We checked 7 multidisciplinary journals on Friday, December 06, 2024 using the Crossref API. For the period November 29 to December 05, we retrieved 18 new paper(s) in 5 journal(s).

Nature

GPT-4o mini: Non-social science research article
Tracking transcription–translation coupling in real time
Nusrat Shahin Qureshi, Olivier Duss
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A central question in biology is how macromolecular machines function cooperatively. In bacteria, transcription and translation occur in the same cellular compartment, and can be physically and functionally coupled 1–4 . Although high-resolution structures of the ribosome–RNA polymerase (RNAP) complex have provided initial mechanistic insights into the coupling process 5–10 , we lack knowledge of how these structural snapshots are placed along a dynamic reaction trajectory. Here we reconstitute a complete and active transcription–translation system and develop multi-colour single-molecule fluorescence microscopy experiments to directly and simultaneously track transcription elongation, translation elongation and the physical and functional coupling between the ribosome and the RNAP in real time. Our data show that physical coupling between ribosome and RNAP can occur over hundreds of nucleotides of intervening mRNA by mRNA looping, a process facilitated by NusG. We detect active transcription elongation during mRNA looping and show that NusA-paused RNAPs can be activated by the ribosome by long-range physical coupling. Conversely, the ribosome slows down while colliding with the RNAP. We hereby provide an alternative explanation for how the ribosome can efficiently rescue RNAP from frequent pausing without requiring collisions by a closely trailing ribosome. Overall, our dynamic data mechanistically highlight an example of how two central macromolecular machineries, the ribosome and RNAP, can physically and functionally cooperate to optimize gene expression.
GPT-4o mini: Non-social science research article
Isoprene nitrates drive new particle formation in Amazon’s upper troposphere
Joachim Curtius, Martin Heinritzi, Lisa J. Beck, Mira L. Pöhlker, Nidhi Tripathi, Bianca E. Krumm, Philip Holzbeck, Clara M. Nussbaumer, Lianet Hernández Pardo, Thomas Klimach, Konstantinos Barmpounis, Simone T. Andersen, Roman Bardakov, Birger Bohn, Micael A. Cecchini, Jean-Pierre Chaboureau, Thibaut Dauhut, Dirk Dienhart, Raphael Dörich, Achim Edtbauer, Andreas Giez, Antonia Hartmann, Bruna A. Holanda, Philipp Joppe, Katharina Kaiser, Timo Keber, Hannah Klebach, Ovid O. Krüger, Andreas Kürten, Christian Mallaun, Daniel Marno, Monica Martinez, Carolina Monteiro, Carolina Nelson, Linda Ort, Subha S. Raj, Sarah Richter, Akima Ringsdorf, Fabio Rocha, Mario Simon, Sreedev Sreekumar, Anywhere Tsokankunku, Gabriela R. Unfer, Isabella D. Valenti, Nijing Wang, Andreas Zahn, Marcel Zauner-Wieczorek, Rachel I. Albrecht, Meinrat O. Andreae, Paulo Artaxo, John N. Crowley, Horst Fischer, Hartwig Harder, Dirceu L. Herdies, Luiz A. T. Machado, Christopher Pöhlker, Ulrich Pöschl, Anna Possner, Andrea Pozzer, Johannes Schneider, Jonathan Williams, Jos Lelieveld
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New particle formation (NPF) in the tropical upper troposphere is a globally important source of atmospheric aerosols 1–4 . It is known to occur over the Amazon basin, but the nucleation mechanism and chemical precursors have yet to be identified 2 . Here we present comprehensive in situ aircraft measurements showing that extremely low-volatile oxidation products of isoprene, particularly certain organonitrates, drive NPF in the Amazonian upper troposphere. The organonitrates originate from OH-initiated oxidation of isoprene from forest emissions in the presence of nitrogen oxides from lightning. Nucleation bursts start about 2 h after sunrise in the outflow of nocturnal deep convection, producing high aerosol concentrations of more than 50,000 particles cm − 3 . We report measurements of characteristic diurnal cycles of precursor gases and particles. Our observations show that the interplay between biogenic isoprene, deep tropical convection with associated lightning, oxidation photochemistry and the low ambient temperature uniquely promotes NPF. The particles grow over time, undergo long-range transport and descend through subsidence to the lower troposphere, in which they can serve as cloud condensation nuclei (CCN) that influence the Earth’s hydrological cycle, radiation budget and climate 1,4–8 .
GPT-4o mini: Non-social science research article
Near-identical macromolecules spontaneously partition into concentric circles
Hao Gong, Yuriko Sakaguchi, Tsutomu Suzuki, Miho Yanagisawa, Takuzo Aida
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GPT-4o mini: Non-social science research article
Author Correction: Autoregulation in rats with transplanted supernumerary kidneys
Ruben F. Gittes, Marcus Rist, Salvador Treves, Andrew Biewener
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GPT-4o mini: Non-social science research article
Macrophages excite muscle spindles with glutamate to bolster locomotion
Yuyang Yan, Nuria Antolin, Luming Zhou, Luyang Xu, Irene Lisa Vargas, Carlos Daniel Gomez, Guiping Kong, Ilaria Palmisano, Yi Yang, Jessica Chadwick, Franziska Müller, Anthony M. J. Bull, Cristina Lo Celso, Guido Primiano, Serenella Servidei, Jean François Perrier, Carmelo Bellardita, Simone Di Giovanni
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The stretch reflex is a fundamental component of the motor system that orchestrates the coordinated muscle contractions underlying movement. At the heart of this process lie the muscle spindles (MS), specialized receptors finely attuned to fluctuations in tension within intrafusal muscle fibres. The tension variation in the MS triggers a series of neuronal events including an initial depolarization of sensory type Ia afferents that subsequently causes the activation of motoneurons within the spinal cord 1,2 . This neuronal cascade culminates in the execution of muscle contraction, underscoring a presumed closed-loop mechanism between the musculoskeletal and nervous systems. By contrast, here we report the discovery of a new population of macrophages with exclusive molecular and functional signatures within the MS that express the machinery for synthesizing and releasing glutamate. Using mouse intersectional genetics with optogenetics and electrophysiology, we show that activation of MS macrophages (MSMP) drives proprioceptive sensory neuron firing on a millisecond timescale. MSMP activate spinal circuits, motor neurons and muscles by means of a glutamate-dependent mechanism that excites the MS. Furthermore, MSMP respond to neural and muscle activation by increasing the expression of glutaminase, enabling them to convert the uptaken glutamine released by myocytes during muscle contraction into glutamate. Selective silencing or depletion of MSMP in hindlimb muscles disrupted the modulation of the stretch reflex for force generation and sensory feedback correction, impairing locomotor strategies in mice. Our results have identified a new cellular component, the MSMP, that directly regulates neural activity and muscle contraction. The glutamate-mediated signalling of MSMP and their dynamic response to sensory cues introduce a new dimension to our understanding of sensation and motor action, potentially offering innovative therapeutic approaches in conditions that affect sensorimotor function.
GPT-4o mini: Non-social science research article
Probabilistic weather forecasting with machine learning
Ilan Price, Alvaro Sanchez-Gonzalez, Ferran Alet, Tom R. Andersson, Andrew El-Kadi, Dominic Masters, Timo Ewalds, Jacklynn Stott, Shakir Mohamed, Peter Battaglia, Remi Lam, Matthew Willson
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Weather forecasts are fundamentally uncertain, so predicting the range of probable weather scenarios is crucial for important decisions, from warning the public about hazardous weather to planning renewable energy use. Traditionally, weather forecasts have been based on numerical weather prediction (NWP) 1 , which relies on physics-based simulations of the atmosphere. Recent advances in machine learning (ML)-based weather prediction (MLWP) have produced ML-based models with less forecast error than single NWP simulations 2,3 . However, these advances have focused primarily on single, deterministic forecasts that fail to represent uncertainty and estimate risk. Overall, MLWP has remained less accurate and reliable than state-of-the-art NWP ensemble forecasts. Here we introduce GenCast, a probabilistic weather model with greater skill and speed than the top operational medium-range weather forecast in the world, ENS, the ensemble forecast of the European Centre for Medium-Range Weather Forecasts 4 . GenCast is an ML weather prediction method, trained on decades of reanalysis data. GenCast generates an ensemble of stochastic 15-day global forecasts, at 12-h steps and 0.25° latitude–longitude resolution, for more than 80 surface and atmospheric variables, in 8 min. It has greater skill than ENS on 97.2% of 1,320 targets we evaluated and better predicts extreme weather, tropical cyclone tracks and wind power production. This work helps open the next chapter in operational weather forecasting, in which crucial weather-dependent decisions are made more accurately and efficiently.
GPT-4o mini: Non-social science research article
Fast ground-to-air transition with avian-inspired multifunctional legs
Won Dong Shin, Hoang-Vu Phan, Monica A. Daley, Auke J. Ijspeert, Dario Floreano
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GPT-4o mini: Non-social science research article
Author Correction: Dynamic transition and Galilean relativity of current-driven skyrmions
Max T. Birch, Ilya Belopolski, Yukako Fujishiro, Minoru Kawamura, Akiko Kikkawa, Yasujiro Taguchi, Max Hirschberger, Naoto Nagaosa, Yoshinori Tokura
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GPT-4o mini: Non-social science research article
Understanding the neural code of stress to control anhedonia
Frances Xia, Valeria Fascianelli, Nina Vishwakarma, Frances Grace Ghinger, Andrew Kwon, Mark M. Gergues, Lahin K. Lalani, Stefano Fusi, Mazen A. Kheirbek
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Anhedonia, the diminished drive to seek, value, and learn about rewards, is a core feature of major depressive disorder 1–3 . The neural underpinnings of anhedonia and how this emotional state drives behaviour remain unclear. Here we investigated the neural code of anhedonia by taking advantage of the fact that when mice are exposed to traumatic social stress, susceptible animals become socially withdrawn and anhedonic, whereas others remain resilient. By performing high-density electrophysiology to record neural activity patterns in the basolateral amygdala (BLA) and ventral CA1 (vCA1), we identified neural signatures of susceptibility and resilience. When mice actively sought rewards, BLA activity in resilient mice showed robust discrimination between reward choices. By contrast, susceptible mice exhibited a rumination-like signature, in which BLA neurons encoded the intention to switch or stay on a previously chosen reward. Manipulation of vCA1 inputs to the BLA in susceptible mice rescued dysfunctional neural dynamics, amplified dynamics associated with resilience, and reversed anhedonic behaviour. Finally, when animals were at rest, the spontaneous BLA activity of susceptible mice showed a greater number of distinct neural population states. This spontaneous activity allowed us to decode group identity and to infer whether a mouse had a history of stress better than behavioural outcomes alone. This work reveals population-level neural dynamics that explain individual differences in responses to traumatic stress, and suggests that modulating vCA1–BLA inputs can enhance resilience by regulating these dynamics.
GPT-4o mini: Non-social science research article
RANK drives structured intestinal epithelial expansion during pregnancy
Masahiro Onji, Verena Sigl, Thomas Lendl, Maria Novatchkova, Asier Ullate-Agote, Amanda Andersson-Rolf, Ivona Kozieradzki, Rubina Koglgruber, Tsung-Pin Pai, Dominic Lichtscheidl, Komal Nayak, Matthias Zilbauer, Natalia A. Carranza García, Laura Katharina Sievers, Maren Falk-Paulsen, Shane J. F. Cronin, Astrid Hagelkruys, Shinichiro Sawa, Lisa C. Osborne, Philip Rosenstiel, Manolis Pasparakis, Jürgen Ruland, Hiroshi Takayanagi, Hans Clevers, Bon-Kyoung Koo, Josef M. Penninger
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During reproduction, multiple species such as insects and all mammals undergo extensive physiological and morphological adaptions to ensure health and survival of the mother and optimal development of the offspring. Here we report that the intestinal epithelium undergoes expansion during pregnancy and lactation in mammals. This enlargement of the intestinal surface area results in a novel geometry of expanded villi. Receptor activator of nuclear factor-κΒ (RANK, encoded by TNFRSF11A ) and its ligand RANKL were identified as a molecular pathway involved in this villous expansion of the small intestine in vivo in mice and in intestinal mouse and human organoids. Mechanistically, RANK–RANKL protects gut epithelial cells from cell death and controls the intestinal stem cell niche through BMP receptor signalling, resulting in the elongation of villi and a prominent increase in the intestinal surface. As a transgenerational consequence, babies born to female mice that lack Rank in the intestinal epithelium show reduced weight and develop glucose intolerance after metabolic stress. Whereas gut epithelial remodelling in pregnancy/lactation is reversible, constitutive expression of an active form of RANK is sufficient to drive intestinal expansion followed by loss of villi and stem cells, and prevents the formation of Apc min -driven small intestinal stem cell tumours. These data identify RANK–RANKL as a pathway that drives intestinal epithelial expansion in pregnancy/lactation, one of the most elusive and fundamental tissue remodelling events in mammalian life history and evolution.
GPT-4o mini: Non-social science research article
In situ spheroid formation in distant submillimetre-bright galaxies
Qing-Hua Tan, Emanuele Daddi, Benjamin Magnelli, Camila A. Correa, Frédéric Bournaud, Sylvia Adscheid, Shao-Bo Zhang, David Elbaz, Carlos Gómez-Guijarro, Boris S. Kalita, Daizhong Liu, Zhaoxuan Liu, Jérôme Pety, Annagrazia Puglisi, Eva Schinnerer, John D. Silverman, Francesco Valentino
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GPT-4o mini: Non-social science research article
Applied body-fluid analysis by wearable devices
Noé Brasier, Joseph Wang, Wei Gao, Juliane R. Sempionatto, Can Dincer, H. Ceren Ates, Firat Güder, Selin Olenik, Ivo Schauwecker, Dietmar Schaffarczyk, Effy Vayena, Nicole Ritz, Maja Weisser, Sally Mtenga, Roozbeh Ghaffari, John A. Rogers, Jörg Goldhahn
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GPT-4o mini: Non-social science research article
Author Correction: Genetic drivers and cellular selection of female mosaic X chromosome loss
Aoxing Liu, Giulio Genovese, Yajie Zhao, Matti Pirinen, Seyedeh M. Zekavat, Katherine A. Kentistou, Zhiyu Yang, Kai Yu, Caitlyn Vlasschaert, Xiaoxi Liu, Derek W. Brown, Georgi Hudjashov, Bryan R. Gorman, Joe Dennis, Weiyin Zhou, Yukihide Momozawa, Saiju Pyarajan, Valdislav Tuzov, Fanny-Dhelia Pajuste, Mervi Aavikko, Timo P. Sipilä, Awaisa Ghazal, Wen-Yi Huang, Neal D. Freedman, Lei Song, Eugene J. Gardner, character(0), character(0), Andres Metspalu, Tõnu Esko, Mari Nelis, Lili Milani, character(0), Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Amy Berrington de Gonzalez, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Hermann Brenner, Jenny Chang-Claude, Georgia Chenevix-Trench, Sarah V. Colonna, character(0), Fergus J. Couch, Angela Cox, Kamila Czene, Mary B. Daly, Peter Devilee, Thilo Dörk, Alison M. Dunning, Miriam Dwek, Douglas F. Easton, Diana M. Eccles, Peter A. Fasching, Olivia Fletcher, Manuela Gago-Dominguez, Montserrat García-Closas, Mark S. Goldberg, Anna González-Neira, Pascal Guénel, Christopher A. Haiman, Per Hall, Ute Hamann, Antoinette Hollestelle, Reiner Hoppe, John L. Hopper, character(0), Anna Jakubowska, Helena Jernström, Esther M. John, Rudolf Kaaks, Elza K. Khusnutdinova, Cari M. Kitahara, Peter Kraft, Vessela N. Kristensen, Diether Lambrechts, Annika Lindblom, Arto Mannermaa, Usha Menon, Kyriaki Michailidou, Rachel A. Murphy, Heli Nevanlinna, Nadia Obi, Kenneth Offit, Paolo Peterlongo, Paul D. P. Pharoah, Dijana Plaseska-Karanfilska, Gad Rennert, Atocha Romero, Emmanouil Saloustros, Marjanka K. Schmidt, Rita K. Schmutzler, Jennifer Stone, Rulla M. Tamimi, Lauren R. Teras, Mary Beth Terry, Melissa A. Troester, Celine M. Vachon, Qin Wang, Clarice R. Weinberg, Robert Winqvist, Alicja Wolk, character(0), Vijay G. Sankaran, Aarno Palotie, Hanna M. Ollila, Taru Tukiainen, Stephen J. Chanock, Reedik Mägi, Pradeep Natarajan, Mark J. Daly, Alexander Bick, Steven A. McCarroll, Chikashi Terao, Po-Ru Loh, Andrea Ganna, John R. B. Perry, Mitchell J. Machiela
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GPT-4o mini: Non-social science research article
Synthetic GPCRs for programmable sensing and control of cell behaviour
Nicholas A. Kalogriopoulos, Reika Tei, Yuqi Yan, Peter M. Klein, Matthew Ravalin, Bo Cai, Ivan Soltesz, Yulong Li, Alice Ting
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GPT-4o mini: Non-social science research article
Author Correction: APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes
Joel W. Blanchard, Leyla Anne Akay, Jose Davila-Velderrain, Djuna von Maydell, Hansruedi Mathys, Shawn M. Davidson, Audrey Effenberger, Chih-Yu Chen, Kristal Maner-Smith, Ihab Hajjar, Eric A. Ortlund, Michael Bula, Emre Agbas, Ayesha Ng, Xueqiao Jiang, Martin Kahn, Cristina Blanco-Duque, Nicolas Lavoie, Liwang Liu, Ricardo Reyes, Yuan-Ta Lin, Tak Ko, Lea R’Bibo, William T. Ralvenius, David A. Bennett, Hugh P. Cam, Manolis Kellis, Li-Huei Tsai
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GPT-4o mini: Non-social science research article
Dietary fructose enhances tumour growth indirectly via interorgan lipid transfer
Ronald Fowle-Grider, Joe L. Rowles, Isabel Shen, Yahui Wang, Michaela Schwaiger-Haber, Alden J. Dunham, Kay Jayachandran, Matthew Inkman, Michael Zahner, Fuad J. Naser, Madelyn M. Jackstadt, Jonathan L. Spalding, Sarah Chiang, Kyle S. McCommis, Roland E. Dolle, Eva T. Kramer, Sarah M. Zimmerman, George P. Souroullas, Brian N. Finck, Leah P. Shriver, Charles K. Kaufman, Julie K. Schwarz, Jin Zhang, Gary J. Patti
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GPT-4o mini: Non-social science research article
Mis-splicing of a neuronal microexon promotes CPEB4 aggregation in ASD
Carla Garcia-Cabau, Anna Bartomeu, Giulio Tesei, Kai Chit Cheung, Julia Pose-Utrilla, Sara Picó, Andreea Balaceanu, Berta Duran-Arqué, Marcos Fernández-Alfara, Judit Martín, Cesare De Pace, Lorena Ruiz-Pérez, Jesús García, Giuseppe Battaglia, José J. Lucas, Rubén Hervás, Kresten Lindorff-Larsen, Raúl Méndez, Xavier Salvatella
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GPT-4o mini: Non-social science research article
Evolution of myeloid-mediated immunotherapy resistance in prostate cancer
Aram Lyu, Zenghua Fan, Matthew Clark, Averey Lea, Diamond Luong, Ali Setayesh, Alec Starzinski, Rachel Wolters, Marcel Arias-Badia, Kate Allaire, Kai Wu, Vibha Gurunathan, Laura Valderrábano, Xiao X. Wei, Richard A. Miller, Eliezer M. Van Allen, Lawrence Fong
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Patients with advanced metastatic castration-resistant prostate cancer (mCRPC) are refractory to immune checkpoint inhibitors (ICIs) 1,2 , partly because there are immunosuppressive myeloid cells in tumours 3,4 . However, the heterogeneity of myeloid cells has made them difficult to target, making blockade of the colony stimulating factor-1 receptor (CSF1R) clinically ineffective. Here we use single-cell profiling on patient biopsies across the disease continuum and find that a distinct population of tumour-associated macrophages with elevated levels of SPP1 transcripts ( SPP1 hi -TAMs) becomes enriched with the progression of prostate cancer to mCRPC. In syngeneic mouse modelling, an analogous macrophage population suppresses CD8 + T cell activity in vitro and promotes ICI resistance in vivo. Furthermore, Spp1 hi -TAMs are not responsive to anti-CSF1R antibody treatment. Pathway analysis identifies adenosine signalling as a potential mechanism for SPP1 hi -TAM-mediated immunotherapeutic resistance. Indeed, pharmacological inhibition of adenosine A2A receptors (A2ARs) significantly reverses Spp1 hi -TAM-mediated immunosuppression in CD8 + T cells in vitro and enhances CRPC responsiveness to programmed cell death protein 1 (PD-1) blockade in vivo. Consistent with preclinical results, inhibition of A2ARs using ciforadenant in combination with programmed death 1 ligand 1 (PD-L1) blockade using atezolizumab induces clinical responses in patients with mCRPC. Moreover, inhibiting A2ARs results in a significant decrease in SPP1 hi -TAM abundance in CRPC, indicating that this pathway is involved in both induction and downstream immunosuppression. Collectively, these findings establish SPP1 hi -TAMs as key mediators of ICI resistance in mCRPC through adenosine signalling, emphasizing their importance as both a therapeutic target and a potential biomarker for predicting treatment efficacy.
GPT-4o mini: Non-social science research article
The oestrous cycle stage affects mammary tumour sensitivity to chemotherapy
Laura Bornes, Lennart J. van Winden, Veerle C. M. Geurts, Beaunelle de Bruijn, Leyla Azarang, Mirthe Lanfermeijer, Marika Caruso, Natalie Proost, Manon Boeije, Jeroen O. Lohuis, Guillaume Belthier, Eulàlia Noguera Delgado, Nadia de Gruil, Judith R. Kroep, Marieke van de Ven, Renee Menezes, Jelle Wesseling, Marleen Kok, Sabine Linn, Annegien Broeks, Huub H. van Rossum, Colinda L. G. J. Scheele, Jacco van Rheenen
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GPT-4o mini: Non-social science research article
New particle formation from isoprene under upper-tropospheric conditions
Jiali Shen, Douglas M. Russell, Jenna DeVivo, Felix Kunkler, Rima Baalbaki, Bernhard Mentler, Wiebke Scholz, Wenjuan Yu, Lucía Caudillo-Plath, Eva Sommer, Emelda Ahongshangbam, Dina Alfaouri, João Almeida, Antonio Amorim, Lisa J. Beck, Hannah Beckmann, Moritz Berntheusel, Nirvan Bhattacharyya, Manjula R. Canagaratna, Anouck Chassaing, Romulo Cruz-Simbron, Lubna Dada, Jonathan Duplissy, Hamish Gordon, Manuel Granzin, Lena Große Schute, Martin Heinritzi, Siddharth Iyer, Hannah Klebach, Timm Krüger, Andreas Kürten, Markus Lampimäki, Lu Liu, Brandon Lopez, Monica Martinez, Aleksandra Morawiec, Antti Onnela, Maija Peltola, Pedro Rato, Mago Reza, Sarah Richter, Birte Rörup, Milin Kaniyodical Sebastian, Mario Simon, Mihnea Surdu, Kalju Tamme, Roseline C. Thakur, António Tomé, Yandong Tong, Jens Top, Nsikanabasi Silas Umo, Gabriela Unfer, Lejish Vettikkat, Jakob Weissbacher, Christos Xenofontos, Boxing Yang, Marcel Zauner-Wieczorek, Jiangyi Zhang, Zhensen Zheng, Urs Baltensperger, Theodoros Christoudias, Richard C. Flagan, Imad El Haddad, Heikki Junninen, Ottmar Möhler, Ilona Riipinen, Urs Rohner, Siegfried Schobesberger, Rainer Volkamer, Paul M. Winkler, Armin Hansel, Katrianne Lehtipalo, Neil M. Donahue, Jos Lelieveld, Hartwig Harder, Markku Kulmala, Doug R. Worsnop, Jasper Kirkby, Joachim Curtius, Xu-Cheng He
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Aircraft observations have revealed ubiquitous new particle formation in the tropical upper troposphere over the Amazon 1,2 and the Atlantic and Pacific oceans 3,4 . Although the vapours involved remain unknown, recent satellite observations have revealed surprisingly high night-time isoprene mixing ratios of up to 1 part per billion by volume (ppbv) in the tropical upper troposphere 5 . Here, in experiments performed with the CERN CLOUD (Cosmics Leaving Outdoor Droplets) chamber, we report new particle formation initiated by the reaction of hydroxyl radicals with isoprene at upper-tropospheric temperatures of −30 °C and −50 °C. We find that isoprene-oxygenated organic molecules (IP-OOM) nucleate at concentrations found in the upper troposphere, without requiring any more vapours. Moreover, the nucleation rates are enhanced 100-fold by extremely low concentrations of sulfuric acid or iodine oxoacids above 10 5 cm −3 , reaching rates around 30 cm −3 s −1 at acid concentrations of 10 6 cm −3 . Our measurements show that nucleation involves sequential addition of IP-OOM, together with zero or one acid molecule in the embryonic molecular clusters. IP-OOM also drive rapid particle growth at 3–60 nm h −1 . We find that rapid nucleation and growth rates persist in the presence of NO x at upper-tropospheric concentrations from lightning. Our laboratory measurements show that isoprene emitted by rainforests may drive rapid new particle formation in extensive regions of the tropical upper troposphere 1,2 , resulting in tens of thousands of particles per cubic centimetre.
GPT-4o mini: Non-social science research article
Author Correction: Intravenous and intracranial GD2-CAR T cells for H3K27M+ diffuse midline gliomas
Michelle Monje, Jasia Mahdi, Robbie Majzner, Kristen W. Yeom, Liora M. Schultz, Rebecca M. Richards, Valentin Barsan, Kun-Wei Song, Jen Kamens, Christina Baggott, Michael Kunicki, Skyler P. Rietberg, Alexandria Sung Lim, Agnes Reschke, Sharon Mavroukakis, Emily Egeler, Jennifer Moon, Shabnum Patel, Harshini Chinnasamy, Courtney Erickson, Ashley Jacobs, Allison K. Duh, Ramya Tunuguntla, Dorota Danuta Klysz, Carley Fowler, Sean Green, Barbara Beebe, Casey Carr, Michelle Fujimoto, Annie Kathleen Brown, Ann-Louise G. Petersen, Catherine McIntyre, Aman Siddiqui, Nadia Lepori-Bui, Katlin Villar, Kymhuynh Pham, Rachel Bove, Eric Musa, Warren D. Reynolds, Adam Kuo, Snehit Prabhu, Lindsey Rasmussen, Timothy T. Cornell, Sonia Partap, Paul G. Fisher, Cynthia J. Campen, Gerald Grant, Laura Prolo, Xiaobu Ye, Bita Sahaf, Kara L. Davis, Steven A. Feldman, Sneha Ramakrishna, Crystal Mackall
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GPT-4o mini: Non-social science research article
Fetal hepatocytes protect the HSPC genome via fetuin-A
Xiao-Lin Guo, Yi-Ding Wang, Yan-Jun Liu, Lei Chu, Hua Zhu, Ye Hu, Ren-Yan Wu, Hong-Yu Xie, Juan Yu, Shui-Ping Li, Zhao-Yang Xiong, Ruo-Yan Li, Fang Ke, Lei Chen, Guo-Qiang Chen, Liang Chen, Fan Bai, Tariq Enver, Guo-Hong Li, Huai-Fang Li, Deng-Li Hong
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GPT-4o mini: Non-social science research article
Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis
Xueqian Zhuang, Qing Wang, Simon Joost, Alexander Ferrena, David T. Humphreys, Zhuxuan Li, Melissa Blum, Klavdija Krause, Selena Ding, Yuna Landais, Yingqian Zhan, Yang Zhao, Ronan Chaligne, Joo-Hyeon Lee, Sebastian E. Carrasco, Umeshkumar K. Bhanot, Richard P. Koche, Matthew J. Bott, Pekka Katajisto, Yadira M. Soto-Feliciano, Thomas Pisanic, Tiffany Thomas, Deyou Zheng, Emily S. Wong, Tuomas Tammela
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GPT-4o mini: Non-social science research article
Author Correction: A virally encoded tRNA neutralizes the PARIS antiviral defence system
Nathaniel Burman, Svetlana Belukhina, Florence Depardieu, Royce A. Wilkinson, Mikhail Skutel, Andrew Santiago-Frangos, Ava B. Graham, Alexei Livenskyi, Anna Chechenina, Natalia Morozova, Trevor Zahl, William S. Henriques, Murat Buyukyoruk, Christophe Rouillon, Baptiste Saudemont, Lena Shyrokova, Tatsuaki Kurata, Vasili Hauryliuk, Konstantin Severinov, Justine Groseille, Agnès Thierry, Romain Koszul, Florian Tesson, Aude Bernheim, David Bikard, Blake Wiedenheft, Artem Isaev
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GPT-4o mini: Non-social science research article
Author Correction: Carbon dioxide capture from open air using covalent organic frameworks
Zihui Zhou, Tianqiong Ma, Heyang Zhang, Saumil Chheda, Haozhe Li, Kaiyu Wang, Sebastian Ehrling, Raynald Giovine, Chuanshuai Li, Ali H. Alawadhi, Marwan M. Abduljawad, Majed O. Alawad, Laura Gagliardi, Joachim Sauer, Omar M. Yaghi
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Do you drink coffee? Ask your gut
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China’s climate investments in Africa must promote mutual benefit
Hong Yang
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Virtual lab powered by ‘AI scientists’ super-charges biomedical research
Helena Kudiabor
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Why breast cancer treatments might work best just after your period
Nick Petrić Howe, Emily Bates
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A step-by-step guide to landing your next job in science
Linda Nordling
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A firm randomly assigned its scientists AI: here’s what happened
Davide Castelvecchi
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The liver converts fructose into lipids to fuel tumours
Hyllana C. D. Medeiros, Sophia Y. Lunt
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What is the best time of the month to treat breast cancer?
Wendy V. Ingman
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What is ageing? Even the field’s researchers can’t agree
Smriti Mallapaty
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Cancer development: Origins in the oesophagus
Lizhe Zhuang, Rebecca C. Fitzgerald
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Science must up its game to support climate finance negotiations
Alexandros Nikas, Natasha Frilingou, Alaa Al Khourdajie, Ajay Gambhir
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Daily briefing: How to get to 100 — centenarian cells teach us about ageing
Flora Graham
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Stress can dull our capacity for joy: mouse brain patterns hint at why
Max Kozlov
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Banish the PDF-hunting blues with these AI and digital tools
Candice P. Chu
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DeepMind AI weather forecaster beats world-class system
Alix Soliman
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Exis memoria
Hannya Kay
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Advising governments about science is essential but difficult. So train people to do it
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Unexpected RNA modification protects bacteria against viral infection
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I help researchers to measure methane at a local level so that we can make global changes
Oscar Allan
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Nature DOI suffix ≠ "/s...": Not a research article
To unlock mutual benefits, don’t restrict US–China genome data transfer
Zhangyu Wang, Li Du
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Nature DOI suffix ≠ "/s...": Not a research article
Where does poetry come from?
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Nature DOI suffix ≠ "/s...": Not a research article
Pandemic policy can learn from arms control
Rebecca Katz
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Nature DOI suffix ≠ "/s...": Not a research article
How to ensure only dying cells rupture
Elliott M. Bernard, Petr Broz
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Nature DOI suffix ≠ "/s...": Not a research article
How provinces and cities can sustain US–China climate cooperation
Fan Dai, Jerry Brown, Zhenhua Xie, Yi Wang, Peng Gong
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Nature DOI suffix ≠ "/s...": Not a research article
Bird-inspired leg enables robots to jump into flight
Aimy A. Wissa
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Nature DOI suffix ≠ "/s...": Not a research article
Where in the world is there potential for tropical-forest regeneration?
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Long orbit
Robert Sommers
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Nature DOI suffix ≠ "/s...": Not a research article
A plastics treaty is urgently needed, but getting it right will take time
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Why the EU must reset its Green Deal – or be left behind
Rabah Arezki, Jean-Pierre Landau, Rick van der Ploeg
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Nature DOI suffix ≠ "/s...": Not a research article
This giant coral is the biggest ever found — November’s best science images
Nisha Gaind
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Nature DOI suffix ≠ "/s...": Not a research article
Fragments of the brain’s myelin proteins train T cells to ward off autoimmune attacks
Hartmut Wekerle, Naoto Kawakami
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Nature DOI suffix ≠ "/s...": Not a research article
US academics: look after foreign students
Christina W. Yao
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Nature DOI suffix ≠ "/s...": Not a research article
Science could solve some of the world’s biggest problems. Why aren’t governments using it?
Helen Pearson
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Daily briefing: Homo erectus, I presume? Footprints show ancient hominins crossed paths
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Sick animals suggest COVID pandemic started in Wuhan market
Smriti Mallapaty
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ChatGPT turns two: how the AI chatbot has changed scientists’ lives
Mariana Lenharo
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Nature DOI suffix ≠ "/s...": Not a research article
Audio long read: AI has dreamt up a blizzard of new proteins. Do any of them actually work?
Ewen Callaway, Benjamin Thompson
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Daily briefing: Earliest-known alphabet found on relics from Syrian tomb
Jacob Smith
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Nature DOI suffix ≠ "/s...": Not a research article
How I put LinkedIn to work for my career as a scientist and entrepreneur
Ashley Ruba
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Nature DOI suffix ≠ "/s...": Not a research article
How close is AI to human-level intelligence?
Anil Ananthaswamy
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Watch this bird-inspired drone leap into the air
Dan Fox
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What’s the secret to living to 100? Centenarian stem cells could offer clues
Smriti Mallapaty
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The contentious genius who made black holes real
Davide Castelvecchi
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Public trust in science can be diminished by communicating uncertainty
Hannah Little
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Great power and great responsibility: how consciousness changes the world
Alan C. Love
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Abundant plant gas forms aerosol particles at high altitude — and could affect the climate
James Allan
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Ageing of stem cells reduces their capacity to form tumours
Tatiana Cañeque, Raphaël Rodriguez
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Daily briefing: What is ageing? Even gerontologists don’t agree
Flora Graham
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A brain circuit that links hunger signals with the jaw movements of eating
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Nature Human Behaviour

How trait impressions of faces shape subsequent mental state inferences
Chujun Lin, Umit Keles, Mark A. Thornton, Ralph Adolphs
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Social and genetic diversity in first farmers of central Europe
Pere Gelabert, Penny Bickle, Daniela Hofmann, Maria Teschler-Nicola, Alexandra Anders, Xin Huang, Michelle Hämmerle, Iñigo Olalde, Romain Fournier, Harald Ringbauer, Ali Akbari, Olivia Cheronet, Iosif Lazaridis, Nasreen Broomandkhoshbacht, Daniel M. Fernandes, Katharina Buttinger, Kim Callan, Francesca Candilio, Guillermo Bravo Morante, Elizabeth Curtis, Matthew Ferry, Denise Keating, Suzanne Freilich, Aisling Kearns, Éadaoin Harney, Ann Marie Lawson, Kirsten Mandl, Megan Michel, Victoria Oberreiter, Brina Zagorc, Jonas Oppenheimer, Susanna Sawyer, Constanze Schattke, Kadir Toykan Özdoğan, Lijun Qiu, J. Noah Workman, Fatma Zalzala, Swapan Mallick, Matthew Mah, Adam Micco, Franz Pieler, Juraj Pavuk, Alena Šefčáková, Catalin Lazar, Andrej Starović, Marija Djuric, Maja Krznarić Škrivanko, Mario Šlaus, Željka Bedić, Friederike Novotny, László D. Szabó, Orsolya Cserpák-Laczi, Tamara Hága, László Szolnoki, Zsigmond Hajdú, Pavel Mirea, Emese Gyöngyvér Nagy, Zsuzsanna M. Virág, Attila Horváth M., László András Horváth, Katalin T. Biró, László Domboróczki, Tamás Szeniczey, János Jakucs, Márta Szelekovszky, Farkas Zoltán, Sándor József Sztáncsuj, Krisztián Tóth, Piroska Csengeri, Ildikó Pap, Róbert Patay, Anđelka Putica, Branislav Vasov, Bálint Havasi, Katalin Sebők, Pál Raczky, Gabriella Lovász, Zdeněk Tvrdý, Nadin Rohland, Mario Novak, Matej Ruttkay, Maria Krošláková, Jozef Bátora, Tibor Paluch, Dušan Borić, János Dani, Martin Kuhlwilm, Pier Francesco Palamara, Tamás Hajdu, Ron Pinhasi, David Reich
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Limited diffusion of scientific knowledge forecasts collapse
Donghyun Kang, Robert S. Danziger, Jalees Rehman, James A. Evans
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Proceedings of the National Academy of Sciences

GPT-4o mini: Non-social science research article
Sustainability of animal-sourced foods and plant-based alternatives
Matin Qaim, Rodolphe Barrangou, Pamela C. Ronald
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GPT-4o mini: Non-social science research article
Permafrost thaw subsidence, sea-level rise, and erosion are transforming Alaska’s Arctic coastal zone
Roger Creel, Julia Guimond, Benjamin M. Jones, David M. Nielsen, Emily Bristol, Craig E. Tweedie, Pier Paul Overduin
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Arctic shorelines are vulnerable to climate change impacts as sea level rises, permafrost thaws, storms intensify, and sea ice thins. Seventy-five years of aerial and satellite observations have established coastal erosion as an increasing Arctic hazard. However, other hazards at play—for instance, the cumulative impact that sea-level rise and permafrost thaw subsidence will have on permafrost shorelines—have received less attention, preventing assessments of these processes’ impacts compared to and combined with coastal erosion. Alaska’s Arctic Coastal Plain (ACP) is ideal for such assessments because of the high-density observations of topography, coastal retreat rates, and permafrost characteristics, and importance to Indigenous communities and oilfield infrastructure. Here, we produce 21st-century projections of Arctic shoreline position that include erosion, permafrost subsidence, and sea-level rise. Focusing on the ACP, we merge 5 m topography, satellite-derived coastal lake depth estimates, and empirical assessments of land subsidence due to permafrost thaw with projections of coastal erosion and sea-level rise for medium and high emissions scenarios from the Intergovernmental Panel on Climate Change’s AR6 Report. We find that by 2100, erosion and inundation will together transform the ACP, leading to 6-8x more land loss than coastal erosion alone and disturbing 8-11x more organic carbon. Without mitigating measures, by 2100, coastal change could damage 40 to 65% of infrastructure in present-day ACP coastal villages and 10 to 20% of oilfield infrastructure. Our findings highlight the risks that compounding climate hazards pose to coastal communities and underscore the need for adaptive planning for Arctic coastlines in the 21st century.
GPT-4o mini: Non-social science research article
Alternative splicing of Clock transcript mediates the response of circadian clocks to temperature changes
Yao D. Cai, Xianhui Liu, Gary K. Chow, Sergio Hidalgo, Kiya C. Jackson, Cameron D. Vasquez, Zita Y. Gao, Vu H. Lam, Christine A. Tabuloc, Haiyan Zheng, Caifeng Zhao, Joanna C. Chiu
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Circadian clocks respond to temperature changes over the calendar year, allowing organisms to adjust their daily biological rhythms to optimize health and fitness. In Drosophila , seasonal adaptations are regulated by temperature-sensitive alternative splicing (AS) of period ( per ) and timeless ( tim ) genes that encode key transcriptional repressors of clock gene expression. Although Clock ( Clk ) gene encodes the critical activator of circadian gene expression, AS of its transcripts and its potential role in temperature regulation of clock function have not been explored. Here, we observed that Clk transcripts undergo temperature-sensitive AS. Specifically, cold temperature leads to the production of an alternative Clk transcript, hereinafter termed Clk -cold, which encodes a CLK isoform with an in-frame deletion of four amino acids proximal to the DNA binding domain. Notably, serine 13 (S13), which we found to be a CK1α-dependent phosphorylation site, is deleted in CLK-cold protein. We demonstrated that upon phosphorylation at CLK(S13), CLK-DNA interaction is reduced, thus decreasing transcriptional activity of CLK. This is in agreement with our findings that CLK occupancy at clock genes and transcriptional output are elevated at cold temperature likely due to higher amounts of CLK-cold isoforms that lack S13 residue. Finally, we showed that PER promotes CK1α-dependent phosphorylation of CLK(S13), supporting kinase-scaffolding role of repressor proteins as a conserved feature in the regulation of eukaryotic circadian clocks. This study provides insights into the complex collaboration between AS and phospho-regulation in shaping temperature responses of the circadian clock.
GPT-4o mini: Non-social science research article
Flow field design and visualization for flow-through type aqueous organic redox flow batteries
Kang Peng, Chenxiao Jiang, Zirui Zhang, Chao Zhang, Jing Wang, Wanjie Song, Yunxin Ma, Gonggen Tang, Peipei Zuo, Zhengjin Yang, Tongwen Xu
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Aqueous organic redox flow batteries (AORFBs), which exploit the reversible redox reactions of water-soluble organic electrolytes to store electricity, have emerged as a promising electrochemical energy storage technology. Organic electrolytes possess fast electron-transfer rates that are two or three orders of magnitude faster than those of their inorganic or organometallic counterparts; therefore, their performance at the electrode is limited by mass transport. Direct adoption of conventional cell stacks with flow fields designed for inorganic electrolytes may compromise AORFB performance owing to severe cell polarization. Here, we report the design of a flow field for flow-through type AORFBs based on three-dimensional multiphysics simulation, to realize the uniform distribution of electrolyte flow and flow enhancements within a porous electrode. The electrolyte flow is visualized by operando imaging. Our results show that multistep distributive flow channels at the inlet and point-contact blocks at the outlet are crucial geometrical merits of the flow field, significantly reducing local concentration overpotentials. The prototype pH-neutral TEMPTMA/MV cell at 1.5 M assembled with the optimized flow field exhibits a peak power density of 267.3 mW cm −2 . The flow field design enables charging of the cell at current densities up to 300 mA cm −2 , which is unachievable with the conventional serpentine flow field, where immediate voltage cutoff of the cell occurs. Our results highlight the importance of AORFB cell stack engineering and provide a method to visualize electrolyte flow, which will be appealing to the field of aqueous flow batteries.
GPT-4o mini: Non-social science research article
Non-Gaussian diffusive fluctuations in Dirac fluids
Sarang Gopalakrishnan, Ewan McCulloch, Romain Vasseur
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Dirac fluids—interacting systems obeying particle–hole symmetry and Lorentz invariance—are among the simplest hydrodynamic systems; they have also been studied as effective descriptions of transport in strongly interacting Dirac semimetals. Direct experimental signatures of the Dirac fluid are elusive, as its charge transport is diffusive as in conventional metals. In this paper, we point out a striking consequence of fluctuating relativistic hydrodynamics: The full counting statistics (FCS) of charge transport is highly non-Gaussian. We predict the exact asymptotic form of the FCS, which generalizes a result previously derived for certain interacting integrable systems. A consequence is that, starting from quasi-one-dimensional nonequilibrium initial conditions, charge noise in the hydrodynamic regime is parametrically enhanced relative to that in conventional diffusive metals.
GPT-4o mini: Non-social science research article
Shortcuts to flexible structures
D. Zeb Rocklin
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GPT-4o mini: Non-social science research article
Autonomous phototaxis of hydrogel swimmers
S. Doruk Cezan, Aaveg Aggarwal, Chuang Li, Hang Yuan, Liam C. Palmer, Monica Olvera de la Cruz, Samuel I. Stupp
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The design of synthetic soft matter capable of emulating the complex behaviors of living organisms, such as sensing and adapting to their environment, remains an important challenge in developing biomimetic materials. Functionalized hydrogels are ideal candidates for such materials since they are highly responsive to their environment and can be operated in water. In this work, we investigate a hybrid bonding hydrogel composed of peptide amphiphile supramolecular nanofibers covalently attached to a photoresponsive network, in which high-aspect-ratio ferromagnetic nanowires are aligned along the length of the sample, designed to swim under oscillating magnetic fields. This hybrid hydrogel swimmer can autonomously swim toward a light source by utilizing photoinduced interactions between supramolecular and covalent networks reminiscent of phototactic swimming in living systems. Using a combination of experimental techniques and a continuum model incorporating photochemistry, magnetoelasticity, and hydrodynamics, we explain the swimming mechanism and predict phototactic behavior. Our work highlights the potential role of hybrid bonding polymers, which leverage the interplay between supramolecular assemblies and covalent networks. We demonstrate how these polymers can be tailored to react dynamically to their environment, paving the way for developing intelligent and autonomous robotic systems.
GPT-4o mini: Non-social science research article
C9orf72-linked arginine-rich dipeptide repeats aggravate pathological phase separation of G3BP1
Margot Van Nerom, Junaid Ahmed, Tamas Lazar, Attila Meszaros, Quentin Galand, Wim De Malsche, Joris Van Lindt, Rita Pancsa, Dominique Maes, Peter Tompa
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The toxic effects of C9orf72-derived arginine-rich dipeptide repeats (R-DPRs) on cellular stress granules in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia remain unclear at the molecular level. Stress granules are formed through the switch of Ras GTPase-activating protein-binding protein 1 (G3BP1) by RNA from a closed inactive state to an open activated state, driving the formation of the organelle by liquid–liquid phase separation (LLPS). We show that R-DPRs bind G3BP1 a thousand times stronger than RNA and initiate LLPS much more effectively. Their pathogenic effect is underscored by the slow transition of R-DPR–G3BP1 droplets to aggregated, ThS-positive states that can recruit ALS-linked proteins hnRNPA1, hnRNPA2, and TDP-43. Deletion constructs and molecular simulations show that R-DPR binding and LLPS are mediated via the negatively charged intrinsically disordered region 1 (IDR1) of the protein, allosterically regulated by its positively charged IDR3. Bioinformatic analyses point to the strong mechanistic parallels of these effects with the interaction of R-DPRs with nucleolar nucleophosmin 1 (NPM1) and underscore that R-DPRs interact with many other similar nucleolar and stress-granule proteins, extending the underlying mechanism of R-DPR toxicity in cells. Our results also highlight characteristic differences between the two R-DPRs, poly-GR and poly-PR, and suggest that the primary pathological target of poly-GR is not NPM1 in nucleoli, but G3BP1 in stress granules in affected cells.
GPT-4o mini: Non-social science research article
Magnetochrome-catalyzed oxidation of ferrous iron by MamP enables magnetite crystal growth in the magnetotactic bacterium AMB-1
Matthieu Amor, Daniel M. Chevrier, Marina I. Siponen, Ramon Egli, Ernesto Scoppola, Lourdes Marcano, Chenghao Li, Fadi Choueikani, Damien Faivre
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Magnetotactic bacteria have evolved the remarkable capacity to biomineralize chains of magnetite [Fe(II)Fe(III) 2 O 4 ] nanoparticles that align along the geomagnetic field and optimize their navigation in the environment. Mechanisms enabling magnetite formation require the complex action of numerous proteins for iron acquisition, sequestration in dedicated magnetosome organelles, and precipitation into magnetite. The MamP protein contains c-type cytochromes called magnetochrome domains that are found exclusively in magnetotactic bacteria. Ablation of magnetochromes in MamP prevents bacteria from aligning with external magnetic fields, showing their importance to maintain this biological function. MamP has been proposed, mostly from in vitro experimentations, to regulate iron redox state and maintain an Fe(II)/Fe(III) balance compatible with magnetite formation via the iron oxidase activity of magnetochromes. To test the proposed function for MamP in vivo in the magnetotactic strain Magnetospirillum magneticum (AMB)-1, we characterized the iron species in chemical MamP-mediated magnetite syntheses as well as in bacteria unable to produce MamP using a combination of physicochemical methodologies. We show that MamP has no apparent control on the speciation and oxidation state of intracellular iron or on the Fe(II)/Fe(III) balance in magnetite. We propose that MamP promotes magnetite growth by incorporating Fe(III) into preexisting magnetite seeds and that magnetite structure and stoichiometry is maintained by further equilibration with dissolved Fe(II) in magnetosome organelles.
GPT-4o mini: Non-social science research article
A multicriteria analysis of meat and milk alternatives from nutritional, health, environmental, and cost perspectives
Marco Springmann
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Reducing meat and dairy intake has been identified as a necessary strategy for mitigating the high environmental impacts food systems are currently having on climate change, biodiversity loss associated with land-use changes, and freshwater use. Having a choice of dedicated meat and milk replacements available to consumers can help in the transition toward more plant-based diets, but concerns about nutritional and health impacts and high costs can impede uptake. Here, we conduct a multicriteria assessment of 24 meat and milk alternatives that integrates nutritional, health, environmental, and cost analyses with a focus on high-income countries. Unprocessed plant-based foods such as peas, soybeans, and beans performed best in our assessment across all domains. In comparison, processed plant-based products such as veggie burgers, traditional meat replacements such as tempeh, and plant milks were associated with less climate benefits and greater costs than unprocessed foods but still offered substantial environmental, health, and nutritional benefits compared to animal products. Our findings suggest that a range of food products exist that when replacing meat and dairy in current diets would have multiple benefits, including reductions in nutritional imbalances, dietary risks and mortality, environmental resource use and pollution, and when choosing unprocessed foods over processed ones also diet costs. The findings provide support for public policies and business initiatives aimed at increasing their uptake.
GPT-4o mini: Non-social science research article
Structure of yeast RAVE bound to a partial V 1 complex
Hanlin Wang, Maureen Tarsio, Patricia M. Kane, John L. Rubinstein
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Vacuolar-type ATPases (V-ATPases) are membrane-embedded proton pumps that acidify intracellular compartments in almost all eukaryotic cells. Homologous with ATP synthases, these multisubunit enzymes consist of a soluble catalytic V 1 subcomplex and a membrane-embedded proton-translocating V O subcomplex. The V 1 and V O subcomplexes can undergo reversible dissociation to regulate proton pumping, with reassociation of V 1 and V O requiring the protein complex known as RAVE (regulator of the ATPase of vacuoles and endosomes). In the yeast Saccharomyces cerevisiae , RAVE consists of subunits Rav1p, Rav2p, and Skp1p. We used electron cryomicroscopy (cryo-EM) to determine a structure of yeast RAVE bound to V 1 . In the structure, RAVE is an L-shaped complex with Rav2p pointing toward the membrane and Skp1p distant from both the membrane and V 1 . Only Rav1p interacts with V 1 , binding to a region of subunit A not found in the corresponding ATP synthase subunit. When bound to RAVE, V 1 is in a rotational state suitable for binding the free V O complex, but in the structure, it is partially disrupted, missing five of its 16 subunits. Other than these missing subunits and the conformation of the inhibitory subunit H, the V 1 complex with RAVE appears poised for reassembly with V O .
GPT-4o mini: Non-social science research article
Caspase-8-dependent autophagy regulates neutrophil infiltration in oral squamous cell carcinoma
Miguel Bernabé-Rubio, Fiona M. Watt
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Oral squamous cell carcinoma (OSCC) is a subtype of head and neck cancer that arises in the multilayered epithelia of the mouth and lips. Although inactivating mutations in CASP8 are frequently found in human OSCC their role in the disease is unknown. To investigate this, we deleted Casp8 in the oral epithelium of adult mice. Loss of Caspase-8 resulted in defects in the tongue epithelial barrier and triggered a neutrophil-rich immune infiltrate distinct from that observed on epidermal Casp8 deletion. Oral Casp8 deletion led to activation of autophagy. Inhibition of autophagy partially rescued epithelial integrity in Casp8 −/− mice, while induction of autophagy in wild type mice resulted in oral barrier defects and excessive neutrophil infiltration. On treatment with the carcinogen 4-nitroquinoline-1-oxide Casp8 −/− mice showed increased susceptibility to developing oral tumors. Depletion of neutrophils reduced tumor incidence, which correlated with a reduction in reactive oxygen species and decreased epithelial DNA damage. Our findings establish a functional link between epithelial integrity, autophagy, and the tumor immune microenvironment, placing Caspase-8 at the center of these processes.
GPT-4o mini: Non-social science research article
Glutamine is critical for the maintenance of type 1 conventional dendritic cells in normal tissue and the tumor microenvironment
Graham P. Lobel, Nanumi Han, William A. Molina Arocho, Michal Silber, Jason Shoush, Michael C. Noji, Tsun Ki Jerrick To, Li Zhai, Nicholas P. Lesner, M. Celeste Simon, Malay Haldar
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Proliferating tumor cells take up glutamine for anabolic processes, engendering glutamine deficiency in the tumor microenvironment. How this might impact immune cells is not well understood. Using multiple mouse models of soft tissue sarcomas, glutamine antagonists, as well as genetic and pharmacological inhibition of glutamine utilization, we found that the number and frequency of conventional dendritic cells (cDCs) is dependent on microenvironmental glutamine levels. cDCs comprise two distinct subsets—cDC1s and cDC2s, with the former subset playing a critical role in antigen cross-presentation and tumor immunity. While both subsets show dependence on glutamine, cDC1s are particularly sensitive. Notably, glutamine antagonism did not reduce the frequency of DC precursors but decreased the proliferation and survival of cDC1s. Further studies suggest a role of the nutrient sensing mechanistic target of rapamycin (mTOR) signaling pathway in this process. Taken together, these findings uncover glutamine dependence of cDC1s that is coopted by tumors to escape immune responses.
GPT-4o mini: Non-social science research article
An innovative strategy for radical-mediated, bidirectional controlled disulfide exchange
Bohan Li, Zhenguo Zhang, Raymond Tio, Jinling Li, Teck-Peng Loh
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Metathesis reactions that operate cleanly and reversibly under biocompatible conditions are crucial in diverse fields such as drug development, chemical biology, and dynamic combinatorial chemistry. This paper introduces an innovative strategy using the commercially available and cost-effective hydroxy(tosyloxy)iodobenzene (HTIB) as a radical initiator, enabling clean and bidirectional disulfide metathesis under biocompatible conditions. Our method facilitates efficient forward reactions by utilizing an excess of one disulfide to shift the equilibrium toward unsymmetrical disulfides, while also ensuring clean reverse reactions by the removal of low boiling point dimethyl disulfide. Furthermore, an alternative intramolecular approach using a cyclic five- or eight-membered disulfide avoids the need for an excess of one disulfide, effectively yielding unsymmetrical disulfide molecules. The radical mechanism of this approach, validated through various control experiments and EPR analysis, enables selective and biocompatible modifications of carbohydrates, drugs, native amino acids, and proteins. This study represents a notable advancement in organic chemistry, with significant implications for biomedical sciences, especially in areas that require precise and gentle biomolecular manipulations, such as protein engineering and therapeutic development.
GPT-4o mini: Non-social science research article
Quantum oscillations in the hole-doped cuprates and the confinement of spinons
Pietro M. Bonetti, Maine Christos, Subir Sachdev
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A long-standing problem in the study of the under-hole-doped cuprates has been the description of the Fermi surfaces underlying the high magnetic field quantum oscillations, and their connection to the higher temperature pseudogap metal. Harrison and Sebastian [ Phys. Rev. Lett. 106 , 226402 (2011)] proposed that the pseudogap “Fermi arcs” are reconstructed into an electron pocket by field-induced charge density wave order. But computations on such a model [Zhang and Mei, Europhys. Lett. 114 , 47008 (2016)] show an unobserved additional oscillation frequency from a Fermi surface arising from the backsides of the hole pockets completing the Fermi arcs. We describe a transition from a fractionalized Fermi liquid (FL*) model of the pseudogap metal, to a metal with bidirectional charge density wave order without fractionalization. We show that the confinement of the fermionic spinon excitations of the FL* across this transition can eliminate the unobserved oscillation frequency.
GPT-4o mini: Non-social science research article
Active doping controls the mode of failure in dense colloidal gels
Tingtao Zhou, John F. Brady
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Mechanical properties of disordered materials are governed by their underlying free energy landscape. In contrast to external fields, embedding a small fraction of active particles within a disordered material generates nonequilibrium internal fields, which can help to circumvent kinetic barriers and modulate the free energy landscape. In this work, we investigate through computer simulations how the activity of active particles alters the mechanical response of deeply annealed polydisperse colloidal gels. We show that the “swim force” generated by the embedded active particles is responsible for determining the mode of mechanical failure, i.e., brittle vs. ductile. We find, and theoretically justify, that at a critical swim force the mechanical properties of the gel decrease abruptly, signaling a change in the mode of mechanical failure. The weakening of the elastic modulus above the critical swim force results from the change in gel porosity and distribution of attractive forces among gel particles, while below the critical swim force, the ductility enhancement is caused by an increase of gel structural disorder. Above the critical swim force, the gel develops a pronounced heterogeneous structure characterized by multiple pore spaces, and the mechanical response is controlled by dynamical heterogeneities. We contrast these results with those of a simulated monodisperse gel that exhibits a nonmonotonic trend of ductility modulation with increasing swim force, revealing a complex interplay between the gel energy landscape and embedded activity.
GPT-4o mini: Non-social science research article
Electrocatalytic nitrate reduction using iron single atoms for sustainable ammonium supplies to increase rice yield
Chunlei Liu, Jingchen Ma, Manting Wang, Jingru Xu, Chao Zhu, Guibing Zhu
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Increasing food production and ensuring drinking water safety have always been a focus of attention, especially for people in underdeveloped regions of the world. Traditional excessive fertilizer applications have increased crop yield but also caused groundwater nitrate pollution. Agricultural irrigating water is an important reservoir for nitrogen (N) (e.g., nitrate) accumulation after fertilization. Ammonium (NH 4 + -N) is a more readily absorbed N form by rice than nitrate (NO 3 − -N). In this study, we proposed a strategy using iron single-atom catalysts (Fe-SAC) to selectively reduce NO 3 − -N to NH 4 + -N from the real paddy field irrigating water to provide sustainable NH 4 + -N supplies for rice uptakes, thereby highlighting decreasing N fertilizer applications and mitigating NO 3 − -N pollution. Then, we constructed a solar-energy-driven electrochemical reactor for NO 3 − -N reduction, with the Fe single atom as the core catalyst, and achieved an average NH 4 + -N selectivity of 80.2 ± 2.6% with no additional energy input. Sustainable NH 4 + -N supplies resulted in a 30.4 % increase in the 100-grain weight of the cultivated rice and a 50% decrease of fertilizer application than those of the fertilization group in the pot experiment, which were one of the best values ever reported. Furthermore, the 15 N isotope tracing results indicated a N use efficiency (NUE) from 15 NO 3 − -N of 71.2 ± 3.2%. Sustainable NH 4 + -N supplies played a key role in promoting rice root development which contributed to the high NUE. Our study shares unique insights in increasing grain yield, reducing fertilizer applications, and preventing nitrate leaching into groundwater.
GPT-4o mini: Non-social science research article
OmpA controls order in the outer membrane and shares the mechanical load
Georgina Benn, Carolina Borrelli, Dheeraj Prakaash, Alex N. T. Johnson, Vincent A. Fideli, Tahj Starr, Dylan Fitzmaurice, Ashton N. Combs, Martin Wühr, Enrique R. Rojas, Syma Khalid, Bart W. Hoogenboom, Thomas J. Silhavy
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OmpA, a predominant outer membrane (OM) protein in Escherichia coli , affects virulence, adhesion, and bacterial OM integrity. However, despite more than 50 y of research, the molecular basis for the role of OmpA has remained elusive. In this study, we demonstrate that OmpA organizes the OM protein lattice and mechanically connects it to the cell wall (CW). Using gene fusions, atomic force microscopy, simulations, and microfluidics, we show that the β-barrel domain of OmpA is critical for maintaining the permeability barrier, but both the β-barrel and CW–binding domains are necessary to enhance the cell envelope’s strength. OmpA integrates the compressive properties of the OM protein lattice with the tensile strength of the CW, forming a mechanically robust composite that increases overall integrity. This coupling likely underpins the ability of the entire envelope to function as a cohesive, resilient structure, critical for the survival of bacteria.
GPT-4o mini: Non-social science research article
eLemur: A cellular-resolution 3D atlas of the mouse lemur brain
Hyungju Jeon, Jiwon Kim, Jayoung Kim, Yoon Kyoung Choi, Chun Lum Andy Ho, Fabien Pifferi, Daniel Huber, Linqing Feng, Jinhyun Kim
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The gray mouse lemur ( Microcebus murinus ), one of the smallest living primates, emerges as a promising model organism for neuroscience research. This is due to its genetic similarity to humans, its evolutionary position between rodents and humans, and its primate-like features encapsulated within a rodent-sized brain. Despite its potential, the absence of a comprehensive reference brain atlas impedes the progress of research endeavors in this species, particularly at the microscopic level. Existing references have largely been confined to the macroscopic scale, lacking detailed anatomical information. Here, we present eLemur, a unique resource, comprising a repository of high-resolution brain-wide images immunostained with multiple cell type and structural markers, elucidating the cyto- and chemoarchitecture of the mouse lemur brain. Additionally, it encompasses a segmented two-dimensional reference and 3D anatomical brain atlas delineated into cortical, subcortical, and other vital regions. Furthermore, eLemur includes a comprehensive 3D cell atlas, providing densities and spatial distributions of non-neuronal and neuronal cells across the mouse lemur brain. Accessible via a web-based viewer ( https://eeum-brain.com/#/lemurdatasets ), the eLemur resource streamlines data sharing and integration, fostering the exploration of different hypotheses and experimental designs using the mouse lemur as a model organism. Moreover, in conjunction with the growing 3D datasets for rodents, nonhuman primates, and humans, our eLemur 3D digital framework enhances the potential for comparative analysis and translation research, facilitating the integration of extensive rodent study data into human studies.
GPT-4o mini: Non-social science research article
K ATP channel–dependent electrical signaling links capillary pericytes to arterioles during neurovascular coupling
Dominic Isaacs, Liuruimin Xiang, Ashwini Hariharan, Thomas A. Longden
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The brain has evolved mechanisms to dynamically modify blood flow, enabling the timely delivery of energy substrates in response to local metabolic demands. Several such neurovascular coupling (NVC) mechanisms have been identified, but the vascular signal transduction and transmission mechanisms that enable dilation of penetrating arterioles (PAs) remote from sites of increased neuronal activity are unclear. Given the exponential relationship between vessel diameter and blood flow, tight control of arteriole membrane potential and diameter is a crucial aspect of NVC. Recent evidence suggests that capillaries play a major role in sensing neural activity and transmitting signals to modify the diameter of upstream vessels. Thin-strand pericyte cell bodies and processes cover around 90% of the capillary bed, and here we show that these cells play a central role in sensing neural activity and generating and relaying electrical signals to arterioles. We identify a K ATP channel–dependent neurovascular signaling pathway that is explained by the recruitment of thin-strand pericytes and we deploy vascular optogenetics to show that currents generated in individual thin-strand pericytes are sent over long distances to upstream arterioles to cause dilations in vivo. Genetic disruption of vascular K ATP channels reduces the arteriole diameter response to neural activity and laser ablation of thin-strand pericytes eliminates the K ATP -dependent component of NVC. Together, our findings indicate that thin-strand pericytes sense neural activity and transform this into K ATP channel–dependent electrometabolic signals that inform upstream arterioles of local energy needs, promoting spatiotemporally precise energy distribution.
GPT-4o mini: Non-social science research article
An integrated picture of the structural pathways controlling the heart performance
Ilaria Morotti, Marco Caremani, Matteo Marcello, Irene Pertici, Caterina Squarci, Pasquale Bianco, Theyencheri Narayanan, Gabriella Piazzesi, Massimo Reconditi, Vincenzo Lombardi, Marco Linari
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The regulation of heart function is attributed to a dual filament mechanism: i) the Ca 2+ -dependent structural changes in the regulatory proteins of the thin, actin-containing filament making actin available for myosin motor attachment, and ii) the release of motors from their folded (OFF) state on the surface of the thick filament allowing them to attach and pull the actin filament. Thick filament mechanosensing is thought to control the number of motors switching ON in relation to the systolic performance, but its molecular basis is still controversial. Here, we use high spatial resolution X-ray diffraction data from electrically paced rat trabeculae and papillary muscles to provide a molecular explanation of the modulation of heart performance that calls for a revision of the mechanosensing hypothesis. We find that upon stimulation, titin-mediated structural changes in the thick filament switch motors ON throughout the filament within ~½ the maximum systolic force. These structural changes also drive Myosin Binding Protein-C (MyBP-C) to promote first motor attachments to actin from the central 1/3 of the half-thick filament. Progression of attachments toward the periphery of half-thick filament with increase in systolic force is carried on by near-neighbor cooperative thin filament activation by attached motors. The identification of the roles of MyBP-C, titin, thin and thick filaments in heart regulation enables their targeting for potential therapeutic interventions.
GPT-4o mini: Non-social science research article
On the control of cell proliferation
D. Thirumalai, Rajsekhar Das, Xin Li
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GPT-4o mini: Non-social science research article
Permafrost instability negates the positive impact of warming temperatures on boreal radial growth
Raquel Alfaro-Sánchez, Andrew D. Richardson, Sharon L. Smith, Jill F. Johnstone, Merritt R. Turetsky, Steven G. Cumming, James M. Le Moine, Jennifer L. Baltzer
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Climate warming can alleviate temperature and nutrient constraints on tree growth in boreal regions, potentially enhancing boreal productivity. However, in permafrost environments, warming also disrupts the physical foundation on which trees grow, leading to leaning trees or “drunken” forests. Tree leaning might reduce radial growth, undermining potential benefits of warming. Here, we found widespread radial growth reductions in southern latitude boreal forests since the 1980s. At mid latitudes, radial growth increased from ~1980 to ~2000 but showed recent signs of decline afterward. Increased growth was evident since the 1980 s at higher latitudes, where radial growth appears to be temperature limited. However, recent changes in permafrost stability, and the associated increased frequency of tree leaning events, emerged as a significant stressor, leading to reduced radial growth in boreal trees at the highest latitudes, where permafrost is extensive. We showed that trees growing in unstable permafrost sites allocated more nonstructural carbohydrate reserves to offset leaning which compromised radial growth and potential carbon uptake benefits of warming. This higher allocation of resources in drunken trees is needed to build the high-density reaction wood, rich in lignin, that is required to maintain a vertical position. With continued climate warming, we anticipate widespread reductions in radial growth in boreal forests, leading to lower carbon sequestration. These findings enhance our understanding of how climate warming and indirect effects, such as ground instability caused by warming permafrost, will affect boreal forest productivity in the future.
GPT-4o mini: Non-social science research article
Nutrient-dense foods and diverse diets are important for ensuring adequate nutrition across the life course
Ty Beal, Swetha Manohar, Lais Miachon, Jessica Fanzo
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The world faces a global challenge of how to meet the nutritional needs of a diverse global population through diets. This paper defines the relative nutritional needs across each stage of the life cycle to support human health and identifies who is nutritionally vulnerable. Findings in this paper suggest that there are biological nutritional vulnerabilities stemming from high micronutrient needs per calorie in certain phases of the life cycle, particularly for infants and young children, women of reproductive age, pregnant and lactating women, and older adults, particularly older women. The paper demonstrates the role of micronutrient-dense animal-source foods and plant-source foods important in meeting essential nutrient needs to support healthy growth, development, and aging across vulnerable stages of the life cycle.
GPT-4o mini: Non-social science research article
TRPC6 is a mechanosensitive channel essential for ultrasound neuromodulation in the mammalian brain
Yumi Matsushita, Kaede Yoshida, Miyuki Yoshiya, Takahiro Shimizu, Satoshi Tsukamoto, Nobuki Kudo, Yuichi Takeuchi, Makoto Higuchi, Masafumi Shimojo
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Ultrasound neuromodulation has become an innovative technology that enables noninvasive intervention in mammalian brain circuits with high spatiotemporal precision. Despite the expanding utility of ultrasound neuromodulation in the neuroscience research field and clinical applications, the molecular and cellular mechanisms by which ultrasound impacts neural activity in the brain are still largely unknown. Here, we report that transient receptor potential canonical 6 (TRPC6), a mechanosensitive nonselective cation channel, is essential for ultrasound neuromodulation of mammalian neurons in vitro and in vivo. We first demonstrated that ultrasound irradiation elicited rapid and robust Ca 2+ transients mediated via extracellular Ca 2+ influx in cultured mouse cortical and hippocampal neurons. Ultrasound-induced neuronal responses were massively diminished by blocking either the generation of action potential or synaptic transmission. Importantly, both pharmacological inhibition and genetic deficiency of TRPC6 almost completely abolished neuronal responses to ultrasound. Furthermore, we found that intracerebroventricular administration of a TRPC6 blocker significantly attenuated the number of neuronal firings in the cerebral cortex evoked by transcranial ultrasound irradiation in mice. Our findings indicate that TRPC6 is an indispensable molecule of ultrasound neuromodulation in intact mammalian brains, providing fundamental understanding of biophysical molecular mechanisms of ultrasound neuromodulation as well as insight into its future feasibility in neuroscience and translational research in humans.
GPT-4o mini: Non-social science research article
Direct simulation and machine learning structure identification unravel soft martensitic transformation and twinning dynamics
Jun-ichi Fukuda, Kazuaki Z. Takahashi
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Phase transition between ordered phases has garnered attention from the viewpoint of materials science as well as statistical physics. One interesting example is martensitic transformation and the resulting formation of twin structures, in which atoms or molecules that form one crystalline phase move in a concerted and diffusionless manner toward another crystalline phase. Recently martensitic transformation has been observed experimentally also in various soft materials. However, the complex internal structures involving many molecules have eluded direct investigation of the dynamical processes of martensitic transformation. Here, we carry out a direct simulation of mesoscale structural transition of a liquid crystalline blue phase (BP) of cubic symmetry, known as BP II. The dynamics is simulated by a Langevin-type equation for the orientational order parameter with thermal fluctuations. We demonstrate that machine-learning-aided analysis of local structures successfully unravels the transformation process from a perfect lattice of BP II to a twinned lattice of another BP (BP I). The nucleation of BP I is initiated by the breakup of junctions of line defects (disclinations), followed by the deformation of disclination network. We further show that twinned BP I is reversibly transformed to a perfect lattice of BP II by temperature variation. Order-parameter-based simulations with machine-learning-aided local structure identification provide valuable insights into not only the martensitic transformation of soft materials but also a wider class of complex structural transitions between ordered phases.
GPT-4o mini: Non-social science research article
Widespread neuroanatomical integration and distinct electrophysiological properties of glioma-innervating neurons
Annie L. Hsieh, Sanika Ganesh, Tomasz Kula, Madiha Irshad, Emily A. Ferenczi, Wengang Wang, Yi-Ching Chen, Song-Hua Hu, Zongyu Li, Shakchhi Joshi, Marcia C. Haigis, Bernardo L. Sabatini
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Gliomas are the most common malignant primary brain tumor and are often associated with severe neurological deficits and mortality. Unlike many cancers, gliomas rarely metastasize outside the brain, indicating a possible dependency on unique features of brain microenvironment. Synapses between neurons and glioma cells exist, suggesting that glioma cells rely on neuronal inputs and synaptic signaling for proliferation. Yet, the locations and properties of neurons that innervate gliomas have remained elusive. In this study, we utilized transsynaptic tracing with an EnvA-pseudotyped, glycoprotein-deleted rabies virus to specifically infect TVA and glycoprotein-expressing human glioblastoma cells in an orthotopic xenograft mouse model, allowing us to identify the neurons that form synapses onto the gliomas. Comprehensive whole-brain mapping revealed that these glioma-innervating neurons (GINs) from brain regions, including diverse neuromodulatory centers and specific cortical layers, known to project to the glioma locations. Molecular profiling revealed that long-range cortical GINs are predominantly glutamatergic, and subsets express both glutamatergic and GABAergic markers, whereas local striatal GINs are largely GABAergic. Electrophysiological studies demonstrate that while GINs share passive intrinsic properties with cortex-innervating neurons, their action potential waveforms are altered. Our study introduces a method for identifying and mapping GINs and reveals their consistent integration into existing location-dependent neuronal networks involving diverse neurotransmitters and neuromodulators. The observed intrinsic electrophysiological differences in GINs lay the groundwork for future investigations into how these alterations relate to the postsynaptic characteristics of glioma cells.
GPT-4o mini: Non-social science research article
Mapping the FF domain folding pathway via structures of transiently populated folding intermediates
Debajyoti De, Nemika Thapliyal, Ved Prakash Tiwari, Yuki Toyama, D. Flemming Hansen, Lewis E. Kay, Pramodh Vallurupalli
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Despite the tremendous accomplishments of AlpaFold2/3 in predicting biomolecular structure, the protein folding problem remains unsolved in the sense that accurate atomistic models of how protein molecules fold into their native conformations from an unfolded ensemble are still elusive. Here, using chemical exchange saturation transfer (CEST) NMR experiments and a comprehensive four-state kinetic model of the folding trajectory of a 71 residue four-helix bundle FF domain from human HYPA/FBP11 we present an atomic resolution structure of a transiently formed intermediate, I2, that along with the structure of a second intermediate, I1, provides a description of the FF domain folding trajectory. By recording CEST profiles as a function of urea concentration the extent of compaction along the folding pathway is evaluated. Our data establish that unlike the partially disordered I1 state, the I2 intermediate that is also formed before the rate-limiting folding barrier is well ordered and compact like the native conformer, while retaining nonnative interactions similar to those found in I1. The slow-interconversion from I2 to F, involving changes in secondary structure and the breaking of nonnative interactions, proceeds via a compact transition-state. Interestingly, the native state of the FF1 domain from human p190-A Rho GAP resembles the I2 conformation, suggesting that well-ordered folding intermediates can be repurposed by nature in structurally related proteins to assume functional roles. It is anticipated that the strategy for elucidation of sparsely populated and transiently formed structures of intermediates along kinetic pathways described here will be of use in other studies of protein dynamics.
GPT-4o mini: Non-social science research article
Shielding the Hägg carbide by a graphene layer for ultrahigh carbon efficiency during syngas conversion
Xueqing Zhang, Zhe Li, Wei Sun, Yuhua Zhang, Jinlin Li, Li Wang
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Fischer-Tropsch synthesis represents a key endeavor aimed at converting nonpetroleum carbon resources into clean fuels and valuable chemicals. However, the current state-of-the-art industrial FTS employing Fe-based catalysts is still challenged by the low carbon efficiency (<50%), mainly attributed to the prominent formation of CO 2 and CH 4 resulting from the nonregulated side water gas shift reaction. Herein, we describe a shielding strategy involving the encapsulation of the active Hägg carbide (χ-Fe 5 C 2 ) by a graphene layer, exhibiting excellent resilience under reaction conditions and exposure to air, thereby eliminating the need for reduction or activation before the Fischer-Tropsch synthesis reaction. The graphene layer helps to stabilize the Hägg carbide active phase, and more importantly, greatly suppresses the side water gas shift reaction. Theoretical calculations suggest that graphene shielding inhibits the water gas shift reaction by reducing the absorption strength of OH x species. Remarkably, the optimum χ-Fe 5 C 2 @Graphene catalyst demonstrates a minimized CO 2 and CH 4 formation of only 4.6% and 5.9%, resulting in a high carbon efficiency (ca. 90%) for value-added products. These results are expected to inspire unique designs of Fe-based nanocomposite for highly efficient FTS with regulated carbon transfer pathways.
GPT-4o mini: Non-social science research article
Spontaneous emergence of straintronics effects and striped stacking domains in untwisted three-layer epitaxial graphene
Martin Rejhon, Nitika Parashar, Lorenzo Schellack, Mykhailo Shestopalov, Jan Kunc, Elisa Riedo
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Emergent electronic phenomena, from superconductivity to ferroelectricity, magnetism, and correlated many-body band gaps, have been observed in domains created by stacking and twisting atomic layers of Van der Waals materials. In graphene, emergent properties have been observed in ABC stacking domains obtained by exfoliation followed by expert mechanical twisting and alignment with the desired orientation, a process very challenging and nonscalable. Here, conductive atomic force microscopy shows in untwisted epitaxial graphene grown on SiC the surprising presence of striped domains with dissimilar conductance, a contrast that demonstrates the presence of ABA and ABC domains since it matches exactly the conductivity difference observed in ABA/ABC domains in twisted exfoliated graphene and calculated by density functional theory. The size and geometry of the stacking domains depend on the interplay between strain, solitons crossing, and shape of the three-layer regions. Interestingly, we demonstrate the growth of three-layer regions in which the ABA/ABC stacking domains self-organize in stable stripes of a few tens of nanometers. The growth-controlled production of isolated and stripe-shaped ABA/ABC domains open the path to fabricate quantum devices on these domains. These findings on self-assembly formation of ABA/ABC epitaxial graphene stripes on SiC without the need of time-consuming and nonscalable graphene exfoliation, alignment, and twisting provide different potential applications of graphene in electronic devices.
GPT-4o mini: Non-social science research article
The essential role of TTC28 in maintaining chromosomal stability via HSPA8 chaperone-mediated autophagy
Ge Zhang, Meiyi Xiang, Liankun Gu, Jing Zhou, Baozhen Zhang, Wei Tian, Dajun Deng
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There are three distinct forms of autophagy, namely, macroautophagy, microautophagy, and HSPA8 chaperone-mediated autophagy (CMA). While macroautophagy is widely recognized as a regulator of chromosomal instability (CIN) through various pathways, the contributions of CMA and microautophagy to CIN remain uncertain. TTC28 , a conserved gene in vertebrates, is frequently mutated and down-regulated in numerous human cancers. This study presents findings demonstrating the interaction between human tetratricopeptide repeat domain 28 (TTC28) and heat shock protein member 8 (HSPA8) and lysosomal-associated membrane protein 2A proteins. The tetratricopeptide repeat domains of TTC28 bind to the C-terminal motif (PTIEEVD) in HSPA8, resulting in the subsequent degradation of TTC28 via CMA/microautophagy. Notably, the baseline frequency of micronuclei (FMN) in human cancer cells with TTC28 knockout cells was three times greater than that in cells with wild-type TTC28 (7.7% vs. 2.3%, P = 4.86E−09). Furthermore, the overexpression of Ttc28 mitigated the impact of TTC28 knockout on FMN (11.9% vs. 4.8%, P = 2.83E−11). Our findings also demonstrate that CMA has a protective effect on genome stability and that TTC28 plays an essential role in the effect of CMA. These results were further supported by the quantification of γH2AX and comet analyses and the analysis of The Cancer Genome Atlas data via bioinformatics. Mechanistically, TTC28 regulates mitosis and cytokinesis, which are involved in the maintenance of genome integrity by CMA. In conclusion, our study demonstrated that TTC28 is not only an HSPA8-mediated CMA/microautophagy substrate but also essential for maintaining chromosomal stability via CMA. Comprehensive TTC28 downregulation may lead to CIN in cancer cells.
GPT-4o mini: Non-social science research article
Understanding the superconductivity and charge density wave interaction through quasi-static lattice fluctuations
Zach Porter, Lingjia Shen, Rajan Plumley, Nicolas G. Burdet, Alexander N. Petsch, Jiajia Wen, Nathan C. Drucker, Cheng Peng, Xiaoqian M. Chen, Andrei Fluerasu, Elizabeth Blackburn, Giacomo Coslovich, David G. Hawthorn, Joshua J. Turner
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In unconventional superconductors, coupled charge and lattice degrees of freedom can manifest in ordered phases of matter that are intertwined. In the cuprate family, fluctuating short-range charge correlations can coalesce into a longer-range charge density wave (CDW) order which is thought to intertwine with superconductivity, yet the nature of the interaction is still poorly understood. Here, by measuring subtle lattice fluctuations in underdoped YBa 2 Cu 3 O 6+ y on quasi-static timescales (thousands of seconds) through X-ray photon correlation spectroscopy, we report sensitivity to both superconductivity and CDW. The atomic lattice shows remarkably faster relaxational dynamics upon approaching the superconducting transition at T c ≈ 65 K. By tracking the momentum dependence, we show that the intermediate scattering function almost monotonically scales with the relaxation distance of atoms away from their average positions above T c and in the presence of the CDW state, while this peculiar trend is reversed for other temperatures. These observations are consistent with an incipient CDW stabilized by local strain. This work provides insights into the crucial role of relaxational atomic fluctuations for understanding the electronic physics cuprates, which are inherently disordered due to carrier doping.
GPT-4o mini: Non-social science research article
Very broad distribution of β sheet registries of the HIV gp41 fusion peptide supports mutational robustness for fusion and infection
Yijin Zhang, Scott D. Schmick, Li Xie, Ujjayini Ghosh, David P. Weliky
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HIV, like other membrane-enveloped viruses, has protein spikes that include a fusion peptide (Fp) segment that binds the host cell membrane and plays a critical role in fusion (joining) viral and cell membranes. The HIV Fp is the ~23 N-terminal residues of the gp41 spike protein. Fp adopts intermolecular antiparallel β sheet structure when lipid fraction cholesterol ≈0.3, which is comparable to host cells. Rotational-echo double-resonance NMR was applied to probe the registries (alignments) of adjacent Fp molecules in membrane-bound sheets. The data were fitted to determine quantitative populations, f(t)’s, of individual antiparallel registries indexed by t, the number of residues in the registry. Both wild-type (WT) and fusion-defective V2E Fp sheets have broad but very different registry distributions, each with at least eight populated registries with f(t) > 0.02, and t WT = 16.1 and ⟨t⟩ V2E = 18.5. The broad WT distribution likely improves mutational robustness for HIV, as Fp is a neutralization epitope of the immune system, and Fp mutations are required for immune evasion during chronic HIV infection. V2E fusion is reduced because longer Fp sheets increase separation between initially apposed membranes. The f(t) WT were well-fitted to free energies that were sums of contributions from sheet length, aligned leucines, and sidechain membrane insertion. The f(t) V2E ’s were similarly well-fitted except there wasn’t the insertion contribution. Relative to V2E, WT fusion is enhanced by deeper membrane insertion of Fp with accompanying greater dislocation of neighboring lipids. This study provides a rare quantitative determination of broad molecular structural distributions by experiment.
GPT-4o mini: Non-social science research article
Killer meiotic drive executed by two alternative conformations of a single protein
Sarah E. Zanders, Gerald R. Smith
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GPT-4o mini: Non-social science research article
Mitigating methane emissions in grazing beef cattle with a seaweed-based feed additive: Implications for climate-smart agriculture
Paulo Meo-Filho, John F. Ramirez-Agudelo, Ermias Kebreab
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The ruminant livestock sector considerably contributes to global greenhouse gas emissions. This study investigates the effectiveness of pelleted bromoform-containing seaweed ( Asparagopsis taxiformis ) (Brominata) as an enteric methane (CH 4 ) inhibitor in grazing beef cattle. The primary objective was to assess the impact of this antimethanogenic additive on enteric CH 4 emissions under real-world farm conditions. Twenty-four beef steers, crossbreeds of Wagyu and Angus, with an average liveweight of 399 ± 21.7 kg, were allocated to two treatment groups: Control and Brominata. These animals underwent regular weigh-ins every 14 d, and measurements of CH 4 , carbon dioxide (CO 2 ), and hydrogen (H 2 ) emissions were conducted using the GreenFeed system. Statistical analysis was conducted using SAS 9.4, wherein the model incorporated fixed effects for treatment, time, their interaction, and a covariate, while accounting for animal variations as a random effect within each phase. Three phases of bromoform intake were identified: a 3-wk ramp-up phase, a 3-wk optimal phase, and a 2-wk decreasing phase. No differences were observed between the weekly initial and final liveweight, average daily gain, and predicted dry matter intake. During optimal and decreasing phases, average enteric CH 4 emissions were significantly reduced in steers that received Brominata supplementation compared to those without supplementation (115 vs. 185 g/d, respectively). Additionally, both groups had similar CO 2 emissions (6.8 vs. 7.2 kg/d), while H 2 emissions were lower in the control group (3.4 vs. 1.8 g/d). The findings suggest that pelleted bromoform-containing feed additive has the potential to reduce enteric CH 4 emissions from grazing beef cattle.
GPT-4o mini: Non-social science research article
Dynamics and mechanism of DNA repair by a bifunctional cryptochrome
Luyao Yan, Xiaodan Cao, Lijuan Wang, Jie Chen, Aziz Sancar, Dongping Zhong
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Photolyase and cryptochrome belong to a group of structurally similar flavoproteins but with two distinct functions of DNA repair as a photoenzyme and signal transduction as a photoreceptor, respectively, under blue-light illumination. Here, we studied a recently discovered bifunctional Chlamydomonas reinhardtii cryptochrome (CraCRY) with focus on its repair of UV-induced pyrimidine-pyrimidone (6-4) photoproduct (6-4PP). We used femtosecond spectroscopy and site-directed mutagenesis to map out the critical elementary steps by following the dynamics of initial reactants, various intermediates, and final products. We observed initial direct ultrafast electron tunneling from the hydroquinone flavin cofactor to 6-4PP in 300 ps through an intervening adenine as a mediator, minimizing the electron bifurcation of a two-step hopping pathway bridged also by the adenine as an intermediate. The subsequent proton transfer (PT) from the neighboring histidine to anionic 6-4PP in 2 ns is critical and competes with the futile back electron transfer in 151 ps. Mutations of either of two histidines in the active site nearly abolish repair, indicating their essential role on repair reactivity and structural integrity. These results elucidate the electron-coupled PT mechanism and the repair photocycle of this bifunctional cryptochrome at the molecular level, further supporting that the hydroquinone flavin is the active state in vivo for dual functions or one of the two functions is excessive.
GPT-4o mini: Non-social science research article
Transcriptional reprogramming primes CD8+ T cells toward exhaustion in Myalgic encephalomyelitis/chronic fatigue syndrome
David S. Iu, Jessica Maya, Luyen T. Vu, Elizabeth A. Fogarty, Adrian J. McNairn, Faraz Ahmed, Carl J. Franconi, Paul R. Munn, Jennifer K. Grenier, Maureen R. Hanson, Andrew Grimson
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Myalgic encephalomyelitis/chronic fatigue syndrome (ME) is a severe, debilitating disease, with substantial evidence pointing to immune dysregulation as a key contributor to pathophysiology. To characterize the gene regulatory state underlying T cell dysregulation in ME, we performed multiomic analysis across T cell subsets by integrating single-cell RNA-seq, RNA-seq, and ATAC-seq and further analyzed CD8+ T cell subpopulations following symptom provocation. Specific subsets of CD8+ T cells, as well as certain innate T cells, displayed the most pronounced dysregulation in ME. We observed upregulation of key transcription factors associated with T cell exhaustion in CD8+ T cell effector memory subsets, as well as an altered chromatin landscape and metabolic reprogramming consistent with an exhausted immune cell state. To validate these observations, we analyzed expression of exhaustion markers using flow cytometry, detecting a higher frequency of exhaustion-associated factors. Together, these data identify T cell exhaustion as a component of ME, a finding which may provide a basis for future therapies, such as checkpoint blockade, metabolic interventions, or drugs that target chronic viral infections.
GPT-4o mini: Non-social science research article
A perspective on the environmental impact of plant-based protein concentrates and isolates
William R. Aimutis, Rohan Shirwaiker
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Plant-based proteins are promoted as nutritious, environmentally safe, and a key element for food security. Numerous studies using environmental life cycle assessments confirmed plant-based meat alternatives are more environmentally favorable than animal-derived meat. However, most missed other factors from protein extraction and concentration that contribute to environmental impact (both positive and negative). Furthermore, few studies examined the entire environmental impact because they overlooked social and nutritional life cycle assessments. Many publications assumed most environmental impact occurred in crop cultivation before high protein products are manufactured. However, industrial plant-based protein extraction, concentration, and purification require large amounts of natural resources, energy, chemicals, and highly specialized equipment seldom accurately assessed from an environmental, social, and nutritional perspective. This paper presents opinions and perspectives on additional information to consider to fully realize environmental benefits of highly proteinaceous plant-based food ingredients. Elements are also discussed we perceive as “hot spots” for future assessments in presenting a complete picture for minimizing environmental impact and how the numerous actors in this supply chain can transform our food system and secure protein availability for future generations.
GPT-4o mini: Non-social science research article
A corollary discharge circuit in human speech
Amirhossein Khalilian-Gourtani, Ran Wang, Xupeng Chen, Leyao Yu, Patricia Dugan, Daniel Friedman, Werner Doyle, Orrin Devinsky, Yao Wang, Adeen Flinker
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When we vocalize, our brain distinguishes self-generated sounds from external ones. A corollary discharge signal supports this function in animals; however, in humans, its exact origin and temporal dynamics remain unknown. We report electrocorticographic recordings in neurosurgical patients and a connectivity analysis framework based on Granger causality that reveals major neural communications. We find a reproducible source for corollary discharge across multiple speech production paradigms localized to the ventral speech motor cortex before speech articulation. The uncovered discharge predicts the degree of auditory cortex suppression during speech, its well-documented consequence. These results reveal the human corollary discharge source and timing with far-reaching implication for speech motor-control as well as auditory hallucinations in human psychosis.
GPT-4o mini: Non-social science research article
In This Issue
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GPT-4o mini: Non-social science research article
Sculpting new visual categories into the human brain
Coraline Rinn Iordan, Victoria J. H. Ritvo, Kenneth A. Norman, Nicholas B. Turk-Browne, Jonathan D. Cohen
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Learning requires changing the brain. This typically occurs through experience, study, or instruction. We report an alternate route for humans to acquire visual knowledge, through the direct sculpting of activity patterns in the human brain that mirror those expected to arise through learning. We used neurofeedback from closed-loop real-time functional MRI to create new categories of visual objects in the brain, without the participants’ explicit awareness. After neural sculpting, participants exhibited behavioral and neural biases for the learned, but not for the control categories. The ability to sculpt new perceptual distinctions into the human brain offers a noninvasive research paradigm for causal testing of the link between neural representations and behavior. As such, beyond its current application to perception, our work potentially has broad relevance for advancing understanding in other domains of cognition such as decision-making, memory, and motor control.
GPT-4o mini: Non-social science research article
Navigated range expansion promotes migratory culling
Yi Zhang, Qingjuan Hu, Yingtong Su, Pan Chu, Ting Wei, Xuefei Li, Chenli Liu, Xiongfei Fu
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Motile organisms can expand into new territories and increase their fitness, while nonmotile viruses usually depend on host migration to spread across long distances. In general, faster host motility facilitates virus transmission. However, recent ecological studies have also shown that animal host migration can reduce viral prevalence by removing infected individuals from the migratory group. Here, we use a bacteria-bacteriophage copropagation system to investigate how host motility affects viral spread during range expansion. We find that phage spread during chemotaxis-driven navigated range expansion decreases as bacterial migration speed increases. Theoretical and experimental analyses show that the navigated migration leads to a spatial sorting of infected and uninfected hosts in the copropagating front of bacteria-bacteriophage, with implications for the number of cells left behind. The preferential loss of infected cells in the copropagating front inhibits viral spread. Further increase in host migration speed leads to a phase transition that eliminates the phage completely. These results illustrate that navigated range expansion of the host can promote the migratory culling of infectious diseases in the migration group.
GPT-4o mini: Non-social science research article
Co-free gradient lithium-rich cathode for high-energy batteries with optimized cyclability
Haotian Yang, Lihang Wang, Yuqiang Li, Zengqing Zhuo, Tianhao Wu, Jie Liu, Ligang Xu, Haozhe Du, Shiqi Liu, Lingqiao Wu, Shu Zhao, Mingxue Tang, Wanli Yang, Haijun Yu
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Lithium-rich layered oxides (LLOs) hold the promise for high-energy battery cathodes. However, its application has been hindered by voltage decay associated with irreversible reactions at high voltages despite decades of intensive efforts. Here, we first theoretically studied the molecular orbitals of Mn-based Li-rich configurations. We found that the π -bond ring formed within the LiMn 6 structure could participate in stable redox reactions as one unit, but Co could disrupt its symmetry. We thus designed and synthesized Co-free concentration-gradient LLOs (CF-CG-LLOs) materials. The combination of concentration gradient and Co removal leads to exceptional capacity retention without any fading over 100 cycles of the pouch cell. More importantly, it exhibits an extraordinarily low voltage decay of 0.15 mV/cycle, accompanied by a high Coulombic efficiency of 99.86%. This concept and demonstration of CF-CG-LLO cathodes reveal a viable avenue toward low-cost, high-energy-density battery cathodes.
GPT-4o mini: Non-social science research article
Animal-sourced foods improve child nutrition in Africa
Makaiko G. Khonje, Matin Qaim
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Child undernutrition remains a widespread public health problem in the Global South, especially in Africa. Childhood stunting—meaning linear growth retardation—is a comprehensive and commonly used indicator of chronic child undernutrition and is mostly the result of insufficient nutrient intake, among other factors. Previous research showed that the consumption of animal-sourced foods (ASF), including meat, dairy, eggs, and fish, is associated with lower rates of child stunting, but reliable evidence for Africa is scant. In Africa, average ASF consumption is low. We use representative panel data from five African countries—Ethiopia, Malawi, Nigeria, Tanzania, and Uganda—with over 32,000 observations from children aged 0 to 5 y to show that ASF consumption increases mean child height-for-age Z-scores (HAZ) by 0.30 ( P < 0.01) and reduces the likelihood of stunting by 6.8 percentage points ( P < 0.01), after controlling for confounding factors. The child nutritional benefits of diets containing ASF are larger than those of purely plant-based diets. Nutritious plant-based foods, such as fruits, vegetables, and legumes, can provide most of the nutrients required and also have positive effects on HAZ, but they are sometimes not available and accessible in sufficient quantities all year round, especially in rural areas. Given the large environmental footprints of livestock farming, initiatives to make food systems more sustainable often call for a strong reduction in ASF consumption. While ASF consumption should be reduced where consumption quantities are high, our results suggest that poor households’ access to ASF in Africa should be further improved to help reduce child undernutrition.
GPT-4o mini: Non-social science research article
Metabolic scaling from cells to catchments
Pablo A. Marquet, Aurora Gaxiola
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GPT-4o mini: Non-social science research article
Texas: A green hydrogen hub to decarbonize the United States and beyond
Haiyang Lin, Andres Hernandez Gonzalez, Chris P. Nielsen, Michael B. McElroy
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As the largest oil and gas producer in the United States, Texas confronts significant challenges in its shift toward decarbonization. This study explores the potential for green hydrogen in Texas as a substitute for current development, underscoring numerous advantages such as ample renewables, established demand, and operational infrastructure. We present an hourly-resolution, cross-sector assessment framework to optimize grid-integrated green hydrogen supply paths from managing local applications to meeting potential export opportunities. The analysis indicates that by 2030, Texas could have over 50 million tons of green hydrogen available at $1.5/kg. Even with the incrementality, deliverability, and temporal matching requirements of 45 V, green hydrogen remains more competitive than blue hydrogen. On the supply side, the grid-electrolysis integration results in synergetic benefits, including overall cost reductions, less curtailment of renewables, and enhanced operational flexibility and reliability. On the demand side, this cost-competitive hydrogen could bring the cost of hydrogen fueling and ammonia production down to $4/kg and $350/ton respectively, with a significant impact in replacing fossil fuels in transport and industry. For most of the states, green hydrogen and ammonia imported from Texas could become an affordable alternative to local supplies. Through both onshore pipelines and offshore shipments, Texas has the potential to develop as a major green fuel supplier, aiding in decarbonization efforts not only for the United States but also beyond.
GPT-4o mini: Non-social science research article
Dissection revisited: Deciphering bodies and ancient medical texts
Andres Pelavski, Esteban Marroquin-Arroyave, Joshua Milgram, Orly Lewis
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Unlike traditional approaches to Greco-Roman medicine, which are strongly based on textual evidence, we addressed some problems, currently debated by historians, through a technique borrowed from the biological sciences: We reenacted an ancient anatomical dissection of the abdominal wall, the peritoneal cavity, and its organs (as described by Galen during the 2nd century CE, in his major treatise Anatomical Proceedings). Our aim was to clarify incongruencies about the text itself—considering the errors generated during its 14-century-long hand-copied manuscript tradition—and infer answers to contextual questions, such as the aim of the author, his audience, and the setting where the dissections took place. This hands-on practical method provided extratextual evidence to ongoing scholarly debates, which until now were mainly approached through textual scrutiny.
GPT-4o mini: Non-social science research article
Colossal magnetoresistance from spin-polarized polarons in an Ising system
Ying-Fei Li, Emily M. Been, Sudhaman Balguri, Chun-Jing Jia, Mira B. Mahendru, Zhi-Cheng Wang, Yi Cui, Su-Di Chen, Makoto Hashimoto, Dong-Hui Lu, Brian Moritz, Jan Zaanen, Fazel Tafti, Thomas P. Devereaux, Zhi-Xun Shen
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Recent experiments suggest a new paradigm toward novel colossal magnetoresistance (CMR) in a family of materials EuM 2 X 2 (M = Cd, In, Zn; X = P, As), distinct from the traditional avenues involving Kondo–Ruderman–Kittel–Kasuya–Yosida crossovers, magnetic phase transitions with structural distortions, or topological phase transitions. Here, we use angle-resolved photoemission spectroscopy and density functional theory calculations to explore their origin, particularly focusing on EuCd 2 P 2 . While the low-energy spectral weight royally tracks that of the resistivity anomaly near the temperature with maximum magnetoresistance ( T MR ) as expected from transport-spectroscopy correspondence, the spectra are completely incoherent and strongly suppressed with no hint of a Landau quasiparticle. Using systematic material and temperature dependence investigation complemented by theory, we attribute this nonquasiparticle caricature to the strong presence of entangled magnetic and lattice interactions, a characteristic enabled by the p - f mixing. Given the known presence of ferromagnetic clusters, this naturally points to the origin of CMR being the scattering of spin-polarized polarons at the boundaries of ferromagnetic clusters. These results are not only illuminating to investigate the strong correlations and topology in EuCd 2 X 2 family, but, in a broader view, exemplify how multiple cooperative interactions can give rise to extraordinary behaviors in condensed matter systems.
GPT-4o mini: Non-social science research article
Utilizing reconstruction achieves ultrastable water electrolysis
Yu Lin, Danji Huang, Qunlei Wen, Ruoou Yang, Bowen Chen, Yi Shen, Youwen Liu, Jiakun Fang, Huiqiao Li, Tianyou Zhai
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The dissolution of active atoms under operating potential will lead to a decline in their oxygen evolution reaction (OER) performance, thus preventing the current highly active catalysts from being practically applicable in industrial water electrolysis. Here, we propose a sequential leaching strategy to utilize the dynamic restructuring and enhance the chemical bond strength for highly active and stable OER. Modeling on nickel-iron sulfides (NiFe-S), we introduced and utilized foreign Mo dopant preleaching as the sacrificial agent to alleviate the oxidation corrosion of partial M─S bonds. Operando spectroscopic reveal that foreign Mo dopant leach from the matrix and then adsorb on the surface of NiFe O(S)OH as molybdate at lower OER potential. The crystal occupation hamiltonian population analysis uncovers that the charge transfer from molybdate into NiFe O(S)OH will enhance bond energy of M─S, thus preventing further S and Fe/Ni leaching. By manipulating ion leaching, the resulting active phase achieves an ultralow overpotential of 250 mV at 400 mA cm −2 and high stability of more than 3,700 h at 100 mA cm −2 . An industrial water electrolysis equipment using our catalysts delivered ultralow energy consumption of 4.30 kWh m −3 H2 and record stability over 250 h (2,300 h lifetime by epitaxial method with 10% attenuation) under a high working current of 8,000 mA. The hydrogen production cost of US$2.46/kg H2 aligns with the green hydrogen cost target set by the European Commission for the coming decade.
GPT-4o mini: Non-social science research article
Correction for Scavia et al., Water quality–fisheries tradeoffs in a changing climate underscore the need for adaptive ecosystem–based management
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GPT-4o mini: Non-social science research article
Correction for Park et al., Specific inhibition of an anticancer target, polo-like kinase 1, by allosterically dismantling its mechanism of substrate recognition
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GPT-4o mini: Non-social science research article
Actin polymerization counteracts prewetting of N-WASP on supported lipid bilayers
Tina Wiegand, Jinghui Liu, Lutz Vogeley, Isabel LuValle-Burke, Jan Geisler, Anatol W. Fritsch, Anthony A. Hyman, Stephan W. Grill
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Cortical condensates, transient punctate-like structures rich in actin and the actin nucleation pathway member Neural Wiskott-Aldrich syndrome protein (N-WASP), form during activation of the actin cortex in the Caenorhabditis elegans oocyte. Their emergence and spontaneous dissolution is linked to a phase separation process driven by chemical kinetics. However, the mechanisms that drive the onset of cortical condensate formation near membranes remain unexplored. Here, using a reconstituted phase separation assay of cortical condensate proteins, we demonstrate that the key component, N-WASP, can collectively undergo surface condensation on supported lipid bilayers via a prewetting transition. Actin partitions into the condensates, where it polymerizes and counteracts the N-WASP prewetting transition. Taken together, the dynamics of condensate-assisted cortex formation appear to be controlled by a balance between surface-assisted condensate formation and polymer-driven condensate dissolution. This opens perspectives for understanding how the formation of complex intracellular structures is affected and controlled by phase separation.
GPT-4o mini: Non-social science research article
Opportunities and challenges of plant proteins as functional ingredients for food production
Lara Etzbach, Susanne Gola, Fabian Küllmer, Ismail-Hakki Acir, Daria Wohlt, Laura Melanie Ignatzy, Stephanie Bader-Mittermaier, Ute Schweiggert-Weisz
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Consumer interest in meat and dairy alternatives drives demand for plant-based protein ingredients. While soy and gluten dominate the market, there is a trend to explore alternative crops for functional ingredient production. The multitude of ingredients poses challenges for food manufacturers in selecting the right protein. We investigated 61 commercially available protein ingredients from various sources, categorizing them based on their protein content into protein-rich flours (protein content less than 50%), protein concentrates (protein content between 50% and 80%), and protein isolates (protein content higher than 80%). Methionine, cysteine, and lysine were decisive for the amino acid score, which even varied between ingredients produced from the same raw material. Such differences were also observed in the protein solubility profiles, characterized by their raw material–specific protein pattern. By focusing on soy, pea, and fava bean ingredients, the broad spectra of emulsifying and foaming properties were illustrated. These ranged from non–emulsifying and non–foaming to high emulsifying capacities of 737 mL/g ingredient and foaming activities of 2,278%, accompanied by a foam stability of 100%. Additionally, we demonstrated that the functionality of ingredients obtained from different batches could vary by up to 24% relative SD. Protein solubility, powder wettability, color, and particle size were determined as key properties for the differentiation of soy, pea, and fava bean protein ingredients by principal component analysis. In our study conclusion, we propose essential measures for overcoming challenges in protein ingredient production and utilization to realize their full potential in fostering sustainable and innovative plant-based food production.
GPT-4o mini: Non-social science research article
RAD51 plays critical roles in DNMT1-mediated maintenance methylation of genomic DNA by dually regulating the ubiquitin ligase UHRF1
Guangxue Liu, Kaiyan Huang, Shiyao Liu, Yali Xie, Jinyan Huang, Tingbo Liang, Pumin Zhang
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RAD51 is related to the bacterial RecA protein and is best known for its role in homologous recombination-mediated repair of DNA damage. Here, we report an unexpected function of RAD51 in the maintenance methylation of genomic DNA, a function that is separable from its role in homologous recombination. First, it acts as an inhibitor of the E3 ubiquitin ligase UHRF1. Deficiency in RAD51 causes excessive ubiquitination and degradation of the DNA methyltransferase DNMT1, leading to the loss of global DNA methylation. Second, RAD51 helps UHRF1 to monoubiquitinate histone H3 to generate DNMT1 recruiting signal. It binds H3 directly, enabling UHRF1 to bind and ubiquitinate H3 more readily. Disrupting the interaction between RAD51 and H3 diminishes DNMT1 recruitment and the failure of maintenance methylation of genomic DNA. Thus, RAD51 dually regulates UHRF1. These results establish RAD51 as a guardian of the integrity of both the genome and the epigenome.
GPT-4o mini: Non-social science research article
Addressing the 2050 demand for terrestrial animal source food
Alison L. Van Eenennaam
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The high emissions intensity of terrestrial animal source food (TASF) and projected increasing demand in low- and middle-income countries (LMIC) have spurred interest in the development of animal-free alternatives and manufactured food items that aim to substitute for meat, milk, and eggs with the promise of reduced environmental impact of producing food. The developing world is the source of 75% of global emissions from ruminants and will house 86% of the world’s human population by 2050. The adoption of cost-effective, genetic, feed and nutrition practices, and improving livestock health in LMIC are seen as the most promising interventions to reduce emissions resulting from projected increased TASF demand though 2050. Genetic improvement is a particularly attractive approach to productivity enhancements, as such improvements are permanent and cumulative. Alternative proteins may play a role in addressing demand for affordable sources of nutrient-dense foods, however, price will be a major factor influencing adoption given 3.1 billion people globally (42%) were currently unable to afford a healthy diet in 2021. Additionally, there is currently a mismatch between the location of alternative protein companies, and both projected increased TASF demand and emissions. To date, the vast majority (>81%) of these companies are based in high-income countries. The sustainability implications of replacing TASF with alternative proteins at scale needs to consider not only environmental metrics but also the wider economic and social sustainability impacts, given the essential role that livestock play in the livelihoods and food security of approximately 1.3 billion people.
Prenatal social disadvantage is associated with alterations in functional networks at birth
Ashley N. Nielsen, Regina L. Triplett, Lourdes M. Bernardez, Ursula A. Tooley, Max P. Herzberg, Rachel E. Lean, Sydney Kaplan, Dominique Meyer, Jeanette K. Kenley, Dimitrios Alexopoulos, David Losielle, Aidan Latham, Tara A. Smyser, Arpana Agrawal, Josh S. Shimony, Joshua J. Jackson, J. Philip Miller, Marcus E. Raichle, Barbara B. Warner, Cynthia E. Rogers, Chad M. Sylvester, Deanna M. Barch, Joan L. Luby, Christopher D. Smyser
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Childhood exposure to social disadvantage is a major risk factor for psychiatric disorders and poor developmental, educational, and occupational outcomes, presumably because adverse exposures alter the neurodevelopmental processes that contribute to risk trajectories. Yet, given the limited social mobility in the United States and other countries, childhood social disadvantage is frequently preceded by maternal social disadvantage during pregnancy, potentially altering fetal brain development during a period of high neuroplasticity through hormonal, microbiome, epigenetic, and immune factors that cross the placenta and fetal blood–brain barrier. The current study examines prenatal social disadvantage to determine whether these exposures in utero are associated with alterations in functional brain networks as early as birth. As part of the Early Life Adversity and Biological Embedding study, mothers were recruited during pregnancy, prenatal social disadvantage was assessed across trimesters, and their healthy, full-term offspring were imaged using resting-state functional magnetic resonance imaging during the first weeks of life. Multivariate machine learning methods revealed that neonatal functional connectivity (FC) varied as a function of prenatal exposure to social disadvantage (n = 261, R = 0.43, R 2 = 0.18), with validation in an independent sample. Alterations in FC associated with prenatal social disadvantage occurred brain-wide and were most pronounced in association networks (fronto-parietal, ventral attention, dorsal attention) and the somatomotor network. Amygdala FC was altered at birth, with a pattern shared across subcortical structures. These findings provide critical insights into how early in development functional networks begin to diverge in the context of social disadvantage and elucidate the functional networks that are most impacted.
Estimates of optimal supplies of animal-sourced foods differ by food system goal and socioeconomic context
Robin R. White, Mary Beth Hall
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Reduced consumption of animal-sourced food (ASF) has been recommended for environmental and human health objectives; however, ASF can be important for food security and diet affordability. We explored country-level relationships among various metrics of food supply, socioeconomic context, food security, diet affordability, and agricultural greenhouse gas emissions (GHGe) to characterize how optimal inclusion ranges for ASF vary with socioeconomic factors and food system goals. Data from 2015 to 2022 for 153 countries were sourced to generate Bayesian Networks representing relationships among the studied food system metrics. Networks were used in simulations to characterize optimal ASF inclusion to achieve environmental, food security, or diet affordability goals based on individual country data. Results are most appropriately interpreted in aggregate rather than as representations of specific countries due in large part to data limitations. Across countries simulated, median total ASF inclusion in the food supply to support food security, GHGe, or affordability objectives was 18.2% ± 12.1%, 11.9% ± 6.8%, and 17.6% ± 8.5%, respectively. Joint optimization for these goals resulted in median ASF inclusion of 15.1% ± 7.2%, with notable regional differences. Although ASF increases were supported in most developing regions, decreases were supported in developed countries. The reported SD in optimal ASF inclusion were considerable, and represented between-country variation. Empirical relationships of food categories to goals consistently favored dairy and egg products over meats. These results support previous literature highlighting the environmental intensity of ASF, but also indicate that moderate ASF supplies contribute to multiple food system goals simultaneously.
Substitution patterns and price response for plant-based meat alternatives
Steffen Jahn, Daniel Guhl, Ainslee Erhard
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Efforts to promote sustainable resource use through reduced meat consumption face challenges as global meat consumption persists. The resistance may be attributed to the lower sales price of meat compared to most plant-based meat alternatives (PBMAs). Addressing this, our research delves into the pivotal question of which PBMAs resonate most with consumers and how pricing affects demand. In a hypothetical restaurant context, we conducted 2 representative studies among 2,126 individuals in the United States to scrutinize preferences for meat, analog, semi-analog, and non-analog burgers. First, in a survey, we assessed rankings of the four burgers, alongside evaluating participants’ genuine consideration of these choices to discern a diverse preference distribution. Subsequently, in an experiment, we examined the influence of prices on participants’ consideration and choice of PBMAs, thereby capturing both phases of the decision-making process. Our survey shows that meat has considerably higher utility and consumer preference than all PBMAs on average, but we also find substantial heterogeneity (i.e., some consumers prefer PBMAs over meat). In the experiment, we establish that there is a negative association between the consideration of meat and PBMA burgers, though consideration of any one PBMA is positively associated with considering other PBMAs. A noteworthy increase in consideration and choice is observed when prices of PBMAs are reduced, while changing the price of the meat burger only has minimal effect on demand. Such findings underscore the importance of affordability beyond price parity in catalyzing the shift toward plant-based diets.
A summer bridge program for first-generation low-income students stretches academic ambitions with no adverse impacts on first-year GPA
Rebecca A. Johnson, Tyler Simko, Kosuke Imai
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A large body of research documents the barriers faced by first-generation, low-income (FGLI) students as “hidden minorities” on elite college campuses. Although existing studies show brief psychological interventions can help mitigate some of these obstacles, universities are investing in more intensive interventions that try to both shift mindsets and mitigate structural disadvantages in FGLI students’ academic preparation. In collaboration with the administrators at a highly selective university, we conducted a randomized controlled trial of a summer bridge program targeted at FGLI students. During summers between 2017 and 2019, we randomly selected 232 out of 418 first-generation or low-income students and invited them to attend an intensive, six-week-long residential summer program featuring courses for academic credit. Students randomized to the control group either interacted with online content offering no academic credit or had no summer intervention. Our preregistered analysis shows that the program encouraged FGLI students to pursue a more ambitious first-year program, increasing the proportion of nonintroductory courses by 7 percentage points. The program also increased the proportion of courses taken for a grade rather than as pass-fail by 6 percentage points. These improvements were accompanied by no discernible impact on first-year grade point averages (GPAs) and academic withdrawal. The findings show the potential to academically integrate FGLI students into selective university communities.
Social dilemma of nonpharmaceutical interventions: Determinants of dynamic compliance and behavioral shifts
Alina Glaubitz, Feng Fu
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In fighting infectious diseases posing a global health threat, ranging from influenza to Zika, nonpharmaceutical interventions (NPI), such as social distancing and face covering, remain mitigation measures public health can resort to. However, the success of NPI lies in sufficiently high levels of collective compliance, otherwise giving rise to recurrent infections that are not only driven by pathogen evolution but also changing vigilance in the population. Here, we show that compliance with each NPI measure can be highly dynamic and context-dependent during an ongoing epidemic, where individuals may prefer one to another or even do nothing, leading to intricate temporal switching behavior of NPI adoptions. By characterizing dynamic regimes through the perceived costs of NPI measures and their effectiveness in particular regarding face covering and social distancing, our work offers insights into overcoming barriers in NPI adoptions.
The costs of competition in distributing scarce research funds
Gerald Schweiger, Adrian Barnett, Peter van den Besselaar, Lutz Bornmann, Andreas De Block, John P. A. Ioannidis, Ulf Sandström, Stijn Conix
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Research funding systems fundamentally influence how science operates. This paper aims to analyze the allocation of competitive research funding from different perspectives: How reliable are decision processes for funding? What are the economic costs of competitive funding? How does competition for funds affect doing risky research? How do competitive funding environments affect scientists themselves, and which ethical issues must be considered? We attempt to identify gaps in our knowledge of research funding systems; we propose recommendations for policymakers and funding agencies, including empirical experiments of decision processes and the collection of data on these processes. With our recommendations, we hope to contribute to developing improved ways of organizing research funding.
Behavioral interventions to motivate plant-based food selection in an online shopping environment
Bhagyashree Katare, Shuoli Zhao
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Encouraging consumption of plant-based food products can help mitigate the impact of dietary choices on climate change. Research suggests that modifying environments in which people make purchasing decisions has the potential to achieve behavioral changes toward sustainable consumption. We examine the impact of two behavioral interventions, carbon footprint labeling, and product categorization, to promote sustainable food selection in an online grocery shopping environment. Online grocery shopping data collected from 2,359 US participants show that carbon footprint labels increased the selection of plant-based food products by 37% and categorization increased it by 25%. A combination of both nudges increased plant-based food selection by 32%. Participants underestimated the environmental impact of different types of foods despite exposure to carbon footprint information. As the global market for online grocery shopping continues to grow, this study presents a potential for simple and scalable interventions in online shopping environments to encourage sustainable choices.
Fact-checking information from large language models can decrease headline discernment
Matthew R. DeVerna, Harry Yaojun Yan, Kai-Cheng Yang, Filippo Menczer
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Fact checking can be an effective strategy against misinformation, but its implementation at scale is impeded by the overwhelming volume of information online. Recent AI language models have shown impressive ability in fact-checking tasks, but how humans interact with fact-checking information provided by these models is unclear. Here, we investigate the impact of fact-checking information generated by a popular large language model (LLM) on belief in, and sharing intent of, political news headlines in a preregistered randomized control experiment. Although the LLM accurately identifies most false headlines (90%), we find that this information does not significantly improve participants’ ability to discern headline accuracy or share accurate news. In contrast, viewing human-generated fact checks enhances discernment in both cases. Subsequent analysis reveals that the AI fact-checker is harmful in specific cases: It decreases beliefs in true headlines that it mislabels as false and increases beliefs in false headlines that it is unsure about. On the positive side, AI fact-checking information increases the sharing intent for correctly labeled true headlines. When participants are given the option to view LLM fact checks and choose to do so, they are significantly more likely to share both true and false news but only more likely to believe false headlines. Our findings highlight an important source of potential harm stemming from AI applications and underscore the critical need for policies to prevent or mitigate such unintended consequences.
Global adherence to a healthy and sustainable diet and potential reduction in premature death
Xiao Gu, Linh P. Bui, Fenglei Wang, Dong D. Wang, Marco Springmann, Walter C. Willett
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The Planetary Health Diet (PHD), also known as the EAT-Lancet reference diet, was developed to optimize global dietary quality while keeping the environmental impacts of food production within sustainable planetary boundaries. We calculated current national and global adherence to the PHD using the Planetary Health Dietary Index (PHDI). In addition, we used data on diet and mortality from three large US cohorts (n = 206,404 men and women, 54,536 deaths) to estimate the total and cause-specific mortality among adults 20 y of age and older that could be prevented by shifting from current diets to the reference PHD. The PHDI varied substantially across countries, although adherence was universally far from optimal (mean PHDI = 85 out of 140). By improving the global PHDI to 120, approximately 15 million deaths (27% of total deaths) could be prevented annually. Estimates of preventable deaths due to this shift ranged from 2.5 million for cardiovascular diseases to 0.7 million for neurodegenerative diseases. Our analysis suggests that adopting healthy and sustainable diets would have major direct health benefits by reducing mortality due to multiple diseases and could contribute substantially to achieving the United Nations Sustainable Development Goals. These numbers of preventable deaths are based on evidence that human biology is similar across racial and ethnic groups, but the exact numerical estimates should be interpreted with caution because some assumptions used for the calculations build on limited data. Refinement of these estimates will be possible when additional regional data on diet and mortality become available.

Science

GPT-4o mini: Non-social science research article
Tlr7 drives sex differences in age- and Alzheimer’s disease–related demyelination
Chloe Lopez-Lee, Lay Kodama, Li Fan, Daphne Zhu, Jingjie Zhu, Man Ying Wong, Pearly Ye, Kendra Norman, Nessa R. Foxe, Laraib Ijaz, Fangmin Yu, Hao Chen, Gillian K. Carling, Eileen R. Torres, Rachel D. Kim, Dena B. Dubal, Shane A. Liddelow, Subhash C. Sinha, Wenjie Luo, Li Gan
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Alzheimer’s disease (AD) and other age-related disorders associated with demyelination exhibit sex differences. In this work, we used single-nuclei transcriptomics to dissect the contributions of sex chromosomes and gonads in demyelination and AD. In a mouse model of demyelination, we identified the roles of sex chromosomes and gonads in modifying microglia and oligodendrocyte responses before and after myelin loss. In an AD-related mouse model expressing APOE4, XY sex chromosomes heightened interferon (IFN) response and tau-induced demyelination. The X-linked gene, Toll-like receptor 7 ( Tlr7 ), regulated sex-specific IFN response to myelin. Deletion of Tlr7 dampened sex differences while protecting against demyelination. Administering TLR7 inhibitor mitigated tau-induced motor impairment and demyelination in male mice, indicating that Tlr7 plays a role in the male-biased type I Interferon IFN response in aging- and AD-related demyelination.
GPT-4o mini: Non-social science research article
Footprint evidence for locomotor diversity and shared habitats among early Pleistocene hominins
Kevin G. Hatala, Neil T. Roach, Anna K. Behrensmeyer, Peter L. Falkingham, Stephen M. Gatesy, Erin Marie Williams-Hatala, Craig S. Feibel, Ibrae Dalacha, Martin Kirinya, Ezekiel Linga, Richard Loki, Apolo Alkoro, Longaye, Malmalo Longaye, Emmanuel Lonyericho, Iyole Loyapan, Nyiber Nakudo, Cyprian Nyete, Louise N. Leakey
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For much of the Pliocene and Pleistocene, multiple hominin species coexisted in the same regions of eastern and southern Africa. Due to the limitations of the skeletal fossil record, questions regarding their interspecific interactions remain unanswered. We report the discovery of footprints (~1.5 million years old) from Koobi Fora, Kenya, that provide the first evidence of two different patterns of Pleistocene hominin bipedalism appearing on the same footprint surface. New analyses show that this is observed repeatedly across multiple contemporaneous sites in the eastern Turkana Basin. These data indicate a sympatric relationship between Homo erectus and Paranthropus boisei , suggesting that lake margin habitats were important to both species and highlighting the possible influence of varying levels of coexistence, competition, and niche partitioning in human evolution.
GPT-4o mini: Non-social science research article
A new vision for American science
Sudip S. Parikh, Marcia K. McNutt, Darío Gil
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America’s scientific success is no accident. It has been powered by a decades-long commitment to federal investment in fundamental research that, in turn, nurtured both domestic and foreign talent and prompted the translation of breakthroughs to fuel the economy, improve health, fortify national security, and inspire awe. The world has benefited from the proliferation of this model, and partnerships between the US and other countries have resulted in game-changing discoveries, from medicines to machine learning. Yet what got America to this point will not get the country to where it needs to go. A new vision is required to respond to an evolving global science and technology ecosystem.
GPT-4o mini: Non-social science research article
Decadal oscillations in the ocean’s largest oxygen-deficient zone
N. N. Duprey, A. D. Foreman, J. D. Carriquiry, C. D. Charles, S. C. Sanchez, H. Vonhof, F. Rubach, R. Rabenstein, M. Rohr, H. Reyes-Bonilla, D. Marconi, D. M. Sigman, G. H. Haug, A. Martínez-García
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The impact of global warming on the ocean’s oxygen-deficient zones (ODZs) is uncertain, partly because of a lack of data on past changes. We report monthly resolved records of coral skeleton–bound nitrogen isotopes (CS-δ 15 N) to reconstruct denitrification in the Eastern Tropical North Pacific (ETNP) ODZ over the last 80 years. The data indicate strong decadal variation in ETNP denitrification, with maxima during the cool North Pacific phase of Pacific Decadal Variability. The maxima in denitrification (and thus oxygen deficiency) were likely due to stronger upwelling that enhanced productivity leading to greater oxygen demand in the thermocline. Prior findings of multidecadal-to-centennial ODZ trends were likely biased by this variability. ODZ evolution over the next century will depend on how global warming interacts with the decadal oscillations.
GPT-4o mini: Non-social science research article
A tetramer of BCL11A is required for stable protein production and fetal hemoglobin silencing
Ge Zheng, Maolu Yin, Stuti Mehta, I-Te Chu, Stacy Wang, Alia AlShaye, Kirstin Drainville, Altantsetseg Buyanbat, Frédérique Bienfait, Karin Tenglin, Qian Zhu, Stuart H. Orkin
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Down-regulation of BCL11A protein reverses the fetal (HbF, α 2 γ 2 ) to adult (HbA, α 2 β 2 ) hemoglobin switch and is exploited in gene-based therapy for hemoglobin disorders. Because of reliance on ex vivo cell manipulation and marrow transplant, such therapies cannot lessen disease burden. To develop new small-molecule approaches, we investigated the state of BCL11A protein in erythroid cells. We report that tetramer formation mediated by a single zinc finger (ZnF0) is required for production of steady-state protein. Beyond its role in protein stability, the tetramer state is necessary for γ-globin gene repression, because an engineered monomer fails to engage a critical co-repressor complex. These aspects of BCL11A protein production identify tetramer formation as a vulnerability for HbF silencing and provide opportunities for drug discovery.
GPT-4o mini: Non-social science research article
PIEZO-dependent mechanosensing is essential for intestinal stem cell fate decision and maintenance
Meryem B. Baghdadi, Ronja M. Houtekamer, Louisiane Perrin, Abilasha Rao-Bhatia, Myles Whelen, Linda Decker, Martin Bergert, Carlos Pérez-Gonzàlez, Réda Bouras, Giacomo Gropplero, Adrian K. H. Loe, Amin Afkhami-Poostchi, Xin Chen, Xi Huang, Stephanie Descroix, Jeffrey L. Wrana, Alba Diz-Muñoz, Martijn Gloerich, Arshad Ayyaz, Danijela Matic Vignjevic, Tae-Hee Kim
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Stem cells perceive and respond to biochemical and physical signals to maintain homeostasis. Yet, it remains unclear how stem cells sense mechanical signals from their niche in vivo. In this work, we investigated the roles of PIEZO mechanosensitive channels in the intestinal stem cell (ISC) niche. We used mouse genetics and single-cell RNA sequencing analysis to assess the requirement for PIEZO channels in ISC maintenance. In vivo measurement of basement membrane stiffness showed that ISCs reside in a more rigid microenvironment at the bottom of the crypt. Three-dimensional and two-dimensional organoid systems combined with bioengineered substrates and a stretching device revealed that PIEZO channels sense extracellular mechanical stimuli to modulate ISC function. This study delineates the mechanistic cascade of PIEZO activation that coordinates ISC fate decision and maintenance.
GPT-4o mini: Non-social science research article
Identification of a factor that accelerates substrate release from the signal recognition particle
Huping Wang, Ramanujan S. Hegde
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The eukaryotic signal recognition particle (SRP) cotranslationally recognizes the first hydrophobic segment of nascent secretory and membrane proteins and delivers them to a receptor at the endoplasmic reticulum (ER). How substrates are released from SRP at the ER to subsequently access translocation factors is not well understood. We found that TMEM208 can engage the substrate binding domain of SRP to accelerate release of its bound cargo. Without TMEM208, slow cargo release resulted in excessive synthesis of downstream polypeptide before engaging translocation factors. Delayed access to translocation machinery caused progressive loss of insertion competence, particularly for multipass membrane proteins, resulting in their impaired biogenesis. Thus, TMEM208 facilitates prompt cargo handover from the targeting to translocation machinery to minimize biogenesis errors and maintain protein homeostasis.
GPT-4o mini: Non-social science research article
Suppression of neurons in circumventricular organs enables months-long survival without water in thirteen-lined ground squirrels
Madeleine S. Junkins, Ni Y. Feng, Dana K. Merriman, Sviatoslav N. Bagriantsev, Elena O. Gracheva
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Water deprivation is a life-threatening condition that engages a protective physiological response to couple osmolyte retention with potentiation of thirst. This response, typical for most mammals, safeguards against short-term water deprivation but fails in the long term. Thirteen-lined ground squirrels ( Ictidomys tridecemlineatus ) use the short-term response during summer, whereas during winter, they lack thirst and survive without water for months. In this work, we show that long-term thirst suppression occurs despite hormonal and behavioral signs of a substantial fluid deficit and originates from hypoactivity of neurons in the circumventricular organs, which exhibit marked functional suppression during winter that blunts their sensitivity to thirst cues. Our work reveals a notable capacity of the evolutionarily conserved brain regions that control fluid homeostasis in mammals to enable long-term survival without water.
GPT-4o mini: Non-social science research article
Realization of one-dimensional anyons with arbitrary statistical phase
Joyce Kwan, Perrin Segura, Yanfei Li, Sooshin Kim, Alexey V. Gorshkov, André Eckardt, Brice Bakkali-Hassani, Markus Greiner
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Low-dimensional quantum systems can host anyons, particles with exchange statistics that are neither bosonic nor fermionic. However, the physics of anyons in one dimension remains largely unexplored. In this work, we realize Abelian anyons in one dimension with arbitrary exchange statistics using ultracold atoms in an optical lattice, where we engineer the statistical phase through a density-dependent Peierls phase. We explore the dynamical behavior of two anyons undergoing quantum walks and observe the anyonic Hanbury Brown–Twiss effect as well as the formation of bound states without on-site interactions. Once interactions are introduced, we observe spatially asymmetric transport in contrast to the symmetric dynamics of bosons and fermions. Our work forms the foundation for exploring the many-body behavior of one-dimensional anyons.
GPT-4o mini: Non-social science research article
Molecular basis of mRNA delivery to the bacterial ribosome
Michael W. Webster, Adrien Chauvier, Huma Rahil, Andrea Graziadei, Kristine Charles, Nataliya Miropolskaya, Maria Takacs, Charlotte Saint-André, Juri Rappsilber, Nils G. Walter, Albert Weixlbaumer
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Protein synthesis begins with the formation of a ribosome-messenger RNA (mRNA) complex. In bacteria, the small ribosomal subunit (30 S ) is recruited to many mRNAs through base pairing with the Shine-Dalgarno (SD) sequence and RNA binding by ribosomal protein bS1. Translation can initiate on nascent mRNAs, and RNA polymerase (RNAP) can promote the recruitment of the pioneering 30 S . Here, we examined 30 S recruitment to nascent mRNAs using cryo–electron microscopy, single-molecule fluorescence colocalization, and in-cell cross-linking mass spectrometry. We show that bS1 delivers the mRNA to the ribosome for SD duplex formation and 30 S activation. Additionally, bS1 and RNAP stimulate translation initiation. Our work provides a mechanistic framework for how the SD duplex, ribosomal proteins, and RNAP cooperate in 30 S recruitment to mRNAs and establish transcription-translation coupling.
GPT-4o mini: Non-social science research article
Systematic in vitro evolution in Plasmodium falciparum reveals key determinants of drug resistance
Madeline R. Luth, Karla P. Godinez-Macias, Daisy Chen, John Okombo, Vandana Thathy, Xiu Cheng, Sindhu Daggupati, Heledd Davies, Satish K. Dhingra, Jan M. Economy, Rebecca C. S. Edgar, Maria G. Gomez-Lorenzo, Eva S. Istvan, Juan Carlos Jado, Gregory M. LaMonte, Bruno Melillo, Sachel Mok, Sunil K. Narwal, Tolla Ndiaye, Sabine Ottilie, Sara Palomo Diaz, Heekuk Park, Stella Peña, Frances Rocamora, Tomoyo Sakata-Kato, Jennifer L. Small-Saunders, Robert L. Summers, Patrick K. Tumwebaze, Manu Vanaerschot, Guoqin Xia, Tomas Yeo, Ashley You, Francisco-Javier Gamo, Daniel E. Goldberg, Marcus C. S. Lee, Case W. McNamara, Daouda Ndiaye, Philip J. Rosenthal, Stuart L. Schreiber, Gloria Serra, Jair Lage De Siqueira-Neto, Tina S. Skinner-Adams, Anne-Catrin Uhlemann, Nobutaka Kato, Amanda K. Lukens, Dyann F. Wirth, David A. Fidock, Elizabeth A. Winzeler
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Surveillance of drug resistance and the discovery of novel targets—key objectives in the fight against malaria—rely on identifying resistance-conferring mutations in Plasmodium parasites. Current approaches, while successful, require laborious experimentation or large sample sizes. To elucidate shared determinants of antimalarial resistance that can empower in silico inference, we examined the genomes of 724 Plasmodium falciparum clones, each selected in vitro for resistance to one of 118 compounds. We identified 1448 variants in 128 recurrently mutated genes, including drivers of antimalarial multidrug resistance. In contrast to naturally occurring variants, those selected in vitro are more likely to be missense or frameshift, involve bulky substitutions, and occur in conserved, ordered protein domains. Collectively, our dataset reveals mutation features that predict drug resistance in eukaryotic pathogens.
GPT-4o mini: Non-social science research article
Aromatic-aliphatic hydrocarbon separation with oriented monolayer polyhedral membrane
Hao Sun, Naixin Wang, Yinghui Xu, Fengkai Wang, Jun Lu, Huanting Wang, Quan-Fu An
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Aromatic - aliphatic hydrocarbon separation is a challenging but important industrial process. Pervaporation membrane technology has the potential for separating these mixtures. We developed an oriented monolayer polyhedral (OMP) membrane that consists of a monolayer of ordered polyhedral particles and is anchored by hyperbranched polymers. It contains a high density of straight, selective nanochannels, enabling the preferential transport of aromatic molecules. Compared with traditional mixed-matrix membranes with random orientations, the OMP membrane improves the pervaporation separation index for aromatic-aliphatic hydrocarbon mixtures with C 6 and C 7 compounds, surpassing the performance of existing membranes by 3 to 10 times. This high performance demonstrates the potential of OMP membranes for hydrocarbon molecular separation and their application in the value-added separation of naphtha feedstocks.
GPT-4o mini: Non-social science research article
Magnetically programmed diffractive robotics
Conrad L. Smart, Tanner G. Pearson, Zexi Liang, Melody X. Lim, Mohamed I. Abdelrahman, Francesco Monticone, Itai Cohen, Paul L. McEuen
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Microscopic robots with features comparable with the wavelength of light offer new ways of probing the microscopic world and controlling light at the microscale. We introduce a new class of magnetically controlled microscopic robots (microbots) that operate at the visible-light diffraction limit, which we term diffractive robots. We combined nanometer-thick mechanical membranes, programmable nanomagnets, and diffractive optical elements to create untethered microbots small enough to diffract visible light and flexible enough to undergo complex reconfigurations in millitesla-scale magnetic fields. We demonstrated their applications, including subdiffractive imaging by using a variant of structured illumination microscopy, tunable diffractive optical elements for beam steering and focusing, and force sensing with piconewton sensitivity.
GPT-4o mini: Non-social science research article
Microscale droplet assembly enables biocompatible multifunctional modular iontronics
Yujia Zhang, Cheryl M. J. Tan, Christopher N. Toepfer, Xin Lu, Hagan Bayley
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Hydrogel iontronic devices can emulate biological functions and communicate with living matter. But the fabrication of miniature, soft iontronic devices according to modular designs has not been achieved. In this work, we report the use of surfactant-supported assembly of freestanding microscale hydrogel droplets to construct various iontronic modules, circuits, and biointerfaces. Chemical modifications of silk fibroin produced a pair of oppositely charged hydrogels. Microscale assembly of various combinations of hydrogel droplets produced iontronic diodes, npn- and pnp-type transistors, and diverse reconfigurable logic gates. Through the incorporation of poly(amino acid)s, we have demonstrated a droplet-based synthetic synapse with ionic polymer–mediated long-term plasticity. Further, our iontronic transistor can serve as a biocompatible sensor to record electrophysiological signals from sheets of human cardiomyocytes, paving a way to the building of miniature bioiontronic systems.
GPT-4o mini: Non-social science research article
Optoelectronic metadevices
Son Tung Ha, Qitong Li, Joel K. W. Yang, Hilmi Volkan Demir, Mark L. Brongersma, Arseniy I. Kuznetsov
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Metasurfaces have introduced new opportunities in photonic design by offering unprecedented, nanoscale control over optical wavefronts. These artificially structured layers have largely been used to passively manipulate the flow of light by controlling its phase, amplitude, and polarization. However, they can also dynamically modulate these quantities and manipulate fundamental light absorption and emission processes. These valuable traits can extend their application domain to chipscale optoelectronics and conceptually new optical sources, displays, spatial light modulators, photodetectors, solar cells, and imaging systems. New opportunities and challenges have also emerged in the materials and device integration with existing technologies. This Review aims to consolidate the current research landscape and provide perspectives on metasurface capabilities specific to optoelectronic devices, giving new direction to future research and development efforts in academia and industry.
Science abstract < 200 char.: Not a research article
In Other Journals
Bianca Lopez, Sarah H. Ross, Sumin Jin, Michael A. Funk, Stella M. Hurtley, Ekeoma Uzogara, Jelena Stajic
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
In Science Journals
Yevgeniya Nusinovich, Ekeoma Uzogara, Sacha Vignieri, Jelena Stajic, Marc S. Lavine, Claire Olingy, Jesse Smith, Catherine Charneski, Di Jiang, Ian S. Osborne, Mattia Maroso, Stella M. Hurtley, Caroline Ash, Yury Suleymanov, Priscilla N. Kelly, Leslie K. Ferrarelli
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
Racing the clock
Cecilia Padilla Iglesias, Erika C. Freeman
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Science abstract < 200 char.: Not a research article
Assessment abuse in African protected areas
Reece Alberts, Francois Retief, Alan Bond, Claudine Roos, Dirk Cilliers
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Science abstract < 200 char.: Not a research article
Researchers and scientific institutions flock to Bluesky
Kai Kupferschmidt
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After recent changes to Elon Musk’s X, a gradual migration in search of the “old Twitter” turns into a stampede
Science abstract < 200 char.: Not a research article
Harness agrifood value chains to help farmers be climate smart
Johan Swinnen, Loraine Ronchi, Thomas Reardon
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Incentives and structures exist to improve farming practices
Science abstract < 200 char.: Not a research article
Droplet-based microprocessors
Jean-Christophe Baret
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Soft devices made of nanoliter hydrogel beads use ions for computation
Science abstract < 200 char.: Not a research article
Children are left behind in Congo’s mpox vaccination drive
Jon Cohen
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Regulatory and liability issues are delaying immunization of the group most vulnerable to severe disease and death
Science abstract < 200 char.: Not a research article
Endothelial inflammation in COVID-19
Peter Libby
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Disrupted endothelial function underlies the multiorgan complications of COVID-19
Science abstract < 200 char.: Not a research article
Mining lithium from brines goes electric
Robert F. Service
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Critical battery metal could be extracted more quickly than in evaporation ponds
Science abstract < 200 char.: Not a research article
Mpox prevention in low-income countries
Xin Yu Yang, Gong Jie Zhang, Ya Bin Zhou
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Science abstract < 200 char.: Not a research article
DNA and deli sandwiches
Luis A. Campos
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On the anniversary of a pivotal patent, a historian probes biotechnology’s origin story
Science abstract < 200 char.: Not a research article
News at a glance
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Science abstract < 200 char.: Not a research article
Fake papers compromise research syntheses
Holly Else
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“Systematic reviews” that aim to extract broad conclusions from many studies are in peril
Science abstract < 200 char.: Not a research article
Micrometer-sized robotic chameleons
Corentin Coulais, Jorik van de Groep
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A multifunctional metamaterial can change shape and steer light simultaneously
Science abstract < 200 char.: Not a research article
‘Dark proteome’ survey reveals thousands of new human genes
Elizabeth Pennisi
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Database confirms that overlooked segments of the genome code for a multitude of tiny proteins
Science abstract < 200 char.: Not a research article
Contemporary hominin locomotor diversity
William E. H. Harcourt-Smith
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Footprints in Kenya show that hominin bipedalism had a complex evolutionary history
Science abstract < 200 char.: Not a research article
Eating the Earth
Joel K. Bourne
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The burgeoning global food trade is a lifeline for billions, but it is fragile and hard on the planet
Science abstract < 200 char.: Not a research article
The philosopher’s intuition Herald of a Restless World: How Henri Bergson Brought Philosophy to the People Emily Herring Basic Books, 2024. 320 pp.
Mary Ellen Hannibal
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A forgotten scholar sought to reconcile subjective experience with the laws of nature
Neither climate laboratory nor knowledge vacuum: What’s at stake for the Global South in the debate around solar geoengineering research
Rose M. Mutiso
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Recently, I sat in a room in Cape Town with African climate scientists , watching them present results from sophisticated models examining how solar geoengineering interventions might affect local weather patterns across the continent. These researchers, primarily climate impact modelers who have expanded their work to include solar geoengineering scenarios, were doing exactly what critics claim the Global South lacks capacity for: producing rigorous, locally relevant climate science.
Misinformation exploits outrage to spread online
Killian L. McLoughlin, William J. Brady, Aden Goolsbee, Ben Kaiser, Kate Klonick, M. J. Crockett
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We tested a hypothesis that misinformation exploits outrage to spread online, examining generalizability across multiple platforms, time periods, and classifications of misinformation. Outrage is highly engaging and need not be accurate to achieve its communicative goals, making it an attractive signal to embed in misinformation. In eight studies that used US data from Facebook (1,063,298 links) and Twitter (44,529 tweets, 24,007 users) and two behavioral experiments (1475 participants), we show that (i) misinformation sources evoke more outrage than do trustworthy sources; (ii) outrage facilitates the sharing of misinformation at least as strongly as sharing of trustworthy news; and (iii) users are more willing to share outrage-evoking misinformation without reading it first. Consequently, outrage-evoking misinformation may be difficult to mitigate with interventions that assume users want to share accurate information.
Exposure to sugar rationing in the first 1000 days of life protected against chronic disease
Tadeja Gracner, Claire Boone, Paul J. Gertler
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We examined the impact of exposure to sugar restrictions within 1000 days after conception on type 2 diabetes and hypertension, leveraging quasi-experimental variation from the end of the United Kingdom’s sugar rationing in September 1953. Rationing restricted sugar intake to levels within current dietary guidelines, and consumption nearly doubled immediately after rationing ended. Using an event study design with UK Biobank data comparing adults conceived just before or after rationing ended, we found that early-life rationing reduced type 2 diabetes and hypertension risk by about 35 and 20% and delayed disease onset by 4 and 2 years, respectively. Protection was evident with in utero exposure and increased with postnatal sugar restriction, especially after 6 months, when eating of solid foods likely began. In utero sugar rationing alone accounted for about one-third of the risk reduction.

Science Advances

GPT-4o mini: Non-social science research article
Revivable self-assembled supramolecular biomass fibrous framework for efficient microplastic removal
Yang Wu, Shixiong Chen, Jun Wu, Fangtian Liu, Chaoji Chen, Bin Ding, Xue Zhou, Hongbing Deng
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Microplastic remediation in aquatic bodies is essential for the entire ecosystem, but is challenging to achieve with a universal and efficient strategy. Here, we developed a sustainable and environmentally adaptable adsorbent through supramolecular self-assembly of chitin and cellulose. This biomass fibrous framework (Ct-Cel) showcases an excellent adsorption performance for polystyrene, polymethyl methacrylate, polypropylene, and polyethylene terephthalate. The affinity for diverse microplastics is attributed to the transformation of multiple intermolecular interactions between different microplastics and Ct-Cel. Meanwhile, the strong resistance of Ct-Cel to multiple pollutants in water enables an enhanced adsorption when coexisting with microorganisms and Pb 2+ . Moreover, Ct-Cel can remove 98.0 to 99.9% of microplastics in four types of real water and maintains a high removal efficiency of up to 95.1 to 98.1% after five adsorption cycles. This work may open up prospects for functional biomass materials for cost-efficient remediation of microplastics in complex aquatic environments.
GPT-4o mini: Non-social science research article
Integrated design of aluminum-enriched high-entropy refractory B2 alloys with synergy of high strength and ductility
Jie Qi, Xuesong Fan, Diego Ibarra Hoyos, Michael Widom, Peter K. Liaw, Joseph Poon
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Refractory high-entropy alloys (RHEAs) are promising high-temperature structural materials. Their large compositional space poses great design challenges for phase control and high strength-ductility synergy. The present research pioneers using integrated high-throughput machine learning with Monte Carlo simulations supplemented by ab initio calculations to effectively navigate phase selection and mechanical property predictions, developing single-phase ordered B2 aluminum-enriched RHEAs (Al-RHEAs) demonstrating high strength and ductility. These Al-RHEAs achieve remarkable mechanical properties, including compressive yield strengths up to 1.7 gigapascals, fracture strains exceeding 50%, and notable high-temperature strength retention. They also demonstrate a tensile yield strength of 1.0 gigapascals with a ductility of 9%, albeit with B2 ordering. Furthermore, we identify valence electron count domains for alloy ductility and brittleness with the explanation from density functional theory and provide crucial insights into elemental influence on atomic ordering and mechanical performance. The work sets forth a strategic blueprint for high-throughput alloy design and reveals fundamental principles governing the mechanical properties of advanced structural alloys.
GPT-4o mini: Non-social science research article
Synthesis of defect-rich La 2 O 2 CO 3 supports for enhanced CO 2 -to-methanol conversion efficiency
Rui Zhang, Xiao Wang, Ke Wang, Huilin Wang, Xudong Sun, Weidong Shi, Shuyan Song, Hongjie Zhang
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Converting CO 2 to methanol is crucial for addressing fuel scarcity and mitigating the greenhouse effect. Cu-based catalysts, with their diverse surface states, offer the potential to control reaction pathways and generate reactive H* species. However, a major challenge lies in oxidizing active Cu 0 species by water generated during the catalytic process. While nonreducible metal oxides are beneficial in stabilizing metallic states, their limited capability to generate surface oxygen vacancies (O V ) hinders CO 2 activation. Herein, we present a strategy by doping Nd into a La 2 O 2 CO 3 (LOC) support, enhancing O V formation by disrupting its lattice dyadicity. This leads to higher Cu 0 concentration and improved CO 2 activation. The resulting Cu/LOC:Nd catalyst notably outperforms Cu/LOC and CuZnAl catalysts, achieving a methanol yield of 9.9 moles of methanol per hour per mole of Cu. Our approach opens up possibilities for enhancing Cu-based catalysts in CO 2 conversion.
GPT-4o mini: Non-social science research article
Chromobacterium biopesticide overcomes insecticide resistance in malaria vector mosquitoes
Chinmay V. Tikhe, Sare Issiaka, Yuemei Dong, Mary Kefi, Mihra Tavadia, Etienne Bilgo, Rodrigo M. Corder, John Marshall, Abdoulaye Diabate, George Dimopoulos
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Vector mosquito control is an integral part of malaria control. The global emergence of insecticide resistance in malaria-transmitting Anophelines has become an impediment and has created an urgent need for novel mosquito control approaches. Here, we show that a biopesticide derived from the soil-dwelling bacterium Chromobacterium sp. Panama ( Csp_P ) kills insecticide-resistant Anopheles mosquitoes, regardless of their resistance mechanisms. In addition, sublethal dose of Csp_P acts as a synergist to now used chemical insecticides across multiple classes. Moreover, Csp_P reduces host-seeking behavior and malaria parasite infection in vector mosquitoes in ways that further decrease transmission. Mosquito glutathione S -transferases are essential for Csp_P ’s mosquito-killing mechanism. Enclosed field trials in Burkina Faso, conducted in diverse ecological settings and supported by a mathematical model, have now demonstrated its potential for malaria control in settings with widespread insecticide resistance.
GPT-4o mini: Non-social science research article
Naturally arising memory-phenotype CD4 + T lymphocytes contain an undifferentiated population that can generate T H 1, T H 17, and T reg cells
Akihisa Kawajiri, Jing Li, Keita Koinuma, Ziying Yang, Hye Jin Yoon, Jaeu Yi, Hiroyuki Nagashima, Minami Ishii, Feng Gao, Kosuke Sato, Shunichi Tayama, Hideo Harigae, Yoichiro Iwakura, Naoto Ishii, Alan Sher, Kazuyoshi Ishigaki, Jinfang Zhu, Kwang Soon Kim, Takeshi Kawabe
Full text
Memory-phenotype (MP) CD4 + T lymphocytes develop from naïve cells via self-recognition at homeostasis. While previous studies defined MP cells as a heterogeneous population that comprises T helper 1 (T H 1)/17–like subsets, functional significance of the T-bet − Rorγt − subpopulation remains unknown. Here we show that MP lymphocytes as a whole population can differentiate into T H 1/17/regulatory T (T reg ) cells to mediate mild and persistent inflammation in lymphopenic environments, whereas naïve cells exhibit strong, T H 1-dominated responses. Moreover, we demonstrate that MP lymphocytes comprise not only T H 1/17-differentiated subsets but a polyclonal, transcriptomically immature “undifferentiated” subpopulation at homeostasis. Furthermore, our data argue that while the T-bet + Rorγt − MP subset is terminally T H 1-differentiated, its undifferentiated counterpart retains the capacity to rapidly proliferate to differentiate into T H 1/17/T reg cells, with the latter response tonically constrained by preexisting T reg cells. Together, our results identify undifferentiated MP CD4 + T lymphocytes as a unique precursor that has a diverse differentiation potential to generate T H 1/17/T reg cells to contribute to pathogenesis of inflammation.
GPT-4o mini: Non-social science research article
Comediation of voltage gating and ion charge in MXene membrane for controllable and selective monovalent cation separation
Xu Wang, Haiguang Zhang, Gaoliang Wei, Jiajian Xing, Shuo Chen, Xie Quan
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Artificial ion channels with controllable mono/monovalent cation separation fulfill important roles in biomedicine, ion separation, and energy conversion. However, it remains a daunting challenge to develop an artificial ion channel similar to biological ion channels due to ion-ion competitive transport and lack of ion-gating ability of channels. Here, we report a conductive MXene membrane with polydopamine-confined angstrom-scale channels and propose a voltage gating and ion charge comediation strategy to concurrently achieve gated and selective mono/monovalent cation separation. The membrane shows a highly switchable “on-off” ratio of ∼9.9 for K + transport and an excellent K + /Li + selectivity of 40.9, outperforming the ion selectivity of reported membranes with electrical gating (typically 1.5 to 6). Theoretical simulations reveal that the introduced high-charge cations such as Mg 2+ enable the preferential distribution of target K + over competing Li + at the channel entrance, and the surface potential reduces the ionic transport energy barrier for allowing K + to pass quickly through the channel.
GPT-4o mini: Non-social science research article
T cell receptor–centric perspective to multimodal single-cell data analysis
Kerry A. Mullan, My Ha, Sebastiaan Valkiers, Nicky de Vrij, Benson Ogunjimi, Kris Laukens, Pieter Meysman
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The T cell receptor (TCR), despite its importance, is underutilized in single-cell analysis, with gene expression features solely driving current strategies. Here, we argue for a TCR-first approach, more suited toward T cell repertoires. To this end, we curated a large T cell atlas from 12 prominent human studies, containing in total 500,000 T cells spanning multiple diseases, including melanoma, head and neck cancer, blood cancer, and lung transplantation. Here, we identified severe limitations in cell-type annotation using unsupervised approaches and propose a more robust standard using a semi-supervised method or the TCR arrangement. We showcase the utility of a TCR-first approach through application of the STEGO.R tool for the identification of treatment-related dynamics and previously unknown public T cell clusters with potential antigen-specific properties. Thus, the paradigm shift to a TCR-first can highlight overlooked key T cell features that have the potential for improvements in immunotherapy and diagnostics.
GPT-4o mini: Non-social science research article
Nanoscale covalent organic framework-mediated pyroelectrocatalytic activation of immunogenic cell death for potent immunotherapy
Xingguang Li, Meng-Lu Gao, Shan-Shan Wang, Yizhi Hu, Dongzhi Hou, Pei-Nian Liu, Huijing Xiang
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The conventional molecular immunogenic cell death (ICD) inducers suffer from poor biocompatibility and unsatisfactory efficacy. Here, a biocompatible nanosized covalent organic framework (nCOF)–based pyroelectric catalyst (denoted as TPAD-COF NPs) is designed for pyroelectric catalysis-activated in situ immunotherapy. TPAD-COF NPs confine organic pyroelectric molecules to rigid TPAD-COF NPs to substantially reduce aggregation and enhance biocompatibility, thus improving pyroelectrocatalytic efficiency. After tumor internalization, TPAD-COF NPs facilitate photothermal tumor ablation under near-infrared (NIR) laser exposure, resulting in effective ICD induction. In addition, TPAD-COF NPs effectively catalyze the conversion of temperature changes to pyroelectric changes, which subsequently react with adjacent O 2 to generate reactive oxygen species, thus triggering robust ICD activation. In vivo evaluation using mouse models confirmed that TPAD-COF NPs evidently inhibited the proliferation of primary and distant tumors and prevented lung metastasis under NIR laser illumination. Therefore, this study opens an avenue for designing nCOF-based catalysts for pyroelectric catalysis-activated in situ immunotherapy.
GPT-4o mini: Non-social science research article
Computation-driven redesign of an NRPS-like carboxylic acid reductase improves activity and selectivity
Kun Shi, Ju-Mou Li, Mu-Qiang Wang, Yi-Ke Zhang, Zhi-Jun Zhang, Qi Chen, Frank Hollmann, Jian-He Xu, Hui-Lei Yu
Full text
Engineering nonribosomal peptide synthetases (NRPSs) has been a “holy grail” in synthetic biology due to their modular nature and limited understanding of catalytic mechanisms. Here, we reported a computational redesign of the “gate-keeper” adenylation domain of the model NRPS-like enzyme carboxylic acid reductases (CARs) by using approximate mechanism-based geometric criteria and the Rosetta energy score. Notably, Mab CAR3 mutants ACA-1 and ACA-4 displayed a remarkable improvement in catalytic efficiency ( k cat / K M ) for 6-aminocaproic acid, up to 101-fold. Furthermore, G418K exhibited an 86-fold enhancement in substrate specificity for adipic acid compared to 6-aminocaproic acid. Our work provides not only promising biocatalysts for nylon monomer biosynthesis but also a strategy for efficient NRPSs engineering.
GPT-4o mini: Non-social science research article
Climate refugia in the Great Barrier Reef may endure into the future
Chaojiao Sun, Craig Steinberg, Eduardo Klein Salas, Camille Mellin, Russell C. Babcock, Andreas Schiller, Neal E. Cantin, Jessica S. Stella, Mark E. Baird, Scott A. Condie, Alistair J. Hobday, Mike Herzfeld, Nicole L. Jones, Xuebin Zhang, Matthew A. Chamberlain, Russ Fiedler, Cody Green, Andrew D. L. Steven
Full text
Although global warming is leading to more frequent mass coral bleaching events worldwide, parts of the Great Barrier Reef (GBR) have consistently escaped severe coral bleaching. Modeling and satellite observations show that climate refugia are created by the upwelling of cooler water to the surface through the interactions of tides and currents with dense reef structures. Here, we use a high-resolution nested regional ocean model to investigate the future status of two relatively large refugia. On the basis of model projections under a high-emission scenario, we find that the upwelling mechanisms will stay active in a warming climate, and these regions are likely to remain approximately more than 1°C cooler than surrounding waters until at least into the 2080s, providing thermal relief to corals. Identification and protection of these refugia may help facilitate reef survival and related biodiversity preservation by allowing their corals time to acclimatize and adapt and ultimately provide source populations to replenish the rest of the reef.
GPT-4o mini: Non-social science research article
High temperatures are associated with decreased immune system performance in a wild primate
Jordan M. Lucore, Jacinta C. Beehner, Amy F. White, Lorena F. Sinclair, Vasco Alexandre Martins, Sarah A. Kovalaskas, Juan Carlos Ordoñez, Thore J. Bergman, Marcela E. Benítez, Andrew J. Marshall
Full text
Rising temperatures due to climate change are predicted to threaten the persistence of wild animals, but there is little evidence that climate change has pushed species beyond their thermal tolerance. The immune system is an ideal avenue to assess the effects of climate change because immune performance is sensitive to changes in temperature and immune competency can affect reproductive success. We investigate the effect of rising temperatures on a biomarker of nonspecific immune performance in a wild population of capuchin monkeys and provide compelling evidence that immune performance is associated with ambient temperature. Critically, we found that immune performance in young individuals is more sensitive to high temperatures compared to other age groups. Coupled with evidence of rising temperatures in the region, our results offer insight into how climate change will affect the immune system of wild mammals.
GPT-4o mini: Non-social science research article
Convergent evolution of berberine biosynthesis
Zhichao Xu, Ya Tian, Jing Wang, Yuwei Ma, Qi Li, Yuanze Zhou, Wanran Zhang, Tingxia Liu, Lingzhe Kong, Yifan Wang, Ziyan Xie, Zhoujie An, Baojiang Zheng, Yuhong Zhang, Chang Cao, Chengwei Liu, Lixia Tian, Chengpeng Fan, Jiushi Liu, Hui Yao, Jingyuan Song, Baozhong Duan, Haitao Liu, Ranran Gao, Wei Sun, Shilin Chen
Full text
Berberine is an effective antimicrobial and antidiabetic alkaloid, primarily extracted from divergent botanical lineages, specifically Coptis (Ranunculales, early-diverging eudicot) and Phellodendron (Sapindales, core eudicot). In comparison with its known pathway in Coptis species, its biosynthesis in Phellodendron species remains elusive. Using chromosome-level genome assembly, coexpression matrix, and biochemical assays, we identified six key steps in berberine biosynthesis from Phellodendron amurense , including methylation, hydroxylation, and berberine bridge formation. Notably, we discovered a specific class of O -methyltransferases (NOMT) responsible for N -methylation. Structural analysis and mutagenesis of PaNOMT9 revealed its unique substrate-binding conformation. In addition, unlike the classical FAD-dependent berberine bridge formation in Ranunculales, Phellodendron uses a NAD(P)H-dependent monooxygenase (PaCYP71BG29) for berberine bridge formation, originating from the neofunctionalization of tryptamine 5-hydroxylase. Together, these findings reveal the convergence of berberine biosynthesis between Coptis and Phellodendron and signify the role of the convergent evolution in plant specialized metabolisms.
GPT-4o mini: Non-social science research article
Interferon response and epigenetic modulation by SMARCA4 mutations drive ovarian tumor immunogenicity
Melica Nourmoussavi Brodeur, Higinio Dopeso, Yingjie Zhu, Ana Leda F. Longhini, Andrea Gazzo, Siyu Sun, Richard P. Koche, Rui Qu, Laura Rosenberg, Pierre-Jacques Hamard, Yonina Bykov, Hunter Green, Laxmi Gusain, Katherine B. Chiappinelli, Melih Arda Ozsoy, M. Herman Chui, Thais Basili, Rui Gardner, Sven Walderich, Elisa DeStanchina, Benjamin Greenbaum, Mithat Gönen, Nicolas Vabret, Britta Weigelt, Dmitriy Zamarin
Full text
Cell-intrinsic mechanisms of immunogenicity in ovarian cancer (OC) are not well understood. Damaging mutations in the SWI/SNF chromatin remodeling complex, such as SMARCA4 (BRG1), are associated with improved response to immune checkpoint blockade; however, the mechanism by which this occurs is unclear. We found that SMARCA4 loss in OC models resulted in increased cancer cell–intrinsic immunogenicity, characterized by up-regulation of long-terminal RNA repeats, increased expression of interferon-stimulated genes, and up-regulation of antigen presentation machinery. Notably, this response was dependent on STING, MAVS, and IRF3 signaling but was independent of the type I interferon receptor. Mouse ovarian and melanoma tumors with SMARCA4 loss demonstrated increased infiltration and activation of cytotoxic T cells, NK cells, and myeloid cells in the tumor microenvironment. These results were recapitulated in BRG1 inhibitor–treated SMARCA4- proficient tumor models, suggesting that modulation of chromatin remodeling through targeting SMARCA4 may serve as a strategy to overcome cancer immune evasion.
GPT-4o mini: Non-social science research article
Nonheme iron catalyst mimics heme-dependent haloperoxidase for efficient bromination and oxidation
Guodong Zhao, Huiling Dong, Kang Xue, Shaoyan Lou, Rui Qi, Xiaohui Zhang, Zhuo Cao, Qi Qin, Bingqing Yi, Haimin Lei, Rongbiao Tong
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The [Fe]/H 2 O 2 oxidation system has found wide applications in chemistry and biology. Halogenation with this [Fe]/H 2 O 2 oxidation protocol and halide (X − ) in the biological system is well established with the identification of heme-iron–dependent haloperoxidases. However, mimicking such halogenation process is rarely explored for practical use in organic synthesis. Here, we report the development of a nonheme iron catalyst that mimics the heme-iron–dependent haloperoxidases to catalyze the generation of HOBr from H 2 O 2 /Br − with high efficiency. We discovered that a tridentate terpyridine (TPY) ligand designed for Fenton chemistry was optimal for FeBr 3 to form a stable nonheme iron catalyst [Fe(TPY)Br 3 ], which catalyzed arene bromination, Hunsdiecker-type decarboxylative bromination, bromolactonization, and oxidation of sulfides and thiols. Mechanistic studies revealed that Fenton chemistry ([Fe]/H 2 O 2 ) might operate to generate hydroxyl radical (HO • ), which oxidize bromide ion [Br − ] into reactive HOBr. This nonheme iron catalyst represents a biomimetic model for heme-iron–dependent haloperoxidases with potential applications in organic synthesis, drug discovery, and biology.
GPT-4o mini: Non-social science research article
Landscape changes caused by the 2024 Noto Peninsula earthquake in Japan
Yo Fukushima, Daisuke Ishimura, Naoya Takahashi, Yoshiya Iwasa, Luca C. Malatesta, Takayuki Takahashi, Chi-Hsien Tang, Keisuke Yoshida, Shinji Toda
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Landscapes are shaped by tectonic, climatic, and surface processes over geological timescales, but we rarely witness the events of marked landscape change. The moment magnitude 7.5 Noto Peninsula earthquake in central Japan was caused by a large thrust faulting, up to nearly 10 meters of slip, that expanded more than 150 kilometers along the fault zone. The deformation field reconstructed from satellite data and field surveys reveals up to 4.4 meters of uplift and associated coastal advance along the entire northern coast of the peninsula, meter-scale systematic movement of the mountain slopes consistent with slip on flexural faults, and activation of secondary inland faults, suggesting synchronized ruptures. The findings show excellent consistency between the coseismic deformation and geomorphic features and provide a vivid example of the role of a major earthquake in landscape formation.
GPT-4o mini: Non-social science research article
Phosphatidylinositol 4,5-bisphosphate drives the formation of EGFR and EphA2 complexes
Pradeep Kumar Singh, Jennifer A. Rybak, Ryan J. Schuck, Amita R. Sahoo, Matthias Buck, Francisco N. Barrera, Adam W. Smith
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Receptor tyrosine kinases (RTKs) regulate many cellular functions and are important targets in pharmaceutical development, particularly in cancer treatment. EGFR and EphA2 are two key RTKs that are associated with oncogenic phenotypes. Several studies have reported functional interplay between these receptors, but the mechanism of interaction is still unresolved. Here, we use a time-resolved fluorescence spectroscopy called PIE-FCCS to resolve EGFR and EphA2 interactions in live cells. We tested the role of ligands and found that EGF, but not ephrin A1 (EA1), stimulated heteromultimerization between the receptors. To determine the effect of anionic lipids, we targeted phospholipase C (PLC) activity to alter the abundance of phosphatidylinositol 4,5-bisphosphate (PIP 2 ). We found that higher PIP 2 levels increased homomultimerization of both EGFR and EphA2, as well as heteromultimerization. This study provides a direct characterization of EGFR and EphA2 interactions in live cells and shows that PIP 2 can have a substantial effect on the spatial organization of RTKs.
GPT-4o mini: Non-social science research article
Impact of air pollution exposure on cytokines and histone modification profiles at single-cell levels during pregnancy
Youn Soo Jung, Juan Aguilera, Abhinav Kaushik, Ji Won Ha, Stuart Cansdale, Emily Yang, Rizwan Ahmed, Fred Lurmann, Liza Lutzker, S. Katherine Hammond, John Balmes, Elizabeth Noth, Trevor D. Burt, Nima Aghaeepour, Anne R. Waldrop, Purvesh Khatri, Paul J. Utz, Yael Rosenburg-Hasson, Rosemarie DeKruyff, Holden T. Maecker, Mary M. Johnson, Kari C. Nadeau
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Fine particulate matter (PM 2.5 ) exposure can induce immune system pathology via epigenetic modification, affecting pregnancy outcomes. Our study investigated the association between PM 2.5 exposure and immune response, as well as epigenetic changes using high-dimensional epigenetic landscape profiling using cytometry by time-of-flight (EpiTOF) at the single cell. We found statistically significant associations between PM 2.5 exposure and levels of certain cytokines [interleukin-1RA (IL-1RA), IL-8/CXCL8, IL-18, and IL-27)] and histone posttranslational modifications (HPTMs) in immune cells (HPTMs: H3K9ac, H3K23ac, H3K27ac, H2BK120ub, H4K20me1/3, and H3K9me1/2) among pregnant and nonpregnant women. The cord blood of neonates with high maternal PM 2.5 exposure showed lower IL-27 than those with low exposure. Furthermore, PM 2.5 exposure affects the co-modification profiles of cytokines between pregnant women and their neonates, along with HPTMs in each immune cell type between pregnant and nonpregnant women. These modifications in specific histones and cytokines could indicate the toxicological mechanism of PM 2.5 exposure in inflammation, inflammasome pathway, and pregnancy complications.
GPT-4o mini: Non-social science research article
Local chemical order enables an ultrastrong and ductile high-entropy alloy in a cryogenic environment
Lifang Sun, Zhufeng He, Nan Jia, Yanxin Guo, Shuang Jiang, Yuliang Yang, Yuxin Liu, Xianjun Guan, Yongfeng Shen, Hai-Le Yan, Peter K. Liaw
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Owing to superior strength-ductility combination and great potential for applications in extreme conditions, high-entropy alloys (HEAs) with the face-centered cubic (FCC) structure have drawn enormous attention. However, the FCC structure limits yield strength and makes the alloys unable to meet ever-increasing demands for exploring the universe. Here, we report a strategy to obtain FCC materials with outstanding mechanical properties in both ambient and cryogenic environments, via exploiting dynamic development of the interstitial-driven local chemical order (LCO). Dense laths composed of the multiscaled LCO domains evolve from planar-slip bands that form in the prior thermomechanical processing, contributing to ultrahigh yield strengths over a wide temperature range. During cryogenic tensile deformation, LCO further develops and promotes remarkable dislocation cross-slip. Together with the deformation-driven transformation and twinning, these factors lead to satisfactory work hardening. The cryogenic loading–promoted LCO, also revealed by ab initio calculations, opens an avenue for designing advanced cryogenic materials.
GPT-4o mini: Non-social science research article
Magnonic superconductivity
Khachatur G. Nazaryan, Liang Fu
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We uncover a superconducting state with partial spin polarization induced by a magnetic field. This state, which we call “magnonic superconductor,” lacks a conventional pairing order parameter but is characterized instead by a composite order parameter that represents the binding of electron pairs and magnons. We rigorously demonstrate the existence of magnonic superconductivity with high transition temperature in one-dimensional and two-dimensional Hubbard models with repulsive interaction. We further show that magnonic Cooper pairs can attract to form higher-charge bound states, which can give rise to charge-6 e superconductivity.
GPT-4o mini: Non-social science research article
Elevating levels of the endocannabinoid 2-arachidonoylglycerol blunts opioid reward but not analgesia
Arlene Martínez-Rivera, Robert N. Fetcho, Lizzie Birmingham, Jin Xu, Ruirong Yang, Careen Foord, Diego Scala-Chávez, Narmin Mekawy, Kristen Pleil, Virginia M. Pickel, Conor Liston, Carlos M. Castorena, Joshua Levitz, Ying-Xian Pan, Lisa A. Briand, Anjali M. Rajadhyaksha, Francis S. Lee
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Converging findings have established that the endocannabinoid (eCB) system serves as a possible target for the development of new treatments as a complement to opioid-based treatments. Here, we show in male and female mice that enhancing levels of the eCB, 2-arachidonoylglycerol (2-AG), through pharmacological inhibition of its catabolic enzyme, monoacylglycerol lipase (MAGL), either systemically or in the ventral tegmental area (VTA) with JZL184, leads to a substantial attenuation of the rewarding effects of opioids in mice using conditioned place preference and self-administration paradigms, without altering their analgesic properties. These effects are driven by cannabinoid receptor 1 (CB1R) within the VTA, as VTA CB1R conditional knockout counteracts JZL184’s effects. Using fiber photometry with fluorescent sensors for calcium and dopamine (DA), we find that enhancing 2-AG levels diminishes opioid reward–related nucleus accumbens (NAc) activity and DA neurotransmission. Together, these findings reveal that 2-AG diminishes the rewarding properties of opioids and provides a potential adjunctive therapeutic strategy for opioid-related analgesic treatments.
GPT-4o mini: Non-social science research article
Activity-driven polymer knotting for macromolecular topology engineering
Jia-Xiang Li, Song Wu, Li-Li Hao, Qun-Li Lei, Yu-Qiang Ma
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Macromolecules can gain special properties by adopting knotted conformations, but engineering knotted macromolecules is a challenging task. Here, we unexpectedly find that knots can be efficiently generated in active polymer systems. When one end of an actively reptative polymer is anchored, it undergoes continual self-knotting as a result of intermittent giant conformation fluctuations and the outward reptative motion. Once a knot is formed, it migrates to the anchoring point due to a nonequilibrium ratchet effect. Moreover, when the active polymer is grafted on a passive polymer, it can function as a self-propelling soft needle to either transfer its own knots or directly braid knots on the passive polymer. We further show that these active needles can create intermolecular bridging knots between two passive polymers. Our finding highlights the nonequilibrium effects in modifying the dynamic pathways of polymer systems, which have potential applications in macromolecular topology engineering.
GPT-4o mini: Non-social science research article
Flexible mechano-optical dual-responsive perovskite molecular ferroelectric composites for advanced anticounterfeiting and encryption
Shengshun Duan, Pinzhen Chen, Yu-an Xiong, Fangzhi Zhao, Zhengyin Jing, Guowei Du, Xiao Wei, Shengxin Xiang, Jianlong Hong, Qiongfeng Shi, Yumeng You, Jun Wu
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Hybrid organic-inorganic molecular ferroelectrics have emerged as promising materials for multifunctional piezoelectric devices. However, they present challenges in practical applications because of their inherent brittleness and poor ductility. Herein, we present a flexible mechano-optical dual-responsive molecular ferroelectric composite by incorporating trimethylchloromethyl ammonium (TMCM)–MnCl 3 into styrene ethylene butylene styrene (SEBS) matrix. The SEBS/TMCM-MnCl 3 exhibits excellent stretchable mechanical properties (tensile strain >1300%, thickness of 30 μm), piezoelectricity, and photoluminescence, enabling advanced visual-tactile–fused anticounterfeiting and encryption applications. Anticounterfeiting and antitampering tags are developed to judge whether the valued items are true or tampered with based on pattern recognition and piezoelectric response, respectively. Additionally, high-security password keyboards featuring triple-layer encryption are designed, offering more password combinations (524,288 times greater than those of traditional password devices relying solely on digital encryption) and enhanced security reliability against cracking attempts. This work can inspire designs of multifunctional optoelectronic materials and enable visual-tactile–fused intelligent applications in human-machine interfaces, information security, and advanced robotics.
GPT-4o mini: Non-social science research article
Real-time viscoelastic deformability cytometry: High-throughput mechanical phenotyping of liquid and solid biopsies
Mohammad Asghari, Sarah Duclos Ivetich, Mahmut Kamil Aslan, Morteza Aramesh, Oleksandr Melkonyan, Yingchao Meng, Rong Xu, Monika Colombo, Tobias Weiss, Stefan Balabanov, Stavros Stavrakis, Andew J. deMello
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In principle, the measurement of mechanical property differences between cancer cells and their benign counterparts enables the detection, diagnosis, and classification of diseases. Despite the existence of various mechanophenotyping methods, the ability to perform high-throughput single-cell deformability measurements on liquid and/or solid tissue biopsies remains an unmet challenge within clinical settings. To address this issue, we present an ultrahigh-throughput viscoelastic microfluidic platform able to measure the mechanical properties of single cells at rates of up to 100,000 cells per second (and up to 10,000 cells per second in real time). To showcase the utility of the presented platform in clinical scenarios, we perform single-cell phenotyping of both liquid and solid tumor biopsies, cytoskeletal drug analysis, and identification of malignant lymphocytes in peripheral blood samples. Our viscoelastic microfluidic methodology offers opportunities for high-throughput, label-free single-cell analysis, with diverse applications in clinical diagnostics and personalized medicine.
GPT-4o mini: Non-social science research article
Sunflower-like self-sustainable plant-wearable sensing probe
Shuang Wang, Yangfan Chai, Huiwen Sa, Weikang Ye, Qian Wang, Yu Zou, Xuan Luo, Lijuan Xie, Xiangjiang Liu
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Powering and communicating with wearable devices on bio-interfaces is challenging due to strict weight, size, and resource constraints. This study presents a sunflower-like plant-wearable sensing device that harnesses solar energy, achieving complete energy self-sustainability for long-term monitoring of plant sap flow, a crucial indicator of plant health. It features foldable solar panels along with all essential flexible electronic components, resulting in a compact system that is lightweight enough for small plants. To tackle the low-energy density of solar power, we developed an ultralow-energy light communication mechanism inspired by fireflies. Together with unmanned aerial vehicles and deep learning algorithms, this approach enables efficient data retrieval from multiple devices across large agricultural fields. With its simple deployment, it shows great potential as a low-cost plant phenotyping tool. We believe our energy and communication solution for wearable devices can be extended to similar resource-limited and challenging scenarios, leading to exciting applications.
GPT-4o mini: Non-social science research article
Mammoth featured heavily in Western Clovis diet
James C. Chatters, Ben A. Potter, Stuart J. Fiedel, Juliet E. Morrow, Christopher N. Jass, Matthew J. Wooller
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Ancient Native American ancestors (Clovis) have been interpreted as either specialized megafauna hunters or generalist foragers. Supporting data are typically indirect (toolkits, associated fauna) or speculative (models, actualistic experiments). Here, we present stable isotope analyses of the only known Clovis individual, the 18-month-old Anzick child, to directly infer maternal protein diet. Using comparative fauna from this region and period, we find that mammoth was the largest contributor to Clovis diet, followed by elk and bison/camel, while the contribution of small mammals was negligible, broadly consistent with the Clovis zooarchaeological record. When compared with second-order consumers, the Anzick-1 maternal diet is closest to that of scimitar cat, a mammoth specialist. Our findings are consistent with the Clovis megafaunal specialist model, using sophisticated technology and high residential mobility to subsist on the highest ranked prey, an adaptation allowing them to rapidly expand across the Americas south of the Pleistocene ice sheets.
GPT-4o mini: Non-social science research article
Boosting 1 H and 13 C NMR signals by orders of magnitude on a bench
Charlotte Bocquelet, Nathan Rougier, Huu-Nghia Le, Laurent Veyre, Chloe Thieuleux, Roberto Melzi, Armin Purea, Daniel Banks, James G. Kempf, Quentin Stern, Ewoud Vaneeckhaute, Sami Jannin
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Sensitivity is often the Achilles’ heel of liquid-state nuclear magnetic resonance (NMR) experiments. This problem is perhaps most pressing at the lowest fields (e.g., 80-MHz 1 H frequency), with rapidly increasing access to NMR through benchtop systems, but also sometimes for higher-field NMR systems from 300 MHz to 1.2 GHz. Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) can address this sensitivity limitation. However, dDNP implies massive and complex cryogenic and high-field instrumentation, which cannot be installed on the bench. We introduce here a compact helium-free 1-T tabletop polarizer as a simple and low-cost alternative. After freezing and polarizing the frozen analyte solutions at 77 K, we demonstrate 1 H signal enhancement factors of 100, with rapid 1-s buildup times. The high polarization is subsequently transferred by 1 H→ 13 C cross polarization (CP) to 13 C spins. Such a simple benchtop polarizer, in combination with hyperpolarizing solid matrices (HYPSOs), may open the way to replenishable hyperpolarization throughout multiple liquid-state NMR experiments.
GPT-4o mini: Non-social science research article
Granular metamaterials with dynamic bond reconfiguration
Zhiqiang Meng, Hujie Yan, Yifan Wang
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Biological materials dynamically reconfigure their underlying structures in response to stimuli, achieving adaptability and multifunctionality. Conversely, mechanical metamaterials have fixed interunit connections that restrict adaptability and reconfiguration. This study introduces granular metamaterials composed of discrete bimaterial structured particles that transition between assembled and unassembled states through mechanical compression and thermal stimuli. These materials enable dynamic bond reconfiguration, allowing reversible bond breaking and formation, similar to natural systems. Leveraging their discrete nature, these materials can adaptively reconfigure their shape and respond dynamically to varying conditions. Our investigations reveal that these granular metamaterials can substantially alter their mechanical properties, like compression, shearing, and bending, offering tunable mechanical characteristics across different states. Furthermore, they exhibit collective behaviors like directional movement, object capture, transportation, and gap crossing, showcasing their potential for reprogrammable functionalities. This work highlights the dynamic reconfigurability and robust adaptability of granular metamaterials, expanding their potential in responsive architecture and autonomous robotics.
GPT-4o mini: Non-social science research article
Bioinspired single-shot polarization photodetector based on four-directional grating arrays capped perovskite single-crystal thin film
Wenzhong Fang, Chengben Liu, Zixin Zhu, Chao Wu, Qunfeng Cheng, Qian Song, Yang Wang, Xintao Lai, Yanlin Song, Lei Jiang, Mingzhu Li
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Polarization photodetectors (pol-PDs) have widespread applications in geological remote sensing, machine vision, biological medicine, and so on. However, commercial pol-PDs use bulky and complicated optical systems with lenses, polarizers, and mechanical spools, which are complex and cumbersome, and respond slowly. Inspired by the desert ants’ compound eyes, we developed a single-shot pol-PD based on four-directional grating arrays capped perovskite single-crystal thin film without other standard polarization optics. Our pol-PD has a high detectivity, two orders of magnitude greater than that of commercial photodetectors, and exhibits high polarization sensitivity. The high performance of our pol-PD is due to the highly crystalline perovskite single-crystal thin film and regular nanograting structure, made by a nanoimprinting crystallization method. Our single-shot pol-PD is a compact on-chip optoelectronic device that demonstrates excellent performance in a wide range of applications including accurate bionic navigation, sharp image restoration in hazy scenes, stress visualization of polymers, and detection of cancerous areas in tissues without histological staining.
GPT-4o mini: Non-social science research article
Late Pleistocene onset of mutualistic human/canid ( Canis spp.) relationships in subarctic Alaska
François Lanoë, Joshua Reuther, Stormy Fields, Ben Potter, Gerad Smith, Holly McKinney, Carrin Halffman, Charles Holmes, Robin Mills, Barbara Crass, Ryan Frome, Kyndall Hildebrandt, Robert Sattler, Scott Shirar, Alida de Flamingh, Brian M. Kemp, Ripan Malhi, Kelsey E. Witt
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Large canids (wolves, dogs, and coyote) and people form a close relationship in northern (subarctic and arctic) socioecological systems. Here, we document the antiquity of this bond and the multiple ways it manifested in interior Alaska, a region key to understanding the peopling of the Americas and early northern lifeways. We compile original and existing genomic, isotopic, and osteological canid data from archaeological, paleontological, and modern sites. Results show that in contrast to canids recovered in non-anthropic contexts, canids recovered in association with human occupations are markedly diverse. They include multiple species and intraspecific lineages, morphological variation, and diets ranging from terrestrial to marine. This variation is expressed along both geographic and temporal gradients, starting in the terminal Pleistocene with canids showing high marine dietary estimates. This paper provides evidence of the multiple ecological relationships between canids and people in the north—from predation, probable commensalism, and taming, to domestication—and of their early onset.
GPT-4o mini: Non-social science research article
N-cadherin antagonism is bronchoprotective in severe asthma models
Nicolas L. Pereira, Niccole Schaible, Abhishek Desai, Eunice C. Chan, Ararat J. Ablooglu, Jacqueline Capuano, Erika Lin, Zheming An, Eric Gebski, William Jester, Sundar Ganesan, Nariman Balenga, Cynthia Koziol-White, Reynold A. Panettieri, Sangita Choudhury, Ramaswamy Krishnan, Kirk M. Druey
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Severe asthma induces substantial mortality and chronic disability due to intractable airway obstruction, which may become resistant to currently available therapies including corticosteroids and β-adrenergic agonist bronchodilators. A key effector of these changes is exaggerated airway smooth muscle (ASM) cell contraction to spasmogens. No drugs in clinical use effectively prevent ASM hyperresponsiveness in asthma across all severities. We find that N-cadherin, a membrane cell-cell adhesion protein up-regulated in ASM from patients with severe asthma, is required for the development of airway obstruction induced by allergic airway inflammation in mice. Inhibition of N-cadherin by ADH-1 reduced airway hyperresponsiveness independent of allergic inflammation, prevented bronchoconstriction, and actively promoted bronchodilation of airways ex vivo. ADH-1 inhibited ASM contraction by disrupting N-cadherin–δ-catenin interactions, which decreased intracellular actin remodeling. These data provide evidence for an intercellular communication pathway mediating ASM contraction and identify N-cadherin as a potential therapeutic target for inhibiting bronchoconstriction in asthma.
GPT-4o mini: Non-social science research article
Triboelectric nanogenerator for high-entropy energy, self-powered sensors, and popular education
Huijing Xiang, Lin Peng, Qiuxiang Yang, Zhong Lin Wang, Xia Cao
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Triboelectric nanogenerator (TENG) has become a promising option for high-entropy energy harvesting and self-powered sensors because of their ability to combine the effects of contact electrification and electrostatic induction to effectively convert mechanical energy into electric power or signals. Here, the theoretical origin of TENG, strategies for high-performance TENG, and its applications in high-entropy energy, self-powered sensors, and blue energy are comprehensively introduced on the basis of the fundamental science and principle of TENG. Besides, a series of work in popular science education for TENG that includes numerous scientific and technological products from our science education base, Maxwell Science+, is emphatically introduced. This topic provides an angle and notable insights into the development of TENG.
GPT-4o mini: Non-social science research article
Nonreciprocal superconductivity
Margarita Davydova, Max Geier, Liang Fu
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We introduce the notion of nonreciprocal superconductors where inversion and time-reversal symmetries are broken, giving rise to an asymmetric energy dispersion. We demonstrate that nonreciprocal superconductivity can be detected by Andreev reflection. In particular, a transparent junction between a normal metal and a nonreciprocal superconductor generally exhibits an asymmetric current-voltage characteristic, which serves as a defining feature of nonreciprocal superconductivity. Unlike the superconducting diode effects, our detection scheme has the advantage of avoiding large critical currents that turn the superconducting state to normal. Last, we discuss candidates for nonreciprocal superconductivity, including graphene, UTe 2 , as well as engineered platforms.
GPT-4o mini: Non-social science research article
Temperature-responsive metamaterials made of highly sensitive thermostat metal strips
Yi Zhang, Wei Zhong Jiang, Yang Pan, Xing Chi Teng, Hang Hang Xu, Han Yan, Xi Hai Ni, Jun Dong, Dong Han, Wei Qiu Chen, Jie Yang, Yi Min Xie, Yang Lu, Xin Ren
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Temperature-responsive metamaterials have remarkable shape-morphing ability during thermal energy conversion. However, integrating the thermal shape programmability, wide-working temperature range, fast temperature response, and actuation into metamaterials remains challenging. Here, we introduce using thermostat metal strips to assemble metamaterials with desirable and balanced temperature-responsive properties, and we systematically investigate the thermal deformation performance. Achieving 70 to 80% of the designed strain requires only 5 seconds of heating. A thermal strain of around 30% is achieved for the assembled metamaterials, surpassing other bimetallic metamaterials by a magnitude of 100 to 200. The actuation capacity of thermostat metal strips exceeds 26 times their weight. Further, by leveraging the highly programmable thermal deformation, the tuneable bandgap range is 3847 to 40,000 hertz. These fully integrated mechanical performances in the multiphysics have great application potential, for example, as soft actuators and soft robots in intelligent structure systems, vibration isolation and noise reduction in hypersonic vehicles, and unique thermal deformation in precision instruments.
GPT-4o mini: Non-social science research article
Fish-inspired dynamic charging for ultrafast self-protective solar-thermal energy storage
Xiaoxiang Li, Jingyi Zhang, Yizhe Liu, Yangzhe Xu, Yixuan Xie, Ting Hu, Benwei Fu, Chengyi Song, Wen Shang, Peng Tao, Tao Deng
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Solar-thermal energy storage (STES) within solid-liquid phase change materials (PCMs) has emerged as an attractive solution to overcome intermittency of renewable energy. However, current storage systems usually suffer from slow charging rates, sacrificed storage capacity, and overheating tendency. Inspired by the thermoregulation behavior of Cyprinid fish, here, we present a quick-responsive, ultrafast, large-capacity, overheating-protective STES strategy. We fabricate a liquid-infused solar-absorbing foam charger that can rapidly advance the receding solid-liquid charging interface to efficiently store solar-thermal energy as latent heat and spontaneously float upward to cease the charging process upon overheating. This bioinspired dynamic charging is adaptable to a variety of PCMs, unlocking the potential for safe and efficient utilization of renewable thermal energy.
GPT-4o mini: Non-social science research article
Atroposelective synthesis of axially chiral imidazo[1,2- a ]pyridines via asymmetric multicomponent reaction
Shibin Hong, Wei Liu, Chongyi Zhang, Xiaoyu Yang
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Imidazo[1,2- a ]pyridines are privileged heterocycles with diverse applications in medicinal chemistry; however, the catalytic asymmetric synthesis of these heterocyclic structures remains underexplored. Herein, we present an efficient and modular approach for the atroposelective synthesis of axially chiral imidazo[1,2- a ]pyridines via an asymmetric multicomponent reaction. By utilizing a chiral phosphoric acid catalyst, the Groebke-Blackburn-Bienaymé reaction involving various 6-aryl-2-aminopyridines, aldehydes, and isocyanides gave access to a wide range of imidazo[1,2- a ]pyridine atropoisomers with high to excellent yields and enantioselectivities. Extensive control experiments underscored the pivotal role of the remote hydrogen bonding donor on the substrates in achieving high stereoselectivity for these reactions. The versatile derivatizations of these atropisomeric products, especially their role as an analog of NOBINs and their facile conversion into unique 6,6-spirocyclic products, further emphasize the merits of this methodology.
GPT-4o mini: Non-social science research article
The crystal and cryo-EM structures of PLCγ2 reveal dynamic interdomain recognitions in autoinhibition
Young-Cheul Shin, Ashlee Marie Plummer-Medeiros, Alison Mungenast, Hyeong-wook Choi, Karen TenDyke, Xiaojie Zhu, Jennifer Shepard, Kristen Sanders, Ningning Zhuang, Liang Hu, Dongming Qian, Kangkang Song, Chen Xu, John Wang, Suresh B. Poda, Maofu Liao, Yu Chen
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Phospholipase C gamma 2 (PLCγ2) plays important roles in cell signaling downstream of various membrane receptors. PLCγ2 contains a multidomain inhibitory region critical for its regulation, while it has remained unclear how these domains contribute to PLCγ2 activity modulation. Here we determined three structures of human PLCγ2 in autoinhibited states, which reveal dynamic interactions at the autoinhibition interface, involving the conformational flexibility of the Src homology 3 (SH3) domain in the inhibitory region, and its previously unknown interaction with a carboxyl-terminal helical domain in the core region. We also determined a structure of PLCγ2 bound to the kinase domain of fibroblast growth factor receptor 1 (FGFR1), which demonstrates the recognition of FGFR1 by the nSH2 domain in the inhibitory region of PLCγ2. Our results provide structural insights into PLCγ2 regulation that will facilitate future mechanistic studies to understand the entire activation process.
GPT-4o mini: Non-social science research article
Cryo-EM structure of a photosystem I variant containing an unusual plastoquinone derivative in its electron transfer chain
Christopher J. Gisriel, Vasily Kurashov, David F. Iwig, Brandon P. Russell, David J. Vinyard, Gary W. Brudvig, John H. Golbeck, K. V. Lakshmi
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Photosystem I (PS I) is a light-driven oxidoreductase responsible for converting photons into chemical bond energy. Its application for renewable energy was revolutionized by the creation of the MenB deletion (Δ menB ) variant in the cyanobacterium Synechocystis sp. PCC 6803, in which phylloquinone is replaced by plastoquinone-9 with a low binding affinity. This permits its exchange with exogenous quinones covalently coupled to dihydrogen catalysts that bind with high affinity, thereby converting PS I into a stable solar fuel catalyst. Here, we reveal the 2.03-Å-resolution cryo-EM structure of a recent MenB variant of PS I. The quinones and their binding environment are analyzed in the context of previous biophysical data, thereby enabling a protocol to solve future PS I hybrids and constructs from this genetically tractable cyanobacterium.
GPT-4o mini: Non-social science research article
Capturing intermediates and membrane remodeling in class III viral fusion
Lenka Milojević, Zhu Si, Xian Xia, Lauren Chen, Yao He, Sijia Tang, Ming Luo, Z. Hong Zhou
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Enveloped viruses enter cells by fusing their envelopes to host cell membranes. Vesicular stomatitis virus (VSV) glycoprotein (G) is a prototype for class III fusion proteins. Although structures of the stable pre- and postfusion ectodomain of G are known, its fusogenic intermediates are insufficiently characterized. Here, we incubated VSV virions with late endosome-mimicking liposomes at pH 5.5 and used cryo–electron tomography (cryo-ET) to visualize stages of VSV’s membrane fusion pathway, capture refolding intermediates of G, and reconstruct a sequence of G conformational changes. We observe that the G trimer disassembles into monomers and parallel dimers that explore a broad conformational space. Extended intermediates engage target membranes and mediate fusion, resulting in viral uncoating and linearization of the ribonucleoprotein genome. These viral fusion intermediates provide mechanistic insights into class III viral fusion processes, opening avenues for future research and structure-based design of fusion inhibition-based antiviral therapeutics.
GPT-4o mini: Non-social science research article
Arabidopsis histone acetyltransferase complex coordinates cytoplasmic histone acetylation and nuclear chromatin accessibility
Chan-Juan Wu, Xin Xu, Dan-Yang Yuan, Zhen-Zhen Liu, Lian-Mei Tan, Yin-Na Su, Lin Li, She Chen, Xin-Jian He
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Conserved type B histone acetyltransferases are recognized for their role in acetylating newly synthesized histones in the cytoplasm of eukaryotes. However, their involvement in regulating chromatin within the nucleus remains unclear. Our study shows that the Arabidopsis thaliana type B histone acetyltransferase HAG2 interacts with the histone chaperones MSI2, MSI3, and NASP, as well as the histones H3 and H4, forming a complex in both the cytoplasm and the nucleus. Within this complex, HAG2 and MSI2/3 constitute a histone acetylation module essential for acetylating histone H4 in the cytoplasm. Furthermore, this module works together with NASP to regulate histone acetylation, chromatin accessibility, and gene transcription in the nucleus. This complex enhances chromatin accessibility near transcription start sites while reducing accessibility near transcription termination sites. Our findings reveal a distinct role for the Arabidopsis type B histone acetyltransferase in the nucleus, shedding light on the coordination between cytoplasmic histone acetylation and nuclear chromatin regulation in plants.
GPT-4o mini: Non-social science research article
Spontaneous snapping-induced jet flows for fast, maneuverable surface and underwater soft flapping swimmer
Haitao Qing, Jiacheng Guo, Yuanhang Zhu, Yinding Chi, Yaoye Hong, Daniel Quinn, Haibo Dong, Jie Yin
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Manta rays use wing-like pectoral fins for intriguing oscillatory swimming. It provides rich inspiration for designing potentially fast, efficient, and maneuverable soft swimming robots, which, however, have yet to be realized. It remains a grand challenge to combine fast speed, high efficiency, and high maneuverability in a single soft swimmer while using simple actuation and control. Here, we report leveraging spontaneous snapping stroke in the monostable flapping wing of a manta-like soft swimmer to address the challenge. The monostable wing is pneumatically actuated to instantaneously snap through to stroke down, and upon deflation, it will spontaneously stroke up by snapping back to its initial state, driven by elastic restoring force, without consuming additional energy. This largely simplifies designs, actuation, and control for achieving a record-high speed of 6.8 body length per second, high energy efficiency, and high maneuverability and collision resilience in navigating through underwater unstructured environments with obstacles by simply tuning single-input actuation frequencies.
GPT-4o mini: Non-social science research article
Dynamically logical modulation for THz wave within a dual gate–controlled 2DEG metasurface
Hongxin Zeng, Xuan Cong, Huifang Zhang, Sen Gong, Tianchi Zhou, Lan Wang, Haoyi Cao, Huajie Liang, Shixiong Liang, Shiqi Wang, Feng Lan, Xun Wang, Ziqiang Yang, Yaxin Zhang, Tie Jun Cui
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High-speed logic modulation of terahertz (THz) waves is crucial for future communications, yet a technology gap persists. Here, we report a dual gate–controlled two-dimensional electronic gas logic modulation metasurface that enables symmetric and asymmetric electron distribution states through independent control of the two electron transport channels. The transition between these two states leads to various response modes in the metasurface and notably increases the diversity of the spectrum transformation, resulting in a multivalued relationship in which each output corresponds to more than one input signal, thus establishing the logical modulation. Our results demonstrate the common logical functions of AND, OR, XOR, XNOR, NOR, and NAND at different frequencies with a modulation speed faster than 250 picoseconds. This work offers a unique avenue for the high-speed, free-space logical operation of THz waves and increases the security of secure communication.
GPT-4o mini: Non-social science research article
High sea surface temperatures were a prerequisite for the development and expansion of the Great Barrier Reef
Benjamin Petrick, Lars Reuning, Alexandra Auderset, Miriam Pfeiffer, Gerald Auer, Lorenz Schwark
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The Great Barrier Reef is the largest reef system in the modern ocean. To date, the influence of temperature on the origin and long-term evolution of the Great Barrier Reef remains enigmatic. Here, we present a 900–thousand year TEX 86 H -derived temperature proxy record from Ocean Drilling Program Site 820 in the Coral Sea. It demonstrates that the onset of reef growth on the outer shelf was preceded by a rise in summer temperature from ~26° to ~28°C at around 700 thousand years ago (marine isotope stage 17). This approximately 2°C rise in summer sea surface temperatures (SSTs) likely resulted in higher carbonate production rates, which were crucial for the formation of the Great Barrier Reef. Subsequently, reconstructed SSTs remained sufficiently warm for the Great Barrier Reef to thrive and evolve continuously. The evolution of the Great Barrier Reef, therefore, appears to be closely linked to SSTs.
GPT-4o mini: Non-social science research article
Renal Angptl4 is a key fibrogenic molecule in progressive diabetic kidney disease
Swayam Prakash Srivastava, Han Zhou, Rachel Shenoi, Myshal Morris, Begoña Lainez-Mas, Leigh Goedeke, Barani Kumar Rajendran, Ocean Setia, Binod Aryal, Keizo Kanasaki, Daisuke Koya, Ken Inoki, Alan Dardik, Thomas Bell, Carlos Fernández-Hernando, Gerald I. Shulman, Julie E. Goodwin
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Angiopoietin-like 4 (ANGPTL4), a key protein involved in lipoprotein metabolism, has diverse effects. There is an association between Angptl4 and diabetic kidney disease; however, this association has not been well investigated. We show that both podocyte- and tubule-specific ANGPTL4 are crucial fibrogenic molecules in diabetes. Diabetes accelerates the fibrogenic phenotype in control mice but not in ANGPTL4 mutant mice. The protective effect observed in ANGPTL4 mutant mice is correlated with a reduction in stimulator of interferon genes pathway activation, expression of pro-inflammatory cytokines, reduced epithelial-to-mesenchymal transition and endothelial-to-mesenchymal transition, lessened mitochondrial damage, and increased fatty acid oxidation. Mechanistically, we demonstrate that podocyte- or tubule-secreted Angptl4 interacts with Integrin β1 and influences the association between dipeptidyl-4 with Integrin β1. We demonstrate the utility of a targeted pharmacologic therapy that specifically inhibits Angptl4 gene expression in the kidneys and protects diabetic kidneys from proteinuria and fibrosis. Together, these data demonstrate that podocyte- and tubule-derived Angptl4 is fibrogenic in diabetic kidneys.
GPT-4o mini: Non-social science research article
In vivo dynamic tracking of cerebral chloride regulation using molecularly tailored liquid/liquid interfacial ultramicro iontronics
Chaoyue Gu, Fanzhen Kong, Sen Liang, Xiang Zhao, Bingjie Kong, Tianhe Jiang, Jianan Yu, Qi Li, Yuqing Lin, Shuo Bai, Yuanhua Shao
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Chloride ion, a pivotal cerebral anion involved in neuronal inhibition, is implicated in various neurodegenerative diseases. Conventional direct faradaic detection based on electron transfers at solid electrode/solution interfaces has been proven ineffective due to the electrochemically inactive nature of Cl − . Here, we present an approach involving molecularly tailored liquid/liquid interfacial ultramicro iontronics (L/L-UIs) supported at ultramicropipettes filled with organic gel containing lipophilic bis-thioureas ionophores, which represents the first application of amperometric methodology based on electrochemical facilitated ion transfers reactions at a soft L/L ultramicrointerface to achieve in vivo sensing of electrochemically inactive ions, and dynamically tracking cerebral Cl − in vivo. Furthermore, evidence of dynamic neuronal Cl − regulation via KCC2 modulated through GABA B receptors was provided, further substantiating GABA B receptor–mediated Cl − -related neuronal inhibition. The proposed L/L-UIs have notable potential for in situ tracking of other crucial electrochemically inactive ions or ionized biomolecules in vivo, thereby facilitating the study of brain diseases and the diagnosis and treatment of related disorders.
GPT-4o mini: Non-social science research article
Molecular principles of the assembly and construction of a carboxysome shell
Peng Wang, Jianxun Li, Tianpei Li, Kang Li, Pei Cing Ng, Saimeng Wang, Vincent Chriscoli, Arnaud Basle, Jon Marles-Wright, Yu-Zhong Zhang, Lu-Ning Liu
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Intracellular compartmentalization enhances biological reactions, crucial for cellular function and survival. An example is the carboxysome, a bacterial microcompartment for CO 2 fixation. The carboxysome uses a polyhedral protein shell made of hexamers, pentamers, and trimers to encapsulate Rubisco, increasing CO 2 levels near Rubisco to enhance carboxylation. Despite their role in the global carbon cycle, the molecular mechanisms behind carboxysome shell assembly remain unclear. Here, we present a structural characterization of α-carboxysome shells generated from recombinant systems, which contain all shell proteins and the scaffolding protein CsoS2. Atomic-resolution cryo–electron microscopy of the shell assemblies, with a maximal size of 54 nm, unveil diverse assembly interfaces between shell proteins, detailed interactions of CsoS2 with shell proteins to drive shell assembly, and the formation of heterohexamers and heteropentamers by different shell protein paralogs, facilitating the assembly of larger empty shells. Our findings provide mechanistic insights into the construction principles of α-carboxysome shells and the role of CsoS2 in governing α-carboxysome assembly and functionality.
GPT-4o mini: Non-social science research article
Respiratory delivery of single low-dose nebulized PFCE-C25 NEs for lymphatic transport and durable stimulation of antitumor immunity in lung cancer
Rong A, Zhaoguo Han, Meifang Zhou, Chaoqun Nie, Mengyuan Zhu, Sijie Cheng, Tianyi Wang, Jing Wang, Zhen Quan, Kaiqi Wang, Shanshan Liu, Xinxin Hu, Haoyu Wang, Jiannan Wang, Yongyi Wu, Xilin Sun
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The currently available immune checkpoint inhibitors (ICIs) often fail to achieve the desired clinical outcomes due to inadequate immune activation, particularly in patients with lung cancer. To reverse this situation, we synthesized inhalable PFCE-C25 nanoemulsions (NEs), which target lymphocyte activation genes (LAG-3) on immune cells within tumor microenvironment and tumor-draining lymph nodes (TDLNs). By combining in vivo 19 F-MR molecular imaging, we investigate the immunological effects of a single low-dose PFCE-C25 NEs in multiple murine lung cancer models, including human immune system (HIS) mouse models, and validated its immunological effects in human TDLNs. The nebulization therapy with PFCE-C25 NEs demonstrated a notable and enduring maturation of dendritic cells (DCs) in TDLNs, leading to systemic immune responses, prolonged survival, the establishment of immune memory, and resistance to tumor rechallenge. Thus, PFCE-C25 NEs successfully demonstrate a promising and efficient approach for enhancing lymphatic transport and sustained activation of antitumor immune responses in lung cancer.
GPT-4o mini: Non-social science research article
Revealing subterahertz atomic vibrations in quantum paraelectrics by surface-sensitive spintronic terahertz spectroscopy
Zhaodong Chu, Junyi Yang, Yan Li, Kyle Hwangbo, Jianguo Wen, Ashley R. Bielinski, Qi Zhang, Alex B. F. Martinson, Stephan O. Hruszkewycz, Dillon D. Fong, Xiaodong Xu, Michael R. Norman, Anand Bhattacharya, Haidan Wen
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Understanding surface collective dynamics in quantum materials is crucial for advancing quantum technologies. For example, surface phonon modes in quantum paraelectrics are thought to be essential in facilitating interfacial superconductivity. However, detecting these modes, especially below 1 terahertz, is challenging because of limited sampling volumes and the need for high spectroscopic resolution. Here, we report surface soft transverse optical (TO1) phonon dynamics in KTaO 3 and SrTiO 3 by surface-sensitive spintronic terahertz spectroscopy that can sense the collective modes only a few nanometers deep from the surface. In KTaO 3 , the TO1 mode softens and sharpens with decreasing temperature, leveling off at 0.7 terahertz. In contrast, this mode in SrTiO 3 broadens substantially below the quantum paraelectric crossover and coincides with the hardening of a sub–milli–electron volt phonon mode related to the antiferrodistortive transition. These observations that deviate from their bulk properties may have implications for interfacial superconductivity and ferroelectricity. The developed technique opens opportunities for sensing low-energy surface collective excitations.
GPT-4o mini: Non-social science research article
FERONIA adjusts CC1 phosphorylation to control microtubule array behavior in response to salt stress
Xin Liu, Liu Wang, Linlin Liu, Yuan Li, Michael Ogden, Marc Somssich, Yutong Liu, Yuwen Zhang, Minyuan Ran, Staffan Persson, Chunzhao Zhao
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Cell wall remodeling is important for plants to adapt to environmental stress. Under salt stress, cortical microtubules undergo a depolymerization-reassembly process to promote the biosynthesis of stress-adaptive cellulose, but the regulatory mechanisms underlying this process are still largely unknown. In this study, we reveal that FERONIA (FER), a potential cell wall sensor, interacts with COMPANION OF CELLULOSE SYNTHASE1 (CC1) and its closest homolog, CC2, two proteins that are required for cortical microtubule reassembly under salt stress. Biochemical data indicate that FER phosphorylates CC1 on multiple residues in its second and third hydrophobic microtubule-binding regions and that these phosphorylations modulate CC1 trafficking and affect the ability of CC1 to engage with microtubules. Furthermore, CC1 phosphorylation level is altered upon exposure to salt stress, which coincides with the changes of microtubule organization. Together, our study outlines an important intracellular mechanism that maintains microtubule arrays during salt exposure in plant cells.
GPT-4o mini: Non-social science research article
Physics-guided deep learning for skillful wind-wave modeling
Xinxin Wang, Haoyu Jiang
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Modeling sea surface wind-waves is crucial for both scientific research and engineering applications. Nowadays, the most accurate wave models are based on numerical methods, which primarily concern the wave spectrum evolution by solving wave action balance partial differential equations. These methods are computationally expensive and limited by incomplete physical representations of wave spectral evolution. Here, we present a deep learning–based wave model trained using observation-merged wave hindcasts. Guided by the physics knowledge that waves are either generated by local current winds or by remote historical winds, this method can directly model significant wave height, bypassing the need for wave spectral information. This feature engineering effectively reduces the complexity of model inputs and outputs. The resulting artificial intelligence method can model 1 year of global significant wave heights at a 0.5° × 0.5° × 1-hour resolution within half an hour on a personal computer, achieving higher accuracy than state-of-the-art numerical wave models.
GPT-4o mini: Non-social science research article
A trafficking regulatory subnetwork governs α V β 6 integrin-HER2 cross-talk to control breast cancer invasion and drug resistance
Horacio Maldonado, Marcel Dreger, Lara D. Bedgood, Theano Kyriakou, Katarzyna I. Wolanska, Megan E. Rigby, Valeria E. Marotta, Justine M. Webster, Jun Wang, Emma V. Rusilowicz-Jones, John F. Marshall, Judy M. Coulson, Iain R. Macpherson, Adam Hurlstone, Mark R. Morgan
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HER2 and α V β 6 integrin are independent predictors of breast cancer survival and metastasis. We identify an α V β 6 /HER2 cross-talk mechanism driving invasion, which is dysregulated in drug-resistant HER2+ breast cancer cells. Proteomic analyses reveal ligand-bound α V β 6 recruits HER2 and a trafficking subnetwork, comprising guanosine triphosphatases RAB5 and RAB7A and the Rab regulator guanine nucleotide dissociation inhibitor 2 (GDI2). The RAB5/RAB7A/GDI2 functional module mediates direct cross-talk between α V β 6 and HER2, affecting receptor trafficking and signaling. Acute exposure to trastuzumab increases recruitment of the subnetwork to α V β 6 , but trastuzumab resistance decouples GDI2 recruitment. GDI2, RAB5, and RAB7A cooperate to regulate migration and transforming growth factor–β activation to promote invasion. However, these mechanisms are dysregulated in trastuzumab-resistant cells. In patients, RAB5A , RAB7A , and GDI2 expression correlates with patient survival and α V β 6 expression predicts relapse following trastuzumab treatment. Thus, the RAB5/RAB7A/GDI2 subnetwork regulates α V β 6 -HER2 cross-talk to drive breast cancer invasion but is subverted in trastuzumab-resistant cells to drive α V β 6 -independent and HER2-independent tumor progression.
GPT-4o mini: Non-social science research article
A general temperature-guided language model to design proteins of enhanced stability and activity
Fan Jiang, Mingchen Li, Jiajun Dong, Yuanxi Yu, Xinyu Sun, Banghao Wu, Jin Huang, Liqi Kang, Yufeng Pei, Liang Zhang, Shaojie Wang, Wenxue Xu, Jingyao Xin, Wanli Ouyang, Guisheng Fan, Lirong Zheng, Yang Tan, Zhiqiang Hu, Yi Xiong, Yan Feng, Guangyu Yang, Qian Liu, Jie Song, Jia Liu, Liang Hong, Pan Tan
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Designing protein mutants with both high stability and activity is a critical yet challenging task in protein engineering. Here, we introduce PRIME, a deep learning model, which can suggest protein mutants with improved stability and activity without any prior experimental mutagenesis data for the specified protein. Leveraging temperature-aware language modeling, PRIME demonstrated superior predictive ability compared to current state-of-the-art models on the public mutagenesis dataset across 283 protein assays. Furthermore, we validated PRIME’s predictions on five proteins, examining the impact of the top 30 to 45 single-site mutations on various protein properties, including thermal stability, antigen-antibody binding affinity, and the ability to polymerize nonnatural nucleic acid or resilience to extreme alkaline conditions. More than 30% of PRIME-recommended mutants exhibited superior performance compared to their premutation counterparts across all proteins and desired properties. We developed an efficient and effective method based on PRIME to rapidly obtain multisite mutants with enhanced activity and stability. Hence, PRIME demonstrates broad applicability in protein engineering.
GPT-4o mini: Non-social science research article
Electrically silent mutants unravel the mechanism of binding−gating coupling in Cys-loop receptors
Nicole E. Godellas, Gisela D. Cymes, Claudio Grosman
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The transduction of extracellular chemical signals into intracellular events relies on the communication between neighboring domains of membrane receptors. In the particular case of Cys-loop receptor channels, five short stretches of amino acids, one per subunit, link the extracellular and transmembrane domains in such a way that the ion permeability of the latter and the affinity for neurotransmitters of the former become tied to each other. Here, using direct functional approaches, we set out to understand the molecular bases of this crucial interdependence through the characterization of total loss-of-current mutations at the interface between domains. Our results indicate that domain−domain proximity plays a previously unnoticed critical role inasmuch as inserting a single residue in each linker rendered the two domains independent of each other. In marked contrast, loss-of-current mutations that leave the linkers’ length unaltered did not compromise the interdomain coupling, but rather, seemed to cause agonist-bound closed receptors to desensitize without appreciably opening.
GPT-4o mini: Non-social science research article
Effectively tuning the quantum Griffiths phase by controllable quantum fluctuations
Beilin Wang, Guopei Ying, Linhai Guo, Zhiyong Lin, Haiwen Liu, Changgan Zeng
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Quantum Griffiths phase (QGP), marked by a quantum Griffiths singularity with a divergent effective critical exponent, has garnered considerable attention in the realm of superconductivity. However, the ability to control QGP remains elusive. Here, we demonstrate that QGP at the LaAlO 3 /KTaO 3 (110) interface can be efficiently modulated by the orientation of applied magnetic field: With a perpendicular field, an anomalous QGP emerges in the low-temperature regime, characterized by a decreasing critical field as temperature lowers; conversely, with a parallel field, a normal QGP arises, where the critical field increases with decreasing temperature. Such opposite characteristics stem from the controllable quantum fluctuations and conductivity corrections under distinct magnetic field orientations. Furthermore, we show the effective tuning of the phase boundary by electrostatic gating, attributed to the gate-controlled quantum fluctuations. These findings not only demonstrate how to experimentally manipulate QGP but also provide a comprehensive understanding of how quantum fluctuations can effectively modulate QGP.
GPT-4o mini: Non-social science research article
Hormone response elements for the thyroid receptor-α include specific distal 5′-flanking DNA
David P. Lohry, Taylor A. Stevens, Tongye Shen, Elias J. Fernandez
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Optimal gene transcription is achieved through precise interactions between transcription factors and their DNA binding sites. We provide evidence that conserved distally located 5′-flanking sequences interact directly with the intrinsically disordered amino-terminal region of the thyroid receptor-α (TRα) to control transcriptional activity. Simulated modeling and dynamics with multiple ChIP-seq–derived sequences consistently reveal specific lysine/arginine–DNA minor groove interactions. The impact of these interactions is to distort DNA structural conformations, and these are also revealed with atomic force microscopy. The importance of the 5′-flanking DNA is further emphasized with reporter gene assays and comparisons with canonical response elements. Overall, the study reveals the inadequacy of current definitions of the DNA hormone response element (HRE) and suggests that future descriptions of the HRE include the conserved distal DNA sequences. The broad impact of this study is further underscored by the common occurrence of Lys/Arg-rich motifs within the intrinsically disordered regions of nuclear receptors.
GPT-4o mini: Non-social science research article
Identification of VISTA regulators in macrophages mediating cancer cell survival
Abdalla M. Abdrabou, Sharif U. Ahmed, Mengqi Jonathan Fan, Bill T. V. Duong, Kangfu Chen, Pei-Ying Lo, Julia M. Mayes, Fatemeh Esmaeili, Amin GhavamiNejad, Hossein Zargartalebi, Randy Singh Atwal, Sichun Lin, Stephane Angers, Shana O. Kelley
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Numerous human cancers have exhibited the ability to elude immune checkpoint blockade (ICB) therapies. This type of resistance can be mediated by immune-suppressive macrophages that limit antitumor immunity in the tumor microenvironment (TME). Here, we elucidate a strategy to shift macrophages into a proinflammatory state that down-regulates V domain immunoglobulin suppressor of T cell activation (VISTA) via inhibiting AhR and IRAK1. We used a high-throughput microfluidic platform combined with a genome-wide CRISPR knockout screen to identify regulators of VISTA levels. Functional characterization showed that the knockdown of these hits diminished VISTA surface levels on macrophages and sustained an antitumor phenotype. Furthermore, targeting of both AhR and IRAK1 in mouse models overcame resistance to ICB treatment. Tumor immunophenotyping indicated that infiltration of cytotoxic CD8 + cells, natural killer cells, and antitumor macrophages was substantially increased in treated mice. Collectively, AhR and IRAK1 are implicated as regulators of VISTA that coordinate a multifaceted barrier to antitumor immune responses.
GPT-4o mini: Non-social science research article
Fine-scale Southern California Moho structure uncovered with distributed acoustic sensing
James Atterholt, Zhongwen Zhan
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Moho topography yields insights into the evolution of the lithosphere and the strength of the lower crust. The Moho reflected phase (PmP) samples this key boundary and may be used in concert with the first arriving P phase to infer crustal thickness. The densely sampled station coverage of distributed acoustic sensing arrays allows for the observation of PmP at fine-scale intervals over many kilometers with individual events. We use PmP recorded by a 100-km-long fiber that traverses a path between Ridgecrest, CA and Barstow, CA to explore Moho variability in Southern California. With hundreds of well-recorded events, we verify that PmP is observable and develop a technique to identify and pick P-PmP differential times with high confidence. We use these observations to constrain Moho depth throughout Southern California, and we find that short-wavelength variability in crustal thickness is abundant, with sharp changes across the Garlock Fault and Coso Volcanic Field.
GPT-4o mini: Non-social science research article
TCF1 dosage determines cell fate during T cell development
Anjali Verma, Bridget Aylward, Fei Ma, Cheryl A. Sherman, Laura Chopp, Susan Shinton, Roshni Roy, Shawn Fahl, Alejandra Contreras, Byron Koenitzer, Parirokh Awasthi, Krystyna Mazan-Mamczarz, Supriyo De, Noah Ollikainen, Xiang Qiu, Remy Bosselut, Ranjan Sen, David L. Wiest, Jyoti Misra Sen
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Loss-of-function studies have shown that transcription factor T cell factor-1 (TCF1), encoded by the Tcf7 gene, is essential for T cell development in the thymus. We discovered that the Tcf7 expression level is regulated by E box DNA binding proteins, independent of Notch, and regulates αβ and γδ T cell development. Systematic interrogation of the five E protein binding elements (EPE1–5) in the Tcf7 enhancer region showed lineage-specific utilization. Specifically, loss-of-function analysis revealed that only EPE3 plays a critical role in supporting αβ T cell development, while EPE1, 3, and 5 regulate the γδ T cell maturation and functional cell fate decision. The importance of EPE3 in supporting both lineages may stem from its unique capacity to interact with the Tcf7 transcriptional start site. Together, these studies demonstrate that the precise dosage of TCF1 expression mediated by distinct EPEs generates a balanced output of T cells from the thymus.
GPT-4o mini: Non-social science research article
The multifunctional use of an aqueous battery for a high capacity jellyfish robot
Xu Liu, Shuo Jin, Yiqi Shao, Sofia Kuperman, Autumn Pratt, Duhan Zhang, Jacqueline Lo, Yong Lak Joo, Amir D. Gat, Lynden A. Archer, Robert F. Shepherd
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The batteries that power untethered underwater vehicles (UUVs) serve a single purpose: to provide energy to electronics and motors; the more energy required, the bigger the robot must be to accommodate space for more energy storage. By choosing batteries composed primarily of liquid media [e.g., redox flow batteries (RFBs)], the increased weight can be better distributed for improved capacity with reduced inertial moment. Here, we formed an RFB into the shape of a jellyfish, using two redox chemistries and architectures: (i) a secondary ZnBr 2 battery and (ii) a hybrid primary/secondary ZnI 2 battery. A UUV was able to be powered solely by RFBs with increased volumetric ( Q ~ 11 ampere-hours per liter) and areal (108 milliampere-hours per square centimeter) energy density, resulting in a long operational lifetime ( T ~ 1.5 hours) for UUVs composed of primarily electrochemically energy-dense liquid (~90% of the robot’s weight).
GPT-4o mini: Non-social science research article
The Hox protein Antennapedia orchestrates Drosophila adult flight muscle development
Gabriela Poliacikova, Aïcha Aouane, Nathalie Caruso, Nicolas Brouilly, Corinne Maurel-Zaffran, Yacine Graba, Andrew J. Saurin
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Muscle development and diversity require a large number of spatially and temporally regulated events controlled by transcription factors (TFs). Drosophila has long stood as a model to study myogenesis due to the highly conserved key TFs involved at all stages of muscle development. While many studies focused on the diversification of Drosophila larval musculature, how distinct adult muscle types are generated is much less characterized. Here, we identify an essential regulator of Drosophila thoracic flight muscle development, the Hox TF Antennapedia (Antp). Correcting a long-standing belief that flight muscle development occurs without the input of Hox TFs, we show that Antp intervenes at several stages of flight muscle development, from the establishment of the progenitor pool in the embryo to myoblast differentiation in the early pupa. Furthermore, the precisely regulated clearance of Hox in the developing flight muscle fibers is required to allow for fibrillar muscle fate diversification, setting these muscles apart from all other adult tubular muscle types.
GPT-4o mini: Non-social science research article
A universal strategy for decoupling stiffness and extensibility of polymer networks
Baiqiang Huang, Shifeng Nian, Li-Heng Cai
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Since the invention of polymer networks such as cross-linked natural rubber in the 19th century, it has been a dogma that stiffer networks are less stretchable. We report a universal strategy for decoupling the stiffness and extensibility of single-network elastomers. Instead of using linear polymers as network strands, we use foldable bottlebrush polymers, which feature a collapsed backbone grafted with many linear side chains. Upon elongation, the collapsed backbone unfolds to release stored length, enabling remarkable extensibility. By contrast, the network elastic modulus is inversely proportional to network strand mass and is determined by the side chains. We validate this concept by creating single-network elastomers with nearly constant Young’s modulus (30 kilopascals) while increasing tensile breaking strain by 40-fold, from 20 to 800%. We show that this strategy applies to networks of different polymer species and topologies. Our discovery opens an avenue for developing polymeric materials with extraordinary mechanical properties.
GPT-4o mini: Non-social science research article
Recent emergence of Arctic atlantification dominated by climate warming
Qiang Wang, Qi Shu, Fan Wang
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The Arctic Ocean’s Eurasian Basin underwent notable atlantification during the 2010s, characterized by warming of the Atlantic Water layer and increased upper ocean salinity. Despite profound implications for the Arctic climate system and marine ecosystems, the primary drivers of this process remain debated. One hypothesis suggested that alternating phases of the atmospheric Arctic Dipole may have mitigated recent atlantification. Here, we use high-resolution model simulations to disentangle the main contributors to atlantification in the Arctic basin. We show that the decline in Arctic sea ice was the dominant driver, while wind variability associated with the Arctic Dipole played a minor role, contributing slightly rather than mitigating the process. The positive phase of the Arctic Oscillation also made a relatively small contribution. Although recent changes in atmospheric circulation over the Greenland Sea tended to reduce warm water inflow through the Fram Strait, this cooling effect on the Arctic Atlantic Water layer was outweighed by the warming induced by sea ice decline.
GPT-4o mini: Non-social science research article
Marine emissions of methanethiol increase aerosol cooling in the Southern Ocean
Charel Wohl, Julián Villamayor, Martí Galí, Anoop S. Mahajan, Rafael P. Fernández, Carlos A. Cuevas, Adriana Bossolasco, Qinyi Li, Anthony J. Kettle, Tara Williams, Roland Sarda-Esteve, Valérie Gros, Rafel Simó, Alfonso Saiz-Lopez
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Ocean-emitted dimethyl sulfide (DMS) is a major source of climate-cooling aerosols. However, most of the marine biogenic sulfur cycling is not routed to DMS but to methanethiol (MeSH), another volatile whose reactivity has hitherto hampered measurements. Therefore, the global emissions and climate impact of MeSH remain unexplored. We compiled a database of seawater MeSH concentrations, identified their statistical predictors, and produced monthly fields of global marine MeSH emissions adding to DMS emissions. Implemented into a global chemistry-climate model, MeSH emissions increase the sulfate aerosol burden by 30 to 70% over the Southern Ocean and enhance the aerosol cooling effect while depleting atmospheric oxidants and increasing DMS lifetime and transport. Accounting for MeSH emissions reduces the radiative bias of current climate models in this climatically relevant region.
GPT-4o mini: Non-social science research article
Inflammatory cytokines disrupt astrocyte exosomal HepaCAM-mediated protection against neuronal excitotoxicity in the SOD1G93A ALS model
Shijie Jin, Yang Tian, Jonathan Hacker, Xuan Chen, Marcela Bertolio, Caroline Reynolds, Rachel Jarvis, Jingwen Hu, Vanessa Promes, Dilara Halim, Fen-Biao Gao, Yongjie Yang
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Astrocyte secreted signals substantially affect disease pathology in neurodegenerative diseases. It remains little understood about how proinflammatory cytokines, such as interleukin-1α/tumor necrosis factor–α/C1q (ITC), often elevated in neurodegenerative diseases, alter astrocyte-secreted signals and their effects in disease pathogenesis. By selectively isolating astrocyte exosomes (A-Exo.) and employing cell type–specific exosome reporter mice, our current study showed that ITC cytokines significantly reduced A-Exo. secretion and decreased spreading of focally labeled A-Exo. in diseased SOD1G93A mice. Our results also found that A-Exo. were minimally associated with misfolded SOD1 and elicited no toxicity to mouse spinal and human iPSC–derived motor neurons. In contrast, A-Exo. were neuroprotective against excitotoxicity, which was completely diminished by ITC cytokines and partially abolished by SOD1G93A expression. Subsequent proteomic characterization of A-Exo. and genetic analysis identified that surface expression of glial-specific HepaCAM preferentially mediates A-Exo’s axon protection effect. Together, our study defines a cytokine-induced loss-of-function mechanism of A-Exo. in protecting neurons from excitotoxicity in amyotrophic lateral sclerosis.
GPT-4o mini: Non-social science research article
Synergistic coordination of diphosphine with primary and tertiary phosphorus centers: Ultrastable icosidodecahedral Ag 30 nanoclusters with metallic aromaticity
Xu-Yang Ding, Chengkai Zhang, Lin-Xi Shi, Jin-Yun Wang, Xin Yang, Li-Yi Zhang, Di Sun, Zhong-Ning Chen
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As versatile ligands with extraordinary coordination capabilities, RPH 2 (R = alkyl or aryl) are rarely used in constructing metal nanoclusters due to their volatility, toxicity, spontaneous flammability, and susceptibility to oxidation. In this work, we designed a primary and tertiary phosphorus-bound diphosphine chelator (2-Ph 2 PC 6 H 4 PH 2 ) to create ultrastable silver nanoclusters with metallic aromaticity. By controlling the deprotonation rate of 2-Ph 2 PC 6 H 4 PH 2 and adjusting the templates, we successfully synthesized two near-infrared emissive nanoclusters, Ag30 and Ag32 , which have analogous icosidodecahedral Ag 30 shells with an I h symmetry. Deprotonated ligand (2-Ph 2 P α C 6 H 4 P β 2− ) exhibits a coordination mode of μ 5 -η 1 (P β ),η 2 (P α ,P β ), which endows a unique metallic aromaticity to Ag30 and Ag32 . The solution-processed organic light-emitting diodes based on Ag30 achieve an external quantum efficiency of 15.1%, representing the breakthrough in application of silver nanoclusters to near-infrared–emitting devices. This work represents a special ligand system for synthesizing ligand-protected coinage metal nanoclusters and opens up horizons of creating nanoclusters with distinct geometries and metal aromaticity.
GPT-4o mini: Non-social science research article
The competing controls of glaciers, precipitation, and vegetation on high-mountain fluvial sediment yields
Dongfeng Li, Ting Zhang, Desmond E. Walling, Stuart Lane, Bodo Bookhagen, Shang Tian, Irina Overeem, Jaia Syvitski, Albert J. Kettner, Edward Park, Michèle Koppes, Rafael J. P. Schmitt, Weiling Sun, Jinren Ni, Todd A. Ehlers
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Investigating erosion and river sediment yield in high-mountain areas is crucial for understanding landscape and biogeochemical responses to environmental change. We compile data on contemporary fluvial suspended sediment yield (SSY) and 12 environmental proxies from 151 rivers in High Mountain Asia surrounding the Tibetan Plateau. We demonstrate that glaciers exert a first-order control on fluvial SSYs, with high precipitation nonlinearly amplifying their role, especially in high–glacier cover basins. We find a bidirectional response to vegetation’s influence on SSY in the Eastern Tibetan Plateau and Tien Shan and identify that the two interacting factors of precipitation and vegetation cover explain 54% of the variability in SSY, reflecting the divergent roles of vegetation in promoting biogenic-weathering versus slope stabilization across bioclimatic zones. The competing interactions between glaciers, ecosystems, and climate in delivering suspended sediment have important implications for predicting carbon and nutrient exports and water quality in response to future climate change.
GPT-4o mini: Non-social science research article
Projections from subfornical organ to bed nucleus of the stria terminalis modulate inflammation-induced anxiety-like behaviors in mice
Jinlin Zhang, Chuantong Xie, Peiyao Xu, Qiuping Tong, Lei Xiao, Jing Zhong
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Peripheral inflammation is closely related to the pathogenesis of sickness behaviors and psychiatric disorders such as anxiety and depression. The circumventricular organs (CVOs) are important brain sites to perceive peripheral inflammatory signals, but few studies have reported their role in inflammation-induced anxiety or depression. Using a mouse model of lipopolysaccharide (LPS)–induced inflammation, we identified a previously unreported role of the subfornical organ (SFO), one of the CVOs, in combating inflammation-induced anxiety. LPS treatment induced anxiety-like and sickness behaviors in mice. Although both the SFO and the organum vasculosum of the lamina terminalis (a CVO) neurons were activated after LPS treatment, only manipulating SFO neurons modulated LPS-induced anxiety-like behaviors. Activating or inhibiting SFO neurons alleviated or aggravated LPS-induced anxiety-like behaviors. In addition, SFO exerted this effect through glutamatergic projections to the bed nucleus of the stria terminalis. Manipulating SFO neurons did not affect LPS-induced sickness behaviors. Thus, we uncovered an active role of SFO neurons in counteracting peripheral inflammation-induced anxiety.
GPT-4o mini: Non-social science research article
The antiviral JNJ-A07 significantly reduces dengue virus transmission by Aedes aegypti mosquitoes when delivered via blood-feeding
Ana L. Rosales-Rosas, Sara Goossens, Winston Chiu, Atreyee Majumder, Alina Soto, Serge Masyn, Bart Stoops, Lanjiao Wang, Suzanne J. F. Kaptein, Olivia Goethals, Leen Delang
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Dengue virus (DENV) is the most widespread mosquito-borne virus worldwide, but no antiviral therapies are available yet. The pan-serotype DENV inhibitor JNJ-A07 has shown potent activity in a mouse model. It remains unknown whether an antiviral drug ingested by mosquitoes could inhibit virus replication and thus reduce transmission to other hosts. Here, we investigated the antiviral activity of JNJ-A07 when administered in the blood meal to Aedes aegypti mosquitoes. JNJ-A07 blocked DENV-2 transmission by the mosquitoes in both pre-exposure and post-exposure settings. In addition, JNJ-A07 remained in the mosquito bodies for 7 days after blood meal. Reductions of DENV systemic infection in the mosquitoes suggested a potential for decreased proportions of DENV outbreaks in a simulated environment when the mosquitoes ingested JNJ-A07 via the blood meal.
GPT-4o mini: Non-social science research article
Cesarean delivery and blood DNA methylation at birth and childhood: Meta-analysis in the Pregnancy and Childhood Epigenetics Consortium
Siwen Wang, Emma Casey, Joanne Sordillo, Sofía Aguilar-Lacasaña, Fernanda Morales Berstein, Richard J. Biedrzycki, Sonia Brescianini, Su Chen, Amy Hough, Elena Isaevska, Woo Jin Kim, Marion Lecorguillé, Sebastian Shaobo Li, Christian M. Page, Jaehyun Park, Stefan Röder, Kristina Salontaji, Gillian Santorelli, Yidan Sun, Sungho Won, Eric Zillich, Lea Zillich, Isabella Annesi-Maesano, S. Hasan Arshad, Mariona Bustamante, Charlotte A. M. Cecil, Hannah R. Elliott, Susan Ewart, Janine F. Felix, Luigi Gagliardi, Siri E. Håberg, Gunda Herberth, Barbara Heude, John W. Holloway, Anke Huels, Wilfried Karmaus, Gerard H. Koppelman, Stephanie J. London, Sunni L. Mumford, Lorenza Nisticò, Maja Popovic, Franca Rusconi, Enrique F. Schisterman, Dan J. Stein, Tabea Send, Henning Tiemeier, Judith M. Vonk, Martine Vrijheid, Joseph Leo Wiemels, Stephanie H. Witt, John Wright, Edwina H. Yeung, Heather J. Zar, Ana C. Zenclussen, Hongmei Zhang, Jorge E. Chavarro, Marie-France Hivert
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Children born via cesarean delivery have a higher risk of metabolic, immunological, and neurodevelopmental disorders compared to those born via vaginal delivery, although mechanisms remain unclear. We conducted a meta-analysis of epigenome-wide association studies to examine the associations between delivery mode and blood DNA methylation at birth and its persistence in early childhood. Participants were from 19 pregnancy cohorts (9833 term newborns) and 6 pediatric cohorts (2429 children aged 6 to 10 years). We identified six CpGs in cord blood associated with cesarean delivery (effect size range: 0.4 to 0.7%, P < 1.0 × 10 −7 ): MAP2K2 (cg19423175), LIM2 (cg01500140), CNP (cg13917614), BLM (cg18247172), RASA3 (cg22348356), and RUNX3 (cg20674490), independent of cell proportions and other confounders. In childhood, none of these CpGs were associated with cesarean delivery, and no additional CpGs were identified. Delivery mode was associated with cell proportions at birth but not in childhood. Further research is needed to elucidate cesarean delivery’s molecular influence on offspring health.
GPT-4o mini: Non-social science research article
Load sharing and accumulated bond fracture in ion-irradiated carbon mat for energy dissipation
Kailu Xiao, Xianqian Wu, Zhen Sang, Vivek Subramanian, Edwin L. Thomas
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Multiwalled carbon nanotube (MWNT) aerogel mats were irradiated with carbon ions to explore the effect of irradiation-induced sp 3 bonds and sp 2 bond defects on ultrahigh strain rate mechanical properties. Energy dissipation was measured using a microprojectile impact test. Specific penetration energy E p * increased strongly with irradiation with a maximum E p * of ~26 megajoules per kilogram, over 200% higher than the previous best energy-absorbing material of pristine MWNT mats and at least an order of magnitude higher than any other material tested at the microscale. Perforation morphologies observed by electron microscopy show that a much larger network region is deformed due to sp 3 bond enhanced load sharing within and between tubes, while defects introduced by the radiation induce more bond, shell, and tube damage leading to strongly enhanced energy dissipation.
GPT-4o mini: Non-social science research article
Genomic heterogeneity and ploidy identify patients with intrinsic resistance to PD-1 blockade in metastatic melanoma
Giuseppe Tarantino, Cora A. Ricker, Annette Wang, William Ge, Tyler J. Aprati, Amy Y. Huang, Shariq Madha, Jiajia Chen, Yingxiao Shi, Marc Glettig, Catherine H. Feng, Dennie T. Frederick, Samuel Freeman, Marta M. Holovatska, Michael P. Manos, Lisa Zimmer, Alexander Rösch, Anne Zaremba, Elisabeth Livingstone, Jacob C. Jameson, Soroush Saghafian, Andrew Lee, Karena Zhao, Luc G.T. Morris, Brendan Reardon, Jihye Park, Haitham A. Elmarakeby, Bastian Schilling, Anita Giobbie-Hurder, Natalie I. Vokes, Elizabeth I. Buchbinder, Keith T. Flaherty, Rizwan Haq, Catherine J. Wu, Genevieve M. Boland, F. Stephen Hodi, Eliezer M. Van Allen, Dirk Schadendorf, David Liu
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The introduction of immune checkpoint blockade (ICB) has markedly improved outcomes for advanced melanoma. However, many patients develop resistance through unknown mechanisms. While combination ICB has improved response rate and progression-free survival, it substantially increases toxicity. Biomarkers to distinguish patients who would benefit from combination therapy versus aPD-1 remain elusive. We analyzed whole-exome sequencing of pretreatment tumors from four cohorts ( n = 140) of ICB-naïve patients treated with aPD-1. High genomic heterogeneity and low ploidy robustly identified patients intrinsically resistant to aPD-1. To establish clinically actionable predictions, we optimized and validated a predictive model using ploidy and heterogeneity to confidently identify (90% PPV) patients with intrinsic resistance to and worse survival on aPD-1. We further observed that three of seven (43%) patients predicted to be intrinsically resistant to single-agent PD-1 ICB responded to combination ICB, suggesting that these patients may benefit disproportionately from combination ICB. These findings highlight the importance of heterogeneity and ploidy, nominating an approach toward clinical actionability.
GPT-4o mini: Non-social science research article
EZH2 directly methylates PARP1 and regulates its activity in cancer
Qingshu Meng, Jiangchuan Shen, Yanan Ren, Qi Liu, Rui Wang, Qiaqia Li, Weihua Jiang, Quan Wang, Yixiang Zhang, Jonathan C. Trinidad, Xiaotong Lu, Tingyou Wang, Yanqiang Li, Chaehyun Yum, Yang Yi, Yongyong Yang, Dongyu Zhao, Clair Harris, Sundeep Kalantry, Kaifu Chen, Rendong Yang, Hengyao Niu, Qi Cao
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DNA repair dysregulation is a key driver of cancer development. Understanding the molecular mechanisms underlying DNA repair dysregulation in cancer cells is crucial for cancer development and therapies. Here, we report that enhancer of zeste homolog 2 (EZH2) directly methylates poly(adenosine diphosphate–ribose) polymerase-1 (PARP-1), an essential enzyme involved in DNA repair, and regulates its activity. Functionally, EZH2-catalyzed methylation represses PARP1 catalytic activity, down-regulates the recruitment of x-ray repair cross-complementing group-1 to DNA lesions and its associated DNA damage repair; on the other hand, it protects the cells from nicotinamide adenine dinucleotide overconsumption upon DNA damage formation. Meanwhile, EZH2-mediated methylation regulates PARP1 transcriptional and oncogenic activity, at least in part, through impairing PARP1-E2F1 interaction and E2F1 transcription factor activity. EZH2 and PARP1 inhibitors synergistically suppress prostate cancer growth. Collectively, our findings uncover an insight of EZH2 functions in fine-tuning PARP1 activity during DNA damage repair and cancer progression, which provides a rationale for combinational targeting EZH2 and PARP1 in cancer.
GPT-4o mini: Non-social science research article
Rhodium-catalyzed atropodivergent hydroamination of alkynes by leveraging two potential enantiodetermining steps
Ruijie Mi, Rongkai Wu, Jierui Jing, Fen Wang, Xiao-Xi Li, Xin Hong, Xingwei Li
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A pair of enantiomers is known to have different biological activities. Two catalysts with opposite chirality are nearly always required to deliver both enantiomeric products. In this work, chiral rhodium(III) cyclopentadienyl complexes are repurposed as efficient catalysts for enantiodivergent and atroposelective hydroamination of sterically hindered alkynes. Products with opposite chirality have been both obtained using the same or closely analogous chiral catalyst in good efficiency and excellent enantioselectivity, and the enantiodivergence was mainly enabled by an achiral carboxylic acid and its silver salt. Mechanistic studies revealed the origin of the enantiodivergence ascribable to the switch of the enantiodetermining step (alkyne insertion versus protonolysis) under acid control, which constitutes a previously unidentified working mode of enantiodivergence by leveraging two elementary steps.
GPT-4o mini: Non-social science research article
Progression of ocean interior acidification over the industrial era
Jens D. Müller, Nicolas Gruber
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Ocean acidification driven by the uptake of anthropogenic CO 2 represents a major threat to ocean ecosystems, yet little is known about its progression beneath the surface. Here, we reconstruct the history of ocean interior acidification over the industrial era on the basis of observation-based estimates of the accumulation of anthropogenic carbon. Across the top 100 meters and from 1800 to 2014, the saturation state of aragonite (Ω arag ) and pH = −log[H + ] decreased by more than 0.6 and 0.1, respectively, with nearly 50% of the progression occurring over the past 20 years. While the magnitude of the Ω arag change decreases uniformly with depth, the magnitude of the [H + ] increase exhibits a distinct maximum in the upper thermocline. Since 1800, the saturation horizon (Ω arag = 1) shoaled by more than 200 meters, approaching the euphotic zone in several regions, especially in the Southern Ocean, and exposing many organisms to corrosive conditions.
Pathways to concealed gun carrying
Justin Lucas Sola
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Understanding the distinction between adolescent and adult pathways to concealed gun carrying can inform interventions to reduce gun violence.
Domain-specific representation of social inference by neurons in the human amygdala and hippocampus
Runnan Cao, Julien Dubois, Adam N. Mamelak, Ralph Adolphs, Shuo Wang, Ueli Rutishauser
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Inferring the intentions and emotions of others from behavior is crucial for social cognition. While neuroimaging studies have identified brain regions involved in social inference, it remains unknown whether performing social inference is an abstract computation that generalizes across different stimulus categories or is specific to certain stimulus domain. We recorded single-neuron activity from the medial temporal lobe (MTL) and the medial frontal cortex (MFC) in neurosurgical patients performing different types of inferences from images of faces, hands, and natural scenes. Our findings indicate distinct neuron populations in both regions encoding inference type for social (faces, hands) and nonsocial (scenes) stimuli, while stimulus category was itself represented in a task-general manner. Uniquely in the MTL, social inference type was represented by separate subsets of neurons for faces and hands, suggesting a domain-specific representation. These results reveal evidence for specialized social inference processes in the MTL, in which inference representations were entangled with stimulus type as expected from a domain-specific process.
Dual pathways of concealed gun carrying and use from adolescence to adulthood over a 25-year era of change
Charles C. Lanfear, David S. Kirk, Robert J. Sampson
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Most homicides in the United States are committed using a handgun, but little research examines gun carrying over critical stages of the life course and changing contexts of violence. Notably, although most of the handgun homicides are committed by adults, most research on concealed gun carrying focuses on adolescents in single cohort studies. Using more than 25 years of longitudinal multicohort data from Chicago, 1994–2021, we show that pathways of concealed gun carrying are distinct between adolescence and adulthood. Adolescent carrying is often age-limited and responsive to direct exposure to gun violence (witnessing and victimization), while adult carrying is a persistent behavior that is less tied to direct exposure. The onset of concealed carry is also a strong predictor of later gun use (shooting or brandishing), and we find distinct patterns of gun use between individuals who first carry in adolescence versus adulthood. We discuss the implications of these dual pathways for research and policies on firearm use.