I checked 6 multidisciplinary journals on Saturday, November 22, 2025 using the Crossref API. For the period November 15 to November 21, I found 26 new paper(s) in 5 journal(s).

Nature

GPT-4o mini: Non-social science research article
Hepatic zonation determines tumorigenic potential of mutant ÎČ-catenin
Alexander Raven, Kathryn Gilroy, Hu Jin, Joseph A. Waldron, Holly Leslie, June Munro, Holly Hall, Rachel A. Ridgway, Catriona A. Ford, Doga C. Gulhan, Nikola Vlahov, Megan L. Mills, Andrew Hartley, Eve Anderson, Sheila Bryson, Nathalie Sphyris, Miryam MĂŒller, Stephanie May, Barbara Cadden, Colin Nixon, Scott H. Waddell, Rachel Guest, Luke Boulter, Nick Barker, Hans Clevers, Hao Zhu, Johanna Ivaska, Douglas Strathdee, Crispin J. Miller, Nigel B. Jamieson, Martin Bushell, Peter J. Park, Thomas G. Bird, Owen J. Sansom
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Oncogenic mutations in phenotypically normal tissue are common across adult organs 1,2 . This suggests that multiple events need to converge to drive tumorigenesis and that many processes such as tissue differentiation may protect against carcinogenesis. WNT–ÎČ-catenin signalling maintains zonal differentiation during liver homeostasis 3,4 . However, the CTNNB1 oncogene—encoding ÎČ-catenin—is also frequently mutated in hepatocellular carcinoma, resulting in aberrant WNT signalling that promotes cell growth 5,6 . Here we investigated the antagonistic interplay between WNT-driven growth and differentiation in zonal hepatocyte populations during liver tumorigenesis. We found that ÎČ-catenin mutations co-operate with exogenous MYC expression to drive a proliferative translatome. Differentiation of hepatocytes to an extreme zone 3 fate suppressed this proliferative translatome. Furthermore, a GLUL and Lgr5 -positive perivenous subpopulation of zone 3 hepatocytes were refractory to WNT-induced and MYC-induced tumorigenesis. However, when mutant CTNNB1 and MYC alleles were activated sporadically across the liver lobule, a subset of mutant hepatocytes became proliferative and tumorigenic. These early lesions were characterized by reduced WNT pathway activation and elevated MAPK signalling, which suppresses zone 3 differentiation. The proliferative lesions were also dependent on IGFBP2–mTOR–cyclin D1 pathway signalling, in which inhibition of either IGFBP2 or mTOR suppressed proliferation and tumorigenesis. Therefore, we propose that zonal identity dictates hepatocyte susceptibility to WNT-driven tumorigenesis and that escaping WNT-induced differentiation is essential for liver cancer.
GPT-4o mini: Non-social science research article
Rare microbial relict sheds light on an ancient eukaryotic supergroup
Marek Valt, TomĂĄĆĄ PĂĄnek, Seda Mirzoyan, Alexander K. Tice, Robert E. Jones, VĂ­t DohnĂĄlek, Pavel DoleĆŸal, Jiƙí MikĆĄĂĄtko, Johana RotterovĂĄ, Pavla HrubĂĄ, Matthew W. Brown, Ivan Čepička
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During the past decade, our understanding of eukaryotic evolution has increased immensely. Newly recognized eukaryotic supergroups have been established1,2,3, and most enigmatic orphan lineages have had their relationships resolved4,5,6. Studies on unicellular protist eukaryotes have also been key to understanding the evolution of mitochondria, the fundamental organelles of the eukaryotic cell, which originated from an alphaproteobacterial ancestor. The retention of ancestral alphaproteobacterial pathways in some protist lineages reveals that the mitochondrion of the last eukaryotic common ancestor was more metabolically versatile than are the highly derived mitochondria that are found in most modern eukaryotes7,8. Here we report the discovery of such a unicellular eukaryote, Solarion arienae gen. et sp. nov., an inconspicuous, free-living heterotrophic protist with two morphologically distinct cell types and a novel type of predatory extrusome. We assign Solarion to the new phylum Caelestes. Together with Provora, hemimastigophoreans and Meteora, they form a new eukaryotic supergroup, Disparia. Moreover, S. arienae has some noteworthy traits associated with the mitochondrial genome; in particular, the mitochondrially encoded secA gene, a remnant of an ancestral alphaproteobacterial protein secretion pathway, which has been lost almost entirely in extant mitochondria9,10. The discovery of S. arienae broadens our understanding of early eukaryotic evolution and facilitates the study of proto-mitochondrial metabolic remnants, shedding light on the complexity of ancestral eukaryotic life.
GPT-4o mini: Non-social science research article
Author Correction: Brahma safeguards canalization of cardiac mesoderm differentiation
Swetansu K. Hota, Kavitha S. Rao, Andrew P. Blair, Ali Khalilimeybodi, Kevin M. Hu, Reuben Thomas, Kevin So, Vasumathi Kameswaran, Jiewei Xu, Benjamin J. Polacco, Ravi V. Desai, Nilanjana Chatterjee, Austin Hsu, Jonathon M. Muncie, Aaron M. Blotnick, Sarah A. B. Winchester, Leor S. Weinberger, Ruth HĂŒttenhain, Irfan S. Kathiriya, Nevan J. Krogan, Jeffrey J. Saucerman, Benoit G. Bruneau
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GPT-4o mini: Non-social science research article
Shared and language-specific phonological processing in the human temporal lobe
Ilina Bhaya-Grossman, Matthew K. Leonard, Yizhen Zhang, Laura Gwilliams, Keith Johnson, Junfeng Lu, Edward F. Chang
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All spoken languages are produced by the human vocal tract, which defines the limited set of possible speech sounds. Despite this constraint, however, there exists incredible diversity in the world’s 7,000 spoken languages, each of which is learned through extensive experience hearing speech in language-specific contexts 1 . It remains unknown which elements of speech processing in the brain depend on daily language experience and which do not. In this study, we recorded high-density cortical activity from adult participants with diverse language backgrounds as they listened to speech in their native language and an unfamiliar foreign language. We found that, regardless of language experience, both native and foreign languages elicited similar cortical responses in the superior temporal gyrus (STG), associated with shared acoustic–phonetic processing of foundational speech sound features 2,3 , such as vowels and consonants. However, only during native language listening did we observe enhanced neural encoding in the STG for word boundaries, word frequency and language-specific sound sequence statistics. In a separate cohort of bilingual participants, this encoding of word- and sequence-level information appeared for both familiar languages in the same individual and in the same STG neural populations. These results indicate that experience-dependent language processing involves dynamic integration of both shared acoustic–phonetic and language-specific sequence- and word-level information in the STG.
GPT-4o mini: Non-social science research article
ZAK activation at the collided ribosome
Vienna L. Huso, Shuangshuang Niu, Marco A. Catipovic, James A. Saba, Timo Denk, Eugene Park, Jingdong Cheng, Otto Berninghausen, Thomas Becker, Rachel Green, Roland Beckmann
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Ribosome collisions activate the ribotoxic stress response mediated by the MAP3K ZAK, which in turn regulates cell-fate consequences through downstream phosphorylation of the MAPKs p38 and JNK 1 . Despite the critical role of ZAK during cellular stress, a mechanistic and structural understanding of ZAK–ribosome interactions and how these lead to activation remain elusive. Here we combine biochemistry and cryo-electron microscopy to discover distinct ZAK–ribosome interactions required for constitutive recruitment and for activation. We find that upon induction of ribosome collisions, interactions between ZAK and the ribosomal protein RACK1 enable its activation by dimerization of its SAM domains at the collision interface. Furthermore, we discover how this process is negatively regulated by the ribosome-binding protein SERBP1 to prevent constitutive ZAK activation. Characterization of novel SAM variants as well as a known pathogenic variant of the SAM domain of ZAK supports a key role of the SAM domain in regulating kinase activity on and off the ribosome, with some mutants bypassing the ribosome requirement for ZAK activation. Collectively, our data provide a mechanistic blueprint of the kinase activity of ZAK at the collided ribosome interface.
GPT-4o mini: Non-social science research article
The Asymmetric Synthesis of an Acyclic N-Stereogenic Amine
Chendan Zhu, Sayantani Das, Marie Sophie Sterling, Nobuya Tsuji, Spencer J. Léger, Frank Neese, Chandra Kanta De, Benjamin List
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Most molecules of chemistry and biology are chiral, leading to mirror image variants, so called enantiomers. However, while the selective chemical synthesis of molecules where the stereogenicity arises from a carbon atom is well-established, enantioselective approaches to nitrogen-stereogenic molecules are much less common,1-3 and in case of acyclic, N-stereogenic amines, even elusive, due to their rapid pyramidal inversion. We describe here the catalytic asymmetric synthesis of stable, acyclic N-stereogenic amines by the addition of enol silanes to nitronium ions that ion pair to a confined chiral anion. In the produced so-called anomeric amines, the commonly observed isomerization is slowed down by two N-oxy-substituents, which hamper nitrogen inversion. The critical stereogenicity creating step challenges previously established stereochemical descriptors of enantiodifferentiation. Computational studies provide additional insight into the origin of the observed stereocontrol. Our work opens up a new avenue to investigate the fascinating and previously underexplored chemistry of enantiopure anomeric amines.
GPT-4o mini: Non-social science research article
Integrator dynamics in the cortico-basal ganglia loop for flexible motor timing
Zidan Yang, Miho Inagaki, Charles R. Gerfen, Lorenzo Fontolan, Hidehiko K. Inagaki
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Flexible control of motor timing is crucial for behaviour 1–4 . Before volitional movement begins, the frontal cortex and striatum exhibit ramping spiking activity, with variable ramp slopes anticipating movement onsets 5–12 . This activity in the cortico-basal ganglia loop may function as an adjustable ‘timer,’ triggering actions at the desired timing. However, because the frontal cortex and striatum share similar ramping dynamics and are both necessary for timing behaviours, distinguishing their individual roles in this timer function remains challenging. Here, to address this, we conducted perturbation experiments combined with multi-regional electrophysiology in mice performing a flexible lick-timing task. Following transient silencing of the frontal cortex, cortical and striatal activity swiftly returned to pre-silencing levels and resumed ramping, leading to a shift in lick timing close to the silencing duration. Conversely, briefly inhibiting the striatum caused a gradual decrease in ramping activity in both regions, with ramping resuming from post-inhibition levels, shifting lick timing beyond the inhibition duration. Thus, inhibiting the frontal cortex and striatum effectively paused and rewound the timer, respectively. These findings are consistent with a model in which the striatum is part of a network that temporally integrates input from the frontal cortex and generates ramping activity that regulates motor timing.
GPT-4o mini: Non-social science research article
Author Correction: AIM2 in regulatory T cells restrains autoimmune diseases
Wei-Chun Chou, Zengli Guo, Hao Guo, Liang Chen, Ge Zhang, Kaixin Liang, Ling Xie, Xianming Tan, Sara A. Gibson, Elena Rampanelli, Yan Wang, Stephanie A. Montgomery, W. June Brickey, Meng Deng, Leslie Freeman, Song Zhang, Maureen A. Su, Xian Chen, Yisong Y. Wan, Jenny P.-Y. Ting
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GPT-4o mini: Non-social science research article
Semantic design of functional de novo genes from a genomic language model
Aditi T. Merchant, Samuel H. King, Eric Nguyen, Brian L. Hie
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Generative genomic models can design increasingly complex biological systems 1 . However, controlling these models to generate novel sequences with desired functions remains challenging. Here, we show that Evo, a genomic language model, can leverage genomic context to perform function-guided design that accesses novel regions of sequence space. By learning semantic relationships across prokaryotic genes 2 , Evo enables a genomic ‘autocomplete’ in which a DNA prompt encoding genomic context for a function of interest guides the generation of novel sequences enriched for related functions, which we refer to as ‘semantic design’. We validate this approach by experimentally testing the activity of generated anti-CRISPR proteins and type II and III toxin–antitoxin systems, including de novo genes with no significant sequence similarity to natural proteins. In-context design of proteins and non-coding RNAs with Evo achieves robust activity and high experimental success rates even in the absence of structural priors, known evolutionary conservation or task-specific fine-tuning. We then use Evo to complete millions of prompts to produce SynGenome, a database containing over 120 billion base pairs of artificial intelligence-generated genomic sequences that enables semantic design across many functions. More broadly, these results demonstrate that generative genomics with biological language models can extend beyond natural sequences.
GPT-4o mini: Non-social science research article
A skin-permeable polymer for non-invasive transdermal insulin delivery
Qiuyu Wei, Zhi He, Zifan Li, Zhuxian Zhou, Ying Piao, Jianxiang Huang, Yu Geng, Runnan Zhang, Yaqi Fu, Jiayi Ye, Yue Yuan, Haoru Zhu, Jiaheng Zeng, Yan Zhang, Quan Zhou, Mingyu Xu, Shiqun Shao, Jianbin Tang, Jiajia Xiang, Rongjun Chen, Ruhong Zhou, Youqing Shen
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Non-invasive skin permeation is widely used for convenient transdermal delivery of small-molecule therapeutics (less than 500 Da) with appropriate hydrophobicities 1 . However, it has long been deemed infeasible for large molecules—particularly polymers, proteins and peptides 2,3 —due to the formidable barrier posed by the skin structure. Here we show that the fast skin-permeable polyzwitterion poly[2-( N -oxide- N,N -dimethylamino)ethyl methacrylate] (OP) can efficiently penetrate the stratum corneum, viable epidermis and dermis into circulation. OP is protonated to be cationic and is therefore enriched in the acidic sebum and paracellular stratum corneum lipids containing fatty acids, and subsequently diffuses through the intercorneocyte lipid lamella. Beneath the stratum corneum, at the normal physiological pH, OP becomes a neutral polyzwitterion, ‘hopping’ on cell membranes, enabling its efficient migration through the epidermis and dermis and ultimately entering dermal lymphatic vessels and systemic circulation. As a result, OP-conjugated insulin efficiently permeates through the skin into the blood circulation; transdermal administration of OP-conjugated insulin at a dose of 116 U kg −1 into mice with type 1 diabetes quickly lowers their blood glucose levels to the normal range, and a transdermal dose of 29 U kg −1 normalizes the blood glucose levels of diabetic minipigs. Thus, the skin-permeable polymer may enable non-invasive transdermal delivery of insulin, relieving patients with diabetes from subcutaneous injections and potentially facilitating patient-friendly use of other protein- and peptide-based therapeutics through transdermal delivery.
GPT-4o mini: Non-social science research article
Rewiring an olfactory circuit by altering cell-surface combinatorial code
Cheng Lyu, Zhuoran Li, Chuanyun Xu, Jordan Kalai, Liqun Luo
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Proper brain function requires the precise assembly of neural circuits during development. Despite the identification of many cell-surface proteins (CSPs) that help guide axons to their targets 1,2 , it remains mostly unknown how multiple CSPs work together to assemble a functional circuit. Here we used synaptic partner matching in the Drosophila olfactory circuit 3,4 to address this question. By systematically altering the combination of differentially expressed CSPs in a single type of olfactory receptor neuron (ORN), which senses a male pheromone that inhibits male–male courtship, we switched its connection nearly completely from its endogenous postsynaptic projection neuron (PN) type to a new PN type that promotes courtship. From this switch, we deduced a combinatorial code including CSPs that mediate both attraction between synaptic partners and repulsion between non-partners 5,6 . The anatomical switch changed the odour response of the new PN partner and markedly increased male–male courtship. We generalized three manipulation strategies from this rewiring—increasing repulsion with the old partner, decreasing repulsion with the new partner and matching attraction with the new partner—to successfully rewire a second ORN type to multiple distinct PN types. This work shows that manipulating a small set of CSPs is sufficient to respecify synaptic connections, paving the way to investigations of how neural systems evolve through changes of circuit connectivity.
GPT-4o mini: Non-social science research article
Prime editing-installed suppressor tRNAs for disease-agnostic genome editing
Sarah E. Pierce, Steven Erwood, Keyede Oye, Meirui An, Nicholas Krasnow, Emily Zhang, Aditya Raguram, Davis Seelig, Mark J. Osborn, David R. Liu
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Precise genome-editing technologies such as base editing 1,2 and prime editing 3 can correct most pathogenic gene variants, but their widespread clinical application is impeded by the need to develop new therapeutic agents for each mutation. For diseases that are caused by premature stop codons, suppressor tRNAs (sup-tRNAs) offer a more general strategy. Existing approaches to use sup-tRNAs therapeutically, however, require lifelong administration 4,5 or show modest potency, necessitating potentially toxic overexpression. Here we present prime editing-mediated readthrough of premature termination codons (PERT), a strategy to rescue nonsense mutations in a disease-agnostic manner by using prime editing to permanently convert a dispensable endogenous tRNA into an optimized sup-tRNA. Iterative screening of thousands of variants of all 418 human tRNAs identified tRNAs with the strongest sup-tRNA potential. We optimized prime editing agents to install an engineered sup-tRNA at a single genomic locus without overexpression and observed efficient readthrough of premature termination codons and protein rescue in human cell models of Batten disease, Tay–Sachs disease and cystic fibrosis. In vivo delivery of a single prime editor that converts an endogenous mouse tRNA into a sup-tRNA extensively rescued disease pathology in a model of Hurler syndrome. PERT did not induce detected readthrough of natural stop codons or cause significant transcriptomic or proteomic changes. Our findings suggest the potential of disease-agnostic therapeutic genome-editing approaches that require only a single composition of matter to treat diverse genetic diseases.
GPT-4o mini: Non-social science research article
Author Correction: A metallic p-wave magnet with commensurate spin helix
Rinsuke Yamada, Max T. Birch, Priya R. Baral, Shun Okumura, Ryota Nakano, Shang Gao, Motohiko Ezawa, Takuya Nomoto, Jan Masell, Yuki Ishihara, Kamil K. Kolincio, Ilya Belopolski, Hajime Sagayama, Hironori Nakao, Kazuki Ohishi, Takashi Ohhara, Ryoji Kiyanagi, Taro Nakajima, Yoshinori Tokura, Taka-hisa Arima, Yukitoshi Motome, Moritz M. Hirschmann, Max Hirschberger
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GPT-4o mini: Non-social science research article
Author Correction: A pangenome and pantranscriptome of hexaploid oat
Raz Avni, Nadia Kamal, Lidija Bitz, Eric N. Jellen, Wubishet A. Bekele, Tefera T. Angessa, Petri Auvinen, Oliver Bitz, Brian Boyle, Francisco J. Canales, Craig H. Carlson, Brett Chapman, Harmeet Singh Chawla, Yutang Chen, Dario Copetti, Samara Correia de Lemos, Viet Dang, Steven R. Eichten, Kathy Esvelt Klos, Amit M. Fenn, Anne Fiebig, Yong-Bi Fu, Heidrun Gundlach, Rajeev Gupta, Georg Haberer, Tianhua He, Matthias H. Herrmann, Axel Himmelbach, Catherine J. Howarth, Haifei Hu, Julio Isidro y Sánchez, Asuka Itaya, Jean-Luc Jannink, Yong Jia, Rajvinder Kaur, Manuela Knauft, Tim Langdon, Thomas Lux, Sofia Marmon, Vanda Marosi, Klaus F. X. Mayer, Steve Michel, Raja Sekhar Nandety, Kirby T. Nilsen, Edyta Paczos-Grzęda, Asher Pasha, Elena Prats, Nicholas J. Provart, Adriana Ravagnani, Robert W. Reid, Jessica A. Schlueter, Alan H. Schulman, Taner Z. Sen, Jaswinder Singh, Mehtab Singh, Nick Sirijovski, Nils Stein, Bruno Studer, Sirja Viitala, Shauna Vronces, Sean Walkowiak, Penghao Wang, Amanda J. Waters, Charlene P. Wight, Weikai Yan, Eric Yao, Xiao-Qi Zhang, Gaofeng Zhou, Zhou Zhou, Nicholas A. Tinker, Jason D. Fiedler, Chengdao Li, Peter J. Maughan, Manuel Spannagl, Martin Mascher
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GPT-4o mini: Non-social science research article
Triplets electrically turn on insulating lanthanide-doped nanoparticles
Zhongzheng Yu, Yunzhou Deng, Junzhi Ye, Lars van Turnhout, Tianjun Liu, Alasdair Tew, Rakesh Arul, Simon Dowland, Yuqi Sun, Xinjuan Li, Linjie Dai, Yang Lu, Caterina Ducati, Jeremy J. Baumberg, Richard H. Friend, Robert L. Z. Hoye, Akshay Rao
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Insulating nanomaterials have large energy gaps and are only electrically accessible under extreme conditions, such as high-intensity radiation and high temperature, pressure or voltage 1,2 . Lanthanide-doped insulating nanoparticles (LnNPs) are widely studied owing to their exceptional luminescence properties, including bright, narrow-linewidth, non-blinking and non-bleaching emission in the second near-infrared (NIR-II) range 3,4 . However, it has not been possible to electrically generate excited states in these insulating nanomaterials under low biases and, therefore, not possible to fabricate optoelectronic devices from these systems. Here we report an electrical excitation pathway to obtain emission from LnNPs. By forming LnNP@organic molecule nanohybrids, in which the recombination of electrically injected charges on the organic molecule is followed by efficient triplet energy transfer (TET) to the LnNP, it is possible to turn on LnNPs under a low operating bias. We demonstrate this excitation pathway in light-emitting diodes (LEDs), with low turn-on voltages of about 5 V, very narrow electroluminescence (EL) spectra and a peak external quantum efficiency (EQE) greater than 0.6% in the NIR-II window 5 . Our LnNP-based LEDs (LnLEDs) also allow for widely tunable EL properties, by changing the type and concentration of lanthanide dopants. These results open up a new field of hybrid optoelectronic devices and provide new opportunities for the electrically driven excitation sources based on lanthanide nanomaterials for biomedical and optoelectronic applications.
GPT-4o mini: Non-social science research article
Connectivity underlying motor cortex activity during goal-directed behaviour
Arseny Finkelstein, Kayvon Daie, MĂĄrton RĂłzsa, Ran Darshan, Karel Svoboda
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Neural representations of information are shaped by long-range input and local network interactions. Previous studies linking neural coding and cortical connectivity have focused on input-driven activity in the sensory cortex1,2,3. Here we studied neural activity in the motor cortex while mice gathered rewards with multidirectional tongue reaching. This behaviour does not require training, allowing us to probe neural coding and connectivity before activity is shaped by extended learning. Motor cortex neurons were tuned to target location and reward outcome, and typically responded during and after movements. We studied the underlying network interactions in vivo by estimating causal neural connections using an all-optical method3,4,5,6. Mapping connectivity between more than 20,000,000 excitatory neuron pairs showed a multi-scale columnar architecture in layer 2/3 of the motor cortex. Neurons displayed local (less than 100 ”m) like-to-like excitatory connectivity according to target-location tuning, and inhibition over longer spatial scales. Connectivity patterns comprised a continuum, with abundant sparsely connected neurons and rare densely connected neurons that function as network hubs. Hub neurons were weakly tuned to target location and reward outcome but influenced more neighbouring neurons. This network of neurons, encoding location and outcome of movements to different motor goals, may be a general substrate for rapid learning of complex, goal-directed behaviours.
GPT-4o mini: Non-social science research article
Tumour-reactive heterotypic CD8 T cell clusters from clinical samples
SofĂ­a Ibåñez-Molero, Johanna Veldman, Juan Simon Nieto, Joleen J. H. Traets, Austin George, Kelly Hoefakker, Anita Karomi, Rolf Harkes, Bram van den Broek, Su Min Pack, Liselotte Tas, Nils L. Visser, Susan E. van Hal-van Veen, Paula AlĂłndiga-MĂ©rida, Maartje Alkemade, Iris M. Seignette, Renaud Tissier, Marja Nieuwland, Martijn van Baalen, Joanna PoĆșniak, Erik Mul, Simon Tol, Sofia Stenqvist, Lisa M. Nilsson, Jonas A. Nilsson, John B. A. G. Haanen, Winan J. van Houdt, Daniel S. Peeper
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Emerging evidence suggests a correlation between CD8 + T cell–tumour cell proximity and anti-tumour immune response 1,2 . However, it remains unclear whether these cells exist as functional clusters that can be isolated from clinical samples. Here, using conventional and imaging flow cytometry, we show that from 21 out of 21 human melanoma metastases, we could isolate heterotypic clusters, comprising CD8 + T cells interacting with one or more tumour cells and/or antigen-presenting cells (APCs). Single-cell RNA-sequencing analysis revealed that T cells from clusters were enriched for gene signatures associated with tumour reactivity and exhaustion. Clustered T cells exhibited increased TCR clonality indicative of expansion, whereas TCR-matched T cells showed more exhaustion and co-modulation when conjugated to APCs than when conjugated to tumour cells. T cells that were expanded from clusters ex vivo exerted on average ninefold increased killing activity towards autologous melanomas, which was accompanied by enhanced cytokine production. After adoptive cell transfer into mice, T cells from clusters showed improved patient-derived melanoma control, which was associated with increased T cell infiltration and activation. Together, these results demonstrate that tumour-reactive CD8 + T cells are enriched in functional clusters with tumour cells and/or APCs and that they can be isolated and expanded from clinical samples. Typically excluded by single-cell gating in flow cytometry, these distinct heterotypic T cell clusters are a valuable source to decipher functional tumour–immune cell interactions and may also be therapeutically explored.
GPT-4o mini: Non-social science research article
Genetic elements promote retention of extrachromosomal DNA in cancer cells
Venkat Sankar, King L. Hung, Aditi Gnanasekar, Ivy Tsz-Lo Wong, Quanming Shi, Katerina Kraft, Matthew G. Jones, Britney Jiayu He, Xiaowei Yan, Julia A. Belk, Kevin J. Liu, Sangya Agarwal, Sean K. Wang, Anton G. Henssen, Paul S. Mischel, Howard Y. Chang
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Extrachromosomal DNA (ecDNA) is a prevalent and devastating form of oncogene amplification in cancer 1,2 . Circular megabase-sized ecDNAs lack centromeres, stochastically segregate during cell division 3–6 and persist over many generations. It has been more than 40 years since ecDNAs were first observed to hitchhike on mitotic chromosomes into daughter cell nuclei, but the mechanism underlying this process remains unclear 3,7 . Here we identify a family of human genomic elements, termed retention elements, that tether episomes to mitotic chromosomes to increase ecDNA transmission to daughter cells. Using Retain-seq, a genome-scale assay that we developed, we reveal thousands of human retention elements that confer generational persistence to heterologous episomes. Retention elements comprise a select set of CpG-rich gene promoters and act additively. Live-cell imaging and chromosome conformation capture show that retention elements physically interact with mitotic chromosomes at regions that are mitotically bookmarked by transcription factors and chromatin proteins. This activity intermolecularly recapitulates promoter–enhancer interactions. Multiple retention elements are co-amplified with oncogenes on individual ecDNAs in human cancers and shape their sizes and structures. CpG-rich retention elements are focally hypomethylated. Targeted cytosine methylation abrogates retention activity and leads to ecDNA loss, which suggests that methylation-sensitive interactions modulate episomal DNA retention. These results highlight the DNA elements and regulatory logic of mitotic ecDNA retention. Amplifications of retention elements promote the maintenance of oncogenic ecDNA across generations of cancer cells, and reveal the principles of episome immortality intrinsic to the human genome.
GPT-4o mini: Non-social science research article
Repulsions instruct synaptic partner matching in an olfactory circuit
Zhuoran Li, Cheng Lyu, Chuanyun Xu, Ying Hu, David J. Luginbuhl, Asaf B. Caspi-Lebovic, Jessica M. Priest, Engin Özkan, Liqun Luo
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Neurons exhibit extraordinary precision in selecting synaptic partners. Although cell-surface proteins (CSPs) that mediate attractive interactions between developing axons and dendrites have been shown to instruct synaptic partner matching 1,2 , the degree to which repulsive interactions have a role is less clear. Here, using a genetic screen guided by single-cell transcriptomes 3,4 , we identified three CSP pairs, Toll2–Ptp10D, Fili–Kek1 and Hbs/Sns–Kirre, that mediate repulsive interactions between non-partner olfactory receptor neuron (ORN) axons and projection neuron (PN) dendrites in the developing Drosophila olfactory circuit. Each CSP pair exhibits inverse expression patterns in the select ORN–PN partners. Loss of each CSP in ORNs led to similar synaptic partner matching deficits as the loss of its partner CSP in PNs, and mistargeting phenotypes caused by overexpressing one CSP could be suppressed by loss of its partner CSP. All CSP pairs are also differentially expressed in other brain regions. Together, our data reveal that multiple repulsive CSP pairs work together to ensure precise synaptic partner matching during development by preventing neurons from forming connections with non-cognate partners.
GPT-4o mini: Non-social science research article
Structural basis of regulated N-glycosylation at the secretory translocon
Melvin Yamsek, Mengxiao Ma, Roshan Jha, Yu Wan, Qianru Li, Frank Zhong, Katherine DeLong, Zhe Ji, Rajat Rohatgi, Robert J. Keenan
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Most human secretory pathway proteins are N-glycosylated by oligosaccharyltransferase (OST) complexes as they enter the endoplasmic reticulum (ER) 1–3 . Recent work revealed a substrate-assisted mechanism by which N-glycosylation of the chaperone glucose-regulated protein 94 (GRP94) is regulated to control cell surface receptor signalling 4 . Here we report the structure of a natively isolated GRP94 folding intermediate tethered to a specialized CCDC134-bound translocon. Together with functional analysis, the data reveal how a conserved N-terminal extension in GRP94 inhibits OST-A and how structural rearrangements within the translocon shield the tethered nascent chain from inappropriate OST-B glycosylation. These interactions depend on a hydrophobic CCDC134 groove, which recognizes a non-native conformation of nascent GRP94. Our results define a mechanism of regulated N-glycosylation and illustrate how the nascent chain remodels the translocon to facilitate its own biogenesis.
GPT-4o mini: Non-social science research article
Electro-generated excitons for tunable lanthanide electroluminescence
Jing Tan, Peng Zhang, Xiaoqing Song, Chunmiao Han, Feng Wang, Jing Zhang, Chunbo Duan, Zhilong Zhang, Sanyang Han, Hui Xu, Xiaogang Liu
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Lanthanide nanocrystals offer unique advantages for electroluminescence (EL) applications, including narrow-band emission, high colour purity and compositionally tunable output1,2,3,4. However, their insulating nature poses a challenge for carrier transport and injection, impeding their application in electrically driven optoelectronic devices5. Here we demonstrate efficient EL from insulating lanthanide fluoride nanocrystals (4 nm; NaGdF4:X; X = Tb3+, Eu3+ or Nd3+) coated with a series of functionalized 2-(diphenylphosphoryl)benzoic acids (ArPPOA). These ligands, featuring donor–phosphine oxide acceptor hybrids with carboxyl and P=O coordination sites, effectively sensitize the luminescence of lanthanide nanocrystals by modulating the intraligand charge transfer characteristics. Ultrafast spectroscopic investigations reveal that strong coupling between ArPPOA and lanthanide nanocrystals facilitates intersystem crossing (ISC; <1 ns) and highly efficient triplet energy transfer to nanocrystals (up to 96.7%). Through careful control of dopant composition and concentration in nanocrystals, we also achieve wide-ranging multicolour EL without altering the device architecture, reaching an external quantum efficiency exceeding 5.9% for Tb3+. This ligand-functionalized nanocrystal platform provides a modular strategy for exciton control in insulating nanocrystal systems, offering a pathway for spectrally precise electroluminescent materials.
GPT-4o mini: Non-social science research article
Topological nodal i-wave superconductivity in PtBi2
Susmita Changdar, Oleksandr Suvorov, Andrii Kuibarov, Setti Thirupathaiah, Grigory Shipunov, Saicharan Aswartham, Sabine Wurmehl, Iryna Kovalchuk, Klaus Koepernik, Carsten Timm, Bernd BĂŒchner, Ion Cosma Fulga, Sergey Borisenko, Jeroen van den Brink
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Most superconducting materials are well understood and conventional—that is, the pairs of electrons that cause the superconductivity by their condensation have the highest possible symmetry. Famous exceptions are the enigmatic high-temperature (high- T c ) cuprate superconductors 1 . Nodes in their superconducting gap are the fingerprint of their unconventional character and imply superconducting pairing of d -wave symmetry. Here, by using angle-resolved photoemission spectroscopy, we observe that the Weyl semimetal PtBi 2 harbours nodes in its superconducting gap, implying unconventional i -wave pairing symmetry. At temperatures below 10 K, the superconductivity in PtBi 2 gaps out its topological surface states, the Fermi arcs, whereas its bulk states remain normal 2 . The nodes in the superconducting gap that we observe are located exactly at the centre of the Fermi arcs and imply the presence of topologically protected Majorana cones around this locus in momentum space. From this, we infer theoretically that robust zero-energy Majorana flat bands emerge at surface step edges. This establishes PtBi 2 surfaces not only as unconventional, topological i -wave superconductors but also as a promising material platform in the ongoing effort to generate and manipulate Majorana bound states.
Nature DOI suffix ≠ "/s...": Not a research article
Google DeepMind won a Nobel prize for AI: can it produce the next big breakthrough?
Elizabeth Gibney
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No one could accuse Demis Hassabis of dreaming small. In 2016, the company he co-founded, DeepMind, shocked the world when an artificial intelligence model it created beat the best human player of the strategy game Go. Then Hassabis set his sights even higher: in 2019, he told colleagues that his goal was to win Nobel prizes with the company’s AI tools. Chemistry Nobel goes to developers of AlphaFold AI that predicts protein structures It took only five years for Hassabis and DeepMind’s John Jumper to do so, collecting a share of the 2024 Nobel Prize in Chemistry for creating AlphaFold, the AI that revolutionized the prediction of protein structures. AlphaFold is just one in a string of science successes that DeepMind has achieved over the past decade. When he co-founded the company in 2010, Hassabis, a neuroscientist and game developer, says his aim was to make “a world-class scientific research lab, but in industry”. In that quest, the company sought to apply the scientific method to the development of AI, and to do so ethically and responsibly by anticipating risks and reducing potential harms. Establishing an AI ethics board was a condition of the firm’s agreement to be acquired by Google in 2014 for around US$400 million, according to media reports. Now Google DeepMind is trying to replicate the success of AlphaFold in other fields of science. “We’re applying AI to nearly every other scientific discipline now,” says Hassabis. Demis Hassabis co-founded DeepMind in 2010.Credit: Antonio Olmos/Guardian/eyevine But the climate for this marriage of science and industry has changed drastically since the release of ChatGPT in 2022 — an event that Hassabis calls a “wake-up moment”. The arrival of chatbots and the large language models (LLMs) that power them led to an explosion in AI usage across society, as well as a scramble by a growing number of well-funded competitors to achieve human-level artificial general intelligence (AGI). Google DeepMind is now racing to release commercial products — including iterations of the firm’s Gemini LLMs — almost weekly, while continuing its machine-learning research and producing science-specific models. The acceleration has made doing responsible AI harder, and some staff are unhappy with the firm’s more commercial outlook, say several former employees. All of this raises questions about where DeepMind is headed, and whether it can achieve blockbuster successes in other fields of science. Nobel bound At Google DeepMind’s slick headquarters in London’s King’s Cross technology hub, gleaming geometric sculptures and the smell of espresso hang in the reception hall. Time is so precious that staff members — thought to number between 500 and 1,000 worldwide — can pick up a scooter to race the few hundred metres from one office to another. It’s a far cry from the humble origins of the company, which sought to build general AI systems by melding ideas from neuroscience and machine learning. “They were absolutely just super geniuses,” says Joanna Bryson, a computer scientist and researcher in AI ethics at the Hertie School in Berlin. “They were these 12 guys that everybody wanted.” The laboratory pioneered the deep-learning AI technique, which uses simulated neurons to learn associations in data after studying real-world examples, as well as reinforcement learning, in which a model learns by trial, error and reward. After applying these to teach models how to play arcade games1 in 2015 and master the ancient game of Go2 in 2016, DeepMind turned its sights to its first scientific problem — predicting the 3D structure of proteins3 from their constituent amino acids. A member of the AlphaFold team examines a prediction of a protein structure.Credit: Alecsandra Dragoi for Nature Hassabis first came across the puzzle of protein structure as an undergraduate at the University of Cambridge, UK, in the 1990s and noted it as being a problem that AI might one day help to solve. AI learning techniques require a database of examples as well as clear metrics of success that guide the model’s progress. Thanks to a long-standing database of known structures and an established competition that judged the accuracy of the predictions, proteins had both. Protein folding ticked a crucial box for Hassabis: it is a ‘root node’ problem that, once solved, opens up branches of downstream research and applications. Those kinds of problem “are worth spending five years or ten years on, and loads of computers and researchers”, he says. What’s next for AlphaFold and the AI protein-folding revolution DeepMind released its first iteration of AlphaFold in 2018, and by 2020, its performance far outstripped that of tools from any other team. Today, a spin-off from DeepMind, Isomorphic Labs, is seeking to use AlphaFold in drug discovery. And DeepMind’s AlphaFold database of more than 200 million protein-structure predictions has been used in a range of research efforts, from improving bee immunity to disease in the face of global population declines to screening for antiparasitic compounds to treat Chagas disease, a potentially life-threatening parasitic infection4. Science is not just a source of problems to solve; the firm tries to approach all of its AI development in a scientific way, says Pushmeet Kohli, who leads the company’s science efforts. Researchers tend to go back to first principles for each problem and try fresh techniques, he says. Staff members at many other AI firms are more like engineers, applying ingenuity but not doing basic discovery, says Jonathan Godwin, chief executive of the AI firm Orbital Materials in London, who was a researcher at Google DeepMind until the end of 2022. John Jumper and Pushmeet Kohli speak to researcher Olaf Ronneberger in the DeepMind offices.Credit: Alecsandra Dragoi for Nature But replicating the success of AlphaFold will be tough: “Not many scientific endeavours work like that,” says Godwin. Unlocking the genome Google DeepMind is throwing its resources at several problems for which it thinks AI could speed development, and which could have “transformative impact”, says Kohli. These include weather forecasting5 and nuclear fusion, which has the potential to become a clean, abundant energy source. The company picks projects through a strict selection process, but individual researchers can choose which to work on and how to tackle a problem, he says. AI models that work on such problems often require specialized data and researchers to program knowledge into them. One project that shows promise, says Kohli, is AlphaGenome, which launched in June as an attempt to decipher long stretches of human non-coding DNA and predict their possible functions6. But the challenge is harder than for AlphaFold, because each sequence yields multiple valid functions. Materials science is another area in which the company hopes that AI could be revolutionary. Materials are hard to model because the complex interactions of atomic nuclei and electrons can only be approximated. Learning from a database of simulated structures, DeepMind developed its GNoME model, which in 2023 predicted 400,000 potential new substances7. Now, Kohli says, the team is using machine learning to develop better ways to simulate electron behaviour, ones that are learnt from example interactions rather than by relying on the principles of physics. The end goal is to predict materials with specific properties, such as magnetism or superconductivity, he says. “We want to see the era where AI can basically design any material with any sort of magical property that you want, if it is possible,” he says. John Jumper and Pushmeet Kohli in the headquarters building.Credit: Alecsandra Dragoi for Nature AI models have a variety of known safety issues, from the risk of being used to create bioweapons to the perpetuation of racial and gender-based biases, and these come to the fore when releasing models into the world. Google DeepMind has a dedicated committee on responsibility and safety that works across the company and is consulted at each major stage of development, says Anna Koivuniemi, who runs its ‘impact accelerator’, an effort to scour society for areas in which AI could make a difference. Committee members stress-test the idea to see what could go wrong, including by consulting externally. “We take it very, very seriously,” she says. Another advantage the firm has is that its researchers are pursuing the kind of AI that the world ultimately wants, says Godwin. “People don’t really want random videos of themselves being generated and put on a social-media network; they want limitless energy or diseases being cured,” he says. But DeepMind now has company in the quest to use AI for science. Some firms that started out making LLMs seem to be coming around to Hassabis’ vision of AI for science. In the past two months, both OpenAI and the Paris-based AI firm Mistral have created teams dedicated to scientific discovery. Company concerns For AI companies and researchers, OpenAI’s 2022 release of ChatGPT changed everything. Its success was “pretty surprising to everyone”, says Hassabis.
Nature DOI suffix ≠ "/s...": Not a research article
Nations at COP30 must cancel fossil-fuel concessions to keep the Paris agreement in reach
Martí Orta-Martínez, Gorka Muñoa, Marcel Llavero-Pasquina, Guillem Rius-Taberner
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The Paris climate agreement requires that countries work to limit global warming to well below 2 °C, and pursue efforts to limit it to 1.5 °C, to avoid devastating climate tipping points. The latter target requires drastic action, even when assuming a small temporary overshoot that is combated by draw-down of atmospheric carbon to lower temperatures later in the century — a presumed best-case scenario for most climate scientists.
Nature DOI suffix ≠ "/s...": Not a research article
How to fix genetic ‘nonsense’: versatile gene-editing tool could tackle a host of diseases
Heidi Ledford
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A cell’s protein-making machinery (artist’s illustration) can be instructed to ignore mutations that would otherwise result in shortened proteins. Credit: Christoph Burgstedt/Science Photo Library A single multipurpose gene-editing tool can correct several genetic conditions by restoring proteins that have been truncated by disease-causing mutations. The method might one day overcome a key stumbling block faced by gene-editing therapies: the need to design a bespoke treatment for each disease. The new approach, called PERT, combines gene editing with engineered RNA molecules that allow protein synthesis to continue even when a mutation in the DNA tells it to stop prematurely. Such mutations are called nonsense mutations, and they comprise nearly one-quarter of known disease-causing DNA variants. Powerful CRISPR system inserts whole gene into human DNA So far, PERT has overcome disease-linked nonsense mutations in mice and in human cells grown in culture, but further testing and refinement are needed before the approach can be studied in people, says David Liu, a chemical biologist at the Broad Institute in Cambridge, Massachusetts, and a co-author of a paper about the technique. If it does prove effective in humans, PERT could drive down the cost and speed up the development of gene-editing therapies for many conditions. “Disease-agnostic approaches like this raise a possibility that, I think, would be incredibly exciting for patients,” says Liu. He and his colleagues published their results on 19 November in Nature1. PERT proposal Liu first dreamt up the idea for PERT a few years ago while preparing for an event called science karaoke at his laboratory’s annual retreat. During this event, each member presents an out-of-the-box idea for a project that could send the lab in a new direction. Singing is not required. For his project, Liu suggested that the team should investigate synthetic RNA molecules called suppressor tRNAs, which allow a cell’s protein-synthesis machinery to read through a nonsense mutation in the DNA and produce a full-length protein. Suppressor tRNAs, Liu proposed, could be inserted into a genome using a technique called prime editing. At the end of his ten-minute presentation, Liu asked his lab if anyone would be interested in taking on the project; a few members volunteered. Personalized gene editing helped one baby: can it be rolled out widely? As the team worked to develop PERT, other researchers published promising results using suppressor tRNAs without gene editing. One group used a virus to shuttle the tRNA into cells2; another encased their tRNAs in fatty particles similar to those used in COVID-19 mRNA vaccines3. Each of these approaches showed promise in animal models with genetic diseases. But viruses can provoke dangerous immune responses, and fatty particles required repeated doses, says Zoya Ignatova, a biochemist at the University of Hamburg in Germany. Gene editing, by contrast, would allow researchers to insert a gene encoding the suppressor tRNA into a recipient’s genome. In theory, no further doses would be needed.
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: The first person to be cited one million times is an AI trailblazer
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Psychedelics and immortality: Nature went to a health summit starring RFK and JD Vance
Max Kozlov
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US health secretary Robert F. Kennedy Jr and JD Vance shared a stage at the MAHA Summit in Washington DC.Credit: Alex Wroblewski/AFP/Getty Washington DC Social-media influencers and anti-ageing entrepreneurs mingled with top US government officials, including the head of the US National Institutes of Health (NIH), at an exclusive event steps from the White House last week. The meeting’s purpose was to discuss the future of health in the United States. Organizers called it the MAHA Summit, referring to US health secretary Robert F. Kennedy Jr’s signature ‘Make America Healthy Again’ movement. Attendees included Kennedy, US vice-president JD Vance, NIH director Jayanta Bhattacharya, US Food and Drug Administration chief Marty Makary and the food activist Vani Hari, who blogs under the name ‘Food Babe’. Sessions at the summit, which Nature attended, covered a wide range of health-related topics, including psychedelics, brain implants and anti-ageing therapies. Academic researchers or clinicians were not among the speakers at the sessions, which were peppered by comments critical of the medical establishment. Trump team backs an unproven drug for autism — but does it work? The conference showcased the influence of the MAHA movement, whose supporters say there is a chronic-disease epidemic in the United States that they blame in part on corruption in the food and pharmaceutical industries. To combat this epidemic, supporters advocate lifestyle choices, such as improving sleep and taking dietary supplements. The movement has ascended rapidly from a loose network of Kennedy supporters into a political force that Vance, speaking at the summit, called “a critical part of our success in Washington”. The event also drew officials from corporate heavyweights, such as Walmart and Google, and biotechnology firms, such as Regeneron Pharmaceuticals in Tarrytown, New York. “We didn’t have anything like this,” Robert Redfield, who led the US Centers for Disease Control and Prevention from 2018 to 2021, during US President Donald Trump’s first term, told Nature at the summit. “Bobby [Kennedy] has gotten industry to sit down with him.” Warm praise The nearly eight-hour summit featured remarks by several officials in Kennedy’s Department of Health and Human Services. Among them were Bhattacharya, who said that the “MAHA movement is an absolutely incredible thing to me”. He added: “I have waited my entire life to see this movement come.” Other speakers included mixed-martial-arts promoter Dana White and actor and comedian Russell Brand. Attendees also heard health advice from Bryan Johnson, a Silicon Valley multimillionaire known for his anti-ageing ‘biohacks’, such as receiving plasma transfusions from his teenage son, and his view that his generation might be first to never die. RFK Jr slings accusations and defends public-health upheaval at fiery hearing Throughout the event, speakers criticized established scientific and medical institutions. Both are frequent targets of Kennedy, who founded Children’s Health Defense, a non-profit organization in Franklin Lakes, New Jersey, that is known for its anti-vaccine advocacy. Among these speakers was Bhattacharya, who said that the NIH, the world’s largest biomedical-research funder, has focused too heavily on small scientific steps instead of “disruptive” or “innovative” research. “What puts lives at risk is doing research that’s incremental,” Bhattacharya said. “All it does is advance the careers of the researchers that do it. It results in publications that don’t get used and aren’t replicable.” Follow the science Makary decried “groupthink that again and again led us astray”, citing as an example public-health recommendations against eating saturated fat. (Kennedy has suggested that saturated fats are part of a healthy diet; the US government has, for decades, recommended limiting saturated-fat consumption.) “We got ‘saturated fat causes heart disease’ wrong for 50 years,” Makary said. “That’s a war we’re going to end.”
Nature DOI suffix ≠ "/s...": Not a research article
The apple of my eye: How I’ve created a plant-health tracker for farmers in Tanzania
Tavares Cebola
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“This photo was taken in August, in the Sing’isi village in Arusha, northern Tanzania, where my colleagues and I were conducting a field visit to farmers. I was demonstrating how to use a mobile app — named KilimoAI — to examine crop leaves. The app, which we’ve developed in-house, works by analysing a photograph of the plant to detect possible disease symptoms. This is part of my role in the Artificial Intelligence and Complexity Systems group at the Nelson Mandela African Institution of Science and Technology in Arusha. I guide projects that aim to apply artificial intelligence to real-world challenges in agriculture, conservation and development. To create the app, my colleagues and I took thousands of photos of plant leaves at farms, of both healthy and diseased crops. So far, we’ve focused on diseases affecting maize (corn), beans (Phaseolus spp.), bananas and potatoes. After collection, images go through a verification process with the help of plant pathologists at the Tanzania Agricultural Research Institute in Arusha. We use this data set to train machine-learning models to distinguish between healthy and diseased plants, and even to classify specific disease types. A portion of the data is set aside for testing, so that we can evaluate the model’s accuracy.
Nature DOI suffix ≠ "/s...": Not a research article
Fishing around offshore wind farms could boost both conservation and green energy
Joachim Claudet, Emma V. Sheehan, Ryan R. E. Stanley
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The extent of offshore wind farms (OWFs) is expected to increase markedly by 2030. The number of conserved areas, including marine protected areas (MPAs), must also rise to help conserve 30% of the world’s oceans under the Kunming–Montreal Global Biodiversity Framework. The two will need to coexist.
Nature DOI suffix ≠ "/s...": Not a research article
Mind-reading devices can now predict preconscious thoughts: is it time to worry?
Liam Drew
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Before a car crash in 2008 left her paralysed from the neck down, Nancy Smith enjoyed playing the piano. Years later, Smith started making music again, thanks to an implant that recorded and analysed her brain activity. When she imagined playing an on-screen keyboard, her brain–computer interface (BCI) translated her thoughts into keystrokes — and simple melodies, such as ‘Twinkle, Twinkle, Little Star’, rang out1. The rise of brain-reading technology: what you need to know But there was a twist. For Smith, it seemed as if the piano played itself. “It felt like the keys just automatically hit themselves without me thinking about it,” she said at the time. “It just seemed like it knew the tune, and it just did it on its own.” Smith’s BCI system, implanted as part of a clinical trial, trained on her brain signals as she imagined playing the keyboard. That learning enabled the system to detect her intention to play hundreds of milliseconds before she consciously attempted to do so, says trial leader Richard Andersen, a neuroscientist at the California Institute of Technology in Pasadena. Smith is one of roughly 90 people who, over the past two decades, have had BCIs implanted to control assistive technologies, such as computers, robotic arms or synthetic voice generators. These volunteers — paralysed by spinal-cord injuries, strokes or neuromuscular disorders, such as motor neuron disease (amyotrophic lateral sclerosis) — have demonstrated how command signals for the body’s muscles, recorded from the brain’s motor cortex as people imagine moving, can be decoded into commands for connected devices. But Smith, who died of cancer in 2023, was among the first volunteers to have an extra interface implanted in her posterior parietal cortex, a brain region associated with reasoning, attention and planning. Andersen and his team think that by also capturing users’ intentions and pre-motor planning, such ‘dual-implant’ BCIs will improve the performance of prosthetic devices. Nancy Smith used a brain–computer interface to make music after a car accident left her paralysed from the neck down.Credit: Caltech Andersen’s research also illustrates the potential of BCIs that access areas outside the motor cortex. “The surprise was that when we go into the posterior parietal, we can get signals that are mixed together from a large number of areas,” says Andersen. “There’s a wide variety of things that we can decode.” The ability of these devices to access aspects of a person’s innermost life, including preconscious thought, raises the stakes on concerns about how to keep neural data private. It also poses ethical questions about how neurotechnologies might shape people’s thoughts and actions — especially when paired with artificial intelligence. Meanwhile, AI is enhancing the capabilities of wearable consumer products that record signals from outside the brain. Ethicists worry that, left unregulated, these devices could give technology companies access to new and more precise data about people’s internal reactions to online and other content. Ethicists and BCI developers are now asking how previously inaccessible information should be handled and used. “Whole-brain interfacing is going to be the future,” says Tom Oxley, chief executive of Synchron, a BCI company in New York City. He predicts that the desire to treat psychiatric conditions and other brain disorders will lead to more brain regions being explored. Along the way, he says, AI will continue to improve decoding capabilities and change how these systems serve their users. “It leads you to the final question: how do we make that safe?” Consumer concerns Consumer neurotech products capture less-sophisticated data than implanted BCIs do. Unlike implanted BCIs, which rely on the firings of specific collections of neurons, most consumer products rely on electroencephalography (EEG). This measures ripples of electrical activity that arise from the averaged firing of huge neuronal populations and are detectable on the scalp. Rather than being created to capture the best recording possible, consumer devices are designed to be stylish (such as in sleek headbands) or unobtrusive (with electrodes hidden inside headphones or headsets for augmented or virtual reality). Still, EEG can reveal overall brain states, such as alertness, focus, tiredness and anxiety levels. Companies already offer headsets and software that give customers real-time scores relating to these states, with the intention of helping them to improve their sports performance, meditate more effectively or become more productive, for example. AI has helped to turn noisy signals from suboptimal recording systems into reliable data, explains Ramses Alcaide, chief executive of Neurable, a neurotech company in Boston, Massachusetts, that specializes in EEG signal processing and sells a headphone-based headset for this purpose. “We’ve made it so that EEG doesn’t suck as much as it used to,” Alcaide says. “Now, it can be used in real-life environments, essentially.” And there is widespread anticipation that AI will allow further aspects of users’ mental processes to be decoded. For example, Marcello Ienca, a neuroethicist at the Technical University of Munich in Germany, says that EEG can detect small voltage changes in the brain that occur within hundreds of milliseconds of a person perceiving a stimulus. Such signals could reveal how their attention and decision-making relate to that specific stimulus. Although accurate user numbers are hard to gather, many thousands of enthusiasts are already using neurotech headsets. And ethicists say that a big tech company could suddenly catapult the devices to widespread use. Apple, for example, patented a design for EEG sensors for future use in its Airpods wireless earphones in 2023. Yet unlike BCIs aimed at the clinic, which are governed by medical regulations and privacy protections, the consumer BCI space has little legal oversight, says David Lyreskog, an ethicist at the University of Oxford, UK. “There’s a wild west when it comes to the regulatory standards,” he says. In 2018, Ienca and his colleagues found that most consumer BCIs don’t use secure data-sharing channels or implement state-of-the-art privacy technologies2. “I believe that has not changed,” Ienca says. What’s more, a 2024 analysis3 of the data policies of 30 consumer neurotech companies by the Neurorights Foundation, a non-profit organization in New York City, showed that nearly all had complete control over the data users provided. That means most firms can use the information as they please, including selling it. Neuralink brain chip: advance sparks safety and secrecy concerns Responding to such concerns, the government of Chile and the legislators of four US states have passed laws that give direct recordings of any form of nerve activity protected status. But Ienca and Nita Farahany, an ethicist at Duke University in Durham, North Carolina, fear that such laws are insufficient because they focus on the raw data and not on the inferences that companies can make by combining neural information with parallel streams of digital data. Inferences about a person’s mental health, say, or their political allegiances could still be sold to third parties and used to discriminate against or manipulate a person. “The data economy, in my view, is already quite privacy-violating and cognitive- liberty-violating,” Ienca says. Adding neural data, he says, “is like giving steroids to the existing data economy”. Several key international bodies, including the United Nations cultural organization UNESCO and the Organisation for Economic Co-operation and Development, have issued guidelines on these issues. Furthermore, in September, three US senators introduced an act that would require the Federal Trade Commission to review how data from neurotechnology should be protected. Heading to the clinic While their development advances at pace, so far no implanted BCI has been approved for general clinical use. Synchron’s device is closest to the clinic. This relatively simple BCI allows users to select on-screen options by imagining moving their foot. Because it is inserted into a blood vessel on the surface of the motor cortex, it doesn’t require neurosurgery. It has proved safe, robust and effective in initial trials4, and Oxley says Synchron is discussing a pivotal trial with the US Food and Drug Administration that could lead to clinical approval. Elon Musk’s neurotech firm Neuralink in Fremont, California, has surgically implanted its more complex device in the motor cortices of at least 13 volunteers who are using it to play computer games, for example, and control robotic hands. Company representatives say that more than 10,000 people have joined waiting lists for its clinical trials. At least five more BCI companies have tested their devices in humans for the first time over the past two years, making short-term recordings (on timescales ranging from minutes to weeks) in people undergoing neurosurgical procedures. Researchers in the field say the first approvals are likely to be for devices in the motor cortex that restore independence to people who have severe paralysis — including BCIs that enable speech through synthetic voice technology. As for what’s next, Farahany says that moving beyond the motor cortex is a widespread goal among BCI developers. “All of them hope to go back further in time in the brain,” she says, “and to get to that subconscious precursor to thought.” Last year, Andersen’s group published a proof-of-concept study5 in which internal dialogue was decoded from the parietal cortex of two participants, albeit with an extremely limited vocabulary. The team has also recorded from the parietal cortex while a BCI user played the card game blackjack (pontoon)6. Certain neurons responded to the face values of cards, whereas others tracked the cumulative total of a player’s hand. Some even became active when the player decided whether to stick with their current hand or take another card. Casey Harrell (with his wife Levana Saxon) uses his brain implant to generate synthetic speech.Credit: Ian Bates/New York Times/Redux/eyevine Both Oxley and Matt Angle, chief executive of BCI company Paradromics, based in Austin, Texas, agree that BCIs in brain regions other than the motor cortex might one day help to diagnose and treat psychiatric conditions. Maryam Shanechi, an engineer and computer scientist at the University of Southern California in Los Angeles, is working towards this goal — in part by aiming to identify and monitor neural signatures of psychiatric diseases and their symptoms7. BCIs could potentially track such symptoms in a person, deliver stimulation that adjusts neural activity and quantify how the brain responds to that stimulation or other interventions. “That feedback is important, because you want to precisely tailor the therapy to that individual’s own needs,” Shanechi says. Shanechi does not yet know whether the neural correlates of psychiatric symptoms will be trackable across many brain regions or whether they will require recording from specific brain areas. Either way, a central aspect of her work is building foundation models of brain activity. Such models, constructed by training AI algorithms on thousands of hours of neural data from numerous people, would in theory be generalizable across individuals’ brains.
Nature DOI suffix ≠ "/s...": Not a research article
Cyberattacks' harm to universities is growing — and so are their effects on research
Diana Kwon
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Harvard University in Cambridge, Massachusetts, experienced a data breach in October. Credit: Ilnur Khisamutdinov/Alamy On 10 November, hackers gained access to a Princeton University database containing the personal information of those in the institution’s community, including alumni, donors and students. In October, similar data breaches occurred at the University of Pennsylvania in Philadelphia and Harvard University in Cambridge, Massachusetts. These incidents are part of a broader trend. Over the past few years, cyberattacks have been on the rise at academic institutions around the globe. Not only are attacks time-consuming and costly to contain and clean up, but they have also caused university employees to lose access to essential digital services, such as e-mail and research software, for weeks — or even months — at a time. “The number of cyberattacks is not relenting,” says Harjinder Singh Lallie, a cybersecurity specialist at the University of Warwick, UK. Universities have been working to implement more robust security systems, but specialists say that academic institutions need to do more to shore up defences, especially against attacks that are assisted by artificial intelligence (AI), which might enable hackers to conduct breaches with greater speed and ease. Toby Murray, a cybersecurity researcher at the University of Melbourne in Australia, says that in today’s political climate, in which competition between countries has been on the rise, “universities remain a really attractive target”. It’s often difficult to trace where attacks come from, but some have been traced to state-sponsored groups, and often involve the use of ransomware, malicious software that blocks data or systems until a payment is made. NEWS: Cyberattacks are hitting research institutions — with devastating effects What makes universities vulnerable? Across all sectors, from government organizations to private companies, cyberattacks have been increasing. Specialists say that universities are particularly vulnerable because of the valuable data they house, such as employee records and intellectual property, and because these institutions are difficult to secure. Many universities have older, outdated security systems as well as diverse digital infrastructures and communities that can make it easy for hackers to infiltrate such systems. “It’s going to get worse,” says David Batho, the director of security at Jisc, an organization that provides digital infrastructure to educational institutions in the United Kingdom. “Prevention is no longer enough. Building resilience is essential.” A UK government survey carried out between August and December last year, revealed that the country’s educational institutions have had a high prevalence of cybersecurity breaches and were more likely to experience such incidents than were other businesses. According to an accompanying report, 91% of higher education institutions and 85% of further education colleges reported having experienced such an incident in the past 12 months. Quantum hacking looms — but ultra-secure encryption is ready to deploy
Nature DOI suffix ≠ "/s...": Not a research article
If the AI bubble bursts, what will it mean for research?
Fred Schwaller
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The surging value of firms such as NVIDIA has fuelled concerns about an AI stock market bubble.Credit: Kent Nishimura/Bloomberg via Getty After years of hype and ballooning investment, the boom in artificial intelligence technology is beginning to show signs of strain. Many financial analysts now agree that there is an ‘AI bubble’, and some speculate it could finally burst in the next few months. In economic terms, the rise of AI is unlike any other tech boom in history — there is now 17 times more investment in AI than in Internet companies before the dot-com crash of the early 2000s. And, valued at around US$4.6 trillion, the AI company NVIDIA was worth more than the economies of every nation except the United States, China and Germany. But AI is not living up the promise of revolutionizing multiple sectors — nearly 80% of companies using AI found it had had no significant impact on their earnings, according to a report from management consulting firm McKinsey, and concerns over the basic architecture of chatbots is leading scientists to say that AI has the potential to harm their research. These doubts over the technology’s utility, and financial viability, is leading analysts and investors to speculate that a crash is coming. Even tech chief executives such as Sam Altman of ChatGPT’s parent company OpenAI in San Francisco, California, have admitted that parts of the field are “kind of bubbly right now”. So, if a crash is imminent, how will it affect AI research and the scientists and engineers who make it happen? Lessons from the noughties Some analysts say that an AI-market collapse would be even more catastrophic than the dot-com crash — a shock that wiped out more than $5 trillion in stock-market value and led to hundreds of thousands of job losses in the tech industry alone. Like those of other tech bubbles before it, the dot-com crash had a lasting impact on computer-science research, says John Turner, an economist and historian at Queen’s University Belfast, UK. “But it wasn’t all bad,” he adds. “In 2000, a lot of highly skilled electronic engineers and computer scientists lost their jobs” and demand for computer-science graduates plummeted, he says. This led to a drop in the numbers of computer-science graduates — but despite this, research output didn’t falter, and the average number of computer-science publications continued to rise each year during and after the dot-com crash (see Dot-com crash aftermath’). Similarly, the roll-out of telecommunication technologies such as mobile phones and the Internet continued unabated. Sources: National Center for Education Statistics; Artificial Intelligence Index Report 2025. Brent Goldfarb, an economist at University of Maryland in College Park, says similar lay-offs in AI researchers and developers would happen were the AI bubble to burst. The biggest impact “would be on the hoard of start-ups jumping on the AI bandwagon, like the tenth AI notetaking app or AI scientist”, he says. OpenAI, Google, NVIDIA and other major AI companies “will likely survive”, he says. “The last thing they’ll do is get rid of their scientific core; that’s the path to the future.” In fact, crashes can have a silver lining: they can take innovation into other sectors when leading scientists change jobs, Turner says. Take, for instance the British bicycle crash of 1896. “Motorcycles, motorcars, the Wright brothers; all can trace their origins to the bicycle bubble,” he says. “The railway ‘manias’ of the nineteenth century left the legacy of railways for the benefit of people, much like the dot-com bubble gave society the Internet.” Liberated researchers Currently, the tech industry eclipses academia when it comes to AI, in terms of both investment and publication output. Some researchers have called this an “AI brain drain”, which sidelines exploratory science in favour of commercial interest1. “If I’m an AI researcher working at OpenAI, why would I go to a university when I earn ten times the salary?” Goldfarb says.
Nature DOI suffix ≠ "/s...": Not a research article
Waste not: how researchers harness pee and poo for science
Hannah Docter-Loeb
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As Mathilde Poyet ushers me through the Global Microbiome Conservancy’s laboratory in Kiel, Germany, I’m met with all sorts of state-of-the-art equipment. It’s an impressive facility, with typical lab apparatus, such as incubators, the latest sequencing devices and anaerobic chambers for culturing bacteria. But the most important stuff in the lab is stored in a freezer at −80 ÂșC. The samples are so crucial that there is a back-up battery system — if the electricity to the freezers goes off, the materials will remain intact. These test-tube samples aren’t some immortality serum or cancer-fighting bacteria: they’re faeces. To be precise, they’re suspended stool samples and bacteria that have been cultured from faeces. But at one point, this was poo that Poyet and her colleagues, including her partner Mathieu Groussin, had collected as part of their work for the Global Microbiome Conservancy (GMbC), of which Groussin is a co-founder. Poyet likes to call the project their “first baby” (one of their real babies, their infant daughter Aelis, joins us in their office as we speak). “We’ve seen all sorts of poop across the Bristol stool scale — all shapes, all sizes, all colours,” says Poyet, referring to the stool classification chart physicians use to assess digestive issues. Poyet and Groussin’s work is predicated on the idea that faeces provide an ideal snapshot of the human gut microbiome: the genetic content of the community of organisms found in intestines. This differs across populations1 and can serve as a health indicator. Most research on the human gut microbiome focuses on populations of European descent. But the GMbC solicits samples that are more globally representative. The samples in the freezer come from as far afield as Ghana, Tanzania, Finland and Thailand. Samples being collected and frozen for the GMbC’s biobank of waste products.Credit: F. Rondon/Global Microbiome Conservancy Over the past nine years of the programme, the team has sampled 50 populations spanning 19 countries. Its members have worked with local scientists, ethics boards and communities to collect the samples, and have taken cars, boats, helicopters and even quadbikes to sample sites. Back in the lab, researchers analyse the stool content, sequence the genetic material of bacteria cultured from samples and store the live samples in their biobank. To outsiders, taking stool samples constantly might seem — and smell — disgusting. In Kiel, the scientists occasionally make “poop soup”, using a vessel called a bioreactor to see the effects of different scenarios on procured bacteria. They do this only a few times a year, because the process can be long and expensive, and the aromas pungent, prompting their more-conventional floor mates to give the workspace the nickname “smelly lab”. But faeces provide a remarkable window into human health. “It’s our best way to interrogate what’s in the gut from healthy people,” says Groussin. “It’s a little bit gross, but that’s just our best way to access this incredible and important biodiversity.” A treasure trove for science With the microbiome a buzzy research topic, other scientists around the globe are taking samples to study it themselves. And as seen during the COVID-19 pandemic, wastewater analysis is a valuable public-health tool — providing scientists with the means to monitor pathogens in the population before an infection surges. “The waste we put into the environment is really data rich,” says Janelle Thompson, an environmental microbiologist at Nanyang Technological University’s Asian School of the Environment in Singapore. Thompson and her team sample Singapore’s wastewater to detect harmful microorganisms in the environment, looking for biological “signals” from organisms or viruses that are shed from the human body. “You can identify where signals are occurring and follow them over time to see when they’re occurring,” she explains. For example, in 2021 and 2022, Thompson and her colleagues were able to identify variants of concern for the coronavirus SARS-CoV-2 at university campus sites and treatment plants2. This was long before these variants became dominant, indicating “minimal silent circulation”, according to the team. The implications of research into human waste span several scientific disciplines. Amid a global fertilizer shortage, some scientists (and farmers) are looking to urine as fertilizer, owing to its nitrogen content. A study in Nature Water3, published earlier this year by a group of researchers at Stanford University, California, created a prototype system that extracts nutrients from urine. The team estimates that its design could generate up to US$4.13 per kilogram of nitrogen recovered. And research published in 20204 shows that urine-based fertilizer might also help to conserve other resources, reducing greenhouse-gas emissions and water use. A researcher pours urine-based fertilizer into a bottle.Credit: Marcin Szczepanski/Lead Multimedia Storyteller, Michigan Engineering As well as a public-health bellwether, stool samples are being used in the development of a potentially life-saving process to treat infections of Clostridium difficile, through transferring healthy faecal bacteria and other microbes from one host to another. C. difficile infections are “really caused by a disturbed microbiota”, explains Josbert Keller, a gastroenterologist at the Haaglanden Medical Centre in The Hague, the Netherlands. Keller was part of a group that published an early clinical trial5 into the effectiveness of faecal transfers, also known as faecal microbiota transplants, in 2013. “If the patient is not able to restore this microbiota, then it can recur and recur, and that’s the moment that faecal microbiota transplants can really cure a patient.” Now, faecal transfers are being looked at as a way to treat obesity6, type 2 diabetes7, Parkinson’s disease8 and other conditions. How to fix a gut microbiome ravaged by antibiotics Something that’s often perceived as disgusting can actually have a lot of intrinsic value, says Bryn Nelson, whose 2022 book Flush: The Remarkable Science of an Unlikely Treasure was described by its publisher as “an urgent exploration of the world’s single most squandered natural resource”. As part of the research and writing process, the former microbiologist spent years looking at the applications of faeces — and found at least 24 fields that take important information from what we consider waste products. Referring to excrement’s ‘ick’ factor, he says: “We just have to kind of get past that hurdle to discover all the information that it contains.” Getting into the field Poyet comes from a wet-lab background. For her PhD, she studied the fruit fly Drosophila suzukii and often spent full days dissecting specimens of the insect. Her research now involves sifting through stool samples to access bacteria that are not exposed to oxygen. Some samples are more foul than others, she says, adding: “What is really gross when working with stool sample is actually when people don’t digest the food, and you can find food almost intact in the stool. I really don’t like it.” For Thompson, working with waste materials was also a natural fit. “I’ve always just been fascinated by the microbial world and then accessing it for human benefit,” she says. “Microbes are slimy, they can be smelly, but I don’t find them gross.” Stools and urine are also something that you get desensitized to over time. Chong Chun Wie, a microbiome researcher at Monash University Malaysia in Subang Jaya, oversees stool-sample collection as part of his work on the human microbiome. His research looks at how the gut microbiome differs across ethnic groups9 in the region. Unlike Poyet and Groussin, he is not involved in fieldwork. Instead, bottles are sent to donors who deposit their samples at home, but there is still handling to be done in the lab. “The more you do it, the more you just get used to it because it’s something you do routinely,” he says. Your friends shape your microbiome — and so do their friends Marissa Ledger, a medical microbiology resident at McMaster University in Hamilton, Canada, studies the history of parasite infections. Ancient fossilized poo samples — decayed organic components that resemble soil — can be incredibly valuable in archaeology and palaeontology. Ledger’s undergraduate training was in anthropology, studying skeletal remains. She soon learnt that studying parasites in preserved faecal matter is a better way to chronicle infectious diseases throughout human history, likening the fossilized stools to time capsules that can yield nuanced details about infections and diets in a community. “When I decided that I wanted to look at parasite infections, understanding that they should have been a huge contributor to disease in the past, I was more like, ‘That’s a really cool goal,” she says. “I never really kind of thought of it as gross until I had the response of people talking to me saying, ‘You study ancient poo? That’s crazy.’” There’s a stronger cultural taboo towards poo than towards pee, observes Marine Legrand, an anthropologist at OCAPI, an interdisciplinary action and research programme in Paris that looks at ways of recycling human waste, such as by using urine as fertilizer. Although funding is available for research on faeces, it seems to be directed more towards medical than agricultural applications. “When we look for funds, it’s easier to find funds to work on pee than to work on poo.” The public restroom
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The singular proposition of trees
Wendy Nikel
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There’s a gravity here that our instruments can’t measure — a force that draws us to the trees. We feel it from the moment we land, but as harried and discordant as we are from the squabbles of our journey and stresses of close-quarter living, it takes days for the four of us to share enough to realize we’re each experiencing, differently, the same thing. For me, it is a presence. A nudge. A gentle hand slowly turning my chin towards the windows, where their white trunks reach skywards and their golden leaves glow in the three-sun dawn. I find myself pressing my fingers to the tempered glass when I’m supposed to be conducting experiments or tidying up the mess hall. My feet work their way into the airlock without conscious reason. Flynn dreams of papery bark unrolling like scrolls of wisdom. He sleepwalks and wakes with a hunger our freeze-dried rations can’t satiate. Avery hears music — a rustle of branches in the generator’s hum, in the static of the comms, in her head. For Cooper, it manifests as phantom smells, carrying flashes of warm childhood memories. The richness of soil. The sharpness of leaves. “Like the woods by Grandpa’s old cabin.” Read more science fiction from Nature Futures We are sojourners in the unknown. Avery insists on documenting our symptoms, but Flynn won’t let her file an official report. It’s curious, yes, but no risk to the mission. And who wouldn’t be a bit jumbled by arriving on a shining new world? By this massive forest of honey-coloured leaves and bright white branches rising skywards, their arms spread out in every direction? We move up the date of our initial excursion. For the first time, consensus comes easily. Our feet are the first to mark the soft and silty soil. Tiny birdlike creatures flit among the trees, as curious about us as we are about them. As we wander, I gather a feather. A leaf. A handful of dirt. A curl of bark. A twig. Flynn photographs the forest. Cooper collects our data. Avery keeps an eye on our vitals from the safety of the habitat. I only notice we’re working in perfect rhythm — shutter click, hygrometer beep, gather, step and step — when I hear her voice humming along. Another tone harmonizes. “Is that your oxygen tank?” It is. Beeping. Hours have passed unnoticed, untroubled. We are deeper into the forest than intended. Farther from the habitat. Somehow, without argument, without discussion, without a single spoken word, we coordinate our movements to connect the extra tank to my suit. It’s a complex process, but I forget which hands are mine as they all work in synchronicity. At the airlock, we extract ourselves from the forest. Climbing inside, limb by limb, is like trying to untangle a length of vines without snapping any branches. We sit, gasping, trying to collect ourselves. Trying to understand this sudden sense of loss. Still breathing in rhythm with the wind. Inside, we go about our separate tasks, but the new-found cohesion prevails. Each role is essential, balanced, aligned, making our previous conflicts seem absurd, our previous views so narrow. The samples whirl in the sequencer like a maple’s samara fruit. One after another, results blink onto the screen, the hive of coordinated pixels displaying the answer I somehow already knew. I must tell the others. And then they’re here. “Every single sample —” “— has exactly the same DNA. It’s as though they’re all —” “— the same thing somehow. Some massive, complex, universal —” “— organism. But wait, I thought I was —” “— speaking. How did you know what I’d —” “— say?”
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: This enigmatic figure reveals a common ancient myth
Flora Graham
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How to defuse a time bomb
Matt Thompson
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I swung up to the Cloudberry Tower in a hot morning drizzle. You could see the place was on the blink from halfway down Dagenham Dock Avenue, the ninth floor flashing green and opal in a lengthy, repeating rhythm. Nothing out of the ordinary. The lobby lay silent and deserted, as they all do these days. Up on ninth, I swiped in and entered the office. Employees shimmered in their nooks like hummingbird wings, faces flipping back to front with every surge peak. Some were translucent — always a bad sign. I checked the manifest. Cubicle 18 was the locus point. First, I’d calibrate the wavefronts. Next, wrap a firewall around the entire grid, and — The inhabitant of cubicle 18 stared up at me, mouth drawn tight with worry. Hair, skin, face — she was as human as me. Neither of us said a word. I don’t know who was more surprised. “You’re auditing?” I finally managed. “Or did they keep someone on?” She looked like my aunt. Her lanyard said Pam Dewsbury. “Did 
 did they send you to remove me?” I indicated my badge. “Travis Ovis, maintenance. Where’s number 18?” “I’m number 18.” I’d heard enough. I said, “That attitude’s hardly going to help you. Don’t you know about the Time bomb?” Pat gave out a sad little laugh. “Right. The Time bomb.” Just to make sure she understood, I explained the Time bomb. ***** Opinion is divided as to whether the population-time-bomb theory has any real validity. It’s simple enough. Over generations, the fertility rate drops below replacement levels and economic meltdown follows. Supposedly. Growth is all. Read more science fiction from Nature Futures Hence the government initiative. Multiplying the citizenry without any of the complications; expanding the horde; getting in on the ground floor. Call it what you like. Invent people to the nth degree — social security, tax codes, even birth certificates — and send your children out into the world. In this case, to the Cloudberry Tower, ninth floor. So it came to be. And the irksome regulations stating that these citizens-without-sin must at least have a physical presence? The vested interests that pushed them through Parliament administrate the holographic technology themselves. Of course they do. Rental of their services equates to roughly the newbies’ wage. Thus, everyone’s happy. Everyone except Pam. “Oh, I know all that,” she said. “I may as well tell you, then. My son Ned helped me out. They used to call people like him hackers, I think. Now they call them data assistants. When we all got the word here about the new directives I asked him to look into alternatives.” “Did he suggest UBI?” “You think I want to spend the rest of my life on universal basic income?” Her worry was turning to righteous anger. “Playing online games all day every day so some analysis centre can extract my neural response data, no thank you.” I couldn’t waste time arguing about it. The inhabitants of the adjacent cubicles had turned a not-unpleasant crimson hue. “Look, if they don’t get you for trespassing, they’ll haul you up for inhibiting growth forecasts. What do you do here anyway? Push files around, probably. Wouldn’t you prefer putting your feet up somewhere?” She tried too hard to look innocent. “Someone has to water the plants. And what about you? Maintenance will be shifting to automation soon enough.” I doubted she was wrong. I’d seen holograms in the backs of cabs, through the windows of ice-bars, occupying park benches, their accompanying projector drones hovering silently overhead. It seemed the Time bomb issue was well on its way to being solved. The tech companies would just have to keep an eye on runaway inflation. You don’t want wages over-matching output. I changed tack. “This is fraud, you know.” The crimson shade surrounding us deepened. “I’ll have to report your presence. Besides, you’re upsetting the transmissions.” She turned back to her desk and swept her fingers over the touch-screen. “Let me show you what Ned turned up. It’s Travis Ovis, right?” A face swam into being. A cold lump formed in my stomach. There was no denying it — the visage was mine. I never knew I looked so good in blue. “There’s one of these for everyone,” Pam said. “Here they sit, biding their time until our overlords decide all of us are fully expendable. Ned believes they’ll even have a voting-rights override.”
Nature DOI suffix ≠ "/s...": Not a research article
Women seem to retract fewer papers than men — but why?
Jenna Ahart
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Are women more careful about their research than men? Or are they more risk-averse?Credit: Westend61/Getty Women are under-represented in medical research generally, but they are even more under-represented when it comes to retracted articles. A new study finds that women’s names filled just 23% of author slots in a sample of nearly 900 retracted articles published in medical journals between 2008 and 2017. “This is a really interesting, creative and robust study,” says Curt Rice, who promotes publishing literacy at the Publishing Unlocked project in Oslo. “The article invites us to dig into issues like negotiations about authorship and the likelihood of scrutiny.” The findings were reported on 19 November in PLoS ONE1. Why retractions data could be a powerful tool for cleaning up science Study author Paul Sebo, an internal-medicine specialist and researcher at the University of Geneva, Switzerland, used an artificial-intelligence tool that infers whether authors are male or female on the basis of their first names. He found women’s names in 16.5% of first-author slots and 12.7% of last-author slots for the retracted papers. By contrast, an earlier study that used a similar tool for predicting author gender found that women accounted for 41–45% of first authors and 26–33% of last authors in all articles from the same selection of journals across the same time frame2. Risk and reward Interpreting the results is fraught. The gender-prediction tools used are imperfect. They do not capture non-binary identities, for example, and can be less accurate with non-Western names than Western ones. But in a manual check of 200 names, Sebo found no mismatches. And the findings themselves don’t come with a clear explanation. In an e-mail to Nature, Sebo wrote that his suspicion is that the disparity stems from how “women are still underrepresented in senior academic roles, lead fewer projects, and therefore may be less exposed to the kinds of responsibilities (and risks) that are more commonly associated with retractions”. “My speculation,” Rice says, “would be that because men are more visible in science in general, their work is getting more scrutiny.”
Nature DOI suffix ≠ "/s...": Not a research article
Of masks and Mayans: Books in brief
Andrew Robinson
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The Mask Bruno J. Strasser & Thomas Schlich Yale Univ. Press (2025) “Masks have signified hope and despair, courage and cowardice, a sense of community and a sense of selfishness.” All of these emotions — known to those who experienced the COVID-19 pandemic — underpin this engrossing, finely illustrated account by historians Bruno Strasser and Thomas Schlich (who was previously a physician). Their discussions cover theatrical performances in ancient Greece, plagues and gas attacks in the First World War and present-day urban smog and surgery, while addressing the crucial issue of mask efficacy. The Maya Myths Mallory E. Matsumoto Thames & Hudson (2025) Deciphering Mesoamerica’s ancient Maya hieroglyphs was a fascinating achievement of the twentieth century. But “about one-third” of some 1,000 distinct hieroglyphs “remain to be deciphered”, notes anthropologist Mallory Matsumoto in her intriguing book about ancient Maya myths. The logical structure of the Maya calendar, which could accurately predict astronomical phenomena such as eclipses, is clear, as is the Maya’s preoccupation with the natural world. But their beliefs — which included human sacrifice — are not. Outcast Oliver Basciano Faber (2025) Leprosy has had a complex, confusing history even after its causative bacterium was identified in 1873. In this gripping account, journalist Oliver Basciano quotes a 1960 novel by Graham Greene, A Burnt-Out Case: “What strange ideas people have about leprosy, doctor.” “They learn about it from the Bible, like sex.” Basciano journeys from Brazil to Japan and Mozambique in search of insights. He concludes that today’s grim image of leprosy stems from a nineteenth-century myth created to justify outcasting those affected. Irrational Together Adam S. Hayes Univ. Chicago Press (2025)
Nature DOI suffix ≠ "/s...": Not a research article
Stop the nonsense: genome editing creates potentially therapeutic transfer RNAs
Kim M. Keeling
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More than 7,000 rare diseases have been identified that collectively afflict 300 million people globally, yet treatments are available for only about 5% of these conditions1. The most efficient strategy for addressing this unmet need would be to develop therapies that are effective against multiple rare disorders. For example, many diseases are associated with gene variants, 11% of which are ‘nonsense’ mutations that cause protein synthesis to be terminated prematurely2. Writing in Nature, Pierce et al.3 describe an advance in a therapeutic approach that could, in principle, treat many disorders caused by a particular type of nonsense variant.
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: What happens to science if the ‘AI bubble’ bursts?
Jacob Smith
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Beyond growth — why we need to agree on an alternative to GDP now
Robert Costanza, Joseph Eastoe, Rutger Hoekstra, Ida Kubiszewski, Daniel W. O’Neill
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Gross domestic product (GDP) was never designed to be a measure of societal well-being. It tracks only market transactions, conflates costs and benefits, and ignores the distribution of income, the contributions of household labour and volunteer work, and social and environmental costs and benefits. In the decades after the Second World War, GDP growth functioned as a reasonable proxy for well-being when rebuilding economies and increasing production and consumption were the main priorities. However, since about 1950, which some call the Anthropocene era, ecological limits, inequality and declining social cohesion have restricted further improvements in well-being. At the same time, the rapid development of artificial intelligence promises fresh opportunities and challenges. Degrowth can work — here’s how science can help Measuring and modelling what truly matters, not just market transactions, is now essential. Processes are under way to develop indicators that move beyond GDP. In May, the United Nations secretary-general António Guterres appointed a High-Level Expert Group to develop such measures, with a focus on balancing economic, social and environmental dimensions of well-being. This initiative builds on the 2015 Sustainable Development Goals (SDGs): target 19 of SDG17 commits governments to adopt beyond-GDP metrics by 2030. Yet progress remains slow. Overcoming decades of structures built around GDP is difficult. Nonetheless, several governments, including those of New Zealand, Scotland, Wales and Bhutan, have experimented with alternatives to GDP1 (see also go.nature.com/3ktuvhv). Others should follow suit, but it will be a steep climb. Shifting all societies from a narrow focus on GDP growth to a comprehensive understanding of the multiple factors that support well-being and prosperity, and of how these factors interact over space and time, demands consensus on another approach2. Over the past seven decades, researchers and institutions have proposed hundreds of alternatives to GDP. Paradoxically, this proliferation has helped GDP to keep its privileged status, by creating the impression that there is little agreement on what sustainable and inclusive well-being means or how to measure it. In fact, there is much that these approaches do agree on. Here, we identify areas of common ground and propose four ways forward: universally adopting the goal of sustainable and inclusive well-being; establishing agreed metrics to evaluate progress towards this goal; developing models that incorporate the drivers and dynamics of well-being; and addressing institutionalized societal ‘addictions’ that reinforce unsustainable behaviours. Embrace sustainable and inclusive well-being The concept of sustainable and inclusive well-being — encompassing the well-being of all people and of the ecosystems that sustain life — is emerging as a widely accepted overarching policy goal that can provide common ground for beyond-GDP metrics, models and policies. By assigning a central role to natural ecosystems and planetary boundaries, the concept acknowledges that human prosperity depends on healthy ecological systems. Respecting ecological limits by constraining the material scale of the economy is therefore a precondition for lasting well-being. It also demands that human societies prevent significant harm to other species, protect the rights of future generations and guarantee that all people today have access to essential resources, services and participatory forms of decision-making. Market workers in Kenya. Employment is a core factor in many indicators of well-being.Credit: Elen Marlen/Getty A 2009 report on the measurement of economic performance and social progress, chaired by economist Joseph Stiglitz, laid the groundwork for moving beyond GDP3. Since then, international bodies, including the UN, the European Commission and the Organisation for Economic Co-operation and Development (OECD), have progressively adopted this conceptual foundation. Full international enforcement should follow; however, this might depend on a more-receptive US administration and stronger demand from civil society. Agree on well-being indicators Converging on an approach to evaluating sustainable and inclusive well-being is important if policymakers and organizations such as the UN are to embed these measures into official reporting and budgetary processes. Studies suggest that this is possible. Although more than 200 beyond-GDP indicators have been proposed, they share many similarities. These indicators often use different terminology to describe contributors to sustainable and inclusive well-being4. For example, ‘health’ might refer to mental health, physical health, health care, child welfare or any of more than 400 variants. Semantic modelling of the components of each indicator, which looks at the similarity between them, nevertheless reveals a high degree of agreement5. Nineteen key components capture a large proportion of the similarity (see ‘Well-being components’). Well-being components These 19 core factors are common to most beyond-GDP indicators5. Human Life satisfaction Health Life expectancy at birth Education Social Crime Civic engagement Governance Income equality Gender equality Built Housing Infrastructure Financial security Employment Per capita consumption Business health Natural Natural capital Water quality Air quality Greenhouse-gas emissions Researchers and policymakers, led by an international convening body such as the UN, should now establish a core set of around 20 components to serve as the backbone of national statistical reporting and UN frameworks. The UN High-Level Expert Group and the ongoing update of the SDGs are already advancing the agenda. The expert group has committed to an inclusive process that invites contributions from all stakeholders. Interested parties are encouraged to submit ideas and insights to help strengthen the emerging global consensus (see go.nature.com/4gcebvr). This month, the expert group launched an online consultation about its progress, and is expected to present its recommendations in the first half of 2026, which falls within the 80th session of the UN General Assembly. After this, intergovernmental processes will consider their recommendations. To build a better world, stop chasing economic growth Other efforts include the UN System of Environmental Economic Accounting and the UN System of National Accounts 2025 initiative, which are revising economic accounts to include more well-being components. The 2024 UN Pact for the Future and recommendations from the secretary-general’s Our Common Agenda report call for measures of progress that complement GDP. But these efforts need help from researchers and the consensus recommendations of the High-Level Expert Group. The UN can also play a central part in strengthening institutional capacity and securing stable funding to support the regular production of national estimates. Advances in citizen science, social-media analytics and remote sensing offer opportunities to reduce costs and improve data reliability. The world is awash with big data, so directing even a fraction of these resources towards measuring sustainable and inclusive well-being would enhance global monitoring and policy effectiveness. Develop dynamic models that go beyond GDP GDP has retained its dominance partly because it is embedded in the models that underpin national accounts and policy analyses. For example, the input–output model developed by economist Wassily Leontief6 tracks monetary flows across sectors and into ‘final demand’, defined as GDP. Why we need to measure people’s well-being — lessons from a global survey Mainstream macroeconomic models also place growth at the centre of policy evaluation. For example, standard computable general equilibrium models assume a high degree of substitutability among factors of production, implying that labour or technology can largely replace natural resources. They neglect environmental limits and exclude well-being, equity and ecological integrity. Most importantly, they are optimization models that are intended to maximize a single objective — GDP — rather than being designed to evaluate policies against multiple goals, as is required for sustainable and inclusive well-being. New models are needed. These must be dynamic, nonlinear and represent the economy as a subsystem of society embedded in the biosphere. Such models must be able to compare resource use and pollution to environmental limits, and social outcomes to the thresholds required to meet human needs7. They must track both stocks (natural, human, social and built capital) and flows (including monetary transactions, ecosystem services and social benefits) and capture their interactions, including feedbacks from transgressing environmental limits. Ecological macroeconomic models, rooted in the field of ecological economics, are one promising approach8. Young people at a cultural arts centre in Kibera, an informal settlement in Nairobi, perform a traditional African dance.Credit: Eva-Maria Krafczyk/dpa/Alamy
Nature DOI suffix ≠ "/s...": Not a research article
George Smoot obituary: Charismatic cosmologist who revealed ripples in the Big Bang’s afterglow
Douglas Scott, Joseph Silk, Tom Broadhurst
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Credit: Eco Clement/UPI/Alamy Cosmologist George Smoot contributed to our understanding of the Universe on the largest scales and at the earliest observable times by measuring temperature variations in the cosmic microwave background. His key experiment in 1992 reported detecting these ‘ripples’ in the microwave sky. Smoot’s discovery, for which he won a share of the Nobel Prize in Physics in 2006, revealed the long-anticipated traces of the formation of structures including stars and galaxies (G. F. Smoot et al. Astrophys. J. 396, L1–L5; 1992). This work led to many similar experiments, which used ever-more-precise measurements to cement our modern description of the Universe. Smoot has died aged 80. How did the Big Bang get its name? Here’s the real story The cosmic microwave background is the radiation from the Big Bang, which marked the beginning of the Universe 13.8 billion years ago. Smoot led the design of the detector that flew on NASA’s Cosmic Background Explorer (COBE) satellite. The data it collected gave a snapshot of variations in the density of matter in the hot, young Universe only about 400,000 years after the Big Bang. The amplitude of these variations aligned closely with predictions assuming that today’s galactic structures were formed under the gravitational influence of dark matter, rather than plasma, from that early time. Smoot was born in Yukon, Florida, the son of a hydrologist and a science teacher. In 1966, he earned degrees in physics and mathematics at the Massachusetts Institute of Technology (MIT) in Cambridge. He remained at MIT for his PhD in experimental particle physics, before joining the research group of Nobel laureate Luis Alvarez at the University of California, Berkeley, and the Lawrence Berkeley National Laboratory, where he built his research career. Smoot was using a high-altitude weather balloon to study cosmic rays, until it crashed into the ocean. His team then explored new research directions, in particular Big Bang cosmology. In the early 1970s, prompted by a theoretical paper from one of us (J. Silk Nature 215, 1155–1156; 1967), he began to study the relic microwave radiation. “My physics colleagues dismissed this work as speculation,” he wrote in his Nobel lecture. “It seemed to me a field ripe for observations that would be important no matter how they came out.” Early results using differential microwave radiometers (DMRs) on U-2 spy planes made it possible to measure how the motion of the Solar System makes one side of the sky seem hotter than the other. Why we still don’t understand the Universe — even after a century of dispute
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Leaders at COP30 should promote solar and wind power over mega-dams
Hong Yang, Xiang Gao, Jianhua Wu, Julian R. Thompson
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The COP30 climate meeting in Brazil is being framed as a ‘conference of implementation’, with the emphasis shifting from making new pledges to fulfilling existing climate commitments by boosting the transition to green energy. As your News feature highlights, China, Brazil and India have made rapid advances in this area (see Nature 647, 20–23; 2025). However, this progress includes the development of large hydropower projects in ecologically fragile regions such as the Himalayas and the Amazon rainforest.
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Standing up for Inuit-led research in Canada’s changing Arctic
Chris Woolston
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As part of her work on the Inuksiutit project, Jessica Penney travelled to Mittimatalik, a community in the northern part of Baffin Island in Nunavut, Canada.Credit: Peter Loovers As a sociologist and an Inuk who was raised in Canada’s northernmost city — Iqaluit in the territory of Nunavut — Jessica Penney has spent much of her professional career studying the country’s Inuit communities. During this time, she has seen growing threats to the food security, cultural practices and mental health of the Inuit and other northern Indigenous peoples. Inspired by her community connection with the people of Nunavut, Penney studies Inuit health, environmental issues and food sovereignty — the right of Indigenous communities to control their own food sources and access — from her current base at Toronto Metropolitan University. She is also a co-investigator on the Inuksiutit Project, an initiative by the University of Aberdeen, UK, and York University in Toronto to promote local control of food in Nunavut. Penney shares with Nature her research journey. Tell us about your path from Iqaluit to a career in academia. Iqaluit may seem small and remote, but with just over 8,000 people, it’s a large town by Inuit standards, and it’s the cultural hub of Nunavut. All of the issues I study as a sociologist — food sovereignty, poverty and the resonance of native traditions — are Nunavut issues. Nature Spotlight: Canada The educational system in Nunavut has some challenges. There’s a serious lack of Inuit teachers and resources. For the last two years of secondary school, I attended an international school on Vancouver Island on a full scholarship. After being exposed to so many cultures, I wanted to attend university abroad and I applied to universities all over the United Kingdom. The University of Glasgow offered me a scholarship in my preferred field of sociology and public policy, so the choice was easy. I stayed at the University of Glasgow for my master’s and PhD degrees, although I never lost my focus on the Indigenous peoples of northern Canada. Every summer, I would go back to Nunavut to work for the health-policy department, so I was able to link up my studies with my actual work. I did my master's in global health, and that also helped me start to see some of the connections between health and social issues in my community, as well as links to environmental issues, especially those relating to climate change. My PhD thesis explored the social, political and economic disruptions caused by the Muskrat Falls hydroelectric project, which dammed the Churchill River in the eastern province of Newfoundland and Labrador and was completed in 2021 at a cost of roughly Can$13 billion (US$9.3 billion). I interviewed local Inuit to document their concerns about the project and its anticipated environmental impacts. The dams changed the lives of locals, including their ability to hunt and fish, and many felt powerless and voiceless as construction went ahead. Why is food sovereignty and security such a pressing issue in Nunavut? Wherever they live, people should always have some control over their food supply. But control is slipping away in Nunavut. Most food has to be shipped from the south, and the few grocery shops in Nunavut are incredibly expensive — with some items priced at two to three times the national average — and stock limited supplies that are often of poor quality. In Nunavut, a family-sized box of cereal can cost nearly Can$18. Traditional methods for harvesting food are also under threat. The sea ice around my hometown of Iqaluit (see ‘Remote research’) and many other northern communities is less stable and dependable than it was a few decades ago, which means that local hunters have a harder time finding and reaching ringed seals (Pusa hispida), a major part of the traditional diet, clothing and culture. Inuit eat seal meat, blubber and organs. They still turn seal skins into trousers and parkas. Hunting, sharing and using seal products is a focus of community bonding and Inuit identity. Climate change isn’t the only challenge. The Canadian government has been considering listing ringed seals as a species of concern, a designation that could greatly limit hunting. As part of this effort, the government surveyed people in Nunavut. As noted by my Inuksiutit Project colleagues, the questionnaire was available only in English and French, which greatly limited input from Inuktut-speaking people who have some of the deepest knowledge of seal populations and have the most at stake. The survey was also conducted online, which limited input from elders and those without iInternet access. In February, I co-authored a piece in The Conversation that documented the ongoing food security crisis faced by Inuit children in Nunavut. Canada’s 2022 Indigenous Peoples Survey found that 80% of Indigenous children in the territory live in households experiencing food insecurity. In that article, my co-authors and I advocated for the renewal of a federal voucher programme that provides Can$500 per child each month for groceries, and another Can$250 for children under four for formula milk and nappies. The programme had been at risk of expiring, which could have been catastrophic. What would you change about how science is conducted in Nunavut?
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Panels of peers are needed to gauge AI’s trustworthiness — experts are not enough
Cong Cheng, Jian Dai, Lulu Yan, Chengliang Wang
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In his World View, Vinay Chaudhri proposes using an expert interview — a ‘Sunstein test’ — to gauge an AI model’s true level of understanding (see Nature 646, 1027; 2025). This is a good way to check technical proficiency, but risks anointing a select group of elites as the arbiters of an AI tool’s ‘trustworthiness’. This would inadvertently reinforce power structures critiqued by Cathy O’Neil in her book review, which highlights that the objectives of AI systems reflect the goals of the select few people who build and control them (see Nature 646, 1048–1049; 2025).
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Synthetic tongue rates chillies’ heat — and spares human tasters
Jenna Ahart
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A contestant winces during in a chilli-eating competition in China. A gel-based synthetic tongue can give a ranking of foods’ spiciness without human discomfort.Credit: AFP/Getty A gel-based artificial tongue can determine the spiciness of a wide range of foods, from the forgiving bell pepper to the more formidable ‘facing heaven’ chili of Sichuan cuisine. The device, as the researchers report1 in ACS Sensors, might be the secret to determining the heat levels of spicy foods without risking any human taste buds. The artificial tongue itself is not a new feat. Scientists have created similar devices that can use electronic sensors to detect sweet, sour, spicy and umami tastes. But the authors of the new paper wanted to focus on spiciness in particular and to measure spice levels as precisely as possible, which is especially important for quality control in food, says co-author Jing Hu, a chemical engineer at the East China University of Science and Technology in Shanghai. Taming the burn The team’s solution was “inspired by the spicy-neutralizing effect of milk”, they write in the paper. Milk “proteins that affect our perception of spiciness” relieve the burn of a spicy dish, explains Carolyn Ross, a food scientist at Washington State University in Pullman. The synthetic tongue is made of a gel that contains milk powder, acrylic acid and choline chloride. When a current is applied to the gel, its chloride and hydrogen ions can conduct electricity because they are mobile. To monitor changes in conductivity, the scientists placed the gel between copper sheets and connected the whole contraption to a workstation that measures the electric current. Capsaicin — the compound that gives chilli peppers their spice — interacts with the milk proteins in the gel to form bulky complexes that disrupt ion flow. As a result, when the tongue encounters capsaicin, its conductivity drops.
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Science on shaky ground: Canadian research shifts in the wake of US cuts
Lesley Evans Ogden
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At the Hospital for Sick Children in Toronto, Canada, children across the country can gain access to promising trials of cancer treatments when standard therapies fail. Among these are several conducted by the Pediatric Brain Tumor Consortium — a network of 15 centres across the United States and Canada that are funded by the US National Cancer Institute (NCI). In August, news broke that the consortium would be stopping people from enrolling in its clinical trials across North America, after losing federal funding beyond March 2026. The decision was handed down by the NCI, part of the US National Institutes of Health (NIH). “The process of closing those studies, not just in Canada, but in the US, is beginning,” says Jim Whitlock, a paediatric oncologist at the Hospital for Sick Children. “This is a real tragedy.” Nature Spotlight: Canada For Whitlock and other Canadian scientists who have collaborations with US partners, the past ten months have been turbulent. With US scientific agencies such as the NIH, the National Oceanic and Atmospheric Administration (NOAA) and the Environmental Protection Agency (EPA) seeing billions of dollars in funding cuts and job losses under the administration of US President Donald Trump, the effects have also been felt in Canada. There, cancelled projects and uncertainty have caused scientists and academics undue stress. Total losses to Canadian science are unclear. Among some US federal grant agencies, it can be difficult to see where the funding goes in Canada and who receives it, says FĂ©lix Proulx-Giraldeau, interim executive director at Evidence for Democracy in Ottawa, which promotes scientific evidence in governmental decision-making. He adds that whereas the NIH has “gold-standard” transparency about funding recipients, information on grants from organizations such as the EPA and the US National Science Foundation can be harder to keep track of. “It’s unequal across the board,” says Proulx-Giraldeau. As for the rationale behind the cuts to research funding, he highlights media reports that suggest some words and phrases — such as those mentioning diversity, equity and inclusion (DEI), transgender research and disparities faced by minority ethnic groups — might be used to flag grants for further scrutiny. “What we’re seeing has us really worried, especially about how these attacks on science translate to attacks on science in Canada, directly and indirectly,” he says. Health divides The Pediatric Brain Tumor Consortium is not the only cancer-trial platform affected by US cuts. As a specialist in acute leukaemia, Whitlock is part of a broader collaboration called the Children’s Oncology Group (COG), which is the world’s largest research organization for childhood and adolescent cancers. The COG operates across more than 220 institutions, with over 100 clinical trials active globally. Of these, 76 involve patients at Toronto’s Hospital for Sick Children. Budget release: Canada courts US researchers and signals wider commitment to science The first whisper of trouble came early on in the year, when Whitlock learnt that certain international research projects would no longer receive NIH funding, a development subsequently confirmed by the COG leadership. Not wanting to halt the group trials taking place at his hospital, Whitlock and his colleagues accessed funding through the hospital’s foundation. However, the longevity of this measure is unclear. “That puts us in a real dilemma,” he says. Other Canadian health researchers are feeling the pressure, too. Meghann Lloyd, a physical-activity and disability researcher at Ontario Tech University in Oshawa, investigates the incidence of preventable health conditions among children with disabilities globally. In June 2024, Lloyd was part of a team that submitted an NIH grant application with a US colleague. “We scored quite well, but just below the funding line,” she says. When they resubmitted a few months later, around the time of the 2024 US election, the proposal fell into what she calls “purgatory”. It was eventually sent back in May 2025 with a note about it “not aligning with the goals of the administration”, says Lloyd. Clinical trials at Toronto’s Hospital for Sick Children have been affected by US funding cuts.Credit: Steve Russell/Toronto Star via Getty Images She adds that it seems as if “disability has been enveloped or absorbed under this anti-equity, diversity and inclusion [rhetoric]”. For resubmission, she says that their application had to be stripped of keywords deemed by the grant officer at her institution and her US colleague as potentially problematic, including ‘inequity’, ‘disparity’ and ‘less access’. Because Lloyd is a full professor who has other projects, it’s not a make-or-break career issue, she says, but: “I’m a little bit nervous about my colleagues’ [careers] in the US.” Bridging the gap The cuts are also a concern for Canada’s early-career researchers, including health scientist Jean-Christophe BĂ©lisle-Pipon at Simon Fraser University in Burnaby, who does not have a tenured position. He studies the ethical, legal and social impacts of medical artificial intelligence, and his core research is NIH-funded. The impact of recent cuts to the agency were huge, he says, “especially in terms of stress”. Although BĂ©lisle-Pipon is salaried, he had to reassure his university’s administrators that his team of about 20 research associates and graduate students, who were supported by a mixture of Canadian grants and an NIH grant, could be paid until the end of the year. And then he needed to talk to his team. Seeing the news about the US budget cuts, “I couldn’t give them formal or firm reassurance that everything will be fine,” says BĂ©lisle-Pipon. Standing up for Inuit-led research in Canada’s changing Arctic Currently, his team’s NIH funding has not been cancelled — but his approach has substantially shifted. In his US funding applications, BĂ©lisle-Pipon now focuses on overall AI governance and oversight, instead of safeguards that relate to access and DEI. “I met with the NIH programme officer, and they reviewed my research programme to make sure that I don’t engage any more on DEI.” However, funding agencies in Canada, such as the Canadian Institutes of Health Research, continue to fund his DEI-focused research, particularly because it relates to ethics in medical AI. “I still think that it’s extremely important,” he says, but he now creates “a wall between the two”, making sure that everything pertaining to governance and ethics of his NIH-funded research is shielded from his Canadian-focused DEI research. Comprehensive national data on the effects of the US cuts in Canada are lacking, but some institutions have been tracking the effects at a local level. Leah Cowen, who is vice-president for research, innovation and strategic initiatives at the University of Toronto, says that 4% of the university’s Can$1.5-billion (US$1.1-billion) annual research funding comes from foreign sources, of which the United States is one. Although that’s a small percentage overall, it “can have very profound impacts”, says Cowen, especially for those staff who have extensive collaborations with US investigators. “The impacts of the US cuts have been changing over time,” she says, because of various US executive orders and subsequent legal challenges. In vaccine-hesitancy research, for example, “we’ve seen programmes in that space specifically paused,” Cowen adds. Leah Cowen at the University of Toronto.Credit: Tim Fraser/Courtesy of the Connaught Fund In response, the University of Toronto launched an emergency research fund last month to support faculty members for up to a year, allowing them to re-engage with US partners. In the interim, the university is encouraging researchers to diversify their funding sources, such as by looking to other international partners. Many scientists who spoke to Nature in October also hoped to see new funding for science in the Canadian government’s budget — released earlier this month, it indeed provided modest relief and optimism for Canadian researchers. Cowen underlines that science spending accounts for just over 1% of all US federal funding, as noted in a February article by editors from the US microbiology community (I. Blader et al. ASM Case Rep. 1, e00043-25; 2025). This means that research cuts will not drastically alter or improve the US national budget, “but will decimate what’s been absolutely critical for US sovereignty and technological innovation and solving global challenges”, she says. Natural resources Cross-border fieldwork is another area that has been imperilled by US funding cuts. In Ann Arbor, Michigan, the Great Lakes Environmental Research Laboratory conducts many environmental-monitoring programmes, including tracking levels of cyanobacterial blooms in waterways used for drinking, fishing and recreation — a task that relies on data from both sides of the US–Canada border. Municipal decisions on adjusting or stopping the drinking-water supply rely on this real-time data.
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Has birds’ mysterious ‘compass’ organ been found at last?
Davide Castelvecchi
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Credit: Suriya Silsaksom/Alamy Pigeons can sense Earth’s magnetic field by detecting tiny electrical currents in their inner ears, researchers suggest. Such an inner compass could help to explain how certain animals can achieve astonishing feats of long-distance navigation. The team performed advanced brain mapping as well single-cell RNA sequencing of pigeon inner-ear cells. Both lines of evidence point to the inner ear as the birds’ ‘magnetoreception’ organ. The results appeared in the Science on 20 November 1. “This is probably the clearest demonstration of the neural pathways responsible for magnetic processing in any animal,” says Eric Warrant, a sensory biology researcher at the University of Lund in Sweden. Studies have suggested that various animals, including turtles, trout and robins, can sense the direction and strength of magnetic fields, although the evidence has sometimes been contested — and the mechanisms have remained controversial. Bird-brained navigation Two leading hypotheses have led the research into how birds sense magnetic fields. One is a quantum-physics effect in retina cells where birds ‘see’ magnetic fields. Another is that microscopic iron oxide particles in the beak could act as tiny compass needles. However, it’s largely unknown where magnetic information is sensed in animals’ brains and how sensory neurons confer sensitivity to electromagnetic changes. In 2011, researchers found hints that magnetic fields triggered pigeons’ vestibular system, the organ that enables vertebrates to sense accelerations (including gravity) and helps them to stay balanced2. The structure is made of three fluid-filled loops which are mutually perpendicular, so they can communicate to the brain the direction of an acceleration by breaking it down into three ‘x, y, z’ components. Compass protein attracts heap of criticism David Keays, a neuroscientist at Ludwig-Maximilian University of Munich in Germany, designed an experiment that could reveal how pigeons’ brains respond to magnetic fields. Keays’ team exposed six pigeons to a magnetic field slightly stronger than Earth’s for just over an hour. The birds’ heads were immobilized and the magnetic field was continually rotated to simulate the heads’ motions with respect to Earth’s geomagnetic field. Next, the team used a method for measuring activation patterns of neurons across the brain — by measuring a genetic marker of cell activity in pigeon brains made transparent by a technique called clearing. Maps of brain activity in birds that had been exposed to magnetic fields were compared to a control group that had not been exposed to magnetic fields. The results showed neuronal activity related to magnetic fields in the brain region that receives input from the vestibular system, as well as in regions that help to integrate various sensory stimuli. This result narrowed down the list of potential compasses to one — the vestibular system — although it did not explain how pigeon neurons can physically sense magnetic fields. A magnetic sense organ In principle, a conducting material in an organism could produce electric currents in response to magnetic fields, giving an animal a ‘magnetic sense’ — a mechanism that has been proposed as early as 1882 by French zoologist Camille Viguier3. In previous research, Keays had looked for a molecular mechanism of this magnetoreception by following inspiration from the biophysics of sharks and skates, which have organs that sense minute electric fields to help them find prey4. These animals express a protein sensitive to changes in neurons’ electrical activity, but modified with a 10-amino-acid-long insertion that allows them to sense electrical currents generated from magnetic fields. Fruit flies’ ability to sense magnetic fields thrown into doubt
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How obesity drugs quiet ‘food noise’ in the brain
Mariana Lenharo
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Drugs such as Ozempic and Mounjaro act on GLP-1 receptors in the brain to regulate appetite. Credit: Oliver Berg/dpa via Alamy The obesity drug tirzepatide, sold as Mounjaro or Zepbound, can suppress patterns of brain activity associated with food cravings, a study suggests. Researchers measured the changing electrical signals in the brain of a person with severe obesity who had experienced persistent ‘food noise’ — intrusive, compulsive thoughts about eating — shortly after the individual began taking the medication. The study is the first to use electrodes to directly measure how blockbuster obesity drugs that mimic the hormone GLP-1 affect brain activity in people, and to hint at how they curb extreme food cravings. “It’s a great strategy to try and find a neural signature of food noise, and then try to understand how drugs can manipulate it,” says Amber Alhadeff, a neuroscientist at the Monell Chemical Senses Center in Philadelphia, Pennsylvania. The findings were published today in Nature Medicine1. Bonus finding Casey Halpern, a neurosurgeon-scientist at the University of Pennsylvania in Philadelphia, and his colleagues did not set out to investigate the effects of obesity drugs on the brain. The team’s goal was to test whether a type of deep brain stimulation — a therapy that involves delivering a weak electrical current directly into the brain — can help to reduce compulsive eating in people with obesity for whom treatments such as bariatric surgery haven’t worked. How to keep weight off after obesity drugs The scientists set up a study in which participants had an electrode implanted into their nucleus accumbens, a region of the brain that is involved in feelings of reward. It also expresses the GLP-1 receptor, notes Christian Hölscher, a neuroscientist at the Henan Academy of Innovations in Medical Science in Zhengzhou, China, “so we know that GLP-1 plays a role in modulating reward here”. This type of electrode, which can both record electrical activity and deliver an electrical current when needed, is already used in people to treat some forms of epilepsy. For the study’s first two participants, the researchers found that episodes of intense food noise were accompanied by a surge in low-frequency brain activity. This pattern suggested that these changes could serve as a measurable sign of compulsive food cravings. The third trial participant, a 60-year-old woman, had just started taking a high dose of tirzepatide — which had been prescribed by her physician to treat type 2 diabetes — when she had the electrode implanted. “We took advantage of this serendipitous opportunity because of the excitement around these drugs,” Halpern says. Food noise silenced
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Introducing the j-metric: a true measure of what matters in academia
Dariusz Jemielniak
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Credit: Adapted from Getty More than half a century ago, information scientist Derek De Solla Price observed that the scientific literature was growing exponentially, doubling every 10–15 years1. Little did he know that this observation would spawn not just a field of study, but an entire industry devoted to counting, measuring, weighing and indexing every aspect of academic output2. Today, the modern academic doesn’t just publish — they generate metrics. They don’t just research — they optimize their h-indices. And they certainly don’t just think up new ideas — they maximize citation counts while maintaining a favourable paper output. Ultimately, they produce ‘units of assessment’, according to the UK Research Assessment Framework (REF), which the United Kingdom uses to allocate ÂŁ2 billion (US$2.7 billion) in public research funding across its universities. They don’t collaborate; they strategically co-author, to maximize citation networks. And they certainly don’t read any more — who has time when there are metrics to massage? The rise of the h-index: when counting became culture It began innocently enough. Twenty years ago, physicist Jorge Hirsch at the University of California, San Diego, proposed the h-index. It was elegantly simple: a scholar with an h-index of n has published n papers that have each been cited at least n times3. Hirsch’s original paper suggested that “for physics, a value for h of about 10–12 might be a useful guideline for tenure decisions at major research universities”. Oh, sweet summer child, to quote a popular line from Game of Thrones. What Hirsch had unleashed was not merely a metric, but a compulsion. Within a decade, the h-index had metastasized across disciplines. And very quickly, rather than a metric, it became a target. Search committees began sorting candidates by h-index; promotion committees set h-index thresholds; graduate students started checking their h-indices with the frequency and anxiety typically reserved for checking a dating app. An explosion of metrics But why stop at one number when you could have dozens? The h-index begat the g-index (which gives more weight to highly cited articles)4, which begat the e-index (to account for citations beyond those considered in the h-index), the a-index (to measure the average number of citations in a researcher’s top papers) and the m-index (which takes career length into account). There is now the i10-index (the number of publications with at least ten citations), the h-core (the core set of papers considered by the h-index) and the contemporary h-index (which adds a decay function, because apparently citations should have a half-life). Each new metric arrived with its own justification, its own formula and its own promise to finally capture the true essence of scholarly impact. To me, metrics are like trying to measure the ocean by counting waves, each new metric promising to quantify them more accurately than the last. The REF, for example, gave us ‘impact case studies’ — documents that describe research impact beyond academia. Australia’s Excellence in Research for Australia (ERA) introduced ‘research quality indicators’ to assess research quality across disciplines. The Leiden Manifesto5 actually had to remind us that “quantitative evaluation should support qualitative, expert assessment” — a bit like reminding people that food should be chewed before swallowing. Naturally, these metrics are justified as ensuring accountability to taxpayers, who surely lie awake at night wondering about h-indices rather than, say, whether scientists have cured cancer or explained consciousness. Meanwhile, the publishers watched and learnt. We now have a panopticon of productivity, in which every citation is counted, every self-citation scrutinized and every collaboration strategically calculated for maximum metric optimization. Enter the j-index: the weight of true scholarship I humbly propose a new, maybe-slightly-ironic, metric. This captures what truly matters in academic work: physical heft. I call it the j-index, and its calculation is refreshingly straightforward: J = W Ă· Y Where W is the total weight (in kilograms) of all books a scientist has authored, and Y is the number of years since the author earned their doctorate. Consider the elegant simplicity. No longer must we worry about citation cartels (in which authors cite each others’ publications to boost citation counts) or gaming the system through self-citation. The j-index is immune to such manipulation — unless the books are printed on heavy paper stock, which should be discouraged through strict guidelines on acceptable paper weights. On the plus side, no longer will scholars insist on softcover editions: just think how many trees we can save!
Nature DOI suffix ≠ "/s...": Not a research article
Budget release: Canada courts US researchers and signals wider commitment to science
Brian Owens
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The contents of Prime Minister Mark Carney’s first federal budget, released on 4 November, came as a relief to many researchers in Canada – because a large cut to the country’s three main research-funding councils failed to materialize. The nation has also poured further investment into attracting international scientists from abroad. With the economic fallout from US President Donald Trump’s tariffs and the planned increases in expenditure on housing, infrastructure and national defence, Canada’s government departments had been asked to plan for 15% cuts in the lead-up to the 2025 budget. The scientific community feared that had those cuts been applied to the funding councils, they would have erased the large, multi-year increase promised in the 2024 budget. Much of this increase had been earmarked for long-overdue salary boosts for PhD students and postdoctoral fellows. Nature Spotlight: Canada In the end, the funding councils were spared the worst of the cuts and asked to find only 2% in savings. Three other areas were exempted from the 15% target: national security and public safety; Indigenous reconciliation; and gender equality, including for people from sexual and gender minorities (LGBTQ+). “Given the context, the fact that the government put science, research and innovation front and centre and said we cannot cut here is extremely encouraging for us,” says FĂ©lix Proulx-Giraldeau, interim executive director of the science-advocacy group Evidence for Democracy in Ottawa. “It shows that they understand that science is central to Canada’s competitiveness in this changing global context.” The 2% cut leaves the planned funding increase from 2024 largely intact. The savings will be found from councils’ operational funding, leaving grants untouched, according to Robert Asselin, chief executive of U15 Canada, an association of 15 of the country’s most research-intensive universities. Asselin also welcomed five-year plans to invest Can$925 million (US$660 million) in artificial-intelligence infrastructure ($800 million of which had been promised in previous budgets), plus $334 million in quantum technologies — calling the plans “a great sign of the government’s commitment to science and technology”. He also hailed a promised $68-million investment over three years to establish the Bureau of Research, Engineering and Advanced Leadership in Innovation and Science (BOREALIS). This would be focused on developing technologies related to national defence. Science on shaky ground: Canadian research shifts in the wake of US cuts But the biggest science-related announcement in the budget was $1.7 billion in new money to attract more than 1,000 high-level international researchers to Canada. That includes $1 billion over 13 years to support new professorships through the Accelerated Research Chairs programme, $133 million over three years for the relocation of PhD students and postdoctoral fellows, and $120 million over 12 years for the recruitment of assistant professors. There will also be $400 million, spread over seven years, to improve research infrastructure to support people who are brought in through the chairs programme. “Canada is the best place to live, and top talent from around the world want to come here because they see opportunities and possibilities to contribute to cutting-edge research,” said finance minister François-Philippe Champagne in his budget speech. “We will make sure that the best and brightest continue to choose Canada to innovate, invent and grow our industry.” Although the initiative is not specifically aimed at US researchers, the budget includes a pledge to create an accelerated immigration pathway for those who already hold US H1-B visas, making the intent clear. “The budget is a reflection of the government’s priorities, and the fact that they came through with real dollars and clear language about science shows real leadership and a clear direction for the future,” says Asselin. “They want to compete and bring the best and brightest here.” Standing up for Inuit-led research in Canada’s changing Arctic
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Insulin cream offers needle-free option for diabetes
Shamini Bundell, Nick Petrić Howe
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Nature DOI suffix ≠ "/s...": Not a research article
AI has a democracy problem — here’s why
Virginia Eubanks
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Rewiring Democracy: How AI Will Transform Our Politics, Government, and Citizenship Bruce Schneier and Nathan E. Sanders MIT Press (2025) The tsunami of writing on artificial intelligence tends towards either bald hype or panicked dystopianism. Proponents say that AI will revolutionize health care, drive business growth and become our new best friend. But for its critics, AI could cause massive unemployment, perpetuate fake news and pose an extinction risk to humankind. Why an overreliance on AI-driven modelling is bad for science In Rewiring Democracy, cybersecurity expert Bruce Schneier and data scientist Nathan Sanders offer a welcome middle path by focusing on practical politics. In a heartfelt, if workmanlike, way, they craft a framework for maximizing the democratic potential of AI. Yet, by shrinking and distorting the vexing political challenges that the world faces today to fit a single solution — AI — they short-change the frustrating glories of living together as human beings. Structured clearly enough, even for readers who know little about AI, the book is rich with concrete examples and absorbing speculation. Schneier and Sanders propose that every aspect of democratic governance — such as negotiating procurement contracts, drafting legal briefs, producing local news or facilitating conversation across political divides — could be enhanced by the thoughtful application of AI developed under public control for public benefit. “Entrenched elected officials, political movements with authoritarian tendencies, and the billionaire class all regard AI as a new tool to consolidate and centralize power,” they write. “But the rest of us, the public, can harness it as a tool to distribute power instead.” For example, a personal “army of AI minions” could extend individual power by making it easier to speak out. AI agents could make political decisions on our behalf, guessing our preferences on the basis of past behaviour and communicating them swiftly to legislators. AI for the people AI, the authors write, could either enrich or undercut different modes of political participation: campaigns, legislation, public administration, courts, organizing and advocacy. AI as is, designed by corporate players and supercharging an already unequal political system, might exacerbate discrimination and harm, allow lobbyists to concentrate their power and leave the most vulnerable people with shoddy digital attorneys rather than pricier human ones. Public AI — designed to enrich democracy — could target government resources more effectively, lower the cost and expertise needed to generate legislation, and simplify the drafting of complaints. AI can supercharge inequality — unless the public learns to control it However, the democratic potential of AI will not be realized unless four conditions are met. First, the commercial AI ecosystem must be reformed, by providing robust public alternatives to technologies that are privately owned and controlled. Second, authoritarian or unethical uses of AI must be resisted by ensuring that “democratic principles 
 govern its development and deployment”. Third, responsible government AI must consider social impacts, weigh the risks and benefits carefully and ensure accountability. Fourth, Schneier and Sanders think, social movements could help to renovate democracy by galvanizing “their constituents to respond to the long-standing democratic threats magnified by AI”. In the final section, Schneier and Sanders describe their vision for nurturing “robust noncorporate alternatives” to commercial tools. Imagining public AI as a “universal economic infrastructure”, like publicly run schools and highways, the authors favour multilateral, anti-monopoly regulation that might allow citizen AI to compete against the products of ‘big tech’ — an approach that the United Nations is discussing. They offer organizing principles for a shared vision of democratic AI, one that is broadly capable, widely available, transparent, meaningfully responsive, actively stripped of its biases, reasonably secure and non-exploitative. Many readers will be sympathetic to these goals. Which is why it is so disappointing that the book’s fundamental premise — that democracy can best be understood as an information system — fatally undermines those objectives. Government is not a machine Think of democracy “as an information system for turning individual preferences into group policy decisions, and then executing those decisions through society”, Schneier and Sanders write. But democracy isn’t a flow chart or an executable piece of computer code. Preferences are formed in the process of governance, not just counted. And as any first-year student of political science can affirm, implementation, particularly at the street level, creates, shapes and modifies policy as often as it executes it. Governments need formal rules and copious, reliable data to function efficiently and fairly. But democracies are also human, value-laden institutions for negotiating the contradictions that come with living together well. The model of government as information system has no place for the sophistication and difficulty of what democracies attempt to accomplish, or the standards to which they are held. A system at Moscow Metro stations recognizes passengers’ faces, allowing people to board trains and make cashless payments for journeys.Credit: Andrey Rudakov/Bloomberg/Getty For example, Schneier and Sanders argue that the purposes of democracy include “peaceful transition of power, majority rule, fair decision-making, better outcomes”. They fail to mention equally crucial aims, such as preventing tyranny, protecting minority rights, balancing conflicting values, stewarding collective wealth and nurturing human capacity. The premise that democracy is an information system obscures the thorniest challenges that AI poses to governance. It assumes that, if everyone has equal access to reliable, accurate and timely data, our disagreements will dissolve. But we live in a world of genuinely incommensurate interests.
Nature DOI suffix ≠ "/s...": Not a research article
Circular DNA has a ticket to ride chromosomes
Noah A. Dusseau, Eunhee Yi
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Cancer cells often contain DNA fragments that have broken away from chromosomes1 and formed a type of circular structure called extrachromosomal DNA (ecDNA)2. These sequences usually have cancer-promoting genes and gene-regulatory sequences that enable tumour growth, adaptation and survival. Unlike cancer-promoting genes residing on chromosomes, which are always inherited by the next generation of cells, genes on ecDNA are reliably inherited only if they tether to chromosomes when cells divide3, and untethered ecDNA can get lost over time as cells replicate. In cell division, ecDNAs are not segregated equally into daughter cells, which means that cancer cells in a tumour can contain varying amounts of cancer-promoting genes. This can complicate treatment and negatively affect clinical outcomes1. Writing in Nature, Sankar et al.4 provide insights into how ecDNA is inherited.
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I encourage women to claim their space in astrophysics and beyond
Kanika Sharma
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Theoretical astrophysicist Debarati Chatterjee has always seen gender for what it is — a social construct. Despite witnessing domestic violence as a child, experiencing sexual harassment as an undergraduate and a PhD student, and being one of the small proportion (around 20%) of astronomers in the world who are women, she hasn’t let her gender define her career. Leaving her home country of India to start a postdoctoral position in Germany in 2010, she saw that prejudices based on race, class and gender also existed in the international scientific community. Chatterjee works in the emerging and male-dominated field of gravitational-wave science. She studies neutron stars — ultra-dense cores that are left over when massive stars collapse — by looking at gravitational waves, or ripples in the fabric of space-time. It’s an approach that brings together several disciplines, including nuclear, particle and condensed-matter physics. On her return to India in 2020, she joined the Inter-University Centre for Astronomy and Astrophysics (IUCAA) in Pune. In June, the 45-year-old was promoted to full professor, becoming the first woman to be awarded this role in the institution’s 37-year history. Her research group generates complex theoretical models to crack the mystery of the interior composition of neutron stars. She also wants more women to pursue science subjects, especially astrophysics, and has held various roles to promote gender equity. She was a core member of the IUCAA’s committee to combat sexual harassment and was part of the Astronomical Society of India’s Working Group for Gender Equity, for which she helped to run campaigns highlighting pioneering work by female Indian scientists. An avid science communicator, this year, Chatterjee launched the Indian branch of the Pint of Science festival — an annual festival that invites scientist to pubs and cafĂ©s to share their latest research — this year across three cities. Chatterjee has also popularized the science behind the planned Laser Interferometer Gravitational-Wave Observatory-India (LIGO-India), which is to be built in a rural area called Hingoli. By delivering talks at schools, universities and astronomy clubs across India, she helps to inspire girls and young women to become scientists. Chatterjee spoke to Nature about how she overcame sexual harassment to become an astrophysicist, and why she promotes gender and racial diversity in her field. What is the great passion that has driven you as a scientist? Curiosity and adventure have always driven me. Since childhood, I have been obsessed with finding solutions, and I don’t rest until I get to the root of the issue. The fact that science can be about addressing extremely complex problems, which can take a lifetime to solve, excites me. Even for someone like Einstein, conundrums in fields such as quantum physics and general relativity were too difficult to solve in his lifetime. During my undergraduate studies at St Xavier’s College in Kolkata, my summer project at the Indian Institute of Astrophysics (IIA) was about understanding how the Sun rotates, a question that remains unanswered. That was when I fell in love with how the academic world works. When I went to the IIA, I realized I didn’t need to pursue a 9-to-5 routine. I saw that some researchers woke up at 10 a.m. and worked past midnight — then they would go off to play badminton until the early hours. I was very attracted to this way of life. Also, visiting observatories such as the Vainu Bappu Observatory in Tamil Nadu, which is in the middle of a forest, felt like an adventure that I was ready to have for the rest of my life. Debarati Chatterjee (front row, second from right) with students at a Pint of Science outreach event.Credit: Kshitij Parshetti/Pint of Science India When did you realize you wanted to tackle racism and sexism in science? There have been countless times during my professional life when I have confronted unfriendly racist or sexist attitudes. I remember one incident when I was a postdoc overseas. A visitor to the laboratory made an incorrect statement during a seminar, and I pointed it out. While I was having this conversation, several members of my institute walked out of the room in protest at my questioning the visitor. Such disrespectful microaggressions were a daily occurrence. As a foreigner, if I didn’t speak the local language, I would be left out during important conversations, which sometimes happened when researchers were socializing. Many of my peers would give up and retreat into isolation. Instead, I learnt to speak five languages with enough fluency that I could give interviews in them. Adapting to new fields of research and work environments is crucial for all early-career researchers, and it is often necessary for people to receive full credit for their contributions and achievements. These days, there are welcome centres that help international students to tackle such issues. At other times, while taking part in official inquiries into why there are so few women in nuclear and particle physics, I have had an institute director barge in demanding to know, “Why is this taking so long?”. These experiences have motivated me to stand up for myself, and to work towards diversity, equity and inclusion to set an example for others who might not speak up because of a lack of support. I have heard from leading female theoretical physicists about how hard their journey has been and why speaking up is necessary. How have you dealt with racism or discrimination in your personal and professional life? During my PhD, I faced many instances of sexual harassment from a senior scientist. I had no choice but to continue my studies, because my living expenses depended on my fellowship. This person often told me that I was not good enough and that my work was inconsequential. The overwhelming pressure of the situation threw me into clinical depression, and I had to consult a therapist. I also took my grievance to the head of the department, who advised me to focus on completing my degree, because I was close to submitting my thesis. Two decades ago, there were hardly any female theoretical physicists at my university, and there was no office to which one could complain. I even trained in martial arts for self-defence at the time. Towards the end of my PhD, I won a German Academic Exchange Service (DAAD) fellowship, which gave me and my work international exposure, and helped me to develop a wide collaboration network. That is how I became an independent researcher who did not have to rely on any senior scientist for advancement. Who has been your biggest influence or mentor, and why?
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Greenhouse-gas emissions should peak by 2030, say researchers
Jacob Smith
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Measles makes a comeback: four charts show where and how
Nicola Jones
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People with measles are barred from entering a hospital in Canada, which has seen a surge in cases of the highly infectious disease in 2025.Credit: Nicole Osborne/The Canadian Press via ZUMA Press A surge in measles cases has cost Canada its official measles-free designation — and the United States looks likely to follow suit. The spike in Canada’s measles rate has been dramatic: so far, there have been 4,843 confirmed cases in 2025, up from just 147 cases in 2024 (see ‘Canadian surge’). Meanwhile, the United States has had more than 1,720 confirmed cases this year, more than in any year in the past three decades. If the disease continues to spread until January 2026, the United States could lose its ‘measles elimination’ status — a label applied to regions that have had no endemic measles transmission for at least 12 months — early next year. Source: Health Infobase, Government of Canada Public-health officials say that the surge in cases in North America is concerning, and possibly a sign of worse things to come. But these outbreaks are not unprecedented in the broader picture. The global number of measles cases was much higher in 2019 (see ‘Up and down and up again’), when Africa was hit hard by outbreaks. And 2024 was particularly bad in Europe; the region saw double the number of measles cases it recorded in 2023, and the United Kingdom declared a national incident. Source: World Health Organization Health officials around the world have been trying to quash measles for decades, with variable success. Countries and regions come and go from the measles-free list frequently. “Elimination is a fragile state,” says William Moss, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. The Americas became the first — and, so far, only — World Health Organization (WHO) region to be declared measles-free, in 2016, but this status didn’t last long, thanks to an outbreak in Venezuela in 2018 that spread to Brazil. The region clawed back its status in 2024, but has now lost it again, thanks to the 10 November decision about Canada, made by the Pan American Health Organization. High bar The WHO recommends that countries vaccinate 95% of children with two doses of measles-containing vaccine. Few countries hit that mark: in the European Union in 2023, for example, only four countries achieved it. “That’s an aspirational goal. A country can eliminate measles without 95% coverage,” notes Moss; outbreaks tend to happen in communities in which the coverage is much lower than the national average. Globally, the rate of measles vaccination with one dose — which provides some protection — has hovered between 81% and 86% for more than a decade, and is currently recovering from a dip that occurred during the pandemic as a result of disruptions in vaccine delivery (see ‘Widespread protection’). Many countries, including the United States and Canada, maintain a rate of around 90% for one dose. Source: UNICEF
Nature DOI suffix ≠ "/s...": Not a research article
On the move: why PhD students study abroad in 2025
Linda Nordling
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When Calvin Santiago Lee decided to look beyond his home in the United States for a PhD position, finances played a decisive part. “I believed that unless I got extremely lucky in the US, there would be little chance of being financially stable during my PhD and having good career prospects thereafter,” says the theoretical computer scientist. The global PhD landscape 2025 His current position working on category theory — a mathematical field related to programming languages and logic — at Reykjavik University in Iceland pays well and provides good work–life balance. “I feel like a valued member of society and can live a comfortable life while pursuing a PhD. I believe that even at top US institutions, this would not be a guarantee.” Lee’s move captures a sentiment shared by many young researchers. When Nature surveyed nearly 3,800 PhD students worldwide in May and June, about one-third were based outside their country of origin (see ‘Mobility of PhD students studying abroad’). Among the 1,232 respondents studying abroad, the most common reason for their move — cited by 43% — was “a lack of funding at home”. That proportion is on a par with Nature’s two previous PhD surveys in 2019 and 2022, when around 45% of those earning a PhD abroad said finances had played a key part in their move. However, in both of those surveys, it was not the top reason. Instead, that was “to experience another culture”, chosen by roughly half of respondents (49% in 2022 and 46% in 2019). But this year, only 35% selected that option. (Note that some options have changed from previous surveys, which might have influenced respondents’ selections.) Other motivations for studying abroad that have seen a drop include “more job opportunities post-study” (from 42% in 2019 to 35% in 2025) and “a lack of, or low quality, programmes at home” (40% in 2019 to 28% in 2025). Altogether, this suggests that students are making more-pragmatic decisions, guided by financial and career considerations rather than by personal exploration. The numbers make sense, says Chris Glass at Boston College in Massachusetts, who researches trends in higher education. He says that shifting visa rules, uncertain post-study work permissions and geopolitical turbulence have “changed the calculus” for prospective PhD students globally. “International doctoral talent today demands tangible economic and scientific returns — not just the promise of experiencing another culture,” he adds. Glass says that students are increasingly asking: “Will I be able to stay and build a research career? Are my skills marketable in the host country — and globally?” He thinks that it’s both an adaptive response to policy headwinds and a sign that students are optimizing their choices for impact and opportunity in a world in which “uncertainty is the norm”. Political push Politics is a minor motivation for moving abroad. Overall, just 7% of respondents say that political reasons influenced their decision, a share that has changed little since Nature asked the question in 2017. How money, politics and technology are redefining the PhD experience But among some nationalities, notably Russians and Americans, the proportion is higher. More than half (56%) of the 16 respondents from Russia studying abroad cited politics as a factor, as did nearly one-quarter (24%) of 46 students from the United States. By comparison, just 4% of respondents from India and 7% of those from China who were studying abroad said the same. US students living and studying abroad said that repressive politics and the current presidential administration’s attitudes towards science and research were key reasons for their choice. Asked to elaborate on her reason for leaving, one woman studying in Switzerland simply wrote: “Trump
” Tensions at home are also thwarting US students’ desire to move back after their PhDs. “I had planned to strongly consider returning to the United States but now those plans are, at a minimum, on hold,” says one in Australia, who requested anonymity out of fear of career repercussions. He says he has “little interest in returning to what amounts to a totalitarian regime” where people like him — a Jewish liberal in a polyamorous relationship — are “effectively targeted for maltreatment, harassment and potentially worse”. He says that most of his friends who are early-career researchers back in the United States either have escape plans or are developing them. Australia is great, he says, because it’s more tolerant than the United States, and the physical infrastructure of roads and buildings “isn’t crumbling, like at home”. It’s also much safer. He used to keep his ‘stop the bleed’ kit clipped to his bag for instant access in case of a mass shooting. “Now, it’s just tucked in the bottom of my backpack.” Russian PhD student Daniil Kiselev studies in France, where he connects with the culture, including this eighteenth-century self-portrait of French painter Joseph Ducreux.Credit: Daniil Kiselev Daniil Kiselev, a PhD student originally from Russia, now at the University of Montpellier in France, left his home country in 2021. At the time, Russia had occupied Crimea, but the full-blown invasion of Ukraine had yet to happen. “Back then, options remained relatively rich. The path to work abroad was demanding, but straight and offered some visibility,” he says.
Nature DOI suffix ≠ "/s...": Not a research article
Fall-prevention clinical trial in rural China shows promising results
Cynthia Swarnalatha, Sallie E. Lamb
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Evidence-based health-care initiatives can have immense clinical benefit. Falls can cause major injuries, particularly for older people; therefore, proven strategies to lessen the risk of falls are needed. Writing in JAMA, Peng et al.1 present the results of a clinical trial evaluating a programme designed to reduce falls.
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: This whale has been spotted alive in the wild for the first time ever
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Bill Gates’s climate comments are a dangerous distraction
Michael E. Mann
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Fifteen years ago, my friend and mentor, climate scientist Stephen Schneider, said something that has stuck with me. When it comes to climate change, the “end of the world” and “good for you” are “the two lowest-probability outcomes”. Extreme heat harms health — what is the human body’s limit? Steve’s aphorism feels especially prescient today. As the 30th United Nations Climate Change Conference (COP30) plays out in BelĂ©m, Brazil, this month, misleading climate messaging in the media espouses both these extremes. At one end, take the actions of billionaire philanthropist Bill Gates. On 28 October, he astounded climate advocates by publishing a manifesto arguing that the climate crisis is less urgent than other major problems that humanity faces (see go.nature.com/23xed). Jarringly, its publication coincided with the devastating Jamaican landfall of potentially the strongest Atlantic hurricane on record, an event that human-caused warming made more likely to happen. Gates wasn’t implying that global warming is “good for you”, but his arguments are adjacent to that sentiment: there has already been enough progress on climate, and we should instead prioritize addressing what he feels are more pressing issues, such as poverty and disease. Despite substantial criticism from me and other climate specialists that this presented a false trade-off between climate action and public health, Gates dug in his heels. “What world do they live in?” he said in an interview with the news outlet Axios, telling reporters that he would “let the temperature go up 0.1 degree to get rid of malaria”. Climate change is also a health crisis — these 3 graphics explain why Indeed, what world is Gates living in? The idea that climate action must come at the expense of efforts to address human health is a provable fallacy. In our book Science Under Siege (2025), public-health scientist Peter Hotez at Baylor College of Medicine in Houston, Texas, and I detail how these challenges are, in fact, inseparable. Human-caused climate change will exacerbate pandemics, as it did for COVID-19, and vector-borne diseases, such as malaria. How Gates or anyone else proposes to “get rid of malaria” in a rapidly warming world is anyone’s guess. This is a strawman argument. Gates’ pivot has been celebrated by climate-change downplayers and fossil-fuel proponents in politics, including US President Donald Trump, and in segments of the media, including the newspapers The Wall Street Journal and New York Post — even if Gates has disavowed their characterizations of his position. Meanwhile, those at the opposite ‘end of the world’ extreme are hardly any more helpful. “It may be too late” announced Robert Hunziker, a freelance writer in Los Angeles, California, just one month ago on the news site Counterpunch. Such narratives of doom are often reinforced by media outlets that overstate the dire nature of the impacts that are baked in, with breathless headlines about supposed tipping points that have already been crossed. This feeds a collective sense of hopelessness. Why we still don’t know the mounting health risks of climate change
Nature DOI suffix ≠ "/s...": Not a research article
How COVAX raced to protect the world from COVID-19
William P. Hausdorff
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Fair Doses: An Insider’s Story of the Pandemic and the Global Fight for Vaccine Equity Seth Berkley Univ. California Press (2025) Most people don’t like getting vaccines, much less seeing their children have needles poked into their thighs and arms. But context can change that. Besieged by terrifying outbreaks of paralytic polio and the spectre of iron-lung respirators, many parents were happy to see their children receiving the first polio vaccinations in the 1950s. Similarly, when I got my first COVID-19 vaccine, it instantly relieved the sense of existential dread that I had felt for almost a year as the death toll rose. The radical plan for vaccine equity Traumatic memories from the pandemic are waning for many. But infectious-disease epidemiologist Seth Berkley thinks the prospect of future pandemics means that it is imperative that we do not forget about the powerful impact of the COVID-19 vaccine. In Fair Doses — a fascinating account of the race to distribute the drug around the world — he attempts to provide readers with a ‘booster shot’ to restore public-health awareness. Berkley is ideally positioned to tell the story. In 2020, he was the chief executive of global-health organization Gavi, the Vaccine Alliance. In the early months of the COVID-19 pandemic, Gavi, along with the Coalition for Epidemic Preparedness and Innovations and others, co-founded COVAX — a worldwide initiative to access, purchase and deliver billions of doses of safe and effective COVID-19 vaccines to those living in low- and middle-income countries (LMICs). The author rightly spends little time on the science of the vaccine or the disease itself. Instead, his aim is to describe the complex and interwoven financial, legal, practical, ethical and political issues involved in securing and equitably distributing vaccines to more than 140 territories. These complexities led to a series of challenges for COVAX leaders. As Berkley recalls, “I thought that this time, because of COVAX, we could tackle a pandemic with a meaningful, global commitment to equity. How wrong I was.” A gargantuan effort COVAX’s goal was wildly ambitious, especially given the world’s abject failure to distribute influenza vaccines equitably a decade earlier during the 2009–10 flu pandemic. With those flu vaccines, Berkley notes that LMICs were left “at the back of queue”. As he highlights, the drugs arrived too late to prevent a substantial burden of disease — and in some countries, essentially didn’t arrive at all. Learn from COVID: Gates’s pandemic prescription By contrast, COVAX was, in many ways, a success. By the end of 2021, more than one billion COVID-19 vaccine doses had been distributed, and two billion had been distributed by the end of 2023. More than half (57%) of the population in the world’s 92 lowest-income countries ended up receiving the one or two doses required (depending on the brand of vaccine) for initial protection, as compared with the global average of 67%. Doses supplied by COVAX are estimated to have averted 2.7 million deaths in low-income countries by the end of 2022. Berkley describes in depth the challenge of raising the billions of dollars needed for the scheme from foundations and governments, which were scrambling to fund their own vaccine programmes. It was this need to attract funds that led COVAX leaders to decide at the outset to invite high-income countries to participate in the initiative. The major attraction for wealthy nations was that COVAX negotiated supply contracts with a wide range of vaccine developers. By joining the initiative, these countries could ensure access to the most safe and effective vaccines, rather than being reliant on whichever vaccine developer they could strike a deal with. Although the decision to involve high-income countries was, according to Berkley, “one of the biggest controversies in setting up COVAX”, it proved successful in helping to attract enough funds up front to purchase vaccines for the world. Initiatives that equitably distribute vaccines during a pandemic can save many lives.Credit: Issam Rimawi/Anadolu Agency/Getty One of the fundamental challenges faced by COVAX leaders when doses started to become available in early 2021 was deciding what equitable distribution would look like. Some countries lacked the infrastructure needed to accept a large number of doses and COVAX didn’t want to send vaccines to countries that couldn’t store or transport them properly. As more doses became available throughout the year, some middle- and higher-income countries that had signed up for COVAX doses managed to procure their own vaccines. That led to a debate about whether they should still be provided with COVAX vaccines that they might not need. Moreover, evidence gradually emerged that many African countries seemed to be less susceptible than elsewhere, on a population-wide basis, to severe COVID-19 disease outcomes. This phenomenon is still not well understood, but it suggested that vaccine needs and demand might be less than previously predicted. Berkley notes the impossibility of devising a transparent algorithm that can integrate all of these factors and output a fair mechanism for vaccine distribution. Ultimately, and controversially, COVAX leaders decided from the outset that the initiative would aim to meet a blanket 20% of the vaccine needs for each country, regardless of other factors. These targets were based on a prediction of how much vaccine could be produced by the end of 2021 — and were later revised upwards. The racial injustice laid bare by COVID must not be forgotten Despite involving wealthy nations in their initiative, COVAX inevitably ended up directly competing for vaccine supplies with these countries, especially when supplies were initially limited, because wealthy countries could pay higher prices and pay up front. Despite manufacturers’ contractual obligations, COVAX sometimes found their vaccine orders delayed or deprioritized compared with those of other purchasers. Some countries went from refusing to share any doses with COVAX — despite having secured many more than their populations needed — to offering leftover doses of vaccines that were about to reach their expiration dates. Some earmarked their donations to particular ‘friendly’ countries, regardless of COVAX’s carefully planned distribution programme, and demanded immediate acceptance of their publicly visible, politically sensitive ‘gifts’, regardless of the readiness of countries to receive them.
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: How ancient humans bred and traded dogs
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Kissing might have evolved 21.5 million years ago
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Why space exploration needs science leadership now — before it’s too late
Gioia Rau
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The past two years have seen a series of milestones in lunar exploration. In February 2024, a commercial lander built by Intuitive Machines in Houston, Texas, did what only superpowers had achieved before: touch down on the Moon and deliver NASA science payloads. Four months later, China’s Chang’e-6 returned the first samples from the far side of the Moon, a site that China plans to build a radio telescope on, in partnership with African nations. Why space exploration must not be left to a few powerful nations The next few years could be just as momentous. In the United States, President Donald Trump proposed US$7 billion for lunar exploration in 2026. His administration’s 2027 priorities go further, calling for investments that “unlock new mission capabilities, enable discoveries, and achieve exploration goals”, including nuclear power, local-resource use and biotechnology in space (see go.nature.com/4812vla). It’s a new era for space exploration, motivated by a mix of geopolitics, potential commerce and discovery. Establishing humans on the Moon, Mars and beyond is no longer just an aspiration: it is driving strategies, markets and missions today. The Artemis Accords — a shared set of principles to enhance the governance of civil exploration and use of outer space — had been signed by 59 nations as of October. Yet science is being left behind. Ensuring that space ambitions remain science-driven is essential if exploration is to yield knowledge and innovation. As an astrophysicist who has worked across government, academia and philanthropy, here I argue that scientific inquiry must guide and shape this next wave of space exploration; I set out five priorities for action. What happens in the next few years will define our future. Embed science in partnerships In space, science is the compass that ensures exploration yields lasting value. As a first step, partnerships between academia, government, industry and philanthropy that are focused on space exploration need to be built — with science in the driving seat. These can align around a shared purpose: missions that deliver both knowledge and scientific and technical progress. Everyone benefits. The record shows that when science leads, it multiplies returns: innovation thrives; economies grow; and national strategies and international partnerships strengthen and drive advances in technologies. For example, Skylab, the first US space station, advanced solar power for human space flight. The Hubble Space Telescope includes modular components that can be replaced or upgraded, demonstrating how modular hardware can enable maintenance in space. The International Space Station is a joint effort between countries including the United States and Russia, demonstrating how scientific partnerships are invaluable for diplomacy. Many national space agencies, and increasingly private actors working in partnership with them, are planning to establish a sustained human presence on the Moon and chart a path toward Mars (see ‘Window of opportunity’). This Moon-to-Mars era must follow past precedents of scientific diplomacy. It must also ensure that scientific return is a core design principle: shaping missions, payloads and infrastructure from the outset, not as an afterthought. If scientists show up early with clear priorities and mission-ready payloads, industry can integrate them, governments can align policy and philanthropy can bridge funding gaps. Window of opportunity The next five years will see dozens of spacecraft* head to the Moon and Mars. Each one is a crucial platform for scientific and technological learning, not least because results are hard won — only about 40% of missions have succeeded since 2023. LaunchNationMission nameMission purposeMission status2023IndiaChandrayaan-3Lunar south-pole lander and roverSuccessful2023RussiaLuna 25Lunar south-pole landerFailed2024ChinaQueqiao-2Relay satellite for far-side commsSuccessful2024ChinaChang’e 6Far-side sample returnSuccessful2024JapanSLIMLunar lander and roversPartial success2024United StatesPeregrine 1Commercial lunar landerFailed2024United StatesIM-1 (Odysseus)Commercial lunar south-pole landerPartial success2025JapanHAKUTO-R Mission 2Commercial lunar lander and roverFailed2025United StatesBlue Ghost 1Commercial lunar lander with NASASuccessful2025United StatesIM-2 (Athena)Commercial lunar lander and roversPartial success2025United StatesESCAPADETo Mars by 2026 to study atmospherePlanned2026ChinaChang’e 7Lunar south pole, orbiter, lander, roverPlanned2026JapanMartian Moons eXploration (MMX)Orbit of Phobos and Deimos and return sample from Phobos to Earth in 2031Planned2026United StatesArtemis IICrewed lunar flybyPlanned2026United StatesBlue Ghost 2Lunar far-side landing with telescopePlanned2026United StatesIM-3Commercial lunar landingPlanned2026United StatesGriffin 1Commercial lunar south-pole landerPlanned2026United StatesBlue Moon Mark 1Lunar lander demonstrationPlanned2026United Statesispace Mission 3Commercial lunar far-side landingPlanned2027IndiaChandrayaan-4Lunar sample return missionPlanned2027RussiaLuna 26Lunar polar orbiterPlanned2027United StatesGateway PPE + HaloLunar orbital station componentsPlanned2027United StatesIM-4Bring technology for later crewed missionsPlanned2027United StatesArtemis IIICrewed landing at south polePlanned2028ChinaChang’e 8Technology demonstration on MoonPlanned2028ChinaTianwen-3Mars sample-return missionPlanned2028India/JapanLUPEXLunar south-pole water-ice explorationPlanned2028United StatesArtemis IVCrewed docking with NASA Gateway lunar space stationPlanned2028United StatesBlue Ghost 3Lunar rover and NASA payloadsPlanned2029United StatesBlue Ghost 4Lunar landing at crater rim with roversPlanned2030ChinaLanyueFirst Chinese astronauts on MoonPlanned2030United StatesArtemis VCrewed lunar landing with Blue Origin landerPlanned2031United StatesArtemis VIDelivery of crew and science module to Gateway and crewed lunar landingPlanned *This table shows missions with publicly available timelines and is not exhaustive. Source: Analysis by G. Rau. For example, NASA’s Commercial Lunar Payload Services (CLPS) initiative exemplifies this new model by procuring delivery services from industry to send science and technology payloads to the Moon more quickly. Yet its commercial timelines and contract structures often lock in technical parameters before science teams can shape key elements such as site access, contamination control and interface standards. If this initiative and other lunar delivery efforts, such as the European Space Agency’s (ESA’s) Argonaut lander or India’s Chandrayaan missions, are to realize their potential, scientific leadership must move upstream in decision-making: shaping selection of landing sites, contamination-control methods and data policies before contracts are signed. Philanthropy can help by financially backing high-risk, high-reward demonstration projects, supporting open-data challenges and creating fellowship programmes that link scientists to commercial payloads. Foundations such as the Breakthrough Initiatives, Washington DC-based Carnegie Science, and Schmidt Sciences and the Simons Foundation, both in New York City, have already catalysed such advances in ground-based astronomy. Similar partnerships must now anchor space exploration in open data, shared tools and talent pipelines. Why space foods aren’t just for space Industry, too, stands to gain. When scientific needs drive standards — for example, reducing exhaust-plume pollution to avoid sample contamination, or minimizing electronic noise to enable radio astronomy — the resulting systems are more robust, interoperable and exportable. The first companies to align with such standards will shape the global supply chain for space development. When scientific requirements shape infrastructure, they improve reliability and operability. A lander or relay network built within scientific tolerances will outperform one optimized only for cost or speed. Science thus becomes not a constraint, but a competitive advantage. Policy can lock in these incentives. For publicly funded lunar and Mars flights, space agencies should reserve a share of payload mass (perhaps 20% or more) for competitively reviewed science projects and require that data are made open within six months of landing. They should tie award fees to science-readiness metrics, such as low radio noise, not just to delivery. Internationally, agencies should set up a science coordination forum under existing frameworks, such as the Artemis Accords, to align emission standards, relay-satellite pointing and site-protection rules. Recognize the Moon’s significance The Moon is more than a stepping stone to Mars and beyond — it is a destination uniquely suited to conducting research. Unlike Earth, it has no atmosphere, liquid water or plate tectonics to erase its history. Its surface is a natural archive of roughly 4.5 billion years of Solar System evolution: from planetary formation and asteroid bombardment to solar and cosmic radiation preserved in the lunar soil, or regolith. Polar craters might contain water ice and organics deposited by ancient comets. Such records could reveal where Earth’s volatile compounds, such as water, came from; whether life’s precursors were common; and how habitable environments emerged. The far side of the Moon is the only place in the inner Solar System that is shielded permanently from radio signals from Earth, making it a unique site for probing the distant Universe and searching for signs of extraterrestrial life. How to chart a moral future for space exploration The lunar surface could host observatories that are impossible to have elsewhere. For example, long-baseline interferometers (devices that combine input from multiple telescopes) operating at visible and ultraviolet wavelengths — ones that would be absorbed by the atmosphere on Earth — could image the surfaces of stars1. By detecting ground vibrations from moonquakes and impacts, seismic arrays might map the Moon’s interior. Networks of reflectors could bounce back laser beams from Earth to test fundamental physics and theories of the Earth–Moon system2. Yet these opportunities are fragile. Rocket exhaust, dust and drilling can contaminate pristine deposits at the lunar poles. Communications satellites orbiting the Moon could spill signals that erase the far side’s radio silence. If scientists simply wait their turn, these crucial sites will be disturbed permanently by others. Moreover, what is constructed on the Moon now will define what is built everywhere else in space. Choices regarding communications, power and mobility infrastructures will shape what science is possible on the lunar surface and beyond, to Mars, asteroids and deep-space orbital platforms. The window for action is now: hardware is flying, sites are being chosen and norms are embedded in contracts and operations. Scientists must step up and study the Moon intensely over the next few years, before it’s too late. Fly payloads that are ready now Despite growing investment in space exploration, many research opportunities remain untapped because instruments are stuck in outdated bureaucratic cycles. NASA’s science budget is expected to face drastic cuts in 2026 and 2027, as federal funds are shifted towards human exploration. Many science missions have long time frames, with launches planned for decades from now, a far cry from the fast and furious approach of the commercial space sector. This cadence gap means that valuable lunar sites could soon be developed without scientific involvement. The fix is simple: fly scientific pathfinder payloads now. Iterate fast, learn fast and scale up what works. Announce payload-delivery opportunities on a rolling schedule that is aligned with confirmed flight windows — then scientists can plan and apply on a predictable cadence. Commercial off-the-shelf parts make it possible to build and fly viable research missions quickly and at a fraction of the cost of bespoke ones. Compact seismometers, neutron spectrometers and radio antennas can hitch rides on commercial landers or piggyback on communication relay satellites. Such projects would complement NASA’s billion-dollar flagship missions and, crucially, ensure that scientists bank essential measurements before lunar environments are irreversibly altered. Potential projects abound. Radio experiments on the lunar far side and prototype optical or UV interferometers could open the way for future experiments. Lightweight seismic and heat-flow sensors can refresh Apollo-era models of the lunar interior, guide the design of human habitats on the surface and constrain moonquake hazards for future infrastructure. Miniature drills and spectrometers could sample volatile compounds that are frozen at the Moon’s poles, revealing how water and organic molecules were delivered. The challenge is coordination. Governments should prioritize ready-to-fly payloads through streamlining of funding channels and speeding up review. An annual budget of at least $1 billion in the United States would match the current pace of commercial international launches. Promising collaboration models include NASA’s Lunar Surface Instrument and Technology Payloads initiative, which selected a dozen instruments in 2024 for short-term delivery, as well as ESA’s Open Space Innovation Platform and Japan’s JAXA small-mission calls. A $50-million philanthropic programme could deploy a dozen small spacecraft for solar physics and planetary sampling or fund a fine-resolution lunar map. Such investments echo how private foundations once underwrote early radio telescopes and genome sequencing: short-cycle, high-risk and catalytic projects. As data volumes from lunar sensors grow, fresh partnerships are pioneering innovative data handling and storage — from relay-based computing on lunar and Martian networks to the first orbital data centres being developed by firms such as Starcloud in Redmond, Washington, among others. Build to fit scientific needs In space, infrastructure is policy. Choices about how and where we build will determine not only what science is possible, but also who can do it.
Nature DOI suffix ≠ "/s...": Not a research article
Lanthanides go electric: promising light emitters used in LEDs
P. James Schuck
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Right now, you are probably being illuminated by a photonic device. Whether it’s an overhead lamp or the screen of your laptop or phone, most modern light sources are based on light-emitting diode (LED) technology, which converts electric energy into photons. Improvements to LEDs — such as colours that are more intense and vivid, a wider colour palette, longer lifespans and streamlined production — are difficult to achieve using conventional materials. Now, Tan et al.1 and Yu et al.2 report LEDs that can address these issues using insulating nanoparticles that contain ions of lanthanides, which are the group of 14 chemical elements from lanthanum to ytterbium in the periodic table.

Nature Human Behaviour

GPT-4o mini: Non-social science research article
Publisher Correction: In silico discovery of representational relationships across visual cortex
Alessandro T. Gifford, Maya A. Jastrzębowska, Johannes J. D. Singer, Radoslaw M. Cichy
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GPT-4o mini: Non-social science research article
A habit and working memory model as an alternative account of human reward-based learning
Anne G. E. Collins
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Reinforcement learning (RL) algorithms have had tremendous success accounting for reward-based learning across species, including instrumental learning in contextual bandit tasks, and they capture variance in brain signals. However, reward-based learning in humans recruits multiple processes, including memory and choice perseveration; their contributions can easily be mistakenly attributed to RL computations. Here I investigate how much of reward-based learning behaviour is supported by RL computations in a context where other processes can be factored out. Reanalysis and computational modelling of 7 datasets ( n = 594) in diverse samples show that in this instrumental context, reward-based learning is best explained by a combination of a fast working-memory-based process and a slower habit-like associative process, neither of which can be interpreted as a standard RL-like algorithm on its own. My results raise important questions for the interpretation of RL algorithms as capturing a meaningful process across brain and behaviour.
GPT-4o mini: Non-social science research article
How the UN is fighting against illegal waste
Ioana Cotutiu, Xiao Wang
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The circular economy is leaving workers behind
SebastiĂĄn Carenzo
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The virtuous narrative of the circular economy is delivered by big corporations, governments, nongovernmental organizations, academics and social movements alike. It fosters reuse and recycling to valorize discarded materials through the fancy sustainable design of new products or processes. And it seems to have an unstoppable global momentum. But why is it so compelling?
Corporate transformation is key to achieving zero waste
Riccardo Torelli
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Emergency mental health co-responders reduce involuntary psychiatric detentions in the USA
Thomas S. Dee, Jaymes Pyne
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Historical efforts to deinstitutionalize those experiencing mental illness in the USA have inadvertently positioned police officers as the typical first responders to emergency calls involving mental health crises and empower them to initiate involuntary psychiatric detentions. Although potentially lifesaving, such detentions are controversial and costly, and they may be medically inappropriate for some of those detained. Here we present evidence from two quasi-experimental designs on the causal effects of a ‘co-responder’ programme that pairs mental health professionals with police officers as first responders on qualified emergency calls. The results indicate that a co-responder programme reduced the frequency of involuntary psychiatric detentions by 16.5% (that is, 370 fewer detentions over 2 years; b = −0.180, 95% confidence interval −0.325 to −0.034) but had no detectable effect on programme-related calls for service, criminal offences or arrests. Complementary results based on incident-level data suggest this reduction reflects both a co-responder’s influence on the disposition of an individual incident and a reduction in future mental health emergencies.
Enduring constraints on grammar revealed by Bayesian spatiophylogenetic analyses
Annemarie Verkerk, Olena Shcherbakova, Hannah J. Haynie, Hedvig SkirgÄrd, Christoph Rzymski, Quentin D. Atkinson, Simon J. Greenhill, Russell D. Gray
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Human languages show astonishing variety, yet their diversity is constrained by recurring patterns. Linguists have long argued over the extent and causes of these grammatical ‘universals’. Using Grambank—a comprehensive database of grammatical features across the world’s languages—we tested 191 proposed universals with Bayesian analyses that account for both genealogical descent and geographical proximity. We find statistical support for about a third of the proposed linguistic universals. The majority of these concern word order and hierarchical universals: two types that have featured prominently in earlier work. Evolutionary analyses show that languages tend to change in ways that converge on these preferred patterns. This suggests that, despite the vast design space of possible grammars, languages do not evolve entirely at random. Shared cognitive and communicative pressures repeatedly push languages towards similar solutions.
Addressing food waste and hunger together
Ioana Mihaela Balan
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Each one of us wastes an average of 79 kg of food annually1. This equates to 1.3 meals per day for each of the 783 million hungry people in the world. In many regions of the world, hunger is not an abstract threat but an everyday reality for some individuals. This is particularly the case in Africa and western Asia, which have recently seen rises in the prevalence of undernourishment: 20% of people in Africa and 12.7% of people in Asia faced hunger in 2024. Hunger is also an increasing threat in many in high-income countries: in the UK, for example, 14.1 million people faced food insecurity in 2024.
Addressing low statistical power in computational modelling studies in psychology and neuroscience
Payam Piray
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Computational modelling is a powerful tool for uncovering hidden processes in observed data, yet it faces underappreciated challenges. Among these, determining appropriate sample sizes for computational studies remains a critical but overlooked issue, particularly for model selection analyses. Here we introduce a power analysis framework for Bayesian model selection, a method widely used to choose the best model among alternatives. Our framework reveals that while power increases with sample size, it decreases as more models are considered. Using this framework, we empirically demonstrate that psychology and human neuroscience studies often suffer from low statistical power in model selection. A total of 41 of 52 studies reviewed had less than 80% probability of correctly identifying the true model. The field also heavily relies on fixed effects model selection, which we demonstrate has serious statistical issues, including high false positive rates and pronounced sensitivity to outliers.
Reframing people in circular economy and sustainable waste management research
Pauline Deutz
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Human behaviour has been identified as a key dynamic in sustainable waste management and circular economy research. Drawing on recent behaviour publications from both fields, this Perspective highlights three issues relating to how they frame people. First, reference to ‘consumers’ in circular economy research contrasts with ‘people’ in some sustainable waste management papers. This represents an artificial separation of approaches to activities that are interwoven; furthermore, it implicitly defines a business agenda for the circular economy. Second, research into behaviour needs a broader methodological approach to identify variable needs and address underlying contextual and structural issues. Third, attention is needed to ongoing inequalities within and between countries that limit the effectiveness of circular economy implementation. Future research in these fields should prioritize human-centred approaches, including critical realism and qualitative methods, to uncover the socio-political constraints on behaviour and guide sustainability strategies that address the needs of people.
To decolonize waste, we must make sure the polluter pays
Maria Raquel Passos Lima
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Making household food waste reduction easier
Katy Tapper, Bethan Thompson, Christian Reynolds, Luiza Toma
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Why culture is key to waste management
Anderson Assuah
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The hidden role of waste pickers in climate resilience
Sonia M. Dias
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A quiet revolution is turning the waste crisis into opportunity
George Baffour Awuah
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Electronic waste is a public health crisis that demands urgent action
Sarker Masud Parvez
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E-waste is increasing at an alarming rate, driven by rapid technological advances and ever shorter product life cycles. More than 62 million tonnes of e-waste were generated globally in 2022, with an expected increase to 82 million tonnes by 2030 (ref. 1). E-waste contains highly toxic substances (including lead, cadmium, mercury, brominated flame retardants and persistent organic pollutants) and a mix of precious metals (such as gold, silver and palladium)2. In many developed countries, e-waste management systems are established and regulated. Yet in many low- and middle-income countries, e-waste recycling is primarily driven by the informal sector: it is typically conducted in unregulated environments and often without the use of protective equipment or modern technologies2. Practices such as open burning, acid leaching and manual dismantling are common. These methods release toxicants into the air, soil and water, which creates widespread community exposure. Workers engaged in dismantling electronic components often suffer impaired renal and hormonal function, as well as increased risk of DNA damage3,4,5. Residents who live near recycling sites have also reported reproductive health effects, which raises concerns about intergenerational impacts6. Moreover, prenatal exposures have been associated with adverse neonatal physiological development7.

Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Loss of conductance between mesophyll symplasm and intercellular air spaces explains nonstomatal control of transpiration
Piyush Jain, Sabyasachi Sen, Fulton E. Rockwell, Robert J. Twohey, Annika E. Huber, Sahil A. Desai, I-Feng Wu, Tom De Swaef, Mehmet M. Ilman, Anthony J. Studer, N. Michele Holbrook, Abraham D. Stroock
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The conventional assumption is that stomatal conductance ( g s ) dominates the regulation of water and carbon dioxide fluxes between leaves and the atmosphere. Here, a nanoreporter of water status at the mesophyll cell surface and local xylem within intact maize leaves documents significant undersaturation of water vapor in the outside-xylem zone (OXZ) and a large loss of conductance of this zone ( g oxz ) at moderate xylem water stress, without stomatal closure or turgor loss. The ratio of the resistances ( 1 / g oxz ) / ( 1 / g s ) serves as a predictive phenotype of undersaturation, nonstomatal regulation of transpiration, errors in standard gas exchange analysis, and an increase of intrinsic water use efficiency ( iWUE ). Cell-scale access to water status reveals symplasmic-apoplasmic disequilibrium and informs a biophysical model that can explain experimental observations quantitatively based on localization of variable conductance to the plasma membrane. This work opens paths of inquiry into the molecular basis and functional consequences of nonstomatal regulation of transpiration.
GPT-4o mini: Non-social science research article
Centuries of compounding human influence on Amazonian forests
Crystal N. H. McMichael, Mark B. Bush, Hans ter Steege, Dolores R. Piperno, William D. Gosling, Majoi N. Nascimento, Umberto Lombardo, Luiz de Souza Coelho, IĂȘda LeĂŁo do Amaral, Francisca DionĂ­zia de Almeida Matos, DiĂłgenes de Andrade Lima Filho, Carolina V. Castilho, Florian Wittmann, Juan Ernesto Guevara-Andino, William E. Magnusson, Rafael P. SalomĂŁo, Oliver L. Phillips, Juan David Cardenas Revilla, Mariana VictĂłria Irume, Maria Pires Martins, Maria Teresa Fernandez Piedade, JosĂ© Ferreira Ramos, Nigel C. A. Pitman, Bruno Garcia Luize, Evlyn MĂĄrcia Moraes de LeĂŁo Novo, Percy NĂșñez Vargas, Thiago Sanna Freire Silva, Eduardo Martins Venticinque, Angelo Gilberto Manzatto, Neidiane Farias Costa Reis, Katia Regina Casula, Euridice N. Honorio Coronado, Juan Carlos Montero, Jochen Schöngart, NicolĂĄs Castaño Arboleda, Abel Monteagudo Mendoza, Charles Eugene Zartman, Rodolfo Vasquez, Bonifacio Mostacedo, John Terborgh, Layon O. Demarchi, Rafael L. Assis, Marcelo Brilhante de Medeiro, Adriano Costa Quaresma, Marcelo Fragomeni Simon, Ana Andrade, JosĂ© LuĂ­s Camargo, Ted R. Feldpausch, Timothy J. Killeen, William F. Laurance, Susan G. W. Laurance, Lorena Maniguaje RincĂłn, Emanuelle de Sousa Farias, Henrique Eduardo Mendonça Nascimento, Bruno Barçante Ladvocat Cintra, Tim R. Baker, Yuri Oliveira Feitosa, Hugo F. MogollĂłn, Alejandro Araujo-Murakami, Roel Brienen, Maria Aparecida Lopes, JosĂ© Leonardo Lima MagalhĂŁes, Helder Lima de Queiroz, James A. Comiskey, Beatriz S. Marimon, Ben Hur Marimon-Junior, Gabriel Damasco, Freddie C. Draper, Roosevelt GarcĂ­a-Villacorta, Aline Lopes, Alberto Vicentini, Fernando Cornejo Valverde, Alfonso Alonso, Francisco Dallmeier, Leandro Valle Ferreira, Vitor H. F. Gomes, Daniel P. P. de Aguiar, Fernanda Antunes Carvalho, Rogerio Gribel, Marcelo Petratti Pansonato, Gerardo A. Aymard C., Paul V. A. Fine, Juan Carlos Licona, Boris Eduardo Villa Zegarra, Vincent Antoine Vos, Luzmila Arroyo, Carlos CerĂłn, Marcos Silveira, Juliana Stropp, Doug Daly, William Milliken, Guido Pardo Molina, Marcos RĂ­os Paredes, Jos Barlow, Erika Berenguer, DĂĄrio Dantas do Amaral, Joice Ferreira, Eliana M. Jimenez, Bente Klitgaard, Maria Cristina Peñuela Mora, Carlos A. Peres, Pablo R. Stevenson, Kyle G. Dexter, Anthony Di Fiore, Isau Huamantupa-Chuquimaco, JosĂ© Luis Marcelo Pena, Toby Pennington, Luciana de Oliveira Pereira, Juan Fernando Phillips, Gonzalo Rivas-Torres, Patricio von Hildebrand, JanaĂ­na Costa Noronha, Edelcilio Marques Barbosa, FlĂĄvia Rodrigues Barbosa, Luiz Carlos de Matos Bonates, Rainiellen de SĂĄ Carpandeo, Hilda Paulette DĂĄvila Doza, Alfredo Fuentes, Ricardo ZĂĄrate GĂłmez, Therany Gonzales, George Pepe Gallardo Gonzales, Yadvinder Malhi, Ires Paula de Andrade Miranda, Linder Felipe Mozombite Pinto, Adriana Prieto, Domingos de Jesus Rodrigues, AgustĂ­n Rudas, J. SebastiĂĄn Tello, CĂ©sar I. A. Vela, Bianca Weiss Albuquerque, Angela Cano, Milena Holmgren, Marcelo Trindade Nascimento, Alexandre A. Oliveira, Maira Rocha, Ademir R. Ruschel, Veridiana Vizoni Scudeller, Rodrigo Sierra, Miles R. Silman, Natalino Silva, Milton Tirado, Maria Natalia Umaña, Corine Vriesendorp, ClĂĄudia Baider, Henrik Balslev, Reynaldo Linares-Palomino, Casimiro Mendoza, Italo Mesones, Germaine Alexander Parada, Miguel N. Alexiades, William Farfan-Rios, Karina Garcia-Cabrera, Walter Palacios Cuenca, Susamar Pansini, Daniela Pauletto, Freddy Ramirez Arevalo, Adeilza Felipe Sampaio, Elvis H. Valderrama Sandoval, Luis Valenzuela Gamarra, Marcelo de Jesus Veiga Carim, JosĂ© Renan da Silva GuimarĂŁes, John J. Pipoly, Fernanda Coelho de Souza, Marcelino Carneiro Guedes, JosĂ© Julio de Toledo, Wegliane Campelo, Terry W. Henkel, Jean-François Molino, Janaina Barbosa Pedrosa Costa, Ima CĂ©lia GuimarĂŁes Vieira, Daniel Sabatier, Alvaro Duque, Daniel Zuleta, Thiago Trindade, Eduardo Kazuo Tamanaha, Fernando Ozorio de Almeida, Kenneth J. Feeley
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Recent evidence suggests that the ecological footprints of pre-Columbian Indigenous peoples in Amazonia persist in modern forests. Ecological impacts resulting from European colonization c. 1550 CE and the Amazonian Rubber Boom c. 1850 to 1920 CE are largely unexplored but could be important additive influences on forest structure and tree species composition. Using environmental niche models, we show the highest probabilities of pre-Columbian and colonial occupation sites, and hence human-induced ecological influences, occurred in forests along rivers. In many areas, the predicted pre-Columbian and colonial distributions overlap spatially with the potential for superimposed ecological influences. Environmental gradients are known to structure Amazonian vegetation composition, but they are also strong predictors of past human influence, both spatially and temporally. Our comparisons of model outputs with relative abundances of Amazonian tree species suggest that pre-Columbian and colonial-period ecological legacies are associated with modern forest composition.
GPT-4o mini: Non-social science research article
The adhesion GPCR ADGRL2 engages Gα13 to enable epidermal differentiation
Xue Yang, Feng He, Vanessa Lopez-Pajares, Douglas F. Porter, Krassimira Garbett, Zurab Siprashvili, Luca Ducoli, Robin M. Meyers, David L. Reynolds, Duy Lan Huong Bui, Audrey Hong, Duy Thanh Nguyen, Yuqing Jing, Smarajit Mondal, Lisa Ko, Shiying Tao, Bharti Singal, Richard Sando, Georgios Skiniotis, Paul A. Khavari
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Homeostasis relies on signaling networks controlled by cell membrane receptors. Although G-protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors, their specific roles in the epidermis are not fully understood. Dual CRISPR-Flow and single cell Perturb RNA-sequencing knockout screens of all epidermal GPCRs were thus performed, uncovering an essential requirement for adhesion GPCR ADGRL2 (latrophilin 2) in epidermal differentiation. Among potential downstream guanine nucleotide-binding G proteins, ADGRL2 selectively activated Gα13. Follow-up tissue knockouts verified that Gα13 is also required for epidermal differentiation. A cryoelectron microscopy structure in lipid nanodiscs showed that ADGRL2 engages with Gα13 at multiple interfaces, including via an interaction between ADGRL2 intracellular loop 3 and a Gα13-specific QQQ glutamine triplet sequence in its GTPase domain. In situ gene mutation of this interface sequence impaired epidermal differentiation, highlighting an essential new role for an ADGRL2-Gα13 axis in epidermal differentiation.
GPT-4o mini: Non-social science research article
Glutathionylated DNA adducts accumulate in mitochondrial DNA and are regulated by AP endonuclease 1 and tyrosyl-DNA phosphodiesterase 1
Yu Hsuan Chen, Martin Esparza Sanchez, Ta I Hung, Jin Tang, Wenyan Xu, Jiekai Yin, Yinsheng Wang, Chia-En A. Chang, Huimin Zhang, Junjie Chen, Linlin Zhao
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Mitochondrial DNA (mtDNA) is crucial for cellular energy production, metabolism, and signaling. Its dysfunction is implicated in various diseases, including mitochondrial disorders, neurodegeneration, and diabetes. mtDNA is susceptible to damage by endogenous and environmental factors; however, unlike nuclear DNA (nDNA), mtDNA lesions do not necessarily lead to an increased mutation load in mtDNA. Instead, mtDNA lesions have been implicated in innate immunity and inflammation. Here, we report a type of mtDNA damage: glutathionylated DNA (GSH-DNA) adducts. These adducts are formed from abasic (AP) sites, key intermediates in base excision repair, or from alkylation DNA damage. Using mass spectrometry, we quantified the GSH-DNA lesion in both nDNA and mtDNA and found its significant accumulation in mtDNA of two different human cell lines, with levels one or two orders of magnitude higher than in nDNA. The formation of GSH-DNA adducts is influenced by TFAM and polyamines, and their levels are regulated by repair enzymes AP endonuclease 1 (APE1) and tyrosyl-DNA phosphodiesterase 1 (TDP1). The accumulation of GSH-DNA adducts is associated with the downregulation of several ribosomal and complex I subunit proteins and the upregulation of proteins related to redox balance and mitochondrial dynamics. Molecular dynamics (MD) simulations revealed that the GSH-DNA lesion stabilizes the TFAM-DNA binding, suggesting shielding effects from mtDNA transactions. Collectively, this study provides critical insights into the formation, regulation, and biological effects of GSH-DNA adducts in mtDNA. Our findings underscore the importance of understanding how these lesions may contribute to innate immunity and inflammation.
GPT-4o mini: Non-social science research article
Dynamics and variegation in the Treg response to Interleukin-2
Kumba Seddu, Kaitavjeet Chowdhary, Molly Henderson, Jakub Tomala, Odhran Casey, Yi Cao, Diane Mathis, Jamie B. Spangler, Christophe Benoist
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Interleukin-2 (IL2) is the key trophic factor for T regulatory (Treg) cells, controlling their differentiation and homeostasis. To understand how temporally regulated responses to IL2 unfold in Tregs, we performed fine time-course analyses, at population and single-cell levels, of changes in chromatin architecture and mRNAs induced by IL2 in Tregs in vivo. The data revealed responses that were largely uniform in rTreg, but diverse among aTregs, matching different STAT5 signal transduction efficiency. Individual Tregs displayed divergences in the preponderance of changes that may be attributed to STAT1 or STAT5 signal transduction downstream of IL2. Chromatin analysis identified an evolving implication of transcription factors that accounted for the waves of responsive genes. Covalent cytokine/Ab complexes that preferentially trigger high- (heterotrimer) or low-affinity (heterodimer) IL2 receptors activated the same signatures, yet with strong quantitative variations, especially in NK cells. Thus, IL2 is not a monolithic activator for Tregs, but a variegated sculptor of Treg identity.
GPT-4o mini: Non-social science research article
Deep learning reveals how cells pull, buckle, and navigate fibrous environments
Abinash Padhi, Arka Daw, Atharva Agashe, Medha Sawhney, Maahi M. Talukder, Mehran M. H. Pour, Mohammad Jafari, Guy M. Genin, Farid Alisafaei, Sohan Kale, Anuj Karpatne, Amrinder S. Nain
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Cells in tissues navigate fibrous environments fundamentally differently than they do on flat substrates, but the establishment of cell forces in physiological fibrous settings remains poorly understood. Although factors such as the stiffness of the extracellular matrix (ECM) are known to drive behaviors, including cell motility on flat nonfibrous substrates, the interplay between fiber architecture and stiffness in fibrous ECM is not known. Here, we find that in fibrous environments, the directionality of mechanical forces overrides ECM stiffness as the primary regulator of contractility in migrating cells. Using an approach combining phase microscopy with deep learning to map forces in real time, termed deep learning-enabled live-cell fiber-force microscopy (DLFM), we reveal that when cells transition between anisotropic and isotropic stress fields, their contractility significantly drops despite encountering stiffer ECM, contrary to the behavior of cells on flat nonfibrous substrates. Unlike the peripheral adhesions observed on flat nonfibrous substrates, cells in fibrous matrices form force-generating adhesions throughout their body, stabilized by out-of-plane mechanical components unique to fiber geometry. Cells exhibit distinct force signatures during migration, division, and differentiation, with temporal signatures that predict stem cell fate. These findings, enabled by combining deep learning and the mechanics of cells and fibers, explain long-standing paradoxical behavior of cells navigating deformable fibrous environments, how they can pull and tug at them, and identify tension anisotropy as a master regulator of cell behavior, with implications for cancer invasion, tissue engineering, and regenerative medicine.
GPT-4o mini: Non-social science research article
Integrating generative AI and physical tests to strengthen claims about emergent phenomena
Weihao Cheng, Zekai Yu
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GPT-4o mini: Non-social science research article
Organic geochemical evidence for life in Archean rocks identified by pyrolysis–GC–MS and supervised machine learning
Michael L. Wong, Anirudh Prabhu, Conel O’D. Alexander, H. James Cleaves, George D. Cody, Grethe Hystad, Marko Bermanec, Wouter Bleeker, C. Kevin Boyce, Andrea Corpolongo, Andrew D. Czaja, Souvik Das, Robert R. Gaines, Daniel D. Gregory, John A. Jaszczak, Emmanuelle J. Javaux, Jaganmoy Jodder, Andrew H. Knoll, Martin Van Kranendonk, Katie M. Maloney, Nora Noffke, Robert Rainbird, Emersyn Slaughter, Eva E. StĂŒeken, Roger E. Summons, Frances Westall, Jasmina Wiemann, Shuhai Xiao, Robert M. Hazen
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Throughout Earth’s history, organic molecules from both abiogenic and biogenic sources have been buried in sedimentary rocks. Most of these organic molecules have been significantly altered by geologic processes through deep time. Nonetheless, the nature and distribution of those ancient fragmentary organic remains have the potential to reveal diagnostic biomolecular information after billions of years of burial. Here, we analyzed 406 fossil, modern biological, meteoritic, and synthetic samples using pyrolysis gas chromatography and mass spectrometry. We explored these analytical data via supervised machine-learning methods to discriminate samples of biogenic vs. abiogenic origin, plant vs. animal phylogenetic affinity, and photosynthetic vs. nonphotosynthetic physiology. Dividing 272 samples with known phylogenetic affinity and physiology into 9 categories, each further divided into 75% training and 25% testing sets, our random forest models accurately predict pairwise assignments of modern vs. fossil or meteoritic organics (100% correct assignments), fossil plant tissues vs. meteoritic organics (97%), modern vs. fossil plant tissues (98%), and modern plants vs. animal tissues (95%). Pairwise comparisons between fossil biogenic samples vs. abiogenic samples resulted in 93% correct classifications, while analysis of modern and ancient photosynthetic vs. nonphotosynthetic samples also resulted in 93% correct assignments. Our analyses demonstrate that molecular biosignatures can survive in ancient fossils and allow for the identification of organismal origins and traits. Consistent with previous morphological and isotopic inferences, we present evidence for biogenic molecular assemblages in Paleoarchean rocks (3.33 Ga) and for photoautotrophy in Neoarchean rocks (2.52 Ga).
GPT-4o mini: Non-social science research article
Slow relaxation and landscape-driven dynamics in viscous ripening foams
Amruthesh Thirumalaiswamy, Clary RodrĂ­guez-Cruz, Robert A. Riggleman, John C. Crocker
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Foams and dense emulsions display complex mechanical behavior, including intermittent rearrangement dynamics, power-law rheology, and slow recovery after perturbation. These effects have long been considered evidence for glassy physics in these and other materials having similar mechanics, such as the cytoskeleton. Here, we study such anomalous mechanics in a simulated wet foam driven by ripening and find behavior that has a different physical origin than that in glasses. Rather, the dynamics is due to a balance of forces from the system’s self-similar potential energy landscape and viscous stress. At the lowest viscosities, bubbles move intermittently, with the system shifting abruptly between shallow potential energy minima. For higher viscosities, in contrast, the bubbles move continuously and the system follows a tortuous, fractal path through high-dimensional configuration space, at higher mean energy than the lower viscosity case. The long-time dynamics and power-law rheology are the direct consequence of the potential energy landscape’s self-similar geometry. Last, we find that the slow recovery of perturbed foams is due to the foam being kinetically rather than energetically trapped in high-energy portions of the energy landscape. Overall, viscous ripening foams follow a biased energy minimization pathway that explores regions of the energy landscape that are qualitatively different (flatter and smoother) than those corresponding to well-annealed glasses.
GPT-4o mini: Non-social science research article
Static morphogen scaling enables proportional growth in a tissue growth model inspired by axolotl limb regeneration
Natalia Lyubaykina, Dunja Knapp, Pietro Tardivo, Maximilian Kotz, Tatiana Sandoval-GuzmĂĄn, Benjamin M. Friedrich
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Axolotls can regenerate lost limbs throughout life, while they continue to grow. This poses the question of how the size and pattern of a regenerating limb is matched to a widely varying animal size. Two interacting signaling molecules, Sonic Hedgehog (SHH) and Fibroblast Growth Factor (FGF8), are produced at opposite sides of the regenerating limb and sustain tissue growth through a pair of oppositely oriented signaling gradients. As the size of the regrowing tissue can vary more than three-fold depending on the size of the animal, it is unclear how the activities of these mutually dependent morphogens are maintained and subsequently terminated to determine appropriate growth. Scaling of limb regeneration suggests a size-dependent adaptation of morphogen gradient parameters. Inspired by this biological example, we theoretically investigate general mechanisms of morphogen-controlled growth arrest and proportional growth. In the proposed mechanism, tissue growth increases the spatial distance between the two morphogen gradients, which eventually arrests morphogen activity and growth. We put forward two distinct scaling scenarios of morphogen gradients: either dynamic scaling with blastema size, where morphogen gradient parameters change dynamically with the growing tissue, or static scaling with animal size, where morphogen gradient parameters stay constant during blastema growth and only depend on animal size. We show that static scaling ensures proportional growth, but dynamic scaling does not. We compare theory predictions to experimental quantification of SHH and FGF8 morphogen gradient parameters at different time-points of regeneration in different-sized animals, indicating static scaling for some morphogen parameters, which is sufficient to ensure proportional growth in our model.
GPT-4o mini: Non-social science research article
The liver talks back: NPY orchestrates attraction of cancer cells and CHK2-dependent clonogenicity in the metastatic niche
Laura Wormser, Valerie Fritz, Melanie Kappelmann-Fenzl, Nicole Rachinger, Pol EscudĂ©, Karin Enderle, Matthias D. Kaufmann, Miriam DĂŒll, Abdo Mahli, Sebastian Zundler, Moritz Leppkes, Stefan Fischer, Felix Elsner, Carol-Immanuel Geppert, Michael Hannus, Susanne Merkel, Michael Erdmann, Claudia GĂŒnther, Katja Evert, Zubeir El Ahmad, Gunter Meister, Elisabetta D’Avanzo, Marc P. Stemmler, Clemens Neufert, Andreas E. Kremer, Georg F. Weber, Thomas Brabletz, Stephan von Hörsten, Reiner Wiest, Raymond Schiffelers, Arndt Hartmann, JĂŒrgen Siebler, Jonel Trebicka, Maximilian Waldner, Markus F. Neurath, Claus Hellerbrand, Anja K. Bosserhoff, Peter Dietrich
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RNA interference (RNAi) therapeutics represent breakthrough discoveries, but their use in cancer remains limited due to hepatocyte-specific targeting. Cancer metastasis is regulated by complex crosstalk between tumor cells and niche-derived factors. However, the molecular mechanisms enabling metastatic seeding and outgrowth in the liver remain incompletely understood, representing a major clinical challenge. We identified neuropeptide Y (NPY) as a promotor of liver metastasis. Hepatocyte-derived NPY attracts metastatic tumor cells to the liver niche. Subsequent microenvironment activation induces TGFÎČ, promoting a vicious cycle of perimetastatic NPY secretion and liver metastasis. Concomitantly, cancer cells upregulate the NPY-5 receptor (Y5R) which is correlated with liver metastasis. NPY-Y5R crosstalk drives chemotactic migration via cAMP and ERK signaling. Moreover, NPY-Y5R activation dephosphorylates checkpoint kinase 2 to promote clonogenicity and proliferation of cancer cells. Lipid nanoparticles (LNPs) are a promising drug delivery vehicle for siRNAs. LNPs carrying siRNA pools targeting NPY were designed, and preclinical studies provided evidence for efficacy for the treatment of liver metastasis. Our findings transform the limitation of hepatocyte specificity of RNA interference into a therapeutic advantage, introducing a paradigm for the treatment of hepatic metastases.
GPT-4o mini: Non-social science research article
Structural insights into the G-protein subtype selectivity revealed by human sphingosine-1-phosphate receptor 3–G q complexes
Momono Yamauchi, Dohyun Im, Shintaro Maeda, Tatsuya Ikuta, Masayasu Toyomoto, Hidetsugu Asada, Yukihiko Sugita, Jun-ichi Kishikawa, Takeshi Noda, Takayuki Kato, Asuka Inoue, So Iwata, Masatoshi Hagiwara
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Sphingosine-1-phosphate (S1P) is one of the most extensively studied bioactive lipids that transduces signals via the S1P receptor (S1PR) family (S1PR1-5), a class of G-protein-coupled receptors (GPCRs), to regulate immune cell migration, vascular permeability, and pain modulation. However, the mechanism for achieving specificity in downstream signaling remains poorly understood. Here, we present cryogenic electron microscopic structures of the S1PR3-G αq complex bound to endogenous agonists: d18:1 S1P or d16:1 S1P. Both agonists shared the same binding pocket and binding mode despite the different signaling intensities of the S1PR3-G αq signal pathway. By comparing the structures of two agonist-bound complexes, combined with mutagenesis studies, we identified key amino acids, Phe119 3.33 and Arg136 3.50 , that play crucial roles in differential agonist recognition and receptor activation. Furthermore, structural comparisons with previously determined S1PR3-G αi complex or G-protein-free S1PR3 structures, along with mutagenesis analysis, revealed dynamic intracellular loop 2 conformations and specific amino acid interactions that contribute to G-protein selectivity. Notably, we identified amino acids at the 34.50 and 34.53 positions within ICL2 as critical for specific interactions with G proteins. These findings provide better understanding of the mechanism of GPCR activation and unique perspectives that can be applied to other class A GPCRs, leading to the possibility of optimized drug development.
GPT-4o mini: Non-social science research article
MAPK signaling and angiopoietin-2 contribute to endothelial permeability in capillary malformations
Sana Nasim, Mariam Baig, Jill Wylie-Sears, Matthew P. Vivero, Patrick Smits, Annegret Holm, Leanna Marrs, Yu Sheng Cheng, Cesar Alves, Anna Pinto, Arin K. Greene, Joyce Bischoff
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Nonsyndromic capillary malformations (CM) are seen predominantly in skin. In Sturge–Weber Syndrome (SWS), CMs occur in the skin, leptomeninges of the brain, and choroid of the eye. >90% of CM are caused by a somatic mutation— GNAQ p.R183Q, the gene encoding the G-protein subunit Gα q . Longitudinal MRI of the brain in one SWS patient suggests developing vascular permeability. We modeled this in a transendothelial electrical resistance assay and found endothelial cells with GNAQ p.R183Q (EC-R183Q) exhibited increased permeability compared to EC wild-type. Increased vascular permeability was confirmed in a Gnaq p.R183Q mouse model. Knockdown of elevated angiopoietin-2 (ANGPT2) in EC-R183Q partially restored the EC barrier, as did a MEK1,2 inhibitor, implicating MAPK/ERK signaling. The combination of ANGPT2 knockdown and trametinib further restored the EC barrier in an additive manner. indicating the two operate in separate pathways. In summary, we found that EC-R183Q exhibits increased permeability, reflecting the compromised endothelial barrier in CMs.
GPT-4o mini: Non-social science research article
An adipo-osteoprogenitor population in the endosteal niche contributes to bone and fat formation in adult mouse bone marrow
Xueyang Liao, Jasmin Koehnken Sawall, Rebecca Seeley, Fangfang Song, Xing Ji, Xiaobin Liu, Chao Song, Fanxin Long
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The adult bone marrow houses progenitors for both osteoblasts and adipocytes, but their precise molecular identity remains to be fully elucidated. Previous studies indicate that Lepr + Cxcl12 + bone marrow stromal cells collectively give rise to both osteoblasts and marrow adipocytes, but the high degree of heterogeneity among those cells calls for further delineation of common or lineage-specific progenitors in vivo. Here, by single-cell RNA-sequencing we identify a small subset of bone marrow stromal cells coexpressing Adipoq and Osx, along with other osteogenic or adipogenic genes. The Adipoq + Osx + cells predominantly reside in the endosteal niche. Intersectional genetic fate mapping with Dre and Cre recombinases demonstrates dual differentiation of osteoblasts and adipocytes from the Adipoq + Osx + cells in vivo. The data support the Adipoq + Osx + cells as adipo-osteoprogenitors contributing to bone and fat formation in the adult mouse bone marrow.
GPT-4o mini: Non-social science research article
Turbulence in the terrestrial magnetosheath: Space–time correlation using the Magnetospheric Multiscale mission
Francesco Pecora, William H. Matthaeus, Antonella Greco, Pablo Dmitruk, Yan Yang, Vincenzo Carbone, Sergio Servidio
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Spatiotemporal correlation of magnetic field fluctuations is investigated using the Magnetospheric Multiscale mission in the terrestrial magnetosheath. The first observation of the turbulence propagator in space emerges through analysis of more than a thousand intervals. Results show clear features of spatial and spectral anisotropy, leading to a distinct behavior of relaxation times in the directions parallel and perpendicular to the mean magnetic field. Full space–time investigation of the Taylor hypothesis reveals a scale-dependent anisotropy of magnetosheath fluctuations that can be compared to the effect of flow propagation on spacecraft frame time decorrelation rates as well as with Eulerian estimates. The turbulence propagator reveals that the amplitudes of the perpendicular modes decorrelate according to sweeping or AlfvĂ©nic propagation mechanisms. The decorrelation time of parallel modes instead does not depend on the parallel wavenumber, which could be due to resonant interactions. Through direct observation, this study provides insight into the space–time structure of turbulent space plasmas, while giving critical constraints for theoretical and numerical models.
GPT-4o mini: Non-social science research article
Evidence of an enhanced near-surface ozone layer at tropical latitudes on Mars
Daniel ViĂșdez-Moreiras, Michael D. Smith, Mike Wolff, Megan A. J. Brown, Frank Daerden, MarĂ­a-Paz Zorzano, VĂ­ctor Apestigue, Ignacio Arruego, Elisa GarcĂ­a, Juan J. JimĂ©nez, Daniel Toledo, Mark T. Lemmon, Elise Wright Knutsen, Alfonso Saiz-Lopez
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Ozone plays a key role in both atmospheric and near-surface chemistry, as well as in UV absorption in planetary atmospheres. Here, we report observations of ozone from the surface of another planet, using the ozone detector included in the Mars Environmental Dynamics Analyzer (MEDA) Radiation and Dust Sensor (RDS) aboard NASA’s Mars 2020 mission, complementing previous space-based and ground-based observations from Earth. Measurements were acquired at Jezero Crater, Mars, at midday, retrieving an average ozone column abundance of 3.8 ± 2.3 ÎŒm-atm (1σ) around aphelion, which fell below uncertainties in northern summer. The retrieved column abundance is in reasonable agreement with previous space-based and ground-based observations from Earth. The measurements of total ozone column abundance around aphelion from Mars 2020 and other missions, together with vertical profile observations from orbit, indicate that ~90% of the observed ozone is confined below 20 km of altitude, the aphelion layer weakly contributing to the total column abundance. These ozone levels below 20 km are 3 to 4 times higher than those predicted by models, challenging current understanding of atmospheric chemistry and composition in the lower atmosphere of Mars. It may be possible that aerosols are reducing the destruction pathways of ozone and/or that unknown active chemistry in the near-surface atmosphere of Mars is at work. Both cases should strongly modify the oxidizing capacity in the lower atmosphere of Mars from current model predictions.
GPT-4o mini: Non-social science research article
QnAs with Jane E. Parker
Sandeep Ravindran
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GPT-4o mini: Non-social science research article
Anisotropic fluorescence emission by diatoms modifies the underwater oceanic light field
Joan Salvador Font-Muñoz, Jorge Arrieta, Marc Sourisseau, Idan Tuval, Gotzon Basterretxea
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Fluorescence in phytoplankton and other autotrophic organisms originates within the cell chloroplasts, where a fraction of the absorbed solar radiation is reemitted at longer wavelengths by photopigments. While traditionally employed as an indicator of physiological status, emerging evidence suggests that natural chlorophyll fluorescence (ChlF) may also play unanticipated functional roles in the marine environment. Here, we examine the ChlF emission fields generated by pennate planktonic diatoms, a key phytoplankton group playing a critical role in global biogeochemical cycles. Using cell micromanipulation experiments, we demonstrate that the ChlF emitted by Pseudo-nitzschia fraudulenta (Bacillariophyceae) is markedly anisotropic, a feature attributed to both the cells’ elongated morphology and the arrangement of chloroplasts within the cytoplasm. In these diatoms, fluorescence is preferentially emitted in the transapical direction, accounting for up to 35% of total emission. However, peak ChlF intensities occur at the cell apices, suggesting that the silica frustule focuses fluorescent light emission along the longitudinal axis. At elevated cell densities (~10 6 cells/L), the underwater light field is modulated by the combined effects of ChlF emission anisotropy and preferential alignment of diatom cells within the water column. Numerical simulations indicate that ChlF intensity can vary by up to 15% depending on whether cells are predominantly aligned—commonly in stratified water columns—or randomly oriented. These results suggest that diatom-driven modulation of the light field through structured ChlF emission may influence microscale optical environments, with potential consequences for processes ranging from intercellular signaling to large-scale phytoplankton dynamics, including remote sensing–based assessments of phytoplankton physiology.
GPT-4o mini: Non-social science research article
Honey bee queen pheromone provides an early warning system to prevent collapsing colonies
Christina M. Grozinger
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GPT-4o mini: Non-social science research article
The X chromosome and the emergence of reproductive isolation
Bret A. Payseur
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GPT-4o mini: Non-social science research article
High-throughput screening for class I peptide MHC binding via yeast surface display
Patrick V. Holec, Kathryn C. Breuckman, Owen Leddy, Forest M. White, Bryan D. Bryson, Michael E. Birnbaum
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T cells rely on short peptides presented by highly polymorphic major histocompatibility complexes (MHCs) to selectively initiate adaptive immune responses. Despite its importance, few techniques can systematically evaluate stable peptide presentation across diverse MHC alleles. Here, we describe a yeast display pipeline that can be deployed to rapidly screen peptides to identify class I pMHC binders across many alleles. Through this, we isolate unique biological phenomena such as alteration of the peptide presentation of HLA-B57 via interaction with the antiviral small molecule abacavir. We apply this approach to multiple pathogen proteomes ( Mycobacterium tuberculosis Type VII secretion substrates, SARS-CoV-2, Dengue, and Zika) to create a comprehensive list of potential T cell antigens. Altogether, this platform acts as a flexible tool to generate large unbiased datasets for class I peptide binding at a speed and scale competitive with the biological systems they represent.
GPT-4o mini: Non-social science research article
The ghost of Bombus past: Investigating the mystery of an extinct bumblebee
Hadil Elsayed, Amro Zayed
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GPT-4o mini: Non-social science research article
Ribonuclease RNase Z is an evolutionarily conserved deAMPylase
Meghomukta Mukherjee, Alex Pon, Timea Goldberg, Krzysztof PawƂowski, Anju Sreelatha
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Protein AMPylation is a highly conserved posttranslational modification in which adenosine monophosphate (AMP) is covalently attached to protein substrates. Our studies revealed that the mitochondrial AMPylase, Selenoprotein O (SelO), regulates cellular metabolism and oxidative stress response through AMPylation of key metabolic enzymes. Remarkably, SelO-mediated AMPylation is conserved in bacteria and humans, yet the enzyme that removes the AMP from modified proteins remains unknown. We show that the ribonuclease, RNase Z, is both necessary and sufficient to catalyze deAMPylation of AMPylated substrates. These results establish RNase Z as a moonlighting enzyme with previously unrecognized functional roles beyond tRNA processing, expanding our understanding of its biological significance. Furthermore, identification of an evolutionarily conserved deAMPylase highlights the importance of reversible AMPylation as a biological regulatory mechanism, akin to well-studied post translational modifications such as protein phosphorylation.
GPT-4o mini: Non-social science research article
Artificial cells with liquid–liquid phase separation–regulated cell-free protein synthesis
Dongdong Fan, Kaini Liang, Bingjie Wu, Michael W. Chen, Chengyu Sun, Lei Sun, Yan Zhang, Yanan Du
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The rapid advancement of synthetic biology has enabled the construction of artificial cells that closely mimic the morphology and functionality of their natural counterparts. However, significant limitations remain in engineering artificial cells capable of regulated protein expression. Here, we demonstrate that engineered polymers containing multivalent association motifs can reversibly regulate translational activity through liquid–liquid phase separation (LLPS)–induced protein aggregation, enabling precise temporal control of cell-free protein synthesis (CFPS) activity. This aggregation mechanism exerts a broad inhibitory effect on various enzymes and facilitates the construction of artificial cells with controllable reaction processes. Leveraging this phenomenon, we have developed a microfluidic platform to fabricate giant unilamellar vesicles (GUVs) that encapsulate CFPS systems, thereby constructing artificial cells with finely tunable protein expression. By incorporating targeted DNA templates, these artificial cells can selectively express specific proteins in response to pH adjustments. Furthermore, in vivo studies using a bile duct ligation mouse model with liver injury further confirmed significant differences in protein expression under alkaline conditions compared to neutral conditions. Our findings highlight the potential of leveraging aggregate dynamics for precise, in situ modulation of protein synthesis within artificial cells, thereby opening avenues for their advanced biomedical applications.
GPT-4o mini: Non-social science research article
QnAs with Graham F. Hatfull
Sarah C. P. Williams
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GPT-4o mini: Non-social science research article
Engineering a spatiotemporal macrophage circuit via STING phase separation to override immune suppression in pancreatic cancer
Xue Yang, Yinlu Wang, Jiaxin Zhou, Siyu Li, Jin Ye, Yu Sun, Mengning He, Kai Fan, Zixin Chen, Fangzheng Tian, Ben Zhao, Jianqiong Zhang, Jinbing Xie, Zebin Xiao, Xiaoyuan Chen, Shenghong Ju
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Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, largely due to its highly immunosuppressive tumor microenvironment (TME), which fuels metastasis and resistance to immunotherapy. Through comprehensive analysis of single-cell RNA sequencing datasets, we identified multiple heterogeneous tumor-associated macrophage (TAMs) subpopulations as key regulators of PDAC progression, which coexpress MRC1 and exert their effects by actively suppressing antitumor immune responses. To overcome this barrier, we developed a spatiotemporal macrophage reprogramming platform that leverages STING phase separation to reprogram TAM plasticity and reshape the immune landscape. This system, MRC1-targeting peptide–M@BLZ945 (PMMB), integrates a colony-stimulating factor 1 receptor (CSF-1R) inhibitor and a STING agonist within a macrophage-mimetic nanostructure, enabling sequential, controlled reprogramming of TAMs. By leveraging STING phase separation, PMMB stabilizes TAMs in an antitumor CD80 + phenotype while preventing excessive inflammation, achieving durable immune activation. In preclinical models, PMMB not only suppresses both primary and metastatic PDAC but also enhances CD8 + T cell infiltration, reinvigorates anti-PD-1 therapy responses, and mitigates immune exhaustion. These findings establish spatiotemporal macrophage circuit engineering via STING phase separation as a cross-scale strategy to override PDAC’s immune barriers and drive next-generation macrophage-targeted immunotherapy. This study paves the way for rationally designed, precision macrophage modulation strategies in solid tumors.
GPT-4o mini: Non-social science research article
Scientific standards suffer from misrepresenting past work
Sandra GonzĂĄlez-BailĂłn, David Lazer
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GPT-4o mini: Non-social science research article
A tripartite protein complex promotes DNA transport during natural transformation in Firmicutes
Marie Dewailly, Yoann Fauconnet, Cécile Ducrot, Anne-Lise Soulet, Nathalie Campo, Raphaël Guerois, J. Pablo Radicella, Patrice Polard, Jessica Andreani, Calum H. G. Johnston
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Natural genetic transformation is a conserved mechanism of bacterial horizontal gene transfer, which is directed entirely by the recipient cell and facilitates the acquisition of new genetic traits such as antibiotic resistance. Transformation proceeds via the capture of exogenous DNA, its internalization in single strand form (ssDNA) and its integration into the recipient chromosome by homologous recombination. While the proteins involved in these steps have mainly been identified, the specific mechanisms at play remain poorly characterized. This study takes advantage of recent advances in structural modeling to explore the uptake of ssDNA during transformation. Using the monoderm human pathogen Streptococcus pneumoniae , we model a tripartite protein complex composed of the transmembrane channel ComEC, and two cytoplasmic ssDNA-binding proteins ComFA and ComFC. Using targeted mutation and transformation assays, we propose that pneumococcal ComEC features a narrow channel for ssDNA passage, and we show this channel is conserved in the diderm Helicobacter pylori . We identify key residues involved in protein–protein and protein–ssDNA interactions in the pneumococcal tripartite complex model and we show them to be crucial for transformation efficiency. Structural modeling reveals that this tripartite protein complex and its interaction with ssDNA are conserved in Firmicutes. Overall, this study validates a tripartite complex required for the internalization of ssDNA during transformation in Firmicutes, providing insights into the molecular mechanisms involved in this horizontal gene transfer mechanism central to bacterial adaptation. It also demonstrates the power of recent structural modeling techniques such as AlphaFold3 as hypothesis generators and guides for designing experiments.
GPT-4o mini: Non-social science research article
A periplasmic zinc capture protein enhances the resistance of Neisseria gonorrhoeae to nutritional immunity
Ian K. Liyayi, Aloke Kumar Bera, Yasiru R. Perera, Nourin Ferdausi, Indu Bhatia, Nicholas Noinaj, Walter J. Chazin, Cynthia Nau Cornelissen, Alison K. Criss
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During microbial infection, mammalian hosts reduce the availability of free metals such as zinc in a process known as nutritional immunity. Pathogens counteract nutritional immunity by expressing gene products that enhance growth in metal-limited conditions. One of the most transcriptionally induced genes in zinc-limited Neisseria gonorrhoeae , ngo1049, encodes a DUF4198 family protein we have named Zcp. This family of proteins is widely distributed in Gram-negative bacteria. Here, we provide the first structural, biochemical, and functional characterization of a DUF4198 protein. Zcp is a periplasmic, homodimeric substrate-binding protein (SBP), which binds one zinc ion per subunit with submicromolar affinity. We identified a zinc binding pocket in each subunit, composed of three histidine residues. Zcp enables maximal growth of N. gonorrhoeae in zinc-limited conditions but is dispensable for zinc uptake, in contrast to the cluster A-I SBP ZnuA, which is required for zinc import. The growth defect of zcp mutant N. gonorrhoeae is rescued by zinc supplementation. Zcp associates with proteins with roles in maintaining cell envelope integrity, and N. gonorrhoeae lacking zcp is more sensitive to envelope-targeting antimicrobials. Zcp enables infectivity of human epithelial cells and neutrophils by zinc-limited N. gonorrhoeae . We conclude that N. gonorrhoeae produces Zcp to buffer periplasmic zinc, which enables ZnuA to balance import of different metals and ensures the bioavailability of zinc for extracytoplasmic zinc-requiring proteins, as part of the coordinated response to host-imposed nutritional immunity.
GPT-4o mini: Non-social science research article
Putative muscle stem cells promote Xenopus tail regeneration by modifying macrophage function via c1qtnf3
Sumika Kato, Takeo Kubo, Taro Fukazawa
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In Xenopus laevis tadpole tail regeneration, lineage-restricted tissue stem cells produce differentiated cells that form regenerated tail tissues, but the behavioral dynamics of tissue stem cells during tail regeneration remain largely unknown. We previously reported that multiple tissue stem/progenitor cells can be efficiently enriched from regeneration buds using the side population (SP) method. Here, we performed trajectory inference using single-cell RNA sequencing data of the SP fraction to construct differentiation trajectories and identify putative tissue stem cell populations that initiate differentiation pathways. We found that complement c1q tumor necrosis factor-related protein 3 ( c1qtnf3 ) is specifically expressed in putative muscle stem cells (MSC) and, using knockdown (KD; CRISPR/Cas9-based F0 crispants) experiments, demonstrated that c1qtnf3 is necessary for tail regeneration. Furthermore, we found that the impaired tail regeneration by c1qtnf3 KD was accompanied by abrogation of macrophage-like cell accumulation at the amputation site. These phenotypes were rescued by macrophage-like cell-specific forced expression of neutrophil cytosolic factor 1 , a gene related to effector molecule production in myeloid cells, suggesting that the impaired tail regeneration by c1qtnf3 KD is due to macrophage dysregulation. Our findings suggest that, in Xenopus , putative MSC modulate macrophage function via c1qtnf3 expression for successful tail regeneration.
GPT-4o mini: Non-social science research article
Emergence of bulk-like structural features and 2D-to-3D transition in boron nanoclusters
Qiang Chen, Hyun Wook Choi, Guang-Feng Wei, Deniz Kahraman, Rui-Nan Yuan, Qin-Wei Zhang, Qiao-Qiao Yan, Xiao-Ni Zhao, Cai-Yue Gao, Yuan-Yuan Ma, Rui Wei, Yilin Gui, Zhi-Pan Liu, Si-Dian Li, Lai-Sheng Wang
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As an electron-deficient element, boron possesses fascinating three-dimensional structures and unconventional chemical bonds. Nanoclusters of boron have also been found to exhibit intriguing structural properties, observed to have predominantly planar structures, in stark contrast to bulk boron allotropes, which are composed of the ubiquitous B 12 icosahedral building blocks. Here, we report observation of the 2D-to-3D transition and bulk-like structural features in the size-selected boron clusters, as revealed by photoelectron spectroscopy, chemisorption experiments, and first-principles calculations. In the small to medium cluster size range, planar boron cluster anions are found to be unreactive and only B 46 – and B 56 – are observed to chemisorb C 2 H 4 and CO under ambient conditions, suggesting major structural transitions at these cluster sizes. Notably, B 56 – is also found to be able to chemisorb and activate CO 2 . The global minimum of B 46 – is found to adopt a core-shell structure (B 2 @B 44 – ), consisting of a B 2 core within a B 44 shell, reminiscent of the interstitial B 2 dumbbells in the high-pressure γ -B 28 form of bulk boron. More remarkably, both the global minimum and the second most stable isomer of B 56 – exhibit nest-like configurations, featuring the iconic B 12 icosahedral core surrounded by a B 44 half-shell (B 12 @ h- B 44 – ), signifying the onset of bulk-like structural characteristics in boron nanoclusters.
GPT-4o mini: Non-social science research article
Marine heatwave decimates fire coral populations in the Caribbean
Emilia C. Dell’Antonio, Lauren Mahoney, Peter J. Edmunds
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Marine heatwaves (MHW) are common destructive events affecting coral reefs. After decades of degradation, the shallow reefs of the United States Virgin Islands have been depleted of scleractinian corals, leaving abundant colonies of the hydrozoan fire coral Millepora dominating the coral community. This dominance ended in 2024 after 84% of Millepora colonies over 43 km of shore were killed by a MHW that brought the hottest October in the 36 y since monitoring began. In August 2024, dead Millepora were rare on these reefs, but by March 2025, severe bleaching created a fire coral graveyard. Decimation of the fire coral biotope shows that these short-term coral winners are unlikely to be future reef builders.
GPT-4o mini: Non-social science research article
Small spaces have large impacts: Microsites determine plant litter decomposition rates in drylands
Heather L. Throop, Marie-Anne de Graaff, Jayne Belnap
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Our understanding of carbon and nutrient dynamics in globally vast and socioeconomically critical dryland ecosystems lags behind mesic systems. Litter decomposition models consistently underestimate measured decomposition in these regions. Both models and measurements largely represent spatially dominant intercanopy areas; however, little litter resides in these interspaces as transport vectors move litter to other microsites such as beneath plant canopies and buried in soil. Abiotic and biotic conditions differ among microsites, but few studies have characterized microsite impacts on decomposition. We collated data on microsites where litter accumulates. In microsites with sufficient available data, we used meta-analysis to test hypotheses on decomposition relative to litter in intercanopy spaces. Decomposition was lower under woody plant canopies than in intercanopy spaces. Buried litter decomposed faster than surface litter. There was no difference in decomposition between surface litter and litter suspended aboveground to simulate standing dead. All microsite contrasts had exceptions, suggesting that site-specific characteristics influence microclimate and subsequent decomposition. Extrapolation of decomposition rates to the landscape-level (using estimates of microsite-specific decomposition rates multiplied by litter pools), suggests that decomposition estimates based on intercanopy data alone underrepresent landscape-level decomposition. Thus, despite advances in the understanding of mechanistic decomposition drivers in drylands advancing, most studies are spatially unrepresentative analyses in intercanopy areas and this will underestimate decomposition at the landscape level. Expanding the ecological relevance of decomposition processes to be useful for predicting larger-scale carbon and nutrient dynamics requires improved characterization of dryland litter distribution, coupled with a mechanistic understanding of decomposition in microsites where litter accumulates.
GPT-4o mini: Non-social science research article
Glyceraldehyde-3-phosphate dehydrogenase homologs as bifunctional gatekeepers of metabolic segregation in Pseudomonas putida
Nanqing Zhou, Caroll M. Mendonca, Austin L. Carroll, Stefan Pate, Manuel Nieto-DomĂ­nguez, Xinyu Chen, Lichun Zhang, Kelly P. Teitel, Nienke K. Dekker, Joshua R. Elmore, Pablo I. Nikel, Jacob R. Waldbauer, Adam M. Guss, Niall M. Mangan, Ludmilla Aristilde
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Metabolically versatile Pseudomonas species can assimilate various glycolytic and gluconeogenic substrates. Simultaneous assimilation is known to segregate carbons from each substrate type into different metabolic pathways. However, the mechanisms of this metabolic segregation remain unresolved. Here, we investigate Pseudomonas putida KT2440 during processing of the sugar glucose through glycolysis versus the phenolic acid ferulate through gluconeogenesis. Metabolome profiling reveals up to twofold less tricarboxylic acid cycle metabolites but up to 10-fold higher metabolites of upper glycolysis, pentose-phosphate, and Entner–Doudoroff pathways in glucose-grown cells compared to ferulate-grown cells. After 13 C-substrate switching, kinetic isotopic profiling captures rapid assimilation of new substrate carbons into initial catabolic pathways, but incorporation into downstream pathways is absent or incomplete. Proteomics identifies a 22-fold higher abundance of one homolog of glyceraldehyde-3-phosphate dehydrogenase (GAPDH, GapA) in cells fed on glucose relative to ferulate, while abundance of another homolog (GapB) remains unchanged. Growth phenotypes and quantitative metabolomics for single and double knockout mutants of these GAPDH homologs indicate only GapA involvement in glycolytic flux, which can be compensated by the Entner–Doudoroff pathway, and distinct preference of GapB with minimal role of GapA for gluconeogenic flux. Accordingly, growth of triple knockout mutant with deletion of gapA , gapB , and edd is possible only when glycolytic and gluconeogenic substrates are provided together to meet metabolic demands in a segregated fashion, but metabolic tradeoffs lead to slow growth. A mathematical, experimentally constrained, model of the GAPDH node shows that tuning of GapA and GapB concentrations enables transition between flux regimes for nutritional adaptability.
GPT-4o mini: Non-social science research article
Heating rate gradient drives mesostructural dynamics in solid propellant under nonequilibrium conditions
Zhi Jiang, Tianhao Wang, Weichen Sheng, Zechen Li, Chengli Mao, Haolin Luo, Yujian Xia, Wenfeng Shangguan, Chaoyang Zhang, Jiaxing Wang
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Rapid, nonequilibrium heating drives mesoscale structural evolution in heterogeneous composite materials under extreme thermal conditions, critically influencing performance in aerospace propulsion and advanced structural applications. However, existing experimental techniques lack the capability to directly observe heterogeneous structural evolution and intercomponent interactions under controlled conditions that closely mimic realistic nonequilibrium thermal fronts. Consequently, theoretical models, which assume equilibrium conditions or neglect dynamic structural evolution, remain insufficiently validated and cannot accurately predict these critical transformation pathways. Here, we developed a gradiated fast-heating system (>20 °C/s) enabling precise control of heating rate gradients within submillimeter transition regions in a single specimen, seamlessly integrated with sequential synchrotron X-ray tomography and radiography to directly visualize internal structural evolution. This approach allowed capture of diverse structural transformation pathways spanning microsecond-to-millisecond timescales under distinct nonequilibrium thermal conditions, revealing the complete sequence from initial pyrolysis through ignition to final burnout. We found that local heating rates, rather than bulk temperatures, dictate void formation dynamics and fragmentation pathways. In regions with high local heating rates, rapid void nucleation within the binder phase created reticulated porous networks, evolving four times faster than curved interfacial voids observed in adjacent regions experiencing lower heating rates. Furthermore, a cascade of heterogeneous component interactions subsequently fragmented the metallic network into isolated clusters, seeding critical ignition hotspots that governed combustion initiation and propagation mechanisms. These findings indicate that kinetic processes, influenced notably by heating rate, play an important role in mesostructural evolution under nonequilibrium conditions.
GPT-4o mini: Non-social science research article
The immunoproteasome regulates ILC2 responses by modulating mitochondrial capacity
PaĂŽline Laurent, Vidyanath Chaudhary, Daqiang Li, Marie Dominique Ah Kioon, Chen Zhang, William H. Miller, Hua Liao, Gang Lin, Carl F. Nathan, Franck J. Barrat
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Type 2 innate lymphoid cells (ILC2s) contribute to type 2 immunity but have also been associated with multiple inflammatory diseases, including airway inflammation and asthma. We report that beyond its function of degrading poly-ubiquitinylated proteins, the immunoproteasome (i-20S) is required for the proper function of ILC2s by controlling their mitochondrial capacity. We found that 90% of the catalytic ÎČ subunits of proteasomes in human ILC2s (hILC2s) are the immuno- (ÎČ5i) rather than constitutive (ÎČ5c) isoform. Specific, noncovalent, reversible inhibition of i-20S ÎČ5i (LMP7) in hILC2s induced ROS production, which inhibited aconitase, leading to altered mitochondrial function and reduced levels of ATP. Reprogramming of metabolic status by an LMP7 inhibitor impaired ILC2 activation, without significant cytotoxicity or preventing their recovery. Hence, the selective inhibition of i-20S in ILC2 cells did not kill them but reversibly depleted their ATP, preventing their activation and cytokine secretion. In mice, proteasome inhibition similarly blocked mitochondrial function and ILC2 activation, preventing airway inflammation in response to IL33 and asthma in response to house dust mites. These findings reveal a previously unappreciated linkage between proteasome blockade, central carbon metabolism, and mitochondrial function and identify a strategy to regulate immune cell metabolism in inflammatory diseases.
GPT-4o mini: Non-social science research article
Cartesian equivariant representations for learning and understanding molecular orbitals
Daniel S. King, Daniel Grzenda, Ray Zhu, Nathaniel Hudson, Ian Foster, Bingqing Cheng, Laura Gagliardi
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Qualitative and quantitative orbital properties such as bonding/antibonding character, localization, and orbital energies are critical to how chemists understand reactivity, catalysis, and excited-state behavior. Despite this, representations of orbitals in deep learning models have been very underdeveloped relative to representations of molecular geometries and Hamiltonians. Here, we apply state-of-the-art equivariant deep learning architectures to the task of assigning global labels to orbitals, namely energies characterizations, given the molecular coefficients from Hartree–Fock or density functional theory. The architecture we have developed, the Cartesian Equivariant Orbital Network ( CEONET ), shows how molecular orbital coefficients are readily featurized as equivariant node features common to all graph-based machine-learned potentials. We find that CEONET performs well at predicting difficult quantitative labels such as the orbital energy and orbital entropy. Furthermore, we find that the CEONET representation provides an intuitive latent space for differentiating orbital character for the qualitative assignment of e.g. bonding or antibonding character. In addition to providing a useful representation for further integrating deep learning with electronic structure theory, we expect CEONET to be useful for automatizing and interpreting the results of advanced electronic structure methods such as complete active space self-consistent field theory. In particular, the ability of CEONET to infer multireference character via the orbital entropy paves the way toward the machine-learned selection of active spaces.
GPT-4o mini: Non-social science research article
A 12,000-year-old clay figurine of a woman and a goose marks symbolic innovations in Southwest Asia
Laurent Davin, Natalie D. Munro, Leore Grosman
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Paleolithic representations of human–animal interaction are rare, with only a few painted or engraved examples recorded in Upper Paleolithic contexts, mostly from Europe. Such scenes, depicting real or imagined interactions, are of major importance for understanding a wide range of past human perspectives, starting with how people conceived of their ontological relationship with the environment and nonhuman beings. In the Early Neolithic in Southwest Asia, shifts in perspective led human communities to manipulate and transform their environment while simultaneously depicting new forms of art featuring human–animal interactions. Here, we describe the recent discovery of the earliest figurine depicting a human–animal interaction—a woman and a goose—from the Late Epipaleolithic (c. 12,000 years cal. BP) village of Nahal Ein Gev II in northern Israel. The artistic techniques and raw materials that were used and the mythological scene that was depicted appear earlier than previous examples, foreshadowing the more monumental changes in symbolic expression that occur in the following Neolithic periods. Through technological, archaeometric, and dermatoglyphic analyses, we demonstrate that this unique figurine was meticulously modeled from clay using innovative techniques that created perspective using form and light. Importantly, the figurine captures a mythological scene between the woman and the goose that is consistent with an animistic belief system. Through our combined multidisciplinary approach, this study provides important original data regarding the antiquity and development of symbolic expression using clay at the end of the Epipaleolithic at a crossroads between early sedentary and fully Neolithic societies in Southwest Asia.
GPT-4o mini: Non-social science research article
Cognitive correlates of human endurance
Daniel H. Aslan, Laura Fenton, S. Duke Han, Mark H. C. Lai, Dylan M. Luong, Tiladia Markarian, Anika Seshadri, Gene E. Alexander, David A. Raichlen
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Recent work suggests combining physical activity with cognitive tasks may have been critical to human evolution and may be beneficial to human brain health today. These combined tasks are key elements of foraging, a lifestyle employed by human ancestors for over 2 My. However, it is unclear whether cognitive engagement during foraging-like tasks impacts endurance, and therefore foraging performance, and whether cognitive adaptations may mitigate these effects. We tested the hypothesis that cognitive engagement during endurance walking increases perceived physical effort without influencing physiological responses, and that enhanced cognition mitigates these effects. Thirty healthy adults ( n female = 17; aged 18 to 53) underwent nonlocomotor cognitive testing and completed two separate randomized endurance tests: one without (Ex) and one with simultaneous executive function tasks (ExCog). For each condition, participants walked on a treadmill for up to 30-min while physiological responses were recorded, and perception of effort was assessed every 2-min using Borg’s rating of perceived exertion (RPE) scale. During the ExCog condition, RPE was significantly greater ( P = 0.005), while energy expenditure was significantly lower ( P = 0.008) compared to the Ex condition. Additionally, we observed significant interactions between cognitive abilities and endurance performance—for example, individuals with greater visuospatial abilities experienced a smaller increase in perceived effort (RPE) in the ExCog condition compared to the Ex condition (FDR P = 0.039). These results indicate that cognitive demands and cognitive abilities associated with foraging distinctly influence endurance, suggesting that evolutionary shifts in human cognitive capacities may have relaxed constraints on endurance foraging performance.
GPT-4o mini: Non-social science research article
Physical models reveal indirect reader protein interactions that facilitate epigenetic crosstalk
Joseph G. Wakim, Andrew J. Spakowitz
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The spatial organization of chromatin is governed by epigenetic factors, including epigenetic marks and the reader proteins that bind them. By dictating the accessibility of genomic loci, epigenetic factors contribute to the physical regulation of gene expression, enabling diverse cellular phenotypes to be encoded by a shared genome in an individual. Epigenetic dysregulation can lead to aberrations in chromatin architecture, contributing to diseases such as neurological disorders and cancers. Despite the known importance of chromatin organization for human health, the physical mechanisms governing chromatin folding remain underspecified. In this work, we develop a physical model of chromatin organization based on contributions from multiple epigenetic factors. Using our model, we evaluate how conditions in the nuclear environment and crosstalk between epigenetic marks affect the compartmentalization of chromatin into dense heterochromatin and loose euchromatin. Our results emphasize the role of reader protein binding in chromatin compartmentalization. We show that reader proteins interact through an indirect mechanism facilitated by the shared chromatin “scaffold” to which they bind. Under a scenario where reader proteins compete for binding sites, we find that indirect interactions affect the program adopted by the chromatin fiber. By isolating indirect modes of epigenetic crosstalk, we demonstrate how the interplay between epigenetic patterning and environmental factors influences chromatin architecture.
GPT-4o mini: Non-social science research article
The lactate sensor NDRG3 decelerates ER-to-Golgi transport through interaction with the long isoform of syntaxin-5
Pia E. Ferle, Niklas Krause, Judith Koliwer, Jörn Michael Völker, Fabia Becker, Alexander Hillebrand, Leonie F. Schröder, Stefanie JÀger, Seby Edassery, Dali Liu, Nevan J. Krogan, Jeffrey N. Savas, Gabriele Fischer von Mollard, Michael Schwake
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BET1, GOSR2, and STX5 variants can cause fatal inherited diseases, including epilepsies, muscular dystrophy, and multisystemic disorders. Together with Sec22b, they form a SNARE complex that mediates fusion of ER-derived vesicles with the ER-Golgi-intermediate compartment and the cis -Golgi. The Sec1/Munc18 protein SCFD1/Sly1 accelerates ER-to-Golgi SNARE complex assembly and membrane fusion, but much less is known about downregulation of ER-to-Golgi trafficking under cellular stress conditions. Here, we identify the lactate and hypoxia sensor protein NDRG3 as a binding partner of the ER-to-Golgi SNARE complex. NDRG3 binds via its C-terminal domain to the N-terminal domain of the long isoform of Stx5, thereby impairing ER-to-Golgi trafficking under hypoxic conditions and elevated intracellular lactate levels. In NDRG3-deficient cells, hypoxia- and lactate-induced inhibition of ER-to-Golgi trafficking is abolished. Our work identifies NDRG3 as a negative regulator of ER-to-Golgi SNARE complex function, mechanistically linking hypoxia and lactate to membrane trafficking in the secretory pathway.
GPT-4o mini: Non-social science research article
Alleviation of negative emotional and pain responses through amygdala-hypothalamic social circuit activation
Xinqi Lu, Guohua Chen, Weizhe Hong, Shuaishuai Hu, Rongfeng K. Hu
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Pain is a multifaceted experience that not only impacts individuals physiologically but also reshapes their emotional well-being and social dynamics. The expression of pain and postpain emotional states is profoundly influenced by social contexts. Recent research has highlighted the pivotal role of social rewards—including empathy, support, and acceptance—in modulating both pain perception and subsequent negative emotional responses. However, how direct manipulation of brain circuits that govern social behaviors and social rewards impacts pain and negative emotional responses remains largely unexplored. Here, we investigated whether direct activation of a newly identified noncanonical social reward circuit—specifically, the projections from the medial amygdala (MeA) to the medial preoptic area (MPOA)—can mitigate pain-related emotional and behavioral responses. Our findings demonstrated that both optogenetic and chemogenetic activation of GABAergic neurons in the MeA significantly reduced freezing and anxiety-like behaviors after shock period as well as pain responses in the hotplate test in both male and female mice. Furthermore, optogenetic activation of the MeA-to-MPOA circuit produced similar behavioral outcomes. Together, our study expands the understanding of neural circuits underlying pain modulation and highlights the critical need to incorporate social and psychological factors into therapeutic approaches designed to improve human health and well-being.
GPT-4o mini: Non-social science research article
OPEN STOMATA 1 activates SLAC1 anion channel primarily through CPK15 in ABA-induced stomatal closure in Arabidopsis
Xin Shen, Kaili Yin, Zhiyu Wang, Zhiwei Zhang, Mengqing Liu, Sheng Luo, Shaowu Xue, Honghong Hu
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The Ca 2+ -independent OST1 and Ca 2+ -dependent protein kinases CPKs both activate the anion channel SLAC1 during ABA-induced stomatal closure pathway. However, the mechanism by which OST1 regulates SLAC1 activation and its relationship with CPKs remain unclear. Here, we identify that OST1 primarily activates SLAC1 in this process through CPK15. Mutation of CPK15 significantly impairs ABA-induced stomatal closure and increases drought sensitivity. OST1 interacts with CPK15 and phosphorylates it at T103, which is essential for ABA-induced stomatal closure. Moreover, CPK15 can phosphorylate eight sites in the N terminus of SLAC1 to activate its anion currents in oocytes. Expression of SLAC1 8D (a phosphomimetic form) in oocytes constitutively activates anion channel activity and effectively restores the impaired ABA-induced stomatal closure of cpk15-1 but not by SLAC1 8A (a phospho-dead form). Furthermore, activated CPK15 by OST1 and Ca 2+ enhances its activity toward SLAC1, and mutations of both OST1 and CPK15 have additive effect on ABA-induced stomatal closure, suggesting that CPK15 activates SLAC1 through both direct and indirect mechanisms. These findings demonstrate the key role of CPK15 in ABA-induced stomatal closure, revealing a connection between OST1 and CPKs in both Ca 2+ -independent and Ca 2+ -dependent pathways in ABA-induced stomatal closure.
GPT-4o mini: Non-social science research article
Autism-associated Scn2a haploinsufficiency disrupts in vivo dendritic signaling and impairs flexible decision-making
Hao Wu, Luqun Shen, Jonathan Indajang, Neil K. Savalia, Timothy G. Johnson, Jiayin Qu, Kevin J. Bender, Alex C. Kwan
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SCN2A is a high-confidence risk gene for autism spectrum disorder. Loss-of-function mutations in Scn2a reduce dendritic excitability in neocortical pyramidal cells. However, the impact of Scn2a haploinsufficiency on dendritic signaling in vivo, particularly during behavior, is unknown. In this study, we used two-photon microscopy to image dendritic calcium transients in deep layer pyramidal cells in the mouse medial frontal cortex. Scn2a +/− mice had diminished coupling between apical and proximal dendritic compartments. Pyramidal tract neurons had abnormal event rates, while intratelencephalic neurons had compartment-specific alterations indicative of diminished dendritic integration. In a matching pennies task, Scn2a +/− mice were inflexible in the face of changing competitive pressure. Apical dendritic tuft in intratelencephalic neurons typically encoded reward and strategy, but these task-specific representations were altered in Scn2a +/− mice. Collectively, the findings demonstrate that Scn2a haploinsufficiency weakens dendritic integration in vivo and disrupts dendritic encoding of task variables during flexible decision-making.
GPT-4o mini: Non-social science research article
Coordinated transfer of DNA between Pol Ξ and Pol Ύ resets microhomology choice during double-strand break repair
Yuzhen Li, Mark Returan, Adele T. Guerin, April M. Averill, Dorcas Oladapo, Sylvie Doublié, Richard D. Wood
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DNA polymerase theta (Pol Ξ)-mediated end joining (TMEJ) initiates DNA double-strand break repair by using short homologies (microhomologies) between single-stranded DNA tails. This repair process is particularly important in cancer cells defective in homologous recombination. The exonuclease function of DNA polymerase delta (Pol ÎŽ) has been identified as an essential component for TMEJ, functioning to remove unpaired bases flanking a microhomology (MH). It is not known if the exonuclease removes all unpaired bases at once and how this removal might affect subsequent MH selection. Here, we reconstituted a functional TMEJ repair process using purified human Pol Ξ and Pol ÎŽ. We find that when Pol ÎŽ exonuclease excises a nucleotide to generate a new 3â€Č terminus, Pol Ξ initiates a new MH search. Pol ÎŽ exonuclease removes a single nucleotide at a time, rather than cleaving an unpaired flap, and then transfers the DNA tail to the polymerase site of Pol Ξ. Specific primer-grasp amino acids in the polymerase domain of Pol Ξ are important for internal MH anchoring. The helicase-like domain of Pol Ξ harbors two activities which are recapitulated in reconstituted reactions: strand-capture to bring single-strand tails together and an ATPase activity that alleviates suppression of TMEJ by ssDNA binding protein RPA. This functional reconstitution of TMEJ advances the understanding of how two polymerases with three enzymatic activities orchestrate double-strand break repair.
GPT-4o mini: Non-social science research article
Capped high-force integrin bond lifetimes and spacing-tuned binding frequency drive rapid fibroblast migration
Jingjing Feng, Keshu Feng, Zhaohui Xiong, Miao Yu, Yuru Hu, Wenxu Wang, Ruihao Xue, Ze Gong, Zheng Liu, Wei Chen
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Cell migration relies on balancing focal adhesion (FA) stability—necessary for traction generation—and turnover—essential for forward translocation. Here, we dissect how integrin binding frequency and force-dependent bond duration jointly regulate this balance in fibroblasts. Using block copolymer micelle nanolithography, we create gold nanoparticle (Au NP) arrays with controlled spacings to vary integrin–ligand binding frequency. In parallel, tension gauge tethers (TGTs) with defined force threshold limit bond lifetime of high-force integrins under cellular traction. We find that intermediate ligand spacing coupled with a moderate rupture threshold dramatically accelerates fibroblast migration—up to twelvefold faster than on denser or sparser substrates. These conditions foster rapid FA turnover and support a dendritic actin architecture driven by lamellipodia, challenging the longstanding view of fibroblasts as inherently slow, mesenchymal movers. Knockout and blocking experiments further identify α5ÎČ1 as the mechanically dominant integrin subtype that plays a pivotal role in supporting this rapid migration. Mechanistically, FAs remain sufficiently stable to generate traction but also disassemble quickly, fostering continuous protrusion–retraction cycles essential for high-speed migration. These findings refine the classic biphasic model of cell migration into a two-dimensional framework that considers ligand spacing (binding frequency) and TGT force thresholds (binding duration). Beyond expanding fundamental understanding of integrin mechanobiology, our results provide broad avenues for tissue engineering and therapeutic applications, where finely tuned adhesion mechanics can markedly modulate cell speed and phenotype.
GPT-4o mini: Non-social science research article
High-resolution single-cell analyses reveal evolutionary constraints and evolvability of sexual circuits in Drosophila
Justin T. Walsh, Ian P. Junker, Yu-Chieh David Chen, Yen-Chung Chen, Helena Gifford, Dawn S. Chen, Yun Ding
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Understanding how the cellular and molecular composition of neural circuits evolves to generate species-specific behaviors remains a major challenge in evolutionary biology and neuroscience. The remarkable diversity of male sexual behaviors among Drosophila species, despite their recent divergence, offers an excellent model for addressing this question. Here, by harnessing single-cell transcriptomics of the sexual circuits labeled by the sex determination gene doublesex ( dsx ) at high resolution, we delineated 84 molecularly distinct dsx + cell types, each mapped to anatomically and functionally defined dsx + neural populations. Our findings revealed a largely conserved cellular architecture, with minimal evolutionary gain or loss of cell types across four Drosophila species. A detailed comparison between Drosophila melanogaster ( D. melanogaster ) and D. yakuba uncovered pervasive heterogeneity in transcriptomic divergence among dsx + cell types. While core cell type identities—defined by the sex determination gene fruitless ( fru ), neurotransmitters, monoamines, and transcription factors—remain highly conserved, we observed striking evolutionary turnover in neuropeptide signaling pathways in a highly cell-type-specific manner, underscoring the role of functional reconfiguration of conserved circuits in behavioral evolution. Further investigation of sex differences in dsx + neurons revealed that male-specific cell types are not more evolutionarily divergent than sex-unbiased ones. Finally, we developed an interactive web resource for data access and characterized marker gene combinations enabling cell-type-specific labeling. Overall, our study provides insights into how neural circuits evolve to encode behavioral diversity and establishes a high-resolution framework for understanding the cellular basis of behavioral adaptation.
GPT-4o mini: Non-social science research article
Genome integrity relies on rapid recycling of DNA Pol III in bacteria
JosĂ© Pablo RascĂłn PĂ©rez, OphĂ©lie d’Udekem d’Acoz, Nicolas Soubry, Wencheng Xu, Baljyot Singh Parmar, Stephanie C. Weber, Rodrigo Reyes-Lamothe
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DNA replication requires precise coordination between DNA unwinding and DNA synthesis. In all domains of life, protein–protein interactions at the replisome maintain proximity between the enzymes that catalyze these two activities. Surprisingly, in bacteria, the replicative DNA polymerase (Pol III), responsible for DNA synthesis, is exchanged every few seconds. How processive synthesis is maintained under these conditions has remained unclear. Here, we use single-molecule microscopy in live cells to show that Pol III rapidly rebinds the replisome within seconds of dissociation. This fast recruitment is driven by an interaction with single-stranded DNA–binding protein (SSB), which enhances Pol III target search efficiency by ~20-fold. Disrupting this mechanism alters replisome stoichiometry, causes single-stranded DNA (ssDNA) accumulation, depletes free SSB, and leads to helicase disassembly and DNA breakage, culminating in genome instability. Our findings reveal a mechanism by which fast polymerase recycling sustains continuous DNA replication and genome integrity.
GPT-4o mini: Non-social science research article
Thalamus–cortex interactions drive cell type–specific cortical development in human pluripotent stem cell–derived assembloids
Masatoshi Nishimura, Shota Adachi, Tomoki Kodera, Akinori Y. Sato, Ryosuke F. Takeuchi, Fumitaka Osakada
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The thalamus is pivotal for the development and function of neural circuits in the cerebral cortex. However, how thalamus–cortex interactions influence human cortical development remains unknown primarily because of the inaccessibility of the human embryonic brain. Here, we demonstrate thalamus-dependent gene expression, circuit organization, and neural activity during corticogenesis using human thalamocortical assembloids (hThCAs). Human cortical (hCOs) and thalamic organoids derived from induced pluripotent stem cells exhibited region-specific gene expression and spontaneous neuronal activity. Upon the fusion of these organoids, hThCAs reconstructed reciprocal thalamus–cortex axonal projections and synaptic connections. Transcriptomic analysis revealed thalamus-dependent acceleration of cortical maturation, with upregulation of programs linked to axon development, subplate/cortical plate identity, and activity-regulated genes. Histological analysis showed expanded progenitor pools and increased deep-layer neurons within hThCAs. Wide-field Ca 2+ imaging demonstrated that wave-like activity originated in the thalamic region and propagated to the cortical region. Furthermore, two-photon Ca 2+ imaging of cortical neurons revealed that synchronous activity emerged exclusively in pyramidal tract neurons and corticothalamic neurons, whereas intratelencephalic neurons remain asynchronous, highlighting cell type–specific circuit integration within hThCAs. These synchronized events were absent in isolated hCOs or in cortico–cortical assembloids, underscoring the specificity of thalamic input. Our findings suggest that diffusible thalamic cues broadly enhance progenitor expansion, while long-range thalamic input organizes cell type–specific synchronous activity. This study demonstrates the thalamus-dependent acquisition of mature cortical phenotypes in a cell type–specific manner in hThCAs, establishing developmental mechanisms linking regional interactions and cell type–specific circuit specification.
GPT-4o mini: Non-social science research article
Contrasting melt regime in the Ice Grounding Zone of Thwaites Glacier, West Antarctica
Ratnakar Gadi, Eric Rignot, Dimitris Menemenlis, Bernd Scheuchl
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The contribution of Thwaites Glacier, Antarctica, to sea level rise is influenced by how quickly warm salty seawater of Circumpolar Deep Water origin melts basal ice near its grounding line. Satellite observations reveal tidally forced kilometer-scale seawater intrusions beneath grounded ice that form an “Ice Grounding Zone” (IGZ) where ice melts vigorously. Although melt rates have been measured at selected sites using Automated phase-sensitive Radar Echo Sounders (ApRES) and Automated Underwater Vehicle (AUV) instruments, their spatial distribution and total magnitude within the IGZ remain uncertain. Here, we present 2D high-resolution simulations of the melt regime of Thwaites Glacier using the Massachusetts Institute of Technology global circulation model ocean model. The model predicts high melt at the entrance of the IGZ, with a quadratic decay inside the IGZ, a linear increase with ocean thermal forcing and a sublinear increase with cavity length. On the slow-moving Thwaites Eastern Ice Shelf, the modeled melt rate is low (10 m/y) due to a flat, shallow ice base, in agreement with in situ observations from AUV and ApRES instruments. On the Thwaites Glacier Tongue (TGT), the modeled melt rate is high (50 m/y) due to a steeper and deeper ice base. The modeled melt rates are consistent with the estimates derived from the satellite. Hence, multiple lines of evidence indicate high melt in the IGZ of TGT, which controls 80% of the glacier mass balance. An updated representation of grounding zones in ice sheet models including seawater intrusions will increase their sensitivity to ocean warming and will revise sea-level projections upward.
GPT-4o mini: Non-social science research article
DDHD2 possesses both lipase and transacylase capacities that remodel triglyceride acyl chains
Lingshuang Wu, Yong Mi Choi, Mohyeddine Omrane, Jiyao Chai, Shujuan Gao, Abdou Rachid Thiam, Daniel Canals, Michael V. Airola
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Hereditary spastic paraplegia subtype SPG54 is a genetic neurological disorder caused by mutations in the DDHD2 gene. Excessive lipid droplet accumulation is observed in the brains of SPG54 patients and DDHD2 knockout mice, consistent with DDHD2’s reported neutral lipase activity. Here, we find recombinant human DDHD2 preferentially hydrolyzes diacylglycerol (DAG) over phospholipids, with a slight preference for DAG over triacylglycerol (TAG). DDHD2 also exhibits transacylase activity, which enables transfer of acyl chains from TAGs to DAGs and monoacylglycerols to remodel the acyl chains of TAGs. A predicted hydrophobic amphipathic helix on DDHD2 is essential for lipid droplet binding in vitro and in cells, and its lack reduces the enzymatic activity and TAG acyl chain remodeling. Adipose triglyceride lipase, but not hormone sensitive lipase, also has transacylation activity and can remodel TAG acyl chains, but to a lesser extent than DDHD2. Taken together, this provides evidence that DDHD2 is a neutral lipid lipase and transacylase whose broad specificity enables TAG acyl-chain remodeling.
GPT-4o mini: Non-social science research article
The telomeric valine–arginine dipeptide repeat protein changes state to diffuse staining in mitosis and represses in vitro translation
Taghreed Al-Turki, Venkata Mantri, Smaranda Willcox, C. Allie Mills, Laura E. Herring, Su-Ji Cho, Hannah Lee, Caliyn Meyer, E. S. Anton, Jack D. Griffith
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Translation of mammalian G-rich telomeric RNA via the Repeat Associated non-AUG (AUG, the mRNA start codon) mechanism can produce proteins consisting of long repeats of valine–arginine (VR) or glycine–leucine (GL) dipeptides. Their role in the cell has not been elucidated. Using confocal laser scanning microscopy combined with antibody staining we previously observed VR sequestered in punctate bodies and liquid droplets in the cytoplasm and nuclei of nonmitotic cells. Here, we report that cells in mitosis show diffuse VR staining throughout the cell, giving these cells a bright appearance. Upon mitotic enrichment using the cyclin-dependent kinase 1 (CDK1) inhibitor RO-3306. RO-3306, 100% of the mitotic cells showed the same diffuse staining. Antibody staining showed colocalization of VR and the L4 ribosomal protein in mitotic cells and in an in vitro firefly luciferase assay, VR depressed translation. Affinity purification combined with mass spectrometry identified ribosomal proteins as the major class of VR interacting proteins in U2OS cells including L4 along with tubulin and proteins related to neural degenerative diseases. This change from a sequestered, punctate state in interphase to dispersed diffuse staining in mitosis, and the affinity of VR for the L4 protein which lines the ribosomal exit tunnel suggests that an oligomerization change of VR may facilitate its involvement in inhibiting of global translation during mitosis. Extension to mouse embryonic cerebral cortical development showed clear staining in the ventricular zone where neural progenitor cells with a high mitotic index proliferate and in the cortical plate where new neurons settle.
GPT-4o mini: Non-social science research article
The first preserved nasal cavity in the human fossil record: The Neanderthal from Altamura
Costantino Buzi, Antonio Profico, Carlos Lorenzo, Giorgio Manzi
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The nose of Neanderthals and its possible adaptation to harsh climatic conditions is a longstanding matter of debate in paleoanthropology. Here, we present and describe the complete inner nasal structures of the early Neanderthal skeleton from Altamura, southern Italy. It represents evidence hitherto unavailable, both for this species and the human fossil record in general, and sheds light on the possible influence of respiratory adaptations on the characteristic Neanderthal facial morphology. Part of the debate has revolved around inner nasal traits proposed as unique adaptations (autapomorphies) of the species Homo neanderthalensis in relation to cold climate, specifically: a vertically oriented medial projection and a medial swelling on the nasal cavity wall alongside the lack of an ossified roof over the lacrimal groove. The lack of complete anatomy in the Neanderthal fossil record further livened the discussion regarding their occurrence. With the description and analysis of this unique finding, we can rule out the existence of such features. In addition, our observations corroborate the hypothesis that the characteristic midfacial morphology of H. neanderthalensis (i.e., the midfacial prognathism) is the result of a combination of factors and not a direct result of respiratory adaptations in the upper airways. Finally, our data provide an enhanced perspective for modeling Neanderthal respiratory performances.
GPT-4o mini: Non-social science research article
An AINTEGUMENTA phosphoswitch controls bilateral stem cell activity during secondary growth
Wei Xiao, Ling Yang, Hengqi Ji, David Molina, Houming Chen, Shan Yu, Yingjing Miao, Dagmar Ripper, Shulin Deng, Martin Bayer, Bert De Rybel, Laura Ragni
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Plant stem cells have the remarkable ability to give rise to distinct tissues and organs throughout development. Two concentric cylinders of actively dividing stem cells are the main drivers of radial thickening during secondary growth, each producing distinct vascular cell types toward the inside and the outside. While the molecular mechanisms underlying their initiation have been well studied, it remains unclear how these stem cell layers determine which cell type is generated. Here, we demonstrate that the cross-talk between the ERECTA (ER) receptor pathway and auxin signaling controls the amount and choice of output tissue in these two stem cell regions. Mechanistically, we show that the ER pathway phosphorylates the transcription factor AINTEGUMENTA (ANT), thereby modulating bilateral stem cell activity and favoring the differentiation of only one type of cell. Our results thus show that the phosphorylation status of ANT regulates root girth and biomass accumulation by influencing bilateral stem cell production. This highlights the critical role of posttranslational modifications in plant growth and development.
GPT-4o mini: Non-social science research article
A quantitative risk assessment framework for mortality due to macroplastic ingestion in seabirds, marine mammals, and sea turtles
Erin L. Murphy, Britta R. Baechler, Lauren Roman, George H. Leonard, Nicholas J. Mallos, Robson G. Santos, Chelsea M. Rochman
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Plastic ingestion has been documented in nearly 1,300 marine species, including every seabird family, marine mammal family, and sea turtle species. Acute mortality, due to obstruction, perforation, or torsion of the gastrointestinal (GI) tract, has been confirmed via necropsy in all three taxa; however, quantitative risk assessment for macroplastic ingestion poses unique challenges, with risk more dependent on probability of discrete events involving diverse plastic types rather than cumulative exposure models (e.g., LC 50 ). We model mortality risk associated with macroplastic ingestion in seabirds, marine mammals, and sea turtles, using data from more than 10,000 necropsies reported in the academic literature and stranding network databases. Employing an adapted Weibull Accelerated Failure Time model, we assess the relationship between the GI load (pieces and volume/animal length) of different plastic types—hard, soft, rubber, or fishing debris—and likelihood of plastic-induced mortality. Overall, 35% of seabirds, 12% of marine mammals, and 47% of sea turtles ingested plastic, and 1.6%, 0.7%, and 4.4% died from plastic, respectively. When modeling plastic together, a 90% chance of mortality was associated with 23 pieces (0.098 cm 3 /cm) in seabirds, 29 pieces (39.89 cm 3 /cm) in marine mammals, and 405 pieces (5.52 cm 3 /cm) in sea turtles (377 for juveniles). The plastic types that posed the greatest risks were rubber for seabirds, soft plastics and fishing debris for marine mammals, and hard and soft plastics for sea turtles. This research furthers scientific understanding of the likelihood of mortality from plastic ingestion and can inform monitoring, risk assessments, and management frameworks.
GPT-4o mini: Non-social science research article
Viscosity of concentrated antibodies from a dynamic model of electrostatics
Keith P. Johnston, Thomas M. Truskett
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GPT-4o mini: Non-social science research article
Interactions between long- and short-term synaptic plasticity transform temporal neural representations into spatial
Qiang Yu, Misha Tsodyks, Haim Sompolinsky, Dietmar Schmitz, Robert GĂŒtig
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Information processing in the brain relies on the transmission of spikes through chemical synapses whose efficacies often depend on their recent firing history. While effects of such short-term plasticity on neural information processing have long been studied, it is unclear how interactions between short-term and long-term plasticity affect the learning abilities of neural networks. Here, we show that long-term changes to the short-term plasticity of individual synaptic connections enable neurons to learn to process temporal sequences of spikes as if they were spatial patterns. This mechanism allows neural circuits to flexibly increase their capacity and robustness at the expense of elevated spiking activity. We further show that neurons with plastic short-term plasticity can learn to discriminate between inputs on the basis of multineuronal spike correlations that extend over space and time. Our model fits recent electrophysiological measurements of short-term plasticity in the mouse and human neocortex and is consistent with the distributions of short-term plasticity induction and recovery. Our theory predicts that the learning rule observed at a given synaptic connection depends on the degree and type of short-term plasticity which is induced by the induction protocol for long-term plasticity.
GPT-4o mini: Non-social science research article
Building the connectome of a small brain with a simple stochastic developmental generative model
Oren Richter, Elad Schneidman
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The architectures of biological neural networks result from developmental processes shaped by genetically encoded rules, biophysical constraints, stochasticity, and learning. Understanding these processes is crucial for comprehending neural circuits’ structure and function. The ability to reconstruct neural circuits, and even entire nervous systems, at the neuron and synapse level, facilitates the study of the design principles of neural systems and their developmental plan. Here, we investigate the developing connectome of Caenorhabditis elegans using statistical generative models based on simple biological features: neuronal cell type, neuron birth time, cell body distance, reciprocity, and synaptic pruning. Our models accurately predict synapse existence, degree profiles of individual neurons, and statistics of small network motifs. Importantly, these models require a surprisingly small number of neuronal cell types, which we infer and characterize. We further show that to replicate the experimentally observed developmental path, multiple developmental epochs are necessary. Our model’s predictions of the synaptic connections and their strength, using multiple reconstructions of adult worms, reflect that it identified much of the shared part of the connectivity graph. Thus, the accuracy of the generative statistical models we use here offers a general framework for studying how connectomes develop and the underlying principles of their design.
GPT-4o mini: Non-social science research article
Structural basis of modified ligand selectivity from N-terminal PAC1R alternative splicing
Jessica J. Lu, Giuseppe Deganutti, Miaomiao Li, Laura J. Humphrys, Yandi Li, Theodore J. Nettleton, Hariprasad Venugopal, Villy Julita, George Christopoulos, Christopher A. Reynolds, Patrick M. Sexton, Denise Wootten, Peishen Zhao, Sarah J. Piper
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The pituitary adenylate cyclase-activating polypeptide (PACAP) 1 receptor (PAC1R) is a class B1 G protein–coupled receptor activated by the endogenous peptide agonists PACAP and vasoactive intestinal peptide (VIP). Alternate splicing within the receptor extracellular domain (ECD) generates the PAC1R short variant (PAC1sR) that has selectively enhanced VIP function compared to the full-length, PAC1R null variant (PAC1nR). However, to date, a comprehensive pharmacological assessment of the downstream signaling outcomes of PAC1sR activation compared to PAC1nR has not been performed, and little information is available to mechanistically understand how ECD splicing may alter ligand engagement. Here, we demonstrated that VIP, but not PACAP, has globally enhanced activity across a broad range of functional endpoints at PAC1sR compared to PAC1nR. Cryo-EM structures of VIP-bound, stimulatory G protein (G s )-coupled PAC1sR and PAC1nR, supported by molecular dynamics (MD) simulations, demonstrate transient engagement of the null loop in PAC1nR, which is absent in PAC1sR, with residues in extracellular loop 2 (ECL2) and the N-terminal helix of the ECD. These interactions result in differential engagement of VIP with these domains and the top of TM2/ECL1 with PAC1sR and PAC1nR. Moreover, MD simulations predicted differential interactions of the G s protein with the two PAC1R variants when bound by VIP that correlate with a greater allosteric influence of the G s protein on VIP affinity at the PAC1sR, relative to PAC1nR. Our study provides insights into the structural basis and functional consequences of PAC1R ECD splicing, increasing understanding of PAC1R ligand selectivity and signaling.
GPT-4o mini: Non-social science research article
Amyloid-beta glycation induces neuronal mitochondrial dysfunction and Alzheimer’s pathogenesis via VDAC1-dependent mtDNA efflux
Firoz Akhter, Asma Akhter, Xiongwei Zhu, Hillary Schiff, Arianna Maffei, Justin T. Douglas, Qifa Zhou, Zhen Zhao, Donghui Zhu
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Glycation, the nonenzymatic attachment of reactive dicarbonyls to proteins, lipids, or nucleic acids, contributes to the formation of advanced glycation end-products (AGEs). In Alzheimer’s disease (AD), amyloid-beta (AÎČ) undergoes posttranslational glycation to produce glycated AÎČ (gAÎČ), yet its pathological role remains poorly understood. Here, we demonstrate that gAÎČ promotes neuronal mitochondrial DNA (mtDNA) efflux via a VDAC1-dependent mechanism, activating the innate immune cGAS-STING pathway. Using aged AD mice and human AD brain samples, we observed cGAS-mtDNA binding and cGAS-STING activation in the neuronal cytoplasm. Knockdown of RAGE, cGAS, or STING, as well as pharmacological inhibition of VDAC1, protected APP mice from mitochondrial dysfunction and Alzheimer’s-like pathology. Neuron-specific cGAS knockdown confirmed its pivotal role in driving neuroinflammation and cognitive deficits. Treatment with ALT-711, an AGE cross-link breaker, alleviated gAÎČ-associated pathology. Furthermore, RAGE inhibition in APP knock-in mice suppressed innate immune activation and disease-associated gene expression, as revealed by spatially resolved transcriptomics. Collectively, our findings establish a mechanistic link between gAÎČ and innate immune activation, identifying VDAC1, the AGE-RAGE axis, and the cGAS-STING pathway as promising therapeutic targets in AD.
GPT-4o mini: Non-social science research article
Substantial planar plastic anisotropy in inorganic Mg 3 Bi 2 single crystals
Tianyu Zhang, Jin Yan, Jin Ke, Peng Zhao, Yuexin Zhou, Yifan Zhou, Sheng Ye, Yao Xu, Baopeng Ma, Shanghao Chen, Jinxuan Cheng, Jiahui Chen, Zhaoyue Yao, Jin Zhang, Feng Cao, Lijun Zhang, Jun Mao, Yuhao Fu, Qian Zhang
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Elucidating the fundamental microscopic mechanisms governing plastic deformation is crucial for the rational design of functional materials with tailored mechanical properties. Recent advances in Mg 3 Bi 2 -based thermoelectric materials have revealed exceptional room-temperature ductility in these compounds. However, the origin of their plastic behavior remains elusive. Herein, we report a pronounced in-plane plastic anisotropy in single-crystalline Mg 3 Bi 2 . Micropillar compression reveals that the observed anisotropy is critically dependent on the activation of single versus double slip systems, and superior plastic deformability can be achieved once the double slip system is activated. The interatomic potential for Mg 3 Bi 2 was developed via the machine learning approach, and molecular dynamics simulations establish that the crystallographic orientation-dependent activation of competing slip systems constitutes the fundamental origin of the plastic anisotropy in Mg 3 Bi 2 . Additionally, our study demonstrates that pyramidal a dislocations play a crucial role in the plasticity of Mg 3 Bi 2 .
GPT-4o mini: Non-social science research article
ATP-dependent actin barbed-end fluctuations at steady state
Madhura Duttagupta, Andrew T. Riley, William M. Brieher
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Actin networks in cells are dynamic and constantly turning over as actin subunits exchange between monomer and polymer pools. Understanding these dynamics in vivo requires a detailed understanding of pure actin behavior in vitro. The prevailing model is treadmilling, which predicts continuous growth of filament barbed ends balanced by continuous shrinkage of pointed ends, while filament length remains roughly constant. While treadmilling has been observed directly at the level of single filaments, length fluctuations—expressed as “length diffusivity”—are much greater than expected, and the origin of these high diffusivity values could not be identified experimentally. By imaging single filaments tethered to glass via α-actinin, we observed frequent, low-amplitude barbed-end fluctuations of ±2–6 subunits per event and rarer, high-amplitude fluctuations of ±50–150 subunits per event. Barbed-end fluctuations depended on adenosine triphosphate (ATP) hydrolysis and release of inorganic phosphate (Pi) and were blocked by phalloidin and barbed-end capping agents. Barbed-end fluctuations consumed an estimated one-third of the ATP at steady state, while two-thirds is still consumed by treadmilling. Fluctuations result in diffusive spreading of filament lengths that exceeds predictions from pure treadmilling yet is lower than previously reported values, suggesting that earlier measurements captured additional sources of variability. Our results provide direct experimental evidence for kinetic models that proposed a dampened form of dynamic instability in pure actin where transient loss of the ATP/ADP‱Pi barbed-end cap leads to rare, large excursions superimposed on more frequent, small fluctuations.
GPT-4o mini: Non-social science research article
Rubisco is slow across the tree of life
Benoit de Pins, Cyril Malbranke, Jagoda JabƂoƄska, Assaf Shmuel, Itai Sharon, Anne-Florence Bitbol, Oliver Mueller-Cajar, Elad Noor, Ron Milo
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Rubisco is the main gateway through which inorganic carbon enters the biosphere, catalyzing the vast majority of carbon fixation on Earth. This pivotal enzyme has long been observed to be kinetically constrained. Yet, this impression is based on kinetic measurements heavily focused on eukaryotic rubiscos, a rather conserved group of low genetic diversity. Moreover, the fastest rubiscos that we know of so far were found among the sparsely sampled prokaryotes. Could there be yet faster rubiscos among the uncharted regions of rubisco’s phylogenetic diversity? Here, we perform a characterization of more than 250 rubiscos from a wide range of bacteria and archaea, thereby doubling the coverage of the diversity of this key enzyme. We assess the distribution of the carboxylation rates at saturating levels of CO 2 , and establish that rubisco is a relatively slow enzyme across the tree of life, never exceeding ≈30 reactions per second at 30 °C. We show that relatively faster subclades share similar evolutionary contexts, involving micro-oxygenic environments or a CO 2 concentrating mechanism. Leveraging a simple machine learning model trained on this dataset, we predict the carboxylation rate for all ≈68,000 sequenced rubisco variants found in nature to date. This study provides the largest and most diverse dataset of natural variants for an enzyme and their associated rates, establishing a solid benchmark for future efforts to predict catalytic rates from sequence data.
GPT-4o mini: Non-social science research article
Defects at play: Shaping the photophysics and photochemistry of ice
Marta Monti, Yu Jin, Gonzalo DĂ­az MirĂłn, Arpan Kundu, Marco Govoni, Giulia Galli, Ali Hassanali
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The mechanisms by which light interacts with ice and the impact of photoinduced reactions are central to our understanding of environmental, atmospheric, and astrophysical processes. However, a microscopic description of the photoproducts originating from ultraviolet (UV) absorption and emission processes has remained elusive. Here, we explore the photochemistry of ice using time-dependent hybrid density functional theory on various models of pristine and defective ice Ih. Our investigation of the excited state potential energy surface of the crystal shows that UV absorption can lead to the formation of hydronium ions, hydroxyl radicals, and excess electrons. One of the dominant mechanisms of decay from the excited to the ground-state involves the recombination of the electron with the hydroxyl radical yielding hydronium-hydroxide ion-pairs. We find that the details of this charge recombination process sensitively depend on the presence of defects in the lattice, such as vacancies and preexisting photoproducts. We also observe the formation of Bjerrum defects following UV absorption; we suggest that, together with hydroxide anions, they are likely responsible for prominent features experimentally detected in long UV exposure absorption spectra, remarkably red-shifted relative to short exposure spectra. Our results highlight the key role of defects in determining the onset of absorption and emission processes in ice.
GPT-4o mini: Non-social science research article
Biodiversity conservation requires consideration of different life history stages
Yan-Fang Song, Xiao-Long Liu, Jia-Jia Liu, Qing-Qing Li, Xian-Qi Li, Wen-Zhu Lu, Wei-Wei Zhou, Zhi-Yong Yuan
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Amid the biodiversity crisis, functional diversity, which is critical for ecosystem stability and conservation planning—faces challenges due to species’ complex life cycles. As the majority of animals, species with complex life histories may have distinct traits and ecological functions at different stages. Using all 557 Chinese anurans, we tested whether adult-based conservation protects entire taxa by analyzing functional trait diversity across life stages. We compiled adult and tadpole traits, mapped spatial diversity patterns, identified hotspots, recognized conservation priority species based on traits at different stages, and tested whether integrating information from different life history stages can effectively conserve functional diversity. Results showed functional diversity hotspots of adults and tadpoles are different. Species’ functional uniqueness between stages were not correlated, with only 18.8% species overlapped in conservation priority lists. Meanwhile, conservation strategies prioritizing species based on adult traits failed to protect tadpole functional diversity. The extent of functional diversity covered by these species was similar to that of randomly chosen species. These findings reject the hypothesis that conservation strategies made based on information of adults can adequately protect whole taxa. Nevertheless, when information from both stages is integrated, the conservation effectiveness has significantly improved. Thus, comprehensive biodiversity protection requires integrated assessments of all stages.
GPT-4o mini: Non-social science research article
Structural basis for Lamassu-based antiviral immunity and its evolution from DNA repair machinery
Matthieu Haudiquet, Arpita Chakravarti, Zhiying Zhang, Josephine L. Ramirez, Alba Herrero del Valle, Paul Dominic B. Olinares, Rachel Lavenir, Massilia AĂŻt Ahmed, M. Jason de la Cruz, Brian T. Chait, Samuel H. Sternberg, Aude Bernheim, Dinshaw J. Patel
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Bacterial immune systems exhibit remarkable diversity and modularity, as a consequence of the continuous selective pressures imposed by phage predation. Despite recent mechanistic advances, the evolutionary origins of many antiphage immune systems remain elusive, especially for those that encode homologs of the structural maintenance of chromosomes (SMC) superfamily, which are essential for chromosome maintenance and DNA repair across domains of life. Here, we elucidate the structural basis and evolutionary emergence of Lamassu, a bacterial immune system family featuring diverse effectors but a core conserved SMC-like sensor. Using cryo-EM, we determined structures of the Vibrio cholerae Lamassu complex in both apo- and dsDNA-bound states, revealing unexpected stoichiometry and topological architectures. We further demonstrate how Lamassu specifically senses dsDNA ends in vitro and phage replication origins in vivo, thereby triggering the formation of LmuA tetramers that activate its Cap4 nuclease domain. Our findings reveal that Lamassu evolved via exaptation of the bacterial Rad50-Mre11 DNA repair system to form a compact, modular sensor for viral replication, exemplifying how cellular machinery can be co-opted for novel immune functions.
GPT-4o mini: Non-social science research article
Female fertility and infant survivorship increase following lethal intergroup aggression and territorial expansion in wild chimpanzees
Brian M. Wood, David P. Watts, Kevin E. Langergraber, John C. Mitani
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Lethal coalitionary intergroup aggression is a conspicuous aspect of wild chimpanzee behavior. Evidence indicates that such violence can lead to territorial expansion, but whether this results in fitness benefits is unknown. Here, we show that female fertility and infant survivorship increased after males in the Ngogo chimpanzee community killed members of neighboring groups and expanded their territory. These findings demonstrate the fitness benefits of intergroup killing in one of our two closest living relatives and contribute to the debate regarding its adaptive significance.
GPT-4o mini: Non-social science research article
The configurational length scale in the self-assembly and modulation of higher-order transient protein structures
Christoph A. Haselwandter, Roderick MacKinnon
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Membrane protein homo-oligomers named higher-order transient structures (HOTS) are formed through cohesive self-interactions in the range of a few k B T . The small magnitude of these interactions underlies the rapid reversibility of HOTS on the timescale of membrane signaling processes, permitting the dynamic modulation of signals. At the same time, weak interactions present an apparent paradox: HOTS should form only if the concentration of a particular protein is sufficiently high to produce oligomerization by mass action. And yet, HOTS are observed experimentally with membrane proteins present in cell membranes at concentrations of only a few per Ό m 2 . In this study, we employ principles of statistical thermodynamics to explain how cells can alter the configurational entropy of the oligomerization reaction, thereby achieving HOTS formation at low concentrations of the protein in the membrane. We propose that this modification of the configurational entropy, a process we call configurational length scaling, is an important aspect of HOTS formation in cell membranes and possibly other cellular compartments.
GPT-4o mini: Non-social science research article
Breast cancer cell coculture induces normal lung fibroblast transition to CAFs, promoting tumor cell dormancy and therapy resistance
Marika L. Klosowski, Kathryn E. Cronise, Eric P. Palmer, Kelly McAuliffe, Claire Stratton, Kelsie Sparks, Kendall T. Malmstrom, Gwyneth Knott-Byars, Qiong Zhou, Hector Esquer, Daniel V. LaBarbera, Daniel P. Regan
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Cancer-associated fibroblasts (CAFs) shape the tumor microenvironment of primary breast tumors to promote tumor progression and therapy resistance. While the lung is a top metastatic site in breast cancer, the origins of lung metastasis-associated fibroblasts and their influence on disseminating tumor cell outgrowth and chemoresistance are poorly understood. Here, we demonstrate the applicability of 2-dimensional and 3-dimensional cocultures of primary human lung fibroblasts (LF) and breast cancer cells (BCC) as models of tumor–stromal interactions in lung metastatic breast cancer. Using these models, we find that BCC lines representing clinically relevant molecular subtypes differentially induce CAF-like phenotypes in primary LFs corresponding with their propensity for lung metastasis. Furthermore, we identify a mechanism by which juxtacrine signaling from LFs to triple negative breast cancer (TNBC) cells promotes expansion of prognostic dormant-like cell subpopulations and instigates autophagy-dependent therapy resistance via integrin and Janus kinase1/2 signaling. A high content kinase inhibitor compound library screen using this model identifies vacuolar protein sorting 34 as a therapeutic vulnerability unique to BCC-LF interaction whose inhibition can resensitize TNBC cells to chemotherapy and relieve LF-mediated extrinsic therapy resistance. Therefore, we propose coculture of primary human LFs and BCC as a reductionist model of interactions between tumor cells and lung-resident stroma and a tool for therapeutic and mechanistic discovery in lung metastatic breast cancer.
GPT-4o mini: Non-social science research article
The cost of thinking is similar between large reasoning models and humans
Andrea Gregor de Varda, Ferdinando Pio D’Elia, Hope Kean, Andrew Lampinen, Evelina Fedorenko
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Do neural network models capture the cognitive demands of human reasoning? Across seven reasoning tasks, we show that the length of the chain-of-thought generated by large reasoning models predicts human reaction times both within tasks—tracking item-level difficulty—and across tasks—capturing broader differences in cognitive demands. This model-to-human alignment shows that out-of-the-box reasoning models reflect core features underlying problem and task complexity in human cognition, without requiring any built-in symbolic mechanisms.
GPT-4o mini: Non-social science research article
Creatine kinase imaging (CKI) for in vivo whole-brain mapping of creatine kinase reaction kinetics
Mark Widmaier, Antonia Kaiser, Pontus Pandurevic, Song-I Lim, André Döring, Zhiwei Huang, Daniel Wenz, Ying Xiao, Yun Jiang, Yan Lin, Lijing Xin
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The creatine kinase (CK) is a key enzyme involved in brain bioenergetics, playing an important role in brain function and the pathogenesis of neurological and psychiatric diseases and cancers. However, imaging its activity noninvasively in the human brain remains a significant challenge. This study aims to advance 31 P magnetic resonance fingerprinting for Creatine Kinase Imaging (CKI). The method was implemented and validated on a clinical 7 Tesla MRI scanner. CKI enables whole-brain mapping of CK forward rate constant, revealing regional differences. Furthermore, a functional CKI (fCKI) study demonstrated a CK activation map in response to visual stimulation, revealing an increase in CK forward rate constant in the visual cortex. The novel imaging modalities, CKI and fCKI, have the potential to offer insights into brain bioenergetics both at rest and during activity, in both healthy and pathological conditions.
GPT-4o mini: Non-social science research article
Longitudinal transformation of mitochondrial metabolism during neurogenesis
Donghoon Lim, Sewon Park, Jong Seung Lee, Hyo Jin Gwon, Yunwoo Nam, Suhyuk Choi, Jongwon Kim, Yeonsu Kim, Geonwoo Park, Woo Yang Pyun, Hyun Woo Park, Seung-Woo Cho, Hyun S. Ahn
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Neural stem cells (NSCs) are valuable in the quest to conquer neurodegenerative diseases due to their capability to reconstruct the damaged neuronal networks. However, deep understanding of the intercellular signaling mechanism controlling the lineage and fate of the stem cells is required before potential clinical applications. Here, we applied nondestructive and label-free electrochemical methods for the longitudinal tracking of NSC respiratory metabolism. Sharp change in the oxygen utilization pattern was observed concomitant to stemness loss and onset of differentiation, suggesting metabolic reprogramming in the transition. Intra- and extracellular profiling of mitochondrial metabolites revealed molecular preference in the extracellular transport rates. Electrochemical emulation of the metabolite release pattern induced acceleration of neurite growth in nearby cells, suggesting paracrine signaling system mediated by mitochondrial metabolites.
GPT-4o mini: Non-social science research article
Cloud fraction response to aerosol driven by nighttime processes
Geoffrey Pugsley, Edward Gryspeerdt, Vishnu Nair
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Aerosol–cloud interactions remain one of the largest uncertainties in the anthropogenic forcing of the climate; a significant contribution to this is due to the aerosol effect on the development of cloud fraction and liquid water path in stratocumulus clouds. Stratocumulus are strongly modulated by the diurnal cycle, but many previous observational studies have primarily focused on the daytime behavior of these clouds. In this work, a Lagrangian framework is used to characterize the day-night variation in the cloud sensitivity to aerosol. It is shown that the cloud fraction response to aerosol is driven by nighttime processes, whereas aerosols play a lesser role in daytime cloud fraction breakup. The liquid water path response reveals that aerosols act to thin the cloud during the daytime; however, this effect is partially offset by other processes during the nighttime. These nighttime cloud processes play an important role in setting the cloud state at the start of the day and hence the daytime cloud evolution, during which stratocumulus clouds have the greatest radiative impact. Our findings are consistent with an aerosol induced suppression of precipitation that acts most effectively at night, when stratocumulus precipitation is strongest. These results highlight a requirement for nighttime observations of marine clouds and an improved representation of the diurnal cycle in model-observation comparisons, especially when assessing climate forcing and the viability of marine cloud brightening.
GPT-4o mini: Non-social science research article
EVOLVE platform, a trispecific T cell engager with integrated CD2 costimulation, for the treatment of solid and hematologic tumors
Oksana A. Sergeeva, Guixian Jin, Mohosin Sarkar, Jennifer Zeiger, Sonali Dhindwal, Shu Shien Chin, Abudukadier Abulizi, Zengzu Lai, Colleen Brown, William G. DeMaria, Donal Ryan, Xingyue An, Hayden J. Karp, Evelyn Teran, Changqing Yuan, Danielle Klaskin, Tracy A. Reeve, Guoying Karen Yu, Eric M. Tam, Susan M. Kaech, Martin Preyer, Louis Matis, Jay S. Fine, Stella A. Martomo, Jeremy S. Myers
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Ten CD3 T cell engagers (TCEs) have received regulatory approval for the treatment of hematologic and solid tumors. However, limited costimulatory signaling essential for sustained T cell effector activity may limit CD3 TCE clinical efficacy and response duration. The CD2 receptor is an attractive costimulation target owing to its association with T cell receptor signaling and favorable expression profile. We show that CD2 costimulation is superior in maintaining T cell viability and effector function relative to other pathways in in vitro chronic stimulation assays. The extracellular domain of CD58, the predominant CD2 ligand, is functional as an antibody fusion, improving bispecific potency. We observe that higher CD3 affinity molecules have the potential for superagonism in the context of an integrated CD2 agonist. Evaluation of TCEs with integrated CD2 costimulation and attenuated CD3 binding identified optimal CD3 affinity agonists that avoid target-independent T cell activation and demonstrated an increased therapeutic index relative to nonattenuated CD3 agonists. This platform shows increased tumor-killing efficacy as compared to CD3 affinity-matched bispecifics for known tumor targets such as HER2, CD20, B7-H4, and UL16-binding protein 2 (ULBP2). We demonstrate that ULBP2-targeted trispecifics with integrated CD2 costimulation and optimized CD3 affinity are superior to higher-affinity CD3 molecules in in vivo mouse efficacy studies. This integrated CD2 costimulation platform, which we termed EVOLVE, represents a next-generation TCE platform to increase T cell effector function in the tumor microenvironment and has the potential to address unmet patient needs by improving the depth and durability of clinical antitumor T cell responses.
GPT-4o mini: Non-social science research article
A chromatin-linked CPL2–PHD2/3 module sustains multiple DNA methylation pathways and Polycomb silencing
Lingrui Zhang, Kai Tang, Tiandan Long, Li-Li Zhang, Peipei Zhu, Fuhua Fan, Jianxin Fu, Chao Zhang, Jian-Kang Zhu
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While multiple chromatin-based epigenetic pathways are well characterized, their genome-wide coordination and hierarchical interplay remain poorly understood. We previously identified the BAH–PHD–CPL2 complex, where AIPP3 binds H3K27me3 via its BAH domain and, in concert with PHD2 and PHD3 (PHD2/3), recruits CPL2 to repress transcription by dephosphorylating RNA Polymerase II. Here, we show that CPL2 and PHD2/3 form a distinct module (CPL2–PHD2/3) that safeguards CHH DNA methylation and silences CHH-methylated sites at transposable elements (TEs) through engagement of multiple DNA methylation pathways. The CPL2–PHD2/3 module physically associates with SUVH4 and SUVH5 (SUVH4/5) to preserve SUVH4/5–CMT2-mediated CHH methylation at a subset of H3K9me2-marked regions. Chromatin enrichment of PHD3 likewise enables the module to sustain RNA-directed DNA methylation (RdDM)-mediated CHH DNA methylation at sites bearing H3K9me2, H3K27me3, or neither. Thus, CPL2–PHD2/3 emerges as a previously underappreciated, multifunctional regulator of plant DNA methylation networks. Unexpectedly, its gene repression function is uncoupled from DNA methylation. CPL2–PHD2/3 represses Polycomb-marked genes by interacting with LHP1 or recognizing hypomethylated H3K4. While it cooperates with LHP1 at a subset of targets, it also independently silences many more genes that LHP1 alone cannot repress, both sets of genes being critical for proper development. This dual, yet largely LHP1-insufficient, repression mode singles out CPL2–PHD2/3 as the essential executor of Polycomb silencing. Together, our findings establish CPL2–PHD2/3 as a chromatin-responsive integrator that spans DNA methylation and Polycomb-associated repression, providing a unifying mechanism for epigenetic control of both TEs and genes across diverse chromatin landscapes.
GPT-4o mini: Non-social science research article
Dynamic extracellular interactions with AMPA receptors
Hana Goldschmidt Merrion, Casey N. Barber, Santosh Renuse, Jevon Cutler, Simion Kreimer, Alexei M. Bygrave, David J. Meyers, W. Dylan Hale, Akhilesh Pandey, Richard L. Huganir
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Synaptic plasticity in the central nervous system enables the encoding, storing, and integrating new information. AMPA (alpha-amino-3-hydroxyl-5-methyl-isoxazole-4-propionic acid)-type glutamate receptors (AMPARs) are ligand-gated ion channels that mediate most fast excitatory synaptic transmission in the brain, and plasticity of AMPARs signaling underlies the long-lasting changes in synaptic efficacy and strength important for learning and memory. Recent work has indicated that the enigmatic N-terminal domain (NTD) of AMPARs may be a critical regulator of synaptic targeting and plasticity of AMPARs. However, few synaptic proteins have been identified that regulate AMPAR plasticity through interactions with AMPAR NTDs. Moreover, the scope of AMPAR NTD interactors that are important for synaptic plasticity remains unknown. Here, we present the dynamic, extracellular interactome for AMPARs during synaptic plasticity. Using surface-restricted proximity labeling and BioSITe-based proteomics, we identified 70 proteins that were differentially labeled by APEX2-tagged AMPARs after induction of chemical long-term potentiation of synapses in cultured neurons. Included in this list, were four members of the IgLON family of GPI-anchored proteins (Ntm, OBCAM/Opcml, Negr1, Lsamp). We show OBCAM and NTM directly interact with the extracellular domains of AMPARs. Moreover, overexpression of NTM significantly attenuates the mobility of surface AMPARs in dendritic spines. These data represent a significant step at uncovering the unexplored extracellular regulation of AMPARs, with broad implications for synapse function and synaptic plasticity.
GPT-4o mini: Non-social science research article
Removing dead trees will not save us from fast-moving wildfires
Dominick A. DellaSala, Brian Buma, Alexandro B. Leverkus, David B. Lindenmayer, Jörg MĂŒller, Karen Price, Diana L. Six, Philip Zylstra, Philip J. Burton
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GPT-4o mini: Non-social science research article
Targeting orthotopic and metastatic pancreatic cancer with allogeneic stem cell–engineered mesothelin-redirected CAR-NKT cells
Yan-Ruide Li, Xinyuan Shen, Enbo Zhu, Zhe Li, Jie Huang, Thuc Le, Catrina Tran, Caius G. Radu, Lili Yang
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Pancreatic cancer (PC) remains one of the leading causes of cancer-related mortality worldwide. The majority of patients are diagnosed at advanced stages, with over 50% presenting with metastatic disease at the time of diagnosis. Although chimeric antigen receptor (CAR)-T cell therapy has shown promise in targeting PC, its clinical efficacy remains limited due to several critical challenges. These include tumor antigen heterogeneity, antigen loss or escape mechanisms, functional exhaustion of CAR-T cells within the tumor microenvironment, as well as inherent limitations of autologous approaches such as high manufacturing costs, prolonged production timelines, and restricted scalability. To address these challenges, we developed allogeneic IL-15–enhanced, mesothelin-specific CAR-engineered invariant natural killer T ( Allo15 MCAR-NKT) cells through gene engineering of human hematopoietic stem and progenitor cells (HSPCs) using a clinically guided culture method. These Allo15 MCAR-NKT cells exhibited robust and multifaceted antitumor activity against PC, driven by both CAR and NK receptor–mediated cytotoxic mechanisms. In orthotopic and metastatic human PC xenograft models, Allo15 MCAR-NKT cells demonstrated superior tumor control, enhanced trafficking and infiltration into tumor sites, sustained effector and cytotoxic phenotypes, and reduced expression of exhaustion markers. Importantly, Allo15 MCAR-NKT cells demonstrated a favorable safety profile, characterized by the absence of graft-versus-host disease and minimal cytokine release syndrome. Collectively, these findings validate Allo15 MCAR-NKT cells as a promising next-generation, off-the-shelf immunotherapeutic approach for PC, with the potential to overcome critical challenges including tumor heterogeneity, immune evasion, and therapeutic resistance, especially in the context of metastatic disease.
GPT-4o mini: Non-social science research article
Joubert syndrome 26 protein enforces compartmentalized motility of a ciliary kinesin
Shimin Wang, Ming Li, Guanghan Chen, Zhe Chen, Kexin Lei, Zeynep Ökten, Shanshan Xie, Tianhua Zhou, Wei Li, Guangshuo Ou
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Cilia are essential cellular antennae that rely on precise motor-driven transport to assemble and function. Two kinesin-2 motors—kinesin-II and OSM-3 in Caenorhabditis elegans —cooperate to transport cargo along cilia, with kinesin-II operating in the middle segment and OSM-3 taking over distally. However, how kinesin-II is spatially confined to prevent its invasion into distal regions remains unclear. Here, we identify Joubert syndrome 26 protein (JBTS-26) as a critical regulator of this motor handover. JBTS-26 localizes to axonemal doublet microtubules in the ciliary middle segment, where it competes with kinesin-II for binding to the IFT-B subunit OSM-5/IFT88. This competition displaces kinesin-II from IFT particles, enabling OSM-3 to assume distal transport. Loss of JBTS-26 allows kinesin-II to invade the distal cilium and slows down IFT. Conversely, JBTS-26 overexpression accelerates IFT by prematurely releasing kinesin-II. Our findings reveal a mechanism for compartmentalized motor regulation and link defective motor handover to ciliopathy pathogenesis.
GPT-4o mini: Non-social science research article
Morphological and genomic responses to hurricanes arise and persist during a biological invasion
Jason J. Kolbe, Sean T. Giery, Ansley S. Petherick, Jonathan B. Losos, Dan G. Bock
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Hurricanes can be a source of strong, episodic natural selection, especially for coastal and island populations. In Anolis lizards, selection favors morphological traits that enhance clinging performance under hurricane-force winds. However, we know little about the longer-term persistence of morphological and genomic responses to these pulse-like events. To address this limitation, we capitalized on the well-documented history of hurricanes and spread of the invasive brown anole lizard, Anolis sagrei , over the past 130 y in the southeastern United States. We used 30 sites with estimates of the number of hurricanes experienced since population establishment. We found that hurricane frequency is consistently related to morphological trait values that increase clinging performance—longer limbs and larger toepads. In contrast, traits with no known connection to clinging ability were not related to hurricane frequency. Our genomic results show that despite a complex genetic architecture for most traits, populations retain a signature of hurricane-mediated selection, with several loci being strongly associated with both hurricane frequency and longer limbs. Further, we found that hurricanes are a more persistent driver of among-population genomic differentiation than other environmental variables. These results solidify hurricanes as a major force shaping morphological and genomic variation in Anolis lizards. They also highlight how the evolutionary trajectories of populations will likely be altered as climate change modifies historical patterns of natural selection, such as those involving extreme weather events.
GPT-4o mini: Non-social science research article
Object continuity through invisible retinal motion at saccadic speed
Melis Ince, Carolin HĂŒbner, Martin Rolfs
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Saccadic eye movements rapidly shift the visual scene across the retina, raising the question of how object correspondence is established between gaze fixations. Using submillisecond video projection, we isolated the role of high-speed retinal motion from saccade-related extraretinal signals. We introduced high-speed motion in a quartet motion display, a classic tool for studying long-distance object correspondence. While motion visibility dropped to chance level at saccadic speeds, even invisible motion robustly biased object correspondence. These results demonstrate that retinal motion alone can support object continuity across saccadic image shifts.
GPT-4o mini: Non-social science research article
Merging different allosteric mechanisms: The case of Escherichia coli glutathione reductase
Alexandra Dashevsky, Anna Vanyushkina, Michal Sharon, Sarel J. Fleishman, Amnon Horovitz
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Cooperative regulation of biomolecular function is critical for the ability of all organisms to respond effectively to environmental changes. Such regulation is often manifested in a sigmoidal dependence of enzyme activity on ligand concentration. Various molecular mechanisms have been proposed to underlie such sigmoidal behavior, but they are usually assumed to occur independently of one another. We hypothesized that coexistence of allosteric mechanisms can lead to complex kinetic behavior and higher or lower cooperativity than expected. A mathematical framework that analyses sigmoidal behavior as a function of two cooccurring mechanisms, hysteresis and homotropic binding cooperativity, was developed. The model shows, for example, that i) the observed cooperativity, as measured by the Hill coefficient, can decrease with increasing binding cooperativity, and that ii) unusually high values of the Hill coefficient can be observed. Our mathematical analysis is shown to be relevant for a mutant of Escherichia coli glutathione reductase with an unusually high value of a Hill coefficient for a dimer of about 1.9, in which hysteresis and binding cooperativity coexist. More generally, our findings imply that the repertoire of allosteric regulation is richer than anticipated and suggest that ultrasensitive control in natural or designed systems may arise even in low-order oligomers.
GPT-4o mini: Non-social science research article
Rac1 promotes proximal tubule kidney repair by coupling the actin cytoskeleton to mitochondrial function
Olga M. Viquez, Meiling Melzer, Shensen Li, Matthew Tantengco, Xinyu Dong, Eric Sha, Jeffery Huang, Evan S. Krystofiak, Rachel C. Hart, Wentian Luo, Christian Warren, Al-Borhan Bayazid, Richard Zhang, Ryoichi Bessho, Volker H. Haase, Cord Brakebusch, Takanari Inoue, Craig Brooks, Matthew H. Wilson, Andrew S. Terker, Juan P. Arroyo, Ambra Pozzi, Roy Zent, Fabian Bock
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The kidney proximal tubule (PT) is a specialized polarized epithelium that functions as a high capacity resorptive machine. PT cells are exquisitely sensitive to ischemia due to their high metabolic rate. The small GTPase Rac1 regulates epithelial function by promoting polarity through its effects on the actin cytoskeleton. We show that Rac1, in the setting of the recovery of the PT from ischemic injury, plays a critical role in reconstituting cellular bioenergetics by promoting actin cytoskeleton formation around damaged mitochondria. This mechanism removes damaged mitochondria through mitophagy and preserves PT metabolic capacity and reabsorption function. Loss of Rac1 causes intracellular lipid accumulation, energy depletion, and PT cell atrophy. Thus, Rac1 promotes the repair of PT cells by enhancing mitochondrial bioenergetics, rather than by regulating cell polarity via a mechanism that links the actin cytoskeleton to metabolic demands and cell morphology.
GPT-4o mini: Non-social science research article
Dysregulated proteostasis in p.A53T-α-Synuclein astrocytes aggravates Lewy-like neuropathology in a Parkinson’s disease iPSC model
Christina Paschou, Olympia Apokotou, Konstantina Charmpi, Anastasios Kollias, Sofia Dede, Martina Samiotaki, Paraskevi N. Koutsoudaki, Sophia Havaki, Francesca Palese, Konstantina Dimoula, Evangelia Emmanouilidou, Vassilis G. Gorgoulis, Era Taoufik, Chiara Zurzolo, Rebecca Matsas, Florentia Papastefanaki
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Alpha-Synuclein (αSyn) plays a central role in Parkinson’s disease (PD), and the p.A53T mutation causes an early-onset familial form of PD with severe manifestations. While its effects on neurons are well studied, its consequences on astrocytes and astrocytic contribution to PD pathology are understudied. Here, we differentiated patient-derived p.A53T-αSyn induced pluripotent stem cells (iPSC) to ventral midbrain astrocytes and characterized them via comprehensive molecular, functional, and proteomic analyses. Gene-corrected and healthy iPSC-derived astrocytes served as controls. To assess the effects of p.A53T-αSyn astrocytes on dopamine neurons, we established neuron–astrocyte cocultures of iPSC-derived control and mutant cells at all combinations. Our analyses uncovered cell-intrinsic pathologies in p.A53T-αSyn astrocytes, such as calcium dyshomeostasis, and accumulation of protein aggregates including those of phosphorylated αSyn. Proteomic and mechanistic studies demonstrated perturbed protein catabolic processes, with associated disturbances in lysosomal function and mTOR signaling. These deficits reduced the endocytic clearance capacity of p.A53T-αSyn astrocytes and their ability to process exogenous αSyn cargo. p.A53T-αSyn dopamine neurons cocultured with p.A53T-αSyn astrocytes displayed Lewy-like pathologies, mirroring the histopathological hallmarks identified in postmortem PD brains and exacerbated neurodegeneration, in anatomical and functional aspects. Control astrocytes mitigated these pathologies, highlighting their neuroprotective role. Additionally, p.A53T-αSyn astrocytes induced PD-relevant pathology Îčn control neurons. Our findings, validated using an isogenic pair, demonstrate a critical impact of p.A53T-αSyn in disrupting astrocytic protein quality control mechanisms and establish astrocytes as active contributors to PD neuropathology. Our two-dimensional coculture model reflects key aspects of PD pathology, offering a relevant platform for mechanistic and drug discovery studies.
Social interactions during foraging may be a key to survival for seabirds in the Southern Ocean
Mark A. Willis
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The potential existential threat of large language models to online survey research
Sean J. Westwood
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The advancement of large language models poses a severe, potentially existential threat to online survey research, a fundamental tool for data collection across the sciences. This work demonstrates that the foundational assumption of survey research—that a coherent response is a human response—is no longer tenable. I designed and tested an autonomous synthetic respondent capable of producing survey data that possesses the coherence and plausibility of human responses. This agent successfully evades a comprehensive suite of data quality checks, including instruction-following tasks, logic puzzles, and “reverse shibboleth” questions designed to detect nonhuman actors, achieving a 99.8% pass rate on 6,000 trials of standard attention checks. The synthetic respondent generates internally consistent responses by maintaining a coherent demographic persona and a memory of its prior answers, producing plausible data on psychometric scales, vignette comprehension tasks, and complex socioeconomic trade-offs. Furthermore, its open-ended text responses are linguistically sophisticated and stylistically calibrated to the level of education of its assigned persona. Critically, the agent can be instructed to maliciously alter polling outcomes, demonstrating an overt vector for information warfare. More subtly, it can also infer a researcher’s latent hypotheses and produce data that artificially confirms them. These findings reveal a critical vulnerability in our data infrastructure, rendering most current detection methods obsolete and posing a potential existential threat to unsupervised online research. The scientific community must urgently develop new data validation standards and reconsider its reliance on nonprobability, low-barrier online data collection methods.
Students’ motives for restricting academic freedom: Viewpoint discrimination and prosocial concerns
Claudia Diehl, Matthias Revers, Richard TraunmĂŒller, Nils B. Weidmann, Alexander Wuttke
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We advance the understanding of so-called “cancel culture” at the university by presenting the results of three survey experiments among university students. Designed in an “adversarial collaboration” among researchers with competing perspectives, these experiments disentangle whether students’ preferences for curtailing academic freedom are based on viewpoint discrimination, professional academic standards, or prosocial concerns. Our findings show that a substantive share of university students support viewpoint-based restrictions on academic discourse. While they also apply academic and prosocial criteria, they apply them more strongly to conservative viewpoints. The results further show that conservative statements are perceived as causing more social harm. However, prosocial concerns do not fully explain the higher demand for ideological viewpoint discrimination. These results are important because they can inform the debate about universities as ideological spaces—a view often invoked in recent government-led attacks on academic freedom.
Waiting time during admission procedures increases social inequalities in higher education
Mélusine Boon-Falleur, Elise Huillery, Coralie Chevallier
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Many domains in life require people to wait to access better outcomes, such as waiting in line to access prized tickets for a show, waiting to obtain a job offer from a selective firm, or being waitlisted for a prestigious university. Although waiting might be perceived as a fair mechanism to allocate resources, it may have unintended consequences on social inequalities as individuals from lower socioeconomic backgrounds (SES) may be less likely to wait. In this study, we investigate socioeconomic differences in waiting behavior during the higher education admission process in France. To do so, we leveraged a unique national database that recorded the admission behavior of every high schooler in France over a period of three years. During the admissions process, students faced a trade-off: They could either accept an immediate offer from a university or wait in the hope of receiving a preferred offer later. Results collected among 274,316 students reveal that low-SES students were significantly less likely to wait for preferred offers, even when controlling for objective costs and benefits of waiting. This led low-SES students to ultimately enroll in programs they liked less and that were less prestigious. These results highlight how admission procedures generating uncertainty and requiring students to wait may inadvertently exacerbate educational inequalities. Such systems, while efficient, can end up favoring students who wait more. This research contributes to current discussions on admission procedure fairness by illustrating that seemingly neutral algorithms can in fact deepen social inequalities if their design rewards patience.
Cultural innovation can increase and maintain biodiversity: A case study from medieval Europe
Adam Spitzig, Manfred Rösch, Jessie Woodbridge, Martin Bauch, Piotr Guzowski, Peter Erhart, Ralph Fyfe, Elena Marinova, Adam Izdebski
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Numerous research efforts have used paleoecological data to reconstruct past biodiversity in Europe. In these projects, researchers have identified increases in biodiversity over the Holocene and hinted at a positive correlation with human population. These are important findings but are not easily translated into effective biodiversity conservation and restoration policy. We argue that, in order to better inform policymaking, studies of past biodiversity dynamics should include analyses of contemporaneous cultural phenomena in order to identify and describe specific anthropogenic drivers of past biodiversity changes. We present an example here, a case study from the Lake Constance region (southwestern Germany), one of the core areas of the Carolingian Empire, the foundational political structure of modern Europe. This uniquely well-documented region offers six fossil pollen profiles characterized by high taxonomic and chronological resolution, archaeobotanical evidence from hundreds of excavation sites, and historical records describing population, commerce, and agriculture dating from the mid-700s CE. These data indicate that a major, sustained increase in plant diversity occurred in the Lake Constance region between 500 and 1000 CE, the formative period of medieval civilization. Plant diversity reached a 4,000-y peak around 1000 CE, making the medieval period a plant diversity optimum in the region. Archaeobotanical evidence independently corroborates this finding. Palynological, archaeobotanical, and archival data suggest that cultural innovations—in agriculture, management, and trade—were the primary drivers of this biodiversity transition and were necessary to maintain elevated levels of plant diversity in the region through the 20th century.
Reply to GonzĂĄlez-BailĂłn and Lazer: Industry control and conflicts of interest in social media research
Isabelle Freiling, Dietram A. Scheufele
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Perception of own centrality in social networks
JaromĂ­r Kováƙík, Juan Ozaita, Angel SĂĄnchez, Pablo Brañas-Garza
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This study explores how individuals perceive their social networks, with a focus on their own positioning. Using experimental methods and network analysis, we show that people have a limited understanding of their social standing in terms of popularity (in-degree) and centrality. Few participants accurately estimate their popularity, and even fewer correctly identify their decile of centrality. A similar pattern emerges for their perceptions of the most popular and central individuals, but we find no correlation between the ability to assess one’s own position and the ability to detect key network members. Popular participants correctly perceive themselves as more popular, although they tend to misjudge their popularity more than less popular peers. They are nonetheless more accurate in estimating their centrality. Perceived centrality is only weakly correlated with actual centrality, but central individuals misperceive both their popularity and centrality to a greater extent. We further show that these misperceptions have real-world implications. Conditional on network positioning, students who see themselves as less popular and less central–and those with more accurate self-perceptions–tend to achieve higher grades, whereas individuals recognized by others as popular and central perform significantly better academically. These findings challenge theoretical models that assume accurate self-awareness of network positions and highlight the need to reconsider the implications for key-player interventions in public health, education, and organizational contexts.

Science

GPT-4o mini: Non-social science research article
Pan-family pollen signals control an interspecific stigma barrier across Brassicaceae species
Yunyun Cao, Xiaoshuang Cui, Yinqing Yang, Lianhui Pan, Fei Yang, Shuyan Li, Dandan Wu, Yuelan Ding, Rui Chen, Nan Wang, Shangjia Liu, Zhaojing Ji, Yuxuan Zhao, Yue Chen, Rui Sun, Shiyu Xian, Lin Yang, Jiyun Hui, Ru Li, Tong Zhang, Shengwei Dou, Gengxing Song, Xiaochun Wei, Yuxiang Yuan, XiaoWei Zhang, Mingming Chen, Xihai Sun, Hen-Ming Wu, Alice Y. Cheung, Qiaohong Duan
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Pre-zygotic interspecific incompatibility prevents hybridization between species limiting interbreeding strategies for crop improvement using wild relatives. The Brassica rapa female self-incompatibility determinant, S -locus receptor kinase (SRK), recognizes interspecific pollen. Here we report the discovery of a pan-Brassicaceae SRK-interacting Interspecific Pollen Signal (SIPS). On B. rapa stigmas, SIPSs from Arabidopsis and other Brassicaceae species target Br SRK and recruit the female fertility regulator FERONIA receptor kinase to increase stigmatic reactive oxygen species and reduce interspecific pollen viability. Arabidopsis sips pollen failed to trigger the interspecific incompatibility responses. Unlike self-incompatibility, which is controlled by the polymorphic S locus, different genetic variants of SRK interacted comparably with SIPS. This study establishes SIPS-SRK as a Brassicaceae-specific ligand-receptor pair that broadly maintains the stigmatic interspecific barrier in self-incompatible species.
GPT-4o mini: Non-social science research article
A global screen for magnetically induced neuronal activity in the pigeon brain
Gregory C. Nordmann, Spencer D. Balay, Thamari N. Kapuruge, Marco Numi, Christoph Leeb, Simon Nimpf, E. Pascal Malkemper, Lukas Landler, David A. Keays
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How animals detect the Earth’s magnetic field remains a mystery in sensory biology. Despite extensive behavioral evidence, the neural circuitry and molecular mechanisms responsible for magnetic sensing remain elusive. Adopting an unbiased approach we employ whole brain activity mapping, tissue clearing, and light sheet microscopy to identify neuronal populations activated by magnetic stimuli in the pigeon ( Columba livia ). We demonstrate robust, light-independent bilateral neuronal activation in the medial vestibular nuclei and the caudal mesopallium. Single-cell RNA sequencing of the semicircular cristae revealed specialized type II hair cells that express the molecular machinery necessary for the detection of magnetic stimuli by electromagnetic induction. Our data supports a model whereby electro-magnetic input from the semicircular canals activates a vestibular-mesopallial circuit within the pigeon brain.
GPT-4o mini: Non-social science research article
CRISPR-Cas–mediated heritable chromosome fusions in Arabidopsis
Michelle Rönspies, Solmaz Khosravi, Ondƙej Helia, Alessandro Valisi, Jiƙí Fajkus, Miloslava FojtovĂĄ, Andreas Houben, Holger Puchta
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The genome of Arabidopsis thaliana consists of 10 chromosomes. By inducing CRISPR-Cas–mediated breaks at subcentromeric and subtelomeric sequences, we fused entire chromosome arms, obtaining two eight-chromosome lines. In one line, both arms of chromosome 3 were fused to chromosome 1. In another line, the arms were transferred to chromosomes 1 and 5. Both chromosome number–reduced lines were fertile. Phenotypic and transcriptional analyses revealed no differences compared with wild-type plants. After crossing with the wild type, the progeny showed reduced fertility. The meiotic recombination patterns of the transferred chromosome arms were substantially changed. Directed chromosome number changes in plants may enable new breeding strategies, redefining linkage groups and establishing genetic barriers. Moreover, our data indicate that plants are highly robust to engineered karyotype changes.
GPT-4o mini: Non-social science research article
The Moon-forming impactor Theia originated from the inner Solar System
Timo Hopp, Nicolas Dauphas, Maud Boyet, Seth A. Jacobson, Thorsten Kleine
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The Moon formed from a giant impact of a planetary body, called Theia, with proto-Earth. It is unknown whether Theia formed in the inner or outer Solar System. We measured iron isotopes in lunar samples, terrestrial rocks, and meteorites representing the isotopic reservoirs from which Theia and proto-Earth might have formed. Earth and the Moon have indistinguishable mass-independent iron isotopic compositions; both define one end of the range measured in meteorites. Combining our results with those for other elements, we performed mass balance calculations for Theia and proto-Earth. We found that all of Theia and most of Earth’s other constituent materials originated from the inner Solar System. Our calculations suggest that Theia might have formed closer to the Sun than Earth did.
GPT-4o mini: Non-social science research article
Multigas adsorption with single-site cooperativity in a metal–organic framework
Kurtis M. Carsch, Henry Z. H. Jiang, Ryan A. Klein, Andrew S. Rosen, Peyton S. Summerhill, Jesse L. Peltier, Adrian J. Huang, Ryan A. Murphy, Matthew N. Dods, Hope A. Silva, Zikri Hasanbasri, Hyunchul Kwon, Sarah L. Karstens, Yuto Yabuuchi, Jonas Börgel, Jordan W. Taylor, Katie R. Meihaus, Karen C. Bustillo, Andrew M. Minor, Kristin A. Persson, Craig M. Brown, R. David Britt, Nicholas P. Stadie, Jeffrey R. Long
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Cooperative gas adsorption in metal–organic frameworks (MOFs) is a rare phenomenon that generally involves long-range communication between multiple binding sites. We demonstrate a MOF containing cobalt(II)–methyl sites that selectively and reversibly capture two carbon monoxide (CO) molecules per site, leading to record-high adsorption capacities at ambient temperatures and pressures. Gas adsorption and structural, spectroscopic, and computational analyses support a mechanism in which binding of one CO molecule triggers a spin transition, followed by binding of a second CO molecule and migratory insertion of the first CO molecule into the cobalt–methyl bond to form an acetyl. The greater binding affinity associated with the second CO results in sigmoidal adsorption isotherms, a hallmark of cooperativity and phase-change materials, despite the absence of long-range interactions within the framework.
GPT-4o mini: Non-social science research article
An archaeal genetic code with all TAG codons as pyrrolysine
Veronika Kivenson, Samantha L. Peters, Guillaume Borrel, Aleksandr Kivenson, Leah T. Roe, Noah X. Hamlish, Khaled Fadhlaoui, Alanna Schepartz, Simonetta Gribaldo, Robert L. Hettich, Jillian F. Banfield
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Multiple genetic codes developed during the evolution of eukaryotes and bacteria, yet no alternative genetic code is known for archaea. We used proteomics to confirm our prediction that certain archaea consistently incorporate pyrrolysine (Pyl) at TAG codons, supporting an alternative archaeal genetic code that we designate the Pyl code. This genetic code has 62 sense codons encoding 21 amino acids. In contrast to monophyletic genetic code distributions in bacteria, the archaeal Pyl code occurs sporadically, indicating that it arose independently in multiple lineages. We discovered that more than 1800 archaeal proteins contain Pyl, increasing the number of such proteins by two orders of magnitude. Additionally, five Pyl transfer RNA (tRNA) pyrrolysyl–tRNA synthetase pairs from Pyl-code archaea were used to introduce Pyl analogs into proteins in Escherichia coli .
GPT-4o mini: Non-social science research article
An Aeromonas variant that produces aerolysin promotes susceptibility to ulcerative colitis
Zhihui Jiang, Ye Wang, Jianfeng Gong, Xin Chen, Dong Hang, Caiping Chen, Xin Hong, Junhao Zhang, Kehui Qiu, Yang Liao, Pengpeng Li, Han Wang, Zhuoxin Yang, Tiantian Qiu, Yuwei Zhou, Zexu Chen, Hairong Zhou, Xinqi Shan, Na Zhou, Lutao Liu, Fan Feng, Feng Su, Hongfeng Ma, Zhifeng Liu, Weiqi He, Lei Fang, Ji Xuan, Zhenji Gan, Xia Gao, Jian Zhang, Huaqun Chen, Fangyu Wang, Xuena Zhang, Minsheng Zhu
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Ulcerative colitis (UC) is a severe inflammatory bowel disease affecting millions of people worldwide, but the factors driving the condition are poorly understood. In tissue samples from individuals with UC, we found that macrophages were depleted from areas of the colon that did not yet exhibit overt epithelial inflammation. We hypothesized that toxins produced by bacteria could impair macrophages and that this could promote wider inflammation. We isolated a variant of Aeromonas genus from stool samples from UC patients, which we termed macrophage-toxic bacteria (MTB), because aerolysin secreted by MTB caused macrophage death. MTB colonized mice under pathogenic conditions and triggered colitis. Antibodies against aerolysin alleviated colitis induced by Aeromonas in mice. In a cohort, UC patients more frequently tested positive for Aeromonas than healthy controls did.
GPT-4o mini: Non-social science research article
Realization of a Rydberg-dressed extended Bose-Hubbard model
Pascal Weckesser, Kritsana Srakaew, Tizian Blatz, David Wei, Daniel Adler, Suchita Agrawal, Annabelle Bohrdt, Immanuel Bloch, Johannes Zeiher
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The competition of different length scales in quantum many-body systems leads to phenomena such as correlated dynamics and nonlocal order. To investigate such effects in an itinerant lattice-based quantum simulator, it has been proposed to introduce tunable extended-range interactions using off-resonant optical coupling to Rydberg states, known as Rydberg dressing. In this work, we use this approach to realize an effective one-dimensional extended Bose-Hubbard model. Harnessing our quantum gas microscope, we probe the correlated out-of-equilibrium dynamics of extended-range repulsively bound pairs and “hard rods.” By contrast, operating near equilibrium, we observe density ordering when adiabatically turning on the extended-range interactions. Our results pave the way to realizing light-controlled extended-range interacting quantum many-body systems.
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. While theory indicates that within-cell selection matters for plasmid evolution, experimental measurement of these dynamics has remained elusive. Here, we measure within-cell fitness of competing Escherichia coli plasmids and characterize 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 due to methylation-based replication control. Moreover, less transcriptionally active plasmids display a within-cell advantage and fix preferentially, favoring gene loss. Critically, fixation depends non-trivially on the interplay between plasmid transcription and translation. Our results show that plasmid evolution is driven by within- and between-cell dynamics.
GPT-4o mini: Non-social science research article
Retinal calcium waves coordinate uniform tissue patterning of the Drosophila eye
Ben Jiwon Choi, Yen-Chung Chen, Claude Desplan
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Optimal neural processing relies on precise tissue patterning across diverse cell types. Here, we show that spontaneous calcium waves arise among non-neuronal support cells in the developing Drosophila eye to drive retinal morphogenesis. These waves are initiated by Cad96Ca receptor tyrosine kinase signaling, triggering phospholipase C–γ–mediated calcium release from the endoplasmic reticulum. A cell type–specific “innexin code” coordinates wave propagation through a defined gap junction network among non-neuronal retinal cells, excluding photoreceptors. Wave intensity scales with ommatidial size, triggering stronger myosin II–driven apical contraction at interommatidial boundaries in larger ommatidia. This size-dependent mechanism compensates for early boundary irregularities, ensuring uniform ommatidial packing that is critical for precise optical architecture. Our findings reveal how synchronized calcium signaling among non-neuronal cells orchestrates tissue patterning in the developing nervous system.
GPT-4o mini: Non-social science research article
Atomic layer bonding contacts in two-dimensional semiconductors
Li Gao, Zhangyi Chen, Zhenghui Fang, Shucao Lu, Xiaofu Wei, He Jiang, Kuanglei Chen, Xiaoyu He, Chao Chen, Wei Shangguan, Jinsen Shang, Huihui Yu, Mengyu Hong, Yang He, Xiankun Zhang, Zheng Zhang, Yue Zhang
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Van der Waals contact between two-dimensional semiconductors and metals has always been inferior to covalent bond contacts used in semiconductor industry because of weak band coupling and low bond strength. Here, we report an atomic layer bonding (ALB) contact with strong band coupling and high interfacial cohesion by establishing a metallic coherent bonding interface between the transition-metal atomic layer of transition-metal dichalcogenides and metals. This contact exhibits ultralow contact resistance and superb thermomechanical stability, comparable to those of covalent bond contacts and surpassing all reported contact configurations. ALB contact formed in monolayer molybdenum disulfide and gold demonstrates a contact resistance of 70 ohm-micrometers and thermomechanical stability up to 400°C and delivers a maximum on-current of 1.1 milliamperes per micrometer after high-temperature annealing, all of which meet industrial integration.
GPT-4o mini: Non-social science research article
The synaptic ectokinase VLK triggers the EphB2–NMDAR interaction to drive injury-induced pain
Kolluru D. Srikanth, Hajira Elahi, Praveen Chander, Halley R. Washburn, Shayne Hassler, Juliet M. Mwirigi, Moeno Kume, Jessica Loucks, Rohita Arjarapu, Rachel Hodge, Lucy He, Khadijah Mazhar, Stephanie I. Shiers, Ishwarya Sankaranarayanan, Hediye Erdjument-Bromage, Thomas A. Neubert, Patrick M. Dougherty, Zachary T. Campbell, Raehum Paik, Theodore J. Price, Matthew B. Dalva
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Phosphorylation of hundreds of protein extracellular domains is mediated by two kinase families but the functional role of these kinases is underexplored. We find that the presynaptic release of the tyrosine-directed ectokinase, vertebrate lonesome kinase (VLK/ Pkdcc ), is necessary and sufficient for the direct extracellular interaction between EphB2 and GluN1 at synapses for phosphorylation of the ectodomain of EphB2 and mediation of injury-induced pain. Pkdcc is an essential gene in the nervous system, and VLK is enriched at synapses and released from neurons in an activity- and soluble N -ethylmaleimide-sensitive factor activating protein receptor (SNARE)–dependent manner to drive extracellular interactions. Our results show that presynaptic sensory neuron–specific VLK knockout attenuates postsurgical pain in mice without changing sensorimotor performance, suggesting that VLK critically regulates synaptic protein-protein interactions and acute pain in response to injury.
GPT-4o mini: Non-social science research article
A cross-linked molecular contact for stable operation of perovskite/silicon tandem solar cells
Boxue Zhang, Junsheng Luo, Haomiao Yin, Qing Li, Siqi Sun, Ningxuan Zhang, Nan Gan, Muhammad Azam, Tae Wan Park, Zhongquan Wan, Chunyang Jia, Mingyang Wei, So Min Park
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Monolithic perovskite/silicon tandem solar cells surpass the power-conversion efficiency limits of single-junction solar cells but face challenges in operational stability. We identified fill factor diminution as a key performance-loss mode in the state-of-the-art tandem architecture. We reveal that widely used hole-selective molecular contacts, which enhance tandem cell performance, undergo thermal degradation that undermines charge transport. At elevated temperatures, the resistance of conventional monomeric contacts increases by about sixfold because of thermal-induced disorder. To stabilize interfacial structures, we introduce in situ synthesized cross-linked molecular contacts based on Schiff base linkages. One-square-centimeter perovskite/silicon tandem solar cells achieved power-conversion efficiencies exceeding 34% (33.61% certified), and three independent devices retained 96.2 ± 1.7% of their initial performance after about 1200-hour maximum power point operation under AM1.5G illumination at 65°C.
GPT-4o mini: Non-social science research article
The 2025 Santorini unrest unveiled: Rebounding magmatic dike intrusion with triggered seismicity
Anthony Lomax, Vasilis Anagnostou, Vasileios Karakostas, Stephen P. Hicks, Eleftheria Papadimitriou
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Magmatic intrusion in Earth’s crust can lead to hazardous volcanic eruptions, but the physical processes involved remain largely hidden from direct observation. We used machine learning–derived seismicity as virtual stress meters at depth to study the disruptive 2025 seismogeodetic unrest in Greece between the Santorini volcano and the epicenter of the devastating moment magnitude 7.7 Amorgos earthquake that occurred in 1956. We show that the cause of unrest was magmatic dike propagation, which we imaged with ~25,000 relocated earthquakes occurring over 2 months. The dike propagated horizontally ~30 kilometers as multiscale rebounding waves of dike opening, magma pressure, and breaking of barriers while triggering intense surrounding seismicity. Our results establish magmatic intrusion as a more complex feedback process than previously recognized and can facilitate physics-based and data-driven modeling and eruption forecasting.
GPT-4o mini: Non-social science research article
Increasing the dimensionality of transistors with hydrogels
Dingyao Liu, Jing Bai, Xinyu Tian, Yan Wang, Binbin Cui, Shilei Dai, Wensheng Lin, Zhuowen Shen, Chun Kit Lai, George G. Malliaras, Shiming Zhang
Full text
Transistors, fundamental to modern electronics, are traditionally rigid, planar, and two-dimensional (2D), limiting their integration with the soft, irregular, and three-dimensional (3D) nature of biological systems. Here, we report 3D semiconductors, integrating organic electronics, soft matter, and electrochemistry. These 3D semiconductors, in the form of hydrogels, realize millimeter-scale modulation thickness while achieving tissue-like softness and biocompatibility. This breakthrough in modulation thickness is enabled by a templated double-network hydrogel system, where a secondary porous hydrogel guides the 3D assembly of a primary redox-active conducting hydrogel. We demonstrate that these 3D semiconductors enable the exclusive fabrication of 3D spatially interpenetrated transistors that mimic real neuronal connections. This work bridges the gap between 2D electronics and 3D living systems, paving the way for advanced bioelectronics systems such as biohybrid sensing and neuromorphic computing.
GPT-4o mini: Non-social science research article
Rebalancing viral and immune damage versus repair prevents death from lethal influenza infection
Hiroshi Ichise, Emily Speranza, Federica La Russa, Tibor Z. Veres, Colin J. Chu, Anita Gola, Beatrice H. Clark, Ronald N. Germain
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Maintaining tissue function while eliminating infected cells is fundamental, and inflammatory damage plays a major contribution to lethality after lung infection. We tested 50 immunomodulatory regimes to determine their ability to protect mice from lethal infection. Only neutrophil depletion soon after infection prevented death from influenza. This result suggests that the infected host passed an early tipping point after which limiting innate damage alone could not rescue lung function. We investigated treatments that could have efficacy when administered later in infection. We found that partial limitation of viral spread together with enhancement of epithelial repair, by interferon blockade or limiting CD8 + T cell–mediated killing of epithelial cells, reduced lethality. This finding highlights the importance of rebalancing repair and damage processes in the survival of pulmonary infections.
GPT-4o mini: Non-social science research article
Noncanonical agonist-dependent and -independent arrestin recruitment of GPR1
Heng Cai, Xiaowen Lin, Lechen Zhao, Maozhou He, Jie Yu, Bingjie Zhang, Yuandi Ma, Xiaohua Chang, Yuxuan Tang, Tianyu Luo, Jie Jiang, Mengna Ma, Wenqi Song, Limin Ma, Xiaojing Chu, Cuiying Yi, Kun Chen, Shuo Han, Cen Xie, Wenqing Shui, Qiang Zhao, Ya Zhu, Beili Wu
Full text
G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors have diverse signaling properties with differential preferences for downstream pathways. Certain receptors, such as the chemerin receptor GPR1, undergo arrestin-mediated internalization but weak G protein signaling. However, the mechanisms of this unusual signaling pattern and its physiological relevance are unclear. We report the structures of GPR1 bound to chemerin and ÎČ-arrestin 1 or ÎČ-arrestin 2 and an agonist-free GPR1–ÎČ-arrestin 1 complex. Upon agonist stimulation, the receptor binds the two arrestins in distinct interaction patterns, which may account for their differential cellular responses. Agonist-independent internalization was mediated by an inactive, constitutively phosphorylated GPR1 that accommodates ÎČ-arrestin 1 in an unconventional pocket together with a fatty acid, which potentially provides a basis for GPR1 modulating lipid accumulation in lipid-overloaded adipocytes.
GPT-4o mini: Non-social science research article
An anion-binding approach to enantioselective photoredox catalysis
Petra Vojáčková, Eric N. Jacobsen
Full text
Photoredox catalysis has emerged as a transformative strategy in synthetic chemistry, enabling a wide variety of valuable chemical reactions through generation of highly reactive radical ion intermediates. Pairing chiral counteranions with cation radical intermediates provides a potentially generalizable tool for controlling absolute stereochemistry in various reactivity contexts. However, ion-pairing effects on the efficiency of photoinduced processes and the reactivity of radical ion pairs impose severe limits on the chiral anions that can be engaged effectively. In this study, we report that association of neutral chiral small-molecule hydrogen-bond donors with the counteranions of cation radical intermediates can achieve enantioselectivity through ion-pairing and other noncovalent interactions. Applications to four different classes of cycloaddition reactions of electron-rich alkene substrates provide cyclic products with up to four new stereocenters in up to 99% enantiomeric excess.
Science abstract < 200 char.: Not a research article
A bacterial toxin disarms gut defenses against inflammation
Sonia Modilevsky, Shai Bel
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Macrophage-toxic bacteria from patients with ulcerative colitis worsen gut inflammation in mice
Science abstract < 200 char.: Not a research article
High-resolution climate model forecasts a wet future
Paul Voosen
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With details as fine as short-term weather forecasts, model achieves newfound accuracy
Science abstract < 200 char.: Not a research article
An ode to change Metamorphosis Oren Harman Basic Books, 2025. 400 pp.
Viviane Callier
Full text
A historian confronts the transformative nature of metamorphosis
Science abstract < 200 char.: Not a research article
In defense of the know-it-all On Pedantry Arnoud S. Q. Visser Princeton University Press, 2025. 344 pp.
Jonathan Wai
Full text
A scholar probes the scorn provoked by the intellectual elite across the ages
Science abstract < 200 char.: Not a research article
‘A sigh of relief’: New malaria drug succeeds in clinical trial as existing treatments falter
Kai Kupferschmidt
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Ganaplacide, developed by Novartis, eases worries about drug resistance—but hard choices loom on how to use it
Science abstract < 200 char.: Not a research article
In Other Journals
Sacha Vignieri, Sarah LempriĂšre, Joana OsĂłrio, Jesse Smith, Michael A. Funk, Di Jiang, Sumin Jin
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
A headless mystery
Andrew Curry
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Archaeologists find evidence that a wave of mass brutality accompanied the collapse of the first pan-European culture
Science abstract < 200 char.: Not a research article
Brazil’s hypocrisy at COP30
José Amorim Reis-Filho, Tommaso Giarrizzo, Friedrich Wolfgang Keppeler, Eurico Noleto-Filho, Marcelo Oliveira Soares, Valter M. Azevedo-Santos, Guilherme O. Longo, Mariana Bender, Rafael A. Magris, Philip M. Fearnside
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Science abstract < 200 char.: Not a research article
As neural organoids advance, ethics races to keep pace
Mitch Leslie
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Scientists, ethicists, and patient advocates mull biology’s latest provocative technology
Science abstract < 200 char.: Not a research article
The retina’s rhythm
Justin P. Kumar
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Calcium waves facilitate the emergence of sight
Science abstract < 200 char.: Not a research article
Engineering chromosome number in plants
Feng Zhang, R. Kelly Dawe
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Chromosome engineering produces a reduced eight-chromosome karyotype in Arabidopsis thaliana
Science abstract < 200 char.: Not a research article
Make the census voluntary? Bad idea, say statisticians
Jeffrey Mervis
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Pending bills in U.S. Congress could degrade data from national surveys
Science abstract < 200 char.: Not a research article
Bolivia’s political transition and COP30
Flora Magdaline BenĂ­tez Romero, Philip M. Fearnside
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Science abstract < 200 char.: Not a research article
The demographic future that we do not know about
Anne Goujon
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Science abstract < 200 char.: Not a research article
Startup pioneers subscription service for space telescope
Daniel Clery
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Blue Skies Space will sell data from its tiny, low-cost UV observatory
Science abstract < 200 char.: Not a research article
Tracking magma with earthquakes
Virginie Pinel
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Linking stress in Earth’s crust and magma flow could help forecast eruptions and associated hazards
Science abstract < 200 char.: Not a research article
Time to laugh
Lindsey Smith Taillie
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Science abstract < 200 char.: Not a research article
In Science Journals
Keith T. Smith, Phil Szuromi, Marc S. Lavine, Jake S. Yeston, Jelena Stajic, Annalisa VanHook, Claire Olingy, Ruirui Qiao, Sacha Vignieri, L. Bryan Ray, Sarah H. Ross, Caroline Ash, Mattia Maroso, Angela Hessler, Madeleine Seale, Courtney Malo, Miguel Torres
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
Brazil’s credibility at stake with drilling
Fabiele do Rocio Lacerda, Ana Paula dos Santos Bertoncin, Renata Ruaro
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Science abstract < 200 char.: Not a research article
Scientific distinctions between coca and cocaine support policy reform
Dawson M. White, Ricardo Soberón Garrido, Caroline S. Conzelman, Wade Davis, Claude Guislain, Anthony Henman, Orlando Adolfo Jara-Muñoz, Martin Jelsma, Susana Mejía, Daniel Montoya-Cataño, Oscar Alejandro Pérez-Escobar, David Alfonso Restrepo, Yenny Alejandra Saavedra-Rojas, Imika Tariru
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Ongoing review of international drug policy should correct long-standing, misguided, and harmful conflation
A megadam test for China and South Asia
Rafael J. P. Schmitt, Brian Eyler
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China has begun construction on what may become the world’s most ambitious effort to harness mighty rivers to generate electricity. The 60-gigawatt Lower Yarlung Tsangpo Hydropower Project portends a new frontier in renewable energy but also reopens long-standing questions about managing rivers that cross national borders and the unintended impacts of hydropower megaprojects on people and ecosystems depending on rivers.
What enables human language? A biocultural framework
Inbal Arnon, Liran Carmel, Nicolas ClaidiĂšre, W. Tecumseh Fitch, Susan Goldin-Meadow, Simon Kirby, Kazuo Okanoya, Limor Raviv, Lucie Wolters, Simon E. Fisher
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Explaining the origins of language is a key challenge in understanding ourselves as a species. We present an empirical framework that draws on synergies across fields to facilitate robust studies of language evolution. The approach is multifaceted, seeing language emergence as dependent on the convergence of multiple capacities, each with their own evolutionary trajectories. It is explicitly biocultural, recognizing and incorporating the importance of both biological preparedness and cultural transmission as well as interactions between them. We demonstrate this approach through three case studies that examine the evolution of different facets involved in human language (vocal production learning, linguistic structure, and social underpinnings).

Science Advances

GPT-4o mini: Non-social science research article
Low-waste, single-step, sustainable extraction of critical metals from deep-sea polymetallic nodules
Ubaid Manzoor, Thomas LĂŒttke, Dierk Raabe, Isnaldi R. Souza Filho
Full text
To support the green energy transition, sustainable supplies of critical metals—60 million (metric) tons of copper, 10 million tons of nickel, and 1 million tons of cobalt—annually by 2050 are essential. These metals are currently sourced from declining terrestrial reserves, making deep-sea polymetallic nodules a promising alternative. However, current metal extraction methods are lengthy and energy and carbon intensive, emitting 45, 28, and 4 tons of carbon dioxide equivalent per ton of nickel, cobalt, and copper, respectively. We present a fossil-free hydrogen plasma–based reduction process, powered by green hydrogen and renewable energy, which condenses calcination, smelting, reduction, and refining into a single-step metal extraction, reducing direct carbon dioxide emissions by up to 90% and improving energy efficiency by up to 18%. In addition, we demonstrate selective copper recovery via a heat treatment requiring no acids or reducing agents, offering a more sustainable and cost-effective pathway for critical metal extraction from polymetallic nodules.
GPT-4o mini: Non-social science research article
A universal 2D-on-SiC platform for heterogeneous integration of epitaxial III-N membranes
Se H. Kim, Hanjoo Lee, Dong-Gwan Kim, Donghan Kim, Seokgi Kim, Hyunsoo Kim, Seoyong Ha, Hyunho Yang, Yunsu Jang, Jangho Yoon, ByoungTak Lee, Jung-Hee Lee, Roy Byung Kyu Chung, Hongsik Park, Sungkyu Kim, Tae Hoon Lee, Hyun S. Kum
Full text
Nonconventional epitaxial techniques, such as van der Waals epitaxy and remote epitaxy, have attracted substantial attention in the semiconductor research community for their capability to repeatedly produce high-quality freestanding films from a single mother wafer. Successful implementation of these techniques depends on creating a robust, uniform two-dimensional (2D) material surface. The conventional method for fabricating graphene on silicon carbide (SiC) is high-temperature graphitization. However, the extremely high temperature required for silicon sublimation (typically above 1500°C) causes step bunching, forming nonuniform multilayer graphene stripes and an unfavorable surface morphology for epitaxial growth. Here, we developed a wafer-scale graphitization technique that allows fast synthesis of single-crystalline graphene at low temperatures by metal-assisted graphitization. In contrast to previous reports, we found annealing conditions enabling SiC dissociation while avoiding silicide formation, producing uniform single-crystalline graphene while maintaining the pristine surface morphology of the substrate. We successfully produce high-quality freestanding single-crystalline III-N (AlN and GaN) membranes on graphene/SiC via the 2D material–based layer transfer technique.
GPT-4o mini: Non-social science research article
An acyclic nucleoside phosphonate effectively blocks the egress of the malaria parasite by inhibiting the synthesis of cyclic GMP
Marie Ali, Rea Dura, Marc-Antoine Guery, Emma Colard-Itté, Thomas Cheviet, Léa Robresco, Laurence Berry, Corinne Lionne, Catherine Lavazec, Antoine Claessens, Suzanne Peyrottes, Kai Wengelnik, Sharon Wein, Rachel Cerdan
Full text
The urgent need for original antimalarial therapies arises from the alarming spread of malaria parasite resistance to existing drugs. A promising candidate, UA2239, an acyclic nucleoside phosphonate with a guanine as nucleobase, demonstrates rapid and irreversible inhibitory effects on Plasmodium parasites. It blocks the active exit process, named egress, of merozoites and gametes from infected erythrocytes. UA2239 disrupts the essential cyclic guanosine monophosphate (cGMP)–dependent egress pathway by decreasing cGMP levels in the parasite, strongly suggesting Plasmodium falciparum guanylyl cyclase α as its primary target. We also uncovered remarkable molecular mechanisms of resistance developed by parasites after prolonged exposure to the drug, which involve mutating not the target itself, but downstream effectors. The unique mechanism of action of UA2239 makes it a valuable first-in-class candidate for further development. Its ability to inhibit both parasite growth and transmission highlights its therapeutic potential as a dual-stage antimalarial agent.
GPT-4o mini: Non-social science research article
Electrochemical C4 alkylation of pyridine derivatives: Enhanced regioselectivity via silane assistance
Zhihao Yang, Xuan Liu, Yi-Xuan Chen, Yuting Gao, Xun Xiao, Hirofumi Maekawa, Tianyuan Zhang, Xin-Qi Hao, Mao-Ping Song
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Pyridine derivatives are valuable biologically active compounds, materials, and ligands; however, traditional methods for site-selective direct functionalization are often hindered by multistep procedures and harsh conditions. Herein, we report the general and efficient electroreductive C4 alkylation of pyridine derivatives with various alkyl bromides with high regioselectivity and good yields. The addition of chlorotrimethylsilane facilitated the in situ formation of an N -trimethylsilyl pyridinium salt, increasing the electron deficiency of the pyridine core and enabling it to preferentially undergo single-electron reduction over alkyl bromides, thereby enhancing both yield and regioselectivity. Furthermore, the C4-alkylated pyridines can undergo subsequent electroreductive C2 alkylation, allowing for the sequential installation of distinct alkyl groups, thereby providing a versatile approach to accessing structurally diverse di- and trifunctionalized pyridines.
GPT-4o mini: Non-social science research article
Balancing selection of climate adaptive loci underlies the success of introduction of Eurasian Tree Sparrows
Yilin Chen, Shuai Zhang, Wenqing Zang, Per G. P. Ericson, Santiago Claramunt, Leo Joseph, Les Christidis, Weiwei Zhai, Fumin Lei, Yanhua Qu
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Human-mediated introductions have enabled species to colonize beyond their native ranges, yet the mechanisms underlying successful establishment remain unclear. We combined genomic and ecological analyses to investigate parallel introductions of the Eurasian Tree Sparrow across continents. Our analyses of genetic structure and demography revealed that introduced populations in North America (European origin) and Australia (Chinese origin) experienced founder effects, with resulting bottlenecks, reduced genetic diversity, and increased inbreeding. Despite the genome-wide loss of diversity, we identified conserved regions of high genetic variation in the introduced populations, potentially maintained through balancing selection of ancestral polymorphisms. Genotype-climate association and genetic offset modeling demonstrated that climate-adaptive genetic variants retained similar frequencies across the native and introduced ranges, likely maintaining similar interactions of genetic components with climate niches. Our findings highlight how retention of adaptive polymorphism facilitates establishment success in the introduced populations, providing a framework for predicting invasion potential through genomic signatures of adaptation.
GPT-4o mini: Non-social science research article
Magmatic immiscibility provides phosphate for prebiotic chemistry
Daniel Weller, Thomas Matreux, Iris B. A. Smokers, Almuth Schmid, Christof B. Mast, Donald B. Dingwell, Dieter Braun, Bettina Scheu
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Phosphorus is essential for extant and nascent life. However, phosphate’s low terrestrial abundance and the poor aqueous solubility of phosphorus-bearing minerals pose major hurdles for prebiotic chemistry. Here, we show that silicate-phosphate immiscibility in volcanic melts could have provided a widely available mechanism for the local enrichment of phosphate. Starting with a phosphorus-enriched Archean melt, we observe that rapid cooling results in the formation of immiscible glassy droplets with up to 21 weight % phosphorus pentoxide, which can be delivered to the surface by volcanic processes. In aqueous leaching, we detect millimolar phosphate concentrations, which enable the synthesis of phosphorylating agents such as polyphosphates and imidazole phosphate with up to 34% yield. These results demonstrate how volcanic processes can enrich phosphate to fuel prebiotic chemistry.
GPT-4o mini: Non-social science research article
Strongly confined mid-infrared to terahertz phonon polaritons in ultrathin SrTiO 3
Peiyi He, Jiade Li, Cong Li, Ning Li, Bo Han, Ruochen Shi, Ruishi Qi, Jinlong Du, Pu Yu, Peng Gao
Full text
Phonon polaritons (PhPs) enable subwavelength light control for infrared sensing, imaging, and optoelectronics, but conventional polar materials have narrow Reststrahlen bands, limiting applications. Materials that support PhPs with broad spectral range, strong field confinement, slow group velocity, and high-quality factor are therefore needed. Here, using monochromatic electron energy loss spectroscopy in a scanning transmission electron microscope, we demonstrate that ultrathin SrTiO 3 membranes have the desired properties. Systematic measurements across varying thicknesses reveal two PhP branches with wide spectral dispersion, strong confinement, and exceptionally slow group velocities spanning from the mid-infrared to terahertz range. Notably, in 3-nanometer-thick membranes, these polaritons exhibit unprecedented confinement factors exceeding 500 and group velocities as low as ~7 × 10 −5 c , rivaling the best-performing van der Waals materials. These findings establish perovskite oxide such as SrTiO 3 as versatile platforms for tailoring light-matter interactions at the nanoscale, providing critical insights for the design of next-generation photonic devices requiring broadband operation and enhanced optical confinement.
GPT-4o mini: Non-social science research article
Oral delivery of aptamer-decorated SICTERS Raman probes for colonoscopy-guided resection and photothermal immunization of microtumors
Xinyi Li, Yuanyuan Qiu, Kai Cui, Wenxian Zhang, Linley Li Lin, Wei Hao, Aoxiang Luo, You Guo, Huan Liu, Wenxuan Dong, Zeyu Xiao
Full text
Endoscopic resection of colon cancer represents an advanced technique in early intervention, but faces the challenges in identifying tumor margins and removing residual lesions. Here, we developed orally administered Raman probes (i.e., BBT-Apt@CS NPs) that enable precise tumor imaging and photothermal ablation. Protected by an enteric coating for colon-targeted release, the inner nanoparticles use a stacking-induced charge transfer–enhanced Raman scattering (SICTERS) mechanism and are functionalized with tumor-targeting aptamers. In a proof-of-concept study using the endoscopic optical fiber, we achieved in situ precise detection of microtumors and effective photothermal ablation of residual lesions at the resection margins, with simultaneous induction of immune memory. In a rechallenge model, mice treated with photothermal therapy on residual lesions exhibited no tumor recurrence. We have optimized endoscopic resection strategies through theranostic Raman probes, thus providing an innovative solution for the minimally invasive precision intervention in colorectal cancer.
GPT-4o mini: Non-social science research article
miRNA-loaded biomimetic nanoparticles orchestrate gut microbe to ameliorate inflammatory bowel disease
Wenjuan Liu, Jinlong Yang, Zibo Wei, Weiwen Kong, Zirong Dong, Yuning Wei, Jie Zhuang, Jianping Qi
Full text
Modulation of gut microbiota has emerged as a promising therapeutic strategy for inflammatory bowel disease (IBD). However, current interventions such as probiotics and fecal microbiota transplantation remain limited by insufficient safety and efficacy. To address this, we engineered commensal Lactobacillus rhamnosus (LGG) using miRNA-loaded biomimetic nanoparticles to enhance its proliferation and indole-3-carboxaldehyde production. By functionalizing bacterial extracellular vesicles (BEVs) derived from LGG with lipid nanoparticles (LNPs), we developed BEV-LNPs that exhibited enhanced targeting efficiency toward LGG compared to Escherichia coli . In vitro and in vivo studies demonstrated that BEV-LNPs showed superior stability in simulated physiological fluids and gastrointestinal environments compared to conventional LNPs. When combined with 5-aminosalicylic acid, the BEV-LNP formulation notably improved outcomes in acute and chronic colitis models, reducing inflammation, restoring epithelial barrier integrity, and promoting microbial balance. This study presents an effective strategy for colitis treatment by leveraging miRNA-loaded nanoparticles.
GPT-4o mini: Non-social science research article
Yellowstone plume drives drainage reorganization in the early Miocene
Dieke Gerritsen, Stuart A. Gilder, Yi-Wei Chen, Michael R. Wack
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The rise of the Yellowstone plume coincided with a shift from orogenic collapse of the Cordillera to Basin and Range extension in the northern Rocky Mountains, yet its impact on regional uplift, sediment dispersal, and drainage patterns remains largely unexplored. Here, we present rock magnetic analyses from eight Oligo-Miocene sedimentary sections in southwestern Montana. Using two complementary datasets, we identify a sharp increase in magnetic mineral concentration immediately after the early Miocene unconformity [~20 million years ago (Ma)], concurrent with a shift in detrital zircon ages, indicating a major provenance shift. We identify bimodal volcanism of the Columbia River Basalt Group as the dominant Miocene source, requiring that the early Miocene Continental Divide lay ~400 kilometers west of its present position. This reorganization, driven by Yellowstone plume–induced uplift, persisted until at least 10 Ma. Our study provides geologically based, temporal, and spatial constraints on dynamic topography previously only estimated from modeling.
GPT-4o mini: Non-social science research article
Far-red light orchestrates antiviral defense in plants
Qian Gong, Linfang He, Fan Huang, Yunjing Wang, Jinchuan Xie, Yiguo Hong, Yule Liu
Full text
Light undergoes dramatic spectral shifts at dusk (sunset) and dawn (sunrise), enhancing insect activity and increasing the risk of insect-borne virus transmission. However, how plants respond to these light changes and associated viral threats remains unclear. Here, we show that far-red (FR) light, enriched in skylight during dusk and dawn, activates plant antiviral defense via phytochrome A (phyA). FR light-induced phyA activation promotes degradation of phytochrome interacting factor 1 (PIF1), which triggers the REVEILLE 7 (RVE7)–enhanced disease susceptibility 1 (EDS1) cascade to enhance salicylic acid (SA) signaling. Furthermore, multiple viruses use their RNA-dependent RNA polymerases to disrupt the phyA–far-red elongated hypocotyl 1 (FHY1) interaction to block phyA nuclear transport, impairing FR light–induced plant defense. Our findings uncover the molecular basis of FR light–mediated plant antiviral defense and reveal a previously unidentified viral counter-defense mechanism, highlighting how plants interpret environmental light cues to adapt to insect-borne viral infections.
GPT-4o mini: Non-social science research article
Stable electron-irradiated [1- 13 C]alanine radicals for metabolic imaging with dynamic nuclear polarization
Catriona H. E. Rooney, Justin Y. C. Lau, Esben S. S. Hansen, Nichlas Vous Christensen, Duy A. Dang, Kristoffer Petersson, Iain D. C. Tullis, Borivoj Vojnovic, Sean Smart, William Myers, Zoe Richardson, Jarrod Lewis, Brett W. C. Kennedy, Alice M. Bowen, Lotte Bonde Bertelsen, Christoffer Laustsen, Damian J. Tyler, Jack J. Miller
Full text
Dissolution dynamic nuclear polarization (dDNP) increases the sensitivity of magnetic resonance experiments by >10 4 -fold, permitting isotopically labeled molecules to be transiently visible in magnetic resonance imaging scans. dDNP mechanistically takes place at ~1 K and requires unpaired electrons and microwaves. These electrons are usually chemical radicals, requiring removal by filtration prior to injection into humans. Alternative sources, such as ultraviolet irradiation, generate lower polarization and require cryogenic transport. We present ultrahigh–dose rate electron irradiation as an alternative for generating nonpersistent radicals in alanine/glycerol mixtures. These are stable for months at room temperature, quench spontaneously upon dissolution, are present in dose-dependent concentrations, and generate comparable nuclear polarization (17%) to trityl radicals used clinically (19%) through a previously unknown mechanism we believe to involve partial ordering and electron-electron interactions. Owing to the large radiation doses required, this process is sterilizing, permits imaging of alanine metabolism in vivo in the rat kidney, and may aid clinically translating dDNP.
GPT-4o mini: Non-social science research article
High-capacity directional information processor using all-optical multilayered neural networks
Guannan Wang, Xiaofei Zang, Teng Zhang, Zhiyu Tan, Ziqing Guo, Yiming Zhu, Xianzhong Chen, Songlin Zhuang
Full text
We propose a directional-diffractive deep neural network (D-D 2 NN) by encoding the wave propagation direction into a D 2 NN, introducing a new degree of freedom and enable high-capacity information processing. The unprecedented capability of metasurfaces in controlling light propagation provides a new opportunity to realize such a D-D 2 NN. We propose and demonstrate a versatile D-D 2 NN using three spin-decoupled metasurfaces. Simultaneous control of geometric and propagation phases is used to realize direction-dependent functionality. High-capacity information processing is demonstrated by controlling the distances between neighboring metasurfaces. The efficacy of our approach is exemplified through the classification of digits and fashion products in two channels and the calculation-like function realized in four channels. Moreover, the proposed D-D 2 NN can divide rich information into multiple channels, enabling high-volume data encryption. The metasurface-enabled deep learning networks with versatile directional functionalities provide a flexible route toward massively parallel processing, pattern recognition, encryption, and artificial intelligence systems.
GPT-4o mini: Non-social science research article
Mapping structures and dynamics with frequency-correlated diffusion exchange
Sophia N. Fricke, Velencia Witherspoon, Jeremy Demarteau, Brett A. Helms, Jeffrey A. Reimer
Full text
Understanding molecular motion in diffusion-driven complex environments is critical for designing sustainable materials and improving chemical processes. Here, we introduce a multidimensional nuclear magnetic resonance (NMR) method that captures how molecular populations exchange across different dynamic regimes. By extending the modulated gradient spin-echo technique to include frequency-frequency correlations, our approach reveals diffusion pathways that are otherwise obscured in heterogeneous systems. Implemented on a unilateral NMR magnet, the method eliminates gradient pulsing constraints and accesses dynamics in the kilohertz regime. We apply this technique to swelling and acid-catalyzed deconstruction of cross-linked and linear polymers to observe how structural heterogeneity evolves over time. By linking molecular motion to topology and chemical state, we extract physical metrics such as fractal surface dimensionality and reaction wavefront velocity, properties inaccessible with standard diffusion measurements. This work expands the capabilities of NMR for probing soft matter, with implications for polymer recycling and materials design.
GPT-4o mini: Non-social science research article
Rapid cancer diagnosis using deep learning–powered label-free subcellular-resolution photoacoustic histology
Byullee Park, Rui Cao, Yilin Luo, Cindy Liu, Yushun Zeng, Yide Zhang, Qifa Zhou, Samuel Davis, Massimo D’Apuzzo, Lihong V. Wang
Full text
Traditional hematoxylin and eosin staining in formalin-fixed paraffin-embedded sections, while essential for diagnostic pathology, is time-consuming, labor intensive, and prone to artifacts that can obscure critical histological details. Label-free ultraviolet photoacoustic microscopy (UV-PAM) has emerged as a promising alternative, offering fast histology-like images without the need for traditional staining and excessive tissue preparation. However, current UV-PAM systems face challenges in achieving the high spatial resolution required for detailed histological analysis and diagnosis. To address this, we developed a subcellular-resolution UV-PAM (SRUV-PAM) system with a 240-nanometer resolution, enabled by the integration of a high numerical aperture (NA) objective lens (NA = 0.64) and the precise piezo actuators for fine scanning control. This configuration allows visualization of detailed nuclear structures. In addition, we demonstrated virtual staining of SRUV-PAM images via cycle-consistent generative adversarial networks and diagnosis of malignant and benign tumors in liver tissues via densely connected convolutional networks DenseNet-121, achieving an area under the receiver operating characteristic curve of 0.902.
GPT-4o mini: Non-social science research article
Carbon catalysts for CO 2 conversion: From carbon emissions to zero-carbon solutions
Zhenhai Xia, Huanyu Jin, Yao Zheng, Yan Jiao, Shizhang Qiao, Denny Gunawan, Rahman Daiyan, Rose Amal, Tom Lawson, Liming Dai
Full text
For millions of years, Earth’s carbon cycle remained stable, but anthropogenic emissions drive severe air pollution and climate change. Addressing this crisis necessitates innovative decarbonization strategies, where carbon catalysts emerge as an innovative solution, replacing critical minerals for zero-carbon emissions. These catalysts can be synthesized from carbon dioxide and used to convert feedstocks into valuable chemicals and fuels, reducing energy demands and emissions while promoting clean energy and green chemical production. In this review, we explore the catalytic mechanisms at the atomic scale by examining the origins and design principles of carbon catalysts for carbon dioxide conversion. A framework is proposed for the rational design of the active sites for carbon-carbon and carbon-nitrogen couplings, facilitating the production of high-value multicarbon (C 2+ ) hydrocarbons and nitrogen-containing chemicals. The potential of these catalysts to transform the energy and chemical industries is highlighted together with key challenges and further directions in carbon science toward sustainable solutions.
GPT-4o mini: Non-social science research article
3D necroprinting: Leveraging biotic material as the nozzle for 3D printing
Justin Puma, Zhen Yang, Evan Johnston, Zixin Zhang, Xiaoyi Lan, Lingzhi Zhang, Hongyu Hou, Zixin He, Ali Afify, Megan A. Creighton, Jianyu Li, Changhong Cao
Full text
Nature has long inspired engineering innovations. Recent advances in biohybrid research have taken this inspiration further by directly integrating biotic materials into engineered systems. Here we report “3D necroprinting,” a biohybrid manufacturing technique that repurposes female mosquito proboscides as high-resolution 3D printing nozzles. The mosquito proboscis, with its unique geometry, structure, and mechanics, enables printed line widths as fine as 20 ÎŒm, surpassing commercially available 36-gauge dispense tips by ~100%. The mosquito proboscis dispense tip can withstand internal pressures of approximately 60 kPa, enabling effective fluid extrusion. Demonstrated applications include high-resolution printing of complex structures such as a honeycomb structure, a maple leaf, and bioscaffolds encapsulating cancer cells and red blood cells, showcasing the versatility and capacity of 3D necroprinting. By introducing biotic materials as viable substitutes to complex engineered components, this work paves the way for sustainable and innovative solutions in advanced manufacturing and microengineering.
GPT-4o mini: Non-social science research article
Rapid fault healing from cementation controls the dynamics of deep slow slip and tremor
Amanda M. Thomas, James M. Watkins, Nicholas Beeler, Melodie E. French, Whitney M. Behr, Mark H. Reed
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Despite its status as one of the most important discoveries in geophysics, the physical mechanism(s) responsible for slow slip events (SSEs) are not well understood. Here, we synthesize observations of deep SSEs in the Cascadia Subduction Zone and argue that rapid, cohesive fault strengthening may control the dynamics of deep SSEs. Cohesive strength is frequently ignored in constitutive laws used to describe fault rheology in numerical simulations of earthquakes and SSEs alike. To demonstrate its importance, we perform and analyze a suite of petrological experiments that simulate fault healing under representative pressure and temperature conditions. We show that significant cohesive strength recovery caused by dissolution-precipitation processes occurs on timescales of just a few hours. Together, our experimental and observational results support the idea that cohesion is a key component of fault strength under SSE conditions and highlight the need for its inclusion in both future experiments and numerical models of fault slip.
GPT-4o mini: Non-social science research article
Proximity-induced chirality at the achiral conductive interface by electrical control of enantiopure ion adsorption
Po-Jung Huang, Yoshio Ando, Miuko Tanaka, Yukito Nishio, Toshiya Ideue, Kouji Taniguchi
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Chirality manipulation of materials has attracted substantial interest in a wide variety of fields in science and technology. Chiral molecular adsorption is a distinct approach for inducing chirality in achiral systems such as organic-inorganic hybrid compounds and nanomaterials. With the proximity effect of adsorbed chiral molecules on inorganic systems in mind, we demonstrate the artificial introduction of chirality to an achiral molybdenum disulfide surface by controlling the adsorption of enantiopure molecular cations via an electric double-layer transistor with chiral ionic liquids. In the electric field–induced conductive interface of molybdenum disulfide, the generation of chirality was confirmed by observing chirality-induced spin selectivity and electrical magnetochiral effect, which are different types of chirality-dependent charge-transport phenomena. The proximity-induced chirality realized in this study via ion-controlled electronics has the potential to advance an emergent academic field called “chiral iontronics” and expand the development of electrically controllable chirality-induced functionalities beyond this work.
GPT-4o mini: Non-social science research article
Targeting cancer-associated fibroblasts for real-time intraoperative tumor identification with a spray-on fluorescent probe
Riley J. Deutsch-Williams, Yuxuan Xie, Zachary Rabinowitz, Marie Goemans, Pratyaksha Wirapati, Claudio Vinegoni, Jonathan CT Carlson, Mikael Pittet, Ralph Weissleder
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Surgical tumor resection is often the only curative option for the nearly 20 million newly diagnosed patients with cancer every year. Fluorescence-guided surgery techniques are being developed in an effort to improve margin detection and surgical resection outcomes, with several systemically administered imaging agents having gained clinical approval. However, it has been challenging to overcome limited margin contrast with current approaches and to navigate procedural complexities of intravenous contrast delivery. We hypothesized that “spray-on probes” with specificity for fibroblast activation protein alpha in peritumoral fibroblasts could improve fluorescence-guided surgery, detect smaller tumors, improve imaging accuracy, and reduce the amount of times a patient is hospitalized. We show that this strategy increases achievable tumor margin contrast by 5- to 10-fold and detects even microscopic cancer deposits. These improvements have the potential to transform patient outcomes by enabling more accurate cancer surgeries, reducing the number of follow-up surgeries, and leading to personalized treatment plans.
GPT-4o mini: Non-social science research article
Benchmarking retrieval-augmented large language models in biomedical NLP: Application, robustness, and self-awareness
Mingchen Li, Zaifu Zhan, Han Yang, Yongkang Xiao, Huixue Zhou, Jiatan Huang, Rui Zhang
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To reduce hallucinations in large language models (LLMs), retrieval-augmented LLMs (RALs) retrieve supporting knowledge from external databases. However, their performance on biomedical natural language processing (NLP) tasks remains underexplored. We introduce Biomedical Retrieval-Augmented Generation Benchmark, a comprehensive evaluation framework assessing RALs across five biomedical NLP tasks and 11 datasets, using four testbeds: unlabeled robustness, counterfactual robustness, diverse robustness, and self-awareness. To improve RALs’ robustness and negative awareness, we propose a detect-and-correct strategy and a contrastive learning approach. Experimental results show that RALs generally outperform standard LLMs on most biomedical tasks, but still struggle with robustness and self-awareness, particularly under counterfactual and diverse scenarios. Our proposed methods significantly improve performance in robustness to unlabeled and counterfactual data, and increase the model’s ability to detect and avoid incorrect predictions. These findings highlight key limitations in current RALs and underscore the need for continued refinement to ensure reliability and accuracy in high-stakes biomedical applications.
GPT-4o mini: Non-social science research article
Two-photon induced coherence without induced emission
Dong-Gil Im, Seung-Yeun Yoo, Chung-Hyun Lee, Jongheon Suh, Yoon-Ho Kim
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At the heart of recent advances in quantum imaging and spectroscopy with undetected photons is the quantum optical effect known as induced coherence without induced emission. This quantum interference effect has enabled access to challenging wavelength regimes for imaging and spectroscopic applications. However, the potential of undetected photon quantum metrology, particularly the enhanced phase sensitivity offered by Fock or N00N states, has not yet been realized, as prior work focused only on single-photon phenomena. Here, we report the observation of two-photon induced coherence without induced emission. Using a two-photon Fock state, we establish quantum coherence between pairs of two-photon spontaneous emission amplitudes, resulting in a doubling of interferometric phase modulation. Specifically, we show that a phase shift ϕ applied to undetected 1016-nanometer photons leads to a 2 ϕ modulation in the detection of 632-nanometer photons. This demonstrates genuine two-photon induced coherence without induced emission and opens possibilities for quantum-enhanced phase measurements using multiphoton coherence without detecting the modulated photons.
GPT-4o mini: Non-social science research article
A ubiquitin-like protein controls assembly of a bacterial type VIIb secretion system
Gabriel U. Oka, Nathanaël Benoit, Axel Siroy, Francesca Gubellini, Esther Marza, Rémi Fronzes
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Type VII secretion systems (T7SS) are protein translocation machines crucial for virulence and bacterial competition in Gram-positive bacteria. Despite their importance, the structural basis for assembly of type VIIb secretion systems (T7SSb), a widely distributed variant in Firmicutes, remains poorly understood. We present the cryo–electron microscopy structure of the T7SSb core complex from Bacillus subtilis , revealing how the ubiquitin-like protein YukD, coordinates assembly of the secretion machinery. YukD interacts extensively with the central channel component YukB and facilitates its association with the pseudokinase YukC, forming a stable building block for channel assembly. Time-lapse microscopy and competition assays demonstrate that YukD is essential for proper T7SSb complex formation and contact-dependent bacterial killing. Our findings reveal how bacteria have adapted a ubiquitin-like protein as a structural regulator for assembling a large secretion complex.
GPT-4o mini: Non-social science research article
AI-driven discovery of dual antiaging and anti-AD therapeutics via PROTAC target deconvolution of a super-enhancer–regulated axis
Yuan Sun, Sai Liu, Long Chen, Zheng Zhou, Xin Yin, Yiting Shi, Haotian Li, Jinran Li, Yi Lu, Wei Jiang, Yongjun Zhao, Tucheng Dai, Tingting Yao, Anbo Li, Xinyu Bi, Beiyu Zhang, Xinai Shen, Zheying Zhu, Guangji Wang, Xinuo Li
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The lack of safe, durable therapeutics that act against both biological aging and Alzheimer’s disease is an unmet clinical need. To bridge this gap, we devised an artificial intelligence (AI)–enabled approach that pairs rapid compound triage with mechanistic target deconvolution. Our AI-driven screening highlighted melatonin (MLT) as a promising candidate. Serum profiling of 161 human individuals confirmed an age-related fall in circulating MLT level, while subsequent in vivo and in vitro experiments showed that MLT rescues cognition, suppresses neuroinflammation, and alleviates senescence phenotypes. Proteolysis targeting chimera (PROTAC)–guided chemoproteomic deconvolution next pinpointed the histone acetyltransferase p300 as MLT’s target. Integrated Cleavage Under Targets and Tagmentation, single-cell RNA sequencing, and spatial transcriptomics revealed that MLT-bound p300 cooperates with specificity protein 1 (SP1) at a brain and muscle ARNT-like protein 1 super-enhancer, elevating histone H3 lysine-27 acetylation and reengaging a circadian-epigenetic program that links redox resilience to neuroprotection. By combining AI-driven discovery with PROTAC-based target mapping and super-enhancer–centric mechanistic resolution, our study identifies MLT as a dual-action candidate and sets out a reproducible “AI-to-clinic” paradigm for multitarget drug innovation in aging-related neurodegeneration.
GPT-4o mini: Non-social science research article
High-strength and fracture-resistant ionogels via solvent-tailored interphase cohesion in nanofibrous composite networks
He Zhang, Wenbin Jia, Mingze Sun, Yuxiang Chen, Xiaoyi Zhang, Hao Li, Xingdao He, Peng Shi, Lizhi Xu
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Ionogels are promising for soft robotics, energy systems, and bioelectronic interfaces due to their high ionic conductivity and environmental stability. However, combining high strength and fracture resistance remains challenging. Here, we report composite ionogels with outstanding mechanical strength (~65.4 megapascal) and fracture energy (~607 kilojoules per square meter), capable of bearing more than 5000 times their own weight. These ionogels are developed by tailoring solvent-solute interactions to create a dense, hyperconnected nanofibrous polymer network. Solvent engineering regulates hydrogen bonding competition, facilitating the formation of robust interphase hydrogen bonds and a soft-hard biomimetic interface. Moreover, their antidrying, breathable nature enables multifunctional electrophysiological monitoring, making them ideal for wearable bioelectronics. Their ionic conductivity, drug-loading capacity, and antibacterial properties allow their use in advanced e-bandages for chronic wound healing. This generalizable strategy for ionogel design opens pathways toward strong, versatile, and biocompatible materials, particularly valuable for next-generation soft materials, wearable electronics, and tissue engineering.
GPT-4o mini: Non-social science research article
Single coadministration of erythrocyte-uricase conjugate and immunosuppressant induces durable immune tolerance for gout therapy
Xiaoqian Nie, Yuehua Liu, Xingyun Yao, Chaohao Wu, Xiaofei Gao
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Uricase (UOX) is effective for treating refractory gout but is limited by antidrug antibody (ADA) formation, which leads to loss of efficacy and infusion reactions. Here, we demonstrate that a single coadministration of erythrocyte-conjugated UOX (UOX-Ery) with an immunosuppressant such as cyclophosphamide (CTX) induces robust and durable antigen-specific immune tolerance. This one-time intervention effectively prevented ADA formation in mice and rats, even after repeated challenges with UOX-Ery or free UOX protein, an outcome not achieved by CTX or UOX plus CTX. This tolerogenic effect relied on splenic uptake of UOX-Ery by myeloid cells, particularly macrophages, and was associated with the expansion of a distinct subset of effector regulatory T cells. Functionally, this immune tolerance enhanced the pharmacokinetics of UOX, sustained long-term control of serum uric acid levels, and attenuated local inflammation within tophus-like lesions. Together, these findings demonstrate that UOX-Ery, combined in a single dose with clinically used immunosuppressants, can effectively treat gout by inducing antigen-specific immune tolerance.
GPT-4o mini: Non-social science research article
Directed self-assembly of 3D interconnected networks
Mingchao Ma, Guillermo A. HernĂĄndez-Mendoza, Baopu Zhang, Zehao Sun, Alfredo Alexander-Katz, Caroline A. Ross
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Directed self-assembly (DSA) of block copolymers (BCPs) has long been included in the semiconductor roadmap as a lithographic pathway to enable continued device scaling. Tremendous progress has been made in generating two-dimensional (2D) BCP patterns with device-relevant features and low defect density and in transferring these patterns to functional materials. Extension of pattern generation into 3D could markedly enhance the utility of BCPs in nanoscale manufacturing, but methods to template and synthesize well-ordered, nontrivial 3D structures are less well developed. Here, we demonstrate a hierarchical DSA method to generate cross-point structures with connected in-plane and out-of-plane segments and controlled orientation angle between the horizontal layers. Various highly ordered, 3D interconnected networks, including ladder and cross-point structures, are produced by combinations of surface modification, BCP periodicity, and topographic templates, expanding the capabilities of BCP-derived nanofabrication.
GPT-4o mini: Non-social science research article
Toward human-resolution haptics: A high-bandwidth, high-density, wearable tactile display
Sylvia Tan, Michael A. Peskhin, Roberta L. Klatzky, J. Edward Colgate
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Despite advances in digitizing vision and hearing, touch still lacks an equivalent digital interface matching the fidelity of human perception. This gap limits the quality of digital tactile information and the realism of virtual experiences. Here, we introduce a step toward human-resolution haptics: a class of wearable tactile displays designed to match the spatial and temporal acuity of the human fingertip. Our device, VoxeLite, is a 0.1-millimeter-thick, 0.19-gram, skin-conformal array of individually addressable soft electroadhesive actuators (“nodes”). As users touch and move across surfaces, VoxeLite delivers high-resolution distributed forces via the nodes. Enabled by scalable microfabrication techniques, the display achieves actuator densities up to 110 nodes per square centimeter, produces stimuli up to 800 hertz, and remains transparent to real-world tactile input. We demonstrate its ability to render small-scale hapticons and virtual textures and transmit physical surfaces, validated through human psychophysics and biomimetic sensing. These findings position VoxeLite as a platform for human-resolution haptics in immersive interfaces, robotics, and digital touch communication.
GPT-4o mini: Non-social science research article
Selective AMPKÎČ1 activation induces fetal hemoglobin in human erythroid cells and sickle cell mice via the noncanonical NRF2 pathway
Yannis Hara, Viktor T. Lemgart, Samuel Lessard, Courtney J. Mercadante, Jean-Antoine Ribeil, Alexandra Hicks, Pauline Rimmele, David R. Light
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Sickle cell disease (SCD), an inherited blood disorder caused by mutation of the ÎČ-globin gene, results in sickle-shaped erythrocytes, organ damage, and increased mortality. Current therapeutic options are limited, and innovative treatments to induce fetal hemoglobin (HbF) are needed. Adenosine monophosphate–activated protein kinase (AMPK) comprises a family of 12 isoforms. In the present study, single-cell RNA sequencing of bone marrow cells revealed that AMPKÎČ1 isoform (AMPKα1ÎČ1Îł1) predominates in the erythroid lineage. AMPKÎČ1 activators increased the expression of HbF in erythroid cells from SCD donors and decreased sickling in vitro through activation of nuclear factor erythroid 2–related factor 2 (NRF2) but independently from direct Kelch-like ECH-associated protein 1 (KEAP1) inhibition, by way of a noncanonical NRF2 pathway, as shown by phosphorylation of Unc-51–like autophagy-activating kinase 1 (ULK1) and sequestosome 1/p62 (SQSTM1). In vivo studies in Townes SCD mice treated with the selective AMPKÎČ1 activator PF-06409577 confirmed increased HbF in circulating erythrocytes, associated with decreased reactive oxygen species and reduced chronic inflammation markers. Collectively, these findings establish selective AMPKÎČ1 activation as a promising therapeutic approach to induce HbF in hemoglobinopathies.
GPT-4o mini: Non-social science research article
A striosomal accumbens pathway drives stereotyped behavior through an aversive Esr1+ hypothalamic-habenula circuit
Thomas Contesse, Buse Yel Bektash, Marta Graziano, Chiara Forastieri, Alessandro Contestabile, Salome Hahne, Felix Jung, Ifigeneia Nikolakopoulou, Eleonora Rubino, Xiao Cao, Vasiliki Skara, Ioannis Mantas, Sarantis Giatrellis, Marie Carlén, Rickard Sandberg, Daniela Calvigioni, Konstantinos Meletis
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The lateral hypothalamic area (LHA) integrates external stimuli with internal states to drive the choice between competing innate or value-driven motivated behaviors. Here, we define a striosomal Tac1+/Tshz1+/Oprm1+ neuron subtype in the nucleus accumbens (ACB) that targets Esr1+ LHA neurons that project to the lateral habenula (LHb). Intersectional cell type–specific and input-output defined optogenetic activation of this ACB-LHA-LHb pathway can progressively induce a negative behavioral state that depends on Esr1+ LHA-LHb neural activity. We found that either activation of the D1+ ACB-LHA projection or inhibition of LHA-LHb neurons defined by ACB inputs can drive reward-independent compulsive-like behaviors that generalize across contexts. We found that these complex yet stereotyped behaviors compete with highly motivated states and can override the drive for natural rewards or social interactions. Our findings reveal a discrete Tac1+ striosomal ACB projection targeting the aversive Esr1+ LHA-LHb pathway as a key circuit that promotes stereotyped and compulsive-like behaviors over goal-directed actions.
GPT-4o mini: Non-social science research article
Capturing aberrant cell behaviors producing defects in human embryos via live imaging
Hiroki Akizawa, Ana Domingo-Muelas, Maria Pardo-Figuerez, Blake Hernandez, Goli Ardestani, Robin M. Skory, Marta Venturas, Piotr Tetlak, Stephanie Bissiere, Denny Sakkas, Carlos Simon, Nicolas Plachta
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The generation of human embryos in vitro has revolutionized reproductive medicine, and also made it possible to study fundamental aspects of early human development. However, human preimplantation embryos often display an array of morphological defects associated with poor development and implantation. Here, we used live-embryo imaging and computational analysis to capture how these defects can be produced in real time. We record various forms of mitotic errors including lagging chromosomes producing micronuclei, multipolar spindles causing abnormal chromosome organization recapitulated by daughter cells, and uncontrolled scattering of condensed chromosomes. In addition, we capture abnormal cleavage furrow dynamics during cytokinesis producing binucleated and enucleated cells. Finally, we find cells with disrupted mitotic progression ultimately leading to blebbing and fragmentation. Thus, these results document specific aberrant cell behaviors producing morphological defects in real time, and indicate that errors during mitosis and cytokinesis represent a major cause of developmental failures in human embryos.
GPT-4o mini: Non-social science research article
Antigen-specific B cell response regulation by IL-10–producing tolerogenic dendritic cells
Konstantina Morali, Juulke Steuten, Fabio Russo, Francesca Romana Santoni de Sio, Charlotte Menage, Valentina Consoli, Andrea Annoni, Silvia Iaia, S. Marieke van Ham, Anja ten Brinke, Silvia Gregori
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B cells regulate immune responses via antibody production and antigen (Ag) presentation. Although B cell depletion is used therapeutically, it may be associated with side effects, highlighting the need for alternative B cell–targeted approaches. While tolerogenic dendritic cells (tolDC) are known to modulate T cell responses, their impact on B cells is poorly defined. We show that IL-10–producing tolDC (DC IL-10 ) regulate B cell responses through direct and indirect mechanisms. DC IL-10 enhances T cell–independent human B cell proliferation and differentiation while suppressing Ag-specific memory B cells via T cell inhibition in vitro and dampen Ag-specific IgG production in preclinical humanized and murine models. These findings reveal a dual mechanism by which DC IL-10 regulates B cell responses, broadening their application as a cell-based approach to treating immune-mediated diseases by targeting both B and T cells.
GPT-4o mini: Non-social science research article
Single atom–cluster synergy in Ag catalysts enables chiral glyceric acid from biomass
Shuguang Xu, Jianmei Li, Jiong Cheng, Ruoyu Li, Xiaoyan Wang, Shengqi Liao, Huaqing Yang, Changwei Hu, Ning Yan
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Accessing optically pure chemicals directly from biomass via chemical catalysis remains challenging because of the need for high selectivity across complex, multistep transformations. Here, we report a robust silver-based catalyst featuring synergistic single atoms and nanoclusters that function as complementary active sites in the anaerobic oxidative carbon-carbon cleavage of bio-derived feedstocks. This catalyst enables the production of optically pure glyceric acid from a broad range of biomass sources including raw biomass with unprecedented yield (59 to 96%) and enantiomeric excess (97 to >99%). Structural and mechanistic studies reveal that silver clusters, stabilized by surface oxygen vacancies, activate dioxygen through π-backbonding, while electron-deficient silver single atoms preferentially bind the chiral substrate via ionic interactions, increasing the energy barrier for mutarotation and preserving its stereochemical identity. Oxygen spillover between the two sites facilitates precise oxidative Cα–CÎČ bond cleavage. Together, these features overcome the longstanding dual challenges of low productivity and poor enantioselectivity in chemocatalytic biomass upgrading.
GPT-4o mini: Non-social science research article
Conserved CD8 T cell vaccines without B cell epitopes drive robust protection against SARS-CoV-2 that is enhanced by intranasal boost
Genghao Chen, Thao Nguyen, Lindsay G. A. McKay, Sravya Sowdamini Nakka, Pan Hu, Julia McBride, Anthony C. Liang, Rachel Olson, James J. Moon, Andrew D. Luster, Anthony Griffiths, Stephen J. Elledge
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The emergence of SARS-CoV-2 variants has challenged the current spike protein–focused COVID-19 vaccine strategy due to neutralizing antibody escape and waning antibody-mediated immunity. In contrast, T cell–mediated immunity targeting conserved epitopes may offer broad and long-lasting protection. However, whether T cells alone can provide sufficient protection remains unclear. Here, we identified both Omicron BA.1–specific and ancestral (Wuhan)–conserved CD8 T cell epitopes in the SARS-CoV-2 spike protein and evaluated them as carrier-protein fusion vaccines in mouse models. Subcutaneous immunizations with two CD8 epitope peptides substantially lowered lung viral load and conferred protection against low-dose viral challenge, but not against high-dose challenge. Notably, intranasal boosting—with or without adjuvant—enhanced lung resident memory T cell responses and conferred potent, durable protection against high-dose infection. These findings emphasize the importance of mucosal vaccination to boost protective T cell immunity against SARS-CoV-2 and support the potential of T cell–based vaccines targeting conserved epitopes for broad immunity against SARS-CoV-2 and other respiratory viral threats.
GPT-4o mini: Non-social science research article
The nonfibrillar multiplexin collagen CLE-1 defines cholinergic synapse identity
Melissa Cizeron, Anaïs Dumas, Suzanne Le Reun, Laure Granger, Maëlle Jospin, Oceane Romatif, Camille Vachon, Delphine Le Guern, Aurore-Cecile Valfort, Jean-Louis Bessereau
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Fast neurotransmission requires the coordinated localization of neurotransmitter receptors opposite presynaptic release sites, which usually relies on the transsynaptic interaction of synaptic adhesion molecules. However, some extracellular proteins have been shown to coordinate pre- and postsynaptic differentiation by more elusive mechanisms. Here, we identify the nonfibrillar collagen CLE-1, a member of the evolutionarily conserved multiplexin family, as a master determinant of synapse identity in Caenorhabditis elegans . C. elegans muscle cells are innervated by both cholinergic and GABAergic motoneurons. The CLE-1B isoform is secreted by motoneurons and localizes to neuromuscular junctions. Loss of CLE-1B causes the relocalization of acetylcholine receptors to GABAergic synapses. We show that CLE-1B positions previously unidentified proteolytic fragments of the extracellular scaffold Punctin/MADD-4 to align acetylcholine receptors with cholinergic terminals and independently modulates receptor abundance. These findings reveal CLE-1 as a dual-function synaptic organizer that integrates spatial and quantitative control of postsynaptic receptor localization to maintain synapse identity.
GPT-4o mini: Non-social science research article
A rapid self-healing polymer mediated by ion aggregates achieves effective encapsulation of sustainable perovskite solar cells
Shuangjie Wang, Tiejun Xin, Yi Zhao, Wenjun Liu, Laju Bu, Xuanhua Li, Guanghao Lu
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Despite the rapid progress of perovskite solar cells (PSCs) toward commercialization, perovskite layers are unstable and contain toxic lead. Encapsulation represents an efficient strategy for improving the stability of PSCs as well as suppressing lead leakage. However, the damage to encapsulation materials during outdoor applications inevitably deteriorates the packaging effect and increases lead leakage. Here we report a damage perception and rapid self-healing encapsulant consisting of alkoxy polyvinylimidazole bis(trifluoromethanesulphonyl)imide (EP). The dynamic ion aggregates in the encapsulant can easily drive the molecular chain movement of EP, thereby achieving rapid damage repair to maintain device stability and inhibit lead leakage. The damaged cracks of EP completely self-heal within 6 minutes at 50°C. The EP encapsulated devices exhibit a lead sequestration efficiency of more than 99% under poor weather. After 1500 hours of damp heat test and 300 thermal cycles, the EP encapsulated devices retain 95.17 and 93.53% of their initial efficiency, respectively.
GPT-4o mini: Non-social science research article
Gene-scale in vitro reconstitution reveals histone acetylation directly controls chromatin architecture
Yohsuke T. Fukai, Tomoya Kujirai, Masatoshi Wakamori, Setsuko Kanamura, Lisa Yamauchi, Somayeh Zeraati, Satoshi Morita, Chiharu Tanegashima, Mitsutaka Kadota, Mikako Shirouzu, Hitoshi Kurumizaka, Takashi Umehara, Kyogo Kawaguchi
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Understanding how epigenetic modifications intrinsically shape gene-scale chromatin architecture remains challenging due to difficulties in reconstituting and characterizing sufficiently long arrays with defined modification patterns. Here, we overcome this barrier by reconstituting 20-kilobase (96-nucleosome) chromatin arrays with modification patterns precisely controlled at 12-nucleosome resolution. Single-molecule microscopy reveals the dynamics governed by hydrodynamic interactions, demonstrating that increasing histone H4 acetylation density enhances structural fluctuations and relaxation times. In vitro Hi-C reveals power-law decay of the nucleosome contacts consistent with the Gaussian chain, which is globally reduced by acetylation. We also observe that heterogeneous modification patterns alone are sufficient to create distinct structural domains reminiscent of higher-order chromatin organization. These findings establish how histone modifications modulate chromatin architecture via changes in local stiffness and nucleosome interactions, providing a quantitative framework for genome organization.
GPT-4o mini: Non-social science research article
3D bioprinted human-scale intestine models for physiological and microbial insights through fluid-driven heterogeneity
Ziqi Gao, Huilong Du, Shuyuan Yu, Qi Li, Ruiqi Shi, Zengliang Jiang, Huayong Yang, Luqi Shen, Hongzhao Zhou
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The small intestine’s intricate structure enables vital functions such as nutrient absorption, microbial defense, and barrier protection, yet replicating its complexity in vitro remains a substantial challenge. We engineered a three-dimensional bioprinted intestinal model featuring biomimetic circular folds and zonated shear stress distribution to recapitulate native physiology. A filament-resolved embedded bioprinting approach enabled high-fidelity fabrication of thin-walled, continuous structures that shaped physiologically relevant flow microenvironments essential for epithelial development. These shear stress patterns regulated tight junctions, secretory activity, and transporter expression, driving region-specific epithelial specialization into barrier or absorptive phenotypes. Coculture with probiotic Lactobacillus plantarum activated localized immune responses and modulated epithelial function through spatially distinct colonization. Regional flow differences governed the transport of nutrient and drug probes via transcellular and paracellular pathways. Quantitative assessment of drug absorption demonstrated strong in vitro–in vivo correlation, validating physiological relevance. By unifying structural, mechanical, and functional complexity, this platform advances intestinal models for studying physiology, host-microbe interactions, and drug transport.
GPT-4o mini: Non-social science research article
Experimental characterization of complex atmospheric flows: A wind turbine wake case study
Nikolas Angelou, Mikael Sjöholm, Torben Krogh Mikkelsen
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Our current understanding of the interaction between the atmosphere and surface obstacles crucial for boundary-layer meteorology, forestry, urban climate, wind engineering, and wind energy is limited mainly to observations acquired in wind tunnel experiments and flow predictions from computational fluid dynamic models. Here, as a case study, we present spatially distributed measurements of a utility-scale wind turbine’s wake using three wind lidars that synchronously scan a volume of the atmosphere. The results reveal not only information of the mean wake flow generated by a wind turbine, such as the distribution of the velocity deficit and its spatial gradients, but also observations of the momentum fluxes that control the interaction between the wake and the surrounding atmospheric flow, which is essential for optimizing wind energy production. The presented remote sensing methodology represents a paradigm shift for atmospheric field studies, enabling unprecedented flow observations.
GPT-4o mini: Non-social science research article
Double-sided annealing to reverse the crystallization direction for efficient and stable flexible FACs-perovskite solar modules
Yuqin Zou, Kyoungwon Choi, Haoliang Wang, He Liu, Haoyang Jiao, Chuanhang Guo, Jinsong Huang
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The application of methylammonium cations makes flexible perovskite solar modules ( f -PSMs) unstable in long term. Here, we report flexible p-i-n structure perovskite modules made of methylammonium-free formamidinium cesium lead iodide (FA 1− x Cs x PbI 3 , x  ≀ 0.1) to improve their stability. Interfacial voids between FA 1− x Cs x PbI 3 layer and hole-transport layers, caused by the limited annealing temperature for f -PSMs, severely disrupt the film structural continuity. A double-sided annealing strategy is used to address this challenge, which markedly reduces the voids at the buried interface and yields homogeneous perovskite films with enlarged grains. The double-sided annealing can flip the phase transition direction from traditional top-down to bottom-up, because of the much higher air temperature above perovskite films, allowing a quick dimethyl sulfoxide evaporation. The f -PSMs achieve an aperture-area power conversion efficiency (PCE) of 19.1% and show ~10% efficiency loss after 107 thermal cycles between −40° and 85°C. The small-area devices retained over 98% of their initial PCE after 1176 hours under one Sun illumination at 85°C.
GPT-4o mini: Non-social science research article
Heterogeneous integration of ultrawide bandgap semiconductors for radio frequency power devices
Hong Zhou, Min Zhou, Mingjie Xiang, Hehe Gong, Guangjie Gao, Chenlu Wang, Yachao Zhang, Kui Dang, Zhihong Liu, Jinfeng Zhang, HangMing Zhang, Yifan Wang, Han Wang, Mengwei Si, Yuhao Zhang, Yue Hao, Jincheng Zhang
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Ultrawide bandgap (UWBG) semiconductors offer high critical electric fields and saturation velocities ideal for radio frequency (rf) devices, but achieving both shallow-level doping and high thermal conductivity ( k T ) in a single material remains difficult. We demonstrate a scalable, exfoliation-based layer-transfer process to heterogeneously integrate gallium oxide (Ga 2 O 3 ) thin films with shallow dopants onto high- k T aluminum nitride (AlN) substrates. This method obviates ion implantation and interfacial dielectric layers used in conventional approaches. A large conduction band offset (3.4 electron volts) at the Ga 2 O 3 /AlN interface improves electron confinement in the Ga 2 O 3 channel. T-gate rf power transistors achieve a maximum oscillation frequency of 90 gigahertz and output power densities of 4.6 watts per millimeter at 2 gigahertz and 4.1 watts per millimeter at 6 gigahertz—among the highest for UWBG devices. A minimal noise figure of 0.48 decibels at 8 gigahertz—among the lowest reported in this frequency range—further highlights the platform’s promise for next-generation rf applications.
GPT-4o mini: Non-social science research article
Mitochondrial NAD + gradient sustained by membrane potential and transport
Shivansh Goyal, Scott N. Lyons, Xiaolu A. Cambronne
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SLC25A51 is required for the replenishment of free nicotinamide adenine dinucleotide (oxidized form) (NAD + ) into mammalian mitochondria. However, it is not known how SLC25A51 imports this anionic molecule to sustain elevated NAD + concentrations in the matrix. Understanding this would reveal regulatory mechanisms used to maintain critical bioenergetic gradients for cellular respiration, oxidative mitochondrial reactions, and mitochondrial adenosine triphosphate (ATP) production. In this work, mutational analyses and localized NAD + biosensors revealed that the mitochondrial membrane potential (Διm) works in concert with charged residues in the carrier’s inner pore to enable sustained import of NAD + against its electrochemical gradient into the matrix. Dissipation of the Διm or mutation of select residues in SLC25A51 led to equilibration of NAD + from the matrix. Corroborating data were obtained with the structurally distinct mitochondrial NAD + carrier from Saccharomyces cerevisiae ( Sc Ndt1p) and mitochondrial ATP transport suggesting a shared mechanism of charge compensation and electrogenic transport in these mitochondrial carrier family members.
GPT-4o mini: Non-social science research article
Porcine airway tissue explant culture at a hydrogel-air interface to model submucosal glands in cystic fibrosis progression and therapy
Kaleb C. Bierstedt, Meng-Hsuan Lin, Wenjie Yu, Ashley L. Cooney, Brian J. Goodell, Huiyu Gong, Alejandro A. Pezzulo, Patrick L. Sinn, Yuliang Xie
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Submucosal glands (SMGs) are critical for airway health; however, replicating their complex structure and function outside the body remains challenging. Here, we establish a method of airway tissue explant culture at a hydrogel-air interface (i.e., AirTECH) using trachea from newborn pigs. After 14 days, AirTECH tissues maintain their natural SMG structures, cell types, gene expression, and defense functions, along with intact surface epithelia, smooth muscle, and cartilage. Using AirTECH tissue as a model, we evaluated SMGs in cystic fibrosis (CF) airway disease progression, where exposure to lipopolysaccharide of Pseudomonas aeruginosa caused abnormal mucus obstruction and overexpression of MUC5AC in SMGs, a characteristic feature of CF airway disease. We also explored the contribution of SMGs in airway gene therapy, where green fluorescent protein–encoding adenovirus vectors were transduced and expressed exclusively in airway surface epithelia but not SMGs. These data support AirTECH as a model to understand SMGs in airway disease and test therapeutic interventions.
GPT-4o mini: Non-social science research article
Transition of pseudorabies virus from latency to reactivation state selectively triggered by pathogenic bacteria
Dan Yang, Miao Yang, Shibang Guo, Huihui Guo, Yafei Li, Yan Kuang, Hang Li, Yibo Zhang, Siyi Zhang, Qingyun Liu, Huanchun Chen, Xiangru Wang
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Pseudorabies virus (PRV) causes severe morbidity and mortality in pigs and must be eradicated from pig populations. The increasing PRV infections in humans—resulting in severe encephalitis, neurological sequelae, and death since 2017 in China—have also posed a public health risk. PRV can establish latency in pigs, potentially leading to disease outbreaks upon reactivation. However, little is known about the PRV reactivation process, particularly in cases with other pathogens coinfection. We found that extraintestinal pathogenic Escherichia coli and Streptococcus suis , common zoonotic bacteria found in pigs, can trigger PRV reactivation, and bacteria up-regulated CXCL1 to enhance STAT3 phosphorylation and nuclear translocation, which triggers PRV reactivation by regulating the transcription of early viral genes. Effective booster immunization significantly reduced PRV reactivation among pigs. Our work highlights the risk of bacterial coinfections on PRV reactivation, emphasizing the importance of adequate immunization for controlling PRV within pigs and reducing zoonotic transmission.
GPT-4o mini: Non-social science research article
Forecast attribution reveals enhanced heat mortality from climate change in British Columbia heatwave
Chin Yang Shapland, Y. T. Eunice Lo, Nicholas J. Leach, Éric Lavigne, Kate Tilling, Dann M. Mitchell
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In 2021, Canada experienced one of the most extreme heatwaves ever seen anywhere on the globe. We use a weather forecast model to attribute health impacts to climate change. We simulate the heatwave as a present-day forecast, a preindustrial-counterfactual scenario, and a future-counterfactual scenario. Despite the extremeness of the event, our analysis shows that, under current climate conditions, we could have still seen up to 30% more heat-related deaths than the number observed. We show that between 11 and 15% of the observed human mortality was attributable to climate change during this event, depending on the conditioning of the atmospheric circulation. We also show that, had “the same event” occurred in the future, the mortality toll is nonlinear compared with the warming trend, and so the future attribution would be even more extreme, 16 to 31%. We argue that this method gives particularly reliable impact attribution results and is therefore strongly defensible in decision-making and legal settings.
GPT-4o mini: Non-social science research article
Visualizing the strong field–induced molecular breakup of C 60 via x-ray diffraction
Kirsten Schnorr, Sven Augustin, Ulf Saalmann, Georg Schmid, Arnaud RouzĂ©e, Razib Obaid, Andre AlHaddad, Nora Berrah, Cosmin I. Blaga, Christoph Bostedt, Manuel Cardosa-Gutierrez, Gabriella Carini, Ryan Coffee, Louis F. DiMauro, Philip Hart, Yuta Ito, Katharina Kubicek, Yoshiaki Kumagai, Jochen KĂŒpper, Yu Hang Lai, Hannes Lindenblatt, Ruth A. Livingstone, Severin Meister, Robert Moshammer, Koji Motomura, Thomas Möller, Kaz Nakahara, Timur Osipov, Gaurav Pandey, Dipanwita Ray, Francoise Remacle, Daniel Rolles, Jan Michael Rost, Ilme Schlichting, RĂŒdiger Schmidt, Simone Techert, Florian Trost, Kiyoshi Ueda, Joachim Ullrich, Marc J.J. Vrakking, Julian Zimmermann, Claus Peter Schulz, Thomas Pfeifer
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Laser-driven dynamics in polyatomic molecules poses a complex many-body problem. Understanding intense light-matter interaction is crucial for steering intramolecular quantum dynamical processes. Here, we record time-resolved x-ray diffraction images of C 60 molecules during and after their interaction with intense near-infrared fields, giving direct access to structural changes of the molecules and their fragmentation in real time. Tuning the intensity of the excitation pulses, we uncover a transition from a weak-field regime of excited but stable molecules to a high-field regime dominated by Coulomb explosion. In the transition region, the molecules expand by up to 50% of their initial size within just 140 fs, with major fragmentation only setting in afterward. This work demonstrates that x-ray diffractive imaging is capable of retrieving time-resolved structural information of large molecules reshaped by intense laser fields. Laser-driven fragmentation is a first step toward observing molecular processes modified by laser fields of increasing intensity.
GPT-4o mini: Non-social science research article
Discovering the dual degradation pathway of emerald green in oil paints: The effects of light and humidity
Sara Carboni Marri, Letizia Monico, Francesca Rosi, Costanza Miliani, Riccardo Vivani, Koen Janssens, Steven De Meyer, Olivier Mathon, Marine Cotte, Manfred Burghammer, Jan Garrevoet, Gerald Falkenberg, Ermanno Avranovich Clerici, Annelies Rios-Casier, Geert Van der Snickt, Aldo Romani
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Emerald green, a copper acetoarsenite pigment, enriched the 19th-century and 20th-century artists’ palettes and caused darkening and fragilities in paintings. The accepted alteration mechanism involves the oxidation of triarsenite ions [(As 3 O 6 ) 3− ] to arsenates (AsO 4 3− ), although questions about the promoting factors and the origin of the oxidized arsenic remain unanswered. This study investigates the primary environmental parameters inducing alteration in the oil binder and elucidates the associated degradation pathways through a multiscale analytical approach, including noninvasive spectroscopic techniques and synchrotron radiation–based x-ray methods. By combining results from a historical oil painting by James Ensor (1860 to 1949) and artificially aged paint mock-ups, we identified ultraviolet A–visible light and humidity (relative humidity ≄ 95%) as key driving factors, inducing a dual degradation pathway: Light promotes surface-stratified arsenic oxidation (As 3+  → As 5+ ) resulting in amorphous As 5+ -rich compounds, whereas a dark, high moisture environment favors arsenolite (As 2 O 3 ) crystallization. In addition, a noninvasive analytical strategy is proposed for monitoring the conservation state of emerald green paints in historical artworks.
GPT-4o mini: Non-social science research article
Renal clearable CRISPR nanosensor targeting mitochondrial DNA mutation for noninvasive monitoring of tumor progression and metastasis
Yanan Li, Yonghua Wu, Ziyue Zheng, Yige Wu, Yongyuan Zhang, Jingjing Zhang, Fenglei Quan, Wen Zhao, Ru Xu, Yiwei Li, Hua Gao, Kaixiang Zhang
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Mitochondrial DNA (mtDNA) mutations are emerging as important molecular features of tumorigenesis. Liquid biopsies, involving analysis of cell-free mtDNA, enable early cancer detection but suffer from low sensitivity due to scarce analytes. Here, we developed a CRISPR/Cas12a-mediated urinary biomarker, termed CasUber, for in vivo monitoring of tumor progression and metastasis. Our results demonstrate that CasUber can deliver a CRISPR detection system into tumor cell mitochondria, leverage the single-nucleotide variant recognition ability and trans-cleavage activity of Cas12a to convert tumor-specific mtDNA mutations into renal-clearable fluorescent biomarkers, and exocytosed along with the natural efflux pathway of damaged mtDNA. As a result, CasUber enables discrimination of ultrasmall tumor lesions (~1 cubic millimeter) and detection of lung tumor nodules earlier than bioluminescence imaging in a blood-lung metastasis model. This renal clearable nanosensor allows in situ recognition of specific gene mutation to generate amplified signals, overcoming the limitation of low mtDNA abundance and enabling noninvasive and ultrasensitive monitoring of tumor progression and metastasis via a simple urine test.
GPT-4o mini: Non-social science research article
Activating PEG host to enable spatially controlled surface functionalization of nanocarriers for biomedical applications
Mingchen Sun, Wei Li, Shaohua Zhang, Daniela A. Wilson
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Surface functionalization with biomolecules transforms nanocarriers by integrating a range of bioderived functionalities; however, conventional methods often yield low efficiency and uneven ligand distribution, and compromise the structural integrity of nanocarriers. Here, we introduce a breakthrough approach that activates the traditionally inert PEG corona, enabling precise and spatially controlled functionalization of nanocarriers with biologically relevant entities. Using fluorescence resonance energy transfer (FRET) between pyrene and FITC, we confirm accurate spatial distribution of ligands. Our method achieves exceptional efficiency and stability, maintaining over 40% of functional molecules across three cycles of washing and resuspension under various aqueous conditions. In vitro assays reveal high biological efficacy, with engineered polymersomes supporting targeted cellular interactions. Functionalization with diverse ligands introduces specific biological functionalities, including mitochondrial targeting, cell migration stimulation, and enhanced receptor-mediated endocytosis. This rapid, efficient, and user-friendly strategy for PEG surface functionalization heralds remarkable advances in nanomedicine and biomaterials.
GPT-4o mini: Non-social science research article
A synthesized framework for the evolutionary origins of avian obligate brood parasitism
Nan Lyu, Xiaoyuan Wu, Yang Zhang, Bo-Wen Zhang, Wei Liang
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The repeated evolution of avian obligate brood parasitism (OBP) across diverse lineages represents a major evolutionary puzzle. While host-parasite coevolution has been extensively studied, the initial conditions favoring OBP emergence remain unclear. Here, we integrate theoretical modeling, paleoclimate mapping, and phylogenetic comparative analyses to identify the key drivers underlying OBP evolution. Our model shows that rising parental care costs, particularly under environmental stress, may favor the emergence of OBP. However, its persistence requires additional life-history adaptations, including increases in fecundity (egg production). Paleoclimatic data support this framework: OBP origins often followed major climatic upheavals with fixations occurring during subsequently more stable periods. Phylogenetic analyses reveal that OBP is associated with high-mortality ecological traits, such as open-habitat use. We also find increased OBP likelihood in both smaller carnivorous and larger herbivorous/omnivorous species, indicating size-dependent trophic constraints. These results provide a unified framework explaining the recurrent evolution of OBP by linking environmental pressures and life-history trade-offs to this remarkable behavioral adaptation.
GPT-4o mini: Non-social science research article
Magnetically responsive nanocultures for direct microbial assessment in soil environments
Huda Usman, Mehdi Molaei, Stephen D. House, Martin F. Haase, Cindi L. Dennis, Tagbo H. R. Niepa
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Cultivating microorganisms in native-like conditions is vital for bioprospecting and accessing now unculturable species. However, there remains a gap in scalable tools that can both mimic native microenvironments and enable targeted recovery of microbes from complex settings. Such approaches are essential to advance our understanding of microbial ecology, predict community functions, and discover previously unidentified biotherapeutics. We present magnetic nanocultures—a high-throughput microsystem for isolating and growing environmental microbes under near-native conditions. These nanoliter-scale bioreactors are encapsulated in semipermeable membranes that form magnetic polymeric microcapsules using iron oxide nanoparticles within polydimethylsiloxane-based shells. This design offers mechanical stability and magnetic actuation, enabling efficient retrieval from soil-like environments. The nanocultures are optimized for optical and biological properties to support microbial encapsulation, growth, and sorting. Our study demonstrates the feasibility of using magnetically responsive microenvironments to cultivate elusive microbes, offering a promising platform for bioprospecting previously uncultured or unknown microbial species.
GPT-4o mini: Non-social science research article
Deep Arctic Ocean warming enhanced by heat transferred from deep Atlantic
Ruizhe Song, Xianyao Chen, Hanwen Bi, Xiaoyu Wang, Longjiang Mu
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Observations since the 1990s reveal widespread warming in the deep and bottom Arctic Ocean. It is historically attributed to geothermal heating, whereas the impacts of global and Arctic climate change on the deep and bottom Arctic Ocean warming remain unresolved. Our study demonstrates that during the recent decades, the Arctic Ocean deep water is warming at 0.020°C/decade in the Eurasian Basin between 2000 and 2600 m, exceeding what can be explained by geothermal heating. We find that the rapid warming in the deep Greenland Basin diminishes its cooling effect on the deep Eurasian Basin via the Fram Strait, leading to the warming in the deep Eurasian Basin. Meanwhile, the Lomonosov Ridge blocks this warming signal from reaching the deep Amerasian Basin, maintaining its relative slow warming rate of 0.003°C/decade. Our findings indicate that the deep Greenland Basin warming has already exerted obvious impacts on the deep Arctic Ocean.
GPT-4o mini: Non-social science research article
ENSO’s changing grip on Bering Sea ice: The emerging control of the North Pacific meridional mode
Jiepeng Chen, Jin-Yi Yu, Chunzai Wang, Jiping Liu, Xin Wang, Sheng Chen, Lei Zhang, Zhuoqi He
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Bering Sea winter sea ice (BSWI), vital for regional climate, ecosystem, and livelihoods, is significantly influenced by El Niño–Southern Oscillation (ENSO). Here, we identify a shift in the ENSO-BSWI relationship. Pre–mid-1990s, traditional eastern Pacific ENSO dominated, driving a positive ENSO-BSWI linkage; post–mid-1990s, more frequent central Pacific (CP) ENSO events reversed this relationship to negative. Observations and model experiments show that CP El Niño coupled with positive-phase North Pacific meridional mode (NPMM) redirects poleward-propagating Rossby wave trains, enhancing Bering Sea southerlies. This suppresses ice advection, intensifies warm air intrusion, and reduces BSWI. Strengthened CP ENSO-NPMM coupling and heightened NPMM variability amplify this teleconnection, increasing its influence on BSWI by 38.9% versus NPMM alone. Our findings underscore the growing role of subtropical and tropical Pacific climate interactions in subarctic sea ice variability and highlight the need for improved climate models that capture ENSO diversity, NPMM dynamics, and subtropical-subarctic teleconnections to enhance BSWI projections under climate change.
GPT-4o mini: Non-social science research article
Matrix mechanical remodeled carrier-free nanosystem for programmable closed-loop reversal of liver fibrosis via STING alkylation
Hongyun Han, Dongrun Yu, Yuxiang Liu, Huizhen Jia, Wenguang Liu
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Extracellular matrix (ECM) sclerosis represents a prominent feature of fibrotic disorders; however, the macrophage response to changes in matrix stiffness and its impact on fibrotic diseases remain unclear. This study reveals a vicious circle of ECM-cell-ECM, where increased ECM hardness activates the STING pathway in macrophages, in turn activates hepatic stellate cells (HSCs), thus enhancing ECM stiffness again and exacerbating liver fibrosis. To reverse liver fibrosis, an innovative carrier-free nanosystem capable of degrading ECM, specifically blocking the STING pathway in macrophages as well as remodeling matrix mechanical, is created. In mouse models, pharmacological STING inhibition via alkylation in macrophages, combined with ECM degradation via matrix metalloproteinases and metal ion–induced macrophage polarization, reduces stromal stiffness and reverses fibrosis. Our findings underscore the antifibrotic potential of matrix mechanical remodeling, demonstrating that concurrent reduction of matrix stiffness and inhibition of STING pathway in macrophages can synergistically promote fibrosis regression. This research establishes a previously unidentified paradigm for liver fibrosis reversal.
GPT-4o mini: Non-social science research article
Nanofluidic-engineered carbon nanotube ion highways in hydrogels enable high-power aqueous zinc-ion batteries
Dewu Lin, Jiapei Li, Mingzhan Wang, Muqiang Jian, Ruihong Pan, Yu Liu, Anquan Zhu, Tian Zhang, Kai Liu, Dongyu Feng, Kunlun Liu, Yin Zhou, Chengkai Yang, Guo Hong, Jin Zhang, Wenjun Zhang
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Quasi-solid polymer electrolytes (QSPEs) for flexible batteries face critical limitations in ion transport efficiency at high currents. We address this with a design of nanofluidic polyacrylamide hydrogel integrating aligned single-walled carbon nanotubes (SWCNTs) as ion highways [SWCNT-embedded polyacrylamide(CPAM)]. Photo-polymerization ensures homogeneous SWCNT distribution, delivering a high ionic conductivity of 30.3 mS cm −1 while shielding polymer matrices from ion collision. Molecular dynamics simulations identify three ion transport modes, dominated by SWCNT-confined pathways. The CPAM-based Zn||Zn cell exhibits ultralong cycling (7000 hours), and Zn|CPAM|Zn 0.25 V 2 O 5 cells retain 80% capacity after 2000 cycles at 40 A g −1 (19.2 kW kg −1 ). Cryogenic operation (−15°C) and pouch cells further demonstrate the robust performance of CPAM. This work transcends conventional compromises of QSPEs, enabling wearables with ultrafast charging/discharging, cryogenic tolerance, and mechanical resilience.
GPT-4o mini: Non-social science research article
Observation of proton tunneling correlated with phonons and electrons in Pd
Takahiro Ozawa, Ryota Shimizu, Isao Harayama, Taro Hitosugi, Daiichiro Sekiba, Katsuyuki Fukutani
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Quantum-mechanical properties substantially affect the dynamics of light particles, including hydrogen. The temperature dependence of the tunneling rate provides a clue to understanding the quantum effects. Important physics behind quantum tunneling involves the correlation with surrounding environment, such as phonons and electrons. However, this correlation is not yet well understood due to the difficulty of directly probing hydrogen hopping. Taking advantage of nuclear reaction analysis and resistance measurements, we successfully observed hydrogen hopping from tetrahedral to octahedral sites in palladium. The hydrogen hopping is observed even at low temperatures owing to the quantum tunneling. The tunneling rate reveals a slightly positive and negative temperature dependence above and below 20 kelvin, respectively. The former is explained by the phonon effects. The latter is attributed to the nonadiabatic effects of conduction electrons, whose coupling constant K was derived to be 0.41 ± 0.03 from its temperature ( T ) dependence described as T 2 K –1 .
GPT-4o mini: Non-social science research article
High-entropy nanoalloys anchored on entropy-compensating two-dimensional oxides for enhanced nanomagnetism
Xiaodi Zhou, Yiqian Du, Huibin Zhang, Bangxin Li, Xuhui Xiong, Xiaowei Lv, Mingyue Yuan, Yihao Liu, Guanyu Chen, Jiacheng Cui, Jian Wang, Jiajun Liu, Hualiang Lv, Renchao Che
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Mitigating detrimental surface effects in nanometals is crucial for advancing applications in quantum magnetic storage and integrated circuits, as size reduction often experiences atomic distortion and vacancy formation, disrupting magnetic domains and electronic transport. Herein, we synthesize nano–high-entropy alloys (HEAs) anchored on two-dimensional high-entropy oxide nanosheets. By leveraging interfacial entropy compensation and the high-entropy effect, the triggered atomic rearrangements alleviate the inhomogeneous stress distribution in magnetic nanoparticles by mitigating unsaturated coordination and surface defects and reinforcing internal distortion, thereby suppressing surface effects. The anchored HEAs demonstrate stable sub–20-nanometer vortex magnetic domains, achieving an 80% enhancement in saturation magnetization and a 135% improvement in permeability, surpassing isolated HEAs and conventional ferromagnetic metals. Moreover, this enhancement enables more than 50% absorption efficiency across the wireless communication spectrum (3.3 to 6.0 gigahertz) with superior thermal stability (300 to 800 kelvins). This study establishes a pathway to enhance nanometal magnetoelectric properties for flexible, high-performance electromagnetic devices.
GPT-4o mini: Non-social science research article
Sabatier principle in designing CO 2 -philic but blocking membranes
Leiqing Hu, Asha Jyothi Gottipalli, Gengyi Zhang, Kieran Fung, Thien Tran, Narjes Esmaeili, Peihong Zhang, Yifu Ding, Kaihang Shi, Haiqing Lin
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Gas transport through polymers follows the sorption-diffusion mechanism, and gas-philic functional groups are often incorporated into polymers to enhance its solubility selectivity and thus separation efficiency. In contrast, we report that polymers exhibiting strong chemisorption toward specific gas molecules can counterintuitively impede their diffusion, illustrated by experimental and simulation studies of CO 2 transport in cross-linked polyamines, paralleling the Sabatier principle observed in catalysis. The CO 2 -philic polyamine membrane attains an unprecedented H 2 /CO 2 selectivity of 1800, making it highly desirable for H 2 purification. The cross-linked polyamines exhibit excellent self-healing properties and processability for fabricating thin-film composite membranes, indicating great promise for industrial separations. Retarded transport by introducing strongly binding groups presents a promising route for designing membranes for various separations.
Critical windows of prenatal heat exposure and preterm birth: Metabolomic study in the Atlanta African American Maternal-Child Cohort
Kaitlin R. Taibl, Priyanka A. Bhanushali, Anne L. Dunlop, Howard H. Chang, Dana Boyd Barr, Youran Tan, Zhihao Jin, Noah Scovronick, Stephanie M. Eick, P. Barry Ryan, Jeremy A. Sarnat, Carmen J. Marsit, Dean P. Jones, Donghai Liang
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Extreme heat is a risk factor for preterm birth (PTB), but the underlying biological pathways remain poorly understood. This study aimed to identify maternal metabolomic signatures associated with prenatal heat exposure and PTB. We conducted a prospective analysis of 215 participants in the Atlanta African American Maternal-Child Cohort (2014 to 2020). Serum samples collected during early and late pregnancy underwent untargeted metabolomic profiling. Daily maximum ambient temperature was estimated at geocoded residential addresses and averaged over three exposure windows: conception to early pregnancy, early to late pregnancy, and conception to late pregnancy. Metabolome-wide association studies were performed for each exposure window and PTB, followed by a meet-in-the-middle analysis. We identified 23 metabolic pathways and four overlapping metabolites, including methionine, proline, citrulline, and pipecolate, associated with both temperature exposure and PTB. These metabolites are involved in amino acid metabolism and oxidative stress regulation. Findings highlight the potential of metabolomics to detect early biological alterations linked to environmental risk and adverse birth outcomes.
Evidence-based water fluoridation policy
David A. Savitz
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A national-scale fluoridation study addresses policy-relevant exposure levels and provides evidence that adverse neurodevelopmental effects do not result from municipal fluoridation.
Testing for racial bias using inconsistent perceptions of race
Nora Gera, Emma Pierson
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Tests for racial bias commonly assess whether two people of different races are treated differently. A fundamental challenge is that, because two people may differ in many ways, factors besides race might explain differences in treatment. Here, we propose a test for bias that circumvents the difficulty of comparing two people by instead assessing whether the same person is treated differently when their race is perceived differently. We apply our method to test for bias in police traffic stops, finding that the same driver is likelier to be searched or arrested by police when they are perceived as Hispanic than when they are perceived as white. Our test is broadly applicable to other datasets where race, gender, or other identity data are perceived rather than self-reported, and the same person is observed multiple times.
Childhood fluoride exposure and cognition across the life course
John Robert Warren, Gina Rumore, Soobin Kim, Eric Grodsky, Chandra Muller, Jennifer J. Manly, Adam M. Brickman
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How are children’s fluoride exposures associated with cognitive test performance in adolescence and midlife? Whereas most prior research has estimated effects of exposure to extremely high levels of fluoride, we consider exposure to levels of fluoride within the range typical in most places and of greatest relevance to policy debates about government water fluoridation. We use data from the nationally representative (United States) High School and Beyond cohort, characterize fluoride exposure from drinking water across adolescence, adjust for confounders, and observe cognitive test performance in both secondary school and at age ~60. We find that children exposed to recommended levels of fluoride in drinking water exhibit modestly better cognition in secondary school, an advantage that is smaller and no longer statistically significant at age ~60.