We checked 7 multidisciplinary journals on Friday, June 06, 2025 using the Crossref API. For the period May 30 to June 05, we retrieved 17 new paper(s) in 6 journal(s).

Nature

GPT-4o mini: Non-social science research article
Maternal iron deficiency causes male-to-female sex reversal in mouse embryos
Naoki Okashita, Ryo Maeda, Shunsuke Kuroki, Kyona Sasaki, Yoko Uno, Peter Koopman, Makoto Tachibana
Full text
GPT-4o mini: Non-social science research article
A multidimensional distributional map of future reward in dopamine neurons
Margarida Sousa, Pawel Bujalski, Bruno F. Cruz, Kenway Louie, Daniel C. McNamee, Joseph J. Paton
Full text
GPT-4o mini: Non-social science research article
Observation of string breaking on a (2 + 1)D Rydberg quantum simulator
Daniel GonzĂĄlez-Cuadra, Majd Hamdan, Torsten V. Zache, Boris Braverman, Milan Kornjača, Alexander Lukin, Sergio H. CantĂș, Fangli Liu, Sheng-Tao Wang, Alexander Keesling, Mikhail D. Lukin, Peter Zoller, Alexei Bylinskii
Full text
GPT-4o mini: Non-social science research article
Coordination environments of Pt single-atom catalysts from NMR signatures
Jonas Koppe, Alexander V. Yakimov, Domenico GioffrÚ, Marc-Eduard Usteri, Thomas Vosegaard, Guido Pintacuda, Anne Lesage, Andrew J. Pell, Sharon Mitchell, Javier Pérez-Ramírez, Christophe Copéret
Full text
Supported metal catalysts that integrate atomically dispersed species with controlled structures lie at the forefront of catalytic materials design, offering exceptional control over reactivity and high metal utilization, approaching the precision of molecular systems 1–3 . However, accurately resolving the local metal coordination environments remains challenging, hindering the advancement of structure–activity relationships needed to optimize their design for diverse applications 1,2 . Although electron microscopy reveals atomic dispersion, conventional spectroscopic methods used in heterogeneous catalysis only provide average structural information. Here we demonstrate that 195 Pt solid-state nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for characterizing atomically dispersed Pt sites on various supports, so called single-atom catalysts (SACs). Monte Carlo simulations allow the conversion of NMR spectra into SAC signatures that describe coordination environments with molecular precision, enabling quantitative assessment of Pt-site distribution and homogeneity. This methodology can track the influence of synthetic parameters, uncovering the impact of specific steps and support types, and can also monitor changes upon reaction. It offers critical insights for the reproducible development of SACs with targeted structures. Beyond SACs, this approach lays the foundation for studying more complex architectures, such as dual-atom or single-cluster catalysts, containing various NMR-active metals.
GPT-4o mini: Non-social science research article
False positives in study of memory-related gene expression
Eran A. Mukamel, Zhaoxia Yu
Full text
GPT-4o mini: Non-social science research article
Ischaemic endothelial necroptosis induces haemolysis and COVID-19 angiopathy
Mike C. L. Wu, Ethan Italiano, Rocko Jarvis-Child, Imala Alwis, Rhyll Smythe, Eduardo A. Albornoz, Jonathan Noonan, Marie Portelli, Marissa Baptista, Jessica Maclean, Pashtana Noori, Jinglu Yang, John D. Lee, James D. McFadyen, Alexandra F. Sharland, Trent M. Woodruff, Andre L. Samson, Amy Rapkiewicz, Tessa J. Barrett, Alan Pham, Simone M. Schoenwaelder, Yuping Yuan, Shaun P. Jackson
Full text
GPT-4o mini: Non-social science research article
Multi-timescale reinforcement learning in the brain
Paul Masset, Pablo Tano, HyungGoo R. Kim, Athar N. Malik, Alexandre Pouget, Naoshige Uchida
Full text
GPT-4o mini: Non-social science research article
Old carbon routed from land to the atmosphere by global river systems
Joshua F. Dean, Gemma Coxon, Yanchen Zheng, Jack Bishop, Mark H. Garnett, David Bastviken, Valier Galy, Robert G. M. Spencer, Suzanne E. Tank, Edward T. Tipper, Jorien E. Vonk, Marcus B. Wallin, Liwei Zhang, Chris D. Evans, Robert G. Hilton
Full text
Rivers and streams are an important pathway in the global carbon cycle, releasing carbon dioxide (CO 2 ) and methane (CH 4 ) from their water surfaces to the atmosphere 1,2 . Until now, CO 2 and CH 4 emitted from rivers were thought to be predominantly derived from recent (sub-decadal) biomass production and, thus, part of ecosystem respiration 3–6 . Here we combine new and published measurements to create a global database of the radiocarbon content of river dissolved inorganic carbon (DIC), CO 2 and CH 4 . Isotopic mass balance of our database suggests that 59 ± 17% of global river CO 2 emissions are derived from old carbon (millennial or older), the release of which is linked to river catchment lithology and biome. This previously unrecognized release of old, pre-industrial-aged carbon to the atmosphere from long-term soil, sediment and geologic carbon stores through lateral hydrological routing equates to 1.2 ± 0.3 Pg C year −1 , similar in magnitude to terrestrial net ecosystem exchange. A consequence of this flux is a greater than expected net loss of carbon from aged organic matter stores on land. This requires a reassessment of the fate of anthropogenic carbon in terrestrial systems and in global carbon cycle budgets and models.
GPT-4o mini: Non-social science research article
Structural insights into human Pol III transcription initiation in action
Qianmin Wang, Yulei Ren, Qianwei Jin, Xizi Chen, Yanhui Xu
Full text
GPT-4o mini: Non-social science research article
Drivers of the extreme North Atlantic marine heatwave during 2023
Matthew H. England, Zhi Li, Maurice F. Huguenin, Andrew E. Kiss, Alex Sen Gupta, Ryan M. Holmes, Stefan Rahmstorf
Full text
North Atlantic Ocean circulation and temperature patterns profoundly influence global and regional climate across all timescales, from synoptic 1 to seasonal 2–4 , decadal 5 , multidecadal 6,7 and beyond 8,9 . During 2023, an extreme and near-basin-scale marine heatwave developed during Northern Hemisphere summer, peaking in July. The warming spread across virtually all regions of the North Atlantic, including the subpolar ocean, where a cooling trend over the past 50–100 years has been linked to a slowdown in the meridional overturning circulation 10,11 . Yet the mechanisms that led to this exceptional surface ocean warming remain unclear. Here we use observationally constrained atmospheric reanalyses alongside ocean observations and model simulations to show that air–sea heat fluxes acting on an extremely shallow surface mixed layer, rather than anomalous ocean heat transport, were responsible for this extreme ocean warming event. The dominant driver is shown to be anomalously weak winds leading to strongly shoaling (shallowing) mixed layers, resulting in a rapid temperature increase in a shallow surface layer of the North Atlantic. Furthermore, solar radiation anomalies made regional-scale warming contributions in locations that approximately correspond to some of the region’s main shipping lanes, suggesting that reduced sulfate emissions could also have played a localized role. With a trend towards shallower mixed layers observed over recent decades, and projections that this will continue into the future, the severity of North Atlantic marine heatwaves is set to worsen.
GPT-4o mini: Non-social science research article
Concurrent loss of the Y chromosome in cancer and T cells impacts outcome
Xingyu Chen, Yiling Shen, Suhyeon Choi, Hany A. Abdel-Hafiz, Mukta Basu, Lena Hoelzen, Martina Tufano, Saravana Kumar Kailasam Mani, Maryam Ranjpour, Jiani Zhu, V. Krishnan Ramanujan, Ekaterina K. Koltsova, Vinicius F. Calsavara, Simon R. V. Knott, Dan Theodorescu
Full text
GPT-4o mini: Non-social science research article
Warming accelerates global drought severity
Solomon H. Gebrechorkos, Justin Sheffield, Sergio M. Vicente-Serrano, Chris Funk, Diego G. Miralles, Jian Peng, Ellen Dyer, Joshua Talib, Hylke E. Beck, Michael B. Singer, Simon J. Dadson
Full text
Drought is one of the most common and complex natural hazards affecting the environment, economies and populations globally 1–4 . However, there are significant uncertainties in global drought trends 4–6 , and a limited understanding of the extent to which a key driver, atmospheric evaporative demand (AED), impacts the recent evolution of the magnitude, frequency, duration and areal extent of droughts. Here, by developing an ensemble of high-resolution global drought datasets for 1901–2022, we find an increasing trend in drought severity worldwide. Our findings suggest that AED has increased drought severity by an average of 40% globally. Not only are typically dry regions becoming drier but also wet areas are experiencing drying trends. During the past 5 years (2018–2022), the areas in drought have expanded by 74% on average compared with 1981–2017, with AED contributing to 58% of this increase. The year 2022 was record-breaking, with 30% of the global land area affected by moderate and extreme droughts, 42% of which was attributed to increased AED. Our findings indicate that AED has an increasingly important role in driving severe droughts and that this tendency will likely continue under future warming scenarios.
GPT-4o mini: Non-social science research article
Molecular gradients shape synaptic specificity of a visuomotor transformation
Mark Dombrovski, Yixin Zang, Giovanni Frighetto, Andrea Vaccari, HyoJong Jang, Parmis S. Mirshahidi, Fangming Xie, Piero Sanfilippo, Bryce W. Hina, Aadil Rehan, Roni H. Hussein, Pegah S. Mirshahidi, Catherine Lee, Aileen Morris, Mark A. Frye, Catherine R. von Reyn, Yerbol Z. Kurmangaliyev, Gwyneth M. Card, S. Lawrence Zipursky
Full text
How does the brain convert visual input into specific motor actions 1,2 ? In Drosophila , visual projection neurons (VPNs) 3,4 perform this visuomotor transformation by converting retinal positional information into synapse number in the brain 5 . The molecular basis of this phenomenon remains unknown. We addressed this issue in LPLC2 (ref. 6 ), a VPN type that detects looming motion and preferentially drives escape behaviour to stimuli approaching from the dorsal visual field with progressively weaker responses ventrally. This correlates with a dorsoventral gradient of synaptic inputs into and outputs from LPLC2. Here we report that LPLC2 neurons sampling different regions of visual space exhibit graded expression of cell recognition molecules matching these synaptic gradients. Dpr13 shapes LPLC2 outputs by binding DIP-Δ in premotor descending neurons mediating escape. Beat-VI shapes LPLC2 inputs by binding Side-II in upstream motion-detecting neurons. Gain-of-function and loss-of-function experiments show that these molecular gradients act instructively to determine synapse number. These patterns, in turn, fine-tune the perception of the stimulus and drive the behavioural response. Similar transcriptomic variation within neuronal types is observed in the vertebrate brain 7 and may shape synapse number via gradients of cell recognition molecules acting through both genetically hard-wired programs and experience.
GPT-4o mini: Non-social science research article
A soft-clamped topological waveguide for phonons
Xiang Xi, Ilia Chernobrovkin, Jan KoĆĄata, Mads B. Kristensen, Eric Langman, Anders S. SĂžrensen, Oded Zilberberg, Albert Schliesser
Full text
GPT-4o mini: Non-social science research article
Author Correction: Methane oxidation to ethanol by a molecular junction photocatalyst
Jijia Xie, Cong Fu, Matthew G. Quesne, Jian Guo, Chao Wang, Lunqiao Xiong, Christopher D. Windle, Srinivas Gadipelli, Zheng Xiao Guo, Weixin Huang, C. Richard A. Catlow, Junwang Tang
Full text
GPT-4o mini: Non-social science research article
Probing condensate microenvironments with a micropeptide killswitch
Yaotian Zhang, Ida Stöppelkamp, Pablo Fernandez-Pernas, Melanie Allram, Matthew Charman, Alexandre P. Magalhaes, Melanie Piedavent-Salomon, Gregor Sommer, Yu-Chieh Sung, Katrina Meyer, Nicholas Grams, Edwin Halko, Shivali Dongre, David Meierhofer, Michal Malszycki, Ibrahim A. Ilik, Tugce Aktas, Matthew L. Kraushar, Nadine Vastenhouw, Matthew D. Weitzman, Florian Grebien, Henri Niskanen, Denes Hnisz
Full text
Biomolecular condensates are thought to create subcellular microenvironments that have different physicochemical properties compared with their surrounding nucleoplasm or cytoplasm 1–5 . However, probing the microenvironments of condensates and their relationship to biological function is a major challenge because tools to selectively manipulate specific condensates in living cells are limited 6–9 . Here, we develop a non-natural micropeptide (that is, the killswitch) and a nanobody-based recruitment system as a universal approach to probe endogenous condensates, and demonstrate direct links between condensate microenvironments and function in cells. The killswitch is a hydrophobic, aromatic-rich sequence with the ability to self-associate, and has no homology to human proteins. When recruited to endogenous and disease-specific condensates in human cells, the killswitch immobilized condensate-forming proteins, leading to both predicted and unexpected effects. Targeting the killswitch to the nucleolar protein NPM1 altered nucleolar composition and reduced the mobility of a ribosomal protein in nucleoli. Targeting the killswitch to fusion oncoprotein condensates altered condensate compositions and inhibited the proliferation of condensate-driven leukaemia cells. In adenoviral nuclear condensates, the killswitch inhibited partitioning of capsid proteins into condensates and suppressed viral particle assembly. The results suggest that the microenvironment within cellular condensates has an essential contribution to non-stoichiometric enrichment and mobility of effector proteins. The killswitch is a widely applicable tool to alter the material properties of endogenous condensates and, as a consequence, to probe functions of condensates linked to diverse physiological and pathological processes.
GPT-4o mini: Non-social science research article
Ancient DNA reveals a two-clanned matrilineal community in Neolithic China
Jincheng Wang, Shi Yan, Zhenguang Li, Jinguo Zan, Yichao Zhao, Jin Zhao, Kui Chen, Xueye Wang, Ting Ji, Cheng Zhang, Tingyu Yang, Tianming Zhang, Rui Qiao, Meilin Guo, Zongyue Rao, Jiashuo Zhang, Guanbo Wang, Zhiyu Ran, Chen Duan, Fan Zhang, Yin Song, Xiaohong Wu, Ruth Mace, Bo Sun, Yuhong Pang, Yanyi Huang, Hai Zhang, Chao Ning
Full text
Studies of ancient DNA from cemeteries provide valuable insights into early human societies, and have strongly indicated patrilocality 1–10 . Here, we analysed ancient DNA alongside archaeological contexts and multiple stable isotopic data from 60 individuals in 2 separate cemeteries at the Fujia archaeological site in eastern China, dating between 2750 and 2500 bce . Our findings suggest the existence of an early-described matrilineal community in the Neolithic period, characterized by high endogamy and a population practicing millet agriculture near the coast. Evidence of intermarriage between individuals in the two cemeteries and the presence of both primary and secondary burials, organized strictly according to maternal clans, underscore a strong sense of social cohesion and identity at Fujia. Bayesian modelling of radiocarbon dates indicates that the two cemeteries were used for approximately 250 years, implying a stable matrilineal lineage spanning at least 10 generations. This study contributes to the ongoing debate in anthropology and archaeology 11 , not only suggesting the existence of a matrilineal society in early human history but also revealing a pair of Neolithic cemeteries organized around two matrilineal clans, furthering our understanding of the early evolution of human societies through kinship systems.
GPT-4o mini: Non-social science research article
Milli-spinner thrombectomy
Yilong Chang, Shuai Wu, Qi Li, Benjamin Pulli, Darren Salmi, Paul Yock, Jeremy J. Heit, Ruike Renee Zhao
Full text
GPT-4o mini: Non-social science research article
Publisher Correction: Metal–support frontier orbital interactions in single-atom catalysis
Xianxian Shi, Zhilin Wen, Qingqing Gu, Long Jiao, Hai-Long Jiang, Haifeng Lv, Hengwei Wang, Jiani Ding, Mason P. Lyons, Alvin Chang, Zhenxing Feng, Si Chen, Yue Lin, Xiaoyan Xu, Pengfei Du, Wenlong Xu, Mei Sun, Yin Li, Bing Yang, Tao Zhang, Xiaojun Wu, Junling Lu
Full text
GPT-4o mini: Non-social science research article
Integrated photonic source of Gottesman–Kitaev–Preskill qubits
M. V. Larsen, J. E. Bourassa, S. Kocsis, J. F. Tasker, R. S. Chadwick, C. GonzĂĄlez-Arciniegas, J. Hastrup, C. E. Lopetegui-GonzĂĄlez, F. M. Miatto, A. Motamedi, R. Noro, G. Roeland, R. Baby, H. Chen, P. Contu, I. Di Luch, C. Drago, M. Giesbrecht, T. Grainge, I. Krasnokutska, M. Menotti, B. Morrison, C. Puviraj, K. Rezaei Shad, B. Hussain, J. McMahon, J. E. Ortmann, M. J. Collins, C. Ma, D. S. Phillips, M. Seymour, Q. Y. Tang, B. Yang, Z. Vernon, R. N. Alexander, D. H. Mahler
Full text
GPT-4o mini: Non-social science research article
Author Correction: DNA-guided transcription factor interactions extend human gene regulatory code
Zhiyuan Xie, Ilya Sokolov, Maria Osmala, Xue Yue, Grace Bower, J. Patrick Pett, Yinan Chen, Kai Wang, Ayse Derya Cavga, Alexander Popov, Sarah A. Teichmann, Ekaterina Morgunova, Evgeny Z. Kvon, Yimeng Yin, Jussi Taipale
Full text
GPT-4o mini: Non-social science research article
Dynamic range and precision of hybrid vision sensors
Minhao Yang, Rodney Douglas, Chenghan Li, Andreas Suess, Hyunsurk Ryu, Christoph Posch, Shoushun Chen, Raphael Berner, Tetsuya Yagi, Boyd Fowler, Tobi Delbruck
Full text
GPT-4o mini: Non-social science research article
Increased CSF drainage by non-invasive manipulation of cervical lymphatics
Hokyung Jin, Jin-Hui Yoon, Seon Pyo Hong, Yu Seok Hwang, Myung Jin Yang, Jieun Choi, Hae Jin Kang, Seung Eun Baek, Cheolhwa Jin, Junho Jung, Hae Jin Kim, Jincheol Seo, Jinyoung Won, Kyung Seob Lim, Chang-Yeop Jeon, Youngjeon Lee, Michael J. Davis, Hyung-Soon Park, Donald M. McDonald, Gou Young Koh
Full text
GPT-4o mini: Non-social science research article
CREM is a regulatory checkpoint of CAR and IL-15 signalling in NK cells
Hind Rafei, Rafet Basar, Sunil Acharya, Yu-Sung Hsu, Pinghua Liu, Deqiang Zhang, Toszka Bohn, Qingnan Liang, Vakul Mohanty, Ranjan Upadhyay, Ping Li, Pravin Phadatare, Merve Dede, Donghai Xiong, Huihui Fan, Corry Mathew Jones, Sebastian Kunz, May Daher, Ana Karen Nunez Cortes, Mayra Shanley, Bin Liu, Sadie Mae Moseley, Chenyu Zhang, Dexing Fang, Pinaki Banerjee, Nadima Uprety, Ye Li, Rejeena Shrestha, Xinhai Wan, Hong Shen, Vernikka Woods, April Lamour Gilbert, Seema Rawal, Jinzhuang Dou, Yukun Tan, Jeong-Min Park, Francia Reyes Silva, Alexander BiederstÀdt, Mecit Kaplan, Xin Ru Jiang, Inci BiederstÀdt, Bijender Kumar, Silvia Tiberti, Madison Moore, Jingling Jin, Ryan Z. Yang, Luis Muniz-Feliciano, Samuel Rosemore, Paul Lin, Gary M. Deyter, Natalie Wall Fowlkes, Abhinav K. Jain, David Marin, Anirban Maitra, Ken Chen, Tobias Bopp, Elizabeth J. Shpall, Katayoun Rezvani
Full text
GPT-4o mini: Non-social science research article
Acetolysis for epoxy-amine carbon fibre-reinforced polymer recycling
Ciaran W. Lahive, Stephen H. Dempsey, Sydney E. Reiber, Ajinkya Pal, Katherine R. Stevenson, William E. Michener, Hannah M. Alt, Kelsey J. Ramirez, Erik G. Rognerud, Clarissa L. Lincoln, Ryan W. Clarke, Jason S. DesVeaux, Taylor Uekert, Nicholas A. Rorrer, Katrina M. Knauer, Gregg T. Beckham
Full text
GPT-4o mini: Non-social science research article
Reply to: False positives in study of memory-related gene expression
Wenfei Sun, Zhihui Liu, Xian Jiang, Michelle B. Chen, Hua Dong, Jonathan Liu, Thomas C. SĂŒdhof, Stephen R. Quake
Full text
GPT-4o mini: Non-social science research article
Subnucleosome preference of human chromatin remodeller SMARCAD1
Pengjing Hu, Jingxi Sun, Hongyao Sun, Kangjing Chen, Youyang Sia, Xian Xia, Qiaoran Xi, Zhucheng Chen
Full text
GPT-4o mini: Non-social science research article
Visualizing dynamics of charges and strings in (2 + 1)D lattice gauge theories
T. A. Cochran, B. Jobst, E. Rosenberg, Y. D. Lensky, G. Gyawali, N. Eassa, M. Will, A. Szasz, D. Abanin, R. Acharya, L. Aghababaie Beni, T. I. Andersen, M. Ansmann, F. Arute, K. Arya, A. Asfaw, J. Atalaya, R. Babbush, B. Ballard, J. C. Bardin, A. Bengtsson, A. Bilmes, A. Bourassa, J. Bovaird, M. Broughton, D. A. Browne, B. Buchea, B. B. Buckley, T. Burger, B. Burkett, N. Bushnell, A. Cabrera, J. Campero, H.-S. Chang, Z. Chen, B. Chiaro, J. Claes, A. Y. Cleland, J. Cogan, R. Collins, P. Conner, W. Courtney, A. L. Crook, B. Curtin, S. Das, S. Demura, L. De Lorenzo, A. Di Paolo, P. Donohoe, I. Drozdov, A. Dunsworth, A. Eickbusch, A. Moshe Elbag, M. Elzouka, C. Erickson, V. S. Ferreira, L. Flores Burgos, E. Forati, A. G. Fowler, B. Foxen, S. Ganjam, R. Gasca, É. Genois, W. Giang, D. Gilboa, R. Gosula, A. Grajales Dau, D. Graumann, A. Greene, J. A. Gross, S. Habegger, M. Hansen, M. P. Harrigan, S. D. Harrington, P. Heu, O. Higgott, J. Hilton, H.-Y. Huang, A. Huff, W. Huggins, E. Jeffrey, Z. Jiang, C. Jones, C. Joshi, P. Juhas, D. Kafri, H. Kang, A. H. Karamlou, K. Kechedzhi, T. Khaire, T. Khattar, M. Khezri, S. Kim, P. Klimov, B. Kobrin, A. Korotkov, F. Kostritsa, J. Kreikebaum, V. Kurilovich, D. Landhuis, T. Lange-Dei, B. Langley, K.-M. Lau, J. Ledford, K. Lee, B. Lester, L. Le Guevel, W. Li, A. T. Lill, W. Livingston, A. Locharla, D. Lundahl, A. Lunt, S. Madhuk, A. Maloney, S. Mandrà, L. Martin, O. Martin, C. Maxfield, J. McClean, M. McEwen, S. Meeks, A. Megrant, K. Miao, R. Molavi, S. Molina, S. Montazeri, R. Movassagh, C. Neill, M. Newman, A. Nguyen, M. Nguyen, C.-H. Ni, K. Ottosson, A. Pizzuto, R. Potter, O. Pritchard, C. Quintana, G. Ramachandran, M. Reagor, D. Rhodes, G. Roberts, K. Sankaragomathi, K. Satzinger, H. Schurkus, M. Shearn, A. Shorter, N. Shutty, V. Shvarts, V. Sivak, S. Small, W. C. Smith, S. Springer, G. Sterling, J. Suchard, A. Sztein, D. Thor, M. Torunbalci, A. Vaishnav, J. Vargas, S. Vdovichev, G. Vidal, C. Vollgraff Heidweiller, S. Waltman, S. X. Wang, B. Ware, T. White, K. Wong, B. W. K. Woo, C. Xing, Z. Jamie Yao, P. Yeh, B. Ying, J. Yoo, N. Yosri, G. Young, A. Zalcman, Y. Zhang, N. Zhu, N. Zobrist, S. Boixo, J. Kelly, E. Lucero, Y. Chen, V. Smelyanskiy, H. Neven, A. Gammon-Smith, F. Pollmann, M. Knap, P. Roushan
Full text
GPT-4o mini: Non-social science research article
Loss of colonic fidelity enables multilineage plasticity and metastasis
Patrizia Cammareri, Michela Raponi, Yourae Hong, Caroline V. Billard, Nat Peckett, Yujia Zhu, Fausto D. Velez-Bravo, Nicholas T. Younger, Donnchadh S. Dunican, Sebastian Ö.-G. Pohl, Aslihan Bastem Akan, Nora J. Doleschall, John Falconer, Mark White, Jean Quinn, Kathryn Pennel, Roberta Garau, Sudhir B. Malla, Philip D. Dunne, Richard R. Meehan, Owen J. Sansom, Joanne Edwards, Malcolm G. Dunlop, Farhat V. N. Din, Sabine Tejpar, Colin W. Steele, Kevin B. Myant
Full text
Cancer cell plasticity enables the acquisition of new phenotypic features and is implicated as a major driver of metastatic progression 1,2 . Metastasis occurs mostly in the absence of additional genetic alterations 3–5 , which suggests that epigenetic mechanisms are important 6 . However, they remain poorly defined. Here we identify the chromatin-remodelling enzyme ATRX as a key regulator of colonic lineage fidelity and metastasis in colorectal cancer. Atrx loss promotes tumour invasion and metastasis, concomitant with a loss of colonic epithelial identity and the emergence of highly plastic mesenchymal and squamous-like cell states. Combined analysis of chromatin accessibility and enhancer mapping identified impairment of activity of the colonic lineage-specifying transcription factor HNF4A as a key mediator of these observed phenotypes. We identify squamous-like cells in human patient samples and a squamous-like expression signature that correlates with aggressive disease and poor patient prognosis. Collectively, our study defines the epigenetic maintenance of colonic epithelial identity by ATRX and HNF4A as suppressors of lineage plasticity and metastasis in colorectal cancer.
Nature DOI suffix ≠ "/s...": Not a research article
Your time is valuable. Don’t give it away just for ‘exposure’
Dritjon Gruda
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Disaster relief needs community trust — authorities must earn it
Maryam Rokhideh
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Speeding up ginseng growth to aid drug discovery
Rachel Brazil
Full text
Nature DOI suffix ≠ "/s...": Not a research article
The polar regions hold crucial scientific secrets — and the time to study them is running out
Marc Macias-Fauria
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Immune cell ‘spies’ give the brain information about the gut
Jacob Smith
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How do I choose a principal investigator for my next postdoc?
Nikki Forrester
Full text
Nature DOI suffix ≠ "/s...": Not a research article
‘You’re just not welcome’: researchers grapple with US plan to revoke Chinese student visas
Natasha Gilbert
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Underwater kelp forests are losing a turf war
Holly Smith
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Y-chromosome loss in cancer and immune cells might worsen treatment outcomes
Nicholas McGranahan, Rahul Roychoudhuri
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How a mysterious epidemic of kidney disease is killing thousands of young men
Carrie Arnold
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: The sweet smell of outer space
Jacob Smith
Full text
Nature DOI suffix ≠ "/s...": Not a research article
European Union’s strict conservation targets should guide global marine policy
Barbara Horta e Costa, Fabrice Stephenson, Joachim Claudet
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Trade wars could affect food security in low-income nations
Huijie Li, Bingcheng Si, Tegbaru Gobezie, Asim Biswas
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: NIH foreign-grant cuts could leave thousands without care worldwide
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Sticky membranes of dead red blood cells obstruct small vessels
Elizabeth Iffrig, Wilbur A. Lam
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How researchers are shining a light on the ‘invisible’ contributions of small-scale fishers
Julie Gould
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Genomics pioneer fired from firm he founded: ‘It was not easy to domesticate me’
Ewen Callaway
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Audio long read: Three ways to cool Earth by pulling carbon from the sky
Jeff Tollefson, Benjamin Thompson
Full text
Nature DOI suffix ≠ "/s...": Not a research article
‘Scienticide’ in Argentina sparks huge protest by researchers
MartĂ­n De Ambrosio, FermĂ­n Koop
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How the natural world is inspiring the robot eyes of the future
Esme Hedley
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Science-integrity project will root out bad medical papers ‘and tell everyone’
Nicola Jones
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Why we should protect the high seas from all extraction, forever
Callum M. Roberts, Emilia Dyer, Sylvia A. Earle, Andrew Forrest, Julie P. Hawkins, Ove Hoegh-Guldberg, Jessica J. Meeuwig, Daniel Pauly, Stuart L. Pimm, U. Rashid Sumaila, Johan Rockström, Mark Lynas
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How I’m bringing the voices of local fishers into ocean policies
Gaoussou Gueye
Full text
Nature DOI suffix ≠ "/s...": Not a research article
See the Milky Way dazzle during a lunar eclipse — May’s best science images
Emma Stoye
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Should there be a national holiday in honour of chemists?
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Cancer more deadly when tumours lack Y chromosomes — and the loss could be contagious
Liam Drew
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Human factors
John Gilbey
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Making robust integrated photonic qubits
Full text
Nature DOI suffix ≠ "/s...": Not a research article
First Chinese mission to sample an asteroid starts its journey
Smriti Mallapaty
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Illustrators call out journals and news sites for using AI art
Kamal Nahas
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Yvonne Choquet-Bruhat obituary: mathematician who established that Einstein’s equations mirror the real world
Mihalis Dafermos
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Brain-reading devices raise ethical dilemmas — researchers propose protections
Kristel Tjandra
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How a freezing pond could kick-start life’s self-replication
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Address the psychological toll of kidney disease
Rongkang Li, Lei Peng, Shaohua Zhang, Song Wu
Full text
Nature DOI suffix ≠ "/s...": Not a research article
NIH grant cuts will axe clinical trials abroad — and could leave thousands without care
Max Kozlov
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Clustering pattern of dwarf galaxies not predicted by models of cosmic structure formation
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Forehead ‘e-tattoo’ tracks how hard you’re thinking
Full text
Nature DOI suffix ≠ "/s...": Not a research article
US–China tariff war threatens global public health
Sijia Liu, Jialao Ma
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Gender equality in research publishing is a responsibility for everyone
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Trump wants to put humans on Mars — here’s what scientists think
Alexandra Witze
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Cancer-fighting CAR T cells show promising results for hard-to-treat tumours
Rachel Fieldhouse
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Exclusive: Inside the thriving wild-animal markets that could start the next pandemic
Jane Qiu
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Web-scraping AI bots cause disruption for scientific databases and journals
Diana Kwon
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Chemical ‘shuttles’ carry large drugs across the blood–brain barrier
Jacob Smith
Full text
Nature DOI suffix ≠ "/s...": Not a research article
CRISPR helps to show why a boy felt no pain
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: CAR-T proves its worth in hard-to-treat solid tumours
Flora Graham
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Simulation of matter–antimatter creation on quantum platforms
Michele Burrello
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Male mice can grow female organs — if their mothers lack iron
Benjamin Thompson, Nick Petrić Howe
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Stop ignoring small-scale fisheries in economic models
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Iron deficiency in pregnant mice causes XY embryos to develop with female characteristics
Shannon Dupont, Blanche Capel
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Ancient carbon released through modern rivers
Li Li
Full text
Nature DOI suffix ≠ "/s...": Not a research article
How to keep astronauts healthy in deep space
Farhan M. Asrar
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Black Death bacterium has become less lethal after genetic tweak
Rachel Fieldhouse
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Researchers who ‘pivot’ into new fields should not be given a citation penalty
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Male mice can grow ovaries if their pregnant mums are iron deficient
Rachel Fieldhouse
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Salary negotiations: a guide for scientists
Julie Gould
Full text
Nature DOI suffix ≠ "/s...": Not a research article
Rare ‘ambidextrous’ protein breaks rules of handedness
Ewen Callaway
Full text

Nature Human Behaviour

GPT-4o mini: Non-social science research article
High variability in LLMs’ analogical reasoning
Andrea Gregor de Varda, Chiara Saponaro, Marco Marelli
Full text
GPT-4o mini: Non-social science research article
Mental graphs structure the storage and retrieval of visuomotor associations
Juliana E. Trach, Samuel D. McDougle
Full text
GPT-4o mini: Non-social science research article
Dissociable habits of response preparation versus response initiation
Yue Du, Adrian M. Haith
Full text
GPT-4o mini: Non-social science research article
Current state and future directions of interventions for neglected tropical diseases
John Owusu Gyapong, Mawuli Gohoho, Alfred Kwesi Manyeh, Mustapha Immurana, Margaret Gyapong
Full text
GPT-4o mini: Non-social science research article
Large language models without grounding recover non-sensorimotor but not sensorimotor features of human concepts
Qihui Xu, Yingying Peng, Samuel A. Nastase, Martin Chodorow, Minghua Wu, Ping Li
Full text
GPT-4o mini: Non-social science research article
More US scientists must speak out
Peter H. Gleick
Full text
A call for psychological and behavioural science on degrowth
Dario Krpan, FrĂ©dĂ©ric Basso, Dallas O’Dell, Jason E. Hickel, Giorgos Kallis
Full text
An interdisciplinary explanation of rule-following in the absence or presence of incentives
Full text
Navigating anti-science policies in environmental public health
Qian Di
Full text
The chronospatial revolution in psychology
Mohammad Atari, Joseph Henrich, Jonathan Schulz
Full text
A semantic embedding space based on large language models for modelling human beliefs
Byunghwee Lee, Rachith Aiyappa, Yong-Yeol Ahn, Haewoon Kwak, Jisun An
Full text
NIH indirect cost cuts will affect the economy and employment
Alyssa H. Sinclair, Mallory J. Harris, Clio Andris, Danielle Cosme, Ellen Peters, Angela Fagerlin, Emily B. Falk, Joshua S. Weitz
Full text
Defusing political animosity in the United States with a cooperative online quiz game
Lucas Woodley, Evan DeFilippis, Shankar Ravi, Joshua D. Greene
Full text
Political expression of academics on Twitter
Prashant Garg, Thiemo Fetzer
Full text
Academics play a vital role in the generation and dissemination of knowledge, ideas and narratives. Social media provide new, more direct ways of science communication. Yet, since not all academics engage with social media, the sample that does so may have an outsized influence on shaping public perceptions of academia through the set topics they engage with and their style and tone of communication. We describe patterns in academics’ expression online using an international dataset covering nearly 100,000 scholars linking their Twitter content to academic records. We document large and systematic variation in politically salient academic expression concerning climate action, cultural and economic concepts. We show that US academics often diverge from the US Twitter population at large in topic focus and style, although academics are not necessarily more extreme in their beliefs. Future work should examine potential impacts on public trust and the reasons why academics express themselves politically on social media.

Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Reply to Apanovich and Weeks: Exceptions exist, as recognized in the paper, but are too rare to challenge the original findings
Gidon Eshel, Avi I. Flamholz, Alon Shepon, Ron Milo
Full text
GPT-4o mini: Non-social science research article
Independent transitions to fully planktonic life cycles shaped the global distribution of medusozoans in the epipelagic zone
Manon Boosten, Camille Sant, Ophélie Da Silva, Samuel Chaffron, Lionel Guidi, Lucas LeclÚre
Full text
Life history traits influence marine species dispersal and habitat colonization. Medusozoans (jellyfish and siphonophores) exhibit diverse life cycles, evolved from an ancestral cycle alternating between a benthic polyp and a pelagic medusa. Despite their ecological importance, factors shaping medusozoan distribution remain poorly understood. By integrating metabarcoding and environmental data from the Tara Oceans expedition with life history traits, we provide global evidence supporting the longstanding hypothesis that benthic polyp presence/absence is a key factor influencing the distribution and abundance of planktonic medusozoans in the surface ocean. We inferred on a time-calibrated phylogeny of Medusozoa multiple transitions to a fully planktonic (holoplanktonic) life cycle, either through polyp loss, acquisition of drifting polyps, or development of polyps parasitizing pelagic organisms. We could associate each transition with a shift toward offshore habitats and the emergence of globally dominant Operational Taxonomic Units (OTUs), whose abundance far exceeds that of any nonholoplanktonic medusozoans in the planktonic realm. The prevalence of holoplanktonic medusozoans in terms of abundance and diversity is broadly observed in coastal and offshore environments, peaking over greater bathymetric depths in tropical and subtropical regions. We show that holoplanktonic and nonholoplanktonic groups interact with distinct yet compositionally similar planktonic communities. Holoplanktonic OTUs occupy more peripheral positions in a plankton interactome, suggesting greater flexibility in biotic interactions, an adaptive trait in rapidly changing planktonic ecosystems. These findings highlight how life cycle evolution shaped the global distribution of medusozoans and suggest that variations in life history may significantly influence how medusozoans respond to global environmental changes.
GPT-4o mini: Non-social science research article
Symmetries and synchronization from whole-neural activity in the Caenorhabditis elegans connectome: Integration of functional and structural networks
Bryant Avila, Pedro Augusto, Alireza Hashemi, David Phillips, Tommaso Gili, Manuel Zimmer, HernĂĄn A. Makse
Full text
Understanding the dynamical behavior of complex systems from their underlying network architectures is a long-standing question in complexity theory. Therefore, many metrics have been devised to extract network features like motifs, centrality, and modularity measures. It has previously been proposed that network symmetries are of particular importance since they are expected to underlie the synchronization of a system’s units, which is ubiquitously observed in nervous system activity patterns. However, perfectly symmetrical structures are difficult to assess in noisy measurements of biological systems, like neuronal connectomes. Here, we devise a principled method to infer network symmetries from combined connectome and neuronal activity data. Using nervous system-wide population activity recordings of the Caenorhabditis elegans backward locomotor system, we infer structures in the connectome called fibration symmetries, which can explain which group of neurons synchronize their activity. Our analysis suggests functional building blocks in the animal’s motor periphery, providing testable hypotheses on how descending interneuron circuits communicate with the motor periphery to control behavior. Our approach opens a door to exploring the structure–function relations in other complex systems, like the nervous systems of larger animals.
GPT-4o mini: Non-social science research article
The tumor suppressor RASSF8: A WAVE interaction partner controlling migration and cohesion of invasive border cells in Drosophila
Mila Y. Höhne, Wiebke Milani, Kirsten Ramlow, Sven Bogdan
Full text
Collective cell migration is a key driver of tissue morphogenesis and cancer invasion. Here, we identified the tumor suppressor Ras association domain-containing protein 8 (RASSF8) as a WAVE interactor required for border cell migration. RASSF8 colocalizes with F-actin and cell adhesion molecules at border cell– border cell contacts. Loss of RASSF8 function results in border cell cohesion defects, a phenotype associated with changes in the localization of the Echinoid (Ed) and Coracle (Cora). Cell-type-specific RNA interference (RNAi) experiments suggest that cohesion defects are caused by changes in localization of Ed rather than E-cadherin. Gain-of-function experiments further revealed reciprocal functional interactions between RASSF8 and WAVE controlling collective border cell movement. Thus, we propose a dual function of RASSF8 in coordinating border cell cluster behavior. RASSF8 is thought to regulate the collective movement of border cells by restricting WAVE function, while it controls the epithelial cluster integrity by regulating cell–cell adhesion and septate junction molecules such as Ed and Cora.
GPT-4o mini: Non-social science research article
In-plane ferroelectricity with high Curie temperatures in nonequilibrium SnSe 1-x S x van der Waals semiconductors
Eli Sutter, Peter Sutter
Full text
While symmetry breaking in 2D ferroelectrics is obviously linked to the single-layer structure, layered (van der Waals) ferroelectrics can have a multitude of underlying mechanisms, making their identification nontrivial and often controversial. This complexity is exemplified by tin chalcogenides whose equilibrium structure, the orthorhombic α-phase with space group Pnma , includes an inversion center and which therefore should not be ferroelectric. Yet, recent work demonstrated polarization switching and ferroelectric domains in few-layer SnS and SnSe. Here, we use in situ electron microscopy and diffraction to determine the mechanism and characteristics of ferroelectricity across the SnSe 1-x S x system. We identify two distinct phases of synthetic SnSe 1-x S x : nonpolar (centrosymmetric) equilibrium (α-phase) crystals and metastable crystals adopting a distorted monoclinic structure, which are in-plane ferroelectrics with Curie temperatures of 320 to 420 °C. A surprising structural plasticity of the ferroelectric crystals during heating/cooling indicates a shallow energy landscape. This in turn suggests absence of a pronounced driving force for conversion to the α-phase that can explain the formation of the nonequilibrium crystals and their stability even after transfer to other supports. Our results highlight opportunities for the discovery of novel ferroelectrics among nonequilibrium van der Waals crystals.
GPT-4o mini: Non-social science research article
Targeted apoptotic immune modulator for the treatment of metastatic EGFR-positive solid tumors
Derrick Broka, Shoshana Klein, Alexei Shir, Babette Schade, Meera Saxena, Athanasia Dasargyri, Anita Jarzebinska, Caroline De Feyter, Davor Bajic, David Colecchia, Lucia D'Amico, Eric Kitas, Elad Hikri, Michal Jerzy Skowicki, Michal Jerzy Okoniewski, Laura Baldino, Besnik Qeriqi, Elisa de Stanchina, Joerg Schreiber, Melanie Buchi, Cornelia G. Palivan, Yaakov Benenson, Alfred Zippelius, Doriano Fabbro, Maurizio Scaltriti, Aviram Mizrachi, Alexander Levitzki, Esteban Pombo-Villar, Maya Zigler
Full text
Aberrant activation and overexpression of the epidermal growth factor receptor (EGFR) occurs in various solid cancers and often correlates with poor outcome. The clinical benefit from EGFR-targeted therapies is usually short-lived, with resistance being driven by tumor heterogeneity and an immunosuppressive tumor microenvironment (TME). To address these limitations, we developed Targeted Apoptotic Immune Modulators (TAIM), a nonviral nanoparticle platform for the targeted delivery of polyinosine:polycytosine (polyIC), to simultaneously induce tumor cell death and activate antitumor immunity. The first TAIM compound, TAR001, was designed as a systemic treatment against metastatic EGFR-positive solid cancers. Here, we present TAR001’s multifaceted mode of action. We demonstrate that TAR001 is selective toward EGFR-overexpressing cancers, provoking a pattern recognition response, apoptosis, cytokine secretion, and antitumor immunity. TAR001 modulates the TME, recruiting and activating both innate and adaptive immune cells. Systemic delivery of TAR001 markedly extends survival and inhibits tumor growth in multiple murine tumor models. TAR001 represents an innovative, safe, multimodal treatment approach with the potential to benefit patients with metastatic head and neck, non–small cell lung cancer, colorectal, renal, and triple-negative breast cancers. This unique modality utilizes a broad range of mechanisms to overcome the tumor’s ability to escape apoptosis and immune cell activation.
GPT-4o mini: Non-social science research article
Phylogenomics reveals the slow-burning fuse of diatom evolution
Andrew J. Alverson, Wade R. Roberts, Elizabeth C. Ruck, Teofil Nakov, Matthew P. Ashworth, Karolina BryƂka, Kala M. Downey, J. Patrick Kociolek, Matthew Parks, Eveline Pinseel, Edward C. Theriot, Simon P. Tye, Andrzej Witkowski, Jeremy M. Beaulieu, Norman J. Wickett
Full text
Evolution is often uneven in its pace and outcomes, with long periods of stasis interrupted by abrupt increases in morphological and ecological disparity. With thousands of gene histories, phylogenomics can uncover the genomic signatures of these broad macroevolutionary trends. Diatoms are a species-rich lineage of microeukaryotes that contribute greatly to the global cycling of carbon, oxygen, and silica, which they use to build elaborately structured cell walls. We combined fossil information with newly sequenced transcriptomes from 181 diverse diatom species to reconstruct the pattern, timing, and genomic context of major evolutionary transitions. Diatoms originated 270 Mya, and after >100 My of relative stasis in morphology and ecology, a radiation near the Jurassic–Cretaceous boundary led to the diversity of habitats and cell wall architectures characteristic of modern diatoms. This transition was marked by a genome duplication and high levels of gene tree discordance. However, short generation times increase the probability of coalescence between speciation events, minimizing the impacts of incomplete lineage sorting and implicating sequence saturation and gene tree error as the main sources of discordance. Nevertheless, a rigorous tree-based approach to ortholog selection resulted in strongly supported relationships, including some that were uncertain previously. Three pulses of accelerated speciation were detected, two of which were associated with the evolution of novel traits and ecological transitions. The first 100 My of diatom evolution was a slow-burning fuse that led to a burst of innovations in ecology, morphology, and life history that are hallmarks of contemporary diatom assemblages.
GPT-4o mini: Non-social science research article
Structure and organization of full-length epidermal growth factor receptor in extracellular vesicles by cryo-electron tomography
Monica Gonzalez-Magaldi, Anuradha Gullapalli, Ophelia Papoulas, Chang Liu, Adelaide Y.-H. Leung, Luqiang Guo, Axel F. Brilot, Edward M. Marcotte, Zunlong Ke, Daniel J. Leahy
Full text
We report here transport of full-length epidermal growth factor receptor (EGFR), Insulin Receptor, 7-pass transmembrane receptor Smoothened, and 13-pass Sodium-iodide symporter to extracellular vesicles (EVs) for structural and functional studies. Mass spectrometry confirmed the transported proteins are the most abundant in EV membranes, and the presence of many receptor-interacting proteins in EVs demonstrates their utility for characterizing membrane protein interactomes. Cryo-electron tomography of EGFR-containing EVs reveals that EGFR forms clusters in both the presence and absence of EGF with a ~3 nm gap between the inner membrane and cytoplasmic density. EGFR extracellular region (ECR) dimers do not form regular arrays in these clusters. Subtomogram averaging of the 150 kDa EGF-bound EGFR ECR dimer yielded a 15 Å map into which the crystal structure of the ligand-bound EGFR ECR dimer fits well. These findings refine our understanding of EGFR activation, clustering, and signaling and establish EVs as a versatile platform for structural and functional characterization of human membrane proteins in cell-derived membranes.
GPT-4o mini: Non-social science research article
Maximum spreading of impacting shear-thinning and shear-thickening drops
Anahita Mobaseri, Satish Kumar, Xiang Cheng
Full text
The maximum spreading of an impacting liquid drop is a key metric for characterizing the fundamental fluid process of drop impact. While extensively studied for Newtonian liquids, how far a non-Newtonian drop can spread upon impacting a solid substrate remains an open question. Here, by combining simulations, experiments, and scaling analyses, we establish a general framework for predicting the maximum spreading of drops of generalized Newtonian liquids, encompassing both shear-thinning and shear-thickening behaviors. Through an analysis of the energy budget at maximum spreading, we identify a characteristic shear rate that governs the viscous dissipation during drop impact. The finding allows us to map the spreading of non-Newtonian drops onto that of Newtonian drops, revealing the quantitative dependence of the maximum spreading diameter on various impact parameters and rheological properties of liquids. Our study addresses the long-standing challenge of understanding the impact dynamics of non-Newtonian drops, and provides valuable guidance for designing non-Newtonian liquids to achieve desired impact outcomes.
GPT-4o mini: Non-social science research article
Transcranial direct current stimulation neuromodulates intracranial cognitive evoked activity in humans
Mireille Tabikh, Tom Quetu, Louis Maillard, Sophie Colnat-Coulbois, Bruno Rossion, Laurent Koessler
Full text
Transcranial direct current stimulation (tDCS) is an easy to use, noninvasive brain stimulation technique that gained prominence for its potential in cognitive rehabilitation. Electroencephalography (EEG), which records electrical brain activity with a high temporal resolution, is well suited to quantify tDCS-induced neuromodulation in humans. However, most studies relying on scalp EEG recordings or event-related potentials showed low reliability and only indirect correlations. Here, we combined intracranial EEG (iEEG) recordings with a sham-controlled tDCS experiment during fast periodic visual stimulation. Anodal (+2 mA) tDCS was applied over the right occipito-temporal cortex for 20 min using two small ring high-definition electrodes. Through the analysis of iEEG signals of 947 intracerebral contacts in 11 drug-resistant epileptic patients, we quantified the neuromodulation of iEEG cognitive evoked responses during (P2 phase) and after (P3 phase) tDCS by comparison to a control phase before tDCS (P1 phase). Significant neuromodulations of face-selective iEEG activity in anterior & posterior temporal lobe and in the occipital lobe were found, with amplitude increases of 3% and 4%, 16% and 13%, and 36% and 33%, during and after tDCS, respectively. Interestingly, despite a unique tDCS session, the face-selective neuromodulation in the right visual occipito-temporal cortex remained significant ( P = 0.015) after tDCS (P3 vs. P1). This iEEG study demonstrates that using low intensity tDCS and small ring electrodes can induce significant electrophysiological effects on a selective cognitive function in humans.
GPT-4o mini: Non-social science research article
High-throughput metabolic engineering of Yarrowia lipolytica through gene expression tuning
Wei Jiang, Shengbao Wang, Daniel Ahlheit, Tommaso Fumagalli, Zhijie Yang, Shreemaya Ramanathan, Xinglin Jiang, Tilmann Weber, Jonathan Dahlin, Irina Borodina
Full text
The challenge of accurately predicting which genetic alternations lead to the desired phenotype necessitates high-throughput metabolic engineering approaches where numerous hypotheses can be tested simultaneously. We describe the CRISPR-Cas9-based method TUNE YALI that enables high-throughput tuning of gene expression in the common industrial yeast Yarrowia lipolytica . The method is based on replacing the promoters of the target genes with native Y. lipolytica promoters of varying strengths or removing the promoters entirely. To demonstrate the method’s capabilities, we created a plasmid library that targets 56 transcription factors (TFs) and changes the expression of each TF to seven different levels. We transformed this library into reference and betanin-producing strains of Y. lipolytica and screened the resulting clones for changes in morphology, thermotolerance, or improved betanin production. The genetic markup of the yeast clones with the desired phenotypic changes was determined by sequencing the inserted plasmids. We identified multiple TFs whose regulatory changes increased thermotolerance, two TFs that eliminated pseudohyphal growth, and several TFs that increased betanin production. Analogous libraries can be designed to target any chosen group of genes and even all the genes. The libraries can be shared and reused, accelerating applied strain development projects and fundamental functional genomics research (TUNE YALI -TF kit and TUNE YALI -TF library are available via AddGene under catalog numbers #1000000255 and #217744).
GPT-4o mini: Non-social science research article
The cell-permeable iron chelator M606 inhibits MYCN-driven neuroblastoma via an E2F3-mediated response
Ruby Pandher, Chengyuan Xue, Laura D. Gamble, Giorgio Milazzo, Simone Di Giacomo, Jayne Murray, Leanna Cheung, Francesca Ferrucci, Marta Palombo, Stefania Purgato, Catherine A. Burkhart, Natalia Fedtsova, Anatoli S. Gleiberman, Andrei A. Purmal, Lioubov Korotchkina, Mikhail A. Nikiforov, Sergei S. Makarov, Thomas J. Telfer, Rachel Codd, Glenn M. Marshall, David A. Scott, Andrei L. Osterman, Andrei V. Gudkov, Giovanni Perini, Michelle Haber, Murray D. Norris
Full text
Despite Myc oncoproteins being major causal factors in human cancer, they remain “undruggable.” The MYCN oncogene is one of the most powerful prognostic markers for the childhood cancer neuroblastoma and represents an important target for developing novel therapeutics. Here, we report the finding and characterization of M606, a selective small molecule inhibitor of MYCN, which was identified by screening a diverse chemical library. M606 reduced MYCN protein levels in neuroblastoma cell lines and upregulated hypoxia-inducible factor 1 alpha (HIF1A). Using siRNA-mediated knockdown of MYCN , c-Myc , or HIF1A in HepG2 and BE(2)-C cells followed by M606 treatment, we demonstrated that Myc downregulation and HIF1A upregulation were two independent effects of M606 treatment. M606 selectively targeted neuroblastoma cell lines expressing higher levels of MYCN protein and delayed neuroblastoma development in the TH-MYCN transgenic mouse model. Metabolomic analysis showed that M606 modulated glucose metabolism, consistent with a hypoxic response and iron deprivation. Biochemical characterization of M606 not only confirmed its iron-chelating properties but also revealed its ability to downregulate MYCN promoter activity, which could be rescued by the addition of iron. Luciferase assays identified the minimal MYCN promoter region required for the M606 response, which contained overlapping E2F transcription factor binding sites. Further evaluation defined a key role for E2F3 in the M606-mediated response. The finding of a potent cell-permeable iron chelator that can chelate iron to directly downregulate MYCN transcription via an E2F3-mediated response represents a potentially valuable therapeutic approach in the treatment of cancers overexpressing Myc oncoproteins.
GPT-4o mini: Non-social science research article
Concerted transport and phosphorylation of diacylglycerol at ER–PM contact sites regulate phospholipid dynamics during stress
Selene Garcia-Hernandez, Jorge Morello-LĂłpez, Richard Haslam, Vitor Amorim-Silva, JosĂ© Moya-Cuevas, Rafael CatalĂĄ, Louise Michaelson, Jessica PĂ©rez-Sancho, Vedrana Marković, Julio Salinas, Johnathan Napier, Yvon Jaillais, NoemĂ­ Ruiz-Lopez, Miguel A. Botella
Full text
A universal response of plants to environmental stresses is the activation of plasma membrane (PM) phospholipase C, which hydrolyzes phosphoinositides to produce soluble inositol phosphate and diacylglycerol (DAG). Because of their conical shape, DAG amounts have to be tightly regulated or they can destabilize membranes. We previously showed that upon stress, Synaptotagmin1 (SYT1) transports DAG from the PM to the endoplasmic reticulum (ER) at ER–PM Contact Sites (CS). Here, we addressed the fate of the incoming DAG in the ER. We show that diacylglycerol kinases (DGKs) DGK1 and DGK2 form a module with SYT1 functionally coupling DAG transport and phosphorylation at ER–PM CS. Although SYT1 and DGK1/DGK2 do not show exclusive ER–PM CS localization, their interaction occurs specifically at ER–PM CS and the removal of ER–PM CS abolishes the interaction. Lipidomic analysis of a dgk1dgk2 double mutant supports that DGK1 and DGK2 phosphorylate DAG at the ER and transcriptomic and phenotypic analyses indicate that SYT1 and DGK1/DGK2 are functionally related. Taken together, our results highlight a mechanism at ER–PM CS that coordinates the transfer of DAG from the PM to the ER by SYT1 upon stress and the concomitant phosphorylation of DAG by DGK1 and DGK2 at the ER. These findings underscore the critical role of spatial coordination in lipid metabolism during stress-induced membrane remodeling.
GPT-4o mini: Non-social science research article
Parallel sensory compensation following independent subterranean colonization by groundwater salamanders ( Eurycea )
Ruben U. Tovar, Brittany A. Dobbins, Nicholas R. Hartman, Sheena Leelani, Thomas J. Devitt, Dana M. GarcĂ­a, Paul M. Gignac, David C. Cannatella, David M. Hillis
Full text
Lineages that have invaded subterranean environments have repeatedly evolved remarkable adaptations to life in darkness. However, observational and experimental studies in additional natural systems are needed to further our understanding of repeated evolution and convergence. In Texas, a radiation of groundwater salamanders (genus Eurycea ), with independent invasions of subterranean karstic environments, offers an opportunity to investigate phenotypic convergence, parallel evolution, and the enhancement and regression of sensory systems. Adaptations to a troglobitic life in this clade include morphological, behavioral, and physiological changes within and among species. Intraspecific and interspecific variation in morphology in response to the selective pressures of life underground allows for detailed examination of physical, behavioral, and physiological changes associated with subterranean adaptation within a comparative phylogenetic framework. We find a correlated change between two sensory systems repeated across multiple subterranean Eurycea lineages: the degeneration of the eye and the expansion of the mechanosensory lateral line. The increase in anterior neuromast organs in subterranean lineages was positively correlated with the expression of pax6 (Paired-box 6), a conserved transcription factor important for vertebrate neurogenesis. Our results show a decreasing trend of PAX6 labeling in the neuromasts of adult surface salamanders ( Eurycea nana ) relative to the maintained labeling in subterranean species ( Eurycea rathbuni ). These lateral line enhancements are correlated with reductions in the development of optic systems in subterranean salamander lineages. Altogether, our findings provide a starting point for future evolutionary developmental investigations examining the genetic underpinnings of adaptive, repeated evolution in a novel system.
GPT-4o mini: Non-social science research article
Macropinosomes are a site of HIV-1 entry into primary CD4 + T cells
Tomoyuki Murakami, Ricardo de Souza Cardoso, Praveen Manivannan, Ya-Ting Chang, Eric Rentchler, Kai-Neng Chou, Yipei Tang, Joel A. Swanson, Philip D. King, Akira Ono
Full text
HIV-1 has been observed to enter target cells at both the plasma membrane and endosomes. However, which pathways mediate its entry into primary CD4 + T cells, the major targets of this virus, remains unclear. Here, we show that HIV-1 can enter primary CD4 + T cells through macropinocytosis, a form of endocytosis. We found that HIV-1 can enter primary CD4 + T cells at both the plasma membrane and internal compartments, while entry into common T cell lines occurred primarily at the plasma membrane. Inhibition of macropinocytosis suppressed HIV-1 internalization into and subsequent fusion with primary CD4 + T cells regardless of the viral coreceptor usage. Microscopic analysis of viral contents exposed to the cytosol confirmed that HIV-1 fusion occurs at the macropinosomal membrane. Finally, the inhibition of macropinocytosis blocked HIV-1 infection of primary CD4 + T cells. Altogether, this study identifies macropinocytosis as one pathway for HIV-1 entry into primary CD4 + T cells.
GPT-4o mini: Non-social science research article
Assembly and activation of the death-inducing signaling complex
Elizabeth Fosuah, Zhangfei Shen, Jiale Xie, Chen Wang, Qingpeng Lin, Tian-Min Fu
Full text
The death-inducing signaling complex (DISC), comprising Fas, Fas-associated death domain (FADD), and caspase-8, initiates extrinsic apoptosis. Using cryogenic electron microscopy (cryo-EM), we show that Fas and FADD death domains (DDs) form an asymmetric 7:5 oligomer, which promotes FADD death effector domain (DED) filament formation. Structural analysis reveals that FADD DED filaments closely resemble caspase-8 tandem DED filaments, suggesting that FADD DED serves as a nucleation scaffold for caspase-8 assembly. These findings provide a mechanistic framework for how DISC assembly initiates apoptosis and amplifies signaling via higher-order oligomerization.
GPT-4o mini: Non-social science research article
Declining coral calcification to enhance twenty-first-century ocean carbon uptake by gigatonnes
Lester Kwiatkowski, Alban Planchat, Marc Pyolle, Olivier Torres, Nathaelle Bouttes, Adrien Comte, Laurent Bopp
Full text
The sensitivity of coral reefs to climate change is well established. As the oceans warm and acidify, the calcification of coral reefs declines with net calcium carbonate dissolution projected under even moderate emissions trajectories. The impact of this on the global carbon cycle is however yet to be accounted for. Here, we use a synthesis of the sensitivity of coral reef calcification to climate change, alongside reef distribution products to estimate alkalinity and dissolved inorganic carbon fluxes resulting from reductions in reef calcification. Using a global ocean biogeochemical model, we simulate the impact on ocean carbon uptake under different emissions scenarios, accounting for uncertainty in present-day calcification rates. Reductions in net coral reef carbonate production can enhance the ocean carbon sink by up to 1.25 GtCO 2 y −1 by midcentury (0.48 GtCO 2 y −1 median estimate) with cumulative ocean carbon uptake up to 13% greater by 2300 (7% median estimate). Our findings indicate that accounting for the coral reef feedback in projections will increase estimates of the remaining carbon budget associated with global warming thresholds, as well as the likelihood that net zero emissions can be achieved without negative emissions.
GPT-4o mini: Non-social science research article
Nucleoporins cooperate with Polycomb silencers to promote transcriptional repression and repair at DNA double-strand breaks
Hongseon Song, Yubin Bae, Sangin Kim, Dante Deascanis, Yujin Lee, Gergely Rona, Ethan Lane, Seo-yeoung Lee, Su-Jung Kim, Michele Pagano, Kyungjae Myung, Younghoon Kee
Full text
DNA double-strand breaks (DSBs) are harmful lesions and major sources of genomic instability. Studies have suggested that DSBs induce local transcriptional silencing that consequently promotes genomic stability. Several factors have been proposed to actively participate in this process, including Ataxia-telangiectasia mutated (ATM) and Polycomb repressive complex 1 (PRC1). Here, we found that disrupting PRC1 clustering disrupts DSB-induced gene silencing. Interactome analysis of PHC2, a PRC1 subunit that promotes the PRC1 clustering, found several nucleoporins found in the nuclear pore complex (NPC). Similar to PHC2, depleting the nucleoporins also disrupted the DSB-induced gene silencing. We found that some of these nucleoporins, such as NUP107 and NUP43, which are members of the Y-complex of NPC, localize to DSB sites. The presence of nucleoporins and PHC2 at DSB regions was interdependent, suggesting that they act cooperatively in the DSB-induced gene silencing. We further found two structural components within NUP107 to be necessary for the transcriptional repression at DSBs: ATM/ Ataxia telangiectasia and Rad3-related-mediated phosphorylation at the Serine37 residue within the N-terminal disordered tail and the NUP133-binding surface at the C-terminus. These results provide a functional interplay among nucleoporins, ATM, and the Polycomb proteins in the DSB metabolism and underscore their emerging roles in genome stability maintenance.
GPT-4o mini: Non-social science research article
Polaron catastrophe within quantum acoustics
Alhun Aydin, Joonas Keski-Rahkonen, Anton M. Graf, Shaobing Yuan, Xiao-Yu Ouyang, ÖzgĂŒr E. MĂŒstecaplıoğlu, Eric J. Heller
Full text
The quantum acoustic framework has recently emerged as a nonperturbative, coherent approach to electron–lattice interactions, uncovering rich physics often obscured by perturbative methods with incoherent scattering events. Here, we model the strongly coupled dynamics of electrons and acoustic lattice vibrations within this framework, representing lattice vibrations as coherent states and electrons as quantum wave packets, in a manner distinctively different from tight-binding or discrete hopping-based approaches. We derive and numerically implement electron backaction on the lattice, providing both visual and quantitative insights into electron wave packet evolution and the formation of acoustic polarons. We investigate polaron binding energies across varying material parameters and compute key observables—including mean square displacement, kinetic energy, potential energy, and vibrational energy—over time. Our findings reveal the conditions that favor polaron formation, which is enhanced by low temperatures, high deformation potential constants, slow sound velocities, and high effective masses. Additionally, we explore the impact of external electric and magnetic fields, showing that while polaron formation remains robust under moderate fields, it is weakly suppressed at higher field strengths. These results deepen our understanding of polaron dynamics and pave the way for future studies into nontrivial transport behavior in quantum materials.
GPT-4o mini: Non-social science research article
Carbon and oxygen isotope evidence for a protoplanetary disk origin of organic solids in meteorites
William M. Lawrence, Geoffrey A. Blake, John Eiler
Full text
Macromolecular organic solids found in primitive meteorites were the main source of carbon delivered to forming planets in the early Solar System. However, the conditions under which this material formed and its subsequent incorporation into growing planetesimals remains a subject of vigorous debate. Here, we show that C isotope variations among these organics in most carbonaceous chondrites are strongly correlated with mass-independent O isotope anomalies exhibited by their host meteorites. As the latter signature has been argued to track abundances of nebular water generated from photochemical processing of CO gas, the C isotope variability of refractory organic solids may relate to this same process. We propose a framework in which CO photolysis simultaneously produces H 2 O and generates a pool of C + ions that serve as precursors for C-rich organic solids, with their C isotope compositions suggesting formation over a relatively narrow and warm range of temperatures in the protoplanetary disk (~200 to 400 K). Two populations of organic precursors with different C isotope compositions became associated with distinct dust reservoirs prior to their delivery to the carbonaceous-chondrite-forming region, which likely resided at lower temperatures (<170 K). This finding places detailed constraints on the location and distribution of chemical reactions that generated both water and organic-rich reservoirs in the early Solar System.
GPT-4o mini: Non-social science research article
Pathophysiologically relevant bisphenol S exposure accelerates aging by disrupting brown adipose tissue–regulated energy metabolism
Man Zhu, Ru Wang, Wei Yi, Beiyi Wu, Zhizhong Deng, Zheng Zhang, Chen Wang, Dingkun Zhang, Tongtong Zhang, Xue Wen
Full text
Bisphenol A (BPA) substitutes are widely used as food contact materials and consumer products, while the effects of pathophysiologically relevant concentrations of BPA substitutes on aging remain unclear. In this study, we used Caenorhabditis elegans ( C. elegans ) to investigate the effects of five BPA substitutes [bisphenol S (BPS), bisphenol B, bisphenol F (BPF), tetramethyl BPF, and 4,4â€Č-(Perfluoropropane-2,2-diyl)diphenol] at pathophysiologically relevant exposure levels during aging and examined the underlying mechanisms using a mouse model. Our results indicated that, among the five BPA substitutes, exposure to pathophysiologically relevant concentrations of BPS (300, 450, and 600 nM) accelerated aging in C. elegans . In mice, exposure to a pathophysiologically relevant concentration of BPS (125 ÎŒg/kg/day, from 4 to 20 mo of age) similarly reduces the life and health span and accelerates aging phenotypes in multiple tissues. Further investigations demonstrated that long-term BPS exposure resulted in a significantly higher accumulation of BPS in brown adipose tissue (BAT) than in other organs. RNA sequencing analysis of BAT revealed that BPS accelerates BAT aging through multiple pathways. Importantly, transplantation of BAT from BPS-exposed mice into BPS-naive mice accelerated aging in recipients. Conversely, transplantation of BAT from unexposed mice into BPS-exposed mice significantly improved their metabolic status and delayed aging. These findings elucidate the impact of pathophysiologically relevant concentrations of BPS on the aging process and suggest that these effects are likely mediated through the disruption of BAT function.
GPT-4o mini: Non-social science research article
Correction for Yin et al., Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling
Full text
GPT-4o mini: Non-social science research article
Correction for Izdebski et al., Unbalanced social–ecological acceleration led to state formation failure in early medieval Poland
Full text
GPT-4o mini: Non-social science research article
The proofreading mechanism of the human leading-strand DNA polymerase Δ holoenzyme
Feng Wang, Qing He, Michael E. O’Donnell, Huilin Li
Full text
The eukaryotic leading-strand DNA polymerase Δ (PolΔ) is a dual-function enzyme with a proofreading 3â€Č-5â€Č exonuclease ( exo ) site located 40 Å from the DNA synthesizing pol site. Errors in PolΔ proofreading can cause various mutations, including C-to-G transversions, the most prevalent mutation in cancers and genetic diseases. PolΔ interacts with all three subunits of the PCNA ring to assemble a functional holoenzyme. Despite previous studies on proofreading of several Pol’s, how PolΔ—or any Pol complexed with its sliding clamp—proofreads a mismatch generated in situ has been unknown. We show here by cryo-EM that a template/primer DNA substrate with a preexisting mismatch cannot enter the exo site of PolΔ–PCNA holoenzyme, but a mismatch generated in situ in the pol site yields three bona fide proofreading intermediates of PolΔ–PCNA holoenzyme. These intermediates reveal how the mismatch is dislodged from the pol site, how the DNA unwinds six base pairs, and how the unpaired primer 3â€Č-end is inserted into the exo site for cleavage. These results unexpectedly demonstrate that PCNA imposes strong steric constraints that extend unwinding and direct the trajectory of mismatched DNA and that this trajectory is dramatically different than for PolΔ in the absence of PCNA. These findings suggest a physiologically relevant proofreading mechanism for the human PolΔ holoenzyme.
GPT-4o mini: Non-social science research article
Structure–function coupling in the first month of life: Associations with age and attention
Ursula A. Tooley, Jeanette K. Kenley, M. Catalina Camacho, Aidan Latham, Dimitrios Alexopoulos, Ashley N. Nielsen, Tara A. Smyser, Barbara B. Warner, Joshua S. Shimony, Jeffrey J. Neil, Joan L. Luby, Deanna M. Barch, Cynthia E. Rogers, Christopher D. Smyser
Full text
How brain structure relates to function is a critical and open question in neuroscience. Here, we characterize regional variation in structure–function coupling, capturing the degree to which a cortical region’s structural connections relate to patterns of coordinated neural activity in healthy, term-born neonates ( n = 239). Regional structure–function coupling is heterogeneously patterned across the cortex, with higher coupling in the auditory, lateral prefrontal, and inferior parietal cortices. Average structure–function coupling is negatively associated with age during the first month of life, with age-associated decreases seen in primary sensory systems, specifically in auditory and somatomotor regions. Age-associated “decoupling” of structure and function reflects increasingly segregated patterns of functional connectivity and increasingly integrated patterns of white matter connectivity with age. Notably, higher structure–function coupling after accounting for age in the dorsal attention, cingulo-opercular, and visual systems at birth is associated with faster visuospatial attention to faces at one year of age. These results yield valuable insight into the development of structural and functional connectivity across the cortex, including how interregional variation in structure–function coupling during the first month of life might shape later attention.
GPT-4o mini: Non-social science research article
Robustness revisited: On the neutral evolution of centrality and localization
Yehonatan Sella, Aviv Bergman
Full text
This study investigates the intricate interplay among neutral landscape structure, mutation rate, recombination rate, and population dynamics in shaping evolutionary robustness. We provide a comprehensive framework that elucidates how different evolutionary forces interact to influence genotypic robustness and localization within haploid and diploid populations. We demonstrate that in haploid populations, high mutation rates relative to recombination typically drive the population toward regions of increased eigencentrality, a graph-theoretic measure of centrality which is correlated while not identical to mutational robustness. On the other hand, recombination increases the localization of the population to a smaller region of genotypic space, while high values of recombination relative to mutation can introduce shifts in distribution away from regions of high eigencentrality and toward attractors of the recombination dynamics. Diploid dynamics further complicate these interactions, showing reduced alignment with eigencentrality under both high mutation and recombination rates, with the exception of structured diploid landscapes where dynamics are still aligned with increasing eigencentrality. Our findings underscore the nuanced dependencies of evolutionary outcomes on both local and global landscape structures as well as evolutionary parameters.
GPT-4o mini: Non-social science research article
Freeze-induced crystallization: An overlooked pathway for mineral genesis in natural waters
Younghoon Won, Sungsik Lee, Seungyeol Lee, SoHyun Park, Jun Lim, Wonyong Choi, Giehyeon Lee
Full text
Natural ice plays salient roles in making the Earth habitable and sustainable. Previously overlooked, its role in chemical processes is now of emerging interest, particularly due to the freeze concentration effect, which can substantially promote chemical reactions during ice formation. We demonstrate here that ice formation can serve as a dynamic and unique pathway for mineral genesis. Freezing solutions containing dissolved manganese and carbonates produced rhodochrosite (Mn II CO 3 ) even under slightly undersaturated conditions. At room temperature, by contrast, this occurred when the solution saturation level was increased by ca. 30,000 times. The cryogenic rhodochrosite formed spherical aggregates of nano-polycrystallites, distinctly different from the cubic monocrystalline particles observed at room temperature. The distinct feature likely resulted from the combined effects of the intensified supersaturation induced by the freeze concentration effect and the low temperatures within liquid-like layers, conditions that make liquid-like layers an exceptional environment for mineral genesis, unlike typical natural water systems. The cryogenic rhodochrosite formation was successfully demonstrated using in situ, real-time X-ray absorption spectroscopy (XAS), enabling direct observation of freeze-induced solid formation. Our findings reveal that freeze-induced crystallization may be an active mineralization pathway, potentially influencing elemental cycles within the cryosphere and contributing to minerals with distinguishing properties and reactivities in the environment.
GPT-4o mini: Non-social science research article
Reply to Larsen and RiisgÄrd: Fluid dynamics of choanocyte chambers
Takumi Ogawa, Shuji Koyama, Toshihiro Omori, Kenji Kikuchi, HélÚne de Maleprade, Raymond E. Goldstein, Takuji Ishikawa
Full text
GPT-4o mini: Non-social science research article
Detection of the knee point in lithium-ion battery degradation using a state-of-charge-dependent parameter
Hyunjae Kim, Inwoo Kim, Minsoo Kim, Seongha An, Hyo Chul Ahn, Dongmin Park, Jun Hee Lee, Chun Yong Kang, Jang Wook Choi
Full text
The rapidly expanding lithium-ion battery (LIB) market has heightened the demand for efficient diagnostics for in-use cells and the reliable grading of used cells. Various purpose-built analysis tools and statistical algorithms have been developed, but often rely on redundant instrumentation and computationally intensive procedures. Here, we propose using the variance of the capacity difference between 0.2C and 1C, Var(Δ Q 0.2C-1C (V) ), based on the strong correlation between the interfacial state of the anode and mode of capacity degradation, as a measure of the health state of individual cells. A single-point “off-board” measurement of Var(Δ Q 0.2C-1C (V) ) indicates whether a particular cell is experiencing self-limiting or accelerating degradation and is thus near a knee point in its cycle life. This assessment additionally provides a quantitative criterion for differentiating used cells for reuse or recycling. Our findings suggest that utilizing state-of-charge-dependent key electrochemical properties enables the cell health to be accurately monitored, thereby promoting sustainability in the expanding battery market.
GPT-4o mini: Non-social science research article
Natural dispersal is better than translocation for reducing risks of inbreeding depression in eastern black rhinoceros ( Diceros bicornis michaeli )
Ronald. V. K. Mellya, J. Grant C. Hopcraft, William Mwakilema, Ernest M. Eblate, Simon Mduma, Bakari Mnaya, Idrissa S. Chuma, Emmanuel S. Macha, Dickson Wambura, Robert D. Fyumagwa, Elizabeth Kilbride, Umer Z. Ijaz, Barbara K. Mable, Anubhab Khan
Full text
Due to increasing anthropogenic impacts, many species survive only in small and isolated populations. Active conservation management to reduce extinction risk includes increasing habitat connectivity, translocations from captive populations, or intensive surveillance of highly protected closed populations. Advances in sequencing technology mean that it is now possible to consider the genomic impacts of such strategies, as a proxy for variation in individual fitness. Using whole genome sequences from critically endangered eastern black rhinoceros ( Diceros bicornis michaeli ), we compare the consequences of different types of conservation efforts, based on cohorts of offspring resulting from parents from different sources. Based on the fraction of the genome in runs of homozygosity (ROH) of different lengths, we found lower inbreeding in offspring of individuals that had either been translocated from ex-situ populations (F ROH>1Mb = 0.047) or dispersed between proximate native populations (F ROH>1Mb = 0.065) compared to the intensively managed closed population from which the migrant moved (F ROH>1Mb = 0.112). However, the benefit of such movement was removed after only a few generations of closed breeding (F ROH>1Mb = 0.149). Although sample size restricted power to detect significance of differences, the relative abundance of highly deleterious mutations was higher for offspring resulting from translocation compared to the other cohorts and this load was sheltered by higher heterozygosity, which could increase risks of inbreeding depression if inbreeding subsequently occurs. In contrast, native dispersers reduced the negative effects of inbreeding without compromising the benefits of past purging of deleterious mutations. Our study highlights the importance of natural dispersal and reiterates the importance of maintaining habitat corridors between populations.
GPT-4o mini: Non-social science research article
Correction for Guo et al., Targeting amyloid-ÎČ in glaucoma treatment
Full text
GPT-4o mini: Non-social science research article
Task difficulty modulates the effect of mind wandering on phase dynamics
Zhengkun Long, Georg Northoff, Xiaolan Fu
Full text
Mind wandering attenuates widespread sensory and motor processing, both of which are mediated by phase coherence. However, it remains unclear i) whether mind wandering impacts both sensory input and motor output processing by modulating ii) neural entrainment to external stimuli, as measured by intertrial phase coherence (ITPC), and specifically iii) whether task difficulty with different degrees of attentional demands moderates the impact of mind wandering on phase coherence. Using the thought-probe method, we assessed participants’ attentional states during different sensory and motor tasks with varying task difficulty. We found that mind wandering decreased ITPC exclusively in less demanding tasks but not in difficult ones, regardless of whether the tasks involved visual input or motor output processing. Our results suggest that external task difficulty may modulate the balance between external and internal cognitive processing (e.g., mind wandering), with simpler tasks facilitating internally oriented cognition and increasing mind wandering. This balance between internal mind wandering and external task difficulty is mediated, in part, by phase coherence, which serves as an underlying neural mechanism. Collectively, our findings support the hypothesis that phase coherence and its dynamics (ITPC) play a key role in mediating the reciprocal balance of internal and external cognition—this suggests their partly shared cognitive-executive resources as entailed by the recently proposed Baseline model of cognition.
GPT-4o mini: Non-social science research article
Evolutionarily conserved BON1 regulates the basal cytosolic Ca 2+ level by calmodulin-independent activation of Ca 2+ pumps in Arabidopsis
Zhan Li, Hyo Jung Kim, Laura Luoni, Carolina Conter, Nicola MasĂš, Francesca Resentini, Peiqiao Xie, Alessandra Astegno, Maria Cristina Bonza, Jian Hua
Full text
Plasma membrane-localized autoinhibited Ca 2+ pumps are essential for maintaining basal cytosolic Ca 2+ levels for regulating growth processes and environmental responses. These pumps are known to be activated by calmodulins to maintain Ca 2+ homeostasis in plants and animals. Here, we demonstrate that the evolutionarily conserved copine protein BON1 is critical for maintaining low cytosolic Ca 2+ concentrations by directly regulating two plasma membrane-localized Ca 2+ pumps ACA8 and ACA10 in Arabidopsis . BON1 interacts with a region within the N-terminal domain of ACA8 and ACA10, preceding the calmodulin binding sites, and stimulates ACA8 activity. This activation can occur without calmodulin binding, indicating that BON1 and calmodulin independently regulate the Ca 2+ pump. Loss of BON1 function results in elevated basal cytosolic Ca 2+ concentrations, which can be partially rescued by overexpressing hyperactive ACA8 or ACA10. Furthermore, we show that BON1 has one high-affinity Ca 2+ binding site in the VWA domain that is critical for activation of ACA8 as well as for BON1 function, suggesting a feedback mechanism for Ca 2+ homeostasis at resting concentrations. Our findings suggest that this Ca 2+ responsive regulatory mechanism extends beyond Arabidopsis , as we show interactions between ACA and BON proteins from algae to flowering plants, pointing to an ancient regulatory mechanism for maintaining low basal cytosolic Ca 2+ . Notably, a human plasma membrane-localized autoinhibited Ca 2+ pump can also be activated by a human BON protein in a yeast functional assay system, suggesting evolutionary conservation in Ca 2+ regulation across species.
GPT-4o mini: Non-social science research article
ATP8B1 regulates PIP2 localization and cleavage of pyroptotic executioner Gasdermin D
Nilam Bhandari, Ashutosh Prince, Mariam R. Khan, C. Alicia Traughber, Kalash Neupane, Shuhui W. Lorkowski, Gregory Brubaker, Elif G. Ertugral, Chandrasekhar R. Kothapalli, George R. Dubyak, Jonathan D. Smith, Kailash Gulshan
Full text
Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis, with symptoms including pruritus, pancreatitis, fat malabsorption, intestinal inflammation, and failure to thrive. High-throughput studies showed interconnection between ATP8B1 and phosphoinositide (PIPs), but the mechanism linking ATP8B1, lipid metabolism, and inflammation remains unclear. Atp8b1 G308V/G308V mouse model, unbiased RNAseq, high-resolution-stimulation emission depltion (STED)-microscopy, and Crispr-Cas9 generated ATP8B1 −/− knockouts in hepatocytes/monocytes/macrophages were used to determine role of ATP8B1 in phosphatidylinositol,4-5-bisphosphate (PIP2) trafficking and inflammation. Human ATP8B1, purified from Sf9 insect cells and reconstituted in proteoliposomes, was used to test cell-free PIP2 flip. Various in-vitro techniques were used for testing direct interaction between PIP2 and ATP8B1. ATP8B1 maintains PIP2 at the inner leaflet of plasma membrane (PM). ATP8B1 flips PIP2 in cells, without altering flip of PE or bulk-endocytosis. ATP8b1 flips PIP2 in a cell-free system. ATP8B1 deletion promotes bile-salt-mediated cholesterol extraction from hepatocytes in a PIP2-dependent manner. PIP2 directly binds to the P-loop of ATP8B1. Unbiased RNAseq showed upregulation of inflammatory cytokines in ATP8b1 −/− immune cells. ATP8B1 −/− monocytes/macrophages showed aberrant lipopolysaccharide (LPS)-induced cleavage of GSDMD, formation of GSDMD pores, and interleukin-1beta (IL1ÎČ) release. Inflammation-resolving efferocytosis was impaired in ATP8B1 −/− macrophages. Biophysical properties of PM were altered in ATP8b1 −/− cells, with the mechanism being disrupted localization of PIP2. Atp8b1 G308V/G308V mice exposed to LPS showed higher plasma IL1ÎČ and lower survival rates vs. WT mice. ATP8B1 maintains PIP2 at the inner leaflet of PM. ATP8b1 directly flips and binds PIP2. ATP8B1 regulates LPS-induced GsdmD cleavage, formation of GsdmD pores, IL1ÎČ release, and mortality in mice.
GPT-4o mini: Non-social science research article
Correction for Yuan et al., Molecular mechanism and functional significance of Wapl interaction with the Cohesin complex
Full text
GPT-4o mini: Non-social science research article
The pumping function of sponge choanocyte chambers
Poul S. Larsen, Hans Ulrik RiisgÄrd
Full text
GPT-4o mini: Non-social science research article
Amortized template matching of molecular conformations from cryoelectron microscopy images using simulation-based inference
Lars Dingeldein, David Silva-Sánchez, Luke Evans, Edoardo D’Imprima, Nikolaus Grigorieff, Roberto Covino, Pilar Cossio
Full text
Characterizing the conformational ensemble of biomolecular systems is key to understand their functions. Cryoelectron microscopy (cryo-EM) captures two-dimensional snapshots of biomolecular ensembles, giving in principle access to thermodynamics. However, these images are very noisy and show projections of the molecule in unknown orientations, making it very difficult to identify the biomolecule’s conformation in each individual image. Here, we introduce cryo-EM simulation-based inference (cryoSBI) to infer the conformations of biomolecules and the uncertainties associated with the inference from individual cryo-EM images. CryoSBI builds on simulation-based inference, a merger of physics-based simulations and probabilistic deep learning, allowing us to use Bayesian inference even when likelihoods are too expensive to calculate. We begin with an ensemble of conformations, templates from experiments, and molecular modeling, serving as structural hypotheses. We train a neural network approximating the Bayesian posterior using simulated images from these templates and then use it to accurately infer the conformation of the biomolecule from each experimental image. Training is only done once on simulations, and after that, it takes just a few milliseconds to make inference on an image, making cryoSBI suitable for arbitrarily large datasets and direct analysis on micrographs. CryoSBI eliminates the need to estimate particle pose and imaging parameters, significantly enhancing the computational speed compared to explicit likelihood methods. Importantly, we obtain interpretable machine learning models by integrating physics-based approaches with deep neural networks, ensuring that our results are transparent and reliable. We illustrate and benchmark cryoSBI on synthetic data and showcase its promise on experimental single-particle cryo-EM data.
GPT-4o mini: Non-social science research article
Cocrystal structure reveals the mechanism of FSP1 inhibition by FSEN1
Sitao Zhang, Amalia H. Megarioti, Joseph M. Hendricks, Junshu Zhou, Qingxiang Sun, Da Jia, James A. Olzmann
Full text
FSP1 is an FAD-dependent oxidoreductase that uses NAD(P)H to regenerate the reduced forms of lipophilic quinone antioxidants, such as coenzyme Q10 and vitamin K. These quinone antioxidants function as radical scavenging agents that prevent the propagation of lipid peroxidation and the induction of ferroptosis. Although several small-molecule inhibitors of FSP1 have been developed and found to sensitize cancer cells to ferroptosis, our understanding of their molecular mechanisms remains limited and no structures of FSP1 in complex with its inhibitors have been solved. Here, we solve the cocrystal structure of FSP1 in complex with the FSP1 inhibitor FSEN1, revealing that FSEN1 binds within the FSP1 substrate-binding pocket. FSEN1 makes key interactions with a critical phenylalanine, which is absent in mouse FSP1, providing an explanation for the selectivity of FSEN1 for human FSP1. These conclusions are supported by mutagenesis of FSP1 and biochemical and cellular assays of FSP1 function. Our findings provide the first cocrystal structure of FSP1 in complex with an inhibitor, enhancing our understanding of the mechanism of FSP1 inhibition and enabling future rational medicinal chemistry efforts to advance FSP1 inhibitors as therapeutics.
GPT-4o mini: Non-social science research article
Circuit complexity and functionality: A statistical thermodynamics perspective
Claudio Chamon, Andrei E. Ruckenstein, Eduardo R. Mucciolo, Ran Canetti
Full text
Circuit complexity, defined as the minimum circuit size required for implementing a particular Boolean computation, is a foundational concept in computer science. Determining circuit complexity is believed to be a hard computational problem. Recently, in the context of black holes, circuit complexity has been promoted to a physical property, wherein the growth of complexity is reflected in the time evolution of the Einstein-Rosen bridge (“wormhole”) connecting the two sides of an anti-de Sitter “eternal” black hole. Here, we are motivated by an independent set of considerations and explore links between complexity and thermodynamics for functionally equivalent circuits, making the physics-inspired approach relevant to real computational problems, for which functionality is the key element of interest. In particular, our thermodynamic framework provides an alternative perspective on the obfuscation of programs of arbitrary length—an important problem in cryptography—as thermalization through recursive mixing of neighboring sections of a circuit, which can be viewed as the mixing of two containers with “gases of gates.” This recursive process equilibrates the average complexity and leads to the saturation of the circuit entropy, while preserving functionality of the overall circuit. The thermodynamic arguments hinge on ergodicity in the space of circuits which we conjecture is limited to disconnected ergodic sectors due to fragmentation. The notion of fragmentation has important implications for the problem of circuit obfuscation as it implies that there are circuits of same size and functionality that cannot be connected via a polynomial number of local moves. Furthermore, we argue that fragmentation is unavoidable unless the complexity classes NP and coNP coincide, a statement that implies the collapse of the polynomial hierarchy of computational complexity theory to its first level.
GPT-4o mini: Non-social science research article
Oxr1 and Ncoa7 regulate V-ATPase to achieve optimal pH for glycosylation within the Golgi apparatus and trans-Golgi network
Shin-ichiro Yoshimura, Tomoaki Sobajima, Masataka Kunii, Akihiro Harada
Full text
Maintenance of pH within membranous organelles is crucial for cellular processes such as posttranslational modifications, ligand–receptor interactions, and proteostasis. The precise mechanisms that determine the luminal pH of each organelle are not fully understood. This study investigated the mechanisms that regulate luminal pH to ensure optimal enzymatic activity. We identified Oxr1 and its paralog Ncoa7, which regulate the vacuolar-type proton pump ATPase (V-ATPase) at the Golgi apparatus and trans-Golgi network (TGN). Oxr1 and Ncoa7 were predominantly localized at the Golgi and TGN membranes, dependent on their binding to various GTP-bound Rab proteins. In vitro experiments using purified recombinant proteins indicated that Oxr1 and Ncoa7 directly bind to the catalytic subunit of V-ATPase, inhibiting its ATP hydrolytic activity via their TLDc domains. We observed significant acidification of the Golgi/TGN lumen in Oxr1- and Ncoa7-depleted cells. Lectin blot analysis demonstrated that depletion of Oxr1 and Ncoa7 led to a defect in protein glycosylation, a major enzymatic posttranslational modification in the Golgi and TGN. Furthermore, depletion of Oxr1 and Ncoa7, along with drug-induced inhibition of glycosylation, increased lysosomal pH and sensitivity to silicon dioxide-induced membrane damage. This apparent lysosomal dysfunction suggested that, in addition to the Golgi and TGN, Oxr1 and Ncoa7 also contribute to the integrity of other organelles. Our findings indicate that Oxr1 and Ncoa7 protect the Golgi and TGN lumen from excess acidification by inhibiting V-ATPase activity and providing an optimal environment for enzymatic activity in the Golgi and TGN.
GPT-4o mini: Non-social science research article
Material properties of biomolecular condensates emerge from nanoscale dynamics
Nicola Galvanetto, Miloơ T. Ivanović, Simone A. Del Grosso, Aritra Chowdhury, Andrea Sottini, Daniel Nettels, Robert B. Best, Benjamin Schuler
Full text
Biomolecular condensates form by phase separation of biological polymers and have important functions in the cell—functions that are inherently linked to their physical properties at different scales. A notable aspect of such membraneless organelles is that their viscoelastic properties can vary by orders of magnitude, but it has remained unclear how these pronounced differences are rooted in the nanoscale dynamics at the molecular level. Here, we investigate a series of condensates formed by complex coacervation of highly charged disordered proteins and polypeptides that span about two orders of magnitude in bulk viscosity. We find that their viscosity is highly correlated with protein translational diffusion and nano- to microsecond chain dynamics. Remarkably, analytical relations from polymer physics can predict condensate viscosity from diffusivity and chain dynamics, and vice versa, even for more hydrophobic disordered proteins and for synthetic polyelectrolytes, indicating a mechanistic link across several decades of length- and timescales. Atomistic simulations reveal that the observed differences in friction—a key quantity underlying these relations—reflect differences in interresidue contact lifetimes as a function of arginine content and salt concentration, leading to the vastly different dynamics among condensates. The rapid exchange of interresidue contacts we observe may be a general mechanism for preventing dynamic arrest in compartments densely packed with polyelectrolytes, such as the cell nucleus.
GPT-4o mini: Non-social science research article
Climate warming increases global oceanic dimethyl sulfide emissions
Sankirna D. Joge, Karam Mansour, Rafel SimĂł, MartĂ­ GalĂ­, Nadja Steiner, Alfonso Saiz-Lopez, Anoop S. Mahajan
Full text
Oceanic dimethyl sulfide (DMS) is the largest natural source of atmospheric sulfur. DMS is biologically produced in seawater and emitted into the atmosphere, where its oxidation products contribute to aerosol formation with consequences for cloud albedo and the Earth’s radiative budget and climate. Climate model projections of how DMS emissions change with global warming are largely uncertain, even contradictory. Here, we use machine-learning models trained with biome-resolved global observations to simulate seawater DMS concentrations (1850 to 2100) using physico-chemical and biological predictors from eight CMIP6 models. The scatter in current projections is largely reduced, and globally averaged seawater DMS concentrations are predicted to decrease in the coming decades. However, global DMS emissions will increase due to rising surface wind speeds and sea surface temperatures which contradicts the current AR6 assessment that the DMS flux will reduce in the future. Concurrence of increasing DMS emissions and declining anthropogenic sulfur dioxide emissions suggests an increase in the relative importance of DMS to sulfate aerosol formation and its climate cooling impact.
GPT-4o mini: Non-social science research article
A mouse model of Jansen’s metaphyseal chondrodysplasia for investigating disease mechanisms and candidate therapeutics
Jakob Höppner, Damla Firat, Mohd Parvez-Khan, Monica Reyes, Patrick Hanna, Prem Swaroop Yadav, Thomas Dean, Karla M. Ramos-Torres, Pedro Brugarolas, Michael T. Collins, Marc N. Wein, Shi Liu, Samuel H. Gellman, Ernestina Schipani, Henry M. Kronenberg, Thomas J. Gardella, Harald JĂŒppner
Full text
Jansen’s metaphyseal chondrodysplasia (JMC) is a rare disorder caused by activating mutations in the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor (PTH1R). Patients exhibit short stature, dysmorphic bones, and severe growth plate abnormalities, as well as hypercalcemia, hypercalciuria, hypophosphatemia, and reduced plasma PTH levels. Humanized PTH1R (hPTH1R) mice expressing the H223R-hPTH1R JMC mutation die early without breeding. We therefore generated and characterized a stable mouse line expressing the T410R-hPTH1R allele, which confers a milder disease phenotype in patients. Mutant mice show near-normal longevity and reproductive capacity yet exhibit a profound skeletal phenotype characteristic of the disease. The long bones of T410R mice are markedly misshapen and have expanded metaphyses with disarrayed chondrocyte zones in growth plates and reduced primary spongiosa. PET/CT scanning revealed diminished uptake of [ 18 F]-sodium fluoride in the growth plate area, consistent with reduced mineralization and vascularization. Genetic ablation of Hdac4 rescued the growth plate abnormalities in T410R mice, thereby establishing the PTH1R-Gαs-cAMP-PKA-SIK3-HDAC4/5 pathway as the main mediator of growth plate abnormalities in JMC. Serum calcium was elevated and endogenous PTH was suppressed in T410R mice, and both parameters could be normalized by acute injection of an optimized PTH inverse agonist peptide. The T410R mouse thus represents a stable animal model of JMC that recapitulates the abnormalities in skeletal development and mineral ion homeostasis which characterize this disease. The mice should help efforts to further define the cellular and molecular mechanisms underlying the JMC phenotype and to develop a potential mode of therapy.
GPT-4o mini: Non-social science research article
Epithelial Regnase-1 inhibits colorectal tumor growth by regulating IL-17 signaling via degradation of NFKBIZ mRNA
Eriko Iguchi, Atsushi Takai, Natsumi Oe, Yosuke Fujii, Mayuki Omatsu, Haruhiko Takeda, Takahiro Shimizu, Takahisa Maruno, Yuki Nakanishi, Masanori Yoshinaga, Takashi Maruyama, Hiroyuki Marusawa, Kazutaka Obama, Osamu Takeuchi, Hiroshi Seno
Full text
Regnase-1 is a ribonuclease that regulates inflammation in immune cells by degrading cytokine mRNA. Regnase-1 was identified as one of the frequently mutated genes in the inflamed colorectal epithelium of patients with ulcerative colitis; however, its significance in intestinal epithelial cells during the tumorigenic process remains unknown. Therefore, we developed an Apc Min/+ mouse model lacking Regnase-1 in intestinal epithelia. Regnase-1 deletion significantly enhanced colon tumor growth accompanied by elevated levels of extracellular signal-regulated kinase (ERK) phosphorylation in tumor tissues. Transcriptome analysis of the tumor tissues revealed that Nfkbiz , a mediator of the interleukin (IL)-17 signaling pathway, was the primary degradative target of Regnase-1 in enterocytes and that Regnase-1 deficiency enhanced IL-17 signaling. The treatment with antibiotics or IL-17-neutralizing antibody canceled the proliferative effect of colon tumors due to Regnase-1 deletion, suggesting the protective role of Regnase-1 against colon tumor growth was dependent on IL-17 signaling triggered by gut microbes. Analysis of the Nfkbiz knockout mouse model demonstrated that the tumor-suppressive effect of Regnase-1 depended on Nfkbiz expression. Remarkably, oral treatment of dimethyl fumarate, a potential inhibitor of Regnase-1 protein inactivation, suppressed tumor growth, downregulated Nfkbiz , and suppressed ERK activation. Furthermore, TCGA data analysis revealed that low Regnase-1 expression in colorectal cancer tissue was related to poor prognosis. Therefore, Regnase-1 represses colon tumor growth by regulating IL-17 signaling via Nfkbiz mRNA degradation. Regnase-1 could be a potential therapeutic target in colon tumors.
GPT-4o mini: Non-social science research article
Rhomboid-mediated cleavage of the immune receptor XA21 protects grain set and male fertility in rice
Satyam Vergish, Xiaoen Huang, Guiyun Zhang, Beatriz de Toledo Franceschi, Jian-Liang Li, Xiao-Xia Wu, Joana Nuraj, Jose C. Huguet-Tapia, Apekshya Parajuli, Xiuhua Chen, Ritu Shekhar, Dali Liu, Wu-Ming Xiao, Shijuan Dou, Guo-zhen Liu, Erica M. Goss, Liya Pi, Sixue Chen, Karen E. Koch, Wen-Yuan Song
Full text
To maintain growth and to successfully reproduce, organisms must protect key functions in specific tissues, particularly when countering pathogen invasion using internal defensive proteins that may disrupt their own developmental processes. The rice immune receptor XA21 confers race-specific resistance against Xanthomonas oryzae pv. oryzae , which causes the deadly disease bacterial leaf blight. Here, we demonstrate that XA21 is cleaved by the rhomboid-like protease OsRBL3b, likely within its transmembrane domain. OsRBL3b mRNA transcripts are preferentially expressed in rice spikelets. Rice plants expressing Xa21 but lacking a functional OsRBL3b displayed impaired anther dehiscence and pollen viability, resulting in male sterility and yield reduction with high levels of XA21 protein present in spikelets during anthesis. In leaves, osrbl3b mutants expressing XA21 had normal levels of this resistance protein and disease immunity. This balance between reproduction and disease resistance through the specific expression of a rhomboid protease may be key to limiting the detrimental effects of an active immune response and may be useful in future for genetic improvement of crops.
GPT-4o mini: Non-social science research article
Study design and the sampling of deleterious rare variants in biobank-scale datasets
Margaret C. Steiner, Daniel P. Rice, Arjun Biddanda, Mariadaria K. Ianni-Ravn, Christian Porras, John Novembre
Full text
One key component of study design in population genetics is the “geographic breadth” of a sample (i.e., how broad a region across which individuals are sampled). How the geographic breadth of a sample impacts observations of rare, deleterious variants is unclear, even though such variants are of particular interest for biomedical and evolutionary applications. Here, in order to gain insight into the effects of sample design on ascertained genetic variants, we formulate a stochastic model of dispersal, genetic drift, selection, mutation, and geographically concentrated sampling. We use this model to understand the effects of the geographic breadth of sampling effort on the discovery of negatively selected variants. We find that samples which are more geographically broad will discover a greater number of variants as compared to geographically narrow samples (an effect we label “discovery”); though the variants will be detected at lower average frequency than in narrow samples (e.g., as singletons, an effect we label “dilution”). Importantly, these effects are amplified for larger sample sizes and fitness effects. We validate these results using both population genetic simulations and empirical analyses in the UK Biobank. Our results are particularly important in two contexts: the association of large-effect rare variants with particular phenotypes and the inference of negative selection from allele frequency data. Overall, our findings emphasize the importance of considering geographic breadth when designing and carrying out genetic studies, especially at biobank scale.
GPT-4o mini: Non-social science research article
Population sequencing for phylogenetic diversity and transmission analyses
Talima Pearson, Tara Furstenau, Colin Wood, Vanessa Rigas, Kylie Drake, Jason Sahl, Sara Maltinsky, Bart J. Currie, Mark Mayo, Carina Hall, Paul Keim, Viacheslav Fofanov
Full text
Genomic diversity in pathogen populations is foundational for evolution and adaptation. Understanding population-level diversity is also essential for tracking sources and revealing detailed pathways of transmission and spread. For bacteria, culturing, isolating, and sequencing the large number of individual colonies required to adequately sample diversity can be prohibitively time-consuming and expensive. While sequencing directly from a mixed population will show variants among reads, they cannot be linked to reveal allele combinations associated with phylogenetic inheritance patterns. Here, we describe the theory and method for using population sequencing directly from a mixed sample, along with a minimal number of individually sequenced colonies, to describe the phylogenetic diversity of a population without haplotype reconstruction. To demonstrate the utility of population sequencing in capturing phylogenetic diversity, we compared isogenic clones to population sequences of Burkholderia pseudomallei from sputum of a single patient. Our results point to the pathogen population being highly structured, suggesting that for some pathogens, sputum sampling may preserve structuring in the lungs and thus present a noninvasive alternative to understanding colonization, movement, and pathogen/host interactions. We also analyzed population sequences of Staphylococcus aureus derived from different people and different body sites to reveal directionality of transmission between hosts and across body sites, demonstrating the power and utility for characterizing the spread of disease and identification of reservoirs at the finest levels. We anticipate that population sequencing and analysis can be broadly applied to accelerate research in a wide range of fields reliant on a foundational understanding of population phylogenetic diversity.
GPT-4o mini: Non-social science research article
Deciphering Ca 2+ permeation and valence selectivity in Ca V 1: Molecular dynamics simulations reveal the three-ion knock-on mechanism
Lingfeng Xue, Nieng Yan, Chen Song
Full text
Voltage-gated calcium (Ca V ) channels are pivotal in cellular signaling due to their selective calcium ion permeation upon membrane depolarization. While previous studies have established the highly selective permeability of Ca V channels, the detailed molecular mechanism remains elusive. Here, we use extensive atomistic molecular dynamics simulations to elucidate the mechanisms governing ion permeation and valence selectivity in Ca V 1 channels. Employing the electronic continuum correction method, we simulated a calcium conductance of approximately 9 to 11 pS, aligning closely with experimental measurement. Our simulations uncovered a three-ion knock-on mechanism critical for efficient calcium ion permeation, necessitating the binding of at least two calcium ions within the selectivity filter (SF) and the subsequent entry of a third ion. In silico mutation simulations further validated the importance of multi-ion coordination in the SF for efficient ion permeation, identifying two critical residues, D706 and E1101, that are essential for the binding of two calcium ions in the SF. Moreover, we explored the competitive permeation of calcium and sodium ions and obtained a valence selectivity favoring calcium over sodium at a ratio of approximately 35:1 under the bication condition. This selectivity arises from the strong electrostatic interactions of calcium ions in the confined SF and the three-ion knock-on mechanism. Our findings provide quantitative insights into the molecular underpinnings of Ca V channel function, with implications for understanding calcium-dependent cellular processes.
GPT-4o mini: Non-social science research article
Label-free high-throughput live-cell sorting of genome-wide random mutagenesis libraries for metabolic traits by Raman flow cytometry
Xixian Wang, Sen Wang, Zhidian Diao, Xibao Hou, Yanhai Gong, Qing Sun, Jiaping Zhang, Lihui Ren, Yuandong Li, Yuetong Ji, Wei Shen, Yifeng Yin, Shi Huang, Xiaojin Song, Qiu Cui, Yingang Feng, Jian Xu, Bo Ma
Full text
A full spontaneous single-cell Raman spectrum captures the metabolic phenome in a label-free and noninvasive manner. However, Raman-activated cell sorting (RACS) of rare target cells from highly heterogeneous systems has remained largely conceptual. Here, we present a positive dielectrophoresis-induced deterministic lateral displacement (pDEP-DLD)-based RACS (pDEP-DLD-RACS), in which a modulated pDEP-DLD force is applied to focus, trap, and functionally sort fast-moving single cells in a wide channel. For pigment- and oil-producing yeasts, pDEP-DLD-RACS shows high sorting accuracy (>90%), high throughput (~600 events min −1 ), high yield (>85%), and long stable running time (~10 h), and can sort rare cells while preserving full cellular vitality. Moreover, label-free sorting directly from a genome-wide random mutagenesis library with >10 5 Aurantiochytrium sp. Mutants, based on intracellular docosahexaenoic acid (DHA) content, produces mutant cells with 58% higher DHA productivity in just two RACS runs over two days, representing two-orders-of-magnitude higher time- and cost-efficiency than conventional approaches. This superior trait arises from global remolding of transcriptomes, including enhanced carbon metabolism, reduced intracellular NADPH synthesis rates, and increased triacylglycerol (TAG) synthesis. By enabling direct screening of metabolic traits from genome-wide mutagenesis libraries, pDEP-DLD-RACS is a powerful platform for synthetic biology.
GPT-4o mini: Non-social science research article
Surface melting–driven hydrogen absorption for high-pressure polyhydride synthesis
Ryuhei Sato, Lewis J. Conway, Di Zhang, Chris J. Pickard, Kazuto Akagi, Kartik Sau, Hao Li, Shin-ichi Orimo
Full text
The synthesis of new polyhydrides with high superconducting T c is challenging owing to the high pressures and temperatures required. In this study, we used machine-learning potential molecular dynamics simulations to investigate the initial stage of polyhydride formation in calcium hydrides. Upon contact with high-pressure H 2 , the surface of CaH 2 melts, leading to CaH 4 formation. This surface melting proceeds via CaH 4 liquid phase as an intermediate state. High pressure reduces not only the hydrogenation (CaH 2 (s) + H 2 (l) ↔ CaH 4 (s)) enthalpy but also the enthalpy for liquid polyhydride formation (CaH 2 (s) + H 2 (l) ↔ CaH 4 (l)). Consequently, this surface melting process becomes more favorable than the fusion of the polyhydride bulk. Thus, high pressure not only shifts the equilibrium toward the polyhydride product but also lowers the activation energy, thereby promoting the hydrogenation reaction. From these thermodynamic insights, we propose structure-search criteria for polyhydride synthesis that are both computationally effective and experimentally relevant. These criteria are based on bulk properties, such as polyhydride (product) melting temperature and pressure-dependent hydrogenation enthalpy, readily determined through supplementary calculations during structure prediction workflows.
GPT-4o mini: Non-social science research article
Template-free 3D programmable magnetization of soft millirobots induced by interlayer stress
Jie Han, Shuideng Wang, Zhiqiang Zheng, Donglei Chen, Wenqi Zhang, Zhi Qu, Mingxing Cheng, Yiqing Yao, Metin Sitti, Lixin Dong
Full text
Soft magnetic miniature devices are crucial for applications in minimally invasive medicine, soft electronics, and robotics. While substantial progress has been made, current magnetic programming techniques are inherently tied to template-based and sequential fabrication processes. These processes limit scalability, precision, and programmability. Here, we present a template-free, integrative strategy that leverages interlayer stress-induced 3D shape morphing in xerogel-PDMS bilayer materials triggered by temperature variations. This process induces preprogrammed deformation and fixes the 3D structure via interlayer stress and solid–liquid phase transition. It is akin to an insect encased in amber, resulting in a soft machine with precisely tailored magnetic domains upon saturated magnetization. The approach eliminates the need for predesigned molds, which offers scalable, template-free programmable magnetization, reducing time and labor costs. The versatility of this method is demonstrated through reconfigurable mechanical behavior in kirigami metamaterial structures, information encryption, and multilegged millirobots. Moreover, by incorporating a nonmagnetic PDMS layer, laser-based engraving and ablation allow simultaneous control of interlayer stress and material properties. This facilitates precise regulation of stress-induced deformation and magnetically responsive regions with 20 ÎŒm resolution and over 1.8 T magnetization strength. This template-free 3D magnetization strategy significantly enhances design flexibility, machining precision, and mass production. It paves the way for advanced multiscale and programmable soft magnetic devices.
GPT-4o mini: Non-social science research article
Histone variant H2A.W7 represses meiotic crossover formation in Arabidopsis heterochromatin
Pallas Kuo, Andrew J. Tock, Xuexia Liu, Stephanie D. Topp, Zhenhui Zhong, Ian R. Henderson, Christophe Lambing
Full text
In eukaryotic genomes, DNA is packaged into nucleosomes to form chromatin. The incorporation of canonical or variant histones into nucleosomes confers different properties and influences chromatin structure to regulate cellular processes, including recombination. During meiosis, DNA double-strand breaks (DSBs) are formed and repaired as interhomolog crossovers. Nucleosome occupancy is generally associated with low crossover frequency, but it remains unclear which histone variants are involved in this process. In Arabidopsis , three variants of H2A coexist: H2A.X, H2A.Z, and H2A.W. Here, we show that H2A.W7 has a suppressive role on meiotic recombination. Genome-wide mapping of the crossover landscape revealed increased centromere-proximal recombination in h2a.w7 . Moreover, H2A.W7 can be recruited to the 3a crossover hotspot via 21-24-nucleotide siRNAs during RNA-directed DNA methylation, causing increased nucleosome occupancy and decreased crossover frequency. Cytological analysis reveals that H2A.W7 restricts heterochromatin clustering during meiosis, which can form a mechanism to limit interhomolog recombination. Conversely, the linker histone H1, of which its loading is known to be restricted by H2A.W, promotes heterochromatin clustering and crossover on a heterochromatic genetic interval. Our study reveals a role for H2A.W7 in repressing crossover formation in Arabidopsis .
GPT-4o mini: Non-social science research article
Transcription-templated assembly of the nucleolus in the Caenorhabditis elegans embryo
Nishant Kodan, Rabeya Hussaini, Stephanie C. Weber, Jane Kondev, Lishibanya Mohapatra
Full text
The nucleolus is a multicomponent structure made of RNA and proteins that serves as the site of ribosome biogenesis within the nucleus. It has been extensively studied as a prototype of a biomolecular condensate whose assembly is driven by phase separation. While the steady-state size of the nucleolus is quantitatively accounted for by the thermodynamics of phase separation, we show that experimental measurements of the assembly dynamics are inconsistent with a simple model of a phase-separating system relaxing to its equilibrium state. Instead, we show that the dynamics are well described by a model in which the transcription of ribosomal RNA actively drives nucleolar assembly. We find that our model of active transcription-templated assembly quantitatively accounts for the rapid kinetics observed in early embryos at different developmental stages, and for different RNA interference (RNAi) perturbations of embryo size. Our model predicts a scaling of the time to assembly with the volume of the nucleus to the one-third power, which is confirmed by experimental data. Our study highlights the role of active processes such as transcription in controlling the placement and timing of assembly of membraneless organelles.
GPT-4o mini: Non-social science research article
Microtubule dynamics are defined by conformations and stability of clustered protofilaments
Maksim Kalutskii, Helmut GrubmĂŒller, Vladimir A. Volkov, Maxim Igaev
Full text
Microtubules are dynamic cytoskeletal polymers that add and lose tubulin dimers at their ends. Microtubule growth, shortening, and transitions between them are linked to GTP hydrolysis. Recent evidence suggests that flexible tubulin protofilaments at microtubule ends adopt a variety of shapes, complicating structural analysis using conventional techniques. Therefore, the link between GTP hydrolysis, protofilament structure and microtubule polymerization state is poorly understood. Here, we investigate the conformational dynamics of microtubule ends using coarse-grained modeling supported by atomistic simulations and cryoelectron tomography. We show that individual bent protofilaments organize in clusters, transient precursors to the straight microtubule lattice, with GTP-bound ends showing elevated and more persistent cluster formation. Differences in the mechanical properties of GTP- and GDP-protofilaments result in differences in intracluster tension, determining both clustering propensity and protofilament length. We propose that conformational selection at microtubule ends favors long-lived clusters of short GTP-protofilaments that are more prone to forming a straight microtubule lattice and accommodating new tubulin dimers. Conversely, microtubule ends trapped in states with unevenly long and stiff GDP-protofilaments are more prone to shortening. We conclude that protofilament clustering is the key phenomenon that links the hydrolysis state of single tubulins to the polymerization state of the entire microtubule.
GPT-4o mini: Non-social science research article
Proofreading and single-molecule sensitivity in T cell receptor signaling by condensate nucleation
William L. White, Hailemikael K. Yirdaw, Ariel J. Ben-Sasson, Jay T. Groves, David Baker, Hao Yuan Kueh
Full text
T cells display the remarkable ability to detect single foreign peptides displayed on target cells, while ignoring highly abundant self-peptides. This selectivity has been explained by kinetic proofreading in the T cell receptor (TCR) signaling pathway, which prevents responses to short-lived binding events regardless of their abundance. However, the biochemical mechanisms that drive kinetic proofreading have remained unclear. Here, using computational modeling, we show that these key signaling properties of the TCR pathway can emerge from the dynamics of linker for activation of T cells (LAT) phosphorylation, diffusion, and condensation following TCR–peptide major histocompatibility complex (pMHC) binding. In this model, time delays in LAT condensate nucleation underlie kinetic proofreading, enabling selective signaling responses to high-affinity pMHC ligands. The cooperativity in the nucleation and growth of LAT condensates also provides a mechanism to amplify weak signals from single high-affinity peptides and for condensates to grow with increasing antigen numbers. In contrast to other models, condensate-nucleation proofreading predicts a dependence of signal strength on pMHC spacing at fixed number, a prediction we validated experimentally using a protein scaffold to present pMHCs at defined intervals. Our results suggest that nucleation-condensation proofreading underlies the remarkable antigen detection capabilities of the TCR signaling pathway.
GPT-4o mini: Non-social science research article
In This Issue
Full text
GPT-4o mini: Non-social science research article
MyD88 knockdown by RNAi prevents bacterial stimulation of tubeworm metamorphosis
Emily Darin, Morgan V. Farrell, Tatyana N. Ali, Josefa Rivera Alfaro, Kyle E. Malter, Nicholas J. Shikuma
Full text
Diverse animals across the tree of life undergo the life-history transition of metamorphosis in response to bacteria. Although immunity has been implicated in this metamorphosis in response to bacteria, no functional connection has yet been demonstrated between immunity and metamorphosis. We investigated a host–microbe interaction involving a marine tubeworm, Hydroides elegans , that undergoes metamorphosis in response to Pseudoalteromonas luteoviolacea , a metamorphosis-inducing marine bacterium. By creating a marine bacteria–mediated RNA interference approach, we show that myeloid differentiation factor 88 (MyD88), a critical immune adaptor for Toll-like receptor and interleukin pathways, is necessary for the stimulation of metamorphosis in response to bacteria. In addition to a developmental role, we show that MyD88 is necessary for survival during exposure to the bacterial pathogen Pseudomonas aeruginosa , showing that Hydroides utilizes MyD88 during both development and an immune response. These results provide a functional characterization of the innate immune system involved in an animal's metamorphosis.
GPT-4o mini: Non-social science research article
Stepwise deactivation of gibberellins during rice internode elongation
Toshiaki Ishida, Yingying Zhang, Hongbo Zhu, Shoko Fudano, Yu Peng, Yoshiya Seto, Kiyoshi Mashiguchi, Jiyun Liu, Zuhua He, Shubiao Zhang, Shinjiro Yamaguchi
Full text
Bioactive gibberellins (GAs) are a class of plant hormones that regulate various aspects of plant growth and development, and several key GA deactivation enzymes have been identified. In rice, non-13-hydroxylated GAs have been shown to be deactivated via 16α,17-epoxidation by a cytochrome P450 monooxygenase, ELONGATED UPPERMOST INTERNODE (EUI/CYP714D1). Although 16,17-dihydro-16α,17-epoxyGA 4 (16α,17-epoxyGA 4 ), the product of EUI from bioactive GA 4 , has shown weak bioactivity on rice seedlings, how 16α,17-epoxyGAs are further deactivated remains elusive. Here, we identify the EUI2 gene, which regulates internode elongation in rice, using a map-based cloning strategy. EUI2 encodes an epoxide hydrolase that hydrolyzes 16α,17-epoxyGAs to 16,17-dihydro-16α,17-dihydroxyGAs. The eui2 mutants are taller than wild-type plants but are shorter than the eui mutants. However, the levels of known bioactive GAs in the uppermost internodes are not significantly increased in the eui2 mutants. Instead, we show that the eui2 mutants accumulate 16α,17-epoxyGA 4 to high levels. We also show that exogenously applied 16α,17-epoxyGA 4 is significantly active in elongating the uppermost internode, although not as potent as GA 4 . Furthermore, we demonstrate that 16α,17-epoxyGA 4 can directly interact with the rice GA receptor, GIBBERELLIN INSENSITIVE DWARF1, in vitro. Taken together, the sequential action of EUI and EUI2 results in the stepwise deactivation of GAs during internode elongation in rice. Our data also suggest that the accumulation of a weakly active GA contributes to the mildly tall phenotype of the eui2 mutants.
GPT-4o mini: Non-social science research article
Deciphering decomposition pathways of high explosives with cryogenic X-ray Raman spectroscopy
Oscar A. Paredes Mellone, Michael H. Nielsen, Jeffrey Thomas Babicz, John Vinson, Trevor M. Willey, Dimosthenis Sokaras
Full text
We employed cryogenic X-ray Raman spectroscopy to investigate the early-stage decomposition of the high explosive molecule hexanitrohexaazaisowurtzitane (CL-20). By systematically varying the radiation dose under cryogenic conditions, we induced the decomposition of the molecule using ionizing radiation and observed the evolution of spectral features at the carbon, nitrogen, and oxygen K edges. Through extensive first-principles calculations, we identified key intermediates in the early stages of the decomposition process, resulting from C–C and C–N bond cleavage which leads to the opening of the internal cage structure. A detailed analysis of spectral trends and fingerprints provided evidence supporting N–NO 2 homolytic cleavage as the primary initial decomposition pathway. The combination of advanced core-level spectroscopy methods and state-of-the-art theoretical calculations enabled a comprehensive characterization of the molecular changes induced by controlled radiation dose exposures. Our findings establish a benchmark for understanding the decomposition chemistry of high-explosive materials, offering important insights into their stability and reactivity under extreme conditions.
GPT-4o mini: Non-social science research article
Suborbital- and millennial-scale monsoon variability during Pleistocene interglacials
Youbin Sun, Ting Wang, Qiuzhen Yin, Steven C. Clemens, Xingxing Liu, Li Ai, Zhipeng Wu, Xiaoke Qiang, Xulong Wang, Hong Chang, Yougui Song, Hendrik Vogel, John Dodson, Andre Berger, Zhisheng An
Full text
Observational and modeling results show that the frequency and amplitude of extreme climatic events have increased significantly in the context of global warming. However, whether abrupt climate changes intensified during past warm periods remains poorly constrained due to the lack of high-resolution geological records. Here, we report a 512-m predominantly lacustrine sedimentary record from the Weihe Basin (North China), revealing that lake levels fluctuated significantly on suborbital (half- and quarter-precession) and millennial timescales over the last 2 Ma. Grain-size results reveal that magnitudes of rapid lake level fluctuations increased dramatically during Pleistocene interglacials, differing from glacial amplification of abrupt climate events recorded in North Atlantic marine sediments. Model results indicate that summer insolation maxima in low-latitude region of both hemispheres can lead to intensified monsoon precipitation in East Asia. Our proxy-model comparison highlights the importance of low-latitude bihemispheric insolation maxima in driving millennial-scale hydroclimatic variability in a warming future.
GPT-4o mini: Non-social science research article
Multiple sources of atmospheric CO 2 activated by AMOC recovery at the onset of interglacial MIS 9
Florian Krauss, Daniel Baggenstos, Jochen Schmitt, Béla Tuzson, James A. Menking, Lars MÀchler, Lucas Silva, Markus Grimmer, Emilie Capron, Thomas F. Stocker, Thomas K. Bauska, Hubertus Fischer
Full text
Using high-precision ice core measurements of CO 2 , ή 13 C–CO 2 , CH 4 , and N 2 O, this study provides carbon isotope constraints on a sizeable, centennial-scale CO 2 jump at the onset of Marine Isotope Stage 9 (MIS 9). The very end of the Heinrich stadial (HS) characterizing Termination IV (T-IV, ca. 343 to 333 ka ago) shows a 250-y-long jump in greenhouse gas concentrations, followed by a 1.3 ka gradual decline back to the initial concentration. During this so-called overshoot, CO 2 and CH 4 reach their highest levels (about 303 ppm and 800 ppb, respectively) over the past 800 ka prior to industrialization. The jump in CO 2 is not accompanied by a change in ή 13 C–CO 2, suggesting that multiple mechanisms contributed to the exceptionally elevated CO 2 values. Following the jump, a slow 0.2‰ enrichment in ή 13 C–CO 2 occurs. We propose that during the jump, the sudden resumption of deepwater formation in the North Atlantic (NA) triggered an amplified release of CO 2 from the Southern Ocean (SO) by a northward shift of the Intertropical Convergence Zone (ITCZ) and the SO westerlies, potentially in combination with a rapid land carbon release. The latter is expected from temporally enhanced wildfire activity related to higher fuel load and regionally changing weather conditions in connection to the ITCZ shift. A combination of marine proxy records and box model simulation suggests that the ή 13 C–CO 2 decrease expected from these processes is compensated by a net temperature increase in global sea surface temperature (SST) at the time of the AMOC resumption.
GPT-4o mini: Non-social science research article
Direct sensing of host ferric iron by an archetype histidine kinase mediates virulence of an enteric pathogen
Yibei Zhang, Gang Xiao, Haoyuan Ding, Qian Zou, Dan Gu, Jiachen Wen, Yonggang Pei, Rongxian Guo, Qiyao Wang, Xiaohui Zhou
Full text
Two-component system (TCS) histidine kinases enable bacterial pathogens to sense environmental signals and regulate adaptive responses during infection. The EnvZ/OmpR TCS, known for its role in osmolarity/pH-dependent regulation of outer membrane porins across bacterial species, is also a central virulence regulator. However, the environmental cues that activate EnvZ/OmpR to trigger pathogenicity have remained unclear, limiting our understanding of host–pathogen interactions. Here, we demonstrate that in Vibrio parahaemolyticus , a major etiological agent of seafood-associated gastroenteritis, EnvZ functions as a direct ferric iron (Fe 3+ ) sensor governing virulence programs. Fe 3+ -EnvZ interaction triggers kinase phosphorylation and activation, enabling transcriptional control of biofilm formation, swarming motility, and type 3/6 secretion systems. An iron-binding-deficient EnvZ mutant (EnvZ Q103A ) abrogated Fe 3+ responsiveness and downstream signaling pathways. In an infant rabbit infection model, Fe 3+ enhanced V. parahaemolyticus intestinal colonization and virulence through EnvZ/OmpR signaling. This study identifies Fe 3+ as the physiological ligand activating the EnvZ/OmpR virulence regulon and provides insight into how enteric pathogens exploit host-derived iron cues to promote infection.
GPT-4o mini: Non-social science research article
Phage-induced protection against lethal bacterial reinfection
Yikun Xing, Haroldo J. Hernandez Santos, Ling Qiu, Samantha R. Ritter, Jacob J. Zulk, Rachel Lahowetz, Kathryn A. Patras, Austen L. Terwilliger, Anthony W. Maresso
Full text
Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, providing almost complete protection against a second lethal infection for animals treated with phage therapy. The activity also reduced infection burden an astounding billion-fold over the control. Reinfection protection requires phage lytic killing of its target bacterium but is independent of additional phage therapy. The effect is not driven by phage alone, lingering phage resistors, or a sublethal inoculum. In vitro phage-lysed bacteria provide partial protection, suggesting a combination of phage-induced lytic activity and immune stimulation by phage treatment is responsible for the effect. These observations imply certain phages may induce host adaptive responses following the lysis of the infecting bacteria. This work suggests phage therapy may contain a dual-action effect, an initial treatment efficacy followed by a long-term protection against reoccurring infection, a therapeutic-vaccination mechanism of action.
GPT-4o mini: Non-social science research article
Short-term study fails to capture negative impacts of livestock intensification on wildlife
Joseph O. Ogutu, Jared A. Stabach, J. Grant C. Hopcraft, Randall B. Boone, Holly T. Dublin, Christopher L. Dutton, Andrew Gichira, Abby Guthmann, Ask L. Herrik, Kay E. Holekamp, Rebekah R. Karimi, Shem C. Kifugo, Peter Leimgruber, Niels Mogensen, Stephen S. Moiko, Joseph M. Mukeka, Harrison Nabaala, Stephen Ndambuki, Lucy M. Njino, Gordon O. Ojwang, Han Olff, Craig Packer, Lemein Parmuntoro, Robin S. Reid, Rehema B. Rioba, Mohammed Y. Said, Jully S. Senteu, Amanda L. Subalusky, Jens-Christian Svenning, Stewart Thompson, Antonio Uzal, Michiel P. Veldhuis, Robert Buitenwerf
Full text
GPT-4o mini: Non-social science research article
CACNA1D is a circadian gene and causes familial advanced sleep phase
John M. Webb, Fayal Abderemane-Ali, Liza Ashbrook, Mingyang Ma, Neha Nibber, Xianlin Zou, Maya Yamazaki, Elizabeth Wohler, Nara Sobreira, Daniel L. Minor, Ying-Hui Fu, Louis J. Ptáček
Full text
Familial advanced sleep phase (FASP) is a heritable human sleep trait characterized by early sleep onset and offset times. We have identified five variants in five different families in the human voltage-gated calcium channel subunit alpha1 D ( CACNA1D ) that cosegregate with FASP. The variants in CACNA1D lead to altered channel dynamics in vitro. A mouse model of the E427K variant has a normal circadian period under constant darkness but displays altered phase shifts in response to light in the subjective night at circadian time (CT) 16 and CT22. Overall, these experiments establish CACNA1D as an FASP gene with altered entrainment, highlighting the ability of human genetics to uncover novel aspects of human circadian regulation.
GPT-4o mini: Non-social science research article
Solution structure and synaptic analyses reveal determinants of bispecific T cell engager potency
Alexander Leithner, Oskar Staufer, Tanmay Mitra, Falk Liberta, Salvatore Valvo, Mikhail Kutuzov, Hannah Dada, Jacob Spaeth, Weijie Zhou, Felix Schiele, Sophia Reindl, Herbert Nar, Stefan Hoerer, Maureen Crames, Stephen Comeau, David Young, Sarah Low, Edward Jenkins, Simon J. Davis, David Klenerman, Andrew Nixon, Noah Pefaur, David Wyatt, Omer Dushek, Srinath Kasturirangan, Michael L. Dustin
Full text
Bispecific T cell engagers (TcEs) link T cell receptors to tumor-associated antigens on cancer cells, forming cytotoxic immunological synapses (IS). Close membrane-to-membrane contact (≀13 nm) has been proposed as a key mechanism of TcE function. To investigate this and identify potential additional mechanisms, we compared four immunoglobulin G1-based (IgG1) TcE Formats (A–D) targeting CD3Δ and Her2, designed to create varying intermembrane distances (A < B < C < D). Small-angle X-ray scattering (SAXS) and modeling of the conformational states of isolated TcEs and TcE–antigen complexes predicted close contacts (≀13 nm) for Formats A and B and far contacts (≄18 nm) for Formats C and D. In supported lipid bilayer (SLB) model interfaces, Formats A and B recruited, whereas Formats C and D repelled, CD2–CD58 interactions. Formats A and B also excluded bulky Quantum dots more effectively. SAXS also revealed that TcE–antigen complexes formed by Formats A and C were less flexible than complexes formed by Formats B and D. Functional data with Her2-expressing tumor cells showed cytotoxicity, surface marker expression, and cytokine release following the order A > B = C > D. In a minimal system for IS formation on SLBs, TcE performance followed the trend A = B = C > D. Addition of close contact requiring CD58 costimulation revealed phospholipase C-Îł activation matching cytotoxicity with A > B = C > D. Our findings suggest that when adhesion is equivalent, TcE potency is determined by two parameters: contact distance and flexibility. Both the close/far-contact formation axis and the low/high flexibility axis significantly impact TcE potency, explaining the similar potency of Format B (close contact/high flexibility) and C (far contact/low flexibility).
GPT-4o mini: Non-social science research article
Multiphasic size-dependent growth dynamics of nanoparticle ensembles
Ji-Hyun Kim, Joodeok Kim, Byung Hyo Kim, Sanggeun Song, Jingyu Kang, Jinho Rhee, Donghee Kim, Hoje Chun, Hyesung Choi, Hyungjin Cho, Yongjoon Kim, Jae Won Jung, Youngju Son, Junhyeok Jung, Kunwoo Park, Sungho Jeon, Minho Lee, Byungchan Han, Won Chul Lee, Dongjun Kim, Taeghwan Hyeon, Jaeyoung Sung, Jungwon Park
Full text
Colloidal nanoparticles are of great interest in modern science and industry. However, the thermodynamic mechanism and dynamics of nanoparticle growth have yet to be understood. Addressing these issues, we tracked hundreds of in-situ growth trajectories of a nanoparticle ensemble using liquid-phase TEM and found that the nanoparticle growth, including coalescence, exhibits nanoparticle size-dependent multiphasic dynamics, unexplainable by current theories. Motivated by this finding, we developed a model and theory for an ensemble of growing nanoparticles, providing a unified, quantitative understanding of the time-dependent mean and fluctuation of nanoparticle size and size-dependent growth rate profiles across various nanoparticle systems and experimental conditions. Our work reveals that the chemical potential in a small nanoparticle strongly deviates from the Gibbs–Thomson equation, shedding light on how it governs the size-dependent growth dynamics of nanoparticles.
GPT-4o mini: Non-social science research article
Himalayan “S-type” granite generated from I-type sources
Huixia Ding, Zeming Zhang, Matthew J. Kohn
Full text
Partial melting of metasedimentary rocks is generally accepted as the source of peraluminous Himalayan leucogranites—they are commonly considered as pure “S-type” (sedimentary source) granites. Here, a uniquely comprehensive geochronological and geochemical dataset shows that partial melting of metaigneous rocks in the eastern Himalaya produced peraluminous leucogranites—these supposed S-type leucogranites have I-type (igneous) sources. Inherited magmatic zircons from leucogranites and metaigneous rocks have indistinguishable ages, trace element compositions, and Hf isotope compositions, distinct from zircons in metasedimentary rocks. Experimentally, partial melting of metagranitic rocks rather than metapelites predicts alkali major element chemistry of these leucogranites better. High ÎŽ 18 O, high 87 Sr/ 86 Sr, and low Δ Nd (t) for Himalayan leucogranites have been used to argue for a metasedimentary rock source, but overlapping values occur in metaigneous rocks. Although sediment-sourced leucogranites also occur, igneous-sourced leucogranites are likely common in large hot orogens. A survey of leucogranite geochemistry across the Himalaya suggests that ~20% might be I-type, with no apparent spatial or temporal bias. I-type leucogranites appear to be rare-metal poor, however. Unlike prior assertions that I-type granites represent juvenile additions to orogens, metaigneous-sourced Himalayan granites more likely represent crustal reworking.
GPT-4o mini: Non-social science research article
Molecular basis for ligand recognition and receptor activation of the prostaglandin D2 receptor DP1
Jiuyin Xu, Yanli Wu, Youwei Xu, Yang Li, Xinheng He, Heng Zhang, James Jiqi Wang, Jingjing Hou, Junrui Li, Wen Hu, Kai Wu, Qingning Yuan, Canrong Wu, H. Eric Xu
Full text
The prostaglandin D2 receptor 1 (DP1), a rhodopsin-like Class A GPCR, orchestrates critical physiological and pathological processes, ranging from sleep regulation to inflammatory responses and cardiovascular function. Despite its therapeutic significance, structural insights into DP1 activation mechanisms have remained elusive. Here, using cryoelectron microscopy (cryo-EM), we determined high-resolution structures of human DP1 in both inactive and active states, with the latter captured in complex with its endogenous agonist PGD2 or the synthetic agonist BW245C, bound to the stimulatory G protein, Gs. Our structures, coupled with functional and mutagenesis studies, unveiled unique structural features of DP1, including an alternative activation mechanism, ligand-selectivity determinants, and G protein coupling characteristics. These molecular insights provide a rational framework for designing selective DP1-targeted therapeutics, both agonists and antagonists, with enhanced specificity and reduced off-target effects, opening broad avenues for treating DP1-associated disorders.
GPT-4o mini: Non-social science research article
Can increasing the size and flexibility of a molecule reduce decoherence and prolong charge migration?
Alan Scheidegger, Nikolay V. Golubev, Jiƙí J. L. Vaníček
Full text
Coherent superposition of electronic states, created by ionizing a molecule, can initiate ultrafast dynamics of the electron density. Correlation between nuclear and electron motions, however, typically dissipates the electronic coherence in only a few femtoseconds, especially in larger and more flexible molecules. We, therefore, use ab initio semiclassical dynamics to study decoherence in a sequence of analogous organic molecules of increasing size and find, surprisingly, that extending the carbon skeleton in propynal analogs slows down decoherence and prolongs charge migration. To elucidate this observation, we decompose the overall decoherence into contributions from individual vibrational modes and show that: 1) The initial decay of electronic coherence is caused by high- and intermediate-frequency vibrations via momentum separation of nuclear wavepackets evolving on different electronic surfaces. 2) At later times, the coherence disappears completely due to the increasing position separation in the low-frequency modes. 3) In agreement with another study, we observe that only normal modes that preserve the symmetry of the molecule induce decoherence. All together, we justify the enhanced charge migration by a combination of increased hole-mixing and the disappearance of decoherence contributions from specific vibrational modes—CO stretching in butynal and various H rockings in pentynal.
GPT-4o mini: Non-social science research article
BRCA2 reversion mutation–independent resistance to PARP inhibition through impaired DNA prereplication complex function
Kyrie Pappas, Matteo Ferrari, Perianne Smith, Subhiksha Nandakumar, Zahra Khan, Serina B. Young, Justin LaClair, Marco Vincenzo Russo, Emmet Huang-Hobbs, Nikolaus Schultz, Wassim Abida, Wouter Karthaus, Maria Jasin, Charles L. Sawyers
Full text
Recent approvals of polymeric adenosine diphosphate ribose (poly(ADP-ribose) polymerase inhibitors (PARPi) for BRCA-mutant metastatic castration resistant prostate cancer necessitate an understanding of the factors that shape sensitivity and resistance. Reversion mutations that restore homologous recombination (HR) repair are detected in ~50 to 80% of BRCA-mutant patients who respond but subsequently relapse, but there is currently little insight into why only ~50% of BRCA-mutant patients display upfront resistance. To address this question, we performed a genome-wide CRISPR screen to identify genomic determinants of PARPi resistance in murine Brca2 Δ/Δ prostate organoids genetically engineered in a manner that precludes the development of reversion mutations. Remarkably, we recovered multiple independent single guide RNAs (sgRNAs) targeting three different members ( Cdt1, Cdc6, and Dbf4 ) of the DNA prereplication complex (pre-RC), each of which independently conferred resistance to olaparib and the next-generation PARP-1 selective inhibitor AZD5305. Moreover, sensitivity to PARP inhibition was restored in Brca2 Δ/Δ , Cdc6-depleted prostate cells by knockdown of geminin, a negative regulator of Cdt1, further implicating the critical role of a functional pre-RC complex in PARPi sensitivity. Furthermore, ~50% of CRPC tumors have copy number loss of pre-RC complex genes, particularly CDT1 . Mechanistically, prostate cells with impaired pre-RC activity displayed rapid resolution of olaparib-induced DNA damage as well as protection from replication fork degradation caused by Brca2 loss, providing insight into how Brca2-mutant cancer cells can escape cell death from replication stress induced by PARP inhibition in the absence of HR repair. Of note, a pharmacologic inhibitor that targets the CDT1/geminin complex (AF615) restored sensitivity to AZD5305, providing a potential translational avenue to enhance sensitivity to PARP inhibition.
GPT-4o mini: Non-social science research article
Reciprocal projections between the globus pallidus externa and cortex span motor and nonmotor regions
Emily A. Ferenczi, Wengang Wang, Anushka Biswas, Trent Pottala, Yihuan Dong, Alison K. Chan, Madeline A. Albanese, Raina S. Sohur, Tingying Jia, Kevin J. Mastro, Bernardo L. Sabatini
Full text
The globus pallidus externa (GPe) is a heterogeneous nucleus of the basal ganglia, with intricate connections to other basal ganglia nuclei, as well as direct connections to the cortex. The anatomic, molecular, and electrophysiologic properties of cortex-projecting pallidocortical neurons are not well characterized. Here, we show that pallidocortical neurons project to diverse motor and nonmotor cortical regions, are organized topographically in the GPe, and segregate into at least two distinct electrophysiological and molecular phenotypes. In addition, we find that the GPe receives direct synaptic input from deep layers of diverse motor and nonmotor cortical regions, some of which form reciprocal connections onto pallidocortical neurons. These results demonstrate the existence of a fast, bidirectional circuit between the GPe and the cortex that is ideally positioned to integrate information about behavioral goals, internal states, and environmental cues to rapidly modulate behavior.
GPT-4o mini: Non-social science research article
Disrupted diencephalon development and neuropeptidergic pathways in zebrafish with autism-risk mutations
Mary E. S. Capps, Anna J. Moyer, Claire L. Conklin, Verdion Martina, Emma G. Torija-Olson, Morgan C. Klein, William C. Gannaway, Caleb C. S. Calhoun, Michael D. Vivian, Summer B. Thyme
Full text
Hundreds of human mutations are linked to autism and related disorders, yet the functions of many of these mutated genes during vertebrate neurodevelopment are unclear. We generated 27 zebrafish mutants with presumptive protein-truncating mutations or specific missense variants corresponding to autism-risk alleles in 17 human genes. We observed baseline and stimulus-driven behavioral changes at larval stages, as well as social behavior differences in lines tested as juveniles. Imaging whole-brain activity revealed a near identical activity map for mutations in the unrelated genes kmt5b and hdlbpa , defined by increased activity mainly in the thalamus and mesencephalon. Mutating 7 of the 17 risk genes resulted in substantial brain size differences, localized to the diencephalon in three cases and more widespread in others. Using RNA sequencing, we further defined molecular drivers of the observed phenotypes for three mutants, identifying targetable disruptions in neuropeptide signaling, neuronal maturation, and cell proliferation. This multimodal screen nominated brain regions, cell types, and molecular pathways that may contribute to autism susceptibility.
GPT-4o mini: Non-social science research article
The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels
Yossef Maatuf, Yishai Kushnir, Alina Nemirovski, Mariana Ghantous, Ariel Iskimov, Alexander M. Binshtok, Avi Priel
Full text
Paracetamol has been used for decades to relieve mild-to-moderate pain. Its analgesic effect is mainly attributed to its metabolite, AM404, acting on cannabinoid receptors or TRPV1 channels in central nervous system (CNS) neurons. Here, we show that AM404 is produced by primary sensory neurons. It inhibits sodium current in nociceptor neurons, blocking action potential (AP) generation and reducing nocifensive behavior in naĂŻve and inflamed rats. We demonstrated that this analgesic effect of AM404 is mediated by its direct inhibition of nociceptive voltage-gated sodium channels (Na V ) 1.8 and 1.7 via the local anesthetic binding site. The Na V 1.8 and 1.7 inhibition was specific for AM404 and not observed with other metabolites of paracetamol. Our findings suggest that the analgesic effect of paracetamol is mediated mainly by direct AM404-induced inhibition of nociceptive sodium channels at the peripheral nociceptor neurons. Our findings lay a foundation for the potential development of AM404 as a selective local analgesic.
GPT-4o mini: Non-social science research article
Modular arrangement of synaptic and intrinsic homeostatic plasticity within visual cortical circuits
Wei Wen, Adriana M. Prada, Gina G. Turrigiano
Full text
Neocortical circuits use synaptic and intrinsic forms of homeostatic plasticity to stabilize key features of network activity, but whether these different homeostatic mechanisms act redundantly or can be independently recruited to stabilize different network features is unknown. Here, we used pharmacological and genetic perturbations both in vitro and in vivo to determine whether synaptic scaling and intrinsic homeostatic plasticity (IHP) are arranged and recruited in a hierarchical or modular manner within layer 2/3 (L2/3) pyramidal neurons in the rodent primary visual cortex (V1). Surprisingly, although the expression of synaptic scaling and IHP was dependent on overlapping signaling pathways, they could be independently recruited by manipulating spiking activity or NMDA receptor (NMDAR) signaling, respectively. Further, we found that changes in visual experience that affect NMDAR activation but not mean firing selectively trigger IHP, without recruiting synaptic scaling. These findings support a modular model in which synaptic and IHP respond to and stabilize distinct aspects of network activity.
GPT-4o mini: Non-social science research article
Anthropogenic iron alters the spring phytoplankton bloom in the North Pacific transition zone
Nicholas J. Hawco, Tim M. Conway, Sacha N. Coesel, Benedetto Barone, Emily A. Seelen, Shun-Chung Yang, Randelle M. Bundy, Paulina Pinedo-Gonzalez, Xiaopeng Bian, Matthias Sieber, Nathan T. Lanning, Jessica N. Fitzsimmons, Rhea K. Foreman, Daniela König, Mora J. Groussman, James G. Allen, Lauren W. Juranek, Angelicque E. White, David M. Karl, E. Virginia Armbrust, Seth G. John
Full text
Industrial activities have increased the supply of iron to the ocean, but the magnitude of anthropogenic input and its ecological consequences are not well-constrained by observations. Across four expeditions to the North Pacific transition zone, we document a repeated supply of isotopically light iron from an atmospheric source in spring, reflecting an estimated 39 ± 9 % anthropogenic contribution to the surface ocean iron budget. Expression of iron-stress genes in metatranscriptomes, and evidence for colimitation of ecosystem productivity by iron and nitrogen, indicates that enhanced iron supply should spur spring phytoplankton blooms, accelerating the seasonal drawdown of nitrate delivered by winter mixing. This effect is consistent with regional trends in satellite ocean color, which show a shorter, more intense spring bloom period, followed by an earlier arrival of oligotrophic conditions in summer. Continued iron emissions may contribute to poleward shifts in transitional marine ecosystems, compounding the anticipated impacts from ocean warming and stratification.
GPT-4o mini: Non-social science research article
Exploring diverse supramolecular tessellation through hierarchical assemblies of nonalternant nanographene
Jian Sun, Ziqi Deng, David Lee Phillips, Junzhi Liu
Full text
Tessellation, as an ancient and fascinating mathematical pursuit, has not only captivated mathematicians but also has attracted chemists’ increasing attention at the molecular level in recent years. Exploring tessellation at the molecular scale is pivotal for gaining profound insights into the effects of tessellation on materials and elucidating the essential design principles for supramolecular tessellation. In this study, we develop a dynamic fullerene host ( 1 ) with three consecutive heptagons, which promotes diverse supramolecular tessellation via hierarchical assembly. In the solid state, molecule 1 arranges itself into a layered square-shaped tessellation in the crystal superstructure. Interestingly, the co-crystal structures of 1 with C 60 and C 70 exhibit highly ordered triangular and rhombic tessellation patterns, respectively, due to the adaptive regulation of heptagons with different curved guests, demonstrating the first series of layered tessellated framework in supramolecular fullerene chemistry. This work not only enriches the development of in-solution supramolecular tessellation but also facilitates the rational design of tessellated 2D layered molecular materials
GPT-4o mini: Non-social science research article
Genomic analyses identify 15 risk loci and reveal HDAC2 , SOX2-OT , and IGF2BP2 in a naturally occurring canine model of gastric cancer
Shawna R. Cook, Sanne Hugen, Jessica J. Hayward, Thomas R. Famula, Janelle M. Belanger, Elizabeth McNiel, Hille Fieten, Anita M. Oberbauer, Peter A. J. Leegwater, Elaine A. Ostrander, Paul J. J. Mandigers, Jacquelyn M. Evans
Full text
Gastric cancer ranks as the fifth most common human cancer worldwide and has a poor survival rate and limited treatment options. Despite the high prevalence and mortality rate, the genetic etiology is largely unknown. In dogs, a clinically and histologically similar disease disproportionately affects two breeds, the Belgian Tervuren and Belgian Sheepdog, which develop the intestinal and diffuse tumor subtypes observed in humans. We performed a Bayesian genome-wide association study and selection analyses in this naturally occurring canine model to elucidate underlying genetic risk factors for gastric cancer and identified 15 associated loci. Variant filtering revealed germline putative regulatory variants for the EPAS1 ( HIF2A ) and PTEN genes and a coding variant in CD101 . Two loci are overrepresented among cases of intestinal tumor subtype. Although closely related to Tervuren and Sheepdogs, Belgian Malinois rarely develop gastric cancer. Across-breed analyses uncovered haplotypes enriched in Malinois at SOX2-OT and IGF2BP2 that are at significantly higher frequency among genome-wide association study controls. Among Tervuren and Sheepdogs, HDAC2 putative regulatory variants were present at comparatively high frequency and were associated with risk of gastric cancer. Here, we describe a complex genetic architecture governing gastric cancer in a dog model, including genes such as PDZRN3 and KLHL29 , that have not been associated with human gastric cancer.
GPT-4o mini: Non-social science research article
CRISPR screen reveals a simultaneous targeted mechanism to reduce cancer cell selenium and increase lipid oxidation to induce ferroptosis
Sophia M. Lamperis, Kaylin M. McMahon, Andrea E. Calvert, Jonathan S. Rink, Karthik Vasan, Madhura R. Pandkar, Eliana U. Crentsil, Zachary R. Chalmers, Natalie R. McDonald, Cameron J. Kosmala, Marcelo G. Bonini, Daniela Matei, Leo I. Gordon, Navdeep S. Chandel, C. Shad Thaxton
Full text
Ferroptosis is a cell death mechanism distinguished by its dependence on iron-mediated lipid oxidation. Cancer cells highly resistant to conventional therapies often demonstrate lipid metabolic and redox vulnerabilities that sensitize them to cell death by ferroptosis. These include a unique dependency on the lipid antioxidant selenoenzyme, glutathione peroxidase 4 (GPx4), that acts as a ferroptosis inhibitor. Synthetic high-density lipoprotein-like nanoparticle (HDL NP) targets the high-affinity HDL receptor scavenger receptor class B type 1 (SR-B1) and regulates cell and cell membrane lipid metabolism. Recently, we reported that targeting cancer cell SR-B1 with HDL NP depleted cell GPx4, which is accompanied by increased cell membrane lipid peroxidation and cancer cell death. These data suggest that HDL NP may induce ferroptosis. Thus, we conducted an unbiased CRISPR-based positive selection screen and target validation studies in ovarian clear cell carcinoma (OCCC) cell lines to ascertain the mechanism through which HDL NP regulates GPx4 and kills cancer cells. The screen revealed two genes, acyl-CoA synthetase long chain family member 4 (ACSL4) and thioredoxin reductase 1 (TXNRD1), whose loss conferred resistance to HDL NP. Validation of ACSL4 supports that HDL NP induces ferroptosis as the predominant mechanism of cell death, while validation of TXNRD1 revealed that HDL NP reduces cellular selenium and selenoprotein production, most notably, GPx4. Accordingly, we define cancer cell metabolic targets that can be simultaneously actuated by a multifunctional, synthetic HDL NP ligand of SR-B1 to kill cancer cells by ferroptosis.
GPT-4o mini: Non-social science research article
Location, location, location: Cholesterol in lipid droplets as a driver of MASH progression
Xiaobo Wang, Ira Tabas
Full text
GPT-4o mini: Non-social science research article
Increasing boreal fires reduce future global warming and sea ice loss
Edward Blanchard-Wrigglesworth, Patricia DeRepentigny, Dargan M. W. Frierson
Full text
Biomass burning can affect climate via the emission of aerosols and their subsequent impact on radiation, cloud microphysics, and surface and atmospheric albedo. Biomass burning emissions (BBEs) over the boreal region have strongly increased during the last decade and are expected to continue increasing as the climate warms. Climate models simulate aerosol processes, yet historical and future Coupled Model Intercomparison Project (CMIP) simulations have no active fire component, and BBEs are prescribed as external forcings. Here, we show that CMIP6 used future boreal BBEs scenarios with unrealistic near-zero trends that have a large impact on climate trends. By running sensitivity experiments with ramped up boreal emissions based on observed trends, we find that increasing boreal BBEs reduces global warming by 12% and Arctic warming by 38%, reducing the loss of sea ice. Tropical precipitation shifts southward as a result of the hemispheric difference in boreal aerosol forcing and subsequent temperature response. These changes stem from the impact of aerosols on clouds, increasing cloud droplet number concentration, cloud optical depth, and low cloud cover, ultimately reducing surface shortwave flux over northern latitudes. Our results highlight the importance of realistic boreal BBEs in climate model simulations and the need for improved understanding of boreal emission trends and aerosol–climate interactions.
GPT-4o mini: Non-social science research article
Single-cell resolution uncovers neighboring cell subtypes that share steroidogenic capacity during fetal testis development
Keer Jiang, Zirui Fu, Philippos Tsourkas, Anbarasi Kothandapani, Tyler Kearse, Sean J. McIlwain, Chloé MayÚre, Serge Nef, Joan S. Jorgensen
Full text
Historically, endocrine cells were perceived to coordinate their output in a uniform manner. Recently however, single-cell technologies have uncovered heterogeneity within these populations, indicating that individual cells may operate as independently regulated units. Using high-resolution tools such as single-molecule fluorescent in situ hybridization (sm-FISH) and single-cell RNA sequencing (scRNA-seq), we investigated the contributions of individual and the collective of fetal Leydig cells to androgen production over time during mouse testis development. Temporal profiles of intratesticular androgens alongside the expression of steroidogenic pathway genes ( Star, Cyp11a1, Cyp17a1, and Hsd3b1 ) from prenatal to perinatal testes demonstrated that the peak in gene expression preceded the peak in androgen production. Spatially, steroidogenic cells were initially observed to be concentrated toward the anterior–posterior poles along the center of the dorsal–ventral axis of the fetal testis at embryonic day (E) 13 and then expanded to a uniform distribution by E16. Next, sm-FISH using probes for individual steroidogenic pathway genes exposed the following findings: gene transcription and processing of individual and combinations of steroidogenic pathway genes are not synchronized among fetal Leydig cells; and some fetal Leydig cells express incomplete sets of genes. Further, sm-FISH and scRNA-seq data corroborated the presence of fetal Leydig and other interstitial cell types harboring incomplete sets of steroidogenic pathway genes throughout developmental stages. Taken together, these findings highlight that fetal steroidogenic gene expression is tightly regulated and that transcript presence among interstitial cell types promotes the possibility that optimal androgen biosynthesis results from a cooperative effort among neighboring steroidogenic cells.
GPT-4o mini: Non-social science research article
Environmental DNA adsorption to chitin can promote horizontal gene transfer by natural transformation
Jacob D. Holt, Yixuan Peng, Triana N. Dalia, Ankur B. Dalia, Carey D. Nadell
Full text
Horizontal gene transfer by natural transformation (NT) is induced in Vibrio cholerae upon attachment to chitin surfaces in the aquatic environment. Here, we show that free environmental DNA adsorbs to chitin surfaces under physiologically realistic conditions. Using live-cell imaging and a fluorescent NT reporter, we demonstrate with cellular resolution microscopy that V. cholerae utilizes chitin-bound DNA as a reservoir for genetic exchange. Additionally, we demonstrate that uptake of DNA from this chitin-bound reservoir requires the forceful retraction of competence type IV pili. These findings uncover a role for retraction force in driving pilus-dependent NT and suggest that chitin particle surfaces can act as hotspots for horizontal gene transfer.
GPT-4o mini: Non-social science research article
Early dynamics of chromatin decompaction drive nuclear stiffening
Irena L. Ivanovska
Full text
GPT-4o mini: Non-social science research article
Spatially resolved DNP-assisted NMR illuminates the conformational ensemble of α-synuclein in intact viable cells
Jaka Kragelj, Rupam Ghosh, Yiling Xiao, Rania Dumarieh, Dominique Lagasca, Sakshi Krishna, Kendra K. Frederick
Full text
The protein α-syn adopts a wide variety of conformations including an intrinsically disordered monomeric form and an α-helical-rich membrane-associated form that is thought to play an important role in cellular membrane processes. However, despite the high affinity of α-syn for membranes, evidence that the α-helical form is adopted inside cells has been indirect. DNP-assisted solid-state NMR on frozen cellular samples can report directly on the entire conformational ensemble. By controlling the distribution of the DNP agent throughout the cellular biomass, such experiments can provide quantitative information upon the entire structural ensemble or provide information about spatially resolved subpopulations. When the polarization agent is dispersed homogeneously throughout the cell, a minority of the α-syn inside HEK293 cells adopts a highly α-helical-rich conformation. When the polarization agent is peripherally localized, the α-helical-rich conformation predominates, indicating that it is preferentially adopted near the cellular periphery. This demonstrates how selectively altering the spatial distribution of the DNP agent can be a powerful tool to observe spatially distinct structural ensembles. This approach paves the way for more nuanced investigations into the conformations that proteins adopt in different areas of the cell.
GPT-4o mini: Non-social science research article
Sensitivity of simulations of Plio–Pleistocene climate with the CLIMBER-2 Earth System Model to details of the global carbon cycle
Judit Carrillo, Michael E. Mann, Irina Marinov, Shannon A. Christiansen, Matteo Willeit, Andrey Ganopolski
Full text
The Earth system model CLIMBER-2 has been used in past work to successfully reproduce the glacial/interglacial cycles of the Plio–Pleistocene and the Mid-Pleistocene Transition (MPT) from predominantly 40 to 100 ky timescale oscillatory behavior as a function of declining volcanic outgassing and regolith removal. In this study, we further examine the sensitivity of this previous work to varying prescribed levels of volcanic outgassing and regolith extent and the long-term dynamics of the global carbon cycle, affecting the exchange and partitioning of carbon between different Earth system reservoirs and therefore global atmospheric CO 2 concentrations. As volcanic outgassing decreases, CO 2 and land carbon storage decrease, while ocean carbon storage, including CaCO 3 sediment, increases. At volcanic outgassing levels below a threshold value of roughly 5.7 Tmol C yr −1 , sea level decreases due to land ice formation, leading to increased carbon accumulation in the ocean and decreased carbon in the CaCO 3 sediment reservoir. Our previous finding of strong hysteresis and path dependence in the glacial/interglacial alternation history [J. Carrillo et al. , Proc. Natl. Acad. Sci. 121, e2322926121 (2024)] appears to be a tenuous climate feature, dependent on the precise representation of carbon cycle processes and, specifically, the numerical precision used in the calculation of certain key state variables in the model’s carbon cycle.
GPT-4o mini: Non-social science research article
Summer solstice optimizes the thermal growing season
Victor Van der Meersch, E. M. Wolkovich
Full text
Multiple studies have recently proposed the summer solstice as a universal cue for major plant physiological processes. While this would have strong implications for fundamental plant biology and climate change forecasting, we currently have no clear mechanisms to explain the emergence and importance of solstice as a cue. Here, we analyze temperature accumulation patterns in relation to the summer solstice across Europe and North America—in past, historical, and projected future climates. We show that, on average, the summer solstice coincides with a thermal optimum during the growing season. However, we also find significant local variation in the timing of this optimum across different climates—suggesting the potential of alternative cues.
GPT-4o mini: Non-social science research article
Multiple cortical systems influence a single vibrissa muscle
Aman Maharjan, Jason M. Guest, Jean-Alban Rathelot, Fiorella M. Gomez Osorio, Peter L. Strick, Marcel Oberlaender
Full text
What is the neural substrate that enables the cerebral cortex to control a single mystacial vibrissa and orchestrate its movement? To answer this question, we injected rabies virus into the intrinsic muscle that protracts the rat C3 vibrissa and used retrograde transneuronal transport to identify the cortical neurons that influence the muscle. A surprisingly diverse set of cortical areas is the origin of disynaptic control over the motoneurons that influence the C3 protractor. More than two thirds of these layer 5 pyramidal neurons (L5PNs) are dispersed in frontal and parietal areas outside the primary motor cortex (vM1). This observation emphasizes the importance of descending motor commands from non-primary motor areas. More than a third of the L5PNs originate from somatosensory areas, such as the barrel field (vS1). The barrel field has been long considered a prototypic model system for studying sensory processing at the level of the cerebral cortex. Even so, we find that the number of L5PNs in vS1, and even their peak density, rivals the number and peak density of L5PNs in vM1. Thus, our results emphasize the importance of the barrel field in processing motor output. The distribution of L5PNs in vM1 and vS1 leads us to propose a model of vibrissa protraction in which vM1 output results in protraction, and vS1 output results in reciprocal inhibition (suppression) of protraction. This paired initiation and suppression of complementary movements may be a general feature of the descending output from the rodent M1 and S1.
GPT-4o mini: Non-social science research article
Updated fossil analyses reveal critical insights into the origins of monotreme lifestyles
Megan R. Whitney
Full text
GPT-4o mini: Non-social science research article
Ethanol induction of FGF21 in the liver is dependent on histone acetylation and ligand activation of ChREBP by glycerol-3-phosphate
Mi Cheong Cheong, Bryan Mackowiak, Hyung Bum Kim, Genaro Hernandez, Tulip Nandu, Kevin Vale, Yuan Zhang, Lauren G. Zacharias, Thomas P. Mathews, Bin Gao, W. Lee Kraus, Steven A. Kliewer, David J. Mangelsdorf
Full text
Ethanol rapidly stimulates the liver to synthesize the hormone fibroblast growth factor 21 (FGF21), which then acts on the brain to elicit a multifaceted protective response. We show that in mice, this induction of FGF21 occurs at the level of gene transcription and is regulated by two byproducts of ethanol metabolism, glycerol-3-phosphate (G3P) and acetyl-CoA. Using cell-based reporter and thermal shift binding assays, we show that G3P binds to a conserved domain and activates the transcription factor carbohydrate-responsive element-binding protein (ChREBP), which regulates the Fgf21 gene promoter. The stimulation of Fgf21 gene transcription by ethanol also requires its metabolism to acetyl-CoA and correlates with histone acetylation. Accordingly, a p300/CBP histone acetyltransferase inhibitor blocks histone acetylation, ChREBP recruitment, and transcriptional activation at the Fgf21 promoter. Together, these findings reveal a dual regulatory mechanism driven by both G3P and acetyl-CoA that explains ethanol’s robust stimulatory effect on Fgf21 and possibly other ChREBP target genes in the liver.
GPT-4o mini: Non-social science research article
Convergent expansions of keystone gene families drive metabolic innovation in Saccharomycotina yeasts
Kyle T. David, Joshua G. Schraiber, Johnathan G. Crandall, Abigail L. Labella, Dana A. Opulente, Marie-Claire Harrison, John F. Wolters, Xiaofan Zhou, Xing-Xing Shen, Marizeth Groenewald, Chris Todd Hittinger, Matt Pennell, Antonis Rokas
Full text
Many remarkable phenotypes have repeatedly occurred across vast evolutionary distances. When convergent traits emerge on the tree of life, they are sometimes driven by the same underlying gene families, while other times, many different gene families are involved. Conversely, a gene family may be repeatedly recruited for a single trait or many different traits. To understand the general rules governing convergence at both genomic and phenotypic levels, we systematically tested associations between 56 binary metabolic traits and gene count in 14,785 gene families from 993 Saccharomycotina yeasts. Using a recently developed phylogenetic approach that reduces spurious correlations, we found that gene family expansion and contraction were significantly linked to trait gain and loss in 45/56 (80%) traits. While 595/739 (81%) significant gene families were associated with only one trait, we also identified several “keystone” gene families that were significantly associated with up to 13/56 (23%) of all traits. Strikingly, most of these families are known to encode metabolic enzymes and transporters, including all members of the industrially relevant MAL tose fermentation loci in the baker’s yeast Saccharomyces cerevisiae . These results indicate that convergent evolution on the gene family level may be more widespread across deeper timescales than previously believed.
Revealing land control dynamics in emerging agricultural frontiers
Olivia del Giorgio, Matthias Baumann, Tobias Kuemmerle, Yann le Polain de Waroux
Full text
The expansion of commodity agriculture into tropical and subtropical woodlands degrades ecosystem functionality, biodiversity, and the livelihood base of millions of people. Understanding where and how agricultural frontiers emerge is thus important. Yet, existing monitoring approaches typically focus on mapping deforestation and do not capture the shifts in land access and ownership that lay the ground for agricultural expansion, thereby missing early stages of frontier development. We develop an approach that captures these early dynamics and apply it to the entire 1,1 million km 2 of the Chaco, a global deforestation hotspot. Through the detection of linear features indicative of land claims and the analysis of their spatial–temporal dynamics, we reveal that the footprint of agricultural frontiers in the region extends far beyond that of deforestation. Most of the Chaco shows signs of land claiming, and although claiming activity is especially concentrated close to active deforestation, emergent claiming in remote parts of the Bolivian and Paraguayan Chaco indicates rapidly growing interest in land in these regions. Finally, the strong spatial correlation between land claiming and the disappearance of smallholder homesteads points to the social repercussions of early agricultural frontier expansion in the Chaco. By offering a transferable template to map land-control indicators at scale, our approach enables a better understanding of frontier processes and more accurate targeting of policy interventions in emerging agricultural frontiers globally.
Reply to Ogutu et al.: Cattle–wild herbivore interaction studies warrant new lenses from community ecology and environmental justice
Bilal Butt, Wenjing Xu
Full text
Measuring historical pollution: Natural history collections as tools for public health and environmental justice research
Shane DuBay, Brian C. Weeks, Pamela E. Davis-Kean, Carl Fuldner, Nyeema C. Harris, Sara Hughes, Bruce O’Brien, Marie Perkins, Cheryl Weyant
Full text
Through the industrial era, pollutants have been unevenly distributed in the environment, disproportionately impacting disenfranchised communities. Redressing the unequal distribution of environmental pollution is thus a question of environmental justice and public health that requires policy solutions. However, data on pollutants for many locations and time periods are limited because environmental monitoring is largely reactive—i.e., pollutants are monitored only after they are recognized as harmful and are circulating in the environment at elevated levels. Without comprehensive historical pollution data, it is difficult to understand the full, intergenerational consequences of pollutants on environmental and human health. We assert that biological specimens in natural history collections are an underutilized source of quantitative pollution data for tracking environmental pollutants over two centuries to inform justice-centered policy solutions. Specifically, we: 1) discuss the need for quantitative pollution data in environmental research and its implications for public health and policy, 2) examine the capacity of biological specimens as tools for tracking environmental pollutants through space and time, 3) present a framework for integrating pollution datasets from specimens with spatially and temporally matched human health datasets to inform and evaluate policy, and 4) identify challenges and research directions associated with the use of quantitative pollution datasets. Biological specimens present a unique opportunity to fill critical gaps that address environmental challenges relevant to public health and policy. This work demands interdisciplinary partnerships and inclusive practices to connect data generated from specimens with urgent questions about environmental health and justice.
The prevalence of functional limitations in the US workforce
Hailey Clark, Bastian Ravesteijn, Kathleen J. Mullen, Nicole Maestas
Full text
This research paper investigates the prevalence of functional limitations among employed adults in the United States and the association between these limitations and medical conditions. The authors administered a survey adapted from the Dutch Functional Abilities List to a nationally representative sample of US adults ages 22 and older, finding that nearly three-quarters of working adults report at least one functional limitation, with an average of nearly six functional limitations per working adult. The most common limitations were in upper body strength and torso range of motion, and with respect to the ambient environment. The study also found that mental illness, arthritis, and substance use disorder are associated with the greatest number of functional limitations in working adults. The findings have implications for economic performance, workforce planning, and social policies to support displaced and vulnerable workers with significant functional limitations. Identifying the occupations and industries with large numbers of workers with functional limitations is critical to addressing short-term labor supply disruptions (e.g., public health crises) and preparing for longer-term workforce needs (e.g., long-term care workers for an aging population).
Estimating wage disparities using foundation models
Keyon Vafa, Susan Athey, David M. Blei
Full text
The rise of foundation models marks a paradigm shift in machine learning: instead of training specialized models from scratch, foundation models are trained on massive datasets before being adjusted or fine-tuned to make predictions on smaller datasets. Initially developed for text, foundation models have also excelled at making predictions about social science data. However, while many estimation problems in the social sciences use prediction as an intermediate step, they ultimately require different criteria for success. In this paper, we develop methods for fine-tuning foundation models to perform these estimation problems. We first characterize an omitted variable bias that can arise when a foundation model is fine-tuned in the standard way: to minimize predictive error. We then provide a set of conditions for fine-tuning under which estimates derived from a foundation model are n -consistent. Based on this theory, we develop fine-tuning algorithms that empirically mitigate this omitted variable bias. To demonstrate our ideas, we study gender wage gap estimation. Classical methods for estimating the adjusted wage gap employ simple predictive models of wages, which can induce omitted variable bias because they condition on coarse summaries of career history. Instead, we use a custom-built foundation model, capturing a richer representation of career history. Using data from the Panel Study of Income Dynamics, we find that career history explains more of the gender wage gap than standard econometric models can measure, and we identify elements of career history that are omitted by standard models but are important for explaining the gap.
Why excluding regenerative grazing skews beef’s carbon profile
Nataliya Apanovich, Deseret Weeks
Full text

Science

GPT-4o mini: Non-social science research article
Measurements of molecular size and shape on a chip
Xin Zhu, Timothy J. D. Bennett, Konstantin C. Zouboulis, Dimitrios Soulias, Michal Grzybek, Justin L. P. Benesch, Afaf H. El-Sagheer, Ünal Coskun, Madhavi Krishnan
Full text
Size and shape are critical discriminators between molecular species and states. We describe a microchip-based high-throughput imaging approach offering rapid and precise determination of molecular properties under native solution conditions. Our method detects differences in molecular weight across at least three orders of magnitude and down to two carbon atoms in small molecules. We quantify the strength of molecular interactions across more than six orders of magnitude in affinity constant and track reactions in real time. Highly parallel measurements on individual molecules serve to characterize sample-state heterogeneity at the highest resolution, offering predictive input to model three-dimensional structure. We further leverage the method’s structural sensitivity for diagnostics, exploiting ligand-induced conformational changes in the insulin receptor to sense insulin concentration in serum at the subnanoliter and subzeptomole scale.
GPT-4o mini: Non-social science research article
Pre-European contact leprosy in the Americas and its current persistence
Maria Lopopolo, Charlotte Avanzi, Sebastian Duchene, Pierre Luisi, Alida de Flamingh, Gabriel Yaxal Ponce-Soto, Gaetan Tressieres, Sarah Neumeyer, Frédéric Lemoine, Elizabeth A. Nelson, Miren Iraeta-Orbegozo, Jerome S. Cybulski, Joycelynn Mitchell, Vilma T. Marks, Linda B. Adams, John Lindo, Michael DeGiorgio, Nery Ortiz, Carlos Wiens, Juri Hiebert, Alexandro Bonifaz, Griselda Montes de Oca, Vanessa Paredes-Solis, Carlos Franco-Paredes, Lucio Vera-Cabrera, José G. Pereira Brunelli, Mary Jackson, John S. Spencer, Claudio G. Salgado, Xiang-Yang Han, Camron M. Pearce, Alaine K. Warren, Patricia S. Rosa, Amanda J. de Finardi, Andréa de F. F. Belone, Cynthia Ferreira, Philip N. Suffys, Amanda N. Brum Fontes, Sidra E. G. Vasconcellos, Roxane Schaub, Pierre Couppié, Kinan Drak Alsibai, Rigoberto Hernåndez-Castro, Mayra Silva Miranda, Iris Estrada-Garcia, Fermin Jurado-Santacruz, Ludovic Orlando, Hannes Schroeder, Lluis Quintana-Murci, Mariano Del Papa, Ramanuj Lahiri, Ripan S. Malhi, Simon Rasmussen, Nicolås Rascovan
Full text
Leprosy, primarily caused by Mycobacterium leprae , is considered a disease introduced into the Americas during European colonization. However, the recent discovery of a second pathogen causing leprosy, M. lepromatosis , mainly found in the Americas, challenges this view. Here, we show that M. lepromatosis infected humans in the Americas before European contact. By screening 389 ancient and 408 contemporary samples, we have expanded the genetic data available for the species. Phylogenetic analyses revealed distinct human-infecting clades of M. lepromatosis , with one dominating North America since colonial times. The presence of millennia-old strains in North and South America indicates M. lepromatosis may have been widespread during the Late Holocene, demonstrating M. lepromatosis leprosy has a long-standing history in the Americas before European arrival.
GPT-4o mini: Non-social science research article
Prehistoric genomes from Yunnan reveal ancestry related to Tibetans and Austroasiatic speakers
Tianyi Wang, Melinda A. Yang, Zhonghua Zhu, Minmin Ma, Han Shi, Leo Speidel, Rui Min, Haibing Yuan, Zhilong Jiang, Changcheng Hu, Xiaorui Li, Dongyue Zhao, Fan Bai, Peng Cao, Feng Liu, Qingyan Dai, Xiaotian Feng, Ruowei Yang, Xiaohong Wu, Xu Liu, Ming Zhang, Wanjing Ping, Yichen Liu, Yang Wan, Fan Yang, Ranchao Zhou, Lihong Kang, Guanghui Dong, Mark Stoneking, Qiaomei Fu
Full text
The human landscape in East and Southeast Asia is vastly complex, and successful retrieval of genome-wide data from prehistoric humans of southern East Asia is sparse. We successfully sampled 127 ancient human genomes from southwestern China. A 7100-year-old female individual from central Yunnan shows a previously unsampled Basal Asian ancestry related to a ghost population that contributed to Tibetan Plateau populations. Central Yunnan populations dating to 5500 to 1400 years before present show an East Asian ancestry distinct from northern or southern East Asian ancestries that contributed to present-day East and Southeast Asians, particularly Austroasiatic speakers, and emphasizes the importance of the Red River valley for proto-Austroasiatic population history. Diverse Asian ancestries are represented in humans sampled from Yunnan, clarifying past population dynamics related to both Tibetan and Austroasiatic origins.
GPT-4o mini: Non-social science research article
Intracellular protein editing enables incorporation of noncanonical residues in endogenous proteins
Jenna N. Beyer, Yevgeniy V. Serebrenik, Kaitlyn Toy, Mohd. Altaf Najar, Emily Feierman, Nicole R. Raniszewski, Erica Korb, Ophir Shalem, George M. Burslem
Full text
The ability to study proteins in their native cellular context is crucial to our understanding of biology. In this work, we report a technology for intracellular protein editing, drawing from split intein–mediated protein splicing, genetic code expansion, and endogenous protein tagging. This approach enables us to rapidly and site-specifically install residues and chemical handles into a protein. We demonstrate the power of this platform to edit cellular proteins, inserting epitopes, protein-specific sequences, and noncanonical amino acids. Notably, we use an endogenous tagging approach to apply our protein editing technology to endogenous proteins with minimal perturbation. We anticipate that the protein editing technology presented in this work will be applied to a diverse set of problems and phenomena in live mammalian cells.
GPT-4o mini: Non-social science research article
Admixture’s impact on Brazilian population evolution and health
Kelly Nunes, Marcos AraĂșjo Castro e Silva, MaĂ­ra R. Rodrigues, Renan Barbosa Lemes, Patricio Pezo-Valderrama, Lilian Kimura, Lucas Schenatto de Sena, JosĂ© Eduardo Krieger, Margareth Catoia Varela, Luiz OtĂĄvio de Azevedo, Luis Marcelo Aranha Camargo, Ricardo G. M. Ferreira, Henrique Krieger, Maria CĂĄtira Bortolini, JosĂ© Geraldo Mill, Putira Sacuena, JoĂŁo F. Guerreiro, Celia M. B. de Souza, Francisco V. Veronese, Fernanda S. L. Vianna, David Comas, Alexandre C. Pereira, Lygia V. Pereira, TĂĄbita HĂŒnemeier
Full text
Brazil, the largest Latin American country, is underrepresented in genomic research despite boasting the world’s largest recently admixed population. In this study, we generated 2723 high-coverage whole-genome sequences from the Brazilian population, including urban, rural, and riverine communities representing diverse ethnic backgrounds. We reveal the impressive genomic diversity of Brazilians, identifying >8 million previously unknown variants, including 36,637 predicted deleterious and potentially affecting population health. We found a positive correlation between these deleterious variants and ancestry. Brazilian genomes are a global haplotype mosaic shaped by nonrandom mating, with peak admixture in the 18th and 19th centuries. Within this diversity, ancestry-specific haplotypes exhibit an uneven spatiotemporal distribution. We also identified putatively selected genes in this diverse population, primarily linked to fertility, immune response, and metabolic traits.
GPT-4o mini: Non-social science research article
BRAF oncogenic mutants evade autoinhibition through a common mechanism
Hugo Lavoie, Ting Jin, Driss Lajoie, Marion Decossas, Patrick Gendron, Bing Wang, Frantisek Filandr, Malha Sahmi, Chang Hwa Jo, Sandra Weber, GeneviĂšve Arseneault, Sasmita Tripathy, Pierre Beaulieu, Doris A. Schuetz, David C. Schriemer, Anne Marinier, William J. Rice, Pierre Maisonneuve, Marc Therrien
Full text
Uncontrolled activation of the rat sarcoma (RAS)–extracellular signal–regulated kinase (ERK) pathway drives tumor growth, often because of oncogenic BRAF mutations. BRAF regulation, involving monomeric autoinhibition and activation by dimerization, has been intensely scrutinized, but mechanisms enabling oncogenic mutants to evade regulation remain unclear. By using cryo–electron microscopy, we solved the three-dimensional structures of the three oncogenic BRAF mutant classes, including the common V600E variant. These mutations disrupted wild-type BRAF's autoinhibited state, mediated by interactions between the cysteine-rich domain and kinase domain, thereby shifting the kinase domain into a preactivated conformation. This structural change likely results from helix αC displacement. PLX8394, a BRAF inhibitor that stabilizes helix αC in an inactive conformation, restored the autoinhibited conformation of oncogenic BRAF, explaining the properties of this class of compounds.
GPT-4o mini: Non-social science research article
Functional polymorphism of CYCLE underlies the diapause variation in moths
Shirui Zheng, Yaohui Wang, Guiyun Li, Sheng Qin, Zhi Dong, Xu Yang, Xiaomiao Xu, Gangqi Fang, Muwang Li, Shuai Zhan
Full text
Diapause is a common seasonal adaptive strategy that regulates annual timing in insects. Very few causal loci underlying diapause variation have yet been identified. By leveraging cross-mapping and genome-wide association analysis, we identified the N terminus of the clock protein CYCLE as a major causal effector underlying embryonic diapause differences in the silk moth. We found that the nondiapause phenotype in polyvoltine strains results from a specific deletion that disrupts an alternative isoform of CYCLE. We further demonstrated that different CYCLE isoforms contribute to a functional diversity in modulating circadian rhythms and diapause, which has been preserved in Lepidoptera for at least 110 million years. Our study proposes a model that explains how adaptive phenotypes can evolve rapidly without affecting related essential functions.
GPT-4o mini: Non-social science research article
ASB7 is a negative regulator of H3K9me3 homeostasis
Liwen Zhou, Zhenxuan Chen, Yezi Zou, Xia Zhang, Zifeng Wang, Hongwen Zhu, Jiahui Lin, Ziyao Huang, Lisi Zheng, Jiali Chen, Miner Xie, Meifang Zhang, Ruhua Zhang, Minglu Zhu, Ziwen Wang, Hu Zhou, Song Gao, Yuxin Yin, Yuanzhong Wu, Tiebang Kang
Full text
The maintenance of H3K9me3 involves the recognition of pre-existing modifications by HP1, which recruits methyltransferase SUV39H1 to methylate the adjacent newly incorporated histones, thereby establishing a positive feedback loop. However, how this positive feedback is restricted to maintain H3K9me3 homeostasis remains largely unknown. Here, we performed an unbiased genome-scale CRISPR-Cas9 screen and identified CUL5 ASB7 E3 ubiquitin ligase as a negative regulator of H3K9me3. ASB7 is recruited to heterochromatin by HP1 and promotes SUV39H1 degradation. During mitosis, CDK1 phosphorylates ASB7, preventing its interaction with SUV39H1, leading to SUV39H1 stabilization and H3K9me3 restoration. Our findings reveal a dynamic circuit involving HP1, SUV39H1, and ASB7 that governs H3K9me3 homeostasis, thereby ensuring faithful epigenetic inheritance and preventing excessive heterochromatin formation.
GPT-4o mini: Non-social science research article
Testing interelectronic interaction in lithium-like tin
Jonathan Morgner, Vladimir A. Yerokhin, Charlotte M. König, Fabian Heiße, Bingsheng Tu, Tim Sailer, Bastian Sikora, ZoltĂĄn Harman, JosĂ© R. Crespo LĂłpez-Urrutia, Christoph H. Keitel, Sven Sturm, Klaus Blaum
Full text
Magnetic moments of bound-electron systems are a sensitive tool for testing fundamental interactions. The g factors of lithium-like ions have been rigorously studied in recent years, enabling insights into the relativistic interelectronic effects. In this work, we present the g -factor measurement of lithium-like tin, accurate to 0.5 parts per billion, as well as ab initio theoretical calculations that include an advanced treatment of the interelectronic interaction. We further improved the prediction by using the experimental result for the hydrogen-like tin g factor, inferring from it the unknown higher-order quantum electrodynamic (QED) effects. The observed agreement independently confirms the revised theory at a previously inaccessible high atomic number Z of 50, where QED effects are considerably larger.
GPT-4o mini: Non-social science research article
A single domestication origin of adzuki bean in Japan and the evolution of domestication genes
Chih-Cheng Chien, Takashi Seiko, Chiaki Muto, Hirotaka Ariga, Yen-Chiao Wang, Chuan-Hsin Chang, Hiroaki Sakai, Ken Naito, Cheng-Ruei Lee
Full text
Adzuki is a central legume in East Asian culinary culture, yet its domestication origin remains debated. Using ~700 accessions across Asia, we show that the initial domestication happened three to five thousand years ago in central Japan during the Jomon period, followed by a range expansion into China and secondary hybridization with Chinese wild populations. We mapped, validated, and dated key genes associated with seed coat color evolution ( VaPAP1 for loss of mottled black and VaANR1 for gain of red colors). The frequency increases of variants affecting key domestication syndrome substantially predated the wild-cultigen divergence. Together, our results resolve the conflict between genetic and archaeological evidence about adzuki origins and reconstruct the evolutionary trajectory of archaeobotanically unobservable traits, consistent with a role of early weak selection during domestication.
GPT-4o mini: Non-social science research article
Mobile integrons encode phage defense systems
Nicolas Kieffer, Alberto Hipólito, Laura Ortiz-Miravalles, Paula Blanco, Thomas Delobelle, Patricia Vizuete, Francisco Manuel Ojeda, Thomas Jové, Dukas Jurenas, Meritxell García-Quintanilla, André Carvalho, Pilar Domingo-Calap, José Antonio Escudero
Full text
Integrons are bacterial genetic elements that capture, stockpile, and modulate the expression of genes encoded in integron cassettes. Mobile integrons (MIs) are borne on plasmids, acting as a vehicle for hundreds of antimicrobial resistance genes among key pathogens. These elements also carry gene cassettes of unknown function ( gcu s) whose role and adaptive value remain unexplored. In this work, we show that gcu s encode phage resistance systems, many of which are newly discovered. Bacteriophage resistance integron cassettes (BRiCs) can be combined and mixed with resistance cassettes to produce multiphage or drug and phage resistance. The fitness costs of BRiCs are variable and dependent on the genetic context and can be modulated by changing the order of cassettes in the array. Hence, MIs act as highly mobile, low-cost defense islands.
GPT-4o mini: Non-social science research article
Pancreatic cancer–restricted cryptic antigens are targets for T cell recognition
Zackery A. Ely, Zachary J. Kulstad, Gurcan Gunaydin, Sudarsana Addepalli, Eva K. Verzani, Marta Casarrubios, Karl R. Clauser, Xilin Wang, Isabelle E. Lippincott, Cedric Louvet, Thomas Schmitt, Kevin S. Kapner, Miles P. Agus, Connor J. Hennessey, James M. Cleary, Sine R. Hadrup, Susan Klaeger, Jennifer Su, Alex M. Jaeger, Brian M. Wolpin, Srivatsan Raghavan, Eric L. Smith, Philip D. Greenberg, Andrew J. Aguirre, Jennifer G. Abelin, Steven A. Carr, Tyler Jacks, William A. Freed-Pastor
Full text
Translation of the noncoding genome in cancer can generate cryptic (noncanonical) peptides capable of presentation by human leukocyte antigen class I (HLA-I); however, the cancer specificity and immunogenicity of noncanonical HLA-I–bound peptides (ncHLAp) are incompletely understood. Using high-resolution immunopeptidomics, we discovered that cryptic peptides are abundant in the pancreatic cancer immunopeptidome. Approximately 30% of ncHLAp exhibited cancer-restricted translation, and a substantial subset were shared among patients. Cancer-restricted ncHLAp displayed robust immunogenic potential in a sensitive ex vivo T cell priming platform. ncHLAp-reactive, T cell receptor–redirected T cells exhibited tumoricidal activity against patient-derived pancreatic cancer organoids. These findings demonstrate that pancreatic cancer harbors cancer-restricted ncHLAp that can be recognized by cytotoxic T cells. Future therapeutic strategies for pancreatic cancer, and potentially other solid tumors, may include targeting cryptic antigens.
GPT-4o mini: Non-social science research article
Sedentary chromosomal integrons as biobanks of bacterial antiphage defense systems
Baptiste Darracq, Eloi Littner, Manon Brunie, Julia Bos, Pierre Alexandre Kaminski, Florence Depardieu, Weronika Slesak, Kevin Debatisse, Marie Touchon, Aude Bernheim, David Bikard, Frédérique Le Roux, Didier Mazel, Eduardo P. C. Rocha, Céline Loot
Full text
Integrons are genetic systems that drive bacterial adaptation by acquiring, expressing, and shuffling gene cassettes. While mobile integrons are well known for spreading antibiotic resistance genes, the functions of the hundreds of cassettes carried by sedentary integrons remain largely unexplored. We show that many of these cassettes encode small variants of known antiphage systems that favor their inclusion in the integron. We also demonstrate that nearly 10% of the integron cassettes in the pandemic Vibrio cholerae strain encode novel antiphage functions. Most of these novel systems have little or no similarity to previously known ones, with several providing defense through cell lysis or growth arrest. Our work highlights the stabilization and prevalence of small antiphage systems within integrons, making them an untapped biobank of defense mechanisms.
GPT-4o mini: Non-social science research article
Activation dynamics traced through a G protein–coupled receptor by 81 1 H- 15 N NMR probes
Feng-Jie Wu, Pascal S. Rieder, Layara Akemi Abiko, Anne Grahl, Daniel HĂ€ussinger, Stephan Grzesiek
Full text
The regulation of G protein–coupled receptor signaling by different orthosteric ligands is thought to occur through shifts in dynamically interconverting, conformational distributions. Such changes in dynamical distributions have been detected so far only by very sparse, often non-native experimental probes at low resolution. Using a recently developed paramagnetic nuclear magnetic resonance (NMR) method, we could assign and follow 81 1 H- 15 N NMR correlations in the ÎČ 1 -adrenergic receptor ÎČ 1 AR at ambient conditions in response to various orthosteric ligands in the absence or presence of a G protein–mimicking nanobody. The comparison reveals the dynamics and mechanism of the central, highly conserved xWIPF 3 motif, contiguous regions of rigid and loose conformational coupling separated by conserved prolines during signal transmission, and the plasticity of the intracellular face in response to transducer binding.
GPT-4o mini: Non-social science research article
Reducing emissions and air pollution from informal brick kilns: Evidence from Bangladesh
Nina Brooks, Debashish Biswas, Sameer Maithel, Grant Miller, Aprajit Mahajan, M. Rofi Uddin, Shoeb Ahmed, Moogdho Mahzab, Mahbubur Rahman, Stephen P. Luby
Full text
We present results from a randomized controlled trial in Bangladesh that introduced operational practices to improve energy efficiency and reduce emissions in 276 “zigzag” brick kilns. Of all intervention kilns, 65% adopted the improved practices. Treatment assignment reduced energy use by 10.5% ( P -value <0.001) and decreased CO 2 and PM 2.5 emissions by 171 and 0.45 metric tons, respectively, per kiln per year. Valuing the CO 2 reductions using a social cost of carbon of 185 USD per metric ton, we find that the social benefits outweigh costs by a factor of 65 to 1. The intervention, which required no new capital investment, also decreased fuel costs and increased brick quality. Our results demonstrate the potential for privately profitable, as well as publicly beneficial, improvements to address environmental problems in informal industries.
GPT-4o mini: Non-social science research article
Predicting expression-altering promoter mutations with deep learning
Kishore Jaganathan, Nicole Ersaro, Gherman Novakovsky, Yuchuan Wang, Terena James, Jeremy Schwartzentruber, Petko Fiziev, Irfahan Kassam, Fan Cao, Johann Hawe, Henry Cavanagh, Ashley Lim, Grace Png, Jeremy McRae, Abhimanyu Banerjee, Arvind Kumar, Jacob Ulirsch, Yan Zhang, Francois Aguet, Pierrick Wainschtein, Laksshman Sundaram, Adriana Salcedo, Sofia Kyriazopoulou Panagiotopoulou, Delasa Aghamirzaie, Evin Padhi, Ziming Weng, Shan Dong, Damian Smedley, Mark Caulfield, Anne O’Donnell-Luria, Heidi L. Rehm, Stephan J. Sanders, Anshul Kundaje, Stephen B. Montgomery, Mark T. Ross, Kyle Kai-How Farh
Full text
Only a minority of patients with rare genetic diseases are currently diagnosed by exome sequencing, suggesting that additional unrecognized pathogenic variants may reside in non-coding sequence. Here, we describe PromoterAI, a deep neural network that accurately identifies non-coding promoter variants which dysregulate gene expression. We show that promoter variants with predicted expression-altering consequences produce outlier expression at both RNA and protein levels in thousands of individuals, and that these variants experience strong negative selection in human populations. We observe that clinically relevant genes in rare disease patients are enriched for such variants and validate their functional impact through reporter assays. Our estimates suggest that promoter variation accounts for 6% of the genetic burden associated with rare diseases.
GPT-4o mini: Non-social science research article
Enamel proteins reveal biological sex and genetic variability in southern African Paranthropus
Palesa P. Madupe, Claire Koenig, Ioannis Patramanis, Patrick L. RĂŒther, Nomawethu Hlazo, Meaghan Mackie, Mirriam Tawane, Johanna Krueger, Alberto J. Taurozzi, Gaudry TrochĂ©, Job Kibii, Robyn Pickering, Marc R. Dickinson, Yonatan Sahle, Dipuo Kgotleng, Charles Musiba, Fredrick Manthi, Liam Bell, Michelle DuPlessis, Catherine Gilbert, Bernhard Zipfel, Lukas F. K. Kuderna, Esther Lizano, Frido Welker, Pelagia Kyriakidou, JĂŒrgen Cox, Catherine Mollereau, Caroline Tokarski, Jonathan Blackburn, JazmĂ­n Ramos-Madrigal, Tomas Marques-Bonet, Kirsty Penkman, ClĂ©ment Zanolli, Lauren Schroeder, Fernando Racimo, Jesper V. Olsen, Rebecca R. Ackermann, Enrico Cappellini
Full text
Paranthropus robustus is a morphologically well-documented Early Pleistocene hominin species from southern Africa with no genetic evidence reported so far. In this work, we describe the mass spectrometric sequencing of enamel peptides from four ~2 million–year-old dental specimens attributed morphologically to P. robustus from the site of Swartkrans in South Africa. The identification of AMELY-specific peptides enabled us to assign two specimens to male individuals, whereas semiquantitative mass spectrometric data analysis attributed the other two to females. A single amino acid polymorphism and the enamel-dentine junction shape variation indicated potential subgroups present within southern African Paranthropus . This study demonstrates how palaeoproteomics can help distinguish sexual dimorphism from other sources of variation in African Early Pleistocene hominins.
GPT-4o mini: Non-social science research article
Programmable gene insertion in human cells with a laboratory-evolved CRISPR-associated transposase
Isaac P. Witte, George D. Lampe, Simon Eitzinger, Shannon M. Miller, Kiara N. BerrĂ­os, Amber N. McElroy, Rebeca T. King, Olivia G. Stringham, Diego R. Gelsinger, Phuc Leo H. Vo, Albert T. Chen, Jakub Tolar, Mark J. Osborn, Samuel H. Sternberg, David R. Liu
Full text
Programmable gene integration in human cells has the potential to enable mutation-agnostic treatments for loss-of-function genetic diseases and facilitate many applications in the life sciences. CRISPR-associated transposases (CASTs) catalyze RNA-guided DNA integration but thus far demonstrate minimal activity in human cells. Using phage-assisted continuous evolution (PACE), we generated CAST variants with >200-fold average improved integration activity. The evolved CAST system (evoCAST) achieves ~10 to 30% integration efficiencies of kilobase-size DNA cargoes in human cells across 14 tested genomic target sites, including safe harbor loci, sites used for immunotherapy, and genes implicated in loss-of-function diseases, with undetected indels and low levels of off-target integration. Collectively, our findings establish a platform for the laboratory evolution of CASTs and advance a versatile system for programmable gene integration in living systems.
GPT-4o mini: Non-social science research article
Predicting and preventing Alzheimer’s disease
Eric Topol
Full text
With all the advances in both the science of aging and artificial intelligence (AI), we are in a propitious position to accurately and precisely determine who is at high risk of developing Alzheimer’s disease years before signs of even mild cognitive deficit. It takes at least 20 years for aggregates of misfolded ÎČ-amyloid and tau proteins to accumulate in the brain along with neuroinflammation that they incite. This provides a long window of opportunity to get ahead of the pathobiological process, both for prediction and prevention.
GPT-4o mini: Non-social science research article
Arctic bird nesting traces back to the Cretaceous
Lauren N. Wilson, Daniel T. Ksepka, John P. Wilson, Jacob D. Gardner, Gregory M. Erickson, Donald Brinkman, Caleb M. Brown, Jaelyn J. Eberle, Chris L. Organ, Patrick S. Druckenmiller
Full text
Polar ecosystems are structured and enriched by birds, which nest there seasonally and serve as keystone ecosystem members. Despite the ecological importance of polar birds, the origins of high-latitude nesting strategies remain obscured by a sparse fossil record. We report an extreme-latitude Arctic avialan assemblage from the Prince Creek Formation of Alaska—the northernmost Late Cretaceous terrestrial ecosystem. Numerous three-dimensionally preserved fossils constitute one of the most taxonomically rich Late Cretaceous avialan assemblages, including members of Hesperornithes, Ichthyornithes, and near-crown or crown birds (Neornithes), recording a previously undocumented interval in avialan evolution. Abundant perinatal fossils represent the oldest evidence of birds nesting at polar latitudes, which demonstrates that birds began using seasonal polar environments for breeding during the Cretaceous, long before their modern descendants.
GPT-4o mini: Non-social science research article
Deep learning–guided design of dynamic proteins
Amy B. Guo, Deniz Akpinaroglu, Christina A. Stephens, Michael Grabe, Colin A. Smith, Mark J. S. Kelly, Tanja Kortemme
Full text
Deep learning has advanced the design of static protein structures, but the controlled conformational changes that are hallmarks of natural signaling proteins have remained inaccessible to de novo design. Here, we describe a general deep learning–guided approach for de novo design of dynamic changes between intradomain geometries of proteins, similar to switch mechanisms prevalent in nature, with atomic-level precision. We solve four structures that validate the designed conformations, demonstrate modulation of the conformational landscape by orthosteric ligands and allosteric mutations, and show that physics-based simulations are in agreement with deep-learning predictions and experimental data. Our approach demonstrates that new modes of motion can now be realized through de novo design and provides a framework for constructing biology-inspired, tunable, and controllable protein signaling behavior de novo.
GPT-4o mini: Non-social science research article
Actin organizes chromosomes and microtubules to ensure mitotic fidelity in the preimplantation embryo
Blake Hernandez, Piotr Tetlak, Ana Domingo-Muelas, Hiroki Akizawa, Robin M. Skory, Goli Ardestani, Mate Biro, Xiaolei Liu, Stephanie Bissiere, Denny Sakkas, Nicolas Plachta
Full text
Following fertilization, the preimplantation embryo undergoes successive rounds of cell division and must accurately propagate the genetic material to ensure successful development. However, early mammalian embryos lack efficient spindle assembly mechanisms, and it remains unclear how error-free chromosome segregation is achieved. In this work, we imaged early mouse embryos and identified a network of nuclear actin cables that organize prophase chromosomes at the nuclear periphery. Following nuclear envelope breakdown, the network contracts and gathers chromosomes toward the cell center. Network contraction was driven by filament disassembly in a myosin II–independent manner. Additionally, we identified a network of branched actin filaments that attenuates metaphase spindle elongation. We also visualized nuclear actin in human embryos, suggesting a conserved role for actin in ensuring mitotic fidelity during early mammalian development.
GPT-4o mini: Non-social science research article
Ecological and evolutionary consequences of changing seasonality
Daniel HernĂĄndez-Carrasco, Jason M. Tylianakis, David A. Lytle, Jonathan D. Tonkin
Full text
Climate change and other anthropogenic drivers alter seasonal regimes across freshwater, terrestrial, and marine biomes. Seasonal patterns affect ecological and evolutionary processes at different ecological levels through changes to gene frequencies, species traits, population dynamics, species interactions, and different facets of biodiversity. We synthesize the mechanisms that determine biological responses to seasonality, to demonstrate how their interconnections can propagate impacts of altered seasonal patterns and complicate predictions. Given the potential for nonlinearities and the propagation of impacts across levels of ecological complexity, we advocate the use of mechanistic approaches that acknowledge species-specific responses to the environment and potential seasonal adaptations.
GPT-4o mini: Non-social science research article
Vapor-assisted surface reconstruction enables outdoor-stable perovskite solar modules
Xiangnan Sun, Wenda Shi, Tianjun Liu, Jinzhan Cheng, Xin Wang, Peng Xu, Wei Zhang, Xiaoming Zhao, Wanlin Guo
Full text
Natural illumination variations in light-dark cycles induce irreversible ion migration in perovskite solar cells, posing substantial challenges to their long-term outdoor operational stability. We addressed this issue by isolating defective octahedra at the perovskite surface using a vapor-deposited polydentate ligand. Surface octahedra isolation suppresses ion migration into the charge transport layer and reduces surface ionic defects, modulating the kinetics of ion migration during light-dark cycles. Our 785-square-centimeter industrial-scale perovskite solar modules achieved a power conversion efficiency (PCE) of 19.6%. Our modules demonstrated enhanced diurnal stability, retaining more than 97% of their initial PCE even after 101 light-dark cycles at 50°C. Our perovskite modules maintained stable power output during 45 days of outdoor operation under severe summer conditions, exhibiting stability comparable with that of the reference silicon cell.
GPT-4o mini: Non-social science research article
From North Asia to South America: Tracing the longest human migration through genomic sequencing
Elena S. Gusareva, Amit Gourav Ghosh, Vladimir N. Kharkov, Seik-Soon Khor, Aleksei Zarubin, Nikita Moshkov, Namrata Kalsi, Aakrosh Ratan, Cassie E. Heinle, Niall Cooke, Claudio M. Bravi, Marina V. Smolnikova, Sergey Yu. Tereshchenko, Eduard W. Kasparov, Irina Khitrinskaya, Andrey Marusin, Magomed O. Razhabov, Maria V. Golubenko, Maria Swarovskaya, Nikita A. Kolesnikov, Ksenia V. Vagaitseva, Elena R. Eremina, Aitalina Sukhomyasova, Olga Shtygasheva, Deepa Panicker, Poh Nee Ang, Choou Fook Lee, Yanqing Koh, See Ting Leong, Changsook Park, Sachin R. Lohar, Zhei Hwee Yap, Soo Guek Ng, Justine Dacanay, Daniela I. Drautz-Moses, Nurul Adilah Binte Ramli, Katsushi Tokunaga, Ian McGonigle, Inaho Danjoh, Andrés Moreno-Estrada, Atsushi Tajima, Hideyuki Tanabe, Yukio Nakamura, Shigeki Nakagome, Tatiana V. Tatarinova, Vadim A. Stepanov, Stephan C. Schuster, Hie Lim Kim
Full text
Genome sequencing of 1537 individuals from 139 ethnic groups reveals the genetic characteristics of understudied populations in North Asia and South America. Our analysis demonstrates that West Siberian ancestry, represented by the Kets and Nenets, contributed to the genetic ancestry of most Siberian populations. West Beringians, including the Koryaks, Inuit, and Luoravetlans, exhibit genetic adaptation to Arctic climate, including medically relevant variants. In South America, early migrants split into four groups—Amazonians, Andeans, Chaco Amerindians, and Patagonians—~13,900 years ago. Their longest migration led to population decline, whereas settlement in South America’s diverse environments caused instant spatial isolation, reducing genetic and immunogenic diversity. These findings highlight how population history and environmental pressures shaped the genetic architecture of human populations across North Asia and South America.
GPT-4o mini: Non-social science research article
Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis
Ruchao Peng, Xin Xu, Binod Nepal, Yikang Gong, Fenglin Li, Max B. Ferretti, Mingyang Zhou, Kristen W. Lynch, George M. Burslem, Sandhya Kortagere, Ronen Marmorstein, Yi-Wei Chang
Full text
Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex. By integrating cryo–electron microscopy single-particle analysis and cryo–electron tomography, we define the influenza RNP as a right-handed, antiparallel double helix with the viral RNA encapsidated in the minor groove. Individual nucleoprotein subunits are connected by a flexible tail loop that inserts into a conserved pocket in its neighbor. We visualize the viral polymerase in RNP at different functional states, revealing how it accesses the RNA template while maintaining the double-helical architecture of RNP by strand sliding. Targeting the tail loop binding interface, we identify lead compounds as potential anti-influenza inhibitors. These findings elucidate the molecular determinants underpinning influenza virus replication and highlight a promising target for antiviral development.
GPT-4o mini: Non-social science research article
3D laminar flow–assisted crystallization of perovskites for square meter–sized solar modules
Buyi Yan, Wanlei Dai, Zheng Wang, Zhiming Zhong, Lei Zhang, Mingqiang Yu, Qianjin Zhou, Qianling Ma, Kangrong Yan, Lu Zhang, Yang (Michael) Yang, Jizhong Yao
Full text
Transforming laboratory-scale perovskite solar cells to large-scale production will require uniform crystallization of the perovskite film. We designed a method to aid the crystallization process by generating well-defined three-dimensional (3D) laminar airflow over square meter–sized perovskite films using a customized 3D-printed structure. The resultant perovskite solar modules with areas of 0.7906 square meters had a certified power conversion efficiency of 15.0% and achieved compliance with three sets of solar cell standards. Our metrics for a 1-year operational study from a 0.5–megawatt peak power perovskite solar farm indicate a 29% higher energy yield per kilowatt of installed capacity compared with that of silicon modules at the same facility that primarily resulted from their temperature-dependent operational characteristics.
GPT-4o mini: Non-social science research article
Expansion in situ genome sequencing links nuclear abnormalities to aberrant chromatin regulation
Ajay S. Labade, Zachary D. Chiang, Caroline Comenho, Paul L. Reginato, Andrew C. Payne, Andrew S. Earl, Rojesh Shrestha, Fabiana M. Duarte, Ehsan Habibi, Ruochi Zhang, George M. Church, Edward S. Boyden, Fei Chen, Jason D. Buenrostro
Full text
Microscopy and genomics are used to characterize cell function, but approaches to connect the two types of information are lacking, particularly at subnuclear resolution. Here, we describe expansion in situ genome sequencing (ExIGS), a technology that enables sequencing of genomic DNA and superresolution localization of nuclear proteins in single cells. Applying ExIGS to progeria-derived fibroblasts revealed that lamin abnormalities are linked to hotspots of aberrant chromatin regulation that may erode cell identity. Lamin was found to generally repress transcription, suggesting variation in nuclear morphology may affect gene regulation across tissues and aged cells. These results demonstrate that ExIGS may serve as a generalizable platform to link nuclear abnormalities to gene regulation, offering insights into disease mechanisms.
GPT-4o mini: Non-social science research article
Attenuation of virulence in Yersinia pestis across three plague pandemics
Ravneet Kaur Sidhu, Guillem Mas Fiol, Pierre LĂȘ-Bury, Christian E. Demeure, Emelyne Bougit, RĂ©mi Beau, Charlotte BaliĂšre, Aurelia Kwasiborski, ValĂ©rie Caro, Jennifer Klunk, Daniel J. Salkeld, Ann Carmichael, NĂŒkhet Varlık, Debi Poinar, David J. D. Earn, Benjamin M. Bolker, Jonathan Dushoff, G. Brian Golding, Nicolas Rascovan, Olivier Dussurget, Edward C. Holmes, Javier Pizarro-CerdĂĄ, Hendrik N. Poinar
Full text
Yersinia pestis has spilled over from wild rodent reservoirs to commensal rodents and humans, causing three historically recorded pandemics. Depletion in the copy number of the plasmid-encoded virulence gene pla occurred in later-dated strains of the first and second pandemics, yet the biological relevance of the pla deletion has been difficult to test. We identified modern Y. pestis strains that independently acquired the same pla depletion as ancient strains and herein show that excision of pla from the multicopy pPCP1 plasmid is accompanied by the integration of a separate full pPCP1 harboring pla into the single-copy pCD1 plasmid, reducing pla dosage. Moreover, we demonstrate that this depletion decreases the mortality of mice in models of bubonic plague but not in the pneumonic and septicemic forms of the disease. We hypothesize that pla depletion may have been selectively advantageous in bubonic plague, owing to rodent fragmentation after pandemic-induced mortality.
GPT-4o mini: Non-social science research article
Conserved brain-wide emergence of emotional response from sensory experience in humans and mice
Isaac Kauvar, Ethan B. Richman, Tony X. Liu, Chelsea Li, Sam Vesuna, Adelaida Chibukhchyan, Lisa Yamada, Adam Fogarty, Ethan Solomon, Eun Young Choi, Leili Mortazavi, Gustavo Chau Loo Kung, Pavithra Mukunda, Cephra Raja, Dariana Gil-HernĂĄndez, Kishandra Patron, Xue Zhang, Jacob Brawer, Shenandoah Wrobel, Zoe Lusk, Dian Lyu, Anish Mitra, Laura Hack, Liqun Luo, Logan Grosenick, Peter van Roessel, Leanne M. Williams, Boris D. Heifets, Jaimie M. Henderson, Jennifer A. McNab, Carolyn I. RodrĂ­guez, Vivek Buch, Paul Nuyujukian, Karl Deisseroth
Full text
Emotional responses to sensory experience are central to the human condition in health and disease. We hypothesized that principles governing the emergence of emotion from sensation might be discoverable through their conservation across the mammalian lineage. We therefore designed a cross-species neural activity screen, applicable to humans and mice, combining precise affective behavioral measurements, clinical medication administration, and brain-wide intracranial electrophysiology. This screen revealed conserved biphasic dynamics in which emotionally salient sensory signals are swiftly broadcast throughout the brain and followed by a characteristic persistent activity pattern. Medication-based interventions that selectively blocked persistent dynamics while preserving fast broadcast selectively inhibited emotional responses in humans and mice. Mammalian emotion appears to emerge as a specifically distributed neural context, driven by persistent dynamics and shaped by a global intrinsic timescale.
GPT-4o mini: Non-social science research article
Pair wave function symmetry in UTe 2 from zero-energy surface state visualization
Qiangqiang Gu, Shuqiu Wang, Joseph P. Carroll, Kuanysh Zhussupbekov, Christopher Broyles, Sheng Ran, Nicholas P. Butch, Jarryd A. Horn, Shanta Saha, Johnpierre Paglione, Xiaolong Liu, J. C. Séamus Davis, Dung-Hai Lee
Full text
Although nodal spin-triplet topological superconductivity appears probable in uranium ditelluride (UTe 2 ), its superconductive order parameter Δ k remains unestablished. In theory, a distinctive identifier would be the existence of a superconductive topological surface band, which could facilitate zero-energy Andreev tunneling to an s-wave superconductor and also distinguish a chiral from a nonchiral Δ k through enhanced s-wave proximity. In this study, we used s-wave superconductive scan tips and detected intense zero-energy Andreev conductance at the UTe 2 (0-11) termination surface. Imaging revealed subgap quasiparticle scattering interference signatures with a -axis orientation. The observed zero-energy Andreev peak splitting with enhanced s-wave proximity signifies that Δ k of UTe 2 is a nonchiral state: B 1 u , B 2 u , or B 3 u . However, if the quasiparticle scattering along the a axis is internodal, then a nonchiral B 3 u state is the most consistent for UTe 2 .
GPT-4o mini: Non-social science research article
Interphase cell morphology defines the mode, symmetry, and outcome of mitosis
Holly E. Lovegrove, Georgia E. Hulmes, Sabrina Ghadaouia, Christopher Revell, Marta Giralt-Pujol, Zain Alhashem, Andreia Pena, Damian D. Nogare, Ellen Appleton, Guilherme Costa, Richard L. Mort, Christoph Ballestrem, Gareth W. Jones, Cerys S. Manning, Ajay B. Chitnis, Claudio A. Franco, Claudia Linker, Katie Bentley, Shane P. Herbert
Full text
During tissue formation, dynamic cell shape changes drive morphogenesis while asymmetric divisions create cellular diversity. We found that the shifts in cell morphology that shape tissues could concomitantly act as conserved instructive cues that trigger asymmetric division and direct core identity decisions underpinning tissue building. We performed single-cell morphometric analyses of endothelial and other mesenchymal-like cells. Distinct morphological changes switched cells to an “isomorphic” mode of division, which preserved pre-mitotic morphology throughout mitosis. In isomorphic divisions, interphase morphology appeared to provide a geometric code defining mitotic symmetry, fate determinant partitioning, and daughter state. Rab4-positive endosomes recognized this code, allowing them to respond to pre-mitotic morphology and segregate determinants accordingly. Thus, morphogenetic shape change sculpts tissue form while also generating cellular heterogeneity, thereby driving tissue assembly.
GPT-4o mini: Non-social science research article
Glacier preservation doubled by limiting warming to 1.5°C versus 2.7°C
Harry Zekollari, Lilian Schuster, Fabien Maussion, Regine Hock, Ben Marzeion, David R. Rounce, Loris Compagno, Koji Fujita, Matthias Huss, Megan James, Philip D. A. Kraaijenbrink, William H. Lipscomb, Samar Minallah, Moritz Oberrauch, Lander Van Tricht, Nicolas Champollion, Tamsin Edwards, Daniel Farinotti, Walter Immerzeel, Gunter Leguy, Akiko Sakai
Full text
Glaciers adapt slowly to changing climatic conditions, with long-term implications for sea-level rise and water supply. Using eight glacier models, we simulated global glacier evolution over multicentennial timescales, allowing glaciers to equilibrate with climate under various constant global temperature scenarios. We estimate that glaciers globally will lose 39 (range, 15 to 55)% of their mass relative to 2020, corresponding to a global mean sea-level rise of 113 (range, 43 to 204) mm even if temperatures stabilized at present-day conditions. Under the +1.5°C Paris Agreement goal, more than twice as much global glacier mass remains at equilibration (53% versus 24%) compared with the warming level resulting from current policies (+2.7°C by 2100 above preindustrial). Our findings stress the need for stringent mitigation policies to ensure the long-term preservation of glaciers.
Science abstract < 200 char.: Not a research article
Radiocarbon dates revise histories of Indigenous societies
Lizzie Wade
Full text
New techniques challenge assumptions about Indigenous responses to European contact
Science abstract < 200 char.: Not a research article
A strange fascination
Zack Savitsky
Full text
Studies of exotic materials called “strange metals” point to a whole new way to understand electricity
Science abstract < 200 char.: Not a research article
The organ farm
Jon Cohen
Full text
Gene-edited pig kidneys are finally moving the long-stymied field of xenotransplantation forward
Science abstract < 200 char.: Not a research article
Hunt for tree rings could yield Africa’s first drought atlas
Paul Voosen
Full text
Records could reveal how much humanity has altered Sahel rains
Science abstract < 200 char.: Not a research article
Trump takes steps toward a radically different NSF
Jeffrey Mervis
Full text
Democrats question latest changes in how the research agency makes grants
Science abstract < 200 char.: Not a research article
Tales from the crypt
Andrew Curry
Full text
The lives of 17th century Milan’s working poor—their health, diet, and drug habits—emerge from thousands of bodies buried under a public hospital
Science abstract < 200 char.: Not a research article
The cost of health
Lara de Macedo Monteiro
Full text
Science abstract < 200 char.: Not a research article
Mind reader?
Jonathan Moens
Full text
A forensic technology developed in India sifts brain recordings for clues to a suspect’s guilt or innocence. Many neuroscientists are skeptical, but it is catching on in other countries
Science abstract < 200 char.: Not a research article
The next best way to teach and learn The Teacher in the Machine: A Human History of Education Technology Anne Trumbore Princeton University Press, 2025. 240 pp.
Jonathan Wai
Full text
Technology always seems poised to revolutionize education— until it doesn’t
Science abstract < 200 char.: Not a research article
A giant telescope shrouded in mystery
Richard Stone
Full text
China is readying to build one of the world’s largest telescopes—but only scant details have emerged
Science abstract < 200 char.: Not a research article
A wave of emotion
Stoyo Karamihalev, Nadine Gogolla
Full text
Sustained brainwide patterns of activity enable emotions to outlast their triggers
Science abstract < 200 char.: Not a research article
U.S. cuts risk backslide on neglected tropical diseases
Martin Enserink
Full text
Crippling pathogens nearing elimination are likely to resurge after sudden loss of funds
Science abstract < 200 char.: Not a research article
China reveals the foreign scientists who will share its rare lunar samples
Dennis Normile
Full text
Seven research teams in six nations get Moon rocks and soil brought to Earth by the Chang’e-5 mission
Science abstract < 200 char.: Not a research article
In Other Journals
Ekeoma Uzogara, Madeleine Seale, Sarah H. Ross, Jack Huang, Sumin Jin, Brad Wible, Di Jiang
Full text
Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
What patents on AI-derived drugs reveal
Janet Freilich, Arti K. Rai
Full text
Less in-depth, in vivo testing before patenting may affect overall research and development
Science abstract < 200 char.: Not a research article
Erratum for the Research Article “Hydro-locking in hydrogel for extreme temperature tolerance” by X. Zhang et al .
Full text
Science abstract < 200 char.: Not a research article
With Trump’s cuts escalating, ‘fear factor’ silences researchers
Warren Cornwall
Full text
Many worry about retribution. But for others, speaking out is worth the risk
Science abstract < 200 char.: Not a research article
30-day forecasts? Weather prediction has room to run
Paul Voosen
Full text
AI models suggest a 2-week limit linked to the “butterfly effect” may not be definite
Science abstract < 200 char.: Not a research article
In Other Journals
Bianca Lopez, Priscilla N. Kelly, Mattia Maroso, Marc S. Lavine, Angela Hessler, Jake S. Yeston, Peter Stern
Full text
Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
In Science Journals
Bianca Lopez, Phil Szuromi, Courtney Malo, Sacha Vignieri, Jelena Stajic, Dennis Hall, Leslie K. Ferrarelli, Corinne Simonti, Mattia Maroso, L. Bryan Ray, Caroline Ash, Jesse Smith, Christiana N. Fogg
Full text
Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
Look beyond the longevity drips and supplements Super Agers Eric Topol Simon & Schuster, 2025. 464 pp.
Eric J. Topol
Full text
There is a path to living longer and healthier that doesn’t require reversing the aging process
Science abstract < 200 char.: Not a research article
Erratum for the Research Article “High cooling performance in a double-loop electrocaloric heat pump” by J. Li et al .
Full text
Science abstract < 200 char.: Not a research article
In Science Journals
Bianca Lopez, Jelena Stajic, Annalisa VanHook, Marc S. Lavine, Sacha Vignieri, Mattia Maroso, Melissa L. Norton, Corinne Simonti, Caroline Ash, Di Jiang, Michael A. Funk, Seth Thomas Scanlon
Full text
Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
Executive order on risky research brings confusion
Kai Kupferschmidt
Full text
Directive aims to restrict gain-of-function studies on microbes and more, but no one knows what’s affected
Science abstract < 200 char.: Not a research article
Tariff war takes toll on labs in China
Richard Stone
Full text
Scientists face higher prices and import bans on equipment and supplies
Science abstract < 200 char.: Not a research article
Cultivating the side hustle
Gertrude Nonterah
Full text
Science abstract < 200 char.: Not a research article
California hummingbirds are evolving fast—because of feeders
Rachel Nuwer
Full text
Beaks have grown longer and larger, and ranges have expanded to follow the feeders
Science abstract < 200 char.: Not a research article
Mosquito-borne viral disease sweeps Indian Ocean islands
Meredith Wadman
Full text
Safety issues with the only available vaccine are complicating the response to chikungunya
Science abstract < 200 char.: Not a research article
Ecologist blurred professional boundaries, report finds
Cathleen O’Grady
Full text
Thomas Crowther has lost his post at ETH ZĂŒrich but denies any misconduct
Science abstract < 200 char.: Not a research article
Project to revive Louisiana coastline runs aground
Warren Cornwall
Full text
Politics and lawsuits imperil plans to divert the Mississippi River to build new land
Science abstract < 200 char.: Not a research article
Low-quality papers surge thanks to public data and AI
Cathleen O’Grady
Full text
Paper mills may drive “industrialization” of shoddy research
Science abstract < 200 char.: Not a research article
Finding strength in sensitivity
Nemanja Stanojević
Full text
Science abstract < 200 char.: Not a research article
AI-designed antibody candidates hit a crucial target
Robert F. Service
Full text
Companies find enticing drug leads that bind to tricky cell membrane proteins
Science abstract < 200 char.: Not a research article
Changing plans
Jacqueline Curtis
Full text
Science abstract < 200 char.: Not a research article
In Science Journals
Bianca Lopez, Wei Wong, Phil Szuromi, Ian S. Osborne, Jelena Stajic, Di Jiang, Kip V. Hodges, Orla Smith, Stella M. Hurtley, Michael A. Funk, Caroline Ash, Mattia Maroso, Marc S. Lavine, Claire Olingy
Full text
Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
Social impacts of glacier loss
Cymene Howe, Dominic Boyer
Full text
More than three-quarters of global glacier mass is projected to disappear under present-day policies
Science abstract < 200 char.: Not a research article
New Products
Full text
A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.
Science abstract < 200 char.: Not a research article
NSF director resigns amid cuts to grants and staff reductions
Jeffrey Mervis
Full text
Sethuraman Panchanathan stepped down soon after Trump team started to terminate agency awards
Science abstract < 200 char.: Not a research article
Sonar tool poised to map sea floor in fine detail
Rachel Berkowitz
Full text
Researchers see promise in “synthetic aperture” devices that mimic giant acoustic cameras
Science abstract < 200 char.: Not a research article
Studies making lasting paradigm shifts are on the rise
Jeffrey Brainard
Full text
New metric identifying “persistently disruptive” papers offers a “bright spot” amid signs of declining innovation
Science abstract < 200 char.: Not a research article
Leprosy was an American scourge long before Europeans arrived
Michael Price
Full text
Scientists find DNA from an enigmatic bacterium in 1000-year-old skeletons
Science abstract < 200 char.: Not a research article
In Other Journals
Di Jiang, Sarah H. Ross, Caroline Ash, Jack Huang, Melissa McCartney, Ian S. Osborne
Full text
Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
NSF cuts reduced grantee diversity
Jeffrey Mervis
Full text
Terminated projects on broadening participation in science were often led by Black scientists, women, and those with disabilities
Science abstract < 200 char.: Not a research article
A pathogen’s Bronze Age spread challenges longstanding link between disease and early agriculture
Andrew Curry
Full text
Close quarters and wool clothing may have spurred recurring fever to become a human specialist
Science abstract < 200 char.: Not a research article
China sets out to sample an unusual asteroid
Dennis Normile
Full text
Kamo‘oalewa, a rare quasi-satellite of Earth, could be a chunk of the Moon
Science abstract < 200 char.: Not a research article
Growing anxious—Are preschoolers matched to their futures?
Mark A. Hanson, Peter D. Gluckman
Full text
Evolutionary and developmental factors may contribute to anxiety in young people
Science abstract < 200 char.: Not a research article
A single gene helps rice handle the heat
Erik Stokstad
Full text
Discovery could preserve grain quality and yields as climate change raises temperatures
Science abstract < 200 char.: Not a research article
Researchers question Abbott’s rapid malaria tests
Catherine Offord
Full text
Reports of false negatives prompted a World Health Organization internal memo, but company denies problems
Fixing the US statistical infrastructure
Nancy Potok, Erica L. Groshen
Full text
Official government statistics are critical infrastructure for the information age. Reliable, relevant, statistical information helps businesses to invest and flourish; governments at the local, state, and national levels to make critical decisions on policy and public services; and individuals and families to invest in their futures. Yet surrounded by all manner of digitized data, one can still feel inadequately informed. A major driver of this disconnect in the US context is delayed modernization of the federal statistical system. The disconnect will likely worsen in coming months as the administration shrinks statistical agencies’ staffing, terminates programs (notably for health and education statistics), and eliminates unpaid external advisory groups. Amid this upheaval, might the administration’s appetite for disruption be harnessed to modernize federal statistics?

Science Advances

Generic title: Not a research article
Erratum for the Research Article: “Rational polyelectrolyte nanoparticles endow preosteoclast-targeted siRNA transfection for anabolic therapy of osteoporosis” by Z. Zhang et al.
Full text
GPT-4o mini: Non-social science research article
Tempo of the Late Ordovician mass extinction controlled by the rate of climate change
Zhutong Zhang, Chuan Yang, Diana Sahy, Ren-bin Zhan, Rong-Chang Wu, Yang Li, Yiying Deng, Bing Huang, Daniel J. Condon, Jiayu Rong, Xian-Hua Li
Full text
The Late Ordovician mass extinction (LOME) included two phases (I and II) of high species turnover that have been hypothetically linked to the Hirnantian glaciation and subsequent rapid warming, respectively. However, the timing and tempo of the LOME remain uncertain, which hinders our understanding of the feedback between the LOME and paleoclimatic change. Here, we present high-precision radioisotopic dates for the Ordovician-Silurian transition in South China that reveal the LOME began at 442.76 + 0.35/−0.22 million years ago, with the two phases lasting for 0.34 + 0.46/−0.34 and 0.06 + 0.31/−0.06 million years, respectively. The rapid switch from icehouse to greenhouse conditions, along with the higher mean rate of temperature change during LOME II, resulted in a much higher mean extinction rate during LOME II than I (71.6% versus 8.4% species loss per 100 thousand years, respectively), implying that the rate of climate change was a primary control on the tempo of the LOME.
GPT-4o mini: Non-social science research article
Superionicity of oxygen-deficient davemaoite and its impact on the deep-Earth oxidation cycle
Zifan Wang, Yu He, Ho-kwang Mao, Duck Young Kim
Full text
Davemaoite (CaSiO 3 perovskite) is an essential mineral in Earth’s lower mantle, thought to be solidified directly from an early magma ocean. Despite its abundance, the impact of defects, particularly oxygen vacancies, on davemaoite’s properties under mantle conditions has not been thoroughly investigated. Here, we use machine learning molecular dynamic simulations to examine the behavior of oxygen-deficient davemaoite structures under high pressures and temperatures. Our simulations reveal its superionic transition driven by oxygen’s diffusion, enhancing electrical conductivities. Our predicted phase diagrams demonstrate that higher oxygen vacancy concentrations expand the superionic phase region. This superionic behavior implies that defective davemaoite could play a critical role in early mantle oxidation and deep-Earth oxygen cycling, providing a potential major source of mobile oxygen in the deep mantle. These findings offer fresh insights into the geodynamic processes in Earth’s early mantle and suggest that oxygen-deficient davemaoite could primarily contribute to the electrical conductivity and oxidation state of the deep lower mantle.
GPT-4o mini: Non-social science research article
Development of enhanced HIV-1 non-nucleoside reverse transcriptase inhibitors with improved resistance and pharmacokinetic profiles
Zhao Wang, Shawn Rumrill, Dongwei Kang, Samuel Desta Guma, Da Feng, Erik De Clercq, Christophe Pannecouque, Chin Ho Chen, Eddy Arnold, Francesc Xavier Ruiz, Xinyong Liu, Peng Zhan
Full text
HIV-1 infection is a manageable chronic condition, with non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) remaining a cornerstone of antiretroviral therapy. Nevertheless, drug resistance to existing therapeutics is a serious and immediate concern. Using structure-based and scaffold-hopping approaches, we designed evolved diarylpyrimidine analogs targeting reverse transcriptase (RT), exploiting chemical space surrounding the NNRTI-binding pocket. We identified compounds 5i3 and 5e2 , with robust antiviral efficacy against wild-type HIV-1 and rilpivirine-resistant strains. Encouragingly, in vitro selection of mutant strains with 5i3 took 39 passages to select resistance, with no phenotypic cross-resistance observed with known RT drugs. Co-crystal structures of wild-type and mutant RT with 5i3 and 5e2 revealed their resilience toward resistance mutations due to enhanced conformational flexibility and positional adaptability. 5i3 exhibited good pharmacokinetic properties and favorable safety profiles, without substantial cytochrome P450 inhibition, and excellent oral bioavailability. These derivatives represent a promising scaffold for the development of anti-HIV drugs.
GPT-4o mini: Non-social science research article
Biogenic origin of secondary eggshell units in dinosaur eggshells elucidates lost biomineralization process in maniraptoran dinosaurs
Shukang Zhang, Seung Choi, Noe-Heon Kim, Junfang Xie, Yong Park, Oliver PlĂŒmper, Albert G. SellĂ©s
Full text
Secondary eggshell units, though rarely observed in modern avian eggshells, are marked structures in non-avian dinosaur eggshells that offer valuable paleobiological insights. Despite their significance, the origins of secondary eggshell units remain understudied, leading to debates in paleontology, including the hypothesis of an abiogenic origin for these structures. Here, we demonstrate that secondary eggshell units in non-avian dinosaur eggshells are biogenic in nature, based on analyses using advanced microscopic techniques. The structural characteristics of these units suggest a formation mechanism similar to that of turtle and crocodile eggshells, with matrix fibers likely initiating their development. Furthermore, a diminishing presence of secondary eggshell units in non-avian maniraptoran dinosaurs points to the evolution of a more refined physiological process for eggshell formation in this lineage. These findings shed light on the evolutionary trajectory of eggshell biomineralization in dinosaurs and their close relatives.
GPT-4o mini: Non-social science research article
Intestinal L-cell mechanoreception regulates hepatic lipid metabolism through GLP-1
Luyang Gao, Ke Yang, Yawen Zhao, Jinshan Zhang, Shaohua Jiang, Rujiao Zhang, Wenxin He, Yuhang Zhao, Qianqian Ye, Geyang Xu
Full text
Glucagon-like peptide–1 (GLP-1), secreted by intestinal L cells, is essential for lowering postprandial glucose levels and regulating hepatic lipid metabolism.We investigate the effects of manipulating Piezo1 in L cells on hepatic lipid metabolism. We found that normal and high-fat diet–fed L cell–specific Piezo1 knockout ( IntL-Piezo1 −/− ) mice exhibited reduced circulating GLP-1 levels, increased hepatic lipid accumulation, decreased ÎČ-catenin expression, and elevated lipogenesis-related genes and proteins, including SREBP1c, PPARÎł, FASN, and ACC. Treatment with exendin-4 improved fatty liver in IntL-Piezo1 −/− mice by stimulating ÎČ-catenin and inhibiting de novo lipogenesis. Intestinal bead implantation stimulated GLP-1 release and inhibited lipid synthesis in livers of diet-induced obese mice but not in IntL-Piezo1 −/− mice. In primary hepatocytes derived from IntL-Piezo1 −/− mice, lipid accumulation and enhanced fatty acid synthesis were associated with reduced ÎČ-catenin expression and impaired nuclear translocation. Exendin-4 treatment alleviated lipid accumulation, which was blocked by the ÎČ-catenin inhibitor nitazoxanide. L-cell mechanoreception is vital for regulating hepatic lipid metabolism through GLP-1.
GPT-4o mini: Non-social science research article
Pan-Pacific low-frequency modes of sea level and climate variability
Christopher M. Little, Stephen G. Yeager, John T. Fasullo, Kristopher B. Karnauskas, Robert S. Nerem, Nishchitha S. Etige
Full text
Tide gauges provide a long observational record that can inform the nature of satellite-era basin-scale sea level trends. However, common signals must be extracted from geographically sparse records. Here, by applying low-frequency component analysis (LFCA) to tide gauge records and surface climate reconstructions, we isolate three coherent modes of Pacific Ocean variability that we ascribe to: a secular, greenhouse gas–driven climate change (LFC1); a nonlinear mode of variability with a reversal around 1980, potentially linked to aerosols (LFC2); and the Interdecadal Pacific Oscillation (LFC3). Although sea level trend patterns reflect the superimposed contribution of all modes, satellite-era trends are dominated by an increasing phase of LFC2: They are thus potentially unrepresentative of both longer-term historical patterns and those expected in the future.
GPT-4o mini: Non-social science research article
Demystifying the drivers of the spring warming asymmetry between Eurasia and North America
Xiuyuan Ding, Gang Chen, Yuan Wang, Lantao Sun
Full text
In spring, global warming exhibits prominent zonal asymmetry at continental scales, with Eurasia warming three times faster than North America during 1979–2021. Meanwhile, snow loss is also highly asymmetric. These changes are critical for regional agriculture and water management, yet the roles of specific forcings behind them remain unclear. Based on hierarchical large-ensemble climate model simulations, ~32 ± 28% of the surface air temperature (SAT) asymmetric trend and 16 ± 13% of the snow cover asymmetric trend between Eurasia and North America are attributable to tropical Pacific variability. Single-forcing experiments reveal that anthropogenic aerosols can induce a comparable asymmetry, accounting for 34 ± 23% (24 ± 17%) of observed SAT (snow cover) asymmetric trends. However, their effects are largely masked by the greenhouse gas forcing. As anthropogenic aerosol emissions are expected to decline, the current warming asymmetry may reverse in the future.
GPT-4o mini: Non-social science research article
Unprecedented stacking-dependent piezoluminescence enhancement in atomically precise superatomic gold nanoclusters
Hua-Yang Ru, Ji-Kun Yang, Ya-Ni Yang, Qiu-Yang Wan, Meng-Jie Zhu, Jia-Hua Hu, Jing Li, Qi Li, Meng Zhou, Gang Li, Gaosong Chen, Yonggang Wang, Lei Jiang, Yuchen Wu, Shuang-Quan Zang
Full text
Deciphering the structure-property relationship between cluster stacking and high-efficiency luminescence of metal nanoclusters is crucial for designing and synthesizing high-performance light-emitting materials and devices. Here, we successfully synthesized two polymorphic gold nanoclusters (Au 8 -C and Au 8 -P) and investigated their stacking-dependent piezoluminescence based on hydrostatic pressure. Under compression, Au 8 -C exhibits notable piezoluminescence enhancement. However, Au 8 -P presents monotonic piezoluminescence quenching. High-pressure structural characterizations confirm the existence of stacking-dependent anisotropic compression in Au 8 -C and Au 8 -P. Under high pressure, the columnar-stacked Au 8 -C shrinks faster along the a axis, increasing the aspect ratio (AR) of the fusiform Au 8 core. However, the layered Au 8 -P is compressed faster along the c axis, reducing the AR and leading to a flatter Au 8 core. High-pressure femtosecond transient absorption, time-resolved photoluminescence, and Raman spectra collaboratively confirm that differentiated anisotropic compression notably suppresses nonradiative loss caused by low-frequency vibrations of the Au 8 core, which is responsible for the piezoluminescence enhancement in Au 8 -C.
GPT-4o mini: Non-social science research article
Development of a targeted oral pharmacologic duodenal exclusion therapy for the treatment of metabolic diseases
Taylor L. Carlson, Kevin Colbert, Marcela Vieira, Florence V. Guerina, Christine L. N. Bryant, Kirk Habegger, Pankaj Jay Pasricha, John Petersen, Steven Polomoscanik, Thomas H. Jozefiak, Ashish Nimgaonkar
Full text
Type 2 diabetes (T2D) and obesity are chronic metabolic diseases with global morbidity and mortality. Decades of evidence from surgical and endoscopic procedures bypassing the duodenum underscore the duodenum’s critical role in regulating glycemia and body weight. Although metabolic surgeries and endoscopic procedures are effective, their invasiveness, cost, and scalability limit patient access. We developed an orally administered mucin complexing polymeric (MCP) drug, designed to replicate duodenal exclusion physiology. MCPs, intended to have electrostatic and covalent cross-linkages with mucin glycoproteins, form extended network structures with resulting alteration of mucus barrier properties. Selective targeting of the duodenum is achieved via pH-based activation chemistry. Following screening for physiochemical properties, pharmacokinetics, and efficacy, GLY-200 emerged as the lead drug candidate replicating duodenal exclusion physiology with improved glycemia, reduced body weight, and modulation of gut hormones in rodent models. This targeted oral therapy holds promise for treatment of T2D and obesity by mimicking duodenal exclusion without the invasiveness of surgery or endoscopic procedures.
GPT-4o mini: Non-social science research article
TAC-C uncovers open chromatin interaction in crops and SPL-mediated photosynthesis regulation
Jingmin Kang, Zhaoheng Zhang, Xuelei Lin, Fuyan Liu, Yali Song, Peng Zhao, Yujing Lin, Xumei Luo, Xiaoyi Li, Yanyan Yang, Wenda Wang, Cuimin Liu, Shengbao Xu, Xin Liu, Jun Xiao
Full text
Cis-regulatory elements (CREs) direct precise gene expression for development and environmental response, yet their spatial organization in crops is largely unknown. We introduce transposase-accessible chromosome conformation capture (TAC-C), a method integrating ATAC-seq and Hi-C to capture fine-scale chromatin interactions in four major crops: rice, sorghum, maize, and wheat. TAC-C reveals a strong association between chromatin interaction frequency and gene expression, particularly emphasizing the conserved roles of chromatin interaction hub anchors and hub genes across crop species. Integrating chromatin structure with population genetics data highlights that chromatin loops connect distal regulatory elements to phenotypic variation. In addition, asymmetrical open chromatin interactions among subgenomes, driven by transposon insertions and sequence variations, contribute to biased homoeolog expression. Furthermore, TaSPL7/15 regulate photosynthesis-related genes through chromatin interactions, with enhanced photosynthetic efficiency and starch content in Taspl7&15 mutant. TAC-C provides insights into the spatial organization of regulatory elements in crops, especially for SPL-mediated photosynthesis regulation in wheat.
GPT-4o mini: Non-social science research article
Phase-change metal ink with pH-controlled chemical sintering for versatile and scalable fabrication of variable stiffness electronics
Simok Lee, Gun-Hee Lee, Inho Kang, Woojin Jeon, Semin Kim, Yejin Ahn, Choong Yeon Kim, Do A Kwon, Michael D. Dickey, Steve Park, Seongjun Park, Jae-Woong Jeong
Full text
Variable stiffness electronics represent the forefront of adaptive technology, integrating rigid and soft electronics in a single system through dynamic mechanical modulation. While gallium’s high modulus tuning ratio and rapid phase transitions make it ideal for transformative electronic systems (TES), its liquid-state instability, high surface tension, and unintended phase transitions during processing pose substantial challenges. Here, we introduce STiffness-Adjustable temperature-Responsive ink (STAR ink), a chemically sinterable gallium composite electronic ink designed to overcome these obstacles. STAR ink enables high-resolution (~50 micrometers) circuit patterning, large-scale batch fabrication, and three-dimensional structure coating at room temperature. Through pH-controlled chemical sintering, STAR ink–based TES exhibits exceptional mechanical tunability (tuning ratio: 1465) and electrical conductivity (2.27 × 10 6 siemens per meter). Demonstrated applications—from multilayered variable stiffness printed circuit boards (PCBs) matching standard PCBs’ complexity to body-temperature responsive neural probe—underscore STAR ink’s potential for reconfigurable electronics across consumer electronics and biomedical devices.
GPT-4o mini: Non-social science research article
Amplified narrowband perovskite photodetectors enabled by independent multiplication layers for anti-interference light detection
Yao Ma, Xinglu Xu, Tengfei Li, Zemin Wang, Nan Li, Xin Zhao, Wei Wei, Xiaowei Zhan, Liang Shen
Full text
Metal-halide perovskite narrowband photodetectors offer a low-cost opportunity to detect specific signals covering a broad spectrum directly. However, the thickness of charge collection narrowing mechanism photodetectors increases recombination, resulting in performance bottlenecks. Here, we demonstrate amplified narrowband photodetectors that combine perovskite single-crystal absorbers and organic multiplication layers. The separation of the multiplication layer controls the density of trap states while amplifying the response of conventional narrowband photodetectors by more than 215 times. The carrier dynamics were characterized by ultrafast measurement, thus verifying the mechanism of response amplification. By analyzing multiplication with different trap states energy levels under charge injection, it is shown that dopants have a wide selection space, providing a feasible path for high-performance narrowband photodetectors. As a result, the external quantum efficiency of 2259% with a 38-nanometer full width at half maximum and the specific detectivity of 4.84 × 10 12 Jones was obtained at 825 nanometers. Last, we demonstrated the anti-interference signal acquisition capability of our photodetector.
GPT-4o mini: Non-social science research article
Photonic antiferromagnetic topological insulator with a single surface Dirac cone
Fujia Chen, Ning Han, Songyang Pu, Rui Zhao, Li Zhang, Qiaolu Chen, Yuze Hu, Mingyu Tong, Wenhao Li, Junyao Wu, Yudong Ren, Xinrui Li, Wenyan Yin, Hongsheng Chen, Rui-Xing Zhang, Yihao Yang
Full text
Antiferromagnetism, characterized by alternating magnetic moments, has garnered renewed interest for its potential applications in spintronics and axion electrodynamics. Its synergy with topology may yield an exotic topological phase unique to a certain magnetic order, termed antiferromagnetic topological insulators (AF TIs). A hallmark signature of AF TIs is the presence of a single surface Dirac cone—a feature typically associated with strong three-dimensional (3D) topological insulators but lacking direct observation. Here, we theoretically and experimentally discover a 3D photonic AF TI protected by the combined symmetry of time reversal and half-lattice translation. By measuring both bulk and surface states, we directly observe the symmetry-protected single-Dirac-cone surface states and their remarkable robustness against random magnetic disorders. To our knowledge, our work constitutes the first realization of photonic AF TIs and photonic analogs of strong 3D topological insulators, opening a chapter for exploring topological photonic devices and phenomena incorporating additional magnetic degrees of freedom.
GPT-4o mini: Non-social science research article
Decoding predicted future states from the brain’s “physics engine”
R. T. Pramod, Elizabeth Mieczkowski, Cyn X. Fang, Joshua B. Tenenbaum, Nancy Kanwisher
Full text
Successful engagement with the physical world requires the ability to predict future events and plan interventions to alter that future. Growing evidence implicates a set of regions in the human parietal and frontal lobes [also known as the “physics network” (PN)] in such intuitive physical inferences. However, the central tenet of this hypothesis, that PN runs forward simulations to predict future states, remains untested. In this preregistered study, we first show that PN abstractly represents whether two objects are in contact with each other, a physical scene property critical for prediction (because objects’ fates are intertwined when they are in contact). We then show that PN (but not other visual areas) carries abstract information about predicted future contact events (i.e., collisions). These findings support the hypothesis that PN contains a generative model of the physical world that conducts forward simulations, serving as the brain’s “physics engine.”
GPT-4o mini: Non-social science research article
Mechanistic insights into the stimulation of the histone H3K9 methyltransferase Clr4 by proximal H3K14 ubiquitination
Yunxiang Du, Maoshen Sun, Zhengqing Li, Xiangwei Wu, Qian Qu, Huasong Ai, Lei Liu
Full text
H3K9 methylation, a conserved heterochromatin marker, is crucial for chromosome segregation and gene regulation. Clr4 is the sole known methyltransferase catalyzing H3K9 methylation in Schizosaccharomyces pombe . Clr4 K455/K472 automethylation and H3K14 ubiquitination (H3K14Ub) are vital activators of Clr4, ensuring appropriate heterochromatin deposition and preventing deleterious silencing. While automethylation’s activation mechanism is uncovered, the mechanism of H3K14Ub’s significantly stronger stimulation on Clr4 remains unclear. Here, we determined the crystal structures of Clr4 bound to ubiquitinated and unmodified H3 peptides at 2.60 and 2.39 angstrom, which revealed a synergistic mechanism underlying the pronounced stimulatory effect: H3K14Ub increases substrate affinity through multivalent interactions and facilitates the allosteric transition of Clr4 from an inactive apo conformation to a hyperactive “catalyzing state,” including conformational changes in the αC-SET-insertion region, autoregulatory loop, and the ÎČ9/10 loop. We finally propose a multilevel structural model for the Clr4 catalytic-regulatory cycle. This work provides structural insights into the interplay between histone modifications and their collective impact on epigenetic regulation.
GPT-4o mini: Non-social science research article
Notch controls APC/C FZR-1 to enable accumulation of chromatin regulators in germline stem cells from Caenorhabditis elegans
David Puerta, Sara Rivera-Martín, Adriån Fragoso-Luna, Susan Strome, Sarah L Crittenden, Judith Kimble, José Pérez-Martín
Full text
Originally known for its function in the cell cycle, the anaphase-promoting complex/cyclosome (APC/C) also plays a crucial role in regulating differentiation and maintaining cell identity. However, the mechanisms by which APC/C mediates developmental processes are not fully understood. In this study, we show that APC/C and its activator FZR-1 regulate the chromatin regulators MES-4 and MES-3. These proteins are part of histone methylation complexes essential for maintaining germline stem cell (GSC) identity in the germ line of Caenorhabditis elegans . APC/C FZR-1 facilitates the degradation of MES-4 and MES-3 when GSCs transition toward differentiating into oocytes. The activity of APC/C FZR-1 is restricted by the Notch signaling pathway provided by the distal tip cell, which is responsible for maintaining the stemness of the GSC pool. This negative regulation enables the accumulation of MES-3 and MES-4 in GSCs, offering an additional component by which niche activity modulates the C. elegans germ line.
GPT-4o mini: Non-social science research article
Association of human-specific expanded short tandem repeats with neuron-specific regulatory features
Qiming Liu, Weidong Tian
Full text
Short tandem repeats (STRs), characterized by high–copy number mutations, represent one of the fastest-evolving genomic elements. However, human-specific expanded STRs (heSTRs) have lacked comprehensive genome-wide characterization. Leveraging 148 human and 26 nonhuman primate haploid genomes, we identified 8813 heSTRs with robust expansions in copy number distributions. Our analysis revealed notable associations between heSTRs and brain- and neuron-specific distal regulatory signals. Potential target genes regulated by heSTRs, identified by incorporating distal regulations, are enriched with neuronal development–related functions and disorders, displaying neuron-specific expression enhancement in humans. Moreover, heSTRs are associated with enhanced chromatin accessibility specifically in human neurons. In addition, heSTRs show substantial association with pathogenic STR loci exhibiting abnormal copy number variations, as reported by cohort studies on schizophrenia and autism. This study underscores the role of heSTRs in both human evolution and disorders, offering valuable insights for future research on STRs from an evolutionary perspective.
GPT-4o mini: Non-social science research article
Experimental demonstration of generalized quantum fluctuation theorems in the presence of coherence
Hui Li, Jie Xie, Hyukjoon Kwon, Yixin Zhao, M. S. Kim, Lijian Zhang
Full text
Fluctuation theorems have elevated the second law of thermodynamics to a statistical realm by establishing a connection between time-forward and time-reversal probabilities, providing invaluable insight into nonequilibrium dynamics. While well established in classical systems, their quantum generalization, incorporating coherence and the diversity of quantum noise, remains open. We report the experimental validation of a quantum fluctuation theorem (QFT) in a photonic system, applicable to general quantum processes with nonclassical characteristics, including quasi-probabilistic descriptions of entropy production and multiple time-reversal processes. Our experiment confirms that the ratio between the quasi-probabilities of the time-forward and any multiple time-reversal processes obeys a generalized Crooks QFT. Moreover, coherence induced by a quantum process leads to the imaginary components of quantum entropy production, governing the phase factor in the QFT. These findings underscore the fundamental symmetry between a general quantum process and its time reversal, providing an elementary toolkit to explore noisy quantum information processing.
GPT-4o mini: Non-social science research article
Real-space investigations of on-surface intermolecular radical transfer reactions assisted by persistent radicals
Huaming Zhu, Junbo Wang, Kaifeng Niu, Yong Zhang, Yi Zhang, Chuan Deng, Peipei Huang, Dengyuan Li, Peinian Liu, Jianchen Lu, Johanna Rosen, Jonas Björk, Jinming Cai, Lifeng Chi, Qing Li
Full text
Synthesizing radicals that have both long lifetimes and high chemical reactivity remains a long-term challenge. Here, persistent phenyl radicals are successfully synthesized on Ag(111) by protecting the carbon radical site by designing the precursor molecule with suitable steric hindrance. As carbon-carbon coupling is prohibited, such radicals remain intact for longer than 6 hours at room temperature on Ag(111). Taking advantage of the long lifetimes, the as-synthesized radicals are directly characterized in the real space at the single-chemical-bond scale by means of bond-resolving scanning tunneling microscopy imaging. Accompanied by the excellent stability, the radicals exhibit high chemical reactivities and facilitate the intermolecular radical transfer reactions at extreme low temperature. The preparation of persistent radicals not only favors the characterization of a surface-stabilized radical in the real space but also aids in illuminating the detailed reaction pathways of subsequent radical-assisted reactions directly.
GPT-4o mini: Non-social science research article
Differential phosphorylation of receptor kinase SlLYK4 mediates immune responses to bacterial and fungal pathogens in tomato
Wanting Zhu, Sen Cao, Mengling Huang, Pengyue Li, Jingjing Ke, Ai Xu, Yang Lin, Jiatao Xie, Jiasen Cheng, Yanping Fu, Daohong Jiang, Xiao Yu, Bo Li
Full text
Bacterial wilt caused by Ralstonia solanacearum is a devastating plant disease. Exopolysaccharide (EPS), a major virulence factor of R. solanacearum , elicits pattern-triggered immunity (PTI) in tomato, but the means by which EPS is recognized in the plant remain poorly understood. We found that tomato non-arginine-aspartate (non-RD) receptor kinase SlLYK4 mediates the perception of R. solanacearum EPS and positively regulates resistance to bacterial wilt. The RD receptor kinases SlLYK1 and SlLYK13 are required for EPS-triggered immune responses and form complexes with SlLYK4. These receptor kinase complexes have dual functions in recognizing bacterial EPS and fungal chitin. Phosphorylation of serine-320 in the juxtamembrane domain of SlLYK4 is essential in EPS- and chitin-mediated signaling, whereas phosphorylation of serine-334 or serine-634 in the C-terminal domain is required for chitin or EPS signaling, respectively. Our results reveal the mechanism underlying EPS recognition in tomato and provide insight into how differential phosphorylation of receptor kinase regulates antibacterial and antifungal immunity.
GPT-4o mini: Non-social science research article
High-affinity PQQ import is widespread in Gram-negative bacteria
Fabian Munder, Marcos Voutsinos, Klaus Hantke, Hari Venugopal, Rhys Grinter
Full text
Pyrroloquinoline quinone (PQQ) is a soluble redox cofactor used by diverse bacteria. Many Gram-negative bacteria that encode PQQ-dependent enzymes do not produce it and instead obtain it from the environment. To achieve this, Escherichia coli uses the TonB-dependent transporter PqqU as a high-affinity PQQ importer. Here, we show that PqqU binds PQQ with high affinity and determine the high-resolution structure of the PqqU-PQQ complex, revealing that PqqU undergoes conformational changes in PQQ binding to capture the cofactor in an internal cavity. We show that these conformational changes preclude the binding of a bacteriophage, which targets PqqU as a cell surface receptor. Guided by the PqqU-PQQ structure, we identify amino acids essential for PQQ import and leverage this information to map the presence of PqqU across Gram-negative bacteria. This reveals that PqqU is encoded by Gram-negative bacteria from at least 22 phyla occupying diverse habitats, indicating that PQQ is an important cofactor for bacteria that adopt diverse lifestyles and metabolic strategies.
GPT-4o mini: Non-social science research article
Asymmetric tacticity navigates the localized metal spin state for sustainable alkaline/sea water oxidation
Yaoda Liu, Lei Li, Xuning Li, Yifan Xu, Dongshuang Wu, Thangavel Sakthivel, Zhixin Guo, Xiaoxu Zhao, Zhengfei Dai
Full text
Anodic oxygen evolution reaction (OER) that involves a spin-dependent singlet-to-triplet oxygen changeover largely restrains the water electrolysis efficiency for hydrogen production. However, the modulation of spin state is still challengeable for most OER catalysts, and there remains a debate on deciphering the active spin state in OER. Here, we pioneered an asymmetric Fe-incorporated NiPS 3 tactic system to retune the metal localized spin for efficient OER electrocatalysis. It is unraveled that the synergistic effect of medium-spin Fe III site and P/S coordination can effectively boost OER activity and Cl resistance selectivity in alkaline/sea water. Resultantly, the Fe/NiPS 3 -based asymmetric electrodes exhibit low cell voltages of 1.50 volts/1.52 volts in alkaline/sea water at 10 milliamperes per square centimeter, together with a sustainable retention for 1000 hours. It also delivers the durable performance in anion exchange membrane water electrolyzers with a low operation voltage at 45°C. This research navigates the atomic localized spin state as the criterion in rationalizing efficient nonprecious alkaline/sea water oxidation electrocatalysts.
GPT-4o mini: Non-social science research article
Sorbate induces lysine sorbylation through noncanonical activities of class I HDACs to regulate the expression of inflammation genes
Yi-Cheng Sin, Breann Abernathy, Zuo-fei Yuan, Jason L. Heier, Justin E. Gonzalez, Laurie L. Parker, Douglas G. Mashek, Yue Chen
Full text
Environmental factors may affect gene expression through epigenetic modifications of histones and transcription factors. Here, we report that cellular uptake of sorbate, a common food preservative, induces lysine sorbylation (Ksor) in mammalian cells and tissue mediated by the noncanonical activities of class I histone deacetylases (HDAC1-3). We demonstrated that HDAC1-3 catalyze sorbylation upon sorbate uptake and desorbylation in the absence of sorbate both in vitro and in cells. Sorbate uptake in mice livers significantly induced histone Ksor, correlating with decreased expressions of inflammation-response genes. Accordingly, sorbate treatment in macrophage RAW264.7 cells upon lipopolysaccharide (LPS) stimulation dose-dependently down-regulated proinflammatory gene expressions and nitric oxide production. Proteomic profiling identified RelA, a component of the NF-ÎșB complex, and its interacting proteins as bona fide Ksor targets and sorbate treatment significantly decreased NF-ÎșB transcriptional activities in response to LPS stimulation in RAW264.7 cells. Together, our study demonstrated a noncanonical mechanism of sorbate uptake in regulating epigenetic histone modifications and inflammatory gene expression.
GPT-4o mini: Non-social science research article
All-integrated multidimensional optical sensing with a photonic neuromorphic processor
Zhijuan Gu, Yang Shi, Zhangming Zhu, Zuhang Li, Mingjie Zou, Changming Yang, Yang Liu, Yu Yu, Xinliang Zhang
Full text
Multidimensional optical sensing is crucial in information technology and modern intelligent systems. Despite advancement in optical sensing, capturing multidimensional light field information remains challenging, typically implemented using cascaded single-dimensional sensors and discrete optoelectrical components for information decoupling. Here, we present an all-integrated multidimensional sensing chip incorporating a light field sensitizer and a photonic neural network processor. The inverse-designed sensitizer projects the multidimensional input into multiple channels; each dimension is then decoupled through the reconfigurable nonlinear neural network. We experimentally achieved 91% high accuracy for single-shot, concurrent sensing of intensity, polarization, and wavelength using a well-trained five-layer neuromorphic system. The fully on-chip system eliminates optical-electrical conversion and offline digital processing, enabling low-latency and high energy efficiency. Moreover, we achieved stabilization and recovery of high-speed signals at 100 gigabytes per second under randomly perturbed polarization and wavelengths. This work shows the potential for low-latency, energy-efficient optical sensing and complex information processing using neuromorphic integrated photonics.
GPT-4o mini: Non-social science research article
Proteomic signatures of corona and herpes viral antibodies identify IGDCC4 as a mediator of neurodegeneration
Michael R. Duggan, Shuojia Yang, Gabriela T. Gomez, Yuhan Cui, Ana W. Capuano, Jingsha Chen, Zhijian Yang, Junhao Wen, Guray Erus, Shannon M. Drouin, David Zweibaum, Qu Tian, Julián Candia, Murat Bilgel, Alexandria Lewis, Abhay Moghekar, Nicholas J. Ashton, PrzemysƂaw R. Kac, Thomas K. Karikari, Kaj Blennow, Henrik Zetterberg, Brion S. Maher, Adam P. Spira, Logan Dumitrescu, Timothy J. Hohman, Rebecca F. Gottesman, Christos Davatzikos, David A. Bennett, Josef Coresh, Luigi Ferrucci, Susan M. Resnick, Robert Yolken, Keenan A. Walker
Full text
Mechanisms underlying the dynamic relationships of viral infections and neurodegeneration warrant examination. Using a community-based cohort of older adults, the current study characterized the neurocognitive (cognitive functioning, brain volumes, Alzheimer’s disease positron emission tomography, and plasma biomarkers) and plasma proteomic (7268 proteins) profiles of four common coronavirus and six herpesvirus antibody titers. Genetic inference techniques demonstrated the associations between viral antibody titers and neurocognitive outcomes may be attributed to altered expression in a subset of mechanistically relevant proteins in plasma. One of these proteins, IGDCC4 (immunoglobulin superfamily deleted in colorectal cancer subclass member 4), was related to 20-year dementia risk, cognitive functioning, and amyloid-ÎČ positivity using data from two independent cohorts, while its plasma and intrathecal abundance were causally implicated in dementia risk and clinically relevant brain atrophy. Our findings illuminate the biological basis by which host immune responses to viruses may affect neurocognitive outcomes in older adults and identify IGDCC4 as an important molecular mediator of neurodegeneration.
GPT-4o mini: Non-social science research article
Whole-brain mapping of basal forebrain cholinergic neurons reveals a long-range reciprocal input-output loop between distinct subtypes
Zhaonan Chen, Yanmei Liu, Yunqi Yang, Lizhao Wang, Meiling Qin, Zhishan Jiang, Min Xu, Siyu Zhang
Full text
Basal forebrain cholinergic neurons (BFCNs) influence cognition and emotion through specific acetylcholine release in various brain regions, including the prefrontal cortices and basolateral amygdala (BLA). Acetylcholine release is controlled by distinct BFCN subtypes, modulated by excitatory and inhibitory inputs. However, the organization of the whole-brain input-output networks of these subtypes remains unclear. Here, we identified two distinct BFCN subtypes—BFCN →ACA and BFCN →BLA —innervating the anterior cingulate cortex (ACA) and BLA, each with unique distributions, electrophysiological properties, and projection patterns. Combining rabies-virus–assisted mapping and triple-plex RNAscope hybridization, we characterized their whole-brain input networks, identifying unique excitatory and shared inhibitory inputs for these subtypes. Moreover, our results reveal a long-range reciprocal input-output loop: BFCN →ACA neurons target the isocortex, their shared excitatory-input source, whereas BFCN →BLA neurons target shared inhibitory-input sources such as the striatum and pallidum, thus enabling dynamic interactions among these BFCN subtypes. Our study deepens understanding of cholinergic modulation in cognition and emotion and provides insights into their functional interactions.
GPT-4o mini: Non-social science research article
Palladium-catalyzed intermolecular asymmetric dearomatizative arylation of indoles and benzofurans
Yang Xi, Youzhi Xu, Linlin Fan, Chenchen Wang, Tingting Xia, Genping Huang, Jingping Qu, Yifeng Chen
Full text
Indoles represent one of the most robust and synthetically versatile classes of heteroaromatic compounds. However, the stereoselective conversion of planar indole rings into three-dimensional indoline skeletons bearing multiple stereogenic centers remains a persistent challenge in organic synthesis. Herein, we describe an intermolecular catalytic asymmetric dearomatization of simple indoles via a palladium-catalyzed three-component cross-coupling reaction. By using readily accessible diazonium salts and aromatic boronic acids as arylative reagents under a ligand-swap strategy, this method enables the efficient construction of 2,3-diarylated indolines. Mechanistic studies reveal that the chiral BiOx ligand governs the highly stereoselective migratory insertion of the aryl-palladium intermediate into the indole’s C═C double bond with complete diastereo- and regioselectivity, whereas the achiral fumarate ligand facilitates the reductive elimination step, as corroborated by density functional theory calculations. Furthermore, this protocol is extended to the dearomative diarylation of benzofurans, affording chiral 2,3-dihydrobenzofuran derivatives with high stereocontrol.
GPT-4o mini: Non-social science research article
Local inhibitory circuits mediate cortical reactivations and memory consolidation
Kristian K. LensjĂž, Ingeborg Nymoen Nystuen, Frederik S. Rogge, Kristin TĂžndel, Arthur Sugden, Inga Shurnayte, Sverre GrĂždem, Anders Malthe-SĂžrenssen, Torkel Hafting, Mark L. Andermann, Marianne Fyhn
Full text
Highly salient events activate neurons across various brain regions. During subsequent rest or sleep, the activity patterns of these neurons often correlate with those observed during the preceding experience. Growing evidence suggests that these reactivations play a crucial role in memory consolidation, the process by which experiences are solidified in cortical networks for long-term storage. Here, we use longitudinal two-photon Ca 2+ imaging alongside paired LFP recordings in the hippocampus and cortex, to show that targeted manipulation of PV + inhibitory neurons in the lateral visual cortex after daily training selectively attenuates cue-specific reactivations and learning, with only minute effects on spontaneous activity and no apparent effect on normal function such as visual cue–elicited responses during training. In control mice, reactivations were biased toward salient cues, persisted for hours after training had ended, and the prevalence of reactivations was aligned with the learning process. Overall, our results underscore a crucial role for cortical reactivations in memory consolidation.
GPT-4o mini: Non-social science research article
Hybrid neural networks in the mushroom body drive olfactory preference in Drosophila
Li-Shan Cheng, Ching-Che Charng, Ruei-Huang Chen, Kuan-Lin Feng, Ann-Shyn Chiang, Chung-Chuan Lo, Ting-Kuo Lee
Full text
In Drosophila melanogaster , olfactory encoding in the mushroom body (MB) involves thousands of Kenyon cells (KCs) processing inputs from hundreds of projection neurons (PNs). Recent data challenge the notion of random PN-to-KC connectivity, revealing preferential connections between food-related PNs and specific KCs. Our study further uncovers a broader picture—an L-shaped hybrid network, supported by spatial patterning: Food-related PNs diverge across KC classes, whereas pheromone-sensitive PNs converge on Îł KCs. α/ÎČ KCs specialize in food odors, whereas Îł KCs integrate diverse inputs. Such spatial arrangement extends further to the antennal lobe (AL) and lateral horn (LH), shaping a systematic olfactory landscape. Moreover, our functional validations align with computational predictions of KC odor encoding based on the hybrid connectivity, correlating PN-KC activity with behavioral preferences. In addition, our simulations showcase the network’s augmented sensitivity and precise discrimination abilities, underscoring the computational benefits of this hybrid architecture in olfactory processing.

Socio-Economic Review

Growing through skills: the integration of transnational dimensions into growth regimes
Cecilia Ivardi, Linda Wanklin
Full text
This article proposes a new conceptualisation of skill formation within growth regimes that integrates a transnational dimension. Drawing on insights from global value chain and managed migration scholarships, skill formation can become a transnational effort coordinated by a dominant growth coalition sourcing skills for economic growth. Focusing on Germany as a least-likely case, this article finds an increase in policies and practices to transfer vocational education and training and manage labour migration, as part of a growth strategy to sustain export-led growth. A coalition of the state and employers supports this strategy, called ‘externalisation’, which unions, political parties, and foreign governments do not oppose. Through the study of externalisation, we advocate for a departure from methodological nationalism when studying growth in 21st-century political economies.
Beyond neoliberalism? Bilateral central bank swaps and changing global financial governance
Ayca Zayim
Full text
Bilateral central bank swap agreements have become the most significant source of emergency liquidity since 2008. The US and China play a key role in the emergent swap networks. Does the rise of China and bilateral swaps signal the emergence of a post-neoliberal global financial order? Based on public texts, data, and interviews in Turkey—one of China’s swap partners—this article explores how the rise of swap lines has influenced the policy space of developing economies. This article shows that swap lines have enabled Turkey to evade IMF conditionality, at least for some time. Despite optimism in scholarship that the emergent policy space can be deployed for developmentalist goals that reverse decades of neoliberal restructuring, this article shows that it can also prolong authoritarian political regimes, deepening inequality and poverty. The paper discusses other dilemmas faced by China’s swap partners surrounding the potential limits of local currency swaps and their long-term sustainability.