I checked 6 multidisciplinary journals on Wednesday, December 24, 2025 using the Crossref API. For the period December 17 to December 23, I found 7 new paper(s) in 5 journal(s).

Nature

GPT-4o mini: Non-social science research article
An integrated view of the structure and function of the human 4D nucleome
Job Dekker, Betul Akgol Oksuz, Yang Zhang, Ye Wang, Miriam K. Minsk, Shuzhen Kuang, Liyan Yang, Johan H. Gibcus, Nils Krietenstein, Oliver J. Rando, Jie Xu, Derek H. Janssens, Steven Henikoff, Alexander Kukalev, Willemin AndrĂ©a, Warren Winick-Ng, Rieke Kempfer, Ana Pombo, Miao Yu, Pradeep Kumar, Liguo Zhang, Andrew S. Belmont, Takayo Sasaki, Tom van Schaik, Laura Brueckner, Daan Peric-Hupkes, Bas van Steensel, Ping Wang, Haoxi Chai, Minji Kim, Yijun Ruan, Ran Zhang, Sofia A. Quinodoz, Prashant Bhat, Mitchell Guttman, Wenxin Zhao, Shu Chien, Yuan Liu, Sergey V. Venev, Dariusz Plewczynski, Ibai Irastorza Azcarate, Dominik SzabĂł, Christoph J. Thieme, Teresa SzczepiƄska, Mateusz ChiliƄski, Kaustav Sengupta, Mattia Conte, Andrea Esposito, Alex Abraham, Ruochi Zhang, Yuchuan Wang, Xingzhao Wen, Qiuyang Wu, Yang Yang, Jie Liu, Lorenzo Boninsegna, Asli Yildirim, Yuxiang Zhan, Andrea Maria Chiariello, Simona Bianco, Lindsay Lee, Ming Hu, Yun Li, R. Jordan Barnett, Ashley L. Cook, Daniel J. Emerson, Claire Marchal, Peiyao Zhao, Peter J. Park, Burak H. Alver, Andrew J. Schroeder, Rahi Navelkar, Clara Bakker, William Ronchetti, Shannon Ehmsen, Alexander D. Veit, Nils Gehlenborg, Ting Wang, Daofeng Li, Xiaotao Wang, Mario Nicodemi, Bing Ren, Sheng Zhong, Jennifer E. Phillips-Cremins, David M. Gilbert, Katherine S. Pollard, Frank Alber, Jian Ma, William S. Noble, Feng Yue
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The dynamic three-dimensional (3D) organization of the human genome (the 4D nucleome) is linked to genome function. Here we describe efforts by the 4D Nucleome Project 1 to map and analyse the 4D nucleome in widely used H1 human embryonic stem cells and immortalized fibroblasts (HFFc6). We produced and integrated diverse genomic datasets of the 4D nucleome, each contributing unique observations, which enabled us to assemble extensive catalogues of more than 140,000 looping interactions per cell type, to generate detailed classifications and annotations of chromosomal domain types and their subnuclear positions, and to obtain single-cell 3D models of the nuclear environment of all genes including their long-range interactions with distal elements. Through extensive benchmarking, we describe the unique strengths of different genomic assays for studying the 4D nucleome, providing guidelines for future studies. Three-dimensional models of population-based and individual cell-to-cell variation in genome structure showed connections between chromosome folding, nuclear organization, chromatin looping, gene transcription and DNA replication. Finally, we demonstrate the use of computational methods to predict genome folding from DNA sequence, which will facilitate the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.
GPT-4o mini: Non-social science research article
Author Correction: Neuroimmune cardiovascular interfaces control atherosclerosis
Sarajo K. Mohanta, Li Peng, Yuanfang Li, Shu Lu, Ting Sun, Lorenzo Carnevale, Marialuisa Perrotta, Zhe Ma, Benjamin Förstera, Karen Stanic, Chuankai Zhang, Xi Zhang, Piotr Szczepaniak, Mariaelvy Bianchini, Borhan R. Saeed, Raimondo Carnevale, Desheng Hu, Ryszard Nosalski, Fabio Pallante, Michael Beer, Donato Santovito, Ali ErtĂŒrk, Thomas C. Mettenleiter, Barbara G. Klupp, Remco T. A. Megens, Sabine Steffens, Jaroslav Pelisek, Hans-Henning Eckstein, Robert Kleemann, Livia Habenicht, Ziad Mallat, Jean-Baptiste Michel, JĂŒrgen Bernhagen, Martin Dichgans, Giuseppe D’Agostino, Tomasz J. Guzik, Peder S. Olofsson, Changjun Yin, Christian Weber, Giuseppe Lembo, Daniela Carnevale, Andreas J. R. Habenicht
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GPT-4o mini: Non-social science research article
Programmable 200 GOPS Hopfield-inspired photonic Ising machine
Nayem Al-Kayed, Charles St-Arnault, Hugh Morison, A. Aadhi, Chaoran Huang, Alexander N. Tait, David V. Plant, Bhavin J. Shastri
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Ising machines offer a compelling approach to addressing NP-hard problems1, but physical realizations that are simultaneously scalable, reconfigurable, fast and stable remain elusive. Quantum annealers, such as D-Wave’s cryogenic hardware, target combinatorial optimization tasks, but quadratic scaling of qubit requirements with problem size limits their scalability on dense graphs2. Here we introduce a programmable, stable, room-temperature optoelectronic oscillator (OEO)-based Ising machine with linear scaling in spin representation. Inspired by Hopfield networks3, our architecture solves fully connected problems with up to 256 spins (65,536 couplings) and >41,000 spins (205,000+ couplings) if sparse. Our system makes use of cascaded thin-film lithium niobate (TFLN) modulators, a semiconductor optical amplifier (SOA) and a digital signal processing (DSP) engine in a recurrent time-encoded loop, demonstrating potential >200 giga operations per second (GOPS) for spin coupling and nonlinearity. This platform achieves the largest spin configuration in an OEO-based photonic Ising machine, enabled by high intrinsic speed. We experimentally demonstrate best-in-class solution quality for max-cut problems of arbitrary graph topologies (2,000 and 20,000 spins) among photonic Ising machines and obtain ground-state solutions for number partitioning4 and lattice protein folding5—benchmarks previously unaddressed by photonic systems. Our system uses inherent noise from high baud rates to escape local minima and accelerate convergence. Finally, we show that embedding DSP—traditionally used in optical communications—within optical computation enhances convergence and solution quality, opening new frontiers in scalable, ultrafast computing for optimization, neuromorphic processing and analogue artificial intelligence.
GPT-4o mini: Non-social science research article
Lesion-remote astrocytes govern microglia-mediated white matter repair
Sarah McCallum, Keshav B. Suresh, Timothy S. Islam, Manish K. Tripathi, Ann W. Saustad, Oksana Shelest, Aditya Patil, David Lee, Brandon Kwon, Katherine Leitholf, Inga Yenokian, Sophia E. Shaka, Connor H. Beveridge, Palak Manchandra, Caitlin E. Randolph, Gordon P. Meares, Ranjan Dutta, Jasmine Plummer, Vinicius F. Calsavara, Riki Kawaguchi, Simon R. V. Knott, Gaurav Chopra, Joshua E. Burda
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Spared regions of the damaged central nervous system undergo dynamic remodelling and exhibit a remarkable potential for therapeutic exploitation1. Lesion-remote astrocytes (LRAs), which interact with viable neurons and glia, undergo reactive transformations whose molecular and functional properties are poorly understood2. Here, using multiple transcriptional profiling methods, we investigated LRAs from spared regions of mouse spinal cord following traumatic spinal cord injury. We show that LRAs acquire a spectrum of molecularly distinct, neuroanatomically restricted reactivity states that evolve after spinal cord injury. We identify transcriptionally unique reactive LRAs in degenerating white matter that direct the specification and function of local microglia that clear lipid-rich myelin debris to promote tissue repair. Fuelling this LRA functional adaptation is the secreted matricellular protein CCN1. Loss of astrocyte-derived CCN1 results in excessive, aberrant activation of local microglia, characterized by abnormal molecular specification, impaired debris processing reflected by the intracellular accumulation of myelin and axon debris, and dysregulated lipid metabolism with distinctive attenuation in lipid droplet accumulation. Mechanistically, we find that CCN1 binds microglial SDC4 to augment lipid storage, linking this signalling axis to a vital repair-associated lipid buffering response in debris-clearing microglia. Accordingly, microglial deficits resulting from astrocyte CCN1 depletion culminate in blunted clearance of white matter debris and impaired neurological recovery from spinal cord injury. Ccn1-expressing white matter astrocytes are induced by local myelin damage and are generated in diverse demyelinating disorders in mice and humans, pointing to their fundamental, evolutionarily conserved role in white matter repair. Our findings show that context-specific cues shape regionally distinct LRA reactivity states with functional adaptations that orchestrate multicellular processes underlying neural repair and influence disease outcome.
GPT-4o mini: Non-social science research article
Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes
Lixin Guo, Bo Zhang, Xia Xue, Xin Zhang, Hanqing Cai, Hongwei Jiang, Lili Zhang, Ping Jin, Xiaojing Wang, Zhifeng Cheng, Suhe Zhang, Jianlin Geng, Yushan Guo, Hanbo Hu, Qingyang Ma, Li Li, Haiwei Du, Han Han-Zhang, Fengtai Xue, Huan Deng, Lei Qian, Wenying Yang, character(0)
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Mazdutide is a once-weekly glucagon and glucagon-like peptide-1 receptor dual agonist developed for the treatment of type 2 diabetes (T2D) 1. This study assessed the efficacy and safety of mazdutide versus dulaglutide in participants with T2D on background oral anti-diabetic drugs. In this randomised phase 3 study, 731 participants with T2D were randomised 1:1:1 to receive mazdutide 4 mg, mazdutide 6 mg or dulaglutide 1.5 mg for 28 weeks. Both mazdutide doses demonstrated non-inferiority and superiority to dulaglutide 1.5 mg in mean change in HbA1c from baseline to week 28, with the least squares (LS) mean treatment difference of −0.24% (p=0.0032) for mazdutide 4 mg and −0.30% (p=0.0003) for mazdutide 6 mg vs dulaglutide 1.5 mg. Significantly greater weight reductions were achieved with mazdutide versus dulaglutide, with LS mean treatment difference of −3.78% for mazdutide 4 mg and −5.76% for mazdutide 6 mg vs dulaglutide (both p<0.0001). Moreover, significantly more participants with mazdutide achieved the composite endpoint of HbA1c <7.0% with ≄5% weight reduction vs dulaglutide 1.5 mg at week 28 (both p<0.0001). The most common treatment-emergent adverse events were diarrhoea, nausea, and vomiting. Our findings showed that 28-week treatment with mazdutide (4 mg and 6 mg) provided superior reductions in HbA1c and body weight compared with dulaglutide 1.5 mg in Chinese participants with T2D. Mazdutide was generally safe, with a higher incidence of gastrointestinal adverse events than dulaglutide.
GPT-4o mini: Non-social science research article
Author Correction: Rolling back human pluripotent stem cells to an eight-cell embryo-like stage
Md. Abdul Mazid, Carl Ward, Zhiwei Luo, Chuanyu Liu, Yunpan Li, Yiwei Lai, Liang Wu, Jinxiu Li, Wenqi Jia, Yu Jiang, Hao Liu, Lixin Fu, Yueli Yang, David P. Ibañez, Junjian Lai, Xiaoyu Wei, Juan An, Pengcheng Guo, Yue Yuan, Qiuting Deng, Yang Wang, Ying Liu, Fei Gao, Junwen Wang, Shahriar Zaman, Baoming Qin, Guangming Wu, Patrick H. Maxwell, Xun Xu, Longqi Liu, Wenjuan Li, Miguel A. Esteban
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GPT-4o mini: Non-social science research article
GTP release-selective agonists prolong opioid analgesic efficacy
Edward L. Stahl, Matthew A. Swanson, Vuong Q. Dang, Michael D. Cameron, Nicole M. Kennedy, Thomas D. Bannister, Laura M. Bohn
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G-protein-coupled receptors act as guanine nucleotide exchange factors (GEFs) and facilitate the activation of heterotrimeric G proteins by exchanging GDP for GTP1. This exchange function is not unidirectional2. Here we demonstrate that an agonist can show selective affinity for an active state that prefers the release of GTP. Specifically, for the mu opioid receptor, we show that several agonists have state-selective affinities for promoting GTP release versus GTP binding. We identify two agonists that show a marked preference for promoting release. In mice, marginally efficacious doses of the release-preferring agonist enhance and prolong the antinociceptive effects of morphine and fentanyl without enhancing the respiratory and cardiac effects of fentanyl. Although these observations are limited to simple measures of thermal nociception, they may point to a way to bifurcate physiological responses to such agonists. We propose that the active-state selectivity of an agonist may determine the preferred direction of the receptor GEF function, which may affect the kinetics and selectivity of the engagement of the receptor with downstream effectors; this may ultimately present a means to disentangle multifaceted drug-induced physiological responses.
GPT-4o mini: Non-social science research article
Human assembloids recapitulate periportal liver tissue in vitro
Lei Yuan, Sagarika Dawka, Yohan Kim, Anke Liebert, Fabian Rost, Robert Arnes-Benito, Franziska Baenke, Christina Götz, David Long Hin Tsang, Andrea Schuhmann, Anna Shevchenko, Roberta Rezende de Castro, Seunghee Kim, Aleksandra Sljukic, Anna M. Dowbaj, Andrej Shevchenko, Daniel Seehofer, Dongho Choi, Georg Damm, Daniel E. Stange, Meritxell Huch
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The development of complex multicellular human in vitro systems holds great promise for modelling disease and advancing drug discovery and tissue engineering 1 . In the liver, despite the identification of key signalling pathways involved in hepatic regeneration 2,3 , in vitro expansion of human hepatocytes directly from fresh patient tissue has not yet been achieved, limiting the possibility of modelling liver composite structures in vitro. Here we first developed human hepatocyte organoids (h-HepOrgs) from 28 different patients. Patient-derived hepatocyte organoids sustained long-term expansion of hepatocytes in vitro and maintained patient-specific gene expression and bile canaliculus features and function of the in vivo tissue. After transplantation, expanded h-HepOrgs rescued the phenotype of a mouse model of liver disease. By combining h-HepOrgs with portal mesenchyme and our previously published cholangiocyte organoids 4–6 , we generated patient-specific periportal liver assembloids that retain the histological arrangement, gene expression and cell interactions of periportal liver tissue, with cholangiocytes and mesenchyme embedded in the hepatocyte parenchyma. We leveraged this platform to model aspects of biliary fibrosis. Our human periportal liver assembloid system represents a novel in vitro platform to investigate human liver pathophysiology, accelerate drug development, enable early diagnosis and advance personalized medicine.
GPT-4o mini: Non-social science research article
Laser spectroscopy and CP-violation sensitivity of actinium monofluoride
M. Athanasakis-Kaklamanakis, M. Au, A. Kyuberis, C. ZĂŒlch, K. Gaul, H. Wibowo, L. Skripnikov, L. Lalanne, J. R. Reilly, Á. KoszorĂșs, S. Bara, J. Ballof, R. Berger, C. Bernerd, A. Borschevsky, A. A. Breier, K. Chrysalidis, T. E. Cocolios, R. P. de Groote, A. Dorne, J. Dobaczewski, C. M. Fajardo Zambrano, K. T. Flanagan, S. Franchoo, J. D. Johnson, R. F. Garcia Ruiz, D. Hanstorp, S. KujanpÀÀ, Y. C. Liu, K. M. Lynch, A. McGlone, N. S. Mosyagin, G. Neyens, M. Nichols, L. Nies, F. Pastrana, S. Rothe, W. Ryssens, B. van den Borne, J. Wessolek, S. G. Wilkins, X. F. Yang
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The apparent invariance of the strong nuclear force under combined charge conjugation and parity (CP) remains an open question in modern physics1,2. Precision experiments with heavy atoms and molecules can provide stringent constraints on CP violation via searches for effects due to permanent electric dipole moments and other CP-odd properties in leptons, hadrons and nuclei3. Radioactive molecules have been proposed as highly sensitive probes for such searches4, but experiments with most such molecules have so far been beyond technical reach. Here we report the production and spectroscopic study of a gas-phase actinium molecule, 227AcF. We observe the predicted strongest electronic transition from the ground state, which is necessary for efficient readout in searches of symmetry-violating interactions. Furthermore, we perform electronic- and nuclear-structure calculations for 227AcF to determine its sensitivity to various CP-violating parameters, and find that a realistic, near-term experiment with a precision of 1 mHz would improve current constraints on the CP-violating parameter hyperspace by 3 orders of magnitude. Our results thus highlight the potential of 227AcF for exceptionally sensitive searches of CP violation.
GPT-4o mini: Non-social science research article
Palaeometabolomes yield biological and ecological profiles at early human sites
Timothy G. Bromage, Christiane Denys, Christopher Lawrence De Jesus, Hediye Erdjument-Bromage, Ottmar Kullmer, Oliver Sandrock, Friedemann Schrenk, Marc D. McKee, Natalie Reznikov, Gail M. Ashley, Bin Hu, Sher B. Poudel, Antoine Souron, Daniel J. Buss, Eran Ittah, JĂŒlide Kubat, Sasan Rabieh, Shoshana Yakar, Thomas A. Neubert
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The science of metabolic profiling exploits chemical compound byproducts of metabolism called metabolites1 that explain internal biological functions, physiological health and disease, and provide evidence of external influences specific to an organism’s habitat. Here we assess palaeometabolomes from fossilized mammalian hard tissues as a molecular ecological strategy to provide evidence of an ancient organism’s relationship with its environment. From eastern, central and southern African Plio-Pleistocene localities of palaeoanthropological significance, we study six fossils from Olduvai Gorge, Tanzania, one from the Chiwondo Beds, Malawi, and one from Makapansgat, South Africa. We perform endogeneity assessments by analysing palaeometabolomes of palaeosols and the effects of owl digestion on rodent bones to enable prudent ecological inferences. Diagenesis is indicated by metabolites of collagenase-producing bacteria2, whereas the preservation of peptides including those of collagen are identified by proteomics. Endogenous metabolites document biological functions and exogenous metabolites render environmental details including soil characteristics and woody cover, and enable annual minimum and maximum rainfall and temperature reconstructions at Olduvai Gorge, supporting the freshwater woodland and grasslands of Olduvai Gorge Bed I3,4,5, and the dry woodlands and marsh of Olduvai Gorge Upper Bed II6. All sites denote wetter and/or warmer conditions than today. We infer that metabolites preserved in hard tissues derive from an extravasated vasculature serum filtrate that becomes entombed within developing mineralized matrices, and most probably survive palaeontological timeframes in the nanoscopic ‘pool’ of structural-bound water that occurs in hard tissue niches7.
GPT-4o mini: Non-social science research article
Transient hepatic reconstitution of trophic factors enhances aged immunity
Mirco J. Friedrich, Julie Pham, Jiakun Tian, Hongyu Chen, Jiahao Huang, Niklas Kehl, Sophia Liu, Blake Lash, Fei Chen, Xiao Wang, Rhiannon K. Macrae, Feng Zhang
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Ageing erodes human immunity, in part by reshaping the T cell repertoire, leading to increased vulnerability to infection, malignancy and vaccine failure 1–3 . Attempts to rejuvenate immune function have yielded only modest results and are limited by toxicity or lack of clinical feasibility 1,3–5 . Here we show that the liver can be transiently repurposed to restore age-diminished immune cues and improve T cell function in aged mice. These immune cues were found by performing multi-omic mapping across central and peripheral niches in young and aged animals, leading to the identification of Notch and Fms-like tyrosine kinase 3 ligand (FLT3L) pathways, together with interleukin-7 (IL-7) signalling, as declining with age. Delivery of mRNAs encoding Delta-like ligand 1 (DLL1), FLT3L and IL-7 to hepatocytes expanded common lymphoid progenitors, boosted de novo thymopoiesis without affecting haematopoietic stem cell (HSC) composition, and replenished T cells while enhancing dendritic cell abundance and function. Treatment with these mRNAs improved peptide vaccine responses and restored antitumour immunity in aged mice by increasing tumour-specific CD8 + infiltration and clonal diversity and synergizing with immune checkpoint blockade. These effects were reversible after dosing ceased and did not breach self-tolerance, in contrast to the inflammatory and autoimmune liabilities of recombinant cytokine treatments 6,7 . These findings underscore the promise of mRNA-based strategies for systemic immune modulation and highlight the potential of interventions aimed at preserving immune resilience in ageing populations.
GPT-4o mini: Non-social science research article
Gene-specific selective sweeps are pervasive across human gut microbiomes
Richard Wolff, Nandita R. Garud
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The human gut microbiome is composed of a highly diverse consortia of species that are continually evolving within and across hosts 1,2 . The ability to identify adaptations common to many human gut microbiomes would show not only shared selection pressures across hosts but also key drivers of functional differentiation of the microbiome that may affect community structure and host traits. However, the extent to which adaptations have spread across human gut microbiomes is relatively unknown. Here we develop a new selection scan statistic named the integrated linkage disequilibrium score (iLDS) that can detect sweeps of adaptive alleles spreading across host microbiomes by migration and horizontal gene transfer. Specifically, iLDS leverages signals of hitchhiking of deleterious variants with a beneficial variant. Application of the statistic to around 30 of the most prevalent commensal gut species from 24 human populations around the world showed more than 300 selective sweeps across species. We find an enrichment for selective sweeps at loci involved in carbohydrate metabolism, indicative of adaptation to host diet, and we find that the targets of selection differ significantly between industrialized populations and non-industrialized populations. One of these sweeps is at a locus known to be involved in the metabolism of maltodextrin—a synthetic starch that has recently become a widespread component of industrialized diets. In summary, our results indicate that recombination between strains fuels pervasive adaptive evolution among human gut commensal bacteria, and strongly implicate host diet and lifestyle as critical selection pressures.
GPT-4o mini: Non-social science research article
Author Correction: Cryo-EM structure of a natural RNA nanocage
Xiaobin Ling, Dmitrij Golovenko, Jianhua Gan, Jinbiao Ma, Andrei A. Korostelev, Wenwen Fang
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GPT-4o mini: Non-social science research article
The global hydrogen budget
Zutao Ouyang, Robert B. Jackson, Marielle Saunois, Josep G. Canadell, Yuanhong Zhao, Catherine Morfopoulos, Paul B. Krummel, Prabir K. Patra, Glen P. Peters, Fraser Dennison, Thomas Gasser, Alexander T. Archibald, Vivek Arora, Gabriel Baudoin, Naveen Chandra, Philippe Ciais, Steven J. Davis, Sarah Feron, Fangzhou Guo, Didier Hauglustaine, Christopher D. Jones, Matthew W. Jones, Etsushi Kato, Daniel Kennedy, JĂŒrgen Knauer, Sebastian Lienert, Danica Lombardozzi, Joe R. Melton, Julia E.M.S. Nabel, Michael O’Sullivan, Gabrielle PĂ©tron, Benjamin Poulter, Joeri Rogelj, David Sandoval Calle, Pete Smith, Parvadha Suntharalingam, Hanqin Tian, Chenghao Wang, Andy Wiltshire
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Hydrogen (H2) will play a part in decarbonizing the global energy system1. However, hydrogen interacts with methane, ozone, and stratospheric water vapour, leading to an indirect 100-year global warming potential of 11 ± 4 (refs. 2,3,4,5). This raises concerns about the climate consequences of increasing H2 use under future hydrogen economies3,5. A comprehensive accounting of H2 sources and sinks is essential for assessing changes and mitigating environmental risks. Here we analyse trends in global H2 sources and sinks from 1990 to 2020 and construct a comprehensive budget for the decade 2010–2020. H2 sources increased from 1990 to 2020, primarily because of the oxidation of methane and anthropogenic non-methane volatile organic compounds, biogenic nitrogen fixation, and leakage from H2 production. Sinks also increased in response to rising atmospheric H2. Estimated global H2 sources and sinks averaged 69.9 ± 9.4 Tg yr−1 and 68.4 ± 18.1 Tg yr−1, respectively, for 2010–2020. Regionally, Africa and South America contained the largest sources and sinks of H2, whereas East Asia and North America contributed the most H2 emissions from fossil fuel combustion. We estimate that rising atmospheric H2 between 2010 and 2020 contributed to an increase in global surface air temperature (GSAT) of 0.02 ± 0.006 °C. GSAT impacts of changing atmospheric H2 in future marker Shared Socioeconomic Pathway scenarios are estimated to remain within 0.01–0.05 °C, depending on H2 usage, leakage rates and CH4 emissions that influence photochemical H2 production.
GPT-4o mini: Non-social science research article
Non-equilibrium snapshots of ligand efficacy at the Ό-opioid receptor
Michael J. Robertson, Arnab Modak, MakaĂ­a M. Papasergi-Scott, Miaohui Hu, Maria Claudia Peroto, Balazs R. Varga, Susruta Majumdar, Ravi Kalathur, Scott C. Blanchard, Georgios Skiniotis
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Distinct ligands for the same G-protein coupled receptor (GPCR) activate intracellular signaling partners to varying extents, but the molecular mechanisms driving these differences remain elusive. Hypothesizing that such differences in signaling efficacy may be captured structurally in intermediate states under non-equilibrium conditions, we implemented a time-resolved (TR) cryo-EM approach to visualize the GTP-induced activation of the GαiÎČÎł heterotrimer by the ÎŒ-opioid receptor (MOR) bound to three ligands displaying partial, full, or super-agonism on the receptor1. We resolved ensembles of conformational states along the G-protein activation pathway, including a previously unobserved intermediate state that enabled us to visualize receptor dynamics as a function of bound ligand. The results demonstrate ligand-dependent differences in state occupancy and conformational stability, with higher ligand efficacy correlating with increased dynamics of the receptor’s transmembrane (TM) helices 5 and 6. Furthermore, we identify key mechanistic differences in the GTP-induced activation of Gi compared to Gs that likely underlie their distinct activation kinetics. Corroborated by molecular dynamics (MD) simulations and single-molecule fluorescence assays, these findings provide a dynamic structural landscape of GPCR-G-protein interactions for ligands of different efficacy and suggest partial agonists may produce a ‘kinetic trap’ during G-protein activation.
GPT-4o mini: Non-social science research article
3D nanolithography with metalens arrays and spatially adaptive illumination
Songyun Gu, Chenkai Mao, Anna Guell Izard, Sarvesh Sadana, Dongping Terrel-Perez, Magi Mettry-Yassa, Wonjin Choi, Wenjie Zhou, Hujie Yan, Ziran Zhou, Travis Massey, Alex Abelson, You Zhou, Sijia Huang, Chiara Daraio, Thejaswi Umanath Tumkur, Jonathan A. Fan, Xiaoxing Xia
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The growing demand for advanced materials, miniaturized devices and integrated microsystems calls for the reliable fabrication of complex, multiscale, three-dimensional (3D) architectures, a need increasingly addressed through light-based and laser-based processes. However, owing to the field-of-view (FOV) limitations of conventional imaging optics, existing 3D laser nanofabrication techniques face fundamental challenges in throughput, proximity error and stitching defects on the path to scaling. Here we present a scalable 3D nanofabrication platform that uses a metalens-generated focal spot array to parallelize two-photon lithography (TPL)1 beyond centimetre-scale write field areas. Metalenses are ideally suited for producing submicron-scale focal spots for high-throughput nanolithography, as they uniquely feature large numerical apertures (NAs), immersion media compatibility and large-scale manufacturability. We experimentally demonstrate a printing system that uses a 12-cm2 metalens array to produce more than 120,000 cooperative focal spots, corresponding to a throughput exceeding 108 voxels s−1. By programmatically patterning the focal spot array using a spatial light modulator (SLM), an adaptive parallel printing strategy is developed for precise greyscale linewidth modulation and choreographed printing of semiperiodic and fully aperiodic 3D geometries. We demonstrate parallel printing of replicated microstructures (>50 M microparticles per day), centimetre-scale 3D architectures with feature sizes down to 113 nm, and photonic and mechanical metamaterials. This work demonstrates the potential of 3D nanolithography towards wafer-scale production, showing how TPL could be used at scale for applications in microelectronics2, biomedicine3, quantum technology4 and high-energy laser targets5,6.
GPT-4o mini: Non-social science research article
Visualizing interaction-driven restructuring of quantum Hall edge states
Jiachen Yu, Haotan Han, Kristina G. Wolinski, Ruihua Fan, Amir S. Mohammadi, Tianle Wang, Taige Wang, Liam Cohen, Kenji Watanabe, Takashi Taniguchi, Andrea F. Young, Michael P. Zaletel, Ali Yazdani
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Many topological phases host gapless boundary modes that can be markedly modified by electronic interactions. Even for the long-studied edge modes of quantum Hall phases1,2, forming at the boundaries of two-dimensional electron systems, the nature of such interaction-induced changes has been elusive. Despite advances made using local probes3,4,5,6,7,8,9,10,11,12,13, key experimental challenges persist: the lack of direct information about the internal structure of edge states on microscopic scales, and complications from edge disorder. Here we use scanning tunnelling microscopy to image pristine electrostatically defined quantum Hall edge states in graphene with high spatial resolution and demonstrate how correlations dictate the structures of edge channels on both magnetic and atomic length scales. For integer quantum Hall states in the zeroth Landau level, we show that interactions renormalize the edge velocity, dictate the spatial profile for co-propagating modes and induce unexpected edge valley polarization, which differs from the bulk. Although some of our findings can be understood by mean-field theory, others show breakdown of this picture, highlighting the roles of edge fluctuations and inter-channel couplings. We also extend our measurements to spatially resolve the edge state of fractional quantum Hall phases and detect spectroscopic signatures of interactions in this chiral Luttinger liquid. Our study establishes scanning tunnelling microscopy as a promising tool for exploring the edge physics of the rapidly expanding group of two-dimensional topological phases, including recently realized fractional Chern insulators.
GPT-4o mini: Non-social science research article
Mazdutide versus placebo in Chinese adults with type 2 diabetes
Dalong Zhu, Jiajun Zhao, Hanqing Cai, Xuan Chu, Shuangling Xiu, Chengwei Song, Zhifeng Cheng, Hongyi Cao, Hongwei Jiang, Lili Zhang, Haifang Wang, Bimin Shi, Yanbing Li, Ming Liu, Bo Feng, Fengtai Xue, Huan Deng, Haoyu Li, Li Li, Yue Li, Qingyang Ma, Lei Qian, character(0)
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Despite advances in type 2 diabetes (T2D) management, unmet needs remain for therapies that effectively control hyperglycaemia while addressing the comorbid metabolic disorders1, 2. Here we assessed the efficacy and safety of the dual glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) agonist mazdutide monotherapy versus placebo in Chinese adults with T2D inadequately controlled with diet and exercise alone. In this phase 3 trial, 320 participants (mean HbA1c of 8.24%, BMI of 28.2 kg/m2, and diabetes duration of 1.9 years) were randomised 1:1:1 to receive weekly subcutaneous injections of mazdutide 4 mg, 6 mg, or placebo for 24 weeks, followed by a 24-week extended mazdutide treatment. At week 24, mazdutide significantly reduced HbA1c versus placebo (primary endpoint): -1.57% with mazdutide 4 mg and -2.15% with mazdutide 6 mg, versus -0.14% with placebo, with treatment differences of -1.43% and -2.02% (both p <0.0001). Significant weight loss at week 24 occurred with -5.61% (4 mg) and -7.81% (6 mg) versus -1.26% (placebo) (both p<0.0001). Additionally, significantly more participants with mazdutide achieved clinically relevant HbA1c target (<7.0%), weight loss goal (≄5%), and composite endpoints (HbA1c <7.0% and weight loss ≄5%) versus placebo (all p <0.0001). The most common adverse events—diarrhoea, decreased appetite, and nausea—were consistent with GLP-1R agonists. These results establish mazdutide monotherapy as an effective intervention providing clinically meaningful glycaemic control and weight reduction alongside a favourable safety profile in this population.
GPT-4o mini: Non-social science research article
Publisher Correction: Covalent targeted radioligands potentiate radionuclide therapy
Xi-Yang Cui, Zhu Li, Ziren Kong, Yu Liu, Hao Meng, Zihao Wen, Changlun Wang, Junyi Chen, Mengxin Xu, Yiyan Li, Jingyue Gao, Wenjia Zhu, Zhixin Hao, Li Huo, Shaoyan Liu, Zhi Yang, Zhibo Liu
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GPT-4o mini: Non-social science research article
NAC controls nascent chain fate through tunnel sensing and chaperone action
Jae Ho Lee, Laurenz Rabl, Martin Gamerdinger, Vaishali Goyal, Katrin Michaela Khakzar, Natalia Moreira Barbosa, Juliana Abramovich, Fabian Morales-Polanco, Ann-Kathrin Köhler, Ekaterina Samatova, Marina V. Rodnina, Elke Deuerling, Judith Frydman
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The nascent polypeptide-associated complex (NAC) is a conserved ribosome-bound factor with essential yet incompletely understood roles in protein biogenesis1. Here, we show that NAC is a multifaceted regulator that coordinates translation elongation, cotranslational folding, and organelle targeting through distinct interactions with nascent polypeptides both inside and outside the ribosome exit tunnel. Using NAC-selective ribosome profiling in C. elegans, we identify thousands of sequence-specific NAC binding events across the nascent proteome, revealing broad cotranslational engagement with hydrophobic and helical motifs in cytosolic, nuclear, ER, and mitochondrial proteins. Unexpectedly, we discover an intra-tunnel sensing mode, where NAC engages ribosomes with extremely short nascent polypeptides inside the exit tunnel in a sequence-specific manner. Moreover, initial NAC interactions induce an early elongation slowdown that tunes ribosome flux and prevent ribosome collisions, linking NAC’s chaperone activity to kinetic control of translation. We propose NAC action protects aggregation-prone intermediates by shielding amphipathic helices, thus promoting cytonuclear folding. NAC also supports mitochondrial membrane protein biogenesis and ER targeting by early recognition of signal sequences and transmembrane domain. Our findings establish NAC as an early-acting, multifaceted orchestrator of cotranslational proteostasis, with distinct mechanisms of action on nascent chains depending on their sequence features and subcellular destinations.
GPT-4o mini: Non-social science research article
An 11-qubit atom processor in silicon
Hermann Edlbauer, Junliang Wang, A. M. Saffat-Ee Huq, Ian Thorvaldson, Michael T. Jones, Saiful Haque Misha, William J. Pappas, Christian M. Moehle, Yu-Ling Hsueh, Henric Bornemann, Samuel K. Gorman, Yousun Chung, Joris G. Keizer, Ludwik Kranz, Michelle Y. Simmons
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Phosphorus atoms in silicon represent a promising platform for quantum computing, as their nuclear spins exhibit coherence times over seconds 1,2 with high-fidelity readout and single-qubit control 3 . By placing several phosphorus atoms within a radius of a few nanometres, they couple by means of the hyperfine interaction to a single, shared electron. Such a nuclear spin register enables high-fidelity multi-qubit control 4 and the execution of small-scale quantum algorithms 5 . An important requirement for scaling up is the ability to extend high-fidelity entanglement non-locally across several spin registers. Here we address this challenge with an 11-qubit atom processor composed of two multi-nuclear spin registers that are linked by means of electron exchange interaction. Through the advancement of calibration and control protocols, we achieve single-qubit and multi-qubit gates with all fidelities ranging from 99.10% to 99.99%. By entangling all combinations of local and non-local nuclear-spin pairs, we map out the performance of the processor and achieve state-of-the-art Bell-state fidelities of up to 99.5%. We then generate Greenberger–Horne–Zeilinger (GHZ) states with an increasing number of qubits and show entanglement of up to eight nuclear spins. By establishing high-fidelity operation across interconnected nuclear spin registers, we realize a key milestone towards fault-tolerant quantum computation with atom processors.
GPT-4o mini: Non-social science research article
Titan’s strong tidal dissipation precludes a subsurface ocean
Flavio Petricca, Steven D. Vance, Marzia Parisi, Dustin Buccino, Gael Cascioli, Julie Castillo-Rogez, Brynna G. Downey, Francis Nimmo, Gabriel Tobie, Baptiste Journaux, Andrea Magnanini, Ula Jones, Mark Panning, Amirhossein Bagheri, Antonio Genova, Jonathan I. Lunine
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The Cassini mission provided unprecedented insights into Saturn’s largest moon, Titan, from its atmosphere to the deep interior1. The moon’s large measured response to the tides exerted by Saturn was interpreted as evidence of the existence of a subsurface ocean2,3. This response, twice the value predicted in pre-Cassini studies, has escaped complete explanation. Here we show that the signature of tidal dissipation in Titan’s gravity field is not consistent with the presence of an ocean. Our results arise from the detection of this signature through a reanalysis of the radiometric data acquired by Cassini with improved techniques. We found that substantial energy is being dissipated in the interior (approximately 3–4 TW, corresponding to a tidal quality factor Q ≈ 5), consistent with recent studies of Titan’s rotational state4. Because the presence of a liquid layer reduces the tidal dissipation generated below it5, these new measurements preclude the existence of a subsurface ocean on Titan and are explained by a model in which dissipation is concentrated in a high-pressure ice layer close to its melting point. This model also reproduces Titan’s observed rotational state and static gravity field self-consistently, reconciling all available geophysical measurements. Efficient ice shell convection can prevent widespread melting and ocean formation, but a slushy high-pressure ice layer is consistent with expectations6, indicating that it probably hosts liquid water pockets. The forthcoming Dragonfly mission to Titan will provide a further test of whether a subsurface ocean exists.
GPT-4o mini: Non-social science research article
Prevalence of Alzheimer’s disease pathology in the community
Dag Aarsland, Anita Lenora Sunde, Diego A. Tovar-Rios, Antoine Leuzy, Tormod Fladby, Henrik Zetterberg, Kaj Blennow, KĂŒbra Tan, Giovanni De Santis, Yara Yakoub, Burak Arslan, Hanna Huber, Ilaria Pola, Lana Grötschel, Guglielmo Di Molfetta, HĂ„vard K. Skjellegrind, Geir Selbaek, Nicholas J. Ashton
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The prevalence of Alzheimer’s disease neuropathological changes (ADNCs), the leading cause of cognitive impairment, remains uncertain. Recent blood-based biomarkers enable scalable assessment of ADNCs 1 . Here we measured phosphorylated tau at threonine 217 in 11,486 plasma samples from a Norwegian population-based cohort of individuals over 57 years of age as a surrogate marker for ADNCs. The estimated prevalence of ADNCs increased with age, from less than 8% in people 58–69.9 years of age to 65.2% in those over 90 years of age. Among participants aged 70 years or older, 10% had preclinical Alzheimer’s disease, 10.4% had prodromal Alzheimer’s disease and 9.8% had Alzheimer’s disease dementia. Furthermore, among those 70 years of age or older, ADNCs were present in 60% of people with dementia, in 32.6% of those with mild cognitive impairment and in 23.5% of the cognitively unimpaired group. Our findings suggest a higher prevalence of Alzheimer’s disease dementia in older individuals and a lower prevalence of preclinical Alzheimer’s disease in younger groups than previously estimated 2 .
GPT-4o mini: Non-social science research article
Astrocyte CCN1 stabilizes neural circuits in the adult brain
Laura Sancho, Matthew M. Boisvert, Trinity Eddy, Jillybeth Burgado, Minerva Contreras, Lara Labarta-Bajo, Ellen Wang, Lisa Tatsumi, Nicola J. Allen
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Neural circuits in many brain regions are refined by experience. Sensory circuits support higher plasticity at younger ages during critical periods—times of circuit refinement and maturation—and limit plasticity in adulthood for circuit stability1,2. How astrocytes, a glial subtype, maintain these differing plasticity levels, and whether they stabilize the properties of sensory circuits in adulthood, remain largely unclear. Here we take a comprehensive approach to address these questions and establish astrocytes as key orchestrators of circuit stability. Combining a transcriptomic approach with ex vivo electrophysiology and in vivo imaging, we identify that astrocytes release CCN1 (refs. 3,4) to maintain synapse and circuit stability in the adult visual cortex. Overexpressing CCN1 in astrocytes during the critical period promotes the maturation of inhibitory neurons, limits ocular dominance plasticity and promotes oligodendrocyte differentiation and maturation. Conversely, knocking out astrocyte CCN1 in adults destabilizes binocular circuits and reduces myelination. This establishes CCN1 as an astrocyte-secreted factor that stabilizes neuronal circuits by coordinating the maturation state of multiple cell types, and demonstrates that the composition and properties of sensory circuits require ongoing maintenance in adulthood, and that these maintenance cues are provided by astrocytes.
GPT-4o mini: Non-social science research article
Spatiotemporal cellular map of the developing human reproductive tract
Valentina Lorenzi, Cecilia Icoresi-Mazzeo, Charlotte Cassie, Nadav Yayon, Elias R. Ruiz-Morales, Carmen Sancho-Serra, Ryan Colligan, Frederick C. K. Wong, Magda Marečková, Elizabeth Tuck, Kenny Roberts, Tong Li, Marc-Antoine Jacques, James Ashcroft, Xiaoling He, Berta Crespo, Batuhan Cakir, Simon Murray, Yong Gu, Alexander V. Predeus, Martin Prete, Iva Kelava, Roger Barker, Luz Garcia-Alonso, John C. Marioni, Roser Vento-Tormo
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The human reproductive tract is essential for species perpetuation and overall health. Its development involves complex processes of sex specification, tissue patterning and morphogenesis, the disruption of which can cause lifelong issues, including infertility 1–5 . Here we present an extensive single-cell and spatial multi-omic atlas of the human reproductive tract during prenatal development to provide insights beyond those that are possible with smaller-scale, organ-focused studies. We describe potential regulators of sexual dimorphism in reproductive organs and pinpoint previously unknown genes involved in MĂŒllerian duct emergence and regression and urethral canalization of the penis. By combining histological features with gene expression and chromatin accessibility data, we define transcription factors and signalling events potentially involved in the regionalization of the MĂŒllerian and Wolffian ducts. We also refine how the HOX code is established in distinct reproductive organs and reveal that the expression of thoracic HOX genes is increased in the rostral mesenchyme of the fallopian tube and epididymis. Our findings further indicate that epithelial regionalization of the fallopian tube and epididymis, which probably contribute to sperm maturation and capacitation, is established during development. By contrast, later events are necessary for regionalization of the uterocervical canal epithelium. Finally, on the basis of single-cell data and fetal-derived organoids, we show that the fetal uterine epithelium is vulnerable to oestrogen-mimicking endocrine disruptors. By mapping sex-specific reproductive tract regionalization and differentiation at the cellular level, our study provides valuable insights into causes and potential treatments of developmental reproductive disorders.
Nature DOI suffix ≠ "/s...": Not a research article
Annual flu vaccines are far from ideal — this is why
Troy Sutton
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Nature DOI suffix ≠ "/s...": Not a research article
‘A serious problem’: peer reviews created using AI can avoid detection
Dalmeet Singh Chawla
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The difficulty of detecting AI-tool use in peer review is proving problematic.Credit: BrianAJackson/iStock via Getty It’s almost impossible to know whether a peer-review report has been generated by artificial intelligence, according to a study that put AI-detecting tools to the test. A research team based in China used the Claude 2.0 large language model (LLM), created by Anthropic, an AI company in San Francisco, California, to generate peer-review reports and other types of documentation for 20 published cancer-biology papers from the journal eLife1. The journal’s publisher makes papers freely available online as ‘reviewed preprints’, and publishes them alongside their referee reports and the original unedited manuscripts. The authors fed the original versions into Claude and prompted it to generate referee reports. The team then compared the AI-generated reports with the genuine ones published by eLife. The AI-written reviews “looked professional, but had no specific, deep feedback”, says Lingxuan Zhu, an oncologist at the Southern Medical University in Lianyungang, China, and a co-author of the study. “This made us realize that there was a serious problem.” The study found that Claude could write plausible citation requests (suggesting papers that authors could add to their reference lists) and convincing rejection recommendations (made when reviewers think a journal should reject a submitted paper). The latter capability raises the risk of journals rejecting good papers, says Zhu. “An editor cannot be an expert in everything. If they receive a very persuasive AI-written negative review, it could easily influence their decision.” The study also found that the majority of the AI reports fooled the detection tools: ZeroGPT erroneously classified 60% as written by a human, and GPTzero concluded this for more than 80%. Differing opinions A growing challenge for journals is the fact that LLMs could be used in many ways to produce a referee report. What is deemed an ‘acceptable’ use of AI also differs depending on whom you ask. In a survey of some 5,000 researchers conducted by Nature earlier this year, 66% of respondents said it wasn’t appropriate to use generative AI to create reviewer reports from scratch. But 57% said it was acceptable to use it to help with peer review by getting it to answer questions about papers. And although AI-detection tools are improving, they struggle to determine how much of a document has been generated using AI. An analysis published last year of referee reports that were submitted to four computer-science conferences estimated that 17% had been substantially modified by chatbots2. It’s not clear, however, whether the referees used AI to improve the reports or to write them entirely. Nature Index 2025 Research Leaders Jeroen Verharen, a neuroscientist at the firm iota Biosciences in Alameda, California, says he is surprised that the AI detectors used by Zhu and his team weren’t better at spotting the AI-written referee reports. But he adds that AI-written reports and associated materials are unlikely to become a widespread problem. If reviewers don’t want to review, he says, “they would just say no”. Conversely, MikoƂaj Piniewski, a hydrologist at the Warsaw University of Life Sciences, argues that it is a growing issue. He says he has already received referee reports that he suspects were written by AI. “LLMs are increasingly being used by peer reviewers, although this is rarely disclosed,” he says. “When I spoke to my colleagues in the field of hydrology, it became clear that each of us had encountered at least one such case as an author in the past two years. At least one of the review reports we received looked very suspicious, and the AI-detection tools we used flagged it as potentially generated by LLMs.” Piniewski adds that he is sure some journal editors are accepting AI-generated referee reports, unwittingly or otherwise. He suggests that a global shortage of peer reviewers could be causing some editors to be more lenient than they should be. “I’m afraid it is largely driven by convenience,” he says.
Nature DOI suffix ≠ "/s...": Not a research article
Could tracking animals’ health help to avert the next pandemic?
Sarah DeWeerdt
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Nature DOI suffix ≠ "/s...": Not a research article
Living water and whispering rocks: Books in brief
Andrew Robinson
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The Whispers of Rock Anjana Khatwa Bridge Street Press (2025) In 1902, on the Caribbean island of Saint Vincent, a group of women reported that water was boiling in the crater of the La SoufriĂšre volcano, accompanied by booming sounds and shaking, but they were ignored by the colonial authorities. The subsequent eruption killed 1,680 islanders. This is one of many global examples of the public’s appreciation of nature in Earth scientist Anjana Khatwa’s enticing book. “Awakening yourself to the whispers of rock”, she says, “can transform the way you connect with and understand the world”. Lo—TEK Water Julia Watson Taschen (2025) Water is “not a resource to be extracted or managed, but a living relative, a system of memory, intelligence, and reciprocity”, says landscape designer Julia Watson. This view underlies the Lo—TEK movement that she spearheads, which draws on Indigenous philosophy that water is a regenerative substance. Her pioneering, lavishly illustrated book contains contributions from many communities, from Bangladesh’s floating farms to China’s dike-pond systems and Micronesia’s traps to catch fish using tide flows. Surviving the Twenty-First Century Noam Chomsky & JosĂ© Mujica Verso (2025) In 2017 and 2022, filmmaker SaĂșl AlvĂ­drez recorded conversations between linguist Noam Chomsky and political activist JosĂ© Mujica, former president of Uruguay. Their discussions range from the risks of climate change to neo-fascism and the wisdom of nature, and make up this brief, thought-provoking book. Despite mutual admiration, the two do disagree at times. For example, Chomsky says that automation will “free people to undertake truly creative and satisfying work”, but Mujica says that “robots work only for their masters!” Warhead Nicholas Wright St. Martin’s Press (2025)
Nature DOI suffix ≠ "/s...": Not a research article
Science in 2026: the events to watch for in the coming year
Miryam Naddaf
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India’s Aditya-L1 spacecraft launched in 2023. Next year, it will observe the Sun during its peak activity phase.Credit: Indian Space Research Organisation via AP/Alamy AI for science Research powered by artificial intelligence made leaps this year, and it is here to stay. AI ‘agents’ that integrate several large language models (LLMs) to carry out complex, multi-step processes are likely to be used more widely, some with little human oversight. The coming year might even bring the first consequential scientific advances made by AI. But heavier use could also expose serious failures in some systems. Researchers have already reported errors that AI agents are prone to, such as the deletion of data. Next year will also bring techniques that move beyond LLMs, which are expensive to train. Newer approaches focus on designing small-scale AI models that learn from a limited pool of data and can specialize in solving specific reasoning puzzles. These systems do not generate text, but process mathematical representations of information. This year, one such tiny AI model beat massive LLMs at a logic test. Gene-editing momentum Next year could see the launch of two clinical trials to develop personalized gene therapies for children with rare genetic disorders. The efforts expand on the treatment of KJ Muldoon, a baby boy with a rare metabolic disorder who received a CRIPSR therapy tailored to correct his specific disease-causing mutation. The team that treated Muldoon plans to seek approval from the US Food and Drug Administration (FDA) to run a clinical trial in Philadelphia, Pennsylvania, that will test gene-editing therapies in more children with rare metabolic disorders. These conditions are caused by variants in seven genes that can be addressed with the same type of gene editing as was used in Muldoon’s therapy. Another team hopes to begin a similar trial for genetic disorders of the immune system next year. Artemis II crew members Victor Glover, Reid Wiseman, Christina Koch and Jeremy Hansen with the Orion crew module.Credit: NASA Massive trial A UK clinical trial of a single blood test that detects around 50 types of cancer before symptoms begin is expected to report results next year. The test screens for bits of DNA that cancer cells release into the blood, and can home in on the tissue type or organ that the signal comes from. The trial involved more than 140,000 participants, and if the results are promising, UK health authorities plan to roll out the tool across hospitals. In April, the biggest regulatory update to clinical trials in the United Kingdom in two decades will come into force. Under the new rules, researchers can seek ethics and regulatory approval in one application. But the law also mandates that all trials involving medicines be publicly registered before recruiting their first participant and that a summary of results be published within 12 months of the end of the trial. The goal is to speed up research, boost the diversity of trial participants and reduce the time it takes for promising treatments to reach the people who need them. Meanwhile, changes proposed by the FDA this month that would require a single clinical trial, rather than two, for new drugs to be approved will continue to unfold in 2026. Heavy lunar traffic Next year is set to be another busy one for Moon missions. NASA’s Artemis II will send four astronauts to fly around the Moon aboard the Orion spacecraft. The ten-day flight is the first crewed lunar mission since the 1970s and will help to prepare for subsequent missions to land on the Moon. China is also preparing to launch the next in its series of lunar probes, Chang’e-7, in August. The mission will use a hopper spacecraft with shock-absorbing capabilities. It aims to arrive near the south pole — a rock- and crater-strewn region known for being challenging to land on. In 2023, India’s Chandrayaan-3 was the first spacecraft to successfully touch down near the lunar south pole. If it achieves a successful landing, Chang’e-7 will hunt for water ice and study moonquakes. The payload module of ESA’s PLATO spacecraft — due to launch in 2026 — undergoes tests in a thermal vacuum chamber.Credit: ESA-Remedia Martian moons and beyond Researchers are also turning their eyes to Mars, with Japan planning to launch its Martian Moons eXploration (MMX) mission to visit the red planet’s two moons, Phobos and Deimos. The spaceship will collect samples of Phobos’s surface and return them to Earth in 2031, which has never been done before. The European Space Agency is planning to launch its planet-hunting satellite PLATO towards the end of next year. Equipped with 26 cameras, PLATO will monitor more than 200,000 bright stars and identify ‘Earth twin’ planets with temperatures that allow liquid water to form. India’s first solar mission, Aditya-L1, will observe the Sun during solar maximum, the peak of a roughly 11-year activity cycle, marked by the highest rates of sunspots, flares and solar storms. The satellite has been sitting in a halo orbit, which allows continuous observation of the Sun, about 1.5 million kilometres from Earth, since last year. Its data will help researchers to build a better picture of the Sun’s surface during the solar maximum. Drill, baby, drill Next year, China’s ocean-drilling ship Meng Xiang is expected to embark on its first scientific expedition. The vessel is designed to drill up to 11 kilometres through oceanic crust into Earth’s mantle and collect samples. The work will help researchers to learn about how the ocean floor forms and what drives its tectonic activity. The Meng Xiang, China’s deep-ocean drilling vessel, is designed to drill through Earth’s crust into the mantle.Credit: Liu Dawei/Xinhua via Alamy
Nature DOI suffix ≠ "/s...": Not a research article
MIT fusion-lab head shot dead: a horror ‘impossible to believe’
Rachel Fieldhouse, Mohana Basu, Elizabeth Gibney
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Nuno Loureiro, director of the Plasma Science and Fusion Center at the Massachusetts Institute of Technology in Cambridge, dies at 47.Credit: Erica Denhoff/Icon Sportswire via Getty Update: On 18 December, the US Attorney for Massachusetts Leah Foley told reporters that Claudio Neves Valente is suspected of killing Nuno Loureiro on 15 December. Neves Valente, who was found dead from a self-inflicted gunshot wound in a storage unit in Salem, New Hampshire, on 18 December, is also thought to have killed two students and injured nine others at Brown University on 13 December. Foley said Neves Valente attended Brown University in the early 2000s and attended the same academic programme in Portugal as Loureiro between 1995 and 2000. Scientists have expressed their shock and sadness following the death of plasma physicist Nuno Loureiro, a researcher at the Massachusetts Institute of Technology (MIT) in Cambridge, who was shot at his home in Brookline, Massachusetts, on Monday. The scientist died from his injuries on Tuesday morning after being shot multiple times. Police say they are investigating his death and treating it as a homicide. Loureiro’s death is the second US university-related tragedy in a week, after two people were killed and nine others were injured in a shooting at Brown University in Providence, Rhode Island, on Saturday. At the time of his death, Loureiro had been the head of MIT’s Plasma Science and Fusion Center, a position he held since May last year. The laboratory hosts more than 250 scientists. This year, Loureiro was given the Presidential Early Career Award for Scientists and Engineers, which is bestowed on researchers who show exceptional potential for leadership. Loureiro was a “brilliant scientist”, who was sharp, kind and had a smart sense of humour, says Stanislav Boldyrev, a plasma physicist at the University of Wisconsin–Madison, who began working with Loureiro in 2017. “It’s a privilege to have a friend like him,” Boldyrev adds. “He was so interested in science, it was almost contagious.” “He shone a bright light as a mentor, friend, teacher, colleague and leader, and was universally admired for his articulate, compassionate manner,” said Dennis Whyte, former director of the Plasma Science and Fusion Center, in a statement. Loureiro was passionate about the potential for fusion as a clean power source and about teaching a new generation of scientists, say colleagues. He thought “that we are really progressing towards finally having electricity from fusion”, says Bruno Soares Gonçalves, a plasma physicist and president of the Institute of Plasmas and Nuclear Fusion in Lisbon, where Loureiro worked until he moved to MIT in 2016. “People in the community are so shocked and extremely saddened,” he says. Nuno Loureiro was a theoretical physicist who was helping to develop clean-energy fusion devices. Credit: Jake Belcher/MIT 'Doing what he loved' Loureiro grew up in Portugal and obtained his PhD in physics at Imperial College London in 2005. He worked in the United Kingdom and Portugal before starting at MIT in 2016. The move was a huge opportunity for Loureiro, which he was eager to take, says Gonçalves. He was “doing what he loved in the place where he was really keen to be”. Loureiro’s work focused on modelling and understanding turbulence in plasma, the super-hot, exotic state of matter composed of charged particles that makes up stars and could one day power fusion reactors on Earth. He studied how plasma behaves inside fusion chambers, particularly its tendency to become unstable, to optimize the operation of future devices.
Nature DOI suffix ≠ "/s...": Not a research article
AI and quantum science take centre stage under Trump — but with little new proposed funding
Jenna Ahart
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A quantum computer. The administration of US President Donald Trump has announced sizable spending prorammes for quantum information science and artificial intelligence.Credit: Kent Nishimura/Bloomberg/Getty For much of US science, 2025 was a year of cancelled grants and budget anxiety — but a few fortunate fields came out ahead. Since President Donald Trump took office in January, artificial intelligence and quantum-information science have sat at the top of his administration’s scientific priorities. And they don’t seem to be leaving any time soon. Trump has ordered his advisers to ensure that the nation is “the unrivaled world leader” in AI and quantum information. The subjects are listed first and second on the administration’s list of research and development priorities. And on 11 December, Trump signed an executive order preventing US states from regulating AI, with the goal of speeding up the technology’s development. But some researchers question the effectiveness of the administration’s programmes to promote quantum science and AI. And some argue that the administration’s strategies might be hampered by some of its other policy changes. Here Nature examines three ways in which the administration aims to move quantum science and AI forwards. Funding opportunities Trump’s budget proposal for the National Science Foundation (NSF) in 2026 largely spared quantum science and AI, with a 3% increase in AI funding and a 0.4% increase in spending on quantum science — in contrast to cancelled research grants and proposals for steep cuts in many other areas. And throughout 2025, both the NSF and the Department of Energy (DoE) have announced new investments in AI and quantum science, including $100 million for AI projects at five US universities. Will AI ever win its own Nobel? Some predict a prize-worthy science discovery soon Steven Rolston, a quantum physicist at the University of Maryland in College Park and chair of the university’s physics department, says that the disparity between fields is visible there: faculty members in fields such as particle astrophysics face deep uncertainty about how much funding they’ll receive and how often they’ll have to reapply for awards. For quantum research, however, the biggest change is that the grant cycle has slowed down because of a US government shutdown and agency staffing changes. “I sort of have survivor’s guilt here,” Rolston says. But quantum science and AI have not been immune to grant cuts. According to data from the non-profit website Grant Witness, the NSF has cancelled 101 grants that mention ’artificial intelligence’ in their abstracts, and 68 grants that mention ‘quantum’ in their abstracts. And although AI and quantum science escaped massive cuts, the administration’s funding increases for these areas “are negligible in scope”, says David Schatsky, an AI-policy researcher at Harvard University in Cambridge, Massachusetts. “The 2026 budget doesn’t reflect — in dollar terms — an increase in focus or commitment to AI and quantum.” The NSF declined Nature’s request for comment, and the White House Office of Science and Technology Policy (OSTP) did not respond. Joining forces To pursue its priorities, the administration is also promoting both new and existing public–private partnerships, most prominently through an initiative, called the Genesis Mission, that was announced in November. The project, headed by the DoE, will make scientific data sets from the 17 US national laboratories available to private companies and academic researchers, who will use those data to build AI models to accelerate scientific research. Among the companies that have signed up to collaborate with federal researchers are Microsoft, IBM and OpenAI. If the AI bubble bursts, what will it mean for research? The administration has promoted public–private partnerships in quantum science as well. Under the National Quantum Initiative, which began during the first Trump administration, quantum-information research centres at five national labs partner with private quantum companies to create prototypes and test new technology. The DoE made an extra $625-million investment in the programme this year, and an executive order outlining the administration’s overarching approach to quantum science is expected soon, says Constanza Vidal Bustamante, a quantum-technology policy researcher at the Center for a New American Security, a think tank in Washington DC.
Nature DOI suffix ≠ "/s...": Not a research article
Immunological sin: how a person’s earliest flu infections dictate life-long immunity
Amanda B. Keener
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Nature DOI suffix ≠ "/s...": Not a research article
Stopping the next flu pandemic
Cassandra Willyard
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Nature DOI suffix ≠ "/s...": Not a research article
Seven feel-good science stories to restore your faith in 2025
Katie Kavanagh
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Renewable-energy milestones were met in 2025, with China being the first country to surpass 1 terawatt in installed solar-power capacity. Credit: Chen Kun/VCG via Getty The biggest science story this year was the political upheaval in the United States. Funding cuts, academic lay-offs and vaccine-sceptic policies have widely been seen as an attack on science, according to critics of President Donald Trump’s administration. The resulting damage to science could last way into the future. But, there were also plenty of positive developments in 2025 that offer hope for the coming years. “From a non-US scientist, it’s somewhat business as usual. You just keep doing your job,” says Glen Peters, a climate-policy researcher at the Cicero Center for International Climate Research in Oslo. Our recent Nature’s 10 package includes many good news stories — and there were many more. From gene-editing firsts to rapid disease containment and policy victories, Nature takes a look at some positive science stories of 2025. Nature’s 10: Ten people who shaped science in 2025 Species recovery This year saw populations of some endangered and near-extinct species bounce back owing to strong conservation efforts. The green sea turtle (Chelonia mydas), which has been endangered since the 1980s, has now moved to ‘least concern’ on the International Union for Conservation of Nature (IUCN) red list. Efforts to protect the turtle’s eggs and measures to prevent their accidental capture in fishing nets have allowed populations to recover. The ampurta (Dasycercus hillieri), a rat-sized Australian marsupial, moved from near-extinction to ‘least concern’ this year. Between 2015 and 2021, ampurta territory expanded by more than 48,000 square kilometres, despite dry conditions and food shortages. Lastly, nations reached a historic milestone for marine conservation in September with the United Nations High Seas Treaty receiving approval from more than 60 countries. The treaty, which will come into effect in January, aims to legally protect biodiversity in international waters and conserve at least 30% of land and sea areas. Ozone hole shrinks The hole in the Antarctic ozone layer has shrunk to its smallest size since 2019, indicating the continued recovery of Earth’s protective upper atmosphere. The ozone hole was first discovered in 1985 and is a result of human-emitted ozone-depleting chlorofluorocarbons (CFCs), such as coolants in refrigerators and aerosol sprays. The Montreal Protocol in 1987 phased out the production and use of CFCs, which has successfully curbed emissions1. Since 1987, the average size of the ozone hole throughout the year has been gradually decreasing in size, with the smallest so far in 2019. The ozone hole is on track to recover completely in the late 2060s, provided efforts to find climate-friendly alternatives to CFCs continues. The hole in the Antarctic ozone layer has continued to shrink.Credit: CAMS Gene-editing successes This year “was a breakthrough year for gene editing”, says David Liu, a chemical biologist at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts. “In 2025, these technologies have achieved a number of medical milestones.” “I view this year as an outstanding one, marked by the launch of many clinical trials,” adds Annarita Miccio, who studies gene therapy at the Imagine Institute at the Necker Hospital for Sick Children in Paris. Huntington’s disease treated for the first time using gene therapy The first gene therapy for Huntington’s disease proved striking, slowing the rate of cognitive decline in participants by 75%. Another gene-therapy trial — for T-cell acute lymphoblastic leukaemia — showed promise with the majority of 11 participating children and adults entering remission2. The new type of CAR-T-cell therapy uses base-editing technology to modify several genes in T cells, helping them to target the cancer cells. Researchers also trialled the first use of a CRISPR technology tailored to an individual this year. Other successes include the first clinical trial for a gene therapy to treat a rare immune disorder called chronic granulomatous disease3, and another that corrected a pathogenic mutation that can cause lung damage and liver disease4. These clinical trials paved the way for developing mutation-specific strategies for rare diseases and demonstrated that collaboration between academia and industry can lead to cures for people with such diseases, says Miccio. Renewable-energy boost Renewable energy surpassed coal as the largest energy source for the first time globally this year. The achievement was helped by China becoming the first country in the world to install 1 terawatt of solar power capacity in May. In the first six months of 2025 alone, China installed new solar systems with a capacity of 256 gigawatts — twice as much as the rest of the world combined. The country plans to add a further 200–300 gigawatts of capacity for solar and wind energy in its five year plan beginning in 2026. What happened at COP30? 4 science take-homes from the climate summit “China and many developing countries are deploying solar and wind [and] electric vehicles at pretty breakneck pace,” says Peters. Around half of the European Union’s demand for electricity came from from renewables in the second and third quarters of this year. Renewable-energy capacity is projected to increase by almost 4,600 gigawatts between 2025 and 2030 — double the capacity deployed between 2019 and 2024. However, greenhouse-gas emissions from fossil fuels reached a new high this year. It remains to be seen whether renewable energy can replace fossil fuels as the dominant global energy sources. Ebola contained
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US–Africa bilateral health deals won’t help against diseases that ignore borders
Paul Adepoju
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Kenyan health workers wait to receive a COVID-19 vaccine supplied by Gavi, the Vaccine Alliance. Credit: Simon Maina/AFP via Getty The United States is rolling out bilateral health agreements across Africa under its America First Global Health Strategy. Its announcement on 4 December of a US$1.6-billion health agreement with Kenya was the first, and signals a shift in how the United States intends to engage with African health systems. Rather than strengthening relevant continental bodies such as the World Health Organization (WHO), the African Union and the Africa Centres for Disease Control and Prevention (CDC), the strategy leans towards one-to-one agreements between governments. The timing could not be more delicate. It follows the United States’ withdrawal of funding from Gavi, the Vaccine Alliance, and the WHO, two international health institutions that African governments rely on for vaccines, coordination and technical support, and the importance of which in the region has grown since the COVID-19 pandemic. Africa finally has its own drug-regulation agency — and it could transform the continent’s health During the pandemic, countries across Africa faced devastating delays in accessing vaccines, medical supplies and diagnostic tools. Front-line responders and laboratories struggled. Surveillance systems had uneven coverage. Outbreak information moved too slowly. Countries negotiated alone for tools they needed but could not secure. In 2022, led by the Africa CDC, African leaders endorsed a New Public Health Order to build continent-wide systems to protect everyone, not just the states with the most leverage. One example is the Continental Cholera Emergency Preparedness and Response Plan for Africa. Developed by the Africa CDC and the WHO, and endorsed by heads of state in August, it outlines how countries should respond to cholera as a single coordinated unit. The plan establishes one team, one plan, one budget and one monitoring framework. It describes how responders can deploy from one country to another rapidly; how national laboratories with sequencing capacity can support testing for neighbours with fewer resources; and how information should flow seamlessly across borders so that no outbreak is hidden by a lack of capacity. Could Africa be the future for genomics research? Another example is Africa’s Health Security and Sovereignty Agenda, which was outlined by the Africa CDC in November. It includes stronger mandates for the CDC, harmonized regulatory pathways, expansion of regional manufacturing and cross-border surveillance systems built on shared data. By contrast, the America First Global Health Strategy prioritizes bilateral health agreements with individual governments, with limited reference to the role of continental bodies. It creates space for parallel systems that might not connect to Africa’s surveillance networks or regulatory structures. This shift raises three concerns.
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How common is Alzheimer’s? Blood-test study holds surprises
Asher Mullard
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Researchers looked for markers of Alzheimer’s disease in more than 11,000 Norwegians.Credit: Tek Image/SPL Nearly one in ten people over the age of 70 have Alzheimer’s disease dementia, shows a first-of-its-kind study that paired blood-based markers and clinical assessments to study the disease in Norway1. That prevalence is in line with previous estimates for some other white populations2. But there were also unexpected differences, including higher disease rates than anticipated in individuals older than 85. “This is very important work from a beautiful Norwegian study,” says Nicolas Villain, a neurologist at Sorbonne University in Paris who was not involved in the research. The study, published today in Nature, shows that blood-based tools can improve epidemiological estimates of neurodegenerative disease. Blood tests are now approved for Alzheimer’s: how accurate are they? But exactly how to use these tests remains controversial, warns Jason Karlawish, a geriatrician and co-director of the Penn Memory Center in Philadelphia, Pennsylvania. Blood-based markers can be helpful for physicians treating people with dementia and for answering research questions, but they aren’t ready to be rolled out widely as health screening tools. “It is the kind of test that, in the wrong hands, could cause a lot of harm,” says Karlawish, who was not involved in the study. From blood to brain To assess the prevalence of Alzheimer’s disease (AD), an international team of researchers turned to the Trþndelag Health (HUNT) study, a prospective research study that started in 1984 and that has collected health data and biological samples from 250,000 Norwegians. Using blood samples from 11,486 individuals in the study aged 58 and above, the team looked at levels of a protein, called tau, that has been phosphorylated at a specific site. Known as pTau217, this blood marker serves as a proxy for the build-up of amyloid plaque in the brain, a hallmark of AD. HUNT-study participants over the age of 70 have undergone cognitive testing, enabling the researchers to compare pTau217 levels with the presence of dementia. Around 10% of participants over the age of 70 had dementia and AD pathology, showing both cognitive impairment and high pTau217, they report. Another 10% had mild cognitive impairments and high pTau217. And 10% had high pTau217 but no signs of cognitive impairment, which the authors refer to as preclinical AD. These findings are broadly in line with expectations, but there were surprises, too. Some 25% of people aged 85–89 had dementia and AD pathology, up from previous estimates of around 7% for men and 13% for women in this age group in Western Europeans3. And the incidence of preclinical AD in younger individuals was 8% in those aged 70–74, down from a previous estimate of around 22%. Anders Gustavsson, a member of the team that compiled the earlier estimates, welcomes the latest data. “I’m not surprised that this study gets somewhat different numbers,” says Gustavsson, who is an adviser to the health-economics consultancy Quantify Research in Stockholm. Alzheimer’s decline slows with just a few thousand steps a day The discrepancies probably reflect selection bias, says study co-author Anita Lenora Sunde, a physician and dementia researcher at Stavanger University Hospital in Norway. Previous estimates were made by recruiting participants for brain scans, and people with dementia might not have wanted to or been able to participate. But other factors could also be at play, says Villain. The latest study uses a high pTau217 threshold to define its preclinical AD population, and so excludes people with intermediate levels of the protein and emerging pathology. “If you lower the threshold, the prevalence suddenly increases,” says Villain. The value of education The study also found that people with lower education levels have higher pTau217 levels.
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Nature's News & Views roundup of 2025
Benjamin Thompson, Andrew Mitchinson, Holly Smith
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Point of no returns: researchers are crossing a threshold in the fight for funding
Gerald Schweiger
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The Hungarian-born physicist Leo Szilard was the inspiration behind the idea of the Szilard point, a term used in cost–benefit analyses of grant proposals.Credit: Bettmann/Getty Competition is a constant fixture of academic life. We compete for positions, promotions, publications and presentations. And we also compete for money, a necessary requirement if we are to continue taking part in the academic endeavour. I spent the early years of my PhD at an Austrian non-academic research institute, where competing for grants was the only way that my colleagues and I could secure funding for our research. Everything else we did, from publishing papers to presenting at conferences, felt designed, ultimately, to help secure the next grant. The system seemed back to front: surely it should be about the science first? Five important financial moves for PhD students In science, there are many more people with ideas than there are public resources to support those ideas, which raises an unavoidable question about how to allocate scarce resources. Determining the best way to do so is extremely difficult. In an egalitarian approach, everyone would receive an equal share, even if that was only a fraction of what their projects would need. An alternative would be to use strict merit criteria, or to allow institutions to decide how they want to distribute resources. Yet the approach that has become most widespread is competition, which is presented as efficient, fair and reliable. Million-dollar questions My main research focuses on using computational tools to analyse intelligent systems, but I have found myself increasingly questioning how the ways in which we fund science shape its outcomes1. Which funding schemes encourage researchers to pursue high-risk research? How do different funding schemes affect scientists themselves, and what ethical issues arise from them? I suspect that because competition had been a constant companion on my path to becoming a professor at the Vienna University of Technology (perhaps even paving the way), I developed a particular interest in analysing its implications. These questions are core topics in metascience, which takes a bird’s-eye view of how research is done and aims to improve its quality, integrity and efficiency. Like many of my colleagues, I work on these topics alongside my main research. Link Introducing the j-metric: a true measure of what matters in academia A concept known as the Szilard point helps to contextualize the issues arising from excessive competition for grants. Named after the Hungarian-born physicist Leo Szilard, who wrote a short story satirizing the bureaucratic nature of scientific funding, this metric describes the threshold at which the total cost of competing for a grant equals (or surpasses) the value of the available funding. These costs are incurred by scientists in writing proposals, by their peers in reviewing them and by the administrative systems that run the process. The question is, which costs more: the research being funded, or the application process itself? GenAI for Africa, a funding call from the European Union’s Horizon Europe programme, probably crosses that threshold. The initiative aims to use generative artificial intelligence to address the societal challenges that many African countries are facing. With a total budget of €5 million (US$5.8 million), the call, which closed in October, invited proposals across four vast domains — agriculture, health care, urban planning and education. Out of 215 submissions, only two projects are expected to be funded, giving a success rate of under 1%. To approximate the overall costs associated with the application process, I used two scenarios. See ‘GenAI for Africa: estimated grant-application costs’. Scenario A In 2023, group of researchers at the University of LĂŒbeck in Germany developed a simulation tool for estimating the costs of grant funding. To arrive at cost estimates for GenAI for Africa applications, I fed this simulation with data from the Interim Evaluation of the Horizon Europe Framework Programme for Research and Innovation (2021–2024). The key inputs are: Time investment. According to the report, “the median consortium coordinator spends 
 36 to 45 person-days per proposal. The effort for contributing consortium partners is typically lower, spending 16 to 25 person-days.” Consortium size. The average consortium size for Horizon projects is likely to be between 12 and 16 partners, according to statistics published by the European Commission. Hourly payment rate of applicants. Hourly rates vary considerably depending on country, sector (industry versus academia), seniority and applicable overheads. To reflect this diversity, I drew on several reference sources from across Europe. To account for differences, I assumed the average cost of an hour’s work to be between €20 and €60. The variation in input values enabled me to produce two cost estimates for GenAI for Africa grant applications: a lower estimate (Scenario A1) and a higher estimate (Scenario A2). The tool automatically accounts for decision-making and administrative costs. Scenario B
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Restoring youth to old immune cells: mRNA therapy turns back the clock
Heidi Ledford
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As people age, immune cells called T cells tend to decline in both quantity and quality. Credit: National Institutes of Health, NIAID/SPL A twice-weekly cocktail of three messenger RNAs can rejuvenate the weary immune systems of aged mice and boost responses to vaccination and cancer treatments, a study has found1. The treatment provides a needed boost to immune cells called T cells, which coordinate immune responses and kill infected cells. As people age, their ability to produce T cells wanes, and the ones they have become less effective. T-cell ageing helps to explain why vaccines are sometimes less effective in older people than in young adults, and why cancer treatments that unleash the immune system against tumours don’t work as well in older adults, says María Mittelbrunn, an immunologist at the Spanish National Research Council in Madrid. Flagging T-cell immunity is also linked to the chronic inflammation associated with many age-related diseases, including some forms of cardiovascular disease. How to make an old immune system young again “T cells, in particular, are one of the cell types that change the most during ageing,” says Mittelbrunn, who was not involved in the study. “To rejuvenate them could have immense consequences.” The work was reported in Nature on 17 December and earlier this month at the American Society of Hematology annual meeting in Orlando, Florida. Targeting T cells T cells are produced in the bone marrow and then travel to a tiny gland called the thymus to mature. In the thymus, they learn to recognize and respond to pathogens such as bacteria or viruses. They also learn not to attack the body’s own healthy cells. But the thymus degrades with age: it begins to shrink and is gradually replaced by fatty tissue. Attempts to reverse this using hormone treatments and other drugs have not worked, says Mirco Friedrich, a haematologist and oncologist at the German Cancer Research Center in Heidelberg, and first author of the study. So, Friedrich and his colleagues decided to take a different approach: rather than treating the thymus directly, they targeted T cells by delivering an experimental therapy to the liver. “Most T cells are in the blood,” Friedrich says. “And the liver receives the body’s whole blood volume.” How quickly are you ageing? What molecular ‘clocks’ can tell you about your health The team began by characterizing the effects of ageing on T cells in mice, cataloguing differences in gene activity and molecular signalling pathways from shortly after birth until the animals were old and frail, at about 20 months of age.
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Trump team plans to break up ‘global mothership’ of climate science
Alexandra Witze
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The National Center for Atmospheric Research in Boulder, Colorado, has been targeted for breakup by the Trump administration.Credit: John Greim/LightRocket/Getty New Orleans, Louisiana The administration of US President Donald Trump intends to dismantle the National Center for Atmospheric Research (NCAR), a world-leading Earth-science centre in Boulder, Colorado. The centre’s modelling and Earth observations underpin a wide range of US and global research, especially on climate. “This facility is one of the largest sources of climate alarmism in the country,” wrote Russell Vought, Trump’s budget director, announcing the planned closure in a post yesterday on the social-media platform X. In a statement, the White House called NCAR “the premier research stronghold for left-wing climate lunacy”. The plan was first reported by USA Today. The White House said that the National Science Foundation (NSF), which provides funding for the centre, “will be breaking up NCAR to eliminate Green New Scam research activities. Any vital functions, such as weather modeling and supercomputing, will be moved under the purview of another entity or location.” On Wednesday, the University Corporation for Atmospheric Research (UCAR) — the non-profit consortium of more than 130 colleges and universities that runs NCAR — received a letter of intent from the NSF regarding the planned break-up of NCAR, consortium president Antonio Busalacchi told Nature. The letter requested information regarding divesting, transferring or restructuring the various components of NCAR. It mentioned NCAR’s research aircraft fleet and its supercomputing center in Cheyenne, Wyoming, as components that might be relocated. “Morale is terrible,” Busalacchi says. US environmental agency halts funding for its main science division Any such action will be challenged by members of Congress. “I for one am not going to let this take place on my watch,” Joe Neguse, a Democrat who represents Boulder in the US House of Representatives, said Wednesday in a virtual address to the American Geophysical Union meeting in New Orleans, Louisiana. Congress sets the federal budget and can direct the US government to fund NCAR. The most recent agreement between the NSF and UCAR, which was signed in 2023, provides US$938 million to run NCAR for five years. Cancelling that award would eliminate the majority of NCAR’s annual budget. The rest of the budget comes from an array of federal and non-federal sources. Central resource News of the intended closure rippled quickly through the Earth-science community, with many starting a #SaveNCAR discussion across social-media platforms. “Dismantling NCAR is like taking a sledgehammer to the keystone holding up our scientific understanding of the planet,” wrote Katharine Hayhoe, a climate scientist at Texas Tech University in Lubbock, on social media, adding that the laboratory is the “global mothership” of atmospheric science. “To me personally, it’s just another unbelievably reckless blow to American science”, says Dawn Wright, an oceanographer and geographer at Esri, a geographic-information-system company in Redlands, California. “If the NSF does follow through with these plans to break up NCAR, that’s just going to decimate a huge chunk of the US climate research that we all depend on.” The NSF established NCAR in 1960 to support US atmospheric-science research that requires computing or other resources beyond the means of any single institution. “If you cancel this, you will devastate atmospheric science,” says a researcher who formerly worked at the NSF and requested anonymity because of the sensitivity of the situation. “That’s different from other sciences that are more distributed.” Trump gutted two landmark environmental reports — can researchers save them? Work at NCAR played a key part in the rise of modern weather and climate forecasting. For instance, the lab pioneered the modern dropwindsonde, a weather instrument that can be released from an aircraft to measure conditions as it plummets through a storm. The technology reshaped the scientific understanding of hurricanes, says James Franklin, an atmospheric scientist and former branch chief of the hurricane specialist unit at the US National Hurricane Center in Miami, Florida.
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Virology’s most wanted: the influenza virus
Bianca Nogrady
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A universal flu vaccine has proved challenging — could it finally be possible?
Neil Savage
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Flu’s link to cardiovascular disease shows why vaccination is essential
Ashish Jha
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Take the News & Views end-of-year quiz: vampire fungus, migratory moths and a 160-year-old mystery
Mary Abraham
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Question 1: Which animals are affected by a ‘vampire fungus’?
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Dogma-defying signalling through G proteins could lead to better pain relief
Andrew B. Tobin
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After decades of meticulous research initiated by the Nobel-prizewinning discovery of G proteins1, you might think that scientists know all there is to know about this crucial family of signalling proteins. Not so. In a paper in Nature by Stahl et al.2, and in a companion paper in Nature Communications by Bohn and Stahl3, researchers describe a twist on G-protein signalling that might hold the key to the rational design of opioid drugs with better pain-relieving capabilities and fewer unwanted side effects than those that are currently available.
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Beauty is in the eye of the beholder
Nathalie Béchon
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“Another one, Boss,” Spooky haphazardly signed with his tentacles. “Mate, that’s your fifth shot. You sure you’re up for it?” The bartender spoke in a low voice, locking eyes with two of Spooky’s. Such a typical human habit — this compulsive need to make eye contact. It would have been far more practical to focus on the tentacles he used to communicate rather than struggling to pick which eye to look at. “Alright, alright, no need for the whole colour show — you really don’t look good in black. A fifth shot it is!” The bartender backpedalled quickly as Spooky’s displeasure became obvious. Quadrinocularis were usually a quiet, docile species, more accustomed to basking in the sun for hours than arguing. Spooky, however, had cultivated a reputation for being irascible. When he got annoyed enough to change colour, most knew to keep their distance. Soon, a small glass of clear liquid was placed before him. The bartender struck a match, and blue flames licked the surface. Spooky flared his pores, greedily absorbing the rising fumes. His entire body shivered in pleasure. Immersed in the heady haze of Smokey Blast, he could almost believe he was back in his reef — rooted, at peace, at home. Life had been simple then. Days spent weaving colour-shows with his brethren, not for profit or spectacle but simply for the joy of creating something beautiful. Occasionally, a predator would stir things up, but the Quadrinocularis’ eyes were excellent at spotting danger. More importantly, life had been static. It was so hard to remember what the reef had been like, now that he had been gone for so long. Only after a few Smokey Blasts could he recall the feeling of the warm currents flowing around him, the hum of his brethren blending into a harmony that resonated deep in his bones. His reef had been small — 20, maybe 30, Quadrinocularis — but their synchronization had been unmatched. Even in the dead of night, there was always a soft pulse of colour, a quiet song of belonging. Then the humans came — driven by greed, curiosity, and their ceaseless need for movement and expansion — and everything fell apart. His homeworld, once serene, was now forever tainted by activity. His reef had lasted longer than most. It wasn’t one of the great northern reefs, where thousands of Quadrinocularis moved as one, their collective shimmer making the sea itself vibrate with colour. There, the ocean was alive with a never-ending symphony. But humans needed space for their buildings, their entertainment, their noise. Like many of his friends, Spooky had left to chase the Universe’s vaunted beauty — only to learn that beauty was a relative concept in the endless expanse of space. Read more science fiction from Nature Futures “Sa’amm pretty, right? Saw this shade — blue, green, pink? And these side eyes? Mmm, top-notch for profile pics! Who cares if I’m lil’? 190 cm’s a dumb human thing. Like, why’s that the standard for models? And last week — last week, you know what they tol’ me? They said I needed a better skin care rou’ine! Smooth skin this, smooth skin that! Some of us like bein’ a liiittle slimy! Discrimination, man, it’s all discrimination!” Spooky ranted. The bartender was fluent in Quadrinocularis tentacle language, but even he struggled to parse the avalanche of signs the wobbly appendages were throwing at him all at once. “Yes, mate, it’s all discrimination,” the bartender nodded sagely. “You’ll get another chance. I’m sure there’s a brand out there looking for a pretty little thing like you.” “All I jus’ wanted was to stay in one place ’n’ look all pretty, ya know? Ain’t that what life’s ’bout? I figured humans were all nuts, runnin’ ’round, never just sittin’ down to soak up the sun for a year or two, ya feel me? Then they come up with this fancy model gig, ’nd I’m like, ‘Hey, that’s perfect for a Quadrinocularis like me!’ Thought I could build my own lil’ reef that way, ya know?” His agitation reached a peak, even his rear tentacles were shaking wildly, turning his signs into an incomprehensible blur. His head began to vibrate, producing a resonant buzz. The bartender sighed, humming noncommittally as he focused on mixing drinks for another customer. When Spooky got like this — his words blurring into song — there was no point in responding anymore.
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Daily briefing: Explore 2025 with Leif Penguinson
Flora Graham, Jacob Smith
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Are we living in a parallel universe? The strange physics of Stranger Things
Jenna Ahart
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In Stranger Things, the supernatural villain Vecna rules a nightmarish parallel world called the Upside Down. Credit: Netflix/Everett/Shutterstock Throughout its five seasons, the Netflix show Stranger Things follows a ragtag group of teenagers and their parents as monsters from another universe — unleashed by the secret work of a government laboratory — wreak havoc on a quaint, fictional town in Indiana. Don’t worry, Demogorgons, Shadow Monsters and psychokinetically gifted 12-year-olds are strictly fictional creations. But the ‘parallel universe’ concept at the core of the show — which is set to conclude its nearly decade-long run at the end of this year — comes from a real scientific theory. And it’s been hotly debated by physicists over the past 75 or so years. ‘Many worlds’ interpretation Although the series is as much in the realm of fantasy as science fiction, Stranger Things nods to many concepts of basic physics. Principles of electromagnetism explain haywire compasses, as well as magnets that spontaneously fall off a refrigerator. And in the third season, the characters save the world by using Planck’s constant during their quest to close a gate to the other universe, called the Upside Down (although the show uses the 2014 value for Planck’s constant, which wouldn’t have been standard in the 1980s setting). Physicists disagree wildly on what quantum mechanics says about reality, Nature survey shows Perhaps the most prominent physics phenomenon mentioned in the programme, however, is the many-worlds interpretation of quantum mechanics. After deducing that their friend might be stuck in the Upside Down, three pre-teen-boy protagonists ask their science teacher how they could travel there. He responds, “You guys have been thinking about Hugh Everett’s many-worlds interpretation, haven’t you?” In the 1950s, the US physicist Hugh Everett really did propose such an explanation for modern physics, and his theory has been collecting devotees ever since. Everett’s work makes sense of a concept that has long baffled quantum physicists: the measurement problem. The question is how a quantum system can seem to be in two states at once — an electron that is simultaneously in two different locations, for example — until the moment the system is observed or measured, when all at once it’s in only one of those states. The most popular explanation for this conundrum, called the Copenhagen interpretation, says that the unobserved electron exists in a hazy quantum state of both options, described only by probabilities, until suddenly, on measurement, it ends up in one. Everett poses an almost fantastical alternative: the electron really exists in both states at once, and after the measurement, an observer sees only one state because the universe branches in two, with each outcome existing in a different world. The countless quantum states of all the world’s particles create an infinite number of universes: hence, many worlds. Controversial theory For many physicists, this idea is a bit far-fetched, particularly because if these many worlds can’t interact, then there’s no way to prove or falsify the theory, says Jorge Pullin, a theoretical physicist at Louisiana State University in Baton Rouge. But for others — including Sean Carroll, a theoretical physicist at Johns Hopkins University in Baltimore, Maryland, who has worked as a science adviser for science-fiction films — the many-worlds interpretation is the most elegant explanation out there. “There are a lot of people who think this is the simplest version of quantum mechanics, and it fits all the data,” he says. Of the many explanations of quantum theory, many worlds is currently the third most popular among quantum physicists, a Nature survey found earlier this year. The sci-fi films that physicists love to watch — from Interstellar to Spider-Man
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Systematic maps reveal how human chromosomes are organized
Elzo de Wit
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When you think of a chromosome, you might imagine an X-shaped structure. But chromosomes take this shape only during cell division; the rest of the time, they adopt a structure that looks amorphous when viewed under a standard microscope. At the molecular level, however, chromosomes are folded in a highly non-random manner, enabling the proper execution of crucial processes such as gene expression, DNA replication and DNA repair. In their flagship paper in Nature1, members of the 4D Nucleome Consortium report the outcome of the first phase of a project that aims to systematically catalogue the 3D organization of human chromosomes in the nucleus and how this changes over time.
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The Nature Podcast festive spectacular 2025
Benjamin Thompson, Nick Petrić Howe
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The quest to hatch a bird-flu vaccine
Charles Schmidt
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I’ve earned my PhD — what now?
Miles Lizak
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Illustration: David Parkins The problem Dear Nature, In December 2024, I finished my PhD in biomedical chemistry in Italy, and I now find myself in that all-too-familiar early-career crisis, struggling to work out what to do next. Research is important to me as a way to contribute meaningfully to a better, healthier world. But I have other life goals, such as becoming financially stable and starting a family, that seem incompatible with the reality of academic life. The cost of living is rising everywhere, and early-career research jobs come with low pay and short contracts. Trying to transition out of academia brings its own frustrations. After years of dedication, I’m treated by those hiring in industry as if I have no real work experience. It feels like starting from zero again. Is this early-career crisis an inevitable part of life after a PhD? How do I navigate a career when my goals and values conflict? Does my passion for research have to be all-consuming? Do I have to choose between research and a reasonable work–life balance? — A melancholy chemist The advice You’re not alone. These are big questions, echoed by newly minted PhD graduates around the world. This is a notoriously challenging time in the career of any young scientist, and it doesn’t mean you’re failing if you’re struggling. Nature’s careers team sought advice from three researchers on how to resolve your problem. Peter Hanenberg, vice-rector for research and innovation at the Catholic University of Portugal in Lisbon, says: “The first step is to recognize that this crisis is something which comes with what it is to be a researcher. An academic career is, to a certain point, a matter of passion, which means it might not be just a job. But the balance should be healthy.” When she completed her neuroscience PhD at Pompeu Fabra University in Barcelona, Spain, last year, Maria del Mar Cajiao Manrique knew that she didn’t want to continue in academia, but she didn’t have a clear idea of the alternatives. “From the time we start university,” she says, “we are shown there’s only one path: bachelor, master, PhD, postdoc, and then more postdocs until you become a principal investigator. It becomes internalized. If someone doesn’t feel like they fit that one path, that’s when they start having this existential crisis: What is it that I’m good at? Have I wasted the past four years on this PhD?” Cajiao Manrique took a three-month contract as a visiting researcher at the Icahn School of Medicine in New York City, then found a position as a medical writer in August this year. She says that going to talks at other research institutions and connecting with PhD holders who have been in similar situations has helped her to broaden her perspective and discover fresh possibilities. An ‘agony aunt’ for working scientists Lynn McAlpine, whose higher-education research at the University of Oxford, UK, focuses on PhD and post-PhD career trajectories, points out that research career paths are not as straightforward as they once were. “Now we see a shift to what we’re calling self-authored careers,” she says, “where people have to take more responsibility for figuring out what they want, what kinds of jobs there are, and find ways to integrate their life–career goals.” McAlpine has investigated how researchers navigate their careers and personal lives after finishing their doctorates. She observed that personal life aims, such as the desire to live close to a partner, have children and achieve financial security, tend to have greater influence in shaping career paths in the long term than do professional aims — such as reaching for a prestigious job title or a dream research project. “There are myriad factors coming into play in the life journey of early-career researchers,” says McAlpine. Your priorities and your opportunities will be affected by variables such as location, age, international mobility and personal values. Sometimes, she says, people seek academic careers, but realize that what they really love is the academic environment. “So maybe they find a job in academia — not as a professor, but working in a museum or university archives, or as a communications officer in a research centre.” One PhD holder, interviewed as part of McAlpine’s research, wanted to relocate with her partner, who was also an academic, but she knew that it would be difficult for both of them to get posts in the same place. “When she got a postdoc in another country, they both moved there, and he took a professional position working in the university museums as a curator. There, he could apply his academic knowledge — until they moved again.” Perseverance McAlpine points to perseverance as a crucial skill from a PhD programme that can be applied at the job-seeking stage. Getting a job is itself a job, she says. In her observations, whether they were looking for an industry job or an academic grant, “the people who were most successful just kept applying. They weren’t put off by not getting an answer or getting a no.” In other words, “it’s a race against your own frustration”, says Cajiao Manrique. After her PhD, she spent months applying for jobs. “I was sitting at my desk nine to five. I sent over 1,000 job applications.” She estimates that she received a response for only about one in every 50 that she sent. Then, Cajiao Manrique went on LinkedIn and started finding communities of PhD graduates who were dealing with the same issues. Through these connections, she learned that her CV was probably being discarded by AI tools. After more research and more conversations, she rewrote her CV to make it ‘industry-ready’, focusing on results rather than technicalities. For example, she changed “performed in vivo experiments to assess A using technique B” to “planned, managed and performed more than X studies, leading a team of Y people, which resulted in the publication of article Z”.

Nature Human Behaviour

GPT-4o mini: Non-social science research article
Large-scale mega-analysis indicates that serial dependence deteriorates perceptual decision-making
Ayberk Ozkirli, Andrey Chetverikov, David Pascucci
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For over a century, research has shown that human perceptual decisions are systematically influenced by prior perceptual experiences, a phenomenon known as serial dependence. It has recently been suggested that serial dependence can improve perceptual decision-making by mitigating uncertainty and reducing variability in perceptual estimates—leading to a superiority effect. However, this claim remains largely untested. Here we present a large-scale analysis, compiling the most extensive dataset of serial dependence studies from the past decade. Contrary to the proposed superiority effect, our findings indicate that serial dependence deteriorates rather than improves perceptual decision-making. These results challenge prevailing models and emphasize the need to rethink serial dependence and its role in human perception, cognition and behaviour.
GPT-4o mini: Non-social science research article
Shared sensitivity to data distribution during learning in humans and transformer networks
Jacques Pesnot Lerousseau, Christopher Summerfield
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Do humans learn like transformers? We trained both humans ( n = 530) and transformer networks on a rule learning task where they had to respond to a query in a sequence. At test, we measured ‘in-context’ learning (generalize the rule to novel queries) and ‘in-weights’ learning (recall past experiences from memory). Manipulating the diversity and redundancy of examples in the training distribution, we found that humans and transformer networks respond in very similar ways. In both types of learner, redundancy and diversity trade off in driving in-weights and in-context learning, respectively, whereas a composite distribution with a balanced mix of redundancy and diversity allows the two strategies to be used in tandem. However, we also found that while humans benefit from dynamic training schedules that emphasize diverse examples early, transformers do not. So, while the same data-distributional properties promote learning in humans and transformer networks, only people benefit from curricula.
A large-scale comparison of divergent creativity in humans and large language models
Dawei Wang, Difang Huang, Haipeng Shen, Brian Uzzi
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Human–machine partnerships are increasingly used to address grand societal challenges, yet knowledge of the comparative strengths of humans and machines to innovate is nascent. Here we compare the ability of humans (N = 9,198) and large language models (LLMs, N = 215,542 observations) to generate novel ideas in an established creativity task. We present three key results. First, human creativity on average is slightly higher than that of LLMs. Second, creativity differences are pronounced at the extremes of the distribution, with humans exhibiting greater variability and higher levels of creativity in the right-hand tail of the distribution. Third, attempts to increase the creativity of LLMs through instructing LLMs to take on genius personas or different demographic roles lifted performance up to a threshold beyond which the output became opposite real-life patterns, whereas strategic prompt-engineering efforts yielded mixed to negative results. We discuss the implications of our findings for human–machine collaboration and problem solving.
Higher-order interactions shape collective human behaviour
Federico Battiston, Valerio Capraro, Fariba Karimi, Sune Lehmann, Andrea Bamberg Migliano, Onkar Sadekar, Angel SĂĄnchez, MatjaĆŸ Perc
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Traditional social network models focus on pairwise interactions, overlooking the complexity of group-level dynamics that shape collective human behaviour. Here we outline how the framework of higher-order social networks—using mathematical representations beyond simple graphs—can more accurately represent interactions involving multiple individuals. Drawing from empirical data including scientific collaborations and contact networks, we demonstrate how higher-order structures reveal mechanisms of group formation, social contagion, cooperation and moral behaviour that are invisible in dyadic models. By moving beyond dyads, this approach offers a transformative lens for understanding the relational architecture of human societies, opening new directions for behavioural experiments, cultural dynamics, team science and group behaviour as well as new cross-disciplinary research.
Indigenization and inclusion in Chinese academia
Jianan Huang, Cong Cao, Hong Liu
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China’s national academies have long served as barometers of academic development and scientific prestige. We use publicly available information to develop a dataset comprising 3,534 academy member profiles spanning 1905 to 2023. Using this dataset, we examine the evolving composition of China’s academic elite. Here we show that despite increasing globalization, the proportion of foreign-educated academy members has declined, while scholars from underrepresented regions—Western China and developing countries (or the Global South)—have benefited from preferential inclusive policies. Some elite-level returnee academics experience research underperformance upon returning. These trends reflect a broader shift towards academic indigenization and have wider implications for meritocracy, mobility and the sustainability of China’s talent strategies. This study examines complex reasons behind the above developments.
Homophobia, economic precarity and the well-being of sexual and gender diverse people in a 153-country survey
Erik Lamontagne, Vincent Leroy, Sean Howell, Sylvie Boyer, Bruno Ventelou
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Here we explore the well-being of sexual and gender diverse (LGBTQ+) people using three socioecological dimensions of homophobia, family, community and national and their socioeconomic status via a convenience sample of 82,324 participants. Participants from the Middle East and North Africa reported the lowest subjective well-being (mean 4.78, s.d. of 2.70), followed by Eastern Europe and Central Asia (mean 5.22, s.d. of 2.13). The Structural Homophobic Climate Index (ÎČ = −1.68, 95% confidence interval (CI) −2.38 to −0.99) and family-level homophobia (ÎČ = −0.84, 95% CI −0.87 to −0.81) were negatively related to LGBTQ+ well-being. Economic precarity significantly interacted with the negative association between homophobia and participants’ well-being. The weight of a country’s homophobic climate on well-being was nearly halved for economically secure participants compared with those economically deprived. Participants unaware of their human immunodeficiency virus status reported the lowest well-being (ÎČ = −0.20, 95% CI −0.23 to −0.16) controlling for homophobia. Public health measures should address homophobic stigma and discrimination, focusing on the lowest socioeconomic strata.

Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
DNA methylation shapes transcription factor binding beyond canonical CpG contexts
Irina Miodownik, Ruben Solozabal, Michael P. O’Hagan, Shira Albeck, Yoav Peleg, Martin Takac, Ariel Afek
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Cytosine methylation is a key epigenetic modification that regulates transcription factor (TF) binding and gene expression. While most current understanding of methylation-sensitive TF binding derives from studies focused exclusively on fully methylated CpG sites, alternative forms—such as non-CpG and hemimethylation—are increasingly recognized as widespread and functionally important, particularly in embryonic stem cells and neurons. However, the direct impact of these alternative methylation contexts on TF–DNA interactions remains poorly defined, largely because current binding assays introduce methylation enzymatically, which precludes strand-specific and position-resolved measurements. Here, we systematically profile the methylation sensitivity of 18 human TFs spanning 11 structural families using chemically synthesized DNA libraries containing position-specific 5-methylcytosines (5mC) in CpG, non-CpG, and hemimethylated contexts, measured via high-throughput protein-binding microarrays. Our results reveal extensive TF sensitivity to methylation state, position, and strand orientation, including strong binding of several TFs to non-CpG and hemimethylated sites. The presence of 5mC can dramatically alter TF–DNA interactions: transforming low-affinity sites into high-affinity ones by enabling new contacts or silencing otherwise favorable motifs through steric hindrance. Genomic analyses further show that the methylation-sensitive sequences identified in vitro are represented within enhancers and regulatory elements, exhibiting distinct methylation patterns across cell types. Together, our findings uncover a previously hidden layer of methylation-dependent TF–DNA recognition, broadening the understanding of epigenetics in transcriptional regulation.
GPT-4o mini: Non-social science research article
A PSAT1 buff of YBX1 transcriptionally sustains HLA-E-mediated evasion of NK immunity
Yangyi Zhang, He Ren, Chaobing Ma, Changhong Shi, Ruigang Yang, Chenxi Wang, Pengfei Feng, Bo Zhang, Chenyu Liu, Zubiao Niu, Yalan Yang, You Zheng, Zhuoran Sun, Ying Zhang, Shinan Zhang, Gerry Melino, Hongyan Huang, Qiang Sun
Full text
Despite great success in certain cancers, immunotherapy made little progress in treating immune cold tumors, largely attributed to an immune-suppressive tumor microenvironment with elusive mechanisms. Here, we report in prostate cancer cells a positive feedback loop driven by phosphoserine aminotransferase 1 (PSAT1) that could be targeted to render effective cytotherapy by natural killer (NK) cells. In the loop, PSAT1 increases Y-box binding protein 1 (YBX1) phosphorylation by microtubule affinity-regulating kinase 2, promoting its nuclear translocation to upregulate PSAT1 transcription. Meanwhile, YBX1 also promotes human leukocyte antigens E (HLA-E) transcription to inactivate NK cells. Consequently, the PSAT1 loop serves as a buff sustaining YBX1/HLA-E expression, suppressing NK killing of prostate cancer cells. Targeting loop molecules, such as PAST1, effectively potentiates tumor suppression by NK cells both in-vitro and in-vivo. Thus, our study uncovered a heretofore unrecognized nonautonomous mechanism for PSAT1, as well as a molecular buff for YBX1, to drive tumor growth by evading NK immunity, providing a promising target for NK cytotherapy of immune cold tumors.
GPT-4o mini: Non-social science research article
Goldilocks zone of lignin: Two extremes of valve lignification lead to silique indehiscence in Brassicaceae
Justin B. Nichol, Logan A. Skori, Muhammad Jamshed, Neil Hickerson, Mendel Perkins, Marcus A. Samuel
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The spring-loaded spontaneous seed dispersal mechanism known as dehiscence, has been a critical plant feature for the successful colonization of land by angiosperms. Although advantageous for seed dispersal, spontaneous dehiscence is largely an unfavorable agronomic trait which historically was selected against during selective breeding of crops to increase seed retention. In canola ( Brassica napus ), a major global oil seed crop, spontaneous or harsh weather-induced fruit shattering at maturity could lead to yield losses from 3 to 50%. Here, we show an extraembryonic role for the ABA-responsive transcription factor, ABSCISIC ACID INSENSITIVE-3 (ABI3) in controlling seed dispersal through mediating lignification of the endocarp b (en b ) layer and the lignified layer (LL) of the valves. The resistance created by these lignified layers is critical for valve opening at maturity as the tensile forces generated during silique drying converge on these fortified cell layers to trigger shatter. We further show that ABI3 functions independent of the patterning genes and functions through transcriptional regulation of NAC-domain transcription factors, NST1 and NST3 , to mediate lignin biosynthesis. Our results show that both excessive and complete absence of lignification could prevent the tensile drying forces from breaking open the pod, leading to fruit indehiscence. As a proof-of-concept, we show that BnABI3 overexpression in canola results in highly lignified, robust siliques that are shatter tolerant. Besides uncovering an extraembryonic role for ABI3, this study has identified spatial distribution and abundance of lignin in the silique valve tissue as the key determinants for silique dehiscence.
GPT-4o mini: Non-social science research article
Anellovirus protein encoded by ORF2/3 functions as the viral replication initiation protein
Nicole Boisvert, Stephanie Thurmond, Carmen Elenberger, Patricio Jeraldo, Cato Prince, Nolan Sutherland, José Melo, Ken Tsheowang, Cameron Dodier, Maciej Nogalski, Dinesh Verma, Geoffrey Parsons, Joseph Cabral
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Anelloviridae is a family of single-stranded DNA viruses that are thought to be nonpathogenic and commensal. Despite their ubiquitous presence in human populations, little is known about the anellovirus mechanism of replication in host cells. We identified the protein coded by ORF2/3 as necessary and sufficient to initiate replication from the minimal origin of replication for viruses of both the Beta- and Alphatorquevirus genera. Supporting this observation, we identified components of the polymerase alpha and BTR (Bloom’s syndrome helicase (BLM), topoisomerase IIIα, RMI1, and RMI2) complexes as interacting with the viral replication initiation protein (Rip) during DNA replication, suggesting a recombination-dependent mechanism of replication that uses host cell machinery to mediate dissolution of replication intermediates. Furthermore, we mapped a 92-bp minimal origin of replication sequence for the Betatorquevirus genus composed of an adenine and thymine (AT)-rich stretch and a portion of the guanine and cytosine (GC)-rich region. Altogether, this study provides insight into the mechanism by which anelloviruses manipulate host cell machinery to facilitate viral genome replication and represents a significant step forward in understanding the complex processes underlying anellovirus replication and persistent infection of these important commensal viruses.
GPT-4o mini: Non-social science research article
Energetic and structural control of polyspecificity in a multidrug transporter
Silas T. Miller, Katherine A. Henzler-Wildman, Srivatsan Raman
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Multidrug efflux pumps are dynamic molecular machines that drive antibiotic resistance by harnessing ion gradients to export chemically diverse substrates. Despite their clinical importance, the molecular principles underlying multidrug promiscuity and energy efficiency remain poorly understood. Using multiparametric deep mutational scanning across eight substrates and two energy conditions, we deconvolute the contributions of substrate recognition, energetic coupling, and protein stability, providing an integrated, high-resolution view of multidrug transport. We find that substrate specificity arises from a distributed network of residues extending beyond the binding site, with mutations that reshape binding, coupling, conformational flexibility, and membrane interactions. Further, we apply a pH-based selection scheme to measure the effect of mutation on pH-dependent transport efficiency. By integrating these data, we reveal a fundamental relationship between efficiency and promiscuity: Highly efficient variants exhibit broad substrate profiles, while inefficient variants are narrower. These findings establish a direct link between energy coupling and polyspecificity, uncovering the biochemical logic underlying multidrug transport.
GPT-4o mini: Non-social science research article
Multicolor photoreactions of the red light–activated channelrhodopsin Chrimson
Johannes Vierock, Joel C. D. Kaufmann, Lukas Faiß, Linda Tillert, Benjamin S. Krause, Paul Fischer, Thi Bich Thao Nguyen, Dietmar Schmitz, Benjamin R. Rost, Franz Bartl, Peter Hegemann
Full text
Channelrhodopsins are light-gated ion channels that are used in modern neurosciences for the precise control of cellular ion fluxes by light. With a peak absorption at 585 nm, Chrimson is the most red-shifted cation-conducting ChR. It is frequently employed in multicolor experiments alongside blue light–sensitive optogenetic tools and is so far the only light-gated ion channel successfully applied in human vision restoration. However, its photoresponses to different wavelengths have not been thoroughly characterized. In this study, we identify multiple interconvertible dark states of Chrimson with distinct absorption and photokinetic properties. Combining electrophysiology and spectroscopy with optogenetic experiments in neurons, we unveil that this dark state heterogeneity is based on distinct protonation dynamics of the counterion complex and alternative retinal isomerization. In neurons, prolonged red illumination reduces Chrimson’s red light sensitivity, which is reflected by a blue shift of the action spectrum. Blue light pulses reverse this shift and increase the excitability in subsequent red-light flashes. This understanding of wavelength-dependent photoreactions in Chrimson will improve the design of multicolor optogenetic experiments and inform strategies for optimizing Chrimson for therapeutic applications.
GPT-4o mini: Non-social science research article
Antibiotic-induced microbiota depletion impairs the proregenerative response to a biological scaffold
Natalie Rutkowski, Brenda Yang, Elise Gray-Gaillard, Anna Ruta, Joscelyn C. MejĂ­as, Michael Patatanian, Christopher Cherry, Nazmiye Celik, Katlin B. Stivers, Shri Ramanujam, Nathan L. Price, Franck Housseau, Drew M. Pardoll, Cynthia L. Sears, Jennifer H. Elisseeff
Full text
Therapeutic biological scaffolds promote tissue repair primarily through the induction of type 2 immunity. However, systemic immunological factors, including aging, sex, and previous infections, can modulate this response. The gut microbiota is a well-established modulator of immune function across organ systems, yet its influence on type 2-mediated repair remains underexplored. Here, we establish a bidirectional relationship between the gut microbiota and biological scaffold-mediated tissue repair. Utilizing a conventionalized germ-free mouse, we demonstrate that scaffold implantation induces compositional and functional changes in the gut microbiome, particularly affecting amino acid biosynthesis. Additionally, in a model of antibiotic-induced microbiota depletion, we show that dysbiosis disrupts key immune regulators of type 2 immunity, including reductions in eosinophils, proregenerative macrophages, and interleukin-4 (IL-4)-producing CD4 + T cells. At 6 wk post–scaffold implantation, we observed a significant decrease in myocytes with centrally located nuclei alongside an upregulation in profibrotic gene expression with antibiotic treatment. These findings provide insights into the influence of the gut microbiota on type 2-mediated tissue repair.
GPT-4o mini: Non-social science research article
Emergent eukaryotic directional sensing via receptor degradation and diffusion
Andrew Goetz, Purushottam Dixit
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Directional sensing enables eukaryotic cells to detect spatial gradients of extracellular ligands, allowing them to orient and migrate within complex environments. Prevalent models explain this computation through a circuit where signaling species with distinct diffusion constants act incoherently on a downstream readout. Here, we propose a fundamentally different mechanism of directional sensing based on simple receptor-level processes. Our model integrates three ubiquitous receptor processes-lateral diffusion, basal ligand-independent activation, and active receptor degradation, THAT together synergize to generate robust directional sensing. In the absence of diffusion, active receptor degradation and basal activity implement an integral feedback that adapts active receptor levels to a ligand-independent set point while depleting receptors in relatively ligand-rich regions. Diffusion then redistributes receptors from regions of relatively low ligand exposure to regions with higher ligand exposure. This creates a spatial mismatch between activity and feedback that drives asymmetric receptor activity relative to the set point. The model predicts an optimal diffusion constant that maximizes polarization, reveals that receptors can encode relative rather than absolute ligand concentrations, and identifies the optimal basal activity that maximizes the signal-to-noise ratio in stochastic regimes. A survey of kinetic parameters across receptor families suggests that this diffusion-degradation synergy constitutes a broadly applicable, receptor-level mechanism for directional sensing.
GPT-4o mini: Non-social science research article
Fishing fleets as ecosystem sentinels
Heather Welch, Brett M. Holycross, Allison A. Cluett, Michael G. Jacox, Caren E. Braby, Matthew W. Callahan, Joshua A. Cullen, Nima Farchadi, Rachel Seary, Jordan T. Watson, Steven J. Bograd, Elliott L. Hazen
Full text
Marine apex predators are promising sentinels for detecting the ecological impacts of climate variability and change. Fishermen are increasingly recognized as marine apex predators, and there are extensive satellite-based geolocation data on fishing vessel activities. Despite this potential, the utility of fishermen as ecosystem sentinels remains unexamined. Using one million vessel positions from 600 U.S. vessels, we assess the effectiveness of fishermen as sentinels for the ecological impacts of Northeast Pacific marine heatwaves on tuna distribution and availability. Fishermen were skillful predictors of extreme northward shifts for albacore and bluefin tunas, and extreme inshore shifts for albacore. Fishermen signaled low albacore availability over a year in advance of a formal fisheries disaster declaration request. Notably, fishermen also indicated true negatives during marine heatwaves: periods of anomalous warming but stable tuna distribution and availability. This information could aid management of transboundary shifts during marine heatwaves of albacore from U.S. to Canadian waters and bluefin from Mexican to U.S. waters. Advanced warning of fisheries disasters could expedite the delivery of relief funds for struggling communities. The number of Earth-orbiting satellites is exponentially rising, generating a wealth of geospatial information on fishing vessels. This rich and growing resource can signal otherwise unobserved ecological impacts, aiding rapid management responses to climate extremes.
GPT-4o mini: Non-social science research article
Phage satellites break into the jumbo era
José R. Penadés
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GPT-4o mini: Non-social science research article
Loss of vitamin C biosynthesis protects from the pathology of a parasitic infection
Gongwen Chen, Ji Hyung Jun, Tobias Wijshake, Edward O. Kwarteng, Yunyang Li, Minwei Yuan, Joseph Rose, Shan Li, Sarah Cobb, Willow Serpa, Brayden Folger, Yafeng Li, Li Li, Weina Chen, James J. Collins, Jipeng Wang, Michalis Agathocleous
Full text
The ability to synthesize essential molecules is sometimes lost in evolution. A classic example is ascorbate (vitamin C), which is synthesized in most animals by L-gulonolactone oxidase (GULO), an enzyme lost multiple independent times in animal evolution. This event is thought to be evolutionarily neutral; however, GULO- deficient animals including humans need to obtain ascorbate from their diet and are prone to ascorbate deficiency and scurvy. We therefore hypothesized that this disadvantage of GULO loss is offset by physiological benefits. Here, we show that ascorbate deficiency benefits mice infected with schistosome parasites, which cause schistosomiasis, a debilitating parasitic disease that afflicts 250 million people. Schistosoma mansoni worms required host ascorbate to produce eggs in vivo. Consequently, ascorbate-deficient mice were protected from schistosomiasis pathologies and transmission. Intermittent ascorbate deficiency protected Gulo -deficient mice from both scurvy and schistosomiasis mortality. The effects of ascorbate on schistosome reproduction were mediated by ascorbate-dependent histone demethylation which promoted vitellocyte development in female schistosomes. We propose that vitamin deficiencies are not always detrimental but can protect animals from pathogens which need to obtain vitamins from their host.
GPT-4o mini: Non-social science research article
Sandball genesis from raindrops
Bertil Trottet, Daisuke Noto, Douglas J. Jerolmack, Hugo N. Ulloa
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In the water cycle, erosion begins with the entrainment of soil by raindrops. The discrete, discontinuous, and three-phase nature of raindrop erosion—at the boundary of fluid and granular mechanics—makes this problem particularly challenging, compared to better-studied sediment transport by river and wind currents. Past research has emphasized particle entrainment by raindrop splash at impact. Here, we report lab and field observations, that uncover a surprisingly rich and efficient postimpact phase. Raindrops impacting a dry, sloping, granular bed spontaneously form “sandballs;” drops of dense suspensions that can grow in mass to a jammed state by sediment entrainment, as they roll downhill like snowballs and magnify soil erosion. Careful control of drop conditions reveals two stable sandball morphologies: peanut-like shapes linked to hydrodynamic instabilities and toroidal forms that undergo mechanical locking from extreme sediment loading, which have potential implications for related problems in bioengineering, pharmaceuticals, and snow physics.
GPT-4o mini: Non-social science research article
A closed-loop microneedle-integrated physiological model for predictive glycemic management
Marco Fratus, Muhammad A. Alam
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Continuous biomarker monitoring and on-demand therapy are essential for chronic disease management, with diabetes being a key example. Although continuous glucose monitoring (CGM) and insulin pumps are moving toward a closed-loop system, it remains difficult to predict how device design influences system performance. Traditional optimization methods are inefficient and empirical: Data-driven algorithms lack interpretability, trial-and-error design is time-consuming, and first-principle models are difficult to integrate at the system level. To address these challenges, we introduce a physics-based framework which integrates microneedle (MN) designs for sensing and therapy with a physiological model of glycemic control. The framework builds compact relationships showing how material, chemical, and geometrical features affect key metrics such as response time, extraction flux, and insulin delivery rate. Specifically, we develop a theory for three sensing MN types (hollow, porous/swellable, and nanostructured MNs) and one therapeutic patch (electro-termo-mechanical device) to create a predictive model for glycemic regulation. By linking device design to system behavior across time and spatial scales, we examine the framework in three cases: How disease progression, MN design, and MN sensitivity affect plasma glucose levels and time-in-range metrics. This work establishes the foundation for a physics-based digital twin for diabetes management, complementing ML, experiments, and numerical models. More broadly, it streamlines patch design, minimizing glycemic events and trial-and-error in next-generation CGM technology.
GPT-4o mini: Non-social science research article
Early emergence of perceptual biases in the secondary somatosensory cortex
Luis Serrano-Fernåndez, Ranulfo Romo, Néstor Parga
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Working memory (WM) is distributed across multiple cortical areas, suggesting that behaviors relying on WM arise from interactions between these regions. In a recent study, we found that during delayed comparison tasks, the first stimulus is not represented veridically in the prefrontal cortex (PFC), but instead is encoded in a systematically warped manner–biased toward the mean of the stimulus distribution. This neural distortion, which emerges already during the stimulus presentation and persists throughout the delay period, closely mirrors a contraction bias observed in behavior. Furthermore, the behavioral responses could be explained by a Bayesian observer model, in which the observer integrates prior expectations with noisy sensory inputs. These results suggest that the geometry of PFC neural trajectories embodies Bayesian estimates that underlie biased decisions. Here, we investigate whether the secondary somatosensory cortex (S2)–a lower-level sensory area also implicated in tactile WM–exhibits a similar encoding structure. Our analyses reveal that although WM-related signals in S2 are less robust than in PFC, the neural state space in S2 shares key geometric features with that of PFC, including a similarly warped representation of stimulus values. These findings suggest that perceptual biases may originate early in the cortical processing stream and are not exclusively shaped by higher-order associative areas. More broadly, our results support a distributed organization of representational warping, in which even sensory areas contribute to the formation of bias-prone representations that guide behavior.
GPT-4o mini: Non-social science research article
Neural crest cell recruitment and reprogramming as central drivers of embryonic limb regeneration
Béryl Laplace-Builhé, Gautier Tejedor, Jholy De La Cruz, Audrey Barthelaix, Frédéric MarmigÚre, Dora SapÚde, Sarah Bahraoui, Lucie Diouloufet, Stéphanie Ventéo, JérÎme Collignon, Christian Jorgensen, Farida Djouad
Full text
Unlike regeneration-competent species, mammals lack epimorphic regeneration capacity, except for the most distal part of their digits. Here, we show that E10.5 mouse embryos can initiate regeneration of their forelimb bud (FB), but this capacity is lost by E12.5. Using comparative transcriptomics and in vivo lineage tracing approaches in the mouse embryo, we were able to identify a population of neural crest–derived cells (NCdCs) reexpressing early NC lineage molecular markers, Wnt1 and Foxd3 , specifically associated with regeneration at E10.5. Functional studies further reveal that these cells are required for FB regeneration and that the regenerative capacity lost in limb buds lacking NCdCs can be restored by exogenous transplantation of neural crest cells at E10.5. This work provides valuable information on the potential and prerequisites for regeneration in mammals.
GPT-4o mini: Non-social science research article
Platelet-engineered CAR-T cells as adjuvant therapy after cancer surgery
Yixin Wang, Edikan Ogunnaike, Huan Yang, Sichen Yuan, Rachel Hong, Allie Barrett, Emem Ebong, Bo Liu, Gianpietro Dotti, Quanyin Hu
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Surgery remains the mainstay treatment for many kinds of solid tumors, while tumor recurrence frequently occurs. Adjuvant therapy can reduce the risk of recurrence and improve the prognosis of surgery. Chimeric antigen receptor (CAR)-T cell therapy can be leveraged as an alternative adjuvant therapy to clear residual cancer cells and prevent tumor recurrence. However, systemic administration of CAR-T often results in insufficient tumor infiltration and side effects to normal organs. Given that platelets can preferentially accumulate at postsurgical wounds, we proposed that conjugating platelets to CAR-T cells may enhance the accumulation of the CAR-T cells within the surgical bed after the resection of solid tumors. In this study, we conjugated platelets to B7-H3.CAR-T cells via click chemistry. In postsurgical human pancreatic cancer mouse models, platelet-CAR-T cells showed enhanced tumor infiltration and elevated antitumor cytokine levels, resulting in superior suppression effects on tumor recurrence, compared with CAR-T cells. Additionally, platelet-CAR-T cells showed enhanced efficacy in inhibiting metastasis and prolonging the survival time of the mice in postsurgical triple-negative breast cancer (TNBC) models. Mechanistic studies revealed that platelet activation could improve the CAR-T cell activity and persistence, as evidenced by an upregulation of genes associated with T cell infiltration and a downregulation of genes related to T cell exhaustion. Finally, we further validated the biosafety profile and efficacy of platelet-CAR-T in a postsurgical patient-derived xenograft TNBC-bearing humanized mouse model. The results suggested that the CAR-T cell strengthened by platelet engineering is a promising adjuvant therapy against postsurgical tumor recurrence.
GPT-4o mini: Non-social science research article
Geography of masting creates greater synchrony in seed scarcity than in seed abundance
Jakub Szymkowiak, Jessie J. Foest, Marcin K. Dyderski, Szymon JastrzÈ©bowski, Maciej K. Barczyk, Andrew Hacket-Pain, MichaƂ Bogdziewicz
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Interannually highly variable and synchronized production of large seed crops by perennial plants, called masting, drives resource pulses and famines with cascading effects on food webs. While the spatial scale of masting synchrony is well documented, it remains unclear how synchrony differs between years of seed abundance and failure, and how such dynamics extend across species and space. These gaps are important to resolve, as they determine the magnitude and spatial extent of masting effects on food webs. Using a 36-y dataset from 431 sites spanning seven dominant tree species in temperate Europe, we provide evidence that seed failures are more spatially synchronized than mast peaks, indicating that regional coherence in seed production is structured primarily by reproductive failure. Among-species synchrony was localized. This suggests that in temperate forests, mobile seed consumers are unlikely to experience coordinated starvation–satiation cycles, in contrast to highly synchronous tropical dipterocarp systems. From an applied perspective, failure years affect seed availability over broad regions, limiting sourcing options for afforestation and restoration, and underscoring the value of spatially explicit masting forecasting. Because mast peaks and failures differ fundamentally in their food web consequences, our findings highlight the need to better understand and anticipate the ecological impacts of synchronized seed scarcity.
GPT-4o mini: Non-social science research article
Structural insights into nonpeptide antagonist inhibition of somatostatin receptor subtype 5
Yang Li, Zhongliang Xing, Wen Hu, Kai Wu, H. Eric Xu, Li-Hua Zhao
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The somatostatin receptor subtype 5 (SSTR5) is a critical pharmacological target involved in neuroendocrine signaling, metabolic regulation, and tumorigenesis. Despite its therapeutic potential, the structural mechanisms underlying SSTR5 inhibition by nonpeptide antagonists remain largely unresolved. In this study, we present high-resolution cryoelectron microscopy structures of human SSTR5 in complex with two selective small-molecule antagonists, antagonist 1 and S5A1, revealing the receptor’s inactive conformation. Both antagonists induce a unique remodeling of extracellular loop 2, which adopts a capping architecture that sterically occludes the orthosteric site, thus preventing agonist access and stabilizing receptor inactivation. Structural analyses and functional experiments elucidate how distinct molecular moieties of the antagonists differentially contribute to inhibitory efficacy, and subtype selectivity. Furthermore, we delineate rational avenues for molecular optimization to enhance therapeutic index and mitigate off-target liabilities. These findings, complementing our previous agonist-bound structures, establish a comprehensive structural foundation for developing improved nonpeptidic SSTR5 antagonists with potential therapeutic applications for type 2 diabetes and related endocrine disorders.
GPT-4o mini: Non-social science research article
Complex multiannual cycles of Mycoplasma pneumoniae : Persistence and the role of stochasticity
Bjarke Frost Nielsen, Sang Woo Park, Emily Howerton, Olivia Frost Lorentzen, Mogens H. Jensen, Bryan T. Grenfell
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The epidemiological dynamics of Mycoplasma pneumoniae is characterized by poorly understood complex multiannual cycles. The origins of these cycles have long been debated, and multiple explanations of varying complexity have been suggested. Using Bayesian methods, we fit a dynamical model to half a century of M. pneumoniae surveillance data from Denmark (1958 to 1995, 2010 to 2025) and uncover a parsimonious explanation for the persistent cycles, based on the theory of quasicycles. The period of the multiannual cycle (approx. 5 y in Denmark) is explained by susceptible replenishment due, primarily, to loss of immunity. While an excellent fit to shorter time series (a few decades), the deterministic model eventually settles into an annual cycle, unable to reproduce the persistent cycles. We find that environmental stochasticity (e.g., varying contact rates) stabilizes the multiannual cycles and so does demographic noise, at least in smaller or incompletely mixing populations. The temporary disappearance of cycles during 1979 to 1985 is explained as a consequence of stochastic mode-hopping. The circulation of M. pneumoniae was recently disrupted by COVID-19 nonpharmaceutical interventions (NPIs), providing a natural experiment on the effects of large perturbations. Consequently, the effects of NPIs are included in the model and medium-term predictions are explored. Our findings highlight the intrinsic sensitivity of M. pneumoniae dynamics to perturbations and interventions, underscoring the limitations for long-term prediction. More generally, our findings provide further evidence for the role of stochasticity as a driver of complex cycles across endemic and recurring pathogens.
GPT-4o mini: Non-social science research article
High-speed X-ray tomography for 4D imaging
Ivan Grega, William Whitney, Vikram Sudhir Deshpande
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Capturing high-rate spatiotemporal deformation of materials in three dimensions (3D) remains a significant challenge with current X-ray imaging techniques. We present a methodology that combines advances in neural rendering techniques with volume correlation methods to accurately reconstruct complex, high-rate 3D spatiotemporal structural evolutions. The fidelity and versatility of the method, which requires no pretraining, are demonstrated for a diverse set of intricate 3D-printed microarchitected solids. Using laboratory-based X-ray tomography, we capture the 3D growth of a high-rate crush band on a timescale of less than 100 ms. By broadening this idea to a stereo X-ray concept, we eliminate the need to rotate the image object, thereby extending the technique to significantly faster timescales. Our neural rendering framework opens possibilities for 3D observations of viscoelastic responses of biological materials to 3D investigations of numerous poorly understood dynamic processes, such as the runaway failure of batteries, all using laboratory X-ray systems.
GPT-4o mini: Non-social science research article
Aducanumab binding to AÎČ 1-42 fibrils alters dynamics of the N-terminal tail while preserving the fibril core
Ravi Shankar Palani, Christopher G. Williams, Dev Thacker, Robert Silvers, Fang Qian, Paul H. Weinreb, Leonard J. Mueller, Sara Linse, Robert G. Griffin
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Aducanumab, a human IgG1 antibody with plaque-clearing effects and modest clinical benefit, binds selectively to aggregated AÎČ via the N-terminal region. Yet, the molecular details of how the antibody engages AÎČ 1-42 fibrils remain unresolved. Using magic-angle spinning NMR, we show that binding of aducanumab preserves the overall architecture of the AÎČ 1-42 fibril core while inducing significant structural and dynamic perturbations in the N-terminal region. Antibody binding markedly reduces flexibility in this domain, with the appearance of side-chain resonances from residues D1, E3, and histidine (likely H6) in dipolar-based experiments. These side chains—previously observed in scalar-coupling spectra of the unbound state—indicate rigidification of residues that were dynamic. The interaction extends to S8 and Y10, indicating broader fibril engagement than the minimal epitope (residues 3 to 7) defined in fragment-based studies. Perturbations in the C-terminal segment (G37–A42) are consistent with its spatial proximity to the antibody-bound N termini of neighboring monomers. Cryo-TEM images reveal fibrils bundling in the presence of aducanumab, consistent with lateral association via antibody cross-linking, supporting a model where surface coating and steric hindrance suppress secondary nucleation. This mode of action restricts monomer access to catalytic sites on the fibril surface, resulting in partial inhibition (~threefold reduction) of secondary nucleation. The effect depends on high avidity and relatively high stoichiometry but is ultimately limited by antibody size relative to N-terminal spacing along the fibril. These findings provide atomic-level insights into aducanumab’s binding mode and supply a structural framework for understanding antibody-mediated fibril recognition and for guiding next-generation therapies targeting AÎČ aggregates in Alzheimer’s disease.
GPT-4o mini: Non-social science research article
A SynB1-conjugated antibody cocktail crosses the blood–brain barrier to produce a therapeutic effect on rabies
Zeheng Ren, Caiqian Wang, Haoran Wang, Qiong Wu, Qingxiu Hou, Xue Qi, Wenna He, Xiaoyu Zhang, Jiawu Wan, Zhen F. Fu, Ming Zhou, Ling Zhao
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Rabies, caused by the neurotropic lyssavirus rabies virus (RABV), is nearly 100% fatal after symptom onset. A fundamental challenge for rabies therapy is that the blood–brain barrier (BBB) prevents peripherally administered neutralizing antibodies from entering the central nervous system (CNS) to clear the infection. In this study, we initially generated four human–mouse chimeric antibodies with preserved neutralizing potency against RABV to increase its translational potential. To achieve brain antibody delivery, we conjugated a lead chimeric antibody (7A3-H) to different cell-penetrating peptides with potential BBB-penetrating capacity (RVG, TGN, THR, and SynB1). In vivo fluorescence imaging revealed that SynB1 conjugation significantly outperformed conjugation with the other peptides in terms of BBB penetration for brain antibody delivery. Furthermore, a triple-antibody cocktail (targeting epitopes II/III/IV of RABV-G) conjugated to SynB1 resulted in 80% survival in mice infected with lethal challenge virus standard (CVS) or dog-originated rabies virus (DRV) strains when it was administered at 5 dpi (when CNS invasion and symptoms were evident). In contrast, the unconjugated cocktail provided only 20% (CVS) or 0% (DRV) survival. Together, these data demonstrated that SynB1-mediated BBB penetration dramatically improved the therapeutic efficacy of anti-RABV antibodies, enabling post-symptom rescue of rabies. This antibody–peptide conjugation strategy provides a proof of concept for advancing rabies therapy, specifically by leveraging peptide-mediated enhancement of BBB penetration.
GPT-4o mini: Non-social science research article
Intrinsic neuronal network organization of a mammalian peripheral nervous system
Larry W. Swanson, Joel D. Hahn, Olaf Sporns
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The vertebrate nervous system is traditionally parceled topographically into central and peripheral divisions. The peripheral nervous system (PNS) in turn is commonly viewed functionally as a set of nerves and ganglia transmitting input and output signals between the central nervous system (CNS) and other bodily systems to regulate physiology and behavior. Here, we collate and analyze neuroanatomical data on putative directed and weighted axonal connections between peripheral ganglia in a mammal (rat). The resulting network reveals a sparse but broad intra-PNS neuronal architecture with over 100 connections among 52 of the 84 sensory and autonomic ganglia identified. Local network differentiation of the associated 52×52 connection matrix (connectome) was examined with cluster analysis. It identified 22 modules (subsystems or subnetworks) within a six-level nested hierarchy, including seven first-order modules and 14 end modules, spatially distributed from rostral to caudal along the CNS–body axis. Global features of the intra-PNS neuronal network based on node (ganglion) centrality measures identified two hubs (the bilateral myenteric plexus ganglia that control digestive tract functionality), no rich club, and small-world properties comparable to those reported for the rat brain. These findings suggest that the PNS is not merely a series of parallel nerves and associated ganglia but instead forms a structured and recurrently connected neuronal network. Its full extent and functional relevance remain to be elucidated using contemporary structure–function neuroscience approaches.
GPT-4o mini: Non-social science research article
Evolution of viral genomes and their clouds of sequence
Karla Kirkegaard
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GPT-4o mini: Non-social science research article
Neural synchrony links sensorimotor cortices in a network for facial motor control
Yuriria VĂĄzquez, Geena R. Ianni, Elie Rassi, Adam G. Rouse, Marc H. Schieber, Faraz Yazdani, Yifat Prut, Winrich A. Freiwald
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Primate societies rely on the production and interpretation of social signals, in particular those displayed by the face. Facial movements are controlled, according to the dominant neuropsychological schema, by two separate circuits, one originating in medial frontal cortex controlling emotional expressions, and a second one originating in lateral motor and premotor areas controlling voluntary facial movements. Despite this functional dichotomy, cortical anatomy suggests that medial and lateral areas are directly connected and may thus operate as a single network. Here, we test these contrasting hypotheses through structural and functional MRI (fMRI) guided electrical stimulation and simultaneous multichannel recordings from key facial motor areas in the macaque monkey brain. These areas include medial facial motor area M3 (located in the anterior cingulate cortex); two lateral face-related motor areas: M1 (primary motor) and PMv (ventrolateral premotor); and S1 (primary somatosensory cortex). Cortical responses evoked by intracortical stimulation revealed that medial and lateral areas can exert significant functional impact on each other. Simultaneous recordings of local field potentials in all facial motor areas further confirm that during facial expressions, medial and lateral facial motor areas significantly interact, primarily in the alpha and beta frequency ranges, whereas during voluntary chewing, coupling occurs at lower frequencies. These functional interactions varied across facial movement types. Thus, at the cortical level, the control of facial movements is not mediated through independent (medial/lateral) functional streams, but results from an interacting sensorimotor network.
GPT-4o mini: Non-social science research article
Competition between glycine and GABA A receptors for gephyrin controls their equilibrium populations at inhibitory synapses
Dorota Kostrz, Stephanie A. Maynard, Serena Camuso, Clemens Schulte, François Laurent, Jean-Baptiste Masson, Hans M. Maric, Charlie Gosse, Antoine Triller, Terence R. Strick, Christian G. Specht
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Glycine receptors (GlyR) and γ-aminobutyric acid type A receptors (GABA A R) are ligand-gated chloride channels that mediate inhibitory neurotransmission throughout the central nervous system. The receptors colocalize widely at inhibitory synapses in the spinal cord and in the brainstem due to their interaction with an overlapping binding site of the synaptic scaffold protein gephyrin, pointing to a direct competition between the different receptor types. We have put this hypothesis to the test using single-molecule approaches to measure receptor–gephyrin interactions in cells and in vitro. We explored the effects of receptor competition at inhibitory synapses in living neurons by measuring the change in the accumulation and effective stabilization energy of glycine receptors in the presence of interfering GABA receptor complexes through single-molecule tracking and diffusion analysis. Second, using molecular tweezers, we quantified the thermodynamic properties of receptor–gephyrin binding, demonstrating direct and reversible competition through the addition of interacting peptides in solution. The relatively low affinity of GABA receptor subunits for gephyrin compared to the glycine receptor raises interesting questions about the role of this competition in synaptic plasticity. We hypothesize that GABA and glycine receptor competition constitutes a molecular system designed to reconcile synapse stability and plasticity at mixed inhibitory synapses.
GPT-4o mini: Non-social science research article
Band pattern formation of erythrocytes in density gradients is due to competing aggregation and net buoyancy
Felix Maurer, Camila Romero, Nikolas Lerch, Thomas John, Lars Kaestner, Christian Wagner, Alexis Darras
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Centrifugation of biological matter in density gradient solutions is a standard method for separating cell types or components. It is also used to separate red blood cells (RBCs) by age, as they lose water and become denser over their lifespan. When the density gradient is prepared with Percoll, discrete bands of RBCs are systematically observed along the gradient, despite the continuous density distribution of RBCs. Early studies suggested that cell aggregation might influence spatial distribution, but it remains debated whether a continuous density population can form discrete bands. We developed a continuity equation incorporating cell aggregation to describe the macroscopic evolution of RBC volume fraction in a density gradient, considering a continuous RBC density distribution. Numerical solutions demonstrate that the competition between net buoyancy and aggregation is sufficient to create band patterns. Our model reproduces the temporal evolution observed in experiments, but also predicts several types of bifurcation-like behaviors for the steady-state patterns in constant gradients, depending on RBC volume fraction and aggregation energy. This demonstrates that the competition between RBC aggregation and net buoyancy is a mechanism driving pattern formation.
GPT-4o mini: Non-social science research article
Derepression of transposable elements in the mouse prefrontal cortex disrupts social behavior
R. Kijoon Kim, Corinne Smith, Natalie L. Truby, Shelbey R. Strandberg, Jessica L. Bell, Nic Carwile, Gabriella M. Silva, Rachael L. Neve, Theingi Aung, Xiaohong Cui, Peter J. Hamilton
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The neurobiological origins of social behaviors are poorly understood. Previous studies have linked the function of a single KrĂŒppel-associated box zinc finger protein (KZFP), ZFP189, in the mouse prefrontal cortex (PFC), with the regulation of transposable elements (TEs), immune genes, and social behaviors. Here, we expand the scope of inquiry to explore the relationship between collective PFC KZFP function and social behaviors by altering the function of the cognate KZFP interacting protein TRIM28 within the PFC of male and female mice. We reprogrammed natural TRIM28 WT by replacing the endogenous, transcriptionally repressive domain with a synthetic, enhanced transcriptional activation domain VP64-p65-Rta (TRIM28 VPR ) or by excising the transcriptional regulatory domain (TRIM28 NFD ). Upon intra-PFC viral-mediated delivery of TRIM28 variants, we observed that inversion of TRIM28 transcriptional control via HSV-TRIM28 VPR selectively produced deficits in social behaviors, without affecting nonsocial behaviors. RNA sequencing of manipulated PFC revealed that HSV-TRIM28 VPR drove transcriptional escape of all classes of TEs, particularly those located within intronic and enhancer regions proximal to downregulated immune genes. HSV-TRIM28 VPR -mediated social deficits were reversible by intra-PFC repletion of interferon cytokines. These data point to PFC KZFP–TRIM28 interactions as necessary to stabilize genomic TEs to enable cis -regulation of key immune gene expression, which enhances organismal capacity for complex, prosocial behaviors.
GPT-4o mini: Non-social science research article
SR-LLM: An incremental symbolic regression framework driven by LLM-based retrieval-augmented generation
Zelin Guo, Siqi Wang, Yonglin Tian, Jing Yang, Hui Yu, Xiaoxiang Na, Levente KovĂĄcs, Li Li, Petros A. Ioannou, Fei-Yue Wang
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Symbolic regression (SR) has regained research prominence as deep learning advancements accelerate the search for analytical models from observational data. However, the vast search space often hinders existing algorithms to yield complex analytical expressions. We present SR-LLM, an SR framework integrating retrieval-augmented generation mechanisms based on large language models (LLM) to achieve incremental learning. Specifically, our framework is capable of leveraging accumulated prior knowledge and past exploration results from external knowledge bases to retrieve the most relevant information for current regression tasks. It first composes prior information into small symbolic groups with the assistance of the LLMs and then utilizes deep reinforcement learning to combine these groups to formulate complex yet explainable analytic expressions that are more easily understood by humans. The capability for efficient knowledge utilization enables our framework to integrate all previous human experiences and exploration results, effectively learning by standing on the shoulders of giants. To validate the effectiveness of our proposed method, we not only test the framework on popular symbolic regression benchmarks but also extend its application to a domain where the explicit optimal model remains controversial: how to analytically describe human car-following behavior based on observed vehicle trajectories? Experiments confirm that our method outperforms on standard benchmarks, successfully rediscovers famous traditional car-following models and discovers new models from empirical trajectory data, achieving both fitting effectiveness and interpretability.
GPT-4o mini: Non-social science research article
MicroRNA164d suppresses the HvNAC92-HvHKT1;5 module to enhance salinity tolerance in barley
Liuhui Kuang, Hongxing Zhou, Tongtong Zhang, Fei Gao, Tao Yan, Zhong-Hua Chen, Qiufang Shen, Guoping Zhang, Lin Li, Dezhi Wu
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Cereal crops (e.g., rice, wheat, maize, and barley) constituted the major component of global human diet and fundamentally changed human society since the dawn of agriculture around 12,000 y ago. Originated and domesticated in different continents and environments, cereal crops vary significantly in their salt tolerance. The High-Affinity K + Transporter1;5s (HKT1;5s) predominately regulate Na + accumulation and salt tolerance in salt-sensitive cereal crops by mediating shoot-to-root Na + exclusion. However, HvHKT1;5 paradoxically promotes root-to-shoot Na + translocation in salt-tolerant barley. Therefore, unravelling the regulatory mechanisms of HvHKT1;5 is critical to understanding the molecular basis of salt tolerance in barley. Here, we demonstrated that a microRNA164d-HvNAC92-HvHKT1;5 module improves salt tolerance via reduced shoot Na + accumulation and increased K + retention in barley, whereas miR164d suppresses HvNAC92 transcription factor to directly downregulate HvHKT1;5 expression. Under salinity condition, the MIR164d -OE, Hvnac92 , and Hvhkt1;5 lines showed significantly reduced root-to-shoot Na + translocation and shoot Na + content compared with the wild-type. In conclusion, we resolve the species-specific function of HKT1;5s in cereal crops by establishing miRNA-guided Na + and K + transport regulation as a regulatory framework for engineering salt-tolerant crops.
GPT-4o mini: Non-social science research article
Crucial roles of mesenchymal Gata2 in murine epididymal development
Allyssa Fogarty, Shuai Jia, Jillian Wilbourne, Claire DuPuis, Fei Zhao
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Androgens drive the morphogenesis and differentiation of the Wolffian duct (WD) into the epididymis, an essential organ for male reproduction, by binding to the androgen receptor (AR). However, it remains unclear whether other transcriptional programs operate beyond the central androgen/AR signaling in promoting WD development. We found that mesenchyme-specific deletion of the transcription factor Gata2 resulted in defective epididymal coiling in the corpus and caudal regions. The defective coiling did not result from androgen signaling deficiency, as there were no abnormalities in testicular androgen production, AR/ Ar expression, or androgen-responsive genes, and dihydrotestosterone supplementation did not restore epididymal coiling in cultured WDs. Instead, Gata2 deletion led to the loss of epididymal identity, as evidenced by the reduced expression of epididymal mesenchymal markers. The epididymal defect persisted into adulthood, with the uncoiled corpus and caudal epididymis exhibiting abnormal epithelial morphology and lumen environments, resulting in an unfavorable environment for sperm storage. Our results demonstrate the androgen-independent role of mesenchymal GATA2 in promoting epididymal development and highlight the importance of proper fetal development in male reproduction.
GPT-4o mini: Non-social science research article
Learning predictive signals within a local recurrent circuit
Toshitake Asabuki, Colleen J. Gillon, Claudia Clopath
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The predictive coding hypothesis proposes that top–down predictions are compared with incoming bottom–up sensory information, with prediction errors signaling the discrepancies between these inputs. While this hypothesis explains the presence of prediction errors, recent experimental studies suggest that prediction error signals can emerge within a local circuit, that is, from bottom–up sensory input alone. In this paper, we test whether local circuits alone can generate predictive signals by training a recurrent spiking network using local plasticity rules. Our network model replicates experimentally observed features of prediction errors, such as biphasic neural activity patterns and context dependency. Our findings shed light on how synaptic plasticity can shape prediction errors and enable the acquisition and updating of an internal model of sensory input within a recurrent neural network.
GPT-4o mini: Non-social science research article
Anyon delocalization transitions out of a disordered fractional quantum anomalous Hall insulator
Zhengyan Darius Shi, T. Senthil
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Motivated by the experimental discovery of the fractional quantum anomalous Hall effect, we develop a theory of doping-induced transitions out of the Μ = 2 / 3 lattice Jain state in the presence of quenched disorder. We show that disorder strongly affects the evolution into the conducting phases described in our previous work. The delocalization of charge 2 / 3 anyons leads to a chiral superconductor through a direct second-order transition for a smooth random potential with long-wavelength modulations. The longitudinal resistance has a universal peak at the associated quantum critical point. Close to the transition, we show that the superconducting ground state is an “Anomalous Vortex Glass” stabilized in the absence of an external magnetic field. For short-wavelength disorder, this transition generically splits into three distinct ones with intermediate insulating topological phases. If instead, the charge 1 / 3 anyon delocalizes, then at low doping the resulting phase is a Reentrant Integer Quantum Hall state with ρ xy = h / e 2 . At higher doping this undergoes a second transition to a Fermi liquid metal. We show that this framework provides a plausible explanation for the complex phase diagram recently observed in twisted MoTe 2 near Μ = 2 / 3 and discuss future experiments that can test our theory in more detail.
GPT-4o mini: Non-social science research article
Convergent mutation trajectories convert functional self-tolerance in IGHV4-34 B cells to genetic tolerance encoded in the antibody
Christopher J. Jara, Sherin Zachariah, Katherine J. L. Jackson, Timothy J. Peters, Etienne Masle-Farquhar, Deborah L. Burnett, Eric Lam, Megan Faulks, Amanda Russell, Lisa Miosge, Stewart Smith, David C. Tscharke, Robert Brink, Christopher C. Goodnow, Joanne H. Reed
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Preventing autoantibody secretion by rendering self-reactive B cells functionally silent through clonal anergy has long posed the question of why fill the circulating B cell repertoire with cells that cannot secrete antibody? Here we address this question from the perspective of B cells that comprise 5 to 10% of the human circulating repertoire, expressing self-reactive surface immunoglobulins employing the IGHV4-34 heavy chain variable element. Using gene targeting to construct mice expressing a representative human IGHV4-34 antibody on the surface of many B cells, we show these cells are prevented from autoantibody secretion by B cell clonal anergy marked by downregulation of surface IgM, induction of tolerance-response mRNAs, and exclusion from the marginal zone and B1 cell subsets. This functionally tolerant state is overridden when the IGHV4-34 B cells cross-react with a virus, which stimulates the self-reactive B cells to hypermutate in germinal centers. Within 16 d of infection, 99% of daughter cells have acquired one of five heavy chain mutations that diminish binding to self but preserve virus binding, and 33% had combined 2 or 3 of these mutations to make their antibodies genetically self-tolerant and virus specific. These results demonstrate, from the perspective of a pathologically important human autoantibody class and the world’s most successful virus vaccine, how human antibody specificity is sculpted in the progeny of anergic B cells to yield antibodies that bind a virus but not self.
GPT-4o mini: Non-social science research article
MTHFR allele and one-carbon metabolic profile predict severity of COVID-19
Boryana Petrova, Caitlin Syphurs, Andrew J. Culhane, Jing Chen, Ernie Chen, Chris Cotsapas, Denise Esserman, Ruth R. Montgomery, Steven H. Kleinstein, Kinga K. Smolen, Kevin Mendez, character(0), Jessica Lasky-Su, Hanno Steen, Ofer Levy, Joann Diray-Arce, Naama Kanarek
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While the public health burden of SARS-CoV-2 infection has lessened due to natural and vaccine-acquired immunity, emergence of less virulent variants, and antiviral medications, COVID-19 continues to take a significant toll. There are thousands of new hospitalizations and hundreds of deaths per week in the United States, many of whom develop long COVID. Early identification of individuals at high risk of severe COVID-19 is key for monitoring and supporting respiratory status and improving outcomes. Therefore, precision tools for early detection of patients at high risk of severe disease can reduce morbidity and mortality. Here, we report an untargeted, longitudinal plasma metabolomics study of COVID-19 patients. One-carbon metabolism, a pathway previously shown as critical for viral propagation and disease progression, and a potential target for COVID-19 treatment, scored strongly as differentially abundant in patients with severe COVID-19. Targeted metabolite profiling revealed that one arm of the one-carbon metabolism pathway, the methionine cycle, is a major driver of the metabolic profile associated with disease severity. Further, genomic data from the profiled patients revealed a genetic contributor to methionine metabolism and identified the C677T allele of the MTHFR gene as a preexisting contributor to disease trajectory—patients that show aberrant one-carbon metabolite levels and that are homozygous for the MTHFR C677T, have higher incidence of severe COVID. Our results raise the possibility that MTHFR variant status may inform precision COVID-19 treatment strategies.
GPT-4o mini: Non-social science research article
Lipid-packing defects are sufficient to modulate membrane insertion and the bound state of α-synuclein
Miah J. Turke, Krishna M. Raghavan, Sofiya Maltseva, Daniel H. S. Kerr, Erin J. Adams, Ka Yee C. Lee
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α-Synuclein is an intrinsically disordered neuronal protein that forms an amphipathic helix when it peripherally binds to lipid membranes. This membrane interaction is integral to the protein’s function but is also associated with its dysfunction. Numerous membrane parameters have been identified to promote α-synuclein binding such as high negative charge and low lipid-packing density, which corresponds to greater lipid-packing defects—increased spacing between lipids conferred through curvature, unsaturation, or small headgroups. Despite α-synuclein’s established preference for negatively charged membranes with packing defects, the specific effects that each parameter has on this interaction remains underexplored. With increasing links between α-synuclein-associated diseases and changes in lipid composition, it has become more important to delineate how changes in membrane parameters affect α-synuclein membrane-interactions. Here, we demonstrate using tryptophan fluorescence spectroscopy that while net negative charge does increase the density of α-synuclein bound to a membrane, lipid-packing defects alone are sufficient for α-synuclein to insert. Not only do our results establish a lipid-packing defect requirement for α-synuclein, but they also reveal a packing defect-dependent shift in the ensemble of binding modes of the protein favoring the insertion of the end of its binding domain—a binding mode which has previously been linked to disease mutants of the protein. Overall, this work establishes the significance of lipid-packing defects in contrast to net negative charge for α-synuclein–membrane binding and proposes a lipid-compositionally dependent shift in α-synuclein’s ensemble of bound conformations, which may be relevant for the protein’s function and dysfunction.
GPT-4o mini: Non-social science research article
A neuromorphic robotic electronic skin with active pain and injury perception
Yuyu Gao, Jianpeng Zhang, Hehua Zhang, Lung Chow, Guangyao Zhao, Guihuan Guo, Chun Ki Yiu, Binbin Zhang, Ya Huang, Jingkun Zhou, Qiang Zhang, Tao Huang, Yuan Guo, Jian Li, Jiyu Li, Xingcan Huang, Zhenlin Chen, Zhenyu Liu, Yuze Qiu, Chuanfei Guo, Xinge Yu
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Humanoid robots with advanced sensory capabilities are increasingly demanded for empathetic, close-contact interactions with humans. Electronic skin (E-skin) is a key enabling technology for such tactile perception. However, current E-skins are limited to basic tactile sensing with simple circuit architecture. Here, we introduce a neuromorphic robotic e-skin (NRE-skin) that not only provides fundamental tactile sensing but also integrates advanced features, such as active pain and injury detection. The NRE-skin encodes dynamic tactile stimuli into neural-like pulse trains and features active pain detection that triggers protective reflexes. Additionally, its injury sensing and modular design enable precise localization of damaged areas and rapid replacement of affected skin. By emulating human sensory and protective systems, the NRE-skin facilitates more natural and safer human–robot interactions.
GPT-4o mini: Non-social science research article
Electroextraction of low-concentration redox-active heavy metals with E Ξ < 0 V from acid mine drainage
Ziyuan Huang, Chunhua Feng, Fengchang Wu, Zhenqing Shi, Yang Wang, Zhuoyu Zhang, Rimei Huang, Weijian Duan, Li Tian, Yijin Lv, Xinying Gong, Zhengjun Gong, Zhi Dang, Fangbai Li
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Electrochemical recovery of heavy metals from acid mine drainage (AMD) offers a sustainable solution to global AMD contamination, yet remains challenged by thermodynamic and kinetic barriers in reducing redox-active metals with negative standard reduction potentials (E ξ < 0 V), especially at low concentrations. Here, using Cd as a model system, we demonstrate that the formation of a metastable intermediate, Cd 2 SO 4 (OH) 2 , plays a crucial role in facilitating the efficient electrochemical reduction of low-concentration Cd(II) to metallic Cd 0 in acidic solutions. A combination of experimental and theoretical analyses reveals that in situ generated OH − at the cathode, in conjunction with bulk-phase SO 4 2− , drives the formation of this metal-inorganic complex, which mediates electron transfer by overcoming redox limitations. By optimizing flow dynamics and incorporating hierarchical electrode configurations, we enhance intermediate formation and achieve 96.81% Cd recovery from real AMD, with effluent Cd concentrations below 0.5 mg L −1 . Economic analysis estimates a net-positive return of 2.32 CNY per ton of treated AMD. Life cycle assessment further shows that the electroextraction process substantially outperforms lime neutralization with respect to all major environmental indicators. This work establishes a mechanistically driven, economically viable, and environmentally superior strategy for recovering valuable metals from AMD, advancing the prospects of circular resource recovery and sustainable wastewater management.
GPT-4o mini: Non-social science research article
Airborne PET nanoplastics alter tobacco’s chemical risk
Miao-Miao Tan, Xiao-Dong Sun, Yue Wang, Jian-Lu Duan, Jing-Ya Ma, Xiao-Yu Liu, Mei-Yan Liu, Yu-Chen Sun, Rong-Xiang Xing, Shu-Guang Wang, Wei Chen, Xian-Zheng Yuan
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Atmospheric micro(nano)plastics (MNPs), including polyethylene terephthalate (PET), enter plants via leaves, accumulating in tissues. Foliar PET nanoplastic exposure alters Nicotiana benthamiana nicotine biosynthesis, favoring the more potent (S)-isomer even without growth inhibition. This accumulation reveals a contamination pathway for combustible consumer products, demonstrating that MNPs-induced alteration of a plant’s endogenous biochemistry represents a significant and previously uncharacterized risk to agricultural sustainability and human health.
GPT-4o mini: Non-social science research article
Repeated major inland retreat of Thwaites and Pine Island glaciers (West Antarctica) during the Pliocene
Keiji Horikawa, Masao Iwai, Claus-Dieter Hillenbrand, Christine S. Siddoway, Anna Ruth Halberstadt, Ellen A. Cowan, Michelle L. Penkrot, Karsten Gohl, Julia S. Wellner, Yoshihiro Asahara, Ki-Cheol Shin, Masahiro Noda, Miyu Fujimoto, character(0), Karsten Gohl, Julia S. Wellner, Adam Klaus, Denise Kulhanek, Thorsten Bauersachs, Steven M. Bohaty, Margot Courtillat, Ellen A. Cowan, Marcelo A. De Lira Mota, Mariana S.R. Esteves, John M. Fegyveresi, Thomas Frederichs, Liang Gao, Anna Ruth Halberstadt, Claus-Dieter Hillenbrand, Masao Iwai, Ji-Hoon Kim, Theresa M. King, Johann P. Klages, Sandra Passchier, Michelle L. Penkrot, Joseph G. Prebble, Waliur Rahaman, Benedict T.I. Reinardy, Johan Renaudie, Delaney E. Robinson, Reed P. Scherer, Christine S. Siddoway, Li Wu, Masako Yamane
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The stability of the West Antarctic Ice Sheet (WAIS), crucial for predicting future sea-level rise, is threatened by ocean-forced melting in the Pacific sector of the Southern Ocean. While some geological records and ice-sheet models suggest WAIS retreat during past warm periods, reliable data constraining the extent of retreat are lacking. Detrital Nd, Sr, and Pb isotope data of sediments recently drilled at International Ocean Discovery Program (IODP) Site U1532 on the Amundsen Sea continental rise manifest repeated alternations in sediment provenance during glacial–interglacial cycles of the Pliocene (5.33 to 2.58 Mya), a time warmer than present. The variations reflect large fluctuations in WAIS extent on the Antarctic continent. A unique high Pb/low Δ Nd signature of sediments found at the onset of glacial intervals (3.88, 3.6, and 3.33 Ma) is attributed to the supply of detritus sourced from plutonic rocks located in the West Antarctic interior. Its isotopic signature at Site U1532 indicates major inland retreat of the WAIS during the preceding interglacials. During peak interglacials, the ice margin had retreated inland, and icebergs rafted and deposited inland-sourced detritus over 500 km across the Amundsen Sea shelf. Subsequent readvance of grounded ice then “bulldozed” these inland-derived fine-grained sediments from the shelf down to the continental slope and rise, resulting in a high Pb/low Δ Nd peak in the rise sediments. Our continuous Pliocene records provide conclusive evidence for at least five major inland retreat events of the WAIS, highlighting the significant vulnerability of the WAIS to ongoing warming.
GPT-4o mini: Non-social science research article
Body ownership gates tactile awareness by reshaping the somatosensory functional connectivity
Alberto Pisoni, Carlotta Fossataro, Alice Rossi Sebastiano, Marcella Romeo, Eleonora Arrigoni, Leonor Josefina Romero Lauro, Nadia Bolognini, Francesca Garbarini
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We all likely agree that tactile experience contributes to the emergence of the feeling of ownership over one’s own body. Is the opposite true? We answered this question by testing whether and how the sense of body ownership gates our tactile experience. In two experiments, we exploited a well-known multisensory illusion (Rubber Hand Illusion) to induce participants to feel a fake hand as belonging to their body, while their own hand was left in a disembodiment state (illusory-phases). After each illusory phase, a tactile stimulus was delivered to either the fake (embodied) hand or the real (disembodied) hand (testing-phases). Experiment 1 shows that the illusory phase significantly modulates the subjective feeling of touch experienced in the testing-phase, increasing tactile sensations when participants observed the fake (embodied) hand being touched (visual-touch), and decreasing them when the real (disembodied) hand was touched (real-touch). Experiment 2 investigated, by using TMS-EEG, the neural mechanism supporting this diametrical modulation of subjective feeling of touch, focusing on alpha-band oscillatory networks as the neural correlate of somatosensory awareness. S1 alpha-band connectivity fully matches the behavioral results, significantly increasing in visual-touch and decreasing in real-touch. In both experiments, a greater embodiment experienced in the illusory-phase significantly predicted higher behavioral and neurofunctional responses to visual-touch and lower responses to real-touch in the testing-phase. Altogether, our findings demonstrate that the sense of body ownership exerts a top-down modulation on tactile awareness and may do so by increasing or decreasing the strength of the somatosensory network involved in tactile awareness.
GPT-4o mini: Non-social science research article
Synaptic integration and competition in the substantia nigra pars reticulata—An experimental and in silico analysis
William Scott Thompson, J. J. Johannes Hjorth, Alexander Kozlov, Wilhelm Thunberg, Gilad Silberberg, Jeanette Hellgren Kotaleski, Sten Grillner
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The substantia nigra pars reticulata (SNr) is a primary output for basal ganglia signaling. It plays an important role in the control of movement, integrating inputs from upstream structures in the basal ganglia, before sending organized projections to a range of targets in the midbrain, brainstem, and thalamus. Here, we present a detailed in silico model of the mouse SNr, including its major afferent inputs. The electrophysiological and morphological properties of SNr neurons are characterized in acute brain slices via whole cell patch-clamp recordings and morphological reconstruction. Using reconstructed morphologies, multicompartmental models of single neurons are instantiated within the NEURON simulation environment and populated with relevant modeled ion channels. Model parameters are optimized via an evolutionary algorithm, such that simulated neurons faithfully reproduce recorded electrophysiological behavior. Using the simulation infrastructure software Snudda , single neuron models are incorporated into a circuit-level model, where the sparse connectivity within the SNr is recreated. We simulate the mouse SNr at scale, featuring realistic volumes and neuronal density. The unique synaptic properties and activity patterns of different afferent sources are captured in silico. Born out of ex vivo data, our model reproduces in vivo firing patterns. Our simulations suggest that paradoxical activity increases in response to experimental inhibition can be explained by lateral connectivity. In addition, our model predicts the functional implications of characteristic short-term synaptic plasticity in the indirect pathway of the basal ganglia. The model can be extended to include additional inputs and be connected with existing models of upstream basal ganglia nuclei to further explore circuit dynamics.
GPT-4o mini: Non-social science research article
Single-nucleus and spatial transcriptomics reveal the cell populations of intercalary meristems in bamboo
Ning Qin, Xin Liu, Shanying Li, Lei Sun, Chuan Chen, Wenrui Lou, Xianke Wang, Pengfei Bao, Bingchen Cao, Huan Zhang, Junwei Gan, Yinguang Hou, Zeyu Fan, Jianlin Liu, Yu Wang, Huanming Yang, Hansheng Zhao
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Intercalary meristems (IcMs), specialized developmental zones that drive rapid stem elongation in monocots, exhibit distinct spatiotemporal dynamics; however, their genetic basis remains poorly understood due to their transient activity and cellular heterogeneity. Moso bamboo ( Phyllostachys edulis )—with its exceptional daily growth rates of up to 114.5 cm, prolonged IcM activity spanning 45 to 60 d, and large, accessible culm structure—provides an ideal system for building a comprehensive IcM cell atlas. Here, we integrated a chromosome-level genome assembly of Moso bamboo with a high-resolution anatomical atlas to delineate three critical developmental stages of IcM activity: the initial cell division phase (ID), the rapid cell division phase (RD), and the rapid cell elongation phase (RE). By combining single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics, we reconstructed a dynamic single-nucleus transcriptomic continuum spanning from proliferative to elongation states. Multiomics integration, along with in situ hybridization and ultrastructural imaging, identified IcM cells as short-columnar cells adjacent to elongating ground tissue parenchyma (Gp) cells, with the IcM1 subpopulation functioning as stem-like cells essential for maintaining the proliferative capacity. Pseudotemporal trajectory analysis revealed transcriptional transitions from stem-like IcM states to differentiated Gp cells. Functional experiments revealed that clrGene008562 , a WOX2 homolog, enhances callus regeneration, indicating its potential role in promoting cell division and differentiation processes relevant to IcM development. These findings provide a comprehensive molecular and cellular framework for understanding IcM function and offer valuable multiomics resources for advancing meristem research in bamboo and other Poaceae species.
GPT-4o mini: Non-social science research article
Uncovering inequalities in new knowledge learning by large language models across different languages
Chenglong Wang, Haoyu Tang, Xiyuan Yang, Yueqi Xie, Jina Suh, Sunayana Sitaram, Junming Huang, Yu Xie, Pengjun Zhao, Zhaoya Gong, Xing Xie, Fangzhao Wu
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As large language models (LLMs) gradually demonstrate their potential to boost productivity and become integral tools for problem-solving in daily life worldwide, understanding the linguistic inequalities they introduce is becoming increasingly important. Prior research has primarily focused on static analyses of disparities in existing knowledge and capabilities of LLMs across languages. However, LLMs are continuously evolving, acquiring new knowledge to provide current, relevant responses and deliver precise, expert-level answers in specific domains. Investigating linguistic inequalities within this dynamic learning process is, therefore, also essential. In this paper, we explore inequalities in new knowledge learning by LLMs across different languages and four key dimensions: effectiveness, transferability, prioritization, and robustness. Through extensive experiments in both in-context learning and fine-tuning settings, with proprietary and open-source models, we reveal four key findings: 1) LLMs face greater challenges in efficiently and accurately learning new knowledge in lower-resource languages; 2) knowledge learned by LLMs tends to be more easily transferred to higher-resource languages than to lower-resource ones; 3) new knowledge in higher-resource languages is more likely to be retained and prioritized; and 4) LLMs are more robust against incorrect or misleading information in higher-resource languages. We further analyze the underlying causes of these inequalities from linguistic perspectives, pretraining characteristics, and tokenizer design, and propose a preliminary mitigation strategy through the lens of linguistic neurons. This work highlights the urgent need to recognize and address emerging linguistic inequalities in the development of LLMs.
GPT-4o mini: Non-social science research article
Locomotion-dependent use of geometric and body cues in humans mapping 3D space
Volker Reisner, Theo A. J. SchÀfer, Leonard König, Misun Kim, Christian F. Doeller
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The ability to represent locations across multiple dimensions of space is a core function of cognitive maps. While the influence of boundary-dependent environmental geometry on spatial representations has been extensively studied in 2D spaces, less is known about the role of boundaries for volumetric spatial memory. Research in humans and other animals has demonstrated distinct processing of the vertical and horizontal spatial dimensions, likely related to species-specific modes of locomotion. Here, we investigate whether different locomotion modes, flying and walking, affect the use of vertical boundaries, leading to possibly distinct volumetric representations. In a Virtual Reality experiment, human participants memorized objects within a symmetric 3D enclosure, and then were asked to replace them in either the familiar or geometrically deformed environments. We found that the flying group exhibited lower vertical than horizontal spatial memory precision, whereas the walking group showed the opposite pattern, an effect related to using their body axis as a vertical “ruler”. Within deformed environments, object replacements in the flying group followed the predictions from a 3D-extended boundary-vector-cell-like computational model of spatial mapping that treated all boundaries equally, whereas those in the walking condition favored a modified model that prioritized the ground boundary. Our findings suggest that gravity-related movement constraints promote different utilization of geometric and body-related cues, resulting in flexible representations of volumetric space.
GPT-4o mini: Non-social science research article
Symmetries and selection rules in photoelectron chiral dichroism
Ofer Neufeld
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Photoelectron circular dichroism (PECD) is a method whereby randomly oriented chiral molecules are irradiated by circularly polarized light (CPL), photoionizing electrons, which are measured in a momentum-resolved manner. This scheme permits chiral light–matter interactions within the electric-dipole approximation (avoiding weak magnetic-dipole interactions), yielding huge chiral signals in the form of a forward–backward asymmetry in photoemission. Recently, more intricate realizations of PECD have been explored where the CPL is replaced with elaborate polarization-tailored light (e.g., bichromatic, noncollinear, etc.), some of which do not even require circularly polarized components, but still lead to massive chiral signals. However, the connection between generalized symmetries and asymmetries of the laser drive and selection rules in PECD have not yet been derived. Here, we formulate this connection analytically from group theory, also predicting two previously unknown selection rules for PECD from fields with dynamical inversion and improper-rotational symmetries. We further propose bichromatic bielliptical fields for breaking symmetries in typical spectra, yielding potentially more information for ultrafast-resolved measurements. We numerically demonstrate all of our results with state-of-the-art ab-initio simulations in the archetypal chiral molecule, Bromochlorofluoromethane, providing predictions for experiments. Our work presents a roadmap for analyzing PECD from tailored light and resolves a long-standing issue in the field. It should motivate theoretical and experimental investigations in novel PECD set-ups.
GPT-4o mini: Non-social science research article
Preservation of anticorrelated brain networks predicts recovery after traumatic brain injury
Samuel B. Snider, Hui Shi, Yelena G. Bodien, Calvin Howard, Xiaoying Sun, Alexandra J. Golby, Karl A. Zimmerman, Guido Bertolini, Sandra Magnoni, Vincent Dunet, Mauro Oddo, Neil S. N. Graham, Emma-Jane Mallas, Federico Moro, Pratik Mukherjee, Nancy R. Temkin, Sonia Jain, David J. Sharp, Brian L. Edlow, Michael D. Fox
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Some patients with moderate to severe traumatic brain injury (TBI) make a full recovery, while others remain severely disabled. Accurate prognostication is important, because withdrawal of life-sustaining therapy based on perceived poor prognosis is the leading cause of death after TBI. Synchronized activity between brain regions, measurable with resting-state functional MRI (rs-fMRI), may underlie neurological recovery. However, which functional connections are critical for recovery, and whether functional connectivity measured shortly after brain injury predicts long-term recovery, is unknown. Here, we analyzed data from three prospective cohorts of patients with moderate or severe TBI (N = 116 patients; 134 controls) who underwent rs-fMRI shortly after injury. The strongest predictor of 6-mo functional outcomes in the Training Cohort (mean cross validation AUC 0.94) and independent Testing Cohort (AUC 0.78; P = 0.001) was functional connectivity between three pairs of brain regions from functionally distinct networks, two of which were anticorrelated. Results were robust to controlling for sedation ( P = 0.02) and level of consciousness at time of MRI ( P = 0.02). Finally, preserved anticorrelations improved the leave-one-out outcome prediction accuracy of an established prognostic score (AUC 0.90 vs. 0.80; P = 0.02). Preserved functional anticorrelations in acutely traumatized brains identify patients with the neurological substrate required for recovery. This biomarker can inform prognostic decisions in patients at high risk for death from withdrawal of life-sustaining therapy.
GPT-4o mini: Non-social science research article
Stabilizing calcium nitride for efficient, long-term electrochemical ammonia synthesis
Ishita Goyal, Hasiya Najmin Isa, Vamsi Vikram Gande, Rohit Chauhan, Meenesh R. Singh
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Electrochemical ammonia synthesis at ambient conditions via calcium-mediated nitrogen fixation holds considerable promise but is impeded by fundamental gaps such as poor gas–liquid interface stability, sluggish hydrogen oxidation reaction (HOR) kinetics, and instability of the critical intermediate calcium nitride. To systematically address these barriers, we i) introduced a high surface-area Ni-based anode specifically selected for enhancing HOR kinetics and minimizing solvent oxidation; ii) substituted the conventionally used tetrahydrofuran solvent with dimethoxyethane (DME) to significantly improve chemical stability; and iii) developed a tailored flow cell configuration to enhance gas–liquid mass transport and stabilize reaction intermediates. Employing in-situ Raman spectroscopy and X-ray photoelectron spectroscopy, we provided direct evidence of stabilized calcium nitride formation, elucidating the crucial roles of solvent stability and electrode composition in sustaining reactive intermediates. As a result of these combined innovations, our system demonstrates substantial performance improvements, achieving a Faradaic efficiency (FE) of 34.35 ± 1.76% in short-term tests and sustaining ~20% FE over extended continuous operation (~56 h). At elevated current densities, the improved gas–liquid interface stability enables robust ammonia production, reaching partial current densities of approximately 219 mA cm − 2 at ~29% FE. Isotope-labeling studies with 15 N 2 confirmed the direct electroreduction of N 2 , while kinetic analyses underscored the impact of anode material selection on HOR efficiency and overall electrochemical stability. These insights establish critical mechanistic understanding and clear design principles for future calcium-mediated electrochemical nitrogen fixation systems, enabling stable, efficient, and selective ammonia synthesis.
GPT-4o mini: Non-social science research article
Multiplex mapping of protein–protein interaction interfaces
Jingxuan He, Ling-Nan Zou, Vidhi Pareek, Stephen J. Benkovic
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We describe peptide mapping through Split Antibiotic Resistance Complementation (SpARC-map), a method to identify the probable interface between two interacting proteins. Our method is based on in vivo affinity selection inside a bacterial host and uses high-throughput DNA sequencing to infer probable protein–protein interaction (PPI) interfaces. SpARC-map uses only routine microbiology techniques, with no reliance on specialized instrumentation, dedicated reagents, or reconstituting protein complexes in vitro. SpARC-map can be tuned to detect PPIs over a broad range of affinities, multiplexed to probe multiple PPIs in parallel, and its nonspecific background can be precisely measured, enabling the sensitive detection of weak PPIs. Using SpARC-map, we recover known PPI interfaces in the p21–PCNA, p53–MDM2, and MYC–MAX complexes. We also use SpARC-map to probe the purinosome, the weakly bound complex of six purine biosynthetic enzymes, where no PPI interfaces are known. There, we identify interfaces that satisfy structural requirements for substrate channeling, as well as protein surfaces that participate in multiple distinct interactions, which we validate using site-specific photocrosslinking in live human cells. Finally, we show that SpARC-map results can impose stringent constraints on machine learning–based structure prediction.
GPT-4o mini: Non-social science research article
Global vaccination coverage and disease incidence in cattle, pigs, and poultry
Alec Gleason, Isabella Impalli, Justin Sheen, Aurelio Cabezas Murillo, Bryan T. Grenfell, Simon A. Levin, Thomas P. Van Boeckel, Ramanan Laxminarayan
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Vaccination against livestock diseases is an effective method to prevent and control the spread of pathogens and reduce antimicrobial consumption and livestock production losses. Systematic data on global vaccination coverage could unlock opportunities to expand these outcomes. In this study, we estimate annual vaccination coverage and disease incidence for 104 cattle, porcine, and poultry diseases in 203 reporting countries and territories between 2005 and 2025 using data from the World Animal Health Information System, the Food and Agriculture Organization, and published literature. We provide 686,559 data points and further evaluate 11 diseases most widely targeted by vaccination programs in 2025. The vaccination coverage for global populations at risk of these diseases in 2025 is as follows: for cattle, 16.64% (95% CI: 16.63 to 16.66) against foot and mouth disease, 33.80% (33.43 to 34.38) against lumpy skin disease, 7.46% (6.71 to 8.81) against Brucella abortus , 11.57% (10.29 to 13.36) against anthrax, and 7.93% (6.27 to 14.09) against rabies. For pigs, 6.56% (6.56 to 6.57) against classical swine fever, 4.96% (3.28 to 8.76) against anthrax, and 8.08% (5.10 to 17.20) against rabies. For poultry, 17.62% (17.37 to 18.04) against Newcastle disease, 16.71% (16.42 to 19.01) against infectious bronchitis, 9.17% (8.59 to 13.67) against infectious laryngotracheitis, 15.04% (14.63 to 18.63) against infectious bursal disease, and 8.81% (7.94 to 11.97) against Marek’s disease. Expanding vaccination efforts in India and Argentina for cattle; China and Russia for pigs; and China, Brazil, and Iran for poultry may yield the greatest reductions in global livestock disease burden.
GPT-4o mini: Non-social science research article
Maintaining microbiota across diverse symbiotic organs in Euprymna scolopes : Insights into shared immune responses
Nidhi Vijayan, John Briseño, Oleg Simakov, Spencer V. Nyholm
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Many animals have multiple organs or tissues that are colonized by diverse microbiota. The female Hawaiian bobtail squid, Euprymna scolopes , has two organs with distinct symbiotic communities: the accessory nidamental gland (ANG) and the light organ (LO). The ANG hosts a bacterial consortium, whereas the LO has a binary relationship with Vibrio fischeri , housed in extracellular crypt spaces as part of the central core (CC). To understand how the host maintains distinct symbiotic communities, we used transcriptomics to identify immune-related genes that are uniquely and similarly expressed in the ANG and LO-CC compared to organs without a known microbiota. Genes such as peptidoglycan recognition proteins EsPGRP2 and EsPGRP3, cathepsin-Z, alkaline phosphatase, and acidic phospholipase exhibited significant upregulation in the symbiotic organs compared to other tissues like gills, skin, mantle, optic lobe, ovaries, and brain. Moreover, EsPGRP2 displayed distinct localization patterns within the ANG, inversely correlating with bacterial presence, whereas the protein was colocalized with V. fischeri in the LO-CC. Notably, 10 different galaxins (EsGal) were uniquely highly expressed in both the ANG and LO-CC, with EsGal1 messenger RNA predominantly localized to the LO-CC epithelium, while EsGal2 and EsGal3 were primarily found in the epithelia of ANG tubules. Furthermore, antimicrobial assays using partial peptides derived from EsGal1 and EsGal2 showed varying and distinct patterns of inhibitory activity for these peptides. In summary, our findings identify similar immune gene families expressed across functionally distinct symbiotic organs in E. scolopes , suggesting that common immunomodulatory factors may maintain distinct symbiotic niches in the host.
GPT-4o mini: Non-social science research article
Intensified tropical cyclone activity in East Asia during the Maunder (solar) Minimum
Kuan-Hui Elaine Lin, Wan-Ling Tseng, Yu-Shiuan Lin, Chen-Ying Lee, Yu-Hsiang Lin, Huang-Hsiung Hsu, Pao-Kuan Wang
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This study reports a tropical cyclone (TC) series reconstructed from documentary records that have been digitized in the REACHES database for the period of 1368–1911. The series has been validated through comparison with early instrumental data from 1884 to 1911 as well as with other reconstructions. TCs in the post-1911 period were also examined and a 653-y long (1368–2020) North Western Pacific TC chronology was studied. The peak TC frequency occurred in the 1650–1680 with a greater amplitude of variabilities in the south and east coasts of China and TC behaviors changed seasonally. The peak TC period corresponded to the Maunder Minimum which was characterized by lower land surface temperature, whereas the temperature reconstructed from marine proxies showed an anomalously warmer sea surface temperature over the western Pacific. Changing thermal contrast between land and sea likely created a more dynamic summer monsoon circulation resulting in active TC activity. This study provides important evidence and implication about the TC behavior in response to ongoing global climate change.
GPT-4o mini: Non-social science research article
Arg–Tyr cation–π interactions drive phase separation and ÎČ-sheet assembly in native spider dragline silk
Hannah R. Johnson, Kevin Chalek, Nesreen Elathram, Andy T. Chau, Anikin Rae Domingo, Julian E. Aldana, Hieu Nguyen, Alexia de Loera, Brianna A. Duarte, Lado Shapakidze, David Onofrei, Galia T. Debelouchina, Christian D. Lorenz, Gregory P. Holland
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Liquid–liquid phase separation (LLPS) is a fundamental principle of protein organization in intrinsically disordered proteins (IDPs) and biomaterials, yet the residue-level interactions that link condensation to structural ordering remain poorly defined. In spider dragline silk, LLPS is believed to initiate the transition from soluble spidroin dope into ÎČ-sheet–rich fibers that provide exceptional toughness, yet how sequence-specific motifs govern this process has been unclear. Here, we combine isotope-edited solution NMR, dynamic nuclear polarization (DNP)–enhanced solid-state NMR, molecular dynamics simulations, and AlphaFold3 modeling to define the molecular role of arginine and tyrosine in Latrodectus hesperus dragline silk. Phosphate triggers LLPS while preserving intrinsic disorder, with arginine exhibiting the largest chemical shift perturbations. Simulations reveal that phosphate displaces hydration water to promote Arg–Tyr cation–π interactions and weaken Arg–poly(Ala) contacts. Solid-state NMR directly detects Arg–Tyr contacts in spun fibers, demonstrating that arginine is partially incorporated into ÎČ-sheet interfaces while tyrosine frequently adopts ÎČ-turn conformations. AlphaFold3 models corroborate these interfacial geometries and reproduce experimental chemical shifts, supporting persistent Arg–Tyr interactions at structured–unstructured boundaries. Together, these results identify Arg–Tyr contacts as critical “sticker” interactions that mediate condensation, nucleate local order, and stabilize fiber architecture. More broadly, this work establishes a mechanistic link between residue-specific chemistry, LLPS, and hierarchical assembly in a structural protein. These insights highlight how weak multivalent interactions bridge disordered and ordered states, providing a general framework for condensate-driven assembly in biology and guiding biomimetic material design.
GPT-4o mini: Non-social science research article
Arabidopsis kinesins KCH3 and KCH7 promote root gravitropism through actin bundling in the stele
Yingzhi Niu, Shuyuan Chen, Zhaoguo Deng, Juan Du, Yangyang Zhou, Ni Fan, Dingding Zhou, Yue Niu, Yang Yang, Lizhe An, Siyi Chen, Yun Xiang, Haodong Chen, Dong Qian
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Root gravitropism is essential for plant adaptation to the environment. The cytoskeleton is known to play a critical role in gravitropism, but the underlying mechanisms remain unclear. In this study, we demonstrate that the Arabidopsis kinesins KCH3 and KCH7 (KCH3/7) are expressed and functionally active in the root stele. The kch3 kch7 ( kch37 ) double mutant exhibits delayed gravitropic responses, while stele-specific expression of either KCH3 or KCH7 rescues this defect. Both the calponin homology (CH) and motor domains of KCH3/7 are essential for mediating gravitropism. In vitro and in vivo assays reveal that KCH3/7 promotes actin filament (F-actin) bundling and its turnover in the root stele. Mutation of KCH3/7 results in altered PIN protein abundance and polarity in the root stele, leading to impaired acropetal auxin transport within the stele and reduced auxin accumulation in the root tip’s columella cells. This ultimately causes defective auxin redistribution during gravistimulation. Collectively, our findings highlight the importance of cytoskeletal organization and dynamics in the root stele for maintaining the auxin gradient in the root tip and for gravistimulation-induced auxin asymmetry.
GPT-4o mini: Non-social science research article
Road expansion risk predicts future hotspots of tropical deforestation
Jayden E. Engert, Carlos M. Souza, Fritz Kleinschroth, F. Yoko Ishida, Stefany P. Costa, Jonas Botelho, William F. Laurance
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Roads act as conduits for human incursions and hence underlie many of humanity’s impacts on nature, including deforestation, wildfires, and natural-resource overexploitation. Unfortunately, existing roadmaps often drastically underestimate the true extent of road networks and future predictions of road-related impacts rely on incomplete and outdated data, undermining development planning and conservation decision-making. Here, we develop a multivariate “road expansion risk” index to identify areas prone to road building and therefore vulnerable to road-related environmental impacts. Using a massive road dataset—137 million 1-ha raster cells drawn from three different sources arrayed across the Amazon and Congo basins and insular Asia-Pacific region—we predict road-prone locations via a statistical model that integrates a range of biophysical, socioeconomic, and administrative data. This highly integrative, large-scale approach allowed us to identify areas likely to experience future road building and regions that may contain unmapped roads. Importantly, our road expansion risk index is a strong predictor of forest loss and degradation and can hence identify future road building and deforestation hotspots, even for the many tropical forest locales with grossly deficient road data.
GPT-4o mini: Non-social science research article
Maladaptive immunity to the microbiota promotes neuronal hyperinnervation and itch via IL-17A
Jeremie Delaleu, Veronica Burstein, Eduard Ansaldo, Ignacio Becaccece, Motoyoshi Nagai, Nicolas Bouladoux, Dan Corral, Andrea Muñoz Zamora, Adelle Ayash, Margery Smelkinson, Lilian Sun, Yasmine Belkaid, Michel Enamorado
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The interaction between the immune system and the somatosensory system plays a fundamental role in the regulation of diverse biological processes. Chronic itch is a common yet hard-to-treat symptom of many inflammatory skin conditions. One hallmark of chronic itch is the hyperinnervation of the skin by sensory fibers, yet what drives this aberrant nerve growth or how it contributes to disease progression remains unclear. Here, we identify IL-17A and immunity to skin microbiota as key triggers of sensory neuron plasticity and pruritus. In a murine model of psoriatic itch, we show that exposure to Staphylococcus aureus prior to experimental psoriasis results in heightened skin inflammation, increased itch, and marked hyperinnervation of CGRPα + sensory neurons. Accordingly, single-nuclei RNA sequencing of dorsal root ganglia reveals that microbiota-driven inflammation induces a regenerative transcriptional program in sensory neurons, including upregulation of axonal growth, injury response, and IL-17RA signaling pathways. Mechanistically, we show that IL-17A/IL-17RA signaling within TRPV1 + sensory neurons drives hyperinnervation and pruritus, establishing a causal link between IL-17A and microbiota-driven immune responses in sensory circuit remodeling. Further, we identify sensory hyperinnervation as a key driver of chronic itch and inflammation. Collectively, we reveal that aberrant IL-17A signaling in sensory neurons, triggered by dysregulated microbiota immunity, promotes neuronal remodeling that amplifies itch and inflammation. These findings provide a framework for targeting microbiota–neuroimmune interactions as a therapeutic strategy for pruritus.
GPT-4o mini: Non-social science research article
Controllable gap junctions by vitamin B 12 and light
Duo Cui, Shuzhang Liu, Xinyu Huang, Xiaohan Alex Tang, Min Zheng, Zonglin He, Rui Xu, Chenbo Sun, Yingjie Xu, Renjun Tu, Peng Zou, Ting Xie, Fei Sun
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Gap junctions mediate rapid signal transduction between contiguous cells, which are indispensable for multicellular organisms to coordinate cellular activities across numerous physiological processes. However, precise control of gap junctions remains elusive. Herein, we present CarGAP, a single-component chemo-optogenetic tool that utilizes the C-terminal adenosylcobalamin (AdoB 12 ) binding domain of a photoreceptor protein (i.e., CarH C ) to achieve reversible control over both vertebrate and invertebrate gap junctions with spatiotemporal precision. The vertebrate CarGAP (i.e., Cx-CarGAP), created by genetically fusing connexins with CarH C in mammalian cells, can efficiently block the gap junction channels through AdoB 12 -induced protein oligomerization and subsequently reinstate them via green light–induced protein disassembly. We further introduced the CarGAP system (i.e., Inx-CarGAP) to the Drosophila ovary, enabling reversible control over the heterotypic gap junctions formed by innexin2 (Inx2) and innexin4 (Inx4, also known as zero population growth, Zpg), thereby uncovering the roles of gap junctions in stem cell–niche interactions. This study illustrates CarGAP as a generalizable chemo-optogenetic tool for interrogating the functions of gap junctions in various biological contexts.
GPT-4o mini: Non-social science research article
ATM interaction with GRP94 modulates oncogenic receptor expression and signaling and microglial activation
Paige E. Burrell, Donald E. Fleenor, Olivia M. Nicholson, Changjuan Shao, Michael B. Kastan
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Ataxia-telangiectasia (A-T), caused by biallelic mutations in the ATM gene, leads to multiple disease phenotypes, including cerebellar neurodegeneration, radiosensitivity, cancer predisposition, immunodeficiency, insulin resistance, and pulmonary inflammation. ATM plays a central role in regulating cellular responses to DNA breakage [M. B. Kastan, J. Bartek, Nature 432 , 316–323 (2004)], but several cellular and physiologic abnormalities associated with ATM dysfunction suggest the possibility of noncanonical roles for ATM as well. Herein, we identified the HSP90 paralogue, GRP94, as an ATM interactor/substrate and found that ATM influences N- glycosylation of GRP94 and its subsequent activation/translocation to the plasma membrane, where it serves as a scaffold protein and stabilizer for several membrane proteins, including receptor tyrosine kinases (RTKs), such as EGFR and IGF1-R. In selected cell types, ATM loss/inhibition resulted in increased cell surface expression of RTKs and overactivation of RTK pathways, alterations that were rescued by specific inhibition of cell surface GRP94. This ATM/GRP94 pathway also regulated the activation of microglial cells, manifest as increased cytokine production and phagocytosis activity associated with ATM loss/inhibition and reversal of that activation with GRP94 inhibition. These results identified GRP94 as an ATM interactor and apparent substrate and demonstrated specific critical regulatory roles for ATM outside of DNA damage signaling. These insights provide potential explanations for several of the phenotypes associated with ATM dysfunction and potential opportunities for novel approaches to blunt clinical symptoms in A-T, and also suggest that other neurodegenerative and inflammatory disorders might benefit from selective inhibition of cell surface GRP94.
GPT-4o mini: Non-social science research article
A conserved hub protein required for peptidoglycan remodeling and cell division in Acinetobacter baumannii
Brent W. Simpson, Amanda B. McLean, M. Stephen Trent
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Gram-negative bacteria build a multilayered cell envelope in which the peptidoglycan layer is sandwiched between an inner membrane of glycerophospholipids and an asymmetric outer membrane composed of glycerophospholipids and lipopolysaccharide (LPS). Acinetobacter baumannii , however, synthesize lipooligosaccharide (LOS), an LPS variant lacking O-antigen. Although LPS/LOS is typically essential, A. baumannii can survive without LOS, offering the opportunity to examine how the Gram-negative envelope remains stable in the absence of this major glycolipid. We previously found that the peptidoglycan biogenesis protein NlpD, an activator of peptidoglycan degradation by cell division amidases, is critical for fitness during LOS deficiency. Here, we show that NlpD is required under these conditions because a second putative amidase activator, WthA (cell wall turnover hub protein A), no longer functions in LOS-deficient cells. Mutants lacking WthA exhibited severe cell-division defects and were synthetically sick with loss of NlpD. Acinetobacter lack canonical periplasmic amidases, raising the question of which enzymes partner with NlpD and WthA. Previous work showed that overexpression of an Acinetobacter ÎČ-lactamase increased denuded peptidoglycan, a product of amidase activity. Guided by this finding, we examined the chromosomally encoded ÎČ-lactamase Oxa51 and found that its coexpression with WthA or NlpD enhanced release of amidase products, suggesting that Oxa51 participates in peptidoglycan degradation and that WthA is an amidase activator. Further, WthA influenced peptidoglycan endopeptidases and lytic transglycosylases through a network of protein interactions. Altogether, these findings identify WthA as a missing regulator in Acinetobacter peptidoglycan biogenesis and a hub that coordinates peptidoglycan turnover and cell division.
GPT-4o mini: Non-social science research article
Neutral theory of cooperative dynamics
Jordi Piñero, Artemy Kolchinsky, Sidney Redner, Ricard Solé
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Mutualistic interactions are widespread in nature, from plant communities and microbiomes to human organizations. Along with competition for resources, cooperative interactions shape biodiversity and contribute to the robustness of complex ecosystems. We present a stochastic neutral theory of cooperator species. Our model shares with the classic neutral theory of biodiversity the assumption that all species are equivalent, but crucially differs in requiring cooperation between species for replication. With low migration, our model displays a bimodal species-abundance distribution, with a high-abundance mode associated with a core of cooperating species. This core is responsible for maintaining a diverse pool of long-lived species, which are present even at very small migration rates. We derive analytical expressions of the steady-state species abundance distribution, as well as scaling laws for diversity, number of species, and residence times. With high migration, our model recovers the results of classic neutral theory. We briefly discuss implications of our analysis for research on the microbiome, synthetic biology, and the origin of life.
GPT-4o mini: Non-social science research article
How lipids speak to nerves
Vincenza Cifarelli
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GPT-4o mini: Non-social science research article
Getting gene expression “just right”
Paul C. Whitford
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GPT-4o mini: Non-social science research article
The neural substrates of behavioral evolution: Divergent behaviors from conserved neurons
Artyom Kopp
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GPT-4o mini: Non-social science research article
Merkel cell mechanotransduction facilitates adult neurogenesis and cognition in an enriched environment
Xing Luo, Qiang Liu, Dezhe Qin, Min Wang, Weixiang Guo
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The tactile system empowers us to act on and interact with the changes of the external environment. In rodents, tactile sensation, a fundamental sense, is largely mediated via the vibrissae and the barrel cortex. However, it remains unclear how tactile perception reshape the brain when exploring a novel environment. Here, we showed that exposure to an enriched environment (EE) failed to enhance adult neurogenesis and cognition in the mice with defective touch perception due to loss of a mechanotransduction channel Piezo2 in Merkel cells. Moreover, we found an EE-activated neuraxis, in which the dentate gyrus received tactile input through a circuit that originated from the somatosensory cortex (S1) and relayed via dopaminergic neurons of the substantia nigra pars compacta (SNc). Defective touch perception diminished the S1 to SNc afferent, thereby reducing dopamine release. Notably, stimulation of the S1 to SNc afferent restored EE-induced adult neurogenesis and cognition in the mice with defective touch perception. Therefore, our study highlighted the important role of intact tactile processing in brain function.
GPT-4o mini: Non-social science research article
The “machinal bypass” and how we’re using AI to avoid ourselves
Deanna M. Kaplan, Roman Palitsky, Charles L. Raison
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GPT-4o mini: Non-social science research article
David John “Davo” Mangelsdorf (1958–2025): A life of science, friendship, and joy
Ronald M. Evans
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David John “Davo” Mangelsdorf passed away on August 3, 2025, in Dallas, Texas at age 67 from an unexpected postsurgical complication. Davo made transformative contributions to nuclear receptor and metabolic biology. He discovered the retinoid X receptor (RXR) during his early years at Salk and, during his career and leadership at UT Southwestern, helped define the roles of orphan nuclear receptors, including LXR and FXR, as well as the metabolic hormones FGF19 and FGF21. This retrospective also reflects on the person behind the science. Davo brought curiosity, humor, and a sense of ease to every interaction. His legacy endures in his discoveries, in the colleagues and trainees he inspired, and in the kindness and laughter he shared throughout his life.
GPT-4o mini: Non-social science research article
Structural insights into human signal peptide peptidase
Gaoxingyu Huang, Xuefei Guo, Jiaoni Wang, Xiaofei Ge, Fang Kong, Zilin Shen, Xu Wang, Chuangye Yan, Jianlin Lei, Yigong Shi, Rui Zhou
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The signal peptide peptidase (SPP) remains the only intramembrane protease family that is yet to be structurally characterized. Here, we report the cryoelectron microscopy (cryo-EM) structures of human SPPL2a in two functional states: ligand-free and inhibitor-bound, at average resolutions of 3.3 and 3.6 Å, respectively. SPPL2a contains nine transmembrane helices with a conserved fold for the SPP and presenilin families. In the ligand-free state, an antiparallel ÎČ-hairpin is already formed near the active site, reminiscent of presenilin 1 (PS1) in its substrate-bound state. Binding by the small molecule inhibitor L685,458 triggers further conformational rearrangement in SPPL2a. Together with the cryo-EM structure of compound E-bound PS1, our findings reveal insights into selective inhibitor recognition and substrate gating by aspartyl intramembrane proteases. Structure-based sequence analysis unveils key differences between the SPP and presenilin families that underlie their function and assembly.
GPT-4o mini: Non-social science research article
Breathing life into the boring billion: Direct constraints from 1.4 Ga fluid inclusions reveal a fair climate and oxygenated atmosphere
Justin G. Park, Michael Naylor Hudgins, Philip Fralick, Jacob T. Shelley, Morgan F. Schaller
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The Mesoproterozoic eon [1.8 to 0.8 billion years ago (Ga)] is a crucial but enigmatic period in Earth’s history. Many facets of this interval remain unresolved, especially how atmospheric evolution influenced and responded to changes in climate and biology. For example, low atmospheric O 2 concentrations are thought to have inhibited the emergence of animals until the Neoproterozoic. Yet, some p O 2 estimates indicate that the critical threshold for animal respiration was exceeded several hundred million years prior. Likewise, low p CO 2 estimates imply glacial climates should prevail. However, this prediction is inconsistent with an apparent billion-year hiatus in glaciation. We test these hypotheses with direct constraints on the Mesoproterozoic atmosphere from analyses of primary fluid inclusions in 1.4 Ga surficial halite, which reveal an atmospheric p O 2 of 7.84 ± 3.05 mbar and a p CO 2 of 2.76 ± 1.66 mbar. We couple these measurements with average inclusion homogenization temperatures of 31.2 ± 7.8 °C. Our results point to an Earth system state characterized by a moderate climate with sufficient O 2 for early animal respiration. These observations reflect a coevolution of life, climate, and the atmosphere, where a largely unrecognized episode of oxygenation and CO 2 drawdown was driven by the breakup of the supercontinent Nuna and the complexification of algal eukaryotes.
GPT-4o mini: Non-social science research article
Behavioral, experiential, and physiological signatures of mind blanking
Esteban Munoz-Musat, Arthur Le Coz, Andrew W. Corcoran, Laouen Belloli, Lionel Naccache, Thomas Andrillon
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Does being awake necessarily mean being conscious of something? This study investigates the phenomenon of mind blanking (MB), characterized by an “emptiness of mind,” comparing it with mind wandering (MW) and on-task (ON) states. Using a sustained attention task and electroencephalogram monitoring, behavioral, and neurophysiological signatures of MB were examined in 62 participants. MB exhibited a specific pattern of behavioral lapses, as well as decreased fast oscillatory activity and complexity over posterior electrodes compared to MW. Functional connectivity analyses revealed decreased long-range interareal connectivity during MB, compared to both ON and MW states. Event-related potentials with source reconstruction and temporal decoding techniques indicated a significant disruption in visual processing during MB, starting from 200 ms post stimulus and echoing into the late-stage of visual processing, suggesting a disruption of conscious access to sensory information during MB. Electroencephalogram-derived markers allowed the prediction of mental states at the trial level, offering a finer view of conscious dynamics than subjective reports alone. Overall, these findings challenge the notion of the wakeful conscious mind as inherently content-oriented, suggesting that MB reflects genuine gaps in the stream of conscious thoughts, arising from disruptions in the generation or accessibility of thought content.
GPT-4o mini: Non-social science research article
Lab on an end: Micromanipulation using the acoustohydrodynamic pillar array as an end effector
Zhuo Chen, Chenhao Bai, Fengyu Liu, Qiang Huang, Toshio Fukuda, Tatsuo Arai, Xiaoming Liu
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The concept of microfluidics has shown considerable promise for advancing chemistry, diagnostics, and biology. However, there have been no guaranteed routes of microfluidics that can achieve widespread adoption in mainstream chemistry and biomedical research. Inspired by the cooperative multiple cilia of biological organisms and tissues to generate flow, we propose an open microfluidic platform, lab on an end (LoE), to pump spatially and temporally continuous flow for multifunctional micromanipulation with the acoustohydrodynamic pillar array as an end effector. LoE brings together the micromanipulation of individual entities, liquid operations, and cell processing onto an acoustic end effector. These operations are mainly driven by acoustic radiation and two unique frequency-dependent microstreaming profiles: out-of-plane vortex near a single pillar and in-plane transmission flow surrounding the entire pillar array. Applications in embryo engineering, local morphological phenotyping of Caenorhabditis elegans for neuron research, efficient chemical reactions, and multifunctional cell processing indicate that the LoE could potentially lead to breakthroughs in understanding and using microfluidics. Its capability of integrating multiple sequential processes, inherent high accessibility, easy use, and low cost provide an end-to-end solution to mainstream chemistry and biomedical research.
GPT-4o mini: Non-social science research article
Interprotomer communication and functional asymmetry in H/ACA snoRNPs
Hemendra Singh Panwar, Timothy J. Vos, Xiaoyan Xie, H. Josh Jang, Hyoungjoo Lee, Ryan D. Sheldon, Evan J. Worden, Ute Kothe
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H/ACA small nucleolar ribonucleoproteins (H/ACA snoRNPs) facilitate essential cellular processes such as RNA modification, folding, and stability. Here, we present multiple cryo-EM structures of endogenous insect H/ACA snoRNPs containing two protomers assembled on a two-hairpin H/ACA snoRNA. By characterizing key protein–protein and protein–RNA interactions, we reveal the coordination of pseudouridylation activity across the two protomers which explains the predominance of two-hairpin structures in eukaryotic H/ACA snoRNAs. Moreover, we found that several mutations in H/ACA proteins associated with dyskeratosis congenita (DC) directly impair pseudouridine formation suggesting how these mutations disrupt RNA modification and ribosome biogenesis in this disease. Additionally, we uncover coordinated structural changes between Nop10, Nhp2, and the N-terminal extensions of Cbf5 in the 3â€Č protomer that resemble active and inactive conformations and may regulate H/ACA snoRNP activity. In summary, this study provides detailed insight into the structure and function of RNA modification-competent H/ACA snoRNPs, which play pivotal roles in cellular processes including ribosome biogenesis, rRNA folding, (m)RNA modification, and telomere maintenance.
GPT-4o mini: Non-social science research article
Turncoat antibodies unmasked in a model of autoimmune demyelination: From biology to therapy
Reza Taghipour-Mirakmahaleh, Françoise Morin, Yu Zhang, Louis Bourhoven, Louis-Charles Béland, Qun Zhou, Julie Jaworski, Anna Park, Juan Manuel Dominguez, Jacques Corbeil, Eoin P. Flanagan, Romain Marignier, Catherine Larochelle, Steven M. Kerfoot, Luc ValliÚres
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Autoantibodies contribute to many autoimmune diseases, yet there is no approved therapy to neutralize them selectively. A popular mouse model, experimental autoimmune encephalomyelitis (EAE), could serve to develop such a therapy, provided we can better understand the nature and importance of the autoantibodies involved. Here, we report the finding of autoantibody-secreting extrafollicular plasmablasts in EAE induced with specific myelin oligodendrocyte glycoprotein (MOG) antigens. Single-cell RNA sequencing reveals that these cells produce nonaffinity-matured IgG antibodies. These include pathogenic antibodies competing for shared binding space on MOG’s extracellular domain. Interestingly, the synthetic anti-MOG antibody 8-18C5 can prevent the binding of pathogenic antibodies from either EAE mice or people with MOG antibody disease. Moreover, an 8-18C5 variant carrying the NNAS mutation, which inactivates its effector functions, can reduce EAE severity and promote functional recovery. In brief, this study provides not only a comprehensive characterization of the humoral response in EAE models but also a proof of concept for a therapy to antagonize pathogenic anti-MOG antibodies.
GPT-4o mini: Non-social science research article
Flat-band tuning and emergent itinerant magnetism in Sr(Co 1− x Pd x ) 2 As 2
Santanu Pakhira, Yongbin Lee, Asish K. Kundu, Farhan Islam, Zhenhua Ning, Volodymyr Smetana, Anja-Verena Mudring, Thomas Heitmann, Elio Vescovo, Liqin Ke, David Vaknin, David C. Johnston
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The interplay between magnetism and flat-band (FB) instability is a central theme in quantum materials research. A striking example is the emergence of magnetic order in a nominally nonmagnetic compound when a flat band is tuned near the Fermi energy ( E F ). In this study, we investigate this phenomenon in the Pauli paramagnet SrCo 2 As 2 , where an FB associated with Co e g orbitals lies close to E F . Remarkably, a minute substitution of the nonmagnetic element Pd onto the Co site ( ∌ 2%) induces antiferromagnetic order with a transition temperature as high as T N = 25 K. Temperature- and magnetic-field-dependent magnetic and transport measurements, complemented by zero-field neutron diffraction, reveal a helical magnetic order for x ≀ 0.10 in Sr(Co 1− x Pd x ) 2 As 2 , transitioning to a complex ferromagnetic state at higher Pd concentrations. Spectroscopic evidence and theoretical band structure calculations demonstrate that electron doping shifts the flat band closer to E F , significantly enhancing the Stoner parameter. This enhancement drives a strong ferromagnetic instability, leading to helical magnetic ordering dominated by in-plane ferromagnetic interactions. The emergence of robust magnetic ordering through substitution with nonmagnetic elements is a unique phenomenon that underscores the pivotal role of flat-band instability in tuning magnetism in itinerant systems.
GPT-4o mini: Non-social science research article
Learning to learn ecosystems from limited data
Zheng-Meng Zhai, Bryan Glaz, Mulugeta Haile, Alan Hastings, Ying-Cheng Lai
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A fundamental challenge in developing data-driven approaches to ecological systems for tasks such as state estimation and prediction is the paucity of the observational or measurement data. For example, modern machine-learning techniques such as deep learning or reservoir computing typically require a large quantity of data. Leveraging synthetic data from paradigmatic nonlinear but non-ecological dynamical systems, we develop a meta-learning framework with time-delayed feedforward neural networks to predict the long-term behaviors of ecological systems as characterized by their attractors. We show that the framework is capable of accurately reconstructing the “dynamical climate” of the ecological system with limited data. Three benchmark population models in ecology, namely the Hastings-Powell model, its variant, and the Lotka-Volterra system, are used to demonstrate the performance of the meta-learning based prediction framework. In all cases, enhanced accuracy and robustness have been achieved using five to seven times less training data as compared with the corresponding machine-learning method trained solely from the ecosystem data. In addition, two real-world ecological benchmark datasets: the microbial time-series dataset and global population dynamics database, are tested to demonstrate the applicability of the meta-learning framework to the real world. A number of issues affecting the prediction performance are addressed.
GPT-4o mini: Non-social science research article
Molecular mechanism of substrate transport by human peroxisomal ABCD3
Meghna Gupta, Nitesh Kumar Khandelwal, Devin J. Seka, Sree Ganesh Balasubramani, Miles Sasha Dickinson, Alexander Myasnikov, Ignacia Echeverria, Robert M. Stroud
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ATP-binding cassette transporters of the D subfamily (ABCD1-3) mediate the export of CoA thioesters of fatty acids from the cytosol into peroxisomes for further oxidation. ABCD3 facilitates the transport of a broad spectrum of substrates, including branched-chain fatty acids, very long-chain fatty acids, bile salt intermediates, and dicarboxylic acids as CoA adducts. Mutations in ABCD3 are associated with defects in congenital bile acid synthesis. Despite its importance, the basis for substrate selectivity and the mechanism of transport by ABCD3 are not well defined. We report the cryogenic sample electron microscopy (cryo-EM) structures of full-length human ABCD3 in its apo state and bound to one of its physiological substrates (phytanoyl-CoA) at resolutions of 3.33 Å and 3.13 Å, respectively. Our biochemical assays reveal that substrate binding induces ATPase activity in ABCD3, suggesting a substrate-dependent conformational change. Structural comparison of the apo and substrate-bound states demonstrates that the substrate interaction brings nucleotide-binding domains closer together, providing a mechanistic basis of substrate-induced ATPase activity. These findings offer critical insights into the transport mechanism of ABCD3 and lay a structural foundation for understanding its role in peroxisomal metabolite import and related diseases.
GPT-4o mini: Non-social science research article
Sensing the shape of a surface by tightly surface-bound filaments
Handuo Shi, Jeffrey Nguyen, Jordan Alexander Huang, Zemer Gitai, Joshua Shaevitz, Benjamin P. Bratton, Ajay Gopinathan, Gregory Grason, Kerwyn Casey Huang
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Understanding the mechanisms that dictate the localization of cytoskeletal filaments is crucial for elucidating cell shape regulation in prokaryotes. The actin homolog MreB plays a pivotal role in maintaining the shape of many rod-shaped bacteria such as Escherichia coli by directing cell-wall synthesis according to local curvature cues. However, the basis of MreB’s curvature-dependent localization has remained elusive. Here, we develop a biophysical model for the energetics of a filament binding to a surface that integrates the complex interplay between filament twist and bending and the two-dimensional surface geometry. Our model predicts that the spatial localization of a filament like MreB with substantial intrinsic twist is governed by both the mean and Gaussian curvatures of the cell envelope, which strongly covary in rod-shaped cells. Using molecular dynamics simulations to estimate the mechanical properties of MreB filaments, we show that their thermodynamic preference for regions with lower mean and Gaussian curvatures matches experimental observations for physiologically relevant filament lengths of ~50 nm. We find that the experimentally measured statistical curvature preference is maintained in the absence of filament motion and after a cycle of depolymerization, repolymerization, and membrane rebinding, indicating that equilibrium energetics can explain MreB localization. These findings provide critical insights into the physical principles underlying cytoskeletal filament localization and suggest design principles for synthetic shape-sensing nanomaterials.
GPT-4o mini: Non-social science research article
Heavy-tailed update distributions arise from information-driven self-organization in nonequilibrium learning
Xin-Ya Zhang, Chao Tang
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Like human decision-making under real-world constraints, artificial neural networks may balance free exploration in parameter space with task-relevant adaptation. In this study, we identify consistent signatures of criticality during neural network training and provide theoretical evidence that such scaling behavior arises naturally from information-driven self-organization: a dynamic balance between the maximum entropy principle that promotes unbiased exploration and mutual information constraint that relates updates with task objective. We numerically demonstrate that the power-law exponent of updates remains stable throughout training, supporting the presence of self-organized criticality. Furthermore, we show that the loss landscape exhibits exponential ruggedness under small perturbations, transitioning to power-law ruggedness at larger scales, in the absence of mini-batch noise, indicating an intrinsic geometric landscape. We also observe a power-law distribution in the intervals between large updates, indicating an intermittent learning process. Together, these findings suggest that neural network learning reflects a nonequilibrium process governed by the fundamental trade-off between randomness and relevance, highlighting its dynamic nature and offering insights into the interpretability of AI systems.
GPT-4o mini: Non-social science research article
Proteasome stress activates YAP/TAZ through the RAP2–MAP4Ks–LATS1/2 pathway and its therapeutic implications in solid tumors
Xin Wang, Yuan Gu, Zhenxing Zhong, Pengcheng Yu, Wenshuai Liu, Rui Zhu, Yu Wang, Zhaocai Zhou, Yihong Sun, Xuefei Wang, Fa-Xing Yu
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Tumor cells heavily depend on proteasome-mediated protein turnover, making the proteasome an attractive therapeutic target. Clinically, proteasome inhibitors are effective against hematologic cancers but show limited success with solid tumors, and the reasons for this difference are not well understood. Activation of yes-associated protein (YAP)/TAZ, the downstream effectors of the Hippo pathway, is a key mechanism behind drug resistance in cancers. Here, we demonstrate that proteasome stress acts as an upstream signal of the Hippo pathway in solid tumor cells. When the proteasome is inhibited, RAP2 undergoes ubiquitination and becomes inactive, which in turn disrupts the RAP2–MAP4Ks–NF2–LATS1/2 signaling pathway, leading to the activation of YAP/TAZ. YAP/TAZ activation promotes cell survival and resistance to proteasome inhibitors. Conversely, blocking YAP/TAZ can overcome this resistance and restore cancer cell sensitivity to these drugs. In diffuse-type gastric cancer—an aggressive solid tumor with a poor prognosis and limited treatment options—combined inhibition of the proteasome and YAP/TAZ effectively suppresses tumor growth. Therefore, this study identifies proteasome stress as an upstream signal of the Hippo pathway and provides a mechanistic basis for combination cancer therapy.
GPT-4o mini: Non-social science research article
PIP 2 corrects an endothelial Piezo1 channelopathy
Ahmed M. Hashad, Mohammad M. Abd-Alhaseeb, Xin Rui Lim, Natalia M. Mathieu, Osama F. Harraz
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Brain capillaries are sensors of neural activity. When a brain region is active, capillary endothelial cells (ECs) sense neuron-derived mediators and elicit a local increase in blood flow (functional hyperemia) to support the rise in metabolic needs. This hyperemic response involves a rapid electrical component and a slower chemical component that involves Gαq PCR (G q PCR) activation by agonists released from neurons. The intravascular forces associated with hyperemia engage mechanosensitive Piezo1-mediated signaling that serves a mechano-feedback control function to facilitate the return of elevated blood flow to basal levels. Whether G q PCR activity influences Piezo1 mechanosensitive signaling has not been explored, despite the potential significant implications of such crosstalk. Using patch-clamp electrophysiology and freshly isolated brain capillary ECs, we demonstrate that prostanoid or muscarinic G q PCR activation facilitates Piezo1 activity. Pharmacological studies revealed the involvement of Gαq and phospholipase C stimulation, as well as downstream phosphatidylinositol-4,5-bisphosphate (PIP 2 ) hydrolysis in Piezo1 activation, but not signaling triggered by metabolites of PIP 2 hydrolysis. Exogenous application of nanomolar-to-micromolar PIP 2 suppressed Piezo1 open probability. Brain capillary ECs from mouse models of Alzheimer’s disease, cerebral small vessel disease, or Piezo1 gain-of-function mutation exhibited higher Piezo1 activity, that was corrected by exogenous ex vivo PIP 2 application. We finally tested in vivo the hypothesis that systemic PIP 2 administration restores functional hyperemia in EC-specific Piezo1 gain-of-function mutant mice suffering impaired blood flow. Our findings provide insights into Piezo1 channel regulation and how it affects neurovascular coupling and cerebral blood flow.
Heterogeneous conditions and power law robustness in intergenerational resource transfers
Matthew A. Cheung, Simon A. Levin
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Organisms in nature and humans in socioeconomic systems alike face tradeoffs between selfish consumption of resources and investment in the welfare of their offspring. Previous work across the disciplines of biology and economics has sought to elucidate this process, develop a theoretical framework to solve for the optimal life history strategy, and deduce implications of these microscopic interactions for the distribution of resources at the macroscopic level. Such theory, however, has failed to account for heterogeneous conditions that various individuals and groupings of kin enjoy, like growth rate advantages for those with greater resource abundance. Furthermore, such emergent trends at the macroeconomic scale lack reconciliation with observations of power law distributions of wealth and income in vivo. We modify and extend an analytical framework here to allow for heterogeneity, and consider the long-term consequences for resource distributions with Pareto initial values. We find that power law phenomena are robust to such processes and, due to sensitivity to the form of the utility curve, higher-order uncertainty may not affect the optimal tradeoff. This stresses the impact of mechanistic choices when translating sociological findings to ecological and economic theory, and suggests future work must consider how social norms and other microscopic complexity can explain emergent patterns or disrupt trends of inequality at the macrolevel.

Science

GPT-4o mini: Non-social science research article
AQP5: A functional gastric cancer stem cell marker in mouse and human tumors
Hui Yi Grace Lim, Swathi Yada, Kazuhiro Murakami, Bernett Teck Kwong Lee, Sowmya Sagiraju, Phyllis Phuah, Tanysha Chi-Ying Chen, Fidelia B. Alvina, Si Hui Tan, Kaushal Krishna Kaslikar, Nur Syahirah Binte Ruhazat, Menaka Priyadharsani Rajapakse, Katzrin Bte Ahmad Murad, Snezhina Kancheva, Liang Thing Tan, Seri Mustafah, Jimmy Bok Yan So, Nick Barker
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Cancer stem cells (CSCs) represent a self-renewing population capable of fueling long-term tumor growth. In gastric cancer, the identity of CSC populations remains unclear. In this study, we established a gastric CSC population marked by the water channel protein aquaporin-5 (AQP5), which resides in human and mouse pyloric tumors. Using multiple organoid and mouse models, we found a requirement for AQP5 + CSCs in both initiating and sustaining cancer progression and demonstrated that AQP5 expression also directly promotes tumor growth and invasion in a WNT, PI3K (phosphatidylinositol 3-kinase), and MAPK (mitogen-activated protein kinase)–dependent manner. Beyond primary cancers, AQP5 further enriches for a functional CSC population in metastatic tumors. Together, our findings support a CSC model in gastric tumors that may have application for therapeutic strategies targeting CSCs.
GPT-4o mini: Non-social science research article
Risks of per- and polyfluoroalkyl substance exposure through marine fish consumption
Wenhui Qiu, Ge Yang, Ling Cao, Shan Niu, Yuzhe Li, Di Fang, Zhaomin Dong, Jason T. Magnuson, Daniel Schlenk, Kenneth M. Y. Leung, Yi Zheng, Zhenzhong Zeng, Lian Feng, Xianming Zhang, Yanxu Zhang, Wenhong Fan, Tao Huang, Jianmin Ma, Minghong Wu, Shu Tao, Chunmiao Zheng
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Global food trade expansion has enriched diets worldwide but also heightened concerns about contaminant spread. Per- and polyfluoroalkyl substances (PFAS) can persist in the environment for decades, yet their risks through food trade remain unclear. The global median estimated daily intake (EDI) of C8-PFAS (perfluorooctanoic acid and perfluorooctane sulfonate) (0.023 nanograms per kilograms per day) was mapped from 212 marine fish species, which indicated higher EDIs in North America, Oceania, and Europe. Furthermore, European countries play a pivotal role in C8-PFAS trade flows, markedly reshaping exposure pathways and driving increased exposure in many nations. These dynamics highlight the importance of establishing food-safety regulations and international trade standards. Although perfluorooctane sulfonate hazard index decreased by 72% after its 2009 regulations, unregulated long-chain PFAS continue to pose elevated risks.
GPT-4o mini: Non-social science research article
Optimal perovskite vapor partitioning on textured silicon for high-stability tandem solar cells
Nengxu Li, Xiuxiu Niu, Zijing Dong, Jingcong Hu, Ran Luo, Shuihua Yang, Qilin Zhou, Zhuojie Shi, Jinxi Chen, Xinyi Du, Ling Kai Lee, Yuduan Wang, Xiao Guo, Xi Wang, Cheng-Wei Qiu, Ming Lin, Rui He, Xueling Zhang, Yifeng Chen, Mengfei Wu, Yi Hou
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Achieving conformal, vapor-deposited perovskite films on industry-standard textured silicon substrates with micrometer-scale pyramids remains challenging because of the complex surface partitioning of perovskite vapors and the effects of nonequilibrium organic and inorganic vapor adsorption. We incorporated 3,3,3-trifluoropropyl-trimethoxysilane to enhance substrate-organic interactions, thereby optimizing surface partitioning and balancing adsorption of perovskite vapors. Vertically uniform perovskite films with minimal phase impurities formed, and nanobeam diffraction confirmed formation of the perovskite cubic phase across different pyramid regions. The resulting tandem devices achieved a power conversion efficiency of 31.3% (1 square centimeter aperture area) and exhibited excellent operational stability, retaining 90% of their initial performance after 1400 hours of continuous 1-sun illumination at 85°C.
GPT-4o mini: Non-social science research article
Ancient genomes illuminate the origins and dynamic history of East Asian cattle
Dawei Cai, Donghee Kim, Naifan Zhang, Xingcheng Wang, Tianshu Li, Jian Li, Chang Li, Shengnan Lian, Xinyue Shao, Songmei Hu, Miaomiao Yang, Jie Zhang, Yongqiang Wang, Qiurong Ruan, Idilisi Abuduresule, Linheng Mo, Wenyan Li, Xiaoning Guo, Wenying Li, Jing Shao, Zhouyong Sun, Yaqi Tian, Hui Wang, Ruilin Mao, Cunshi Zhu, Xiaoyang Wang, Xiaoyan Ren, Weilin Wang, Yan Ding, Pengcheng Zhang, Liping Yang, Jianen Cao, Yu Dang, Da Ha, Wei Zhang, Linshan He, Chunxue Wang, Lixin Wang, Quanchao Zhang, Jing Yuan, Xiaohong Wu, Chao Ning, Choongwon Jeong
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The evolutionary history of domesticated cattle in East Asia for the past 5000 years remains largely obscure. Here, we investigated the origins and evolution of cattle genetic diversity in China by analyzing shotgun genome sequences of 166 ancient bovines spanning a 10,000-year period and encompassing now-extinct East Asian aurochs and domesticated cattle from key archaeological cultures. East and North Asian aurochs were distinct from western aurochs, although East Asian aurochs harbored approximately 15% western ancestry. The first domesticated cattle in the Yellow River region derived approximately 10% of their ancestry from local aurochs with an uneven genome-wide distribution. Early cattle from Xinjiang were genetically distinct and partially contributed to the later northern Chinese cattle. Indicine admixture became widespread only in the Medieval period in northern China.
GPT-4o mini: Non-social science research article
Electrode strain dynamics in layered intercalation battery cathodes
Tianxiao Sun, Guannan Qian, Ruqing Fang, Guibin Zan, Zhichen Xue, Stephen E. Trask, Arturo Gutierrez, Wenlong Li, Shimao Deng, Luxi Li, Wenbing Yun, Piero Pianetta, Guihua Yu, Jason R. Croy, William C. Chueh, Juner Zhu, Yijin Liu
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Rechargeable batteries using electrodes based on intercalation chemistry exhibit notable cyclability, yet their performance still suffers from chemomechanical degradation. In this study, by combining a suite of operando microscopy methods, we explored electrode strain evolution and observed intricate particle cluster rearrangement under electrochemical stimuli. We show that early-stage strain accumulation in intercalation cathodes occurs during the period of interparticle charge transfer and redox reactions stemming from asynchronous coupling and decoupling between chemical (de)intercalation and physical grain motion. This interplay drives heterogeneous redox activity, localized charge equilibration, and multiscale strain cascades that propagate through an asynchronous network of chemical-mechanical interactions. Together, these findings reveal how collective particle dynamics and hierarchical strain transmission dictate electrode deformation and degradation in intercalation cathodes.
GPT-4o mini: Non-social science research article
Extending the temperature range of the Cmcm phase of SnSe for high thermoelectric performance
Tian Gao, Yi Wen, Shulin Bai, Lizhong Su, Haonan Shi, Rong Liu, Sining Wang, Yixuan Hu, Shibo Liu, Dongrui Liu, Shan Liu, Chao Liang, Xiaokun Feng, Xiaoqian Wang, Yongxin Qin, Xiang Gao, Bingchao Qin, Cheng Chang, Peikang Bai, Li-Dong Zhao
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Thermoelectric power generation requires high dimensionless figure of merit ZT across broad temperatures. The two-dimensional phonon and three-dimensional charge transports enable n-type– Pnma tin selenide (SnSe) crystals to show a peak ZT of ~3.0 at 748 kelvin. In this work, we focused on the high-symmetry Cmcm phase to boost two-dimensional phonon and three-dimensional charge transports and extended the high-performance ( ZT ~ 3.0) plateau. By simultaneously broadening the Cmcm -phase stability window and enhancing lattice symmetry through lead alloying, we extended the high performance from a single temperature point to a wide temperature range of ~250 kelvin in rock salt–like Cmcm SnSe crystals rendered n-type through chlorine doping. An average ZT of ~3.0 was achieved between 673 and 923 kelvin, with a conversion efficiency of ~19.1% under a temperature difference of ~572 kelvin.
GPT-4o mini: Non-social science research article
High-throughput single cell omics using semipermeable capsules
Denis Baronas, Simonas Norvaisis, Justina Zvirblyte, Greta Leonaviciene, Vincenta Mikulenaite, Karolis Goda, Vytautas Kaseta, Karolis Sablauskas, Laimonas Griskevicius, Simonas Juzenas, Linas Mazutis
Full text
Biological systems are inherently complex and heterogeneous. Deciphering this complexity increasingly relies on high-throughput single-cell omics methods and tools that efficiently probe the cellular phenotype and genotype. Here we present a versatile technology based on semipermeable capsules (SPCs), tailored for a variety of high-throughput nucleic acid assays, including single-cell genome and mRNA sequencing, and fluorescence-activated cell sorting-based isolation of individual transcriptomes based on nucleic acid marker of interest. Being biocompatible, the SPCs support single-cell cultivation and clonal expansion over long periods of time thereby overcoming a fundamental limitation of droplet microfluidics platforms. Overall, the SPCs represent customizable and broadly applicable tool for easy-to-use, scalable single-cell omics applications that are built on multi-step biochemical reactions.
GPT-4o mini: Non-social science research article
Conformational landscape adaptations enable processive phosphorylation by Src family kinases
Yixin Cui, Rustam Ali, Mary Clay, Paolo Rossi, Aizhuo Liu, Darong Yang, Nancy R. Gough, Terrence Geiger, Charalampos G. Kalodimos
Full text
Processive phosphorylation by kinases enables the rapid multisite modification of signaling hubs, serving to integrate signals during time-sensitive cellular events. To achieve processivity, multiple catalytic cycles must occur before substrate dissociation, making rapid turnover rates essential. Src family kinases processively phosphorylate multisite substrates. Using nuclear magnetic resonance spectroscopy, we identified a transient intermediate state within the Src conformational ensemble, positioned between its active and inactive states. This intermediate state facilitates the rapid release of adenosine diphosphate following adenosine triphosphate hydrolysis, ensuring efficient catalytic turnover. Depletion of the intermediate state abrogated processive phosphorylation by Src, Lck, and Hck, impairing function. These findings reveal that the conformational ensemble of Src family kinases has evolved to incorporate a transient state that underpins their capacity for processive substrate phosphorylation.
GPT-4o mini: Non-social science research article
State-independent ionic conductivity
J. Barclay, J. M. Williamson, H. Litt, S. J. Cowling, K. Shimizu, A. A. Freitas, S. Poppe, J. Sturala, Y. Sun, M. Kohout, A.-J. Avestro, J. N. Canongia Lopes, C. Groves, J. C. Jones, P. R. McGonigal
Full text
Liquids lend themselves to high ionic conductivities because of their molecular-level positional and orientational disorder, which enables the free movement of ions. However, there is an unavoidable steep drop in ionic conductivity upon phase transition from a fluid state to the more ordered solid state. Here, we describe organic salts that maintain the same ionic conductivity mechanism across transitions between three states of matter, from an initial isotropic liquid to a liquid crystalline state and then to a crystalline solid. We achieved this property by minimizing the ion-pairing interactions between mobile ions and highly diffuse counterions that assemble in a stepwise manner to preserve conformational flexibility across phase transitions. This state-independent ionic conductivity opens up opportunities to exploit liquid-like ionic conductivity in organic solids.
GPT-4o mini: Non-social science research article
All-optical synthesis chip for large-scale intelligent semantic vision generation
Yitong Chen, Xinyue Sun, Longtao Tan, Yizhou Jiang, Yin Zhou, Wenjun Zhang, Guangtao Zhai
Full text
Large-scale generative artificial intelligence (AI) is facing a severe computing power shortage. Although photonic computing achieves excellence in decision tasks, its application in generative tasks remains formidable because of limited integration scale, time-consuming dimension conversions, and ground-truth-dependent training algorithms. We produced an all-optical chip for large-scale intelligent vision generation, named LightGen. By integrating millions of photonic neurons on a chip, varying network dimension through proposed optical latent space, and Bayes-based training algorithms, LightGen experimentally implemented high-resolution semantic image generation, denoising, style transfer, three-dimensional generation, and manipulation. Its measured end-to-end computing speed and energy efficiency were each more than two orders of magnitude greater than those of state-of-the-art electronic chips, paving the way for acceleration of large visual generative models.
GPT-4o mini: Non-social science research article
A second planetesimal collision in the Fomalhaut system
Paul Kalas, Jason J. Wang, Maxwell A. Millar-Blanchaer, Bin B. Ren, Mark C. Wyatt, Grant M. Kennedy, Maximilian Sommer, Thomas M. Esposito, Robert J. De Rosa, Michael Fitzgerald
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The nearby star Fomalhaut is orbited by a compact source, Fomalhaut b, which has previously been interpreted as either a dust-enshrouded exoplanet or a dust cloud generated by the collision of two planetesimals. Such collisions are rarely observed but their debris can appear in direct imaging. We report Hubble Space Telescope observations that show the appearance in 2023 of a second point source around Fomalhaut, resembling the appearance of Fomalhaut b twenty years earlier. We interpret this additional source as a dust cloud produced by a recent impact between two planetesimals. The positions and motion of two impact-generated dust clouds over twenty years provide constraints on the collisional dynamics in the debris belt.
GPT-4o mini: Non-social science research article
Here comes the Sun
H. Holden Thorp
Full text
Even though 2025 presented many troubling challenges for science, there was a bright spot: It was the first year in which more power was generated worldwide from renewable energy, including wind and solar, than from coal. The situation came very close to “peak carbon,” the point at which fossil fuel emissions peak for the world and then start to decline. That milestone may now be only a few years away. These encouraging changes were mainly a result of the greater availability of solar and wind energy technology and cheaper lithium batteries to run electric cars and store solar energy. Because of these achievements, Science has selected “Rise of the Renewables” as its Breakthrough of the Year.
GPT-4o mini: Non-social science research article
Extreme plate boundary localization promotes shallow earthquake slip at the Japan Trench
J. D. Kirkpatrick, H. M. Savage, C. Regalla, S. Shreedharan, C. Ross, H. Okuda, U. Nicholson, K. Ujiie, R. Hackney, M. Conin, P. Pei, S. Satolli, J. Zhang, P. Fulton, M. Ikari, S. Kodaira, L. Maeda, N. Okutsu, S. Toczko, N. Eguchi, character(0), P. Bellanova, C. Brown, M. Brunet, M. R. Castillo, Y.-C. Chang, M.-L. Doan, J. Everard, A. Fintel, J. Ford, R. Fukuchi, A. Gough, H. Guo, D. GĂŒrer, M. Hagino, Y. Hamada, H. Hosono, M.J. Jurado, A. Ijiri, T. Ishikawa, M. Iwai, T. Jeppson, N. Kamiya, T. Kanamatsu, A. LaPlante, W. Lin, A. Miyakawa, Y. Morono, Y. Nakamura, C. Pizer, T. Rasbury, R. Robertson, K. Schaible, H. Sone, C. Sun, T. Uchida, P. Vannucchi, A. Yamaguchi, Y. Yamamoto, T. Yoshimoto
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The 2011 Mw9.1 Tohoku-oki earthquake is exceptional among great earthquakes for having peak slip of ~50-70 m on the shallowest portion of the plate boundary megathrust. Drill cores and geophysical logs from International Ocean Discovery Program Expedition 405 demonstrate that the megathrust preferentially develops at the top or base of the pelagic clay in the sedimentary layers present on the incoming Pacific Plate, where pronounced contrasts in physical properties occur. This results in a narrow, weak fault located at a major mechanical contact between frontal prism mud and subducted sediments, which enhances the tendency for shallow seismic slip, suggesting the Japan Trench may be more susceptible to ruptures with large shallow slip than margins without weak clays.
GPT-4o mini: Non-social science research article
A cellular basis for heightened gut sensitivity in females
Archana Venkataraman, Eric E. Figueroa, Joel Castro, Fernanda Castro Navarro, Deepanshu Soota, Stuart M. Brierley, David Julius, Holly A. Ingraham
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Visceral pain disorders, such as irritable bowel syndrome, exhibit a marked female prevalence. Enhanced signaling between enterochromaffin (EC) cells in the gut epithelium and mucosal sensory nerve fibers likely contributes to this sex bias. We identified an estrogen-responsive paracrine pathway in which two enteroendocrine cell types, peptide YY (PYY)–expressing L cells and serotonergic EC cells, communicate to increase gut sensitivity in females. We demonstrate that estrogen signaling up-regulates the bacterial metabolite short-chain fatty acid receptor Olfr78 on colonic L cells, increasing PYY release and their sensitivity to acetate. Elevated PYY acts on neighboring EC cells by means of NPY1R, thereby enhancing serotonin release and gut pain. We propose that hormonal fluctuations, in conjunction with internal (stress) or environmental (diet) factors, amplify this local estrogen-responsive colonic circuit, resulting in maladaptive gut sensitivity.
GPT-4o mini: Non-social science research article
Xanthomonas coordinates type III–type II effector synergy by activating fruit-ripening pathway
Trang Thi-Thu Phan, Rodrigo Silva Araujo Streit, Gerald V. Minsavage, Joachim Kilian, Paloma de los Angeles Aguilera, Nan Wang, Nicolas Brich, Robert Morbitzer, Edda von Roepenack-Lahaye, Brice Charleux, Boris Szurek, Priscila Oliveira de Giuseppe, Concetta Licciardello, Jeffrey B. Jones, Paulo J. P. L. Teixeira, Gabriela Felix Persinoti, Mario Tyago Murakami, Chang Liu, Jan Grau, Thomas Lahaye
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Plant cell walls harbor vast carbohydrate reserves, yet how pathogens unlock them remains unclear. We show that the citrus canker pathogen Xanthomonas citri subsp. citri ( Xcc ) mobilizes cell wall sugars by hijacking a fruit-ripening program through the type III effector PthA4, which activates the ripening coordinator CsLOB1. CsLOB1 induces approximately 100 genes, many encoding enzymes involved in cell wall breakdown. In the nonfruiting species Nicotiana benthamiana , CsLOB1 likewise promotes Xanthomonas growth, showing that its activity is not strictly dependent on a ripening program. Transcriptomics and reporter assays revealed PthA4-dependent activation of the Xcc xylan CUT system, triggered by host-derived xylose and including a type II–secreted xylanase. Thus, PthA4-driven cell wall remodeling activates bacterial xylan use, establishing a TIII–TII effector feedforward loop that fuels Xcc proliferation.
GPT-4o mini: Non-social science research article
Chromatin buffers torsional stress during transcription
Jin Qian, Lucyna Lubkowska, Shuming Zhang, Chuang Tan, Yifeng Hong, Xiaomeng Jia, Robert M. Fulbright, James T. Inman, Taryn M. Kay, Joshua Jeong, Glenn Hauk, Deanna Gotte, James M. Berger, Mikhail Kashlev, Michelle D. Wang
Full text
During eukaryotic transcription, Pol II must overcome nucleosome obstacles and, because of DNA’s helical structure, must also rotate relative to DNA, generating torsional stress. However, there is limited understanding of how Pol II transcribes through nucleosomes while supercoiling DNA. Here, we determined that Pol II generates a torque of 9 pN·nm alone and 13 pN·nm with TFIIS, making it a powerful rotary motor. When Pol II encounters a nucleosome, passage becomes more efficient on a chromatin substrate than on a single-nucleosome substrate, demonstrating that chromatin significantly buffers torsional stress during transcription. Furthermore, topoisomerase supercoiling relaxation allows Pol II to transcribe through multiple nucleosomes. Our results reveal a role of chromatin beyond the more conventional view of it being just a roadblock to transcription.
GPT-4o mini: Non-social science research article
Multistep genomics on single cells and live cultures in subnanoliter capsules
Ignas Mazelis, Haoxiang Sun, Arpita Kulkarni, Theresa L. Torre, Allon M. Klein
Full text
Single-cell sequencing methods uncover natural and induced variation between cells. Many functional genomic methods, however, require multiple steps that cannot yet be scaled to high throughput, including assays on living cells. Here we develop capsules with amphiphilic gel envelopes (CAGEs), which selectively retain cells and large analytes while being freely accessible to media, enzymes and reagents. Capsules enable high-throughput multistep assays combining live-cell culture with genome-wide readouts. We establish methods for barcoding CAGE DNA libraries, and apply them to measure persistence of gene expression programs in cells by capturing the transcriptomes of tens of thousands of expanding clones in CAGEs. The compatibility of CAGEs with diverse enzymatic reactions will facilitate the expansion of the current repertoire of single-cell, high-throughput measurements and their extension to live-cell assays.
GPT-4o mini: Non-social science research article
Carbonated ultramafic igneous rocks in Jezero crater, Mars
Kenneth H. Williford, Kenneth A. Farley, Briony H.N. Horgan, Brad Garczynski, Allan H. Treiman, Sanjeev Gupta, Alexander J. Jones, Sandra Siljeström, Elise ClavĂ©, Lisa Mayhew, Jeffrey T. Osterhout, Eleni Ravanis, Kathryn M. Stack, Sarah Fagents, Candice C. Bedford, Tanja Bosak, Sergei V. Bykov, David Flannery, Kevin P. Hand, Michael W. M. Jones, Linda Kah, Athanasios Klidaras, Justin Maki, Lucia Mandon, Elias Mansbach, Francis M. McCubbin, Justin I. Simon, Anushree Srivastava, Kyle Uckert, Roger C. Wiens, Sanna Alwmark, Julene Aramendia, Robert Barnes, Pierre Beck, James F. Bell, Sylvain Bernard, Rohit Bhartia, Michael S. Bramble, Adrian J. Brown, Adrian Broz, Denise Buckner, David C. Catling, Edward Cloutis, Stephanie Connell, Andrea Corpolongo, Andrew D. Czaja, Erwin Dehouck, Teresa Fornaro, Olivier Forni, Nikole C. Haney, Keyron Hickman-Lewis, William Hug, Ari Koeppel, Juan Manuel Madariaga, JesĂșs MartĂ­nez-FrĂ­as, Jorge I. NĂșñez, Brendan J. Orenstein, Yu Yu Phua, Cedric Pilorget, Nicolas Randazzo, ClĂ©ment Royer, Eva L. Scheller, Nicole Schmitz, Susanne Schröder, Mark A. Sephton, Shiv Sharma, Sunanda Sharma, David Shuster, Kimberly P. Sinclair, Andrew Steele, Christian Tate, Benjamin Weiss, Amy J. Williams, Z. Uriah Wolf, R. Aileen Yingst
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The Perseverance rover landed in Jezero crater on Mars, which once contained a lake of liquid water. We report the rock properties encountered by Perseverance during a ten-kilometer traverse extending over 400 meters in elevation, from beneath Jezero's western sedimentary fan to the upper crater rim. These rocks consist of coarse-grained olivine, magnesium- and iron-carbonates, silica, and phyllosilicates, including some of the oldest materials exposed within Jezero. We infer these rocks formed by olivine accumulation in an igneous system of layered intrusions, followed by exposure to water and carbon dioxide that caused extensive carbonation of the silicate minerals. Aqueous alteroverlingation is more pronounced at lower elevations. Higher elevation exposures on the crater rim appear similar to olivine-rich rocks distributed over the wider Nili Fossae region.
GPT-4o mini: Non-social science research article
Trifluoromethylation of alkyl electrophiles with 11 C- or 18 F-labeled fluoroform for PET applications
Chao Wang, Paul DeMent, Susovan Jana, Jinsoo Hong, Victor W. Pike, Wei Liu
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Continued development of positron emission tomography (PET) tracers is essential for advancing molecular imaging in biomedical research and clinical diagnostics. A long-standing limitation in radiochemistry for PET imaging has been the lack of general methods for radiolabeling trifluoromethyl (CF 3 ) groups at C(sp 3 ) sites, despite their growing prevalence in bioactive molecules and radiopharmaceuticals. Here, we present a general approach for late-stage installation of either a [ 18 F]CF 3 or [ 11 C]CF 3 group at a C(sp 3 ) site. This method leverages unusual copper-mediated radiotrifluoromethylation of alkyl halides and alkyl carboxylic acids by halogen atom transfer and photoredox catalysis, respectively. More than 50 complex molecules and pharmaceutical agents were efficiently labeled with fluorine-18 ( 18 F) or carbon-11 ( 11 C). Two long-sought-after radioligands, [ 18 F]SL25.1188 and [ 18 F]PS13, were synthesized, providing longer-lived 18 F analogs of their 11 C counterparts with great promise for human PET imaging.
GPT-4o mini: Non-social science research article
A bacterial nutrition strategy for plant disease control
Shanzhi Wang, Lisong Zhu, Meng Tian, Wenyi Wu, Xu Hu, Xuan Li, Jiyang Wang, Ying Zhu, Jiaqing Xu, Baohui Mou, Jiyun Yang, Fuhao Cui, Dayong Li, Jie Cheng, Zhilong Liu, Ming-An Wang, Linlu Qi, Weiwei Jin, Zhao-Qing Luo, Pei Zhou, Yong-Hwan Lee, Brian Staskawicz, Sheng Yang He, Wenxian Sun
Full text
Xanthomonas spp. cause serious diseases in more than 400 plant species. The conserved AvrBs2 family effectors are among the most important virulence factors in xanthomonads, but how AvrBs2 promotes infection remains elusive. We found that AvrBs2 is a glycerophosphodiesterase-derived synthetase that catalyzes uridine 5â€Č-diphosphate-α- d -galactose into a sugar phosphodiester, bis-(1,6)-cyclic dimeric α- d -galactose-phosphate, which is referred to as xanthosan. Xanthosan is synthesized by AvrBs2 in host cells and released into apoplastic spaces. Xanthomonas bacteria uptake xanthosan through the XanT transporter and hydrolyze it through the XanP phosphodiesterase for nutrition. AvrBs2, XanT, and XanP form a xanthosan “generation-uptake-utilization” system to provide a dedicated nutritional strategy to feed xanthomonads. Furthermore, elucidation of the AvrBs2-XanT-XanP virulence mechanism inspired us to develop an “anti-nutrition” strategy that should be applicable to control a wide variety of Xanthomonas diseases.
GPT-4o mini: Non-social science research article
A human pan-disease blood atlas of the circulating proteome
MarĂ­a Bueno Álvez, Sofia Bergström, Josefin Kenrick, Emil Johansson, Mikael Åberg, Murat Akyildiz, Ozlem Altay, Hilda Sköld, Konstantinos Antonopoulos, Emmanouil Apostolakis, Yasin Hasan Balcioglu, Anna Bergström, Göran Bergström, Sophia Björkander, Suzanne Egyhazi Brage, Petter Brodin, Lynn Butler, Sara Cajander, Hanna Danielsson, Murat Dayangac, Gizem Dinler-Doganay, Levent Doğanay, Gunilla Enblad, Malin Enblad, Linn Fagerberg, Sara Falck-Jones, Anna FĂ€rnert, Mattias Forsberg, Laura Gonzalez, Anders Gummesson, Karin Gunnarsson, Iva Gunnarsson, Ulf Gyllensten, Göran Hesselager, Andreas Hober, Martin Höglund, Marie Holmqvist, Begum Horuluoglu, Rebecka Hultgren, Maria Jesus Iglesias, Helena Janols, Fredric Johansson, Anette Johnsson, Lars Klareskog, David Kotol, Inger Kull, Marika Kvarnström, Maximilian Julius Lautenbach, Ulrika Liljedahl, Henrik Lindman, Cecilia Lindskog, Miklos Lipcsey, Ingrid E. Lundberg, Adil Mardinoglu, Erik MelĂ©n, Lingqi Meng, Anne-Sophie Merritt, Jan Mulder, Mai Thi-Huyen Nguyen, Jessica Nordlund, Anna Norrby-Teglund, Antonella Notarnicola, Piotr Nowak, Jacob Odeberg, Per Oksvold, Tomas Olsson, Leonid Padyukov, Karlis Pauksens, Fredrik Piehl, Elisa Pin, Fredrik PontĂ©n, Natallia Rameika, Anton Reepalu, Joy Roy, Jochen M. Schwenk, Meltem Sen, Antti Siika, Oscar E. Simonson, Åsa Sivertsson, Tobias Sjöblom, Evelina Sjöstedt, Lovisa Skoglund, Anna Smed-Sörensen, Klara SondĂ©n, Anders Sönnerborg, Karin StĂ„lberg, Kristoffer StrĂ„lin, Jonas SundĂ©n-Cullberg, Christopher Sundling, Thanadol Sutantiwanichkul, Fernanda Costa Svedman, Mattias Svensson, Elisabet Svenungsson, Tadepally Lakshmikanth, Khue Hua Tran-Minh, Hasan TĂŒrkez, Christian Unge, Per Venge, Marie Wahren-Herlenius, Jakob Woessmann, Hong Yang, Umit Haluk Yeßilkaya, Meng Yuan, Mujdat Zeybel, Cheng Zhang, Wen Zhong, Martin Zwahlen, Kalle von Feilitzen, Peter Nilsson, Fredrik Edfors, Mathias UhlĂ©n
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The human blood proteome provides a holistic readout of health states through the assessment of thousands of circulating proteins. In this study, we present a pan-disease resource to enable the study of diverse disease phenotypes within a harmonized proteomics dataset. By profiling protein concentrations across 59 diseases and healthy cohorts, we identified proteins associated with age, sex, and body mass index, as well as disease-specific signatures. This study highlights shared and distinct protein patterns across conditions, demonstrating the power of a unified proteomics approach to uncover biological insights. The dataset, covering 8262 individuals and up to 5416 proteins, serves as an online resource for exploring disease-specific protein profiles and advancing precision medicine research.
GPT-4o mini: Non-social science research article
Intracellular competition shapes plasmid population dynamics
Fernando Rossine, Carlos Sanchez, Daniel Eaton, Johan Paulsson, Michael Baym
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From populations of multicellular organisms to selfish genetic elements, conflicts between levels of biological organization are central to evolution. Plasmids are extrachromosomal, self-replicating genetic elements that face selective pressures from their hosts but also compete within the host cell for replication resources. Although theory indicates that within-cell selection matters for plasmid evolution, experimental measurement of these dynamics has remained elusive. We measured within-cell fitness of competing Escherichia coli plasmids and characterized their drift and selective dynamics. We made synthetic plasmid dimers that can be split in a controlled way to create balanced competition, which we probed experimentally. Incompatible plasmids coexist for an extended time owing to methylation-based replication control. Moreover, less transcriptionally active plasmids display a within-cell advantage and fix preferentially, favoring gene loss. Critically, fixation depends nontrivially on the interplay between plasmid transcription and translation. Our results show that plasmid evolution is driven by within- and between-cell dynamics.
Science abstract < 200 char.: Not a research article
In Other Journals
Jesse Smith, Di Jiang, Priscilla N. Kelly, Sarah LempriĂšre, Joana OsĂłrio, Brad Wible, Jelena Stajic
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
Seafloor telecom cable turned into giant earthquake detector
Paul Voosen
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Dense seismic array more than 4000 kilometers long promises new views of Earth’s interior
Science abstract < 200 char.: Not a research article
New materials could supercharge computer memory chips
Robert F. Service
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Ferroelectrics could bolster “flash” memory in AI data centers and autonomous robots
Science abstract < 200 char.: Not a research article
A century of modern cosmology
Wendy L. Freedman
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Edwin Hubble’s measurement of a galaxy beyond the Milky Way led to the discovery of cosmic expansion
Science abstract < 200 char.: Not a research article
A new preprint server welcomes papers written and reviewed by AI
Celina Zhao
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With human peer review struggling to keep pace with machine-generated science, aiXiv enlists bots to help
Science abstract < 200 char.: Not a research article
Wildfires mobilize soil pollutants
Xiaohui Liu, Ruonan Wang, Caicai Xie, Ying Liu
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Science abstract < 200 char.: Not a research article
Runners-up
Jocelyn Kaiser, Martin Enserink, Mitch Leslie, Daniel Clery, Andrew Curry, Celina Zhao, Adrian Cho, Jon Cohen, Erik Stokstad
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Science abstract < 200 char.: Not a research article
The green giant
Tim Appenzeller
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Images of China’s clean energy infrastructure reveal a transformation of unmatched scale and speed
Science abstract < 200 char.: Not a research article
Tricks for treats
Brian H. Kvitko, Jonathan M. Jacobs
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Plant pathogens use secreted effectors to trick plant cells into providing sugary treats
Science abstract < 200 char.: Not a research article
Good morning, sunshine
Tim Appenzeller
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The seemingly unstoppable growth of renewable energy is Science ’s 2025 Breakthrough of the Year
Science abstract < 200 char.: Not a research article
Reevaluating PFAS exposure risks from marine fish
Jennifer Sun, Elsie M. Sunderland
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A modeling analysis suggests that legacy PFAS in marine fish have declined on a global scale
Science abstract < 200 char.: Not a research article
The burden of silence
Stephanie Bailey
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Science abstract < 200 char.: Not a research article
Safeguards for military robotics are impeded by the realities of warfare
Aude G. Billard
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Science abstract < 200 char.: Not a research article
Pathways of pain
Amélie Joly, Irene Miguel-Aliaga
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Estrogen tunes a cross-talk between hormone-secreting cells in the mouse gut to regulate visceral pain
Science abstract < 200 char.: Not a research article
NIH’s proposed caps on open-access publishing fees roil community
Phie Jacobs
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Change to be implemented next year drew more than 900 comments, most of them critical
Science abstract < 200 char.: Not a research article
Cutting cake into a slice of life
Yuanxing Xia
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Science abstract < 200 char.: Not a research article
Soil Hg re-emissions erode control efforts
Jing Wei, Huan Zhong, Wenli Tang
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Science abstract < 200 char.: Not a research article
The internet’s deepest infrastructure The Web Beneath the Waves Samanth Subramanian Columbia Global Reports, 2025. 128 pp.
Ananya
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Stakeholders vie for control of the underwater cables that underlie modern communications
Science abstract < 200 char.: Not a research article
Scientific production in the era of large language models
Keigo Kusumegi, Xinyu Yang, Paul Ginsparg, Mathijs de Vaan, Toby Stuart, Yian Yin
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With the production process rapidly evolving, science policy must consider how institutions could evolve
Science abstract < 200 char.: Not a research article
Listening to the languages of nature Life on a Little-Known Planet Elizabeth Kolbert Crown, 2025. 320 pp.
Gillian Bowser
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A journalist’s collected works probe the dazzling complexity of Earth’s ever-changing ecosystems
Science abstract < 200 char.: Not a research article
2025 AAAS Kavli Science Journalism Award winners named
Earl Lane, Emily Hughes
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Science abstract < 200 char.: Not a research article
Breakdowns of the year
Jeffrey Mervis, Martin Enserink, Rachel Bernstein
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What went wrong in the world of science
Science abstract < 200 char.: Not a research article
In Science Journals
Sacha Vignieri, Yury Suleymanov, Jack Huang, Jake S. Yeston, Marc S. Lavine, Guillermo Oliver, Claire Olingy, Ekeoma Uzogara, Yevgeniya Nusinovich, Corinne Simonti, Michael A. Funk, Phil Szuromi, Priscilla N. Kelly, Caroline Ash, Madeleine Seale, Baljit S. Khakh, Melissa L. Norton, Leslie Ferrarelli
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
NSF pares back grant-review process to ease workload
Jeffrey Mervis
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Memo cites reduced staff, but some say move also aims to elevate White House priorities
Recent discoveries on the acquisition of the highest levels of human performance
Arne GĂŒllich, Michael Barth, David Z. Hambrick, Brooke N. Macnamara
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Scientists have long debated the origins of exceptional human achievements. This literature review summarizes recent evidence from multiple domains on the acquisition of world-class performance. We review published papers and synthesize developmental patterns of international top scientists, musicians, athletes, and chess players. The available evidence is highly consistent across domains: (i) Young exceptional performers and later adult world-class performers are largely two discrete populations over time. (ii) Early (e.g., youth) exceptional performance is associated with extensive discipline-specific practice, little or no multidisciplinary practice, and fast early progress. (iii) By contrast, adult world-class performance is associated with limited discipline-specific practice, increased multidisciplinary practice, and gradual early progress. These discoveries advance understanding of the development of the highest echelons of human achievement.

Science Advances

GPT-4o mini: Non-social science research article
RIPK1 inhibition reduces biliary injury and fibrosis in primary sclerosing cholangitis
Pierre-Antoine Soret, Virginie Steunou, Julien Hedou, Juliette Tokgozoglu, Valeria Pistorio, Amine Majdi, Nadia Darwane, Jean-Louis Delaunay, Siham Benyahia, Laetitia Dinard, Tatiana Ledent, InÚs Metatla, Chiara Guerrera, Marie Lhomme, Maharajah Ponnaiah, JérÎme Galon, Patrick Soussan, Lawrence Serfaty, Christophe Corpechot, Chantal Housset, Tounsia Aït-Slimane, Franck Verdonk, Olivier ChazouillÚres, Dominique Wendum, Vlad Ratziu, Sara Lemoinne, Axelle Cadoret, Nicolas Chignard, Jérémie Gautheron
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Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with no effective curative therapies. Necroptosis, a regulated necrotic cell death pathway controlled by receptor-interacting protein kinase 1 (RIPK1), has emerged as a potential driver of inflammation and fibrosis in chronic liver disorders. We investigated the role of necroptosis in PSC and whether RIPK1 inhibition could modify disease course and progression. Spatial profiling of human PSC biopsies revealed that necroptosis primarily affects cholangiocytes, while apoptosis was more frequent in hepatocytes and nonbiliary cells. In vitro, necroptosis inhibition protected cholangiocytes, and RIPK1 deletion conferred resistance to TNF-mediated cytotoxicity. In a murine model of PSC, pharmacological RIPK1 inhibition reduced cholestatic injury, hepatic inflammation, and biliary fibrosis. Multiomic analyses comprehensively demonstrated reprogramming toward wild-type–like profiles following treatment. These findings identify necroptosis as a critical effector in PSC and highlight RIPK1 inhibition as a promising disease-modifying approach, opening the door to targeted necroptosis-based therapies for this otherwise untreatable disease.
GPT-4o mini: Non-social science research article
A plant NLR receptor activates auxin signaling through Aux/IAAs-ARF19 and YUC8-TIR1/AFBs to promote callose-mediated antiviral defense
Tongqing Yang, Ruizhen Zhao, Ruoxin Mei, Hongmin Cui, Zixuan Ding, Yanan Wen, Qian Wu, Zhengqiang Chen, Shen Huang, Chunli Wang, Lu Hong, Wenyu Zuo, Zhongkai Zhang, Min Zhu, Leiyun Yang, Zhengguang Zhang, Suomeng Dong, Yi Xu, Xiaorong Tao
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Phytohormone signaling pathways are crucial for defense against pathogens mediated by pattern recognition receptors and nucleotide-binding leucine-rich repeat (NLR) immune receptors. The induction of auxin signaling by immune receptors for antiviral immunity is poorly understood despite its notable role in plant defense against viral pathogens. Here, we report that plant NLR Sw-5b initiates and amplifies auxin signaling through auxin/indole-3-acetic acid (Aux/IAAs)–ARF19 and YUC8–transport inhibitor response1/auxin-signaling F-box (TIR1/AFB) modules to promote callose-mediated antiviral defense. Upon recognizing viral effector, Sw-5b associates with and relieves repressors Aux/IAAs on transcription factor ARF19. ARF19 then activates callose synthase gene GSL5/8 to deposit callose at plasmodesmata, inhibiting viral cell-to-cell spread. Meanwhile, ARF19 activates auxin biosynthesis gene YUC8 to boost auxin production; this further amplifies callose deposition signaling via TIR1/AFB receptors and Aux/IAAs-ARF19–glucan synthase-like (GSL) module, thereby restricting the virus in localized cell death. Our findings provide valuable insights into the mechanism by which plant immune receptors induce phytohormone signaling pathways to combat pathogens.
GPT-4o mini: Non-social science research article
A poxvirus model reveals general correlates of antigen presentation and immunogenicity for viral CD8 + T cell epitopes
Matthew J. Witney, Nathan P. Croft, Yik Chun Wong, Stewart Smith, Inge E.A. Flesch, Erica Keller, Leon CW Lin, Yanli Li, Nicole L. La Gruta, Anthony W. Purcell, David C. Tscharke
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CD8 + T cells are essential effectors in antiviral immunity that kill infected cells displaying viral peptide epitopes on major histocompatibility complex class I (MHC I). The pathways underpinning antigen presentation on MHC I are well known, but we lack a quantitative understanding of the relationships between source proteins and presented epitopes and how these relate to immunogenicity. We used mass spectrometry to interrogate vaccinia virus infection to reveal that up to 90% of epitopes were presented as fast as their source proteins were translated, but that protein amounts failed to correlate with epitope levels. Unexpectedly, epitope levels on infected cells also failed to correlate with immunogenicity. However, by extending our analysis to produce the first measurements of viral epitope levels from infected mice, we found a significant but moderate correlation with immunogenicity. These data provide empirical evidence for and against several associations that to date have been assumed or are not well resolved.
GPT-4o mini: Non-social science research article
Dynamic control of molecular transport MXene transistor membranes
Aaditya Pendse, Arjun V. Yennemadi, Thomas J. Ferron, Anthony van Buuren, Armin VahidMohammadi, Teng Zhang, Yury Gogotsi, Martin Z. Bazant, Aleksandr Noy
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Controlled spatial confinement and surface properties of lamellar 2D nanomaterial membranes could enhance many precision separation processes. Traditionally, researchers view channel dimensions, surface properties, and permeation rates of these membranes as intrinsic properties that cannot be modulated in operando. We report that gate voltage applied to the conducting laminar MXene membrane can modulate the permeation rate of ions and neutral solutes, as well as its effective size rejection. In operando wide-angle x-ray scattering measurements reveal that these changes are not driven by electrically induced variations in the d spacing of the MXene layers. Instead, experimental data and continuum electrokinetic modeling reveal that ion transport through the MXene channels is primarily affected by Donnan equilibrium at the membrane-solution interface. We also report a strong increase in the permeation rates through the membrane under a low-frequency ac voltage gating regime that we attribute to diffusioosmotic flow oscillations induced in the membrane. Overall, MXene “transistor” membranes provide a previously unidentified approach to dynamic control of molecular separations.
GPT-4o mini: Non-social science research article
High-order expansion of neural ordinary differential equation flows
Dario Izzo, Sebastien Origer, Giacomo Acciarini, Francesco Biscani
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Artificial neural networks, widely recognized for their role in machine learning, are also transforming the study of ordinary differential equations (ODEs), bridging data-driven modeling with classical dynamical systems as well as enabling the development of infinitely deep neural models. However, their practical applicability remains, in this context, constrained by the opacity of the learned dynamics, which operate as black-box systems with limited explainability, thereby hindering trust in their deployment. Existing approaches for the analysis of neurally driven dynamical systems are now scarce and restricted to first-order gradient information due to computational constraints, thereby limiting the depth of achievable insight. Here, we introduce event transition tensors as a new tool containing high-order differential information that provides a rigorous mathematical description of NeuralODE dynamics on event manifolds. We demonstrate its versatility across diverse applications: characterizing uncertainties in a data-driven prey-predator control model, analyzing neural optimal feedback dynamics, and mapping landing trajectories in a three-body neural Hamiltonian system. In all cases, our method allows for the interpretability of NeuralODEs and their analytical verification by expressing their behavior through previously unknown explicit mathematical structures. The neural dynamics are thereby fully encapsulated within a set of compact, computationally efficient tensors, which retain all the necessary information for rigorous system analysis and certification. Our findings contribute to a deeper theoretical foundation for event-triggered neural differential equations and provide a mathematical construct for explaining complex system dynamics.
GPT-4o mini: Non-social science research article
VNUT-mediated ATP release suppresses T helper 1 (T H 1) cell differentiation via the P2X7R-JNK-FOXO3a-Eomes signaling cascade
Bolong Wu, Linlin Sheng, Ziyi Feng, Xiaohu Wang, Ligong Chen
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Extracellular ATP (eATP), a well-recognized danger signal and immune activator, is implicated in the activation, differentiation, and function of T cells, directly or indirectly. Yet, how T cells release ATP themselves and its effects remain poorly investigated. Here, we found vesicular nucleotide transporter (VNUT), critical for vesicular ATP storage/release, is highly expressed in T H 1 cells and selectively restricts their differentiation and effector functions. Mechanistically, VNUT facilitates lysosomal ATP import and its extracellular release upon T cell receptor engagement. This eATP then activates the purinergic receptor P2X7R and downstream SRC kinase, triggering a signaling cascade involving heightened Ca 2+ influx and hyperphosphorylation of JNK and FOXO3a, which ultimately impairs Eomes-directed IFN-Îł production in T H 1 cells. Genetic/pharmacological of VNUT inhibition significantly potentiates T H 1 effector functions against Listeria infection and transplanted tumors. These findings identify VNUT as a critical checkpoint in limiting T H 1 immunity, coupling vesicular ATP transport to transcriptional control via the P2X7R-JNK-FOXO3a-Eomes axis, offering a target for treating infection and cancer.
GPT-4o mini: Non-social science research article
Advances in machine learning–enhanced microfluidic cell sorting
Haodong Li, Jie Bai, Xiaxian Ma, Linwei Li, Yuanchao Liu, Xiaoyan Liu, Shaofei Shen, ChweeTeck Lim
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Cell sorting, essential for diagnostics and early intervention, has evolved from conventional methods to sophisticated microfluidic approaches. These miniaturized systems leverage precise hydrodynamic control, facilitating major advances in tumor cell isolation, single-cell analysis, and biomarker detection. However, the vast imaging data generated by these microfluidic techniques necessitate advanced computational methods. Machine learning, particularly computer vision and deep learning, now offers transformative capabilities for automated feature extraction, pattern recognition, and real-time classification, enhancing sorting accuracy, accelerating diagnostics, and informing clinical decisions. This review synthesizes the convergence of microfluidics and machine intelligence, examining their synergistic roles in flow-field optimization, cellular classification, and error correction. While highlighting breakthroughs in diagnostic sensitivity and analytical throughput, we critically address challenges including model generalizability and hardware-software integration. Last, we provide an outlook on multimodal data fusion and the development of on-chip intelligent systems, proposing a roadmap for advancing precision medicine through embedded, adaptive biosensing platforms.
GPT-4o mini: Non-social science research article
Immunometabolic insights into the foreign body response
Srinidhi Venkatesan, Dauda L. Mshelia, Chima V. Maduka
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Differences in energy use by immune cells cause long-lasting inflammation, with higher glucose uptake strongly linked to the formation of scar tissue around implanted materials.
GPT-4o mini: Non-social science research article
Resident phagocytes promote non–cell-autonomous fragmentation of apoptotic cells
Jascinta P. Santavanond, Georgia K. Atkin-Smith, Irene Lozano-GonzĂĄlez, Joan Roncero-Carol, Lanzhou Jiang, Amy L. Hodge, Dilara C. Ozkocak, Kelin Zhao, Daniel H. D. Gray, Marco J. Herold, Andrew J. Kueh, Gemma F. Ryan, Rochelle Tixeira, Michael F. Olson, Mark D. Hulett, Amy A. Baxter, Ivan K. H. Poon, Esteban Hoijman
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Phagocytosis of apoptotic cells maintains tissue homeostasis and regulates inflammation. A proposed facilitator of apoptotic cell clearance is the fragmentation of these cells into apoptotic bodies (ApoBDs) through cell-autonomous processes involving caspases and cytoskeletal rearrangement. Although this fragmentation process is considered a hallmark of apoptosis, its progression in tissue environments remains underexplored. Here, we examine the in vivo apoptotic dynamics of mouse thymocytes and pluripotent cells from zebrafish embryos. We show that the in vivo biogenesis of ApoBDs is independent of known cell-intrinsic regulators. Instead, fragmentation depends on actin-rich protrusions from neighboring resident phagocytes, which mechanically compress apoptotic cells to break them into smaller particles. Four-dimensional in vivo tracking of apoptotic cells reveals that both phagocyte-mediated fragmentation and phagocytosis are size sensitive, indicating that apoptotic size reduction mediated by phagocytes enhances their own clearance abilities. This non–cell-autonomous fragmentation ensures rapid apoptotic cell clearance, crucial for maintaining tissue homeostasis in physiological settings.
GPT-4o mini: Non-social science research article
Clinical-grade iPSC-derived chondrogenic micropellets for treating advanced cartilage defects
Yoojun Nam, Narae Park, Jinhyeok Choi, Kijun Lee, Si Hwa Choi, Jang-Woon Kim, SeonJu Choi, Chang Pyo Hong, Jennifer Lee, Joon-Yong Jung, Soon Nam Oh, Yeri Alice Rim, Ji Hyeon Ju
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Induced pluripotent stem cell (iPSC)–derived chondrogenic tissues represent a promising alternative for treating cartilage defects in chronic degenerative joint conditions such as osteoarthritis (OA). Cartilage tissue has limited self-repair capacity, and although allogeneic transplantation has potential, a less invasive delivery method could enhance the efficacy of cell-based therapies. The aim of this study was to develop iPSC-derived “minimal injectable unit” chondrogenic micropellets (MIUChons) for delivery via intra-articular injections for OA therapy. To create transplantable allogeneic cartilage tissue, we optimized good manufacturing practice or clinical-grade production of iPSC-derived injectable chondrogenic spheroids and tested them in OA animal models. MIUChons were delivered to damaged cartilage through a single injection. In vivo and in vitro analyses demonstrated that MIUChon treatment effectively reduced cartilage degeneration and deterioration. In addition, injecting MIUChons into the intra-articular cavity improved arthritis symptoms. Overall, MIUChons offer a strategy for treating cartilage deterioration via intra-articular injection in patients with OA.
GPT-4o mini: Non-social science research article
The mechanism of action of digoxin requires the sodium-dependent inactivation of the sodium-calcium exchanger
Kyle Scranton, Scott John, Marina Angelini, Rui Zhang, Andreas Schwingshackl, Joshua I. Goldhaber, Riccardo Olcese, Michela Ottolia
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For more than two centuries, digoxin has been used to treat heart failure by increasing the strength of cardiac contraction and, more recently, is used for heart rate control. The proposed, yet unproven, mechanism underlying digoxin’s positive inotropic effect is as follows: By inhibiting the Na + -K + ATPase (NKA), digoxin partially dissipates the transmembrane Na + gradient, which is used by the Na + -Ca 2+ exchanger (NCX1) to extrude Ca 2+ from myocytes, thus causing accumulation of cytosolic Ca 2+ and therefore increased cardiac contractility. Here, we demonstrate that digoxin critically relies on a specific allosteric regulation of NCX1, known as Na + -dependent inactivation, to exert its positive inotropic effect, establishing the precise mechanism of action of this historic drug. These findings identify a distinct molecular target for the development of positive inotropes that avoid the undesirable effects associated with the blockade of NKA. As the structural information for the region involved with NCX1 Na + -dependent inhibition is well resolved, we provide the mechanistic foundation for drug development.
GPT-4o mini: Non-social science research article
Architecture and energy transfer of coccolithophore photosystem I with a huge light-harvesting antenna system
Xiao-Meng Sun, Kang Li, Fei-Yu He, Hao-Jie Wang, Hai-Long Chen, Quan Wen, He-Yuan Liu, Fang Zhao, Xiu-Lan Chen, Yu-Xiang Weng, Jun Gao, Lu-Ning Liu, Yu-Zhong Zhang, Long-Sheng Zhao
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Coccolithophores play important roles in global biogeochemical cycles and climate change and are characterized by their cell surfaces covered with calcium carbonate coccoliths. Their capacity to thrive in dynamic marine ecosystems is underpinned by efficient photosynthetic adaptation. Here, we elucidated the structure of a photosystem I-light-harvesting complex I (PSI-LHCI) supercomplex from coccolithophore Emiliania huxleyi by cryo–electron microscopy, ultrafast spectroscopy, and computational simulations. The PSI core is encircled by 35 LHCIs that are organized in six layers with repetitive, fiber-like arrangements, forming a giant PSI-LHCI supercomplex. Increased levels of chlorophylls c and carotenoids in LHCIs enhance the absorption of blue/green light. Time-resolved spectral analysis and computational simulations both revealed that the large number of pigments forms an extensive pigment network, ensuring efficient energy transfer from peripheral LHCIs to the PSI core. Our study provides insights into the assembly and energy transfer of coccolithophore PSI-LHCI and delineates the evolutionary variation of red-lineage PSI-LHCIs.
GPT-4o mini: Non-social science research article
Heterophase RuO 2 oxygen evolution catalyst for durable proton exchange membrane water electrolysis
Guanzhen Chen, Ruihu Lu, Zechao Zhuang, Hao Fei, Xintong Li, Xuewen Zhang, Chao Ma, Jiena Weng, Jian Wang, Jingzhi Shang, Tao Gan, Yu Wang, Ziyun Wang, Yunhu Han
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Dissolution of ruthenium (Ru) species under harsh anode operating conditions severely impedes the commercialization of non–iridium (Ir) proton exchange membrane water electrolyzers (PEMWEs). Here, we propose a catalyst design strategy that engineers phases beyond conventional atomic ordering, constructing a heterophase MoRuO x catalyst (AC-MoRuO x ). This catalyst achieves 10 milliamperes per square centimeter in an acidic oxygen evolution reaction with merely 180-millivolt overpotential while operating stably for >3000 hours. In PEMWE devices, AC-MoRuO x delivers record durability at industrial current densities: ≄2000 hours at 1.0 ampere per square centimeter and 1000 hours at 1.5 amperes per square centimeter. We demonstrate that heterophase architecture and atomic arrangements reconfigure electronic structures and phase distribution, simultaneously optimizing active-site density and structural integrity. This breakthrough resolves the long-standing activity-stability trade-off in ruthenium-based catalysts.
GPT-4o mini: Non-social science research article
GPNMB is a biomarker for lysosomal dysfunction and is secreted via LRRK2-modulated lysosomal exocytosis
Erin C. Bogacki, Gustavo Morrone Parfitt, Adriana Cunha, George Longmore, Selina Wray, Patrick A. Lewis, Susanne Herbst
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Genome-wide association studies have identified Glycoprotein Nmb ( GPNMB ) as a risk factor for Parkinson’s disease. The risk allele increases GPNMB transcription and GPNMB protein levels in the CSF highlighting GPMNB as a potential biomarker for Parkinson’s disease. However, a lack of knowledge of GPNMB’s function and mechanism of secretion has hindered an interpretation of secreted GPNMB levels. In this study, we assessed the mechanism of GPNMB secretion by macrophages, the primary cell type expressing GPNMB in the brain. We show that GPNMB is secreted in response to lysosomal stress via lysosomal exocytosis and highlight the Parkinson’s disease risk factor LRRK2 as a strong modulator of GPNMB secretion.
GPT-4o mini: Non-social science research article
SLFN14 functions as a P-TEFb inhibitor to modulate the transcription of HIV-1 and cellular genes
Shu-min Chen, Ling Ma, Zhen Wang, Quan-jie Li, Rui Zhou, Jing Wang, Ji-wei Ding, Jian-yuan Zhao, Dong-rong Yi, Yong-xin Zhang, Sai-sai Guo, Xin-lu Wang, Xiao-yu Li, Zhen-long Liu, Shan Cen
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The Schlafen ( SLFN ) gene family encodes different growth regulatory factors known to participate in cell growth, differentiation, tumorigenesis, and the immune response against virus infection. However, the molecular mechanisms underlying their functions remain largely incomplete. In this study, we report that the SLFN family member SLFN14 has potent anti–HIV-1 activity. Specifically, SLFN14 binds to the positive transcription elongation factor b (P-TEFb), thereby preventing HIV-1 Tat-mediated recruitment of P-TEFb to the HIV-1 promoter and causing an arrest of viral transcription. Furthermore, this P-TEFb–targeted inhibiting activity also allows SLFN14 to regulate the transcription of a subset of cellular genes. Thus, our data identify SLFN14 as an inhibitor of the important transcription elongation factor P-TEFb complex, which unveils the crucial role of SLFN14 in both cellular antiviral defense and other important cellular processes that rely on the function of this complex.
GPT-4o mini: Non-social science research article
Interleukin-2 is a potent latency reversal agent in people with treated HIV-1
Michael L. Freeman, Brian M. Clagett, Konstantin Leskov, Daniela Moisi, George A. Yendewa, Scott F. Sieg, Gregory M. Laird, Jonathan Karn, Jeffrey M. Jacobson, Benigno Rodriguez, Michael M. Lederman
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Eliciting HIV-1 expression from latently infected CD4 + T cells allows these rare reservoir cells to become targets of the immune system and may also result in death of reservoir cells via virus-induced cytopathy. We asked whether administration of recombinant interleukin-2 (rIL-2) to people with HIV-1 (PWH) on antiretroviral therapy (ART) would induce HIV-1 replication and activate cellular immunity. Nine men with ART-suppressed HIV-1 completed a single 4-day cycle of rIL-2 administration. Plasma HIV-1 RNA levels rose from <20 copies per milliliter at entry to a mean of 301 copies per milliliter at day 7 (an average increase of 0.82 log 10 ; P = 0.008). In addition, we observed robust natural killer and T cell activation, with a modest increase in regulatory T cell–like cells. Thus, rIL-2 appears to be one of the most potent latency-reversing agents tested in PWH on ART.
GPT-4o mini: Non-social science research article
Piezo-photocatalysis over high-nuclearity titanium-oxide cluster via lead heterocoordination enhances activity by piezoelectric effect
Linping Liu, Guanyun Zhang, Jiachen Ma, Dexin Wang, Juan Wang, Lixia Xuan, Junshuo Nie, Guo Wang, Yifeng Wang
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Piezoelectric materials usually exist in solid-state forms with obscure structures, hindering atomic-level understanding of structure-property relationships. Here, we report the piezoelectric high-nuclearity titanium-oxide molecular cluster, Ti 26 Pb 10 , constructed via a dopant metal coordination strategy. The cluster framework comprises 26 Ti atoms linked by binuclear units, with 10 Pb 2+ ions anchored through distinct coordination: 2 embedded and 8 surface exposed. Ti 26 Pb 10 displays a piezoelectric constant 5.5 times higher than PbTiO 3 , as confirmed by piezoresponse force microscopy. Density functional theory simulations reveal stress-induced lattice distortion and bandgap shifts. Critically, leveraging piezo-photocatalytic synergy, Ti 26 Pb 10 enables ultraefficient tetracycline degradation, achieving a rate 15 times faster than PbTiO 3 under combined light and ultrasound, with a superior synergy factor. Mechanistic studies indicate that local electric fields coupled with light excitation promote 1 O 2 generation. This work extends titanium-oxide clusters into piezo-photocatalysis and provides a rational design paradigm for multifield synergistic catalysis and atomic-level structure-activity insights.
GPT-4o mini: Non-social science research article
Mechanism of cotranslational modification of histones H2A and H4 by MetAP1 and NatD
Denis Yudin, Mateusz Jaskolowski, Ziyi Fan, Nicolas Burg, Sowmya Chandrasekar, Alfred M. Lentzsch, Alain Scaiola, Adrian Bothe, Elke Deuerling, Martin Gamerdinger, Shu-ou Shan, Nenad Ban
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The replication-dependent histones H2A and H4 are among the most highly expressed proteins in eukaryotes during the S phase to ensure packaging of replicated chromosomes. Nearly all newly synthesized H2A and H4 are N-terminally acetylated by N-terminal acetyltransferase D (NatD) following excision of the initiator methionine by methionine aminopeptidases (MetAPs). These modifications influence chromatin function, but how they occur cotranslationally on these exceptionally abundant and small proteins was not understood. Here, we show that the nascent polypeptide-associated complex controls the cotranslational modification of histones H2A and H4 by recruiting NatD and the upstream enzyme MetAP1 to ribosomes. MetAP1 and NatD cooperate on the ribosome to create a confined environment for the efficient sequential modification of the nascent histone chain. Our work provides a mechanistic model for the early steps of histone maturation.
GPT-4o mini: Non-social science research article
Stress granule dynamics govern TOR reactivation and growth recovery during post-heat stress adaptation
Zhaochen Zhong, Suyun Yang, Danmei Liu, Zhenwen Liu, Wei Zhao, Xuehong Shen, Fei Wang, Yanlin Liu, Tongda Xu, Xiaofeng Fang, Yan Xiong
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The conserved target of rapamycin (TOR) pathway and stress granules (SGs) play crucial roles in stress adaptation and survival. However, their interplay in plants remains largely unknown. Here, we elucidate the complex relationship between TOR signaling and SG dynamics in Arabidopsis . In contrast to the positive regulatory role observed in mammals, we show that TOR signaling is dispensable for heat-induced SG formation in plants. Furthermore, heat stress induces the sequestration of TOR and its core complex components, RAPTOR1B and LST8, into SGs. TOR activity is rapidly suppressed by heat stress, independently of SG formation. In contrast, TOR reactivation following heat stress relief is dependent on the rate of SG disassembly, implicating SG recovery dynamics as a key regulator of TOR reactivation. These findings reveal a layer of TOR regulation and highlight the potential of modulating SG dynamics to orchestrate plant growth and stress adaptation.
GPT-4o mini: Non-social science research article
Direct recruitment of TONSOKU by the N-terminal tails of histone variants H2A.X and H2A.W coordinates DNA repair
Qi Li, Chenhui Zhao, Yiyi Guo, Yuxue Bai, Jie Liu, Xu Jin, Yue Yuan, Yannick Jacob, Jie Dong
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Histone variants play crucial roles in DNA replication and repair. The plant TONSOKU (TSK) requires histone H3.1 unmethylated at lysine 27 for DNA repair at replication forks, but how TSK is recruited to double-strand break (DSB) sites remains unclear. In this study, we show that the leucine-rich repeat (LRR) domain of TSK recognizes the N-terminal tails of histone variants H2A.X and H2A.W—key for DNA repair in euchromatin and heterochromatin, respectively—but not the H2A.Z variant. A unique motif containing multiple basic and acidic residues (BAR motif) in H2A.Z prevents TSK binding. Moreover, disrupting TSK-H2A.X/W binding impairs TSK-mediated DNA repair. Genetic analyses reveal functional complementation between H2A.X and H2A.W in DNA repair, with the H2A.X N terminus being essential. This study reveals a previously unrecognized, H2A.X/W-dependent mechanism for recruiting the DNA repair protein TSK, highlighting the critical role of their N-terminal tails in plant DNA repair.
GPT-4o mini: Non-social science research article
Designing functional magnetic cloaks for real-world geometries
Yusen Guo, Alberto Paganini, Harold S. Ruiz
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Magnetic cloaking enables objects to become undetectable to external magnetic fields while leaving those fields unperturbed. Existing demonstrations rely on idealized cylindrical or spherical shapes, limiting their practical relevance. Here, we introduce a physics-based optimization framework that designs magnetic cloaks for arbitrarily shaped structures by directly solving Maxwell’s equations under spatial material constraints. Our method produces continuous, spatially varying permeability profiles that preserve field uniformity around complex geometries, including faceted and multi-lobed configurations. Using material parameters drawn from commercially available superconductors, we demonstrate low-distortion cloaking performance with permeability values within manufacturable ranges. This approach establishes a route to customizable magnetic shields for real-world components and lays the groundwork for future applications in extreme magnetic environments, such as fusion energy systems and precision instrumentation.
GPT-4o mini: Non-social science research article
Artifact-free ultralow-temperature DNP-enhanced NMR of molecular assemblies at natural isotopic abundance
Quentin Reynard-Feytis, Subhradip Paul, Sabine Hediger, Gaël De Paëpe
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Magic-angle spinning dynamic nuclear polarization (MAS-DNP) has greatly increased solid-state NMR sensitivity, enabling multidimensional correlation experiments (e.g., 13 C– 13 C and 13 C– 15 N) at natural isotopic abundance. Yet, these experiments often suffer from t 1 -noise, an artifact that obscures weak cross-peaks, especially in natural abundance samples. Here, we present a method to suppress t 1 -noise in 13 C– 13 C double-quantum–single-quantum (DQ-SQ) spectra by converting DQ coherences into longitudinal two-spin order ( zz -terms), enabling selective removal of uncoupled 13 C magnetization. This zz -filter, compatible with both J - and dipolar-based sequences, markedly improves the spectral quality on both commercial (100 K) and custom-built helium-spinning (30 K) MAS-DNP setups. Up to a fivefold increase in signal-to-noise ratio in the indirect dimension allows detection of previously hidden long-range correlations, including intermolecular contacts. This method yields the first artifact-free 13 C– 13 C DQ-SQ spectrum at 30 K, expanding the analytical reach of MAS-DNP NMR for characterizing molecular assemblies at natural abundance.
GPT-4o mini: Non-social science research article
Single-nucleus multiomics reveals the disrupted regulatory programs in three brain regions of sporadic early-onset Alzheimer’s disease
Andi Liu, Citu Citu, Nitesh Enduru, Xian Chen, Chia-Hao Tung, Tirthankar Sinha, Sofia E. Sepulveda, Astrid M. Manuel, Damian Gorski, Brisa S. Fernandes, Meifang Yu, Paul E. Schulz, Lukas M. Simon, Claudio Soto, Zhongming Zhao
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Sporadic early-onset Alzheimer’s disease (sEOAD) represents a substantial but less-studied subtype of Alzheimer’s disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type–specific transcriptomic changes and linked candidate cis - regulatory elements (cCREs) across brain regions. We prioritized eight conservative transcription factors in glial cells in multiple brain regions, including RFX4 in astrocytes and IKZF1 in microglia, which are implicated in regulating sEOAD-associated genes. Moreover, we identified the top 25 altered intercellular signaling between glial cells and neurons, highlighting their regulatory potential on gene expression in receiver cells. We reported 33 cCREs linked to sEOAD-associated genes overlapped with late-onset AD risk loci, and found that, in addition, sEOAD cCREs are enriched for neuropsychiatric disorder risk variants. This atlas helps dissect transcriptional and chromatin dynamics in sEOAD, providing a key resource for AD research.
GPT-4o mini: Non-social science research article
Unconventional CD8 + T cell surveillance of cytomegalovirus via Qa-1/HLA-E–restricted epitope recognition
Shanelle P. Reilly, Madison L. Smith, Samantha M. Borys, Céline FugÚre, Delia Demers, Michael J. Hogan, David Zemmour, Laurent Brossay
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Nonclassical CD8 + T cells can compensate for classical CD8 + T cell effector responses during murine cytomegalovirus (MCMV) infection. Through a combination of motif-based discovery, predictive algorithms, AlphaFold3 structural modeling, and biological assays, we identified multiple MCMV and human cytomegalovirus (HCMV) peptides that bind to Qa-1 and HLA-E, respectively. In the mouse system, we demonstrated that these virally encoded antigens stimulate Qa-1–restricted CD8 + T cells ex vivo, which can be tracked using MCMV peptide–loaded Qa-1 tetramers. Adoptive transfer of predominantly Qa-1 tetramer + CD8 + T cells into RAG-1–deficient mice protects them from mortality, underscoring the critical role of these cells in host defense. Single-cell RNA (scRNA)/TotalSeq and single-cell T cell receptor sequencing (scTCR-seq) reveal the expansion of unique TCR αÎČ clonotypes, indicating convergent antigen specificity. Together, our findings uncover a conserved and functionally important nonclassical CD8 + T cell axis mediated by Qa-1/HLA-E modulating adaptive immunity independent of classical major histocompatibility complex class I (MHC-I) pathways and present previously unidentified opportunities for vaccine development.
GPT-4o mini: Non-social science research article
Structural basis of VLCFA chain-length determination by the KCS6-CER2 complex in plants
Yang Wang, Zeyuan Guan, Qiang Wang, Hebing Wang, Xiaolin Yin, Zhifeng Zhu, Zhou Gong, Yujiao Qin, Alisdair R. Fernie, Xiuxin Deng, Feng Zhu, Ping Yin, Yunjiang Cheng
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Very-long-chain fatty acids (VLCFAs) govern plant adaptation and development in a chain length–dependent manner. The elongation of VLCFAs is mediated by 3-ketoacyl–coenzyme A synthase (KCS) and ECERIFERUM2 (CER2) family protein cofactors, but the structural basis and mechanistic principles underlying chain-length determination remain elusive. Here, we report cryo–electron microscopy structures of citrus KCS6-CER2 and KCS6–CER2-like1 complexes, unveiling a kinked elongation tunnel whose hydrophobicity and volume determine VLCFA chain length. KCS6 functions as a catalytic module elongating VLCFAs up to chain length of 28 carbons (C28). CER2 family proteins further extend the tunnel formed by the KCS6 subunit, thus elongating VLCFAs to chain lengths longer than C28. These findings provide a plant-specific structural framework for VLCFA chain-length modulation and lay a foundation for engineering VLCFA biosynthesis for the improvement of crop resilience and VLCFA industrial value.
GPT-4o mini: Non-social science research article
MAP4K1 and MAP4K2 regulate ABA-induced and Ca 2+ -mediated stomatal closure in Arabidopsis
Kota Yamashita, Sotaro Katagiri, Hinano Takase, Yangdan Li, Anzu Oishi, Airi Otoguro, Yoshiaki Kamiyama, Shota Yamauchi, Yuh-Shuh Wang, Atsushi Takemiya, Izumi C. Mori, Hannes Kollist, Taishi Umezawa
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Abscisic acid (ABA)–induced stomatal closure limits water loss from plants under drought stress. To investigate the signaling pathways involved in ABA-induced stomatal closure, we performed a phosphoproteomic analysis of ABA-treated Arabidopsis guard cell protoplasts (GCPs). We found that ABA-responsive phosphorylation of MITOGEN-ACTIVATED PROTEIN 4 KINASE 1 (MAP4K1) was significantly down-regulated in SnRK2-disrupted mutants. Subsequent biochemical assays showed that Ser 479 of MAP4K1 is directly phosphorylated by SRK2E/OST1, a central ABA kinase. Mutational analyses of MAP4K1 and MAP4K2 revealed that both kinases positively regulate ABA-induced stomatal closure and that Ser 479 of MAP4K1 is required for this phenotype. In map4k1map4k2 double mutants, stomatal closure was induced by applying exogenous Ca 2+ but not H 2 O 2 . Electrophysiological experiments showed that MAP4K1/2 is required for ABA-dependent activation of Ca 2+ -permeable channels in GCPs. Together, our results indicate that SnRK2 and MAP4K function as a signaling module to regulate the Ca 2+ -mediated pathway in ABA-induced stomatal closure.
GPT-4o mini: Non-social science research article
Topoisomerase III-beta protects from immune dysregulation and tumorigenesis
Md Rasel Al Mahmud, Simone Andrea Baechler, Anjali Dhall, Sourav Saha, Hongliang Zhang, Laura Bassel, Shuling Zhang, Min-Jung Lee, Nahoko Sato, Shraddha Rastogi, Suresh Kumar, Muhammad S. Alam, Liton Kumar Saha, Beverly A. Mock, Valentina M. Factor, Yves Pommier
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Topoisomerase III-beta (Top3b) reduces nucleic acid torsional stress and intertwining generated during RNA and DNA metabolism while protecting the genome from pathological R-loops, which otherwise result in DNA breakage and genome instability. By studying Top3b knockout mice ( Top3b -KO), we find that the loss of Top3b accelerates the development of spontaneous atypical lymphoid hyperplasia and lymphomas arising in spleens and lymph nodes, organs with prominent Top3b expression. Aging Top3b -KO mice also display splenomegaly and systemic immune alterations including neutrophilia and lymphopenia consistent with chronic inflammation. At the molecular level, Top3b deficiency causes genome-wide R-loop accumulation in splenocytes as measured by CUT&Tag sequencing. Increased R-loops are associated with genomic breaks and activation of immune signaling pathways including innate and adaptive immune cell signaling, IL-4 signaling, FAK signaling, and cGAS-STING. In addition, knocking-out Top3b promotes the rapid development of syngeneic EL4 T cell lymphomas. In conclusion, our work implies that Top3b protects from lymphoma, tumorigenesis, and immune dysregulations.
GPT-4o mini: Non-social science research article
Multicellular force coordination constructs microchannel networks for barrier-free metastasis across extracellular matrix
Huan Gao, Bo Cheng, Guorui Jin, Yulong Han, Qi Tian, Yan Zhou, Xiwen Zhao, Yan Liu, Chunyu Cao, Lizhe Zhu, Juan Zhang, Lin Wang, Binghe Xu, Hui Guo, Min Lin, Jin Yang, Feng Xu
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The extracellular matrix (ECM) acts as a primary physical barrier to cancer metastasis. While individual cancer cells can remodel ECM to create microchannel-like paths of least resistance, this cell-centric view overlooks the coordinated dynamics of multicellular communication. Here, we reveal that cancer cells collaboratively reprogram ECM to construct interconnected microchannel networks functioning as “superhighways” for barrier-free metastasis. Combining live-cell imaging, atomic force microscopy, and optical tweezers, we decode that the indispensable step in microchannel network construction is organized cross-convergence of adjacent channels. The convergence is precisely directed by mechanical bridges composed of aligned collagen bundles between adjacent channels, which transmit orientation cues to induce multicellular force coordination. Integrating single-cell sequencing and off-lattice agent-based model, we identify mechanically responsive leader cells enriched for integrin-RhoA/YAP signaling and matrix metalloproteinase 14, which sense bridge cues and initiate cross-convergence. Collectively, our findings unveil a self-organized metastatic network and its mechanobiological mechanisms, offering a previously unidentified framework and potential therapeutic insights for cancer metastasis.
GPT-4o mini: Non-social science research article
Programmable acoustofluidic engineering for creating gradient biomaterials
Yujing Lu, Ye He, Jianping Xia, Mingyuan Liu, Joseph Rich, Ke Jin, Ruoyu Zhong, Kaichun Yang, Jiao Qian, Ying Chen, Ke Li, Zhiteng Ma, Tony Jun Huang
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Gradient biomaterials that exhibit spatially varying physical, chemical, or biological properties can be used in various applications such as tissue engineering, organoid development, mechanobiology, and spatially controlled drug delivery. However, current fabrication methods often suffer from limited gradient precision, restricted material compatibility, and poor reproducibility. Here, we introduced gradient regulation via acoustofluidic dynamic engineering (GRADE), a programmable system to generate high-fidelity gradient biomaterials across different material systems. By incorporating focused interdigital transducers with the pulsed surface acoustic wave actuation, GRADE can achieve tunable and directional acoustic streaming (0 to 22 millimeters per second), which allows accurate regulation of the gradient magnitude and length. Its open microchannel design enables nondestructive extraction of centimeter-scale gradients and supports device reuse, enhancing practicality and scalability. In contrast to magnetic or electrospinning techniques that are limited to specific material types, the GRADE approach supports composition-independent fluid manipulation of a diverse group of biomaterials and cross-linking methods, thus providing greater versatility and translational potential. Furthermore, we demonstrate stiffness-dependent mechanosensation in stem cells cultured on customized gradient substrates, which validates the platform’s usability. The experimental results show that GRADE has the ability to uncover mechanobiological responses in physiologically relevant contexts. All these results establish GRADE as a powerful and versatile platform for gradient biomaterial fabrication. It shows broad potential to advance both fundamental research and translational biomedical applications.
GPT-4o mini: Non-social science research article
Florigen and cytokinin signaling antagonistically regulate FLOWERING LOCUS T-LIKE1 to drive a florigen relay that facilitates inflorescence development in rice
Moeko Sato, Yuki Sakamoto, Mari Tanaka, Jun Ito, Yuko Nomura, Yurika Morishita, Ken-ichiro Taoka, Masafumi Mikami, Masaki Endo, Hidemi Kitano, Sachihiro Matsunaga, Hiroyuki Tsuji
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Plant reproductive development involves a series of transitions, with the shoot apical meristem (SAM) transitioning into the inflorescence meristem (IM) and then the floral meristem (FM). In rice ( Oryza sativa ), the florigens Heading date 3a (Hd3a) and RICE FLOWERING LOCUS T1 play central roles in these transitions. The plant hormones auxin and cytokinin shape the morphologies associated with each transition, but little is known about the factors that integrate florigen function with phytohormone signaling during these transitions. Here, we show that in rice, Hd3a activates the transcription of FT-LIKE1 ( OsFTL1 ), which encodes a mobile FT-like protein that promotes the transition from the IM to the FM, whereas cytokinin signaling suppresses its transcription. We performed single-cell resolution three-dimensional imaging to elucidate the spatiotemporal distribution of Hd3a, cytokinin, and auxin signaling during the SAM-to-IM and IM-to-FM transitions, finding that Hd3a accumulation and cytokinin signaling occupy opposite domains in the IM. Hd3a accumulated at the center of the meristem and activated the OsFTL1 promoter, while OsFTL1 was present throughout the IM, suggesting that a “florigen relay” consisting of Hd3a from the leaves moves to the SAM and induces OsFTL1 expression within the SAM. We propose an antagonistic mechanism mediated by Hd3a and cytokinin that modulates the abundance of OsFTL1 and thus regulates reproductive development in rice.
GPT-4o mini: Non-social science research article
Photoredox-controlled chemo-divergent, regio-, and stereoselective difunctionalization of olefins via switchable SO 2 reintegration
Jiuli Xia, Lihan Zhu, Zhiguang Lv, Yunliang Guo, Lefeng Lin, Jiaqiong Sun, Guangfan Zheng, Qian Zhang
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While radical difunctionalization offers substantial potential for molecular diversification, existing methodologies predominantly focus on styrenes and activated alkenes, leaving fundamental light olefins (e.g., ethylene and propylene) largely unexplored. Moreover, achieving stereoselective transformations of light olefins remains a formidable challenge. Here, we present a visible-light–mediated photoredox-catalyzed chemo-divergent and regioselective radical difluoromethylation/polyfluoroarylsulfonylation and difluoromethylation/polyfluoroarylation of structurally diverse alkenes through switchable sulfur dioxide reintegration. The method demonstrates broad applicability across styrenes, unactivated alkenes, and gaseous ethylene/propylene substrates. The photocatalyst functions as a switch, and Sodium difluoromethanesulfinate (CF 2 HSO 2 Na) acts as a bifunctional reagent, enabling controllable divergence radical conversion via radical-polar crossover pathways. Notably, chiral alcohol–derived polyfluoroarenes efficiently induce stereoselectivity control in the coupling of alkyl radicals with sulfur dioxide via dynamic kinetic resolution. Density functional theory calculations indicate noncovalent interaction between alkyl/aryl groups and polyfluorocarbons plays critical roles for the ultralong-distance (>9 atoms) stereochemical induction. The key to achieving chemo-divergent and stereocontrolled transformations lies in the precise sorting of a dynamic intermediate pool containing alkyl radicals, sulfonyl radicals, and anions.
GPT-4o mini: Non-social science research article
Integrating theory and empirical patterns: Fish body size distributions, life history traits, and environmental flows in streams
Taylor Woods, Daniel J. McGarvey, Matthew J. Cashman, Michael R. Meador, Daren M. Carlisle, Ken Eng, Darin A. Kopp, Kelly O. Maloney
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Individual size distributions (ISDs) are prominent in ecological research and may support resource managers with ecosystem-scale objectives. We use a database of individual size measurements for US stream fishes to test for direct and indirect effects of traits, flow regimes, and land use on the interspecific ISD exponent. Path analysis indicates that traits have strong, direct effects on ISD. Flow and land use effects on the exponent are largely indirectly mediated by their influences on species traits. ISD exponents increase (abundances of larger-bodied individuals increase, relative to smaller-bodied) when environments favor higher trophic levels, warmer thermal tolerances, and periodic life histories. Alternatively, ISD exponents decrease in systems that favor opportunistic life histories. Our flexible modeling framework that includes direct and indirect effects of traits, flow regimes, and land use on ISD could be expanded to incorporate additional variables that interact with flow (e.g., temperature and physical habitat) to assess of effects of multiple stressors on aquatic ecosystem functioning.
GPT-4o mini: Non-social science research article
Gazing into the flames: A guide to assessing the impacts of climate change on landscape fire
Hamish Clarke, Francesca Di Giuseppe, Lynn Johnston, Jennifer Marlon, Trent Penman, Andrew J. Pitman, Guido R. van der Werf, Mike D. Flannigan
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Widespread impacts of landscape fire on ecosystems, societies, and the climate system itself have heightened the need to understand the potential future trajectory of fire under continued climate change. However, the complexity of fire makes climate change impact assessment challenging. The climate system influences fire in many ways, including through vegetation, fuel dryness, fire weather, and ignition. Furthermore, fire’s impacts are highly diverse, spanning threats to human and ecological values and beneficial ecosystem and cultural services. Here, we discuss the art and science of projecting climate change impacts on landscape fire. This not only includes how fire, its drivers, and its impacts are modeled, but critically it also includes how projections of the climate system are developed. By raising and discussing these issues, we aim to foster the development of more robust and useful fire projections, help interpret existing assessments, and support society in charting a course toward a sustainable fire future.
GPT-4o mini: Non-social science research article
Neurexin regulates mechanical nociceptive sensitization by central inhibition in Drosophila
Zhu Meng, Junhua Geng, Yichen Sun, Lizhong Xu, Yu Zhao, Mengzhu Ou, Yuedong Wang, Junhai Han, Pengyu Gu, Wei Xie
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Synaptic adhesion molecules play a crucial role in shaping neural circuits and behavior, yet their contribution to nociceptive processing remains poorly understood. Here, we investigate how the synaptic organizer Neurexin regulates mechanical nociception in Drosophila larvae. Using genetic, behavioral, and circuit-level analyses, we demonstrate that loss of neurexin induces mechanical nociceptive sensitization, which depends on a specific cluster of central cholinergic neurons in the subesophageal zone. These neurons drive sensitization through a C4da-Goro circuit, where Neurexin modulates presynaptic GABA B receptor signaling to control nociceptive excitability. Our findings establish Neurexin as a key of nociceptive sensitization and uncover a synaptic mechanism for tuning nociceptive thresholds, with implications for understanding chronic pain and sensory circuit dysfunctions in neurodevelopmental disorders.
GPT-4o mini: Non-social science research article
Vertical covalent organic framework interlayer channels enable ultraselective molecular separations
Songjun Fang, Yu Liao, Jiahao Tang, Mingxiu Tang, Fuxin Zheng, Zhenxiang Pan, Yingnan Feng, Gang Han
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This work addresses the long-standing challenge of insufficient permselectivity in two-dimensional (2D) covalent organic framework (COF) membranes by developing a generalizable and potentially scalable self-templating interfacial assembly method to synthesize vertically aligned 2D COF polycrystalline nanofilms. Experiments and molecular simulations reveal that molecular amphiphilicity-driven spontaneous confinement and directional alignment of framework-building units at the organic/aqueous interface instigate the vertical growth of COF monolayers. The superior sieving ability of sub–4 angstrom interlayer nanochannels enables vertically aligned COF membranes to efficiently intercept salt ions, electrically neutral small molecules, and hazardous chemicals, outperforming conventional COF membranes. The implemented strategy can be extended to other building blocks and framework topologies, opening up avenues for fine-tuning the pore structure of 2D COF membranes.
GPT-4o mini: Non-social science research article
Multimaterial 3D printed soft robots with embedded actuation and sensing
Zixiao Zhu, Dong Wang, Mengjie Zhang, Le Dong, Qinghua Yu, Chengru Jiang, Xiaoyang Zhu, Mei Chen, Kun Zhou, Guoying Gu
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Soft robots require the seamless integration of actuation and sensing units to achieve autonomy and adaptability behaviors. This demands conformal, stretchable, and spatially distributed electronic components—an unmet challenge with conventional design and fabrication methods due to complex three-dimensional (3D) geometries, multimaterial integration, and mechanical-electrical mismatches between rigid electronics and soft bodies. Here, we present a design and fabrication framework for autonomous soft robots with embedded actuation and sensing. We develop an integrated digital light processing and direct ink writing 3D printing technology to fabricate soft robots with embedded and conformal 3D electronics in an automated manner. To ensure both electrical and mechanical stability under large deformation, we introduce a structural design strategy incorporating lattice metamaterials, wavy interconnects, and discretized printed circuit boards. By combining the fabrication and design methods, we demonstrate soft robots with multimodal actuation, real-time tactile sensing, wireless communication, tactile-to-visual feedback, and autonomous obstacle avoidance. Our approach paves the way for the development of electronics-integrated autonomous soft robots.
GPT-4o mini: Non-social science research article
The asynchronous rise of Northern Hemisphere alpine floras reveals general responses of biotic assembly to orogeny and climate change
Wenna Ding, Richard H. Ree, Michael R. May, Philipp Brun, Oskar Hagen, Dirk N. Karger, Alexander Skeels, LoĂŻc Pellissier, Yaowu Xing, Niklaus E. Zimmermann
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Understanding how biotic assembly processes responded to past geoclimatic changes is key to explaining the origins of mountain biodiversity and the causes of regional disparities in species richness. Here, we jointly reconstructed geographic ranges and biome-niche evolution for 34 diverse plant clades across five major Northern Hemisphere mountain systems and quantified how late Neogene cooling increased arctic-alpine habitat connections across regions. We reveal that, while alpine floras originated asynchronously and were assembled through distinct evolutionary processes over the past 30 million years, general biological responses to orogeny and environmental change are apparent. Across regions, in situ diversification was consistently elevated during heightened phases of tectonic activity. Over the past 5 million years, enhanced arctic-alpine connectivity facilitated biotic interchange and positioned the boreal-arctic region as a major biogeographic crossroads linking Eurasia and North America.
GPT-4o mini: Non-social science research article
Observation of moiré plasmonic skyrmion clusters
Lan Zhang, Lipeng Wan, Weimin Deng, Liang Hou, Jumin Qiu, Qiushun Zou, Tongbiao Wang, Daomu Zhao, Tianbao Yu
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Skyrmions are topological defects belonging to nontrivial homotopy classes in particle theory. Their remarkably stable topology has recently been observed in electromagnetic waves. For the evanescent fields near a surface, this has been realized so far only for elementary optical skyrmions, with a fixed skyrmion number. Here we report, both in theory and experiment, the concept of moiré plasmonic skyrmion clusters, where multiskyrmions are nested to form a large optical skyrmion cluster. By leveraging twistronics engineering of plasmonic nanostructures, we demonstrate both periodic and quasi-periodic optical skyrmions, revealing a large degree of topological control. In a misaligned composite nanostructure, the rapid inverting of optical skyrmion number is achieved, which is explained by a lattice model. This topological change of moiré plasmonic skyrmion clusters can serve as a precise beacon of the relative alignment deviation between composite nanostructures.
GPT-4o mini: Non-social science research article
What if eye...? Computationally recreating vision evolution
Kushagra Tiwary, Aaron Young, Zaid Tasneem, Tzofi Klinghoffer, Akshat Dave, Tomaso Poggio, Dan-Eric Nilsson, Brian Cheung, Ramesh Raskar
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Natural selection has produced diverse vision systems, from simple patches of photoreceptors to complex camera eyes, representing just one set of evolutionary outcomes. Computational evolution offers a way to systematically test hypotheses, isolate individual factors, and ask the “why” questions behind vision. We recreate vision evolution by coevolving eyes and behaviors in embodied agents and use this to illuminate principles shaping vision across different levels of the Marr’s hierarchy. This leads to three key findings: First, we provide computational evidence that task-specific selection drives bifurcation in eye evolution. Second, we reveal how optical innovations naturally emerge to resolve fundamental trade-offs between light collection and spatial precision. Third, we uncover scaling laws between visual acuity and neural processing that provide insights into long-standing hypothesis behind eye and brain size. Our work introduces a paradigm that uses embodied artificial intelligence (AI) as hypothesis-testing machines that can help accelerate discoveries in vision science.
GPT-4o mini: Non-social science research article
Phosphorylation of shiftless is important for inhibiting the programmed −1 ribosomal frameshift
Yueli Zhang, Zhijian Li, Huihui Chong, Pengjiao Hou, Wei Hao, Mengyun Li, Zhicheng Liu, Wei Jia, Bo Qin, Yuxian He, Sheng Cui
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Shiftless (SFL) is a broad-spectrum inhibitor of programmed −1 ribosomal frameshift (−1 PRF) and exhibits various antiviral activities. Here, we characterized human SFL structurally and biochemically. The 2.0-angstrom resolution crystal structure of SFL reveals a boat-like module comprising an N-terminal helical bundle and three zinc fingers at the C terminus. A hyperphosphorylation loop (HPL) buried between the helical bundle and the zinc finger 1 harbors four phosphorylated residues (p-S249, p-T250 p-T253, and p-S256), which are important to protein folding. SFL forms monomers in solution and binds the HIV-1 −1 PRF sequence with nanomolar affinity ( K D  = 5.7 nanomolar). Disruption of HPL phosphorylation decreased the RNA binding affinity and undermined the SFL-mediated −1 PRF inhibition of various viruses. Proximity-dependent biotinylation identified three cellular Ser/Thr kinases—EEF2K, NEK9, and PBK—that phosphorylate SFL in cells. These findings shed light on the mechanisms underlying −1 PRF regulation by SFL and provide insights into the role of SFL in virus inhibition.
GPT-4o mini: Non-social science research article
lncRNA LINC-PINT controls lymphatic function and inflammatory profile in lymphedema
Nathalie Laugero, Claire Peghaire, Léna Verdu, Elisa Balzan, Tangra Draia-Nicolau, Roxane Sylvestre, Julie Malloizel-Delaunay, Alessandra Bura-RiviÚre, Florent Morfoisse, Anne-Catherine Prats, Eric Lacazette, Barbara Garmy-Susini
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Lymphedema is a lymphatic dysfunction leading to an accumulation of fluid and fat in the arm or leg. Here, we performed noncoding RNA profiling of human breast cancer–induced secondary lymphedema. We identified the long intergenic non–protein coding RNA, P53-induced transcript ( LINC-PINT ), as essential for the lymphedema development. LINC-PINT is the most expressed lncRNA in human lymphatic endothelial cells (LECs) under stress condition. Knocking down LINC-PINT in LECs promotes the expression of inflammation-related genes. Mechanistically, ATAC-seq revealed that LINC-PINT induces the transcription of genes involved in lymphangiogenesis and immune cell adhesion by increasing chromatin accessibility. Notably, LINC-PINT deficiency impairs LEC proliferation, migration, and sprouting. Conditional deletion of Lnc-Pint in mouse lymphatic endothelium (Lnc-Pint lecko ) leads to a reduction in dermal lymphatic network density. Lnc-Pint lecko mice exhibit decreased lymphedema, reduced dermal backflow, fibrosis, and inflammation. Our findings unveil a crucial molecular role of LINC-PINT in lymphatic function and hold substantial clinical implications for lncRNA as biomarker of lymphedema.
GPT-4o mini: Non-social science research article
Direct trapping of the transport-segment DNA by the central domain of type IIA topoisomerases
Yuhui Xin, Runqi Xian, Congrong Liu, Oujia Zhang, Zihe Rao, Xuemei Li, Yutao Chen
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Type IIA topoisomerases modulate DNA topology by coordinating the cleavage of gate-segment DNA and the passage of transport-segment DNA—a mechanism conserved across species and essential for diverse cellular processes. While gate-segment interactions have been extensively studied, direct structural evidence of transport-segment capture has remained elusive, limiting our understanding of the full catalytic cycle. Here, we present a cryo–electron microscopy structure of the T4 bacteriophage topoisomerase II with a transport-segment DNA bound directly to its central domain. The structure reveals conformational rearrangements in the central domain that accommodate the transport-segment DNA, suggesting an alternative sequence of events in which the enzyme sliding along the loosely bound religated gate segment may precede transport-segment passage through the coiled-coil gate. Supported by mutational and biochemical assays, our findings provide previously unidentified mechanistic insights and open potential avenues for the development of next-generation type IIA topoisomerase inhibitors.
GPT-4o mini: Non-social science research article
The evolution of cheaper workers facilitated larger societies and accelerated diversification in ants
Arthur Matte, Benoit Guénard, Shubham Gautam, Fumika Azuma, Julian Katzke, Francisco Hita Garcia, Thomas van de Kamp, Evan P. Economo
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Trade-offs between quantity and quality are common in the organization and evolution of biological, technological, and economic systems. In social insects, shifts from solitary organisms to complex societies bring this dilemma to the colony scale: producing fewer robust units or many cheaper ones. We investigate how cuticle investment, a major nutritional cost, shaped the evolution of ant societies and diversification. Using a computer vision approach on three-dimensional x-ray microtomography scans of 880 specimens from 507 species, we show that larger colonies were facilitated by reducing exoskeleton investment rather than miniaturizing workers. Reduced cuticle investment was associated with accelerated diversification rates in ants, whereas other candidates—colony size and worker size—did not correlate with diversification. Diet and climate had measurable but secondary effects on cuticle investment. Our results support a hypothesis whereby evolving cheaper but more numerous units through reduced investment in structural tissues was a strategic trend in the evolution and diversification of complex insect societies.
GPT-4o mini: Non-social science research article
Natural variants of AGL80.5 and FPA.3 contribute to bud break timing in poplar by controlling auxin biosynthesis
Lianzheng Li, Rui Huang, Zhuoying Jin, Donghai Zhang, Mengjiao Zhang, Liang Xiao, Peng Li, Jiaxuan Zhou, Chongde Tian, Leishi Zhong, Mingyang Quan, Lijun Liu, Qinsong Yang, Deqiang Zhang, Qingzhang Du
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The molecular mechanisms governing phenological characteristics and local adaptation in woody perennials remain largely unexplored. Here, we identified that AGAMOUS-LIKE 80 ( PtoAGL80.5 ) and FLOWERING TIME CONTROL PROTEIN FPA ( PtoFPA.3 ) were simultaneously associated with photoperiod factors and bud break (BB) timing in Populus tomentosa . Transgenic experiments in growth chamber and two latitudinal field trials confirmed their positive roles in promoting BB. Both are activated by the canonical phenological regulator SUPPRESSOR OF OVEREXPRESSION OF CO 1 , which, in turn, up-regulates the auxin biosynthesis gene TRYPTOPHAN AMINOTRANSFERASE–RELATED ( PtoTAR2.1 ), accelerating BB via auxin pathway. As superior haplotypes, PtoFPA.3 HAP1 binds PtoAGL80.5 HAP1 messenger RNA to elevate protein, up-regulating PtoTAR2.1 and increasing indole-3-acetic acid accumulation. Under future climate scenarios, frequencies of PtoFPA.3 HAP1 and PtoAGL80.5 HAP1 are predicted to decline, narrowing BB variance across populations. This genetic regulatory network governing BB timing via the auxin pathway in perennial plants provides insights for molecular design breeding and ecological conservation amid climate change.
GPT-4o mini: Non-social science research article
Persistent glycolysis defines pathological foreign body–associated inflammation to polymeric implants
Christian Rempe, Neal Callaghan, Lauren Fong-Hollohan, Sarah Nersesian, Zachary Froom, Kyle Medd, Ibrahim Ahmed, Tobias Karakach, Jeanette E. Boudreau, Michael Bezuhly, Locke Davenport Huyer
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The clinical deployment of nondegradable polymeric medical devices is hindered by unresolving inflammation that drives localized fibrosis. This inflammatory niche is distinct; phagocytic macrophages remain persistently activated by biomolecular signals adsorbed to the implant surface, exhibiting profibrotic behavior. Increasingly, alterations to metabolic regulation offers insight into chronically inflamed macrophage function, which remains unexplored in peri-implant inflammation. Here, ex vivo profiling of metabolic dependence and capacity in peri-implant tissues revealed persistent glycolytic reliance by macrophages up to 6 weeks postimplantation. Expression of glucose transporter 1 (GLUT1) increased temporally and with proximity to the implant interface in glycolytically dependent cells, paired with increased capacity for biosynthetic pathways. Glycolytic dependence was notable in multinucleated macrophages, hallmark to the phagocytic behavior of implant pathology. Transcriptomic assessment correlated the up-regulation of pathological wound healing to cells where the capacity for glucose import was highest, highlighting glycolysis as the definitive metabolic system in persistent peri-implant inflammation.
GPT-4o mini: Non-social science research article
Humpback whale genomes reflect the increased efficiency of commercial whaling
Fabricio Furni, Martine Bérubé, Marcos Suårez-Menéndez, Eduardo R. Secchi, Randall R. Reeves, Jooke Robbins, Camilla F. Speller, Per J. PalsbÞll
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Genetic diversity is declining globally, a trend that may particularly affect exploited populations that must adapt to rapid environmental change and other threats. Estimated genomic changes in effective population size mirrored known whaling history and shifts in technology. In the Southern Ocean, a comparison of genomes from historical and contemporary populations indicated that the contemporary genomes have less diversity and an elevated realized mutation load for moderately deleterious mutations, likely due to the effects of whaling. Our results demonstrate that the relatively recent, brief, and marked depletion of humpback whale populations by whaling likely had subtle but discernible, negative, and lasting effects on the whales’ genomes. Thus, even as some humpback whale populations are now recovering to pre-exploitation numbers, they likely do so with a diminished adaptive capacity in the face of future conditions and threats.
GPT-4o mini: Non-social science research article
Flexible low-voltage organic transistors with a transit frequency of 40 MHz and an on/off current ratio of 10 orders of magnitude
Ute Zschieschang, Hagen Klauk
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Organic thin-film transistors (TFTs) are of interest for flexible displays, sensors, and circuits. For all these applications, the TFTs must have a large on/off current ratio and a high transit frequency. A major challenge is to simultaneously maximize the on/off ratio and the transit frequency, because a high transit frequency requires a small channel length, which often leads to short-channel effects, including a large off-state drain current. Here, we lift this fundamental compromise and demonstrate organic TFTs that exhibit a complete absence of detrimental short-channel effects for channel lengths down to 300 nm, making it possible to simultaneously achieve the largest on/off current ratio (10 10 ) and the highest transit frequency (40 MHz) reported to date for flexible organic TFTs, despite the fact that these TFTs operate at very low voltages (≀3 V). These organic TFTs therefore meet the fundamental static and dynamic performance requirements for flexible, high-frequency, low-voltage, low-power electronic systems.
GPT-4o mini: Non-social science research article
A nanolaser with extreme dielectric confinement
Meng Xiong, Yi Yu, Yury Berdnikov, Simon Klinck Borregaard, Adrian Holm Dubré, Elizaveta Semenova, Kresten Yvind, Jesper MÞrk
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The interaction between light and matter can be enhanced by spatially concentrating the light field and extending photon dwell time. Plasmonic structures can provide strong light confinement but suffer from ohmic losses. Recent advances in dielectric nanostructures enable strong light localization without metallic losses. However, previous studies primarily focused on minimizing the optical mode volume without adequately addressing light-matter interactions. Here, we demonstrate a nanolaser that colocalizes photons and excited carriers within a dielectric nanobridge. This extreme dielectric confinement of both light and matter yields a subdiffraction-limited mode volume and a subwavelength carrier volume without lateral quantum confinement. We observe a strong correlation between the mode field and carrier distribution, where enhanced mode localization produces stronger carrier confinement. By suppressing carrier surface recombination, this platform not only enables continuous-wave lasing at room temperature but also achieves a substantially reduced lasing threshold. We quantify the intensified interaction with an interaction volume, generalizing mode volume to a broad class of active media.
GPT-4o mini: Non-social science research article
Asymmetries-induced nonlinear dynamic behaviors enable versatile modulation strategy for insect-scale robotics
Yanting Gong, Zhongbin Guo, Kaijun Zhang, Dazhe Zhao, Tingxu Lan, Chengyue Lu, Yuan Ma, Junwen Zhong
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Developing versatile insect-scale robots that can handle various unstructured scenarios with a simple design remains a critical challenge. Here, we introduce a single electromagnetic actuator-driven insect-scale robot, developed by integrating geometric and mass asymmetries into a deformable hexagonal frame. This asymmetric configuration induces nonlinear dynamic behaviors in the robot, allowing it to perform a variety of complex actions (e.g., forward and backward locomotion, active flipping, and lateral movement) and respond to challenging scenarios (e.g., granular media and safe landing) through posture transitions. To facilitate the behavior modulation and design optimization of the proposed insect-scale robot, a nonlinear dynamic model is established to map the relationship between motion behaviors and input parameters. Last, an untethered prototype that can work in outdoor environments is constructed to further demonstrate the practical applications.
GPT-4o mini: Non-social science research article
In situ NMR–guided design of alkaline electrochemical ammonia synthesis
Ruipeng Luo, Anna BergljĂłt GunnarsdĂłttir, Ruud L. E. G. Aspers, Evan Wenbo Zhao
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As a low-carbon and decentralized ammonia synthetic method, lithium-mediated electrochemical synthesis has shown promising Faradaic efficiencies and reaction rates. Nevertheless, challenges including low energy efficiency and long-term stability need to be addressed. Here, we develop and apply in situ NMR methodology to reveal a range of reaction mechanisms, including plating of metallic lithium and the concurrent corrosion, nitrogen splitting on lithium metal, protonolysis of lithium nitride, and the formation of lithium ethoxide. Guided by the NMR insights, we demonstrate a biphasic alkaline-organic lithium-mediated electrochemical ammonia synthesis coupled with value-added organic conversion via alcohol and furfural oxidation. This approach provides a strategy to increase the anodic charge utilization and improve the overall energy efficiency of lithium-mediated ammonia synthesis.
GPT-4o mini: Non-social science research article
Observing momentum conservation at temporal interfaces in synthetic frequency dimension
Yanyan He, Zhaohui Dong, Guangzhen Li, Penghong Yu, Xiaoxiong Wu, Xianfeng Chen, Luqi Yuan
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Electromagnetic wave dynamics at the temporal interface (TI), defined as the abrupt change of material properties in time, is fundamentally different from the counterpart at the spatial interface. The cornerstone for understanding the temporal scattering process for waves links to the momentum conservation for the state projections on the energy bands at the TI. Here, we experimentally construct various TIs in synthetic frequency dimension and study temporal scattering processes over the whole band. Different temporal operation scenarios are studied, including band shifting, band unfolding/folding, and also band variation in a two-dimensional case. We develop the spectral tomography method to retrieve wave function distributions after wave scatterings at different TIs and then demonstrate the momentum conservation over the whole band. Our work provides a flexible experimental platform for realizing TIs in the optical frequency range and studying the fundamental temporal scattering processes for photons.
GPT-4o mini: Non-social science research article
A hydroxyl group dictates handedness, pitch, and mechanics in a crystalline covalent helical polymer
Ravichandran Khazeber, Divina Xavier, Kana M. Sureshan
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Helical polymers are fascinating materials, yet retaining their helicity in the solid state remains a key challenge for practical applications. Here, we present a regiospecific topochemical azide-alkyne cycloaddition for synthesizing crystalline covalent helical polymers via a single–crystal–to–single–crystal transformation. Building on our prior glycine-proline–based systems, we investigated the effect of subtle modification: introducing a hydroxyl group to the proline unit. This minor change induced a helicity reversal (left- to right-handed) and a substantial reduction in pitch (8.9 to 4.9 Å). Single-crystal x-ray diffraction revealed that this profound reordering is driven by intra- and intermolecular hydrogen bonds (C─H⋯O and O─H⋯N), acting as supramolecular bridges between helices, enabling denser packing. Consequently, the glycine-hydroxyproline–based polymer exhibited markedly enhanced mechanics, with a Young’s modulus of 18.57 ± 2.01 GPa and hardness of 1.09 ± 0.13 GPa, surpassing natural collagen. This study provides insights into controlling polymer topology and mechanics through subtle modifications, establishing a powerful paradigm for the design of next-generation helical materials with tailored functionalities.
GPT-4o mini: Non-social science research article
Growth hormone is required for hippocampal engram cell maturation
Chang-Ho Kim, HyoJin Park, Chuljung Kwak, Dae Hee Han, Yeojin Jung, Binod Timalsina, Ilgang Hong, Yeonjun Kim, Yong-Seok Lee, Nam-Kyung Yu, Jun Cho, Bong-Kiun Kaang
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Memory is stored in specialized cells known as engram cells, but the molecular mechanisms underlying this process remain unclear. We discovered that the initial translation leading to growth hormone (GH) synthesis in engram cells is required for their maturation in the mouse dentate gyrus. Time-course experiments with a translation inhibitor suggested that the key molecule is immediately translated during learning. We identified GH as the crucial factor, specifically translated within the first few minutes of consolidation in engram cells. Blocking GH activity with a dominant-negative (G118R) mutation blocked engram maturation, whereas facilitating activity-dependent GH uptake alleviated engram maturation deficits caused by translation inhibition. Together, our findings propose GH as a key mediator of hippocampal engram cell maturation.
GPT-4o mini: Non-social science research article
Phosphorus-lithium double-helix nanoribbons
Chuang Hou, Huan Lu, Yi Liu, Qilong Wu, Nathampapop Jobsri, Siyuan Liu, Liren Wang, Qiang Gao, Jiamin Wu, Byunghun Oh, Ryoto Yanagisawa, Xin Wu, Masahiro Nomura, Wanlin Guo, Naoji Matsuhisa, Guoan Tai
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Phosphorus nanoribbons combine the tunable bandgap and high mobility with the inherent anisotropy of one-dimensional systems, offering promise for functional electronics, but their intrinsic low stability hinders practical applications. Here, we report phosphorus-lithium double-helix nanoribbons with a well-ordered helical architecture and high structural stability under harsh conditions such as in air up to 225°C, water, and even acidic solutions. Comprehensive experimental characterizations and theoretical analyses show that the stability arises from a synergistic combination of Zintl phase formation between phosphorus and lithium atoms, noncovalent interhelical interactions, and geometric protection offered by the distinctive helical architecture. The nanoribbons show tunable optical properties dependent on temperature, thickness, and polarization state. It is demonstrated that these properties enabled nanoribbon-based hydrogels with self-healability and highly efficient photothermal conversion, showing a general approach for stabilizing active low-dimensional materials and paving the way for applying phosphorus-based nanostructures in biomedical engineering and quantum technologies.
GPT-4o mini: Non-social science research article
Frog vocal sacs-inspired soft acoustic system with continuously tunable resonance for sound emission and stethoscopic sensing
Chuting Liu, Peiyan Dong, Jiantao Wang, Zhikang Deng, Jinan Luo, Chang Liu, Jingzhi Wu, Kaiyuan Tan, Jiajun Pan, Rongkuan Han, Yuanfang Li, Lvjie Chen, Xinyi Qu, Jianfeng Ma, Qinghong Zhou, Bojun Yan, Yu Ran, Dalun Rong, Jianping Jiang, Bo Li, Tian-Ling Ren, Jianhua Zhou, Yancong Qiao
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To overcome limitations of flexible thermoacoustic devices in low-frequency emission and sensing, we present a resonance-adjustable graphene sound device (RAGSD) inspired by frog vocal sacs. Integrating laser-induced graphene (LIG) with a deformable cavity, RAGSD provides continuous tuning from 922.12 to 1762.90 hertz. A dynamic, continuously tunable electro-mechano-acoustical model explains the mechanism and predicts frequency with R 2 = 0.990 . In emission, a 25.34-decibel sound pressure level gain was observed at resonance, enabling controllable, frequency-selective voice amplification for personalized output. In sensing, the LIG piezoresistive readout delivers sensitive transduction, while resonance matching amplifies weak, high-frequency cardiac sounds. Wearable tests on healthy volunteers and patients recorded clear S1/S2 and pathological murmurs. Integrated with AuscNet-H, a deep learning algorithm designed for heart sound classification, the system achieved 99.375% accuracy across four clinical classes. Under inflation, no false negatives occurred, and misclassifications among similar diseases were fewer than with a commercial electronic stethoscope. These results demonstrate a practical path toward intelligent, wearable auscultation.
GPT-4o mini: Non-social science research article
CRISPRa-mediated disentanglement of the Dux-MERVL axis in the 2C-like state, totipotency, and cell death
Paul Chammas, Sheila Q. Xie, Lessly P. Sepulveda-Rincon, Bryony J. Leeke, Marian H. Dore, Dirk Dormann, Ryan T. Wagner, Ning Chang, Peter L. Jones, Michael T. McManus, Mohammad M. Karimi, George Young, Michelle Percharde
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Transposable elements (TEs) are powerful cis-regulatory drivers of gene expression, particularly during early development when many TEs become de-repressed. MERVL elements are transiently up-regulated in mouse totipotent two-cell (2C) embryos during major zygotic genome activation (ZGA) and 2C-like cells in vitro. One of the most powerful activators of MERVL is the pioneer transcription factor, Dux. However, apparent differences lie in the requirement for Dux versus MERVL activation in embryos. Moreover, sustained Dux activation causes cell toxicity, which may or may not be linked to MERVL. Using a CRISPR activation system, we unpick the relative role of Dux and MERVL in ZGA, totipotent-like characteristics, and cell toxicity. We find that MERVL activation drives a portion of the Dux-dependent transcriptome, sufficient for expanded fate potential, but not other totipotency features. Conversely, Dux-induced pathology is independent of MERVL activation and involves the proapoptotic factor, Noxa. Our study highlights the complexity of the Dux-MERVL transcriptional network and uncovers a previously unknown player in Dux-driven pathology.
GPT-4o mini: Non-social science research article
EGFR activation requires cholesterol interaction at the inner leaflet of the plasma membrane
Do-Hyeon Kim, Minh-Triet Hong, Eduard V. Bocharov, Soyeon Park, Yaroslav V. Bershatsky, Pavel E. Volynsky, Eui Kim, Roman G. Efremov, Wonhwa Cho, Seung-Yeol Park, Sung Ho Ryu
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Signal transduction by the human epidermal growth factor receptor (EGFR) is modulated by its ligands as well as by the various compounds on the plasma membrane (PM), including cholesterol. Here, using single-molecule coimmunoimmobilization, we found that cholesterol in the inner leaflet of PM plays an essential role in ligand-dependent EGFR activation. This was done by direct and quantitative examination of the interaction between EGFR and cholesterol on the PM of a living cell. Structural analysis using molecular dynamics simulations and nuclear magnetic resonance spectroscopy further revealed that cholesterol in the inner leaflet is critically important for the transition of the dimeric transmembrane domain (TMD) of the receptor to the active conformation. We also identified the specific pattern of residues Ile 640 -Gly 641 -Leu 642 of EGFR TMD regulating inner leaflet cholesterol binding and ligand-activated EGFR by screening via site-directed mutagenesis. Our results indicate that cholesterol in the inner leaflet of PM is a key checkpoint of EGFR activation triggered by EGF.
GPT-4o mini: Non-social science research article
GPNMB, LRRK2, and lysosome exocytosis in Parkinson’s
Suzanne R. Pfeffer
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When two genes linked to increased Parkinson’s risk converge on a lysosome, LRRK2 mutation enhances lysosomal release of soluble GPNMB potentially contributing to synuclein pathology.
GPT-4o mini: Non-social science research article
Nanosheet-bridged metal-organic framework membranes for durable hydrocarbon separation under high pressure
Quan Zhao, Mingang Zhao, Wen Wang, Ziheng Song, Jianyu Wang, Yongjun Tian, Qianfeng Pan, Hanze Ma, Sheng Yuan, Shilin Guo, Yuhan Yang, Yanshuo Li, Rongfei Zhou, Guangwei He, Zhongyi Jiang
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Metal-organic framework (MOF) membranes have garnered notable interest in molecular separation. However, their high-pressure application is severely hampered by the mechanical fragility stemming from weak interactions at grain boundaries. Inspired by the cuttlebone’s wall-cavity structure, we develop a class of nanosheets-bridged MOF membranes (NB-MOFs). These graphene oxide nanosheets act as a rigid wall, bridging soft MOF grains and dispersing accumulated stresses at grain boundaries under external loadings, thereby preventing structural cracking and enhancing the mechanical robustness of crystal membranes. By fine-tuning the morphology and content of nanosheets, the optimized NB–ZIF-8 membranes are endowed with unprecedented 50-bar pressure resistance and superior C 3 H 6 /C 3 H 8 separation performance, with a separation factor >240 maintained above 300 hours at industry-relevant pressure. We also confirm our strategy’s versatility by fabricating pressure-resistant NB–ZIF-67 membrane and commercial polymer-supported NB-MOF membranes. We envision that our strategy will establish a platform for developing durable crystalline membranes and unlock their potential in real-world scenarios.
GPT-4o mini: Non-social science research article
Microbubble-induced erosion releases micro- and nanoplastics into water
Dunzhu Li, Varvara Bolikava, Yunhong Shi, Songheng Jin, Richard Unitt, Emmet D. Sheerin, Peiying Kang, Liwen Xiao, Xiaocheng Pan, Christopher Hill, Manuel Ruether, Linfei Zhao, Qidong Yin, Bo Zhao, Qiliang Zhu, Hua Qin, Ming Cheng, John E. Sader, Jing Jing Wang, John J. Boland
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Micro- and nanoplastics (MNPs) are pervasive micropollutants in aquatic environments and along shorelines. Their release is predominantly attributed to mechanical abrasion or ultraviolet exposure, both requiring substantial external energy inputs. The role of aquatic factors (e.g., air bubbles) in the generation of MNPs is poorly understood. Here we show microbubbles that spontaneously form on seven typical plastics across a wide temperature range (25° to 95°C) and in various water types (deionized, tap, river, and marine water) can erode plastic surfaces and drive MNP release. Nucleation, expansion, and movement of microbubbles generate shear stresses capable of dislodging polymer protrusions at surface defect sites. This sweeping action, combined with the unbalanced surface tension forces at the three-phase contact line, generates O-shaped ring structures composed of accumulated polymers, which ultimately fragment leading to the release of MNPs into the aquatic environment. Our findings demonstrate that microbubble-induced erosion represents a low-energy pathway for micropollutant release.
GPT-4o mini: Non-social science research article
Cell wall–derived mechanical signals control cell growth and division during root development
Noemi Svolacchia, Marco Marconi, Julian Elijah Politsch, Federico Vinciarelli, Michela De Nittis, Elena Salvi, Mariana Sotelo-Silveira, Alessio Terenzi, Gaia Bertolotti, Claudia Testi, Giancarlo Ruocco, Raffaele Dello Ioio, Riccardo Di Mambro, Paolo Costantino, Krzysztof Wabnik, Sabrina Sabatini
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Organogenesis emerges from the interplay between genetic and physical interactions within a growing cellular system. While numerous studies have explored how genetic and molecular networks regulate cell activity, the impact of physical interactions and the resulting mechanical constraints on organ development remains poorly understood. In this study, we combine extensive genetic analysis, live imaging, and mechanical measurements with spatiotemporal computational modeling to show that, in the Arabidopsis root, changes in the mechanical properties of elongating cell walls influence growth and division rate of neighboring meristematic cells, thereby shaping root development. We propose that the cell wall serves as a crucial source of both autonomous and nonautonomous mechanical signals, providing a compelling example of how mechanical forces contribute to organ growth and development.
Does humidity matter? Prenatal heat and child health in South Asia
Kathryn McMahon, Kathy Baylis, Stuart Sweeney, Chris Funk
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Heat extremes pose substantial health risks during pregnancy and early childhood. High humidity exacerbates heat strain, but its long-term effects on health remain poorly understood. We compare the effect of prenatal exposure to extreme humid heat versus heat alone on child growth in South Asia, where high rates of child stunting meet rapidly accelerating hot-humid extremes. After adjusting for sociodemographic, seasonal, and spatial confounders, we use within-community variation in children’s ages to isolate the impact of prenatal exposures. We find that hot-humid exposures are much more detrimental to health than hot temperatures alone, with the potential to increase stunting in South Asia by over 3 million children by 2050. These findings underscore the importance of accounting for humidity when estimating and localizing climate change impacts.