I checked 6 multidisciplinary journals on Wednesday, December 11, 2024 using the Crossref API. For the period December 04 to December 10, I found 13 new paper(s) in 4 journal(s).

Nature

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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Most birds can navigate seamlessly between aerial and terrestrial environments. Whereas the forelimbs evolved into wings primarily for flight, the hindlimbs serve diverse functions such as walking, hopping and leaping, and jumping take-off for transitions into flight1. These capabilities have inspired engineers to aim for similar multimodality in aerial robots, expanding their range of applications across diverse environments. However, challenges remain in reproducing multimodal locomotion, across gaits with distinct kinematics and propulsive characteristics, such as walking and jumping, while preserving lightweight mass for flight. This trade-off between mechanical complexity and versatility2 limits most existing aerial robots to only one additional locomotor mode3,4,5. Here we overcome the complexity–versatility trade-off with RAVEN (Robotic Avian-inspired Vehicle for multiple ENvironments), which uses its bird-inspired multifunctional legs to jump rapidly into flight, walk on the ground, and hop over obstacles and gaps similar to the multimodal locomotion of birds. We show that jumping for take-off contributes substantially to the initial flight take-off speed6,7,8,9 and, remarkably, that it is more energy efficient than taking off without the jump. Our analysis suggests an important trade-off in mass distribution between legs and body among birds adapted for different locomotor strategies, with greater investment in leg mass among terrestrial birds with multimodal gait demands. Multifunctional robot legs expand the opportunities to deploy traditional fixed-wing aircraft in complex terrains through autonomous take-offs and multimodal gaits.
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 MĂŒller, 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
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
Near-identical macromolecules spontaneously partition into concentric circles
Hao Gong, Yuriko Sakaguchi, Tsutomu Suzuki, Miho Yanagisawa, Takuzo Aida
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Although separation is entropically unfavourable, it is often essential for our life1,2. The separation of very similar macromolecules such as deoxyribonucleic acids (DNAs) and their single nucleotide variants is difficult but holds great advantage for the progress of life science3. Here we report that a particular liquid–liquid phase separation (LLPS) at a solid–liquid interface led to the partitioning of DNAs with nearly identical structures. We found this intriguing phenomenon when we did drop-casting onto a glass plate an aqueous ammonium sulfate dispersion of phase-separated droplets comprising a homogeneous mixture of poly(ethylene glycol) (PEG) samples with different termini. Even when the molecular weights of their PEG parts were identical to each other, terminally different PEGs spread competitively at the solid–liquid interface and partitioned into micrometre-scale concentric circles. We found that this competitive spreading was induced by an ammonium sulfate layer spontaneously formed on the glass surface. We successfully extended the above mechanism to partitioning a mixture of nearly identical DNAs into concentric circles followed by their selective extraction using the salting-in effect. We could isolate a human cancer-causing single nucleotide variant in 97% purity from its 1:1 mixture with the original DNA.
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
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 HernĂĄndez 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. KrĂŒger, Andreas KĂŒrten, 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
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
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 GarcĂ­a, Laura Katharina Sievers, Maren Falk-Paulsen, Shane J. F. Cronin, Astrid Hagelkruys, Shinichiro Sawa, Lisa C. Osborne, Philip Rosenstiel, Manolis Pasparakis, JĂŒrgen 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-ÎșΒ (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
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
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, JérÎme Pety, Annagrazia Puglisi, Eva Schinnerer, John D. Silverman, Francesco Valentino
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Most stars in today’s Universe reside within spheroids, which are bulges of spiral galaxies and elliptical galaxies1,2. Their formation is still an unsolved problem3,4,5. Infrared/submillimetre-bright galaxies at high redshifts6 have long been suspected to be related to spheroid formation7,8,9,10,11,12. Proving this connection has been hampered so far by heavy dust obscuration when focusing on their stellar emission13,14,15 or by methodologies and limited signal-to-noise ratios when looking at submillimetre wavelengths16,17. Here we show that spheroids are directly generated by star formation within the cores of highly luminous starburst galaxies in the distant Universe. This follows from the ALMA submillimetre surface brightness profiles, which deviate substantially from those of exponential disks, and from the skewed-high axis-ratio distribution. Most of these galaxies are fully triaxial rather than flat disks: the ratio of the shortest to the longest of their three axes is half, on average, and increases with spatial compactness. These observations, supported by simulations, reveal a cosmologically relevant pathway for in situ spheroid formation through starbursts that is probably preferentially triggered by interactions (and mergers) acting on galaxies fed by non-coplanar gas accretion streams.
GPT-4o mini: Non-social science research article
Applied body-fluid analysis by wearable devices
NoĂ© Brasier, Joseph Wang, Wei Gao, Juliane R. Sempionatto, Can Dincer, H. Ceren Ates, Firat GĂŒder, 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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Wearable sensors are a recent paradigm in healthcare, enabling continuous, decentralized, and non- or minimally invasive monitoring of health and disease. Continuous measurements yield information-rich time series of physiological data that are holistic and clinically meaningful. Although most wearable sensors were initially restricted to biophysical measurements, the next generation of wearable devices is now emerging that enable biochemical monitoring of both small and large molecules in a variety of body fluids, such as sweat, breath, saliva, tears and interstitial fluid. Rapidly evolving data analysis and decision-making technologies through artificial intelligence has accelerated the application of wearables around the world. Although recent pilot trials have demonstrated the clinical applicability of these wearable devices, their widespread adoption will require large-scale validation across various conditions, ethical consideration and sociocultural acceptance. Successful translation of wearable devices from laboratory prototypes into clinical tools will further require a comprehensive transitional environment involving all stakeholders. The wearable device platforms must gain acceptance among different user groups, add clinical value for various medical indications, be eligible for reimbursements and contribute to public health initiatives. In this Perspective, we review state-of-the-art wearable devices for body-fluid analysis and their translation into clinical applications, and provide insight into their clinical purpose.
GPT-4o mini: Non-social science research article
JWST sighting of decameter main-belt asteroids and view on meteorite sources
Artem Y. Burdanov, Julien de Wit, Miroslav BroĆŸ, Thomas G. MĂŒller, Tobias Hoffmann, Marin Ferrais, Marco Micheli, Emmanuel Jehin, Daniel Parrott, Samantha N. Hasler, Richard P. Binzel, Elsa Ducrot, Laura Kreidberg, MichaĂ«l Gillon, Thomas P. Greene, Will M. Grundy, Theodore Kareta, Pierre-Olivier Lagage, Nicholas Moskovitz, Audrey Thirouin, Cristina A. Thomas, Sebastian Zieba
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Asteroid discoveries are essential for planetary-defense efforts aiming to prevent impacts with Earth1, including the more frequent2 megaton explosions from decameter impactors3−6. While large asteroids (≄100 km) have remained in the main belt since their formation7, small asteroids are commonly transported to the near-Earth object (NEO) population8,9. However, due to the lack of direct observational constraints, their size-frequency distribution —which informs our understanding of the NEOs and the delivery of meteorite samples to Earth—varies significantly among models10−14. Here, we report 138 detections of the smallest asteroids (âȘ† 10 m) ever observed in the main belt, which were enabled by JWST’s infrared capabilities covering the asteroids’ emission peaks15 and synthetic tracking techniques16−18. Despite small orbital arcs, we constrain the objects’ distances and phase angles using known asteroids as proxies, allowing us to derive sizes via radiometric techniques. Their size-frequency distribution exhibits a break at ~ 100 m (debiased cumulative slopes of q = − 2.66 ± 0.60 and − 0.97 ± 0.14 for diameters smaller and larger than ~ 100 m, respectively), suggestive of a population driven by collisional cascade. These asteroids were sampled from multiple asteroid families —most likely Nysa, Polana and Massalia— according to the geometry of pointings considered here. Through additional long-stare infrared observations, JWST is poised to serendipitously detect thousands of decameter-scale asteroids across the sky, probing individual asteroid families19 and the source regions of meteorites13,14 “in-situ”.
GPT-4o mini: Non-social science research article
A framework for neural organoids, assembloids and transplantation studies
Sergiu P. Pașca, Paola Arlotta, Helen S. Bateup, J. Gray Camp, Silvia Cappello, Fred H. Gage, JĂŒrgen A. Knoblich, Arnold R. Kriegstein, Madeline A. Lancaster, Guo-Li Ming, Gaia Novarino, Hideyuki Okano, Malin Parmar, In-Hyun Park, Orly Reiner, Hongjun Song, Lorenz Studer, Jun Takahashi, Sally Temple, Giuseppe Testa, Barbara Treutlein, Flora M. Vaccarino, Pierre Vanderhaeghen, Tracy Young-Pearse
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As the field of neural organoids and assembloids rapidly expands, there is an emergent need for guidance and advice on designing, conducting and reporting experiments to increase the reproducibility and utility of these models. Here, our consortium– representing specialized laboratories from around the world– presents a framework for the experimental process that ranges from ensuring the quality and integrity of human pluripotent stem cells to characterizing and manipulating neural cells in vitro, and from transplantation techniques to considerations for modeling human development, evolution, and disease. As with all scientific endeavors, we advocate for rigorous experimental designs tailored to explicit scientific questions, and transparent methodologies and data sharing, to provide useful knowledge for both current research practices and for developing regulatory standards.
GPT-4o mini: Non-social science research article
Quantum error correction below the surface code threshold
character(0), Rajeev Acharya, Dmitry A. Abanin, Laleh Aghababaie-Beni, Igor Aleiner, Trond I. Andersen, Markus Ansmann, Frank Arute, Kunal Arya, Abraham Asfaw, Nikita Astrakhantsev, Juan Atalaya, Ryan Babbush, Dave Bacon, Brian Ballard, Joseph C. Bardin, Johannes Bausch, Andreas Bengtsson, Alexander Bilmes, Sam Blackwell, Sergio Boixo, Gina Bortoli, Alexandre Bourassa, Jenna Bovaird, Leon Brill, Michael Broughton, David A. Browne, Brett Buchea, Bob B. Buckley, David A. Buell, Tim Burger, Brian Burkett, Nicholas Bushnell, Anthony Cabrera, Juan Campero, Hung-Shen Chang, Yu Chen, Zijun Chen, Ben Chiaro, Desmond Chik, Charina Chou, Jahan Claes, Agnetta Y. Cleland, Josh Cogan, Roberto Collins, Paul Conner, William Courtney, Alexander L. Crook, Ben Curtin, Sayan Das, Alex Davies, Laura De Lorenzo, Dripto M. Debroy, Sean Demura, Michel Devoret, Agustin Di Paolo, Paul Donohoe, Ilya Drozdov, Andrew Dunsworth, Clint Earle, Thomas Edlich, Alec Eickbusch, Aviv Moshe Elbag, Mahmoud Elzouka, Catherine Erickson, Lara Faoro, Edward Farhi, Vinicius S. Ferreira, Leslie Flores Burgos, Ebrahim Forati, Austin G. Fowler, Brooks Foxen, Suhas Ganjam, Gonzalo Garcia, Robert Gasca, Élie Genois, William Giang, Craig Gidney, Dar Gilboa, Raja Gosula, Alejandro Grajales Dau, Dietrich Graumann, Alex Greene, Jonathan A. Gross, Steve Habegger, John Hall, Michael C. Hamilton, Monica Hansen, Matthew P. Harrigan, Sean D. Harrington, Francisco J. H. Heras, Stephen Heslin, Paula Heu, Oscar Higgott, Gordon Hill, Jeremy Hilton, George Holland, Sabrina Hong, Hsin-Yuan Huang, Ashley Huff, William J. Huggins, Lev B. Ioffe, Sergei V. Isakov, Justin Iveland, Evan Jeffrey, Zhang Jiang, Cody Jones, Stephen Jordan, Chaitali Joshi, Pavol Juhas, Dvir Kafri, Hui Kang, Amir H. Karamlou, Kostyantyn Kechedzhi, Julian Kelly, Trupti Khaire, Tanuj Khattar, Mostafa Khezri, Seon Kim, Paul V. Klimov, Andrey R. Klots, Bryce Kobrin, Pushmeet Kohli, Alexander N. Korotkov, Fedor Kostritsa, Robin Kothari, Borislav Kozlovskii, John Mark Kreikebaum, Vladislav D. Kurilovich, Nathan Lacroix, David Landhuis, Tiano Lange-Dei, Brandon W. Langley, Pavel Laptev, Kim-Ming Lau, Loïck Le Guevel, Justin Ledford, Joonho Lee, Kenny Lee, Yuri D. Lensky, Shannon Leon, Brian J. Lester, Wing Yan Li, Yin Li, Alexander T. Lill, Wayne Liu, William P. Livingston, Aditya Locharla, Erik Lucero, Daniel Lundahl, Aaron Lunt, Sid Madhuk, Fionn D. Malone, Ashley Maloney, Salvatore Mandrà, James Manyika, Leigh S. Martin, Orion Martin, Steven Martin, Cameron Maxfield, Jarrod R. McClean, Matt McEwen, Seneca Meeks, Anthony Megrant, Xiao Mi, Kevin C. Miao, Amanda Mieszala, Reza Molavi, Sebastian Molina, Shirin Montazeri, Alexis Morvan, Ramis Movassagh, Wojciech Mruczkiewicz, Ofer Naaman, Matthew Neeley, Charles Neill, Ani Nersisyan, Hartmut Neven, Michael Newman, Jiun How Ng, Anthony Nguyen, Murray Nguyen, Chia-Hung Ni, Murphy Yuezhen Niu, Thomas E. O’Brien, William D. Oliver, Alex Opremcak, Kristoffer Ottosson, Andre Petukhov, Alex Pizzuto, John Platt, Rebecca Potter, Orion Pritchard, Leonid P. Pryadko, Chris Quintana, Ganesh Ramachandran, Matthew J. Reagor, John Redding, David M. Rhodes, Gabrielle Roberts, Eliott Rosenberg, Emma Rosenfeld, Pedram Roushan, Nicholas C. Rubin, Negar Saei, Daniel Sank, Kannan Sankaragomathi, Kevin J. Satzinger, Henry F. Schurkus, Christopher Schuster, Andrew W. Senior, Michael J. Shearn, Aaron Shorter, Noah Shutty, Vladimir Shvarts, Shraddha Singh, Volodymyr Sivak, Jindra Skruzny, Spencer Small, Vadim Smelyanskiy, W. Clarke Smith, Rolando D. Somma, Sofia Springer, George Sterling, Doug Strain, Jordan Suchard, Aaron Szasz, Alex Sztein, Douglas Thor, Alfredo Torres, M. Mert Torunbalci, Abeer Vaishnav, Justin Vargas, Sergey Vdovichev, Guifre Vidal, Benjamin Villalonga, Catherine Vollgraff Heidweiller, Steven Waltman, Shannon X. Wang, Brayden Ware, Kate Weber, Travis Weidel, Theodore White, Kristi Wong, Bryan W. K. Woo, Cheng Xing, Z. Jamie Yao, Ping Yeh, Bicheng Ying, Juhwan Yoo, Noureldin Yosri, Grayson Young, Adam Zalcman, Yaxing Zhang, Ningfeng Zhu, Nicholas Zobrist
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Quantum error correction [1, 2, 3, 4] provides a path to reach practical quantum computing by combining multiple physical qubits into a logical qubit, where the logical error rate is suppressed exponentially as more qubits are added. However, this exponential suppression only occurs if the physical error rate is below a critical threshold. Here, we present two below-threshold surface code memories on our newest generation of superconducting processors, Willow: a distance-7 code, and a distance-5 code integrated with a real-time decoder. The logical error rate of our larger quantum memory is suppressed by a factor of \(\varLambda \mathrm{=2.14}\pm 0.02\) when increasing the code distance by two, culminating in a 101-qubit distance-7 code with 0.143% ± 0.003% error per cycle of error correction. This logical memory is also beyond break-even, exceeding its best physical qubit’s lifetime by a factor of \(2.4\pm 0.3\). Our system maintains below-threshold performance when decoding in real time, achieving an average decoder latency of 63 ÎŒs at distance-5 up to a million cycles, with a cycle time of 1.1 ÎŒs. We also run repetition codes up to distance-29 and find that logical performance is limited by rare correlated error events occurring approximately once every hour, or \(3\)\(\times \)\({10}^{9}\) cycles. Our results present device performance that, if scaled, could realize the operational requirements of large scale fault-tolerant quantum algorithms.
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
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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Synthetic receptors that mediate antigen-dependent cell responses are transforming therapeutics, drug discovery and basic research1,2. However, established technologies such as chimeric antigen receptors3 can only detect immobilized antigens, have limited output scope and lack built-in drug control3,4,5,6,7. Here we engineer synthetic G-protein-coupled receptors (GPCRs) that are capable of driving a wide range of native or non-native cellular processes in response to a user-defined antigen. We achieve modular antigen gating by engineering and fusing a conditional auto-inhibitory domain onto GPCR scaffolds. Antigen binding to a fused nanobody relieves auto-inhibition and enables receptor activation by drug, thus generating programmable antigen-gated G-protein-coupled engineered receptors (PAGERs). We create PAGERs that are responsive to more than a dozen biologically and therapeutically important soluble and cell-surface antigens in a single step from corresponding nanobody binders. Different PAGER scaffolds allow antigen binding to drive transgene expression, real-time fluorescence or endogenous G-protein activation, enabling control of diverse cellular functions. We demonstrate multiple applications of PAGER, including induction of T cell migration along a soluble antigen gradient, control of macrophage differentiation, secretion of therapeutic antibodies and inhibition of neuronal activity in mouse brain slices. Owing to its modular design and generalizability, we expect PAGERs to have broad utility in discovery and translational science.
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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Fructose consumption has increased considerably over the past five decades, largely due to the widespread use of high-fructose corn syrup as a sweetener1. It has been proposed that fructose promotes the growth of some tumours directly by serving as a fuel2,3. Here we show that fructose supplementation enhances tumour growth in animal models of melanoma, breast cancer and cervical cancer without causing weight gain or insulin resistance. The cancer cells themselves were unable to use fructose readily as a nutrient because they did not express ketohexokinase-C (KHK-C). Primary hepatocytes did express KHK-C, resulting in fructolysis and the excretion of a variety of lipid species, including lysophosphatidylcholines (LPCs). In co-culture experiments, hepatocyte-derived LPCs were consumed by cancer cells and used to generate phosphatidylcholines, the major phospholipid of cell membranes. In vivo, supplementation with high-fructose corn syrup increased several LPC species by more than sevenfold in the serum. Administration of LPCs to mice was sufficient to increase tumour growth. Pharmacological inhibition of ketohexokinase had no direct effect on cancer cells, but it decreased circulating LPC levels and prevented fructose-mediated tumour growth in vivo. These findings reveal that fructose supplementation increases circulating nutrients such as LPCs, which can enhance tumour growth through a cell non-autonomous mechanism.
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 ValderrĂĄbano, 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, EulĂ lia 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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The response of breast cancer to neoadjuvant chemotherapy (NAC) varies substantially, even when tumours belong to the same molecular or histological subtype1. Here we identify the oestrous cycle as an important contributor to this heterogeneity. In three mouse models of breast cancer, we show reduced responses to NAC when treatment is initiated during the dioestrus stage, when compared with initiation during the oestrus stage. Similar findings were observed in retrospective premenopausal cohorts of human patients. Mechanistically, the dioestrus stage exhibits systemic and localized changes, including (1) an increased number of cells undergoing epithelial-to-mesenchymal transition linked to chemoresistance2,3,4 and (2) decreased tumour vessel diameter, suggesting potential constraints to drug sensitivity and delivery. In addition, an elevated presence of macrophages, previously associated with chemoresistance induction5, characterizes the dioestrus phase. Whereas NAC disrupts the oestrous cycle, this elevated macrophage prevalence persists and depletion of macrophages mitigates the reduced therapy response observed when initiating treatment during dioestrus. Our data collectively demonstrate the oestrous cycle as a crucial infradian rhythm determining chemosensitivity, warranting future clinical studies to exploit optimal treatment initiation timing for enhanced chemotherapy outcomes.
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 PicĂł, Andreea Balaceanu, Berta Duran-ArquĂ©, Marcos FernĂĄndez-Alfara, Judit MartĂ­n, Cesare De Pace, Lorena Ruiz-PĂ©rez, JesĂșs GarcĂ­a, Giuseppe Battaglia, JosĂ© J. Lucas, RubĂ©n HervĂĄs, Kresten Lindorff-Larsen, RaĂșl MĂ©ndez, Xavier Salvatella
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The inclusion of microexons by alternative splicing occurs frequently in neuronal proteins. The roles of these sequences are largely unknown, and changes in their degree of inclusion are associated with neurodevelopmental disorders1. We have previously shown that decreased inclusion of a 24-nucleotide neuron-specific microexon in CPEB4, a RNA-binding protein that regulates translation through cytoplasmic changes in poly(A) tail length, is linked to idiopathic autism spectrum disorder (ASD)2. Why this microexon is required and how small changes in its degree of inclusion have a dominant-negative effect on the expression of ASD-linked genes is unclear. Here we show that neuronal CPEB4 forms condensates that dissolve after depolarization, a transition associated with a switch from translational repression to activation. Heterotypic interactions between the microexon and a cluster of histidine residues prevent the irreversible aggregation of CPEB4 by competing with homotypic interactions between histidine clusters. We conclude that the microexon is required in neuronal CPEB4 to preserve the reversible regulation of CPEB4-mediated gene expression in response to neuronal stimulation.
GPT-4o mini: Non-social science research article
Author Correction: Global potential for natural regeneration in deforested tropical regions
Brooke A. Williams, Hawthorne L. Beyer, Matthew E. Fagan, Robin L. Chazdon, Marina Schmoeller, Starry Sprenkle-Hyppolite, Bronson W. Griscom, James E. M. Watson, Anazélia M. Tedesco, Mariano Gonzalez-Roglich, Gabriel A. Daldegan, Blaise Bodin, Danielle Celentano, Sarah Jane Wilson, Jonathan R. Rhodes, Nikola S. Alexandre, Do-Hyung Kim, Diego Bastos, Renato Crouzeilles
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GPT-4o mini: Non-social science research article
Publisher Correction: Spatially restricted immune and microbiota-driven adaptation of the gut
Toufic Mayassi, Chenhao Li, Åsa Segerstolpe, Eric M. Brown, Rebecca Weisberg, Toru Nakata, Hiroshi Yano, Paula Herbst, David Artis, Daniel B. Graham, Ramnik J. Xavier
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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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The maintenance of genomic integrity in rapidly proliferating cells is a substantial challenge during embryonic development1,2,3. Although numerous cell-intrinsic mechanisms have been revealed4,5,6,7, little is known about genome-protective effects and influences of developmental tissue microenvironments on tissue-forming cells. Here we show that fetal liver hepatocytes provide protection to haematopoietic stem and progenitor cell (HSPC) genomes. Lineage tracing and depletion in mice demonstrated that delayed hepatocyte development in early fetal livers increased the chromosomal instability of newly colonizing HSPCs. In addition, HSPCs developed tolerance to genotoxins in hepatocyte-conditioned medium, suggesting that hepatocytes protect the HSPC genome in a paracrine manner. Proteomic analyses demonstrated the enrichment of fetuin-A in hepatocyte-conditioned medium but not in early fetal livers. Fetuin-A activates a Toll-like receptor pathway to prevent pathogenic R-loop accumulation in HSPCs undergoing DNA replication and gene transcription in the fetal liver. Numerous haematopoietic regulatory genes frequently involved in leukaemogenic mutations are associated with R-loop-enriched regions. In Fetua-knockout mice, HSPCs showed increased genome instability and susceptibility to malignancy induction. Moreover, low concentrations of fetuin-A correlated with the oncogenesis of childhood leukaemia. Therefore, we uncover a mechanism operating in developmental tissues that offers tissue-forming cell genome protection and is implicated in developmental-related diseases.
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, LucĂ­a Caudillo-Plath, Eva Sommer, Emelda Ahongshangbam, Dina Alfaouri, JoĂŁo 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 KrĂŒger, Andreas KĂŒrten, Markus LampimĂ€ki, 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, AntĂłnio TomĂ©, 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
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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Ageing is associated with a decline in the number and fitness of adult stem cells1,2. Ageing-associated loss of stemness is posited to suppress tumorigenesis3,4, but this hypothesis has not been tested in vivo. Here we use physiologically aged autochthonous genetically engineered5,6 mouse models and primary cells5,6 to demonstrate that ageing suppresses lung cancer initiation and progression by degrading the stemness of the alveolar cell of origin. This phenotype is underpinned by the ageing-associated induction of the transcription factor NUPR1 and its downstream target lipocalin-2 in the cell of origin in mice and humans, which leads to functional iron insufficiency in the aged cells. Genetic inactivation of the NUPR1–lipocalin-2 axis or iron supplementation rescues stemness and promotes the tumorigenic potential of aged alveolar cells. Conversely, targeting the NUPR1–lipocalin-2 axis is detrimental to young alveolar cells through ferroptosis induction. Ageing-associated DNA hypomethylation at specific enhancer sites is associated with increased NUPR1 expression, which is recapitulated in young alveolar cells through DNA methylation inhibition. We uncover that ageing drives functional iron insufficiency that leads to loss of stemness and tumorigenesis but promotes resistance to ferroptosis. These findings have implications for the therapeutic modulation of cellular iron homeostasis in regenerative medicine and in cancer prevention. Furthermore, our findings are consistent with a model whereby most human cancers initiate at a young age, thereby highlighting the importance of directing cancer prevention efforts towards young individuals.
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, AgnĂšs 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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Nature DOI suffix ≠ "/s...": Not a research article
The liver converts fructose into lipids to fuel tumours
Hyllana C. D. Medeiros, Sophia Y. Lunt
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It is well established that tumour cells consume more of the sugar glucose than do non-proliferating normal cells1, a phenomenon known as the Warburg effect. Another type of sugar, fructose, has emerged as an alternative potential fuel for tumour growth. Writing in Nature, Fowle-Grider et al.2 reveal the surprising process that enables cancer cells to benefit from fructose.
Nature DOI suffix ≠ "/s...": Not a research article
What is the best time of the month to treat breast cancer?
Wendy V. Ingman
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As well as preparing the body for potential pregnancy, the menstrual cycle affects the function of many cell types in a range of organs. Variations in the ovarian hormones oestrogen and progesterone across the cycle might also influence response to cancer therapies. Writing in Nature, Bornes et al.1 reveal that the menstrual cycle modifies sensitivity to breast cancer treatment. This result raises new therapeutic possibilities. Could breast cancer survival rates improve by giving chemotherapy to individuals at a specific time of the month?
Nature DOI suffix ≠ "/s...": Not a research article
Virtual lab powered by ‘AI scientists’ super-charges biomedical research
Helena Kudiabor
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Nature DOI suffix ≠ "/s...": Not a research article
Why breast cancer treatments might work best just after your period
Nick Petrić Howe, Emily Bates
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Nature DOI suffix ≠ "/s...": Not a research article
A step-by-step guide to landing your next job in science
Linda Nordling
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Nature DOI suffix ≠ "/s...": Not a research article
‘A truly remarkable breakthrough’: Google’s new quantum chip achieves accuracy milestone
Davide Castelvecchi
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Nature DOI suffix ≠ "/s...": Not a research article
Money for nothing: Books in brief
Andrew Robinson
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Nature DOI suffix ≠ "/s...": Not a research article
The first rocks from the Moon’s far side are in this geologist’s hands
Smriti Mallapaty
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Nature DOI suffix ≠ "/s...": Not a research article
Will humans ever speak wolf? A scientist unravels the complexities of animal chatter
Benjamin Thompson
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Nature DOI suffix ≠ "/s...": Not a research article
Banish the PDF-hunting blues with these AI and digital tools
Candice P. Chu
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Nature DOI suffix ≠ "/s...": Not a research article
Richard Dawkins’s book of the dead is haunted by ghosts of past works
Nathaniel Comfort
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Nature DOI suffix ≠ "/s...": Not a research article
DeepMind AI weather forecaster beats world-class system
Alix Soliman
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Nature DOI suffix ≠ "/s...": Not a research article
Stress can dull our capacity for joy: mouse brain patterns hint at why
Max Kozlov
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Nature DOI suffix ≠ "/s...": Not a research article
Exis memoria
Hannya Kay
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Nature DOI suffix ≠ "/s...": Not a research article
Father time: the physicist on a mission to build the world’s first nuclear clock
Elizabeth Gibney
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Nature DOI suffix ≠ "/s...": Not a research article
The revolutionary economist who became the unlikely leader of Bangladesh
Ehsan Masood
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Nature DOI suffix ≠ "/s...": Not a research article
I work to protect South Korea’s people against earthquakes
Dave Tacon
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Stress-induced joylessness leaves a distinct mark on the brain
Jacob Smith
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Nature DOI suffix ≠ "/s...": Not a research article
What’s next for Syria’s science: a view from Nature’s reporter who was a refugee
Miryam Naddaf
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Science could solve some of the world’s biggest problems. Why aren’t governments using it?
Flora Graham
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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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Many organisms can transition smoothly from one mode of locomotion to another, often by using the same body parts. For example, flying fish use their fins to steer underwater, and these same structures turn into wings when the fish begin to glide above the water’s surface1. Such versatility is an endless source of inspiration for engineers, but using the same locomotor modules to perform different movements can create trade-offs, because these manoeuvres often have opposing requirements2.
Nature DOI suffix ≠ "/s...": Not a research article
Nine books to help shape your science career in 2025
Anne Gulland
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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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Inflammation, the movement of immune cells to an area of infection or injury, is important for tackling infections and restoring health. When the inflammatory process gets out of control, however, the result is conditions such as arthritis and inflammatory bowel disease. A key factor in initiating and maintaining an inflammatory response is the release of proteins or other molecules, known as damage-associated molecular patterns (DAMPs), from dying cells. Writing in Nature, Pourmal et al.1 describe how the protein NINJ1, which enables DAMPs to escape from dying cells2, is kept inactive in the cell membranes of living cells.
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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Nature DOI suffix ≠ "/s...": Not a research article
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
AI weatherman: the DeepMind researcher making faster, more accurate forecasts
Davide Castelvecchi
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Nature DOI suffix ≠ "/s...": Not a research article
This fearless science sleuth risked her career to expose publication fraud
Holly Else
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Nature DOI suffix ≠ "/s...": Not a research article
This doctor raised the alarm about a deadly mpox outbreak that went global
Max Kozlov
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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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‘Horror autotoxicus’, a term coined by the German immunologist Paul Ehrlich1, describes the drastic consequences that occur when the immune system turns from protecting us against microorganisms and cancer to attacking healthy tissues. This attack becomes especially ‘horrible’ when immune cells invade the brain, sparking inflammation and ultimately destruction of the complex and vulnerable local tissue. Writing in Nature, Kim et al.2 describe a hitherto disregarded process that contributes to keeping autoimmune brain disease at a minimum.
Nature DOI suffix ≠ "/s...": Not a research article
Pregnancy restructures the brain to prepare for childbirth and parenthood
Clare McCormack, Moriah Thomason
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Brain changes during pregnancy have been mapped in detail for the first time. Writing in Nature Neuroscience, Pritschet et al.1 report a case study of a single participant who completed magnetic resonance imaging (MRI) scans at 26 timepoints: 4 before pregnancy, 15 during pregnancy and 7 in the first 2 years after childbirth. The researchers detect widespread anatomical changes throughout the brain, which might reflect the refinement of neuronal connections in preparation for birth and caring for a child.
Nature DOI suffix ≠ "/s...": Not a research article
Loose ends
Myna Chang
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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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Nature DOI suffix ≠ "/s...": Not a research article
Bad bar charts are pervasive across biology
Amanda Heidt
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Nature DOI suffix ≠ "/s...": Not a research article
Wuhan lab samples hold no close relatives to virus behind COVID
Smriti Mallapaty
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Nature DOI suffix ≠ "/s...": Not a research article
Watch this bird-inspired drone leap into the air
Dan Fox
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Nature DOI suffix ≠ "/s...": Not a research article
Microbiome interventions for children raise the ethical stakes
Sam Jones
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Nature DOI suffix ≠ "/s...": Not a research article
Human body’s ageing ‘clock’ ticks faster after heat stress
Heidi Ledford
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Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: Wuhan lab samples hold no close relatives to virus behind COVID
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
This PhD student helped to win a major pay hike for Canadian researchers
Brian Owens
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Nature DOI suffix ≠ "/s...": Not a research article
How fast is your brain ageing? Proteins in blood offer clues
Miryam Naddaf
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Nature DOI suffix ≠ "/s...": Not a research article
A 60-minute guide to landing your next job in science
David Payne
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Nature DOI suffix ≠ "/s...": Not a research article
Abundant plant gas forms aerosol particles at high altitude — and could affect the climate
James Allan
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Aerosol particles in the atmosphere affect the formation and properties of clouds, and their effects are therefore important to include in models of weather and climate. However, the uncertainties in estimating the size of these effects have remained stubbornly high1. Particles can either be directly emitted into the atmosphere or formed from scratch through chemical reactions involving gaseous precursors. Previously identified precursors include sulfurous gases2 generated by volcanoes, microorganisms and fossil-fuel burning, for example; iodine produced by marine algae3; and certain members of a class of organic compounds called terpenes, which are produced by trees4. Two papers published in Nature now report laboratory experiments5 and atmospheric observations6 showing that isoprene, an abundant gas produced by plants, should be added to this select list.
Nature DOI suffix ≠ "/s...": Not a research article
Ageing of stem cells reduces their capacity to form tumours
Tatiana Cañeque, Raphaël Rodriguez
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What is the effect of ageing on cancer? Writing in Nature, Zhuang et al.1 report a surprising twist in our understanding of how ageing affects cancer risks.
Nature DOI suffix ≠ "/s...": Not a research article
Daily briefing: What is ageing? Even gerontologists don’t agree
Flora Graham
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Nature DOI suffix ≠ "/s...": Not a research article
Andrew V. Schally obituary: Nobel prizewinner who transformed cancer therapies with research into brain hormones
Renzi Cai, Medhi Wangpaichitr
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Nature DOI suffix ≠ "/s...": Not a research article
The climate-crusading lawyer who sued Switzerland over global warming — and won
Richard Monastersky
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Nature DOI suffix ≠ "/s...": Not a research article
How fast is the Universe expanding? This astronomer took cosmology closer to an answer
Davide Castelvecchi
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Nature DOI suffix ≠ "/s...": Not a research article
The daring doctor behind a world-first treatment for autoimmune disease
Smriti Mallapaty
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Nature DOI suffix ≠ "/s...": Not a research article
Publishers are selling papers to train AIs — and making millions of dollars
Diana Kwon
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Nature DOI suffix ≠ "/s...": Not a research article
A science mega-programme is taking shape in the EU: what it means for researchers
David Matthews
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Proceedings of the National Academy of Sciences

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
Cavity-enhanced superconductivity in MgB 2 from first-principles quantum electrodynamics (QEDFT)
I-Te Lu, Dongbin Shin, Mark Kamper Svendsen, Hannes HĂŒbener, Umberto De Giovannini, Simone Latini, Michael Ruggenthaler, Angel Rubio
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Strong laser pulses can control superconductivity, inducing nonequilibrium transient pairing by leveraging strong-light matter interaction. Here, we demonstrate theoretically that equilibrium ground-state phonon-mediated superconductive pairing can be affected through the vacuum fluctuating electromagnetic field in a cavity. Using the recently developed ab initio quantum electrodynamical density-functional theory approximation, we specifically investigate the phonon-mediated superconductive behavior of MgB 2 under different cavity setups and find that in the strong light–matter coupling regime its superconducting transition temperature T c can be enhanced at most by ≈ 10% in an in-plane (or out-of-plane) polarized and realistic cavity via photon vacuum fluctuations. The results highlight that strong light–matter coupling in extended systems can profoundly alter material properties in a nonperturbative way by modifying their electronic structure and phononic dispersion at the same time. Our findings indicate a pathway to the experimental realization of light-controlled superconductivity in solid-state materials at equilibrium via cavity materials engineering.
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
Amino acids modulate liquid–liquid phase separation in vitro and in vivo by regulating protein–protein interactions
Xufeng Xu, Aleksander A. Rebane, Laura Roset Julia, Kathryn A. Rosowski, Eric R. Dufresne, Francesco Stellacci
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Liquid–liquid phase separation (LLPS) is an intracellular process widely used by cells for many key biological functions. It occurs in complex and crowded environments, where amino acids (AAs) are vital components. We have found that AAs render the net interaction between proteins more repulsive. Here, we find that some AAs efficiently suppress LLPS in test tubes (in vitro). We then screen all the proteinogenic AAs and find that three specific AAs, including proline, glutamine, and glycine, significantly suppressed the formation of stress granules (SGs) in U2OS and HeLa cell lines (in vivo) irrespective of stress types. We also observe the effect in primary fibroblast cells, a viable cell model for neurodegenerative disorders. Kinetic studies by live-cell microscopy show that the presence of AAs not only slows down the formation but also decreases the saturating number and prevents the coalescence of SGs. We finally use sedimentation-diffusion equilibrium analytical ultracentrifuge (SE-AUC) to demonstrate that the suppression effects of AAs on LLPS may be due to their modulation in protein–protein and RNA–RNA interactions. Overall, this study reveals an underappreciated role of cellular AAs, which may find biomedical applications, especially in treating SG-associated diseases.
GPT-4o mini: Non-social science research article
High-temperature high-k polyolefin by rational molecular design
Jing Hao, Irene Mutegi, Madhubanti Mukherjee, Harikrishna Sahu, Ashish Khomane, Omer Yassin, Rampi Ramprasad, Gregory A. Sotzing, Yang Cao
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Polymer film dielectrics are highly favored for capacitive energy storage due to the inherent advantages of high breakdown strength, low dielectric loss, and ease of processing. High-density renewables conversion and harsh-condition electrification further emphasize the need for high-temperature, high-k polymers. A unique design strategy is developed to augment high-temperature polyolefins with improved dielectric constant, via the integration of phenyl pendants hanging off the rigid bicyclic backbone. The impacts of the pendant polarizability and steric positioning on dielectric constant, bandgap, glass-transition temperature ( T g ), and high-field, high-temperature dielectric characteristics have been investigated. The orientational polarization of the polar phenyl pendants with rotational degree of freedom imparts cyclic olefins with enhanced dielectric constants, while maintaining the large bandgap, and high glass-transition temperature ( T g > 170 °C). Among these synthesized polymers, m-PNB-BP stands out with a remarkable dielectric constant of 4 at a high sub- T g temperature of 150 °C, and a high discharged density of 8.6 J/m 3 at 660 MV/m. This study unveils a different path for designing high-temperature polymers with enhanced dielectric constants, particularly beneficial for capacitive energy storage.
GPT-4o mini: Non-social science research article
Structural insights into the assembly and energy transfer of haptophyte photosystem I–light-harvesting supercomplex
Fei-Yu He, Long-Sheng Zhao, Xin-Xiao Qu, Kang Li, Jian-Ping Guo, Fang Zhao, Ning Wang, Bing-Yue Qin, Xiu-Lan Chen, Jun Gao, Lu-Ning Liu, Yu-Zhong Zhang
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Haptophyta represents a major taxonomic group, with plastids derived from the primary plastids of red algae. Here, we elucidated the cryoelectron microscopy structure of the photosystem I–light-harvesting complex I (PSI–LHCI) supercomplex from the haptophyte Isochrysis galbana . The PSI core comprises 12 subunits, which have evolved differently from red algae and cryptophytes by losing the PsaO subunit while incorporating the PsaK subunit, which is absent in diatoms and dinoflagellates. The PSI core is encircled by 22 fucoxanthin-chlorophyll a / c -binding light-harvesting antenna proteins (iFCPIs) that form a trilayered antenna arrangement. Moreover, a pigment-binding subunit, L iFP , which has not been identified in any other previously characterized PSI–LHCI supercomplexes, was determined in I. galbana PSI–iFCPI, presumably facilitating the interactions and energy transfer between peripheral iFCPIs and the PSI core. Calculation of excitation energy transfer rates by computational simulations revealed that the intricate pigment network formed within PSI–iFCPI ensures efficient transfer of excitation energy. Overall, our study provides a solid structural foundation for understanding the light-harvesting and energy transfer mechanisms in haptophyte PSI–iFCPI and provides insights into the evolution and structural variations of red-lineage PSI–LHCIs.
GPT-4o mini: Non-social science research article
The gas|liquid interface eclipses the liquid|liquid interface for glucose oxidase rate acceleration in microdroplets
Lynn E. Krushinski, Patrick J. Herchenbach, Jeffrey E. Dick
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The curious chemistry observed in microdroplets has captivated chemists in recent years and has led to an investigation into their ability to drive seemingly impossible chemistries. One particularly interesting capability of these microdroplets is their ability to accelerate reactions by several orders of magnitude. While there have been many investigations into which reactions can be accelerated by confinement within microdroplets, no study has directly compared reaction acceleration at the liquid|liquid and gas|liquid interfaces. Here, we confine glucose oxidase, one of life’s most important enzymes, to microdroplets and monitor the turnover rate of glucose by the electroactive cofactor, hexacyanoferrate (III). We use stochastic electrochemistry to monitor the collision of single femtoliter water droplets on an ultramicroelectrode. We also develop a measurement modality to robustly quantify reaction rates for femtoliter liquid aerosol droplets, where the majority of the interface is gas|liquid. We demonstrate that the gas|liquid interface accelerates enzyme turnover by over an order of magnitude over the liquid|liquid interface. This is the first apples-to-apples comparison of reaction acceleration at two distinct interfaces that indicates that the gas|liquid interface plays a central role in driving curious chemistry.
GPT-4o mini: Non-social science research article
Architecture of the Sap S-layer of Bacillus anthracis revealed by integrative structural biology
AdriĂ  Sogues, Kendra Leigh, Ethan V. Halingstad, Sander E. Van der Verren, Adam J. Cecil, Antonella Fioravanti, Alexander J. Pak, Misha Kudryashev, Han Remaut
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Bacillus anthracis is a spore-forming gram-positive bacterium responsible for anthrax, an infectious disease with a high mortality rate and a target of concern due to bioterrorism and long-term site contamination. The entire surface of vegetative cells in exponential or stationary growth phase is covered in proteinaceous arrays called S-layers, composed of Sap or EA1 protein, respectively. The Sap S-layer represents an important virulence factor and cell envelope support structure whose paracrystalline nature is essential for its function. However, the spatial organization of Sap in its lattice state remains elusive. Here, we employed cryoelectron tomography and subtomogram averaging to obtain a map of the Sap S-layer from tubular polymers that revealed a conformational switch between the postassembly protomers and the previously available X-ray structure of the condensed monomers. To build and validate an atomic model of the lattice within this map, we used a combination of molecular dynamics simulations, X-ray crystallography, cross-linking mass spectrometry, and biophysics in an integrative structural biology approach. The Sap lattice model produced recapitulates a close-to-physiological arrangement, reveals high-resolution details of lattice contacts, and sheds light on the mechanisms underlying the stability of the Sap layer.
GPT-4o mini: Non-social science research article
The shard test and nanoporomechanics reverse classical paradigm of cement hydration being contractive
RaĂșl E. Marrero Rosa, Tapiwanashe Bhibho, Ahmet A. DƑnmez, Gianluca Cusatis, Zdeněk P. BaĆŸant
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Le Chatelier in 1887 and Powers in 1947 demonstrated that the volume of nanoscale C-S-H (calcium silicate hydrate) particles formed during hydration is smaller than the combined volume of the reactants—the anhydrous Portland cement and water. Hydration has thus been considered as contractive. An experiment shows that the opposite is true above the nanoscale. The porous skeleton of cement paste expands as the growing C-S-H particles push each other apart, similar to crystal growth pressure. This is significant for high-performance concretes (HPC) with low water-cement ratios (w/c ≀ 0.4), where chemical self-desiccation lowers pore relative humidity by 40%, compared to just 1% in traditional concretes (w/c ≈ 0.5). Standard American Society for Testing and Materials (ASTM) C1608 tests, using 10 mm thick water-immersed specimens, show large shrinkage because the half-time of water ingress is many decades, unable to offset shrinkage-causing self-desiccation. The present experiment, using a laser microscopy-topography technique, proves the opposite—expansion, evidenced by measuring the length changes of water-immersed HPC shards 0.5 mm thick in which the diffusion halftime, only about one hour, allows continuous resaturation of pores, canceling self-desiccation. The faster diffusion (halftime of one hour) enables continuous pore resaturation, preventing shrinkage. When sealed with paraffin oil, the shards self-desiccate and shrink. These findings align with studies since 2015, showing that models excluding hydration expansion cannot fit test data across various specimen sizes and sealing conditions. The results suggest that standardized ASTM tests for the so-called chemical shrinkage in modern concretes with very low water-cement ratios are misleading and need revision.
GPT-4o mini: Non-social science research article
Modeling protein motions through reinforcement learning
Alireza Ghafarollahi, Markus J. Buehler
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GPT-4o mini: Non-social science research article
Climate warming drives population trajectories of freshwater fish
Timothy M. Brown, Joseph O’Connor, Martin J. Genner
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Climate change has emerged as a key threat to biodiversity, leading to broad-scale shifts in distributions of marine and terrestrial species as they attempt to track thermally suitable habitat. By contrast, our understanding of climate responses of freshwater species is relatively undeveloped, limiting our knowledge of whether projected warming will lead to freshwater biodiversity loss. Here, we linked a multicontinental database of riverine fish population abundance time series collected from 1958 to 2019 to temperature data from the same period. Across the sampled localities, waters warmed by 0.21 °C per decade (annual maximum of monthly temperatures). We tested whether fish responded to this change by i) increasing abundance at the cooler poleward limit of species distributions—predicted if warming has opened new opportunities—and ii) decreasing abundance toward the equatorward limit of distributions—predicted if temperatures have exceeded tolerance thresholds. We found that observed population trends were consistent with both of these expected patterns from climatic warming and that the trends were more pronounced in time series covering the longer time periods of 30+ y. The responses consistent with climate change were most evident in species with larger body sizes, higher trophic levels, river–sea migratory behavior, and more widespread distributions. Moreover, positive abundance responses to warming were more likely at higher altitudes where conditions tend to be cooler. These findings indicate that projected future warming will likely lead to widespread shifts in riverine community structure, including abundance declines at the trailing edge of species distributions.
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 WĂŒhr, 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 ÎČ-barrel domain of OmpA is critical for maintaining the permeability barrier, but both the ÎČ-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 ~œ 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
Two distinct populations of dark comets delineated by orbits and sizes
Darryl Z. Seligman, Davide Farnocchia, Marco Micheli, Olivier R. Hainaut, Henry H. Hsieh, Adina D. Feinstein, Steven R. Chesley, Aster G. Taylor, Joseph Masiero, Karen J. Meech
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Small bodies are capable of delivering essential prerequisites for the development of life, such as volatiles and organics, to the terrestrial planets. For example, empirical evidence suggests that water was delivered to the Earth by hydrated planetesimals from distant regions of the Solar System. Recently, several morphologically inactive near-Earth objects were reported to experience significant nongravitational accelerations inconsistent with radiation-based effects, and possibly explained by volatile-driven outgassing. However, these “dark comets” display no evidence of comae in archival images, which are the defining feature of cometary activity. Here, we report detections of nongravitational accelerations on seven additional objects classified as inactive (doubling the population) that could also be explainable by asymmetric mass loss. A detailed search of archival survey and targeted data rendered no detection of dust activity in any of these objects in individual or stacked images. We calculate dust production limits of ∌ 10, 0.1 , and 0.1 kg s − 1 for 1998 FR 11 , 2001 ME 1 , and 2003 RM with these data, indicating little or no dust surrounding the objects during the observations. This set of dark comets reveals the delineation between two distinct populations: larger, “outer” dark comets on eccentric orbits that are end members of a continuum in activity level of comets, and smaller, “inner” dark comets on near-circular orbits that could signify a different different population. These objects may trace various stages in the life cycle of a previously undetected, but potentially numerous, volatile-rich population that may have provided essential material to the Earth.
GPT-4o mini: Non-social science research article
AI-boosted and motion-corrected, wireless near-infrared sensing system for continuously monitoring laryngeal muscles
Yihan Liu, Arjun Putcha, Gavin Lyda, Nanqi Peng, Salil Pai, Tien Nguyen, Sicheng Xing, Shang Peng, Yiyang Fan, Yizhang Wu, Wanrong Xie, Wubin Bai
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Neuromuscular diseases pose significant health and economic challenges, necessitating innovative monitoring technologies for personalizable treatment. Existing devices detect muscular motions either indirectly from mechanoacoustic signatures on skin surface or via ultrasound waves that demand specialized skin adhesion. Here, we report a wireless wearable system, Laryngeal Health Monitor (LaHMo), designed to be conformally placed on the neck for continuously measuring movements of underlying muscles. The system uses near-infrared (NIR) light that features deep-tissue penetration and strong interaction with myoglobin to capture muscular locomotion. The incorporated inertial measurement unit sensor further decouples the superposition of signals from NIR recordings. Integrating a multimodal AI-boosted algorithm based on recurrent neural network, the system accurately classifies activities of physiological events. An adaptive model enables fast individualization without enormous data sources from the target user, facilitating its broad applicability. Long-term tests and simulations suggest the potential efficacy of the LaHMo platform for real-world applications, such as monitoring disease progression in neuromuscular disorders, evaluating treatment efficacy, and providing biofeedback for rehabilitation exercises. The LaHMo platform may serve as a general noninvasive, user-friendly solution for assessing neuromuscular function beyond the anterior neck, potentially improving diagnostics and treatment of various neuromuscular disorders.
GPT-4o mini: Non-social science research article
Some coral reef communities may degrade and change but persist
Nancy Knowlton
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GPT-4o mini: Non-social science research article
The legacy of DDT lives on in the Southern California Bight
Amalia Aruda Almada
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GPT-4o mini: Non-social science research article
Photoinduced ultrafast multielectron transfer and long-lived charge-accumulated state in a fullerene-indacenodithiophene dumbbell triad
Chong Wang, Bo Wu, Yang Li, Ying Jiang, Tianyang Dong, Shen Zhou, Chunru Wang, Chunli Bai
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Photoinduced ultrafast multielectron transfer (m-ET) and long-lived charge-accumulated states in single molecules hold promise for light-energy conversion and utilization. However, compared to single-electron transfer (s-ET), m-ET tends to be thermodynamically and kinetically unfavorable. Here, we construct a dumbbell-shaped fullerene-indacenodithiophene triad, IT2 , modified with two C 60 units in the donor indacenodithiophene. Exciting the C 60 units, ultrafast m-ET occurs with a time constant of 0.5 ps, accumulating two holes with a lifetime of 10 ÎŒs. Benefitting from a larger driving force, lower reorganization energy, and smaller structural changes, the rate of m-ET is 23 times faster than that of s-ET, and the lifetime of the m-ET product is 1.4 × 10 5 times longer than that of the s-ET products. These attributes endow IT2 with superior photocatalytic performance in multielectron oxidation reactions. This is an instance of achieving faster m-ET and a longer m-ET product lifetime than s-ET in a single molecule. This finding provides unique insights for the construction and application of intramolecular m-ET and charge accumulation systems in photocatalysis and molecular devices.
GPT-4o mini: Non-social science research article
Fluctuating charge-density-wave correlations in the three-band Hubbard model
Peizhi Mai, Benjamin Cohen-Stead, Thomas A. Maier, Steven Johnston
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The high-temperature superconducting cuprates host unidirectional spin- and charge-density-wave orders that can intertwine with superconductivity in nontrivial ways. While the charge components of these stripes have now been observed in nearly all cuprate families, their detailed evolution with doping varies across different materials and at high and low temperatures. We address this problem using nonperturbative determinant quantum Monte Carlo calculations for the three-band Hubbard model. Using an efficient implementation, we can resolve the model’s fluctuating spin and charge modulations and map their evolution as a function of the charge transfer energy and doping. We find that the incommensurability of the charge modulations is decoupled from the spin modulations and decreases with hole doping, consistent with experimental measurements at high temperatures. These findings support the proposal that the high-temperature charge correlations are distinct from the intertwined stripe order observed at low-temperature and in the single-band Hubbard model.
GPT-4o mini: Non-social science research article
Regulation of ROS signaling by TIGAR induces cancer-modulating responses in the tumor microenvironment
Eric C. Cheung, Douglas Strathdee, David Stevenson, Jack Coomes, Karen Blyth, Karen H. Vousden
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The consequences of reactive oxygen species (ROS) in cancer cells are complex and have been shown to both promote and retard tumorigenesis in different models. In mouse models of pancreatic ductal adenocarcinoma (PDAC), loss of the antioxidant defense gene Tigar results in both a reduction in the development of early pancreatic intraepithelial neoplasia and an increase in invasive and metastatic capacity, accompanied by decreased survival of mice lacking pancreatic TIGAR. We previously demonstrated that increased ROS following loss of TIGAR promotes various cancer cell–intrinsic changes that contribute to metastatic capacity, including epithelial to mesenchymal transition, enhanced migration and invasion, and an increase in ERK signaling. In this study, we show that pancreatic overexpression of TIGAR decreases metastatic capacity and migratory phenotypes in an aggressive model of PDAC, consistent with the concept that dynamic modulation of TIGAR in PDAC contributes to the development and progression of these tumors. Using TIGAR deficient and overexpressing mouse models, we find that the impact of modulation of TIGAR and ROS in PDAC cells also has a profound effect on the normal stromal cells surrounding the tumor. Loss of TIGAR promotes the production of cytokines by cancer cells that induce changes in the surrounding fibroblasts to adopt a tumor-supportive phenotype. Furthermore, these cytokines also attract macrophages that support PDAC dissemination and metastasis. Taken together our work shows that TIGAR-modulated ROS in PDAC can control cell intrinsic and extrinsic changes to impact tumor aggression.
GPT-4o mini: Non-social science research article
Enhancement of bacterial rheotaxis in non-Newtonian fluids
Bryan O. Torres Maldonado, Albane Théry, Ran Tao, Quentin Brosseau, Arnold J. T. M. Mathijssen, Paulo E. Arratia
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Many microorganisms exhibit upstream swimming, which is important to many biological processes and can cause contamination of biomedical devices and the infection of organs. This process, called rheotaxis, has been studied extensively in Newtonian fluids. However, most microorganisms thrive in non-Newtonian fluids that contain suspended polymers such as mucus and biofilms. Here, we investigate the rheotactic behavior of Escherichia coli near walls in non-Newtonian fluids. Our experiments demonstrate that bacterial upstream swimming is enhanced by an order of magnitude in shear-thinning (ST) polymeric fluids relative to Newtonian fluids. This result is explained by direct numerical simulations, revealing a torque that promotes the alignment of bacteria against the flow. From this analysis, we develop a theoretical model that accurately describes experimental rheotactic data in both Newtonian and ST fluids.
GPT-4o mini: Non-social science research article
Density amplifiers of cooperation for spatial games
Jakub Svoboda, Krishnendu Chatterjee
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Spatial games provide a simple and elegant mathematical model to study the evolution of cooperation in networks. In spatial games, individuals reside in vertices, adopt simple strategies, and interact with neighbors to receive a payoff. Depending on their own and neighbors’ payoffs, individuals can change their strategy. The payoff is determined by the Prisoners’ Dilemma, a classical matrix game, where players cooperate or defect. While cooperation is the desired behavior, defection provides a higher payoff for a selfish individual. There are many theoretical and empirical studies related to the role of the network in the evolution of cooperation. However, the fundamental question of whether there exist networks that for low initial cooperation rate ensure a high chance of fixation, i.e., cooperation spreads across the whole population, has remained elusive for spatial games with strong selection. In this work, we answer this fundamental question in the affirmative by presenting network structures that ensure high fixation probability for cooperators in the strong selection regime. Besides, our structures have many desirable properties: (a) they ensure the spread of cooperation even for a low initial density of cooperation and high temptation of defection, (b) they have constant degrees, and (c) the number of steps, until cooperation spreads, is at most quadratic in the size of the network.
GPT-4o mini: Non-social science research article
Proteomic characterization of a foraminiferal test’s organic matrix
Fiorella Prada, Liti Haramaty, Oded Livnah, Racheli Shaul, Sigal Abramovich, Tali Mass, Yair Rosenthal, Paul G. Falkowski
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Foraminifera are unicellular protists capable of precipitating calcite tests, which fossilize and preserve geochemical signatures of past environmental conditions dating back to the Cambrian period. The biomineralization mechanisms responsible for the mineral structures, which are key to interpreting palaeoceanographic signals, are poorly understood. Here, we present an extensive analysis of the test-bound proteins. Using liquid chromatography–tandem mass spectrometry, we identify 373 test-bound proteins in the large benthic foraminifer Amphistegina lobifera , the majority of which are highly acidic and rich in negatively charged residues. We detect proteins involved in vesicle formation and active Ca 2+ trafficking, but in contrast, do not find similar proteins involved in Mg 2+ transport. Considering findings from this study and previous ones, we propose a dual ion transport model involving seawater vacuolization, followed by the active release of Ca 2+ from the initial vacuoles and subsequent uptake into newly formed Ca-rich vesicles that consequently enrich the calcification fluid. We further speculate that Mg 2+ passively leaks through the membrane from the remaining Mg-rich vesicles, into the calcifying fluid, at much lower concentrations than in seawater. This hypothesis could not only explain the low Mg/Ca ratio in foraminiferal tests compared to inorganic calcite, but could possibly also account for its elevated sensitivity to temperature compared with inorganically precipitated CaCO 3 .
GPT-4o mini: Non-social science research article
Hapalindole Q suppresses autophagosome−lysosome fusion by promoting YAP1 degradation via chaperon-mediated autophagy
Yali Wu, Shaonan Wang, Zhicong Guo, Min Sun, Zhen Xu, Yu Du, Fahui Zhu, Yajuan Su, Zhou Xu, Yi Xu, Xu Gong, Ruan Fang, Jiaojiao Hu, Yan Peng, Zhaowen Ding, Cong Liu, Ang Li, Weiwei He
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Autophagy is a conserved catabolic process crucial for maintaining cellular homeostasis and has emerged as a promising therapeutic target for many diseases. Mechanistically novel small-molecule autophagy regulators are highly desirable from a pharmacological point of view. Here, we report the macroautophagy-inhibitory effect of hapalindole Q, a member of the structurally intriguing but biologically understudied hapalindole family of indole terpenoids. This compound promotes the noncanonical degradation of Yes-associated protein 1 (YAP1), the downstream effector of the Hippo signaling pathway, via chaperone-mediated autophagy, disrupting proper distribution of Rab7 and suppressing autophagosome−lysosome fusion in macroautophagy. Its binding to YAP1 is further confirmed by using biophysical techniques. A preliminary structure−activity relationship study reveals that the hapalindole Q scaffold, rather than the isothiocyanate group, is essential for YAP1 binding and degradation. This work not only identifies a macroautophagy inhibitor with a distinct mechanism of action but also provided a molecular scaffold for direct targeting of YAP1, which may benefit the development of therapeutics for both autophagy-related and Hippo−YAP-related diseases.
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 HĂ€gg 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 HĂ€gg 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 HĂ€gg 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
Early human collective practices and symbolism in the Early Upper Paleolithic of Southwest Asia
Omry Barzilai, Ofer Marder, José-Miguel Tejero, Avner Ayalon, Miryam Bar-Matthews, Talia Abulafia, Ron Lavi, Mae Goder-Goldberger, Maayan Shemer, Lotan Edeltin, Alexander Wiegmann, Amos Frumkin, Avshalom Karasik, Gal Yasur, Reuven Yeshurun, Irit Zohar, Francesco Berna, Mark Hans, Jerold S. Goldberg, Yvonne McDermott, Linda Spurlock, Ariel Pokhojaev, Waseem Habashi, Hila May, Rachel Sarig, Israel Hershkovitz
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Identifying communal rituals in the Paleolithic is of scientific importance, as it reflects the expression of collective identity and the maintenance of group cohesion. This study provides evidence indicating the practice of deep cave collective rituals in the Levant during the Early Upper Paleolithic (EUP) period. It is demonstrated that these gatherings occurred within a distinct ritual compound and were centered around an engraved object in the deepest part of Manot Cave, a pivotal EUP site in southwest Asia. The ritual compound, segregated from the living areas, encompasses a large gallery partitioned by a cluster of remarkable speleothems. Within this gallery, an engraved boulder stands out, displaying geometric signs suggesting a unique representation of a tortoise. Isotopic analysis of calcite crusts on the boulder’s grooves revealed alignment with values found in speleothems from the cave dated to ~37 to 35 ka BP. Additionally, meticulous shape analysis of the grooves’ cross-section and the discernible presence of microlinear scratches on the grooves’ walls confirmed their anthropogenic origin. Examination of stalagmite laminae (36 ka BP) near the engraved boulder revealed a significant presence of wood ash particles within. This finding provides evidence for using fire to illuminate the dark, deep part of the cave during rituals. Acoustic tests conducted in various cave areas indicate that the ritual compound was well suited for communal gatherings, facilitating conversations, speeches, and hearing. Our results underscore the critical role of collective practices centered around a symbolic object in fostering a functional social network within the regional EUP communities.
GPT-4o mini: Non-social science research article
Global rarity of high-integrity tropical rainforests for threatened and declining terrestrial vertebrates
Rajeev Pillay, James E.M. Watson, Andrew J. Hansen, Patrick Burns, Anne Lucy Stilger Virnig, Christina Supples, Dolors Armenteras, Pamela GonzĂĄlez-del-Pliego, Jose Aragon-Osejo, Patrick A. Jantz, Jamison Ervin, Scott J. Goetz, Oscar Venter
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Structurally intact native forests free from major human pressures are vitally important habitats for the persistence of forest biodiversity. However, the extent of such high-integrity forest habitats remaining for biodiversity is unknown. Here, we quantify the amount of high-integrity tropical rainforests, as a fraction of total forest cover, within the geographic ranges of 16,396 species of terrestrial vertebrates worldwide. We found up to 90% of the humid tropical ranges of forest-dependent vertebrates was encompassed by forest cover. Concerningly, however, merely 25% of these remaining rainforests are of high integrity. Forest-dependent species that are threatened and declining and species with small geographic ranges have disproportionately low proportions of high-integrity forest habitat left. Our work brings much needed attention to the poor quality of much of the forest estate remaining for biodiversity across the humid tropics. The targeted preservation of the world’s remaining high-integrity tropical rainforests that are currently unprotected is a critical conservation priority that may help alleviate the biodiversity crisis in these hyperdiverse and irreplaceable ecosystems. Enhanced efforts worldwide to preserve tropical rainforest integrity are essential to meet the targets of the Convention on Biological Diversity’s 2022 Kunming-Montreal Global Biodiversity Framework which aims to achieve near zero loss of high biodiversity importance areas (including ecosystems of high integrity) by 2030.
GPT-4o mini: Non-social science research article
“One Health” needs ecology
John L. Gittleman
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GPT-4o mini: Non-social science research article
Sequence complexity and monomer rigidity control the morphologies and aging dynamics of protein aggregates
Ryota Takaki, D. Thirumalai
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Understanding the biophysical basis of protein aggregation is important in biology because of the potential link to several misfolding diseases. Although experiments have shown that protein aggregates adopt a variety of morphologies, the dynamics of their formation are less well characterized. Here, we introduce a minimal model to explore the dependence of the aggregation dynamics on the structural and sequence features of the monomers. Using simulations, we demonstrate that sequence complexity (codified in terms of word entropy) and monomer rigidity profoundly influence the dynamics and morphology of the aggregates. Flexible monomers with low sequence complexity (corresponding to repeat sequences) form liquid-like droplets that exhibit ergodic behavior. Strikingly, these aggregates abruptly transition to more ordered structures, reminiscent of amyloid fibrils, when the monomer rigidity is increased. In contrast, aggregates resulting from monomers with high sequence complexity are amorphous and display nonergodic glassy dynamics. The heterogeneous dynamics of the low and high-complexity sequences follow stretched exponential kinetics, which is one of the characteristics of glassy dynamics. Importantly, at nonzero values of the bending rigidities, the aggregates age with the relaxation times that increase with the waiting time. Informed by these findings, we provide insights into aging dynamics in protein condensates and contrast the behavior with the dynamics expected in RNA repeat sequences. Our findings underscore the influence of the monomer characteristics in shaping the morphology and dynamics of protein aggregates, thus providing a foundation for deciphering the general rules governing the behavior of protein condensates.
GPT-4o mini: Non-social science research article
Simultaneous visualization of membrane fluidity and morphology defines adhesion signatures of cancer cells
Takahisa Matsuzaki, Mai Fujii, Hayata Noro, Shodai Togo, Mami Watanabe, Masami Suganuma, Shivani Sharma, Naritaka Kobayashi, Ryuzo Kawamura, Seiichiro Nakabayashi, Hiroshi Y. Yoshikawa
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We developed an advanced optical microscope for the simultaneous visualization of membrane fluidity and morphology to define cell adhesion signatures. This microscope combines ratiometric spectral imaging of membrane fluidity and interferometric imaging of membrane morphology. As a preliminary demonstration, we simultaneously visualized the interface between a giant unilamellar vesicle (GUV) and a glass substrate at different temperatures. We identified more fluid regions of the membrane and membrane adhesion sites (conversely, low-fluidic, ordered membrane domains correlate with nonadhered regions). This microscopic system was applied to human breast cancer cell lines with different malignancies; then, we identified adhesion signature of cancer cells: 1) low-fluidic, ordered membrane domains at the cell periphery and 2) large fluidic deviation at the nonadhered region. Inhibition of the cholesterol synthesis pathway suppresses the ordered membrane domains at the cancer cell periphery; thus, high level of cholesterol supports the appearance. Furthermore, an inhibitor of the unsaturated lipid synthesis pathway suppressed the large fluidic deviation at the nonadhered region; variation of unsaturated lipids contributes to heterogeneity of the cancer membrane. Therefore, our advanced optical microscopy enables us to couple membrane physical properties with cell adhesion, leading to definition of adhesion signatures of broad cell types, not just for cancer cells, that regulate life phenomena.
GPT-4o mini: Non-social science research article
Leukemia inhibitory factor (LIF) receptor amplifies pathogenic activation of fibroblasts in lung fibrosis
Hung N. Nguyen, Yunju Jeong, Yunhye Kim, Mari Kamiya, Yaunghyun Kim, Humra Athar, Peter J. Castaldi, Craig P. Hersh, Jaivardhan A. Menon, Jessie Wong, Ian Chan, William M. Oldham, Robert F. Padera, Nirmal S. Sharma, Lynette M. Sholl, Marina Vivero, Gerald F. M. Watts, Rachel S. Knipe, Katharine E. Black, Lida P. Hariri, Jeong H. Yun, Louis T. Merriam, Ke Yuan, Edy Y. Kim, Michael B. Brenner
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Fibrosis drives end-organ damage in many diseases. However, clinical trials targeting individual upstream activators of fibroblasts, such as TGFÎČ, have largely failed. Here, we target the leukemia inhibitory factor receptor (LIFR) as an “autocrine master amplifier” of multiple upstream activators of lung fibroblasts. In idiopathic pulmonary fibrosis (IPF), the most common fibrotic lung disease, we found that lung myofibroblasts had high LIF expression, and the fibroblasts in fibroblastic foci coexpressed LIF and LIFR. In IPF, fibroblastic foci are the “leading edge” of fibrosis and a key site of disease pathogenesis. TGFÎČ1, one of the principal drivers of fibrosis, up-regulated LIF expression in IPF fibroblasts. We found that TGFÎČ1, IL-4, and IL-13 stimulations of fibroblasts require the LIF-LIFR axis to evoke a strong fibrogenic effector response in fibroblasts. In vitro antibody blockade of LIFR on IPF lung fibroblasts reduced the induction of profibrotic genes after TGFÎČ1 stimulation. Silencing LIF and LIFR reduced profibrotic fibroblast activation following TGFÎČ1, IL-4, and IL-13 stimulations. We also demonstrated that LIFR amplified profibrotic stimuli in precision-cut lung slices from IPF patients. These LIFR signals were transduced via JAK2, and STAT1 in IPF lung fibroblasts. Together, we find that LIFR drives an autocrine circuit that amplifies and sustains pathogenic activation of IPF fibroblasts. Targeting a single, downstream master amplifier on fibroblasts, like LIFR, is an alternative therapeutic strategy that simultaneously attenuates the profibrotic effects of multiple upstream stimuli.
GPT-4o mini: Non-social science research article
Inertia-induced mixing and reaction maximization in laminar porous media flows
Michael A. Chen, Sang Hyun Lee, Peter K. Kang
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Solute transport and biogeochemical reactions in porous and fractured media flows are controlled by mixing, as are subsurface engineering operations such as contaminant remediation, geothermal energy production, and carbon sequestration. Porous media flows are generally regarded as slow, so the effects of fluid inertia on mixing and reaction are typically ignored. Here, we demonstrate through microfluidic experiments and numerical simulations of mixing-induced reaction that inertial recirculating flows readily emerge in laminar porous media flows and dramatically alter mixing and reaction dynamics. An optimal Reynolds number that maximizes the reaction rate is observed for individual pore throats of different sizes. This reaction maximization is attributed to the effects of recirculation flows on reactant availability, mixing, and reaction completion, which depend on the topology of recirculation relative to the boundary of the reactants or mixing interface. Recirculation enhances mixing and reactant availability, but a further increase in flow velocity reduces the residence time in recirculation, leading to a decrease in reaction rate. The reaction maximization is also confirmed in a flow channel with grain inclusions and randomized porous media. Interestingly, the domain-wide reaction rate shows a dramatic increase with increasing Re in the randomized porous media case. This is because fluid inertia induces complex three-dimensional flows in randomized porous media, which significantly increases transverse spreading and mixing. This study shows how inertial flows control reaction dynamics at the pore scale and beyond, thus having major implications for a wide range of environmental systems.
GPT-4o mini: Non-social science research article
Hydrogen ejection from hydrocarbons: Characterization and relevance in soot formation and interstellar chemistry
Josie Hendrix, Diptarka Hait, Hope A. Michelsen, Martin Head-Gordon
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Polycyclic aromatic hydrocarbons (PAHs) play a major role in the chemistry of combustion, pyrolysis, and the interstellar medium. Production (or activation) of radical PAHs and propagation of their resulting reactions require efficient dehydrogenation, but the preferred method of hydrogen loss is not well understood. Unimolecular hydrogen ejection (i.e., direct C─H bond fission) and bimolecular radical abstraction are two main candidate pathways. We performed a computational study to characterize the role of H ejection, particularly as a driver for radical-centric hydrocarbon-growth mechanisms and particle formation. Electronic structure calculations establish that C─H bond strengths span a broad range of energies, which can be weaker than 30 kcal/mol in some C 9 and C 13 PAH radicals. At T > 1200 K, calculated thermal rates for hydrogen ejection from weak C─H bonds at zigzag sites on PAH radicals are significantly larger than typical H-abstraction rates. These results are highly relevant in the context of chain reactions of radical species and soot inception under fuel-rich combustion conditions. Furthermore, calculated microcanonical rates that include the additional internal energy released by bond formation (e.g., ring closure to yield C 9 H 9 ) yield significantly higher rates than those associated with full thermalization. These microcanonical considerations are relevant to the astrochemical processes associated with hydrocarbon growth and processing in the low-density interstellar environment.
GPT-4o mini: Non-social science research article
Identification of 10,000-year-old rice beer at Shangshan in the Lower Yangzi River valley of China
Li Liu, Jianping Zhang, Jingbo Li, Yahui He, Zhongzhe Gao, Leping Jiang
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The origins of rice domestication and the beginnings of alcoholic fermentation in China are intriguing research topics, with the Shangshan culture in the Lower Yangzi River region being a focal point of archaeological investigations. This study employs a multiproxy approach (phytolith, starch, and fungi) to analyze microfossil remains associated with pottery vessels from the earliest phase of the Shangshan site (ca. 10,000 to 9,000 cal. BP). The results indicate that rice was consumed as a dietary staple and used for brewing fermented beverages with a qu starter containing Monascus mold and yeast as fermentation agents. The fermentation ingredients included rice, supplemented with other cereals (Job’s tears, Panicoideae, and Triticeae), acorn, and lily. This rice-fungi-based multiplant brewing method marked the earliest-known alcoholic fermentation technique in East Asia. The emergence of this fermentation technology is attributable to the early development of rice domestication and the arrival of the wet-warm Holocene climate, which was favorable for fungal growth. These alcoholic beverages likely played a pivotal role in ceremonial feasting, highlighting their ritual function as a driving factor that may have stimulated the intensive utilization and widespread cultivation of rice in Neolithic China.
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
Sustainable production of bioplastic monomers using a microbial production chassis
Mattheos A. G. Koffas
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GPT-4o mini: Non-social science research article
Endo-IP and lyso-IP toolkit for endolysosomal profiling of human-induced neurons
Frances V. Hundley, Miguel A. Gonzalez-Lozano, Lena M. Gottschalk, Aslan N. K. Cook, Jiuchun Zhang, Joao A. Paulo, J. Wade Harper
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Plasma membrane protein degradation and recycling are regulated by the endolysosomal system, wherein endocytic vesicles bud from the plasma membrane into the cytoplasm and mature into endosomes and then degradative lysosomes. As such, the endolysosomal system plays a critical role in determining the abundance of proteins on the cell surface and influencing cellular identity and function. Highly polarized cells, like neurons, rely on the endolysosomal system for axonal and dendritic specialization and synaptic compartmentalization. The importance of this system to neuronal function is reflected by the prevalence of risk variants in components of the system in several neurodegenerative diseases, ranging from Parkinson’s to Alzheimer’s disease. Nevertheless, our understanding of endocytic cargo and core endolysosomal machinery in neurons is limited, in part due to technical limitations. Here, we develop a toolkit for capturing EEA1-positive endosomes (termed Endo-IP) and TMEM192-positive lysosomes (termed Lyso-IP) in stem cell-derived induced neurons (iNeurons). We demonstrate its utility by revealing the endolysosomal protein landscapes for stem cells and cortical-like iNeurons, and profiling endosomes in response to potassium-mediated neuronal depolarization. Through global profiling of endocytic cargo, we identify hundreds of transmembrane proteins, including neurogenesis and synaptic proteins, as well as endocytic cargo with predicted SNX17 or SNX27 recognition motifs. By contrast, parallel lysosome profiling reveals a simpler protein repertoire, reflecting in part temporally controlled recycling or degradation for many endocytic targets. This system will facilitate mechanistic interrogation of endolysosomal components found as risk factors in neurodegenerative disease.
GPT-4o mini: Non-social science research article
KDM5D histone demethylase mediates p38α inactivation via its enzymatic activity to inhibit cancer progression
Jingying Chen, Ting Wang, Dongzhe Zhang, Huiling Wang, Zhiang Huang, Zhongxin Yang, Jizhuo Li, Tianyi Hu, Xin Wang, Xia Li
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The p38 MAP kinase (MAPK) signaling pathway plays pivotal roles in various cellular processes. Phosphorylation serves as a canonical way to regulate p38α activation through a phosphorylation cascade. Thus, understanding the mechanism governing p38α phosphorylation is important. The present study demonstrated that p38α undergoes methylation at K165, which promote its phosphorylation in tumor cells. Inhibition of p38α methylation impairs p38α phosphorylation, repressing tumor progression in vitro and in vivo. Mechanistically, KDM5D is a demethylase that interacts with p38α, mediating demethylation at K165 and inhibiting p38α phosphorylation. Moreover, KDM5D is expressed at low levels in non–small cell lung cancer (NSCLC), and high KDM5D expression is positively correlated with cancer survival. KDM5D markedly inhibits cell proliferation and migration via inactivating p38α, thereby slowing cancer progression in xenograft models. In summary, these findings highlight KDM5D as a demethylase of p38α at K165, elucidating a unique role for lysine demethylation in integrating cytoplasmic kinase-signaling cascades. The present results revealed the critical role of KDM5D in suppressing tumor progression, suggesting that KDM5D can serve as a potential drug target for combating hyperactive p38α-driven lung cancer.
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
Understanding paralogous epilepsy–associated GABA A receptor variants: Clinical implications, mechanisms, and potential pitfalls
Anthony S. H. Kan, Ali S. Kusay, Nazanin A. Mohammadi, Susan X. N. Lin, Vivian W. Y. Liao, Gaetan Lesca, Sabrine Souci, Mathieu Milh, Palle Christophersen, Mary Chebib, Rikke S. MĂžller, Nathan L. Absalom, Anders A. Jensen, Philip K. Ahring
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Recent discoveries have revealed that genetic variants in Îł-aminobutyric acid type A (GABA A ) receptor subunits can lead to both gain-of-function (GOF) and loss-of-function (LOF) receptors. GABA A receptors, however, have a pseudosymmetrical pentameric assembly, and curiously diverse functional outcomes have been reported for certain homologous variants in paralogous genes (paralogous variants). To investigate this, we assembled a cohort of 11 individuals harboring paralogous M1 proline missense variants in GABRA1 , GABRB2 , GABRB3, and GABRG2. Seven mutations (α1 P260L , α1 P260S , ÎČ2 P252L , ÎČ3 P253L , ÎČ3 P253S , Îł2 P282A , and Îł2 P282S ) in α1ÎČ2/3Îł2 receptors were analyzed using electrophysiological examinations and molecular dynamics simulations. All individuals in the cohort were diagnosed with developmental and epileptic encephalopathy, with a median seizure onset age of 3.5 mo, and all exhibited global developmental delay. The clinical data for this cohort aligned with established GABA A receptor GOF but not LOF cohorts. Electrophysiological assessments revealed that all variants caused GOF by increasing GABA sensitivity by 3- to 23-fold. In some cases, this was accompanied by LOF traits such as reduced maximal current amplitude and enhanced receptor desensitization. The specific subunit mutated and whether the mutation occurred in one or two subunits within the pentamer influenced the overall effects. Molecular dynamics simulations confirmed similar structural changes from all mutations, but with position-dependent asymmetry. These findings establish that paralogous variants affecting the 100% conserved proline residue in the M1 transmembrane helix of GABA A R subunits all lead to overall GOF traits. The unexpected asymmetric and mixed effects on receptor function have broader implications for interpreting functional analyses for multimeric ion-channel proteins.
GPT-4o mini: Non-social science research article
A genetically encoded anomalous SAXS ruler to probe the dimensions of intrinsically disordered proteins
Miao Yu, Andrey Yu. Gruzinov, Hao Ruan, Tom Scheidt, Aritra Chowdhury, Sabrina GiofrĂš, Ahmed S. A. Mohammed, Joana Caria, Paul F. Sauter, Dmitri I. Svergun, Edward A. Lemke
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Intrinsically disordered proteins (IDPs) adopt ensembles of rapidly fluctuating heterogeneous conformations, influencing their binding capabilities and supramolecular transitions. The primary conformational descriptors for understanding IDP ensembles—the radius of gyration ( R G ), measured by small-angle X-ray scattering (SAXS), and the root mean square (rms) end-to-end distance ( R E ), probed by fluorescent resonance energy transfer (FRET)—are often reported to produce inconsistent results regarding IDP expansion as a function of denaturant concentration in the buffer. This ongoing debate surrounding the FRET-SAXS discrepancy raises questions about the overall reliability of either method for quantitatively studying IDP properties. To address this discrepancy, we introduce a genetically encoded anomalous SAXS (ASAXS) ruler, enabling simultaneous and direct measurements of R G and R E without assuming a specific structural model. This ruler utilizes a genetically encoded noncanonical amino acid with two bromine atoms, providing an anomalous X-ray scattering signal for precise distance measurements. Through this approach, we experimentally demonstrate that the ratio between R E and R G varies under different denaturing conditions, highlighting the intrinsic properties of IDPs as the primary source of the observed SAXS-FRET discrepancy rather than shortcomings in either of the two established methods. The developed genetically encoded ASAXS ruler emerges as a versatile tool for both IDPs and folded proteins, providing a unified approach for obtaining complementary and site-specific conformational information in scattering experiments, thereby contributing to a deeper understanding of protein functions.
GPT-4o mini: Non-social science research article
Intracortical recordings reveal the neuronal selectivity for bodies and body parts in the human visual cortex
Jesus Garcia Ramirez, Michael Vanhoyland, N. A. Ratan Murty, Thomas Decramer, Wim Van Paesschen, Stefania Bracci, Hans Op de Beeck, Nancy Kanwisher, Peter Janssen, Tom Theys
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Body perception plays a fundamental role in social cognition. Yet, the neural mechanisms underlying this process in humans remain elusive given the spatiotemporal constraints of functional imaging. Here, we present intracortical recordings of single- and multiunit spiking activity in two epilepsy surgery patients in or near the extrastriate body area, a critical region for body perception. Our recordings revealed a strong preference for human bodies over a large range of control stimuli. Notably, body selectivity was driven by a distinct selectivity for body parts. The observed body selectivity generalized to nonphotographic depictions of bodies including silhouettes and stick figures. Overall, our study provides unique neural data that bridge the gap between human neuroimaging and macaque electrophysiology studies, laying a solid foundation for computational models of human body processing.
GPT-4o mini: Non-social science research article
Kinetic principles of chemical cross-link formation for protein–protein interactions
Kai-Michael Kammer, Terese Eisgruber, Peter Heid, Riccardo Pellarin, Florian Stengel
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Proteins play a central role in most biological processes within the cell, and deciphering how they interact is key to understand their function. Cross-linking coupled with mass spectrometry is an essential tool for elucidating protein–protein interactions (PPIs). Despite its importance, we still know surprisingly little about the principles that underlie the process of chemical cross-link formation itself and how it is influenced by different physicochemical factors. To understand the molecular details of cross-link formation, we have set up a comprehensive kinetic model and carried out simulations of protein cross-linking on large protein complexes. We dissect the contribution on the cross-link yield of parameters such as amino acid reactivity, cross-linker concentration, and hydrolysis rate. Our model can compute cross-link formation based solely on the structure of a protein complex, thereby enabling realistic predictions for a diverse set of systems. We quantitatively show how cross-links and mono-links are in direct competition and how the hydrolysis rate and abundance of cross-linker and proteins directly influence their relative formation. We show how cross-links and mono-links exist in an “all-against-all” competition due to their simultaneous formation, resulting in a nonintuitive network of interdependence. We show that this interdependence is locally confined and mainly limited to direct neighbors or residues in direct vicinity. These results enable us to identify the optimal cross-linker concentration at which the maximal number of cross-links is formed. Taken together, our study establishes a comprehensive kinetic model to quantitatively describe cross-link formation for PPIs.
GPT-4o mini: Non-social science research article
Sulfur isotope anomalies in coal combustion: Applications to the present and early Earth environments
Yanan Shen, Qixin Zhang, Yilun Xu, Menghan Li, Mark H. Thiemens
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The observation of mass-independent sulfur isotope fractionations (S-MIF) in Archean–Paleoproterozoic rocks has been instrumental in constraining oxygen levels on early Earth. The S-MIF effect, experimentally demonstrated to result from photochemical reactions, has now been observed in coal combustion, expanding our understanding of this phenomenon. Our study reveals that the negative Δ 33 S anomalies produced by coal combustion are consistent with similar anomalies observed in present-day sulfate aerosols in Beijing, China, and the black crust sulfates formed on building stones, monument walls, and sculptures in Europe that contribute to carbonate stone deterioration and cultural heritage damage. This finding provides independent evidence for a critical role of atmospheric sulfate from coal combustion in maintaining isotopic balance and offers an effective method for tracing sulfate aerosol sources. These insights are vital for developing more effective regulatory policies to control air pollution and protect public health. Given that coal energy production remains a significant issue in climate science, accurately mapping the global distribution of its by-products is imperative.
GPT-4o mini: Non-social science research article
Distinguishing deception from its confounds by improving the validity of fMRI-based neural prediction
Sangil Lee, Runxuan Niu, Lusha Zhu, Andrew S. Kayser, Ming Hsu
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Deception is a universal human behavior. Yet longstanding skepticism about the validity of measures used to characterize the biological mechanisms underlying deceptive behavior has relegated such studies to the scientific periphery. Here, we address these fundamental questions by applying machine learning methods and functional magnetic resonance imaging (fMRI) to signaling games capturing motivated deception in human participants. First, we develop an approach to test for the presence of confounding processes and validate past skepticism by showing that much of the predictive power of neural predictors trained on deception data comes from processes other than deception. Specifically, we demonstrate that discriminant validity is compromised by the predictor’s ability to predict behavior in a control task that does not involve deception. Second, we show that the presence of confounding signals need not be fatal and that the validity of the neural predictor can be improved by removing confounding signals while retaining those associated with the task of interest. To this end, we develop a “dual-goal tuning” approach in which, beyond the typical goal of predicting the behavior of interest, the predictor also incorporates a second compulsory goal that enforces chance performance in the control task. Together, these findings provide a firmer scientific foundation for understanding the neural basis of a neglected class of behavior, and they suggest an approach for improving validity of neural predictors.
GPT-4o mini: Non-social science research article
Ecosystem stability relies on diversity difference between trophic levels
Yizhou Liu, Jiliang Hu, Jeff Gore
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The stability of ecological communities has a profound impact on humans, ranging from individual health influenced by the microbiome to ecosystem services provided by fisheries. A long-standing goal of ecology is the elucidation of the interplay between biodiversity and ecosystem stability, with some ecologists warning of instability due to loss of species diversity while others arguing that greater diversity will instead lead to instability. Here, by considering a minimal two-level ecosystem with multiple predator and prey species, we show that stability does not depend on absolute diversity but rather on diversity differences between levels. We found that increasing diversity in either level first destabilizes but then stabilizes the community (i.e., a reentrant stability transition). We therefore find that it is the diversity difference between levels that is the key to stability, with the least stable communities having similar diversities in different levels. An analytical stability criterion is derived, demonstrating quantitatively that the critical diversity difference is determined by the correlation between how one level affects another and how it is affected in turn. Our stability criterion also applies to consumer–resource models with other forms of interaction such as cross-feeding. Finally, we show that stability depends on diversity differences in ecosystems with three trophic levels. Our finding of a nonmonotonic dependence of stability on diversity provides a natural explanation for the variety of diversity-stability relationships reported in the literature, and emphasizes the significance of level structure in predicting complex community behaviors.
GPT-4o mini: Non-social science research article
Structural basis of the allosteric regulation of cyanobacterial glucose-6-phosphate dehydrogenase by the redox sensor OpcA
Sofia Doello, Dmitry Shvarev, Marius Theune, Jakob Sauerwein, Alexander Klon, Erva Keskin, Marko Boehm, Kirstin Gutekunst, Karl Forchhammer
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The oxidative pentose phosphate (OPP) pathway is a fundamental carbon catabolic route for generating reducing power and metabolic intermediates for biosynthetic processes. In addition, its first two reactions form the OPP shunt, which replenishes the Calvin-Benson cycle under certain conditions. Glucose-6-phosphate dehydrogenase (G6PDH) catalyzes the first and rate-limiting reaction of this metabolic route. In photosynthetic organisms, G6PDH is redox-regulated to allow fine-tuning and to prevent futile cycles while carbon is being fixed. In cyanobacteria, regulation of G6PDH requires the redox protein OpcA, but the underlying molecular mechanisms behind this allosteric activation remain elusive. Here, we used enzymatic assays and in vivo interaction analyses to show that OpcA binds G6PDH under different environmental conditions. However, complex formation enhances G6PDH activity when OpcA is oxidized and inhibits it when OpcA is reduced. To understand the molecular basis of this regulation, we used cryogenic electron microscopy to determine the structure of Synechocystis G6PDH and the G6PDH–OpcA complex. OpcA binds the G6PDH tetramer and induces conformational changes in the active site of G6PDH. The redox sensitivity of OpcA is achieved by intramolecular disulfide bridge formation, which influences the allosteric regulation of G6PDH. In vitro assays reveal that the level of G6PDH activation depends on the number of bound OpcA molecules, which implies that this mechanism allows delicate fine-tuning. Our findings unveil a unique molecular mechanism governing the regulation of the OPP in Synechocystis .
GPT-4o mini: Non-social science research article
Temporal control of acute protein aggregate turnover by UBE3C and NRF1-dependent proteasomal pathways
Kelsey L. Hickey, Alexandra Panov, Enya Miguel Whelan, Tillman SchÀfer, Arda Mizrak, Ron R. Kopito, Wolfgang Baumeister, Rubén Fernåndez-Busnadiego, J. Wade Harper
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A hallmark of neurodegenerative diseases (NDs) is the progressive loss of proteostasis, leading to the accumulation of misfolded proteins or protein aggregates, with subsequent cytotoxicity. To combat this toxicity, cells have evolved degradation pathways (ubiquitin–proteasome system and autophagy) that detect and degrade misfolded proteins. However, studying the underlying cellular pathways and mechanisms has remained a challenge, as formation of many types of protein aggregates is asynchronous, with individual cells displaying distinct kinetics, thereby hindering rigorous time-course studies. Here, we merge a kinetically tractable and synchronous agDD-GFP system for aggregate formation with targeted gene knockdowns, to uncover degradation mechanisms used in response to acute aggregate formation. We find that agDD-GFP forms amorphous aggregates by cryo-electron tomography at both early and late stages of aggregate formation. Aggregate turnover occurs in a proteasome-dependent mechanism in a manner that is dictated by cellular aggregate burden, with no evidence of the involvement of autophagy. Lower levels of misfolded agDD-GFP, enriched in oligomers, utilizes UBE3C-dependent proteasomal degradation in a pathway that is independent of RPN13 ubiquitylation by UBE3C. Higher aggregate burden activates the NRF1 transcription factor to increase proteasome subunit transcription and subsequent degradation capacity of cells. Loss or gain of NRF1 function alters the turnover of agDD-GFP under conditions of high aggregate burden. Together, these results define the role of UBE3C in degradation of this class of misfolded aggregation-prone proteins and reveals a role for NRF1 in proteostasis control in response to widespread protein aggregation.
GPT-4o mini: Non-social science research article
Representation of a perceptual bias in the prefrontal cortex
Luis Serrano-FernĂĄndez, Manuel BeirĂĄn, Ranulfo Romo, NĂ©stor Parga
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Perception is influenced by sensory stimulation, prior knowledge, and contextual cues, which collectively contribute to the emergence of perceptual biases. However, the precise neural mechanisms underlying these biases remain poorly understood. This study aims to address this gap by analyzing neural recordings from the prefrontal cortex (PFC) of monkeys performing a vibrotactile frequency discrimination task. Our findings provide empirical evidence supporting the hypothesis that perceptual biases can be reflected in the neural activity of the PFC. We found that the state-space trajectories of PFC neuronal activity encoded a warped representation of the first frequency presented during the task. Remarkably, this distorted representation of the frequency aligned with the predictions of its Bayesian estimator. The identification of these neural correlates expands our understanding of the neural basis of perceptual biases and highlights the involvement of the PFC in shaping perceptual experiences. Similar analyses could be employed in other delayed comparison tasks and in various brain regions to explore where and how neural activity reflects perceptual biases during different stages of the trial.
GPT-4o mini: Non-social science research article
Single-molecule diffusivity quantification in Xenopus egg extracts elucidates physicochemical properties of the cytoplasm
Alexander A. Choi, Coral Y. Zhou, Ayana Tabo, Rebecca Heald, Ke Xu
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The living cell creates a unique internal molecular environment that is challenging to characterize. By combining single-molecule displacement/diffusivity mapping (SM d M) with physiologically active extracts prepared from Xenopus laevis eggs, we sought to elucidate molecular properties of the cytoplasm. Quantification of the diffusion coefficients of 15 diverse proteins in extract showed that, compared to in water, negatively charged proteins diffused ~50% slower, while diffusion of positively charged proteins was reduced by ~80 to 90%. Adding increasing concentrations of salt progressively alleviated the suppressed diffusion observed for positively charged proteins, signifying electrostatic interactions within a predominately negatively charged macromolecular environment. To investigate the contribution of RNA, an abundant, negatively charged component of cytoplasm, extracts were treated with ribonuclease, which resulted in low diffusivity domains indicative of aggregation, likely due to the liberation of positively charged RNA-binding proteins such as ribosomal proteins, since this effect could be mimicked by adding positively charged polypeptides. Interestingly, in extracts prepared under typical conditions that inhibit actin polymerization, negatively charged proteins of different sizes showed similar diffusivity suppression consistent with our separately measured 2.22-fold higher viscosity of extract over water. Restoring or enhancing actin polymerization progressively suppressed the diffusion of larger proteins, recapitulating behaviors observed in cells. Together, these results indicate that molecular interactions in the crowded cell are defined by an overwhelmingly negatively charged macromolecular environment containing cytoskeletal networks.
GPT-4o mini: Non-social science research article
DPF2 reads histone lactylation to drive transcription and tumorigenesis
Guijin Zhai, Ziping Niu, Zixin Jiang, Fei Zhao, Siyu Wang, Chen Chen, Wei Zheng, Aiyuan Wang, Yong Zang, Yanpu Han, Kai Zhang
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Lysine lactylation (Kla) is a new type of histone mark implicated in the regulation of various functional processes such as transcription. However, how this histone mark acts in cancers remains unexplored due in part to a lack of knowledge about its reader proteins. Here, we observe that cervical cancer (CC) cells undergo metabolic reprogram by which lactate accumulation and thereby boosts histone lactylation, particularly H3K14la. Utilizing a multivalent photoaffinity probe in combination with quantitative proteomics approach, we identify DPF2 as a candidate target of H3K14la. Biochemical studies as well as CUT&Tag analysis reveal that DPF2 is capable of binding to H3K14la and colocalizes with it on promoters of oncogenic genes. Notably, disrupting the DPF2–H3K14la interaction through structure-guided mutation blunts those cancer-related gene expression along with cell survival. Together, our findings reveal DPF2 as a bona fide H3K14la effector that couples histone lactylation to gene transcription and cell survival, offering insight into how histone Kla engages in transcription and tumorigenesis.
GPT-4o mini: Non-social science research article
Intricate ribosome composition and translational reprogramming in epithelial–mesenchymal transition
Chloé Morin, AgnÚs Baudin-Baillieu, Flora Nguyen Van Long, Caroline Isaac, Laure Bidou, Hugo Arbes, Pauline François, Roxane M. Pommier, Annie Adrait, Akari Saku, Stephanie Gran-Ruaz, Camélia Machkouri, Christophe Vanbelle, Romain Morichon, Mathieu Boissan, Frédéric Catez, Anthony Ferrari, Anne-Pierre Morel, Yohann Couté, Sophie Chat, Emmanuel Giudice, Reynald Gillet, Alain Puisieux, Caroline Moyret-Lalle, Jean-Jacques Diaz, Olivier Namy, Virginie Marcel
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Epithelial–mesenchymal transition (EMT) involves profound changes in cell morphology, driven by transcriptional and epigenetic reprogramming. However, evidence suggests that translation and ribosome composition also play key roles in establishing pathophysiological phenotypes. Using genome-wide analyses, we reported significant rearrangement of the translational landscape and machinery during EMT. Specifically, a cell line overexpressing the EMT transcription factor ZEB1 displayed alterations in translational reprogramming and fidelity. Furthermore, using riboproteomics, we unveiled an increased level of the ribosomal protein RPL36A in mesenchymal ribosomes, indicating precise tuning of ribosome composition. Remarkably, RPL36A overexpression alone was sufficient to trigger the acquisition of mesenchymal features, including a switch in the molecular pattern, cell morphology, and behavior, demonstrating its pivotal role in EMT. These findings underline the importance of translational reprogramming and fine-tuning of ribosome composition in EMT.
GPT-4o mini: Non-social science research article
Origin of fast charging in solid-state batteries revealed by Cryo-transmission X-ray microscopy
Jiaxuan Liu, Yajie Song, Qingsong Liu, Wei Zhao, Hanwen An, Zinan Zhou, Zihan Xu, Menglu Li, Biao Deng, Jiajun Wang
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The interface issue poses a limitation on the fast charging of solid-state batteries (SSBs), with the high-impedance non-Faraday electric field serving as a pivotal factor. However, the mechanism of fast-charging capability degradation triggered by the dynamic evolution of non-Faraday electric fields remains unclear due to the lack of particle-scale nondestructive detection techniques. Here, we dissect the generation and elimination processes of non-Faradaic electric field in segments using the developed operando cryogenic transmission X-ray microscopy (Cryo-TXM). This method accurately tracks the ion self-balancing pathways in LiNi 0.8 Co 0.1 Mn 0.1 O 2 (NCM811) post-fast-charging, elucidating the high polarization during late charging caused by exacerbated irreversible local electric field. By intermittently applying reverse potential during fast charging to alleviate the exacerbation of non-Faradaic electric field at the cathode interface, we achieved a roughly 400% reversible capacity increase of SSBs at 10 C. This insightful dynamic imaging method effectively captures and resolves the transient, opaque signals within SSBs, significantly enhancing their fast-charging performance.
GPT-4o mini: Non-social science research article
Ancient evolutionary origins of hepatitis E virus in rodents
Wendy K. Jo, Murilo Henrique Anzolini Cassiano, Edmilson Ferreira de Oliveira-Filho, Sebastian BrĂŒnink, Adiya Yansanjav, Mesele Yihune, Alyona I. Koshkina, Alexander N. Lukashev, Leonid A. Lavrenchenko, Vladimir S. Lebedev, Ayodeji Olayemi, Umaru Bangura, MĂłnica Salas-Rojas, Álvaro Aguilar-SetiĂ©n, Elisabeth Fichet-Calvet, Jan Felix Drexler
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Hepatitis E virus (HEV; family Hepeviridae ) infections cause >40,000 human deaths annually. Zoonotic infections predominantly originate from ungulates and occasionally from rats, highlighting the zoonotic potential of rodent-associated hepeviruses. We conducted host genomic data mining and uncovered two genetically divergent rodent-associated hepeviruses, and two bat-associated hepeviruses genetically related to known bat-associated strains. We thus analyzed 2,565 liver specimens from 108 rodent and shrew species sampled from globally understudied regions and hosts in Africa, Asia, and Latin America during 2011-2018 for hepeviruses by RT–PCR. We detected 63 positive field samples (2.5%, 95% CI 1.9-3.1) from 14 animal species, including two coinfections with genetically divergent strains and significant variation ( X 2 , P < 0.001) in detection rates between study sites. Strain-specific qRT–PCR assays showed virus concentrations between 9.2 × 10 2 and 3.2 × 10 9 copies/g. We recovered 24 near-complete hepeviral genomes from rodents, shrews, and bats, all showing three partially overlapping open reading frames (ORFs), some including putative late domains that may be associated with quasi-envelopment. Rodent-derived hepeviruses grouped into five clades clustering in basal sister relationship to human- (31 to 84% distance in translated ORF1-3) and rat-associated HEV. Parsimony-based analyses and cophylogenetic reconciliations revealed that rodents were predominant sources of hepeviral cross-order host shifts. Bayesian ancestral state reconstructions substantiated a direct origin of human-associated HEV in ungulates such as swine and camelids (posterior probability 0.8), whereas the nonrecent evolutionary origins of human- and ungulate-associated HEV were projected to rodent hosts (posterior probability > 0.9). Our results elucidate the genealogy of human HEV and warrant increased surveillance and experimental risk assessments for rodent-associated hepeviruses.
Long-term employment and health effects of active labor market programs
Martin Baekgaard, SĂžren Albeck Nielsen, Michael Rosholm, Michael Svarer
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Active labor market programs (ALMPs) are widely used to speed up return to work among the unemployed. We examine their long-run effects on employment- and health-related outcomes for different target groups, arguing that ALMPs are associated with heterogeneous effects for different target groups and may even detrimentally influence the mental health for the most disadvantaged groups. To this end, we use evidence from randomized controlled trials conducted in Denmark in 2005–2008, in which treatment groups were exposed to intensified active labor market policies in the form of more frequent compulsory meetings with case workers and/or early activation and estimate effects over a period of 10 y. In line with expectations, we find that while ALMPs have the potential to increase labor market participation among resourceful clients even 10 after the original intervention, they have long-run negative effects on the mental health for the most disadvantaged groups among the unemployed. The negative effects are entirely driven by clients who already prior to the trial had mental health issues. These findings suggest that the effects of ALMPs are lasting, but at the same time greatly depend on how they fit with the resources of clients.
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.
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.
Informing public health protection under new patterns of wildfire smoke
Jason D. Sacks
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Patterns of linguistic simplification on social media platforms over time
N. Di Marco, Edoardo Loru, Anita Bonetti, Alessandra Olga Grazia Serra, Matteo Cinelli, Walter Quattrociocchi
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Understanding the impact of digital platforms on user behavior presents foundational challenges, including issues related to polarization, misinformation dynamics, and variation in news consumption. Comparative analyses across platforms and over different years can provide critical insights into these phenomena. This study investigates the linguistic characteristics of user comments over 34 y, focusing on their complexity and temporal shifts. Using a dataset of approximately 300 million English comments from eight diverse platforms and topics, we examine user communications’ vocabulary size and linguistic richness and their evolution over time. Our findings reveal consistent patterns of complexity across social media platforms and topics, characterized by a nearly universal reduction in text length, diminished lexical richness, and decreased repetitiveness. Despite these trends, users consistently introduce new words into their comments at a nearly constant rate. This analysis underscores that platforms only partially influence the complexity of user comments but, instead, it reflects a broader pattern of linguistic change driven by social triggers, suggesting intrinsic tendencies in users’ online interactions comparable to historically recognized linguistic hybridization and contamination processes.
Dynamical theory of complex systems with two-way micro–macro causation
John Harte, Micah Brush, Kaito Umemura, Pranav Muralikrishnan, Erica A. Newman
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In many complex systems encountered in the natural and social sciences, mechanisms governing system dynamics at a microscale depend upon the values of state variables characterizing the system at coarse-grained, macroscale (Goldenfeld and Woese, 2011, Noble et al., 2019, and Chater and Loewenstein, 2023). State variables, in turn, are averages over relevant probability distributions of the microscale variables. Neither inferential Top–Down nor mechanistic Bottom–Up modeling alone can predict responses of such scale-entwined systems to perturbations. We describe and explore the properties of a dynamic theory that combines Top–Down information-theoretic inference with Bottom–Up , state-variable-dependent mechanisms. The theory predicts the functional form of nonstationary probability distributions over microvariables and relates the trajectories of time-evolving macrovariables to the form of those distributions. Analytic expressions for the time evolution of Lagrange multipliers from Maxent solutions allow for rapid calculation of the time trajectories of state variables even in high dimensional systems. Examples of possible applications to scale-entwined systems in nonequilibrium chemical thermodynamics, epidemiology, economics, and ecology exemplify the potential multidisciplinary scope of the theory. A worked-out low-dimension example illustrates the structure of the theory and demonstrates how scale entwinement can result in slowed recovery from perturbations, reddened time series spectra in response to white-noise input, and hysteresis upon parameter displacement and subsequent restoration.
Conditional cooperation with longer memory
Nikoleta E. Glynatsi, Ethan Akin, Martin A. Nowak, Christian Hilbe
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Direct reciprocity is a wide-spread mechanism for the evolution of cooperation. In repeated interactions, players can condition their behavior on previous outcomes. A well-known approach is given by reactive strategies, which respond to the coplayer’s previous move. Here, we extend reactive strategies to longer memories. A reactive- n strategy takes into account the sequence of the last n moves of the coplayer. A reactive- n counting strategy responds to how often the coplayer cooperated during the last n rounds. We derive an algorithm to identify the partner strategies within these strategy sets. Partner strategies are those that ensure mutual cooperation without exploitation. We give explicit conditions for all partner strategies among reactive-2, reactive-3 strategies, and reactive- n counting strategies. To further explore the role of memory, we perform evolutionary simulations. We vary several key parameters, such as the cost-to-benefit ratio of cooperation, the error rate, and the strength of selection. Within the strategy sets we consider, we find that longer memory tends to promote cooperation. This positive effect of memory is particularly pronounced when individuals take into account the precise sequence of moves.
The long-term impact of debt relief for indigent defendants in a misdemeanor court
Lindsay Bing, Rebecca Goldstein, Helen Ho, Devah Pager, Bruce Western
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US courts regularly assess fines, fees, and costs against criminal defendants. Court-related debt can cause continuing court involvement and incarceration, not because of new crimes, but because of unpaid financial obligations. We conducted an experiment with 606 people found guilty of misdemeanors in Oklahoma County, Oklahoma. Study participants were randomly selected to receive relief from all current and prior fines and fees assessed for criminal charges in the county. Fee relief reduced jail bookings 21 mo after randomization and the effect persisted over 44 mo of follow-up. Although fee relief reduced incarceration, financial sanctions had no effect on indicators of lawbreaking. Instead, the control group (who obtained no relief from fines and fees) were rearrested at significantly higher rates because of open arrest warrants for nonpayment. These results indicate the long-term and criminalizing effects of legal debt, supporting claims that financial sanctions disproportionately harm low-income defendants while contributing little to public safety.

Science

GPT-4o mini: Non-social science research article
Room-temperature exceptional plasticity in defective Bi 2 Te 3 -based bulk thermoelectric crystals
Tingting Deng, Zhiqiang Gao, Ze Li, Pengfei Qiu, Zhi Li, Xinjie Yuan, Chen Ming, Tian-Ran Wei, Lidong Chen, Xun Shi
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The recently discovered metal-like room-temperature plasticity in inorganic semiconductors reshapes our knowledge of the physical properties of materials, giving birth to a series of new-concept functional materials. However, current room-temperature plastic inorganic semiconductors are still very rare, and their performance is inferior to that of classic brittle semiconductors. Taking classic bismuth telluride (Bi 2 Te 3 )–based thermoelectric semiconductors as an example, we show that antisite defects can lead to high-density, diverse microstructures that substantially affect mechanical properties and thus successfully transform these bulk semiconductors from brittle to plastic, leading to a high figure of merit of up to 1.05 at 300 kelvin compared with other plastic semiconductors, similar to the best brittle semiconductors. We provide an effective strategy to plastify brittle semiconductors to display good plasticity and excellent functionality simultaneously.
GPT-4o mini: Non-social science research article
A microRNA is the effector gene of a classic evolutionary hotspot locus
Shen Tian, Yoshimasa Asano, Tirtha Das Banerjee, Shinya Komata, Jocelyn Liang Qi Wee, Abigail Lamb, Yehan Wang, Suriya Narayanan Murugesan, Haruhiko Fujiwara, Kumiko Ui-Tei, Patricia J. Wittkopp, AntĂłnia Monteiro
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In Lepidoptera (butterflies and moths), the genomic region around the gene cortex is a “hotspot” locus, repeatedly implicated in generating intraspecific melanic wing color polymorphisms across 100 million years of evolution. However, the identity of the effector gene regulating melanic wing color within this locus remains unknown. We show that none of the four candidate protein-coding genes within this locus, including cortex , serve as major effectors. Instead, a microRNA (miRNA), mir-193 , serves as the major effector across three deeply diverged lineages of butterflies, and its role is conserved in Drosophila . In Lepidoptera, mir-193 is derived from a gigantic primary long noncoding RNA, ivory , and it functions by directly repressing multiple pigmentation genes. We show that a miRNA can drive repeated instances of adaptive evolution in animals.
GPT-4o mini: Non-social science research article
A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors
Ting-Hui Lin, Xueyong Zhu, Shengyang Wang, Ding Zhang, Ryan McBride, Wenli Yu, Simeon Babarinde, James C. Paulson, Ian A. Wilson
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In 2024, several human infections with highly pathogenic clade 2.3.4.4b bovine influenza H5N1 viruses in the United States raised concerns about their capability for bovine-to-human or even human-to-human transmission. In this study, analysis of the hemagglutinin (HA) from the first-reported human-infecting bovine H5N1 virus (A/Texas/37/2024, Texas) revealed avian-type receptor binding preference. Notably, a Gln 226 Leu substitution switched Texas HA binding specificity to human-type receptors, which was enhanced when combined with an Asn 224 Lys mutation. Crystal structures of the Texas HA with avian receptor analog LSTa and its Gln 226 Leu mutant with human receptor analog LSTc elucidated the structural basis for this preferential receptor recognition. These findings highlight the need for continuous surveillance of emerging mutations in avian and bovine clade 2.3.4.4b H5N1 viruses.
GPT-4o mini: Non-social science research article
A conserved bacterial genetic basis for commensal-host specificity
Karina Gutiérrez-García, Kevin Aumiller, Ren Dodge, Benjamin Obadia, Ann Deng, Sneha Agrawal, Xincheng Yuan, Richard Wolff, Haolong Zhu, Ru-Ching Hsia, Nandita Garud, William B. Ludington
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Animals selectively acquire specific symbiotic gut bacteria from their environments that aid host fitness. To colonize, a symbiont must locate its niche and sustain growth within the gut. Adhesins are bacterial cell surface proteins that facilitate attachment to host tissues and are often virulence factors for opportunistic pathogens. However, the attachments are often transient and nonspecific, and additional mechanisms are required to sustain infection. In this work, we use live imaging of individual symbiotic bacterial cells colonizing the gut of living Drosophila melanogaster to show that Lactiplantibacillus plantarum specifically recognizes the fruit fly foregut as a distinct physical niche. L. plantarum establishes stably within its niche through host-specific adhesins encoded by genes carried on a colonization island. The adhesin binding domains are conserved throughout the Lactobacillales, and the island also encodes a secretion system widely conserved among commensal and pathogenic bacteria.
GPT-4o mini: Non-social science research article
Active-reset protein sensors enable continuous in vivo monitoring of inflammation
H. Zargartalebi, S. Mirzaie, A. GhavamiNejad, S. U. Ahmed, F. Esmaeili, A. Geraili, C. D. Flynn, D. Chang, J. Das, A. Abdrabou, E. H. Sargent, S. O. Kelley
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Continuous measurement of proteins in vivo is important for real-time disease management and prevention. Implantable sensors for monitoring small molecules such as glucose have been available for more than a decade. However, analysis of proteins remains an unmet need because the lower physiological levels require that sensors have high affinities, which are linked to long complexation half-lives ( t 1/2 ~20 hours) and slow equilibration when concentrations decrease. We report active-reset sensors by use of high-frequency oscillations to accelerate dissociation, which enables regeneration of the unbound form of the sensor within 1 minute. When implemented within implanted devices, these sensors allow for real-time, in vivo monitoring of proteins within interstitial fluid. Active-reset protein sensors track biomarker levels on a physiological timescale for inflammation monitoring in living animals.
GPT-4o mini: Non-social science research article
The complete telomere-to-telomere sequence of a mouse genome
Junli Liu, Qilin Li, Yixuan Hu, Yi Yu, Kai Zheng, Dengfeng Li, Lexin Qin, Xiaochun Yu
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The current reference genome of Mus musculus , GRCm39, has major gaps in both euchromatic and heterochromatic regions associated with repetitive sequences. In this work, we have sequenced and assembled the telomere-to-telomere genome of mouse haploid embryonic stem cells. The results reveal more than 7.7% of previously uncovered sequences of the mouse genome, including ribosomal DNA arrays and pericentromeric and subtelomeric regions, as well as an additional 140 genes predicted to be protein-coding. This study helps to address knowledge gaps in the mouse genome.
GPT-4o mini: Non-social science research article
Target-conditioned diffusion generates potent TNFR superfamily antagonists and agonists
Matthias Glögl, Aditya Krishnakumar, Robert J. Ragotte, Inna Goreshnik, Brian Coventry, Asim K. Bera, Alex Kang, Emily Joyce, Green Ahn, Buwei Huang, Wei Yang, Wei Chen, Mariana Garcia Sanchez, Brian Koepnick, David Baker
Full text
Despite progress in designing protein-binding proteins, the shape matching of designs to targets is lower than in many native protein complexes, and design efforts have failed for the tumor necrosis factor receptor 1 (TNFR1) and other protein targets with relatively flat and polar surfaces. We hypothesized that free diffusion from random noise could generate shape-matched binders for challenging targets and tested this approach on TNFR1. We obtain designs with low picomolar affinity whose specificity can be completely switched to other family members using partial diffusion. Designs function as antagonists or as superagonists when presented at higher valency for OX40 and 4-1BB. The ability to design high-affinity and high-specificity antagonists and agonists for pharmacologically important targets in silico presages a coming era in protein design in which binders are made by computation rather than immunization or random screening approaches.
GPT-4o mini: Non-social science research article
Imperfect wound healing sets the stage for chronic diseases
Paul Martin, Carlos Pardo-Pastor, R. Gisli Jenkins, Jody Rosenblatt
Full text
Although the age of the genome gave us much insight about how our organs fail with disease, it also suggested that diseases do not arise from mutations alone; rather, they develop as we age. In this Review, we examine how wound healing might act to ignite disease. Wound healing works well when we are younger, repairing damage from accidents, environmental assaults, and battles with pathogens. Yet, with age and accumulation of mutations and tissue damage, the repair process can devolve, leading to inflammation, fibrosis, and neoplastic signaling. We discuss healthy wound responses and how our bodies might misappropriate these pathways in disease. Although we focus predominantly on epithelial-based (lung and skin) diseases, similar pathways might operate in cardiac, muscle, and neuronal diseases.
GPT-4o mini: Non-social science research article
Recent global temperature surge intensified by record-low planetary albedo
Helge F. Goessling, Thomas Rackow, Thomas Jung
Full text
In 2023, the global mean temperature soared to almost 1.5K above the pre-industrial level, surpassing the previous record by about 0.17K. Previous best-guess estimates of known drivers including anthropogenic warming and the El Niño onset fall short by about 0.2K in explaining the temperature rise. Utilizing satellite and reanalysis data, we identify a record-low planetary albedo as the primary factor bridging this gap. The decline is apparently caused largely by a reduced low-cloud cover in the northern mid-latitudes and tropics, in continuation of a multi-annual trend. Further exploring the low-cloud trend and understanding how much of it is due to internal variability, reduced aerosol concentrations, or a possibly emerging low-cloud feedback will be crucial for assessing the current and expected future warming.
GPT-4o mini: Non-social science research article
Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin
Alexander Carver, Tai-Yuan Yu, Luke A. Yates, Travis White, Raymond Wang, Katie Lister, Maria Jasin, Xiaodong Zhang
Full text
Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central player of several crucial processes in repairing DNA and protecting genome integrity, forms filaments on DNA, which are tightly regulated. One of these RAD51 regulators is FIGNL1, that prevents persistent RAD51 foci without or after DNA damage and genotoxic chromatin association in cells. The cryogenic electron microscopy structure of FIGNL1 in complex with RAD51 reveals that FIGNL1 forms a non-planar hexamer and RAD51 N terminus enclosure in the FIGNL1 hexamer pore. Mutations in pore loop or catalytic residues of FIGNL1 render it defective in filament disassembly and are lethal in mouse embryonic stem cells. Our study reveals a unique mechanism for removing RAD51 from bound substrates and provides the molecular basis for FIGNL1 in maintaining genome stability.
GPT-4o mini: Non-social science research article
Science and America’s challenge
Heather Wilson
Full text
Today, more than at any time since World War II, the United States is being challenged scientifically on the global stage. Unfortunately, the nation is not meeting the moment. With a new administration in the wings, the country must begin to monitor scientific advancements to avoid technological surprise and develop strategies to close the critical technologies gap.
GPT-4o mini: Non-social science research article
Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs
Nishith R. Reddy, Hasna Maachi, Yini Xiao, Milos S. Simic, Wei Yu, Yurie Tonai, Daniela A. Cabanillas, Ella Serrano-Wu, Philip T. Pauerstein, Whitney Tamaki, Greg M. Allen, Audrey V. Parent, Matthias Hebrok, Wendell A. Lim
Full text
Immune homeostasis requires a balance of inflammatory and suppressive activities. To design cells potentially useful for local immune suppression, we engineered conventional CD4 + T cells with synthetic Notch (synNotch) receptors driving antigen-triggered production of anti-inflammatory payloads. Screening a diverse library of suppression programs, we observed the strongest suppression of cytotoxic T cell attack by the production of both anti-inflammatory factors (interleukin-10, transforming growth factor–ÎČ1, programmed death ligand 1) and sinks for proinflammatory cytokines (interleukin-2 receptor subunit CD25). Engineered cells with bespoke regulatory programs protected tissues from immune attack without systemic suppression. Synthetic suppressor T cells protected transplanted beta cell organoids from cytotoxic T cells. They also protected specific tissues from unwanted chimeric antigen receptor (CAR) T cell cross-reaction. Synthetic suppressor T cells are a customizable platform to potentially treat autoimmune diseases, organ rejection, and CAR T cell toxicities with spatial precision.
GPT-4o mini: Non-social science research article
A transient neurohormonal circuit controls hatching in fish
Deodatta S. Gajbhiye, Genevieve L. Fernandes, Itay Oz, Yuni Nahmias, Matan Golan
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Hatching is a critical event in the life history of oviparous species. The decision to hatch is often carefully timed to coincide with favorable conditions that will improve survival through early life stages. However, how the relevant cues are relayed to trigger hatching remains unknown. In this work, we show that thyrotropin-releasing hormone (Trh) is the neuroendocrine activator of hatching in zebrafish. To elicit hatching, Trh neurons form a transient circuit that deposits the peptide into the embryo’s circulation. Trh also activates hatching in a distantly related fish species that separated more than 200 million years ago. Our results reveal an evolutionarily conserved neuroendocrine circuit that controls a major life event in oviparous fish species.
GPT-4o mini: Non-social science research article
Programming tissue-sensing T cells that deliver therapies to the brain
Milos S. Simic, Payal B. Watchmaker, Sasha Gupta, Yuan Wang, Sharon A. Sagan, Jason Duecker, Chanelle Shepherd, David Diebold, Psalm Pineo-Cavanaugh, Jeffrey Haegelin, Robert Zhu, Ben Ng, Wei Yu, Yurie Tonai, Lia Cardarelli, Nishith R. Reddy, Sachdev S. Sidhu, Olga Troyanskaya, Stephen L. Hauser, Michael R. Wilson, Scott S. Zamvil, Hideho Okada, Wendell A. Lim
Full text
To engineer cells that can specifically target the central nervous system (CNS), we identified extracellular CNS-specific antigens, including components of the CNS extracellular matrix and surface molecules expressed on neurons or glial cells. Synthetic Notch receptors engineered to detect these antigens were used to program T cells to induce the expression of diverse payloads only in the brain. CNS-targeted T cells that induced chimeric antigen receptor expression efficiently cleared primary and secondary brain tumors without harming cross-reactive cells outside of the brain. Conversely, CNS-targeted cells that locally delivered the immunosuppressive cytokine interleukin-10 ameliorated symptoms in a mouse model of neuroinflammation. Tissue-sensing cells represent a strategy for addressing diverse disorders in an anatomically targeted manner.
GPT-4o mini: Non-social science research article
Programming liquid crystal elastomers for multistep ambidirectional deformability
Yuxing Yao, Atalaya Milan Wilborn, Baptiste Lemaire, Foteini Trigka, Friedrich Stricker, Alan H. Weible, Shucong Li, Robert K. A. Bennett, Tung Chun Cheung, Alison Grinthal, Mikhail Zhernenkov, Guillaume Freychet, Patryk Wąsik, Boris Kozinsky, Michael M. Lerch, Xiaoguang Wang, Joanna Aizenberg
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Ambidirectionality, which is the ability of structural elements to move beyond a reference state in two opposite directions, is common in nature. However, conventional soft materials are typically limited to a single, unidirectional deformation unless complex hybrid constructs are used. We exploited the combination of mesogen self-assembly, polymer chain elasticity, and polymerization-induced stress to design liquid crystalline elastomers that exhibit two mesophases: chevron smectic C (cSmC) and smectic A (SmA). Inducing the cSmC-SmA–isotropic phase transition led to an unusual inversion of the strain field in the microstructure, resulting in opposite deformation modes (e.g., consecutive shrinkage or expansion and right-handed or left-handed twisting and tilting in opposite directions) and high-frequency nonmonotonic oscillations. This ambidirectional movement is scalable and can be used to generate Gaussian transformations at the macroscale.
GPT-4o mini: Non-social science research article
Climate change extinctions
Mark C. Urban
Full text
Climate change is expected to cause irreversible changes to biodiversity, but predicting those risks remains uncertain. I synthesized 485 studies and more than 5 million projections to produce a quantitative global assessment of climate change extinctions. With increased certainty, this meta-analysis suggests that extinctions will accelerate rapidly if global temperatures exceed 1.5°C. The highest-emission scenario would threaten approximately one-third of species, globally. Amphibians; species from mountain, island, and freshwater ecosystems; and species inhabiting South America, Australia, and New Zealand face the greatest threats. In line with predictions, climate change has contributed to an increasing proportion of observed global extinctions since 1970. Besides limiting greenhouse gases, pinpointing which species to protect first will be critical for preserving biodiversity until anthropogenic climate change is halted and reversed.
GPT-4o mini: Non-social science research article
Ecological erosion and expanding extinction risk of sharks and rays
Nicholas K. Dulvy, Nathan Pacoureau, Jay H. Matsushiba, Helen F. Yan, Wade J. VanderWright, Cassandra L. Rigby, Brittany Finucci, C. Samantha Sherman, Rima W. Jabado, John K. Carlson, Riley A. Pollom, Patricia Charvet, Caroline M. Pollock, Craig Hilton-Taylor, Colin A. Simpfendorfer
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The true state of ocean biodiversity is difficult to assess, and there are few global indicators to track the primary threat of overfishing. We calculated a 50-year Red List Index of extinction risk and ecological function for 1199 sharks and rays and found that since 1970, overfishing has halved their populations and their Red List Index has worsened by 19%. Overfishing the largest species in nearshore and pelagic habitats risks loss of ecomorphotypes and a 5 to 22% erosion of functional diversity. Extinction risk is higher in countries with large human coastal populations but lower in nations with stronger governance, larger economies, and greater beneficial fisheries subsidies. Restricting fishing (including incidental catch) and trade to sustainable levels combined with prohibiting retention of highly threatened species can avert further depletion, widespread loss of population connectivity, and top-down predator control.
GPT-4o mini: Non-social science research article
Dissecting the hydrogen bond network of water: Charge transfer and nuclear quantum effects
Mischa FlĂłr, David M. Wilkins, Miguel de la Puente, Damien Laage, Giuseppe Cassone, Ali Hassanali, Sylvie Roke
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The molecular structure of water is dynamic, with intermolecular hydrogen (H) bond interactions being modified by both electronic charge transfer and nuclear quantum effects (NQEs). Electronic charge transfer and NQEs potentially change under acidic or basic conditions, but such details have not been measured. In this work, we developed correlated vibrational spectroscopy, a symmetry-based method that separates interacting from noninteracting molecules in self- and cross-correlation spectra, giving access to previously inaccessible information. We found that hydroxide (OH − ) donated ~8% more negative charge to the H bond network of water, and hydronium (H 3 O + ) accepted ~4% less negative charge from the H bond network of water. Deuterium oxide (D 2 O) had ~9% more H bonds compared with water (H 2 O), and acidic solutions displayed more dominant NQEs than basic ones.
GPT-4o mini: Non-social science research article
Pathways to reduce global plastic waste mismanagement and greenhouse gas emissions by 2050
A. Samuel Pottinger, Roland Geyer, Nivedita Biyani, Ciera C. Martinez, Neil Nathan, Molly R. Morse, Chao Liu, Shanying Hu, Magali de Bruyn, Carl Boettiger, Elijah Baker, Douglas J. McCauley
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Plastic production and plastic pollution have a negative effect on our environment, environmental justice, and climate change. Using detailed global and regional plastics datasets coupled with socioeconomic data, we employ machine learning to predict that, without intervention, annual mismanaged plastic waste will nearly double to 121 million metric tonnes (Mt) [100 to 139 Mt 95% confidence interval] by 2050. Annual greenhouse gas emissions from the plastic system are projected to grow by 37% to 3.35 billion tonnes CO 2 equivalent (3.09 to 3.54) over the same period. The United Nations plastic pollution treaty presents an opportunity to reshape these outcomes. We simulate eight candidate treaty policies and find that just four could together reduce mismanaged plastic waste by 91% (86 to 98%) and gross plastic–related greenhouse gas emissions by one-third.
Science abstract < 200 char.: Not a research article
Trump picks an ‘outsider’ and NIH critic to lead agency
Jocelyn Kaiser
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Jay Bhattacharya, who has analyzed NIH funding and ripped U.S. COVID-19 policies, could overhaul key funder
Science abstract < 200 char.: Not a research article
Home sweet home
T. Jarrod Smith, Karen Guillemin
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Sugar-binding adhesins enable bacteria to persist in specific host niches
Science abstract < 200 char.: Not a research article
In Science Journals
Corinne Simonti, Caroline Ash, Brent Grocholski, Marc S. Lavine, Bianca Lopez, Michael A. Funk, Sacha Vignieri, Wei Wong, Stella M. Hurtley, L. Bryan Ray, Yury Suleymanov, Mattia Maroso, Claire Olingy, Mark S. Aldenderfer, Catherine Charneski
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Highlights from the Science family of journals
Science abstract < 200 char.: Not a research article
EU needs groundwater ecosystems guidelines
Tiziana Di Lorenzo, Enrico Lunghi, Cristina Aanei, Florian Altermatt, Roman Alther, Isabel R. Amorim, Raluca I. Băncilă, AdriĂ  Bellvert, Anna Blomberg, Paulo A. V. Borges, Traian Brad, Anton Brancelj, David Brankovits, Pedro Cardoso, Francesco Cerasoli, Claire A. Chauveau, LuĂ­s Crespo, Michael Csader, Teo Delić, Mattia Di Cicco, Christophe J. Douady, Louis Duchemin, Arnaud Faille, Barbara Fiasca, Cene FiĆĄer, Jean-Francois Flot, Rosalina Gabriel, Diana M. P. Galassi, Laura Garzoli, Christian Griebler, Clemens Karwautz, Marius I. Kenesz, Lara Konecny-DuprĂ©, Thomas Lilley, Florian Malard, Alejandro MartĂ­nez, Melissa B. Meierhofer, Giuseppe Messana, AndrĂ©s MillĂĄn, Vangelis Mizerakis, NataĆĄa Mori, Veronica Nanni, Giuseppe Nicolosi, Pedro OromĂ­, Susana PallarĂ©s, Fernando Pereira, Ana Sofia P. S. Reboleira, Mattia SaccĂČ, Alice Salussolia, David SĂĄnchez-FernĂĄndez, Serban M. Sarbu, Andrei S̗tefan, Fabio Stoch, Agostina Tabilio Di Camillo, Stefano Taiti, Ilaria Vaccarelli, Valeria Valanne, Maja Zagmajster, Valerija ZakĆĄek, Carina Zittra, Stefano Mammola
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Science abstract < 200 char.: Not a research article
War-torn Ukraine is breeding drug-resistant bacterial strains
Richard Stone
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Urgent action underway to bolster treatments and prevent dangerous microbes from spilling across borders
Science abstract < 200 char.: Not a research article
Speaking for myself
Ogochukwu Joseph Uweru
Full text
Science abstract < 200 char.: Not a research article
How the brain hatches an escape
Francesco Argenton, Yoav Gothilf
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A neuroendocrine circuit controls when fish larvae are ready to hatch
Science abstract < 200 char.: Not a research article
Synthetic gene circuits drive disease-fighting T cells
Marco L. Davila, Renier Brentjens
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Immune cells can be programmed to deliver targeted therapies in models of brain and inflammatory disease
Science abstract < 200 char.: Not a research article
Scopes monkey trial, in context Keeping the Faith: God, Democracy, and the Trial That Riveted a Nation Brenda Wineapple Random House, 2024. 544 pp.
Vassiliki Betty Smocovitis
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A writer reexamines the 20th-century showdown between science and religion
Science abstract < 200 char.: Not a research article
On the origins of organisms The Origin of Life Aleksandr I. Oparin Moscovky Rabotchii, 1924.
Antonio Lazcano
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The heterotrophic theory of the origin of life turns 100
Science abstract < 200 char.: Not a research article
Extending prosperity to Mexican seas
Octavio Aburto-Oropeza, Catalina LĂłpez-SagĂĄstegui, Alejandro Robles, Exequiel Ezcurra
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Science abstract < 200 char.: Not a research article
Storm warnings for FDA and CDC
Jennifer Couzin-Frankel, Phie Jacobs
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Science abstract < 200 char.: Not a research article
Controversial study redraws classical picture of the neuron
Sofia Quaglia
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Fine-grained imaging of mouse brain cells suggests “pearling” of axons that may help with signaling
Science abstract < 200 char.: Not a research article
Continuous monitoring with a shake
Sihong Wang
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Oscillating signals rapidly reset a sensor for real-time protein detection in the body
Science abstract < 200 char.: Not a research article
Editorial Expression of Concern
H. Holden Thorp
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Science abstract < 200 char.: Not a research article
‘Brutal’ math test raises the bar for AI
Zack Savitsky
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Model-stumping benchmark shows human experts remain on top—for now
Science abstract < 200 char.: Not a research article
In Other Journals
Marc S. Lavine, Corinne Simonti, Keith T. Smith, Caroline Ash, Yevgeniya Nusinovich, Yury Suleymanov, L. Bryan Ray
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Editors’ selections from the current scientific literature
Science abstract < 200 char.: Not a research article
Act on a mandate to protect research subjects’ privacy
Leslie E. Wolf, Natalie Ram
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Congress called for the protection of data from legal process
Science abstract < 200 char.: Not a research article
Beneath Antarctica’s ice, a fiery future may await
Paul Voosen
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Researchers probe volcanoes’ response to a changing world
Science abstract < 200 char.: Not a research article
Breaking the glass
Sofia Moutinho
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Latin America is a leader in nonprofit open-access journals. But it struggles to give them global visibility

Science Advances

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
Full text
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
Full text
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
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
Full text
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
Full text
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
Structural and molecular properties of mumps virus inclusion bodies
Hiroshi Katoh, Ryuichi Kimura, Tsuyoshi Sekizuka, Kohei Matsuoka, Mika Hosogi, Yuki Kitai, Yukiko Akahori, Fumihiro Kato, Michiyo Kataoka, Hirotaka Kobayashi, Noriyo Nagata, Tadaki Suzuki, Yasuyuki Ohkawa, Shinya Oki, Makoto Takeda
Full text
Viral RNA synthesis of mononegaviruses occurs in cytoplasmic membraneless organelles called inclusion bodies (IBs). Here, we report that IBs of mumps virus (MuV), which is the causative agent of mumps and belongs to the family Paramyxoviridae , displayed liquid organelle properties formed by liquid-liquid phase separation. Super-resolution microscopic analysis of MuV IBs demonstrated that nucleocapsid and phospho (P)-proteins formed a cage-like structure and that the viral polymerase adopted a reticular pattern and colocalized with viral RNAs. In addition, we characterized host RNAs localized in MuV IBs by a spatial transcriptome analysis, and found that RNAs containing G-quadruplex motif sequences (G4-RNAs) were concentrated. An in vitro phase separation assay showed that the G4-RNAs interacted with the P protein and enhanced condensation in P droplets. Together, our data show that MuV generates IBs with a characteristic cage-like structure and host G4-RNAs play an important role in forming MuV IBs.
GPT-4o mini: Non-social science research article
Charting the transcriptomic landscape of primary and metastatic cancers in relation to their origin and target normal tissues
Neel Sanghvi, Camilo Calvo-Alcañiz, Padma S. Rajagopal, Stefano Scalera, Valeria Canu, Sanju Sinha, Fiorella Schischlik, Kun Wang, Sanna Madan, Eldad Shulman, Antonios Papanicolau-Sengos, Giovanni Blandino, Eytan Ruppin, Nishanth Ulhas Nair
Full text
Metastasis is a leading cause of cancer-related deaths, yet understanding how metastatic tumors adapt from their origin to their target tissues remains a fundamental challenge. To address this, we assessed whether primary and metastatic tumors more closely resemble their tissues of origin or target tissues in terms of gene expression. We analyzed expression profiles from multiple cancer types and normal tissues, including single-cell and bulk RNA sequencing data from both paired and unpaired patient cohorts. Primary tumors were overall more transcriptomically similar to their tissues of origin, while metastases shifted toward their target tissues. However, pathway-level analysis highlighted critical metabolic and immune transcriptomic changes toward target tissues during metastasis in both primary and metastatic tumors. In addition, primary tumors exhibited higher activity in cancer hallmarks such as “Activating Invasion and Metastasis” when compared to metastases. This comprehensive analysis provides a transcriptome-wide view of the processes through which cancer tumors adapt to their metastatic environments before and after metastasis.
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
Full text
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
Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies
Kumar Nagarathinam, Andreas Scheck, Maurice Labuhn, Luisa J. Ströh, Elisabeth Herold, Barbora Veselkova, Sarah Tune, Johannes T. Cramer, Stéphane Rosset, Sabrina S. Vollers, Dorothea Bankwitz, Matthias Ballmaier, Heike Böning, Edith Roth, Tanvi Khera, Henrike P. Ahsendorf-Abidi, Oliver Dittrich-Breiholz, Jonas Obleser, Michael Nassal, Hans-Martin JÀck, Thomas Pietschmann, Bruno E. Correia, Thomas Krey
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Hepatitis C virus (HCV) infection causes ~290,000 annual human deaths despite the highly effective antiviral treatment available. Several viral immune evasion mechanisms have hampered the development of an effective vaccine against HCV, among them the remarkable conformational flexibility within neutralization epitopes in the HCV antigens. Here, we report the design of epitope-focused immunogens displaying two distinct HCV cross-neutralization epitopes. We show that these immunogens induce a pronounced, broadly neutralizing antibody response in laboratory and transgenic human antibody mice. Monoclonal human antibodies isolated from immunized human antibody mice specifically recognized the grafted epitopes and neutralized four diverse HCV strains. Our results highlight a promising strategy for developing HCV immunogens and provide an encouraging paradigm for targeting structurally flexible epitopes to improve the induction of neutralizing antibodies.
GPT-4o mini: Non-social science research article
Optimal repetitive readout of single solid-state spins determined by Fisher information
Zhiyuan Zhao, Shaoyi Xu, Qian Shi, Yu Chen, Xi Kong, Zhiping Yang, Mengqi Wang, Xiangyu Ye, Pei Yu, Ya Wang, Tianyu Xie, Fazhan Shi, Jiangfeng Du
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Quantum systems, including superconducting circuits, trapped ions, quantum dots, solid-state defects, etc., have achieved considerable advancements in readout fidelity. However, the widely used threshold method disregards the importance of temporal characteristics of the signal during continuous measurements, leading to information loss. Here, we applied Fisher information to quantify the potential enhancement by using the temporal information. We proposed an optimal data processing method and derived the condition for equality to the error constrained by Fisher information. Applying this method to the single-shot readout of a 13 C nuclear spin of nitrogen-vacancy center marks a 33.8 ± 1.2% error reduction compared to the threshold method, improving the fidelity to 99.649(5)%. The versatility of our method is further demonstrated through the single-shot readout of charge states. This work illustrates the advantage of using photon arrival time for improving readout fidelity without upgrading experimental hardware. The method of using Fisher information to analyze readout fidelity also holds promise for broad applicability to other systems.
GPT-4o mini: Non-social science research article
Transcription-coupled changes in genomic region proximities during transcriptional bursting
Hiroaki Ohishi, Soya Shinkai, Hitoshi Owada, Takeru Fujii, Kazufumi Hosoda, Shuichi Onami, Takashi Yamamoto, Yasuyuki Ohkawa, Hiroshi Ochiai
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The orchestration of our genes heavily relies on coordinated communication between enhancers and promoters, yet the mechanisms behind this dynamic interplay during active transcription remain unclear. Here, we investigated enhancer-promoter (E-P) interactions in relation to transcriptional bursting in mouse embryonic stem cells using sequential DNA/RNA/immunofluorescence–fluorescence in situ hybridization analyses. Our data reveal that the active state of specific genes is characterized by specific proximities between different genomic regions and the accumulation of transcriptional regulatory factors. Mathematical simulations suggest that an increase in local viscosity could potentially contribute to stabilizing the duration of these E-P proximities. Our study provides insights into the association among E-P proximity, protein accumulation, and transcriptional dynamics, paving the way for a more nuanced understanding of gene-specific regulatory mechanisms.
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
Neuronal circuit mechanisms of competitive interaction between action-based and coincidence learning
Eyal Rozenfeld, Moshe Parnas
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How information is integrated across different forms of learning is crucial to understanding higher cognitive functions. Animals form classic or operant associations between cues and their outcomes. It is believed that a prerequisite for operant conditioning is the formation of a classical association. Thus, both memories coexist and are additive. However, the two memories can result in opposing behavioral responses, which can be disadvantageous. We show that Drosophila classical and operant olfactory conditioning rely on distinct neuronal pathways leading to different behavioral responses. Plasticity in both pathways cannot be formed simultaneously. If plasticity occurs at both pathways, interference between them occurs and learning is disrupted. Activity of the navigation center is required to prevent plasticity in the classical pathway and enable it in the operant pathway. These findings fundamentally challenge hierarchical views of operant and classical learning and show that active processes prevent coexistence of the two memories.
GPT-4o mini: Non-social science research article
Experimental demonstration of the equivalence of entropic uncertainty with wave-particle duality
Daniel Spegel-Lexne, Santiago Gómez, Joakim Argillander, Marcin PawƂowski, Pedro R. Dieguez, Alvaro Alarcón, Guilherme B. Xavier
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Wave-particle duality is one of the most notable and counterintuitive features of quantum mechanics, illustrating that two incompatible observables cannot be measured simultaneously with arbitrary precision. In this work, we experimentally demonstrate the equivalence of wave-particle duality and entropic uncertainty relations using orbital angular momentum (OAM) states of light. Our experiment uses an innovative and reconfigurable platform composed of few-mode optical fibers and photonic lanterns, showcasing the versatility of this technology for quantum information processing. Our results provide fundamental insights into the complementarity principle from an informational perspective, with implications for the broader field of quantum technologies.
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
An extragenital cell population contributes to urethra closure during mouse penis development
Ciro Maurizio Amato, Xin Xu, Humphrey Hung-Chang Yao
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The penis, the organ that bears reproductive and psychological importance, is susceptible to birth defects such as hypospadias or incomplete closure of urethra along the penis shaft. We discover that proper urethral closure in mouse embryos requires a unique mesenchymal cell population originated from outside of the penis. These “extragenital” cells, marked by a lineage marker Nr5a1 , migrate from the inguinal region into the embryonic penis and facilitate urethra closure by interacting with adjacent periurethral cells via the epidermal growth factor pathway. Ablation of Nr5a1 + cells leads to severe hypospadias and alters cell differentiation in the penis. This discovery highlights the indispensable role of Nr5a1 + extragenital cells in urethra closure, shedding light on the biology of penis formation and potential implications for human hypospadias.
GPT-4o mini: Non-social science research article
X-ray–induced acoustic computed tomography: 3D X-ray absorption imaging from a single view
Siqi Wang, Prabodh Kumar Pandey, Gerald Lee, Rick J. P. van Bergen, Leshan Sun, Yifei Xu, Liangzhong) Xiang
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Computed tomography (CT) scanners are essential for modern imaging but require around 600 projections from various angles. We present x-ray–induced acoustic computed tomography (XACT), a method that uses radiation-induced acoustic waves for three-dimensional (3D) x-ray imaging. These spherical acoustic waves travel through tissue at 1.5 × 10 3 meters per second, much slower than x-rays, allowing ultrasound detectors to capture them and generate 3D images without mechanical scanning. We validate this theory by performing 3D numerical reconstructions of a human breast from a single x-ray projection and experimentally determining 3D structures of objects at different depths. Achieving resolutions of 0.4 millimeters in the XZ plane and 3.5 millimeters in the XY plane at a depth of 16 millimeters, XACT demonstrates the ability to produce 3D images from one x-ray projection, reducing radiation exposure and enabling gantry-free imaging. XACT shows great promise for biomedical and nondestructive testing applications, potentially replacing conventional CT.
GPT-4o mini: Non-social science research article
Dynamic silicone hydrogel gauze coatings with dual anti-blood adhesion mechanism for rapid hemostasis and minimal secondary damage
Xiubin Xu, Yanting Chen, Yunlong Li, Xin Li, Jian Bai, Xusheng Jiang, Danfeng Yu, Xu Wu, Xi Yao
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Hemostatic materials that can rapidly control bleeding without causing secondary damage or sharp pain upon removal are receiving increasing demands in acute trauma treatments and first-aid supplies. Here, we report the development of a dynamic silicone hydrogel coating on medical gauze to enable rapid hemostasis and synergistic anti-blood adhesion properties. The silicone hydrogel can spontaneously form oriented cross-linked structures on fibrous medical gauze through a solution-processing method to achieve macroscopic superhydrophobicity with microscopic surface slipperiness, resulting in excellent anti-blood adhesion with the on-wound peeling force at ~0 millinewton. The development of dynamic silicone hydrogel coating on medical gauze enables a unique integration of advanced features including instant bleeding control, excellent anti-blood adhesion, and excellent air permeability. The proposed strategy is also suitable for scalable production, making it promising in the applications of trauma management.
GPT-4o mini: Non-social science research article
Magnetic kirigami dome metasheet with high deformability and stiffness for adaptive dynamic shape-shifting and multimodal manipulation
Yinding Chi, Emily E. Evans, Matthew R. Clary, Fangjie Qi, Haoze Sun, Saarah Niesha CantĂș, Catherine M. Capodanno, Joseph B. Tracy, Jie Yin
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Soft shape-shifting materials offer enhanced adaptability in shape-governed properties and functionalities. However, once morphed, they struggle to reprogram their shapes and simultaneously bear loads for fulfilling multifunctionalities. Here, we report a dynamic spatiotemporal shape-shifting kirigami dome metasheet with high deformability and stiffness that responds rapidly to dynamically changing magnetic fields. The magnetic kirigami dome exhibits over twice higher doming height and 1.5 times larger bending curvature, as well as sevenfold enhanced structural stiffness compared to its continuous counterpart without cuts. The metasheet achieves omnidirectional doming and multimodal translational and rotational wave-like shape-shifting, quickly responding to changing magnetic fields within 2 milliseconds. Using the dynamic shape-shifting and adaptive interactions with objects, we demonstrate its applications in voxelated dynamic displays and remote magnetic multimodal directional and rotary manipulation of nonmagnetic objects without grasping. It shows high-load transportation ability of over 40 times its own weight, as well as versatility in handling objects of different materials (liquid and solid), sizes, shapes, and weights.
GPT-4o mini: Non-social science research article
Metasurface spectrometers beyond resolution-sensitivity constraints
Feng Tang, Jingjun Wu, Tom Albrow-Owen, Hanxiao Cui, Fujia Chen, Yaqi Shi, Lan Zou, Jun Chen, Xuhan Guo, Yijun Sun, Jikui Luo, Bingfeng Ju, Jing Huang, Shuangli Liu, Bo Li, Liming Yang, Eric A. Munro, Wanguo Zheng, Hannah J. Joyce, Hongsheng Chen, Lufeng Che, Shurong Dong, Zhipei Sun, Tawfique Hasan, Xin Ye, Yihao Yang, Zongyin Yang
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Conventional spectrometer designs necessitate a compromise between their resolution and sensitivity, especially as device and detector dimensions are scaled down. Here, we report on a miniaturizable spectrometer platform where light throughput onto the detector is instead enhanced as the resolution is increased. This planar, CMOS-compatible platform is based around metasurface encoders designed to exhibit photonic bound states in the continuum, where operational range can be altered or extended simply through adjusting geometric parameters. This system can enhance photon collection efficiency by up to two orders of magnitude versus conventional designs; we demonstrate this sensitivity advantage through ultralow-intensity fluorescent and astrophotonic spectroscopy. This work represents a step forward for the practical utility of spectrometers, affording a route to integrated, chip-based devices that maintain high resolution and SNR without requiring prohibitively long integration times.
GPT-4o mini: Non-social science research article
Sex-dimorphic tumor growth is regulated by tumor microenvironmental and systemic signals
Xianfeng Wang, Hongcun Bao, Yi-Chun Huang, Anindita Barua, Chun-Ming Lai, Jie Sun, Youfang Zhou, Fei Cong, Shangyu Gong, Chih-Hsuan Chang, Wu-Min Deng
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Tumor growth and progression involve coordinated regulation by internal, microenvironmental, and systemic signals and often display conspicuous sexual dimorphism. The mechanisms governing the integration and coordination of these signals, along with their sex-based differences, remain largely unknown. Using a Drosophila tumor model originating from nonreproductive tissue, we show that female-biased tumor growth involves multifaceted communications among tumor cells, hemocytes, and neuroendocrine insulin-producing cells (IPCs). Notch-active tumor cells recruit hemocytes carrying the tumor necrosis factor–α (TNF-α) homolog Eiger to the tumor microenvironment (TME), activating the c-Jun N-terminal kinase (JNK) pathway in tumor cells, instigating the sexually dimorphic up-regulation of cytokine Unpaired 2 (Upd2). Upd2, in turn, exerts a distal influence by modulating the release of a Drosophila insulin-like peptide (Dilp2) from IPCs. Dilp2 then activates the insulin signaling in the tumor, thereby fostering sexual-dimorphic tumor growth. Together, these findings reveal a relay mechanism involving the TME and systemic signals that collectively control the sexual dimorphism of tumor growth.
GPT-4o mini: Non-social science research article
Size-dependent guest-memory switching of the flexible and robust adsorption characteristics of layered metal-organic frameworks
Satoshi Watanabe, Shotaro Hiraide, Homare Arima, Akiko Fukuta, Miyuki Mori, Hideki Tanaka, Minoru T. Miyahara
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Flexible-robust metal-organic frameworks (MOFs), which exhibit unique hybrid nature comprising both flexible and rigid framework characteristics, exhibit high potential for hydrocarbon separations. However, no clear guidelines have been established to regulate their hybrid characteristics owing to limited understanding of their adsorption mechanism. This study investigates the effects of the particle size of a flexible-robust MOF on its adsorption and structural transition behaviors. The robust nature originates from the structural transition of a metastable guest-free structure, while its flexible nature arises from another guest-free structure. The type of guest-free structure is predominantly determined by the particle size; particles below the critical size are trapped in the metastable guest-free structure. Notably, the critical size varies with the type of guest molecule to be removed; consequently, the difference in critical size results in guest-memory characteristics, enabling guest-free structure switching. These results underscore the importance of controlling the particle size to fine-tune hybrid adsorption characteristics of flexible-robust MOFs.
GPT-4o mini: Non-social science research article
Plankton food web structure and productivity under ocean alkalinity enhancement
NicolĂĄs SĂĄnchez, Silvan U. Goldenberg, Daniel BrĂŒggemann, Cornelia Jaspers, Jan Taucher, Ulf Riebesell
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Ocean alkalinity enhancement (OAE) is a nature-based technology for CO 2 removal and storage, but little is known about its environmental safety. We tested a CO 2 -equilibrated OAE deployment in a close-to-natural community using in situ mesocosms in the oligotrophic subtropical North Atlantic and assessed metazoan zooplankton to inform about food web stability, structure, and production. In addition, a literature review complemented experimental results by summarizing physiological responses of marine animals to decreasing proton concentrations, or increased pH. The food web studied proved resistant, and zooplankton physiologically tolerant, to the OAE tested. We observed short-term effects of OAE on zooplankton reproduction and productivity, which were likely trophically mediated. Yet, these did not affect zooplankton populations or their nutritional value as food for fish. Our study demonstrates an environmentally safe OAE application, but also stresses the risks of more intense OAE options, and the vulnerabilities of other marine ecosystems.
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 Fernåndez-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 ÎČ1 and influences the association between dipeptidyl-4 with Integrin ÎČ1. 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
A trafficking regulatory subnetwork governs α V ÎČ 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 ÎČ 6 integrin are independent predictors of breast cancer survival and metastasis. We identify an α V ÎČ 6 /HER2 cross-talk mechanism driving invasion, which is dysregulated in drug-resistant HER2+ breast cancer cells. Proteomic analyses reveal ligand-bound α V ÎČ 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 ÎČ 6 and HER2, affecting receptor trafficking and signaling. Acute exposure to trastuzumab increases recruitment of the subnetwork to α V ÎČ 6 , but trastuzumab resistance decouples GDI2 recruitment. GDI2, RAB5, and RAB7A cooperate to regulate migration and transforming growth factor–ÎČ 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 ÎČ 6 expression predicts relapse following trastuzumab treatment. Thus, the RAB5/RAB7A/GDI2 subnetwork regulates α V ÎČ 6 -HER2 cross-talk to drive breast cancer invasion but is subverted in trastuzumab-resistant cells to drive α V ÎČ 6 -independent and HER2-independent tumor progression.
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
Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission
Paula-Josefina Gomez-Gonzalez, Antima Gupta, Laura G. Drought, Avnish Patel, John Okombo, Mariëtte van der Watt, Ryan Walker-Gray, Kyra A. Schindler, Anna Y. Burkhard, Tomas Yeo, Sunil K. Narwal, Talia S. Bloxham, Christian Flueck, Eloise M. Walker, Joshua A. Rey, Kate J. Fairhurst, Janette Reader, Heekuk Park, Harry G. Pollard, Lindsay B. Stewart, Luke Brandner-Garrod, Mojca Kristan, Geert-Jan Sterk, Youri M. van Nuland, Emilia Manko, Donelly A. van Schalkwyk, Yang Zheng, Rob Leurs, Koen J. Dechering, Anna Caroline C. Aguiar, Rafael V. C. Guido, Dhelio B. Pereira, Patrick K. Tumwebaze, Samuel L. Nosbya, Philip J. Rosenthal, Roland A. Cooper, Mike Palmer, Tanya Parkinson, Jeremy N. Burrows, Anne-Catrin Uhlemann, Lyn-Marié Birkholtz, Jennifer L. Small-Saunders, James Duffy, David A. Fidock, Alan Brown, Mark Gardner, David A. Baker
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Cyclic nucleotide–dependent phosphodiesterases (PDEs) play essential roles in regulating the malaria parasite life cycle, suggesting that they may be promising antimalarial drug targets. PDE inhibitors are used safely to treat a range of noninfectious human disorders. Here, we report three subseries of fast-acting and potent Plasmodium falciparum PDEÎČ inhibitors that block asexual blood-stage parasite development and that are also active against human clinical isolates. Two of the inhibitor subseries also have potent transmission-blocking activity by targeting PDEs expressed during sexual parasite development. In vitro drug selection experiments generated parasites with moderately reduced susceptibility to the inhibitors. Whole-genome sequencing of these parasites detected no mutations in PDEÎČ but rather mutations in downstream effectors: either the catalytic or regulatory subunits of cyclic adenosine monophosphate–dependent protein kinase (PKA) or in the 3-phosphoinositide-dependent protein kinase that is required for PKA activation. Several properties of these P. falciparum PDE inhibitor series make them attractive for further progression through the antimalarial drug discovery pipeline.
GPT-4o mini: Non-social science research article
Ultrathin rubbery bio-optoelectronic stimulators for untethered cardiac stimulation
Zhoulyu Rao, Faheem Ershad, Ying-Shi Guan, Fernanda C. Paccola Mesquita, Ernesto Curty da Costa, Marco A. Morales-Garza, Angel Moctezuma-Ramirez, Bin Kan, Yuntao Lu, Shubham Patel, Hyunseok Shim, Kuan Cheng, Wenjie Wu, Tahir Haideri, Xiaojun Lance Lian, Alamgir Karim, Jian Yang, Abdelmotagaly Elgalad, Camila Hochman-Mendez, Cunjiang Yu
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Untethered electrical stimulation or pacing of the heart is of critical importance in addressing the pressing needs of cardiovascular diseases in both clinical therapies and fundamental studies. Among various stimulation methods, light illumination–induced electrical stimulation via photoelectric effect without any genetic modifications to beating cells/tissues or whole heart has profound benefits. However, a critical bottleneck lies in the lack of a suitable material with tissue-like mechanical softness and deformability and sufficient optoelectronic performances toward effective stimulation. Here, we introduce an ultrathin (<500 nm), stretchy, and self-adhesive rubbery bio-optoelectronic stimulator (RBOES) in a bilayer construct of a rubbery semiconducting nanofilm and a transparent, stretchable gold nanomesh conductor. The RBOES could maintain its optoelectronic performance when it was stretched by 20%. The RBOES was validated to effectively accelerate the beating of the human induced pluripotent stem cell–derived cardiomyocytes. Furthermore, acceleration of ex vivo perfused rat hearts by optoelectronic stimulation with the self-adhered RBOES was achieved with repetitive pulsed light illumination.
GPT-4o mini: Non-social science research article
Gene acquisition by giant transposons primes eukaryotes for rapid evolution via horizontal gene transfer
Andrew S. Urquhart, Emile Gluck-Thaler, Aaron A. Vogan
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Horizontal gene transfer (HGT) disseminates genetic information between species and is a powerful mechanism of adaptation. Yet, we know little about its underlying drivers in eukaryotes. Giant Starship transposons have been implicated as agents of fungal HGT, providing an unprecedented opportunity to reveal the evolutionary parameters behind this process. Here, we characterize the ssf gene cluster, which contributes to formaldehyde resistance, and use it to demonstrate how mobile element evolution shapes fungal adaptation. We found that ssf clusters have been acquired by various distantly related Starships , which each exhibit multiple instances of horizontal transfer across fungal species (at least nine events, including between different taxonomic orders). Many ssf clusters have subsequently integrated into their host’s genome, illustrating how Starships shape the evolutionary trajectory of fungal hosts beyond any single transfer. Our results demonstrate the key role Starships play in mediating rapid and repeated adaptation via HGT, elevating the importance of mobile element evolution in eukaryotic biology.
GPT-4o mini: Non-social science research article
Laser-induced adhesives with excellent adhesion enhancement and reduction capabilities for transfer printing of microchips
Chenglong Li, Shun Zhang, Jing Jiang, Suhao Wang, Shuchang He, Jizhou Song
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Transfer printing based on tunable and reversible adhesive that enables the heterogeneous integration of materials is essential for developing envisioned electronic systems. An adhesive with both adhesion enhancement and reduction capabilities in a rapid and selective manner is challenging. Here, we report a laser-induced adhesive, featuring a geometrically simple shape memory polymer layer on a glass backing, with excellent adhesion modulation capability for programmable pickup and noncontact printing of microchips. Selective and rapid laser heating substantially enhances the adhesive’s adhesion strength from kilopascal to megapascal within 10 ms due to the shape fixing effect, allowing for precise and programmable pickup. Conversely, the enhanced adhesion can be quickly reduced and eliminated within 3 ms through the shape recovery effect, enabling noncontact printing. Demonstrations of transfer printing microlight-emitting diodes (LEDs) and mini-LEDs onto various low-adhesive flat, rough, and curved surfaces highlight the unusual capabilities of this adhesive for deterministic assembly.
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.
Antidepressant use in spatial social networks
Balázs Lengyel, GergƑ Tóth, Nicholas A. Christakis, Anikó Bíró
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Social networks may help individuals maintain their mental health. Most empirical work based on small-scale surveys finds that cohesive social networks are critical for mental well-being, while diverse networks are considered less important. Here, we link data on antidepressant use of 277,344 small-town residents to a nationwide online social network. The data enable us to examine how individuals’ mental health care is related to the spatial characteristics of their social networks including their ties in the local community and connections to distant communities. We find that, besides the cohesion of social networks around home, the diversity of connections to distant places is negatively correlated with the probability of antidepressant use. Spatial diversity of social networks is also associated with decreasing dosage in subsequent years. This relationship is independent from the local access to antidepressants and is more prevalent for young individuals. Structural features of spatial social networks are prospectively associated with depression treatment.
Heat disproportionately kills young people: Evidence from wet-bulb temperature in Mexico
Andrew J. Wilson, R. Daniel Bressler, Catherine Ivanovich, Cascade Tuholske, Colin Raymond, Radley M. Horton, Adam Sobel, Patrick Kinney, Tereza Cavazos, Jeffrey G. Shrader
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Recent studies project that temperature-related mortality will be the largest source of damage from climate change, with particular concern for the elderly whom it is believed bear the largest heat-related mortality risk. We study heat and mortality in Mexico, a country that exhibits a unique combination of universal mortality microdata and among the most extreme levels of humid heat. Combining detailed measurements of wet-bulb temperature with age-specific mortality data, we find that younger people who are particularly vulnerable to heat: People under 35 years old account for 75% of recent heat-related deaths and 87% of heat-related lost life years, while those 50 and older account for 96% of cold-related deaths and 80% of cold-related lost life years. We develop high-resolution projections of humid heat and associated mortality and find that under the end-of-century SSP 3–7.0 emissions scenario, temperature-related deaths shift from older to younger people. Deaths among under-35-year-olds increase 32% while decreasing by 33% among other age groups.
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.