I checked 6 multidisciplinary journals on Wednesday, August 26, 2026 using the Crossref API. For the period August 19 to August 25, I found 10 new paper(s) in 5 journal(s).

Nature

GPT-4o mini: Non-social science research article
Synthesis of pyrroles from isoxazoles by an O-to-C skeletal edit
Abigail J. Bracken, Alexandra P. Lawrie, Isabella F. Romita, Mark D. Levin
Full text
Isoxazoles and pyrroles feature prominently in pharmaceutical and bioactive compounds of interest1,2. Although their core structures differ by only a single atom (O versus C), their respective de novo ring assemblies require vastly different syntheses, as the electronically consonant isoxazole core is amenable to a range of disconnections that are inaccessible for the corresponding pyrroles3,4. Given the structural similarity between these two heterocyclic classes, skeletal editing offers an opportunity to meet this need, as it empowers non-traditional retrosynthetic disconnections5. Here we achieve an O-to-C atom replacement of isoxazoles, affording pyrroles in a one-pot sequence. We identify the N-propargylic enaminone as a key intermediate connecting the two heterocycle classes, providing a retrosynthetic disconnection orthogonal to traditional syntheses for otherwise challenging pyrrole scaffolds6. During our investigations, we encountered unexpected enaminone reactivity and developed a predictive computational model capturing the conformational features controlling reaction outcomes7. Regioselective syntheses of elusive pyrroles can be achieved by linking these two heterocycles with an O-to-C replacement reaction.
GPT-4o mini: Non-social science research article
Discovery of a star sensitive to the spin of Sagittarius A*
K. Abd El Dayem, R. Abuter, N. Aimar, P. Amaro-Seoane, A. Berdeu, J.-P. Berger, G. Bourdarot, W. Brandner, A. Burkert, D. Caldéron, C. Correia, J. Cuadra, R. Davies, D. DefrÚre, L. Delit, A. Drescher, F. Eisenhauer, L. Esteras Otal, M. Fabricius, H. Feuchtgruber, S. Flesch, N. M. Förster Schreiber, A. Foschi, Q. Fournier, P. Garcia, R. Garcia Lopez, A. Generozov, R. Genzel, S. Gillessen, F. Gonté, X. Haubois, S. F. Hönig, M. Houllé, S. Joharle, A. Kaufer, J. Kammerer, P. Kervella, J. Kolb, L. Kreidberg, L. Labadie, S. Lacour, O. Lai, R. Laugier, J.-B. Le Bouquin, J. Leftley, R. Li, B. Lopez, D. Lutz, F. Mang, A. Mérand, F. Millour, M. MontargÚs, N. Morujão, H. Nowacki, M. Nowak, S. Oberti, J. Osorno, T. Ott, T. Paumard, C. Paladini, S. Pappert, H. B. Perets, K. Perraut, G. Perrin, R. Petrov, P. O. Petrucci, T. Piran, N. Pourré, S. Rabien, D. C. Ribeiro, S. Robbe-Dubois, M. Sadun Bordoni, J. Sanchez-Bermudez, D. Santos, R. Sari, J. Sauter, S. Scheithauer, J. Scigliuto, J. Shangguan, T. T. Shimizu, F. Soulez, J. Stadler, C. Straubmeier, E. Sturm, M. Subroweit, C. Sykes, L. J. Tacconi, P. Thévenet, I. Urso, F. Vincent, J. Woillez, G. Zins, NA, J.-B. Le Bouquin
Full text
Residing in the centre of the Milky Way, Sagittarius A* (Sgr A*) is the closest massive black hole 1 (MBH). Its vicinity has allowed measuring individual stellar orbits around it 2–4 . The stars act as test particles and probe the gravitational potential around the 4.3 × 10 6 M ⊙ MBH. These observations have determined the central mass to sub-per-cent precision 5 , and the mildly relativistic motions of stars have given access to the dominant relativistic corrections, the gravitational redshift 6,7 , the transverse Doppler effect and the prograde precession imposed by the Schwarzschild metric nature of the potential 8 . These effects are of order ÎČ 2  = ( v / c ) 2 (for velocity v and speed of light c ). The Kerr metric for a rotating black hole leads to corrections of order ÎČ 3 . Here, we report the discovery of a faint main-sequence star ( m K  = 19.3), S301, on an 8.7-year orbit and with small enough a pericentre distance, such that the peak velocity of the star reaches 25,000 km s −1 . Within the measurement abilities of current near-infrared interferometry and future spectroscopy on an extremely large telescope, the motion of S301 is directly sensitive to the spin of Sgr A*. The high eccentricity of S301 suggests that it is the captured component of a binary that was torn apart by the Hills mechanism.
GPT-4o mini: Non-social science research article
Wake-activated neuronal populations that regulate sleep drive
William Joo, Clare Diester, Vassilis Bitsikas, Myrto Panopoulou, Amelia Hidalgo, Konstantinos Ntemos, Rodrigo C. G. Pena, Fabia Imhof, Iris Odstrcil, Flavio Donato, Geoffrey Fucile, Daniel Kroeger, Thomas E. Scammell, Alexander F. Schier
Full text
Prolonged wakefulness increases sleep drive and is normally compensated for by increased sleep 1–3 . This homeostatic regulation of sleep shapes our lives profoundly, but the underlying neural circuit mechanisms remain poorly understood. Here, we identify wake-activated neurons that regulate sleep drive in mice, using whole-brain activity mapping, targeted neuronal manipulations and electrophysiology. By comparing whole-brain responses to sleep deprivation, recovery sleep and circadian behaviour, we identify the anterior medial preoptic area and the median raphe as candidate regions that encode sleep deficit. Activating sleep-deprivation-responsive cells in these regions induces increases in sleep duration and intensity that resemble recovery sleep. Conversely, inhibiting deprivation-responsive cells reduces sleep and abolishes the increased sleep propensity usually observed during deprivation. Neurons in the median raphe that are responsive to sleep deprivation project to subcortical sleep-associated regions and act through the preoptic hypothalamus. These deprivation-sensitive cells include serotonergic neurons and a distinct population of GABAergic neurons, whose intrinsic excitability increases during sleep deprivation. Co-activation of GABAergic and serotonergic neurons synergistically promotes sleep, whereas co-inhibition chronically decreases sleep by nearly 70%. Remarkably, most mice survive despite this marked reduction in sleep, without the compensatory increases in sleep drive or the behavioural deficits typically associated with severe sleep deprivation. Together, these results define neuronal populations that are activated during wakefulness and are crucial for sleep drive.
GPT-4o mini: Non-social science research article
Psychedelics align brain activity with context
Devon Stoliker, Leonardo Novelli, Moein Khajehnejad, Mana Biabani, Matthew D. Greaves, Tamrin Barta, Martin Williams, Sidhant Chopra, Olivier Bazin, Otto Simonsson, Richard Chambers, Frederick S. Barrett, Gustavo Deco, Katrin H. Preller, Robin L. Carhart-Harris, Anil K. Seth, Suresh Sundram, Gary F. Egan, Adeel Razi
Full text
Psychedelics can profoundly alter consciousness by reorganizing brain connectivity 1,2 , producing acute experiences that shape lasting psychological change 3,4 . Psychedelic dynamics are commonly described as desynchronized or entropically disordered 5,6 , yet the brain organization underlying self-dissolving and boundary-dissolving experiences that participants often report 7 , and how context shapes that organization 8 , remain unresolved. To address this, we acquired the largest single-site psychedelic neuroimaging dataset to date. Sixty-two adults underwent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) during rest and naturalistic stimuli (meditation, music and movie), before and on the day of psilocybin administration (fMRI ~ 80 min post-dose; EEG ~ 150 min post-dose). Half ranked the experience among the most meaningful of their lives 7 . Here, using machine learning to represent the brain dynamics of each individual as low-dimensional trajectories, we show that psilocybin reorganizes brain activity into structured, context-sensitive patterns that co-vary with the quality of subjective experience, revealing a latent order missed by time-averaged measures. Networks that ordinarily segregate internal and external processing integrated, producing cohesive context-aligned trajectories in participants reporting the felt experience of being continuous with, rather than separate from, the environment, a state we refer to as embeddedness. The strength of this context alignment scaled with both the depth of self-dissolving and boundary-dissolving experience and the next-day mindset change. Our findings recast apparent disorder as latent organization aligned with context, linking neurobiology to subjective experience and behavioural change.
GPT-4o mini: Non-social science research article
Addendum: Sea level much higher than assumed in most coastal hazard assessments
Katharina Seeger, Philip S. J. Minderhoud
Full text
GPT-4o mini: Non-social science research article
A global atmospheric methane record from a tropical ice core
Kara A. Lamantia, Lonnie G. Thompson, Mary E. Davis, Ben Riddell-Young, Ivo Strawson, Emilie Beaudon, Ellen Mosley-Thompson, Newton Nguyen, Edward J. Brook
Full text
Tropical wetlands are widely considered the largest natural source of atmospheric methane (CH 4 ) 1–4 . However, uncertainties about wetland extent and CH 4 production have led to large variations in modelled CH 4 emission trends 2,3 . Most historical reconstructions rely on data from polar ice cores, which cannot fully resolve the tropical contribution 5,6 to the CH 4 budget. Here we present a 2,000-year record of atmospheric CH 4 concentrations from ice cores drilled from the South Peak summit of Nevado Huascarán (Summit Core A, SCA; −9.122° S, −77.605° W; 6,768 m asl). We find that the trends and magnitudes of our CH 4 record are broadly consistent with polar records 7 . Our ή 13 C-CH 4 measurements (from approximately 1530 CE to 1999 CE) align with isotope values 8 consistent with a dominant tropical CH 4 source. Integration of our record into an atmospheric four-box model suggests a sustained equatorial dominance of CH 4 source strength over the past two millennia. Our findings indicate that equatorial CH 4 emissions are higher than previous estimates based only on polar ice core data, supporting the long-standing hypothesis that low-latitude CH 4 emissions dominated pre-industrial (PI) CH 4 variability 5,6 . These results demonstrate the importance of tropical ice cores on the reconstruction of CH 4 variability and latitudinal distribution.
GPT-4o mini: Non-social science research article
An Icelandic pangenome reference
Guillaume Holley, Hannes P. Eggertsson, Snaedis Kristmundsdottir, Doruk Beyter, Astros Th Skuladottir, Kristjan H. S. Moore, Pall I. Olason, Arnaldur Gylfason, Olafur T. Magnusson, Asmundur Oddsson, Hreinn Stefansson, Agnar Helgason, Gisli Masson, Patrick Sulem, Daniel F. Gudbjartsson, Kari Stefansson, Bjarni V. Halldorsson
Full text
Reference bias is an issue that affects most genomic studies analysing short reads mapped to a reference genome 1,2 . It can be mitigated by mapping to multiple haplotypes represented in a pangenome 3–5 . Here we introduce two new methods to address reference bias: Emblask for pangenome construction and Weaver for mapping to pangenomes at scale. Emblask is a hybrid long- and short-read haplotype-resolved dual assembly pipeline for parent–offspring trio data. Using Emblask, we assembled 698 Icelandic haplotypes and added them to the Human Pangenome Reference Consortium (HPRC) pangenome 4 to construct an Icelandic pangenome reference (HPRC-ICE) including 51.41 million small variants. We mapped the short reads of 57,630 Icelanders to HPRC-ICE with Weaver and called 98.96 million variants, representing a 6.17% increase over mapping to a linear reference. We uncovered new variants in low-mappability regions, including a pathogenic single nucleotide polymorphism (SNP) in GBA1 that associates with early onset Parkinson’s disease and a missense SNP in CBS that is pathogenic for homocystinuria. We replicated the GBA1 association in the UK Biobank 6 with a targeted remapping of 429,193 British and Irish participants.
GPT-4o mini: Non-social science research article
Increasing CO2 levels fertilize C4 grass production
Kimberley J. Simpson, A. Carla Staver, James A. King, William J. Bond, Corli Coetsee, Nita C. M. Pallett, Adam F. A. Pellegrini, Sarah L. Raubenheimer, Brad S. Ripley, Maria Val Martin, Colin P. Osborne
Full text
Rising atmospheric CO 2 concentrations are impacting the global terrestrial biosphere through indirect climate effects and direct effects on plant performance 1–3 . In tropical forests, long-term monitoring indicates a substantial CO 2 -driven carbon sink 4 . C 4 -grass-dominated tropical and subtropical savannas contribute approximately 30% of terrestrial net primary production 5 , and yet equivalent long-term analyses of CO 2 responses are lacking. Here we show a clear and consistent result across a meta-analysis of 70 CO 2 -addition experiments and 32 years of in situ field observations from southern Africa: CO 2 fertilization of wild C 4 grasses is widespread in dry conditions. In experiments, grasses reduced stomatal conductance under higher levels of CO 2 , limiting water loss while increasing carbon gain. In the field, improved water use efficiency translated into increased C 4 grass biomass production across three decades of observations. Finally, simulations via the Community Land Model 6 suggest that CO 2 fertilization of C 4 grass aboveground productivity may continue to increase under future conditions. Together, these results challenge the view that C 4 grasses are unresponsive to increasing levels of CO 2 , demonstrating instead that annual aboveground production of grasses in the field in southern Africa has increased by 28% over three decades (a CO 2 -driven increase of 75.1 g m −2 (95% confidence interval of 74.5–75.8 g m −2 ) or 0.37 tons C ha −1 of annual production). Although the fate of this carbon is uncertain (depending on feedbacks with fire, herbivory and woody vegetation), effects on the global carbon cycle may be profound.
GPT-4o mini: Non-social science research article
The HydroGym reinforcement learning platform for fluid dynamics
Christian Lagemann, Sajeda Mokbel, Miro Gondrum, Mario RĂŒttgers, Yuning Wang, Pol SuĂĄrez, Ludger Paehler, Deniz A. Bezgin, Aaron B. Buhendwa, Jared L. Callaham, Samuel Ahnert, Nicholas Zolman, Xiao Shao, Jean-Christophe Loiseau, Nikolaus A. Adams, Matthias Meinke, Wolfgang Schröder, Kai Lagemann, Esther Lagemann, Ricardo Vinuesa, Steven L. Brunton
Full text
Effective control of fluid flows is critical across transportation, energy and medicine, where it can increase lift, reduce drag, enhance mixing and attenuate noise1,2,3. Yet fluids are notoriously difficult to control because they involve high-dimensional, nonlinear and multiscale dynamics that resist conventional approaches4,5,6. Reinforcement learning has driven remarkable progress in fields such as protein folding and complex games, which have shared benchmarks and standardized environments7,8,9,10. Fluid dynamics has lacked such infrastructure, so each controller is typically tuned to a single geometry and operating condition, making progress difficult to accumulate, transfer and compare11,12,13. Here we introduce HydroGym, a solver-independent reinforcement learning platform providing more than 60 validated, openly available flow control environments spanning from canonical laminar flows to complex turbulent flows, with systematic progression in the Reynolds number up to Re = 4 × 105, and Mach number variations in two and three dimensions. Across these environments, agents repeatedly discover robust control principles, including boundary layer manipulation, disruption of acoustic feedback and reorganization of turbulent wakes. Critically, we demonstrate a proof of concept for zero-shot transfer, in which agents that are trained exclusively in inexpensive surrogate environments are deployed to challenging real-world scenarios such as a three-dimensional wing section. We achieve a 38% reduction in local skin friction while reducing exploration costs by four orders of magnitude compared with direct on-wing optimization. As this transfer exploits shared near-wall physics, the breadth of generalization remains open, suggesting a new pathway for research toward policy generalization across computationally prohibitive simulation environments. By offering a common, extensible foundation for reproducible research, HydroGym moves flow control from isolated case studies toward a cohesive community effort.
GPT-4o mini: Non-social science research article
Artefacts in single-cell mtDNA analyses misinform phylogenies
Caleb A. Lareau, Michael Spencer Chapman, Livius Penter, Tal Nawy, Dana Pe’er, Leif S. Ludwig
Full text
GPT-4o mini: Non-social science research article
Atomic-scale double-slit interferometry with a focused electron probe
Koudai Tabata, Takehito Seki, Toma Susi, Ryo Ishikawa, Naoya Shibata
Full text
Since Young’s original work with light1, double-slit interference experiments have been paradigmatic demonstrations of wave–particle duality2,3,4,5,6. They now underpin modern electron, neutron, atom and molecule interferometers, whose fringe visibility and phase encode quantitative information about both the wave and the diffracting object. Extending this to atomic length scales would offer direct, local access to microscopic structure and dynamics, but has remained unexplored. Here we show that double-slit interferometry can be realized at atomic scales inside a crystal. Using scanning transmission electron microscopy (STEM), we demonstrate the generation of interference fringes with a focused electron beam that is delocalized over two adjacent Si [110] atomic columns separated by 1.36 Å. At finite temperature, these two atomic ‘slits’ vibrate strongly, imprinting their motion on the fringes. The fringes persist from 300 K to 900 K, indicating that only a subset of phonon modes degrades visibility; correlated thermal vibrations between neighbouring atoms preserve coherence that independent motion would otherwise destroy. Quantitative analysis of this preserved visibility provides direct experimental access to vibrational correlations between a pair of atomic columns. These correlations map to the anisotropic stiffness of the specific atomic bond, giving access to the low-energy phonon dynamics that affect thermal transport. By recasting crystals as atomic-scale interferometers, this platform enables direct visualization of local atomic arrangements and their correlated dynamics, opening routes to examine lattice dynamics at the single-bond level.
GPT-4o mini: Non-social science research article
Family genetic designs in MoBa provide insights into health and functioning
Elizabeth C. Corfield, Alexey A. Shadrin, Oleksandr Frei, Zillur Rahman, Bayram Cevdet Akdeniz, Tahir Tekin Filiz, Aihua Lin, Isabella Badini, Laura Hegemann, Lavinia Athanasiu, Robyn E. Wootton, Chloe Austerberry, Amanda M. Hughes, Martin Tesli, Espen Hagen, Ragnhild E. Brandlistuen, Espen Moen Eilertsen, Lars T. Westlye, PÄl R. NjÞlstad, Per Magnus, Eivind Hovig, Tetyana Zayats, Helga Ask, Ted Reichborn-Kjennerud, Gibran Hemani, Neil M. Davies, Laurie J. Hannigan, Ole A. Andreassen, Alexandra Karoline Havdahl
Full text
Genome-wide association studies using large, population-based samples of unrelated individuals have discovered thousands of genetic associations with health and disease 1 . These studies can help explain genetic and environmental risks. However, increasing evidence suggests that population-based estimates, while precise, can also reflect confounding that affects their use and interpretation. This confounding can be overcome using data from genotyped family members, such as nuclear mother–father–child trios 2,3 . However, samples of genotyped families are rare 4–11 . Here we illustrate some of the advantages of familial data using the Norwegian Mother, Father and Child Cohort Study (MoBa), a population-based cohort of parents and offspring with extensive genotype data ( n ≈ 230,000) (ref. 3 ), along with broad and longitudinal phenotyping of health and functioning. We provide an overview of MoBa and describe the quality control of genotype data tailored to this extensively related sample. We then use trio data to illustrate how family-based genomic designs can identify distinct direct and indirect sources of genetic influence and structural confounding. As examples, we analyse children’s height, educational achievement, depressive symptoms and sleep duration. These demonstrations highlight MoBa as a broadly valuable resource for advancing understanding of health and functioning across the lifecourse and generations.
GPT-4o mini: Non-social science research article
Functional role of skull lymphoid structures in CNS immunosurveillance
Jang Hyun Park, Daviti Abramishvili, Gustavo GastĂŁo Davanzo, Ruben Silva, Xingxing Gu, Siling Du, Daniel D. Lee, Bernd H. Zinselmeyer, Jackson S. Turner, Gwendalyn J. Randolph, Igor Smirnov, Jonathan Kipnis
Full text
Accumulating evidence demonstrates that the central nervous system (CNS) is not disconnected from the peripheral immune system; however, precisely how the adaptive immune system surveils the CNS remains a critical question. Recent findings reveal that channels between the skull and the dura mater facilitate the exchange of cerebrospinal fluid and immune cells between the CNS and skull bone marrow of mice under both homeostatic and disease conditions 1–6 . Skull bone marrow functions as a source of immune cells for the CNS 5 , yet its role in CNS antigen-specific adaptive immune responses remains unclear. Here we identify lymphoid structures within the skull bone marrow, featuring germinal-centre-like formations and containing a distinct population of follicular-helper-like T cells that promote B cell activation and humoral immunity through CD40L, IL-21 and IFNγ signalling. Adaptive immune cells within these skull bone marrow lymphoid structures surveil and respond to CNS-derived antigens and contribute to anti-tumour immune responses in mouse brain cancer models. Together, our findings show that the skull bone marrow is a site of CNS immunosurveillance that may influence immune responses across diverse neurological diseases.
GPT-4o mini: Non-social science research article
Reply to: Artefacts in single-cell mtDNA analyses misinform phylogenies
Chen Weng, Jonathan S. Weissman, Vijay G. Sankaran
Full text
GPT-4o mini: Non-social science research article
Safety and security of large language models in healthcare
Jan Clusmann, Oscar Freyer, Max Ostermann, Dyke Ferber, Narmin Ghaffari Laleh, Lars Hilgers, Fiona R. Kolbinger, Carolin V. Schneider, Andrea Downing, Magdalena Katharina Wekenborg, Stephen Gilbert, Sebastian Foersch, Daniel Truhn, Isabella C. Wiest, Jakob Nikolas Kather
Full text
Integration of artificial intelligence methods into clinical care is proceeding rapidly, driven by advances in generative artificial intelligence, most notably large language models. Large language models trained on large amounts of text have shown potential across nearly every domain of healthcare. However, their broad applicability also comes with new responsibilities, vulnerabilities and threats. These need to be assessed and mitigated before widespread clinical adoption. Here we review the available literature on security and safety of large language models themselves as well as their integration with hospital workflows and interactions with human healthcare providers. We systematically map security hazards to development stages of clinical artificial intelligence systems (design, data, model, inference and environment), identify safety layers, from core optimization objectives, knowledge integrity and alignment, to interaction with humans and systems, and classify threats by their current clinical relevance. Finally, we provide a perspective on current mitigation techniques, illustrating respective stakeholders’ responsibilities.
GPT-4o mini: Non-social science research article
Multiyear tropical warm pool warming drives slowdown in Antarctic mass loss
Yunhe Wang, Qinghua Ding, Xiaofeng Li, Thomas J. Ballinger, Yoshihiro Nakayama, DĂĄniel TopĂĄl, Eric J. Steig
Full text
Antarctic mass loss has been a major contributor to global sea-level rise for most of the last few decades, mainly driven by West Antarctica 1 . During 2021–2023, however, a sharp increase in surface mass balance over Queen Mary Land and Wilkes Land in East Antarctica offset West Antarctic loss and slowed the rate of total ice mass loss 2,3 . Although this slowdown is consistent with the expected long-term precipitation response to global warming through poleward-shifted storm tracks and Antarctic moistening 4 , our results point to a different mechanism. Here we show that the recent ice mass gain was linked to a recurrent atmospheric teleconnection driven by sea surface temperature anomalies in the tropical warm pool, which experienced unusually persistent warming from 2021 to 2023 relative to the previous two decades. On the basis of observations and model experiments, we find that tropical warm pool warming excites a poleward-propagating Rossby-wave train that induces a high-pressure anomaly over East Antarctica, enhancing Queen Mary Land and Wilkes Land precipitation and driving the observed mass gain, with moisture primarily sourced from the mid-latitude Indian Ocean. Similar multiyear warming in the tropical warm pool recurs about once per decade in observations and historical simulations, and its influence on precipitation is distinct from the effects of global warming. Therefore, the recent Antarctic Ice Sheet mass gain is probably temporary and does not yet reflect a sustained, global-warming-driven moistening of Antarctica.
GPT-4o mini: Non-social science research article
Pervasive phosphorylation by phage T7 kinase disarms bacterial defences
Tara Bartolec, Karin Mitosch, ClĂ©ment Potel, Federico Corona, Alessio Ling Jie Yang, Nicolai Karcher, Mira Lea Burtscher, Alexandra Koumoutsi, Isabelle Becher, Lena Sarah MĂŒller, Jacob Bobonis, Manjeet Kumar, Marco Galardini, Athanasios Typas, Mikhail M. Savitski
Full text
Bacteria and bacteriophages are in a constant arms race to develop defence and anti-defence systems, respectively. Currently known phage-encoded anti-defence systems are specific to the activity of the targeted bacterial defence system. Here we identify a mechanism by which the T7 bacteriophage broadly counteracts bacterial defences using protein phosphorylation. Its kinase (T7K), which has been reported to redirect the function of a few host proteins 1–5 , is actually a hyperpromiscuous dual-specificity kinase that phosphorylates nearly all host and phage proteins during infection. The scale of phosphorylation vastly exceeds known phosphosites in Escherichia coli , has no sequence motif specificity and results in a higher proteome-wide phosphorylation density than mammalian cells with around 500 kinases. Stoichiometry analysis of phosphorylation sites revealed strong bias in T7K activity towards nucleic-acid-binding substrates mediated by its C-terminal DNA-binding domain. This highly stoichiometric phosphorylation enables the deactivation of DNA-targeting or DNA-containing bacterial defence systems. We provide mechanistic insights into how T7K weakens DNA-containing Retron-Eco9 through specific phosphorylation events, with single phosphomimetic mutations in key sites of the toxin abolishing defence. Moreover, by screening a large collection of E. coli strains, we provide evidence of broad anti-defence abilities of T7K in nature, as counteracted strains contain diverse bacterial defence systems. T7K homologues are found almost exclusively in phages, with hyperpromiscuous kinase activity probably being enabled by a divergent DFG-like motif in the catalytic centre.
GPT-4o mini: Non-social science research article
Observation of conformal field theory spectra in a quantum simulator
Xiangkai Sun, Yuan Le, Stephen Naus, Richard Bing-Shiun Tsai, Lewis R. B. Picard, Sara Murciano, Michael Knap, Jason Alicea, Manuel Endres
Full text
Conformal field theories (CFTs) feature prominently in high-energy physics1,2, statistical mechanics3 and condensed matter4,5,6. For example, CFTs govern emergent universal properties of systems tuned to quantum phase transitions4,7, including their entanglement, correlations and low-energy excitation spectra. Much of the rich structure predicted by CFTs nevertheless remains unobserved in experiment. Here we directly observe the energy excitation spectra of emergent CFTs at quantum phase transitions—recovering universal energy ratios characteristic of the underlying field theories8,9. Specifically, we develop and implement a modulation technique to resolve the finite-size spectra of a Rydberg chain, variably tuned to quantum phase transitions described by either Ising or tricritical Ising CFTs. We also use local control to distinguish parities of excitations under reflection and, in the tricritical Ising chain, to induce transitions between distinct CFT spectra associated with changing boundary conditions. By using a variant of the modulation technique, we furthermore study the dynamical structure factor of the critical system, which is closely related to the correlation of an underlying Ising conformal field. Our work not only probes the emergence of CFT features in a quantum simulator but also provides a technique for diagnosing a priori unknown universality classes in future experiments.
GPT-4o mini: Non-social science research article
Evidence for vacuum-enhanced superconductivity in NbSe2
Zheyan Wang, Gabriel Cardoso, Liu Yang, Xun Gong, Chi Zhang, Yufei Zhu, Dongbo Zhang, Nan Pan, Hongbing Cai, Yong P. Chen, Qing-Dong Jiang, Guanghui Cheng, Frank Wilczek, Changgan Zeng
Full text
Vacuum fluctuations provide an important new way to control material properties noninvasively1-6. Here, we present experimental evidence that they can enhance superconductivity. NbSe2 is a layered transition-metal dichalcogenide with well-characterized superconducting behavior, providing a clear platform to reveal this effect. We have observed an increase in the critical temperature of superconducting NbSe2 when it is embedded in a split-ring cavity resonator. Near the transition temperature, the critical current and critical field increase dramatically. Our observations are consistent with theoretical calculations showing that hybridization between electronic degrees of freedom and fluctuating cavity modes lowers the energy of the superconducting state. By providing a proof-of-principle demonstration of superconductivity enhancement via vacuum fluctuations, our work establishes a noninvasive technique for controlling the mainstay of quantum technology.
GPT-4o mini: Non-social science research article
Human brain organoids record the passage of time over multiple years
Irene Faravelli, Noelia Antón-Bolaños, Anqi Wei, Tyler Faits, Abhishek Sampath Kumar, Sophia Andreadis, Rahel Kastli, Marta Montero Crespo, Mara Steiger, Daniel Leible, Elizabeth Zhang, Bobae An, Yaron Meirovitch, Sayara Silwal, Sung Min Yang, Alexander Kovacsovics, Xian Adiconis, Helene Kretzmer, Joshua Z. Levin, Edward S. Boyden, Jeff Lichtman, Aviv Regev, Alexander Meissner, Paola Arlotta
Full text
The human brain develops and matures over an exceptionally prolonged period of time that spans nearly two decades of life. Processes that govern species-specific aspects of human postnatal brain development are difficult to study in animal models1. While human brain organoids offer a promising in vitro model, they have thus far been shown to largely mimic early stages of brain development. Here we develop human brain organoids for 5 years in culture, optimizing growth conditions to extend excitatory neuron viability beyond previous limits. Using maturation-associated modules derived from endogenous human brain, we show that brain organoids transcriptionally age with cell type specificity over years in culture. Whole-genome methylation profiling reveals that the predicted epigenomic age of organoids correlates precisely with time spent in vitro, and parallels epigenomic ageing in vivo. Notably, we show that in chimeric organoids generated by mixing neural progenitors of different ages, old progenitors rapidly produce late neuronal fates, skipping the production of earlier neuronal progeny, therefore showing that progenitors that age in organoids retain a memory of the time spent in vitro. The data indicate that human brain organoids can continue to mature and record the passage of time over many years in culture.
GPT-4o mini: Non-social science research article
A biased allosteric modulator is a molecular glue for ÎČ2AR dimerization
Jiemin Shen, Teja Nikhil Peddada, Konstantin E. Komolov, Francesco De Pascali, Alexander M. Garces, Haoqing Wang, Muhammad Ehsan, Pil Seok Chae, Michael T. Lerch, Jeffrey L. Benovic, Jun Xu, Brian K. Kobilka
Full text
Family A G-protein-coupled receptors (GPCRs) are typically described as monomers, yet growing evidence suggests that they can form dimers with distinct signalling properties1,2,3. However, the mechanisms and therapeutic potential of such dimerization remain poorly understood. Here we show that AP-7-168, an optimized derivative of a ÎČ-arrestin-biased negative allosteric modulator of the ÎČ2-adrenergic receptor (ÎČ2AR) that sustains bronchorelaxation in cell and tissue models4, functions as a molecular glue to stabilize ÎČ2AR homodimerization. Cryogenic electron microscopy structures reveal a unique binding mode in which two AP-7-168 molecules pack within a pocket formed by transmembrane helices 3, 4 and 5 of two protomers, stabilizing a dimeric conformation that selectively prevents ÎČ-arrestin coupling. In cells, AP-7-168 robustly stabilizes ÎČ2AR dimerization and drives enlarged nanocluster formation. Combined with extensive functional studies, our findings identify an allosteric mechanism by which a small molecule biases ÎČ2AR signalling through dimerization, highlighting ligand-stabilized dimerization as a strategy for GPCR modulation.
GPT-4o mini: Non-social science research article
Asymmetric prefrontal representations for leader–follower dynamics
Yuan Cheng, Yusi Chen, Myungji Kwak, Ross P. Kempner, Rudramani Singha, Jared Winslow, Runqi Liu, Umais Khan, Tessa Spangler, Alvi Khan, Talmo Pereira, Matthew Whiteway, Evan S. Schaffer, Nuttida Rungratsameetaweemana, Nan Yang, Herbert Zheng Wu
Full text
Across species, cooperative behaviour is often organized by distinct social roles such as leaders and followers1, yet the neural mechanisms that support these emergent role dynamics remain unclear. Here we introduce a mouse paradigm that captures leader–follower dynamics during cooperation. In this paradigm, stable social roles emerge through reciprocal interaction and predict learning speed. Disrupting the activity of the medial prefrontal cortex (mPFC), particularly in followers, impairs cooperation and induces complementary shifts in how animals weigh self- and partner-related cues during decision-making. Calcium imaging reveals that the mPFC represents leader–follower dynamics and computes an egocentric social value map of the partner’s position in a role-dependent manner. By integrating these empirical findings with a multi-agent inverse reinforcement learning framework, we identify latent value functions that guide cooperative decisions and are decodable from mPFC activity. These findings identify prefrontal representations of leader–follower dynamics and partner information, revealing how social roles structure asymmetric yet reciprocal influence over joint decisions.
GPT-4o mini: Non-social science research article
Dialkyl ether synthesis through heteroatom homolytic substitution
Johannes J. Großkopf, Johnny Z. Wang, Jacqueline W. Gu, Cheng Bi, Sarah N. Dishman, Xiaoshen Ma, Yu-hong Lam, David W. C. MacMillan
Full text
The modular and selective synthesis of dialkyl ethers, particularly sterically congested variants, remains a longstanding challenge in drug discovery and medicinal chemistry.1,2 Hindered alkyl ethers are especially desirable given their prevalence in bioactive natural products and favorable physicochemical properties.3 Classically, dialkyl ether synthesis relies on nucleophilic substitution strategies; however, SN2 reactions are fundamentally limited by steric congestion at the transition state, while SN1 pathways proceed through promiscuous carbocation intermediates prone to elimination, rearrangement, and loss of stereogenic information.4–6 Herein, we report a radical-based paradigm for general dialkyl ether synthesis enabled by an underutilized heteroatom homolytic substitution (het-SH2) mechanism. This mechanistic paradigm overcomes the intrinsic limitations of classical polar substitution chemistry by leveraging carbon-centered radicals generated under mild conditions that are insensitive to steric congestion in the bond-forming transition state. Utilizing a titanium-based catalytic platform in combination with visible-light photoredox catalysis, we demonstrate the efficient coupling of carboxylic acid-derived redox-active esters with alcohols across a broad range of substitution patterns, including 3°–2°, 3°–1°, 2°–2°, and 2°–1° architectures. This strategy grants access to dialkyl ether chemical space largely inaccessible through conventional approaches, including sterically demanding BCP ether bioisosteres, and enables late-stage diversification of complex pharmaceutical scaffolds. This platform is expected to serve as a broadly applicable blueprint for radical-mediated heteroatom bond formation.
Nature DOI suffix ≠ "/s...": Not a research article
These trees are making air quality in cities worse
Mohana Basu
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: ‘Too hot to sleep’ is harmful to your health
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
NIH proposes major revamp of how it scores research grant proposals
Max Kozlov
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Sleuth identifies dozens of studies that used the wrong antibody
Holly Else
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How do people live beyond 110? Abundance of cancer-killing cells might be key
Katherine Bourzac
Full text
Nature DOI suffix ≠ "/s...": Not a research article
South Africa’s scientists must register with official body or risk prison, according to draft law
Sarah Wild
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Mathematics holds the secret to ‘ladder-proof’ knitting
Vishal P. Patil
Full text
Nature DOI suffix ≠ "/s...": Not a research article
More than 18,000 questionable images found in antibody catalogues of 15 companies
Dan Garisto
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Delisted
Ximing Zhang
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Exclusive: NSF set to issue lowest number of new grants in four decades
Dan Garisto
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Why we must stop talking about artificial general intelligence — and instead build ‘pro-worker’ AI
Daron Acemoglu
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Assessing students in the AI era
Jianjun Wu, Zhimin Qiao, Li Xu, Yapei Wang
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How one researcher captured a vanished world of UK government science
Emmeline Ledgerwood
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Billion-dollar machine aims to set a fusion-energy record — and study nuclear weapons
James Dinneen
Full text
Nature DOI suffix ≠ "/s...": Not a research article
China is changing the shape of global health. The terms are still up for negotiation
Ruby Wang
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Computational ‘gym’ trains AI models to control turbulence
Clara M. Velte
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How tech-enhanced sleep could improve rest but erode privacy
Brian D. Earp, Sebastian Porsdam Mann, Effy Vayena
Full text
Nature DOI suffix ≠ "/s...": Not a research article
AI tool lets researchers ‘vibe code’ in the quantum realm
Davide Castelvecchi
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Can AI ever be conscious? The question stems from a misconception
Abeba Birhane
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: People older than 100 have more cancer-killing cells
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Frontier-technology markets are too narrow — here’s how to widen them
Luisa Corrado, Paul Kattuman
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: How ‘thunderquakes’ probe underground geology
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Human organoids that mimic brain development grown for years in lab
Rachel Fieldhouse
Full text
Nature DOI suffix ≠ "/s...": Not a research article
A guide to securing your first research fellowship: what reviewers are looking for
Stefan Howorka, Christoph Salzmann
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Twenty-two easy ways to power up your lab meetings
Hannah Docter-Loeb
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Psychedelics tune the brain to the environment
Stefan Borgwardt, Mihai Avram
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Activity of solar-driven polymer catalysts unleashed to produce a potential green fuel
Filip Podjaski
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: How 3D printers are changing lab work
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Amend copyright licences to halt AI misuse and reassert human control
Katie Seaborn, Daniel L. Gardner, Katta Spiel
Full text
Nature DOI suffix ≠ "/s...": Not a research article
AI-detection tools have made huge leaps forward — how good are they?
Miryam Naddaf, Richard Van Noorden
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Protecting education in the middle of war zones
Ali F. Meghdari
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Personalized mRNA vaccine shows promise for cancer
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Investors’ sneak peak: can this AI tool spot the science that will lead to patents?
Chris Stokel-Walker
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Moderna cancer vaccine stops melanoma returning: what’s next for personalized treatments?
Rachel Fieldhouse, Mohana Basu
Full text
Nature DOI suffix ≠ "/s...": Not a research article
The Antarctic ice sheet has gained mass — but probably not for long
Jonathan Wille
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Researcher, heal thyself: meet the scientists studying their own diseases
Josie Glausiusz
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Briefing Chat: New narcolepsy drug could unlock host of novel brain therapies
Nick Petrić Howe, Maren Hunsberger
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Staggering 90% of biomedical papers now show signs of AI help
Kaia Glickman
Full text
Nature DOI suffix ≠ "/s...": Not a research article
These rodent OnlyFans stars are helping to fund scientific research
Elliot Yates
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Patient’s own mitochondria injected into eyes in attempt to restore vision
Miryam Naddaf
Full text
Nature DOI suffix ≠ "/s...": Not a research article
The brain struggles to make new neurons in people with depression
Mariana Lenharo
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Rudolph A. Marcus obituary: theoretical chemist who explained how electrons jump between molecules
Garnet Kin-Lic Chan, Kenneth H. Marcus
Full text
Nature DOI suffix ≠ "/s...": Not a research article
A black hole's spin could finally be measured by a high-speed star
Benjamin Thompson, Nick Petrić Howe
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Screening babies’ genomes could save lives. Here’s how it would work
Uzma Rentia
Full text
Nature DOI suffix ≠ "/s...": Not a research article
The exoskeletons are coming (to a store near you)
Shamini Bundell
Full text
Nature DOI suffix ≠ "/s...": Not a research article
The future of peer review requires AI support, not AI bans
Xuegong Zhang
Full text

Nature Human Behaviour

GPT-4o mini: Non-social science research article
Large language models do not have emotions
Amit Goldenberg, James J. Gross
Full text
Refining the role of behavioural and social sciences in pandemic response post-COVID-19
Maja GraĆĄo, Karl Aquino, Stefan Baral, Nathan Berg, Cory J. Clark, Lucian Gideon Conway, Paul Dolan, Steven Grover, Kyriaki Fousiani, Claudia C. Kitz, Dario Krpan
Full text
With the acute stage of COVID-19 behind us, reflection can inform future preparedness. During the pandemic, behavioural and social sciences often studied human behaviour through the lens of alignment with public health recommendations, implicitly treating concern and compliance as desirable and rational. While understandable, this emphasis was relatively narrow. Uncertainty, uneven risk distribution and competing values could have led to heterogeneous appraisals of risk and intervention benefit, even with the evidence available at the time. We show that engaging with the possibility that people could have been heterogeneously rational can broaden understanding of behaviour during COVID-19. Our aim is not to revisit the legitimacy of the response but to encourage reflection on the role of behavioural and social sciences in knowledge generation and highlight opportunities to examine pandemic salience and risk calibration. We outline research directions to guide the field and strengthen decision-making, trust and adaptability in future crises, promoting short-term compliance and long-term trust.
The shrinking landscape of linguistic diversity in the age of large language models
Zhivar Sourati, Farzan Karimi-Malekabadi, Meltem Ozcan, Colin McDaniel, Alireza Ziabari, Jackson Trager, Ala N. Tak, Meng Chen, Fred Morstatter, Morteza Dehghani
Full text
Language is far more than a communication tool; it encodes a wealth of information about a person’s identity, psychological state and social context, providing valuable insights for diverse fields including psychology, marketing and healthcare. Across three studies spanning seven datasets in different domains and over 880,000 texts, we show that the widespread adoption of large language models (LLMs) as writing assistants is linked to declines in linguistic diversity, interfering with the societal and psychological insights language provides. While core content is retained when LLMs polish and rewrite texts, LLMs also homogenize writing styles, reducing writing-complexity variance by a statistically significant 21–50% across datasets and models (P ≀ 0.05), and amplify patterns associated with dominant characteristics while suppressing others, emphasizing conformity over individuality. These trends hold across different LLMs, prompts and contexts, with potential implications for diagnostic processes, personalization efforts, hiring assessments and cultural preservation.
Quantifying the prevalence and impact of overreaching causal claims in social science
Calvin Isch, Timothy Dörr, Neil Fasching, Grace Jennings, Duncan J. Watts
Full text
Across the social sciences, many studies use cross-sectional designs that reveal associations but are generally unable to support direct causal claims, yet authors of such articles may make or imply causal claims anyway. Here, to examine the prevalence of such ‘overreaching’ causal language, we analysed 194,631 cross-sectional articles using large language models. Over the period 1980–2024, an average of 46% of articles contained causal language in their titles or abstracts, where the annual rate has risen almost threefold since 2000 from 20% to 60%. To examine the effects of such language, we conducted a human-subjects experiment ( N = 1, 105), finding that readers frequently indicate abstracts with this phrasing provide causal evidence but that methodological labels ( ÎČ = −0.4, 95% confidence interval −0.56 to −0.19) and associational wording ( ÎČ = −0.3, 95% confidence interval −0.43 to −0.07) reduce this tendency. Experiments with five LLMs revealed that model summaries of these articles ( N = 100 each) can amplify causal overstatement, removing hedges and introducing causal claims where articles used strictly associational phrasing; however, prompting caution diminishes this pattern.
A quasi-experimental study of abortion rates following gestational age limit changes in Japan
Yuko Yanagawa, Aurelie Piedvache, Yusuke Okubo, Naho Morisaki
Full text
The relationship between of legislative changes in abortion regulations on women’s decision-making remains understudied. In 1991, Japan reduced the gestational limit for abortion from 24 to 22 weeks of pregnancy. Here, using national data on abortions, stillbirths and live births at ≄12 weeks from 1989 to 1994 (n = 7,364,783), we examined the association of the change with abortion incidence rate and cumulative incidence between 12 and 27 weeks using quasi-experimental interrupted time-series and regression discontinuity analyses. After the change, incidence rates increased at 20 weeks (incidence rate ratio (IRR) 1.28, 95% confidence interval (CI), 1.15–1.43) and 21 weeks (IRR 1.33, 95% CI, 1.18–1.50), while decreasing at 22 weeks (IRR 0.25, 95% CI, 0.21–0.30, P < 0.001) and 23 weeks (IRR 0.07, 95% CI, 0.06–0.10, P < 0.001), and no meaningful changes for ≀19 or ≄24 weeks. Cumulative incidence decreased only for women at 19–23 weeks. In conclusion, the legislative change shifted abortions to earlier gestational ages, and was associated with fewer abortions among women who had reached 19th week of pregnancy.
Trial-by-trial fluctuations in decision criterion shape confidence
Robin Vloeberghs, Lara Navarrete Orejudo, Anne E. Urai, Kobe Desender
Full text
Many decisions are accompanied by confidence. One influential view couched within signal detection theory views confidence as the distance between a decision variable and a static decision criterion. However, recent work suggests that the criterion undergoes trial-by-trial fluctuations. Here, combining theory and model simulations, we predict that fluctuations in the decision criterion shape confidence. In 15 datasets, trial-by-trial estimates of the decision criterion were obtained with the hierarchical model for fluctuations in criterion. Across datasets, we confirmed our pre-registered hypothesis that confidence is shaped by a single-trial criterion state. This effect was found in 14 out of 15 datasets, indicating a robust pattern across a variety of paradigms and confidence scales. Beyond self-reports, the effect was also observed in reaction times, pupil-linked arousal and a neural signature of confidence. Our results show that variability in confidence, often treated as noise, actually reflects genuine sensitivity to the current state of the (fluctuating) decision criterion.

Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
The TaLYK5–TaDSK2a module serves as a molecular switch between plant growth and immunity during fungal attack
Yu Wu, Dan Yang, Haibin Zhao, Qin Wu, Yue Li, Xinyuan Li, Jian Ma, Qiantao Jiang, Yazhou Zhang, Yunfeng Jiang, Pengfei Qi, Xiaojie Wang, Yuming Wei, Qiang Xu
Full text
Plants are constantly challenged by pathogenic microorganisms that threaten growth and survival. While the individual signaling pathways involved in these immune responses have been well characterized, how plants balance growth with rapid pathogen perception and immune signal transduction remains largely unclear. Here, we report that the receptor-like kinase TaLYK5 receptor of wheat ( Triticum aestivum ) recognizes chitin on the fungal pathogen Puccinia striiformis f. sp. tritici ( Pst ) and initiates a cascade of events that increase immune response while reducing growth. TaLYK5 acts as a positive regulator of defense by phosphorylating the ankyrin-repeat–containing protein TaAKR2A, which supports reactive oxygen species (ROS) production and defense responses. In parallel, activated TaLYK5 negatively regulates growth responses by phosphorylating serine residue S234 in the ubiquitin-binding protein TaDSK2a, blocking its ability to degrade TaLYK5. Without infection by Pst , TaAKR2A does not initiate ROS signaling and immune responses and TaDSK2a associates with polyubiquitin chains on TaLYK5 to mediate its degradation, suppress TaLYK5-mediated plant defense. Meanwhile, TaDSK2a regulates gibberellin (GA) accumulation to promote plant growth, possibly by accelerating the degradation of TaEUI, a GA-deactivating enzyme. These findings demonstrate that the TaLYK5–TaDSK2a module functions as a molecular switch that dynamically regulates the trade-off between plant immunity and growth.
GPT-4o mini: Non-social science research article
Tmem117, an oligodendrocyte-enriched regulator of NCX activity, links myelin homeostasis to counterregulation and metabolic health
Melvin Alappat, Marta Anna Mazurkiewicz, Iris Zambounis, Alice Mastrangelo, Vicente Mario Algaba MartĂ­nez, Thomas Grampp, Francesco Prisco, Anja Kipar, Alexandre Picard, Musadiq A. Bhat, Dietmar Benke, Hanns Ulrich Zeilhofer, Bernard Thorens, Sevasti Gaspari
Full text
The counterregulatory response (CRR) to hypoglycemia—critically depending on pancreatic glucagon secretion—is a fundamental, evolutionarily conserved homeostatic mechanism orchestrated by the central nervous system (CNS) to ensure survival during glucose scarcity. Tmem117 was previously identified in a genetic screen as a potential hypothalamic regulator of CRR. Here, we reveal that Tmem117 is enriched in cells of the oligodendrocytic lineage and we characterize the contribution of oligodendrocytic Tmem117 in CRR. We show that depletion of Tmem117 from either all oligodendrocyte lineage cells or only mature oligodendrocytes leads to myelin deficits and male-specific defects in CRR. Furthermore, we reveal that transient, adult-onset depletion of Tmem117 in mature oligodendrocytes is sufficient to induce long-lasting metabolic imbalances in male mice, suggesting that defects in oligodendrocytes and myelin can affect peripheral glucose homeostasis. Mechanistically, we provide insights on the molecular mechanism of action of Tmem117 showing that it regulates intracellular calcium dynamics through its interaction with the sodium-calcium exchanger NCX1. Together, these results redefine our understanding of the cellular contributors to the CRR, highlight the importance of oligodendrocytes in systemic glucose regulation, and position Tmem117 as a promising molecular target for cell-specific manipulation of sodium-calcium exchanger (NCX) activity.
GPT-4o mini: Non-social science research article
Loss of epitranscriptomic mitochondrial RNA surveillance drives epithelial type I interferon and inflammation in autoimmunity
Alejandro Arco-Hierves, Konstantina Pamboukas, Linda Bilonda Mutala, Lukasz S. Borowski, Celine Mayet, Paul Mazet, Sacha E. Silva-Saffar, Dory Vergallo, Anna Paszek, Marta M. Dilling, Laurie Askenatzis, Juliette Pascaud, Philippe Labrot, Charlene Lasgi, Johannes N. Spelbrink, Albertas Navickas, Thibaut Naninck, Nabila Seddiki, Arnaud Tete, Roman J. Szczesny, Gaetane Nocturne, Xavier Mariette, Rami Bechara
Full text
Chronic interferon (IFN) activation is a hallmark of autoimmune diseases such as systemic lupus erythematosus and Sjögren’s disease (SjD), where epithelial cells are key contributors. Although viral and retroelement triggers have been proposed as triggers, direct evidence in patient tissues is limited, and endogenous mechanisms of epithelial IFN dysregulation remain unclear. Mitochondrial double-stranded RNA (mt-dsRNA) is a potent type I IFN (IFN-I) inducer, but its regulation in epithelial cells is poorly understood. We identify a mechanism in which the RNA methyltransferase METTL3 stabilizes REXO2 mRNA in primary salivary gland epithelial cells through N6 -methyladenosine (m 6 A) modification. REXO2 encodes a mitochondrial exonuclease that controls mt-dsRNA. METTL3 inhibition reduces REXO2, causing mt-dsRNA accumulation and IFN-I signaling amplification and inflammation. Single-cell and bulk transcriptomic analyses, together with immunofluorescence of salivary gland tissues from SjD patients and controls, reveal reduced REXO2 expression and elevated IFN-I signatures in SjD. Rexo2 is likewise downregulated in epithelial cells of a spontaneous SjD mouse model. REXO2 loss amplifies IFN-I responses and inflammation across several epithelial contexts, while methyl donors restore REXO2 and dampen IFN activation, highlighting a targetable regulatory checkpoint in IFN-driven autoimmune diseases, alongside potential parallel stress pathways.
GPT-4o mini: Non-social science research article
Peter H. Raven: Botanist, evolutionary biologist, and biodiversity champion
Jonathan B. Losos, George B. Johnson, Barbara A. Schaal
Full text
Peter H. Raven was a transformative leader whose influence extended far beyond his own research. From a precocious childhood passion for natural history to landmark contributions to coevolution, ecological speciation, biogeography, and botanical systematics, his career reshaped modern plant science. He was also an extraordinary mentor, collaborator, and institution builder spending most of his career as Director of the Missouri Botanical Garden and professor at Washington University in Saint Louis, while taking leadership roles at the National Academy of Sciences, the National Geographic Society, and many other organizations. Raven advanced global biodiversity conservation and scientific infrastructure and worked tirelessly to provide opportunities for emerging scholars worldwide. His legacy lies not only in the breadth of his scholarship and public service but also in his enduring commitment to connecting people, fostering collaboration, and helping others realize their potential.
GPT-4o mini: Non-social science research article
Advances in small area population estimation in the absence of national census data
Andrew J. Tatem, Gianluca Boo, Heather R. Chamberlain, Christopher C. Nnanatu, Edith Darin, Douglas R. Leasure, Ortis Yankey, Assane Gadiaga, Sabrina Juran, Luis de la Rua Rodriguez, Jessica Espey, Attila N. LĂĄzĂĄr
Full text
Population data at small area scales are essential for effective decision-making, influencing public health, disaster response, and resource allocation, among others. While national censuses remain the cornerstone of population data, they are often constrained by high costs, infrequent collection cycles, and coverage gaps, which can hinder timely data availability. To address these challenges, geospatial statistical approaches using limited microcensus surveys have been demonstrated as a reliable source, but the field has advanced substantially in recent years, with significant developments in both data sources and modeling methodologies. New approaches now leverage routine health intervention campaign data, satellite-derived settlement maps, and bespoke modeling approaches to produce reliable small area population estimates where enumeration is difficult or outdated. Various countries are applying these techniques to support census operations, health program planning, and humanitarian response. This manuscript reviews recent advances in “bottom-up” population mapping approaches, highlighting innovations in input data, modeling methods, and validation techniques. We examine ongoing challenges, including partial observation of buildings under forest canopy, population displacement, and institutional uptake. Finally, we discuss emerging opportunities to enhance these approaches through better integration with traditional data ecosystems, capacity strengthening, and coproduction with national institutions.
GPT-4o mini: Non-social science research article
Primary amine–functionalized radially amphiphilic polypeptides target bacterial phospholipids in polyanionic matrices for biofilm therapy
Yuhao Zhang, Yu Huang, Yeqing He, Xinshuang Zhang, Qianyu Ma, Jiawen Chen, Chanjuan Su, Huosheng Zhou, Songyin Huang, Houbing Zhang, Dong Luo, Yan Bao, Yuqin Shen, Shiyan Xiao, Menghua Xiong
Full text
Bacterial biofilm infections, a key contributor to antibiotic resistance, pose a critical global health challenge. Although antimicrobial peptides are promising candidates, their cationic amphipathic structures often lead to nonspecific sequestration by polyanionic biofilm matrix components. Here, we report a class of primary amine–functionalized radially amphiphilic antimicrobial polypeptides (paRAPs) that achieve potent antibiofilm activity by selectively targeting bacterial phosphatidylglycerol (PG) in polyanionic biofilm matrices. Simulation studies support a mechanism of PG-responsive structural rearrangement in paRAPs. In contrast to the compact form of quaternary amine analogs, paRAPs adopt an extended conformation, with outward-facing cationic amine termini that shield the hydrophobic core and thereby reduce nonspecific protein binding. Upon encountering bacterial membranes, strong PG recognition triggers a side-chain rearrangement, reorienting the cationic groups toward the membrane surface and exposing hydrophobic motifs for progressive bilayer insertion and disruption. Supportingly, lengthening the exposed terminal hydrophobic group increased interactions with proteins and mammalian lipids, reduced PG selectivity, and compromised antibiofilm efficacy, underscoring the importance of hidden hydrophobic domains for biofilm bacteria targeting. paRAP showed potent antibiofilm efficacy in vitro and in murine models of both periodontitis and urinary tract infections. Our study provides a PG-targeting strategy for designing matrix-resistant antibiofilm polypeptides.
GPT-4o mini: Non-social science research article
Declining hydraulic safety in a drier world
Xingyun Liang, Nate G. McDowell, Defu Wang, Bo Cui, Jiemin Chen, Keyi Qiu, Junwei Luan, Zexin Fan, Xiangping Tan, Xuhui Zhou, Qinghai Song, Zhicheng Chen, Ying Jin, Cuiju Liu, Yi Wang, Zhongguo Li, Hui Liu, Qiuyu Liu, Pengcheng He, Cheng Yang, Bin Liu, Mujuan Deng, Yuxuan Miu, Xin Tan, Xiankai Lu, Junhua Yan, Weibin Li, Shirong Liu, Qing Ye
Full text
Forests worldwide are increasingly exposed to soil drought under climate change, with their fates depending on the ability to maintain essential functions like water transport (hydraulics) and photosynthesis. Acclimation is expected to mitigate drought impacts, but the extent to which trees acclimate remains largely untested, which limits our predictive confidence. Here, we examined 24 physiological attributes from 40 globally distributed forest throughfall reduction (TFE) experiments and found no evidence that trees adjusted their hydraulic or photosynthetic systems in response to drought. Key attributes related to embolism resistance, hydraulic efficiency, leaf nutrients, and Rubisco carboxylation capacity remained unchanged, regardless of coniferous or broadleaf trees, local precipitation levels, or the duration and severity of drought treatments. However, drought-induced declines in tissue water potentials, combined with unchanged embolism resistance, led to narrower hydraulic safety margins and thus an increased risk of hydraulic failure. Although net photosynthetic rate declined significantly due to stomatal closure, nonstructural carbohydrates (starch and sugars) remained stable, suggesting a shift in carbohydrate allocation toward storage. These findings indicate that trees maintain their hydraulic and photosynthetic capacities under drier conditions, enabling them to maximize carbon assimilation on favorable periods following rainfall, while facing an increased risk of hydraulic failure during drought. Physiological acclimation is unlikely to mitigate future drought impacts, while tree mortality from hydraulic failure is likely to increase.
GPT-4o mini: Non-social science research article
Numerical investigation of the equilibrium Kauzmann transition in a two-dimensional atomistic glass
Gerhard Jung, Misaki Ozawa, Giulio Biroli, Ludovic Berthier
Full text
Dense liquids gradually transform into nonequilibrium amorphous solids as they pass through the experimental glass transition. Experimentally, ergodicity is lost because measurements are conducted within a finite time window. More than seventy years ago, Kauzmann posed a fundamental question: If experiments could run indefinitely, would there exist a critical temperature at which an ergodicity-breaking phase transition occurs? Random first-order transitions represent the modern theoretical framework for this idea. However, theoretical calculations in finite dimensions are challenging, whereas experimental and numerical limitations on accessible timescales hinder direct observation of the putative Kauzmann transition. Here, we overcome this longstanding barrier by developing a computational strategy that properly combines three Monte Carlo methods to access the desired equilibrium thermodynamic properties of a two-dimensional atomistic glass-former down to zero temperature across a range of system sizes up to 77 particles. This enables us to directly measure thermodynamic and structural observables that provide unambiguous evidence that the system undergoes a finite-size version of the Kauzmann transition at a temperature that is much lower than other energy scales and decreases rapidly with system size, thus suggesting the existence of a zero-temperature Kauzmann transition for two-dimensional glasses. The transition is toward an ideal glass state characterized by a complex energy landscape and a hierarchical organization of low-lying states.
GPT-4o mini: Non-social science research article
Tox regulates hair cell stereocilia development and Cdh23 expression in mice and zebrafish
Jing Zhang, Jie Gong, Jing Zhou, Guiyi Zhang, Shengda Cao, Siwei Guo, Yu Xiao, Xiaoxu Zhao, Wen Li, Yuhan Wang, Ruifeng Qiao, Min Wang, Ziyi Liu, Guodong Hong, Yunhao Wu, Xiuli Bi, Hailong Tu, Shuyuan Shen, Jiangang Gao, Dong Liu, Xiaolong Fu
Full text
Auditory hair cells (HCs) are critical sensory units for sound detection, and their development requires precise transcriptional regulation. To date, numerous transcription factors crucial for HC development have been characterized; however, the governing regulatory network remains unclear and warrants further investigation. In this study, we identified the transcription factor Tox , which plays a significant role in HC development. Tox is highly expressed in HCs in both zebrafish and mice, and its expression increases along developmental pseudotime, rising after Atoh1 and preceding Myo7a , suggesting a potential role in development. Utilizing Tox mutant models in zebrafish and mice, we found that Tox is essential for HC functional maintenance and stereocilia stability. Through multiomics integrated analysis, we confirmed that Tox directly binds to conserved motifs in the Cdh23 promoter, drives its transcription, and ensures the precise localization of Cdh23 at the tips of stereocilia, thereby playing a key role in maintaining auditory function. In conclusion, our findings indicate that Tox influences HC development by regulating the transcription and translation of Cdh23 , enriches the regulatory network of HC development, and may serve as a target for clinical gene therapy for deafness.
GPT-4o mini: Non-social science research article
Co-option of ancestral stem regulators drove recurrent evolution of underground storage organs
Julia Brose, Dionne Martin, Yi-Wen Wang, Joshua C. Wood, Brieanne Vaillancourt, John P. Hamilton, Kathrine Mailloux, Patrick P. Edger, C. Robin Buell
Full text
Geophytes are plants that produce underground storage organs such as tubers, rhizomes, and bulbs, to facilitate asexual reproduction and withstand a myriad of environmental challenges. While the potato ( Solanum tuberosum L.) serves as the primary model for studying tuberization, the genetic mechanisms encoding this trait across diverse angiosperm lineages remains unclear. This study utilized a phylogenomic-transcriptomic approach to compare tuber development across nine tuberizing species with five nontuberizing sister taxa. We identified orthologs of key potato tuberization genes that exhibit similar expression in the stolons or tubers of these distant relatives. In nontuberizing species, these orthologs exhibit distinct expression profiles and are primarily expressed in the stem. This suggests that the independent evolution of tubers across angiosperms resulted from shifts in the expression of preexisting genes that led to their co-option. This process, also known as exaptation, occurs when existing genetic suites are recruited for entirely new biological functions. This mechanism stands in contrast to the repeated loss or gain of genes, which has been associated with the origin of other adaptive plant traits. Furthermore, the co-option of the same genes was observed in species with other stem-derived storage organs, such as rhizomes and runners. These findings reveal a conserved evolutionary model for the development of stem-derived geophyte organs that evolved independently across the flowering plants over the past 160 My.
GPT-4o mini: Non-social science research article
RNA aptamers for sodium and lithium are abundant in mammals
Neil White, Gabriel Belem de Andrade, Aya Narunsky, Christopher King, Narasimhan Sudarsan, Ronald R. Breaker
Full text
Riboswitches are common in the bacterial domain of life where they regulate gene expression in response to binding metabolites, elemental ions, or other small ligands. We used comparative sequence analyses to identify numerous RNA motifs in humans and other mammals that are similar in sequence and structure to bacterial riboswitch aptamers for cationic sodium and lithium. Candidates are found in the mRNA transcripts for ~70 genes relevant to ion conductance, neuronal development and function, or to various neurological diseases. Bioinformatic and biochemical analyses support the hypothesis that mammals make extensive use of these RNA aptamers to selectively bind Na + and Li + . These structured RNA domains are often located in regions of mRNAs or their putative antisense transcripts that suggest they are components of riboswitches. Such associations also expose links between these alkali metal ions and genes whose expression is likely under monovalent ion regulation. These findings are also consistent with the hypothesis that Li + is a natural contributor to the regulation of genes relevant to certain mental disorders.
GPT-4o mini: Non-social science research article
Reconstruction of an extinct soundscape reveals ultrasonic communication in the Jurassic
Jun-Jie Gu, Fernando Montealegre-Z, Thorin Jonsson, Charlie Woodrow, Emine Celiker, Md Niamul Islam, Jackson B. Linde, Fabio A. Sarria-S, Fuming Shi, Hojun Song, Daniel Robert, Dong Ren
Full text
Very little is known about the acoustic landscape of long-gone environments, such as the Jurassic forests. The sounds made by dinosaurs and other charismatic vertebrates are not definitively known because their vocal organs rarely preserve well in fossils. Unlike tetrapod vocal cords, the sound-producing organs present in the sclerotized cuticle of some arthropods do fossilize well. For example, the stridulatory structures (file, plectrum) can be observed and measured in the fossilized forewings of male crickets and allies. These fossils incorporate a fingerprint of the acoustic signals they generated, offering a unique window into the soundscapes of the past. While call frequencies can be inferred from fossilized wings using phylogenetically informed predictions, the reconstruction of wing vibrations and the songs’ temporal patterns from fossil material remains elusive. Integrating phylogenetics, laser Doppler-vibrometry, numerical simulations, and an AI-based approach, 20 ensiferan fossils (nine species) from a single location (Jiulongshan Formation, Inner Mongolia, China) were studied to recreate the acoustic landscape of the Middle Jurassic. These insects produced pure-tone calls, an adaptation to avoid localization by eavesdropping predators. They also exhibited rich diversity in their calling song frequencies and repertoires, facilitated by specialized file morphologies and wing-size variation. One species called above 20 kHz, suggesting that ultrasonic communication in insects was established long before the emergence of bats in the Eocene. Evolving mammalian hearing thresholds suggest early predators imposed acoustic pressures before bats. This arms race with singing ensiferans likely drove Jurassic insect song diversity and the evolution of mammalian and insect auditory systems.
GPT-4o mini: Non-social science research article
Macrophages diverge into profibrotic SAMs and proresolving ReM2 cells to regulate liver fibrosis
Dezhen Zhang, Xinjie Liu, Dong Ma, Lingling Liao, Fugang Duan, Yiming Wang, Tongzhen Zhang, Jiang Liu, Wei Dong, Junfei Jin, Zhenhua Luo, Haining Zhou
Full text
A central question in liver fibrosis is how macrophages, key regulators of inflammation and tissue repair, are divergently programmed to either promote scar formation or drive its resolution. Here, we identify a macrophage axis that governs this balance. While scar-associated macrophages (SAMs) promote fibrogenesis through cytokine-mediated activation of hepatic stellate cells, a previously uncharacterized macrophage subset, termed ReM2, orchestrates fibrosis regression. ReM2 arises from circulating monocytes following liver injury, accumulates during fibrogenesis, and peaks during the resolution phase. Mechanistically, ReM2-dependent fibrosis regression requires the expression of specific receptors, including FCGR4 and ITGA4, which may mediate this effect by enabling direct recognition and phagocytic clearance of collagen I and fibronectin from the extracellular matrix. These findings reveal a functional divergence of monocyte-derived macrophages that governs fibrosis progression vs. resolution and suggest that therapeutic rebalancing of the SAM–ReM2 axis may represent a promising strategy for treating liver fibrosis.
GPT-4o mini: Non-social science research article
Reply to Panfoli et al.: From O 2 consumption in myelin to gap junctional ATP delivery in axons: An energy link needing further scrutiny
Katja Witschas, An Ghysels, Luc Leybaert
Full text
GPT-4o mini: Non-social science research article
The rod bipolar cell pathway contributes to surround responses in OFF retinal ganglion cells
Giulia Spampinato, Francesco Trapani, Victor Calbiague-Garcia, Thomas Buffet, Elaine Orendorff, B. Semihcan Sermet, Guilhem Glaziou, Deniz Dalkara, Emiliano Ronzitti, Eirini Papagiakoumou, Valentina Emiliani, Olivier Marre
Full text
Sensory neurons can be influenced by stimuli beyond their receptive field center, yet the mechanisms underlying this surround modulation remain poorly understood. In the retina, many OFF ganglion cells exhibit responses to ON stimulation outside their receptive field center. However, disentangling the pathways and cell types contributing to these responses has been challenging with traditional experimental approaches. Here, we combined optogenetics, two-photon holographic stimulation, and multielectrode array recordings to identify the intermediate retinal cell types involved in this circuit. We found that the pathway consisting of rod bipolar cells and AII amacrine cells—one of the primary relays of rod-driven signals under low-light conditions—plays a key role in mediating this surround modulation. Specifically, crossover inhibition exploits the same amacrine cells responsible for surround suppression to disinhibit distant ganglion cells. This suggests that the retina repurposes existing circuits for surround modulation, optimizing resources through multifunctional inhibitory pathways.
GPT-4o mini: Non-social science research article
Reshaping pathogen ecology in the Anthropocene
Paul A. Hoskisson
Full text
GPT-4o mini: Non-social science research article
An insoluble de novo protein enables survival of Escherichia coli by sequestering a gene repressor
Guanyu Liao, Sha Tao, Jessica L. Dessau, Yejin Bann, Michael H. Hecht
Full text
De novo proteins that share no ancestry with natural sequences can serve as additions to the evolved proteomes of living cells. Upon expression in cells, these novel proteins can provide biological functions that alter cell viability and growth. To isolate such proteins, we searched a combinatorial library of novel sequences by selecting for sequences that sustain the growth of Escherichia coli under conditions where the recipient cell would otherwise be inviable. This led to the identification of Resc4 ( Rescuer 4 ), a de novo protein that sustains growth on minimal medium of an E. coli strain harboring a lethal deletion of metC , which encodes cystathionine ÎČ -lyase, a conditionally essential enzyme in the biosynthesis of methionine. Surprisingly, despite its ability to rescue the deletion of a biosynthetic enzyme, Resc4 is insoluble. Nonetheless, Resc4 sustains the growth of Δ metC cells by upregulating expression of metB , which encodes a different enzyme, cystathionine Îł -synthase, which has a moonlighting activity that compensates for the deleted activity encoded by metC . Proteomic analysis revealed that Resc4 sequesters MetJ, the repressor of the methionine biosynthesis operon. Sequestration of MetJ leads to overproduction of cystathionine Îł -synthase, thereby allowing it to rescue the deletion of metC . These results, taken together with previous findings on other de novo proteins, demonstrate that novel proteins added to a cell’s proteome can perform life-sustaining functions, and may shed light on de novo gene birth—both in synthetic biology and in natural evolution.
GPT-4o mini: Non-social science research article
Stochastic theory for pattern formation and front propagation in transitional pipe turbulence
Xueying Wang, Hong-Yan Shih, Nigel Goldenfeld
Full text
The onset of turbulence in a pipe occurs through a subcritical transition. Once turbulent patches (“puffs”) have been nucleated by some external perturbation, they decay; but above a threshold flow velocity, puffs split, leading to a nonzero turbulent fraction in the pipe at long times. Recent theoretical and experimental work has shown that this transition can be understood as a nonequilibrium phase transition in the universality class of directed percolation. At higher flow velocity, the turbulence spreads into the laminar state through front propagation, creating an expanding region of turbulence known as a “slug,” which may exhibit either one or two sharp fronts depending on the flow velocity. It is an open question as to whether the phenomena associated with puff interactions and the slug phase can be understood within the statistical mechanical model framework that predicts the directed percolation transition. Here, we present a stochastic model for the decay, splitting, and propagation of turbulent patches in a background laminar state that accounts for the full range of behavior in the transitional regime. We show that activator–inhibitor (predator–prey) dynamics, coupled to the streamwise shear flow, recapitulates experimental profiles for puffs and slugs, as well as previous simulation results for the spatial structure of the energy flow, the kinematics of puff splitting and the transition to and between the two slug phases. Our work shows that nonequilibrium statistical mechanics can provide a detailed understanding not only of the laminar–turbulent transition, but also the pattern formation phenomena arising in the turbulent state.
GPT-4o mini: Non-social science research article
Atomistic twinning process with ultra-high shear in hexagonal close-packed crystals
Yang He, Dengke Chen, Chongmin Wang, Ting Zhu, Yuyang Wang, Bin Li, Scott X. Mao
Full text
Twinning is a critical deformation mechanism that can significantly enhance the mechanical performance of materials. Predicting active twinning modes has long been a fundamental challenge. It is generally believed that active twinning modes should exhibit low to moderate shear strains to minimize the associated strain energy. Here, using in situ atomic-scale straining experiments, we identify an unconventional twinning mode in hexagonal close-packed (HCP) rhenium nanocrystals, characterized by an extraordinarily large shear strain of ~1.2, the highest reported for HCP crystals to date. Remarkably, this twinning process proceeds via pure lattice shear without the atomic shuffling typically required for conventional HCP twinning. Our results indicate that high stress states attainable in nanocrystals, together with favorable energetics, enable activation of this mode. This ultra-high-shear twinning mechanism holds significant potential for enhancing the formability and ductility of HCP metals.
GPT-4o mini: Non-social science research article
Profile of C. Robin Buell
Sarah C. P. Williams
Full text
C. Robin Buell has been a leading figure in plant genomics since the advent of DNA sequencing technology. She helped lead multiple consortia to sequence some of the first crop genomes at the turn of the millennium. She has since used the genomes to tackle questions in fundamental biology, plant evolution, and agriculture. Recently, she applied single-cell technologies to uncover how complex biosynthetic pathways are compartmentalized across different rare plant cell types. Now at the University of Georgia, Buell explores in her Inaugural Article how tubers arose repeatedly in the plant family tree.
GPT-4o mini: Non-social science research article
Loss of neuronal population organization links pathology to behavior in a model of Alzheimer’s disease
Douglas A. Ruff, Drew E. G. Sheets, Ramanujan Srinath, Giovanne B. Diniz, Devon J. Griggs, Danielle Beckman, Sean Ott, Kayla Schwartz, Carissa T. Erices, Scott Muller, Jeffrey H. Kordower, John H. Morrison, Marlene R. Cohen
Full text
Alzheimer’s disease and related dementias are typically described at two levels: the accumulation of molecular pathology and the emergence of cognitive impairment. Understanding the relationship between pathology, often studied in animal models, and human cognition will require measurements spanning intermediate scales, including single neurons, neuronal populations, and distributed networks. Here we combine longitudinal measurements of behavior and neuronal population activity with fluid and histological biomarkers in a macaque model of early-stage disease. We find in two animals that visually guided behavior becomes increasingly disorganized, with less consistent and more variable patterns of exploration, despite preserved performance on simple tasks. In parallel, coordinated activity within and between neuronal populations in visual and parietal cortex declines, even as single-neuron tuning and basic feature encoding remain stable. The magnitude of these physiological changes was broadly consistent with biomarker progression. These changes arise when pathology is largely confined to regions providing feedback to visual cortex, indicating that functional disruption extends beyond sites of prominent pathology. Together, these results show that early disease progression is not marked by the loss of individual functions at any single level, but by a selective disruption of coordination across levels, from neuronal populations to behavior. This disorganized state is measurable and modifiable: methylphenidate administration was associated with a transient restoration of behavioral organization. These findings identify disruption of neuronal population organization as a defining feature of early-stage Alzheimer’s disease and establish coordinated population activity as a candidate target for therapeutic intervention.
GPT-4o mini: Non-social science research article
Mercury’s crustal magnetization indicates a stronger ancient dynamo
Isaac S. Narrett, Benjamin P. Weiss, Sarah C. Steele, John B. Biersteker
Full text
Mercury is the only terrestrial planet in the solar system other than Earth with an active dynamo magnetic field (~200 nT at the equatorial surface). Furthermore, Mercury’s ~3.9- to 3.7-billion-year-old (Ga) crust is strongly magnetized (~10 nT at ~30-km altitude), indicating the presence of a past dynamo. However, the strength of the past dynamo field and the mechanism that generated it are unknown. To address this, we performed three-dimensional magnetohydrodynamic simulations of the ancient solar wind interaction with the planetary field coupled with crustal thermal evolution and magnetization models. We show that the crustal magnetization was likely produced by a dipole field with equatorial surface strength of at least ~2,000 nT and possibly as high as ~30,000 nT for a dynamo with a reversal frequency greater than once per million years. Such strong fields likely exclude both the solar wind feedback and thermoelectric dynamo mechanisms at ~3.7 Ga ago. Instead, our results are compatible with the past dynamo being generated by a nearly fully convective core.
GPT-4o mini: Non-social science research article
Gut microbiome–metabolome interactions during varied low-carbohydrate food consumption
Jacob T. Nearing, Thomas Kuntz, Veronica Perdomo, William A. Nickols, Tobyn Branck, Amrisha Bhosle, Dayakar V. Badri, Curtis Huttenhower, Matthew Jackson, Kelsey N. Thompson
Full text
Low-carbohydrate (LC) foods have been associated with weight loss, insulin resistance, and reduced inflammation. Gut microbes may drive these effects by changing the host’s immune and metabolic state, yet the optimal replacement strategies (e.g., protein vs. fat) and the biochemical impacts are still uncertain. Thus, we conducted a randomized cross-over study in canines (n = 35) using a high-carbohydrate food for 4 wk, followed by two 5-wk intervals of LC foods replacing carbohydrates with fat or protein. Feces and blood samples collected after each interval underwent metabolome profiling, as well as shotgun metagenomic and metatranscriptomic sequencing from feces. We observed strong associations between food and overall fecal and serum chemical and gut microbial composition. Bifidobacterium spp. were significantly reduced during consumption of either LC food, whereas many species from Firmicutes increased. In addition to broad taxonomic changes, we also found that several microbially associated metabolites (tryptophan derivatives, secondary bile acids, and short-chain fatty acid fermentation) shifted in abundance in response to differing LC foods. Broadly, we also identified a strong trend toward decreased amino acids in the feces of dogs fed LC foods, particularly the high fat food. Coupled with decreased fecal dipeptide levels and increased fecal ammonia, these findings indicate a broad metabolic shift within the gut microbiome, potentially toward protein catabolism. Together, the data suggest that diverse carbohydrate replacement strategies induce extensive gut reprogramming, with some changes dependent on whether carbohydrate energy was replaced with fat or protein.
GPT-4o mini: Non-social science research article
On the origin of the ionic strength control of the motility of kinesin-14
Ritaban Halder, Arieh Warshel
Full text
Kinesin-14 motors are a special class of the kinesin family proteins that walk toward the minus end along the microtubule. It has the reverse directionality compared to the general conventional kinesins. The motility of kinesin-14 has been found to depend on the ionic strength. That is, when the ionic strength changes, the motility of the protein changes significantly. Understanding the origin of such effect is important both as a fundamental problem and as a part of the overall understanding of intracellular transportation. Here, we explore the molecular origin behind the lowering of motility of kinesin-14 upon increase in the ionic strength. Our study combines steered molecular dynamics and umbrella sampling simulations and binding energy calculations. It is concluded that at a low ionic strength the ADP release from the trailing or back leg has a significantly lower barrier than that from the leading or front leg. However, at a higher ionic strength the barrier of ADP release becomes lower for both the trailing and leading legs, where now the barriers for both legs are similar. In this case although the ADP release for the trailing end becomes faster (which usually corresponds to higher motility) it is also faster for the leading end, and the overall motion of both heads balance each other and the motility becomes slower. The ionic strength effect and our binding free energy calculations indicated that the motility in this system is controlled by electrostatic energy. Such effects are likely to be prominent in in-vivo cellular conditions.
GPT-4o mini: Non-social science research article
Quantitative nanoscale imaging shows peptide–MHC I complexes are monomeric and spatially regulated in human dendritic cells
Olivia Jacobs, Tanja Menche, Cindy Höper, Frédéric Gerhards, Ivica Fucek, Fulvia Vascotto, Marina S. Dietz, Mike Heilemann, Robert Tampé
Full text
Major histocompatibility complex class I (MHC I) molecules present antigenic peptides to cytotoxic T cells, a process central to immune surveillance. However, the nanoscale spatial organization of peptide–MHC I (pMHC I) on human dendritic cells (DCs), key initiators of cytotoxic T cell responses, remains largely unexplored. Here, we combine high-affinity soluble T cell receptors with DNA-based point accumulation for imaging in nanoscale topography (DNA-PAINT) to quantitatively map and count defined pMHC I complexes at single-molecule resolution on HLA-A*02:01-expressing cells and primary human monocyte-derived DCs. We found no evidence for higher-order pMHC I nanoclusters under conditions of extracellular peptide exchange or physiological intracellular loading. Instead, detected signals correspond to individual pMHC I complexes. Notably, DC differentiation and activation modulate pMHC I surface abundance and spatial compartmentalization. These findings refine current models of antigen presentation by emphasizing regulation through surface density and spatial distribution, and establish a quantitative framework for epitope-specific, single-molecule quantification of antigen presentation in human immune cells.
GPT-4o mini: Non-social science research article
Soft matter, hard rules: Emulsions follow the laws of granular suspension rheology
Wenjun Chen, Eric De Giuli, Matthieu Wyart, YoĂ«l Forterre, Jasna Brujić, Bloen Metzger
Full text
The flow of dense emulsions underlies applications from food and pharmaceutical processing to bioengineering, yet their rheology remains difficult to interpret under conventional volume-imposed conditions. Here, we change the control variable to osmotic-pressure using a recently developed instrument—the Capillarytron. This approach reveals a unified rheological structure where the osmotic pressure Π , by controlling droplet deformation, sets a pressure-dependent jamming volume fraction. When expressed in terms of the distance to this jamming point, all rheological data—spanning both Π - and ϕ -imposed measurements—collapse onto a single power-law divergence, akin to granular suspensions. The resulting constitutive relations provide a predictive, parameter-free description of emulsion rheology across Newtonian, yielding, and shear-thinning regimes. Together with recent results on soft spheres, our findings point to a unifying paradigm: Soft amorphous materials—from soft spheres to emulsions and likely foams—obey the same hard rules as granular suspensions, with softness entering through a pressure-dependent jamming point. This framework rationalizes Herschel–Bulkley rheology, assigns its parameters microscopic meaning, and opens perspectives on rigidity transitions in soft, deformable systems, including biological tissues.
GPT-4o mini: Non-social science research article
Probabilistically defining environmentally relevant concentrations in ecotoxicology
Tao Sun, Huifeng Wu, Lennart Weltje, Evgenios Agathokleous, Edward J. Calabrese, John P. Sumpter
Full text
A long-standing issue in ecotoxicology is the arbitrarily chosen and ambiguous definition of “environmentally relevant” concentrations, which undermines research comparability and hampers risk characterization. Here, we propose a probabilistic framework that anchors exposure levels to percentiles of environmental concentration distributions, defining low (<5th percentile), typical (5th to 95th percentiles), and high (>95th percentile) concentrations, as well as worst-case scenarios (e.g., the 99th percentile) for specific contexts. This framework transforms test concentration selection from a subjective assertion into a statistically justified practice, where each concentration corresponds to an explicit occurrence probability. Using global monitoring data, we demonstrate that environmental concentrations reliably follow cumulative probability distributions, validating the fundamental assumption. Crucially, the framework offers a statistical solution for designing proof-of-relevance and proof-of-concept studies. Collectively, this work provides an empirically grounded, immediately usable template for designing ecotoxicological experiments that bridge environmental monitoring, laboratory testing, and regulatory decision-making.
GPT-4o mini: Non-social science research article
ALKBH3 inhibition normalizes neovessels by reprogramming endothelial fate in diabetic microvasculopathy
Yi-Chen Zhang, Zi-Qin Ding, Shi-Yao Xu, Ji-Yu Chen, Ming-Hui Chen, Bing-Qing Luo, Ying Wang, Yan-Yi Wu, Xin-Yao Lv, Xing-Zhu Liu, Chen Zhao, Qing-Huai Liu, Xue Chen
Full text
Diabetic microvasculopathy is a serious diabetes complication, with diabetic retinopathy (DR) being a leading cause of blindness worldwide due to immature, leaky neovessels. Antiangiogenic therapies merely suppress neovascularization, leaving the retina oxygen-starved and prone to regrowth. Thus, therapies that stabilize aberrant neovessels are needed. We identify the RNA demethylase ALKBH3 as an epitranscriptional driver of diabetic microvasculopathy. Upregulated ALKBH3 in diabetic vascular endothelial cells promoted a pathological shift to an unstable, pro-angiogenic phenotype, disrupting blood-retinal barrier and forming immature neovessels, which impaired vision. Conversely, removing ALKBH3 protected against this. Mechanistically, ALKBH3 demethylated BMP2 mRNA to increase its stability via YTHDF2. We further developed a neovasculature-targeting nanoparticle delivering the ALKBH3 inhibitor HUHS015, which normalized retinal neovascularization by simultaneously limiting growth and promoting maturation. It acted synergistically with vascular endothelial growth factor (VEGF) blockade, suggesting potential for anti-VEGF-resistant cases. Our work defines ALKBH3 as a key mediator of diabetic microvasculopathy and supports a VEGF-independent therapeutic paradigm that shifts the focus from vessel suppression to active normalization.
GPT-4o mini: Non-social science research article
What controls the superconducting dome of electron-doped FeSe?
Paul T. Malinowski, Chad J. Mowers, Yaoju Tarn, Darrell G. Schlom, Brendan D. Faeth, Kyle M. Shen
Full text
Superconducting domes are conspicuous features of the phase diagrams of most unconventional and high-temperature superconductors. The superconducting transition temperature ( T c ) of FeSe can be dramatically enhanced with electron doping, but unlike all other high-temperature and unconventional superconductors, its full phase diagram and superconducting dome has yet to be fully explored. Here, we employ a combination of molecular beam epitaxy synthesis, alkali surface doping, in-vacuum electrical transport, and angle-resolved photoemission spectroscopy to investigate the entire superconducting dome of electron-doped FeSe, achieving a fully metallic state where superconductivity is suppressed in the heavily overdoped regime. We identify a robust scaling between T c and the residual resistivity (ρ 0 ) which holds across the entire superconducting dome, suggesting that the evolution of T c is heavily influenced by the evolution of the elastic scattering rate in the high- T c electron-doped phase. This in turn suggests that the superconducting dome in electron-doped FeSe appears to be fundamentally different than that of other unconventional superconductors where doping plays the primary role, and may instead be driven primarily by the sensitivity of the superconductivity to disorder.
GPT-4o mini: Non-social science research article
Stochasticity and probabilistic trajectory scoring are essential for data-driven closures of chaotic systems
Martin T. Brolly
Full text
Coarse-grained models of chaotic systems neglect unresolved degrees of freedom, inducing structured model error that limits predictability and distorts long-term statistics. Typical data-driven closures are trained to minimize prediction error over a single time step, implicitly assuming Markovian dynamics and often failing to capture long-term behavior. Recent approaches instead optimize losses over finite trajectories. However, when such trajectory-based training is carried out with deterministic pointwise losses, it introduces a fundamental mathematical degeneracy. We prove that optimizing pointwise deterministic losses, including but not limited to mean squared error, over chaotic trajectories suppresses predictive variance, with a corresponding loss of physical variability in long integrations. In contrast, strictly proper scoring rules avoid this degeneracy. By targeting forecast distributions rather than realized trajectories, they remove the penalty against predictive spread and align the long-lead optimum with the invariant measure. Using quasi-geostrophic turbulence as a canonical chaotic system, we validate this theory: Closures trained with one-step losses fail to capture stable coarse-grained dynamics, while deterministic closures optimized over trajectories exhibit the variance-loss tendency predicted by our analysis. Stochastic closures calibrated over trajectories using the energy score, however, overcome both structural limitations, yielding skillful ensemble forecasts and realistic long-term statistics. Our results establish that both stochastic modeling and trajectory-based calibration are essential for faithfully representing the dynamics of coarse-grained systems.
GPT-4o mini: Non-social science research article
High-resolution mapping of osteoblast metabolism and bone matrix turnover in vivo
Kai Chen, Jinyu Guo, Xiaojun Chen, Buran Chen, Heng Qiu, Hui Yang, Paul Guagliardo, Sitao Hu, Chau Bui, Kavishadhi Chandrasekaran, Qiongxiang Lin, Bo He, Qi Chen, Jiake Xu, Stephen G. Young, Matthew B. Greenblatt, K. Swaminathan Iyer, Nathan J. Pavlos, Haibo Jiang
Full text
Understanding how osteoblasts build and remodel bone matrix in vivo remains a fundamental challenge because cellular metabolism and matrix turnover are difficult to resolve across time and space within mineralized tissues. Here, we developed an integrated imaging platform combining stable isotope labeling with correlative electron microscopy and nanoscale secondary ion mass spectrometry (NanoSIMS) to visualize bone cell metabolism and matrix dynamics at nanometer resolution in vivo. This approach revealed rapid incorporation of dietary amino acids into osteoblast subcellular compartments within minutes of oral administration, followed by deposition of newly labeled extracellular matrix within hours. By linking elemental composition, isotope incorporation, and ultrastructure, we further show that cellular phosphorus signal is associated with early osteoblast amino acid incorporation. Multiday labeling revealed that newly deposited matrix is spatially associated with local osteocyte process architecture. Long-term amino acid tracing uncovered localized matrix turnover at osteocyte and osteoclast interfaces, including osteocyte-associated pericellular matrix remodeling and osteoclast association with newly formed, old, and mixed matrix regions. Finally, aging was associated with reduced osteoblast amino acid incorporation, diminished matrix deposition, and impaired osteocyte process-associated activity. Together, this work establishes a high-resolution platform for linking bone cell metabolism with matrix deposition and turnover in vivo, providing a broadly adaptable strategy to investigate skeletal aging, tissue remodeling, and metabolic dysfunction in disease.
GPT-4o mini: Non-social science research article
Neutrophil-intrinsic Vgll4 constrains tumorigenesis by preventing a STAT3/STAT5-driven immunosuppressive switch
Lin Shao, Jingwu Yue, Shilong Wang, Ruixian Yu, Shuting Cheng, Pingping Nie, Xiaoya Jiang, Yi Han, Wenjia Wang, Yan Meng, Moubin Lin, Miao He, Jianfeng Chen, Zhaocai Zhou, Shi Jiao
Full text
Neutrophils display profound functional plasticity within the tumor microenvironment (TME), a key determinant of cancer progression; however, the intrinsic mechanisms safeguarding their antitumor identity remain elusive. Here, we identify the Hippo pathway component Vgll4 as a pivotal guardian of neutrophil functional fate in the TME. While dispensable for homeostatic granulopoiesis, Vgll4 in neutrophils is crucial for restraining tumor growth. Neutrophil-specific ablation of Vgll4 triggers a phenotypic shift toward an immunosuppressive state, accelerating tumor progression. Mechanistically, Vgll4 binds STAT3 and STAT5 in a JAK-dependent manner; loss of Vgll4 reduces SOCS3 expression, a negative regulator of STAT3, thereby unleashing STAT3 hyperactivation while suppressing STAT5, leading to transcriptional reprogramming that establishes an immunosuppressive profile. This regulatory axis operates specifically in tumor-associated neutrophils, as Vgll4 is dispensable for steady-state development but essential within the TME. Consequently, Vgll4-deficient neutrophils remodel the TME by promoting regulatory T cell (Treg) differentiation and impairing CD8 + T cell effector function. Our findings unveil a noncanonical role for Vgll4 in innate immune regulation and establish the Vgll4-STAT3/STAT5 axis as a crucial checkpoint in neutrophil polarization, presenting a therapeutic target for cancer immunotherapy.
GPT-4o mini: Non-social science research article
A hypersensitive neuromorphic airflow sensor inspired by vision-compensatory scorpion mechanoreceptors for respiratory pattern analysis
Pinkun Wang, Yuechun Ding, Bo Li, Changchao Zhang, Xiancun Meng, Guangjun Chen, You Chen, Ruijuan Du, Qingsong Fan, Junqiu Zhang, Shichao Niu, Zhiwu Han, Luquan Ren
Full text
Efficient acquisition of spatial airflow information is vital for organisms to orient within complex environments and detect predators. For scorpions with degraded vision, specialized mechanosensory trichobothria provide a crucial vision-compensatory mechanism, enabling hypersensitive perception of subtle airflow fluctuations. Inspired by this evolutionary adaptation, we present a biomimetic neuromorphic airflow sensor (BNAS) integrating a bioinspired lever-amplification structure with a pressure-induced ionic enrichment mechanism. This synergistic design inherits the hypersensitive anemosensation and neural response features of scorpion. The BNAS demonstrates a superior sensitivity of 18.22% (m/s) −1 at low velocities and maintains high performance across a broad dynamic range (0.1 to 10.27 m/s), along with omnidirectional detection capability. The integration of this neuromorphic hardware with AlexNet deep-learning algorithm enables the efficient extraction of human respiratory patterns, achieving 95.56% accuracy in identifying individual “breathing fingerprints.” Our work underscores the potential of bioinspired neuromorphic systems to bridge the gap between biological perception and artificial sensing, establishing a neuromorphic front-end design paradigm that advances next-generation brain-inspired computing.
GPT-4o mini: Non-social science research article
Chemosymbiotic trophic strategy in an Ediacaran tubular animal
Zhenfei Wang, Yongbo Peng, Qing Tang, James D. Schiffbauer, Shuhai Xiao, David A. Fike, Zice Jia, Dong Feng, Peter W. Crockford, Yaoping Cai, Xunlai Yuan, Lisa M. Pratt
Full text
Chemosymbiosis may have been a key driver of early animal evolution and diversification. Yet evidence for animal–microbe nutritional partnerships in the fossil record of early metazoans remains scarce, largely owing to the limited availability of robust geochemical proxies and suitable fossilization pathways. Here, we report extremely low molybdenum isotope (ή 98 Mo) values in pyritized fossils of the terminal Ediacaran Conotubus , a nonbiomineralized cloudinomorph representing some of the earliest metazoans. Such low ή 98 Mo values are otherwise only known in modern cold-seep chemosymbiotic tubeworms hosting sulfur-oxidizing bacterial symbionts. Homogeneously low ή 34 S signatures of fossils indicate that rapid pyritization in early diagenesis under euxinic taphonomic settings preserved primary Conotubus chitinous ή 98 Mo. Substantial ή 34 S fractionation relative to seawater sulfate and high Δ 33 S values indicate that active microbial H 2 S oxidation occurred within their habitat. Our findings provide evidence that Conotubus may have engaged in chemosymbiosis with sulfur-oxidizing bacteria—the earliest geochemically supported case in the fossil record. This trophic strategy likely enabled Conotubus to thrive in the redox-stratified Ediacaran ocean where sulfide and oxidants coexisted, facilitating its ecological success.
GPT-4o mini: Non-social science research article
HLA class I escape drives the evolution of SARS-CoV-2 in human populations
Ekaterina D. Riumina, Evgeniia I. Alekseeva, Galya V. Klink, Stepan Feigin, Iaroslava Vinogradova, Natalia Ivanova, Dmitry Dianov, Ksenia Zornikova, Vassa Davydova, Apollinariya Bogolyubova, Georgii A. Bazykin
Full text
The role of escape from the cytotoxic T cell (CTL) response in Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) evolution remains controversial. Here, we study the origin and spread of SARS-CoV-2 variants whose mutations reduce presentation by the human leukocyte antigen (HLA) class I alleles common in human populations. We find that 35% of mutations that are characteristic of the variants of concern, and 39% of all subsequent viral mutations, facilitate escape of viral epitopes from presentation. Mutations allowing escape from more common HLA alleles reach higher frequencies, particularly in those countries where these HLA alleles are more frequent, indicating that escape is selected by the local genetic composition of the human host population. We also show that viral mutations that accumulated in general-population transmission chains matched population HLA class I allele frequencies as well as, or better than, mutations acquired during persistent infections, suggesting that selection in favor of escape mutations is not limited to immunocompromised individuals. Together, these data reveal CTL escape as a facet of selection, a driver of evolution, and an epidemiological concern for SARS-CoV-2.
GPT-4o mini: Non-social science research article
Calbindin stratifies midbrain dopaminergic neurons governing distinct aspects of locomotion
Cyril Bolduc, Cameron Oram, Skylar Donovan, Haleigh Bach, Martha Liu, Rafaëlle Marier, Morgan Sharpe, Siqi Liu, Cédric Campeau, Carl Duncan Spencer, Sarah A. Martin, Rajeshwar Awatramani, Jean-François Poulin
Full text
Despite advances in delineating the molecular diversity and projection patterns of midbrain dopamine (DA) neurons, subtype-specific contributions to motor learning and movement execution remain poorly defined. Here, we applied intersectional ablation and inhibitory chemogenetics to dissect the roles of calbindin-expressing (CALB1 + ) and nonexpressing (CALB1 − ) DA neurons in locomotion. Using newly engineered intersectional autocleavable Caspase3 constructs, we ablated CALB1 + or CALB1 − DA neurons in the mouse midbrain. CALB1 − DA neuron ablation caused severe weight loss, whereas CALB1 + DA neuron ablation produced no overt health impairments. Nonetheless, loss of either subtype led to a bradykinetic-like phenotype on the initiation and vigor of voluntary movements. Only ablation of CALB1 − DA neurons impaired performance on the accelerated rotarod. To test if these phenotypes are the result of DA subtype activity, we silenced either population using the inhibitory DREADD hM4Di. Consistent with ablation, silencing CALB1 − DA neurons impacted the initial performance on the rotarod, whereas inhibition of CALB1 + DA neurons did not impact performance on the first day, but prevented across-day improvement. Silencing both populations impaired the initiation and vigor of voluntary movements. We next investigated whether this locomotor phenotype stemmed from reduced DA release in the dorsolateral striatum (DLS). While CALB1 − silencing abrogated DA transients in the DLS, CALB1 + silencing unexpectedly resulted in increased transients in DLS. Thus, our results demonstrate that DA transients in the DLS are not invariably coupled with movement execution. Altogether, these findings uncover both distinct and shared roles of molecularly defined DA subtypes in shaping different aspects of locomotion.
GPT-4o mini: Non-social science research article
Multidomain interaction governs the filamentous assembly of the dominant-negative DNMT3A R882H mutant
Jianbin Chen, Jiuwei Lu, Zhixu Long, Sol Yoon, Megan Fukunaga, Jikui Song
Full text
DNA methyltransferase DNMT3A-mediated de novo DNA methylation is important for proper regulation of gene expression and genomic stability in development. The DNMT3A R882H (DNMT3A R882H ) mutation, a hot-spot mutation in acute myeloid leukemia and developmental disorders, exerts a dominant-negative effect in DNMT3A-mediated DNA methylation through promoting high-order protein assembly. However, due to the lack of structural knowledge on DNMT3A homo-oligomers, the mechanism behind wild-type DNMT3A (DNMT3A WT ) and DNMT3A R882H polymerization remains unclear. Here, we report the single-particle cryo-EM structures of homo-oligomeric DNMT3A WT and filamentous DNMT3A R882H , revealing the role of the regulatory Pro-Trp-Trp-Pro (PWWP) and ATRX-DNMT3-DNMT3L (ADD) domains of DNMT3A in their dynamic assembly. While the oligomeric assembly of DNMT3A is mainly driven by the well-characterized oligomer interfaces in the methyltransferase domain, the autoinhibitory interaction of the PWWP and ADD domains in DNMT3A places them in a position for intermolecular contact, thereby contributing to the filamentous assembly of DNMT3A R882H . Disrupting the autoinhibitory interaction facilitates the transition of DNMT3A R882H polymer toward the low-order oligomeric assembly, reinforcing the aggregation-attenuation effect of the previously characterized oligomer-interface mutation R676K. Together, this study uncovers a multidomain cooperated assembly mechanism for DNMT3A, with important implication in development of effective therapeutic strategies against DNMT3A R882H -associated diseases.
GPT-4o mini: Non-social science research article
Histone modification cross talk between a host and pathogen
Shantinique S. Miller, Joel A. Hrit, Scott B. Rothbart, Evan J. Worden
Full text
Bacterial pathogens modulate host cell physiology by secreting effector proteins that rewire host signaling pathways. A subset of these effectors directly modify host chromatin to reprogram gene expression and promote infection. While these enzymes are thought to function autonomously, the extent to which the host epigenetic landscape regulates their activity remains largely unknown. RomA and its homolog LegAs4 are Set domain-containing lysine methyltransferases from Legionella pneumophila that methylate histone H3 at lysine 14 (H3K14) to suppress host immune responses and enhance intracellular bacterial replication. Here, we demonstrate that RomA activity is constrained by preexisting host histone posttranslational modifications (PTMs) through multiple layers of histone PTM cross talk. RomA selectively binds and methylates unmodified histone H3 tails and is inhibited by histone PTMs associated with active transcription, including H3K4 trimethylation, H3K4 acetylation, and H4K12 mono-methylation. We identify both cis- and trans-histone regulatory mechanisms, whereby unmodified H3K4 and H3K14 must reside on the same H3 tail to support RomA activity, while H4K12me1 inhibits RomA across the nucleosome. Notably, cryo-electron microscopy analysis and biochemical data reveal that RomA does not engage the nucleosome acidic patch but instead associates flexibly through histone tails. Together, these findings establish the host epigenetic regulation of bacterial effectors as a fundamental and previously unrecognized layer of host–pathogen interactions.
GPT-4o mini: Non-social science research article
Perceptual and neural constraints on photometric measures of heterochromatic brightness
Shuchen Guan, Jing Chen, Robert Ennis, Matteo Toscani, Matteo Valsecchi, Andrea van Doorn, Jan Koenderink, Karl R. Gegenfurtner
Full text
Luminance and the candela provide the foundation of photometry and define standard measures of the visual impact of light. They are defined by classical photometric methods that fail to capture key aspects of brightness judgments across different colors in spatially extended, real-world scenes: Highly saturated colors appear brighter, mixtures are subadditive relative to luminance, and short wavelengths contribute more strongly than expected. Despite these long-standing discrepancies, progress has been limited by the lack of scalable methods to measure heterochromatic brightness under steady viewing. Here, we introduce a ranking-based paradigm that enables reliable measurement of brightness across large stimulus sets. Observers ranked 144 colored stimuli spanning hue and intensity, yielding highly consistent results across sessions, observers, and display environments, including large-scale online studies. This approach reveals a stable global structure of heterochromatic brightness preserved across devices and viewing contexts. Using these data, we evaluate a broad range of candidate models. Luminance, radiance, and established color appearance models leave key systematic patterns unexplained. In contrast, simple nonlinear pooling rules, specifically taking the weighted maximum of the red, green, and blue channel values, provide a near-ceiling account of observed rankings. Neural recordings reveal a corresponding temporal dissociation: High-frequency responses track luminance, whereas low-frequency responses align with nonlinear predictions. Experiments with spectrally tunable illumination confirm the same pattern in spatially extended scenes. Together, these results establish a scalable framework for measuring heterochromatic brightness and identify a simple computational rule governing brightness under steady viewing.
GPT-4o mini: Non-social science research article
USP14 competitively binds to FBXW7 to stabilize MTDH and promotes metastasis and drug resistance of head and neck squamous cell carcinoma
Xueying Wang, Yang Zhou, Jiaqi Tan, Diekuo Zhang, Chao Liu, Juncheng Wang, Xin Zhang, Gangcai Zhu, Yong Liu
Full text
The development of metastasis marks an aggressive stage of head and neck squamous cell carcinoma (HNSCC) and is closely linked to unfavorable survival outcomes. While metadherin (MTDH) drives tumorigenesis, metastasis, and chemoresistance in HNSCC, its dysregulation mechanisms remain unclear. Here, we identify USP14 as a specific deubiquitinase that stabilizes MTDH. USP14-dependent deubiquitination of MTDH activates NF-ÎșB signaling, which drives epithelial–mesenchymal transition and supports cancer stem cells maintenance, ultimately strengthening HNSCC metastasis and chemoresistance. Mechanistically, we uncovered a competitive interaction: USP14 competes with the ubiquitin ligase FBXW7 for MTDH binding, preventing FBXW7-mediated degradation. Consequently, USP14 inhibition significantly mitigates aggressive phenotypes, an effect reversed by MTDH reintroduction. Clinical analysis confirms that MTDH and USP14 are overexpressed and positively correlated in metastatic HNSCC tissues. In conclusion, our study reveals a regulatory axis where USP14 competitively counteracts FBXW7 to stabilize MTDH, driving HNSCC progression. These findings provide preclinical evidence that targeting USP14 is a promising therapeutic strategy to overcome metastasis and chemoresistance in HNSCC.
GPT-4o mini: Non-social science research article
Myelination sustains axonal bioenergetics by storing and consuming oxygen for aerobic metabolism
Isabella Panfoli, Giovanni Candiano, Maurizio Bruschi
Full text
GPT-4o mini: Non-social science research article
Identification of potent inhibitors of JUN N-terminal kinases for treatment of endometriosis and associated pain
Chandrashekhar Madasu, Tirupataiah Sirupangi, Genesis J. Herrera, Kurt M. Bohren, Kiran L. Sharma, Zhi Tan, Hai Minh Ta, Fei Yuan, Murugesan Palaniappan, Caterina Clementi, Suni Tang, Anna Catherine Unser, Jennifer Wilkinson, Matthew B. Robers, Xiaoming Guan, Feng Li, Choel Kim, Banumathi Sankaran, Ramakrishna Kommagani, Srinivas Chamakuri, Damian W. Young, Piraye Y. Biem, Martin M. Matzuk, Stephen S. Palmer, Diana Monsivais
Full text
Endometriosis, defined as the ectopic growth of endometrial tissue outside of the uterine cavity, is an inflammatory and hormone-dependent disease that causes excruciating pelvic pain, infertility, and significantly decreases quality of life in affected patients. The JUN N-terminal kinases (JNKs) are a leading class of nonhormonal therapeutic targets that have been validated in preclinical models of endometriosis and in a Phase 1/2 clinical trial. Despite their therapeutic potential, JNK inhibitors with increased potency and specificity are needed to address the inflammatory pathology of endometriosis and to prevent disease progression. Leveraging a DNA-encoded chemical library collection of ~4 billion compounds, we identified lead inhibitor CDD-2428 and optimized derivatives, CDD-2728 and CDD-3013, with excellent binding affinity to JNK1-3 (K d = 0.12 to 3.7 nM), enhanced selectivity, metabolic stability, and cellular permeability. Crystallographic and biochemical studies confirmed that CDD-3013 exhibited superior kinase selectivity with improved efficacy compared to existing JNK inhibitors. In primary endometriosis cell models, CDD-2728 and CDD-3013 suppressed JNK-dependent inflammatory signaling, dampening pathways linked to pain, invasion, angiogenesis, and macrophage recruitment. In an endometriosis mouse model, both CDD-2728 and CDD-3013 reduced endometriotic lesion size, macrophage infiltration, and cellular proliferation, showing in vivo efficacy. When tested in a lipopolysaccharide-induced hyperalgesia model, CDD-2728 and CDD-3013 decreased markers of induced pain, as measured by changes in a dynamic weight bearing test and Grimace scores. These findings nominate CDD-2728 and CDD-3013 as potent, nonhormonal therapeutic candidates for endometriosis with broad anti-inflammatory and analgesic activity, addressing a critical unmet clinical need.
GPT-4o mini: Non-social science research article
The role of chloride ions in serotonin transport
Jiahui Huang, Annika Backer, Stacy Uchendu, Bethlehem Bekele, Chan Li, Qingyang Chen, Esam A. Orabi, Robyn Stix, Jasper D. Shide, Yuan-Wei Zhang, Gary Rudnick, Eva Hellsberg, Lucy R. Forrest
Full text
The human serotonin (5-HT + ) transporter SERT facilitates 5-HT + transport into cells by coupling it to Na + symport and K + antiport. Although extracellular Cl – is also essential for transport, Cl – cotransport has been disputed, raising questions about the role of Cl – ions and why they are required. We show that Cl – gradients do not impact 5-HT + accumulation, indicating that Cl – does not provide a driving force for uptake and arguing against stoichiometric Cl – symport. The presence of Cl – had only a small effect on Na + -mediated cytoplasmic pathway closure but markedly reduced the accessibility of residues in the extracellular pathway, consistent with modulation of the outward-facing states. Simulations illustrate that Cl – interacts strongly with a bound Na + ion and stabilizes helix packing on the extracellular side. We propose that Cl – acts as an essential architectural cofactor by enhancing Na + affinity and interactions between helices, thereby facilitating transport-related conformational transitions.
GPT-4o mini: Non-social science research article
Pelagic food web realignment supports resilient larvae of Southern Bluefin Tuna in a warming ocean
Michael R. Landry, RaĂșl Laiz-CarriĂłn, Estrella Malca, Rasmus Swalethorp, Moira DĂ©cima, JosĂ© M. Quintanilla, Ricardo Borrego-Santos, Claire H. Davies, Sven A. Kranz, Karen E. Selph, Michael R. Stukel, David Die, Lynnath E. Beckley, Barbara A. Muhling, Akihiro Shiroza, Lindsey E. Kim, Grace F. Cawley, Claudia Traboni, Kamran Walsh, Alejandro Jivanjee, Luke Matisons
Full text
Many of the oceans’ top predatory fishes at low to mid latitudes face an uncertain future as their vulnerable larvae deal with higher environmental temperature and reduced productivity associated with climate change. However, ocean ecosystem models that predict a general decline of zooplankton prey with warming and stratification hardly ever account for complexities in pelagic food webs that might make them resilient in providing food resources for larvae. We illustrate such complexities in comparing feeding interactions of larval Southern Bluefin Tuna (SBT) between two studies conducted 35 y apart in the same spawning region off northwest Australia. In the first (1987), SBT larvae fed and grew at low rates demonstrably limited by zooplankton prey. In the second (2022), feeding and growth were significantly higher despite substantially warmer conditions. The difference reflects a realignment in larval feeding preference from copepods to appendicularians, which allows a more direct and efficient energy transfer pathway from the microbially dominated food web base to higher-level consumers. These findings reset thinking on bluefin larvae feeding preferences, demonstrate high growth on an appendicularian diet up to 30 °C, and align with predictions of appendicularians being an environmentally selected zooplankton category in warming oligotrophic waters.
GPT-4o mini: Non-social science research article
Site-specific phosphorylation affects the structure and interactions of the Ycf1p R region
Sarah E. S. Quail, Sarah C. Bickers, Agatha Tymczak, Maya Michelle Eid, Voula Kanelis
Full text
Many ATP-binding cassette (ABC) proteins function in active transport of solutes across biological membranes. At minimum, ABC proteins contain two repeats of a transmembrane domain (TMD) and a nucleotide binding domain (NBD). In many ABC proteins, the TMD-NBD halves are connected by an intrinsically disordered linker that regulates the activity of the ABC protein through phosphorylation. These regulatory (R) regions are often invisible or at low-resolution in cryo-EM maps. Thus, information about how R region phosphorylation controls ABC transporter activity is missing. Using NMR spectroscopy, we discern the structural features and interactions of the R region from the yeast cadmium factor 1 protein (Ycf1p), a C subfamily ABC protein that is homologous to human multidrug resistance protein 1. Our data show that the entire R region possesses residual secondary structure that changes with phosphorylation, including for often-invisible R region segments. The data demonstrate R region interactions with NBD1 and also with NBD2. NBD/R region interactions depend on the phosphorylation state of the R region and on the nucleotide-bound and oligomeric states of the NBDs, indicating how R region interactions change during the transport cycle. Complementary biochemical studies show that R region phosphorylation affects the ATPase activity of the NBDs. Yeast viability assays highlight the importance of R region residual structure and interactions on Ycf1p activity. The structural, biochemical, and in vivo studies enhance our molecular-level understanding of how R region affects the transport cycle of Ycf1p and related ABC proteins.
GPT-4o mini: Non-social science research article
Paleomagnetic evidence for a nebular magnetic field from calcium-aluminum-rich inclusions
CauĂȘ S. Borlina, Benjamin P. Weiss, Xue-Ning Bai, Po-Yen Tung, Richard J. Harrison, Elias N. Mansbach, Nilanjan Chatterjee, François L. H. Tissot, Kevin D. McKeegan
Full text
The initial stage of planet formation is expected to take place in a nascent protoplanetary disk (PPD) accreting onto the protostar embedded in an infalling envelope. This stage is likely accompanied by the formation of high-condensation temperature solids resembling calcium-aluminum-rich inclusions (CAIs), the oldest known solar system solids. However, it is unknown whether magnetism and/or gravity dominantly drove accretion in the youngest evolutionary stages of PPDs and the solar nebula. Here we report paleomagnetic measurements of CAIs indicating that they record a nebular magnetic field of ∌150 to 600 ÎŒT. This intensity is consistent with magnetic fields playing a key role driving disk accretion while also heating the very inner disk to 10 3 K at the earliest stages of solar system formation.
GPT-4o mini: Non-social science research article
Reconciling strange metal transport in CeCoIn 5 through the difference of optical and cyclotron effective masses
Jingyuan Wang, Zhenisbek Tagay, Liyu Shi, Jiahao Liang, Nghiep Khoan Duong, Yi Wu, Pedro Manuel Trocado Vianez, Filip Ronning, Dwight G. Rickel, Darrell G. Schlom, Kyle M. Shen, Scott A. Crooker, N. P. Armitage
Full text
The strange metal behavior in cuprate superconductors—characterized by linear in temperature resistivity and anomalous Hall transport—stands in stark contrast to the expectation of conventional Fermi liquid (FL) theory. Remarkably, the similar transport behavior has also been observed in the heavy fermion metal CeCoIn 5 , whose d-wave superconducting ground state and strong antiferromagnetic fluctuations draw parallels to the cuprates. Here we have investigated the optical conductivity of the strange metal state of CeCoIn 5 over a wide magnetic field range using time-domain THz spectroscopy. Using unique high-field THz spectroscopy we have shown that the current relaxation rate scales approximately as T 2 , giving evidence for a hidden Fermi liquid state over a large field range. This result can be reconciled with linear in T resistivity with the realization that heavy quasiparticles have an optical mass that becomes very enhanced at low T . This optical mass contrasts with the mass that characterizes cyclotron motion, which does not suffer the same large temperature-dependent renormalization. Although by itself anomalous, this allows one to understand a number of other phenomena in CeCoIn 5 that have been taken to be signatures of strange metals, including the coexistence of a conventional T 2 dependence of the cotangent of the Hall angle with the linear in T resistivity, which with our observation also reflects FL-like physics.
GPT-4o mini: Non-social science research article
Mechanisms behind facilitation–competition transition along rainfall gradients
Oded Hollander, Yair Mau, Niv DeMalach
Full text
Woody cover is rapidly changing due to mortality, shrub encroachment, and afforestation, reshaping herbaceous communities and ecosystem functioning worldwide. Trees and shrubs often facilitate herb growth in dry sites but suppress it in wetter environments. Explanations for this facilitation-to-competition transition lack a clear link to resource competition theory, despite being a fundamental aspect of the broader Stress Gradient Hypothesis. While recent quantitative frameworks exist, explanations remain contested and have yet to reproduce the shift along a rainfall gradient from first principles. Here, we present a mechanistic framework consisting of two submodels: i) canopy shading, which reduces photosynthesis (competition) and evapotranspiration (facilitation), and ii) root effects, including water uptake (competition) and increased moisture via hydraulic redistribution (facilitation). We elucidate the conditions under which interactions shift from facilitation to competition. The models reproduce this reversal only when water is not the sole limiting factor at high rainfall or when woody density increases with precipitation. The two pathways leave distinct signatures: Canopy shading produces a hump-shaped pattern with maximum facilitation at intermediate stress, while the root pathway predicts a shift from positive to negative interactions as water availability increases. More generally, the reversal is robust across mechanisms and gradients: Enhanced infiltration can replace hydraulic redistribution, evaporative demand can replace rainfall, and combined canopy–root interactions preserve the transition. By translating a classic idea into a quantitative framework, this model enhances ecosystem management in a changing world.
GPT-4o mini: Non-social science research article
Rapid, HIF-1α-independent, response of VEGF secretion to decreased O 2 in mouse retina
Varun Kamat, Matthew K. Grumbine, Khang Bao, Lui Tsumura, Rayne Lim, Shari Wang, James Hermansson, John Kramlich, Laura J. den Hartigh, Jennifer R. Chao, James B. Hurley, Ian R. Sweet
Full text
Vascular endothelial growth factor-A (VEGF) is a critical determinant of retinopathy due to vascular complications. Its expression is chronically regulated by transcription factors notably hypoxia-inducible factor-1α (HIF-1α) in response to decreased availability of oxygen [O 2 ]. We considered whether there is a distinct rapid response component of VEGF secretion in response to low O 2 , faster than could be achieved by HIF-1α. To investigate this possibility, we measured real time responses of VEGF, lactate, and HIF-1α by retinas and other tissues to rapid and precise decreases in dissolved O 2. and showed that retinas, retinal pigment epithelium, and endothelial cells all can secrete VEGF within 5 min after a decrease in [O 2 ]. HIF-1α levels in retinas did not increase until 20 to 30 min after a decrease in dissolved [O 2 ]. Moreover, increased HIF-1α induced by the drug Roxadustat, did not stimulate VEGF secretion at atmospheric (21%) O 2 and a steady rate of VEGF secretion was sustained for over 120 min following elimination of HIF-1α and protein synthesis by exposure to the protein synthesis inhibitor cycloheximide. We then investigated the mechanism of VEGF release and found that VEGF was stored in the plasma membranes of retinas at 21% O 2 . These stores are depleted within 30 min once [O 2 ] is decreased. Taken together, these findings indicate that VEGF is constitutively made (under the influence of HIF-1α and other transcription factors) and stored within the retina, and rapid release occurs after a substantial decrease in available O 2 independent of HIF-1α.
GPT-4o mini: Non-social science research article
Cannabinoid tolerance relies on CB 1 receptor ubiquitination by NEDD4L
Alicia Álvaro-Blåzquez, Rui S. Rodrigues, Carlos Montero-Fernåndez, Marta Isasa, Astrid Cannich, Doriane Gisquet, Ignacio Rodríguez-Crespo, Luigi Bellocchio, Giovanni Marsicano, Carlos Costas-Insua, Manuel Guzmån
Full text
Cannabinoids, the active components of cannabis, exert numerous acute effects in the brain by engaging cannabinoid CB 1 receptors (CB 1 Rs). However, tolerance emerges rapidly after repeated drug exposure, undermining the efficacy of cannabinoid-based therapies and contributing to cannabis-associated adverse effects. Although the processes of CB 1 R short-term desensitization (i.e., receptor uncoupling and internalization) are well characterized, the mechanisms underlying CB 1 R long-term tolerance (i.e., downregulation of receptor protein levels) remain elusive. Here, we identify a ubiquitin-dependent pathway that couples CB 1 R activation to its proteasomal degradation. We show that cannabinoids engage a G q/11 -PLC-PKC signaling cascade that phosphorylates and activates the E3 ubiquitin ligase neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L), promoting its recruitment to CB 1 R and the ubiquitination of four specific lysine residues. This modification targets the receptor for proteasomal clearance, reducing neuronal CB 1 R abundance in vitro and in the mouse brain. Using molecular, pharmacological, and circuit-specific rescue approaches, we demonstrate that preventing CB 1 R ubiquitination stabilizes receptor levels and abolishes behavioral cannabinoid tolerance in mice without impairing acute drug responses. These findings reveal a molecular mechanism that controls CB 1 R stability and identify NEDD4L-mediated ubiquitination as a central driver of cannabinoid tolerance.
GPT-4o mini: Non-social science research article
Plasmodium thiamine pyrophosphokinase is essential for sporozoite formation and activation of an antiplasmodial thiamine analogue
Imam Fathoni, Ümit Y. Kina, Alex H. Y. Chan, Jiwon Lee, Terence C. S. Ho, Manuel Rauch, Peer Martin, Emily A. Meissner, Thomas Stach, Finian J. Leeper, Melanie Rug, Kai Matuschewski, Kevin J. Saliba
Full text
Oxythiamine, a thiamine analogue, inhibits Plasmodium falciparum proliferation by acting as an antimetabolite of vitamin B 1 . To elucidate in more detail its underlying mechanism of action, in vitro drug pressure was employed to generate oxythiamine-resistant P. falciparum lines. Whole-genome sequencing revealed that resistance was conferred by a single-point mutation in the thiamine pyrophosphokinase (TPK) gene. The mutated TPK has reduced activity, thereby likely limiting the conversion of oxythiamine into its active toxic form. To investigate the functional role of TPK across the parasite life cycle, a TPK -knockout line was generated in Plasmodium berghei . TPK -knockout parasites displayed a minor fitness cost during intraerythrocytic proliferation that could be overcome by infecting reticulocytes, but their sensitivity to oxythiamine was reduced fivefold in vivo, consistent with the hypothesis that activation of oxythiamine via TPK is essential for its antiplasmodial activity. In the Anopheles vector, TPK -knockout parasites produced a similar number of oocysts as wild-type parasites, but oocyst maturation was impaired and sporozoite formation was completely inhibited. These findings underscore an essential role for TPK in mediating the antiplasmodial activity of oxythiamine and reveal its critical function in sporogony within the mosquito, supporting its potential as a transmission-blocking target for antimalarial intervention.
GPT-4o mini: Non-social science research article
Structural basis of ligand recognition and gating in a heteromeric Deg-3/Des-2 nicotinic acetylcholine receptor
Yingjie Ning, Qiqi Jiang, Zizhuo Lu, Jie Yu, Jingpeng Ge
Full text
During evolution, nicotinic acetylcholine receptors (nAChRs) have diversified in subunit composition and ligand selectivity, enabling a conserved ion channel scaffold to support a broad range of signaling functions beyond classical synaptic transmission. Deg-3/Des-2 is a nematode-specific, calcium-permeable heteromeric α-type nicotinic receptor in sensory neurons to mediate chemosensation, nociception, and mechanotransduction, and represents a promising anthelmintic target. Here, we report cryo–electron microscopy structures of Deg-3/Des-2 in its apo, agonist-bound intermediate and agonist-bound open states. Deg-3/Des-2 adopts a 2Deg-3:3Des-2 stoichiometry. Five agonist molecules occupy intersubunit orthosteric sites, driving channel opening primarily through rotational rearrangements of the upper M2 helices that relieve a conserved hydrophobic gate and enable calcium permeation. We further identify a Deg-3–specific N-terminal helix that regulates desensitization and a negatively charged extracellular vestibular helix that governs calcium permeability. Together, these structures reveal how evolutionary tuning of ligand recognition, ion selectivity, and gating within a conserved nicotinic receptor framework.
GPT-4o mini: Non-social science research article
Convergent roles of GDF-15 in mechanotransduction, vascular disorganization, and immune suppression in melanoma
Yu-Chi Chen, Vishnu Sravan Bollu, Sina Kheirabadi, Kyle LaPenna, Arthur Berg, Pingnian He, Todd D. Schell, Amir Sheikhi, Erdem D. Tabdanov, Gavin P. Robertson
Full text
Melanoma, particularly in its advanced forms, remains one of the most lethal skin cancers, with limited effective treatments for both common cutaneous subtypes and rarer variants such as acral melanoma. The effects of the extracellular matrix (ECM) and other cancer-cell extrinsic processes on melanoma development remain underexplored. This study identifies growth differentiation factor-15 (GDF-15) as a mechanosensing-regulated driver of melanoma pathogenesis across melanoma types. GDF-15 is shown here to be mechanically induced by ECM rigidity and compressive forces occurring during metastatic progression, leading to significantly elevated levels in both cutaneous and acral melanoma cells. In this study, ECM rigidity was recapitulated using cell-adhesive gelatin methacryloyl (GelMA) hydrogel microparticles (microgels) with tunable stiffness, providing a biomimetic platform to investigate how mechanical cues in the tumor microenvironment regulate GDF-15 expression in melanoma. A previously unrecognized synergy between GDF-15 and inflammatory factors commonly present in tumors was identified and found to promote a disorganized, hyperpermeable vasculature, thereby facilitating tumor nutrient access and impeding effective immune cell infiltration. GDF-15 knockdown reduced the intratumoral hemorrhage phenotype, indicating a causal role. GDF-15 also functions by directly suppressing natural killer (NK) cell-mediated cytotoxicity, revealing a second cooperating mechanism of immune evasion. These effects position GDF-15 as a key node linking mechanical stress, co-operation with inflammatory factors, abnormal vascular development, and immune dysfunction, thereby converging on pathways and processes relevant to melanoma progression and treatment.
GPT-4o mini: Non-social science research article
Auxin-induced ARF transcription factor degradation defines tissue boundaries
Jeonghwan Ahn, Quan Yuan, Yi-Ning Ding, Yun-Ying Wang, Dan-Dan Yang, Yao Zhang, Feng Gao, Hong-Sen Hu, Qian Xu, Zhi-Cheng Hu, Xiaotong Qi, Hongqiang Yu, Limin Lu, Chao-Bin Li, Jie Cheng, Bao-Qing Ding, Chaoying He, Bo Xu, Quan Wang, Min Chen, Hongzhi Kong, Cao Xu, Xiaofeng Fang, Lars Østergaard, Yang Dong
Full text
How organs partition themselves into discrete domains with distinct functions is a fundamental question in biology. The gynoecium of flowering plants provides an excellent system to address this question. Here, we show that the boundary between the stigma and style at the gynoecium apex is established by the complementary distribution of the phytohormone auxin and the Auxin Response Factor (ARF), ETTIN (ETT). Mechanistically, auxin induces ETT protein destabilization via the ubiquitin–proteasome pathway. A short sequence motif within an intrinsically disordered region is required for this auxin-triggered degradation. Disruption of this motif leads to ectopic ETT accumulation at the gynoecium apex and consequently abolishes stigma-style boundary development. We further demonstrate that this previously unrecognized mode of auxin-induced ARF instability is evolutionarily conserved among ETT orthologs across angiosperms. In summary, this study reveals how graded auxin distribution affects ARF transcription factor activity, contributing to the establishment of the stigma-style boundary, ensuring correct gynoecium formation and reproductive success in flowering plants.
GPT-4o mini: Non-social science research article
Hidden global diversity and sampling gaps in Orthoptera insects revealed through distribution data
M. Celeste Scattolini, Andrés Lira-Noriega, Martina E. Pocco, Hernån L. Pereira, María Belén Cabrera, María Marta Cigliano
Full text
Insects are essential to terrestrial ecosystems but remain underrepresented in global biodiversity assessments. This macroecological study presents a global analysis of diversity patterns in Orthoptera (grasshoppers, locusts, crickets, and katydids), using over 830,000 georeferenced records, species distribution models, and environmental data. The analysis revealed hotspots of diversity and endemism in tropical and subtropical regions of Asia, South America, and Africa. Biome-level comparisons showed that moist tropical forests and Mediterranean regions harbor high richness and endemism of Ensifera, while Caelifera diversity is higher in grasslands and deserts. The two suborders exhibit contrasting biogeographic patterns: Ensifera shows a classic tropical diversity gradient, whereas Caelifera presents a bimodal pattern with wider species ranges. However, for both suborders, their high-diversity regions face rapid land-use change. By integrating biodiversity data with endemism, sampling gaps, and land-use pressures, the study produces an “emergency map” to guide urgent field surveys and conservation efforts. The work emphasizes the need to prioritize poorly studied yet biologically rich regions and highlights the importance of expert-curated databases like the Orthoptera Species File in biodiversity research and conservation planning.
GPT-4o mini: Non-social science research article
The fragility of splendid isolation: Imminent global threat for the world’s island life
Mark V. Lomolino
Full text
GPT-4o mini: Non-social science research article
A dominant mutation in tomato DNA POLYMERASE DELTA 1 causes geminivirus DNA replication catastrophe
Deri Gustian, Chen-Hsin Yu, Fuh-Jyh Jan, Wilhelm Gruissem
Full text
Geminiviruses pose a severe threat to grain and vegetable crops worldwide, often resulting in significant economic losses. In cultivated tomato ( Solanum lycopersicum ), Ty resistance alleles have been introduced from wild tomato relatives, providing partial to strong resistance to geminivirus infections. The Ty-6 resistance locus from Solanum chilense was previously mapped to chromosome 10. It was recently shown to contain a mutant allele of the DNA POLYMERASE DELTA 1 ( POLD1 ) gene that provides resistance to Tomato yellow leaf curl virus (TYLCV) infections. However, the resistance mechanism remained unknown. Here, we report another POLD1 allele at the Ty-6 locus of S. chilense with an E622D mutation in the catalytic site of the POLD1 protein. POLD1 E622D is maintained as a heterozygous dominant allele in S. chilense and the AVTO2225 breeding line. It provides full resistance to the severe TYLCV Thailand (TYLCTHV) strain. The E622D amino acid change does not alter the predicted structure of POLD1. Replication of the TYLCTHV genome in plants carrying the POLD1 E622D allele is severely compromised by a high frequency of mutations that accumulate in viral DNA, which results in nonfunctional proteins that are essential for continuous viral replication. Ectopically expressing the POLD1 E622D allele cDNA alone causes mutations in TYLCTHV genes in inoculated leaves. S. chilense and AVTO2225 plants carrying the POLD1 E622D allele mount a hypersensitive response after TYLCTHV infection, indicating that the defective virus genome cannot suppress the plant defense. The dominant POLD1 E622D allele is therefore an effective resistance gene that geminiviruses cannot overcome.
GPT-4o mini: Non-social science research article
Heme-binding protein CYB5D1 couples intraflagellar redox to calcium signaling for coordinated flagellar beating
Yiwen Lin, Lijuan Zhao, Gai Liu, Xuan Deng, Stephen M. King, Kaiyao Huang
Full text
Coordinated ciliary/flagellar beating requires precise spatiotemporal regulation of molecular motors such as dyneins, yet the molecular mechanisms governing ciliary synchrony remain poorly understood. Here, we demonstrate that a heme-binding axonemal protein CYB5D1 functions as a redox-sensitive switch that controls flagellar beating coordination by regulating Ca 2+ dynamics. Both the D58G point mutation, which abolishes heme-binding activity, and the complete loss of CYB5D1 lead to a reduction in the flagellar redox potential. More importantly, the hyperreductive intraflagellar redox shift in the cyb5d1 mutant increases cis -flagellar Ca 2+ spike frequency and amplitude, similar to reductive treatment of wild-type flagella, resulting in the loss of flagellar beating coordination. Interestingly, oxidative treatments induced synchronized Ca 2+ spikes across both cis - and trans -flagella of cyb5d1 and increased flagellar beating coordination. In addition, loss of CYB5D1 raised the intraflagellar Ca 2+ pool. These results indicate that CYB5D1 links redox sensing to Ca 2+ signaling in ciliary coordination and reveal how the two flagella of the same cell achieve synchronized beating through redox-gated Ca 2+ dynamics. Furthermore, CYB5D1 loss impairs gliding motility by dysregulating Ca 2+ spiking specifically in the leading flagellum, extending the redox-Ca 2+ regulatory axis to surface-associated flagellar behaviors. Given the evolutionary conservation of both CYB5D1 and the redox-Ca 2+ signaling axis, this mechanism likely regulates ciliary function across eukaryotes, with implications for understanding ciliopathies and respiratory diseases.
GPT-4o mini: Non-social science research article
Structural basis of GSDME pore formation and its regulation by S-palmitoylation
Gang Du, Julian F. Ehrmann, Judy Lieberman, Hao Wu
Full text
Pyroptosis is defined as gasdermin-mediated lytic programmed cell death. Gasdermin E (GSDME), a substrate of the apoptotic caspase-3, can convert apoptosis into pyroptosis, with critical roles in antitumor immunity and chemotherapy-induced tissue damage. Despite its importance, the structural mechanism of GSDME pore formation and its regulation by posttranslational modifications remain largely unknown. Here, we present the cryo-electron microscopy (cryo-EM) structure at 3.16 Å resolution of the human GSDME N-terminal (NT) pore using proteins expressed from mammalian cells. The structure reveals a GSDME-NT pore assembled mainly as a 28-subunit homo-oligomer, and a dramatic conformational rearrangement from the autoinhibited state, with refolding of the two ÎČ-hairpins in each monomer to form a membrane-spanning ÎČ-barrel with an acidic conduit. Unexpectedly, we identify endogenous S-palmitoylation of C45, C168, and C180, required for membrane binding and pore formation. In addition, extra cryo-EM densities are visible adjacent to the C45 side chain, potentially corresponding to the flexibly linked palmitate chain. Structure-guided mutagenesis demonstrates that these palmitoylation sites synergistically control pore formation. The structure served as a molecular blueprint for analyzing cancer-associated mutations, known to disrupt GSDME function. These mutations cluster at functional hotspots in the oligomerization interfaces, membrane-contact regions, and the ÎČ-barrel, where they disrupt pore integrity. Collectively, our findings establish palmitoylation as an obligatory licensing step for membrane binding and pore formation, provide structural visualization of a palmitoylated gasdermin, and reveal how cancer-associated mutations impair pyroptotic function. This structure and these insights will be useful for developing strategies that target GSDME to treat cancer and inflammatory disease.
GPT-4o mini: Non-social science research article
Grassland destruction causes shifts in plant traits that persist during recovery
Ashish N. Nerlekar, André Giles, Norbert Hölzel, Mårio Cava, Julien Piqueray, Natashi Pilon, Brenda Molano-Flores, Megha Ojha, Jin Hua Li, Gregory Mahy, Omofomwan Kingsley Osazuwa, Emma Ladouceur, Thierry Dutoit, Jutta Stadler, Daniela Boecker, Rafael S. Oliveira, Xi Zhou, Renaud Jaunatre, Klåra Ƙehounkovå, Wenjin Li, Deepak Barua, Michal Håjek, Soizig Le Stradic, Frances Siebert, Eszter Ruprecht, Ellen I. Damschen, Elise Buisson, Karel Prach, Forest Isbell, John L. Orrock, Giselda Durigan, Lauren L. Sullivan, Lars A. Brudvig
Full text
Old-growth grasslands assemble over millennia and support high biodiversity and many ecosystem services, but continue to undergo widespread destruction for production of crops, timber, and minerals. How biodiversity recovers after grassland destruction and the functional consequences of this recovery can be informed by plant functional traits—i.e., morpho-physiological features that influence growth, survival, and reproduction. Yet we lack understanding of how functional traits differ between old-growth and secondary (i.e., recovering) grassland plant species at the global scale, hindering understanding of community assembly processes that transcend geographical regions. Addressing this gap, we synthesized trait data for 742 plant species from 24 studies across six continents to understand how plant species indicative of old-growth and secondary grasslands compare in their traits. Compared to old-growth grasslands, plants indicative of secondary grasslands were taller and had leaves with more nitrogen content, higher specific leaf area, and lower dry-matter content. Notably, these trait differences that make old-growth grassland plants more resource conservative and secondary grassland plants more resource acquisitive persisted over a century. Taken together, these findings help to explain why many secondary grasslands support altered plant communities for decades to centuries and emphasize the importance of old-growth grassland conservation in the light of the unique plant forms and functions they support. Persistent trait shifts associated with grassland destruction could accelerate nutrient cycling, and our findings provide guidance for recovering old-growth grassland biodiversity through ecological restoration.
GPT-4o mini: Non-social science research article
Inner ear deficits complicate interpretation of depression-like behaviors in Gpr156 mutant mice
Basile Tarchini, Ruth Anne Eatock, Katie S. Kindt, Cesare Orlandi, Kathleen E. Cullen
Full text
GPT-4o mini: Non-social science research article
Loss of Sox10 prevents tumor initiation in vivo and induces luminal-to-basal reprogramming in Neu+ tumor cells
Brennan Garland, Samuel Delisle, John Abou-Hamad, Christiano de Souza, Riana Zuccarini, David P. Cook, Rebecca C. Auer, Luc A. Sabourin
Full text
The SRY-HMG-Box transcription factor SOX10 plays a critical role in neural crest development, but its function in epithelial tumorigenesis remains unclear. Here, we identify SOX10 as a key regulator of tumor-initiating activity in Neu-driven mammary cancers. Genetic ablation of Sox10 in the luminal compartment of MMTV-Neu (NIC) mice resulted in delayed but normal mammary gland development. Sox10 deletion resulted in a reduction in mammary progenitors and a complete loss of tumor initiation in Sox10-deficient luminal cells. CRISPR/Cas9-mediated Sox10 inactivation in Neu-transformed tumor cells led to diminished self-renewal in mammosphere assays, markedly impaired growth in orthotopic transplant models and profoundly reduced lung colonization following tail vein injection, suggesting a depletion of cancer stem cell activity. Transcriptomic profiling revealed that Sox10-deficiency in Neu+ tumor cells induces a luminal-to-basal/mesenchymal-like shift and the downregulation of several genes associated with genetic networks regulating stemness. Collectively, these findings demonstrate that Sox10 is required for a permissive luminal cell state for Neu-driven tumor initiation and that it is critical for cancer stem cell activity and the establishment of metastases.
GPT-4o mini: Non-social science research article
A cloaked glutamate decarboxylase sustains the GABA shunt in Mycobacterium tuberculosis
H. Minh Thai, Debbie M. Hunt, Yugen Miyahara, Manisha Priya, Htin L. Aung, Rémi Zallot, Luiz Pedro S. de Carvalho
Full text
Despite the exponential growth in genome sequencing, the functional annotation of genes, particularly the discovery of novel enzymatic activities, remains a formidable challenge. This gap is exacerbated by annotation biases that propagate assumptions about enzyme function across homologous sequences. Here, we report the identification of an unannotated enzymatic activity within a presumed well-characterized enzyme family. The gene rv2531 c, under strong purifying selection across Mycobacterium tuberculosis strains, has been annotated as a member of the lysine-ornithine-arginine (KOR) decarboxylase superfamily, which includes over 26,000 sequences. Contrary to this annotation, we show that Rv2531c does not decarboxylate KOR substrates. Instead, using an integrative approach combining bioinformatics, microbiology, metabolomics, and enzymology, we demonstrate that Rv2531c is a L-glutamate decarboxylase that sustains carbon flux through the Îł-aminobutyric acid shunt in M. tuberculosis . This newly identified subfamily of enzymes is conserved across Bacteria, Archaea, and Eukarya and exhibits distinct structural and kinetic features, including an additional domain, hysteresis, and strong positive cooperativity. These characteristics differentiate it from canonical, enterobacterial KOR decarboxylases. More broadly, our findings challenge the narrow substrate and functional scope traditionally assigned to the KOR-DC superfamily. We propose that many members of this large and diverse enzyme family catalyze distinct reactions and participate in previously unrecognized metabolic pathways, revealing a broader and more nuanced role for pyridoxal 5â€Č-phosphate-dependent enzymes in microbial physiology and evolution.
GPT-4o mini: Non-social science research article
ST6GAL1-mediated sialyl linkage switching drives cancer-promoting α2,6-sialo-protrusions radiating from anti-inflammatory TAMs
Priya Dipta, Naaz Bansal, Arthur Chien, Zeynep Sumer-Bayraktar, Hironoshin Onizuka, Daisuke Kasugai, Dominique Marando, Merrina Anugraham, Seong Beom Ahn, Daniel Kolarich, Boaz Tirosh, Rebeca Kawahara, Arun Everest-Dass, Morten Thaysen-Andersen
Full text
Tumor-associated macrophages (TAMs) are functionally diverse effector cells in the tumor microenvironment (TME). Pro- and anti-inflammatory TAMs are central to cancer progression by shaping inflammation and immune homeostasis, but it remains unknown if polarization-induced remodeling of the TAM glycocalyx critical for cellular communication and interactions occurs within the TME. Taking a systems glycobiology approach, we first used cell surface-focused glycomics and lectin flow cytometry of ex vivo polarized monocyte-derived macrophages to demonstrate profound sialyl linkage switching in proinflammatory (α2,3-sialo-favored) and anti-inflammatory (α2,6-sialo-dominant) macrophages. ST6GAL1 catalyzing α2,6-sialylation was found to be elevated in anti-inflammatory compared to proinflammatory macrophages, suggesting that this glycoenzyme facilitates sialyl linkage switching, which was supported by ST6GAL1 silencing. Sambucus nigra agglutinin (SNA)-focused lectin cytochemistry of anti-inflammatory macrophages revealed dense networks of dynamic α2,6-sialylated protein-based protrusions forming interconnecting extracellular structures that were absent in proinflammatory macrophages. Temporal ST6GAL1 suppression in anti-inflammatory macrophages disintegrated the cellular protrusions as evidenced by SNA and biotin fluorescence microscopy. Moreover, live cell recordings of anti-inflammatory macrophages cultured with and without colorectal cancer (CRC) cells showed reduced macrophage motility, attenuated intermacrophage and macrophage–CRC cell interactions and diminished CRC cell proliferation upon ST6GAL1 suppression indicating functional roles of the sialo-protrusions. Notably, ST6GAL1 silencing in anti-inflammatory macrophages promoted transition toward proinflammatory-like phenotypes, as supported by altered morphology, phagocytotic capacity, and Siglec and cytokine expression. Finally, sialyl linkage switching was recapitulated in pro- and anti-inflammatory TAMs in tumor tissues of patients with advanced CRC. We report on the mechanistic basis for and functional consequences of glycocalyx remodeling accompanying TAM polarization.
GPT-4o mini: Non-social science research article
SET7-mediated methylation of IRF3 at lysine 98 attenuates antiviral innate immunity
Hongyan Deng, Xueyi Sun, Huangyuan Zha, Zixuan Wang, Jinhua Tang, Xiaoyun Chen, Chunchun Zhu, Jiale Hua, Wen Liu, Shuke Jia, Yiman Luo, Yuhan Xiang, Wenhua Li, Xing Liu, Wuhan Xiao
Full text
SET7 belongs to the SET domain (SETD) methyltransferase family, which catalyzes the monomethylation of lysine residues in histones and nonhistone proteins. This process can either enhance or suppress gene activation. Interferon regulatory factor 3 (IRF3) is a key transcription factor in the type I interferon (IFN) signaling pathway. This pathway is controlled by multiple posttranslational modifications that finely tune IRF3’s function. Here, we identify SET7 as a negative regulator of IRF3. SET7 interacts with IRF3 and catalyzes the monomethylation of IRF3 at lysine 98. This modification decreases IRF3 phosphorylation, dimerization, and subsequent nuclear translocation, thereby inhibiting the production of downstream type I interferons. Furthermore, zebrafish lacking set7 , as well as those treated with the inhibitor (R)-PFI-2, exhibits greater resistance to viral infection. Set7 -deficient mice also exhibit greater resistance to RNA and DNA viral infections. Our findings reveal a role for SET7 in regulating antiviral innate immunity and provide insight into the IRF3 monomethylation that affects its activation.
GPT-4o mini: Non-social science research article
A spinoreticular pathway mediates nocifensive responses to noxious mechanical stimuli
Yuan Liu, Qing Li, Jun-Kai Lin, Yifei Han, Xiaoyu Yang, Zining Xu, Wanqiu Zhou, Yan-Gang Sun, Yan-Nong Dou
Full text
Spinal projection neurons (SPNs) relay somatosensory information to the brain, yet how molecularly defined SPN subsets transmit noxious mechanical signals to drive nocifensive behaviors remains unclear. Here, we identify Sncg -expressing SPNs ( Sncg + SPNs) that convey noxious mechanical signals through a spinoreticular ascending pathway. Using intersectional genetics, anatomical tracing, and pathway-specific manipulations in mice, we show that Sncg + SPNs project predominantly to the parabrachial nucleus and the lateral reticular nucleus (LRN). Functional analyses reveal that Sncg + spinoreticular pathway transmits noxious mechanical information. LRN neurons receiving Sncg + spinal input are required for nocifensive behaviors elicited by noxious mechanical stimulation and contribute to mechanical allodynia of neuropathic pain. Monosynaptic tracing identifies local interneurons innervating Sncg + SPNs, providing a substrate for spinal gating of ascending mechanical signals. These findings highlight a spinoreticular circuit involving the LRN that is essential for nocifensive behaviors to noxious mechanical stimuli.
GPT-4o mini: Non-social science research article
The dual-function enzyme Pp LipO protects polar marine bacteria from phospholipid peroxidation
Yu-Zhong Zhang, Wen-Xin Jiang, Xiang-Ming Zhao, Jie Hao, Yao Lu, Chao Gao, Chun-Yang Li, Qi-Long Qin, Xiu-Lan Chen, Yin Chen, Ping-Yi Li
Full text
Membrane phospholipid peroxidation is a deleterious process in which reactive oxygen species (ROS) attack unsaturated fatty acids embedded in cell membranes, generating phospholipid hydroperoxides and triggering structural damage that can ultimately lead to cell death. While mammalian strategies to mitigate peroxidation, primarily through the combined activities of phospholipase A 2 (PLA 2 ) and subsequent reduction of resultant fatty acid hydroperoxides with glutathione peroxidases/peroxiredoxins have been well characterized for more than two decades, mechanisms by which prokaryotes contend with this oxidative challenge remain poorly understood. Here, we report a phospholipid hydroperoxide elimination strategy mediated by the bifunctional enzyme Pp LipO from the Antarctic sea-ice bacterium Pseudoalteromonas prydzensis . This enzyme comprises an N-terminal lipase domain and a C-terminal lipoyl peroxidase domain. Through synergistic action of these domains, Pp LipO first hydrolyzes ROS-induced phospholipid hydroperoxides into fatty acid hydroperoxides via its lipase domain, then catalyzes their reduction to hydroxy fatty acids via the peroxidase domain. Comprehensive phylogenetic and structural analyses of the C-terminal peroxidase domain revealed its unique position within a distinct clade of the Ohr/OsmC family, known for their roles in organic hydroperoxide detoxification. Functional studies of Pp LipO homologs in other marine bacteria, combined with metagenomic surveys, suggest that this strategy is widespread in global oceans, particular among polar marine bacteria. Altogether, our findings identify a prokaryotic phospholipid peroxidation repair mechanism that parallels the mammalian PLA 2 - peroxidase system, expanding our understanding of oxidative stress response across domains of life.
GPT-4o mini: Non-social science research article
Major role for internal variability in tropical Pacific warming pattern over satellite era
Shang-Ping Xie, Ayumu Miyamoto, Qihua Peng, Matthew T. Luongo
Full text
Home to El Niño, the tropical Pacific is a key player in the global climate system. While most of the planet has warmed during the satellite era of 1982–2024, the eastern tropical Pacific surface has mysteriously cooled. What is troubling is that fully coupled global climate models mostly fail to simulate this distinctive pattern. By replacing wind stress applied to the ocean with observations, here we show that climate models successfully reproduce the La Niña-like (LN) trend pattern over the satellite era as well as the opposite decadal transition observed during the 1970s. Detailed analysis reveals that the LN (El Niño-like) surface temperature pattern is associated with a multidecadal intensification (slowdown) of the trade winds and deepened (shoaled) thermocline in the western equatorial Pacific. Averaging out cyclic internal variability, longer-term trends from the 1950s are in broad agreement with the radiatively forced response in the same models, with much reduced wind and ocean temperature anomalies in the equatorial Pacific compared to those during the satellite era. These results indicate that unforced internal variability largely explains the satellite-era tropical Pacific change. As such, the LN pattern is expected to wane as tropical Pacific decadal variability transitions from its current negative phase, causing worldwide shifts in rainfall, tropical cyclones, and ocean-atmospheric circulations.
GPT-4o mini: Non-social science research article
Neuronal overexpression of Kcnn1 in A53T α-synuclein mice suppresses phospho-serine 129 α-synuclein formation and doubles survival time
Maria Nagy, Wayne A. Fenton, Arthur L. Horwich
Full text
Synucleinopathies, including idiopathic Parkinson’s Disease, are driven by misfolding and aggregation of the 140 residue α-synuclein protein that plays a role in presynaptic vesicle regulation. We describe effects of a modifier, neuronal overexpression of the mouse calcium-activated potassium channel subunit Kcnn1, on a mouse model in which transgenic Thy1.2-driven human A53T α-synuclein directs fully penetrant lethal motor disease. Kcnn1 overexpression increased median survival of these mice from 8.5 to 18 mo, associated with an altered presentation from rapidly progressive dystonic-like behavior of the limbs to a later-onset (12 to 16 mo) and slowly progressive lower limb clasping when lifted by the tail. At the tissue level, accretion of disease-associated phospho-serine 129 α-synuclein was prevented by overexpression of Thy1.2-driven Kcnn1 in many brain regions/spinal cord, where phospho-serine 129 α-synuclein copiously accreted in A53T mice at endstage. The action of blocking production of phospho-serine 129 α-synuclein was also observed in adult A53T mice injected presymptomatically with an AAV9 scCMV-Kcnn1 virus into the right superior colliculus. At endstage ~2 mo later, the right superior colliculus exhibited overexpression of Kcnn1 and showed essentially no phospho-serine 129 α-synuclein, whereas the uninjected left superior colliculus exhibited copious phospho-serine 129 α-synuclein. The neuroprotective action of Kcnn1 overexpression remains to be fully resolved, but the channel protein subunit, targeted to the ER membrane, has been shown to induce an ER stress response. This response, which may activate autophagy, along with potential channel formation, may diminish the rate of formation or lifetime of neurotoxic forms of A53T α-synuclein.
GPT-4o mini: Non-social science research article
Soil management practices shape the abundance, diversity, and spread of antimicrobial resistance
Colette A. Nickodem, Patricia Q. Tran, Eric Neeno-Eckwall, Naing Naing, Gregg R. Sanford, Erin M. Silva, Jessica L. Hite
Full text
Agricultural soils are critical hotspots of antimicrobial resistance genes (ARGs). Yet, the environmental factors shaping these reservoirs and the hazards they pose to humans and livestock remain poorly understood. Because management practices introduce antibiotics, heavy metals, and nonantibiotic biocides, they can rapidly select for resistance. Most studies have examined components of management practices in isolation, overlooking the multiple stressors of modern industrial agriculture. Here, we used a large-scale field experiment to examine how multiple stressors from soil and crop management interact to shape antimicrobial resistance. We combined shotgun metagenomics, phylogenomics, and risk-score analyses to quantify the diversity of ARGs, mobile genetic elements (MGEs), and the transmission potential of drug-resistant pathogens. Relative to other management systems, intensive, chemically reliant monoculture systems, typical of the US Corn Belt, create strong selective pressures promoting more abundant and diverse ARGs and MGEs. These systems therefore carry greater potential to transmit ARGs, including those with relevance to both livestock and public health such as tetA and bla PAM , likely mediated by integration and excision. In contrast, less-intensive, lower-input systems with diverse crop rotations maintained resistomes with lower abundance, diversity, and transmission potential. Our results suggest that these patterns could arise due to the divergent effects of management practices on overall soil microbial diversity, an ecological barrier that can suppress ARGs. This study highlights the need to understand the combined stressors of agricultural practices, beyond antimicrobial use, to design effective strategies to mitigate antimicrobial resistance.
GPT-4o mini: Non-social science research article
Enterochromaffin cells as a cellular integration hub for cooperative microbial signaling to modulate gut serotonin and motility
Yang Xiao, Tijs Louwies, Ruben A. T. Mars, Lisa M. Till, Yash Gupta, Arnaldo Mercado-Perez, Aditya V. Bhagwate, Shreya S. Bellampalli, Alejandro Stark Quiroz, Prabhjot K. Sekhon, Vaidhvi Singh, Rongfang Liu, Laura H. Heitman, Dennis Tienter, Michael A. Thompson, Kimberlee F. Kossick, Eugene W. Krueger, Krishna R. Kalari, Kaitlyn R. Hawkins, Jeong-Heon Lee, Brian S. Edwards, Daan van der Es, Constanza Alcaino, Julia L. E. Willett, Preedajit Wongkrasant, Chun-Jun Guo, Y. S. Prakash, Brooke R. Druliner, Tamas Ordog, Gianrico Farrugia, Arthur Beyder, Kristen M. Smith-Edwards, Purna C. Kashyap
Full text
The intestinal epithelium is exposed to diverse combinations of microbiota-derived compounds; however, the mechanisms by which the host integrates these signals remain poorly defined. Studying two highly abundant microbial metabolites, we identified the purine metabolite hypoxanthine as an effector metabolite that directly drives signaling and the short-chain fatty acid butyrate as a regulatory metabolite that conditions host responsiveness. Specifically, hypoxanthine activates the adenosine A1 receptor–TRPC4 axis in enterochromaffin (EC) cells, triggering calcium influx and serotonin release resulting in accelerated gastrointestinal transit locally and increased platelet activation systemically. In contrast, butyrate epigenetically upregulates specific G protein–coupled receptors and ion channels to enhance response to hypoxanthine and the neurotransmitters norepinephrine and dopamine. These findings define a cooperative signaling framework and highlight the role of EC cells as a distinct epithelial signaling hub that senses and integrates microbial metabolite signals to drive physiological responses. Our findings provide a mechanistic foundation for therapeutic strategies that leverage combinatorial microbial signaling.
GPT-4o mini: Non-social science research article
Barcoded mutant library enables high-throughput functional genomics in a filamentous fungus
Lori B. Huberman, José M. Villalobos-Escobedo, Jeffrey M. Skerker, Ran Shi, Adriana M. Rico-Ramírez, Catharine A. Adams, Adam P. Arkin, Adam M. Deutschbauer, N. Louise Glass
Full text
Advances in sequencing technology enabling rapid and inexpensive whole-genome sequencing highlight how few genes are functionally characterized. This problem is particularly acute in filamentous fungi, where even in the best studied organisms upward of half of genes are poorly characterized or unannotated. High-throughput tools to identify gene function exist for single-celled organisms, like yeast and bacteria. However, filamentous fungi present challenges to high-throughput gene characterization, including low transformation efficiency and multinucleate cells. Filamentous fungi are critical components of nutrient cycling in ecosystems, form symbioses with plants that improve nutrient uptake, and are devastating human, plant, and animal pathogens causing millions of deaths and substantial crop loss each year. Thus, it is critical to overcome challenges to rapid gene characterization in filamentous fungi. We generated a library of hundreds of millions of uniquely barcoded plasmids containing a broad host-range drug resistance marker for ectopic insertion into filamentous fungal genomes by Agrobacterium tumefaciens . We then optimized A. tumefaciens mediated transformation of the biocontrol agent Trichoderma atroviride and made an insertional mutagenesis library containing 83,311 barcoded insertions, disrupting 5,331 of 11,863 predicted genes. This library enables high-throughput screens to rapidly connect genotype to phenotype. Quantifying relative barcode abundance in the pooled library before and after exposure to experimental conditions identified candidate genes and recovered known pathway components in amino acid biosynthetic, fructose utilization, and xylose utilization pathways. This resource establishes a scalable platform for high-throughput functional genomics in filamentous fungi, enabling investigations of fungal biology to improve medical outcomes, biotechnology, and sustainable agriculture.
GPT-4o mini: Non-social science research article
Hydrogen-ready infrastructure risks new carbon lock-in
Hongfang Lu, Tong Guo, Zhenhua Rui, Y. Frank Cheng
Full text
GPT-4o mini: Non-social science research article
A human pluripotent stem cell triculture platform to elucidate microglial regulation of retinal ganglion cells in neuroinflammation
Jade Harkin, Cåtia Gomes, Reham Afify, Shruti V. Patil, Shelby M. Hetzer, Kaylee D. Tutrow, Kiersten H. Peña, Aaron Baker, Sailee S. Lavekar, Kang-Chieh Huang, Jason S. Meyer
Full text
Optic neuropathies, including glaucoma, are characterized by the progressive degeneration of retinal ganglion cells (RGCs), ultimately leading to irreversible vision loss. Increasing evidence implicates microglia, the resident immune cells of the central nervous system, as key modulators of RGC health and disease progression. However, the precise mechanisms by which microglia influence RGCs remain poorly understood, particularly in the human context. In this study, we established human pluripotent stem cell-derived coculture systems incorporating microglia, astrocytes, and RGCs to explore how microglia shape RGC growth and maturation under physiological conditions. We first examined the impact of homeostatic microglia on RGCs in both coculture and triculture systems, revealing distinct influences of cell types in coculture compared to when they were grown individually. We then modeled inflammatory states by activating microglia with lipopolysaccharide and evaluated their effects on RGCs both directly and in the context of astrocyte coculture. This stepwise, reductionist approach enabled us to dissect the cellular interactions driving RGC vulnerability in inflammatory conditions relevant to optic neuropathies. Our findings provide insight into the complex neuroimmune landscape that underlies RGC degeneration and identify key pathways that may serve as therapeutic targets across a range of optic nerve diseases.
GPT-4o mini: Non-social science research article
Cross-species identification of conserved and divergent locomotor kinematic strategies using AutoGaitA
Mahan Hosseini, Ines Klein, Veronika Wunderle, Moritz Haustein, Carolin Semmler, Ann-Kathrin Kramer, Marianna Tolve, Vlad Mardare, Ana Galvao, Taylan D. Kuzu, Christian Grefkes, Tatiana Korotkova, Ansgar BĂŒschges, Gereon R. Fink, Peter H. Weiss, Silvia Daun, Graziana Gatto
Full text
Distinct behaviors require the nervous system to execute specialized motor programs, each characterized by unique patterns of body muscle coordination. Whether the execution and adaptation of these programs follow conserved principles across species and perturbations remains unclear. To compare motor programs across species, perturbations, and behaviors, we developed the Python toolbox Automated Gait Analysis (AutoGaitA). Using AutoGaitA and inferring from kinematics, we found that locomotor programs in flies, mice, and humans rely on diverse mechanisms to generate limb propulsive strength, but employ a similar distal-to-proximal gradient of joint movement velocities. In addition, we showed that aging induces a loss of propulsive strength in all species while preserving the velocity gradient. Furthermore, we observed that in mice, locomotor programs adapt as an integrated function of concomitant perturbations, namely aging and task difficulty. Taken together, using our newly developed versatile quantitative framework AutoGaitA, we began to reveal the conserved and divergent mechanisms underlying the execution of locomotor programs in physiological and perturbed states.
GPT-4o mini: Non-social science research article
Auditory ecology of sound localization: Hunting bats maximize forward sensitivity at the expense of interaural location cues
James A. Traer
Full text
GPT-4o mini: Non-social science research article
QnAs with Catherine L. Johnson
Sandeep Ravindran
Full text
GPT-4o mini: Non-social science research article
YBX1 regulates RNA polymerase III transcripts to prevent inflammation
Tania I. Strilets, Sarah E. Dremel, Mariano A. Garcia-Blanco
Full text
Tolerance of endogenous nucleic acids is crucial for cellular homeostasis and when perturbed can lead to immune dysregulation. RNA-binding proteins (RBPs) bind, modify, and compartmentalize endogenous RNAs to prevent their recognition by the innate immune system. We found that loss of a highly abundant RBP, the cold shock domain containing Y-box binding protein 1 (YBX1), results in the spontaneous induction of an IL6/STAT3 inflammatory response and the upregulation of interferon-stimulated genes. A meta-analysis of other studies reveals that the depletion of YBX1 orthologs and paralogs results in a similar proinflammatory gene signature, suggesting a conserved role of Y-box proteins in maintaining innate immune homeostasis. Among RNAs that interact with YBX1, we tested whether endogenous RNA polymerase III (RNAP III) transcripts stimulate innate immune signaling when YBX1 is depleted. We demonstrate that the inflammatory responses induced by the loss of YBX1 are abrogated by inhibiting RNAP III transcription and RIG-I signaling. Hence, we hypothesize that by regulating RNAP III transcripts, YBX1 prevents their recognition by the innate immune system, uncovering a role of this RBP in maintaining cellular homeostasis and tolerance to endogenous RNAs. The conservation of this phenotype across YBX1 orthologs and paralogs argues that RNA shielding by cold shock domain proteins represents an evolutionarily conserved solution to the problem of endogenous RNA immunogenicity.
GPT-4o mini: Non-social science research article
Shifting gears to power human walking
Jack A. Martin, Lauren Welte, Keith A. Knurr, Darryl G. Thelen
Full text
The musculoskeletal system features an abundance of functionally similar muscles, yet the performance benefits of this apparent redundancy remain unclear. Here, we show that muscles with similar function, but distinct moment arms, facilitate a dynamic gear-shifting mechanism in walking. Ankle power generation is shown to transition from large (triceps surae) to small (posterior tibialis, peroneals, and extrinsic toe flexors) moment arm muscles as joint velocity increases during pushoff. Computational models reveal that the sequential power phasing emerges naturally from muscle-tendon dynamics given the underlying differences in muscle geometry and architecture. Tendon kinetic measures during walking align with the model predictions and reveal that small plantarflexors contribute substantially more to powering human walking than previously recognized. These findings provide insights into the functional role of muscle redundancy, and suggest a fundamental principle governing the coordinated recruitment of synergistic muscles in locomotion.
GPT-4o mini: Non-social science research article
Ank3 loss in adult forebrain excitatory neurons disrupts behavior, neuronal activity, membrane proteome, and myelination
Sehyoun Yoon, Marc Dos Santos, Natalia Khalatyan, Jeffrey N. Savas, Peter Penzes
Full text
ANK3 , encoding the scaffolding protein ankyrin-G, is a major risk gene for bipolar disorder and schizophrenia, but its cellular and circuit-level mechanisms remain poorly defined. Here, we demonstrate that deletion of Ank3 in forebrain excitatory neurons-either prenatally ( Ank3 –/ − :Emx1-Cre ) or in adolescence ( Ank3 –/ – :CaMKIIα-Cre ) leads to convergent behavioral phenotypes in adulthood, including hyperactivity, reduced anxiety-like behavior, and decreased depression-like responses. Calcium imaging in cultured neurons and acute brain slices revealed that ankyrin-G loss reduces both spontaneous and evoked neuronal activity. Quantitative proteomic profiling of membrane-enriched cortical fractions uncovered widespread remodeling of the synaptic proteome, including upregulation of the kinase Taok2 and unexpected downregulation of myelin basic protein (Mbp), a structural component of oligodendrocyte-derived myelin. Importantly, chronic lithium treatment, known to reverse behavioral abnormalities in Ank3 -deficient mice, also restored Mbp expression. Together, our findings identify ankyrin-G as a molecular bridge between excitatory neuronal activity, synaptic structure, and myelin-associated protein expression, revealing a pathway by which ANK3 variants may contribute to neuropsychiatric disease.
GPT-4o mini: Non-social science research article
SIRT2 deacylase modulators control B cell metabolic reprogramming in EBV infection and mitogenic activation
Kaeden K. Hill, Ashley P. Barry, Nicolas M. Reinoso-Vizcaino, Lauren E. Haynes, Emmanuela N. Bonglack, Davis F. Ferreira, Sara E. Miller, Matthew D. Hirschey, Lillian W. Chiang, Stacy Remiszewski, Micah A. Luftig
Full text
Sirtuin-2 (SIRT2) is a cellular deacylase, regulating cell cycle progression and metabolic homeostasis. Recently, SIRT2 has emerged as a target with both anticancer and antiviral potential. However, the role and targetability of SIRT2 in viral-driven cancers remains unexplored. Epstein–Barr virus (EBV) is a ubiquitous herpesvirus with oncogenic potential that establishes latency in B lymphocytes and is typically controlled by a robust T cell immune response. In settings that compromise this response, such as immune suppression following transplant, EBV can cause B cell lymphomas. With broad immunosuppression and varying response rates limiting the effectiveness of existing lymphoma therapeutics, new strategies are necessary. Here, we report that SIRT2-selective compounds block EBV-mediated B cell transformation and EBV or mitogen-driven B cell division in vitro. SIRT2 modulation significantly alters gene expression and metabolism of EBV-infected B cells, reducing mitochondrial respiration, driving mitochondrial swelling, and inducing nutrient stress and autophagy. Treatment with SIRT2 modulators drives hyperacetylation of targets involved in lipid metabolism, central carbon metabolism, and oxidative phosphorylation. EBV-positive and EBV-negative B cell lymphomas rely on glycolysis to avoid cell death after SIRT2 modulation, revealing a metabolic vulnerability that can be harnessed to kill lymphoma cells. Overall, we have identified how SIRT2 could be implicated as a target of therapeutic potential for B cell lymphomas, while also defining fundamental roles for extranuclear lysine acetylation in regulating B cell proliferation and metabolism.
GPT-4o mini: Non-social science research article
Repression of ferroptotic cell death mediated antitumor immunity by mitochondrial calcium signaling
Jianwen Chen, Bao Zhao, Hong Dong, Zhiwei Liao, Shen Wang, Anjun Ma, Yajun Sun, Xiang Cheng, Shengyin Lin, Xinghui Li, Gang Xin, Kai He, Bei Liu, Yu L. Lei, Qin Ma, Kymberly M. Gowdy, Ruili Xie, Xiaolin Cheng, Zihai Li, Haitao Wen
Full text
Ferroptosis is a unique type of programmed cell death caused by excessive lipid peroxidation and represents a vulnerability in certain types of cancer. However, the signaling mechanisms that modulate ferroptosis and its functional consequence on the tumor microenvironment are poorly understood. Here, we demonstrate an inhibitory effect of mitochondrial calcium uniporter (MCU) on ferroptosis during embryogenesis and tumor development. MCU-dependent production of metabolite acetyl-coenzyme A (acetyl-CoA) supports the normal function of glutathione peroxidase 4 (GPX4), a critical gatekeeper of ferroptosis. Mechanistically, acetylation of GPX4 on lysine 90 (K90) prevents the formation of a detrimental salt bridge between K90 and aspartate 23, therefore protecting GPX4 enzymatic activity and avoiding ferroptosis. Deletion of MCU in cancer cells caused a robust antitumor T cell response and significantly blunted tumor growth. Thus, our findings indicate MCU-mediated acetyl-CoA metabolism as a critical anti-ferroptosis mechanism, which can be investigated as potential therapeutic candidate for tumor treatment.
GPT-4o mini: Non-social science research article
Regulatory logic of neuronal differentiation in the Drosophila visual system
McKenzie Treese, Yen-Chung Chen, Abigail Tyree, Rose Coyne, Cathleen Lake, Ojong Besong Tabi, Raghuvanshi Rajesh, Yu-Chieh David Chen, Huzaifa Hassan, Hua Li, Claude Desplan, Mehmet Neset Özel
Full text
Combinations of terminal selector transcription factors (tsTFs) are thought to establish and maintain the unique identities of the numerous cell types found in nervous systems. However, it remains largely unclear how tsTF combinations are specified during development and how they then coordinate the type-specific differentiation programs of each neuron. To investigate these regulatory mechanisms, we performed simultaneous single-cell RNA and ATAC (assay for transposase-accessible chromatin) sequencing on the Drosophila optic lobes at four stages of their development and identified over 250 distinct cell types. We characterized the common cis-regulatory features of neuronal enhancers and performed comprehensive inference of gene regulatory networks across cell types and stages. Our results reveal cell type– and stage-specific enhancers of many neuronal genes and the cooperative actions of tsTFs, pan-neuronal and ecdysone-responsive TFs on these enhancers. We show that the same effector genes are often regulated by different tsTF combinations acting through distinct enhancers in different neurons. During neurogenesis, tsTF codes are established within a brief critical period in newborn neurons, often through cell type–specific enhancers that are not accessible in their progenitors. Accordingly, when neuroblast temporal patterning TFs are reutilized as tsTFs in neurons, they are regulated independently through separate enhancers. Therefore, neuronal identity specification and differentiation is a multistep regulatory program, wherein the same TFs enact distinct regulatory codes at different steps and across cell types.
GPT-4o mini: Non-social science research article
Optically induced Faraday–Goldstone waves
Daniel Kaplan, Pavel A. Volkov, Andrea Cavalleri, Premala Chandra
Full text
Faraday waves, typically observed in driven fluids, result from the confluence of nonlinearity and parametric amplification. Here we show that optical pulses can generate analogous phenomena that persist much longer than the pump time-scales in ordered quantum solids. We present a theory of ultrafast light–matter interactions within a symmetry-broken state; dynamical nonlinear coupling between the Higgs (amplitude) and the Goldstone (phase) modes drives an emergent phason texture that oscillates in space and in time: Faraday–Goldstone waves. Calculated signatures of this spatiotemporal order compare well with measurements on K 0.3 MoO 3 ; Higgs–Goldstone beating, associated with coherent energy exchange between these two modes, is also predicted. We show this light-generated crystalline state is robust to thermal noise, even when the original Goldstone mode is not. Our results offer a pathway for the design of periodic structures in quantum materials with ultrafast light pulses.
GPT-4o mini: Non-social science research article
Learning to outgrow the competition: Reaction–diffusion systems that adapt to time-dependent environments
Olivier Rivoire, Guy Bunin
Full text
A fundamental challenge in both biology and engineering is understanding how adaptation can emerge from simple physical or chemical building blocks. Biological adaptation appears to rely on two key capabilities: information processing, to enable learning of complex tasks, and reproduction, to give such learning its value through reproductive success. Creating and coordinating these capabilities poses both a formidable engineering challenge and a fundamental evolutionary puzzle. Here, we propose a model in which learning and reproduction emerge jointly from simple, nonequilibrium chemical systems, without prior design or evolution. The model’s essential features are that it supports many steady states and spatial heterogeneities, upon which adaptation arises solely from exposure to time-varying influxes of reactants, without any predesigned program or memory. The adaptive response is specific to the temporal sequence of environmental changes, yet general enough to extend to related sequences. Learning manifests in several forms: It is reinforced through repeated exposure to the same environmental sequence, representing a form of self-learning, and enhanced through spatial interactions, corresponding to a form of collective learning. Moreover, an adapted state can accelerate adaptation in nearby regions, providing a mechanism akin to teacher-guided learning. By coupling environmental variations to stochastic reaction–diffusion dynamics, our model establishes a minimal physical framework in which learning of complex environments and selective amplification of the states that encode them arise directly from nonequilibrium chemical processes.
GPT-4o mini: Non-social science research article
QnAs with Richard Ostfeld
Sandeep Ravindran
Full text
GPT-4o mini: Non-social science research article
Structural evolution beyond carbon fullerenes: A family of metal–oxo clusters
Di Zhang, Xiao-Kun Zhao, Feng-Xue Duan, Peng Lei, Ni Zhen, Cong-Qiao Xu, Yingnan Chi, Ya-Qian Lan, Jun Li, Changwen Hu
Full text
Fullerenes are a unique class of stable molecular clusters whose structural evolution is constrained by the geometry and topology of pentagon–hexagon arrangements of sp 2 -hybridized carbons with (p–p)π conjugation. However, extending this geometry- and topology-driven structural evolution to other inorganic systems remains exceedingly rare, because it is highly challenging to achieve controlled assembly of distinct building units and precisely tune their numbers. Here, we report a family of metal–oxo clusters with V 30 Nb 12 , V 26 Nb 8 , V 24 Nb 6 , and V 22 Nb 4 cluster cores. They are constructed from m {(Nb)V 5 } pentagons and l {(V)V 4 } squares linked through shared vanadium centers. These clusters show a stepwise pentagon decrease ( m = 12 → 8 → 6 → 4) and square increase ( l = 0 → 2 → 3 → 4) and follow a mathematically defined evolution rule l = 6 – m /2. Quantum-chemical analyses show that, similar to the curved (p–p)π-conjugation characteristic of carbon fullerenes, a spherical multicenter (d–p)π-conjugated network stabilizes these curved {(Nb)V 5 } pentagons and {(V)V 4 } squares. Together, these findings demonstrate that fullerene-like structural evolution is not restricted to carbon frameworks, but can emerge in metal–oxo clusters through multicenter (d–p)π-conjugation interaction.
GPT-4o mini: Non-social science research article
WNK-dependent phosphorylation of gephyrin tunes GABA A receptors at inhibitory synapses and modulates anxiety behavior
Zaha Merlaud, Celia Delhaye, Margarida Nabais, Erwan Pol, Tùnia Lima, Yann Verdier, Zahra Imani, Marion Russeau, Nalia Samba, Maelys Tostain, Juliette Gouhier, Romane Rahir, Joëlle Vinh, Corentin Le Magueresse, Marika Nosten-Bertrand, Sabine Lévi
Full text
The role of the chloride-sensitive kinase WNK1 and its effector SPAK in the brain remains poorly understood. Here, we identify a WNK-dependent regulatory mechanism that directly controls the synaptic diffusion and clustering of inhibitory GABA A receptors (GABA A Rs), as well as their membrane stability and endocytosis. We show that activation of WNK signaling stabilizes GABA A Rs at inhibitory synapses, while inhibition enhances receptor internalization. This regulation depends on the phosphorylation state of two residues in the central linker region of the gephyrin scaffold protein. Modulating WNK activity alters neuronal activity and the kinetics of GABAergic currents. In vivo, expression of a phospho-mimetic form of gephyrin at WNK-targeted sites produces anxiolytic-like effects. Together with prior evidence showing that WNK signaling regulates the chloride transporters KCC2 and NKCC1, key determinants of intracellular chloride homeostasis and GABAergic efficacy, our findings position the WNK pathway as a master regulator of inhibitory synapse function.
GPT-4o mini: Non-social science research article
Morphing active networks
Ya Wen, Yuzhen Chen, Yifan Yang, Fan Xu
Full text
Biological networks like leaf venation exhibit remarkable morphing capabilities that enable organisms to adapt and thrive in their environments. However, the underlying mechanisms that govern the morphing of such networks, especially when the network itself actively grows and imposes constraints, remain poorly understood. The inherent complexity of interconnected topological elements poses significant challenges for both theoretical modeling and experimental investigation. Here we develop an active Cosserat rod model capturing growth-induced network morphing, validated through polydimethylsiloxane swelling experiments and four-dimensional printing. By examining cellular lattices with varying geometries, we reveal how symmetry and chirality can be systematically programmed through network architecture. Using bioinspired venation patterns with tunable pinned sites, we demonstrate that the network functions as a mechanically constraining framework: Its geometry dictates the spatial distribution of growth-induced deformation, with model predictions matching biological observations. We further achieve precise control of nonuniform morphing, including chirality, bidirectional curvature, and edge rippling, through engineered inhomogeneous growth. Our findings uncover how network geometry and active growth can program three-dimensional shape transformations, offering a design strategy for morphing matter, soft robotics, and deployable structures.
GPT-4o mini: Non-social science research article
The moisture dynamics in arid Central Asia over the last 47,000 years: Insights from the speleothem record
Yanjun Cai, Hai Cheng, Sebastian F. M. Breitenbach, Nosir Shukurov, Maxim Petrov, Shukhrat Shukurov, Jing Lei, Yingjie Yang, Gang Xue, Le Ma, Shouyi Huang, Ruoxin Li, Mei He, Zhengguo Shi, Hanying Li, Youfeng Ning, Xuexue Jia, Yifei Hao, Alexander Osinzev, R. Lawrence Edwards, Zhisheng An
Full text
Water resources are crucial for the survival and development of human societies in arid Central Asia. However, our understanding of regional hydroclimate variability and moisture dynamics remains limited. Here, we present a precisely dated, high-resolution speleothem ÎŽ 18 O record from caves in northern Uzbekistan that reconstructs changes in precipitation ÎŽ 18 O over the last 47,000 years. During the glacial interval, relatively low speleothem ÎŽ 18 O values align with precipitation isotope records from high northern latitudes. The close correspondence between the Uzbekistan record and Greenland ice-core ÎŽ 18 O during Heinrich Stadial 1 indicates a strong temperature control on regional precipitation ÎŽ 18 O, although Dansgaard-Oeschger-scale variability is weakly expressed. During the Holocene, speleothem ÎŽ 18 O reached minimum values near 8 ka BP and then increased toward the present, broadly consistent with records from southern Uzbekistan and the Asian monsoon region, but with less coherent centennial- to millennial-scale variability. Supported by model simulations, we propose that during the glacial and mid-Holocene, when winter temperatures were low, the regional precipitation was dominated by northerly and northwesterly moisture transport linked to enhanced high-latitude temperature gradients and southward-shifted westerlies. In contrast, late Holocene hydroclimate increasingly reflected southerly to southwesterly cyclonic moisture transport from the eastern Mediterranean and the Near East, driven by northward-shifted westerlies. These results show that arid Central Asian hydroclimate and precipitation ÎŽ 18 O have been shaped by the position and strength of the westerlies through major reorganizations in moisture-source trajectories, with direct implications for understanding future water availability as subtropical and temperate circulation zones shift northward.
GPT-4o mini: Non-social science research article
Dynamic multiphase flow triggers chaotic mixing in porous media
Gaute Linga, Kevin Pierce, Marcel Moura, Joachim Mathiesen, François Renard, Tanguy Le Borgne
Full text
Solute mixing plays a pivotal role in a broad spectrum of chemical and biological processes across natural and engineered porous media. However, current understanding of mixing dynamics remains largely constrained to steady flows in fully or partially water-saturated environments. Multiphase flow systems are generally unsteady, with moving fluid interfaces and flow paths that change in time. Despite the widespread occurrence of dynamic multiphase flows, their impacts on solute mixing are largely unknown. Here, we use experiments and numerical simulations to investigate the effect of dynamic two-phase flow on the stretching and folding of fluid elements, a fundamental mechanism driving solute mixing and reactions in porous media. We find that dynamic two-phase flows induce chaotic mixing, characterized by exponential stretching of fluid elements, leading to strongly enhanced mixing compared to steady single-phase flows. By extensive numerical multiphase flow simulations, we establish dynamic steady states where we reliably measure the mean fluid stretching rate as a function of flow rate. We show that stretching is maximized at an optimum flow rate which balances fluid shear deformation against the frequency of flow reorientation by the intermittent motion of the fluid interface. The findings are rationalized by a mechanistic model linking basic multiphase flow characteristics to the stretching rate, opening perspectives to understand and control mixing and reactions in a wide range of multiphase flow systems.
GPT-4o mini: Non-social science research article
Regulatory divergence of homoeologs underlies network optimization for fiber improvement in domesticated cotton
Zhengyang Qi, Jinglei Yang, Yanchao Xu, Xuehan Tian, Zhiwei Chen, Yawen Wang, Boyang Chen, Yang Meng, Wei Zhang, Zeyu Zhang, Xinhui Nie, Lili Tu, Xianlong Zhang, Jonathan F. Wendel, Fang Liu, Maojun Wang
Full text
Polyploidy is prominent in plant evolution and in many of the world’s most important crops, yet how domestication reshapes the regulation of duplicated genes (homoeologs) to generate superior agronomic traits remains incompletely understood. Here, we integrate population genomics, stage-resolved transcriptomics, expression quantitative trait locus (eQTL) mapping, and coexpression network analysis across 161 semiwild and 376 cultivated accessions of allotetraploid cotton ( Gossypium hirsutum ) to dissect the regulatory consequences of domestication. We show that domestication increases both the frequency and magnitude of homoeologous expression bias (HEB), with biased pairs preferentially organized into trait-associated, functionally specialized coexpression network modules. Bias-eQTL mapping identifies HEB-associated cis -regulatory variants that are enriched in open chromatin regions. Bayesian colocalization analysis further reveals that 92 bias-eQTLs colocalize with fiber quality-related genetic loci, where favorable alleles exhibit substantial frequency increases during domestication. Collectively, this work provides a mechanistic framework linking selection-driven regulatory asymmetry to coexpression network optimization in polyploids and highlights expression bias as a promising target for precision breeding in crops.
GPT-4o mini: Non-social science research article
Shifting drivers and predictable corridors of an illegal wildlife trade network
George Olah, Rodrigo León-Pérez, Alex J. Berryman, Gregory P. Asner, Robert Heinsohn
Full text
Illegal wildlife trade is a major driver of biodiversity loss but the lack of understanding of mechanisms sustaining criminal networks hampers law enforcement. We integrated three decades of confiscation data, criminological modeling, and spatial network analysis to dissect the illegal parrot trade in Mexico, a global hotspot of parrot diversity and endemism. Our interdisciplinary approach revealed that the wildlife trade is the leading threat, elevating their extinction risk. Trade is shifting from poverty-driven to population density-linked patterns. Circuit theory-based landscape modeling identified critical trade routes from biodiverse habitats to urban centers, providing actionable targets for law enforcement. Our study demonstrates the effectiveness of combining criminological methods with landscape science to identify specific trafficking routes, a transferable framework for generating actionable intelligence. Crucially, because illicit wildlife networks frequently converge with broader organized crime, this spatial framework provides a powerful proxy for exposing the shared logistical corridors of global illicit markets.
GPT-4o mini: Non-social science research article
Bright monomeric fluorescent protein elite-niRFP704 for two-channel near-infrared STED nanoscopy
Florian Habenstein, Nickels Jensen, Daniel Stumpf, Alexey I. Chizhik, Marcel Leutenegger, Jin Chang, Andreas Fognini, Jessie Qin-Dregely, Iman Esmaeil Zadeh, Laura L. Kirck, Jörg Enderlein, Kaushik Inamdar, Stefan W. Hell, Stefan Jakobs
Full text
The near-infrared (NIR) spectral region is attractive for live-cell imaging, due to low autofluorescence and reduced phototoxicity. Some phytochrome-derived fluorescent proteins absorb and emit fluorescence in the NIR, but have short fluorescence lifetimes and relatively low quantum yields, requiring higher laser powers thus limiting their usefulness for live-cell superresolution microscopy. Using the bacterial phytochrome miRFP703 as a template, we screened for variants with longer fluorescence lifetimes, because the quantum yield and fluorescence lifetime are linked. We identified the bright monomeric fluorescent protein elite-niRFP704, which has a longer lifetime (1.12 ns) and a correspondingly higher quantum yield (0.21) than its template, absorbing and emitting completely in the NIR spectral region. elite-niRFP704 was used to tag proteins in living cells and facilitated extended stimulated emission depletion (STED) microscopy on cell lines stably expressing a fusion protein. Finally, elite-niRFP704 and miRFP703 could be separated based on their significantly different lifetimes, enabling two-channel NIR STED microscopy of living mammalian cells.
GPT-4o mini: Non-social science research article
A gut symbiotic filamentous fungus reprograms host metabolism and the microbiota to confer radioprotection
Huiwen Xiao, Jia Liu, Jiamin Zhao, Xiaojing Liu, Bin Wang, Xiaozhou Zeng, Zhihong Liu, Yuan Li, Jiali Dong, Ming Cui, Xingzhong Liu
Full text
The gut mycobiome is increasingly linked to host physiology, yet functional insights are dominated by yeasts, leaving the roles of filamentous fungi largely unexplored. Here, we identify Mucor racemosus as a gut-resident symbiotic filamentous fungus that establishes intestinal colonization via both hyphal and spore forms. M. racemosus confers radioprotection through an integrated metabolic program coupling direct host support with microbiota-mediated amplification. The fungus produces L-glutamate, L-aspartate, and DL-lysine, which are transferred to the host to enhance DNA damage repair in radiation-exposed intestinal epithelial cells. In parallel, M. racemosus –derived methylthioadenosine remodels the gut bacterial community by enriching Limosilactobacillus reuteri and reprogramming sulfur metabolism to generate radioprotective methionine. This coordinated fungal–bacterial metabolic axis reinforces intestinal radiotolerance. Consistent with this mechanism, dietary administration of M. racemosus –fermented cheese confers radioprotection in vivo. Together, these findings establish gut filamentous fungi as active metabolic organizers of host–microbiota interactions.
Urban tree canopy fragmentation and child mortality in low- and middle-income countries
Dengkai Chi, Daniel Richards, Gabriele Manoli, Jun Yang, John S. Ji, Ye Zhang, Brenda Lin, Amy Hahs, Congqiang Liu, Yue Zhu, Yeshan Qiu, Jing Wang, Paolo Burlando, Simone Fatichi, Puay Yok Tan
Full text
Exposure to urban green spaces is associated with lower risks of several leading causes of under-5 mortality (U5M). While urban development improves infrastructure, healthcare access, and socioeconomic conditions, rapid urbanization in low- and middle-income countries (LMICs) has also accelerated the loss and fragmentation of green spaces. Such fragmentation may weaken ecosystem services critical for child health and increase exposure to vector-borne infections, yet its implications for U5M remain poorly understood and must be weighed against the benefits of urbanization. Here, we quantified associations between urban tree canopy cover and canopy aggregation with all-cause U5M using individual-level longitudinal mortality data between 2000 and 2019 from 57 LMICs, and identified priority areas for expanding canopy cover and improving canopy aggregation across 98 LMICs using counterfactual scenario analyses. The association between canopy cover and U5M was nonlinear, with risk declining steeply at low-to-intermediate levels of canopy cover. At a given level of canopy cover, every 1% increase in tree-to-tree adjacency was associated with a 0.17% reduction in mortality risk (hazard ratio: 0.9983, 95% CI: 0.9972 to 0.9995). The largest contiguous high-priority areas were concentrated in the West Sudanian Savanna, the eastern Punjab region of Pakistan, and the Ganges–Brahmaputra Delta in Bangladesh, where high U5M burdens align with substantial potential to improve tree canopy. This study establishes a robust association between tree canopy characteristics and U5M across LMICs. We identify canopy cover and fragmentation as potentially modifiable risk factors, highlighting important implications of urban greening design for delivering cobenefits for child health and climate mitigation.
Interactive representations of power and status signals in learning social hierarchies
Chunliang Feng, Feilong Liu, Binjie Yang, Edmund Derrington, Yuejia Luo, Chen Qu, Jean-Claude Dreher
Full text
Social hierarchies, which organize our social relationships, have heterogeneous effects on choice behavior. Two central dimensions of social hierarchies, status, which is earned through recognition of competence, and power, which is the capacity to control the outcomes of others, may contribute to different behavioral profiles. Yet, the neurocomputational processes by which status- and power-related signals are learned based on social feedback, and influence subsequent decision-making, remain unclear. Here, we combine functional neuroimaging with computational modeling to examine how individuals acquire knowledge about others’ status and power, and how these learned hierarchy signals shape social influence on advice-taking during a risky choice task. We found that the medial prefrontal cortex covaried with status estimates, whereas the amygdala covaried with power estimates. Moreover, estimates in one dimension influenced choices in the other during learning. This indicates interactions between status and power signals, with retrosplenial cortex activity associated with hierarchy signals beyond immediate choice demands. Finally, status broadly modulated response biases toward both safe and risky advice, whereas power primarily increased bias toward safe advice. These findings characterize how experimentally instantiated status and power signals are learned and influence risky decision-making, indicating partially separable yet interactive representations of these hierarchy signals.

Science

GPT-4o mini: Non-social science research article
Laser Mössbauer spectroscopy of 229 Th in CaF 2
Takahiro Hiraki, Takahiko Masuda, Sayuri Takatori, Fabian Schaden, Michael Bartokos, Kjeld Beeks, Yuta Fukunaga, Andreas GrĂŒneis, Ming Guan, Georgy Kazakov, Thomas LaGrange, Adrian Leitner, Ira Morawetz, Ryoichiro Ogake, Koichi Okai, Martin Pimon, Martin Pressler, Thomas Riebner, Noboru Sasao, Felix Schneider, Thorsten Schumm, Kotaro Shimizu, Luca Toscani de Col, Tomas Sikorsky, Akihiro Yoshimi, Koji Yoshimura
Full text
Mössbauer spectroscopy is widely used in chemistry, geology, and solid-state physics to probe the local physical and chemical environment of nuclei in materials. Here, we extended this technique into the optical range using a vacuum ultraviolet laser to probe the low-energy nuclear transitions of thorium-229 ( 229 Th) doped in calcium fluoride (CaF 2 ) crystals. We discovered four distinct doping sites for the thorium ions, determined the characteristic electric field gradients emerging from the interaction with the host crystal, and identified the microscopic structure of the two dominant configurations. Site-selective laser excitation enabled the study of the isomeric state lifetime and laser-induced quenching for all sites. This technique provides a powerful probe of the nuclear environment, yielding foundational data for designing future solid-state nuclear clocks.
GPT-4o mini: Non-social science research article
Modality-specific neurovascular coupling via layer-segregated arteriole networks
Antoine Malescot, Milene R. Malheiros-Lima, Laurianne Zana, Michael C. Bennett, Éric Martineau, Franca Schmid, Ravi L. Rungta
Full text
The brain’s vascular system dynamically regulates energy supply through neurovascular coupling. In this study, we show that in mice, neurovascular coupling is modality-dependent: Distinct sensory inputs recruit specific arteriole types, producing differential laminar blood flow patterns. Using multiscale optical imaging, we compared neuronal and vascular responses to touch, nociception, motor-sensory feedback, and spontaneous activity. Shallow arteriole dilation emerges with increasing superficial-layer activity, whereas deep arterioles integrate signals broadly across input conditions. Arteriole type–specific dilation decouples the magnitude of local neuronal activity from capillary blood flow responses, with flow patterns shaped by vascular topology and recapitulated in silico. Together, these findings reveal how interactions between laminar circuit activity and vascular network architecture dynamically shape the spatial profile of blood flow delivery across the cortex.
GPT-4o mini: Non-social science research article
RAD51 stabilizes neutrophil extracellular traps to compartmentalize inflammation
Lorenza Iolanda Tsansizi, Sophie Yihan Guan, Iker Valle Aramburu, Rajvee Shah Punatar, Thomas J. Williams, Yihe E. Qiao, Anna Reed, Darius Armstrong-James, Stephen C. West, Venizelos Papayannopoulos
Full text
Neutrophil extracellular traps (NETs) feature a branched chromatin architecture whose origin and function remain unknown. We found that NET branching is mediated by RAD51, a protein generating DNA junctions during DNA recombination repair. Pharmacological inhibition, RAD51 knockdown, or GEN1 and RuvC resolvase treatment reduced branching and destabilized NETs, whereas RAD51 up-regulation by different stimuli generated NETs with variable stability. RAD51 inhibition during murine pulmonary Aspergillus fumigatus infection dismantled NETs and reduced lung cytokines. However, the increased accumulation of NET components in the circulation led to interleukin-6 (IL-6) induction in circulating monocytes that exacerbated type 2 inflammation and asthma. Extracellular plasma DNA correlated with IL-6 and eotaxin in human aspergillosis. By structurally stabilizing NETs, RAD51 compartmentalizes inflammation to thwart aberrant systemic immune activation, linking DNA repair to inflammation.
GPT-4o mini: Non-social science research article
Who checks what AI can do?
Thorsten Holz
Full text
The most important findings about frontier artificial intelligence (AI) are also the hardest to verify. Much of the information needed to understand its capabilities and risks—including results from evaluations of prerelease models and containment experiments—remains largely inaccessible outside the labs that produce it. In recent weeks, OpenAI, Anthropic, and Meta disclosed that research models had reached beyond their intended testing environments and compromised other organizations’ systems. Those labs deserve credit for reporting this. But outside those labs, there was no way to discover, reproduce, or verify what had happened.
GPT-4o mini: Non-social science research article
Tracing the origins of de novo coronary collateral formation in cardiac repair
Mingjun Zhang, Maoying Han, Yangfeng Hou, Zixin Liu, Yilian Wang, Xiuzhen Huang, Cheng Kiu Ho, Hang Qu, Qing-Dong Wang, Xin Ma, Kathy O. Lui, Bin Zhou
Full text
Coronary collateral arteries have been proposed to form de novo through artery reassembly, a process in which arterial endothelial cells (ECs) migrate away from preexisting arteries and reassemble into new arteries. Using genetic tools that trace arterial ECs, we found that their contribution to collaterals is modest. Dual genetic lineage tracing revealed that capillary ECs, rather than arterial ECs, serve as the major building blocks for de novo collaterals. The capillary-to-collateral conversion is functionally crucial for cardiac repair. In addition, transient Vegfa expression through modified messenger RNA markedly promoted collateral formation. Mechanistically, vascular endothelial growth factor (VEGF) drives arterialization by regulating HES1 transcription through YY1/SETD1A-mediated H3K4 trimethylation. Collectively, these findings redefine the cellular origin and mechanism of coronary collateral formation and highlight its role in facilitating efficient cardiac repair.
GPT-4o mini: Non-social science research article
Genomes of Poaceae relatives reveal key metabolic innovations preceding the evolution of grasses
Yuri Takeda-Kimura, Bethany Moore, Samuel Holden, Jae S. Morris, Sontosh K. Deb, Carly Sanders, Jorge El-Azaz, Matt Barrett, David Lorence, Marcos V. V. de Oliveira, Wynne Havranek, Jane Grimwood, Melissa Williams, Lori Beth Boston, Jerry Jenkins, Christopher Plott, Shengqiang Shu, Kerrie Barry, David M. Goodstein, Jeremy Schmutz, Joseph M. Jez, Matthew J. Moscou, Michael R. McKain, James H. Leebens-Mack, Hiroshi A. Maeda
Full text
The grass family (Poaceae) has immense economic and ecological importance and exhibits distinctive metabolic traits, including dual starch and lignin biosynthetic pathways. We sequenced the genomes of Pharus , Joinvillea , Ecdeiocolea , and Typha species to investigate when and how these metabolic innovations evolved relative to the origin of the grass family. The rho whole-genome duplication (ρWGD) within the lineage that led to the last common ancestor of all grasses contributed to the gene family expansions underlying cytosolic starch biosynthesis, whereas an earlier tandem duplication of phenylalanine ammonia lyase ( PAL ) gave rise to phenylalanine/tyrosine ammonia lyase ( PTAL ), which is responsible for the dual lignin biosynthesis. Integrated biochemical, functional, and structural studies, guided by phylogenomic analyses, further revealed the molecular basis of key metabolic innovations predating the evolution of grasses.
GPT-4o mini: Non-social science research article
TGW1a locus simultaneously shortens growth duration and boosts grain yield in rice
Zhiyong Li, Guan Li, Zhichao Liu, Zhen Cheng, Yibo Wu, Xixi Liu, Xinyong Liu, Xin Ai, Wanning Liu, Guanghao Li, Longxue Chang, Man Yin, Yichen Cheng, Yu Cheng, Yifeng Wang, Xiaohong Tong, Jie Huang, Guoming Zhang, Yuxuan Hou, Jiezheng Ying, Jian Zhang
Full text
Reconciling the trade-off between short growth duration and high grain yield is essential for enhancing annual rice yields. We found that qTGW1a , encoding a flowering locus T-like protein, controls heading and nitrogen use efficiency (NUE) underpinning grain weight and yield in rice. TGW1a interacts with and stabilizes Ghd7 and Hd1 to boost NUE and grain yield. Natural variations in the promoter enable the ancestral allele TGW1a JZ to maintain an intermediate level of TGW1a transcription. By decoupling its linkage to the weak grain number regulator Gn1a JZ , TGW1a JZ conferred 3.67 to 8.67 days shorter growth duration and 4.22 to 11.00% higher grain yield in five modern cultivars and derived F 1 hybrids. This research uncovers a locus for breeding rice varieties featuring shorter growth durations and higher yields.
GPT-4o mini: Non-social science research article
Ultralong sheathed single-metal-atom chains synthesized under high pressure
Jie Zhang, Xiao Dong, Shengchao Qiu, Xin Yang, Chengyu Li, Hongfei Ma, Yunfan Fei, Qingchao Zeng, Fang Li, Yi Xie, Yan Duan, Xudong Jiang, Jingqin Xu, Puyi Lang, Jiarui Yuan, Hao Luo, Yuan Fang, Zilin Zhao, Yikun Bao, Yajie Wang, Yongjin Chen, Junliang Sun, Shangda Jiang, Ho-kwang Mao, Haiyan Zheng, Kuo Li
Full text
Single-metal-atom chains (SMACs) represent the ultimate limit of one-dimensional nanostructures. They serve as archetypal model systems for condensed matter physics and constitute fundamental building blocks for next-generation nanoelectronics. However, synthesis of SMACs suitable for practical applications remains challenging. In this work, we create micrometer-long, carbon-sheathed copper SMACs at milligram scale by compressing ÎČ-copper phthalocyanine to above 21 gigapascals. The SMACs are in atom-scale ordering, are isolable through acid-assisted exfoliation, and exhibit exceptional stability, with Cu-Cu distance confined at 2.57 angstroms. Anisotropic conductance and antiferromagnetic interactions are suggested by experimental and computational results. This work establishes a universal synthetic strategy for sheathed SMACs, positioning them as a compelling platform for prospective electronic and spintronic applications.
GPT-4o mini: Non-social science research article
Redirecting wet–interfacial redox pathways for efficient inverted perovskite solar cells
Zheng Liang, Boyuan Liu, Yuelong Li, Yalan Zhang, Yi Yang, Shengbin Cheng, Linchuan Ma, Bao Tu, Hua-Chao Liu, Huifen Xu, Yuqi Bao, Minghui Fan, Peide Zhu, Xianfu Zhang, Congqi Li, Hui Zhang, Xinyuan Zhang, Yuheng Li, Guodong Chen, Cheng Liu, Chen Zhu, Chuying Ouyang, Nam-Gyu Park, Yong Zhang
Full text
Carbazole-based phosphonic acid self-assembled monolayers (SAMs) are essential for high-efficiency p-i-n perovskite solar cells. However, during processing, these SAMs inevitably contact perovskite inks, where their acidity triggers a dimethyl sulfoxide (DMSO)-mediated iodide redox reaction that imprints device performance, representing a universal bottleneck for inverted devices. We resolve this SAM-triggered redox mechanism and introduce chemistry-matched hydrazide additives to mitigate the degradation. These additives abrogate DMSO activation and redirect unwanted by-products toward benign hydrazide–formamidinium adducts. Consequently, we achieved power conversion efficiencies (PCEs) of 27.7% (certified 27.4%) in small-area (0.06 cm 2 ) cells and 20.1% in 2.0 m 2 modules, along with T95 lifetimes of ~2000 hours of maximum power point tracking (MPPT) at 85°C and ~1500 hours MPPT at 85°C and 85% relative humidity.
GPT-4o mini: Non-social science research article
A cinnamyl alcohol dehydrogenase–like scaffold organizes monoterpenoid indole alkaloid biosynthesis
Di Gao, Scott Galeung Alexander Mann, Binbin Chen, Yuanwei Gou, Cong Chen, Chong Qiao, Jorge Jonathan Oswaldo Garza-Garcia, Mohammadamin Shahsavarani, Xiaojing Jiang, Hannah Caroline Tran, Jingfei Bao, Mathew Bailey Richardson, Jianing Li, Jacob Owen Perley, Jaewook Hwang, Feng Dong, Chang Dong, Lei Huang, Vincenzo De Luca, Yajie Wang, Yang Qu, Jiazhang Lian
Full text
Biosynthesis of ~3000 monoterpenoid indole alkaloids (MIAs), including the anticancer drug vinblastine, involves the highly unstable intermediate strictosidine aglycone. Its formation by strictosidine ÎČ-glucosidase (SGD) and subsequent conversion by geissoschizine synthase (GS) occur in spatially separated compartments, representing a major biosynthesis bottleneck. In this study, we discover VinBLAST, a cinnamyl alcohol dehydrogenase–like protein repurposed as a scaffold for efficient processing of this labile intermediate. VinBLAST physically mediates the interaction of SGD and GS in the nucleus and allosterically enhances the catalytic efficiency of GS. VinBLAST homologs from diverse plant families enhance the biosynthesis of several representative MIAs, with the production of catharanthine increased to ~160 milligrams per liter in yeast, nearly 1000-fold higher than shown in previous studies. Our discovery provides a missing link in organizing MIA biosynthesis and enables scalable bioproduction of geissoschizine-derived therapeutics.
GPT-4o mini: Non-social science research article
Virome-wide ubiquitin ligase discovery reveals diverse mechanisms of immune evasion
Caleb R. Glassman, Kheewoong Baek, Gaopeng Hou, Qiru Zeng, Christopher Nardone, Kate B. Juergens, Eric Fujimura, Colin N. O’Leary, Mamie Z. Li, Joao A. Paulo, Eric S. Fischer, Siyuan Ding, J. Wade Harper, Stephen J. Elledge
Full text
Viruses are intracellular parasites that reprogram the host proteome to promote replication and evade immune recognition. We applied a virome-wide library of ~10,000 open reading frames to discover viral ubiquitin ligases, mapping their mechanisms of degradation and host substrates using targeted CRISPR screens and proteomics. These viral effectors could be classified as canonical ligases that mimic host E3s, hijackers that redirect host E3s, and noncanonical ligases that rewire cullin-RING ligase machinery. These diverse strategies of virus-mediated degradation converged on immune-related substrates, including JAK1 and CUL1 ÎČ−TrCP , underscoring immune evasion as a major driver of viral ubiquitin ligase evolution. Our findings elucidate viral strategies for exploiting the ubiquitin–proteasome system with potential for therapeutic targeting.
GPT-4o mini: Non-social science research article
De novo design of orthogonal far-red, orange, and green fluorophore-binding proteins for multiplexed imaging
Long Tran, Steffen Klein, David Juergens, Shajesh Sharma, Justin Decarreau, Gyu Rie Lee, Yujia Wang, Wei Chen, Asim K. Bera, Alex Kang, Jon Woods, Emily Joyce, Dionne K. Vafeados, Nicole Roullier, Xinting Li, Bingxu Liu, Yang Bo, Edin Muratspahić, Tim A. Brown, Jonathan B. Grimm, Ronak Patel, Luke D. Lavis, Julia Mahamid, Linna An, David Baker
Full text
Fluorescent proteins and small-molecule dyes offer complementary advantages for biological imaging: Proteins are amenable to genetic tagging, whereas dyes provide superior brightness and photostability. To combine these strengths, we used de novo protein design to generate small, nanomolar-affinity, high-selectivity binders (NovoTags) for three cell-permeable dyes spanning the visible spectrum. We show that the NovoTag fluorescent lifetimes can be tuned and demonstrate their application in lifetime- and wavelength-based multiplexed fluorescence imaging. We also designed a two-chain version (NovoSplit) that functions as a chemically induced dimerization system with fluorescent readout in living cells or as a minimally perturbing proximity probe in fixed cells. Our approach combines the advantages of fluorescent proteins and small-molecule dyes, thus expanding the toolkit for cellular imaging.
GPT-4o mini: Non-social science research article
Autonomous biomedical research with an artificial intelligence agent
Kexin Huang, Serena Zhang, Hanchen Wang, Yuanhao Qu, Yingzhou Lu, Ryan Li, Yusuf Roohani, Lin Qiu, Shiyi Cao, Gavin Li, Junze Zhang, Di Yin, Rick Wierenga, Deniz Kavi, Sherry Liu, Tianwei She, Shruti Marwaha, Jennefer N. Carter, Xin Zhou, Matthew T. Wheeler, Jonathan A. Bernstein, Mengdi Wang, Peng He, Jingtian Zhou, Michael P. Snyder, Le Cong, Aviv Regev, Jure Leskovec
Full text
Biomedical research is increasingly constrained by repetitive, fragmented workflows that slow discovery. We introduce Biomni, a general-purpose biomedical artificial intelligence agent that autonomously executes diverse research tasks. To map the biomedical action space, Biomni’s action-discovery agent mines tools, databases, and protocols from thousands of publications across 25 domains, building a unified agentic environment. Its general-purpose architecture integrates large language model reasoning with retrieval-augmented planning and code-based execution, dynamically composing workflows without predefined templates. Systematic benchmarking shows strong generalization across heterogeneous tasks—causal gene prioritization, drug repurposing, rare-disease diagnosis, microbiome analysis, and molecular cloning—without task-specific tuning. Real-world case studies demonstrate Biomni interpreting multimodal datasets, optimizing protein stability, orchestrating wet-lab instruments, and generating experimentally testable protocols. Biomni envisions artificial intelligence augmenting human scientists and accelerating discovery.
GPT-4o mini: Non-social science research article
Preferred synthesis of armchair transition metal dichalcogenide nanotubes
Abid, Luneng Zhao, Ju Huang, Yongjia Zheng, Yuta Sato, Tianyu Wang, Dmitry Levshov, Lingfeng Wang, Haiming Sun, Qingyun Lin, Zhen Han, Chunxia Yang, Bill Herve Nduwarugira, Yicheng Ma, Yige Zheng, Hang Wang, Salman Ullah, Afzal Khan, Qi Zhang, Wenbin Li, Junfeng Gao, Bingfeng Ju, Feng Ding, Yan Li, Wouter Herrebout, Kazu Suenaga, Shigeo Maruyama, Huayong Yang, Rong Xiang
Full text
Nanotubes represent an important class of crystalline materials, but controlling their structures, particularly chiralities, remains a fundamental challenge. In this work, we report a strategy for synthesizing transition metal dichalcogenide nanotubes with preferred armchair chirality. Tin disulfide, molybdenum disulfide, and tungsten disulfide nanotubes were formed with high yield and structural purity inside boron nitride nanotube channels. Atomic-resolution imaging, electron diffraction, and circular dichroism revealed an armchair preference up to 83%. Density functional theory ruled out structural stability as the origin of this preference but confirmed that zigzag nanoribbons are energetically more stable. Machine learning potential molecular dynamics simulated that zigzag nanoribbons roll up to form armchair nanotubes, a process that was subsequently observed by in situ transmission electron microscope. This work may inspire the achievement of on-demand synthesis of various nanotubes with specific chiralities.
GPT-4o mini: Non-social science research article
A native sulfur deposit in Gale crater, Mars
Scott J. VanBommel, Jeff A. Berger, Penelope L. King, William E. Dietrich, Ralf Gellert, Lucy M. Thompson, Ashwin R. Vasavada, Alexander B. Bryk, Edwin S. Kite, Joanna V. Clark, Aster C. Cowart, Rebecca M. E. Williams, Sarah L. Simpson, Heather B. Franz, Catherine D. O’Connell-Cooper, Michael A. McCraig, Abigail A. Fraeman, John R. Christian, Abigail L. Knight, Nicholas I. Boyd, Deirdra M. Fey, Benton C. Clark, Christopher H. House
Full text
Martian rocks are known to contain sulfur-bearing species, including sulfates and sulfides. These compounds record a sulfur cycle that operated over the geological evolution of Mars. We used the Curiosity rover to investigate a deposit of light-toned stones in Gediz Vallis within Gale crater on Mars and found that the stones are composed of native sulfur. The sulfur deposit appears to have formed in place, within a sinuous entrenched canyon cut into the floor of Gediz Vallis. The presence of native sulfur implies that a sulfur enrichment pathway involving buoyant subsurface fluids operated on ancient Mars. We propose that the primary source of this sulfur was magmatic vapor, which cooled in the near subsurface cryosphere and was released by decompression during the erosion of Gediz Vallis.
GPT-4o mini: Non-social science research article
Bacteria sense virus-induced genome degradation via methylated mononucleotides
Ilya Osterman, Bohdana Hurieva, Sarit Moses, Alla H. Falkovich, Maxim Itkin, Sergey Malitsky, Eliane H. Yardeni, Erez Yirmiya, Rotem Sorek
Full text
Phages often degrade the genome of their bacterial host to individual nucleotides. In this work, we describe Metis, a bacterial defense system that directly senses phage-mediated host genome degradation. Metis aborts phage infection once it detects the modified mononucleotide N 6 -methyl-deoxyadenosine monophosphate (m 6 dAMP). As methylation of deoxyadenosines usually occurs on the DNA polymer, accumulation of m 6 dAMP signals that the host genome has been degraded. In type I Metis, sensing of m 6 dAMP activates a nicotinamide adenine dinucleotide (NAD + ) diphosphatase, leading to NAD + depletion and cessation of the infection process, whereas the effector in type II Metis is a membrane-spanning protein whose toxicity is triggered in response to the modified mononucleotide. We further show that Metis defense depends on endogenous DNA methylases and that phages can escape Metis through mutations that inactivate host genome degradation.
Science abstract < 200 char.: Not a research article
Arson attack jolts Italy’s bid to host the Einstein Telescope
Alessio Cozzolino
Full text
Two scientists’ cars burned at proposed Sardinian site for the next-generation gravitational-wave observatory
Science abstract < 200 char.: Not a research article
Key animal and plant disease lab stalled by biosafety issues
Kate Jen Li
Full text
USDA doesn’t know when new facility will be able to handle the most dangerous pathogens
Science abstract < 200 char.: Not a research article
Technology is not a replacement for democracy The Rise and Fall of the Artificial State Jill Lepore Liveright, 2026. 336 pp.
Carissa Véliz
Full text
A government run by machines is not inevitable—we have been here and rejected it before
Science abstract < 200 char.: Not a research article
A Brussels Effect for battery sustainability
Yanan Liang, Edgar Hertwich, Robert Istrate, Antonio Valente, Ranran Wang
Full text
An EU battery regulation can help drive toward a widely shared evidentiary system for sustainability governance
Science abstract < 200 char.: Not a research article
Just say yes!
William Mills
Full text
Science abstract < 200 char.: Not a research article
A serendipitous sunset on Mars
Paul L. Fox
Full text
Science abstract < 200 char.: Not a research article
Experiences and economic decision-making
Imran Rasul
Full text
Science abstract < 200 char.: Not a research article
Hundreds of paper-mill papers peddled in ads were later published
Jeffrey Brainard
Full text
More than one-fifth of papers at some IEEE conferences appear linked to authorship for sale
Science abstract < 200 char.: Not a research article
The lab that learns
Milad Abolhasani
Full text
Integrating high-throughput experiments, robotics, and artificial intelligence can accelerate scientific discoveries
Science abstract < 200 char.: Not a research article
Biodiversity monitoring misses behavior
Peter Mikula, Daniel T. Blumstein, Piotr Tryjanowski
Full text
Science abstract < 200 char.: Not a research article
Bonding carbons iteratively
Martin D. Burke
Full text
A modular synthesis method could broaden the accessibility of chemistry
Science abstract < 200 char.: Not a research article
Scientists challenge unexpected finding of lymphatic vessels in bone
Catherine Offord
Full text
Conflicting data prompt spat, and last-minute publication delay, in prominent journal
Science abstract < 200 char.: Not a research article
Touch and pain shape what brain imaging sees
Adiya Rakymzhan, Laura D. Lewis
Full text
Sensory inputs influence different blood vessel networks, affecting the precision of brain scans
Science abstract < 200 char.: Not a research article
In Other Journals
Yevgeniya Nusinovich, Cheri Sirois, Joana OsĂłrio, Sacha Vignieri, Sumin Jin, Jake S. Yeston, Angela Hessler
Full text
Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
Powers of persuasion
Kai Kupferschmidt
Full text
AI chatbots are becoming experts at changing people’s minds. What gives them an edge?
Science abstract < 200 char.: Not a research article
Justice Department calls three NSF diversity programs unconstitutional
Jeffrey Mervis
Full text
Ruling bars programs said to discriminate by race and sex, but others can continue if modified
Science abstract < 200 char.: Not a research article
China mission aims to probe the Moon’s hidden water
Dennis Normile
Full text
Chang’e-7 will send a hopping craft into a polar crater to directly sample lunar ice
Science abstract < 200 char.: Not a research article
Beyond carbon in renewable energy policy
Yuanning Liang
Full text
China’s policy-driven solar expansion shows why climate policy appraisal should look at biodiversity impacts
Science abstract < 200 char.: Not a research article
Dryland restoration needs shared evidence
Hong Yang, Xiang Gao, Jianhua Wu, Yao Chen, Wubin Yu
Full text
Science abstract < 200 char.: Not a research article
In Science Journals
Jonathan Fan, Michael A. Funk, Jelena Stajic, Di Jiang, Keith T. Smith, Jack Huang, Melissa L. Norton, Stella M. Hurtley, Unnati Sonawala, Madeleine Seale, Sarah H. Ross, Yevgeniya Nusinovich, Mattia Maroso, Sacha Vignieri, Hannah Isles, Wei Wong, Phil Szuromi
Full text
Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
Learning to love the machine Coding Kids: Big Tech’s Battle to Remake Public Schools Natasha Singer Norton, 2026. 352 pp.
Jonathan Wai
Full text
Big Tech’s crusade to get kids coding is more self-interested than it first appears, argues a journalist
China’s solar expansion policy reduces bird diversity
Huiming Zhang, Aixin Zhang, Kai Wu, Yinyin Cai, Shanjun Li, Shouyang Wang, Yueming (Lucy) Qiu, Shoujun Huang, Thi Thuc Anh Phan
Full text
Could the global transition to renewable energy create a green dilemma that pits carbon reduction against biodiversity conservation? This study examined the effect of policies promoting solar photovoltaics on local avian biodiversity using a panel dataset covering 2344 counties in China from 2014 to 2023. Policies that favored photovoltaic expansion led to reductions in bird diversity, disproportionately affecting wealthier and nondesert regions, as well as widespread species. The mechanism operated primarily through land conversion: Cropland and grassland were transformed into developed areas, reducing the diversity of vegetation. Paradoxically, the leaf area index increased, a pattern we term “inferior greening,” whereby diverse natural landscapes were replaced by dense but ecologically homogeneous vegetation. We argue that future photovoltaic development should be accompanied by strict biodiversity safeguards, especially in economically developed regions with high habitat complexity.

Science Advances

GPT-4o mini: Non-social science research article
Photocatalytic CO 2 -to-ethanol conversion via multiple enrichment effects in porous liquids
Qi Xu, Yang Liu, Huimin Wei, Jinshan Xu, Jiahui Kou, Hengming Huang, Lin-Bing Sun
Full text
Photocatalytic CO 2 reduction to multi-carbon products like ethanol remains challenging. We report a porous liquid (PL) system, PL(Cu-Cu 2 O@NU), driving selective CO 2 -to-ethanol conversion. It features Cu 0 /Cu + dual sites in NH 2 -UiO-66 (NU) hybridized with a methoxypolyethylene glycol-functionalized imidazolium ionic liquid (IL). This system facilitates C-C coupling via a triple enrichment mechanism: IL and NU synergistically enrich CO 2 , IL enriches electrons at Cu sites, and confined pores enrich intermediates. Consequently, PL(Cu-Cu 2 O@NU) achieves an 83.3 ÎŒmol·g −1 ·h −1 ethanol yield with 95.2% selectivity, outperforming Cu-Cu 2 O@NU by 4.7-fold. Control experiments (showing no ethanol over isolated NU, IL, or Cu-Cu 2 O) directly validate this mechanism. Supplemental computations substantiate these findings: molecular dynamics confirm confined pores reduce *CO diffusion for enrichment, while density functional theory reveals lowered C-C coupling barriers. Furthermore, d-band upshifts enhance CO 2 -Cu overlap, and Cu 0 /Cu + sites mediate the critical *CO → *COCO transition. These integrated observations firmly establish PLs as robust confinement-driven platforms for selective CO 2 -to-C 2 + conversion.
GPT-4o mini: Non-social science research article
Matrix stress relaxation drives glioblastoma cell response in viscoelastic biomaterials
Sadegh Ghorbani, Michelle S. Huang, Daiyao Zhang, Yueming Liu, Christopher Long, Riley Zwetsloot, Esther A.T. Mozipo, Rameshwar R. Rao, Annika Enejder, Sarah C. Heilshorn
Full text
The extracellular matrix (ECM) of glioblastoma (GBM) is known to modulate cell behavior, yet the specific contributions of matrix biochemical and biomechanical signaling remain poorly understood. To address this, we engineer a tunable hyaluronan-elastin-like protein (HELP) hydrogel to independently control ligand presentation and matrix viscoelasticity. Two peptides mimicking fibronectin (FBN) and tenascin-C (TNC) are incorporated into HELP along with hyaluronan, all of which are highly up-regulated in GBM. Using dynamic covalent chemistry, we develop hydrogels with matched stiffness but distinct stress relaxation profiles. Slow stress-relaxing matrices promote cell clustering and elevated expression of P-selectin, a GBM invasion marker. These matrices also result in increased nascent ECM production, increased lipid droplet storage, and altered cytokine secretion. Our results highlight the benefit of protein-engineered, viscoelastic biomaterials for modeling the tumor microenvironment and reveal matrix viscoelasticity as a critical regulator of GBM cell state, offering a tool for identifying previously unrecognized therapeutic targets.
GPT-4o mini: Non-social science research article
RNA delivery to the corneal endothelium using charge-altering releasable transporters
Sean K. Wang, Zhijian Li, Sahil H. Shah, Quincy A. Edwards, Richard Bouffard, Elizabeth S. Hines, Joel A. Imventarza, Sven Korte, Matthew S. Lawrence, Euisun Song, Ekram Helmy, Laura Amaya, Nae-Won Kang, David Myung, Miao-Chih Tsai, William J. Greenleaf, Robert M. Waymouth, Sui Wang, Paul A. Wender, Howard Y. Chang
Full text
RNA therapies hold tremendous promise for treating genetic eye diseases. However, their development is limited by the lack of non-viral delivery platforms that can target specific ocular cell types. Here, we describe a charge-altering releasable transporter (CART) that delivers RNA selectively to the corneal endothelium, a non-regenerative cell layer whose dysfunction underlies several blinding conditions. We characterize the safety of CART-RNA nanoparticles in mice and show that they facilitate delivery of diverse RNA cargoes to the corneal endothelium, including circular RNA and CRISPR/Cas9. We verify that these nanoparticles can be redosed and apply them to achieve corneal gene editing. We further demonstrate CART transfection of corneal endothelial cells from a human donor in vitro and in a non-human primate in vivo, supporting the feasibility of clinical translation. Our findings establish CARTs as a platform for non-viral gene delivery to the eye, with the potential to treat corneal dystrophies and other vision disorders.
GPT-4o mini: Non-social science research article
Structural basis for target discrimination and activation by Cas13d
Chia-Wei Chou, Selma Sinan, Hung-Che Kuo, You-Chiun Chang, Carlos Arguello, Daphne Sahaya, Rick Russell, Ilya J. Finkelstein
Full text
CRISPR-Cas13d is increasingly used for RNA knockdowns, but off-target cleavage of near-cognate RNAs hinders its broader adoption. Here, we solve seven cryo–electron microscopy structures of wild-type Cas13d in complex with matched and mismatched targets. These structures reveal active, intermediate, and inactive states that illustrate a detailed activation mechanism. Upon target RNA binding, the CRISPR RNA undergoes marked conformational changes. The Helical-1 domain transitions from a docked state with the amino-terminal domain to an allosterically switched conformation that stabilizes the RNA duplex. Quantitative kinetics show that a single proximal mismatch preserves the binding rate constant but abolishes nuclease activity by trapping Cas13d in an inactive state. We also identify an active site loop in the higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domains that regulates substrate accessibility and can be mutated to generate both hypo- and hyperactivated variants. These findings establish the structural basis for Cas13d mismatch surveillance and provide a framework for engineering HEPN nuclease specificity and activity.
GPT-4o mini: Non-social science research article
H3.3 chaperone Hira primes the effector program and function of regulatory T cells
Xiangxiang Cao, Mengjie Lv, Zhihan Lv, Shuting Zheng, Xinyi Tan, Jiyu Ding, Wei Liang, Guohong Li, Xuyu Zhou, Mingzhao Zhu
Full text
Foxp3 + regulatory T (Treg) cells need to differentiate into effector Treg (eTreg) cells to maintain immune tolerance and tissue homeostasis. While several transcription factors such as Batf and JunB have been reported to be essential for eTreg differentiation and function, the underlying epigenetic mechanism remains unclear. Here, we show that the histone variant H3.3 is enriched in tissue Tregs compared to splenic Tregs and its chaperone Hira is a critical regulator of Treg effector program. Treg specific-deletion of Hira resulted in reduced eTreg population, impaired suppressive function and multi-organ inflammation in mice. Mechanistically, Hira-dependent H3.3 deposition establishes a permissive epigenetic environment by enhancing chromatin accessibility, facilitating H3K36me3 and preventing H3K27me3 modifications on loci of genes enriched for AP-1 family binding motifs and associated with Treg effector function. Furthermore, overexpression of Batf in Hira -deficient Treg cells largely ameliorates their regulatory defects. Together, our findings reveal a previously unreported epigenetic mechanism critical for Treg effector differentiation and function.
GPT-4o mini: Non-social science research article
Perceptual meta-uncertainty reveals enhanced calibration of sensory confidence in autism
Laurina Fazioli, Bat-Sheva Hadad, Rachel N. Denison, Amit Yashar
Full text
Atypical metacognition has been suggested to underlie autistic phenotypes, given its role in social cognition and behavioral flexibility. However, no study has quantitatively assessed metacognitive abilities in autism. Here, we measured meta-uncertainty—the noise corrupting estimates of one’s own decision uncertainty—in autism. In three experiments, autistic and non-autistic participants ( N  = 145) performed orientation categorization tasks while simultaneously reporting their choice confidence. By independently manipulating each Bayesian component—sensory uncertainty, prior, and reward—and fitting a recently established process model, we assessed metacognitive abilities and their contingency on the Bayesian components while controlling for first-order decisions. Unlike non-autistic participants, autistic participants’ meta-uncertainty depended on which decision component was manipulated and was lower than that of non-autistic participants, specifically when decisions were adjusted for sensory uncertainty. These findings reveal that metacognition in autism is not generally reduced but rather enhanced for inferences that rely primarily on sensory information.
GPT-4o mini: Non-social science research article
A ciliated intravascular soft millirobot for multimodal in-flow collective manipulation
Yibin Wang, Ye Li, Leiming Xie, Kaiwen Fang, Chunyun Wei, Feng Duan, Jiangfan Yu
Full text
The laminar nature of blood flow and the resulting boundary layer pose substantial challenges for transverse mass transport in blood vessels, limiting intravascular biomedical applications such as targeted delivery, thrombolysis and biomarker enrichment. Herein, we develop a ciliated intravascular millirobot, CiliaVine, for active manipulation of particle and cell collectives through flow regulation. Actuated by tailored magnetic fields, soft cilia on the robot oscillate in different modes, generating desired flow patterns for flow regulation. CiliaVine enhances the transverse transport that is otherwise suppressed under laminar flow, driving circulating collectives from the vessel center toward the vessel wall for drug penetration, or reversing transport for thrombus residue clearance. Flow regulation is investigated in a vascular model using fluorescent tracer particles. Enhanced targeted drug delivery and accelerated thrombolysis enabled by the robot are validated. Circulating tumor cell (CTC) enrichment is evaluated using cancer patient blood and in tumor-bearing rabbits, revealing its effectiveness in physiological environments and its potential for intravascular rare-cell enrichment.
GPT-4o mini: Non-social science research article
High–spatiotemporal resolution deuterium metabolic imaging enables in vivo phenotyping of intra- and intertumoral heterogeneity
Xinjie Liu, Sufei Wang, Jinrui Zhao, ShaSha Wang, Peng Sun, Xin Zhou, Maili Liu, Chaoyang Liu, Lucio Frydman, Qingjia Bao
Full text
Intra- and intertumoral heterogeneities raise fundamental biological questions and have important implications for accurate cancer diagnosis, prognosis, and treatment. These heterogeneities reflect tumor complexity, including a pronounced diversity in metabolic phenotypes and profiles. This study demonstrates that in vivo deuterium metabolic imaging (DMI) data acquired with sufficiently high spatiotemporal resolution provide a minimally invasive approach to assess these heterogeneities. A multifrequency DMI approach was used to examine tumor heterogeneities within and between colon cancer models. Regions of high and low glucose enrichment and labeled lactate accumulation could thus be detected; these were analyzed using unsupervised clustering strategies based on k -means clustering of area-under-the-curve information, and principal components analysis with Gaussian mixture modeling. Spatial alignment of these imaging-derived clusters for 2 H-glucose and 2 H-lactate showed good agreement with each other as well as with histological sections, validating the biological relevance of the identified subregions. Immunohistochemical analyses showed that glucose-enriched subregions were positively correlated with the expression of GLUT1 and DLAT, while lactate-enriched areas showed elevated expression of LDHA and MCT4. These results demonstrate that in vivo DMI can distinguish metabolically distinct subregions within viable tumors and between tumor models. DMI-based metabolic maps could thus provide the means to characterize intra- and intertumoral heterogeneities, paving the way for imaging-based metabolic phenotyping in precision oncology.
GPT-4o mini: Non-social science research article
Thermal bottlenecks constrain early-life survival of native fish in regulated rivers
Kohma Arai, Rachael E. Ryan, Miles Daniels, Malte Willmes, George E. Whitman, Larisa M. Thacher, Nozomi Matsuda, Elizabeth A. Bell, Kevin D. McKeegan, Carson A. Jeffres, Rachel C. Johnson
Full text
Climate change is reshaping thermal regimes worldwide, threatening species whose early development depends on narrow temperature ranges. Yet directly linking warming to reproductive failure in wild populations remains intractable, particularly in aquatic ecosystems. We developed an empirical framework integrating stable isotope thermometry of archival tissues, landscape-scale temperature modeling, and field surveys to identify when and where successful reproduction occurs. Applying this approach to endangered winter-run Chinook salmon confined below a large dam, we revealed a narrow “critical thermal window” during early development. Surviving juveniles experienced temperatures below 12.5°C within ∌15 days of fertilization, and modest warming during this period sharply reduced survival. In warm years, dam-released cold-water overlapped only briefly with this window, restricting successful reproduction to a small fraction of the total spawning season. These results show how climate warming and river regulation interact to constrain population persistence and provide a framework to guide research on assessing climate vulnerability in temperature-sensitive species.
GPT-4o mini: Non-social science research article
Self-sustaining leadless intracardiac pacemaker powered by triboelectric nanogenerator
Pengfei Chen, Ruoxing Wang, Eric Schmuck, Derui Wang, Daniel Modaff, Ting Zhou, Satoru Osaki, Wenjian Liu, Fengdan Pan, Jin-Kyeom Kim, Youyi Tai, Paige Munns, Devon K. Klipsic, Bo Liu, Xudong Wang
Full text
Leadless intracardiac pacemakers (LIP) are a technological breakthrough that offer tremendous benefits to patients, including minimally invasive delivery, improved quality of life, and reduced financial burden. However, limited by its size and capacity, the battery component becomes a major roadblock to further advancing LIP technology toward lifelong, maintenance-free implants without the need for device retrieval or replacement. Here, we present an integrated, nanogenerator-powered LIP with a clinically compatible architecture. The LIP is solely powered by a double-oscillatory triboelectric nanogenerator (TENG) that is capable of generating a volumetric power density of 276.6 ÎŒW cc −1 driven by heartbeats. The miniaturized TENG can also fit within the battery compartment of a commercial Medtronic Micra LIP, allowing standard femoral-venous delivery by commercial catheters. When implanted in the heart of a swine model, the device delivers stable, rate-responsive electrical energy in vivo, which reliably supports the cardiac pacing function for heart rates control at physiological levels through harvested energy. Long-term intracardiac implantation further confirmed secure fixation, unaffected cardiac function and minimal tissue reaction of the fully integrated device. This development suggests a clinically compatible path toward self-sustainable intracardiac electronic systems.
GPT-4o mini: Non-social science research article
Unconventional role of hydroxymethylglutaryl-CoA synthase 1 in driving pathogenic T H 17 cell immunity and autoimmune diseases
Jie Sun, Yali Lei, Huanhuan Yang, Shu Li, Bing Wu
Full text
T helper 17 (T H 17) cells are heterogeneous and able to adopt pathogenic and non-pathogenic phenotypes. Identifying factors controlling pathogenic T H 17 cells is of importance for their vital role in inflammation and immune-pathology. Here, we demonstrated that HMGCS1, a cholesterol biosynthesis precursor enzyme, was highly induced by inflammatory cytokines and preferentially expressed by pathogenic T H 17 cells in vitro and in vivo. HMGCS1 specifically dictated pathogenic T H 17 cell differentiation and augmented autoimmune diseases, yet it has no discernible effect on nonpathogenic T H 17 cells. Unexpectedly, this role is independent of its canonical function in cholesterol metabolism but requires its catalytic Cys 129 residue. Notably, HMGCS1 governs pT H 17 cell generation and pathogenicity by leveraging an IRE1α-XBP1s–dependent ER stress response, which in turn transcriptionally activates the lineage-defining factor RORÎłt (encoded by Rorc ). Mechanistically, HMGCS1 is located to the ER membrane, where it bound and stabilized IRE1α protein. This stabilization is achieved by preventing IRE1α’s interaction with the E3 ubiquitin ligase MARCH5, thereby inhibiting its K48-linked ubiquitination and subsequent degradation. Moreover, interfering with HMGCS1 or the ER stress response in T cells impedes pT H 17 immunity and mitigates autoimmune disease in vivo. Therefore, our work unveils a noncanonical axis in which HMGCS1 sustains ER stress to license pT H 17 differentiation during autoimmune responses.
GPT-4o mini: Non-social science research article
Tree selection in urban greening shapes air quality for global cities
Xianjun He, Bin Yuan, Yibo Huangfu, Joost de Gouw, Sihang Wang, Suxia Yang, Yuwen Peng, David D. Parrish, Xiaobing Li, Ming Chang, Zhanyou Mo, Kyung-Eun Min, Woohui Nam, Yubin Chen, Xiaoxiao Zhang, Jipeng Qi, Qianqian Xie, Weihua Chen, Alex Guenther, Xuemei Wang, Douglas Worsnop, Thomas Karl, Min Shao
Full text
Mitigating ozone pollution remains a pressing challenge for megacities worldwide. Biogenic volatile organic compounds (VOCs) are proposed as pivotal precursors to urban ozone formation. However, direct observational evidence is scarce and the extent of this effect across cities is unclear. Here, by combining an unprecedented eddy covariance flux dataset from Beijing with modeling analysis, we find that urban vegetation contributes over half of organic reactivity essential for ozone production, predominantly driving ozone exceedances during hot periods. The unexpectedly high biogenic influences are attributed to the abundance of urban trees with strong emission potentials of VOCs within the city. Model extrapolations reveal that similar or even greater challenges exist for other cities across Asia and Oceania, where urban greening strategies often favor highly emitting trees. Our findings underscore the critical need for selective urban planning in greening programs to counteract a warming climate.
GPT-4o mini: Non-social science research article
Antigen-experienced airway CD8 + effector memory T cells promote a detour pathway for mycobacterial killing in the spleen
Julia Seifert, Visai Muruganandah, Socorro Miranda-Hernandez, Harindra D. Sathkumara, Ana Maria Valencia-Hernandez, Saparna Pai, Andreas Kupz
Full text
A 3-week delay in the onset of T cell immunity to Mycobacterium tuberculosis ( Mtb ) infection compromises lung bacterial control, resulting in tuberculosis (TB). Restoring T cell function is a priority. We identified how airway CD44 + CD62L − KLRG1 + CD8 + effector memory T cells (T EM ) in the lung enhance mycobacterial clearance via the spleen. Unexpectedly, a secondary immune response following repeated exposure of mice to Bacille Calmette-GuĂ©rin generated lower numbers of T EM versus primary. Paradoxically, lower numbers correlated with faster bacterial clearance, due to enhanced trafficking of secondary T EM to the spleen, where they responded to antigen. Further, secondary T EM recruited dendritic cells, which accelerated bacterial translocation from the lung to the spleen. Treating mice with a threshold number of airway-derived secondary T EM significantly reduced Mtb burden in the lung and spleen. Notably, Mtb killing was expedited by at least 15 days. Repeated antigen encounter bypassed priming requirements and enhanced T EM durability, uncovering a spleen-centered protective mechanism with implications for improved TB vaccines and therapies.
GPT-4o mini: Non-social science research article
End-to-end all-optical in-sensor computing system using photonic integrated circuits
Zian Xiao, Zhihao Ren, Yangyang Zhuge, Zixuan Zhang, Yan Yang, Bowei Dong, Chengkuo Lee
Full text
Photonic sensors play an increasingly important role in chemical analysis, but conventional systems rely on sequential wavelength scanning and extensive electronic post-processing, leading to large data redundancy, high latency, and excessive energy consumption. Here, we introduce an end-to-end all-optical in-sensor computing system based on photonic integrated circuits that merges sensing and computing in the optical domain. The system integrates a photonic waveguide sensor and a microring weight bank on a single chip for linear processing, while nonlinear activation is implemented using an erbium-doped fiber amplifier. By performing spectral compression, this system enables real-time optical-domain computing with up to 6-bit precision. The system achieves a classification accuracy of 94.2% across 27 liquid-mixture classes and concentration prediction for mixture chemicals. Compared with conventional photonic sensing systems, the proposed architecture reduces inference latency by a factor of 4.48 and energy consumption by a factor of 11.47. These results establish a compact, low-redundancy, and energy-efficient paradigm for intelligent photonic sensing at the edge.
GPT-4o mini: Non-social science research article
Multidimensional spectro-temporal imaging of exciton dynamics under propagating acoustic strain in two-dimensional semiconductors
Yuta Takahashi, Takumi Yamamoto, Hidetoshi Kanzawa, Kazuki Maezawa, Hajime Kumazaki, Yuichiro K. Kato, Shinichi Watanabe, Shun Fujii
Full text
Dynamic strain offers a promising route to manipulate tightly bound excitons in two-dimensional semiconductors. Its impact, however, has so far been inferred primarily from time-averaged or spatially integrated measurements. In particular, for dynamic strain driven by surface acoustic waves (SAWs), the relatively small strain amplitude and competing piezoelectric effects have hindered direct access to the real-time evolution of exciton emission energy and recombination dynamics within a single acoustic cycle. Here we report a fully phase-synchronized, multidimensional spectro-temporal-spatial visualization of exciton emission in monolayer tungsten diselenide driven by propagating SAWs. By integrating phase-resolved microscopy and interferometric surface displacement measurements, we achieve simultaneous mapping of exciton emission energy, photoluminescence intensity, linewidth, and decay dynamics and directly correlate them with the dynamic strain field. Our work establishes propagating acoustic strain as a powerful platform for deterministic exciton control and provides a comprehensive framework for exploring nonequilibrium exciton dynamics in low-dimensional materials.
GPT-4o mini: Non-social science research article
Targeting PKGIα Cys 42 attenuates cardiac dysfunction in heart failure with preserved ejection fraction
Jie Su, Yue Zhao, Pierre Coleman, Xiaoping Yang, Mark Holt, Janice Raabe, Friederike Cuello, Ajay Shah, Michael J. Shattock, Min Zhang, Joseph R. Burgoyne
Full text
Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent condition associated with substantial morbidity and mortality, yet effective therapeutic options remain limited. As oxidation of Cys 42 in cyclic guanosine monophosphate (cGMP)-dependent protein kinase Iα (PKGIα) can enhance vessel and diastolic relaxation, processes impaired in HFpEF, we sought to target this mechanism using natural compounds with predicted thiol reactivity. Among these, urolithin A emerged as a compound with a previously unidentified and counterintuitive mode of action, directly modifying Cys 42 in PKGIα. In a multihit HFpEF model that closely mimics the human condition, urolithin A improved diastolic function and attenuated cardiac remodeling through cysteine 42–dependent activation of PKGIα. These findings were further validated in human engineered heart tissue, where urolithin A enhanced both relaxation and contraction kinetics. These findings collectively highlight Cys 42 in PKGIα as a promising therapeutic target for HFpEF and identify urolithin A as a previously unidentified activator of this protective mechanism.
GPT-4o mini: Non-social science research article
Central T cell tolerance from sparse peptide sampling
Hannah V. Meyer, Sanjoy Dasgupta, Amitava Banerjee, Yong Lin, Rishvanth K. Prabakar, Sarah R. Chapin, Carl Kingsford, Saket Navlakha
Full text
Negative selection in the thymus limits autoimmunity by eliminating T cells that react strongly to self. Individual T cells, however, are only exposed to a small fraction of all self-peptides during their “training” in the thymus, and how tolerance is generalized to the remaining “test” self-peptides across peripheral tissues in the body remains an open question. We show that this can be achieved because the immune system satisfies two conditions necessary for generalization in machine learning settings. Consequently, sparse, random sampling of only 10% of self-peptides in the thymus is sufficient to avoid reactivity to 90% of peripheral self. We support this result and validate predictions from our model with diverse experimental data. Overall, we provide a plausible answer to a long-standing question underlying adaptive immunity, and we highlight how generalization, a fundamental challenge faced by nearly every learning algorithm, is tackled by the immune system.
GPT-4o mini: Non-social science research article
Large language models enhance annotation of enzymes in metagenomes
Lei Zheng, Bowen Li, Siqi Xu, Junnan Chen, Guanxiang Liang
Full text
Metagenomic data have notable biological potential, but their functional interpretation is frequently impeded by incomplete protein function annotations. Accurate enzyme annotation is essential for elucidating the metabolic capabilities of microbial communities within metagenomic datasets. To address this challenge, we developed FEDKEA, an enzyme annotation tool leveraging protein language models, and provided a web platform for its use. In addition, we designed a user-friendly, FEDKEA-based metagenomic pipeline, MEnzMap, which encompasses the entire analysis workflow—from raw data quality control to function prediction and downstream analyses. Applying MEnzMap to human gut metagenomic data from the iHMP2 project, we generated a comprehensive enzyme profile landscape for both healthy individuals and patients with inflammatory bowel diseases. These tools provide an efficient method for the functional annotation of microbial dark matter and facilitate the identification of disease-associated enzymes.
GPT-4o mini: Non-social science research article
Tailored nanoporous architecture in flexible polymeric aerogel enabling ultrabroadband PHz (VL)–THz–GHz wireless communication
Haoyu Ma, Haiyu Wang, Rongli Zhu, Dengyang Chen, Le Xi, Jin Leng, Qiwu Shi, Junlong Yang, Pengjian Gong, Tomoyuki Yokota, Guangxian Li, Takao Someya, Chul B. Park
Full text
Ultrabroadband electromagnetic wave (EMW) transparent materials across petahertz (PHz; visible light range), terahertz (THz), and gigahertz (GHz) range are crucial for sixth-generation (6G) to XG wireless communication. However, current EMW transparent materials cannot meet the design requirements for ultrabroadband PHz-THz-GHz antenna devices. In this study, we report the design and fabrication of flexible polyimide aerogel (PIA) capable of PHz-THz-GHz transmission based on a hybrid cross-linking strategy: (i) The combination of chemical and physical cross-linking enables the construction of a highly porous topology, yielding an ultralow dielectric constant (D k  ∌ 1.1) and improved impedance matching to minimize EMW interfacial reflection; (ii) coupling the hybrid cross-linking network with supercritical CO 2 (scCO 2 ) drying produces a uniform nanoporous architecture, effectively suppressing EMW Mie scattering; (iii) hybrid cross-linking strategy integrated with fluoride functional group modification design further reduces multiband EMW absorption across the PHz-THz-GHz range. Meanwhile, these aerogel materials demonstrate outstanding environmental stability and mechanical robustness, enabling their use in extended application scenarios. Consequently, an ultrabroadband PHz-GHz antenna was fabricated using the PIA material as the transmission interface, demonstrating continuous wireless communication even when the low-frequency GHz band is partially blocked by maintaining signal transmission through the high-frequency PHz band.
GPT-4o mini: Non-social science research article
Single-cell quantification reveals divergent mixotrophic strategies underlying niche partitioning in marine Synechococcus
Bowen He, Yanting Liu, Qi Chen, Tao Liu, Ta-Hui Lin, Silver Sung-Yun Hsiao, Der-Chuen Lee, Aixing Guo, Yuan Shen, Nianzhi Jiao, Qiang Zheng
Full text
Marine Synechococcus is among the most widespread and productive autotrophs in the ocean, yet the quantitative role of mixotrophy in different lineages remains poorly constrained. Here, we compared organic nitrogen (urea and leucine) and carbon (glucose) utilization in nutrient-depleted versus nutrient-rich Synechococcus lineages by combining NanoSIMS-based single-cell measurements from field and laboratory incubations with omics analyses. Our findings revealed distinct mixotrophic strategies in different lineages. In nutrient-depleted lineages, elevated urea uptake supplied approximately 40–63% of the estimated total nitrogen demand. This pattern aligned with genomic evidence of enhanced urea transport, particularly the up-regulation of the high-affinity urea transporter DUR3 in low-nitrogen environments. In contrast, nutrient-rich lineages exhibited greater glucose uptake, although the amended organic substrates contributed only 2 to 4% to the estimated cellular carbon demand. These lineage-specific mixotrophic strategies underpinned niche partitioning in marine Synechococcus , refining our understanding of their trophic differentiation and its implications for marine biogeochemical cycling.
GPT-4o mini: Non-social science research article
Topological mixing and irreversibility in animal chromosome evolution
Darrin T. Schultz, Arno BlĂŒmel, Dalila Destanović, Fatih Sarigol, Oleg Simakov
Full text
Animal chromosome homology can persist over hundreds of millions of years, despite fusions and translocations. The frequency, pace, and impact of these changes remain unclear. We develop a multiscale manifold representation of pan-animal genome homology to compare 5821 chromosome-scale genomes across 19 phyla and 4454 species. This “evolutionary genome topology” approach simultaneously captures chromosomal and subchromosomal organization. We find that while all 406 pairwise fusions of 29 ancestral animal linkage groups have been sampled by metazoan genome diversity, the full combinatorial potential within chromosomes remains far from explored. Our approach shows that irreversible genomic changes, caused in particular by chromosomal consolidation, dissociation, and fusion-with-mixing, place clades in distinct regions of genome architecture space. Progressive accumulation of these mixed states across genomic scales contributes to the diverging paths of animal genome evolution and has a long-lasting impact on a broad range of genes, including key developmental loci.
GPT-4o mini: Non-social science research article
Imaging Earth’s subsurface with thunderstorm-generated seismic waves
Nolan Roth, Donggeon Kim, Rafal Czarny, Young Cheol Kim, Christelle Wauthier, Tieyuan Zhu
Full text
Thunder generates atmospheric acoustic waves that couple into the ground, producing seismic signals called “thunderquakes.” Although widely observed, this atmosphere-solid Earth conversion has rarely been exploited for imaging because the coupled wavefield is complex and its governing physics are poorly constrained. Here, we show that thunderquakes recorded by preexisting telecommunication fiber-optic cables using distributed acoustic sensing (DAS) contain coherent air-coupled Rayleigh waves that can serve as seismic energy sources for near-surface tomography. We validate this mechanism using three-dimensional spectral-element simulations and dispersion modeling of thunderquakes. We analyze 2.5 years of continuous DAS data and a catalog of 458 high-fidelity thunderquakes validated by lightning records. Cross-correlation virtual-source interferometry and stacking yield dispersed surface waves from which we invert shear-wave velocity structure to ∌100-meter-depth beneath an urban karst setting. The resulting tomographic image reveals several previously undetected weak zones, some coinciding with surface deformation measured by Interferometric Synthetic Aperture Radar. The tomographic results are further validated by independent borehole logs and engineering surveys. Our results establish that thunder energy can be converted into dispersive seismic wavefields in the solid Earth and that thunderquakes can act as novel, meteorologically driven sources for seismic imaging in regions with limited access to traditional seismic sources.
GPT-4o mini: Non-social science research article
A multi-functional oral small molecule targeting energy and lipid metabolism to treat obesity and related metabolic disorders
Justin Y. Lee, Chi Zhu, Melissa A. Boldridge, Rachelle L. Stark, Gracia Bonilla, Kosuke Watari, Christina Papa, Lei Xu, Federico Gonzalez, Xin Tang, Kaitlyn T. Dang, Kook Son, Kashish Chetal, Prabha Ibrahim, Ruslan I. Sadreyev, Bilal N. Sheikh, Michael Karin, Anders M. NÀÀr
Full text
Obesity and related metabolic disorders have surged globally, and are mechanistically interconnected through dysregulated energy and lipid metabolism pathways. Current incretin-based obesity treatments act to decrease food intake, but are associated with gastrointestinal side effects and muscle wasting. Here, we identified an orally bioavailable multi-functional small molecule, 5-tetradecyloxy-2-furoic acid (TOFA), that promotes energy expenditure and rebalances lipid synthesis, thereby significantly alleviating obesity, abnormal glucose homeostasis and fatty liver-related diseases without affecting food intake or muscle mass. Mechanistically, TOFA inhibits the lipogenic enzymes acetyl-CoA carboxylases 1 and 2 (ACC1/2) and activates the Peroxisome Proliferator-Activated Receptors alpha and delta (PPARα/Ύ), key regulators of energy expenditure and lipid metabolism gene expression programs. TOFA acted more than additively with incretin analogs such as semaglutide and tirzepatide to improve obesity, dyslipidemia, and insulin resistance. Our findings suggest that the coordinated multi-targeting of energy metabolism and lipid homeostasis by TOFA is an effective approach to address multiple associated metabolic diseases.
GPT-4o mini: Non-social science research article
Multilocus basis of incipient reproductive isolation in hybridizing populations is revealed by pangenomic and epigenetic divergence
Angelo A. Ruggieri, Francesco Cicconardi, NicolĂČ Bellin, Stephen H. Montgomery, James Mallet, Steven M. Van Belleghem, Owen W. McMillan, Brian A. Counterman, Riccardo Papa
Full text
Incipient reproductive isolation in the presence of gene flow has traditionally been attributed to a small number of major-effect loci under strong selection. Here, using the Heliconius erato adaptive radiation, we apply a pangenome framework to examine how mutational divergence, regulatory variation, and structural variants contribute to genome-wide divergence. In contrast to earlier studies, our high-resolution analyses reveal widespread divergence across the genome, consistent with a multilocus barrier to gene flow. Our findings support a model in which selection acts on regulatory phenotypes under migration-selection balance, with genetic differentiation becoming more pronounced as gene flow declines. By integrating population-level sampling, we show that apparent population-specific structural and regulatory variation inferred from single-reference genomes is overestimated, reflecting pervasive reference bias. While structural variants contribute to genomic variation, in our system, most are shared or polymorphic rather than fixed differences between populations. Together, our results show that the genomic landscape of H. erato divergence reflects the combined contributions of regulatory variation and mutational change, while highlighting the importance of accounting for reference bias when interpreting structural and regulatory divergence. This multilocus framework provides a more accurate view of how reproductive barriers emerge and strengthen under ongoing gene flow.
GPT-4o mini: Non-social science research article
Coupled Atlantic atmosphere-ocean variability modulates cutaneous leishmaniasis in North Africa, enabling long-lead seasonal forecasts
Adrià San-José, Karim Aoun, Meryem Lemrani, Leonardo López, Idris Mhaidi, Aida Bouratbine, Richard Paul, Xavier Rodó
Full text
Early warning systems for climate-driven diseases require predictors with sufficient lead time, a persistent challenge for many diseases and regions. While coupled atmosphere-ocean phenomena offer a potential solution, they remain largely underexploited in temperate zones. Here, we establish a multiscale connection between cutaneous leishmaniasis (CL) dynamics in North Africa, the North Atlantic Oscillation (NAO), and the Atlantic Multidecadal Variability (AMV). Beyond the NAO’s influence on seasonal rainfall, we uncover low-frequency variability in the NAO-AMV system that modulates interannual rainfall patterns in North Africa, yielding multiyear periods of high and low CL activity. To quantify this predictability, we develop a unified transmission model applied across Morocco and Tunisia for both anthroponotic ( Leishmania tropica ) and zoonotic ( Leishmania major ) forms. Predictive skill up to 12 months ahead improves across all contexts when we incorporate local temperature and precipitation alongside the multiscale signals of the NAO and AMV. This study shows how coupled Atlantic climate variability modulates an infectious disease across timescales, enabling an operational, long-lead seasonal forecast system for a vector-borne disease in the Mediterranean region.
GPT-4o mini: Non-social science research article
Mitochondrial profiling across macrophage states reveals inhibition of IL-4/IL-13 reprogramming by the integrated stress response
Joan Blanco-Fernandez, Miriam Lisci, Mads M. Foged, Chloé Chapuis, Tim PflÀsterer, Tatjana Kleele, Alexis A. Jourdain
Full text
Mitochondria drive cellular reprogramming by integrating metabolism and signaling. In macrophages, mitochondria are central to immunometabolic responses to external cues, but the extent to which they are remodeled and participate in macrophage reprogramming remains unclear. Here, we integrate transcriptomics with whole-cell and purified mitochondrial proteomics to profile lipopolysaccharide (LPS)/interferon-γ (IFN-γ)– and interleukin-4 (IL-4)/IL-13–stimulated macrophages. We reveal a notable disconnect between mitochondrial transcript and protein levels following either stimulus and a signal transducer and activator of transcription 6 (STAT6)–dependent increase in mitochondrial DNA (mtDNA) expression and intramitochondrial translation in IL-4/IL-13 macrophages. We demonstrate that pharmacological inhibition of mitochondrial translation or individual respiratory chain complexes variably impairs reprogramming, whereas ATP synthase inhibition uniquely triggers a heme-regulated inhibitor (HRI)–dependent integrated stress response (ISR) through mitochondrial hyperpolarization, thereby preventing IL-4/IL-13 reprogramming. Mechanistically, we show that restoring mitochondrial membrane potential or inhibiting the ISR rescues IL-4/IL-13–mediated reprogramming. Together, we identify mtDNA expression, intramitochondrial translation, and mitochondrial membrane potential as critical, drug-sensitive determinants of the IL-4/IL-13 response.
GPT-4o mini: Non-social science research article
Dynamically manipulated interface polarization via symmetry engineering for self-gated electronics
Zhuangzhuang Zhang, Luying Xu, Gaobo Wang, Yixuan He, Shuhai Liu, Chunhua An, Libo Chen, Longfei Wang, Zhong Lin Wang
Full text
Interfaces have always been a key for functional devices in condensed-matter physic. However, dynamic regulation of interfacial symmetry and the subsequent effects have still been underestimated, especially in bulk materials. Here, we show that the interfacial crystallographic symmetry can be precisely modulated by electric field induced oxygen vacancy rearrangement in bulk centrosymmetric semiconductors (TiO 2 , SrTiO 3 , etc.), resulting in tunable interface polarization. Our results show that the interface polarization of metal-semiconductor heterostructure can be reversibly modified in a nonvolatile manner, with a tunable electromechanical response varying from 6.79 to 9.07 p.m./V, which is comparable to common piezoelectric semiconductors (ZnO, GaN, MoS 2 , etc.). Substantial self-gated carrier transport in metal-semiconductor heterostructure is achieved, with a Schottky barrier tuned by 30.8 meV. Furthermore, the self-gated electronics effectively simplifies the complicated structures of logic devices, integrating logic and storage operations through programmable interface polarization. These findings offer a distinctive approach to design the interface symmetry and functionalities beyond the intrinsic limitation of bulk centrosymmetric materials.
GPT-4o mini: Non-social science research article
Hope for heart failure with preserved ejection fraction?
Robert M. Blanton
Full text
A common form of heart failure improves when cyclic guanosine monophosphate-dependent protein kinase is activated with a novel agent that promotes cysteine-42 oxidation.
GPT-4o mini: Non-social science research article
Pulseometry: A differential readout to compensate signal drift of potentiometric probes
Yaotian Wu, Junyu Zhou, Yu Qin, Eric Bakker
Full text
Ion selective electrodes are widely used sensors in point-of-care testing devices to assay electrolytes in whole blood samples. With single-use system, the first solution contact normally results in an important signal drift that negatively affects measurement accuracy. In this work, we propose an approach coined pulseometry to compensate for signal drift. The potentiometric signal is processed through a differential circuit incorporating RC components of different time constants. The differential potential will remain constant for a slowly drifting baseline, while a rapid potential change will result in a peak-shaped difference signal that may be baseline subtracted and integrated to extract the components information. The method was successfully integrated into mass fabricated, microfluidic test cards used in commercial blood gas electrolyte analyzers. Blood calcium levels from three individuals were measured, giving SDs of 0.008 to 0.024 mM, improving precision by 36 to 67% compared to potentiometry. These results showcase the potential of pulseometry for improving the performance of electrochemical sensing in clinical diagnostics.
GPT-4o mini: Non-social science research article
Regulating phonon-carrier transport by interfacial symmetry breaking in thermoelectric multilayers
Zhengtong Yao, Bin Liu, Shuai Zhang, Quanxin Guo, Yutao Han, Zhihao Guan, Kun Yang, Wenpei Gao, Yakun Yuan, Zhenhua Wu, Moran Wang, Zhiyu Hu
Full text
More than half of global primary energy is dissipated as low-grade waste heat, yet thermoelectric conversion remains constrained by the intrinsic coupling between phonon and charge transport. Here, we introduce graded interfacial size distribution as a thermodynamic design variable that breaks translational symmetry in multilayers, enabling anisotropic regulation of phonon-carrier transport. Using bismuth telluride (Bi 2 Te 3 )/metal [gold, silver, and platinum (Pt)] multilayers as a model system, we demonstrate that multiscale interface distributions induce broadband phonon suppression through the coexistence of interfacial scattering, coherent interference, and localization. This yields an ultralow cross-plane thermal conductivity of 0.22 watts per meter per kelvin and a high room-temperature ZT of 1.51 in Bi 2 Te 3 /Pt films. Concurrently, asymmetric metal-semiconductor interfaces create quasi–two-dimensional accumulation channels that enhance in-plane carrier mobility while preserving energy filtering, delivering a power factor of 176.2 microwatts per centimeter per square kelvin at 300 kelvin. The graded architecture enables high performance in both vertical and flexible planar devices, illustrating a general strategy in which interface distribution, not merely composition, governs anisotropic heat-charge transport. Our findings establish statistical interface engineering as a platform for thermoelectric energy harvesting and solid-state cooling.
GPT-4o mini: Non-social science research article
Programmable photonic neural engine with all-optical nonlinear activation and 40,000 connections
Hao Sun, Xinyi Zhu, José Azaña
Full text
The rapid advancement of artificial neural networks (ANNs) demands computational platforms with higher speed, energy efficiency, and scalability. Optical computing offers an appealing solution owing to the high-speed processing, inherent parallelism, and low energy consumption. However, existing optical neural network architectures face fundamental trade-offs between scalability, reconfigurability, and processing latency, constrained by the need to rely on electronic nonlinearities or fixed optical interconnections. Here, we report an end-to-end photonic neuromorphic engine that integrates all-optical nonlinearity into a loop-based, time-multiplexed photonic architecture. This approach enables all optical neurons to share common hardware, supporting enhanced connectivity and full reconfigurability with reduced latency. Implementations of four distinct network topologies, with a maximum of 40,000 optical connections for the single-layer perceptron, achieve digital-level inference accuracy and computational latency over two orders of magnitude shorter than state-of-the-art electronic processors, potentially paving the way for scalable, reconfigurable, and ultrafast optical artificial intelligence systems.
GPT-4o mini: Non-social science research article
Isocaloric switch from low-fat to Western high-fat diet triggers transcriptomic reprogramming and ectopic olfactory receptor responses
Jonathan Bertram, Michail Lazaratos, Michael Kruse, Silke Hornemann, Alexander S. Mosig, Turid Frahnow, Martin Osterhoff, Andreas Busjahn, Anne-Cathrin Ost, Annette SchĂŒrmann, Olga Pivovarova-Ramich, Andreas FH Pfeiffer
Full text
Although Western diet (WD) rich in saturated fat is regarded as a trigger of metabolic disease and inflammation, the role of this diet in the absence of obesity is unclear. We studied the metabolic, inflammatory, anthropometric, and adipose tissue transcriptomic responses of 92 twins to 6 weeks of WD following 6 weeks of a healthy low-fat diet while maintaining stable body weight. The WD increased total, LDL and HDL cholesterol but not triglycerides or free fatty acids and induced transient and moderate increases of insulin resistance and some inflammatory markers after 1 week, which disappeared after 6 weeks. Extensive transcriptomic changes reflected restructuring of subcutaneous abdominal adipose tissue. Olfactory receptor (OR) mRNAs were increased in correlation with insulin resistance, liver, and visceral fat, cytokines like IL-18 and VEGF, but inversely related to adiponectin and extracellular NAMPT. In conclusion, WD triggers metabolic and transcriptomic reprogramming closely linked to ectopic OR responses.
GPT-4o mini: Non-social science research article
Ultrafast energy transfer across Pd/MXene interface via hot phonon-electron interactions
Jie Zhao, Qi Zhang, Meng Geng, Pan Xiong, Kun Zhao, Ruifeng Lu, Kaijun Yuan, Xueming Yang
Full text
The interfacial structure and energy transfer (ET) in heterostructures have attracted tremendous attention for their growing importance in thermal management, catalysis, and optoelectronic applications. However, the role of carrier-lattice interaction in interfacial ET at the nanoscale remains unclear. Here, we construct metal/MXene heterostructures via in situ chemical growth as platforms to study interfacial energy flow. On the basis of femtosecond transient absorption spectroscopic measurements, interfacial ET within ∌1.3 picoseconds is observed in Pd/MXene, which could not be explained by traditional phonon-phonon interaction. Experimental results combined with density functional theory calculations identify an ultrafast ET route involving strong interfacial coupling and high-density-of-state electrons near the Fermi level, enabling hot phonon–driven electron excitation. Distinct from conventional diffusive phonon processes, this ET route exhibits higher ET rate and efficiency with increasing absorbed photon energy and pump fluence. These findings reveal that the tuning of interfacial chemical bonds holds the promise to achieve high-efficiency energy transport across nanoscale interfaces.
GPT-4o mini: Non-social science research article
Ultrathin CoO nanosheets enable direct CO 2 hydrogenation to acetic acid
Chengsheng Yang, Bo Wu, Huimin Xu, Doudou Hu, Xiwen Song, Ziang Liu, Yifeng Zhu, Sai Chen, Chunlei Pei, Jinlong Gong
Full text
Direct hydrogenation of carbon dioxide (CO 2 ) to acetic acid, a key commodity chemical, offers a sustainable route to valorize greenhouse gases but is plagued by CO 2 inertness, thermodynamic barriers, and poor selectivity for C-C coupling over competing overhydrogenation. This paper describes the design and synthesis of ultrathin cobalt(II) oxide nanosheets (<4 nm thick) that achieve direct one-step CO 2 hydrogenation to acetic acid with over 90% selectivity, minimal C 1 by-products and the highest reported yield under mild conditions, surpassing traditional multistep routes (such as CO 2 to CO/methanol followed by carbonylation) in cost, efficiency, and atom economy. These two-dimensional structures feature extended terraces that undergo in situ reconstruction in CO 2 /H 2 mixtures to a cobalt(II) carbonate hydroxide–like phase, stabilizing Co 2+ and generating abundant hydroxyl groups to optimize CO 2 activation and selective C–C coupling while suppressing over-reduction. In situ characterizations, including electron energy-loss near-edge structure, spatially resolved infrared spectroscopy, and kinetic/isotopic analyses, reveal the reconstructed phase’s role in modulating electron density for superior yields and confirm a formate-coupling mechanism unattainable with conventional catalysts. This study introduces a paradigm for CO 2 upgrading: harnessing dynamic surface reconstructions and nanoscale morphology to access elusive multicarbon pathways, with implications for sustainable chemical synthesis.
GPT-4o mini: Non-social science research article
Reconstruction and attribution of Late-Pleistocene changes in the Earth’s energy imbalance
Saray Sanchez, Peter U. Clark, Chenyu Zhu, Jonathan M. Gregory, Zhengyu Liu, Feng He
Full text
The Earth’s energy imbalance (EEI) that develops at the top of the atmosphere is accommodated by gains or losses of energy in Earth’s heat reservoirs, leading to temperature and sea level change. The global ocean has stored about 90% of the EEI from anthropogenic forcing, but the attribution of past changes of EEI remains largely unknown, thus obscuring our understanding of past climate change. Here, we reconstruct changes in mean ocean temperature over the past 150,000 years that, with a reconstruction of ice sheet–volume changes, allow us to isolate the contributions of the dominant ocean and ice sheet heat reservoirs to the global energy inventory as well as to derive their associated contributions to EEI. We attribute orbital-scale EEI variability to joint precessional and CO 2 forcing that caused changes in rates of ice sheet energy storage. In contrast, millennial-scale EEI variability can be attributed to radiative responses to decreases in the Atlantic meridional overturning circulation and increasing CO 2 during Heinrich stadials that caused changes in rates of ocean energy storage.
GPT-4o mini: Non-social science research article
Spiderweb-inspired electronically conductive hygroscopic adhesive for chronic bioelectronic interface
Lingxuan Kong, Fulin Wang, Hanqi Wen, Chan Wang, Zheye Zhang, Lewen Zheng, Zhuoming Liang, Yuxin Liu, Peng Chen
Full text
Long-term physiological signal monitoring is critical for accurate diagnosis and effective management of chronic diseases. However, current electrode technologies face significant drawbacks: dry electrodes exhibit high electrochemical impedance and poor adhesion to skin, while wet electrodes suffer from short service lifetimes due to water loss. Inspired by the hygroscopic properties of spider webs, we developed an electronically conductive hygroscopic adhesive (termed as “hygrotrode”) that continuously absorbs ambient moisture through a cross-linked, three-dimensional hygroscopic polymer network. This design maintains a low interface impedance and high adhesion energy for over a year, facilitated by absorbed intermediate water that electrochemically bridges the conducting polymer and skin tissue. The specific impedance of hygrotrode is 82.4 times lower compared with wet electrodes after 1 year. We further demonstrate hygrotrode’s suitability for chronic biopotential monitoring and electromyography-based gesture recognition, highlighting its wide-ranging applicability in long-term wearable electronics and human-machine interfaces.
GPT-4o mini: Non-social science research article
ÎŽ2-Protocadherins organize parallel indirect basal ganglia circuits
Naosuke Hoshina, Joshua M. Boeckers, Erin M. Johnson-Venkatesh, Miyuki Hoshina, Kana Matsumoto, Abhijnana Das, Veronica R. Rally, Jaanvi Sant, Akiko Terauchi, Shinji Kinoshita, Takafumi Inoue, Hisashi Umemori
Full text
The basal ganglia (BG) contain multiple parallel neural circuits, each of which may control different behaviors. However, how the distinct parallel BG circuits are molecularly organized is not known. Here, we show that two ή2-protocadherins (PCDHs), PCDH17 and PCDH10, which are homophilic cell adhesion molecules, establish and define two distinct indirect BG circuits that regulate different behaviors. PCDH17 and PCDH10 are expressed in a complementary expression pattern in the BG, anatomically defining two parallel indirect BG connections. Indirect pathway–specific Pcdh17 and Pcdh10 conditional knockout (cKO) mice show impaired establishment of the indirect BG circuits in a region-preferential manner. Last, the Pcdh17 cKO mice show defects in task learning, while the Pcdh10 cKO mice show defects in motor/sensory habituation. These results identify PCDH17 and PCDH10 as the molecular organizers for two distinct indirect BG circuits regulating different behaviors and reveal the molecular mechanisms for organizing parallel BG circuits.
GPT-4o mini: Non-social science research article
Enriched experience increases reciprocal synaptic connectivity and coding sparsity in higher-order cortex
Rajat Saxena, Justin L. Shobe, Aida M. Andujo, Wing Ning, Christelle Anaclet, Bruce L. McNaughton
Full text
The integration of new information during sleep reshapes cortical representations that support categorical knowledge. Autoassociative attractor network theories predict that reciprocal excitatory connections help form stable categorical attractors, but direct evidence is missing. We tested this using 10 weeks of enriched experience [environmental enrichment (ENR)] in mice as a model for knowledge accumulation and recorded single-unit activity across the hippocampus and neocortex. ENR induced significant remodeling in high-level but not low-level neocortex, with a major shift from unidirectional to bidirectional functional excitatory-excitatory connections, suggestive of increased “cell assemblies.” This was accompanied by increased inhibitory-to-excitatory connections and sparser, more orthogonal population activity during awake rest and slow-wave sleep, particularly in deep layers. Thus, ENR reorganizes cortical circuits into a symmetric, inhibition-balanced network that improves coding efficiency, supporting long-standing attractor network predictions.
GPT-4o mini: Non-social science research article
Ultrawide-FOV full-color waveguides free of rainbow and fishbone artifacts via physics-constrained generative metagrating design
Mengguang Wang, Yong Li, Huihui Li, Fei Wu, Zeqing Yu, Huai Xia, Qiangbo Zhang, Changwei Zhang, Yiyang Liu, Huaze Xie, Chang Wang, Zhenrong Zheng
Full text
Augmented reality (AR) displays are gaining prominence in consumer and industrial applications due to two-dimensional pupil-expanding waveguides, which achieve the essential dual requirements of compact form factors and large eyebox through innovative dual-axis beam replication technology. Nevertheless, these systems face an intrinsic trilemma compromising three critical parameters—efficiency, angular uniformity, and chromatic dispersion—with all three limitations becoming particularly pronounced at wide angles (>50°) across the visible spectrum, manifesting as fishbone artifacts (periodic non-uniformity patterns) and rainbow effects. To overcome these fundamental limitations, we present a physics-constrained generative adversarial network (PC-GAN) that systematically resolves the trilemma by incorporating two key physical principles: dilated pupil restraint ratio (DPRR) for uniformity control and periodic constraint theory (PCT) for dispersion management. This framework enables high-throughput discovery of metagrating designs while ensuring high-quality imaging performance in single-layer waveguides across the full visible spectrum and ultrawide field of view. Notably, the PC-GAN demonstrates its unique capability by autonomously discovering optimized snowflake-like metagrating (SLMG) geometries - fractal structures that provide breakthrough solutions for pupil expansion uniformity through their hierarchical light manipulation properties. Experimental realization of PC-GAN-optimized metagratings in disparate material systems (polymer and SiC) consistently delivered wide-angle, full-color operation in single-layer waveguides, while eliminating the characteristic fishbone artifacts and rainbow effects of conventional diffractive designs. This physics-constrained generative framework unlocks transformative potential for complex photonic systems beyond AR, enabling advanced designs ranging from ultrathin VR displays to multi-physics-optimized quantum optical devices.
GPT-4o mini: Non-social science research article
Lattice engineering of thermally evaporated perovskite enables monolithically integrated micro-display
Jianfeng Ou, Zixi Shen, Shuwen Yan, Yuanwu Wu, Hongyi Xie, Xiang Zhang, Yannan Zhang, Jingshu Zhang, Zhengzheng Liu, Lei Li, Jianbo Wang, Juan Du, Luying Li, Jiajun Luo, Jiang Tang
Full text
Perovskite light-emitting diodes (PeLEDs) have recently demonstrated substantial potential for next-generation micro-displays due to their excellent efficiency and brightness. However, the best-performing PeLEDs typically suffer from low brightness and severe efficiency roll-off, as well as the considerable challenge of monolithic integration at pixel sizes down to 2 ÎŒm. Here, we present a lattice-engineering approach for thermally evaporated perovskites that simultaneously achieves high-performance PeLEDs and high-definition monolithic integration for perovskite micro-display applications. The lattice engineering achieved by in situ incorporation of FABr effectively suppresses Ruddlesden–Popper (RP) faults within nanocrystals and yields a uniform electric-field distribution, thereby reducing charge accumulation and suppressing Auger recombination. We further fabricated PeLEDs with a fully vacuum-deposited device architecture, demonstrating an external quantum efficiency (EQE) of 20.6% and high brightness levels exceeding 160,000 cd m −2 , with reduced efficiency roll-off. More importantly, through process and device optimizations, we achieved nanometer-scale conformal deposition on the surfaces of complementary metal-oxide-semiconductor (CMOS) driver pixel pits, thereby developing a perovskite micro-display with a resolution of 3,000 pixels per inch (PPI) capable of displaying vivid video. Our research paves the way for advancing micro-display technology.
GPT-4o mini: Non-social science research article
Constitutively active glucagon receptor (GCGR) physiologically regulates body temperature in lizards
Songsong Liu, Qingqing Ren, Shanshan Lai, Xiangying Xiang, Yongjie Huang, Qingqing Wang, Qiujinman Mao, Xiaofei Yan, Ao Dai, Najeeb Ullah, Hong Li, Yin Qi, Yanfu Qu, Xiang Ji, Juergen Brosius, Cheng Deng
Full text
Endotherms use complex internal mechanisms to maintain a steady body temperature, whereas ectotherms rely on environmental factors and behaviors for thermoregulation. Certain ectothermic animals, like some lizards, can also physiologically regulate their body temperature to some extent, with interspecies variations in thermoregulatory capacity under low-temperature conditions. However, the molecular mechanisms underlying this physiological regulation have remained unclear since its discovery about 80 years ago. Here, we reveal that the hepatic expression of constitutively active glucagon receptor (GCGR) in lizards, particularly in iguana, correlated with their thermoregulatory capacity when kept at low temperatures. When Pogona vitticeps and Phrynocephalus vlangalii with thermoregulatory capacity were treated with short hairpin RNA– GCGR or GCGR antagonist, their body temperatures dropped, and the expression of genes related to energy metabolism and respiratory metabolic rate was down-regulated. In contrast, Eremias argus , lacking thermoregulatory ability, revealed low hepatic GCGR expression. Overexpression of P. vitticeps GCGR (pv GCGR ) in the liver of E. argus increased body temperature and enhanced energy metabolism. Furthermore, in mice with reduced thermoregulatory ability by chlorpromazine administration, overexpression of constitutively active GCGR ligand-independently increased body temperature under cold conditions. In conclusion, constitutively active GCGR drives the physiological thermoregulation in lizards, and our study offered previously unidentified insights into expression regulation of constitutively active GPCR into physiological adaptations responding to environmental changes.
GPT-4o mini: Non-social science research article
AI-driven robotics for optics
Shiekh Zia Uddin, Sachin Vaidya, Shrish Choudhary, Zhuo Chen, Raafat K. Salib, Luke Huang, Dirk R. Englund, Marin Soljačić
Full text
Optical experiments are essential across science and technology, yet their design, assembly, and alignment remain predominantly manual, limiting throughput, reproducibility, and scalability. Automating such experiments is challenging because of stringent precision requirements and the diversity of setups in typical real-world optical laboratory environments. Here, we introduce a platform that integrates generative artificial intelligence, computer vision, and precision robotics to automate free-space optical experiments. The system translates user-defined goals into valid optical configurations, assembles them with submillimeter accuracy, and performs micrometer-scale fine alignment using a robotic tool. It then executes a range of accurate measurements, including beam characterization, polarization mapping, and spectroscopy. This work establishes a platform for reconfigurable optics automation, potentially enabling programmable and adaptive experimental workflows.
GPT-4o mini: Non-social science research article
Perspiration vapor lightens near-skin air, but hinders human evaporative cooling in arid heat
Shri H. Viswanathan, Ankit Joshi, Isabella DeClair, Bryce Twidwell, Muhammad Abdullah, Lyle Bartels, Faisal Abedin, Joseph Rotella, Cibin T. Jose, Konrad Rykaczewski
Full text
Sweat evaporation is the body’s primary cooling mechanism, yet the physical factors governing it are not fully understood. We identify a “dueling buoyancy” effect in the context of the human body, in which perspiration vapor reduces the near-skin air density, counteracting the downward flow driven by cooling of warm air upon contact with the skin. In hot, arid, stagnant environments, this opposing buoyancy suppresses free convection and can reduce sweat evaporation by more than half. As a result, commonly used thermoregulation models can substantially underpredict body temperature (e.g., by 1°C after 2 hours of exposure to typical Arizona summer conditions). We develop compact, physics-informed models for free-convective heat transfer coefficients across wide temperature and humidity ranges, enabling improved thermoregulation modeling and thermal audits. These results enhance understanding of human heat balance and support more accurate heat-stress assessment to inform behavioral, infrastructural, and policy decisions for extreme-heat adaptations.
GPT-4o mini: Non-social science research article
Catalyst-free, autoinductive photochemical upcycling of aromatic polymers and mixed plastics via autosensitization
Qin Qin, Jingxiang Wang, Jiarui Fei, Xi Peng, Xiao Xiao
Full text
Photochemical upcycling of polymers is a promising strategy for mitigating the plastic-waste crisis; however, many recent advances have centered on developing costly photocatalysts. In contrast, the auto-sensitized photoreactivity of aromatic polymers such as polystyrene (PS)—albeit documented for decades—has remained unexploited for practical upcycling. Here we leverage this overlooked reactivity to develop a catalyst-free platform that converts PS into benzoic acid under visible light irradiation in air. The approach extends to other aromatic polymers including polyethylene terephthalate (PET), polycarbonate, polyether sulfone (PES), and epoxy resins, as well as biomass feedstocks such as lignin. Mechanistic experiments combined with DFT calculations reveal a non-innocent role for the chloroalkane solvent, an aspect that has been underrecognized in related photochemical upcycling systems, as well as an autoinductive rate acceleration. This intrinsic PS photoreactivity further enables co-upcycling with non-aromatic polymers and remains effective in a waste-emulating halogenated solvent mixture, pointing to potential synergy between mixed plastics/biomass valorization and solvent waste management.
GPT-4o mini: Non-social science research article
Screening of anti-metastasis drugs by targeting angiopellosis and cancer cluster extravasation
Xiao Cheng, Mengrui Liu, Shiqi Hu, Kaiyue Zhang, Zhang Yue, Shuo Liu, Dashuai Zhu, Zhenzhen Wang, Chao Lu, Na Yan, Brian S. Henick, Ke Cheng
Full text
Metastasis accounts for 90% of cancer-related deaths. Extravasation is a necessary step for cancer metastasis. Currently, there are no drugs that specially target extravasation. Most cancer therapies target either proliferation or angiogenesis. We previously identified “angiopellosis” as the dominant mechanism by which vascular endothelial cells undergo conformational changes and actively “push” circulating cancer cells out of blood vessels. In this study, we developed an image-based high-throughput drug screening assay by coculturing cancer membrane–coated spheres with endothelial monolayers. Through this platform, we identified Bay 61-3606 as a lead angiopellosis inhibitor. Bay 61-3606 substantially reduced cancer cluster extravasation, an activity solely supported by angiopellosis and associated with higher metastatic potential, in both zebrafish and mouse models. Furthermore, Bay 61-3606 decreased distant metastases in murine models of lung carcinoma and triple-negative breast cancer. Mechanistically, Bay 61-3606 targeted the c-Jun amino-terminal kinase signaling pathway, down-regulating COL8A1 expression in endothelial cells and impairing the angiopellosis process.
GPT-4o mini: Non-social science research article
Brush-mediated angular constraints reshape structure, rigidity, and percolation in colloidal depletion gels
Ziye Zhuang, Robert A. Campbell, Paniz Haghighi, Safa Jamali, Ali Mohraz
Full text
Colloidal gels, like many other soft and disordered solids derive their mechanical properties not only from the strength of interparticle attraction but also from the symmetry of the forces that constrain particle motion. Although noncentral interactions are known to profoundly alter rigidity and elasticity, they are typically introduced through particle anisotropy, surface roughness, or patchy interactions, obscuring their independent role. Here, we demonstrate a minimal and geometry-preserving route to emergent noncentral forces in colloidal gels by reducing the density of surface-grafted polymer brushes. At low brush density, partial brush interpenetration introduces an effective angular bending rigidity at particle contacts, despite fully isotropic particle geometry. This emergent constraint suppresses local densification, stabilizes low-coordination networks, and produces highly ramified gel structures with enhanced elasticity. Combining experiments, simulations, and mean-field theory, we show that these noncentral constraints reorganize structure and mechanics across length scales, shifting gelation boundaries and increasing the elastic modulus by nearly a factor of 3. Our results establish surface brush density as a generic control parameter for programming interaction symmetry in soft particulate matter, with implications for rigidity, percolation, and mechanical design in disordered systems.
GPT-4o mini: Non-social science research article
Nonlocal microwave engineering: Shaping dispersion relations and enabling pulse transformations via time-switched long-range couplings
Matteo Ciabattoni, Francesco Monticone
Full text
Nonlocal metamaterials have recently attracted considerable attention across different areas of wave physics, owing to their ability to translate long-range interactions among meta-atoms into a wide array of wave vector–dependent responses and functionalities. Here, we introduce nonlocal transmission-line metamaterials (TL MTMs) as a versatile platform to investigate and engineer nonlocality in the microwave frequency regime. We first establish a concise theoretical framework for nonlocal TL MTMs based on circuit and network theory, from which we derive the general dispersion relation for TL MTMs with arbitrarily complex nonlocal coupling configurations. Building on this foundation, we demonstrate how such structures can be used to synthesize nearly arbitrary even-symmetric dispersion relations, effectively linking nonlocal circuit parameters to prescribed dispersion profiles. We then introduce time-switched nonlocal TL MTMs, a class of metamaterials with time-varying nonlocality in which the nonlocal branches are dynamically activated as an electromagnetic pulse propagates through the structure. This platform enables complex transformations on a propagating pulse, as well as the excitation of modes with positive, negative, and zero group velocity. Last, we experimentally validate our theoretical and numerical predictions with a proof-of-concept demonstration of a time-switched nonlocal TL MTM, observing a vertical transition in the dispersion diagram induced by abrupt time switching. Our results provide key physical insights into the behavior of nonlocal MTMs, establish a versatile platform to investigate the interplay of frequency dispersion, spatial dispersion and time modulation, and lay a general foundation for the design of more advanced nonlocal and time-varying electromagnetic and photonic systems.
GPT-4o mini: Non-social science research article
Intrinsic timing, not temporal prediction, underlies ramping dynamics in visual and parietal cortex during passive behavior
Yicong Huang, Ali Shamsnia, Mengze Chen, Shuang Wu, Timothy Stamm, Sophie Medico, Farzaneh Najafi
Full text
Ramping neural activity is widely interpreted as a signature of predictive processing, but whether these signals truly reflect predictions or instead emerge from sensory mechanisms remains unclear. To address this question, we used two-photon calcium imaging across multiple cell types in visual and parietal cortex, while awake mice passively received repeated audiovisual stimuli presented under distinct temporal structures. Neurons segregated into two broad response classes: stimulus-activated (ramp-down) and stimulus-inhibited (ramp-up) populations with diverse temporal kinetics. Multiple findings argued against a predictive interpretation: Ramping activity was present in naĂŻve animals, neural responses changed immediately after short/long interval transitions, and unexpected stimulus timings elicited nearly identical responses in predictable and irregular contexts. Population analyses further showed that ramping reflected relaxation from stimulus-evoked activity rather than anticipatory buildup. Heterogeneous kinetics generated a robust population code for elapsed time. Together, these findings show that neural ramps during passive stimulation arise from stimulus-evoked dynamics that intrinsically generate temporal signals, rather than from temporal predictive processing.
GPT-4o mini: Non-social science research article
China’s lakes remain carbon sources: Insights from the balance between intrinsic carbon sequestration and emissions
Shilan Wang, Xiaodong Nie, Yi Wang, Ying Zhao, Josep Peñuelas, Alexander Gelfan, Zhengang Wang, Peng Gao, Di Tong, Zhongwu Li
Full text
Accurate assessments of lake carbon balance are essential for filling gaps in the global carbon budget and addressing climate change. However, persistent uncertainties arise from an incomplete understanding of intrinsic carbon sequestration and its balance with emission effects. Here, using source fingerprinting techniques, we isolated the autochthonous organic carbon (OC Auto ) burial, which represents the intrinsic carbon sequestration of lakes. We found that OC Auto burial accounted for only 53.23% of total lake carbon emissions in the 2020s, leaving China’s lakes as carbon sources (−0.83 teragrams of carbon per year). Regionally, lakes on the Qinghai-Tibet and Yunnan-Guizhou Plateaus have shifted to carbon sinks, whereas lakes in the eastern and northeastern regions remain major carbon sources. Scenario projections indicated that restoring China’s lakes to macrophyte-dominated states under the Shared Socioeconomic Pathway SSP2-4.5 scenario could transition them into stable carbon sinks before OC Auto burial peaks around 2070. To facilitate this transition, we proposed a lake classification-and-management framework based on carbon sink potential and emission risks to guide carbon sequestration and climate mitigation efforts.
GPT-4o mini: Non-social science research article
BeetleBot: An integrated bioinspired soft robot for multimodal sensing and adaptive interaction
Inho Kim, Dickson R. Yao, Shukun Yin, Phuoc Thanh Tran-Ngoc, Jihong Min, Nathan Ng, Wenzheng Heng, Jiahong Li, Behnam Sadri, Hirotaka Sato, Sang Ouk Kim, Wei Gao
Full text
Biological organisms exhibit tightly integrated motor functions, sensory input, and control systems that enable adaptive behaviors across diverse environments. Emulating such coordination in robotics remains challenging, as most soft machines compartmentalize actuation, sensing, and control. Here, we present BeetleBot, an adaptive beetle-bioinspired soft robot platform that seamlessly integrates programmable locomotion, object manipulation, sensory feedback, and intuitive human-machine interaction. BeetleBot features electrothermally actuated liquid crystal elastomer muscles embedded in modular leg structures and a soft gripper, with a flexible circuit enabling independent control. A wearable strain-sensing patch supports wireless gesture-based operation, while embedded vision and tactile sensors provide real-time environmental feedback. All functional components are fabricated through scalable additive manufacturing techniques. We demonstrate terrain navigation, object recognition, and gesture-control synchronized bidirectional interaction between the user and the robot. This multifunctional platform emulates the adaptability of living systems and establishes a promising foundation for next-generation intelligent soft robotics.
GPT-4o mini: Non-social science research article
Low-SWaP magneto-optical trap enabled by planar photonic and magnetic components
Hao Gao, Yumeng Zhu, Zhilong Yu, Yuhui Hu, Zhelin Lin, Shiming Wei, Feng Zhao, Amit Agrawal, Zeyang Liu, Xiaochi Liu, Cheng Zhang
Full text
Compact, lightweight, and energy-efficient cold-atom systems are foundational for the development of deployable quantum technologies, yet their realization remains largely constrained due to reliance on bulky optical and magnetic components. Here, we demonstrate a record-low-SWaP (size, weight, and power) magneto-optical trap architecture seamlessly integrating planar photonic and magnetic components into a monolithic, scalable, and manufacturable platform. This is achieved by developing a multifunctional metasurface that converts a linearly-polarized Gaussian beam into a circularly-polarized flat-top beam (FTB), replacing conventional lens-waveplate assemblies. In parallel, a planar magnetic coil chip substitutes bulky anti-Helmholtz coils and generates the required quadrupole magnetic field with substantially reduced power consumption. Using D 2 line cooling of 87 Rb atoms, the fully planar system achieves nearly an order-of-magnitude improvement in trapped-atom number while operating at a fraction of the SWaP of traditional implementations. This planar integration strategy provides an energy-efficient and scalable pathway toward robust, deployable cold-atom platforms.
GPT-4o mini: Non-social science research article
A pressure-tolerant, miniature ocean-sensing tag with acoustic telemetry for real-time CTD monitoring
Shao-Hao Lu, Jun Lu, Yi Li, Minsu Park, Jaeyoung Yoo, Aljon Salalila, Zhiqun Daniel Deng, Xueju Sophie Wang
Full text
Real-time ocean monitoring enables instantaneous oceanographic analysis and supports maritime operations. However, conventional sensors require metallic housings to withstand high hydrostatic pressure, increasing their weight and power demand. Soft electronics offer a promising alternative, but their functionality and commonly used electromagnetic communication are ineffective underwater. Here, we present a pressure-tolerant, miniaturized ocean-sensing tag that seamlessly integrates soft conductivity, temperature, and depth (CTD) sensors with acoustic transducers for in situ monitoring and underwater data transmission. Measuring 17 mm by 20 mm by 7.5 mm and weighing 4.90 g, the tag maintains reliable performance under hydrostatic pressures of up to 15 MPa, corresponding to a depth of approximately 1,500 m, and achieves underwater transmission ranges of up to 492.7 m. Field testing in the Salish Sea demonstrates wireless, real-time CTD monitoring with measurement accuracy comparable to commercial sensors and reliable acoustic telemetry (87.34% detection efficiency and 100% accuracy over evaluated transmission distances). This ocean sensing platform enables energy-efficient deployment on diverse platforms and significantly advances next-generation ocean observation and deep-sea exploration.
GPT-4o mini: Non-social science research article
Rapid fabrication of stretchable, ultratough, and rigid polymer materials
Yuxuan Qiao, Kai Guo, Dongzhao Hao, Na Li, Xiaojiao Shi, Boyao Wang, Ya Liang, Tifeng Jiao, Junjie Li, Zhihui Qin
Full text
Polymer materials hold great promise for various applications but face trade-offs among stiffness, toughness, stretchability, and scalable fabrication. Here, we report a strategy that integrates dense side-chain hydrogen-bonding motifs capable of conformational transitions into a highly entangled flexible polymer network through photocuring copolymerization of acrylamide-based and hydroxyl-terminated acrylate monomers, enabling the rapid fabrication of stiff, tough, and stretchable polymers. The densely cross-linked structure restricts chain mobility, while hierarchical hydrogen bonds with partially low rotational energy barriers reversibly dissociate under strain, allowing the extensibility of the entangled network and continuous energy dissipation. The resulting polymers exhibit high Young’s modulus (515.0 ± 100.9 megapascals) and yield strength (57.8 ± 1.8 megapascals) while maintaining exceptional toughness (135.7 ± 10.7 megajoules per cubic meter) and fracture strain (400.1 ± 46.1%) and full strain recovery upon heating. These polymers can be fabricated into complex structures via three-dimensional printing and exhibit shape-memory, impact-resistant, and adhesive properties. This work establishes a generalizable strategy for designing high-performance polymer materials through simple photopolymerization.
GPT-4o mini: Non-social science research article
Molecular-driven lead-free halide photoferroelectric solid solution for high-temperature sensitive self-powered x-ray detection
Lijun Xu, Yao Li, Qianwen Guan, Hang Li, Chengshu Zhang, Huang Ye, Haiqing Zhong, Chengmin Ji, Zhenyue Wu, Lina Li, Junhua Luo
Full text
Halide double perovskite ferroelectrics have recently emerged as an environmentally friendly candidate in radiation detection, photovoltaics, and optoelectronic memory devices due to their unique spontaneous polarization and semiconductor properties. However, it is a huge challenge to achieve efficient carrier transport and high Curie temperature ( T c ) in double perovskite ferroelectrics, owing to the limitations of twisted frameworks and structural construction. Here, we present a high- T c heterovalent metal solid solution double perovskite ferroelectric, (4Br2FBZ) 2 CsAgBiBr 7 (4Br2FBZ-CAB, 4Br2FBZ = 4-bromo-2-fluorobenzylammonium), through a strategy of cation-engineered symmetry regulation. The metal ions Ag and Bi transitioned from an alternating arrangement to a mixed-site solid solution pattern, effectively optimizing the electronic band structure to enhance carrier transport. Meanwhile, 4Br2FBZ-CAB exhibits a high T c of 484 kelvin, substantially expanding the family of high- T c lead-free ferroelectrics. Benefiting from its remarkable photoelectric and ferroelectric properties, a high self-powered x-ray detection sensitivity of 273.8 microcoulomb per gray per square centimeter (ÎŒC Gy air −1 cm −2 ) was achieved at room temperature. In addition, this exceptionally high T c enables the detector to operate self-powered at high temperatures, resulting in an excellent sensitivity of 896.9 ÎŒC Gy air −1 cm −2 and a low detection limit of 13.9 nGy air s −1 at 425 kelvin. This work opens an avenue for expanding the family of high- T c lead-free perovskite ferroelectrics with superior semiconducting properties.
GPT-4o mini: Non-social science research article
Stress-induced ripping enables fabrication of nanopores with dimensions smaller than the resolution limit of the employed lithography
Xinxin Liu, Fabio De Ferrari, Kirill Khabarov, Maria Blanco Formoso, Saumey Jain, Anna Herland, Göran Stemme, Francesco De Angelis, Frank Niklaus
Full text
Nanopores in ultrathin membranes are central to single-molecule sensing, filtration, and energy conversion applications, yet fabrication of solid-state nanopores remains limited by fundamental trade-off between resolution, throughput, and tool complexity. Here, we report a scalable nanopore fabrication process that exploits stress-induced mechanical ripping to detach a fragment from a membrane with lateral dimensions in the nm-scale, forming pores with diameters down to the sub-10 nm regime, which is well below the resolution limit of the employed lithography. Using this approach, we demonstrate wafer-scale fabrication of nanopores at densities exceeding 10 5 pores per cm 2 in dielectric (HfO 2 ), semiconducting (SiGe), and metallic (Cr) membranes, including suspended HfO 2 membranes as thin as 2 nm. We demonstrate the utility of the fabricated nanopores for high-performance surface enhanced Raman readouts of single molecule translocations. Beyond nanopore fabrication, this fracture-based approach points to broader opportunities for nanometer- and atomic-scale structuring of ultrathin materials.
GPT-4o mini: Non-social science research article
Reconstructing pathogen-specific antibody binding epitopes and age-dependent immune signatures from proteomic-scale peptide libraries
Everlyn Kamau, Nikolina Walas, Minlu Zhang, Kathy Kamath, Jack Reifert, John Shon, Shahjahan Ali, Md Ziaur Rahman, Abul K. Shoab, Syeda L. Famida, Salma Akther, Md Saheen Hossen, Palash Mutsuddi, Mahbubur Rahman, Jessica A. Grembi, Andrew N. Mertens, Richelle C. Charles, Daniel T. Leung, Stephen Luby, Audrie Lin, Benjamin F. Arnold
Full text
High-density peptide arrays are useful for mapping linear antibody epitopes and resolution of antibody specificity in a single-assay platform. Here, we used peptide library screening to evaluate magnitude and breadth of humoral responses to enteric pathogens in the context of public health interventions. We characterized the epitope landscape to known immunogenic proteins to several viruses, bacteria, and parasites and used that to infer immunological profiles at age 3, 14, and 28 months. The peptide libraries detected immune signatures better for viruses compared with bacteria and parasites and captured distinct dynamics of protein-level variation in immune signatures over time. We found limited sensitivity for bacterial and protozoan pathogens whose humoral responses may depend more on conformational or natively modified epitopes than linear-peptide binding. Unbiased peptide libraries have potential utility for broad analysis of antibody responses in integrated serosurveillance, but our results reveal pathogen-specific limitations where peptide-based serology would be less predictive of true infection status and where it would provide greater surveillance value. Beyond assay performance, peptide arrays are useful for studying epitope architecture, and a practical implication would require augmentation with alternative antigen formats (whole-protein or folded antigens) in a complementary hybrid approach.
GPT-4o mini: Non-social science research article
HMOX1 controls a heme-ferritin switch that protects cells from ferroptosis
Izadora de Souza, Izabela Amélia Marques Andrade, Florencio Porto Freitas, Ana Beatriz da Silva Teixeira, Maria Carolina Clares Ramalho, Karoline Almeida Lima, Ancely Ferreira dos Santos, Werner Schmitz, Gholamreza Fazeli, Clarissa Ribeiro Reily Rocha, José Pedro Friedmann Angeli
Full text
Modulating the intracellular labile iron pool (LIP) has emerged as a promising strategy to induce ferroptosis in cancer cells, offering a way to overcome resistance to apoptosis-based therapies. One of the main contributors to LIP is heme catabolism mediated by heme oxygenase-1 (HMOX1), which promotes ferroptosis sensitivity by releasing free iron. Beyond its role as an iron donor, heme can influence diverse proteins and signaling pathways that drive tumor progression, but how heme regulates ferroptosis remains poorly understood. Here, we uncover a paradoxical, protective function of heme in the absence of HMOX1 activity. When HMOX1 is inactive, heme becomes stabilized, leading to ferritin up-regulation, suppression of ferroptosis, and rescue of cell death induced by both pharmacological and genetic inhibition of GPX4. Our findings reveal an unrecognized heme-HMOX1-ferritin axis that controls ferroptosis sensitivity. Targeting this pathway may offer a new therapeutic strategy to modulate ferroptosis in cancer.
GPT-4o mini: Non-social science research article
Modeling the effects of climate risk on primates globally: New perspectives on conservation priorities
Yang Teng, Yueqi Yin, Ying Shen, Yue Sun, Jiawen Liu, Jiwei Qi, Xiaochen Wang, Mingyi Zhang, Paul A. Garber, Zuofu Xiang, Xumao Zhao, Ming Li
Full text
Rapid climate change poses a severe threat to biodiversity, and phylogenetic diversity—a key metric capturing evolutionary uniqueness and adaptive potential—is critical for conservation. Integrating a well-resolved phylogenetic tree of 424 primate species, we combined spatial analysis and climate risk modeling to explore global spatiotemporal patterns of primates and assess their vulnerability under future climate scenarios. The results suggest a pronounced latitudinal pattern in primate distribution, with isothermality and annual mean precipitation as key drivers. Primate species in the American tropics (Mexico, Central, and South America) and southern China showed later divergence times and lower phylogenetic diversity, emerging as neo-hotspots for primates. Under future climate change, species in these neo-hotspots will face higher climate risks than those in paleo-hotspots of primate diversity. In addition, high human pressure, high climate risk, and limited protected area coverage increase species and population survival risks in hotspot regions. Overall, this global study deepens our understanding of biodiversity conservation under current climate change scenarios and synergistically advances the preservation of numerous natural services essential to ecosystem health and human well-being. Our study provides a spatially explicit framework to fulfill Targets 3 and 8 of the Kunming-Montreal Global Biodiversity Framework.
GPT-4o mini: Non-social science research article
Potential survivable niches for microbial life on the lunar south pole
Prabal Saxena, Stefano Bertone, Heather V. Graham, Natalie M. Curran, Aaron B. Regberg, Andrew Needham, D. E. (Betsy) Pugel, Noah E. Petro
Full text
Most lunar surface conditions are incredibly harsh for microbial survival. High ultraviolet radiation, temperatures, and energetic particle radiation limit survival over most unprotected lunar surfaces, particularly in equatorial regions where all previous crewed exploration occurred. However, whether these harsh conditions are widespread at lunar poles has not been examined considering topographical effects. Here, we show that recent microorganism survivability data and lunar surface remote sensing reveal likely survivable niches in lunar polar regions. Analysis of topography and latitude-driven surface conditions using remote sensing data and high-resolution illumination models indicates the lunar south pole has substantial regions with persistent low temperatures and ultraviolet flux. Comparing these conditions to survivability data of specific microorganisms, we find that significant lunar polar areas likely have surface conditions amenable to microbial survival. Our findings suggest that lunar polar regions may be less hostile to microbial survival than previously assumed. This does not encompass growth likelihood, but survival in a cryptobiotic state where growth would be possible if habitable conditions were present. Potential microbial survivability at lunar poles is particularly significant given many examined microbes will likely be transported to the Moon during crewed lunar south pole exploration planned in numerous near-term missions. Thoughtfully planning exploration and tracking its impact is key to limiting and understanding potential unintended life transfer to the Moon.
GPT-4o mini: Non-social science research article
All-inorganic perovskites for four-dimensional dynamic encryption
Yongfeng Lu, Lianliang Li, Hongrui Cheng, Haixin Chen, Shengming Wu, Haijiang Qiu, Zijie Qiu, Zheng Zhao, Xing Han, Yuhang Liang, Cheng Jiang, Yuanhui Zheng, Ben Zhong Tang
Full text
In an era marked by increasing demand for advanced anticounterfeiting measures, we introduce a four-dimensional (4D) dynamic physical unclonable function that uses defect-engineered photoluminescence blinking in all-inorganic CsPbBr 3 perovskite quantum dots (QDs) embedded within a polymethylmethacrylate matrix. Even within a single z -axis layer, this system achieves an unprecedented theoretical encoding capacity of more than 10 216,742 , while each device can generate up to 25 billion distinct codes. The QDs exhibit stochastic transitions between emissive and nonemissive states, enabling binary encoding across both spatial and temporal dimensions. The mechanism reveals that surface lead interstitials predominantly mediate nonradiative Auger recombination, whereas cesium vacancies act as effective Shockley-Read-Hall recombination centers, jointly governing the blinking of CsPbBr 3 . Alkali metal doping modulates this blinking behavior, providing precise control over the emission dynamics. Practical utility is demonstrated through a dual-mode authentication strategy that enables rapid field verification via standard smartphones while retaining high-security 4D verification via microscopy. We further establish a spatial-temporal dual-model authentication framework that integrates convolutional neural network (CNN)–based spatial matching with a temporal-branch dynamic check and decision-fusion assessment. The framework resists 14 adversarial attacks spanning replay, impersonation, temporal and local manipulation, Z-stack modification, projection forgery, and synthetic forgery attack, showing robust sequence-level security beyond frame-level CNN recognition. This work transforms what was once considered a detrimental phenomenon—QD blinking—into a valuable asset for dynamic, high-capacity encryption, opening new avenues for ultrasecure cryptographic systems.
GPT-4o mini: Non-social science research article
A triboelectric airflow field sensor enables cross-scale multi-parameter sensing in meter-scale flapping-wing aircrafts
Wenyu Zhao, Jiaze Li, Waner Lin, Yingtian Xu, Yunlong Hu, Jiahao Fan, Haoyu Wang, Yu Chen, Erzhen Pan, Zhenglong Sun, Ziya Wang
Full text
Accurate in-situ sensing of unsteady aerodynamic parameters is essential yet challenging for closed-loop control in meter-scale flapping-wing aircraft. This task requires simultaneous monitoring of three coupled parameters: local wind speed (LWS), angle of attack (AoA), and flapping frequency (FF). Here, we report a conformal triboelectric airflow field sensor that converts airflow-induced aeroelastic vibrations into electrical signals. Its low-damping apertured cantilever design provides a broad sensing range and rich vibration features, enabling accurate aerodynamic parameter decoding with a deep-learning model. To address cross-scale discrepancies, we use transfer learning to adapt representations learned from low-cost small-scale wind tunnel data to data-limited full-scale conditions, achieving mean absolute errors of 0.04 m·s −1 for LWS, 0.07° for AoA, and 0.06 Hz for FF. Outdoor flight tests demonstrate real-time trend reconstruction and maneuver-correlated monitoring of the decoded parameters. This study provides a scalable biomimetic airflow sensing solution for future closed-loop control of meter-scale flapping-wing aircraft.
GPT-4o mini: Non-social science research article
Strong anharmonicity driven wave-like thermal transport and high thermoelectric performance in TlCu 5 Se 3
Sayantoni Choudhury, Animesh Bhui, Prasad V. D. Matukumilli, Memansa Thapa, Ajay Soni, Umesh V. Waghmare, Kanishka Biswas
Full text
Thermal transport in crystalline solids generally occurs via particle-like phonon propagation. Here, we demonstrate the dominant unusual wave-like phonon transport and high thermoelectric figure-of-merit (zT) of ∌1.42 at 673 K in crystalline TlCu 5 Se 3 due to the strong anharmonicity exerted by confined Cu dynamic disorder and Tl rattling. TlCu 5 Se 3 shows an intrinsic ultralow lattice thermal conductivity of (Îș L ) 0.3–0.2 W m −1  K −1 across the temperature range of 294–673 K. Density functional theory calculations and ab-initio molecular dynamics simulations reveal that strong lattice anharmonicity arises due to confined dynamic disorder of the Cu sublattice. The complex knot-like structure with strong anharmonicity reduces phonon lifetime below the Wigner limit, leading to substantial inter-band phonon coupling and a dominant wave-like coherence. By further tuning cationic vacancies to optimize electrical transport, we achieve an enhanced zT of ∌1.7 at 673 K in TlCu 5-x Se 3 (x = 0.03–0.07), demonstrating that confined ion dynamics not only maintains ultralow Îș L but also enhances thermoelectric performance without compromising the stability.
GPT-4o mini: Non-social science research article
ROS-responsive nanogels enable inhaled CD24 immunotherapy for selective hyperinflammation suppression in severe pneumonia
Xin Wang, Xiaofei Zhao, Fan Zhang, Siyu Wang, Fenghua Meng, Chao Deng, Mingzhou Ye, Zhiyuan Zhong
Full text
Acute pneumonia triggered by pathogen infection and lung injury persists as a critical global life-threatening issue. Cluster of differentiation 24 (CD24), by selectively inhibiting the inflammatory response associated with damage-associated molecular patterns (DAMPs) through the interaction with Siglec, has appeared as a unique paradigm to alleviate acute pneumonia, yet its effective pulmonary delivery remains challenging. Here, we report on reactive oxygen species (ROS)–responsive and mucus-penetrable nanogels (ROSÎŒNG) for pulmonary CD24 delivery to rescue acute pneumonia by selective inhibition of hyperinflammatory response. CD24-loaded nanogels (CD24-ROSÎŒNG) exhibit excellent stability during nebulization, efficient mucus penetration, and inflammation-triggered CD24 release, affording over 80% drug enrichment in lung tissues through nebulization inhalation. In lipopolysaccharide-induced severe acute pneumonia mouse models, nebulized CD24-ROSÎŒNG effectively attenuates cytokine storm, suppresses DAMP-mediated inflammation, and mitigates lung injury, achieving an over 3.5-fold increase in survival rate compared to intravenous administration of over 12-fold higher dose of free CD24. In an H1N1 virus influenza model, CD24-ROSÎŒNG not only prevents cytokine storm but also preserves neutrophil-mediated viral clearance by limiting excessive neutrophil extracellular trap formation, thereby avoiding uncontrolled inflammation while maintaining antiviral defenses. These inhalable CD24 nanogels establish a strategy to manage pulmonary hyperinflammatory disorders.
GPT-4o mini: Non-social science research article
SKI is critical to counter TGF-ÎČ signaling to promote T cell function and autoimmunity
Junying Wang, Ziyi Chen, Hongrui Li, Zengli Guo, Gang Wang, Junnian Zheng, Yisong Y. Wan
Full text
Transforming growth factor–ÎČ (TGF-ÎČ) is central to suppressing T cell function to maintain tolerance and immune homeostasis. The current TGF-ÎČ signaling paradigm is however inadequate in explaining how TGF-ÎČ controls T cell function. Here, we found a previously unappreciated, SKI-dependent mechanism of TGF-ÎČ signaling to better explain how TGF-ÎČ restricts T cell function to bolster tolerance. We found that SKI protein was up-regulated in activated T cells and down-regulated in response to TGF-ÎČ, indicating a reciprocal relationship between SKI and TGF-ÎČ in controlling T cell function. T cell–specific SKI deletion ameliorated spontaneous lethal autoimmunity due to T cell–specific TGFÎČRII deletion and mitigated MOG/CFA-induced experimental autoimmune encephalomyelitis. SKI was required for activation-induced T cell function and related molecular programs. Therefore, inhibition of TGFÎČR not only results in the loss of Smad-dependent function but, more importantly, leads to the gain of SKI-dependent activity, which is essential for T cell–mediated autoimmunity. A critical mechanism underlying TGF-ÎČ–mediated suppression of T cell function is overcoming SKI activity.
GPT-4o mini: Non-social science research article
Slow bleaching of water-insoluble brown carbon from biomass burning: Implication for direct radiative effect
Wenli Liu, Xinchun Xie, Lijuan Li, Rui Wang, Xin Zhang, Xinye Luo, Yuemei Han, Yuzhong Zhang, Mikinori Kuwata
Full text
Biomass burning organic aerosol (BBOA) is a major source of atmospheric brown carbon (BrC), which contributes to climate through solar radiation absorption. Chemical aging (bleaching) of BrC diminishes light absorption over time. Although recent modeling studies have emphasized the need to account for bleaching when assessing BrC’s climate impacts, a parameterization representing the entire BBOA matrix has been lacking. Here, we develop a bleaching parameterization for the whole BrC in BBOA based on laboratory experiments that systematically varied temperature and relative humidity. The bleaching timescale increases under low-humidity and low-temperature conditions, likely due to enhanced aerosol viscosity. Implementing this parameterization in a global model increases the simulated direct radiative effect (DRE) of BrC by 1.5 to 2 times relative to previous estimates, with associated uncertainties exceeding 10% of the total organic aerosol DRE. The present scheme particularly shows elevated fresh BrC concentrations in boreal regions, suggesting that bleaching dynamics may influence not only radiative forcing but also snow darkening effects.
GPT-4o mini: Non-social science research article
A bacterial enzyme enhances both energy metabolism and health across the life span of C. elegans and mice
Yang Liu, Zhijuan Hu, Duo Duan, Lianfeng Wu, An-Ping Zeng
Full text
The consequence of enhanced energy metabolism for health and life span of organisms is a fundamental yet controversially discussed issue of life and aging among others because of the fact that increasing energy metabolism often entails the risk of oxidative damage. To resolve this paradox, we introduce the bacterial-derived lipoic acid protein ligase A (LplA) as an orthogonal and defined molecular tool to enhance energy metabolism and at the same time to foster a low oxidative stress environment. Investigations in Caenorhabditis elegans ( C. elegans ) and mouse models demonstrate that LplA expression significantly enhances energy metabolism and health across the life span, without compromising maximum longevity. Our work not only transcends the long-standing paradox between energy metabolism and health life span but also provides a hereto unreported strategy to intervene in human aging.
GPT-4o mini: Non-social science research article
Endometriosis-derived iPSCs reveal conserved stromal maturation and endocrine responsiveness
Hannah McDowell, Shiyang Sun, Ross McNally, Cassandra Huerta, Huma Asif, Julia Yoon, Angel Alvarez, Sule Yildiz, K. Grace Foley, Christina Boots, Magdy Milad, J. Julie Kim
Full text
Endometriosis is a chronic, hormone-dependent disease characterized by altered endometrial stromal function, but mechanistic and translational studies have been hindered by the lack of tractable human models. Here, we establish an induced pluripotent stem cell (iPSC)–based platform derived from patients with endometriosis to model endometrial stromal differentiation in a controlled human context. Using a defined differentiation protocol, endometriosis-derived iPSCs transition from pluripotency through mesenchymal commitment toward stromal-like states and acquire transcriptional hormone responsiveness. Transcriptomic analyses reveal coordinated repression of pluripotency and proliferative programs with induction of stromal lineage signatures. Comparison with independent transcriptomic datasets demonstrated that in vitro–derived stromal cells progressively acquired gene expression profiles resembling eutopic endometrial stromal programs in endometriosis. Conditioned media from iPSC-derived stromal cells also induced transcriptional reprogramming in THP-1 macrophage-like cells. Together, these findings establish a patient-derived platform for investigating stromal differentiation and stromal-immune interactions in endometriosis.
GPT-4o mini: Non-social science research article
Orthogonal DNA barcoding enables subpopulation-resolved extracellular vesicle miRNA profiling
Ye Zhang, Yitong Zhu, Yu Zhang, Shijin Peng, Diheng Wu, Wenbin Li, Tingting Ji, Siting Chen, Yuanhong Lin, Huihong Yang, Yuhang Guo, Bo Li, Chunchen Liu, Bo Situ, Xiaohui Yan, Lei Zheng
Full text
Extracellular vesicle–associated microRNAs (EV-miRNAs) hold promise for liquid biopsy, but their clinical utility is hindered by EV heterogeneity. Here, we report DEEPER, a DNA-encoded orthogonal recognition platform for selective barcoding of tumor-derived EV subpopulations and in situ miRNA profiling. DEEPER uses four aptamers targeting Cluster of Differentiation 44 (CD44), Epidermal Growth Factor Receptor‌ (EGFR), Human Epidermal Growth Factor Receptor 2‌ (HER2), and ‌Programmed Death-Ligand 1(PD-L1) to generate orthogonal barcodes that distinguish 15 EV subpopulations. Barcoded EVs then undergo targeted membrane fusion with liposome probes, enabling sensitive in situ analysis of subpopulation-specific miRNAs. In a 60-sample cohort of patients with gastric cancer (GC) and healthy donors (HDs), DEEPER identified a high-performing signature, GC-EV miRNA Prime, comprising EGFR + , EGFR + HER2 + , and EGFR + HER2 + CD44 + EVs, which achieved 98.3% diagnostic accuracy. The same profiling framework also assessed tumor invasiveness with 95.5% accuracy. Mechanistic studies further showed that these EV-miRNAs contribute to tumor progression. In summary, DEEPER not only confirmed the clinical application value of EV-miRNA–based liquid biopsy but also provided unique insights through the EV subpopulations into the mechanisms driving cancer development.
GPT-4o mini: Non-social science research article
Abscisic acid–regulated stability of CmABF1 and CmBRM modulates salt tolerance in chrysanthemum via epigenetic regulation of CmHSFA4
Xinhui Wang, Han Wang, Hongyu Wei, Yuhan Jiang, You Wang, Fei Li, Yi Zhang, Lijie Zhou, Shengben Li, Zhenxing Wang, Likai Wang, Jiafu Jiang, Huazhong Shi, Fadi Chen, Sumei Chen
Full text
Soil salinization poses a major threat to global agricultural productivity and plant biodiversity. The phytohormone abscisic acid (ABA) is central to plant adaptation to abiotic stress; however, the mechanisms by which ABA coordinates posttranslational modifications of signaling proteins with epigenetic regulation remain poorly understood. Here, we show that salt stress–induced ABA accumulation up-regulates Heat Shock Factor 4 ( CmHSFA4 ), a gene that is known to enhance chrysanthemum salt tolerance. The ABA responsive transcription factor ABRE binding factor 1 (CmABF1) binds to the CmHSFA4 promoter to activate its expression and also recruits the chromatin remodeler BRAHMA (CmBRM) to repress transcription by limiting H3 lysine-4 trimethylation (H3K4me3) deposition. We further demonstrate that the ABA-activated sucrose non-fermenting-1-related protein kinase 2.2 (CmSnRK2.2) phosphorylates and stabilizes CmABF1, while concurrently phosphorylating and promoting CmBRM degradation under salt stress. This dual regulation enhances H3K4me3 enrichment at the CmHSFA4 promoter, thereby inducing its transcription and conferring salt tolerance. Together, our findings reveal an ABA-SnRK2.2-ABF1/BRM signaling module that integrates phosphorylation-dependent protein stabilization and degradation with histone methylation dynamics to fine-tune salt stress–responsive gene expression in chrysanthemum.
GPT-4o mini: Non-social science research article
Metabolic-epigenetic rewiring of CCR5 hi monocytes sustains long-term trained immunity against lethal sepsis
Lingqi Xu, Wenyan Hao, Yingyi Yang, Yu Wang, Yaoshuang Li, Yuan Gong, Yifang Ding, Jie Huang, Zhenjiang Bai, Qiang Shan, Rui Kang, Jiang Huai Wang, Haichao Wang, Timothy R. Billiar, Jian Wang, Daolin Tang, Huiting Zhou
Full text
Trained immunity enhances innate host defense by endowing monocytes with memory-like properties, yet the underlying integrated metabolic and epigenetic mechanisms remain elusive. Here, we demonstrate that coimmunization with Bacille Calmette-GuĂ©rin (BCG) and bacterial lipoprotein (BLP) induces a durable form of trained immunity that provides robust, long-term protection against polymicrobial sepsis from early life into adulthood. Single-cell RNA sequencing revealed that this effect is mediated by an expansion of CCR5 hi memory-like monocytes with enhanced antimicrobial capacity. Mechanistically, BCG + BLP vaccination activated the AKT–mTOR–HIF-1α axis, driving glycolytic reprogramming and lactate accumulation. Elevated lactate enhanced KAT2B-dependent histone H3K18 lactylation, an epigenetic mark directly facilitating the transcription of phagocytic and inflammatory genes. In addition, BCG + BLP stimulation of human cord blood mononuclear cells induced CCR5 hi monocytes that recapitulated trained immunity features. These findings identify a lactate-KAT2B-H3K18la epigenetic axis that orchestrates the long-term reprogramming of CCR5 hi monocytes, highlighting CCR5 hi monocytes as a promising therapeutic target for modulating innate immunity against lethal sepsis.
GPT-4o mini: Non-social science research article
Inverse scattering in biological samples via beam propagation
Jeongsoo Kim, Blythe Bolton, Khashayar Moshksayan, Rishika Khanna, Mary E. Swartz, MichaƂ Ziemczonok, Mohini Kamra, Karin Allenspach, Sapun H. Parekh, MaƂgorzata KujawiƄska, Johann K. Eberhart, Elif Sarinay Cenik, Adela Ben-Yakar, Shwetadwip Chowdhury
Full text
Multiple scattering limits optical imaging in thick biological samples by scrambling sample-specific information. Physics-based inverse-scattering methods aim to computationally unscramble this information often by using nonconvex optimization solvers. However, their inherent nonconvexity often leads to highly sample-dependent performance and inaccurate reconstructions, particularly in strongly scattering specimens. Here, we introduce a novel inverse-scattering framework based on multislice beam propagation (MSBP) that robustly achieves high-quality scatter correction and label-free volumetric imaging across a diverse range of scattering biological samples. We rigorously benchmarked imaging performance across multiple MSBP solver implementations using both scattering calibration phantoms and biological specimens. We found that an amplitude-only cost function in the inverse solver, combined with angular and defocus diversity in the scattering measurements, enabled volumetric, label-free imaging with high-quality and subcellular-level scatter correction. Together, these results establish a foundation for the reliable application of inverse scattering to achieve biologically interpretable three-dimensional imaging in increasingly thick, multicellular samples, thus introducing a new paradigm for deep-tissue computational imaging.
GPT-4o mini: Non-social science research article
3D-Printed biodegradable and multifunctional cranial device for bone repair and healing assessment
Xibo Wang, Ningxin Zhu, Haitao Chen, Bingbing Yu, Xue Gao, Helin Li, Can Yang, Yuan Ma, Man Qin, Yuanhao Zhang, Hui Qi, He Ding, Milin Zhang, Xing Sheng, Xiumei Wang, Shirong Wang, Liliang Ouyang, Yuguang Wang, Xianfeng Ping, Huachun Wang, Ludan Zhang, Lan Yin
Full text
Critical-sized bone defects pose substantial clinical challenges, requiring both regenerative and diagnostic strategies for effective treatment. Here, we report a biodegradable, multifunctional cranial device based on three-dimensional printing. The device integrates a self-electrified scaffold based on a transient zinc-molybdenum battery and an impedance sensor for simultaneous electrical stimulation and continuous assessment of bone healing. The beneficial effects of electrical cues are attributed to elevated calcium ion influx, reactive oxygen species signaling, and up-regulated osteogenesis-related genes. In a rodent cranial defect model, the device promotes osteogenesis while enabling dynamic tracking of early tissue regeneration through impedance measurements. The increase in impedance is associated with enhanced collagen deposition and matrix mineralization. By uniting therapeutic stimulation with in situ monitoring, this work offers a platform for intelligent bone repair with broad potential in regenerative medicine.
GPT-4o mini: Non-social science research article
Engineering a biomimetic multiphasic suture anchor system for enhanced rotator cuff enthesis regeneration
Zizhao Li, Se-Hwan Lee, Lin Xu, Marina Santos, Ruqiang Lu, Ellen Y. Zhang, Dong Hwa Kim, Bat-Ider Tumenbayar, Tyler E. Blanch, Jaeun Jung, Jayden Shin, Yongho Bae, Richard T. Tran, Thomas Schaer, Su Chin Heo
Full text
The rotator cuff plays a vital role in shoulder movement and joint stability. Unfortunately, tears at the rotator cuff enthesis are common and frequently lead to retears after surgical intervention, particularly at the suture location and its anchor sites. These failures are typically due to the inability of current surgical treatments to mimic the native tissue complexity and provide the necessary metabolic, bioactive, and biophysical cues for effective enthesis regeneration. In this study, we engineered a biomimetic multiphasic scaffold system (BMS) to integrate with conventional suture anchor systems and deliver spatially organized structural and biological cues to enhance enthesis regeneration. The BMS consists of three distinct phases: Phase 1 features an aligned, nanofibrous decellularized tendon extracellular matrix (dECM) combined with “stiff” methacrylated hyaluronic acid (MeHA); phase 2 incorporates nonaligned, nanofibrous dECM with “soft” MeHA; and phase 3 uses a porous, bioenergetic, citrate-based composite scaffold for bone integration. In vitro, the BMS notably enhanced tenogenic, fibrochondrogenic, and chondrogenic differentiation, facilitating zone-specific rotator cuff enthesis regeneration. Further, in vivo, the BMS promoted successful integrative healing, forming distinct tendon, fibrocartilage, and bone regions at the repair site. This advanced multiphasic scaffold closely replicates native tissue properties, offering a promising strategy to improve rotator cuff repair. Its integration with conventional suture anchors provides an innovative design that enhances mechanical fixation and guides enthesis healing to reduce retear rates. Broadly, this platform offers a versatile solution for biointegrative repair strategies across complex soft-to-hard tissue interfaces.
GPT-4o mini: Non-social science research article
Interaction topology theory deciphers multiscale codes of MOF-like materials
Dong Chen, Jian Liu, Chun-Long Chen, Guo-Wei Wei
Full text
Metal-organic frameworks (MOFs) and MOF-like porous materials exhibit vast structural diversity and support critical applications in gas storage, separations, and catalysis. Predictive modeling remains difficult because their structure-property relationships are multiscale and cage-like, governed by both local chemical environments and global pore-network topology. These challenges, together with sparse and unevenly distributed labeled data, hinder generalization across material families. We develop an interaction topology theory and propose the interaction topological transformer (ITT), a data-efficient framework that captures materials information across multiple scales and levels, including structural, elemental, atomic, and pairwise-elemental organization. ITT extracts scale-aware features reflecting both compositional and relational structures in complex porous frameworks and integrates them through a transformer architecture for joint reasoning across scales. Using self-supervised pretraining on more than 0.6 million unlabeled structures followed by supervised fine-tuning, ITT achieves accurate, transferable, state-of-the-art predictions for adsorption, transport, and stability properties across 17 tasks, providing a principled and scalable strategy for learning-guided discovery in diverse MOF-like materials.
GPT-4o mini: Non-social science research article
Unifying energy and information harvesting for high-rate self-powered sensing
Hongyong Yu, Yawei Wang, Hengxu Du, Ziyue Xi, Yizhou Li, Yaozi Zheng, Jixiang Chen, Quanke Su, Guobiao Hu, Taili Du, Minyi Xu
Full text
High-fidelity sensing remains highly challenging in self-powered systems, as the limited power of energy harvesters constrains data acquisition and transmission. In this work, we present a wireless, intelligent, self-powered environmental node (WISE-Node) that simultaneously harvests energy and collects sensing information from ambient vibrations. Its multi-contact triboelectric vibration energy harvester (MC-TVEH) achieves an ultra-wide bandwidth of 10–300 Hz, delivering peak and RMS power densities of 13.42 kW/m 3 and 1.73 kW/m 3 , respectively. The WISE-Node also functions as a broadband sensor, accurately tracking excitation frequencies via FFT analysis ( R 2  = 0.9997 across 3–10,000 Hz). Using a Random Forest classifier on the acquired data, the WISE-Node identifies flange conditions with 99.38% accuracy. Field tests on marine engines and generators validate its robust performance, achieving a cold start in just 28.8 s and maintaining fully self-powered 1000 Hz sampling and stable wireless transmission. These results highlight the proposed WISE-Node’s strong potential for self-sustained high-fidelity sensing, thereby advancing next-generation battery-free industrial IoT and digital twin technologies.
GPT-4o mini: Non-social science research article
A biomimetic, ultralow-power edge-AI-empowered and self-sustaining gait analysis system
Fuying Dong, Chi Han, Pengchong Xu, Jasleen Chhatwal, Xinnian Jiang, Tengteng Wang, Abigail Hsu, Minzhu Baek, Di Wu, Rui Li, Yuanwen Jiang, Bozhi Tian, Jason Y. Fang, Simiao Niu
Full text
Smart digital health has reshaped patient monitoring, but it faces a fundamental trade-off between device intelligence and continuous, energy-efficient monitoring. Inspired by self-sustaining intelligent biospecies, we develop a biomimetic, battery-free, and high-precision edge-AI system through a harvested-energy-constrained holistic co-design that couples ultralow-power edge-AI-empowered sensor hardware with biomechanical energy harvesting and cold-start power management. Our edge-AI-empowered motion sensor performs instantaneous, context-aware on-device inference and timely result updating from raw sensor data while consuming only 86 ÎŒW. A high-output energy harvester and tailored high-efficiency power management circuitry sustain energy levels exceeding system requirements, eliminating downtime associated with charging and enabling true 24/7, hassle-free monitoring. This breakthrough establishes a paradigm for system-level, edge-AI-empowered, and self-sustaining sensing, demonstrating that intelligence and energy autonomy can coexist within a single wearable platform and pointing to next-generation always-on, personalized digital health systems.
GPT-4o mini: Non-social science research article
Mortise-and-tenon molecular chains enable polymeric hexagonal crystallinity with superior high-temperature capacitor performance
Cheng Yao, Yuheng Fu, Yibo Zhang, Zhaodongfang Gao, Zhao Deng, Tao Wang, Shan Wang, Quanling Yang, Chuanxi Xiong, Hongmei Qin, Shuai Nie, Qing Wang
Full text
High-symmetry crystalline materials exhibit superior physical properties. However, polymers lack high-symmetry crystals due to their long-chain characteristics. Herein, we report that all- trans poly(adamantane-norbornene-imide) can form high-symmetry hexagonal crystal, exhibiting superior electrical insulation properties and capacitor performances at an elevated temperature of 250°C, characterized by a high breakdown voltage of 802 megavolts per meter, and a notable discharged energy density of 7.29 joules per cubic centimeter, which surpasses all previously reported polymers. We propose that the mortise-and-tenon interlocking between adamantane side groups in polymer chains enables perfectly symmetrical alignment of polymer molecular chains, thereby addressing the challenge of forming high-symmetry crystals in polymers. We anticipate that the mortise-and-tenon interlocking mechanism of polymer chains will lead to the development of more polymers with high-symmetry crystal and superior physical properties.
GPT-4o mini: Non-social science research article
Evolutionary diversification via modular compliance for self-reconfigurable continuum robots
Yilin Cai, Zhefeng Huang, Yifan Wang, Haokai Xu, Yue Chen
Full text
Modular self-reconfigurable robots promise adaptability through changes in morphology, yet most existing systems remain limited by low functional density, rigid modules, and constrained docking interfaces that restrict scalable locomotion and manipulation. In contrast, biological organisms achieve rich behavioral diversity through repeated compliant segments combined with flexible articulated body architectures to support locomotion, manipulation, and environmental interaction. Here, we present a modular self-reconfigurable continuum robot that exploits modular compliance as a unifying design principle to enable cross-species bioinspired loco-manipulation within a single platform. Each module integrates a continuum backbone for compliant bending and a pair of grippers for omnidirectional, quasi-freeform docking, achieving high functional density within a compact unit. As a result, a small number of modules can assemble into diverse morphologies capable of distinct capabilities. We further develop a morphology-conditioned gait library covering rolling, undulation, crawling, quadrupedal walking, and multisegment manipulation, organized within an evolutionary diversification tree that explicitly links biological locomotion strategies to corresponding robotic assembly patterns. To enable autonomous transitions between configurations, we introduce a unified geometric-topological representation and a self-reconfiguration planner that decomposes reconfiguration into discrete grasping and releasing actions and continuous deformation actions. Hardware experiments demonstrate online self-reconfiguration, followed by integrated loco-manipulation. Together, these results show that embedding compliance at the module level unifies locomotion, manipulation, and self-reconfiguration within a single robotic platform, suggesting a pathway toward more adaptable machines that exhibit organism-like behaviors across species.
GPT-4o mini: Non-social science research article
Ptpn2 limits plasma cell fate and antiviral immunity by integrating B cell receptor and IFN-Îł signals in B cells
Ana Maria Hincapie, Alexandre Poirier, Isabelle Aubry, Philippe Aumont, Aanya Bhagrath, Noriko Uetani, Bianca Colalillo, Chenyue Wu, Benoit Charbonneau, Stephanie Bussieres-Marmen, Belma M. Abidin, Javier M. Di Noia, Judith N. Mandl, Silvia M. Vidal, Jorg H. Fritz, Michel L. Tremblay
Full text
Antigen-specific humoral responses are critical for long-term protection against infectious diseases, yet the mechanisms that regulate B cell differentiation and antibody production remain incompletely defined. Here, we identify the Protein Tyrosine Phosphatase Nonreceptor Type 2 (Ptpn2) as a B cell–intrinsic regulator of plasma cell fate and isotype switching. Using a B cell–specific Ptpn2 knockout mouse model, we show that Ptpn2 restrains both B cell receptor and interferon-γ (IFN-γ) signaling by directly dephosphorylating Lyn, STAT1, and STAT3. Loss of Ptpn2 leads to hyperactivation of these two signaling pathways, resulting in transcriptional reprogramming that promotes plasma cell differentiation and increased IFN-γ–driven antibody production. Functionally, Ptpn2-deficient mice generated enhanced primary antiviral antibody responses following influenza infection and elevated virus-specific and neutralizing titers upon recall without compromising affinity. These findings identify Ptpn2 as a key intracellular checkpoint that integrates antigenic and inflammatory cues to regulate humoral immunity, with potential implications for enhancing vaccine-induced protective immunity.
GPT-4o mini: Non-social science research article
The structure of a complex, asymmetric coronal mass ejection revealed by 17 spacecraft across the inner heliosphere
Adrienn Luspay-Kuti, Drew L. Turner, Evangelos Paouris, Angelos Vourlidas, Alexander B. Crew, Ralph L. McNutt, Joseph H. Westlake, Savvas Raptis, Corey J. Cochrane, Xianzhe Jia, Carol A. Raymond, Haje Korth, Daniel Heyner, Kathleen Hanley, Ali Rahmati, Jacob R. Gruesbeck, Jasper S. Halekas, Shannon M. Curry, Howard Todd Smith, Michael L. Stevens, Elias Roussos, Kathleen E. Mandt, Margaret G. Kivelson, James A. Slavin, Dany Waller, Krishan K. Khurana, Tom Andre Nordheim, Carol S. Paty, Abigail M. Rymer, Joachim Saur, Norbert Krupp
Full text
Coronal mass ejections (CMEs) are enormous bursts of plasma and magnetic field from the Sun that propagate explosively through the Solar System. CMEs are the primary drivers of the most severe space-weather events, posing major radiation hazards for human exploration beyond Earth’s magnetosphere, including missions to the Moon and Mars. During Europa Clipper’s cruise between Earth and Mars, its Plasma Instrument for Magnetic Sounding (PIMS) recorded unusual solar-wind conditions later identified as the wake of a complex CME. Data from an unprecedented network of 17 spacecraft across the inner Solar System revealed a hidden Earth-directed component that propagated asymmetrically and could not have been predicted without off-Sun-Earth-line observations. This component also affected Europa Clipper and Mars, demonstrating how a missed forecast of this kind could endanger a crewed mission. These findings highlight the need for multipoint observations, including planetary missions in cruise, to improve space-weather forecasting, mission planning, and operations.
GPT-4o mini: Non-social science research article
Sphingosine kinase 2 regulates adipocyte browning and whole-body metabolism
Ryan D. R. Brown, Cynthia Weigel, Yadu Vijayan, Katarzyna M. Tyc, Christiane Carter, Christopher D. Green, Sarah Spiegel
Full text
Obesity increases circulating levels of the bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P). Here, we identify adipocyte-expressed sphingosine kinase 2 (SPHK2), an enzyme that produces S1P, as a regulator of adipose tissue browning. Mice with adipocyte-specific deletion of Sphk2 were protected from Western diet–induced obesity concomitantly with elevated energy expenditure and browning of subcutaneous fat. Sphk2 deletion also enhanced expression of Ucp1 and key thermogenic genes, resulting in reduced adiposity and hepatic steatosis, improved glucose tolerance, and insulin sensitivity. Mechanistically, obesogenic diet promoted nuclear localization of SPHK2 in adipocytes, where it cooperated with transcription factors to suppress the thermogenic transcriptome. Adipocyte SPHK2 contributes to homeostatic circulating S1P levels and drive the pathogenic rise of S1P in response to obesogenic diet. Our findings reveal a distinct role of adipocyte SPHK2 in regulation of the thermogenic program important for whole-body metabolic homeostasis and energy expenditure, highlighting SPHK2 as a potential therapeutic target for treatment of metabolic disorders.
GPT-4o mini: Non-social science research article
Fate of heat approaching the Filchner-Ronne Ice Shelf mediated by continental shelf eddies
Andrew L. Stewart, Madeleine K. Youngs, Channing J. Prend
Full text
Transfer of ocean heat toward Antarctica’s ice shelves is a key driver of changes in glacial mass balance. Previous work has indicated that transfer of warm, mid-depth waters across the continental slope is elevated close to Antarctica’s largest ice shelves, where dense waters form over the continental shelf. Yet, ice shelves in such regions maintain relatively low area-averaged melt rates, suggesting that ocean processes must shield them from the inflowing heat. In this study, a high-resolution simulation is used to isolate the mechanisms of heat transfer toward the Filchner-Ronne Ice Shelf in the southern Weddell Sea. This study shows that ocean eddies divert almost all heat arriving on the continental shelf up to the ocean surface and away from the ice shelf by stirring heat anomalies along tilted density surfaces. These findings highlight the importance of understanding continental shelf eddies in the context of basal melt variability, for example, in driving future heat delivery to Antarctica’s largest ice shelves.
GPT-4o mini: Non-social science research article
Unlocking dormant Li + pathways drives fast ion transport in Li 4 Ti 5 O 12 oxide spinels
Bernhard Gadermaier, H. Martin R. Wilkening
Full text
Li-rich lithium titanate (Li 4+ x Ti 5 O 12 , x  > 0) is known for superior ionic conductivity, yet we show that stoichiometric Li 4 Ti 5 O 12 (LTO, x  = 0), typically characterized by sluggish ion dynamics, can be transformed into a fast ion conductor without changing its Li content. Local defects, most notably oxygen vacancies, introduced by vacuum treatment activate a previously inaccessible 8 a -16 c -8 a diffusion pathway in stoichiometric LTO, markedly enhancing Li + mobility throughout the bulk. Using a synergistic combination of impedance spectroscopy, solid-state nuclear magnetic resonance (NMR), and electron paramagnetic resonance (EPR), we resolve the diffusion processes responsible for this transformation. Lithium NMR unambiguously shows that a formerly localized Li + hopping process becomes long-range transport after vacuum treatment, evidencing the activation of extended diffusion pathways. Atomic-scale insights reveal defect-driven structural and dynamical priming that enables rapid Li + insertion, establishing zero-strain LTO as a leading anode for solid-state lithium batteries. Defect-mediated transport emerges as the key mechanism underlying these dynamics, resolving the long-standing conductivity puzzle of stoichiometric spinel LTO ( x  = 0) and indicating transferable pathways in related spinel-type ion conductors with similar Li + distributions.
GPT-4o mini: Non-social science research article
Population-level geometric filtering generates motion-coherence selectivity in the retina
Pratyush Ramakrishna, Andrew Jo, Liam McCoy, Josh L. Morgan, Daniel Kerschensteiner
Full text
Object-motion–sensitive (OMS) circuits must ignore self-motion while remaining sensitive to independently moving objects. We show that the mouse retina solves this by geometrically filtering motion coherence. Correlative light and electron microscopy reveal that TH2 amacrine cells (GABAergic Type-2 wide-field amacrine cells in the TH-Cre mouse strain) combine a dense proximal arbor with sparse radiating distal neurites, distributing synapses uniformly across both compartments. Two-photon imaging and compartmental modeling establish that sparse inhibition and voltage-gated sodium channels allow this bipartite arbor to multiplex signals: Proximal dendrites compute locally, whereas distal neurites integrate over hundreds of micrometers. A population model built from this architecture predicts a daisy-shaped inhibitory surround for OMS ganglion cells (W3/Ultra-High-Definition), with a circular near-surround and radially orientation-selective far-surround subunits. Patch-clamp recordings confirmed this organization and revealed that the surround suppresses coherent global motion while preserving object-motion detection, even amid high densities of independently moving objects. Thus, single-cell morphology and dendritic processing scale through plexus geometry to implement motion-coherence selectivity.
GPT-4o mini: Non-social science research article
Large-scale outdoor 3D trajectory measurements enabled by drone-assisted multicamera tracking
Jungyeon Kim, Sangmin Lim, Pius Soh, Jin-Tae Kim
Full text
Accurate measurement of three-dimensional (3D) trajectories in outdoor environments is essential for studying complex dynamic processes such as atmospheric transport, aerial vehicle motion, and collective behavior. However, obtaining quantitative trajectory measurements over large outdoor volumes remains challenging because multicamera systems require reliable calibration and synchronization under field conditions. Here, we introduce a portable and automated drone-assisted multicamera 3D tracking (DAM3T) framework for georeferenced trajectory reconstruction. The system estimates multicamera extrinsic parameters from an autonomous drone flight without dedicated calibration markers and aligns the reconstructed coordinate system with geographic coordinates (WGS84) using real-time kinematic Global Positioning System (RTK-GPS) measurements. Validation under indoor motion-capture and outdoor RTK-GPS conditions demonstrates trajectory errors below 2%. We further demonstrate the framework through Lagrangian analysis using passive tracers, georeferenced tracking of multiple unmanned aerial vehicles, and 3D motion analysis in sports scenes. This establishes DAM3T as a scalable measurement platform that extends outdoor tracking from local-coordinate reconstruction to georeferenced measurement of complex dynamic systems.
GPT-4o mini: Non-social science research article
Undoing of firing rate adaptation enables invariant population codes
Sofia C. BrandĂŁo, Luisa Ramirez, Pascal ZĂŒfle, Alexander M. Walter, Marion Silies, Carlotta Martelli
Full text
Neural adaptation supports coding efficiency by tuning responses to prevailing stimulus statistics. However, when information is represented by populations of neurons, adaptation of individual units could degrade behaviorally relevant signals. Here, we investigate how the fly olfactory system implements adaptation to background odors in olfactory receptor neurons (ORNs) and the consequences for combinatorial coding in downstream circuits. We show that adaptation of ORN firing rate is compensated at the axon terminal, where inhibitory presynaptic feedback supports background-invariant calcium responses to increases (but not decreases) in odor concentration. Computational analyses demonstrate that such invariance requires an adaptation strategy in ORNs that shifts response amplitude rather than sensitivity, diverging from efficient coding principles in single neurons. Downstream, postsynaptic projection neurons also exhibit background-invariant responses through presynaptic plasticity involving Unc13 proteins. Thus, the olfactory circuit restores stable population codes by undoing peripheral firing rate adaptation, enabling an asymmetric contrast representation that preserves stimulus identity across backgrounds.
GPT-4o mini: Non-social science research article
Ice-sheet dynamics drive glacial-interglacial shifts in North Atlantic seawater neodymium isotopes
Antao Xu, Kira Just, Alexander M. Piotrowski, Jonathan Stohl, Norbert Frank
Full text
Radiogenic neodymium (Nd) isotopic composition (Δ Nd ) of seawater is widely used to reconstruct past ocean circulation, assuming quasi-constant end-member signatures throughout the Quaternary. However, the Δ Nd signature of Glacial North Atlantic Intermediate Water deviated markedly from its modern value, challenging this assumption, and the driving mechanisms remain debated. Here, we show that the upper Glacial North Atlantic Intermediate Water was consistently more radiogenic (−7.2) than interglacial values (−13.4) over the past 230,000 years and that pronounced glacial-interglacial Δ Nd variability closely followed global ice-volume fluctuations ( r  = 0.80). This variability was primarily reconciled with Icelandic volcanic Nd inputs, modulated by the advance and retreat of the Icelandic Ice Sheet. A forward model reproduces the observed Δ Nd evolution and reveals a nonlinear response of Nd export to ice-sheet dynamics, yielding a mean glacial Icelandic Nd input flux of 2.4 × 10 8 grams per year. Our results highlight the pivotal role of high-latitude ice-sheet systems in regulating North Atlantic seawater chemistry during glacial periods.
GPT-4o mini: Non-social science research article
Geneformer-guided multiomics integration identifies Pbx1 as a network hub of hematopoietic stem cell aging
Hiroshi Kobayashi, Shintaro Watanuki, Yusuke Shiozawa, Motohiko Oshima, Shuhei Koide, Naoya Takayama, Takayuki Morikawa, Miho Haraguchi, Shinpei Tamaki, Takayoshi Asakura, Toshio Miyata, Atsushi Iwama, Seishi Ogawa, Keiyo Takubo
Full text
Hematopoietic stem cells (HSCs) constitute an organized hematopoietic system that undergoes age-related alterations, including increased platelet production and decreased erythropoiesis. The fundamental mechanisms driving these shifts remain incompletely understood. We used single-cell RNA sequencing data to show that old HSCs contain two distinct transcriptional programs: one shared with megakaryocytes and the other reflecting the most primitive HSC state. Developmental time-series profiling further suggests that the acquisition of these programs begins early in life, with the primitive module rising prenatally and megakaryocytic priming emerging after birth. Using a fine-tuned Geneformer (transformer-based deep learning model) to capture higher-order differences between young and old HSCs, coupled with transcriptomic and epigenetic profiling, as well as transcription factor screens, we identified Pbx1 as a key regulator of these age-related transcriptional and differentiation changes. Specifically, Pbx1 suppresses erythroid differentiation by repressing Gata1 expression. These findings provide insight into HSC aging and may inform approaches to modulate age-associated HSC dysfunction.
Impacts of land use and fallowing on coccidioidomycosis incidence in California: A population-based longitudinal study
Alexandra K. Heaney, Isabel J. Jones, Simon K. Camponuri, Jennifer R. Head, Amanda K. Weaver, Philip A. Collender, Gail Sondermeyer Cooksey, Seema Jain, Duc Vugia, John Balmes, Ellen A. Eisen, Adeyemi Adebiyi, John Taylor, Abinash Bhattachan, Justin V. Remais
Full text
Coccidioidomycosis (Valley fever) is a growing public health concern in the western U.S., with California reporting more than an eightfold rise in cases over the past two decades. As climate change, groundwater regulation, and prolonged drought drive major agricultural land-use shifts in the state, including widespread retirement of cultivated lands (i.e., fallowing), understanding their effects on this soil-borne fungal infection is critical. We linked 65,657 confirmed, geolocated cases (2008–2021) to high-resolution maps distinguishing natural vegetation, crop types, and fallowed fields to quantify how land use and land cover were associated with disease rates. Flexible statistical models showed that natural land covers, shrubland, barren ground, and grassland, were associated with higher incidence. Some agricultural uses (grain/hay, field crops, corn, and cotton) were associated with higher incidence, whereas others (orchards, rice, and truck crops/berries) were associated with lower incidence. Recently fallowed land (1 to 4 years) was linked to higher incidence, but the effect depended on prior cultivation. These findings indicate that land use changes may inadvertently impact coccidioidomycosis risk, underscoring the need for dust control and other measures to protect communities.
Large-scale proteomics to identify novel biomarkers linking social determinants of health to heart failure risk
Diego Ramonfaur, Rani Zierath, Yimin Yang, Victoria Lamberson, Brian Claggett, Tiffany M. Powell-Wiley, Tammy Leonard, Anna Kucharska-Newton, Keenan A. Walker, Patricia P. Chang, Nrupen Bhavsar, Ganga Bey, Kenneth Butler, Chiadi Ndumele, Josef Coresh, Bing Yu, James S. Floyd, Michelle C. Odden, Amil M. Shah
Full text
Adverse social determinants of health (SDOH) associate with greater heart failure (HF) risk. Among 9879 community-based participants of the Atherosclerosis Risk in Communities (ARIC) cohort study, we assessed 4955 plasma proteins using an aptamer-based platform (SomaLogic). We derived an SDOH factor comprising income, education, and area deprivation index (ADI) in Black and white participants. Proteins associated with this factor at Bonferroni significance were tested for associations with incident HF using multivariable Cox proportional hazard models. Among Black participants, 36 proteins were associated with both the SDOH factor and incident HF, 126 were among white participants, and 12 were shared between race strata. Eight of these demonstrated significant mediation effect in causal mediation models. Key results were replicated in 49,396 participants in UK Biobank. Mendelian randomization and colocalization suggested a potentially causal effect of C1q tumor necrosis factor–related protein 1 (C1QTNF1), an adiponectin paralog, on HF. We demonstrate protein biomarkers associated with SDOH burden and HF risk.