a 24.9% increase in hydrogen output at 1.8 V. Techno-economic analysis demonstrates that the ME-AWE strategy enables a 10.6% reduction in total AWE capital cost for large-scale hydrogen production plants using off-grid wind power. Built with existing industrial infrastructure, this ME-AWE strategy offers a scalable and low-cost solution for improving AWE efficiency and advancing impurity-assisted catalysis in green hydrogen production.
GPT-4o mini: Non-social science research article
Hierarchical friction memory leads to subdiffusive configurational dynamics of fast-folding proteins
Anton Klimek, Benjamin A. Dalton, Lucas Tepper, Roland R. Netz
Full text
Proteins often exhibit subdiffusive configurational dynamics, the origins of which are still unresolved. We investigate the impact of non-Markovian friction and the free-energy landscape on the dynamics of fast-folding proteins in terms of the mean squared displacement (MSD) and the mean first-passage-time (MFPT) of the folding reaction coordinate. We find the friction memory kernel from published molecular dynamics simulations to be well-described by a hierarchical multiexponential function, which gives rise to subdiffusion in the MSD for times shorter than the longest memory time, while for longer times the confining free-energy landscape produces subdiffusion. Thus, for a wide range of times, friction memory effects in fast-folding proteins dominate the scaling behavior of the MSD compared to effects due to the folding free-energy landscape. As a consequence, Markovian models are insufficient to fully capture the folding dynamics, as quantified by the MSD and the MFPT, even when including coordinate-dependent friction. Our results demonstrate the importance of memory effects in protein folding and conformational dynamics and explicitly show that subdiffusion in fast-folding protein dynamics originates mainly from memory effects, not from the free-energy landscape and not from coordinate-dependent friction.
GPT-4o mini: Non-social science research article
How earthquakes organize stress
Emily E. Brodsky, Gaspard Farge
Full text
Stress is not uniform in the Earth. Therefore, we must use natural experiments to measure the distribution of stresses and related quantities, rather than single values. For instance, dynamic triggering shows that faults are uniformly distributed over their loading cycles in Southern California. The probability that a fault ruptures across a barrier measures the in situ energy distribution. Fault roughness reflects the distribution of strength. These natural experiments produce observable distributions that are surprisingly consistent and suggest some degree of self-organization in the Earth’s crust. Once established, the functional form of the distributions can be used to track changes in response to earthquakes as well as to distinguish fundamentally different fault systems. Transient fault locking before stress release in laboratory experiments can be interpreted as a consequence of self-organization of fault stress. The robust self-organization of multiple variables in earthquake systems suggests that the most consequential mechanical outcome of earthquakes may be the redistribution of stress and the strain energy associated with it. The low friction on a fault during seismic slip as inferred by temperature measurements of the Tohoku earthquake is consistent with dissipation playing a secondary role to this redistribution process. Through stress redistribution and interaction, subduction zone faults tend to synchronize, perhaps due to their geometric simplicity, while the continental system of Southern California cannot synchronize, perhaps due to the complexity of the fault network. Earthquakes organize stress in the crust and produce a suite of well-defined, consistent distributions.
GPT-4o mini: Non-social science research article
BacA(SbmA) importer of legume symbiotic NCR peptides: Protein architecture, function, and evolutionary implications
Markus F. F. Arnold, Siva Sankari, Michael Deutsch, Charley C. Gruber, Francisco J. Guerra-Garcia, Konstantinos Beis, Graham C. Walker
Full text
Some legumes encode families of NCR (Nodule-Cysteine-Rich) peptides that cause their rhizobial partners to terminally differentiate during the development of a nitrogen-fixing symbiosis. Sinorhizobium meliloti, whose plant hosts Medicago truncatula and Medicago sativa express ca. 600 NCR peptides during root nodule development, possesses a symbiotically essential BacA Sm protein that imports certain NCR peptides into the cytoplasm. This import permits proteolytic degradation of the NCR peptides, thereby protecting the endocytosed bacteria from their antimicrobial peptide-like lethality, while also allowing certain NCR peptides to undergo their symbiotically critical interactions with cytoplasmic components, for example heme-sequestration in the case of NCR247. Our study employed 54 S. meliloti bacA Sm missense mutants (35 to cysteine and 19 to glycine) that we tested for protein production, ability to establish a nitrogen-fixing symbiosis, and their susceptibility to killing by higher levels of the NCR247 and the Bac7(1-35) peptides. We also used the Single Cysteine Accessibility Method to make topological inferences. Our detailed genetic, biochemical, structural, and physiological analyses have revealed that BacA Sm and SbmAhomodimers function as finely tuned transporters, whose structures can be relatively easily disrupted by single amino acid changes. Our finding that several mutations that differentially separate nitrogen-fixation, NCR247 import, and Bac7(1-35) import map to the lining of the peptide-binding cavity suggests a molecular explanation underlying the paradoxical observation that SbmA/BacAs from pathogens can fully replace BacA Sm , whereas BacAs from other rhizobia cannot.
GPT-4o mini: Non-social science research article
Global nutritional equity of fishmeal and aquaculture trade flows
Laura G. Elsler, Jessica A. Gephart, Jessica Zamborain-Mason, Tim Cashion, Max Troell, Rosamond L. Naylor, Rahul Agrawal Bejarano, Christopher D. Golden
Full text
Aquaculture, the single fastest growing food sector, is central to achieving key Sustainable Development Goals (e.g., SDG 2: Zero Hunger). Linking the nutrient composition of >2,800 aquatic species with >2 million fishmeal and farmed fish transactions in international aquatic food trade between 2015 and 2019, we examined aquaculture’s nutritional flows and distributional equity. We found that aquaculture provided adequate intakes for nearly a quarter of a million individuals, on average, across 14 key nutrients, and for up to 2.7 billion individuals for several nutrients, such as Vitamin B 12 . The vast majority of these nutrients (76.8%) were domestically retained, contributing to the nutritional security of producer countries. With most internationally traded nutrients originating from nutritionally vulnerable countries (57.7% for fishmeal and 66.3% for farmed aquatic foods), rethinking existing distribution policies with nutrition as the primary objective may help unlock the full potential of aquaculture to eliminate hunger and malnutrition.
GPT-4o mini: Non-social science research article
Integration of fear learning and fear expression across the dorsoventral axis of the hippocampus
Marco N. Pompili, Noé Hamou, Sidney I. Wiener
Full text
Classically, the dorsal and ventral hippocampus are thought to play distinct roles in fear conditioning, with the dorsal hippocampus primarily handling information about environmental cues and contexts, and the ventral hippocampus more involved in emotional processing. Both functions are essential for the learning and expression of conditioned fear responses, but how these processes are integrated remains largely unexplored. In this study, we simultaneously recorded single-unit activity from the dorsal and ventral hippocampus during fear conditioning in male rats to identify the neural dynamics that may underlie these processes and their integration. As fear expression emerged, shifts in neural firing patterns were observed in both regions, with a stronger shift in ventral hippocampal activity, as expected. However, contrary to the prevailing view of the ventral hippocampus as central to anxiety and fear regulation, surprisingly, fear expression-related neuronal responses were more predominant in the dorsal hippocampus. In contrast, ventral hippocampal neuronal activity was more closely linked with the acquisition of conditioned fear. These features were combined in cell assemblies that emerged during fear conditioning, composed of both dorsal fear expression-responsive neurons and ventral fear learning-responsive cells. These multifactorial engrams, distributed along the hippocampal dorsoventral axis, provide a potential substrate for integrating fear acquisition and expression, thereby coordinating associative learning.
GPT-4o mini: Non-social science research article
Bridging unpaired single-cell multimodal data for integrative analyses with SuperMap
Chao Deng, Xinyi Ma, Hui Lu, Hongyu Zhao, Jingsi Ming, Tao Wang
Full text
Current single-cell profiling technologies enable the capture of multiple cellular modalities, providing valuable insights into complex biological systems. While a substantial amount of single-cell multimodal data has been generated and accumulated, most of these datasets are unpaired, characterized by distinct feature spaces and a lack of cell-wise correspondence. The absence of explicit linkages between modalities poses a fundamental challenge for data integration and interpretation. To address this, we introduce SuperMap, a statistical learning method designed for the integrative analyses of unpaired multimodal data. SuperMap directly learns cross-modal mappings from unpaired data to effectively bridge and link different modalities, facilitating a variety of downstream analysis tasks. Comprehensive benchmarking and real-world applications demonstrate the superior performance of SuperMap in enhancing cell-type identification, improving diagonal integration, enabling regulatory analysis, and revealing epigenomic priming events to specify cell differentiation directions for trajectory inference.
GPT-4o mini: Non-social science research article
Engineering chimeric antigen receptor CD4 T cells for Alzheimer’s disease
Pavle Boskovic, Rotem Shalita, Wenqing Gao, Hailey Vernon, Yu Lin Deng, Marco Colonna, Robbie G. Majzner, Ido Amit, Jonathan Kipnis
Full text
Alzheimer’s disease (AD) is the prevailing cause of age-associated dementia worldwide. Current standard of care relies on antibody-based immunotherapy. However, antibody-based approaches carry risks for patients, and their effects on cognition are marginal. Increasing evidence suggests that T cells contribute to AD onset and progression. Unlike the cytotoxic effects of CD8 + cells, CD4 + T cells capable of regulating inflammation show promise in reducing pathology and improving cognitive outcomes in mouse models of AD and in aging. Here, we sought to exploit the beneficial properties of CD4 + T cells while circumventing the need for TCR and peptide–MHC antigen discovery, thereby providing a potential universal therapeutic approach. To achieve this, we engineered CD4 + T cells with chimeric antigen receptors (CARs) targeting fibrillar forms of aggregated amyloid-ÎČ. Our findings demonstrate that optimized CAR-T cells can alter amyloid deposition in the dura and reduce parenchymal pathology in the brain. Furthermore, we observed that CAR-T treatment promotes the expansion and recruitment of endogenous CD4 + T cells into the brain parenchyma and leptomeninges. In summary, we established the feasibility of amyloid plaque–specific CAR-T cells as a potential therapeutic avenue for AD. These findings highlight the potential of CD4 + CAR-T therapy not only to modify amyloid pathology but also to reshape the immune landscape of the CNS, paving the way for future development of cellular immunotherapies for neurodegenerative disease.
GPT-4o mini: Non-social science research article
Larval zebrafish minimize energy consumption during hunting via adaptive movement selection
Thomas Darveniza, Robert Wong, Shuyu I. Zhu, Zac Pujic, Biao Sun, Matthew Levendosky, Ramesh Agarwal, Michael H. McCullough, Geoffrey J. Goodhill
Full text
Animals must balance behavioral goals with the energetic costs of movement. How such trade-offs are implemented algorithmically during natural behavior, and how they adapt to changing energetic constraints, remains poorly understood. Here we show that larval zebrafish adjust their motor strategies during prey hunting to minimize energy expenditure. Using high-speed video tracking and 3D computational fluid dynamics simulations, we quantified the energy costs (in Joules) of different movement types across three developmental stages. While the structure of discrete movement types (“bouts”) remained stable with age, their selection probabilities changed depending on their energetic cost, such that more expensive bouts were always used less frequently. This relationship was conserved across development despite shifts in the relative costs of different bouts. A reinforcement learning model trained to catch prey while minimizing energy use reproduced this relationship, demonstrating that it is an energetically optimal strategy. Furthermore, when fish were reared in a high-viscosity environment that altered energetic costs, they readapted their movement probabilities to preserve the same energy-based control rule, demonstrating active optimization rather than a predetermined developmental program. These findings reveal how goal-directed animals can dynamically regulate movement selection to minimize energetic costs, even under changing environmental and biomechanical conditions. Our results provide a quantitative link between biomechanics, development, behavior, and computational control theory in a freely moving animal.
GPT-4o mini: Non-social science research article
Order parameters and phase transitions of continual learning in deep neural networks
Haozhe Shan, Qianyi Li, Haim Sompolinsky
Full text
Continual learning (CL) enables animals to learn new tasks without erasing prior knowledge. CL in artificial neural networks (NNs) is challenging due to catastrophic forgetting, where new learning degrades performance on older tasks. While various techniques exist to mitigate forgetting, theoretical insights into when and why CL fails in NNs are lacking. Here, we present a statistical-mechanics theory of CL in deep, wide NNs, which characterizes the network’s input–output mapping as it learns a sequence of tasks. It gives rise to order parameters (OPs) that capture how task relations and network architecture influence forgetting and anterograde interference, as verified by numerical evaluations. For networks with a shared readout for all tasks (single-head CL), the relevant-feature and rule similarity between tasks, respectively measured by two OPs, are sufficient to predict a wide range of CL behaviors on classic benchmark tasks. In addition, the theory predicts that increasing the network depth can effectively reduce interference between tasks, thereby lowering forgetting. For networks with task-specific readouts (multihead CL), the theory identifies a phase transition where CL performance shifts dramatically as tasks become less similar, as measured by another task-similarity OP. While forgetting is relatively mild compared to single-head CL across all tasks, sufficiently low similarity leads to catastrophic anterograde interference, where the network retains old tasks and interpolates new training data perfectly but completely fails to generalize new learning. Our results delineate important factors affecting CL performance and offer theoretical insights into common heuristics for mitigation of forgetting.
GPT-4o mini: Non-social science research article
Nonlinear diffusion and decay of a blob of turbulence spreading into a quiescent fluid
Takumi Matsuzawa, Minhui Zhu, Nigel Goldenfeld, William T. M. Irvine
Full text
Turbulence, left unforced, evolves under its own dynamics, invading surrounding quiescent fluid as it decays. A ubiquitous and familiar phenomenon, this fundamental aspect of turbulence has resisted the marriage of principled theory and experiment with no universal law yet capturing its evolution. Conventional flow chamber experiments have been hampered by boundary effects or strong mean flows that obscure the intrinsic dynamics of relaxation to quiescence. To circumvent these limitations, we create a spatially localized blob of turbulence using eight converging vortex generators focused at the center of a water tank, and observe its decay and expansion over decades in time using particle image velocimetry with logarithmic time sampling. The blob initially expands and decays until it reaches the walls of the tank and eventually transitions to a second regime of approximately spatially uniform decay. We interpret the turbulent dynamics as an interplay of nonlinear diffusion with associated steep fronts separating the turbulent and quiescent regions, and nonlinear decay, as described by the Kolmogorov–Barenblatt equation. We find direct evidence for this model within the expansion phase and decay phases of our turbulent blob and use it to account for the detailed behavior we observe. Our work provides a detailed spatially resolved narrative for the behavior of turbulence once the forcing is removed, and demonstrates unexpectedly that the turbulent cascade leaves an indelible footprint far into the decay process.
GPT-4o mini: Non-social science research article
Dual inhibition of mTOR and calcineurin pathways mitigates missing self–induced NK cell–mediated microvascular rejection
Sarah Hamada, Jack Beadle, Alice Koenig, Basile Sugranes, John Ferdinand, Chien-Chia Chen, Virginie Mathias, Maeva Eloudzeri, Thomas Barba, Helena Paidassi, Carole Saison, Valérie Dubois, Emmanuel Morelon, Thierry Walzer, Antoine Marcais, Maud Rabeyrin, Marion Rabant, Patrick Bruneval, Maud Racapé, Jean Paul Duong Van Huyen, Menna R. Clatworthy, Candice Roufosse, Olivier Thaunat
Full text
The inability of graft endothelial cells to deliver HLA-I-dependent inhibitory signals to recipient natural killer (NK) cells (missing self, MS), drives donor-specific antibody-independent microvascular inflammation (MVI), leading to graft failure. This study aimed to elucidate the signaling pathways involved in MS-associated NK cell activation and explore therapeutic strategies. Analyses of kidney graft biopsies identified calcium signaling pathways and mTOR as a key regulator of MS-induced NK cell activation. Two experimental models were developed to mimic the pathological condition: in vitro cocultures of human NK cells with allogeneic microvascular endothelial cells and a murine heart transplantation model. These models showed that while calcineurin inhibitor (CNI) alone had a limited impact, combining CNI with mTOR inhibitors (mTORinh) synergistically reduced NK cell activation and endothelial damage. In a pilot clinical study involving 50 renal transplant recipients with MS-associated NK cell–mediated microvascular inflammation, patients who tolerated mTORinh introduced on top of CNI at diagnosis demonstrated reduced MVI lesions and improved graft survival compared to a historical cohort left on CNI and mycophenolate mofetil. This translational study identifies mTOR inhibition as a pivotal adjunct to CNI in mitigating MS-associated NK cell–mediated inflammation, potentially improving long-term graft outcomes.
GPT-4o mini: Non-social science research article
Next-gen geothermal could bring clean power to much more of the planet
Stephen Battersby
Full text
GPT-4o mini: Non-social science research article
Functional and antigenic constraints on the Nipah virus fusion protein
Brendan B. Larsen, Sheri Harari, Risako Gen, Cameron Stewart, David Veesler, Jesse D. Bloom
Full text
Nipah virus is a highly pathogenic virus in the family Paramyxoviridae that utilizes two distinct surface glycoproteins to infect cells. The receptor-binding protein (RBP) binds host receptors whereas the fusion protein (F) merges viral and host membranes. Here, we use nonreplicative pseudoviruses to safely measure the effects of all F single amino acid residue mutations on its cell entry function and neutralization by monoclonal antibodies. We compare mutational tolerance in F with previous experimental measurements for RBP and show that F is much more functionally constrained than the RBP. We also identify mutationally intolerant sites on the F trimer surface and core that are critical for proper function, and describe mutations that are candidates for stabilizing F in the prefusion conformation for vaccine design. We quantify how F mutations affect neutralization by six monoclonal antibodies, and show that the magnitude of mutational effects on neutralization varies among antibodies. Our measurements of mutational effects on Nipah virus F predict the ability of the antibodies to neutralize the related Hendra virus. Overall, our work defines the functional and antigenic constraints on the F protein from an important zoonotic virus.
GPT-4o mini: Non-social science research article
Lipid nanoparticle GM-CSF replacement for autoimmune pulmonary alveolar proteinosis
Liming Lian, Bora Jang, Sebastian G. Huayamares, Avraham Shakked, Kara Gentry, Ryan Zenhausern, Afsane Radmand, Elisa Schrader Echeverri, Vaunita C. Parihar, Ricardo C. Guerrero-Ferreira, Randi Calkins, Daryll Vanover, Philip J. Santangelo, Hyejin Kim, James E. Dahlman
Full text
Granulocyte–macrophage colony-stimulating factor (GM-CSF) deficiency drives autoimmune pulmonary alveolar proteinosis (aPAP), a disease characterized by impaired macrophage-mediated clearance of pulmonary surfactants. Clinical data suggest that inhaled recombinant GM-CSF reduces symptoms in aPAP patients, providing a rationale for mRNA-based GM-CSF replacement therapies. However, these require effective mRNA delivery after nebulization. Here, we report the iterative in vivo design of a lipid nanoparticle, named nebulized lung delivery 2 (NLD2), that efficiently delivers mRNA after nebulization. NLD2 carrying GM-CSF mRNA transfected alveolar macrophages in vivo, leading to interleukin-10 pathway activation and subsequent surfactant lipoprotein clearance. In a preclinical disease model of aPAP, GM-CSF mRNA delivery reduced surfactant protein thickness more than recombinant GM-CSF. These data support continued exploration of nebulized lipid nanoparticle therapies for aPAP.
GPT-4o mini: Non-social science research article
Ion transport control in electrolytes via electrochemical doping
Zhiwei Li, Yinghong Xu, Wanheng Lu, Xinglong Pan, Langyuan Wu, Wei Li Ong, Netanel Shpigel, Gang Chen, Ghim Wei Ho
Full text
Doping to control carrier (electron or hole) transport is foundational to modulate the properties of semiconductors, enabling the development of homojunctions and heterojunctions for integrated electronics. Unlike semiconductors with unipolar charge-carrier dominance, both cations and anions in electrolytes are mobile, which is undesirable for many applications. Here, we report a universal strategy to dope electrolytes such that the ion transport can be unipolar by incorporating electroactive polymers within hydrogels that interact discriminately with one type of ion via redox and binding mechanisms, leaving the counterions mobile. This transforms the system into an active, selective conductor that directs ion flow with high precision. We demonstrate the generality of this strategy using a wide range of electroactive polymers and ions. Particularly, we use emeraldine base and leucoemeraldine base, derived from polyaniline to create both n-type and p-type conductors with high ion selectivity. This electrolyte doping strategy has significant implications beyond the developed thermoelectrochemical devices with boosted performance, with potential applications in supercapacitors, batteries, and electrochemical sensors.
GPT-4o mini: Non-social science research article
A daily cycle of White Collar Complex dephosphorylation sustains circadian rhythmicity in Neurospora
Bin Wang, Xiaoying Zhou, Jennifer J. Loros, Jay C. Dunlap
Full text
The transcription factor complex White Collar Complex (WCC) functions both as a photoreceptor and as the circadian positive element. In response to light, WCC acutely activates ~5% of all genes, whereas in the dark it influences expression of about 40% of the transcriptome. Among WCC targets is frq , which is acutely light-activated through the pLRE ( proximal Light-Response Element ) and circadian-regulated through the C-box ( Clock-box ) promoter element that is not responsible for light-driven expression. The FRQ–FRH complex (FFC), which includes CK-1a, represses WCC activity at the C-box by phosphorylating WCC at >95 sites, but FFC has no described role in the light. We validated the expectation that FFC also silences C-box promoters in constant light, thereby confirming two classes of WCC targets: C-box -like genes that are normally repressed in light and pLRE -like genes that remain light-active despite FFC-driven WCC phosphorylation. Derepression of C-box -like promoters in frq -null fungi may explain reported noncircadian phenotypes such as reduced virulence and conidiation. Reanalysis of WCC circadian regulation revealed that, while most WCC is phosphorylated and repressed at dusk, subsequent circadian activation results from transient dephosphorylation of only a small subset of the WCC pool. This small active pool drives frq expression, nucleating the FFC, which rephosphorylates WCC to repress it again, generating a phosphorylation/dephosphorylation cycle that can persist for days without new WCC synthesis. The realization that both FFC and WCC are regulated primarily through phosphorylation rather than protein turnover leaves the circadian oscillator looking much like a “phoscillator,” emphasizing the primacy of posttranslational regulation in timekeeping.
GPT-4o mini: Non-social science research article
Whole-body central processing of lateral line inputs encodes flow direction relative to the center-of-mass
Elias T. Lunsford, Martin Carbo-Tano, Claire Wyart
Full text
From shifting visual scenes to tactile deformations and fluid motion, animals interpret patterns of sensory flow around their body to construct internal models and produce adaptive behavior. Understanding how such transformations are encoded in the brain remains incomplete. To tackle this question, we leverage the lateral line of larval zebrafish as a tractable system sensitive to fluid motion and used to steer navigation, feed, and avoid predators. By presenting stimuli of either direction to neuromasts along the body, we mapped hindbrain responses via high-resolution calcium imaging. Our findings challenge the notion that central lateral line processing lacks topographic structure by revealing a simple, yet powerful principle centered on an egocentric spatial framework: the direction and location of local flow motions are encoded in reference to the animal’s center-of-mass. Brainstem neurons that encode flow toward the center-of-mass broadly project to form bilateral connections onto reticulospinal neurons that coordinate forward locomotion while those that encode flow away from the center-of-mass displayed a more selective and unilateral projection profile to command neurons eliciting turns. This simple representation enables the brain to register complex flow patterns and provides a robust basis for behavioral action selection. Our finding represents a shift from purely somatotopic encoding toward an integrative representation of axial position and directionality along the horizontal plane combined, revealing a central principle for encoding spatiodirectional cues. This study advances our understanding of how complex mechanosensory inputs select appropriate motor outputs via simple egocentric neural maps in the hindbrain.
GPT-4o mini: Non-social science research article
Synaptogyrin-3 plays a critical role in addiction-related dopamine dysfunction and behavioral maladaptations
Emily G. Peck, Soren D. Emerson, Alyson M. Curry, Kimberly M. Holter, Paige M. Estave, Jonathon P. Sens, Olivia A. Colarusso, Sean P. Farris, Drew D. Kiraly, Robert W. Gould, Brian A. McCool, Erin S. Calipari, Katherine M. Holleran, Sara R. Jones
Full text
Cocaine use disorder is marked by deficits in dopamine signaling; however, the molecular mechanisms driving these deficits remain unclear. The synaptic vesicle protein Synaptogyrin-3 (Syngr3) has recently garnered attention for its association with disorders involving dopamine dysfunction and impaired cognition. Here, we found low Syngr3 expression in the ventral tegmental area (VTA) of men who died of cocaine overdose and in male rats that had chronically self-administered cocaine. Syngr3 was confirmed to be in dopamine neurons, and its expression was correlated with dopamine markers in both humans and rats. Syngr3 levels showed a robust inverse correlation with motivation to self-administer cocaine in the rat model. Moreover, viral overexpression of Syngr3 in VTA dopamine neurons improved cognitive flexibility and substantially reduced cocaine reinforcement and drug-taking behavior. Finally, Syngr3 overexpression prevented cocaine-induced dopamine deficits. These findings establish Syngr3 as a key dopamine regulator and potential therapeutic target for cocaine use disorder.
GPT-4o mini: Non-social science research article
A photosynthetic–respiratory electron transport chain chimera based on photosystem I and cytochrome c oxidase on graphene oxide
Xiaoping Zhu, Matthew J. Kummer, Carolyn E. Lubner, Vasily Kurashov, William Carr, John H. Golbeck, Robert A. Niederman, Lev G. Mourokh, Shelley D. Minteer, Paul G. Falkowski, Michele Vittadello
Full text
The self-assembly of enzyme proteins on 2D nanomaterials has enabled the construction and functional control of viable biochemical pathways. However, enzymatic cascades, which combine essential components of the photosynthetic and respiratory electron transport chains in tandem, have thus-far remained elusive. Herein, we have investigated a galvanic biohybrid nanosystem coupling photosystem I and cytochrome c oxidase on the surface of graphene oxide nanosheets in colloidal suspension. The oriented immobilization of the enzymes was facilitated by Ni-coordination sites tethered to the carbon basal plane, with negligible parasitic O 2 consumption. Transient absorption and electrochemical measurements provided evidence of electron transfer between donors and acceptors, leading to light-induced O 2 consumption of up to 70 out of 120 O 2 molecules/s/CcO unit. Graphene oxide behaves as an electronic reservoir and as an electroactive support, enabling electron transport, in concert with cytochrome c , as well as small-molecule redox mediators and reductants. This study provides a state-of-the-art approach for the exploration of photoelectron transfer in membrane-free suspensions of nanosurface-anchored photosynthetic–respiratory enzymatic chains.
GPT-4o mini: Non-social science research article
Global stratospheric methane loss from satellite observations
Qiang Fu, Cong Dong
Full text
Stratospheric CH 4 oxidation represents both an important sink in the global CH 4 budget and a major source of stratospheric water vapor and hydrogen radicals, exerting strong influences on global climate and ozone chemistry. Yet, the magnitude of stratospheric CH 4 chemical loss remains highly uncertain, with previous estimates largely relying on chemistry-climate models (CCMs). Here, we present an observationally based estimate of stratospheric CH 4 loss ( L STR ), derived from the CH 4 diabatic flux across the isentropic surface fitted to the tropical tropopause, using satellite measurements of CH 4 concentration, temperature, and radiative heating rates for 2007–2010. We obtain an L STR of 49.8 ± 7.8 Tg/y, compared with 38.1 Tg/y estimated from reanalysis, and 25.7 Tg/y (range: 19.6 to 35.9 Tg/y) derived from CCMs, indicating that both reanalysis and CCMs systematically underestimate stratospheric CH 4 loss. We show that discrepancies in global CH 4 diabatic fluxes from the reanalysis and CCMs, when compared with observations, are mainly driven by biases in CH 4 concentrations and further enhanced by errors in temperature and radiative heating. Substituting our observational estimate for the model-based stratospheric loss in the bottom-up global CH 4 budget reduces the reported imbalance for the 2000s from 23 to 3 Tg/y, bringing it into close agreement with the 5 Tg/y (range: −4 to 13 Tg/y) imbalance inferred from top-down estimates. These findings highlight the critical role of observational constraints on L STR in reconciling the global CH 4 budget. They also carry important implications for understanding stratospheric water vapor and ozone chemistry.
GPT-4o mini: Non-social science research article
Photoenzymatic Csp 3 –Csp 3 bond formation via enzyme-templated radical–radical coupling
Yi Liu, Daniel G. Oblinsky, Gianluca Dell’Orletta, Nico Di Fonte, Damien Sorigue, Claire G. Page, Isabella Daidone, Gregory D. Scholes, Todd K. Hyster
Full text
Cross-couplings are essential reactions in modern chemical synthesis, enabling the rapid construction of complex molecules from simple precursors. Transition metal catalysts are prized for these transformations because their reactivity and selectivity can be tuned via judicious selection of the metal and ligand. Although enzymes offer analogous opportunities for tuning via protein engineering, their application to cross-coupling remains limited, as nature relies on alternative paradigms for building molecular complexity. Here, we report the cross-coupling of alkyl halides and benzylic carboxylic acids using an engineered flavin-dependent lactate monooxygenase—a photoenzyme. The enzyme achieves this feat by exploiting the redox versatility of the flavin cofactor. Stoichiometric experiments, ultrafast spectroscopy, and computational studies support a mechanism in which photoexcited flavin quinone initiates the reaction via oxidative decarboxylation to generate a benzylic radical. The resulting flavin semiquinone can reduce the alkyl halide to form a second organic radical within the protein active site, which rapidly engages in C(sp 3 )–C(sp 3 ) bond formation. A variant was engineered to control the stereochemical outcome of this radical–radical coupling event, highlighting the ability of the protein to alter the energetic barrier for a mechanistic step that is traditionally understood to be near barrierless. This work demonstrates that the scope for nonnative reaction mechanisms in biocatalysis far exceeds previously established bounds and has potential to solve a variety of reactivity challenges in cross-coupling chemistry.
GPT-4o mini: Non-social science research article
Allosteric coupling between PIP 2 and Ca 2+ binding sites gates TMEM16A channels
Jie Xu, Ana Santa-Cruz, Aishwarya Chandrashekar, Takeharu Kawano, R. Charles Kissell, Mehreen Zaka, Zhe Zhang, Meng Cui, Diomedes E. Logothetis, Leigh D. Plant
Full text
TMEM16A channels conduct Ca 2+ -activated Cl − currents that underlie essential physiological processes including epithelial secretion, smooth muscle contraction, and sensory transduction. Channel activation requires both intracellular Ca 2+ and the signaling phospholipid phosphatidylinositol 4,5-bisphosphate (PIP 2 ), yet the molecular basis of this dual regulation has remained unclear. Using gating molecular-dynamics simulations and structure-guided electrophysiology, we show that PIP 2 and Ca 2+ cooperatively gate TMEM16A through an allosterically coupled electrostatic network centered on the α4 helix. Specific PIP 2 headgroup phosphate interactions are essential for coupling Ca 2+ binding to channel opening, while the PIP 2 acyl chains engage hydrophobic surfaces of the helix to stabilize the open conformation. Disrupting either component of this lipid–protein interface reduces apparent PIP 2 affinity and impairs activation, whereas long-chain PIP 2 fully restores wild-type activity. These interactions act in concert with Ca 2+ -dependent structural rearrangements that widen the conduction pathway and enable Cl − permeation. Our findings establish that both the headgroup phosphates and acyl chains of PIP 2 play indispensable and complementary roles in TMEM16A gating. This mechanism defines a cooperative lipid–ion activation process that provides a general framework for understanding phosphoinositide regulation of ion channels and offers opportunities for structure-based design of TMEM16A modulators.
GPT-4o mini: Non-social science research article
Human mitotic spindles as active liquid crystals: From collective behaviors to discrete filaments
Suryanarayana Maddu, Colm P. Kelleher, Mustafa Basaran, Thomas MĂŒller-Reichert, Michael J. Shelley, Daniel J. Needleman
Full text
How thousands of microtubules (MTs) and molecular motors self-organize into spindles remains poorly understood. By combining static, nanometer-resolution, large-scale electron tomography reconstructions and dynamic, optical-resolution, polarized light microscopy, we test an active liquid crystal continuum theory of mitotic spindles in human tissue culture cells. At micron length scales, probed by optical microscopy, the continuum theory accurately captures spindle morphology and fluctuation spectra, indicating that local interactions-polymerization, alignment, diffusion, and polar transport-govern the collective behaviors of MTs in human mitotic spindles. Electron tomography data enables tests of the continuum theory at submicron scales, revealing that chromosome-attached kinetochore microtubules (KMTs) show distinctive lateral organization not explained by the coarse-grained theory, while the non-KMTs that make up the bulk of the spindle follow the theory down to ∌300 nm length scales. At length scales below ∌300 nm, fluctuations arising from the intrinsic discreteness of the microtubule ensemble dominate over the collective correlations predicted from the continuum theory. Taken together, these findings show that an active liquid-crystal theory can quantitatively capture the self-organization of human mitotic spindles on long length scales and provides a means to measure the spindle’s material properties, while also pointing to the existence of additional processes contributing to the behaviors of KMTs.
GPT-4o mini: Non-social science research article
Genetic recording of pancreatic beta cell proliferation
Huan Zhao, Hui Chen, Zhixin Kang, Xiuzhen Huang, Jingting Zhu, Zixin Liu, Xiuxiu Liu, Ximeng Han, Jie Lu, Bin Zhou
Full text
Pancreatic beta cell generation and proliferation primarily rely on the self renewal of preexisting beta cells, making precise quantification of beta cell proliferation essential for understanding pancreatic homeostasis and pathogenesis. However, previous methods had limitations and were unable to trace beta cell proliferation in vivo over extended periods. Here, we developed beta cell ProTracer, a genetic system that uses dual recombinase technology to enable continuous and cell type-specific recording of beta cell proliferation in mice. The beta cell ProTracer system allows for the quantification of the proliferation rate of adult pancreatic beta cells during homeostasis and in response to injury or drug treatment. Clonal analysis of the proliferated beta cell population reveals a uniform proliferative capacity among these cells. Our findings enhance the understanding of beta cell proliferation dynamics in homeostasis, repair, and regeneration.
GPT-4o mini: Non-social science research article
Structural analysis of rhodopsin states in megabody complexes
David Salom, Diana S. Suder, Wei Huang, Arum Wu, Els Pardon, Jan Steyaert, Philip D. Kiser, Derek J. Taylor, Shane Gonen, Krzysztof Palczewski
Full text
Rhodopsin, the most intensively studied G protein–coupled receptor (GPCR), is activated by light-induced isomerization of its chromophore 11- cis -retinal. This study employed cryogenic electron microscopy (cryo-EM) to investigate rhodopsin structure using a megabody (Mb7) as a negative allosteric modulator. Three distinct cryo-EM structures were solved: ground-state rhodopsin, photoactivated rhodopsin, and apo-rhodopsin, all in complex with Mb7. Photoactivated rhodopsin and apo-rhodopsin, both in complex with Mb7, maintain a conformation remarkably similar to ground-state rhodopsin rather than adopting a Meta-II-like conformation. Structural elements, including the conserved residues of the NPxxY motif and the ionic lock, remain in positions corresponding to inactive rhodopsin. The megabody forms extensive interactions with rhodopsin’s extracellular loop 2, N terminus, and glycans. The findings demonstrate that Mb7 stabilizes photoactivated rhodopsin in a Meta-I-like conformation, preventing progression to the active Meta-II state through specific immobilization of the extracellular domain. This work establishes a foundation for cryo-EM-guided discovery of ligands modulating rhodopsin.
GPT-4o mini: Non-social science research article
Structural and mechanistic diversity of glycogen phosphorylases from gut bacteria
Keigo Shobu, Mayu Takai, Hiroki Tanino, Yohta Fukuda, Tsuyoshi Inoue
Full text
Glycogen phosphorylase (GP) plays a central role in glycogen metabolism. While the structure and regulation of mammalian GPs have been extensively studied, the corresponding mechanisms in gut bacterial GPs remain poorly understood. Here, we investigate GPs from Escherichia coli ( Ec GP), Segatella copri ( Sc GP), and Dorea longicatena ( Dl GP), which represent three phylogenetic clades of GPs, using enzymatic assays, cryo–electron microscopy (cryo-EM), and X-ray crystallography. We find that Sc GP forms a unique pentamer that undergoes adenosine monophosphate (AMP)-dependent assembly into a dimer-of-pentamer, which inhibits activity by restricting substrate access to the catalytic site. Ec GP exists in equilibrium among monomers, dimers, and tetramers, with AMP promoting tetramer dissociation and enhancing catalytic efficiency. In contrast, Dl GP remains predominantly monomeric and is unresponsive to AMP. These findings uncover structural and regulatory diversity among gut bacterial GPs. Notably, the oligomeric states of GPs modulate substrate accessibility and enzyme activation, suggesting a distinct mode of allosteric regulation beyond the canonical T-to-R transition model. Because bacterial GPs contribute to the generation of glucose, their regulation may influence the composition of gut-derived metabolites that affect host glucose homeostasis and insulin sensitivity. Our study provides mechanistic insight into the structural and functional diversity of gut bacterial GPs and lays a foundation for future exploration of microbiome-mediated metabolic interactions.
GPT-4o mini: Non-social science research article
Universal relation between spectral and wavefunction properties at criticality
Simon Jiricek, Miroslav Hopjan, Vladimir Kravtsov, Boris Altshuler, Lev Vidmar
Full text
Quantum-chaotic systems exhibit several universal properties, ranging from level repulsion in the energy spectrum to wavefunction delocalization. On the other hand, if wavefunctions are localized, the energy levels exhibit no level repulsion and their statistics is Poisson. At the boundary between quantum chaos and localization, however, one observes critical behavior, not complying with any of those characteristics. An outstanding open question is whether there exists yet another type of universality, which is genuine for the critical point. Previous work suggested that there may exist a relation between the global characteristics of the energy spectrum, such as the spectral compressibility χ , and the degree of wavefunction delocalization, expressed via the fractal dimension D 1 of the Shannon–von Neumann entropy in a preferred (e.g., real-space) basis. Here, we study physical systems subject to local and nonlocal hopping, both with and without time-reversal symmetry, with the Anderson models in dimensions three to five being representatives of the first class, and the random banded matrices as representatives of the second class. Our thorough numerical analysis supports the validity of the simple relation χ + D 1 = 1 in all systems under investigation. Hence, we conjecture that it represents a universal property of a broad class of critical models. Moreover, we test and confirm the accuracy of our surmise for a closed-form expression of the spectral compressibility in the one-parameter critical manifold of random banded matrices. Based on these findings, we derive a universal function D 1 ( r ) of the averaged level spacing ratio r , which is valid for a broad class of critical systems.
GPT-4o mini: Non-social science research article
Sound reasons for tympanic hearing in mammalian precursors
Lars Schmitz
Full text
GPT-4o mini: Non-social science research article
Parasitic castration by a viral protein tyrosine phosphatase targeting the host cell cycle checkpoint protein Rad9A
Hongshuai Gao, Mujuan Guo, Xin Yang, Rongmin Hu, Kun Wu, Lan Pang, Xiqian Ye, Jianhua Huang, Xuexin Chen, Zhizhi Wang
Full text
Parasitic castration is a widespread strategy where parasites hijack host reproductive resources, yet the key molecular mechanisms driving this phenomenon remain poorly understood. Here, we reported that parasitization by the parasitic wasp Cotesia vestalis triggers apoptosis-mediated castration in the larval testes of its lepidopteran host, Plutella xylotella . Such a phenomenon was mediated by CvBV_22-9 , a testis-enriched protein tyrosine phosphatase (PTP) encoded by Cotesia vestalis bracovirus (CvBV), a domesticated virus endogenized in the wasp. Similarly, a homolog of CvBV_22-9, encoded by the Microplitis manilae bracovirus, is involved in testis castration by inducing apoptosis in parasitized fall armyworm, Spodoptera frugiperda . Mechanistically, CvBV_22-9 binds to a cell cycle checkpoint protein, Rad9A, but does not alter its tyrosine phosphorylation level. Crucially, CRISPR-Cas9 knockout of Rad9A causes embryonic lethality and severe testis defects. Validation in Drosophila melanogaster shows that testis-specific expression of CvBV_22-9 or Rad9A knockdown induces apoptosis, while combined targeting synergistically enhances this effect, suggesting a conserved function of both proteins in insects. Our study uncovers a regulatory mechanism where a parasitoid wasp deploys a domesticated viral PTP that functions as a pseudophosphatase to induce Rad9A-mediated apoptosis and disrupt host testis development and spermatogenesis. This mechanism highlights a sophisticated strategy of host exploitation by parasitoid wasps, providing insights for the biocontrol of lepidopteran pests.
GPT-4o mini: Non-social science research article
Dual quantum locking: Dynamic coupling of H 2 and H 2 O sublattices in hydrogen-filled ice
Loan Renaud, Tomasz Poreba, Simone Di Cataldo, Alasdair Nicholls, LĂ©on Andriambariarijaona, Maria Rescigno, Richard Gaal, Michele Casula, A. Marco Saitta, Livia Eleonora Bove
Full text
Hydrogen hydrates (HH) are a unique class of materials composed of hydrogen molecules confined within crystalline water frameworks. Among their multiple phases, the filled ice structures, particularly the cubic C2 phase, exhibit exceptionally strong host–guest interactions due to ultra-short H 2 -H 2 O distances and a 1:1 stoichiometry leading to two interpenetrated identical diamond-like sublattices, one comprised of water molecules, the other of hydrogen molecules. At high pressures, nuclear-quantum effects involving both hydrogen molecules and the water lattice become dominant, giving rise to a dual-lattice quantum system. In this work, we explore the sequence of pressure- and temperature-driven phase transitions in HH, focusing on the interplay between molecular rotation, orientational ordering, lattice symmetry breaking, and hydrogen bond symmetrization. Using a combination of computational modeling based on classical and path-integral molecular dynamics, quantum embedding, and high pressure experiments, including Raman spectroscopy and synchrotron X-ray diffraction at low temperatures and high pressures, we identify signatures of quantum-induced ordering and structural transformations in the C2 phase. Our findings reveal that orientational ordering in HH occurs at much lower pressures than in solid hydrogen, by inducing structural changes in the water network and enhancing the coupling of water and hydrogen dynamics. This work provides insights into the quantum behavior of hydrogen under extreme mechanochemical confinement and establishes hydrogen-filled ices as a promising platform for the design of hydrogen-rich quantum materials.
GPT-4o mini: Non-social science research article
A ribosomally synthesized and posttranslationally modified peptide with ADP-ribosylation
Sijia Guo, Suze Ma, Lulu Song, Jun Wang, Tonghai Liu, Wupeng Yan, Wei Zhang, Zixin Deng, Wei Ding, Qi Zhang
Full text
Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a fertile ground for uncovering new enzymatic chemistry and structural complexity. Here, we describe minviopeptin, an unusual ADP-ribosylated triceptide accessed through heterologous expression of a cryptic biosynthetic gene cluster. Structural and functional analyses reveal a combination of crosslinking, ADP-ribosylation, and oxidative peptide cleavage, underscoring the capacity of RiPP pathways to generate densely functionalized molecular scaffolds. By revealing ADP-ribosylation as a previously unrecognized RiPP modification and exposing reactivity within radical SAM and nonheme iron enzymes, this work broadens the landscape of RiPP biosynthetic chemistries and offers opportunities for natural product diversification and peptide engineering.
GPT-4o mini: Non-social science research article
Identifying genome-by-childhood trauma interactions for depression using a forest-based approach in the UK Biobank and Adolescent Brain Cognitive Development Study
Yue Hu, Jeffrey R. Gruen, Heping Zhang
Full text
Depression is shaped by both genetic and environmental factors, but genome-wide interaction studies (GWIS) often lack power to detect complex gene–environment (G × E) interactions. We applied a forest-based machine learning approach to 38,018 UK Biobank (UKB) participants, examining interactions between 285,677 single-nucleotide polymorphisms (SNPs) and three trauma types (childhood, adult, and catastrophic trauma). While GWIS detected no significant interactions, we identified 8,225 potentially important SNP–environment pairs across 1,732 genes, with childhood trauma contributing most prominently. Stratified heritability was higher among childhood trauma–exposed individuals (13.3%) versus those unexposed (6.0%). Many identified genes overlapped with known psychiatric risk loci and accounted for most of the SNP-based heritability. Thirteen top genes were replicated in the Adolescent Brain Cognitive Development Study. Our findings highlight the polygenic G × E nature of depression and the critical role of childhood trauma in modulating genetic risk, demonstrating the value of forest-based methods in detecting complex gene–environment interactions.
GPT-4o mini: Non-social science research article
High-speed in situ tomographic imaging at lab scale
Abdallah Aly, M. Taher A. Saif
Full text
GPT-4o mini: Non-social science research article
Bimodal dynamics of viscous pearls
Auriane Huyghues Despointes, Abhijit Kumar Kushwaha, JérÎme Fresnais, Tadd Truscott, David Quéré
Full text
Droplets on super-repellent materials adopt the shape of pearls, which makes them highly mobile, owing to the conjunction of low contact line pinning with small dynamical friction. This property is especially valuable when drops are viscous, a case where we expect super-repellency to minimize the friction associated with viscosity. Here, we report that viscous droplets on highly repellent inclines can have two modes of descent, depending on the way they are deposited: either they run at the fast speed expected for pearls or they are 30 to 60 times quicker, which defines a super-fast regime of motion. We show that this effect relies on the tenuousness of the contact with the substrate. Consequently, this contact can be dynamically “erased” by the insertion of a cushion of air, which makes droplets glide at a speed both high and independent of their viscosity. We characterize these lubricating films (thickness and onset of appearance) and finally show that super-fast pearls initiated on a superhydrophobic (SH) surface can maintain their velocity and shape even on a hydrophilic solid.
GPT-4o mini: Non-social science research article
Electrotunable coupling between an epsilon-near-zero thin film and conducting polymer nanoantennas
Yulong Duan, Suraya Kazi, Dongqing Lin, Longzhu Liu, Magnus P. Jonsson
Full text
Plasmonic resonances in nanostructured conducting polymers provide a compelling route to actively tunable nanophotonics and metasurfaces, owing to their ability to be dynamically modulated through electrochemical doping. Although their lower mobility limits resonance quality compared to noble metal plasmonics, we experimentally demonstrate that the resonances of conducting polymer nanoantennas can effectively couple to epsilon-near-zero (ENZ) mode of an underlying thin indium tin oxide layer, in a manner analogous to noble metal plasmon–ENZ interactions. We show that the coupling strength can be modulated reversibly via electrical bias or chemical redox control, enabling dynamic tuning of electromagnetic field enhancement in the ENZ layer with a modulation depth exceeding 90%. These findings establish conducting polymer nanoantennas as a versatile platform for reconfigurable ENZ-based photonic systems, paving the way for nanophotonic devices with tunable linear and nonlinear optical functionalities.
GPT-4o mini: Non-social science research article
Methionine-specific nonreversible bioconjugation: Advancing precision protein modification
Shirui Wang, Zhenguo Zhang, Raymond Tio, Bohan Li, Joycelyn Yi Xin Khoo, Teck-Peng Loh
Full text
We present a methionine-selective, nonreversible bioconjugation strategy that employs activated allylic bromides under mild, aqueous reaction conditions compatible with various peptides and proteins. Compared with conventional allylic bromides, our method improves conjugate stability and suppresses nonspecific reactivity under the examined reaction conditions. This method enables methionine-preferred labeling of peptides and proteins, and provides proof-of-concept applications in covalent inhibitor design and protein functionalization. As a complementary addition to existing methionine bioconjugation strategies, this chemistry expands the toolkit available for protein modification and chemical biology research.
GPT-4o mini: Non-social science research article
Charge acceleration without radiation
Y. Aharonov, D. Collins, S. Popescu
Full text
The existence of electromagnetic radiation—radio waves, microwaves, light, X-rays, and so on—is one of the most important physical phenomena, and our ability to manipulate them is one of the most significant technological achievement of humankind. Underlying this ability is our understanding of how radiation is produced: Whenever an electric charge is accelerated, it radiates. Or, at least, this is how it has been hitherto universally thought. Here, we prove that quantum mechanically electric charges can be accelerated without radiating. The physical setup leading to this behavior is relatively simple (once one knows what to do), but its reasons are deep: It relies on the fact that quantum mechanically particles can be accelerated even when no forces act on them, via the Aharonov–Bohm effect. As we argue, the effect presented here is just the tip of an iceberg–it implies the need to reconsider the basic understanding of radiation. Finally, it seems clear that the effect goes far beyond electromagnetism and applies to any kind of radiation.
GPT-4o mini: Non-social science research article
High-speed atomic force microscopy reveals a surface-catalyzed elongation mechanism of the fungal functional amyloid hydrophobin RolA
Nao Takahashi, Tatsuya Kimura, Yuki Terauchi, Takumi Tanaka, Natsuki Abe, Akira Yoshimi, Takahiro Watanabe-Nakayama, Keietsu Abe
Full text
Hydrophobins are functional amyloids conserved in filamentous fungi. They act as a protective coat in the fibrous form, called rodlet. Rodlets further assemble to form dense films where they are bundled and densely aligned, contributing to the hydrophobicity of the mycelium surface. The mechanism of this dense film formation is completely unknown. Here, we used high-speed atomic force microscopy to directly observe the structural dynamics of rodlet bundling and subsequent film formation by hydrophobin RolA from the industrial fungus Aspergillus oryzae at a single-fibril level, and we revealed the film-formation mechanism. Rodlet elongation occurred at both ends and was discontinuous, alternating between periods when rodlets could elongate (growth state) and could not elongate (pause state). This suggests an equilibrium of two distinct structural states at the rodlet ends. We also identified a pathway, termed “surface-catalyzed elongation,” in which elongation is promoted by lateral interactions between bundled rodlets. Surface-catalyzed elongation decreased the energy barrier of both structural switching between growth and pause states and elongation at rodlet ends, doubling the elongation rate in bundled rodlets. The rodlet surface could be considered as a catalyst for the elongation of neighboring rodlets. Surface-catalyzed elongation could contribute to rodlet bundling, whereby rodlets tend to form oriented domain structures; our Monte Carlo simulations confirmed this. The concept we propose here provides a clear explanation of the mechanism by which rodlets form a dense coat on the cell surface.
GPT-4o mini: Non-social science research article
Dominant inverse nonlinear energy cascades in coastal and inner shelf waters
Annalisa De Leo, Chang He, Alessandro Stocchino
Full text
As well known, almost 80% of the total oceanic kinetic energy is contained within the mesoscale eddies, but the cross-scale energy transfers linking eddy generation and dissipation remain an open question. The Earth rotation controls the generation of mesoscale eddies that transfer energy toward larger scales via an inverse cascade, but a transfer to small scale is needed for dissipation: a coexistence of transfers is indeed required. However, the turbulent energy cascade, responsible for oceanic circulation energy balance and nutrient mixing, involves such a large range of scales making extremely challenging the investigation of the full spectrum of processes. This study examines how energy and enstrophy cascade across ocean scales in the inner shelf of the Great Bay Area of the South China Sea using high-resolution numerical simulations. By applying coarse-graining techniques, the results reveal a predominant inverse energy cascade scenario driven by the interplay between background stratification and rotation, particularly in areas affected by the Pearl River’s freshwater influx. Geographical heterogeneity significantly influences these dynamics, with shallow inlets experiencing increased frictional drag and energy dissipation due to complex bathymetry, while open-water areas show heightened submesoscale activity. Seasonal monsoon cycles further modulate these processes, with summer winds amplifying nonlinear energy transfers through increased wind stress and river discharge, in contrast to the tidally dominated, quasi-steady flows observed in winter. Understanding how wind and tide affect ocean mixing can help to develop more accurate climate models and better strategies for protecting coastal ecosystems.
GPT-4o mini: Non-social science research article
TRIM21enhances IL-17A signaling and drives autoimmune myocarditis by promoting TRAF3 lysosomaldegradation in cardiac fibroblasts
Yahui Song, Xuege Huang, Lin Wei, Wenwen Shen, Jiapeng Gao, Kai Hou, Bin Yang, Yi Wang, Guang Hu, Wei Xu, Jing Guo, Wenlong Lin, Min Li
Full text
Myocarditis is a potentially fatal disease that can progress to inflammatory dilated cardiomyopathy (DCMi), a condition that is a leading cause of noncongenital heart failure in young adults. However, the mechanisms driving the transition from acute myocarditis to DCMi remain poorly understood. Although IL-17A-mediated inflammation is a well-known driver of this progression, the intracellular regulators that sustain and amplify this response remain unclear. Here, we identify the E3 ubiquitin ligase TRIM21, which is upregulated in the hearts of DCMi patients and experimental autoimmune myocarditis (EAM) mice, as a key amplifier of IL-17A-driven inflammation in cardiac fibroblasts (CFs), promoting disease progression and fibrosis. TRIM21 deficiency significantly attenuates EAM progression, reducing inflammatory cell infiltration and fibrotic remodeling. Mechanistically, TRIM21 is induced by IL-17A in CFs and promotes K27-linked polyubiquitination and lysosomal degradation of TRAF3, a negative regulator of IL-17A signaling, thereby establishing a self-reinforcing IL-17A-TRIM21–TRAF3 positive feedback loop. Finally, specific knockdown of TRIM21 in CFs via the AAV9-Postn strategy effectively alleviates EAM severity. These findings identify TRIM21 as an intracellular mediator of sustained IL-17A signaling in myocarditis and highlight its potential as a therapeutic target for preventing progression to DCMi.
GPT-4o mini: Non-social science research article
Single-cell transcriptomics of the Drosophila ring gland identifies the SoxN–Vvl complex as a key regulator of juvenile hormone biosynthesis
Yuhan Luo, Nan Chen, Yue Gao, Wei Luo, Shanshan Liu, Yang Li, Hanyue Wang, Xiangbin Gao, Jiawei Chen, Haosheng Ye, Kirst King-Jones, Subba Reddy Palli, Sheng Li, Suning Liu
Full text
Juvenile hormone (JH) is essential for maintaining juvenile status and promoting reproduction in insects, yet the transcriptional regulation of JH biosynthesis remains poorly understood. Previous transcriptomic studies of the Drosophila ring gland—which is composed of the corpus allatum (CA), prothoracic gland (PG), and corpora cardiaca (CC)—have treated the ring gland as a single tissue. As a result, these approaches lacked the resolution necessary to dissect JH biosynthesis and its regulation in a cell-type-specific manner. To overcome this limitation, we performed single-cell RNA sequencing (scRNA-seq) of 7,919 cells isolated from the larval ring glands. This analysis resolved distinct transcriptional profiles for the CA, PG, and CC, and enabled the identification of CA-specific transcription factors. Among them, SoxNeuro (SoxN), was found to be essential for JH biosynthesis and functionally important for both metamorphosis and reproduction. We further demonstrate that SoxN physically interacts with Ventral veins lacking (Vvl) to form a transcriptional complex that directly regulates Jhamt , a rate-limiting enzyme in JH biosynthesis, via a defined promoter region. Together, this work presents a single-cell transcriptomic atlas of the Drosophila ring gland and identifies the SoxN–Vvl complex as a critical regulator of JH biosynthesis, offering insight into the transcriptional control of insect endocrine function.
GPT-4o mini: Non-social science research article
A method to study and enhance the energy efficiency of soft electrostatic actuators
Steven L. Zhang, Toshihiko Fukushima, Sophie Kirkman, Soo Jin Adrian Koh, Philipp Rothemund, Christoph Keplinger
Full text
Actuators drive robotic motion, and their energy conversion efficiency is a key performance metric that informs power consumption. Soft electrostatic actuators promise new opportunities for bioinspired and wearable robotics, being driven by electrical signals and producing high-speed, muscle-like motion. Unlike electromagnetic motors, for which efficiency has been systematically studied, efficiency of soft actuators lacks a standardized definition and measurement method, highlighting the need for a unified framework for the evaluation of their efficiency. Here, we propose a comprehensive method to study electrical-to-mechanical energy conversion in soft electrostatic actuators by analyzing closed cycles on planes spanned by work-conjugate variables: voltage–charge and force–position; our experimental setup allows us to prescribe and measure in real-time all work-conjugate variables and thus, to evaluate efficiency as function of load, electric potential, frequency, and actuator materials. We introduce a practical work cycle to evaluate actuators, and, using Peano-HASEL (Hydraulically Amplified Self-healing ELectrostatic) actuators as a model system, we reveal that efficiency is highly dependent on applied voltage, force, and actuation frequency; within the tested range of parameters, we measure a maximum efficiency of 63.6%, which is more than three times the previously reported value for HASEL actuators. We further study energy losses inherent in mechanical and electrical cycles. We show the general applicability of our method across different electrostatic actuators by applying it to a pure-shear dielectric elastomer actuator (DEA), demonstrating efficiencies up to 62.9%. This comprehensive method will facilitate the study and development of electrostatic actuators for the next generation of highly efficient soft robots.
GPT-4o mini: Non-social science research article
Sensory integration, temporal prediction, and rule discovery reflect interdependent inference processes
Lucas Benjamin, Benjamin Morillon, Valentin Wyart
Full text
Deciphering the structure of variable sensory input is key to building an accurate model of one’s environment. Humans can accumulate evidence from sequences of stimuli to estimate their sensory statistics, predict the timing of upcoming stimuli, but also discover rules governing sequence generation. However, whether these three forms of inference operate independently or synergistically remains untested. Here, we report selective interactions between sensory integration, temporal prediction, and rule discovery in humans. Participants were exposed to rhythmic sequences of 10 stimuli governed or not by a latent rule—a predictable change in stimulus statistics after five stimuli—and then asked to predict the 10th stimulus from incomplete sequences. Individual differences in sensory integration timescale for rule-free sequences predicted efficient rule discovery. Conversely, discovering the latent rule shaped the timescale and format of sensory integration for rule-based sequences. Tampering with the rhythmicity of stimulus presentation impaired rule discovery without affecting sensory integration accuracy. Selective perturbations of recurrent neural networks trained in the same conditions confirmed these specific interactions. Together, these findings provide insights into the flexibility of human inferences based on variable yet predictable sensory input.
GPT-4o mini: Non-social science research article
Evolutionary bioenergetics of sporulation
Canan Karakoç, William R. Shoemaker, Jay T. Lennon
Full text
Energy is required for the expression and maintenance of complex traits. In many habitats, however, free energy available to support biosynthesis is in vanishingly short supply. As a result, many taxa have evolved persistence strategies that support survival in unfavorable environments. Among these is sporulation, an ancient bacterial program governed by a large genetic network that requires energy for both regulation and execution. Yet sporulation is a last resort, initiated when cellular energy is nearly exhausted. To resolve this paradox, we quantified the energetic cost of sporulation in units of ATP by integrating time-resolved genome, transcriptome, and proteome profiles. The full cost of the spore cycle, including both formation and revival, ranks among the most energy-intensive processes in the bacterial cell, requiring almost 10 10 ATP and consuming about 10% of the total energy budget. The majority of this cost arises from translation, membrane synthesis, and protein turnover. Despite its considerable upfront investment, sporulation enables long-term survival and becomes optimal when harsh conditions extend over timescales of months or longer. This trade-off between immediate cost and delayed benefit helps explain when sporulation is maintained or replaced by alternative strategies. By incorporating our estimates into mechanistic models, we show how metabolic constraints shape sporulation efficiency, while genome-wide mutation accumulation data reveal that even modest energetic burdens can become visible to selection, influencing the evolutionary fate of this complex and widespread trait.
GPT-4o mini: Non-social science research article
Optogenetic control of transition to metamorphosis
Changyuan Wang, Denis F. Faerberg, Yuka Sekine, Takeaki Ozawa, John J. Tyson, Robert A. Marmion, Stanislav Y. Shvartsman
Full text
System identification approaches are commonly used in engineering to infer simple yet predictive models of complex systems from their responses to time-dependent perturbations. Here, we apply this strategy at the whole organism scale, establishing a predictive model of commitment to metamorphosis in Drosophila . At this critical point in animal development, the larva stops feeding and proceeds to take on the adult form. The neuroendocrine circuits governing commitment to metamorphosis assess the growth and patterning programs, eventually triggering the production of systemic hormones that terminate growth and initiate metamorphosis. Previous studies of these circuits relied on relatively static genetic perturbations and starvation experiments. Here, we take advantage of optogenetic approaches in Drosophila to flexibly perturb a key signaling node within the endocrine gland in otherwise undisturbed larvae. We used this approach to infer parameters in a compact mathematical model and demonstrate that it makes accurate predictions of larval commitment to metamorphosis. Our work paves the way for quantitative studies of other juvenile-to-adult transitions, including mammalian puberty, which relies on strikingly similar mechanisms.
GPT-4o mini: Non-social science research article
Strategy evolution on temporal hypergraphs
Xiaochen Wang, Lei Zhou, Alex McAvoy, Zhenglong Tian, Aming Li
Full text
Individuals interact and cooperate in structured systems. Many studies represent this structure using static networks, where each link represents a permanent connection between two nodes. However, real interactions are generally not time-invariant and are often not pairwise. Recently, progress has been made in modeling higher-order interactions using hypergraphs, where a link may connect more than two individuals. Here, we study cooperation on temporal hypergraphs, capturing the time-varying, higher-order interactions seen in empirical systems. We find that temporal hypergraphs can promote cooperation compared with static networks, and the latter may even underestimate the cooperation-boosting effects of constrained, local interactions. We further show that cooperation can be facilitated by temporal hypergraphs with sparse components and higher-order interactions. Importantly, when the size of group interactions (hyperedges) is comparable to the population size, relatively small hyperedge sizes best facilitate cooperation. Synthetic and empirical hypergraphs alike affirm our findings, illuminating how temporal, higher-order interactions profoundly shape the evolution of cooperation.
GPT-4o mini: Non-social science research article
Multiple formation pathways for amino acids in the early Solar System based on carbon and nitrogen isotopes in asteroid Bennu samples
Allison A. Baczynski, Ophélie M. Mcintosh, Danielle N. Simkus, Hannah L. McLain, Jason P. Dworkin, Daniel P. Glavin, Jamie E. Elsila, Mila Matney, Christopher H. House, Katherine H. Freeman, Harold C. Connolly, Dante S. Lauretta
Full text
Samples collected from the carbonaceous near-Earth asteroid Bennu and delivered to Earth by NASA’s OSIRIS-REx mission contain organic molecules relevant to prebiotic chemistry. Stable isotopic measurements of extraterrestrial soluble organic matter provide critical insights into the formation pathways and alteration histories of such molecules, which hold significance for understanding the origins of life. We leverage state-of-the-art techniques for picomolar-scale isotopic analyses of amino acids in samples of Bennu and, for comparison, the carbonaceous meteorite Murchison. We report intramolecular ÎŽ 13 C values for glycine, which have not previously been measured in extraterrestrial materials; molecular-averaged ÎŽ 13 C values for amino acids, aldehydes, and ketones; and ÎŽ 15 N values for glycine, ÎČ-alanine, and D/L-glutamic acid. Intramolecular carbon isotope patterns of glycine in Bennu contrast with those in Murchison, suggesting distinct formation pathways. We explore several formation mechanisms and hypothesize that the observed glycine in Murchison formed dominantly by a Strecker-like synthesis under aqueous conditions, whereas the glycine currently found in Bennu may have formed mainly by modified radical–radical reactions in primordial ices at the cold, outer reaches of the early Solar System and retained its isotopic values throughout accretion and multiple episodes of aqueous alteration. This hypothesis is supported by the highly 15 N-enriched ÎŽ 15 N values in Bennu amino acids (+170 to 277‰). Differences in the ÎŽ 15 N values of D- and L-glutamic acid (Δ = 87‰) in Bennu affirm published reports of enantiomeric differences in meteoritic amino acids and challenge the assumption of isotopic uniformity between amino acid chiral pairs.
GPT-4o mini: Non-social science research article
Ufd2p promotes efficient crossover formation by destabilizing Top2p during meiosis
Taicong Tan, Yanan Zhao, Yinghong Chen, Yali Mi, Jiaxin Zeng, Peng Du, Tingting Han, Yawen Liu, Ning Li, Jun Kong, Liying Wang, Yang Yu, Mulin Jun Li, Liangran Zhang, Wei Li, Chao Liu
Full text
Proper crossover (CO) formation in meiosis serves dual roles in ensuring accurate chromosome segregation and generating genetic diversity. However, the molecular mechanisms underlying CO number and distribution remain incompletely understood. Previous studies have implicated the ubiquitin–proteasome system in CO regulation, but specific regulators and mechanisms are poorly defined. Here, we identify the E3 ubiquitin ligase Ufd2p as a key regulator promoting efficient CO formation through a focused genetic screen in Saccharomyces cerevisiae . Deletion of UFD2 significantly reduces CO frequency by enhancing the strength of CO interference. Integrated multiomics analysis indicates that Ufd2p targets Topoisomerase II (Top2p) for ubiquitination and subsequent proteasomal degradation during meiosis. Deletion of UFD2 results in Top2p accumulation, which resolves DNA negative supercoils excessively and enhances CO interference in the nucleus, ultimately reducing CO numbers. We further show that the mammalian homolog of Ufd2p, UBE4B, plays a conserved role in promoting efficient CO formation by regulating TOP2A-dependent DNA negative supercoils dynamics. Notably, expression of mouse or human UBE4B in yeast restores CO formation and meiotic progression in UFD2 deletion cells, demonstrating functional conservation across species. Together, our work identifies Ufd2p as a previously uncharacterized regulator of CO formation and provides important insights into the conserved molecular mechanism, which operates through Top2p-mediated supercoils homeostasis.
GPT-4o mini: Non-social science research article
No evidence that haplodiploidy favors the evolution of eusociality
Rosa Bonifacii, Louis Bell-Roberts, Alan Grafen, Stuart West
Full text
The potential role of haplodiploid sex determination in promoting the evolution of altruism and eusociality has been the subject of intense debate for over 50 y. Different theoretical models have suggested that haplodiploidy influences relatedness in a way that either does or does not make it easier for altruism to evolve. This debate over the “haplodiploidy hypothesis” can only be resolved with a decisive empirical test that controls for potential phylogenetic bias. Here we critically examine the current state of evidence for an adaptive link between haplodiploidy and eusociality, applying phylogenetically informed methods to ensure that statistical tests reflect independent evolutionary transitions. Using data from 5,678 species, across all major insect orders, we find no evidence that haplodiploidy favors an increased rate of eusocial evolution. We show that this result is robust to: a) different analytical approaches; b) alternative ways of defining both eusociality and haplodiploidy; and c) uncertainty in eusociality assignments. Our analyses suggest that previously reported associations between haplodiploidy and eusociality are likely to have been artifacts, false-positive results primarily driven by a high transition rate to eusociality within the Hymenoptera. This high transition rate could be explained by any factor associated with that group, such as parental care, monogamy, or the possession of a powerful sting.
GPT-4o mini: Non-social science research article
Coviretinopathy: COVID-19-induced VEGF-dependent retinopathy
Xiaolu Wang, Xu Jing, Ziheng Guo, Siwen Long, Xiaoting Sun, Sofia Appelberg, Gerald M. McInerney, Mikael Adner, Yihai Cao
Full text
COVID-19 has been associated with high prevalences of retinal diseases in humans. However, cellular and molecular mechanisms that underlie the COVID-19-associated retinopathy remains unknown. Here, we deployed a mouse COVID-19 model to investigate the causative link between SARS-CoV-2 infection and retinopathy development. Our data showed that COVID-19-induced pulmonary hypoxia triggered systemic hypoxia and markedly augmented VEGF expression levels in the retina and plasma. High VEGF levels altered vascular structures and functions in the retina, resulting in neovascularization, vascular disorganization, and increased leakiness. We deployed a terminology of coviretinopathy to accurately describe these COVID-19-induced pathological changes in the retina. Consequently, blocking VEGF by a specific neutralizing antibody (VEGF blockade) completely ablated the COVID-19-associated vascular changes in the retina. Together, these findings provide mechanistic insights into the COVID-19-associated retinopathy and propose a therapeutic paradigm for effective treatment of coviretinopathy.
GPT-4o mini: Non-social science research article
A microfluidic band-pass filter for flexible fiber separation
Zhibo Li, Clément Bielinski, Anke Lindner, Blaise Delmotte, Olivia du Roure
Full text
The control of particle trajectories in structured microfluidic environments has significantly advanced sorting technologies, most notably through deterministic lateral displacement (DLD). While previous works have largely targeted rigid, near-spherical particles, the sorting of flexible, anisotropic objects such as fibers remains largely unexplored. Here, we combine experiments and simulations to demonstrate how tilted pillar arrays enable efficient, length-based separation of flexible fibers. We find that these arrays act as band-pass filters, selectively inducing lateral migration in fibers whose lengths are close to the array period. Fibers significantly shorter or longer exhibit small lateral deviation. This migration arises from the interplay of fluid–structure interactions between fibers and the complex flow and steric interactions with the pillars. Depending on their length, fibers exhibit distinct transport regimes: short fibers zigzag in between pillars following the flow, intermediate length fibers exhibit wrapping and jumping from one pillar to another, leading to lateral displacement, and long fibers deform extensively, following mixed zigzag-jump trajectories with small lateral migration. We identify the mechanical tension that develops in the fiber when wrapped around the pillars as the driving mechanism of cross-streamline transport. Leveraging this band-pass effect, we designed a highly efficient separation device to collect monodisperse fiber suspensions. Our findings not only expand the functional scope of DLD-like systems but also open avenues for understanding transport of anisotropic objects in porous media.
GPT-4o mini: Non-social science research article
Intravenous infusion of engineered megakaryocytes to produce oncolytic platelets in vivo for enhanced cancer immunotherapy
Yinxian Yang, Shenqiang Wang, Xueying Shi, Xudong Chen, Ruyi Zhou, Tao Sheng, Xiaofeng Chen, Jinpeng Han, Yan Xu, Qing Wu, Yuqi Zhang, Hongjun Li, Jicheng Yu, Zhen Gu
Full text
Tumor-targeted delivery of oncolytic viruses (OVs) via systemic administration could not only expand virotherapy beyond primary tumors to widespread metastases, but also improve clinical adherence and convenience. We here engineer megakaryocytes encapsulating oncolytic adenovirus type 5 (M-Ad5) to produce oncolytic platelets in vivo by leveraging the thrombopoiesis process. Upon intravenous administration, M-Ad5 travels through the lungs, where it can release OVs-harbored therapeutic platelets into circulation under pulmonary turbulence microenvironments. Under the shelter of platelets, OVs resist inactivation by neutralizing antibodies and actively target widespread noninjectable cancer lesions. Intravenous infusion of M-Ad5 to mice with A549 lung cancer could significantly inhibit tumor growth and prolong survival. In multiple mouse tumor models, M-Ad5 induced a robust antitumor immune response by reprogramming the immunosuppressive tumor microenvironment, and potentiated the response to immune checkpoint inhibitors by recruiting more immune cells. We demonstrated that M-Ad5 in combination with PDL1 inhibitors activated tumor antigen-specific CD8 + T cells and memory T cells, thereby suppressing the growth of CT26 colorectal cancer metastasis, and preventing postsurgical B16F10 cancer recurrence and metastatic spread, as well as providing long-term immune protection against the rechallenged tumors.
GPT-4o mini: Non-social science research article
A c-Cbl/Cbl-b antagonist inhibits EGFR ubiquitylation and sustains EGFR phosphorylation to enhance corneal re-epithelialization
Kate Tarvestad-Laise, Robert C. Monsen, Brandon L. M. Crotchett, Jamie S. Rush, Srinivasrao Ganipisetti, Rajachandrasekhar Valmon, Lynn DeLeeuw, Joseph Burlison, John O. Trent, Brian P. Ceresa
Full text
Growth factor receptor signaling is a critical component of tissue growth, homeostasis, and wound healing. However, receptor desensitization limits the use of exogenous growth factors as a restorative agent therapeutically. An example of this is the epidermal growth factor receptor (EGFR) in the corneal epithelium. Despite laboratory data indicating that EGFR activity accelerates corneal re-epithelialization in mice and rabbits, the clinical administration of EGF to damaged corneal epithelium has limited impact due to the attenuated signaling that occurs following sustained growth factor administration. We hypothesized that inhibition of receptor desensitization would prolong receptor activity and enhance tissue homeostasis. Having previously identified the E3 ubiquitin ligase, c-Cbl, as a key negative regulator of EGFR signaling in the corneal epithelium, we have developed a class of small molecule inhibitors of EGFR binding to CBL family proteins using virtual screening with experimental validation. Through multiple rounds of structural optimization, we have identified compound 3-120. This compound was designed to compete with phosphotyrosine 1045 of the EGFR for binding to c-Cbl. Compound 3-120 binds to c-Cbl with an ~10-fold higher affinity than phosphoEGFR, reduces EGFR ubiquitylation by 40%, and increases the magnitude of ligand-stimulated EGFR phosphorylation by 30 to 40%. Ultimately, this compound can enhance the restoration of corneal epithelial debridement wounds. Thus, compound 3-120 is an antagonist that specifically disrupts EGFR ubiquitylation to sustain receptor signaling.
GPT-4o mini: Non-social science research article
Antagonism of RNA silencing in the yellow fever mosquito, Aedes aegypti , by the nsP2 protein of the prototype alphavirus
Adarsh K. Gupta, Michael R. Wiley, Kevin M. Myles
Full text
Alphaviruses establish persistent infections in mosquito vectors despite robust antiviral RNA interference (RNAi) pathways, suggesting that they employ mechanisms to counteract host immunity. We demonstrate that the nsP2 protein of Sindbis virus (SINV), the prototype alphavirus, functions as a viral suppressor of RNA silencing in Aedes aegypti mosquitoes. Using a SINV mutant (2V) that prevents cleavage at the nsP2–nsP3 junction, we show that proper proteolytic processing to release mature nsP2 is essential for efficient viral replication in mosquitoes with intact RNAi pathways. Replication defects in the 2V mutant were rescued in Dicer-2 ( Dcr-2 ) null mutant mosquitoes or by expressing the mature nsP2 protein. Biochemical assays revealed that recombinant nsP2 directly binds double-stranded RNA and inhibits Dicer-mediated processing into small interfering RNAs (siRNAs). Furthermore, mosquitoes infected with the 2V mutant exhibited higher ratios of virus-derived siRNAs per viral RNA compared to wild-type infections, confirming that mature nsP2 suppresses the RNAi response. Our findings provide compelling evidence that nsP2 antagonizes RNA silencing in mosquito vectors, representing a critical adaptation that facilitates alphavirus replication.
GPT-4o mini: Non-social science research article
Gustatory avoidance of fatty acids by Aedes aegypti depends on an arthropod-specific TRP channel
Subash Dhakal, Angela E. Bontempo, Ramandeep Singh, Pratik Dhavan, Craig Montell
Full text
Mosquito-disease vectors, such as Aedes aegypti , use their sense of taste before deciding whether to consume a blood meal, or fly away. However, the molecular mechanisms controlling gustatory decisions in mosquitoes are largely unknown. The transient receptor potential (TRP) channel, Painless1 (Pain1), is an intriguing candidate for participating in Ae. aegypti taste since pain1 transcripts are detected in gustatory receptor neurons (GRNs). The Drosophila homolog, painless ( pain ) is also expressed in GRNs, where it is required for sensing allyl-isothiocyanate. Here, to identify additional gustatory roles for pain homologs, we first focused on Drosophila pain , which is widely expressed in multiple GRN classes. We demonstrated that pain mutations eliminated gustatory attraction to low fatty acids levels, repulsion to high levels, and fatty acid-induced action potentials. The attraction and repulsion depended on pain expression in different GRN classes. In contrast to Drosophila , when Aedes contacts fatty acids, they induce gustatory rejection only. Aedes pain1 is expressed in taste organs, and is required for gustatory avoidance of fatty acids, and for fatty acid-induced action potentials. Given that Pain homologs are found in insects but not vertebrates, Pain1 represents an intriguing target for developing repellents to diminish biting, and transmission of infectious agents by mosquito disease vectors.
GPT-4o mini: Non-social science research article
Leaderless RiPPs expand the repertoire of fungal secondary metabolites
Sung Chul Park, Livia D. S. Oster, Jacob Golan, Jillian Myers, Anne Pringle, Milton T. Drott, Nancy P. Keller
Full text
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are secondary metabolites produced by bacteria, plants, animals, and fungi. Canonical fungal RiPP precursors possess a leader sequence cleaved during maturation. The first RiPPs described in fungi were the MSDIN-derived peptides responsible for the toxicity of lethal Amanita mushrooms. In this study, we upend the conventional understanding of fungal RiPPs, discovering a subclass that has diversified and lacks a leader sequence, an empirical example of leaderless RiPPs in fungi. We use a combinatorial analysis of NMR and MS/MS with an updated bioinformatic pipeline to pair MSDIN genes to leaderless peptides in Amanita phalloides , a European species spreading in California. Leaderless MSDIN transcripts are expressed several orders of magnitude more than most canonical MSDINs, with significantly higher expression in invasive populations. Our results redefine the understanding of fungal RiPP architectures and suggest differential regulation of non-canonical RiPPs may contribute to the invasion biology of the world’s deadliest mushroom.
GPT-4o mini: Non-social science research article
Synaptic transmission: Munc13 assembles onto PI(4,5)P 2 -rich domains into trimers that cooperate to capture vesicles
Feng Li, Abhijith Radhakrishnan, Sudhanshu Gautam, Gabriel Diaz, Ramalingam Venkat Kalyana Sundaram, Jeff Coleman, Hong Zheng, Kirill Grushin, Matthieu Chavent, James E. Rothman, Frederic Pincet
Full text
Munc13-1 is a key protein involved in priming synaptic vesicles for rapid release at the presynaptic plasma membrane. It was previously revealed that Munc13-1 cycles between at least two alternate conformations, an upright (open) molecular conformation organized as a trimer and a lateral (closed) conformation organized as a hexagon. Munc13 binds PI(4,5)P 2 , a plasma membrane phospholipid essential for vesicle docking and fusion. We report that Munc13 is recruited to PI(4,5)P 2 domains induced by a Syntaxin-1A juxta-membrane peptide in supported bilayers. Statistical analysis of the copy numbers of Munc13 within the domains suggests that Munc13 exists in clusters of three molecules, i.e., it assembles into trimers. The trimeric clusters disappear with engineered interface mutations disrupting the upright trimers in cryo-EM as well as reconstituted vesicle priming suggesting the trimers observed on bilayers are identical to the upright trimer structures. These upright trimers can also be identified by cryo-electron tomography on vesicles containing PI(4,5)P 2 and Syntaxin-1A. Clusters of 3 or more Munc13 trimers forming on PI(4,5)P 2 domains efficiently capture phosphatidylserine-containing small unilamellar vesicles via their C 2 C domains, as shown by the effect of mutations that disrupt synaptic vesicle binding in synapses. We propose a two-step model for vesicle priming: i) synaptic vesicles are captured by clusters of upright trimers of Munc13 that self-assemble within PI(4,5)P 2 enriched domains; ii) these trimers transition into lateral hexamers when vesicles have bound and the transition would be promoted when the closed conformation of Munc13 is stabilized by diacylglycerol binding, resulting from Ca 2+ -dependent hydrolysis of PI(4,5)P 2 .
GPT-4o mini: Non-social science research article
Intramolecular noncovalent trans ring restricting free rotation of σ single bond enhances photosynthesis of hydrogen peroxide
Yaru Guo, Youxing Liu, Lu Li, Yachao Xu, Zheng Lin, Zongqiang Sun, Mingchuan Luo, Shaojun Guo, Xuliang Deng
Full text
Solar energy–driven hydrogen peroxide (H 2 O 2 ) synthesis from atmospheric oxygen and water represents a sustainable and highly promising avenue for the production of this essential chemical. Covalent organic frameworks (COFs) offer a molecular platform for the direct conversion of solar energy to H 2 O 2 , however, they are persistently plagued by the recombination of photogenerated charge carriers, a phenomenon induced by σ-bond rotation under light irradiation, which typically leads to sluggish conversion kinetics and suboptimal efficiency. We herein present a molecular engineering strategy involving the construction of noncovalent trans rings (Nc-TRs) within COFs. This approach entails the precise introduction of noncovalent interactions between donor and acceptor moieties, thereby constraining the free rotation of σ bonds and substantially suppressing the recombination of photogenerated charge carriers. Experimental and theoretical investigations demonstrate that the incorporation of Nc-TR within TAPT-DHBD COFs reduces the molecular dihedral angle from 37.33° to 0°, thereby optimizing molecular coplanarity and prolonging the photogenerated charge carrier lifetime by 820% compared to TAPT-TPD COFs devoid of Nc-TRs. Our findings further reveal that TAPT-DHBD COFs exhibit 5.0-fold and 3.6-fold enhancements in H 2 O 2 photocatalytic conversion kinetics and solar-to-chemical conversion (SCC) efficiency, respectively, relative to TAPT-TPD COFs. We further demonstrate that H 2 O 2 solutions generated in the flow-type photocatalytic system under solar irradiation exhibit a record-high antibacterial efficacy of 10 7 cfu s −1 , and achieve a 100% wound healing rate within 7 d, markedly outperforming commercial physiological saline.
GPT-4o mini: Non-social science research article
Phylogenomic synteny reveals paleohexaploid-derived genomic blocks across Asteraceae
Tao Feng, Michael McKibben, John Lovell, Richard Michelmore, Loren H. Rieseberg, Michael S. Barker, M. Eric Schranz
Full text
The Asteraceae (Compositae) is the largest flowering plant family, ubiquitous in most terrestrial communities, and morphologically diverse. A two-step, ancient whole genome triplication (paleohexaploidization) occurred at approximately the same time as the evolutionary innovation and adaptive radiation of the family during the middle Eocene. Despite its importance, the consequences of this triplication have yet to be tracked in context of the Asteraceae genome evolution. To do so, we applied a synteny oriented phylogenomic analysis of 23 Asterales genomes. We identified 16 genomic groups that date back to the common diploid ancestor of all Asteraceae. Each group underwent triplication, resulting in 48 genomic blocks (16 × 3) that collectively represent the ancestral Asteraceae genome, excluding the early-diverging lineages which do not share the second step. We then analyzed the evolutionary dynamics of the 48 genomic blocks across the Asteraceae phylogeny. We found that modern Asteraceae genomes are genetic mosaics of three progenitor genomes, shaped by genomic exchanges, chromosomal rearrangements, and gene fractionation. One hundred fifty-seven genes retained three paleohexaploid-derived syntenic paralogs across most Asteraceae species. Transcription factors and auxin-related genes are significantly overrepresented in these triplets, and expression of the paleohexaploidy paralogs is spatiotemporally differentiated. These genes are involved in the development of floral capitula, a remarkable morphological innovation of the family. The discovery of the 157 triplicated genes can direct further study to understand the evolutionary innovation, and the synteny-phylogenomic framework provides a comparative framework to characterize newly sequenced Asteraceae genomes.
GPT-4o mini: Non-social science research article
Mining lysine post-translational modification sites by integrating protein language model representations with structural context
Mengqi Luo, Xiaohong Zhu, Chen Bai, Arieh Warshel, Luonan Chen
Full text
Lysine (Lys/K) residues serve as major hubs for post-translational modifications (PTMs) owing to the chemical versatility of their Δ-amino groups, giving rise to diverse regulatory functions. Accurate and efficient identification of modified lysine residues therefore requires computational models that can effectively capture both sequence and structural information while minimizing domain-specific feature engineering. In this study, we propose a unified deep learning framework for lysine PTM site identification that integrates sequence representations derived from a protein language model with atom-level three-dimensional structural features. This framework can be consistently applied to multiple lysine PTM types using a shared modeling strategy. As an application, we used the model to predict potential PTM site on human C-type lectin domain family 12 member A (hCLEC12A) and evaluated their functional relevance through all-atom molecular dynamics simulations. The simulations indicate that the predicted lysine residues influence the stability and binding behavior of the hCLEC12A-antibody 50C1 complex. Overall, this work presents an integrative computational framework for lysine PTM site mining and functional analysis.
More social interactions, more polarization? The evidence is not there
Beate Völker, Rense Corten, Gerald Mollenhorst
Full text
Climate-driven reduction in biomass production of the Eurasian steppe coincides with nomadic migration during the first millennium CE
Feng Chen, Xiaoen Zhao, Weipeng Yue, Shijie Wang, Yong Zhang, Youping Chen, Mao Hu, Jan Esper, Ulf BĂŒntgen, Fredrik Charpentier Ljungqvist, Amy E. Hessl, Max C. A. Torbenson, Yujiang Yuan, MartĂ­n A. Hadad, Fidel A. Roig, Honghua Cao, Heli Zhang, Yaqun Liang, Fahu Chen
Full text
Although it is generally accepted today that climate and other environmental factors affected past human societies at different spatiotemporal scales, direct linkages are difficult to determine, and correlation should not be confused with causation. Here, we use a tree-ring width network of multimillennial chronologies from inner Eurasia to reconstruct annual changes in Net Primary Productivity (NPP) back to 200 BCE. Our findings reveal that episodes of reduced NPP around the 70s–100s, 360s–380s, and 470s–560s CE likely contributed to the westward and southward migration of nomadic people from their homelands in northwestern China and Mongolia. Although prolonged multidecadal periods of climate-induced low NPP served as tipping points for agricultural and pastoral subsistence systems, the inherent mobility of nomadic communities not only enabled them to adapt to adverse environmental conditions but also facilitated a widespread dispersal of ethnic groups.
Reply to Völker et al.: On the evidence of increased close friendships in societies
Stefan Thurner, Markus Hofer, Jan Korbel
Full text
Commodity frontiers expand more slowly into tropical forests where forest smallholders are present
Marie Pratzer, Patrick Meyfroidt, Maria Vallejos, Tobias Kuemmerle
Full text
The expansion of commodity agriculture into tropical forests leads to major social–ecological impacts. Yet little is known about where and how the capitalized actors driving this expansion interact with smallholders, particularly where smallholders live inside the forest. Two alternative outcomes of their interactions on deforestation are plausible: accelerated deforestation as all actors compete for land (i.e., land rush hypothesis) or, alternatively, slower deforestation as actors hinder each other’s expansion (i.e., competition hypothesis). We test these hypotheses for two global deforestation hotspots: the Dry Chaco and the Chiquitano Forests (together nearly 1 million km 2 ), using a land-systems representation that captures spatially overlapping land-use actors. We integrate satellite-based forest-loss time series with an independent reconstruction of land-system change from 2000 to 2023 in a Bayesian regression framework. This reveals three key findings: First, capitalized agriculture has expanded mainly over areas used by forest-dependent smallholders and Indigenous communities, indicating strongly intensifying land competition. Second, where forest-dwelling smallholders persist, their presence can mitigate deforestation pressure from expanding commodity frontiers. Third, the presence of either forest-dwelling smallholders or conservation areas maintains forest cover, but their combined presence does not amplify the protection effect. Overall, our findings show that interactions between agribusinesses and smallholders are key factors that shape the social–ecological outcomes of frontier expansion in the tropics. Accounting for land-system overlaps in research and policymaking on frontiers can therefore improve efforts to safeguard forests while supporting traditional livelihoods, especially in contested, rapidly changing landscapes.
Leveraging probabilistic forecasts for dengue preparedness and control: The 2024 Dengue Forecasting Sprint in Brazil
Eduardo Correa Araujo, Luiz Max Carvalho, Fabiana Ganem, LuĂŁ Bida Vacaro, Leonardo S. Bastos, LaĂ­s Picinini Freitas, Iasmim Ferreira de Almeida, Marcio Bastos, Ramila Alencar, Lucas Bianchi, RaĂșl CapellĂĄn, Xiang Chen, Oswaldo Cruz, Americo Cunha, Haridas K. Das, Chloe Fletcher, Raquel Martins Lana, Rachel Lowe, Daniela LĂŒhrsen, Giovenale Moirano, Paula Moraga, Lucas M. Stolerman, Fernanda Valente, ClĂĄudia Torres Codeço, FlĂĄvio C. Coelho
Full text
Forecast models are a key decision-support tool for public health authorities in managing epidemics, feeding into early warning systems, scenario evaluations, and an empirical basis for resource allocation. In Brazil, improving dengue forecasting became a priority in response to the unprecedented increase in cases, which surpassed the total of the previous decade and expanded to new regions. The Infodengue-Mosqlimate consortium launched the Infodengue-Mosqlimate Dengue Challenge 2024 (IMDC24), or Dengue Forecast Sprint, bringing together six international teams provided with cases and climate covariates data to generate actionable forecasts for 2024 and 2025 seasons in five diverse Brazilian states, leveraging advanced machine learning and classical statistical models. This paper outlines the structure and findings of the IMDC24. The performance of the models varied between years and locations, and no single model consistently excelled, especially during 2024’s unprecedentedly large season. This performance variability highlighted the need for ensemble approaches. The ensemble models developed are presented as the main results of this collaborative development. As intended, the ensemble models have been adopted by Brazilian public health authorities to help with planning and response to the forecasted 2025 dengue epidemics across the country.
Social information creates self-fulfilling prophecies in judgments of pain, vicarious pain, and cognitive effort
Aryan Yazdanpanah, Heejung Jung, Alireza Soltani, Tor D. Wager
Full text
Expectations can shape perception and potentially lead to self-fulfilling prophecies such as placebo effects that persist or grow over time. Nonetheless, whether and how unreinforced and unconditioned social cues (i.e., suggestions about future experiences that have not been reinforced with reward or punishment) can create and sustain such effects is unknown. We conducted a set of experiments in which participants (N = 111) experienced stimuli eliciting somatic pain (heat), vicarious pain (videos of others in pain), and cognitive effort (a mental-rotation task), at three intensity levels each. Before each stimulus, participants viewed a social cue that ostensibly indicated ratings from 10 other participants but was in fact randomized to a high or low mean aversiveness level independent of actual stimulus intensity. Across all tasks, participants’ expectations and experience ratings shifted in line with the cues, with high-aversive cues leading to higher perceived aversiveness. Computational modeling and behavioral analysis revealed lower learning rates for prediction errors inconsistent with the trial’s cue value (e.g., better than expected for high-aversive cues) and higher learning rates for prediction errors consistent with the cue value (e.g., worse than expected for high-aversive cues). These findings reveal a confirmation bias in learning: people update more when outcomes align with expectations. Combined with expectation effects on perception, this bias helps sustain social cue effects. Together, these mechanisms show how social information can shape perception and learning, giving rise to self-fulfilling prophecies.
A systematic map of methods for assessing societal benefits of Earth science information
Casey C. O’Hara, Mabel Baez-Schon, Rebecca Chaplin-Kramer, Samantha H. Cheng, Alejandra Echeverri, Gillian L. Galford, Rachelle K. Gould, Cristina L. Mancilla, Maura C. Muldoon, Gerald G. Singh, Priscilla Baltezar, Yusuke Kuwayama, Stephen Polasky, Amanda D. Rodewald, Richard P. Sharp, Elizabeth J. Tennant, Jiaying Zhao, Benjamin S. Halpern
Full text
Remotely sensed Earth science information (ESI) has become increasingly central to addressing global challenges, yet its societal value, i.e., the difference ESI makes in real-world decisions and outcomes, is rarely quantified. In this study, we systematically map peer-reviewed literature that explicitly assesses the societal value of ESI across instrumental, intrinsic, and relational value types, and the diversity of approaches used to assess those values. Drawing from 13,823 publications across Scopus, Web of Science, and a curated library of ESI valuation studies, we identify 171 studies that applied ESI in a decision context and used a valuation method to compare outcomes with and without ESI. The majority of these studies employed decision analysis methods (e.g., Value of Information, Cost–Benefit Analysis), focusing primarily on quantitative instrumental values (e.g., profit, crop yield, lives saved), particularly in agricultural contexts. A smaller set of studies applied preference elicitation methods (e.g., stated preference, surveys, interviews, focus groups) to capture qualitative benefits and relational values including quality of life improvements, empowerment, and procedural justice. Many excluded studies demonstrated scientific value of ESI but did not explicitly translate that into societal value, revealing the need for a more systematic approach to ESI valuation. By promoting a more inclusive, interdisciplinary, and flexible portfolio of valuation methods, we aim to expand our understanding of the societal benefits of ESI to help guide investment in future missions, enhance public support, and ensure that science and policy goals are well aligned.
Conservation and environmental management reimagined: Toward anti-oppressive futures
Laura German, Jesse Abrams, Cory L. Struthers, Sherry Pictou, C. Brock Woodson, Suneel Kumar, Tommy Cabe, Roger Merino, Elizabeth King
Full text
Conservation and environmental management are under increased scrutiny as the embeddedness of oppressive practices has gained wider societal and scholarly attention. As conservation and environmental practitioners and scholars grapple with foundational assumptions and practices of the field, there remains a pressing need to identify persistent problematic legacies and articulate a positive vision for conservation grounded in an ethic of justice. To help advance this conversation, we present a framework of four intersecting dimensions of oppression: 1) the physical or material manifestations of conservation and environmental management; 2) the knowledge practices and assumptions that inform and underpin conservation and environmental visions and decision-making; 3) the modes of governance associated with conservation and environmental practice; and 4) the forms of relational praxis implicitly and explicitly endorsed and/or imposed in conservation and other environmental arenas. We explain the framework through an analysis of the legacy of fortress conservation, then illustrate the framework’s wider application to diagnose ongoing elements of oppression in other environmental arenas (wildland fire, riverine flows). We then review prominent strategies and visions for moving forward for both nature and people to highlight both positive steps being taken and the utility of the framework in ensuring emergent environmental paradigms avoid the pitfalls of the past. Viewing each dimension of oppression as moveable levers to promote antioppressive conservation futures, we conclude with a set of questions to help conservation and environmental management scientists and practitioners identify where oppression might be manifest in their own work, and begin to embody antioppressive practices.
Religious markers reduce perceived trustworthiness in a Muslim-majority country
Joshua Hellyer, Johanna Gereke, Ozan Aksoy, Emily Hellriegel, Reinhard Schunck
Full text
First impressions often hinge on visible cues, leading people to infer the trustworthiness of strangers from their appearance and dress. While religiosity is generally associated with greater perceived trustworthiness, little is known about how visible religious markers, such as clothing and grooming styles, shape trust judgments in Muslim-majority societies, where such signals are widespread and easily recognizable. We examine this question using a large-scale vignette experiment embedded in a nationally representative face-to-face survey in Turkey. By experimentally varying profile characteristics, we identify the causal effect of a Muslim headscarf or beard on perceived trustworthiness. Contrary to expectations, individuals displaying these religious badges are generally viewed as less trustworthy than otherwise identical profiles, even by highly religious respondents. Mediation analyses show that these effects arise because religious badges signal multiple attributes, not only religiosity but also political orientation and physical attractiveness—and that these inferred meanings differ by gender: women’s headscarves and men’s beards prompt distinct patterns of inference. These findings show that visible religious markers shape trust judgments through multivalent social inferences rather than perceived piety alone. The results highlight how observers draw on broader social and political associations when interpreting religious markers, providing evidence on how public expressions of religion affect everyday trust judgments.
Scaling laws for function diversity and specialization across socioeconomic and biological complex systems
Vicky Chuqiao Yang, James Holehouse, Hyejin Youn, José Ignacio Arroyo, Sidney Redner, Geoffrey B. West, Christopher P. Kempes
Full text
Function diversity, the range of tasks individuals perform, and specialization, the distribution of function abundances, are fundamental to complex adaptive systems. In the absence of overarching principles, these properties have appeared domain-specific. Here, we introduce an empirical framework and a mathematical model for the diversification and specialization of functions across disparate systems, including bacteria, federal agencies, universities, corporations, and cities. We find that the number of functions grows sublinearly with system size, with exponents from 0.35 to 0.57, consistent with Heaps’ law. In contrast, cities exhibit logarithmic scaling. To explain these empirical findings, we generalize the Yule-Simon model by introducing two key parameters: a diversification parameter that characterizes how existing functions inhibit the creation of new ones and a specialization parameter that describes how a function’s attractiveness depends on its abundance. Our model enables cross-system comparisons, from microorganisms to metropolitan areas. The analysis suggests that what drives the creation of new functions depends on the system’s goals and structure: federal agencies tend to ensure comprehensive coverage of necessary functions; cities tend to slow the creation of new occupations as existing ones expand; and cells occupy an intermediate position. Once functions are introduced, their growth follows a remarkably universal pattern across all systems.
What is the general Welfare: Welfare economic perspectives on equity
Charles F. Manski
Full text
Researchers cannot definitely interpret what the framers of the United States Constitution intended when they wrote of the “general Welfare.” Nevertheless, researchers can conjecture by specifying social welfare functions that aim to express the preferences of the population. An extensive literature in welfare economics addresses the matter. Nevertheless, economists have often simplified policy analysis by assuming that individuals have homogeneous, consequentialist, and self-centered preferences. Individuals may hold heterogeneous private and distributional preferences. To enhance policy analysis, economists should specify social welfare functions that express the richness and variety of actual personal preferences. The possibilities are vast. I focus on preferences for equity. There has been much controversy regarding interpretation of equity, a term that public discourse has used in vague and conflicting ways. Specifying social welfare functions that formally express different interpretations of equity will not eliminate disagreements, but it should clarify concepts and reduce the inconsistencies that afflict verbal communication.
The psychological ability to adopt recommended coping responses reduced infections during the COVID-19 pandemic
Lasse Hyldig Hansen, Frederik JĂžrgensen, Michael Bang Petersen
Full text
During the COVID-19 pandemic, a key question for researchers and authorities was to understand the psychological motivations that sustained public engagement in protective behavior such as physical distancing and hygienic protection. While feelings of threat were rampant during the pandemic, theories of health psychology have highlighted appraisals related to the ability to cope (e.g., the feeling of being able to adhere cost-effectively to government advice) and argued that coping appraisals are superior predictors of motivations to protect the self against risks. In this study, we conducted a massive population-based comparison of the association between, on the one hand, threat appraisals and coping appraisals and, on the other hand, protection against actual infection during the COVID-19 pandemic. We built a unique Danish data infrastructure that links surveys of ~8% of the adult population (N = 386,633) with the individual results of the 123 million COVID-19 tests performed during 22 mo of the COVID-19 pandemic. Controlling for a comprehensive range of sociodemographic measures and employing panel data to bolster internal validity, we observe that stronger coping appraisals are consistently associated with lower individual probability of COVID-19 infection risk. We find no consistent evidence of a similar association for threat appraisals. Threat appraisals rather seem to index individual feelings of infection exposure. As appeals to fear also have unintended negative consequences (including anxiety, fatigue, and stigmatization), the findings offer strong support for relying on coping-oriented public health policy and communication in future societal crises in the domain of health and beyond.

Science

GPT-4o mini: Non-social science research article
More than mitigation: The role of forests in climate adaptation
Josephine Elena Reek, Constantin M. Zohner, Gabriel Reuben Smith, Susan C. Cook-Patton, Pieter De Frenne, Paolo D’Odorico, Marius G. Floriancic, Robert B. Jackson, Julia A. Jones, James W. Kirchner, Marysa LaguĂ«, Yuting Liang, Yuta J. Masuda, Robert I. McDonald, Luke A. Parsons, Benedict S. Probst, June T. Spector, Thales A. P. West, Nicholas H. Wolff, Florian Zellweger, Thomas W. Crowther
Full text
Forests regulate global and local climates in ways that impact human well-being. In this Review, we discuss the scale-dependent mechanisms through which forests regulate climate, highlighting their contributions to global mitigation and local adaptation. Locally, forests tend to buffer temperatures, cooling in warm conditions and warming in cold ones. In regions that naturally support dense forest cover, trees contribute to global cooling primarily through carbon uptake, with some offsetting from albedo-related warming. By enhancing rainfall interception, evapotranspiration, and cloud formation, forests also influence the hydrological cycle, lowering flood risks in humid regions but often reducing downstream water availability, especially in drier climates. Collectively, these interacting processes show that the greatest climate benefits occur where forests are native, highlighting their importance for both climate adaptation and mitigation.
GPT-4o mini: Non-social science research article
A small polymerase ribozyme that can synthesize itself and its complementary strand
Edoardo Gianni, Samantha L. Y. Kwok, Christopher J. K. Wan, Kevin Goeij, Bryce E. Clifton, Enrico S. Colizzi, James Attwater, Philipp Holliger
Full text
The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural complexity impede self-replication and preclude their spontaneous emergence. Here we describe QT45: a 45-nucleotide polymerase ribozyme, discovered from random sequence pools, that catalyzes general RNA-templated RNA synthesis using trinucleotide triphosphate (triplet) substrates in mildly alkaline eutectic ice. QT45 can synthesize both its complementary strand using a random triplet pool at 94.1% per-nucleotide fidelity, and a copy of itself using defined substrates, both with yields of ~0.2% in 72 days. The discovery of polymerase activity in a small RNA motif suggests that polymerase ribozymes are more abundant in RNA sequence space than previously thought.
GPT-4o mini: Non-social science research article
Myelin sheaths in the central nervous system can withstand damage and dynamically remodel
Donia Arafa, Julia van de Korput, Philipp N. Braaker, Kieran P. Higgins, Niels R. C. Meijns, Katy L. H. Marshall-Phelps, Julia Meng, Daniel Soong, Eleonora Scalia, Kyle Lathem, Marcus Keatinge, Claire Richmond, Anna Klingseisen, Marja Main, Sarah A. Neely, David W. Hampton, Greg J. Duncan, Geert J. Schenk, Marie Louise Groot, Siddharthan Chandran, Ben Emery, Antonio Luchicchi, Maarten H. P. Kole, Anna C. Williams, David A. Lyons
Full text
Myelin damage is a hallmark of several neurological disorders, but how it occurs remains to be fully understood. In this study, we found that early damage in zebrafish and rodent demyelination models is characterized by myelin swelling. We show, through live imaging, that myelin swelling does not always lead to myelin loss and that swellings can sometimes resolve, allowing sheaths to remodel. Increased neuronal activity during early demyelination exacerbates myelin damage, whereas reducing neuronal activity mitigates myelin swelling in both zebrafish and mice. In human multiple sclerosis tissue, myelin swelling is also dynamic and is prominent around active lesions. Our data indicate that myelin swelling is a conserved feature of demyelination and that damage to myelin sheaths can resolve, opening opportunities for targeting human disease.
GPT-4o mini: Non-social science research article
Detecting supramolecular organic nanoparticles during heat wave
Renyi Zhang, Yixin Li, Jiayun Zhao, Bianca Aridjis-Olivos, Lijun Zhao, Veronica Kowalewski, Maisha Kabir, Natalie M. Johnson, Erik R. Nielsen, Sarah D. Brooks, Yue Zhang, Arnold Vedlitz, Weston Porter, Simon W. North, Wanhe Li, Michael W. Young, John H. Seinfeld, Yuhan Wang, Yuan Wang
Full text
New particle formation (NPF) represents a major source of tropospheric fine aerosols. A common viewpoint is that NPF hinges thermodynamically on the volatility of condensing species and is unfavorable at high temperatures. From an intensive field campaign, we observed frequent NPF events during a heat wave. Size-resolved chemical composition of nanoparticles down to 3 nanometers was first measured, unraveling a dominant presence of carboxylic acids. Our work uncovers a spontaneous mechanism to produce supramolecular nanoparticles through self-assembly of organic acids. This discovery explains not only the unexpected NPF at high temperatures but also its ubiquitous occurrence under diverse atmospheric conditions. As global warming leads to more frequent and intense heat waves, our findings open avenues for assessing the impacts of aerosols on cloud formation, public health, and climate.
GPT-4o mini: Non-social science research article
Structural ontogeny of protein-protein interactions
Aerin Yang, Hanlun Jiang, Kevin M. Jude, Deniz Akpinaroglu, Stephan Allenspach, Alex Jie Li, James Bowden, Carla Patricia Perez, Liu Liu, Po-Ssu Huang, Tanja Kortemme, Jennifer Listgarten, K. Christopher Garcia
Full text
Understanding how protein binding sites evolve interactions with other proteins could hold clues to targeting “undruggable” surfaces. We used synthetic coevolution to engineer new interactions between naïve surfaces, simulating the de novo formation of protein complexes. We isolated seven distinct structural families of protein Z-domain complexes and found that synthetic complexes explore multiple shallow energy wells through ratchet-like docking modes, whereas complexes formed by natural binding sites converged in a deep energy well with a relatively fixed geometry. Epistasis analysis of a machine learning–estimated fitness landscape revealed “seed” contacts between binding partners that anchored the earliest stages of encounter complex formation. Our results suggest that “silent” surfaces have a shallower energy landscape than natural binding sites, disfavoring tight binding, likely owing to evolutionary counterselection.
GPT-4o mini: Non-social science research article
Functional gradients facilitate tactile sensing in elephant whiskers
Andrew K. Schulz, Lena V. Kaufmann, Lawrence T. Smith, Deepti S. Philip, Hilda David, Jelena Lazovic, Michael Brecht, Gunther Richter, Katherine J. Kuchenbecker
Full text
Keratin composites enable animals to hike with hooves, fly with feathers, and sense with skin. Mammalian whiskers are elongated keratin rods attached to tactile skin structures that extend the animal’s sensory volume. We investigated the whiskers that cover Asian elephant ( Elephas maximus ) trunks and found that they are geometrically and mechanically tailored to facilitate tactile perception by encoding contact location in the amplitude and frequency of the vibrotactile signal felt at the whisker base. Elephant whiskers emerge from armored trunk skin and shift from a thick, circular, porous, stiff base to a thin, ovular, dense, soft tip. These functional gradients of geometry, porosity, and stiffness independently tune the neuromechanics of elephant trunk touch to facilitate highly dexterous manipulation while ensuring whisker durability.
GPT-4o mini: Non-social science research article
Gas-depleted planet formation occurred in the four-planet system around the red dwarf LHS 1903
Thomas G. Wilson, Anna M. Simpson, Andrew Collier Cameron, Ryan Cloutier, Vardan Adibekyan, Ancy Anna John, Yann Alibert, Manu Stalport, Jo Ann Egger, Andrea Bonfanti, Nicolas Billot, Pascal Guterman, Pierre F. L. Maxted, Attila E. Simon, SĂ©rgio G. Sousa, Malcolm Fridlund, Mathias Beck, Anja Bekkelien, SĂ©bastien Salmon, ValĂ©rie Van Grootel, Luca Fossati, Alexander James Mustill, Hugh P. Osborn, Tiziano Zingales, Matthew J. Hooton, Laura Affer, Suzanne Aigrain, Roi Alonso, Guillem Anglada, Alexandros Antoniadis-Karnavas, Tamas BĂĄrczy, David Barrado Navascues, Susana C. C. Barros, Wolfgang Baumjohann, Thomas Beck, Willy Benz, Federico Biondi, Xavier Bonfils, Luca Borsato, Alexis Brandeker, Christopher Broeg, Lars A. Buchhave, Maximilian Buder, Juan Cabrera, Sebastian Carrazco Gaxiola, David Charbonneau, SĂ©bastien Charnoz, David R. Ciardi, Karen A. Collins, Kevin I. Collins, Rosario Cosentino, Szilard Csizmadia, Patricio E. Cubillos, Shweta Dalal, Mario Damasso, James R. A. Davenport, Melvyn B. Davies, Magali Deleuil, Laetitia Delrez, Olivier D. S. Demangeon, Brice-Olivier Demory, Victoria DiTomasso, Diana Dragomir, Courtney D. Dressing, Xavier Dumusque, David Ehrenreich, Anders Erikson, Emma Esparza-Borges, Andrea Fortier, Izuru Fukuda, Akihiko Fukui, Davide Gandolfi, Adriano Ghedina, Steven Giacalone, Holden Gill, MichaĂ«l Gillon, Yilen GĂłmez Maqueo Chew, Manuel GĂŒdel, Pere Guerra, Maximilian N. GĂŒnther, Nathan Hara, Avet Harutyunyan, Yuya Hayashi, RaphaĂ«lle D. Haywood, Rae Holcomb, Keith Horne, Sergio Hoyer, Chelsea X. Huang, Masahiro Ikoma, Kate G. Isaak, James A. G. Jackman, Jon M. Jenkins, Eric L. N. Jensen, Daniel Jontof-Hutter, Yugo Kawai, Laszlo L. Kiss, Ben S. Lakeland, Jacques Laskar, David W. Latham, Alain Lecavelier des Etangs, Adrien Leleu, Monika Lendl, Jerome de Leon, Florian Lienhard, Mercedes LĂłpez-Morales, Christophe Lovis, Michael B. Lund, Rafael Luque, Demetrio Magrin, Luca Malavolta, Aldo F. MartĂ­nez Fiorenzano, Andrew W. Mayo, Michel Mayor, Christoph Mordasini, Annelies Mortier, Felipe Murgas, Norio Narita, Valerio Nascimbeni, Belinda A. Nicholson, Göran Olofsson, Roland Ottensamer, Isabella Pagano, Larissa Palethorpe, Enric PallĂ©, Hannu Parviainen, Marco Pedani, Francesco A. Pepe, Gisbert Peter, Matteo Pinamonti, Giampaolo Piotto, Don Pollacco, Ennio Poretti, Didier Queloz, Samuel N. Quinn, Roberto Ragazzoni, Nicola Rando, David Rapetti, Francesco Ratti, Heike Rauer, Federica Rescigno, Ignasi Ribas, Ken Rice, George R. Ricker, Paul Robertson, Thierry de Roche, Laurence Sabin, Nuno C. Santos, Dimitar D. Sasselov, Arjun B. Savel, Gaetano Scandariato, Nicole Schanche, Urs Schroffenegger, Richard P. Schwarz, Sara Seager, Ramotholo Sefako, Damien SĂ©gransan, Avi Shporer, AndrĂ© M. Silva, Alexis M. S. Smith, Alessandro Sozzetti, Manfred Steller, Gyula M. SzabĂł, Motohide Tamura, Nicolas Thomas, Amy Tuson, StĂ©phane Udry, Andrew Vanderburg, Roland K. Vanderspek, Julia Venturini, Francesco Verrecchia, Nicholas A. Walton, Christopher A. Watson, Robert D. Wells, Joshua N. Winn, Roberto Zambelli, Carl Ziegler
Full text
The radii of small exoplanets form two populations, super-Earths and sub-Neptunes, separated by a gap known as the radius valley. This could be produced by the removal of some atmospheres by stellar or internal heating, or the lack of an initial envelope. We use transit photometry and radial velocity measurements to detect and characterize four exoplanets orbiting LHS 1903, a red dwarf star in the Milky Way’s thick disk. The planets have orbital periods from 2.2 to 29.3 days, and span the radius valley within a single planetary system. The derived densities indicate that LHS 1903 b is rocky, while LHS 1903 c and LHS 1903 d have extended atmospheres. The most distant planet from the host star, LHS 1903 e, has no gaseous envelope, indicating it formed from gas-depleted material.
GPT-4o mini: Non-social science research article
Fishing ban halts seven decades of biodiversity decline in the Yangtze River
Fangyuan Xiong, Zhongyang Li, SĂ©bastien Brosse, Julian D. Olden, Steven J. Cooke, Bo Yang, Ying Lu, Wenqi Gao, Wei Xin, Yushun Chen
Full text
China’s rapid economic development has triggered an unparalleled freshwater biodiversity crisis since the 1950s. To restore fisheries resources, the Yangtze River Fishing Ban was implemented in 2021 to cease all basin-wide commercial fishing. We evaluate the effectiveness of this large-scale conservation action by assessing fish communities across mainstem habitats before and after the ban (2018 to 2023). The seven-decadal biodiversity loss was halted with improvements in fish biomass, body condition, species diversity, and initial recovery of threatened species. Eliminating fishing pressure was likely key to this recovery, in addition to actions targeting water quality improvement, hydrological and riparian habitat restoration, and vessel traffic reduction. Ambitious conservation actions can halt biodiversity loss in the Yangtze River, bringing hope for biodiversity recovery in other large rivers.
GPT-4o mini: Non-social science research article
Recruitment of bifunctional regulator thermospermine to methylated ribosomes directs xylem fate
Donghwi Ko, Raili Ruonala, Alexandre Faille, Eva Hellmann, Hanna Help, Huili Liu, Ronni Nielsen, Anders Haakonsson, Nuria De Diego, Anja Paatero, Mariia V. Shcherbii, Karolina Stefanowicz, Sanja Ćavar Zeljković, Tine Drud Lundager Rasmussen, Ondrej Novak, Zsuzsanna Bodi, Gugan Eswaran, Brecht Wybouw, Matthieu Bourdon, Cristina Urbez, Xiaonan Liu, Kari Salokas, Tiina Öhman, Tanya Waldie, Petri Törönen, Sedeer el-Showk, Martin Balcerowicz, Fabrice Besnard, Xiaomin Liu, Patrick Perkins, Serina Mazzoni-Putman, Julia P. Vainonen, Maija Sierla, Mikko J. Frilander, Susanne Mandrup, Teva Vernoux, Karin Ljung, Alejandro Ferrando, Miguel A. Blazquez, Liisa Holm, Rupert Fray, Markku Varjosalo, Ottoline Leyser, Ville O. Paavilainen, Ari Pekka MĂ€hönen, Anna Stepanova, Jose Alonso, Steffen Heber, Robert Malinowski, Finn Kirpekar, Alan J. Warren, YkĂ€ Helariutta
Full text
Polyamines are often associated with ribosomes and are thought to stabilize their integrity. In Arabidopsis , the polyamine thermospermine (tSpm) affects xylem cell fate. tSpm induces translation of SUPPRESSOR-OF-ACAULIS51 (SAC51) and SAC51-LIKEs (SACLs), which inhibit heterodimerization of the xylem development proteins LONESOME-HIGHWAY (LHW) and TARGET-OF-MONOPTEROS5. Here, we report a methyltransferase, OVERACHIEVER, that methylates the peptidyl transferase center of the 25 S ribosomal RNA (rRNA). Residue m 3 U2952 promotes functional tSpm binding to a specific site connecting the P-site transfer RNA (tRNA) with rRNA residues in the peptidyl transferase center. This interaction enhances the translation of SACLs but inhibits that of LHW. Our study uncovers the dependency between a conserved rRNA base methylation and a polyamine in orchestrating cell fate decisions, highlighting a role for the ribosome chemical landscape in translational regulation.
GPT-4o mini: Non-social science research article
Transcription factor Etv3 controls the tolerogenic function of dendritic cells
Nicholas M. Adams, Daniel Martinez-Krams, Eduardo Esteva, Ai C. Ra, Allegra Iliadi Alexiou, Hua Jin, Tae Jin Yun, Rayan Sleiman Tellaoui, Tenny Mudianto, Emily Vollmer, Ekaterina Novikova, Yanjun Tan, William Huntley, Oleg Krichevsky, Igor Dolgalev, Peter Izmirly, Jill P. Buyon, Andre L. Moreira, Amanda W. Lund, Boris Reizis
Full text
Dendritic cells (DCs) facilitate the maintenance of immunological tolerance in the steady state. We report that transcription factor Etv3 is preferentially expressed in mature DCs, including tissue-derived migratory DCs (migDCs), and facilitates their homeostatic maturation and CCR7-dependent migration. Mice with global or DC-specific deletion of Etv3 manifested the expansion of CD25 low regulatory T (T reg ) cells, spontaneous activation of conventional T cells, and multiorgan T cell infiltration. Etv3 deficiency exacerbated TLR7-driven systemic lupus erythematosus (SLE)–like disease, supporting the reported genetic association of human ETV3 with SLE. Etv3-deficient migDCs up-regulated multiple costimulatory molecules, including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the T reg cell abnormalities. These results identify Etv3 as an essential regulator of the tolerogenic function of DCs and implicate it in the regulation of human autoimmunity.
GPT-4o mini: Non-social science research article
Dihydroxyhexanoic acid biosynthesis controls turgor in pathogenic fungi
Naoyoshi Kumakura, Takayuki Motoyama, Keisuke Miyazawa, Toshihiko Nogawa, Julien Pernier, Katsuma Yonehara, Mayuko Sato, Yumi Goto, Kaori Sakai, Nobuaki Ishihama, Kaisei Matsumori, Pamela Gan, Kiminori Toyooka, Sandrine LĂ©vĂȘque-Fort, Hiroyuki Koshino, Takeshi Fukuma, Richard J. O’Connell, Ken Shirasu
Full text
Many plant pathogenic fungi penetrate host surfaces mechanically, using turgor pressure generated by specialized infection cells called appressoria. These appressoria develop semipermeable cell walls and accumulate osmolytes internally to create turgor by osmosis. Although melanin is known to be important for turgor generation, the mechanism underlying wall semipermeability remains unclear. By using reverse genetics, we identified that the enzymes PKS2 and PBG13 are required for forming the semipermeable barrier in fungi causing anthracnose and rice blast diseases. These enzymes synthesize 3,5-dihydroxyhexanoic acid polymers that are essential for pathogenicity. These polymers reduce cell wall permeability and generate turgor, independently of melanization. Our findings uncover a mechanism of fungal turgor generation, linking enzyme function to pathogen penetration and disease potential, presenting new targets for disease control.
GPT-4o mini: Non-social science research article
Poxvirus attack of antiviral defense pathways unleashes an effector-triggered NF-ÎșB response
Brenna C. Remick, Joshua Q. Mao, Andrew G. Manford, Ami D. Gutierrez-Jensen, Allon Wagner, Michael Rape, Grant McFadden, Masmudur M. Rahman, Moritz M. Gaidt, Russell E. Vance
Full text
Effector-triggered immunity (ETI) is a form of pathogen sensing that involves detection of pathogen-encoded virulence factors or “effectors.” To discover ETI pathways in mammals, we developed a screening approach in which we expressed individual virulence factors in a human monocyte cell line and assessed transcriptional responses by RNA sequencing. We identified a poxvirus effector, myxoma virus M3.1, which elicited an antiviral nuclear factor ÎșB (NF-ÎșB) response. NF-ÎșB was unleashed by an ETI pathway that sensed M3.1 attack of two antiviral complexes: zinc finger antiviral protein and TBK1. NF-ÎșΒ activation occurred because the proteins inhibited by M3.1—N4BP1, ZC3H12A, and TBK1—are negative regulators of NF-ÎșB. Our study established a systematic approach for the discovery of ETI pathways, and the results illustrated how negative regulators of immune responses may function in pathogen sensing.
GPT-4o mini: Non-social science research article
Enhanced Li-ion diffusion improves N 2 -to-NH 3 current efficiency at 100 mA cm −2
Qiang Zhang, Huamin Li, Peiping Yu, Pengyu Liu, Ning Sun, Yiyan Wang, Chunlai Tu, Yiping Liu, Yan Wang, Xinyang Yue, Linlin Ma, Wen Wen, Jinyang Xu, Zhaofeng Liang, Jingyuan Ma, Fei Song, Zheng Liang, Hao Sun, Daishun Ling, Hongyan Liang, Feng Liu, Yongfeng Hu, Tao Cheng, Jun Li
Full text
Electrochemical lithium (Li)–mediated nitrogen (N 2 ) reduction could enable production of ammonia (NH 3 ) at ambient temperatures and pressures, offering a route to reduce carbon emissions in the chemical sector. However, NH 3 productivity is often limited by sluggish Li-ion desolvation and diffusion at the solid electrolyte interphase (SEI). Here, we present a concerted desolvation:diffusion layered SEI architecture that provides abundant Li-ion flux for efficient N 2 conversion toward NH 3 production at high current densities. The SEI comprises stacked inorganic layers with low ion-binding affinity and high ion-conductivity functionalities that increase Li-ion flux by two orders of magnitude. This design strategy achieved N 2 electroreduction in a 2 M lithium difluoro(oxalato)borate electrolyte with a Faradaic efficiency of 98% and an energy efficiency of 21% for NH 3 production at 100 milliamperes per square centimeter (mA cm −2 ). The system sustained an 80% Faradaic efficiency over 40 hours, after which performance declined.
GPT-4o mini: Non-social science research article
Disappearance of a massive star in the Andromeda Galaxy due to formation of a black hole
Kishalay De, Morgan MacLeod, Jacob E. Jencson, Elizabeth Lovegrove, Andrea Antoni, Erin Kara, Mansi M. Kasliwal, Ryan M. Lau, Abraham Loeb, Megan Masterson, Aaron M. Meisner, Christos Panagiotou, Eliot Quataert, Robert Simcoe
Full text
When a massive star reaches the end of its lifetime, its core collapses and releases neutrinos that drive a shock into the outer layers (the stellar envelope). A sufficiently strong shock ejects the envelope, producing a supernova. If the shock fails to eject it, the envelope is predicted to fall back onto the collapsing core, producing a stellar-mass black hole (BH) and causing the star to disappear. We report observations of M31-2014-DS1, a hydrogen-depleted supergiant in the Andromeda Galaxy. In 2014, it brightened in the mid-infrared, then from 2017 to 2022, it faded by factors of ≳ 10 4 in optical light (becoming undetectable) and ≳ 10 in total light. We interpret these observations, and those of a previous event in NGC 6946, as evidence for failed supernovae forming stellar-mass BHs.
GPT-4o mini: Non-social science research article
Genomic approaches to accelerate American chestnut restoration
Jared W. Westbrook, Joanna Malukiewicz, Qian Zhang, Avinash Sreedasyam, Jerry W. Jenkins, Vasiliy Lakoba, Sara Fitzsimmons, Jamie Van Clief, Kendra Collins, Stephen Hoy, Cassie Stark, Lake Graboski, Eric Jenkins, Thomas M. Saielli, Benjamin T. Jarrett, Lucinda J. Wigfield, Lauren M. Kerwien, Ciera Wilbur, Alexander M. Sandercock, J. Hill Craddock, Susanna Keriö, Tetyana Zhebentyayeva, Shenghua Fan, Austin M. Thomas, Albert G. Abbott, C. Dana Nelson, Xiaoxia Xia, James R. McKenna, Caleb Kell, Melissa Williams, LoriBeth Boston, Christopher Plott, Florian Carle, Jack Swatt, Jack Ostroff, Steven N. Jeffers, Kathleen McKeever, Erica Smith, Thomas J. Ellis, Joseph B. James, Paul Sisco, Andrew Newhouse, Erik Carlson, William A. Powell, Frederick V. Hebard, John Scrivani, Caragh Heverly, Martin Cipollini, Brian Clark, Eric Evans, Bruce Levine, John E. Carlson, David Goodstein, Jack Orebaugh, Zamin K. Yang, Madhavi Z. Martin, Joanna Tannous, Tomås A. Rush, Nancy L. Engle, Timothy J. Tschaplinski, Jane Grimwood, Jeremy Schmutz, Jason A. Holliday, John T. Lovell
Full text
More than a century after two introduced pathogens killed billions of American chestnut trees, introgression of resistance alleles from Chinese chestnuts has contributed to the recovery of self-sustaining populations. However, progress has been slow because of the complex genetic architecture of resistance. To better understand blight resistance, we compared reference genomes, gene expression responses, and stem metabolite profiles of the resistant Chinese and susceptible American chestnut species. To accelerate resistance breeding, we conducted large-scale phenotyping and genotyping in hybrids of these species. Simulation and inoculation experiments suggest that significant resistance gains are possible through selectively breeding trees with an average of 70 to 85% American chestnut ancestry. The resources developed in this work are foundational for breeding to create diverse restoration populations with sufficient disease resistance and competitive growth.
GPT-4o mini: Non-social science research article
Molecular solar thermal energy storage in Dewar pyrimidone beyond 1.6 MJ/kg
Han P. Q. Nguyen, Alexander J. Maertens, Benjamin A. Baker, Nathan M.-W. Wu, Zihao Ye, Qingyang Zhou, Qianfeng Qiu, Navneet Kaur, David B. Berkinsky, Katherine E. Shulenberger, K. N. Houk, Grace G. D. Han
Full text
Storing sunlight in a compact and rechargeable form remains a central challenge for solar energy utilization. Molecular solar thermal (MOST) energy storage systems, which harness photon energy and release it as heat on demand, provide a direct approach, but have long failed to meet practical benchmarks. Inspired by the architecture of DNA, we report a pyrimidone-based MOST system that stores energy in the strained Dewar photoisomer upon excitation at 300 nm. Designed with sustainability in mind, the system operates solvent-free and remains compatible with aqueous environments while overcoming one of the field’s greatest hurdles: the controlled extraction and transfer of stored heat. When catalyzed by acid, the Dewar isomer releases enough heat to boil water (~0.5 mL). These advances help point the way toward decentralized solar heat storage and off-grid energy solutions.
GPT-4o mini: Non-social science research article
Mechanisms linking cytoplasmic decay of translation-defective mRNA to transcriptional adaptation
Mohamed A. El-Brolosy, Atharv Oak, An T. Hoang, Yassine Damergi, André Fischer, Reuben A. Saunders, Jingchuan Luo, Amer Balabaki, Jeremy Guez, Troy W. Whitfield, Seth R. Goldman, Arash Latifkar, Yuancheng Ryan Lu, Didier Y. R. Stainier, Konrad J. Karczewski, Olivia Corradin, Jonathan S. Weissman
Full text
Transcriptional adaptation (TA) is a genetic robustness mechanism through which mutant messenger RNA (mRNA) decay induces sequence-dependent up-regulation of so-called adapting genes. How cytoplasmically generated mRNA fragments affect nuclear transcription remains poorly understood. Using genome-wide CRISPR screens, we uncover ILF3 as an RNA binding protein connecting cytoplasmic mRNA decay and transcription during TA and show that it is required for a range of TA substrates. ILF3 is enriched at adapting genes’ RNAs, and its artificial recruitment through dCas13 promotes gene expression. Using tiling oligonucleotide screens, we identify trigger RNA fragments that activate adapting genes when introduced into cells. Further functional dissection reveals a critical role for homology between trigger and target sequences. These findings enhance our molecular understanding of TA and inform the design of programmable oligonucleotides for gene expression augmentation.
GPT-4o mini: Non-social science research article
Taking a sharp turn
Theresa A. Maldonado
Full text
This week, the American Association for the Advancement of Science (AAAS, the publisher of Science ) convenes its annual meeting in Phoenix, Arizona. The meeting’s theme, “Science at Scale,” stands in stark contrast to the diminishing of science by the current US federal administration. Amid political attempts to weaken science, this gathering of people from academia, industry, government, business, medicine, law, ethics, and other sectors is an opportunity to look to the future.
GPT-4o mini: Non-social science research article
Metallic Ξ-phase tantalum nitride has a thermal conductivity triple that of copper
Suixuan Li, Chuanjin Su, Zihao Qin, Ahmet Alatas, Martin Kunz, Takahiro Yamada, Shelly D. Kelly, Mary H. Upton, Anthony Gironda, Jiyong Zhao, Bora Kalkan, Wanli Yang, Toshihiro Aoki, Yongjie Hu
Full text
Efficient heat dissipation is fundamentally limited by intrinsic scattering mechanisms that cap the thermal conductivity of metallic materials such as copper to ~400 watts per meter-kelvin. Here we report the experimental realization of single-crystalline Ξ-phase tantalum nitride (Ξ-TaN), a metastable transition metal nitride predicted to overcome this limitation. We measured a room-temperature thermal conductivity of ~1100 watts per meter-kelvin, nearly three times that of copper. Synchrotron-based inelastic x-ray scattering revealed a distinctive phonon band structure with a large acoustic-optical gap and phonon bunching, which suppress phonon-phonon scattering. Ultrafast optical spectroscopy confirmed exceptionally weak electron-phonon coupling and validated first-principles calculations. These findings redefine the thermal transport limits of metallic materials and open new opportunities for advancing thermal management in electronics and power systems.
GPT-4o mini: Non-social science research article
Mitochondrial control of fuel switching via carnitine biosynthesis
Christopher Auger, Hiroshi Nishida, Bo Yuan, Guilherme Martins Silva, Masanori Fujimoto, Mark Li, Daisuke Katoh, Dandan Wang, Melia Granath-Panelo, Jihoon Shin, Rose Witte, Jin-Seon Yook, Anthony R. P. Verkerke, Alexander S. Banks, Sheng Hui, Lijun Sun, Shingo Kajimura
Full text
Environmental adaptation often involves a shift in energy utilization toward mitochondrial fatty acid oxidation, which requires carnitine. Besides dietary sources of animal origin, carnitine biosynthesis from trimethyllysine (TML) is essential, particularly for those who consume plant-based diets; however, its molecular regulation and physiological role remain elusive. Here, we identify SLC25A45 as a mitochondrial TML carrier that controls carnitine biosynthesis and fuel switching. SLC25A45 deficiency decreased the carnitine pool and impaired mitochondrial fatty acid oxidation, shifting reliance to carbohydrate metabolism. Slc25a45 -deficient mice were cold-intolerant and resistant to lipid mobilization by glucagon-like peptide-1 receptor agonist (GLP-1RA), rendering them resistant to adipose tissue loss. Our study suggests that mitochondria serve as a regulatory checkpoint in fuel switching, with implications for metabolic adaptation and the efficacy of GLP-1RA–based anti-obesity therapy.
Science abstract < 200 char.: Not a research article
Keeping cells fit
Xavier Rambout, Lynne E. Maquat
Full text
Fragments of aberrant cytoplasmic mRNA pair with nuclear RNAs to augment transcription
Science abstract < 200 char.: Not a research article
Driving forward the restoration of an American icon
Steven H. Strauss, Gancho T. Slavov
Full text
Genome-informed breeding and new transformation approaches could improve disease resistance of the American chestnut tree
Science abstract < 200 char.: Not a research article
RNA comes close to copying itself
Robert F. Service
Full text
Some RNA molecules can create their own mirror images, suggesting similar molecules could have sparked life
Science abstract < 200 char.: Not a research article
In Science Journals
Marc S. Lavine, Jesse Smith, Keith T. Smith, Phil Szuromi, Madeleine Seale, Sacha Vignieri, Melissa L. Norton, John Foley, Bianca Lopez, Mattia Maroso, Di Jiang, Yevgeniya Nusinovich, Sarah H. Ross, Michael A. Funk, Jake S. Yeston, Leoma Bere
Full text
Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
e-Waste trade drives environmental injustice
Lizeng Peng, Chuan Jin
Full text
Science abstract < 200 char.: Not a research article
Projects on silty Himalayan rivers raise alarms
Athar Parvaiz
Full text
Dredging and mining river sediments can raise flood risks and threaten infrastructure, scientists say
Science abstract < 200 char.: Not a research article
Using markets to adapt to climate change
Simon Greenhill, Solomon Hsiang, Clare Balboni, Lint Barrage, Ian W. Bolliger, Judson Boomhower, Delavane Diaz, Hannah Druckenmiller, Teevrat Garg, Miyuki Hino, Harrison Hong, Carolyn Kousky, Jeremy Martinich, Ishan Nath, Kimberly L. Oremus, R. Jisung Park, Toan Phan, Jonathan Proctor, Will Rafey, Marcus C. Sarofim, Wolfram Schlenker, Benjamin Simon
Full text
Research shows if and when markets can help limit the harms from climate change
Science abstract < 200 char.: Not a research article
Layered interface transports ions swiftly
Claudio Ampelli
Full text
A hierarchical solid-electrolyte interphase can produce ammonia under industrial operating conditions
Science abstract < 200 char.: Not a research article
Endangered Species Act changes threaten reefs
Colin J Anthony, Colin Lock, Steven Mana‘oakamai Johnson, Shinichiro Maruyama, Laurie J Raymundo
Full text
Science abstract < 200 char.: Not a research article
Rare, dangerous side effects from COVID-19 vaccines explained
Gretchen Vogel, Kai Kupferschmidt
Full text
Scientists discover why adenovirus-based shots caused life-threatening blood clots and bleeding in some patients
Science abstract < 200 char.: Not a research article
In Other Journals
Bianca Lopez, Marc S. Lavine, Joana OsĂłrio, Yevgeniya Nusinovich, Corinne Simonti, Keith T. Smith, Yury Suleymanov
Full text
Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
Giant primate research center may become sanctuary
David Grimm
Full text
Oregon university votes to explore NIH offer to transform national facility
Science abstract < 200 char.: Not a research article
The bottleneck of fat burning
Angela M. Ramos-Lobo, Pierre Maechler
Full text
A mitochondrial transport protein promotes carnitine synthesis in mice when fat consumption is needed
Science abstract < 200 char.: Not a research article
Building a better working dog
David Grimm
Full text
More than half of canines trained to help people with disabilities fail to graduate. Can science help?
Science abstract < 200 char.: Not a research article
Revive Brazil’s soy moratorium
Gustavo Magalhães de Oliveira, Philip M. Fearnside, Jan Börner
Full text
Science abstract < 200 char.: Not a research article
Stewarding AI in agriculture research
Ismahane Elouafi
Full text
Science abstract < 200 char.: Not a research article
Imagining the rich lives of invertebrates Daughter of Mother-of-Pearl Mandy-Suzanne Wong Graywolf Press, 2026. 168 pp.
Barbara J. King
Full text
A writer’s evocative meditations invite readers to consider the often-overlooked creatures on their own terms
Science abstract < 200 char.: Not a research article
The invisible scientist
Anne Trolard
Full text
Science abstract < 200 char.: Not a research article
Polar Year plans heat up
Richard Stone
Full text
Geopolitics cast shadow over preparations for 2032 effort to study poles
Science abstract < 200 char.: Not a research article
The elusive nature of consciousness A World Appears Michael Pollan Penguin, 2026. 320 pp.
Ned Block
Full text
A writer grapples with neuroscience’s hardest problem
Science abstract < 200 char.: Not a research article
Rest to repair
Kamsi Nwangwu, Michelle Monje
Full text
Neuronal activity exacerbates myelin damage in the acute period after injury

Science Advances

GPT-4o mini: Non-social science research article
Navigating high-dimensional processing parameters in organic photovoltaics via a multitier machine learning framework
Yaping Wen, Yipu Zhang, Haibo Ma
Full text
Optimizing organic photovoltaic (OPV) performance requires navigating the high-dimensional, interdependent processing parameters governing bulk heterojunction morphology. To address this, we have constructed a standardized database integrating donor/acceptor pairs, nine key fabrication parameters, and device efficiencies, consolidating over a decade of experimental results. Leveraging this resource, we developed a three-tiered machine learning framework using gradient boosting regression trees. The strategy progresses from single-parameter baseline models to stage-combined models that capture intraprocess synergies, culminating in a global nine-parameter optimization model. This final model achieves a Pearson correlation of >0.9 and a success rate of >80% in identifying optimal multiparameter configurations. Validation on 78 external systems, each containing a previously unseen donor or acceptor, demonstrates robust generalization with >75% accuracy in predicting the optimal or secondary condition for individual parameters. This work establishes a practical, data-driven framework for accelerating the rational optimization of OPV photoactive layers.
GPT-4o mini: Non-social science research article
Octopamine and tyramine dynamics predict learning rate phenotypes during associative conditioning in honey bees
Lester P. Sands, Hong Lei, Seth R. Batten, Alec Hartle, Terry Lohrenz, Leonardo Barbosa, Dan Bang, Peter Dayan, William M. Howe, Brian H. Smith, Pendleton R. Montague
Full text
Biogenic amines are fundamental for physiological homeostasis and behavioral control in both vertebrates and invertebrates. Monoamine neurotransmitters released in target brain regions conjointly regulate adaptive learning and plasticity. However, our understanding of these multianalyte mechanisms remains nascent, in part due to limitations in measurement technology. Here, during associative conditioning in honey bees, we concurrently tracked subsecond fluctuations in octopamine, tyramine, dopamine, and serotonin in the antennal lobe, where plasticity influences odorant representations. By repeatedly pairing an odorant with subsequent sucrose delivery, we observed individual differences in the conditioned response to odor, which occurred after a variable number of pairings (learners) or not at all (non-learners). The distinction between learners and non-learners was reflected in neurotransmitter responses across experimental conditions. The speed of learning, the number of pairings prior to a proboscis extension reflex, could be predicted from monoamine opponent signaling (octopamine-tyramine), from both the first presentation of the odorant alone, prior to any pairing with sucrose, and the first conditioned response to the odorant, coming after a number of sucrose pairings. These results suggest that monoamine signaling phenotypes may relate directly to the now widely reported socially relevant genetic differences in honey bee learning.
GPT-4o mini: Non-social science research article
Spatially anion-confined electrolyte enables high-rate and durable anode-free sodium batteries
Jiangchun Chen, Jingwen Jiang, Sicong Wang, Hao Lan, Mengyao Tang, Qiaonan Zhu, Shuai Dong, Jiawei Wang, Dandan Yu, Jinhui Zhao, Hua Wang
Full text
Anode-free sodium batteries (AFSBs) with near-theoretical energy density hold great promise for next-generation sustainable energy storage systems. However, their practical implementation is impeded by the low operating rate threshold (<1 milliampere per square centimeter) and poor cycling stability, owing to dendritic sodium (Na) growth. Here, a high-rate and durable AFSB is successfully realized via a spatially anion-confined electrolyte strategy. Specifically, positively charged nanoparticles are introduced into the electrolyte to selectively anchor anions, generating localized contact ion pair–dominated solvation to facilitate rapid Na + desolvation at electrode interface and form an anion-derived solid electrolyte interphase. Meanwhile, rapid ion transport in the bulk electrolyte is maintained by the solvent-separated ion pair solvation structure in the nanoparticle periphery. These factors conjointly enable flat and dense Na deposition at high current densities. Consequently, an energy-type Na(Ni 1/3 Fe 1/3 Mn 1/3 )O 2 ||Al full cell exhibits an energy density of 415.6 watt-hour per kilogram cathode+anode even at 1 C (2.1 milliamperes per square centimeter) with 70.2% capacity retention over 400 cycles. A power-type Na 3 V 2 (PO 4 ) 3 ||Al cell achieves a trebled operation current density compared to the state-of-the-art AFSBs, exhibiting an unprecedented 5-C rate (3.8 milliamperes per square centimeter) with 70.0% capacity retention over 1400 cycles. This strategy presents a potentially universal approach for high-rate alkali metal batteries.
GPT-4o mini: Non-social science research article
VapC36-mediated intrinsic stress adaption is required for copper tolerance and pathogenesis of Mycobacterium tuberculosis
Arun Sharma, Gopinath Chattopadhyay, Manisha Singh, Munmun Bhasin, Prabhakar Babele, Raghavan Varadarajan, Ramandeep Singh
Full text
Here, we have used a comprehensive, system-wide approach to delineate the function of the virulence-associated proteins B and C 36 (VapBC36) toxin-antitoxin (TA) system in Mycobacterium tuberculosis pathophysiology. We show that VapC36 interacts with cognate and noncognate antitoxins. We demonstrate that serX is degraded in vitro by VapC36. We show that VapC36 binds copper, which enhances its ribonuclease activity. Furthermore, we report that deletion of vapBC36 or vapC36 enhances the susceptibility of M. tuberculosis upon exposure to copper in vitro. Compared to the wild-type strain, Δ BC36 was attenuated for growth in guinea pigs. However, deletion of either vapC36 or vapBC36 did not affect M. tuberculosis growth in mice. Compared to the wild-type strain, the in vivo susceptibility of Δ C36 and Δ BC36 strains was increased in copper-fed mice. Together, these findings have enhanced our understanding of the regulation and contribution of TA systems in mycobacterial pathophysiology.
GPT-4o mini: Non-social science research article
Competitive-binding buried interlayer for year-round reproducible perovskite solar cells
Yansong Ge, Weiwei Meng, Zixi Yu, Haibing Wang, Guoyi Chen, Shengjie Du, Lishuai Huang, Chen Wang, Xuzhi Hu, Fang Yao, Xiaojuan Cao, Jiwei Liang, Mingming Hu, Chen Tao, Weijun Ke, Guojia Fang
Full text
Homogenizing the upper surface through posttreatment has made great progress in perovskite solar cells. In contrast to the exposed surface, there are no practical remedies if imperfections form randomly at the hidden buried interface after perovskite film generation. Here, we reveal a severe distribution of residual lead iodide, voids, and grain-surface concavities at the buried interface, which severely trap carriers in inactive regions. To address these challenges, we introduce a potassium dihydrogen phosphate competitive-binding interlayer that systematically reduces residual solvents at the buried interface through strong chemical interactions. Homogenized buried interface along with facilitated perovskite film quality and charge extraction have been achieved, enabling year-round improvements in photovoltaic performance and reproducibility. The resultant devices achieve a champion power conversion efficiency (PCE) of 26.3% (certified at 25.8%) for a 0.07–square centimeter device and 25.17% for a 1.028–square centimeter device. The device also demonstrates exceptional stability, maintaining 97% of its initial PCE after 1000 hours of continuous maximum power point tracking.
GPT-4o mini: Non-social science research article
Isothiocyanate-mediated cyclization of phage-displayed peptides enables discovery of macrocyclic binders
Liwen Bai, Ting Dan, Peng Cheng, Xiaoqin Yang, Hua Xiang, Weikang Zhai, Yifei Chen, Rong Huang, Qi Wang, Kai Li, Jinming Gao, Xinxiang Lei
Full text
Cyclic peptides exhibit advantages in binding protein targets with high affinity and competency in inhibiting protein-protein interactions. Cyclic peptide phage display with more than a billion variants is an invaluable tool in drug discovery. However, achieving efficient peptide cyclization on phages remains a challenge because of the limited availability of reaction sites, which also restrict scaffold diversity. Here, we report an isothiocyanate-derived cross-linker featuring dual reactive groups: a bromide that covalently attaches to cysteine thiols and a thiocyanogen that selectively forms a thiourea bridge with either the N-terminal amino group or Δ-amines of lysine, depending on pH. This strategy enables pH-modulated cyclization. At pH 6.5, head–to–side chain cyclization occurs, and at pH 9.5, side chain–to–side chain ligation is performed. Both processes simultaneously generate thiourea scaffolds. To demonstrate the versatility and biocompatibility of this approach, we constructed cyclic peptide libraries using both cyclization methods and successfully selected binders for several targets, including cyclophilin D, murine double minute 2, and Keap1, with dissociation constants ranging from micromolar to nanomolar. Given the broad pharmacological potential of the thiourea moiety, this phage display library opens previously unidentified chemical space with high scaffold diversity and the integration of a proven pharmacophore for the development of cyclic peptide therapeutics.
GPT-4o mini: Non-social science research article
Silencer variants are key drivers of gene up-regulation in Alzheimer’s disease
Di Huang, Ivan Ovcharenko
Full text
The genetic mechanisms of ~90% of Alzheimer’s disease (AD)–associated variants residing in noncoding DNA remain poorly understood. To address this, we developed a deep learning framework that integrates bulk histone modification data with single-cell open chromatin profiles to evaluate the regulatory potential of noncoding variants. This model identified 1457 silencer and 3084 enhancer AD-associated variants in dorsolateral prefrontal cortex, classifying gene loci as silencer-only (SL), enhancer-only (EN), or dual-function (ENSL). EN loci predominantly regulate housekeeping metabolic processes, SL loci (including MS4A6A and HLA-D ) are linked to immune responses (with ~70% substantially up-regulated in AD microglia), while ENSL loci are implicated in neurofibrillary tangle assembly. Our model achieves robust power in assessing the impact of regulatory variants, with ~70% directional concordance with experimental results. It identified rs636317 as a putative causal silencer variant, distinguishing it from a neutral variant located 11 base pairs away. This study advances understanding of the AD-associated regulatory landscape and provides a framework for ascertaining noncoding variants in AD pathogenesis.
GPT-4o mini: Non-social science research article
Genetic legacy and recent cross of two ancient lineages underlie the rebound of the world’s rarest primate
Xian Hou, Shengkai Pan, Jiliang Xu, Li Hu, Weiming He, Xin Liu, Siying Huang, Zhongru Gu, Zhenzhen Lin, Yangkang Chen, Wei Li, Tao Luo, Xinrui Zhao, Qingyan Dai, Peng Cao, Feng Liu, Xiaotian Feng, Qiaomei Fu, Jiang Zhou, Jinliang Wang, Xiangjiang Zhan
Full text
Despite a recent mass extinction, a few species have bounced back from the brink, but little is known about their intrinsic mechanisms. Hainan gibbons ( Nomascus hainanus ) feature a mysterious rebound, from ~13 individuals in 2003 to 42 currently. Using reliable genomic data from the fecal samples of 18 gibbons, generated through a systematically established pipeline, and from four museum specimens, our analyses reveal that Hainan gibbons have the smallest effective population size and low genetic diversity but, unexpectedly, low inbreeding and genetic load among threatened primates assessed thus far. This results from a millennial expansion mitigating bottleneck effects and a high local recombination maintaining selection efficiency. Notably, we uncover two cryptic lineages, whose recent crosses led to new family groups with increased heterozygosity. Our study reveals the importance of demographic history, genome architecture, and behavioral regulation in the recovery of endangered species and highlights the great potential of fecal genomic research in conservation biology.
GPT-4o mini: Non-social science research article
Tunable 3D optohydrodynamic torques from optical phase gradient–driven colloidal assemblies
Xiao Li, Chenchen Liu, Zongpeng Huang, Jack Ng, Fan Nan
Full text
Optohydrodynamic manipulation offers a versatile, noninvasive, and reconfigurable approach for controlling microscopic objects. Here, we present a strategy for generating tunable three-dimensional optohydrodynamic torques through phase gradient–driven nanoparticle assemblies. Using programmable optical ring vortices (Laguerre-Gaussian beams), we assemble and rotate colloidal clusters with certain particle numbers, whose induced hydrodynamic flows apply switchable in-plane and out-of-plane torques on target particles. Torque control is achieved via two mechanisms: (i) reversing the handedness of circular polarization to break rotational symmetry and (ii) displacing optical ring vortices and modulating cluster rotation speed. These complementary controls provide robust, high-resolution torques tuned in arbitrary directions. As a proof of concept, we demonstrate full three-dimensional orientation control of a single cell. This framework greatly expands the capabilities of optohydrodynamic systems by explicitly incorporating light-driven interparticle interactions and establishes a foundation for advanced applications in biophysics, microrobotics, and biomedical engineering.
GPT-4o mini: Non-social science research article
RTX-family toxin EhxA drives morphological remodeling and thrombogenesis in RBCs during enterohemorrhagic Escherichia coli infection
Sungbin Choi, Hanjin Park, Ok-Nam Bae, Yiying Bian, Hanhyeok Im, Han Young Chung
Full text
Enterohemorrhagic Escherichia coli (EHEC) causes thrombotic microangiopathy, yet the red blood cell (RBC)–centered mechanism has remained unclear. We identify the RTX-family hemolysin EhxA as the driver of RBC-mediated thrombogenesis. Deletion of ehxA abolishes Ca 2+ influx, phosphatidylserine (PS) exposure, progression from discocyte to echinocyte to spherocyte, thrombin generation, RBC-endothelium adhesion, and RBC aggregation. Genetic complementation restores these readouts to wild type, and purified EhxA in bacteria-free assays recapitulates them while localizing to intact RBC membranes. By contrast, Δ stx2 mutants do not elicit these RBC phenotypes, distinguishing this pathway from Shiga toxin–dependent effects. Multiple regression quantifies the link between PS exposure, morphology, and procoagulant outputs. In rats, infection with wild type increased RBC remodeling and venous thrombosis, whereas infection with Δ ehxA did not. Together, the data define an EhxA-Ca 2+ -PS pathway that drives RBC structural remodeling and procoagulant activation during EHEC infection and nominate RTX toxins as targets for preventing toxin-induced coagulopathies.
GPT-4o mini: Non-social science research article
Halting predicted vertebrate declines requires tackling multiple drivers of biodiversity loss
Pol Capdevila, Duncan O’Brien, Valentina Marconi, Thomas F. Johnson, Robin Freeman, Louise McRae, Christopher F. Clements
Full text
Conservation policies aiming to halt biodiversity loss often focus on globally prevalent threats like habitat loss and exploitation, yet direct and interactive effects of multiple threats remain poorly quantified. Here, we go beyond prior meta-analyses or species-level studies by providing a global, population-level empirical analysis of threat interactions by examining 3129 vertebrate population time series worldwide with documented exposure to single and multiple threats. Populations affected solely by habitat loss or exploitation do not exhibit the steepest declines; instead, disease, invasive species, pollution, and climate change are associated with faster declines. Interactive threats contribute more to population declines than temporal or spatial variation. Counterfactual analyses reveal that mitigating multiple threats is essential to achieving nonnegative vertebrate population trends and halting biodiversity loss.
GPT-4o mini: Non-social science research article
Antigen-specific T H 17 cells offset the age-related decline in durable T cell immunity
Ines Sturmlechner, Abhinav Jain, Jingjing Jiang, Hirohisa Okuyama, Yunmei Mu, Maryam Own, Cornelia M. Weyand, Jörg J. Goronzy
Full text
Older adults are susceptible to infections in part due to waning of immune memory. To uncover mechanisms of a long-lasting immune memory, we contrasted varicella zoster virus antigen–specific memory T cell responses in adults vaccinated at young (<20 years) or older age (>50 years) with a live-attenuated vaccine conferring durable protection only when given at young age or with an adjuvanted component vaccine eliciting long-lasting immunity in older adults. Unlike VZV-specific CD4 + T cells, CD8 + T cells exhibited profound age-sensitive changes including memory subset shifts, reduced T cell receptor diversity, and loss of stem-like features. Vaccination of older adults with the adjuvanted vaccine did not restore CD8 + defects but selectively enhanced T helper 17 (T H 17) CD4 + T cells and prevented their conversion into regulatory T cells, likely through lipid metabolic regulation. Thus, durable vaccine efficacy with aging relies on antigen-specific T H 17 cells that compensate for CD8 + T cell defects.
GPT-4o mini: Non-social science research article
Animal-associated jumbo phages as widespread and active modulators of gut microbiome ecology and metabolism
LinXing Chen, Antonio Pedro Camargo, Yiting Qin, Eugene V. Koonin, Haoyu Wang, Yuanqiang Zou, Yi Duan, Hao Li
Full text
Huge phages are widespread in the biosphere, yet their prevalence and ecology in the human gut remain poorly characterized. Here, we report Jug (jumbo gut) phages with genomes of 360 to 402 kilobase pairs that comprise ~1.1% of the reads in human gut metagenomes, and are predicted to infect Bacteroides and/or Phocaeicola . Although three of the four major groups of Jug phages shared >90% genome-wide sequence identity, their large terminase subunits exhibited only 38 to 57% identity, suggesting horizontal acquisition from other phages. Over 1500 genomes of Jug phages were recovered from human and animal gut metagenomes, revealing their broad distribution, with largely shared gene content suggestive of frequent cross-animal-host transmission. Jug phages displayed high gene transcription activities, including the gene for a calcium-translocating P-type ATPase not detected previously in phages. These findings broaden our understanding of huge phages and highlight Jug phages as potential major players in gut microbiome ecology.
GPT-4o mini: Non-social science research article
Climate, ecological dynamics, and the seasonal distribution of birds in mountains
Marius Somveille, Benjamin G. Freeman, Frank A. La Sorte, Mao-Ning Tuanmu
Full text
Biodiversity is unevenly distributed along elevational gradients. The predominant hypothesis is that macroevolutionary dynamics and climatic niche conservatism explain today’s elevational patterns of biodiversity, but the alternative energy efficiency hypothesis emphasizes modern ecological interactions related to energy budgets. We test these competing hypotheses by examining seasonal elevational ranges for 10,998 bird populations in 34 mountain regions. Multiple lines of evidence support the energy efficiency hypothesis, including that many mountain birds do not seasonally track their thermal niche with high fidelity while simulation models based on optimal energy balancing under current environmental conditions yield predictions that tightly match empirical data. Our results reveal that altitudinal migration, which is widespread yet considerably understudied, is a behavioral mechanism fulfilling the same ecological function as long-distance latitudinal migration. Overall, this work provides a better understanding and predictive capacity for mountain birds under global change.
GPT-4o mini: Non-social science research article
Gas vortex discovery in butterfly microcavities for constructing ultrasensitive gas sensors
Xinyuan Zhou, Yinxia Sun, Manqing Qi, Lindong Ma, Xiaomin Song, Xiaomeng Yin, Hang Wang, Zhenpeng Wang, Kun Li, Tie Wang
Full text
Gas sensors are pivotal for environmental monitoring and medical diagnostics but usually face the sensitivity-stability trade-off in trace-gas detection. Conventional sensitivity-enhancement strategies rely on reactive surface modifications, which may risk long-term stability, whereas inefficient gas-solid interaction time limits detection sensitivity. Here, we find gas vortex effects in butterfly wings that can prolong molecular residence time and apply this bioinspired mechanism to gas sensor design to resolve this trade-off. We establish a universal design rule: Periodic microcavities with diameter-to-height ratios of 1 to 1.33 generate centralized vortices that prolong molecular residence time by 85% and optimize mass transfer efficiency, as validated through computational fluid dynamics, fluorescence tracking, and Sherwood number analysis. This geometric principle enables metal oxide (ZnO, In 2 O 3 , Co 3 O 4 , and WO 3 ) sensors to achieve ultralow detection limits (0.8 to 30 parts per billion) while maintaining long-period stability. A four-channel microsensor array leveraging vortex-enhanced microstructures enables real-time profiling of human breath biomarkers. This work resolves the classical sensitivity-stability conflict through geometric fluidic control rather than material chemistry.
GPT-4o mini: Non-social science research article
The allosteric landscape of the Src kinase
Antoni Beltran, Mohsin M. Naqvi, Andre J. Faure, Ben Lehner
Full text
Enzymes catalyze the reactions of life and are the targets of many drugs. Most inhibitors bind conserved active sites, frequently lacking specificity. Targeting allosteric sites can increase specificity, reduce toxicity, and allow fine-tuning of activity; however, most allosteric sites in enzymes are unmapped. Here, we present a comprehensive experimental allosteric map of the Src protein kinase. We quantify the effects of more than 50,000 single and double amino acid substitutions on activity and abundance and use thermodynamic modeling to disentangle changes in fold stability and catalysis. The comprehensive energy landscape reveals that allostery across the kinase domain is extensive, directionally biased, and modulated by its regulatory domains. Inhibitory—but not activating—allosteric mutations show a strong distance-dependent decay away from the active site. Using the map, we identify multiple potentially druggable allosteric sites not previously reported in Src or other kinases. Our results establish a framework for comprehensive mapping of allostery in kinases and other enzymes important for medicine and biotechnology.
GPT-4o mini: Non-social science research article
Matrix-bound nanovesicles as epigenetic modulators of myeloid cells
HĂ©ctor Capella-MonsonĂ­s, Jiayang Rong, Bharadwaj Chirravuri, William D’Angelo, Hēth R. Turnquist, George Hussey, Stephen F. Badylak
Full text
Extracellular vesicles (EV) represent a conserved and highly efficient mechanism for cell-to-cell communication. Matrix-bound nanovesicles (MBV) are a recently identified type of EV embedded within the extracellular matrix with potent local and systemic immunomodulatory effects on myeloid cells. These effects are durable and last beyond the predicted life span of differentiated myeloid cells such as macrophages. The present study investigated MBV-directed epigenetic modification in myeloid precursors as a potential explanation for their prolonged immunomodulatory effects. Flow cytometry and ATAC sequencing studies show that MBV are internalized by myeloid cell progenitors in the bone marrow and in macrophages after terminal differentiation. This internalization is coincident with epigenetic changes that are associated with modulation of macrophage responses to inflammatory stimuli. Furthermore, MBV treatment differentially alters chromatin accessibility as a function of cell differentiation state (i.e., myeloid progenitor versus macrophage). The present study shows the epigenetic effects of MBV on myeloid cells, representing a potential avenue to exploit the therapeutic potential of biologic scaffold materials.
GPT-4o mini: Non-social science research article
Robust room-temperature ferroelectricity in the wide-bandgap semiconductor Ga 2 O 3
Jiaying Shen, Weng Fu Io, Chang Liu, Yiyang Wen, Han Wu, Yilin Cao, Yongtao Yang, Dianmeng Dong, Fan Zhang, Songhua Cai, Wei Ren, Xianran Xing, Yang Zhang, Zhenping Wu, Jianhua Hao
Full text
For decades, the integration of power handling and nonvolatile memory has been fundamentally impeded by the incompatibility between wide-bandgap semiconductors and ferroelectric materials. We resolve this challenge by demonstrating robust room-temperature ferroelectricity in epitaxial metastable Îș-Ga 2 O 3 , grown via industry-compatible metal-organic chemical vapor deposition, creating an intrinsically ferroelectric wide-bandgap semiconductor. Through systematic characterization including piezoresponse force microscopy, polarization hysteresis measurements, and positive up–negative down tests, we provide conclusive evidence of stable ferroelectric switching down to 5-nanometer thickness—exceeding conventional ferroelectric limits—via a unique octahedral-tetrahedral transformation. Ferroelectric tunnel junctions achieve giant tunneling electroresistance exceeding 10 5 . This fundamental discovery in a mainstream semiconductor challenges conventional materials paradigms and enables monolithic integration of power and memory functionalities on a unified platform.
GPT-4o mini: Non-social science research article
Privacy-preserving data analysis using a memristor chip with colocated authentication and processing
Zhengwu Liu, Zhongrui Wang, Chenchen Ding, Bohan Lin, Jianshi Tang, Bin Gao, Ngai Wong, Huaqiang Wu
Full text
Privacy-preserving data analysis is essential in health care applications to safeguard sensitive patient information while enabling medical monitoring and diagnostics. However, existing solutions generally separate security from analysis modules and memory from computation units, creating hardware and energy overheads that constrain their use in resource-limited medical devices. Here, we introduce the memristor-based colocated authentication and processing (CLAP) system, which achieves security-analysis integration through embedding physical unclonable functions within compute-in-memory architecture. To resolve the incompatibilities between these two features, we propose a differential stochastic mapping method by applying information theory principles. We demonstrate CLAP on a 130-nanometer memristor chip, validating its versatility across diverse information processing tasks. In an electrocardiogram data collection task, CLAP achieves device authentication with an area under the curve of 99.46% and efficient signal compression with a software-level percentage root mean square difference. CLAP demonstrates 146.0-fold energy efficiency gain and 17.6-fold area reduction, providing intrinsically secure hardware solutions that enhance both privacy preservation and computational efficiency for health care applications.
GPT-4o mini: Non-social science research article
Electrochemically deuterated silane synthesis with D 2 O
Chao Gao, Min Liu, Youai Qiu
Full text
Deuterium-labeled silanes are of great significance in organic synthesis and drug discoveries, yet obtaining versatile deuterated silanes efficiently and selectively under electrochemical conditions using green deuterium sources remains enormously challenging. Herein, facile and general electrochemical deuteration of silanes using D 2 O as the economical deuterium source was reported. A variety of alkyl- and aryl-substituted silanes can be smoothly converted into the corresponding products with excellent levels of deuterium incorporation and yields. Furthermore, this protocol enables 10-gram-scale preparation under high current conditions, underscoring the potential in industry applications. Mechanistic studies have revealed that a catalytic amount of nickel may form a pivotal silicon-nickel intermediate, reversing the polarity of silicon and thereby facilitating the subsequent reactions.
GPT-4o mini: Non-social science research article
Primate dexterous hand movements are controlled by functionally distinct premotoneuronal systems
Tomohiko Takei, Tomomichi Oya, Kazuhiko Seki
Full text
Dexterous hand movements are uniquely developed in primates and indispensable for their daily activities. Traditionally, they were thought to depend primarily on the evolutionarily “newer” direct corticomotoneuronal (CM) pathway. However, recent studies suggest that the “older” indirect corticospinal pathways, mediated by spinal premotor interneurons (PreM-INs), also contribute, highlighting the need to clarify their functional differences. Here, we recorded neuronal activity from PreM-INs and CM cells in macaques during a precision grip task to compare their roles in generating hand muscle activity. Our results show that PreM-INs exert stronger facilitation across a broader set of muscles, promoting synergistic coactivation, whereas CM cells provide more selective facilitation, enabling control of relatively individual muscles. Decomposition analysis further revealed that these systems correspond to different control modes—synergy-based and individual-based control—balancing stability and flexibility. These findings redefine our understanding of primate dexterous hand control as emerging from the cooperative integration of evolutionarily distinct premotoneuronal systems.
GPT-4o mini: Non-social science research article
Nonlinear optical extreme learner via data reverberation with incoherent light
Bofeng Liu, Xu Mei, Sadman Shafi, Tunan Xia, Iam-Choon Khoo, Zhiwen Liu, Xingjie Ni
Full text
Artificial neural networks have revolutionized fields from computer vision to natural language processing, yet their growing energy and computational demands threaten future progress. Optical neural networks promise greater speed, bandwidth, and energy efficiency but suffer from weak optical nonlinearities. Here, we demonstrate a low-power, incoherent-light-compatible optical extreme learner that leverages “data nonlinearity” from optical pattern reverberations, eliminating reliance on intrinsic nonlinear materials. By encoding input data in the spatial polarization distribution of a tailored optical cavity and allowing light to pass through it multiple times, we achieve nonlinear transformations at extremely low optical power. Coupled with a simple trainable readout, our optical learner consistently outperforms linear digital networks in standard image classification tasks and XOR benchmarks, delivering accuracy matching fully nonlinear digital models. Our compact, energy-efficient approach substantially reduces complexity, cost, and energy consumption, paving the way for practical, scalable all-optical machine learning platforms.
GPT-4o mini: Non-social science research article
Three-dimensional printing of nanomaterials-based electronics with a metamaterial-inspired near-field electromagnetic structure
Jian Teng, Samuel H. Hales, Xin Yang, Jared Anklam, Saebom Lee, Yu Liu, Dwipak Prasad Sahu, Leibin Li, Cordelia Latham, Xi Tian, Derrick Wong, Taylor E. Greenwood, John S. Ho, Yong Lin Kong
Full text
Three-dimensional (3D) printing can create freeform architectures and electronics with unprecedented versatility. However, the full potential of electronic 3D printing has so far been limited by the inability to selectively anneal the printed materials, especially on temperature-sensitive substrates. Here, we achieve highly selective and rapid volumetric heating of 3D-printed nanomaterials and polymers in situ by focusing microwaves using a metamaterial-inspired near-field electromagnetic structure (Meta-NFS). In contrast to previous work, the Meta-NFS achieves the spatial resolution and power density needed to 3D print freeform microstructures where the electronic and mechanical properties can be locally programmed even within optically opaque materials. By broadening the material palettes compatible with 3D printing, near-field microwave 3D printing with Meta-NFS enables classes of electronics that are otherwise challenging to create.
GPT-4o mini: Non-social science research article
Ozone photochemistry in fresh biomass burning smoke over the United States
Lixu Jin, Matthew M. Coggon, Wade Permar, Julieta F. Juncosa Calahorrano, Brett B. Palm, Georgios I. Gkatzelis, Michael A. Robinson, Ilann Bourgeois, Samuel R. Hall, Jeff Peischl, Kirk Ullmann, Joel A. Thornton, Carsten Warneke, Frank Flocke, Emily V. Fischer, Robert J. Yokelson, Lu Hu
Full text
The first 5 hours of aging in biomass burning plumes can strongly affect ozone photochemistry. We examine how volatile organic compounds (VOCs), nitrogen oxides, and nitrous acid influence hydroxyl radical, ozone, and peroxyacetyl nitrate (PAN) based on three aircraft campaigns over the United States. Our analyses reveal variable, highly elevated hydroxyl radical concentrations in the first 2 hours, resulting in evident fire-to-fire variability in VOCs oxidation and in ozone and PAN production. About 40 to 70% of the variability is explained by chemical aging. Ozone production in the plumes is usually VOC-limited for the first 2 hours and then nitrogen oxide limited downwind. Box model results for hydroxyl radical, ozone, and most VOCs, using the full, explicit Master Chemical Mechanism (MCM) mechanism, suggest no major gaps in the current best knowledge of gas-phase chemistry. However, the MCM sometimes overestimates PAN due to underestimated nitrogen oxide sinks. GEOS-Chem, a widely used chemical transport model with a reduced mechanism, generally underperforms because of incomplete VOC representation. We identify these critical pathways to guide future model development.
GPT-4o mini: Non-social science research article
A dual role of Arabidopsis PAL nuclear localization in fine tuning flavonoid biosynthesis
Linhui Sun, Zifeng Yang, Xiaotong Shan, Nan Wang, Zile Liu, Xiang Gao, Yangnan Gu, Qiao Zhao
Full text
The phenylpropanoid pathway is essential for plant development and environmental adaptation, producing metabolites such as flavonoids, lignin, and salicylic acid. Phenylalanine ammonia-lyase (PAL) catalyzes the first committed step in this pathway and has long been viewed as a cytoplasmic enzyme. Here, we reveal that PAL responds to elevated flavonoid levels in Arabidopsis by undergoing phosphorylation and relocating to the nucleus. Nuclear sequestration of PAL reduces its cytoplasmic abundance and enzymatic activity, resulting in rapid suppression of phenylpropanoid metabolic flux. In parallel, nuclear-localized PAL interacts with the transcription factor TT8, disrupting MBW complex formation and down-regulating flavonoid biosynthetic genes. This dual mechanism enables PAL to act as a metabolic feedback regulator that dynamically adjusts flavonoid production in response to internal metabolic states. Our findings redefine PAL as both a biosynthetic enzyme and a responsive integrator of cellular metabolic status, establishing a previously unknown paradigm for feedback control in plant specialized metabolism.
GPT-4o mini: Non-social science research article
Divergent stem cell mechanisms govern the primary body axis and appendage regeneration in the axolotl
Liqun Wang, Li Song, Chao Yi, Jing Zhou, Zhouying Yong, Yan Hu, Xiangyu Pan, Na Qiao, Hao Cai, Wandong Zhao, Rui Zhang, Lieke Yang, Lei Liu, Guangdun Peng, Elly M. Tanaka, Hanbo Li, Yanmei Liu, Ji-Feng Fei
Full text
Exploring the fundamental mechanisms of organ regeneration is crucial for advancing regenerative medicine. The axolotl tail represents an opportunity to study regeneration of the primary axis including segmented muscle, vertebrae, and skin. During tail development, muscle stem cells (MuSCs) displayed expected specificity to the muscle lineage. Tail amputation, however, induced expansion of MuSC potential yielding clonal contribution to muscle, connective tissue including cartilage, pericytes, and fibroblasts. This expanded potential was not observed during limb regeneration, and cross-transplantation showed that these differences in potential are likely intrinsically determined. Single-cell RNA sequencing profiling revealed that tail MuSCs revert to an embryonic mesoderm–like state. Through genetic manipulation involving the overexpression of constitutively active transforming growth factor–ÎČ (TGF-ÎČ) receptors or Smad7 (antagonist of TGF-ÎČ signaling) in MuSCs, we demonstrated that the levels of TGF-ÎČ signal determine the fate outcome of MuSCs to connective tissue lineage or muscle, respectively. Our findings illustrate that variation in MuSCs may represent a fundamental difference between regeneration of primary axis versus appendage.
GPT-4o mini: Non-social science research article
E7 11-19 placement and orientation dictate CD8 + T cell response in structurally defined spherical nucleic acid vaccines
Jeongmin Hwang, Tonatiuh A. Ocampo, Vinzenz Mayer, Janice Kang, Krishna S. Paranandi, Young Jun Kim, Zhenyu Han, John P. Cavaliere, Sergej Kudruk, Jochen H. Lorch, Chad A. Mirkin
Full text
To develop effective nanostructured immunotherapeutics, identifying structural parameters that maximize immune response is essential. Spherical nucleic acids (SNAs) provide a modular platform for coordinated antigen-adjuvant delivery, where subtle structural differences can markedly influence potency. Herein, three SNAs were designed with HLA-A2–restricted HPV16 E7 11-19 peptide and CpG adjuvant, nearly identical in composition but differing in antigen presentation. All enhanced dendritic cell activation and CD8 + T cell cytotoxicity in primary human cells compared to peptide-CpG admixture; however, one variant, N-HSNA, elicited the strongest response, inducing ~8-fold higher interferon-γ secretion and ~2.5-fold greater cytotoxicity. In tumor-bearing AAD mice, N-HSNA reduced tumor burden by ~3.5-fold, prolonged survival, and expanded CD8 + T cells. Transcriptomic profiling revealed up-regulation of activation genes and suppression of exhaustion markers. In patient-derived HPV + head and neck cancer spheroids, N-HSNA enhanced cytotoxicity ~2.5-fold, establishing antigen placement and orientation as key parameters for translational cancer immunotherapy.
GPT-4o mini: Non-social science research article
Occurrence of major earthquakes is as stochastic as smaller ones
Zakaria Ghazoui, Jean-Robert Grasso, Arnaud Watlet, Corentin Caudron, Abror Karimov, Yusuke Yokoyama
Full text
Seismic hazard estimates rely on interevent time distributions between earthquakes of a given magnitude. In the Himalaya, recurrence intervals are usually modeled as cyclic or quasiperiodic, whereas globally, they range from periodic and clustered to random. Statistical analyses of a 6000-year lake-sediment seismic record, calibrated against regional instrumental data, worldwide paleoseismic records, and synthetic seismic catalogs, demonstrate that time intervals between large earthquakes ( M  ≄ 6.5, based on shaking intensity thresholds calibrated locally) robustly follow a Poisson distribution. Second-order fluctuations indicate event clustering. These observations contradict periodic or quasiperiodic recurrence models. Comparisons with paleoseismic data from other tectonic settings and realistic synthetic catalogs confirm the robustness and broad applicability of these findings. Thus, major earthquakes appear as stochastic as smaller ones, challenging recurrence models derived from limited datasets and substantially increasing seismic hazard estimates.
GPT-4o mini: Non-social science research article
Deep-sea fish reveal an alternative developmental trajectory for vertebrate vision
Lily G. Fogg, Stamatina Isari, Jonathan E. Barnes, Jagdish Suresh Patel, N. Marshall, Walter Salzburger, Fanny de Busserolles, Fabio Cortesi
Full text
Vertebrate vision relies on two photoreceptor types: cones for bright light and rods for dim light. The current dogma is that vertebrates develop cone-dominated retinas first, adding rods later. Here we show that larval deep-sea fishes have “hybrid” photoreceptors, expressing cone-specific genes in rod-like cells. Through development, they either retain these rod-like cones (in Maurolicus mucronatus ) or transition to true rods expressing rod-specific genes and transcription factors (in Vinciguerria mabahiss and Benthosema pterotum ). Unlike most marine fish larvae, which inhabit brightly lit waters, deep-sea fish larvae experience deeper and dimmer environments. By combining rod-like morphology with cone-like molecular machinery, hybrid photoreceptors likely maximize visual performance under such conditions. Consistently, spectral maxima predictions and environmental light estimations suggest tuning to the prevailing light environment throughout life. Our findings provide molecular, morphological, and functional evidence for the evolution of an alternative developmental trajectory for vertebrate vision.
GPT-4o mini: Non-social science research article
Resolving emergent transient oscillations in gene circuits with a growth-coupled model
Hari R. Namboothiri, Ayush Pandey, Chelsea Y. Hu
Full text
Synthetic gene circuits often behave unpredictably in batch cultures, where shifting physiological states are rarely accounted for in conventional models. Here, we find that degradation-tagged protein reporters could exhibit transient oscillatory expression, which standard single-scale models do not capture. We resolve this discrepancy by developing Gene Expression Across Growth Stages (GEAGS), a dual-scale modeling framework that explicitly couples intracellular gene expression to logistic population growth. Using a chemical reaction network model with growth phase–dependent rate-modifying functions, GEAGS accurately reproduces the observed transient oscillations and identifies amino acid recycling and growth-phase transition as key drivers. We reduce the model to an effective form for practical use and demonstrate its adaptability by applying it to layered feedback circuits, resolving long-standing mismatches between model predictions and measured dynamics. These results establish GEAGS as a generalizable platform for predicting emergent behaviors in synthetic gene circuits and underscore the importance of multiscale modeling for robust circuit design in dynamic environments.
GPT-4o mini: Non-social science research article
Robotic conformal 4D printing of liquid crystal elastomers
Christopher Chung, Huan Jiang, Alston X. Gracego, Martin L. Dunn, Kai Yu
Full text
Four-dimensional (4D) printing of liquid crystal elastomers (LCEs) serves as a promising approach to create reversibly shape-changing structures for diverse applications, including soft robotics, deployable systems, and adaptive surfaces. Central to programming these shape transformations is the spatial alignment of microscale liquid crystal mesogens. Existing 4D printing methods for LCEs are constrained by the alignment of mesogens within 2D planes, thereby limiting the range of achievable deformation. This work presents a robotic direct-ink-writing conformal 4D printing technology that enables deposition of LCEs onto complex, nonplanar 3D substrates. An algorithm is developed to generate printing paths, point normals, and control codes to guide the motion of a six-axis robotic arm. Conformal printing is demonstrated on various surfaces with different printing paths, and the resulting shape-changing behaviors are studied to highlight the unlocked design space. Integration with 3D scanning further allows printing onto substrates with unknown geometries, such as egg surfaces, which enables applications in on-demand protective coatings and structural repair.
GPT-4o mini: Non-social science research article
Critical quantum metrology robust against dissipation and nonadiabaticity
Jia-Hao LĂŒ, Wen Ning, Fan Wu, Ri-Hua Zheng, Ken Chen, Xin Zhu, Zhen-Biao Yang, Huai-Zhi Wu, Shi-Biao Zheng
Full text
Critical systems near quantum phase transitions were predicted to be useful for improvement of metrological precision, thanks to their ultrasensitive response to tiny variations of the control Hamiltonian. However, realizing criticality enhanced quantum metrology is experimentally challenging, mainly owing to decoherence and critical slowing down associated with the corresponding quantum state preparation. We circumvent these problems by making use of the critical behaviors in the Jaynes-Cummings model, to which the signal field is coupled. The information is encoded in the qubit’s excitation number, which displays a divergent changing rate at the critical point, and is extremely robust against decoherence and nonadiabatic effects. We demonstrate such a metrological protocol in a superconducting circuit, where an Xmon qubit, interacting with a resonator, is used as a probe for estimating the amplitude of a microwave field. The measured quantum Fisher information exhibits a critical quantum enhancement, confirming the potential for quantum metrology.
GPT-4o mini: Non-social science research article
YORU: Animal behavior detection with object-based approach for real-time closed-loop feedback
Hayato M. Yamanouchi, Ryosuke F. Takeuchi, Naoya Chiba, Koichi Hashimoto, Takashi Shimizu, Fumitaka Osakada, Ryoya Tanaka, Azusa Kamikouchi
Full text
The advent of deep learning methodologies for animal behavior analysis has revolutionized neuroethology studies. However, the analysis of social behaviors, characterized by dynamic interactions among multiple individuals, continues to represent a major challenge. In this study, we present “YORU” (your optimal recognition utility), a behavior detection approach leveraging an object detection deep learning algorithm. Unlike conventional approaches, YORU directly identifies behaviors as “behavior objects” based on the animal’s shape, enabling robust and accurate detection. YORU successfully classified several types of social behaviors in species ranging from vertebrates to insects. Furthermore, YORU enables real-time behavior analysis and closed-loop feedback. In addition, we achieved real-time delivery of photostimulation feedback to specific individuals during social behaviors, even when multiple individuals are close together. This system overcomes the challenges posed by conventional pose estimation methods and presents an alternative approach for behavioral analysis.
GPT-4o mini: Non-social science research article
A near-complete map of human cytosolic degrons and their relevance for disease
Vasileios Voutsinos, Kristoffer E. Johansson, Fia B. Larsen, Martin GrĂžnbĂŠk-Thygesen, Nicolas Jonsson, Emma Holm-Olesen, Giulio Tesei, Amelie Stein, Douglas M. Fowler, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Full text
Degrons are short protein segments that direct proteins for degradation via the ubiquitin-proteasome system, ensuring the removal of signaling proteins and clearance of misfolded proteins. We have performed a large-scale screen of more than 200,000 30-residue peptides from more than 5000 human cytosolic proteins, achieving 99.7% coverage. We find that 19% of peptides act as strong degrons, 30% as intermediate, and 51% as non-degrons. We identify both known and previously unidentified degradation signals and show that most depend on the E1 ubiquitin-activating enzyme and the proteasome. Structural mapping shows that many degrons are buried and likely become active upon protein unfolding. Training of a machine learning model allowed us to describe the degron properties and predict the cellular abundance of missense variants that operate by forming degrons in exposed and disordered protein regions, thus providing a mechanism of pathogenicity for germline coding variants at such positions.
GPT-4o mini: Non-social science research article
Electrically pumped single-mode microlasers with omnidirectional radiation for optical broadcasting communication
Feifan Xu, Jushi Liu, Yimeng Sang, Tao Tao, Junlong Kou, Jianping Liu, Ting Zhi, Zhe Zhuang, Rong Zhang, Bin Liu
Full text
Semiconductor whispering gallery mode (WGM)–visible microlasers are promising compact, on-chip light sources for high-speed visible-light communication due to their small footprints, high Q factors, and in-plane emission. However, achieving fabrication robustness, precise mode selection, narrow linewidths, and low thresholds for WGM-visible microlasers remains challenging. Here, we report a scalable strategy to fabricate continuous-wave, electrically pumped WGM blue microlasers based on III-nitride semiconductors with low threshold current densities and high slope efficiencies across diverse diameters from 10 to 160 micrometers. This high performance was achieved through effective vertical optical confinement by the waveguide structures and minimal sidewall scattering from atomically smooth surfaces. We further converted the laser cavity from a microdisk to a microring, which suppresses high-order WGMs and allows for single-mode operation with a high Q factor of 17,066. The omnidirectional in-plane radiation of WGM microlasers demonstrates angle-independent, high-modulation bandwidths, enabling synchronous broadcasting communication with high data transmission rates.
GPT-4o mini: Non-social science research article
Deep learning–integrated multilayer thermal gradient sensing platform for real-time blood flow monitoring
Youngmin Sim, Yosep Park, Kyeongha Kwon
Full text
Blood flow monitoring is fundamental for assessing cardiovascular health and identifying vascular complications. Traditional Doppler ultrasound methods require bulky equipment and specialized expertise, while recent thermal sensing approaches face limitations due to blood vessel depth variability beneath the skin. We present a soft electronic platform that integrates multilayer thermal sensing with deep learning algorithms to simultaneously measure blood flow rate and vessel depth. The device uses a wireless system with thermal sensing modules, featuring strategically positioned thermistors in separate layers to capture thermal gradients at different heights from the skin surface. Deep learning processes multilayer thermal patterns to extract both parameters in real time. Validation through benchtop testing, finite element analysis, and on-body trials demonstrates accurate measurements across relevant flow rates and vessel depths. Integration with photoplethysmography enhances continuous blood pressure monitoring accuracy compared to conventional approaches, particularly during dynamic physiological changes. This technology offers potential for personalized cardiovascular monitoring, early detection of hemodynamic events, and skin graft surveillance.
GPT-4o mini: Non-social science research article
Unraveling design principles of protein landscapes in photosynthetic membranes in plant chloroplasts
Ashraf Mohamed, Yuval Garty, Hui Min Olivia Oung, Sujith Puthiyaveetil, Kajwal K. Patra, Andrea Tagliabue, Steven Lenhert, Dana Charuvi, Reinat Nevo, Helmut Kirchhoff, Doran I. G. B. Raccah
Full text
The supramolecular organization of proteins within photosynthetic membranes is crucial for energy conversion in plants. Here, we introduce an analytical and computational pipeline that integrates high-resolution cryo–scanning electron microscopy, biochemical quantification, advanced Monte Carlo computer simulations, and statistical methods to elucidate the elusive protein landscapes of grana membranes in intact Arabidopsis leaves. Our integrated analysis challenges the prevailing view that particles on the exoplasmic fracture faces in freeze-fracture samples represent photosystem II exclusively. Instead, these particles also include cytochrome b 6 f complexes. Furthermore, our steric clash analysis demonstrates that stacked membranes contain a mixture of larger PSII supercomplexes (C 2 S 2 M 2 and C 2 S 2 ) in addition to a smaller complex (C 2 ). This suggests that in vivo PSII supercomplexes exist in an equilibrium distribution of differing sizes. Furthermore, we discovered that, although size exclusion effects govern the global protein arrangement, local packing exhibits orientational order indicative of lateral attractive protein-protein interactions.
GPT-4o mini: Non-social science research article
Mesothelial cells promote peritoneal invasion and metastasis of ascites-derived ovarian cancer cells through spheroid formation
Kaname Uno, Masato Yoshihara, Yoshihiko Yamakita, Kazuhisa Kitami, Shohei Iyoshi, Mai Sugiyama, Yoshihiro Koya, Tomihiro Kanayama, Haruhito Sahara, Satoshi Nomura, Kazumasa Mogi, Emiri Miyamoto, Hiroki Fujimoto, Kosuke Yoshida, Satoshi Tamauchi, Akira Yokoi, Nobuhisa Yoshikawa, Kaoru Niimi, Yukihiro Shiraki, Jonas Sjölund, Hidenori Oguchi, Kristian Pietras, Atsushi Enomoto, Akihiro Nawa, Hiroyuki Tomita, Hiroaki Kajiyama
Full text
Patients with epithelial ovarian cancer (EOC) are often diagnosed with peritoneal metastasis and ascites, the accumulation of intraperitoneal fluid containing nonmalignant cells. However, the interactions between EOC and nonmalignant cells before peritoneal metastasis remain unclear. To investigate this, whole EOC spheroids were observed using a multiphoton microscope, and their invasion ability was assessed. Mesothelial cells were identified as notable components of ascites through morphological assessment, immunohistochemical/immunofluorescence staining, and single-cell RNA sequencing analyses. Almost all EOC cells were spheroids, with 60% containing mesothelial cells. EOC cells quickly generate aggregated spheroids with mesothelial cells, and these aggregated cancer-mesothelial spheroids (ACMSs) invade collagen or mesothelial layers. Mesothelial cells forming ACMSs initiated the invasion. RNA sequencing analysis revealed marked RNA expression changes in mesothelial cells, whereas the changes in EOC cells were minor. Transforming growth factor–ÎČ1–stimulated mesothelial cells showed increased invadopodium formation along with fascin-1 up-regulation. These findings suggest that EOC cells alter mesothelial cells through ACMSs, thereby elucidating the rapid spread of EOC in the abdominal cavity.
GPT-4o mini: Non-social science research article
Highly efficient production of nitrite and nitrate from air at the gas-water interface of nanobubbles
Sandeep Bose, Saeed Bahadorikhalili, Yuanyi He, Hamidreza Samouei, Richard N. Zare
Full text
We report a simple, one-step conversion of air to nitrogen oxyanions (NO x − ), i.e., nitrate (NO 3 − ) and nitrite (NO 2 − ), at the gas-water interface (GWI) of nanobubbles (NBs). The nanobubble generator is placed inside an aqueous solution of 50 ÎŒM Fe 2+ to enhance the production of hydroxyl radicals (OH‱) by initiating Fenton’s reaction at the GWI. The formation of NO x − does not require any external potential or radiation. The NO x − production rate using NBs is found to be 60.4 ± 1.21 ÎŒM hour −1 , which shows a fourfold increase in the production as compared to the same reaction performed in microbubbles (15 ÎŒM hour −1 ), which is the result from an enhanced electric field strength at the GWI. We propose that this nitrogen-fixation approach presents a promising pathway for an eco-friendly, energy-efficient, and scalable solution for NO x − -based sustainable fertilizer production.
GPT-4o mini: Non-social science research article
Membrane-associated periodic skeleton regulates major forms of endocytosis in neurons through a signaling-driven positive feedback loop
Jinyu Fei, Yuanmin Zheng, Caden LaLonde, Yuan Tao, Ruobo Zhou
Full text
Endocytosis enables neurons to internalize molecules, maintaining homeostasis and responsiveness. The neuronal membrane–associated periodic skeleton (MPS), an actin spectrin–based cytoskeletal lattice, is known to restrict clathrin-mediated endocytosis (CME) in axons, but its broader role in other neuronal compartments and endocytic pathways remains unclear. Here, we show that all four major endocytic pathways—CME, caveolin-, flotillin-, and fast endophilin–mediated endocytosis—are spatially gated by the MPS and occur exclusively within MPS-free “clearing” zones throughout all neuronal compartments. Disrupting the MPS broadly enhances both basal and ligand-induced endocytosis. We also identify a previously unknown feedback loop in which ligand-triggered endocytosis activates extracellular signal–regulated kinase signaling, promoting protease-mediated spectrin cleavage and MPS disruption, which in turn facilitates further endocytosis. Furthermore, the MPS limits amyloid precursor protein endocytosis, thereby suppressing AÎČ42 production and linking MPS integrity to neurodegeneration. Our findings establish the MPS as a dynamic, signal-responsive modulator coupling membrane trafficking with cortical cytoskeletal organization and neuronal health.
GPT-4o mini: Non-social science research article
Experimental quantum state certification by actively sampling photonic entangled states
Michael Antesberger, Mariana M. E. Schmid, Huan Cao, Borivoje Dakić, Lee A. Rozema, Philip Walther
Full text
Entangled quantum states are essential ingredients for many quantum technologies, but they must be validated before they are used. As a full characterization is prohibitively resource intensive, recent work has focused on developing methods to efficiently extract a few parameters of interest, in a so-called verification framework. Most existing approaches are based on preparing an ensemble of nominally identical and independently distributed (IID) quantum states and then measuring each copy of the ensemble. However, this leaves no states left for the intended quantum tasks and the IID assumptions do not always hold experimentally. To overcome these challenges, we experimentally implement quantum state certification (QSC), which measures only a subset of the ensemble, certifying the fidelity of multiple copies of the remaining states. We use active optical switches to randomly sample from sources of two-photon Bell states and three-photon GHZ (Greenberger-Horn-Zeilinger) states, reporting statistically sound fidelities in real time without destroying the entire ensemble. In addition, our QSC protocol removes the assumption that the states are identically distributed (but still assumes independent copies); can achieve close N −1 scaling, in the number of states measured N ; and can be implemented in a device-independent manner. Together, these benefits make our QSC protocol suitable for benchmarking large-scale quantum computing devices and deployed quantum communication setups relying on entanglement in both standard and adversarial situations.
GPT-4o mini: Non-social science research article
VMAT2 dysfunction impairs vesicular dopamine uptake, driving its oxidation and α-synuclein pathology in DJ-1–linked Parkinson’s neurons
Leonie M. Heger, Francesco Gubinelli, Andreas J. Huber, Aida Cardona-Alberich, Matteo Rovere, Ulf Matti, Stephan A. MĂŒller, Sankarshana R. Nagaraja, Lena Jaschkowitz, Martina Schifferer, Wolfgang Wurst, Stefan F. Lichtenthaler, Christian Behrends, Sivakumar Sambandan, Lena F. Burbulla
Full text
Parkinson’s disease (PD) is characterized by α-synuclein accumulation and dopaminergic neuron degeneration, with dopamine (DA) oxidation emerging as a key pathological driver. However, the mechanisms underlying this neurotoxic process remain unclear. Using PD patient-derived and CRISPR-engineered induced pluripotent stem cell midbrain dopaminergic neurons lacking DJ-1, we identified defective sequestration of cytosolic DA into synaptic vesicles, which culminated in DA oxidation and α-synuclein pathology. In-depth proteomics, state-of-the-art imaging, and ultrasensitive DA probes uncovered that decreased vesicular monoamine transporter 2 (VMAT2) protein and function impaired vesicular DA uptake, resulting in reduced vesicle availability and abnormal vesicle morphology. Furthermore, VMAT2 activity and vesicle endocytosis are processes dependent on adenosine 5â€Č-triphosphate (ATP), which is notably reduced in DJ-1–deficient dopaminergic neurons. ATP supplementation restored vesicular function and alleviated DA-related pathologies in mutant dopaminergic neurons. This study reveals an ATP-sensitive mechanism that regulates DA homeostasis through VMAT2 and vesicle dynamics in midbrain dopaminergic neurons, highlighting enhanced DA sequestration as a promising therapeutic strategy for PD.
GPT-4o mini: Non-social science research article
Structure-based design of an opioid receptor modulator for enhanced morphine analgesia
Yue Wang, Ping Luo, Haiyan Xu, Li Zhan, Kensuke Sakamoto, Mingyu Li, Jing Wang, Xi-Ping Huang, Jianhui Zhou, Tao Liu, Yanrui Suo, Wenjia Fan, Xinheng He, Youwei Xu, Yongjie Cai, Chao Wang, Yuxi Zhao, Antao Dai, Yali Lai, Qingning Yuan, Wen Hu, Kai Wu, Dehua Yang, Xi Cheng, Xiaojie Lu, Brian Krumm, Terry Kenakin, Jian Zhang, Bryan L. Roth, Zhaobing Gao, H. Eric Xu, Youwen Zhuang
Full text
The alarming rates of deaths due to opioid overdose present an urgent need for safer opioid analgesics. Positive allosteric modulators (PAMs) of opioid receptors (ORs) offer a promising approach to enhance opioid efficacy while reducing risks of overdose. In this study, we unveil the selective mechanism of PAM modulation of the OR family through structure elucidation of the ÎŽ-opioid receptor and ÎŒ-opioid receptor (ÎŒOR) bound to orthosteric agonists and PAMs BMS986187 (BMS187) and BMS986122 (BMS122). In addition, we uncovered an unexpected but conserved allosteric site across the transmembrane helices TM2 to TM4 of ORs, occupied by BMS187 but not BMS122. Leveraging these structural insights, we designed 9-(5-(4-chlorophenyl)furan-2-yl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1 H -xanthene-1,8(2 H )-dione (MPAM-15), whose αÎČ cooperativity factor is 33-fold higher than BMS122 and threefold higher than BMS187, indicating markedly stronger positive allosterism. Animal studies demonstrate that MPAM-15 shows excellent brain penetration and enhances morphine-induced antinociception without exacerbating respiratory depression or constipation. Molecular dynamics simulations revealed that MPAM-15 promotes and stabilizes the conformational equilibrium of ÎŒOR toward the canonical active state, providing a mechanistic basis for its enhanced allosteric potency. These discoveries substantially advance our understanding of OR allosteric mechanism and pave the way for the structure-based development of allosteric opioid analgesics.
GPT-4o mini: Non-social science research article
In situ coagulation environment regulation–assisted thrombus clearance via hydrogenated silicon-based nanothrombolytics
Ya-Xuan Zhu, Zhixin Chen, Yanling You, Yihan Chen, Wenjie Yu, Xue Guan, Piao Zhu, Jie Yang, Min Ge, Xiaojun Chen, Han Lin, Jianlin Shi
Full text
Thrombotic disorders remain among the leading causes of global mortality, yet current thrombolytic therapies are limited by poor targeting specificity and inadequate microenvironmental modulation, resulting in suboptimal efficacy and serious side effects. Here, we developed a hydrogen-generating nanothrombolytic agent that enables enzymatic clot dissolution in combination with intelligent microenvironment reprogramming. Specifically, we assembled urokinase, a clinical thrombolytic drug, with hydrogenated silicene (SiH) nanosheet and fibrinogen, a substrate of coagulation reaction, to promote thrombolysis. Functionally, SiH nanosheet plays multiple roles in the nanothrombolytics: blocking the functional sites of urokinase to durably inhibit its activity in circulation to prevent systemic bleeding, followed by urokinase reactivation in response to SiH nanosheet self-degradation and prothrombotic microenvironment regulation through the in situ hydrogen generation, which mitigates the oxidative stress of vascular endothelial cells and inhibits their release of procoagulant factors. This microenvironment-adaptive thrombolysis strategy offers a promising paradigm for the precise management of thrombotic emergencies.
GPT-4o mini: Non-social science research article
Bacterial metabolic remodeling by convergent evolution unlocks nutrient availability after a host switch
Amy C. Pickering, Jamie Gorzynski, Grace Taylor-Joyce, Rhodri Evans, Willow Fox, Pedro Melo, Joana Alves, Hannah Schlauch, Fiona Sargison, Gonzalo Yebra, Natalie Ring, J. Ross Fitzgerald
Full text
New pathogens typically arise from host jump events between species. Staphylococcus aureus is a multihost pathogen responsible for a global burden of human disease and a leading cause of intramammary infection in dairy cattle. Here, we demonstrate that following historical human-to-bovine host switch events, S. aureus has undergone adaptive metabolic remodeling in response to distinct nutrient availability in the dairy niche. In particular, we found that bovine S. aureus has evolved the capacity for protease-mediated degradation of casein, a protein abundant in bovine milk, to access nutrients for proliferation. This phenotype has evolved convergently in different S. aureus lineages via mutations in distinct gene loci driving overexpression of the protease aureolysin. Together, we have dissected a key host-adaptive trait, which facilitates the enzymatic release of nutrients from a substrate specific to the new host milieu. These findings highlight the remarkable evolutionary plasticity of a major bacterial pathogen underpinning its multihost species tropism.
GPT-4o mini: Non-social science research article
Expansive spatial pattern of AÎČ deposition in patients with cerebral amyloid angiopathy: A three-dimensional surface-to-depth analysis
Hideki Hayashi, Rie Saito, Akinori Miyashita, Takeshi Ikeuchi, Mari Tada, Kohei Akazawa, Osamu Onodera, Kazuki Tainaka, Akiyoshi Kakita
Full text
Cerebral amyloid angiopathy (CAA) is a neurodegenerative condition characterized by amyloid-ÎČ (AÎČ) deposition in small vessel walls, often coexisting with Alzheimer’s disease due to impaired AÎČ clearance. However, the spatial distribution of AÎČ within the human brain remains unclear as the vascular network’s complexity and scale hinder visualization by conventional thin-slice analysis. To address this, we performed three-dimensional (3D) volumetric imaging of the cerebrovascular network and AÎČ deposition in autopsied brains with CAA using advanced tissue clearing and light-sheet fluorescence microscopy, labeling for smooth muscle actin (SMA) and AÎČ. We found prominent AÎČ deposition and SMA loss in leptomeningeal and superficial cortical segments, which were anatomically contiguous with deeper AÎČ-positive segments, indicating a surface-to-deep progression pattern of AÎČ extension. The perivascular plaque density was significantly lower around AÎČ-positive vessels. This technology may provide further insights into CAA pathology and is recommended for research on the 3D pathology of neurological disorders.
GPT-4o mini: Non-social science research article
Type one protein phosphatases (TOPPs) catalyze EIN2 dephosphorylation to regulate ethylene signaling in Arabidopsis
Meifei Su, Qianqian Qin, Jing Zhang, Yingdong Li, Ailin Ye, Suomin Wang, Suiwen Hou
Full text
Type one protein phosphatases (TOPPs) widely modulate phytohormone signaling and stress responses, but their roles in ethylene signaling remain unknown. This study reveals a reciprocal regulatory relationship between TOPPs and ethylene insensitive 2 (EIN2)–mediated ethylene signaling. We identified that ethylene can induce TOPPs ’ expression, and topp1/4/5 mutants exhibited partial ethylene insensitivity with reduced EIN3 protein. Mechanistically, TOPPs function upstream of EIN2 and interact with its carboxyl-terminal domain (CEND) to dephosphorylate the S655 residue. This site-specific dephosphorylation promotes EIN2 stability and EIN2 CEND nuclear accumulation, thereby activating ethylene responses. Notably, EIN2 S655A -YFP/ein2-5 plants displayed constitutive ethylene responses and improved salt tolerance. Further investigation showed that EIN3/EIN3 like 1 (EIL1) activates TOPPs ’ expression by binding to their promoters, amplifying ethylene signaling accordingly. Together, our finding establishes TOPPs as key regulators in ethylene signaling and reveal a dephosphorylation switch mechanism governing EIN2 function, providing critical insight into how EIN2 posttranslational modifications mediate plant stress adaptation.
GPT-4o mini: Non-social science research article
Can we bend the curve: Trends in global biodiversity scenarios
Flavia Aschi, Stefan C. Dekker, David LeclĂšre, Alexandra Marques, Christian Neumann, Geanderson Ambrosio, Detlef P. van Vuuren
Full text
Internationally, it has been agreed to halt and reverse biodiversity loss, a commitment partly underpinned by model-based scenario analyses showing that bending the trend is possible. These scenarios provide insights into alternative future biodiversity trends and their drivers. Our meta-analysis differentiates scenarios that project biodiversity loss and that halt or reverse the trend based on their quantitative outcomes and explores their key characteristics such as scenario assumptions, drivers of loss, biodiversity indicators and models used. We found that bending-the-curve studies are scarce, and mostly do no account for climate change, which risks suggesting that the trend can be bent too easily. Our findings indicate that bending is only achievable with integrated efforts across different sectors, such as nature conservation, sustainable food production, diet change, and reduced food waste. To better support policymaking, scenarios should be based on model intercomparisons and use standardize indicators to allow comparisons across studies, account for additional drivers of loss to represent the real threats to biodiversity, and include more ambitious cross-sectoral actions to effectively bend the curve.
GPT-4o mini: Non-social science research article
Diffusiophoretic transport of colloids in porous media
Mobin Alipour, Yiran Li, Haoyu Liu, Amir A. Pahlavan
Full text
Chemical gradients are ubiquitous in porous media flows, from tidal salt gradients in aquifers to irrigation-driven gradients in soils and ionic gradients from metabolic activity in tissues. Although chemical gradients are known to drive diffusiophoretic migration of colloids, these nonequilibrium forces have largely been ignored in porous media flows. Under typical subsurface conditions, flow velocities within preferential pathways exceed phoretic velocities by orders of magnitude, suggesting that diffusiophoresis would be limited to stagnant pockets. Here, using microfluidic experiments, numerical simulations, and theoretical modeling, we show that even moderate solute gradients, typical of natural mixing, can markedly alter colloid transport. We uncover a previously overlooked effect: cross-streamline phoretic migration within preferential flow pathways, which changes macroscopic dispersion by orders of magnitude and suppresses the impact of geometric disorder on transport. Our findings challenge classical models of colloid transport, highlighting the broad implications of solute gradients for technological, biomedical, and environmental applications.
GPT-4o mini: Non-social science research article
Chiral hinge–surface transport across dimensions in three-dimensional magneto-optical topological materials
Hua-Shan Lai, Yan-Chen Zhou, Ze-Qun Sun, Cheng He, Yan-Feng Chen
Full text
Chiral boundary states with perfect conducting channels are essential characteristics of magnetic topological materials. Prominent examples include the one-dimensional (1D) chiral edge and 2D chiral surface states found in 2D and 3D quantum Hall materials under magnetic fields, respectively. However, these boundary states are restricted to specific fixed dimensions, so they hardly facilitate cross-dimensional energy and information transport. Here, we fabricate a unique 3D photonic antiferromagnetic topological insulator with net zero magnetization that can simultaneously support different-dimensional hinge states and unpaired surface Dirac cones on neighboring facets. Owing to the chiral anomaly present in a finite-size sample, the gapless surface Dirac cone, neighbored by facets with surface Dirac masses of opposite signs, is further converted, exhibiting 2D planar one-way propagation. In conjunction with 1D hinge states, we experimentally observe a closed chiral loop for nonreciprocal hinge–surface transport across dimensions in topological photonics, similar to that theoretically proposed in 3D quantum anomalous Hall materials. Our findings enrich the chiral boundary features of 3D magnetic topological insulators and offer a topological strategy for exploring ideal cross-dimensional devices.
GPT-4o mini: Non-social science research article
Circular RNA circHomer1 mediates hippocampal functions via ribonucleoprotein granule transport and dendritic targeting of synaptic RNAs
Ying Cai, Zhongyu Zheng, Haoyu Xu, Yao Zhu, José C. Zepeda, Brad A. Grueter, Xiaojie Wang, Taeyun Ku, Yangyang Duan, Hayley Wing Sum Tsang, Wing-Yu Fu, Amy Kit Yu Fu, Nikolaos Mellios, Hovy Ho-Wai Wong, Kwok-On Lai, Jacque Pak Kan Ip
Full text
Circular RNAs are backspliced, closed-loop RNAs previously believed to be noncoding by-products formed during transcription. Increasing evidence suggests that circular RNAs have crucial functions in the brain, such as regulating neuronal transmission and synaptic plasticity. However, the specific molecular mechanisms by which circular RNAs function remain largely unexplored. Here, we investigated how circHomer1 , a brain-enriched circular RNA derived from the Homer1 gene, affects hippocampus-dependent learning and memory. Our results demonstrate that circHomer1 plays a vital role in mediating the dendritic targeting of messenger RNAs that encode postsynaptic proteins by acting as a molecular bridge between the motor protein Kinesin 1 and core components of neuronal ribonucleoprotein granules, including Fused in Sarcoma and Fragile X Mental Retardation Protein, at dendrites. This interaction influences synaptic function, the structural morphology of dendritic spines, and hippocampus-dependent spatial learning and memory. Thus, our study highlights a role of circular RNAs in mediating synaptic messenger RNA targeting to shape dendritic spines and consequently neuronal functions.
GPT-4o mini: Non-social science research article
Extracellular vesicles mediate stem cell signaling and systemic RNAi in planarians
Vidyanand Sasidharan, Laura Ancellotti, Viraj Doddihal, Carolyn Brewster, Frederick Mann, Mary Cathleen McKinney, Joseph Varberg, Eric Ross, Fengyan Deng, Kexi Yi, Alejandro SĂĄnchez Alvarado
Full text
Planarian flatworms are known for their remarkable regenerative capacity; however, the precise intercellular communication mechanisms underlying this process remain unsolved. Here, we report the discovery and characterization of abundant extracellular vesicles (EVs) in planarians. Using imaging and molecular analysis, we show conservation of biogenesis, morphology, and protein composition of planarian EVs. Environmental stressors significantly elevate EV release, indicating that planarians dynamically regulate vesicle production. Functionally, planarian EVs mediate intercellular communication by transferring regulatory signals: We find that they shuttle small RNAs that effect systemic RNA interference (RNAi) throughout the organism. Notably, gene knockdown experiments reveal a crucial role for AGO-3, a member of the Argonaute family of proteins, in modulating the association of small interfering RNAs with EVs, linking the intracellular RNAi machinery to EV-based signaling. These findings highlight EVs as pivotal mediators of cell-cell communication in planarians, with broad implications for understanding the coordination of gene regulation and tissue regeneration in animals.
GPT-4o mini: Non-social science research article
Magnetoelectric nanoparticles drive TAF9B + T H 2 cell expansion to alleviate inflammation
Jia Song, Lulu Liu, Ziqi Liu, Shuo Liu, Zhang Zhang, Xinyu Liu, Boon Chin Heng, Yaojin Wang, Dan Lu, Xuehui Zhang, Xuliang Deng
Full text
Stimuli-responsive nanomaterials represent a promising platform for immunomodulation. However, their application in orchestrating T cell responses remains limited. Here, we develop a biomimetic magnetoelectric nanoparticle (DC@CFO/BFO) by coating core-shell CoFe 2 O 4 @BiFeO 3 particles with dendritic cell membranes to enable selective targeting of CD4 + T cells. Under magnetic field stimulation, DC@CFO/BFO localizes to ribosomes and enhances protein synthesis by modulating electrostatic interactions at the ribosomal exit tunnel. This ribosome-targeted modulation promotes type II immune response via IL-4 induction and TAF9B-dependent transcriptional programming, thereby enhancing T helper 2 (T H 2) cell proliferation. In murine models of colitis and arthritis, both systemic administration of DC@CFO/BFO and adoptive transfer of magnetoelectricity-responsive T H 2 cells attenuated inflammation and restored immune homeostasis. In contrast, these effects were abrogated in Taf9b -deficient T cells, underscoring the essential role of TAF9B in mediating this response. Collectively, our findings identify magnetoelectric nanocomposites as a potent tool for T cell engineering and highlight a translational strategy for the treatment of autoimmune inflammation.
GPT-4o mini: Non-social science research article
Complex perishable technologies from the North American Great Basin reveal specialized Late Pleistocene adaptations
Richard L. Rosencrance, Geoffrey M. Smith, Katelyn N. McDonough, Christopher S. Jazwa, Mariya Antonosyan, Elizabeth A. Kallenbach, Thomas J. Connolly, Brendan J. Culleton, Kathryn Puseman, Megan McGuinness, Dennis L. Jenkins, Daniel O. Stueber, Pam E. Endzweig, Patrick Roberts
Full text
Structurally and functionally complex technologies were a defining element of Late Pleistocene societies, but physical examples of them remain extremely rare in the archaeological record because most were made from perishable raw materials. The sparse material record of those myriad technologies limits our ability to formulate nuanced models about this critical period in human history. We present radiocarbon, Zooarchaeology by Mass Spectrometry, and other taxonomic identification data from two of the largest Late Pleistocene perishable assemblages in the world, Cougar Mountain Cave and Paisley Caves, Oregon, US. These data include 66 radiocarbon dates on 55 items made from 15 different plant and animal taxa, including the oldest known physical remains of sewn hide. We provide data on eyed bone needles from four regional sites, showing that they are among the finest bone needles made in the Pleistocene. Our study illuminates the complex interplay of culture, climate, and technology in the Pleistocene.
GPT-4o mini: Non-social science research article
Fungal infection drives metabolic reprogramming in epithelial cells via aerobic glycolysis and an alternative TCA cycle shunt
Aize Pellon, Shervin Dokht Sadeghi Nasab, Gholamreza Bidkhori, James S. Griffiths, Stefania Vaga, Neelu Begum, Mariana Blagojevic, Nitesh Kumar Sigh, Natalia K. Kotowicz, Ifeanyi Uzochukwu, Adrien Le Guennec, Rhonda Henley-Smith, Harry Gregson-Williams, Frederick Clasen, Miranda Pryce, Nadia Karimpour, Richard Cook, Juan Anguita, Jonathan P. Richardson, Selvam Thavaraj, Julian R. Naglik, Saeed Shoaie, David L. Moyes
Full text
Candida albicans –induced immunometabolic changes drive complex responses in immune cells. However, whether and how C. albicans causes remodeling of oral epithelial cell (OEC) metabolism is unclear. Here, we use in vitro experiments and patient biopsies to demonstrate that OECs undergo metabolic reprogramming when infected by C. albicans independently of candidalysin secretion, increasing glycolysis and decreasing tricarboxylic acid (TCA) cycle activity. Glycolysis and glucose transport inhibition show that these pathways support OEC cytokine release, highlighting the partial control of antifungal epithelial immunity by cellular metabolism. However, glucose supplementation disrupts OEC responses both in vitro and in vivo, suggesting that the fungus benefits from these metabolic shifts and that increased aerobic glycolysis in OECs is detrimental. Genome-scale metabolic modeling predicted a shutdown of the TCA cycle and a previously unidentified role for glutamic-oxaloacetic transaminase 1 (GOT1) in response to C. albicans , which was subsequently shown to be important for OEC survival during infection. This study reveals a fundamental role for hexose metabolism and identifies a GOT1-mediated TCA cycle shunt in regulating OEC survival and immune responses during mucosal fungal infections.
GPT-4o mini: Non-social science research article
Interface-engineered plasmonic covalent organic framework nanofilms on TiO 2 nanotubes for universal mass spectrometry imaging
Yizhu Xu, Xinzhou Wu, Weifeng Li, Jiadu Hu, Xiran Chen, Yingying Chen, Zhibin Yin, Wei Hang
Full text
Covalent organic frameworks (COFs) hold promise for surface-assisted laser desorption/ionization mass spectrometry imaging (MSI), yet their integration with plasmonic nanostructured platforms remains unexplored. Here, we report a liquid-liquid interfacial self-assembly strategy to construct plasmonic gold nanoparticle–decorated COF nanofilms on titanium dioxide nanotubes. This hierarchical design synergizes plasmonic enhancement, efficient charge transfer, and enhanced ionization efficiency, achieving sensitivity improvement over conventional matrices. The plasmonic platform affords universal compatibility with currently available biosample preparation protocols including imprinting, stamping, and cryo-sectioning for multitissue MSI. The first whole-plant imprinting MSI of Vigna unguiculata reveals tissue-specific distributions of three pollutants with distinct translocation rate and endogenous metabolites. In addition, 10-micrometer resolution lipid mapping was achieved in stamped fingerprints and cryo-sectioned murine brains. Moreover, we successfully visualized ischemic stroke biomarkers in rat brains for interrogating the pathogenesis of focal ischemia. Our findings highlight the advantages of plasmonic COF nanofilms on titanium dioxide nanoarrays for universal matrix-free MSI in complex biological systems, bridging advanced materials and life science applications.
GPT-4o mini: Non-social science research article
Electrolyte design for aqueous batteries
Hu Hong, Qingshun Nian, Xun Guo, Qing Li, Chunyi Zhi
Full text
Aqueous batteries, with their inherent safety, operational simplicity, and cost-effectiveness, have emerged as promising candidates for grid-scale energy storage applications. However, the relatively low output voltage of aqueous systems continues to limit their achievable energy density. The aqueous electrolyte occupies a central role in addressing this limitation because it mediates ion transport and interfacial reactions at both the cathode and anode; accordingly, advances in electrolyte design are indispensable to meet future performance demands. In this review, we elucidate the core bottlenecks in aqueous electrolyte design, distill molecular-level design principles, and outline feasible pathways for future practical implementation. We aim to guide the development of next-generation aqueous electrolytes that harmonize outstanding electrochemical performance, thereby accelerating the transition from laboratory concepts to transformative energy solutions.
GPT-4o mini: Non-social science research article
Hybrid female sterility due to cohesin protection errors in mouse oocytes
Warif El Yakoubi, Bo Pan, Takashi Akera
Full text
Hybrid incompatibility can lead to lethality and sterility of F1 hybrids, promoting speciation. The cell biological basis underlying hybrid incompatibility remains largely unknown, especially in mammals. Here, we found that female hybrids between Mus musculus domesticus and Mus spicilegus mice are sterile due to the failure of homologous-chromosome separation in oocyte meiosis, producing aneuploid eggs. This nondisjunction phenotype was driven by the mislocalization of the cohesin protector, SGO2, along the chromosome arms instead of its typical centromeric enrichment, resulting in cohesin overprotection. The upstream kinase, BUB1, showed a higher activity in hybrid oocytes, explaining SGO2 mistargeting. Higher BUB1 activity was not observed in mitosis, consistent with viable hybrid mice. Cohesion defects were also evident in hybrid mice from another genus, Peromyscus , wherein cohesin protection is weakened. Defective cohesion in oocytes is a leading cause of reduced fertility. Our work provides evidence that a major cause of human infertility may play a positive role in mammalian speciation.
GPT-4o mini: Non-social science research article
Optoacoustically augmented magnetic guidewire for radiation-free minimally invasive therapies
Fan Wang, Xianqiang Bao, Erdost Yildiz, Yan Yu, Xosé Luís Deån-Ben, Wenbin Kang, Shuaizhong Zhang, Devin Sheehan, Ren Hao Soon, Jelena Zinnanti, Daniel Razansky, Metin Sitti
Full text
Endovascular interventions are essential for treating cerebrovascular diseases, yet their monitoring methods commonly rely on ionizing radiation and contrast agents, posing unnecessary risks to patients and clinicians. We present a multifunctional optoacoustically augmented magnetic guidewire (OptoMaG) that integrates optoacoustic imaging with magnetic navigation to enable radiation-free, image-guided interventions. The ~250-micrometer flexible guidewire incorporates a 460-nanometer luminescent core with an enhanced optoacoustic signature and a FePt magnetic tip for precise, steerable control. Proof-of-concept studies show that OptoMaG can be actively navigated with external magnetic fields to traverse a 3D human-scale cerebrovascular phantom and accurately reach target brain sites. Beyond navigation, the FePt tip enables localized thermal ablation under remote radiofrequency stimulation, highlighting its theranostic potential for tumor treatment. In addition, OptoMaG functions as a light source for photodynamic therapy, selectively activating photosensitizers to destroy tumor cells while preserving healthy tissue. Collectively, OptoMaG provides a safe, radiation-free platform merging real-time navigation with targeted therapeutic capabilities.
GPT-4o mini: Non-social science research article
Hydrostatic pressure induces strong leakage of dissolved organic matter from “marine snow” particles
Peter Stief, Jutta Niggemann, Margot Bligh, Hagen Buck-Wiese, Urban WĂŒnsch, Michael Steinke, Jan-Hendrik Hehemann, Ronnie N. Glud
Full text
Marine snow forms at the ocean surface, sinks to depth, and ultimately enables carbon sequestration in the seabed. Fast-sinking marine snow particles, such as diatom aggregates, encounter a rapid increase in hydrostatic pressure during their descent. Using incubations in rotating pressure tanks, we found that pressure levels corresponding to 2- to 6-kilometer water depth induce leakage of dissolved organic matter (DOM) from diatom aggregates equivalent to ~50% of their initial carbon contents. The leaked DOM proved to be diatom-derived and changed the amount and composition of DOM in the surrounding seawater substantially. Ultrahigh-resolution mass spectrometry, high protein-like fluorescence, and low carbon:nitrogen ratios classified the leaked DOM as labile. The bioavailability of leaked DOM was demonstrated by its rapid utilization by a pelagic microbial community, leaving mainly recalcitrant DOM behind. Pressure-induced DOM leakage likely weakens the gravitational “biological carbon pump” and supplies labile DOM to the pelagic microbiome of the deep ocean.
GPT-4o mini: Non-social science research article
The ocean’s biological carbon pump under pressure
Jack J. Middelburg
Full text
Increasing hydrostatic pressure induces the release of dissolved organic matter from rapidly settling marine particles and contributes to the depth attenuation of carbon fluxes.
GPT-4o mini: Non-social science research article
OsRNS4-mediated cross-kingdom RNA interference is inhibited by Ustilaginoidea virens effector SCRE2 to promote infection in rice
Han Gao, Anfei Fang, Wu Yang, Shanshan Qiu, Xinhang Zheng, Shanzhi Wang, Jing Fan, Hailong Guo, Fuhao Cui, Yong-Hwan Lee, Jiyang Wang, Wenxian Sun
Full text
The Ustilaginoidea virens effector SCRE2 has been previously identified to be an essential virulence factor. To elucidate molecular mechanisms underlying SCRE2 virulence function, we identify that SCRE2 interacts with Oryza sativa S-like ribonuclease family member OsRNS4. As a catalytically inactive RNase, OsRNS4 positively regulates rice immunity, depending on its RNA binding ability. OsRNS4 is unconventionally secreted through tetraspanin-positive extracellular vesicles (EVs). OsRNS4 binds to certain groups of rice miRNAs, whereas SCRE2 prevents the binding of OsRNS4 to miRNAs. Especially, OsRNS4-bound miR528-5p in rice is detected in false smut balls and silences the gene UvSfk1 essential for U. virens virulence. Thus, OsRNS4 might act as a carrier to transport miRNAs from rice into fungi, which target the virulence genes in U. virens and thereby contributes to rice resistance against fungal pathogens. As an unidentified counter-defense mechanism, SCRE2 suppresses cross-kingdom RNA interference to promote infection through inhibiting OsRNS4 binding to miRNAs.
GPT-4o mini: Non-social science research article
Introgressed mitochondrial fragments from archaic hominins alter nuclear genome function in modern humans
Qiong Zhu, Jinning Zhang, Weichen Zhou, Shen-Ao Liang, Shengmiao Wang, Xinyu Cai, Fuyuan Li, Jin Li, Guojie Zhang, Huijuan Feng, Qiaomei Fu, Joshua M. Akey, Feng Zhang, Li Jin, Shuhua Xu, Hong-Xiang Zheng, Lu Chen
Full text
Archaic introgression introduced functionally relevant variants into modern humans, yet small-scale insertions remain understudied. Here, we leverage 2519 modern human genomes and four high-coverage archaic hominin genomes to systematically characterize nuclear mitochondrial DNA segments (NUMTs). We uncover 483 polymorphic NUMTs across globally diverse human populations and 10 in archaic genomes. By combining overlap with Neanderthal-derived and Denisovan-derived haplotypes, phylogenetic analyses, insertion time estimates, and haplotype colocalization, we identify five NUMTs introduced into modern humans via archaic hominin introgression. Functional analyses reveal that introgressed NUMTs can modulate gene expression, including allele-specific up-regulation of the immune-related gene RASGRP3 , and reshape three-dimensional chromatin structure at loci such as SCD5 and HNRNPD . These findings highlight an underappreciated mechanism by which archaic mitochondrial fragments shape nuclear genome function and evolution. Our study reframes NUMTs not as passive genomic fossils but as dynamic elements influencing modern human diversity and adaptation.
GPT-4o mini: Non-social science research article
Overcoming host restrictions to enable continuous passaging of GII.3 human norovirus in human intestinal enteroids
Gurpreet Kaur, Sue E. Crawford, Sara Javornik Cregeen, Anil Surathu, B. Vijayalakshmi Ayyar, Carmen V. Apostol, Hoa Nguyen Phuc, Khalil Ettayebi, Aaya Boussattach, Xi-Lei Zeng, Sarah E. Blutt, Harsha Doddapaneni, Donna M. Muzny, Cristian Coarfa, Ramakrishnan Anish, B. V. Venkataram Prasad, Robert L. Atmar, Sasirekha Ramani, Mary K. Estes
Full text
The establishment of human intestinal enteroids (HIEs) as a model for human norovirus (HuNoV) replication has been transformative for studying this leading cause of gastroenteritis. However, indefinite passaging of HuNoVs in HIEs remained a challenge, necessitating the use of patient stool samples as viral inocula. Using RNA-seq, we identified CXCL10, CXCL11, and CCL5 as up-regulated chemokines, suggesting their potential as host restriction factors. TAK-779, a CXCR3/CCR5/CCR2 antagonist, enhanced GII.3 HuNoV replication and viral spread in a dose- and time-dependent manner, enabling successful passaging of GII.3 HuNoV in two different HIE lines and generation of viral stocks. Sequencing passaged virus revealed one consensus change in the major capsid protein and several dynamic adaptations, suggesting emergence of variants. TAK-779 also enhanced replication of GI.1 and GII.17 strains, but not GII.4, suggesting strain-specific host interactions. This breakthrough in passaging provides insight into HuNoV-host interactions, establishes a scalable in vitro system for virus propagation, and opens avenues for structural, biochemical, and therapeutic studies.
GPT-4o mini: Non-social science research article
Oriented cell divisions induce basal progenitors and regulate neural expansion across tissues and species
Benoit Boulan, Marine Lacomme, Amin Benadjal, Miranda Krueger, Ko Currie, Anna La Torre, Alain Chédotal, Michel Cayouette
Full text
Nervous system expansion relies on progenitor proliferation, yet its regional and evolutionary regulation is incompletely understood. While basally dividing progenitors are implicated in neocortical growth, their developmental origins and relevance beyond the cortex remain unclear. We show here that double inactivation of spindle orientation regulators GPSM2 and SAPCD2 in mice completely reorients progenitor divisions in both the neocortex and retina. This shift increases basal progenitors over sixfold in the neocortex and induces their ectopic emergence in the retina, resulting in extra cell layers and ~30% tissue enlargement. Single-cell RNA sequencing reveals that the induced basal progenitors in the cortex resemble human outer radial glia, and both cortical and retinal progenitors show altered Hippo signaling. Last, macaque and human retinas display twice as many reoriented divisions as the mouse and naturally contain basal progenitors. These findings show that division orientation is critical for regulating neural progenitor output and scaling tissue growth.
GPT-4o mini: Non-social science research article
Noninvasive photoacoustic computed mesoscopy for longitudinal brain imaging
Shijie Ruan, Wei Qin, Linyang Li, Tingting Li, Baochen Li, Xiao Liang, Lei Xi
Full text
Photoacoustic imaging has become a powerful tool for visualizing the brain morphology, function, and metabolism. However, severe optical scattering and high-frequency acoustic attenuation within the brain degrade the performance of photoacoustic brain imaging. To address such limitation, we propose a line scanning–based photoacoustic computed mesoscopic (PACMes) approach for noninvasive, high-resolution, and longitudinal visualization of cerebral vasculature inside the intact mouse brain. This technique uses converging near-infrared (NIR) lines scanned at multiple angles for tight optical excitation; a low-frequency, full-ring ultrasound transducer array for high-sensitivity detection; and a compound reconstruction algorithm integrating filtered back-projection and optical localization of photoacoustic signals to recover the image. We perform long-term (>5 months), noninvasive imaging of the entire cortex of mice through the intact scalp and skull with a field of view of 13 millimeters and a spatial resolution of 33 micrometers. The results demonstrate the potential of PACMes for investigating brain function and disease.
GPT-4o mini: Non-social science research article
Self-modifying percolation governs detachment in soft suction wet adhesion
Abdallah Aly, M. Taher A. Saif
Full text
Aquatic animals such as octopuses use soft suction cups to solve the persistent challenge of wet attachment on rough surfaces. Detachment has long been described as smooth drainage governed by a Reynolds-type pressure gradient. Combining spatiotemporal pressure mapping with confocal imaging of the fluid layer between a suction cup-substrate interface, we reveal a two-stage, nonequilibrium pathway for pressure equalization that challenges this conventional view. Suction-induced elastic deformation dynamically remodels the interfacial fluid, producing a self-coupled pressure channel system. Stage I is governed by an outward-moving invasion-percolation suction front with diffusion-like scaling. When internal suction falls below a critical value, the network opens globally, and stage II follows classical Poiseuille drainage. This mechanism defines a self-modifying percolation in which the flow remodels its own pathways, which advances our understanding of biological suction and viscous adhesion and suggests design principles for long-lived wet adhesives and hydrogel microfluidics.
GPT-4o mini: Non-social science research article
Observation of super-ballistic Brownian motion in liquid
Jason Boynewicz, Michael C. Thumann, Mark G. Raizen
Full text
Brownian motion is a foundational physical process characterized by a mean squared displacement that scales linearly in time in thermal equilibrium, known as diffusion. At short times, the mean squared displacement becomes ballistic, scaling as t 2 . This effect was predicted by Einstein in 1907 and recently observed experimentally. We report that this picture is only true on average; by conditioning specific initial velocities, we predict theoretically and confirm by experiment that the mean squared displacement becomes super-ballistic, with a power scaling law of t 5 / 2 . This result is due to the colored noise of incompressible fluids, resulting in a nonzero first moment for the thermal force when conditioned on nonzero initial velocities. These results are a step toward the unraveling of nonequilibrium dynamics of fluids.
GPT-4o mini: Non-social science research article
Single-molecule localization microscopy reveals the molecular organization of endogenous membrane receptors
Patrick Eiring, Maximilian J. Steinhardt, Nele Bauer, Cornelia Vogt, Umair Munawar, Seungbin Han, Thomas Nerreter, Hermann Einsele, K. Martin KortĂŒm, Sören Doose, Markus Sauer
Full text
Super-resolution microscopy in combination with genetic labeling methods allows imaging of single proteins in cells. However, visualizing endogenous proteins on primary cells remains challenging due to the use of sterically demanding antibodies for labeling. Here, we demonstrate how immunolabeling conditions and antibody cross-linking influence the quantification and identification of membrane receptor stoichiometry on cells using single-molecule localization microscopy. We developed an optimized immunolabeling and analysis protocol and demonstrate the performance of the approach by resolving the molecular organization of endogenous CD45, CD69, and CD38 on Jurkat T cells. To demonstrate the usefulness of the method for immunotherapy applications, we investigated the interaction of primary multiple myeloma cells with the therapeutic monoclonal antibodies daratumumab and isatuximab and a polyclonal anti-CD38 antibody. Our approach might lay the foundation for improved personalized diagnostics and treatment with therapeutic antibodies.
GPT-4o mini: Non-social science research article
Volcanism-induced collapse and recovery of the Atlantic meridional overturning circulation under glacial conditions
Guido Vettoretti, Ruei-Jia Hu, Ingo Bethke, Kirstin KrĂŒger, Michael Sigl, Stephen Outten, Jaimei Lin, Roman Nuterman, Anders Svensson, Peter Ditlevsen, Markus Jochum
Full text
Volcanic eruptions have considerable impacts on climate across various timescales; however, it remains uncertain if, and how, volcanic activity could drive climate change over multiple millennia. Here we incorporate realistic volcanic forcing into a large ensemble of glacial era–coupled atmosphere-ocean model simulations. These simulations are constrained by sulfate records from ice cores, which help estimate the timing of past major eruptions. We investigate how volcanic eruptions may have occasionally triggered abrupt climate change during the last glacial period. Our results show that very large equatorial eruptions can induce large changes in the Atlantic Meridional Overturning Circulation via atmospheric and ocean circulation changes and air-sea buoyancy fluxes, potentially pushing the climate system between persistent warm and cold states lasting millennia. A simplified perspective of the dynamics shows how unforced natural climate variability may exert a stabilizing influence decades after an eruption, especially as the system nears a tipping point.
GPT-4o mini: Non-social science research article
Nanocollision promotes locomotion of dendritic cells for tumor therapy
Qiangyuan Zhu, Shenglan Liu, Lei Chen, Xin Wang, Jiayi Liu, Cen Gao, Rongbing Tang
Full text
Mechanical stimuli originating from extracellular matrix have been proved to affect antitumor immunity by regulating dendritic cell (DC) locomotion. However, the immunological consequences of ultrasmall bioparticle–induced nanocollision remain largely an unexplored realm despite its ubiquitous and incessant occurrence within the in vivo milieu. Herein, we disclose that nanocollisions caused by endogenous bioparticles, such as extracellular vesicles, can induce localized membrane deformations. This spatially confined mechanical input activates Piezo1 at collision sites and promotes myosin IIA phosphorylation–mediated F-actin stabilization, enhancing DC intrinsic motility. Subsequent diffusion of Ca 2+ up-regulates chemotaxis machinery, improving their capacity of tumor microenvironment patrolling and lymph node homing for antitumor immunity. This finding reveals a previously unidentified mechanoimmunological mechanism of immune surveillance. To accelerate the translation of this mechanism into clinical therapeutics, we developed an ultrasound-responsive nanocollision generator using gas-liquid-solid triphase conversion. This system achieves precise nanocollision to augment DC locomotion, promoting antitumor immunity in vivo.
GPT-4o mini: Non-social science research article
Discovery and preclinical evaluation of monoclonal antibodies and bispecific engagers targeting the NKG2A inhibitory receptor
Seungmin Shin, Yae-Jin Kim, Bernard J. C. Macatangay, Joshua C. Cyktor, Margaret G. Hines, Ze-Yu Sun, Kong Chen, John W. Mellors, Dimiter S. Dimitrov, Wei Li, Du-San Baek
Full text
NK and T cells are key effectors that eliminate cancer cells, but upregulation of the inhibitory receptor NKG2A on these cells attenuates antitumor immune responses. To counteract NKG2A inhibitory signaling, we identified two specific fully human monoclonal anti-NKG2A antibodies that block HLA-E ligand binding. These antibodies activated NK cells and enhanced antibody-dependent cellular cytotoxicity of tumor-targeting IgG1s both in vitro and in vivo. Bispecific engagers (BiNKs), generated by fusing NKG2A antibodies with tumor targeting binders, promoted immune synapse formation and directed cytotoxicity of NK and CD8 + T cells toward cancer cells. In a human PBMC-engrafted NSG mouse xenograft lung cancer model, an anti-HER2 × anti-NKG2A BiNK markedly inhibited tumor growth as a monotherapy or in combination with pertuzumab. Cell depletion studies revealed that the BiNK enhanced antitumor activity of both NK and T cells. NKG2A blockade with potent and specific, fully human antibodies and BiNKs show promise for further development as cancer immunotherapeutics.
GPT-4o mini: Non-social science research article
Wildfire smoke PM 2.5 and mortality rate in the contiguous United States: A causal modeling study
Min Zhang, Edgar Castro, Alexandra Shtein, Adjani A. Peralta, Mahdieh Danesh Yazdi, Xiao Wu, Joel D. Schwartz, Robert O. Wright, Yaguang Wei
Full text
The relationships between chronic exposure to wildfire smoke PM 2.5 (particulate matter with aerodynamic diameter of ≀2.5 ÎŒm) and mortality remain poorly understood, with causal evidence being particularly scarce. In this ecological study, we used a doubly robust method, incorporating flexible generalized propensity score estimation that captured potential nonlinearity and interactions among confounders and relaxed the distribution form assumption for exposure, to estimate the effects of annual exposure to wildfire smoke PM 2.5 on all-cause and cause-specific mortality in the contiguous United States from 2006 to 2020. We found that wildfire smoke PM 2.5 was associated with increased mortality rate for all studied outcomes, except for deaths from transport accidents or falls, which served as negative outcome controls. Wildfire smoke PM 2.5 was responsible for ~24,100 all-cause deaths per year in the contiguous United States. The exposure-response curve for all-cause mortality increased monotonically, with no evidence of a “safe” threshold. Among the six cause-specific outcomes, mortality from neurological disease showed the greatest increase per 0.1 ÎŒg/m 3 increase in smoke PM 2.5 exposure. Our study provided robust evidence for the chronic effect of wildfire smoke PM 2.5 on mortality, underscoring the urgent need for targeted measures to mitigate the substantial and escalating burden of wildfires.
GPT-4o mini: Non-social science research article
Injury-induced electrochemical coupling triggers organ growth
Jinghui Liu, Elisa Nerli, Charlie Duclut, Amit S. Vishen, Naomi Berbee, Sylvia Kaufmann, Cesar Ponce, Aristides B. Arrenberg, Frank JĂŒlicher, Rita Mateus
Full text
Organ injury triggers nonneuronal electric currents essential for regeneration. However, the mechanisms by which electrical signals are generated, sensed, and transmitted upon damage to promote organ growth remain unclear. Here, we uncover that organ repair relies on dynamic electrochemical coupling between membrane potential depolarization and intracellular signaling, essential to activate cell proliferation. By subsecond live imaging of locally injured zebrafish larval fins, we identify events across time and space: a millisecond, long-range, membrane depolarization gradient, followed by second-persistent intracellular calcium responses. In the subsequent hour, voltage sensing phosphatase senses the injury-driven membrane potential change and autonomously translates the electric signal intracellularly, promoting tissue-wide cell proliferation. Connecting these dynamics with an electrodiffusive model showed that ionic fluxes and electric potential become coupled in the fin’s interstitial space, enabling organ-wide signal spreading. Our work reveals the coupling between fast electrical signals and slower intracellular signaling, ensuring complete organ recovery.
GPT-4o mini: Non-social science research article
Day-to-day fluctuations in cognitive precision predict the domain-general intention-behavior gap
Daniel J. Wilson, Cendri A. Hutcherson
Full text
The idea that better cognitive functioning helps to close the gap between goals and behavior seems self-evident, yet empirical work has found unusually weak interindividual associations between cognitive task performance and real-world, goal-relevant outcomes. Here, we resolve this paradox by shifting from trait-level to state-level analysis. Leveraging a microtask design to measure daily fluctuations in cognitive function, goal setting and goal progress, mood, sleep, and motivation over a 12-week intensive longitudinal study of university students ( N  = 184, time points = 9248), we show that within-person upswings in domain-general cognitive processing precision precede and predict same-day self-reported goal setting and achievement across both academic and nonacademic domains, even controlling for other factors. A one-standard-deviation change in cognitive precision had an effect statistically equivalent to ~40 min of work, with similar or larger predictive effects compared to fluctuations in mood/motivation and no moderation by trait-level self-control or conscientiousness. Our work addresses long-standing controversies and highlights the power of intraindividual analysis to reveal relationships missed by cross-sectional approaches.
GPT-4o mini: Non-social science research article
In vivo functional profiling and structural characterization of the human GLP1R A316T variant
Liliane El Eid, Yusman Manchanda, Gregory Austin, Kieran Deane-Alder, Roxana-Maria Rujan, Zamara Mariam, Affiong I. Oqua, Matthew J. Belousoff, Jorge Bernardino de la Serna, Kyle W. Sloop, Guy A. Rutter, Alex Montoya, Dominic J. Withers, Steven J. Millership, Karim Bouzakri, Ben Jones, Christopher A. Reynolds, Patrick M. Sexton, Denise Wootten, Giuseppe Deganutti, Alejandra Tomas
Full text
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective therapies for type 2 diabetes (T2D) and obesity, yet patient responses are variable, with GLP1R gene variation potentially linked to therapeutic outcomes. A GLP1R natural missense variant, A316T, protects against T2D and cardiovascular disease. Here, we generated and characterized a human GLP1R A316T mouse model. Human GLP1R A316T/A316T mice displayed lower fasting blood glucose versus wild-type littermates even under metabolic stress, as well as slower weight gain and alterations in islet cytoarchitecture, glucagon secretion, and liver metabolism under a high-fat, high-sucrose diet. This was however associated with blunted responses to pharmacological GLP-1RAs in vivo. Further investigations in ÎČ cell models demonstrated that human GLP1R A316T exhibits characteristics of constitutive activation but dampened GLP-1RA responses. Results are further supported by cryo-EM analyses and molecular dynamics simulations of GLP-1R A316T structure, collectively demonstrating that the A316T variant governs basal GLP-1R activity and pharmacological responses to GLP-1R–targeting therapies.
GPT-4o mini: Non-social science research article
High-efficiency methane consumption by atmospheric methanotrophs in subsurface karst caves: The irrefutable methane sink
Xiaoyan Liu, Xiaoyu Cheng, Yiming Zhang, Rui Zhao, Weiqi Wang, Yang Li, Zhong-Qiang Chen, Xincheng Qiu, Olli H. Tuovinen, Ian D. Bull, Richard P. Evershed, Hongmei Wang
Full text
Subsurface karst systems represent substantial but underexplored methane sinks, yet the identities and activities of cave-dwelling methanotrophs remain poorly characterized. We detected increased methane oxidation rates from 2.9 ± 0.1 to 90.7 ± 4.5 ng·g −1 ·hour −1 while supplied with 2 to 500 parts per million (ppm) CH 4 to cave sediments. Atmospheric methanotroph Upland Soil Clusters Îł (USCÎł), responsible for this oxidation, was further assigned to three genera within the family Candidatus ( Ca .) Methyloligotrophaceae, including two previously unrecognized genera. Nano-scale secondary ion mass spectrometry (NanoSIMS) imaging and the produced 13 C-PLFAs (phospholipid fatty acids) and 13 CO 2 in 13 CH 4 -fed microcosm confirmed methane as both carbon and energy sources. These methanotrophs exhibited low half-saturation constant ( K m ; 138.8 ± 15.8 ppm), high carbon assimilation efficiency (>50%), and metabolic versatility, as revealed by metagenomics and metatranscriptomics analyses. By extrapolating global distribution of Ca. Methyloligotrophaceae and comparing methane oxidation rates between caves and soil ecosystems, we conservatively estimate that subsurface karst in southwest China sequester ~0.56 Tg CH 4 annually. These findings highlight the ecological importance of karst ecosystems as a previously overlooked methane sink.
GPT-4o mini: Non-social science research article
Stress ensemble in the BNST mediates comorbid anxiety and sleep disruption
Haiyan Sun, Zhentong Qiu, Xin Liu, Yan Li, Xu Zhao, Yanqin Zhou, Qingchen Guo, Kunwei Wu, Jun Ma, Junping Chen, Jun-Li Cao, Shuming An
Full text
Anxiety and insomnia are highly comorbid; however, the underlying brain-circuit mechanisms remain inadequately explored. Here, we identify a dual-functional ensemble within the bed nucleus of the stria terminalis (BNST) that modulates both anxiety-like behaviors and insomnia through distinct neural circuits. Specifically, a subset of BNST neurons exhibits enhanced activity in response to anxiety-related cues and during wakefulness. Activation of these ensemble neurons exacerbates anxiety-like behaviors and reduces non–rapid eye movement (NREM) sleep in chronic restraint stress (CRS) mice. Conversely, inactivation of these neurons alleviates anxiety-like behaviors and promotes NREM sleep. In addition, anxiolytic-hypnotic medication attenuates BNST stress ensemble hyperactivity, mitigating both phenotypes. Furthermore, BNST stress ensembles project divergently to the dorsal raphe nucleus (DRN) and the preoptic area (POA): DRN-projecting neurons selectively modulated anxiety, whereas POA-projecting neurons specifically regulated sleep-wake states. These findings suggest that hyperactive BNST stress ensembles are responsible for inducing anxiety-like behaviors and disrupting sleep in CRS mice and achieve the modality specificity through their divergent downstream targets.
GPT-4o mini: Non-social science research article
Photoinduced femtosecond spin-flip assisted by a single-mode linear phonon
Na Wu, En Wang, Daqiang Chen, Chao Lian, Yaxian Wang, Sheng Meng
Full text
Optical manipulation of spin-flip on a picosecond to femtosecond timescale has long been pursued to innovate next-generation electronic devices. However, understanding the ultrafast spin-electron-lattice coupled dynamics remains challenging, especially when the system is driven far from equilibrium. Here, we demonstrate an ultrafast light-induced spin-flip within 300 fs in Fe 3 GeTe 2 , a prototypical two-dimensional itinerant ferromagnet. Notably, by varying the laser fluence, we identify three distinct regimes that emerge assisted by a photoinduced single linear phonon mode, namely demagnetization, spin-flip, and spin-melting. We resolve the dominant role of displacively excited A 1g phonons, while nonequilibrium electron occupation is essential to break the degeneracy of the spin up and down states and lower the spin-flip energy barrier. Accompanying the spin-flip, we also observe a sign change of the Berry curvature, implying involvement of nontrivial band topology. Our results provide a general guidance for optical manipulation of spin orders, holding promises for advancing future spintronics and information technology.
GPT-4o mini: Non-social science research article
Lunar chronology model with the Chang’e-6 farside samples and implications for the early impact history
Zongyu Yue, Sheng Gou, Yexin Wang, Huacheng Li, Gregory Michael, Jianzhong Liu, Shujuan Sun, Yangting Lin, Kaichang Di, Qiuli Li, Yi Chen, Wei Yang, Bin Xie, Sen Hu, Shouding Li, Bo Zheng, Tianqiao Mao, Xianhua Li, Fuyuan Wu
Full text
The radiometric ages of the returned samples are the cornerstone of lunar cratering chronology models. However, all the previous samples were from the lunar nearside and the radiometric ages of those samples that can be associated with particular surfaces are <4.0 billion years. On 25 June 2024, Chang’e-6 successfully returned 1.935-kilogram samples from the lunar farside. The samples included local basalts with an age of 2807 ± 3 million years and the norites with an age of 4247 ± 5 million years likely corresponding to the age of the South Pole–Aitken basin. With these radiometric ages, we refined the lunar chronology function (CF) and verified that it is still consistent with a combination of an exponential decrease and a linear rate. We further derived the impacting rate and found it supports a smooth decay instead of abrupt changes of the impactor flux at early times. The refined lunar CF can be used to obtain more reliable ages for unsampled lunar areas and provide critical constraint for the lunar early impact history.
The emergence of cooperative behaviors, norms, and strategies across five diverse societies
Dorsa Amir, Richard E. Ahl, Matthew R. Jordan, Hannah Bolotin, Michael Bogese, Gorana T. GonzĂĄlez, Tara Callaghan, Lawrence S. Sugiyama, Emily Otali, Patrick Tusiime, Samantha Bangayan, J. Josh Snodgrass, Katherine McAuliffe
Full text
Human cooperation involves a set of interconnected behaviors that develop in conjunction with the cultural environment. Despite recent advances in Western, industrialized contexts, we know far less about how cooperative behaviors emerge across cultures, how normative environments shape their development, and how these behaviors relate to one another. Here, we examined the development of four cooperative behaviors—fairness, trustworthiness, forgiveness, and honesty—in children ( N  = 413) aged 5 to 13 from five societies: urban United States, rural Uganda, Canada, Peru, and the hunter-horticulturalist Shuar of Ecuador. We also collected normative judgments from peers ( N  = 163) and adults ( N  = 86) of each community. We find substantial variation in cooperative behaviors and norms across populations, but, more generally, that children’s behaviors and norms tend to converge toward community-specific norms in middle childhood. We also identify three cooperative strategies—maximization, generic cooperation, and partner-contingent cooperation—whose prevalence shifts with age and differs across societies. Together, these findings illuminate how cooperative behavior develops within and across cultures.
School discipline disparities increase when neighborhood Black population changes
Jennifer Candipan, Chantal A. Hailey
Full text
The racial landscape of US neighborhoods shifted tremendously over the past decade, raising questions about how these changes are reflected in local schools. This study combines school zone shapefiles with census and Civil Rights Database data to explore whether neighborhood racial change in Black populations predicts changes in Black-white school suspension disparities from 2010 to 2018. We find that racial disparities in suspensions increased, particularly in neighborhoods experiencing substantial shifts in Black populations. These increases were especially pronounced in suburban and rural areas with shifting Black populations and all predominantly White neighborhoods. Although school discipline reforms aimed to reduce racial disparities, they only declined in certain types of neighborhoods, most notably in urban areas. Our findings advance insights into processes of school and neighborhood change, school discipline, and racial stratification, with broad policy implications.